Assessment of Paraesthesias

Assessment of
paraesthesias
Straight to the point of care
Last updated: Nov 01, 2018

Table of Contents
Overview 3
Summary 3
Theory 4
Aetiology 4
Emergencies 14
Urgent considerations 14
Diagnosis 16
Approach 16
Differentials overview 32
Differentials 36
Guidelines 72
References 73
Images 80
Disclaimer 88
Assessment of paraesthesias Overview
Summary
Paraesthesias are abnormal sensory symptoms typically characterised as tingling, prickling, pins and
needles, or burning sensations. They may be transient or persistent, limited in distribution or generalised,
OVERVIEW
and may involve any portion of the body innervated by sensory or afferent nerve fibres. They may occur in
isolation or in association with reduced or absent sensation. The symptoms usually occur spontaneously.
Paraesthesias can be caused by a dysfunction or abnormality affecting any level of the somatosensory
pathway. However, the most common causes affect peripheral sensory nerves.
The somatosensory pathway

Primary afferent or sensory nerve fibres originate as unmyelinated nerve endings in the epidermis or as
myelinated nerve fibres associated with sensory receptor structures in the dermis. They are organised
distally as cutaneous branches of peripheral nerves or as the sensory components of mixed sensory
and motor peripheral nerves, such as the median nerve in the hand or the tibial nerve in the leg. In the
extremities, the peripheral sensory nerves become components of either the brachial plexus for the upper
extremities or the lumbosacral plexus for the lower limbs. Proximal to the plexus, sensory nerve fibres remain
combined with the motor nerve fibres in the spinal nerve roots, with the sensory nerve fibres projecting
centrally to the dorsal root ganglion. The dorsal root ganglia contain the sensory neuronal cell bodies and are
found alongside the spinal cord for the neurons innervating the extremities and trunk, or in the cranial nerve
nuclei in the brainstem for the cranial nerves. The central process of the dorsal root ganglion neuron extends
centrally, via the dorsal root, into the dorsal horn of the spinal cord, or from the cranial nerve sensory nuclei,
with central projections through the thalamus and ultimately to the somatosensory cortex.
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Assessment of paraesthesias Theory
Aetiology
Paraesthesias may be due to conditions that affect sensory function at the level of the peripheral nerve or,
less commonly, at the level of the dorsal root ganglion, dorsal sensory nerve roots, spinal cord, or brain.
THEORY
The underlying conditions may be inherited or acquired. A knowledge of the anatomy of the somatosensory
pathways is required to understand the patterns of paraesthesia produced by different processes.
Nerve compression or injury

Focal nerve entrapment syndromes can lead to paraesthesias in the distribution of the involved peripheral
nerve if sensory nerve fibres are involved. Sensory symptoms usually appear first, followed by motor
weakness in the distribution of the affected nerve. Symptoms typically follow the pattern of the distribution of
the nerve distal to the site of compression or entrapment. Common entrapment neuropathies include:
• Median neuropathy at the wrist (carpal tunnel syndrome)

• Ulnar neuropathy at the elbow (cubital tunnel syndrome)
• Fibular (peroneal) neuropathy at the knee
• Neuropathy of the lateral femoral cutaneous nerve of the thigh (meralgia paraesthetica)
• Trigeminal neuropathy or neuralgia due to micro-vascular compression at the entry zone of the nerve
into the pons
Rarer entrapment neuropathies include tibial neuropathy at the ankle (tarsal tunnel syndrome) and
cutaneous sensory neuropathy of the dorsal branches of the spinal nerves in selected dermatomes (T2-T6)
unilaterally on the upper back (notalgia paraesthetica).
Vascular[1] [2] or mass[3] [4] [5] lesions of various types can lead to peripheral nerve compression or
entrapment and present with paraesthesias.
Entrapment syndromes involving the brachial or lumbosacral plexus can be produced by traumatic injury to
the plexus, or by vascular abnormalities (e.g., haemangioma),[6] or by direct carcinomatous invasion of the
plexus by a metastatic tumour or lymphoma.
Entrapment syndromes involving the dorsal spinal nerve roots are divided into cervical, thoracic, and
lumbosacral radiculopathies, depending on the nerve root affected, and can be produced by spondylosis,
stenosis, intervertebral disc herniation, or mass compression.[7] [8] [9] Spinal cord compression syndromes
can occur as a result of spine trauma such as vertebral compression fractures, intervertebral disc herniation,
primary or metastatic spinal tumour,[10] vascular malformations,[8] or infection.
Nerve demyelination and/or axonal degeneration

Multiple sclerosis
• A relapsing and remitting focal inflammatory disorder of the central nervous system (CNS) clinically
defined by two episodes of neurological dysfunction separated in space and time. Lesions can affect
the brain, spinal cord, or optic nerves. Lesions that affect the somatosensory pathway in the spinal
cord, brainstem, or somatosensory cortex can produce paraesthesias. Rarely, a patient may present
with numb chin syndrome as an early manifestation of multiple sclerosis, where there are unilateral
chin paraesthesias.[11]
Neuromyelitis optica spectrum disorder (NMOSD or Devic's disease)
4 This PDF of the BMJ Best Practice topic is based on the web version that was last updated: Nov 01, 2018.
• Auto-antibodies (NMO-IgG) disrupt key ion channels on the surface of astrocytes in the CNS that
ultimately leads to optic nerve (loss of vision) and spinal cord dysfunction (paraesthesias, weakness,
and bowel and bladder dysfunction).
Acute disseminated encephalomyelitis
THEORY
• An acute monophasic inflammatory disorder of the CNS, pathologically similar to multiple sclerosis,
which produces encephalitis with constitutional symptoms. Frequently triggered by an antecedent
infection or vaccination.
Acute inflammatory demyelinating polyradiculoneuropathy (AIDP)
• The most commonly encountered variant of Guillain-Barré syndrome. A demyelinating polyneuropathy

characterised by an immune-mediated attack on the myelin sheath or Schwann cells of sensory and
motor nerves. The characteristic clinical presentation is of a progressive symmetric muscle weakness
affecting lower extremities before upper extremities, and proximal muscles before distal muscles,
accompanied by paraesthesias in the feet and hands.
Chronic inflammatory demyelinating polyradiculoneuropathy (CIDP)
• An acquired, demyelinating, peripheral neuropathy of presumed autoimmune aetiology. The course is

usually either chronic progressive (over the course of 8 weeks or more) or relapsing and remitting. The
clinical phenotype consists of proximal and distal symmetric weakness, distal sensory loss, and absent
reflexes.
Chronic inflammatory demyelinating sensory polyradiculopathy
• An acquired demyelinating condition that preferentially affects large myelinated fibres of the posterior
roots. Presents with gait ataxia, large-fibre sensory loss, and paraesthesias.
Anti-myelin-associated glycoproteins (MAG) peripheral neuropathy
• Rare CIDP-like condition affecting mainly middle aged men where auto-antibodies against MAG cause
paraesthesias (hands and feet), tremor, and ataxia.
Distal symmetric polyneuropathy
• A length-dependent or distally predominant peripheral neuropathy, which is symmetric in distribution,

and may involve pure sensory or mixed sensory and motor nerves. It may involve primarily small
unmyelinated sensory nerve fibres exclusively, but more commonly involves both large and small
sensory and motor nerve fibres. It may occur as a consequence of a variety of acquired causes,
including infectious, inflammatory, toxic, endocrine, metabolic, and nutritional conditions. It is the most
common clinical manifestation of peripheral nerve disease, the classic 'stocking and glove' distribution
of sensory and motor symptoms and findings. It may be due to demyelination, axonal degeneration, or
a combination of both pathological processes affecting the peripheral nerves.[12] [13]
Endocrine or metabolic disease

Diabetes mellitus
• Hyperglycaemia initiates a process of nerve damage affecting peripheral nerve fibres and Schwann
cells. The pathophysiology is complex and includes oxidative and nitrosative stress, redox imbalance,
5
endothelial dysfunction, perturbations in prostaglandin metabolism, and direct hypoxia and ischaemia
of nerve trunks and ganglia. These changes impair mitochondrial function and neurotrophic support.
Ongoing hyperglycaemia produces progressive damage and loss of peripheral nerve fibres and
impaired sensory function.
THEORY
Hypertriglyceridaemia
• High triglyceride levels are associated with a predominantly sensory axonal length dependent
polyneuropathy that often presents with burning paraesthesias in the feet. The cause is unknown.
Uraemia
• A clinical syndrome of metabolic abnormalities and fluid, electrolyte, and hormone imbalance that
develops in the context of deteriorating renal function. Patients develop a generalised peripheral
neuropathy mediated by toxic substances that accumulate in the blood, and may also develop focal
nerve entrapment syndromes such as carpal tunnel syndrome or median nerve neuropathy. Uraemic
encephalopathy may also occur.
Hypocalcaemia
• Calcium plays a crucial role in neural function, and hypocalcaemia produces a range of neurological
signs and symptoms including paraesthesias affecting the fingertips, toes, and perioral region.
Hypothyroidism
• Produces a peripheral neuropathy with paraesthesias, but the mechanism is not understood.
Hypothyroidism can also produce specific entrapment neuropathies of which median nerve neuropathy
is the most common.
Nutritional deficiency
Vitamin B12 deficiency[14] [15]
• Vitamin B12 is critical in the production of S-adenosylmethionine, which is thought to be important

in neural function. It is also an essential co-factor in haematopoiesis. Vitamin B12 deficiency usually
manifests as a macrocytic anaemia with or without paraesthesias, but paraesthesias may be the only
presenting feature in some cases.
• Subacute combined degeneration of the cord is a severe complication of vitamin B12 deficiency.
Vitamin B6 deficiency or excess[15]
• Vitamin B6 is an important co-factor in amino acid and glycogen metabolism. Neurological symptoms
are wide ranging and include distal limb numbness, paraesthesias, and weakness with impaired
vibration and proprioception and sensory ataxia. Other signs include seborrhoeic dermatitis, atrophic
glossitis with ulceration, and angular cheilosis.
Vitamin B1 deficiency[15]
• Thiamine is an important co-factor in carbohydrate metabolism. Deficiency produces symptoms

of resting tachycardia, weakness, and decreased deep tendon reflexes. Some patients develop a
peripheral neuropathy. Patients also have associated cardiac abnormalities and vocal cord paralysis.
Vitamin E deficiency[15]
• Vitamin E is an important lipid-soluble antioxidant nutrient. Deficiency produces nerve damage.

Peripheral neuropathy is a late manifestation, with spinocerebellar ataxia and visual changes occurring
earlier.
Copper deficiency[16]
THEORY
• Copper deficiency produces anaemia and neurodegeneration, which manifests with progressive
spasticity, ataxia, and a peripheral sensory neuropathy. Causes include copper-deficient total
parenteral nutrition, gastric bypass surgery, and zinc toxicity.
Drug or toxin exposure

Alcohol
• Chronic high alcohol intake produces a peripheral polyneuropathy, although the aetiology is unclear.
The neuropathy is partly related to the direct toxic effects of alcohol and partly due to associated
vitamin and mineral deficiencies. Sensory symptoms predominate, but motor, proprioceptive, and
autonomic manifestations also occur.
• The polyneuropathy is known as dying-back neuropathy. Symptoms start distally. Initially, patients
develop numbness of the soles, followed by paraesthesias of feet and legs, especially at night.
Paraesthesias slowly progress proximally, and become painful (described as burning or lancinating).
Paraesthesias of the fingers and hands often appear once symptoms extend above the ankle level.
Motor signs include weakness and muscle wasting.
• Patients may also develop loss of proprioception (giving rise to abnormal gait independent of
cerebellar problems) and, rarely, autonomic dysfunction.
Drug-induced
• Common causes of peripheral neuropathy include chemotherapy agents (cisplatin, vincristine, cytosine
arabinoside, thalidomide, paclitaxel), antibiotics (metronidazole, nitrofurantoin), antiretroviral agents
(zidovudine, stavudine, lamivudine),[17] and antiepileptics (phenytoin). Paraesthesia is one of the
most commonly reported adverse drug reactions of topiramate, a drug used to treat a number of
neuropsychiatric conditions including alcohol dependence, essential tremor, binge-eating disorder,
bulimia nervosa, migraine, and epilepsy.[18]
Heavy metals
• Lead, arsenic, mercury, and thallium can cause a peripheral sensory polyneuropathy. Toxicity can
result from a range of occupational, environmental, or recreational exposures. Thallium exposure may
also occur through contamination of cocaine, heroin, and herbal products. There is increasing concern
about mercury exposure from contaminated fish.[19]
Hexane
• Hexane, from glue-sniffing behaviour or industrial exposure, can produce neurotoxicity that is attributed
to 2,5-hexanedione formed from the parent compound. Patients develop a dying-back neuropathy
similar to that produced by alcohol.
Ingested neurotoxins
7
• Ciguatera toxin is an odourless and tasteless toxin found in reef fish, most commonly barracuda,
grouper, red snapper, eel, amberjack, sea bass, and Spanish mackerel. The toxin is not destroyed by
cooking. Eating ciguatera-contaminated fish results in poisoning. Symptoms begin 6 to 8 hours after
ingestion and include paraesthesias, abdominal pain, nausea, vomiting, diarrhoea, dizziness, and
THEORY
vertigo.
• Saxitoxin, one of the most potent natural toxins, is produced by some species of marine dinoflagellates
and cyanobacteria and accumulates in shellfish. The toxin acts on voltage-gated sodium channels and
prevents nerve conduction. Ingestion of contaminated shellfish produces paralytic shellfish poisoning.
Symptoms begin within 30 minutes of ingestion and include paraesthesias of the lips, tongue, and
gums, which then rapidly progress to involve the extremities. Headaches, ataxia, and motor and
cranial nerve abnormalities may also occur.
Radiation
• Post radiation-induced brachial plexopathy or lumbosacral plexopathy may occur if the nerves are in
the field of external beam radiation. Symptoms may manifest years after the initial radiation exposure.
In addition, late effects of radiation to the pelvis may include a cauda equina syndrome or lumbosacral
polyradiculopathy.[20]
Macrovascular disease
Stroke or transient ischaemic attack
• An ischaemic or haemorrhagic stroke in the somatosensory cortex may cause paraesthesias and
loss of sensation in the face or extremities. If the stroke affects the brainstem, patients may also have
symptoms of weakness, as the motor and sensory pathways in the brainstem are in close proximity.
An isolated infarct of the splenium (posterior portion of the corpus callosum) has been found to rarely
cause hemibody paraesthesias as the only manifestation.[21]
Migraine
• Some migraine headaches are associated with an aura that includes focal or unilateral neurological
symptoms. These may include paraesthesias on the face or the extremities, as part of the
headache[22] or as a complication of medication (e.g., those containing ergot derivatives used to treat
the migraine).[23]
Peripheral vascular disease
• Paraesthesia is one of the classic signs of limb ischaemia, along with pain, pallor, cold, absent pulses,
and paralysis. The paraesthesia is usually in a 'glove and stocking' distribution.
Other cerebrovascular disease
• Unilateral paraesthesias may rarely be associated with other vascular abnormalities in the brain
and spinal cord, including cavernous malformations[8] and intravascular lymphoma.[24] Cavernous
malformations most often occur in the brain but can also rarely affect extra-cranial areas such as
the spinal cord, leading to paraesthesias in the extremities.[8] Intravascular large B-cell lymphoma
is a rare form of diffuse large B-cell lymphoma that presents with CNS involvement in 75% to 85%
of patients. Neurological symptoms include sensory and motor neuropathies, paraesthesia, muscle
weakness, hemiparesis, meningoradiculitis, dysarthria, aphasia, seizures, transient visual loss, vertigo,
and impaired cognitive function.[24]
Infection
THEORY
HIV
• HIV produces a peripheral neuropathy that may be due partly to direct infection of dorsal root ganglia
and partly to neurotoxic cytokines secreted by locally invading macrophages. Neuropathy may also
be produced by associated infections. CMV can produce a polyradiculopathy in immunosuppressed
patients, especially those with AIDS.
Human T-lymphotropic virus (HTLV)
• HTLV is a retrovirus that can cause a progressive myelopathy (tropical spastic paraparesis) resulting
in leg weakness, back pain, paraesthesias, and bowel and bladder dysfunction. It has also been
implicated as a cause of sensory polyneuropathies.
Leprosy
• A chronic infectious disease caused by Mycobacterium leprae that affects the skin and peripheral
nerves, producing characteristic skin lesions with sensory and/or motor deficits.
Lyme disease ( Borrelia burgdorferi )
• Lyme disease is a zoonotic infection caused by a spirochete of the genus Borrelia , which is
transmitted to humans by ticks. Radiculopathy is a complication of the disease. Peripheral neuropathy
is a late complication of CNS involvement.
Herpes zoster infection (shingles)
• A viral infection that disseminates through regional lymph nodes to the liver, spleen, and other
cells within the reticuloendothelial system. Symptoms appear when the infection spreads from
the reticuloendothelial system to the skin and mucous membranes. Initial symptoms are pain and
paraesthesia. These are shortly followed by a characteristic rash in the affected dermatome.
Herpes simplex infection
• Causes oral, genital, and ocular ulcers. Patients report a localised paraesthesia that forms part of
the prodrome prior to the onset of the ulcers. The paraesthesia may be the only symptom in some
patients.
Neurosyphilis
• An STD caused by Treponema pallidum . Associated with primary (local), secondary (disseminated),
and tertiary (end-organ complications including neurosyphilis) disease. Neurosyphilis can produce
a polyradiculopathy that usually affects the lower limbs. It can also produce damage to the dorsal
column of the spinal cord, producing a syndrome called tabes dorsalis. Key features of tabes dorsalis
include Argyll-Robertson pupils, ataxia, loss of deep tendon reflexes, and loss of proprioception,
vibration, and position sense.
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Psychogenic disorders
Panic attacks with hyperventilation
• Patients may report perioral and distal extremity paraesthesias that are associated with anxiety or
THEORY
panic symptoms and hyperventilation. An extremely common cause of paraesthesias.

Conversion and somatisation disorders
• Caused by an underlying psychiatric condition. The distribution of the paraesthesias may be focal
or hemifacial or hemibody, but does not correlate with a pathological lesion or abnormality of the
underlying sensory pathway.
Vasculitic or inflammatory disease

Vasculitic conditions can produce either mononeuritis multiplex (a condition of progressive motor and
sensory deficits in the distribution of specific peripheral nerves) or a polyneuropathy. Vasculitic neuropathies
are often painful.[25] Peripheral sensory neuropathy may also occur due to direct immune-mediated nerve
inflammation caused by auto-antibodies or a reaction to monoclonal protein deposition. In some cases, a
combination of these aetiologies is present. Causes include:
• Vasculitis associated with connective-tissue diseases such as systemic lupus erythematosus

(SLE) and rheumatoid arthritis. SLE is associated with a distal symmetric sensory neuropathy with
progressive distal lower extremity paraesthesias, which may progress to involve motor nerve fibres[26]
• Polyarteritis nodosa, a vasculitic condition that affects only medium-sized blood vessels. Associated
abnormalities include arthritis, purpura or other skin manifestations, abdominal pain due to abdominal
organ ischaemia, and renal failure[27]
• Churg-Strauss syndrome, a vasculitic condition that affects small- and medium-sized blood vessels.
Associated abnormalities include asthma, eosinophilia, and abnormal infiltrates on chest x-ray.[25] [28]
[29] [30]
• Granulomatosis with polyangiitis (formerly known as Wegener's granulomatosis), a vasculitis affecting
small- and medium-sized blood vessels with lesions of the nasal passages, lungs, and kidneys[31] [32]
[33]
• Microscopic polyangiitis, a vasculitic condition that affects small vessels. Associated abnormalities
include palpable purpura or other skin manifestations, pulmonary rales, hypertension, heart failure,
and renal failure
• Sjogren's syndrome may be associated with small- or large-sensory nerve fibre damage. Small-
fibre damage produces burning paraesthesias, whereas large-fibre damage produces ataxia or gait
imbalance. Cranial neuropathies and autonomic neuropathy may also occur[34] [35] [36]
• Sarcoidosis (neurosarcoidosis) can cause peripheral nerve damage, although facial palsy is the most
common manifestation
• Disorders of monoclonal protein production result in neuropathy due to protein deposition and
inflammation in the peripheral nerves. Disorders include Waldenstrom's macroglobulinaemia,
monoclonal gammopathy of uncertain significance, multiple myeloma, cryoglobulinaemia, and
amyloidosis
• Neuro-Behcet's disease can rarely present with spinal cord inflammatory lesions causing
paraesthesias and weakness in the extremities[37]
• Wartenberg’s migrant sensory neuritis is a limited, immune-mediated, mononeuritis affecting sensory
nerves only. Presents with abrupt onset of painful paraesthesias in the distribution of one or multiple
cutaneous or sensory nerves (most commonly peripheral limb nerves, but also the trigeminal nerve
and truncal branches), either sequentially or simultaneously. Paraesthesias can be preceded by
painful sensations (stabbing, burning, tingling) in the same area, and stretching of the affected nerve
(e.g., by kneeling) may precipitate symptoms.[38] [39]
THEORY
Genetic disorders
Inherited causes for peripheral sensory neuropathy may include genetic mutations that affect the structure of
the nerve fibre, leading to peripheral neuropathy or plexopathy. The most common causes are the following.
• Charcot-Marie-Tooth disease (hereditary motor and sensory neuropathy): caused by mutations that
affect either myelin (producing demyelination) or formation of the axon (producing axonal neuropathy).
The inheritance may be autosomal dominant or recessive, depending on the form. The key symptom is
motor weakness, but sensory symptoms including paraesthesias also occur.
• Hereditary sensory and autonomic neuropathy: this is a group of genetic disorders that produce
autonomic dysfunction and analgesia. The inheritance may be autosomal dominant or recessive,
depending on the form. Patients may present with painless injuries to their extremities (due to lack of
sensation) or with burning paraesthesias in the extremities.
• Hereditary neuropathy with liability to pressure palsies: an autosomal dominant condition caused
by a deletion of a region on chromosome 17 that includes the PMP-22 gene. Patients present with
relapsing and remitting symptoms of nerve entrapment. The syndrome may involve isolated or multiple
compressive neuropathies or a brachial plexopathy depending on the peripheral nerve involved.
Inborn errors of metabolism produce defects in downstream metabolism and a build-up of upstream
metabolic intermediates in the cytoplasm, leading to cellular damage. A peripheral neuropathy results either
from axonal damage or from demyelination. Demyelination is usually produced by damage to Schwann cells,
but may also be caused by defective myelin synthesis.
• Adult polyglucosan body disease is a glycogen-branching enzyme deficiency. The deficiency leads
to the formation of polyglucosan bodies within nerve fibres. These bodies are toxic and lead to nerve
damage. The condition presents in mid-to-late adulthood with paraesthesias or sensory loss in the
lower extremities, progressive upper and lower motor neuron dysfunction, sphincter dysfunction
(incontinence), and dementia.[40] It is caused by multiple mutations in the GBE1 gene.[40] [41]
• Tangier's disease is caused by a defect in HDL production, leading to deposition of cholesterol
esters and cellular toxicity in various tissues including peripheral nerve Schwann cells. Patients
develop paraesthesias and motor weakness due to a sensori-motor peripheral neuropathy. Orange-
coloured tonsils are characteristic of the disease. Some patients present in childhood with symptoms
affecting the lower extremities, whereas others present later in later with symptoms affecting the upper
extremities.[42] [43]
• Refsum's disease is a peroxisomal disorder that produces accumulation of phytanic acid. It presents at
a young age with retinitis pigmentosa, peripheral polyneuropathy, and cerebellar ataxia.
• Fabry's disease, due to alpha-galactosidase deficiency, is an X-linked recessive disorder of glycolipid
storage that affects male patients from an early age (usually <10 years old). The involved gene is
located on the long arm of the X chromosome, between Xq21.33 and Xq22. Associated systemic
conditions include chronic renal insufficiency, early cardiac or cerebrovascular disease, and corneal
opacifications. Female carriers may have milder symptoms, with onset later in life. The peripheral
neuropathy affects small unmyelinated nerve fibres, thus burning paraesthesias are prominent
symptoms, located in the hands, feet, and distal lower extremities. Patients may also report reduced
11
sweat output. Patients also have angiokeratomas and characteristic darkening of their skin in a
'bathing suit' distribution due to a macular rash.[44]
• Krabbe's disease or globoid cell leukodystrophy is an autosomal recessive disorder produced by
deficiency of galactocerebrosidase enzyme. It leads to decreased formation of myelin in the CNS and
THEORY
peripheral nerves. Infantile-, juvenile-, and adult-onset forms of the disease exist. Infantile onset is
the most severe and fatal. Patients present with burning paraesthesias and muscle weakness due to
sensori-motor neuropathy. Some patients also develop cognitive impairment or upper motor neuron
signs due to demyelination in the CNS.[45] [46]
• Friedreich's ataxia, caused by an expanded trinucleotide repeat sequence in the frataxin gene,
presents with progressive limb ataxia and axonal sensory neuropathy with pyramidal tract signs
(weakness and upgoing toes to plantar stimulation) in the setting of absent deep tendon reflexes, and
cardiomyopathy. Clinical symptoms develop in childhood or young adulthood.
• Adrenomyeloneuropathy is an X-linked recessive disorder that causes the abnormal accumulation of
very-long-chain fatty acids. It primarily affects young adult males, although female carriers may also
have neurological involvement, and presents primarily with spastic paraplegia, adrenal insufficiency,
and, occasionally, peripheral neuropathy and myelopathy.[47] [48]
• Spinocerebellar ataxia syndromes are a group of autosomal dominant inherited neuro-degenerative
conditions. Some subtypes are associated with sensory neuropathy (types 1 to 4, 8, 18, 23, 24, 15,
27) in addition to ataxia and other features such as pyramidal and extra-pyramidal dysfunction.
• Niemann-Pick disease, or acid sphingomyelinase deficiency, can produce peripheral neuropathy and
retinal abnormalities.[49] However, this presentation is unusual as most patients have shortened life
spans and do not live long enough to develop these symptoms.
• Subacute necrotising encephalomyelopathy (Leigh's disease) is a severe neuro-degenerative
disease of infancy that can include peripheral neuropathy in addition to psychomotor delay, seizures,
ophthalmoplegia, ataxia, dystonia, seizures, and vomiting.[50] [51] The condition is usually fatal in
infancy or early childhood.
• Abetalipoproteinaemia, or Bassen-Kornzweig syndrome, is an autosomal recessive disorder of
defective lipoprotein metabolism and may present with sensory neuropathy in childhood in addition to
other neurological features such as mental retardation, retinitis pigmentosa, and ataxia.[52]
Other causes
Partial epilepsy
• Partial seizures involving the somatosensory cortex may cause stereotyped hemifacial or hemibody
sensory symptoms such as paraesthesias.
Paraneoplastic sensory neuropathy
• A range of cancers can lead to a peripheral neuropathy. The cause is usually related to nerve
entrapment by the tumour, side effects of treatment, nutritional deficiencies, or metabolic
derangements. However, some patients develop a paraneoplastic peripheral neuropathy in the
absence of these causes, which occurs in association with a variety of anti-neuronal antibodies
including anti-Hu and anti-CRMP-5. The neuropathy may precede the diagnosis of cancer by many
years and be the only clinical indication of an occult malignancy. The exact mechanism is not
understood but is thought to be related to cross-reactivity of the anti-neuronal antibodies with tumour
antigens.
Numb chin syndrome
• Unilateral paraesthesias or anaesthesia of the chin may present as an initial manifestation of occult
malignancy and should always be investigated thoroughly as to the underlying cause.[11] [53] It may
also be the initial manifestation of multiple sclerosis. It may also occur subsequent to dental or oral
surgery.
THEORY
Peripheral neuropathy after bariatric surgery
• Sensory predominant, distal polyneuropathy has been found to occur more frequently in patients
after bariatric surgery compared with other types of abdominal surgery.[54] Malnutrition related to the
perioperative period seems to be the most significant risk factor for development of predominantly
sensory, distal polyneuropathy.[54] Rapid loss of a large amount of body weight most likely results in
several nutritional deficiencies, and subsequently the development of the polyneuropathy.
13
Assessment of paraesthesias Emergencies
Urgent considerations
(See Differentials for more details)
Guillain-Barré syndrome, acute inflammatory demyelinating

polyradiculoneuropathic (AIDP) form
This condition has an abrupt onset, typically with paraesthesias starting in the toes and progressing
proximally over hours or days. The ascending paralysis can affect respiratory muscle function and lead to
respiratory failure or arrest if the condition is not recognised and treated. Patients may also develop acute
dysautonomia with potentially life-threatening fluctuations in blood pressure and heart rate. The diagnosis
depends on recognition of the clinical features, including the rapid onset and progression of the symptoms,
and is confirmed by the finding of albuminocytological dissociation on cerebrospinal fluid (CSF) examination
and characteristic findings on electromyogram (EMG). Suspected AIDP requires close monitoring of
neurological and respiratory function and early institution of treatment with emergent plasma exchange or
intravenous immunoglobulin.
EMERGENCIES
Stroke
Ischaemic or haemorrhagic strokes present with acute onset of neurological symptoms, which may include
paraesthesias. The location and extent of the stroke determines the severity of the neurological deficit,
associated neurological symptoms and findings, and the risk of damage to adjacent brain tissue from
swelling of the infarcted brain tissue. Large strokes in the cerebral hemispheres or haemorrhagic strokes in
the brainstem pose an immediate risk of brainstem compression or herniation. The diagnosis is based on
clinical history and neurological examination, with supporting evidence from neuro-imaging such as head
computed tomography (CT) or brain magnetic resonance imaging (MRI).
Spinal cord compression

Spinal cord compression, either acutely from traumatic injury or a spinal cord infarct, or subacutely from a
metastatic or primary mass lesion compressing the spinal cord, requires urgent diagnosis and treatment.
Patients may develop irreversible loss of neurological function and, in some cases, respiratory function.
A spinal cord compression syndrome is suspected based on the history and examination findings, and
confirmed using neuro-imaging (MRI) of the suspected segments of the spinal cord. Surgical decompression
or treatment with high-dose steroids is required to reduce oedema of the spinal cord tissue and prevent
further loss of neurological function.
Transverse myelitis
Transverse myelitis is an acute inflammatory lesion in the spinal cord that usually involves one or two spinal
segments. Patients may present with a spinal cord syndrome of weakness and numbness and bowel/
bladder incontinence. Depending on the location of the lesion, respiratory muscle control may be affected
and become life-threatening. The diagnosis depends on clinical history and examination, followed by neuro-
imaging (MRI) of the spinal cord and lumbar puncture with CSF exam. If recognised early, treatment with
high-dose intravenous corticosteroids may reduce oedema and prevent further loss of function.
Acute disseminated encephalomyelitis

Acute disseminated encephalomyelitis is a central demyelinating disease that appears following infection
(usually viral) or vaccination, or sometimes spontaneously. Patients present with an acute encephalitis,
Assessment of paraesthesias Emergencies
and may develop rapid neurological decline with coma and seizures. Brain and spinal cord MRI reveal
characteristic lesions. Patients require intravenous corticosteroid therapy such as methylprednisolone. If the
response to steroids is inadequate, plasma exchange or intravenous immunoglobulin may be used.[61] [62]
Vasculitic neuropathy
Patients who present with a clinical syndrome of mononeuritis multiplex (pain, followed by paraesthesias
and weakness in multiple single peripheral nerve distributions) should be suspected to have vasculitis and
need urgent evaluation to confirm the diagnosis. Initial tests for specific disease markers should be sent.
Immunosuppressive therapy should be initiated as soon as possible. If left untreated, patients are likely to
experience further loss of neurological function and devastating multi-organ damage. Definitive diagnosis
requires a tissue biopsy.
Partial seizures
Focal or partial seizures involving the somatosensory cortex may cause stereotyped episodes of hemifacial
and/or hemibody sensory symptoms such as transient paraesthesias. These may be isolated events or part
EMERGENCIES
of the aura initiating a complex partial seizure. An electroencephalogram (EEG) may identify epileptiform
activity or a focal, localising abnormality. Neuro-imaging may reveal evidence of a structural lesion or
other process that has caused the seizure. It is important to identify this subset of patients as they can be
effectively treated with anticonvulsant medications.
15
Assessment of paraesthesias Diagnosis
Approach
Paraesthesias can be caused by a wide range of conditions affecting the nervous system at any level. Most
patients have a peripheral neuropathy but all causes should be considered. The clinical history and physical
examination narrow the differential diagnosis and guide the need for further investigations. The aim of the
examination is to determine whether the pathology is likely to be affecting the peripheral nerves, plexuses,
dorsal spinal roots, spinal cord, or brain, and to identify additional signs of the underlying cause.
Diabetic neuropathy, hypocalcaemia, vitamin deficiencies, drug toxicity, and minor infections such as shingles
or herpes simplex virus can usually be diagnosed clinically or with laboratory testing. All other peripheral
neuropathies require electromyography (EMG) with nerve conduction studies to confirm and characterise the
neuropathy. Imaging is required if the history and examination suggest a plexopathy, a radiculopathy, or a
lesion affecting the spinal cord, brainstem, or brain.
Characteristics of the paraesthesias

Description
• It is important to characterise the paraesthesias being experienced by the patient. The patient should
be encouraged to describe their symptoms in detail in their own words. Common descriptions include
burning, stabbing, pins and needles, prickling, stinging, and sharp shooting pains. It is important to
establish if there is an associated loss of sensation, and if it is in the same area as the paraesthesias.
Painful paraesthesias suggest an inflammatory or ischaemic process such as vasculitis. Shooting
pains are characteristic of nerve entrapment. Burning pains are characteristic of paraesthesias
affecting small unmyelinated fibres. Paraesthesias may occur as part of a migraine aura or have
an onset at the same time as the headache, and they typically last <1 hour from the onset of the
headache.
Onset
• It is important to establish if the symptoms had a sudden onset or if they evolved over seconds,
DIAGNOSIS
minutes, hours, days, or weeks. A sudden onset suggests stroke or trauma. Symptoms that evolve
over several seconds suggest epilepsy. Symptoms that evolve over minutes suggest migraine, panic
attack, or fish poisoning (if the patient has ingested fish within the previous 8 hours). An insidious
onset is characteristic of inherited neuropathies.
Differential diagnoses of paraesthesias based on the chronicity of symptom onset

Created by BMJ Knowledge Centre using information from Dr Caroline M. Klein
DIAGNOSIS
Duration and severity
• The patient should be asked whether the symptoms are constant or relapsing and remitting, and
whether there has been any symptom progression. A history of similar previous symptoms should be
sought. Muscle pain, atrophy, or weakness in the same anatomical distribution as the paraesthesias
indicates a sensori-motor peripheral neuropathy (often a sign of more advanced disease).
Localisation
• The location of the symptoms indicates the level of the lesion.
17
Peripheral nervous system causes of paraesthesias according to the pattern and level of the lesion
DIAGNOSIS
Central nervous system and non-neurological causes of
paraesthesias according to the pattern and level of the lesion
• Localised symptoms indicate a peripheral mononeuropathy or a plexopathy if in the distribution of
one or more peripheral nerves, or a radiculopathy if in the distribution of a dermatome. If symptoms
suggest a peripheral mononeuropathy, a more detailed history should be taken to assess for focal
nerve entrapment syndromes.
• Paraesthesias affecting the first three digits of the affected hand suggest carpal tunnel
syndrome. Symptoms are usually worse at night (awakening patient from sleep) and
exacerbated by prolonged wrist extension such as driving, typing on a keyboard, or reading a
newspaper. Patients may also have pain in the wrist or hand possibly extending into the forearm,
elbow, or shoulder.
• Paraesthesias affecting the fourth and fifth digits suggest ulnar neuropathy, which may be
induced by prolonged or repetitive flexion of the elbow or repetitive leaning on the elbow.
• Paraesthesias in the lateral leg or dorsal foot may indicate fibular (peroneal) neuropathy.
Patients may also have a foot drop. The nerve compression is usually due to repetitive crossing
of the knees or prolonged kneeling, crouching, or squatting, but a history of trauma or previous
knee surgery may also be present.
• Paraesthesias in the medial aspect of the foot suggest tibial neuropathy, which is relatively rare.
• Burning paraesthesias with increased sensitivity to touch or pressure in the anterolateral thigh
region suggest meralgia paraesthetica, produced by compression of the lateral cutaneous nerve
of the thigh.
• Paraesthesia characterised by persistent itching, localised unilaterally on the upper back, is
called notalgia paraesthetica. Symptoms may include pain, tingling, numbness, or increased
sensitivity to light touch in the affected area. Notalgia paraesthetica is thought to be due to
compression of the dorsal or sensory branches of the spinal nerves, from dermatomes T2 to T6,
by paraspinal muscle spasm or by bony degenerative changes in the spine at these levels.[63]
• Paraesthesias in the distribution of the trigeminal nerve indicate trigeminal neuropathy.
DIAGNOSIS
• Generalised unilateral symptoms involving the face or extremities suggest spinal cord or brain
pathology. Muscle pain, atrophy, or weakness in the same anatomical distribution as the paraesthesias
may also suggest involvement of a spinal nerve root, spinal cord, or brain. Spinal pain with radiation
into the extremity where the paraesthesias are reported, or bowel or bladder incontinence, may
indicate a radicular or spinal nerve root aetiology.
• Unilateral paraesthesias or anaesthesia of the chin (numb chin syndrome) may present as an
initial manifestation of occult malignancy and should always be investigated thoroughly as to the
underlying cause.[11] [53] It may also be the initial manifestation of multiple sclerosis. It may also
occur subsequent to dental or oral surgery.
Specific patterns
• Important patterns to recognise include rapidly progressive paraesthesias, numbness and weakness
beginning in the extremities indicating acute inflammatory demyelinating polyradiculoneuropathy
(AIDP), pain followed by paraesthesias, and weakness in multiple single peripheral nerve distributions
indicating mononeuritis multiplex, or unilateral symptoms that may indicate brain or spinal cord lesions.
• AIDP should be distinguished from chronic inflammatory demyelinating polyneuropathy (CIDP)
and chronic inflammatory demyelinating sensory polyradiculopathy (CISP). CIDP can produce a
19
similar progressive pattern as AIDP, but over a longer time course (8 weeks). CIDP can also cause
relapsing and remitting symptoms. CISP produces slowly progressive sensory symptoms without
motor symptoms.
• Dying-back neuropathy is a pattern seen with various toxicities (including alcohol and hexane) in which
symptoms begin in the lower extremities and gradually progress proximally, becoming painful and
involving the upper extremities once symptoms reach ankle level.
• Stereotyped episodes of hemifacial or hemibody sensory symptoms such as transient paraesthesias,
and occurring in isolation or in association with automatisms or altered level of consciousness or
responsiveness, should prompt suspicion of partial epilepsy. The paraesthesias typically evolve over a
few seconds.
• In distal symmetric polyneuropathy (DSP) there are symmetrically distributed symptoms of
paraesthesias (usually tingling paraesthesias with or without associated asleep- or dead-type
numbness in the same areas) and usually later muscle weakness. Symptoms are progressive from
onset, and may be intermittently present initially, then become more constant. Symptoms begin in the
toes and extend proximally in both legs to the level of the knees, at which point the distal fingertips of
both hands typically become involved. If small sensory nerve fibres are affected, burning pains and
allodynia (painful sensations elicited by normally non-noxious stimuli, such as light touch) are usually
reported by the patient.
• In peripheral neuropathy after bariatric surgery there are symmetric sensory symptoms of asleep-
or dead-type numbness and paraesthesias in the hands and feet, occasionally with some muscle
weakness in these same regions; insidious more often than acute or sub-acute onset of symptoms;
aching, sharp, or burning pains in hands and feet.
General medical history

Constitutional symptoms
• Weight loss, night sweats, and/or fatigue may be present in infection, neoplastic disease, or a range of
inflammatory conditions. Dry eyes or mouth may indicate Sjogren's syndrome.
Skin and joint changes
DIAGNOSIS
• Ulcers, purpura, rash, or darkening of the skin may suggest peripheral vascular disease, infection,
vasculitis, monoclonal protein production, sarcoidosis, or an inborn error of metabolism. Arthralgias,
joint swelling, or stiffness may indicate a rheumatological condition.
Cardiovascular/respiratory symptoms
• Lightheadedness or syncope with standing may indicate autonomic dysfunction, which occurs in
hereditary sensory and autonomic neuropathy, severe diabetic neuropathy, Sjogren's syndrome, and
some inborn errors of metabolism. Chest pain or palpitations at the onset of the paraesthesias may
indicate stroke. Chronic cough or shortness of breath may indicate diaphragmatic involvement due
to pathology affecting the cervical spinal roots. An upper respiratory or gastrointestinal illness may
precede the onset of AIDP.
Past medical illnesses
• It is important to establish if the patient has any of the following underlying conditions: diabetes
mellitus (level of control and complications of diabetic retinopathy and nephropathy), rheumatological
disorders (systemic lupus erythematosus, Sjogren's syndrome, rheumatoid arthritis, vasculitides),
cancer, spinal cord injury or surgery, infectious disease (HIV, hepatitis, syphilis), stroke, coronary
artery disease, alcohol abuse, nutritional deficiency, renal failure (including symptoms of uraemia), or
thyroid disease.
Surgical history
• A history of bariatric surgery within prior 12-24 month period, especially in association with rapid loss
of a large amount of body weight, could be the cause of peripheral neuropathy after bariatric surgery.
Medication history
• Current and previous therapies should be carefully documented. Known causative medications include
chemotherapy agents (cisplatin, vincristine, cytosine arabinoside, thalidomide, paclitaxel), antibiotics
(metronidazole, nitrofurantoin), antiretroviral agents (zidovudine, stavudine, lamivudine), and
antiepileptics (phenytoin). Non-prescription vitamins and supplements should also be documented,
especially those containing vitamin B6 (vitamin B6 overdose can cause a peripheral neuropathy).
Previous radiotherapy to the axilla or pelvis may indicate radiation nerve damage, even if the exposure
occurred years before the onset of symptoms.
Dietary history
• A history of malnutrition or adherence to a specialised diet, such as a low-protein, vegetarian, or vegan

diet, may lead to specific nutritional deficiencies.
Family history
• A positive family history of paraesthesias or sensory impairment may indicate an inherited neuropathy
or an inborn error of metabolism. A family history of acquired diseases such as compression
neuropathies, autoimmune disease, cancer, amyloidosis, diabetes, multiple sclerosis, or migraine may
also be present.
Social/occupational history
• A history of smoking should raise suspicion of a paraneoplastic syndrome. A history of occupational,
DIAGNOSIS
environmental, or recreational exposure to heavy metals may indicate heavy metal toxicity. The
presence of risk factors for HIV exposure or infection should prompt suspicion of HIV neuropathy.
Psychiatric history
• Panic attacks with hyperventilation are very common causes of paraesthesias. Patients report
associated symptoms of anxiety or panic including an overwhelming sense of impending doom.
Physical symptoms include chest pain, palpitations, and shortness of breath with perioral and bilateral
paraesthesias in the hands and feet and an associated carpopaedal spasm. More rarely, a history
of psychiatric symptoms and/or psychological or physical trauma may indicate a conversion or
somatisation disorder.
General examination
Initial
• Fever may indicate infection. Lymphadenopathy may indicate infection (HIV, herpes simplex, Lyme
disease) or systemic inflammatory disease. Diabetes or cardiovascular disease should be considered
21
if the patient is overweight or obese. Weight loss may be a sign of underlying malignancy. Vascular
assessment of the lower limb may reveal reduced or absent peripheral pulses in peripheral vascular
disease.
Head/eyes/ears/nose/throat
• Carotid bruits should prompt suspicion of stroke. Dry oral mucous membranes may indicate Sjogren's
syndrome.
Skin
• Purpura or rash suggests infection or vasculitis. Blistering in a dermatomal pattern in the area of the
patient's paraesthesias indicates shingles. Skin colour changes or thickening of the skin may indicate
monoclonal protein production, sarcoidosis, or an inborn error of metabolism. A shiny, oily, or scaly
appearance of the legs and loss of hair over the dorsum of the foot may indicate ischaemia due to
peripheral vascular disease.
Bone and joints
• High arched feet (pes cavus) and/or hammer-toe deformities may indicate an inherited peripheral
neuropathy. Characteristic joint deformities may be present with underlying rheumatological conditions.
Scoliosis may indicate osteoporosis, which may predispose the patient to spinal compression
fractures. Tenderness to palpation along the spinal column suggests a radiculopathy due to spinal
disease.
Rectal examination
• Should be performed to assess anal tone. A decrease in anal tone indicates a radiculopathy or spinal
cord lesion and requires urgent assessment.
Funduscopy
• May reveal diabetic retinopathy in a diabetic patient.

DIAGNOSIS
Neurological examination
Sensory system
• The neurological examination should focus in detail on the areas that correspond to the patient's
symptoms, but a general neurological examination should also be carried out to identify additional
clues to the underlying diagnosis. The first step is to examine the sensory modalities in all four
extremities, with additional testing in the areas where the patient is reporting the paraesthesias.
• Light touch is tested with a cotton wisp. Temperature is tested using a cold or warm stimulus. Pinprick
is tested using the sharp end of a safety pin or other standard stimulus-producing tool, which should
be single-use only and disposed of appropriately after being used on each patient. Joint position sense
is tested using the DIP joints of the big toe or middle finger. Vibration is tested using a 128-Hz tuning
fork placed at the DIP joint of the big toe or middle finger. The examination may reveal one of the
following patterns.
• Sensory loss in the distribution of a single peripheral nerve indicates a peripheral

mononeuropathy. Palpation of an individual peripheral nerve or specific provocative testing
(such as Tinel's or Phalen's sign) may elicit the paraesthesias, indicating a nerve entrapment
syndrome.
• Sensory loss in the distribution of multiple peripheral nerves indicates multiple
mononeuropathies or a plexopathy.
• Symmetric 'glove and stocking' distribution of sensory loss indicates a peripheral
polyneuropathy.
• Sensory loss in a dermatomal distribution indicates a radiculopathy. The corresponding spinal
nerve is also affected and the distribution of the spinal nerve should also be tested for sensory
loss.
• A sensory spinal level on the trunk suggests spinal cord pathology.
• Unilateral sensory loss affecting the face or extremities indicates a spinal cord or brain lesion.
Motor system
• The presence of muscle atrophy should be noted. Weakness or atrophy in the same distribution as the
sensory loss indicates a mixed peripheral sensori-motor neuropathy (if the peripheral nerve distribution
is affected), involvement of a spinal root (if a dermatome and myotome are affected), or spinal cord
or brain pathology. Loss of deep tendon reflexes indicates a peripheral lesion. Increased deep tendon
reflexes, upgoing plantar reflex, and muscle spasticity indicate a spinal cord or brain lesion.
Gait
• Abnormalities to note include a wide-based or ataxic or unsteady gait, a foot drop or difficulty walking
due to weakness, or spasticity of the lower limbs. The patient should be asked to stand with a narrow
base and then close their eyes and maintain their balance (Romberg's test); this is a test of dorsal
column function. Asking the patient to walk on their tiptoes and on their heels allows assessment of
the strength of the calf muscles and the foot and toe extensors. Tandem gait (walking heel-to-toe in a
straight line) is a very sensitive test of general gait stability.
• Gait imbalance and incoordination usually indicate a sensory ataxia, which is seen in vitamin B12,
vitamin E, and copper deficiencies; severe diabetic neuropathy; alcoholic neuropathy; neurosyphilis;
CIDP; paraneoplastic sensory neuropathy; Sjogren's syndrome; and some inborn errors of
DIAGNOSIS
metabolism. Gait abnormalities due to central nervous system (CNS) disease can be seen in multiple
sclerosis or acute disseminated demyelinating encephalomyelitis. A clumsy gait may be related to foot
drop, as seen in fibular (peroneal) neuropathy or Charcot-Marie-Tooth disease. Patients with spinal
cord compression may have difficulty walking due to spasticity and/or muscle weakness in the lower
extremities.
Cerebellar function
• Should be assessed by testing the patient's ability to perform heel-to-shin and finger-to-nose-to-finger
manoeuvres. This helps to detect cerebellar pathology in patients with alcohol abuse, paraneoplastic
disease, or CNS disease.
Cranial nerve assessment
• Abnormalities may occur in a range of conditions including multiple sclerosis (usually affecting the
optic nerve), trigeminal neuropathy, fish poisoning, Lyme disease, Sjogren's syndrome, monoclonal
protein production, and some inborn errors of metabolism.
• Assessment of cranial nerve function should therefore be performed as part of the assessment:
the pupils should be equal, round, and reactive to light stimulation. Optic disc pallor on funduscopic
23
examination may indicate optic atrophy due to multiple sclerosis. Facial sensation to light touch,
temperature, and pinprick stimulation should be tested. If a sensory abnormality is found on the face,
additional testing of corneal reflexes with a wisp of cotton should be performed to further confirm
trigeminal dysfunction on the affected side. Facial, trapezius, and sternocleidomastoid muscle strength
and symmetry should be assessed.
Peripheral nerve involvement

Further diagnostic testing is guided by the history and physical examination findings, and consists of
laboratory tests to identify the underlying cause and electrophysiological studies to confirm and characterise
the type of peripheral neuropathy.
Metabolic or endocrine tests
• One of the most important tests is a 2-hour glucose tolerance test (or at a minimum, a fasting glucose
or HbA1c test). HbA1c is useful to detect poor glycaemic control in patients with known diabetes and
may be elevated. Serum calcium, vitamin D, and PTH levels should be measured if hypocalcaemia is
suspected. Serum magnesium levels should also be measured in these patients and may be reduced;
hypocalcaemia occurring in the context of hypomagnesaemia does not resolve until magnesium levels
are corrected. An elevated serum TSH and a low free T4 suggest hypothyroidism.
Heavy metals, toxin, or drug levels
• Tests should be ordered if there is a history of potential exposure to a heavy metal. Whole blood lead
levels are elevated in lead toxicity, and 24-hour urinary arsenic, mercury, or thallium levels are elevated
with the corresponding heavy metal toxicity. Serum ciguatera toxin and saxitoxin levels should be
measured if fish poisoning is suspected. Urine hexanediol and hexenol levels should be measured if
hexane toxicity is suspected.
• There is no specific laboratory test for alcoholic neuropathy, but LFTs should be measured in patients
with a history of alcoholism and typically show elevated gamma-GT, AST, and ALT (with AST>ALT).
• Drug-induced neuropathy should resolve once the causative medications are discontinued.
DIAGNOSIS
Vitamin levels
• Vitamins B12, B1, B6, and E and methylmalonic acid levels should be measured in patients who
are at risk for these deficiencies. Symptoms should resolve if a therapeutic trial of supplementation
is instigated. Transketolase activity in whole blood or RBC may also be used to test for vitamin B1
deficiency, and typically increases after the addition of thiamine. Copper levels can be measured to
exclude copper deficiency if this is suspected. Zinc levels may be elevated if the deficiency is produced
by zinc toxicity. Serum vitamin B12 may also be decreased. Excess vitamin B6 supplementation (i.e.,
>50 mg/day) can also cause sensory peripheral neuropathy. Checking blood levels of vitamin B6 can
help to determine if deficiency or toxicity is present.
Lumbar puncture (LP)
• If patients are suspected to have AIDP based on the clinical features, an urgent LP with cerebrospinal
fluid (CSF) examination is required, and shows the characteristic finding of albuminocytological
dissociation (elevated CSF protein with normal CSF cell counts). Patients with suspected CIDP
or CISP, based on the clinical pattern, also require LP with CSF examination, which shows
albuminocytological dissociation. In patients with peripheral neuropathy after bariatric surgery, a
lumbar puncture will show increased protein with a normal white cell count.
Infective markers
• HIV neuropathy should be suspected in known HIV-positive patients. An HIV antibody test should be
performed if HIV infection is suspected.
• Human T-lymphotropic virus (HTLV) type I and II antibodies should be tested for in at-risk individuals.
• A skin smear of skin lesions should be performed in patients with suspected leprosy; Mycobacterium
leprae is isolated.
• Viral cultures or PCR of skin lesions confirm HSV infection in patients with typical lesions. Serum anti-
HSV-1 and HSV-2 antibodies should be measured to identify the subtype of the virus.
• Shingles, caused by varicella zoster infection, is a clinical diagnosis, but PCR of lesions can be used if
the diagnosis is in doubt.
• Serum RPR test or VDRL test should be performed if neurosyphilis is suspected. If serology is
negative and neurosyphilis remains a concern, CSF analysis for VDRL must be performed before the
diagnosis can be excluded or confirmed.
• Serum Lyme ELISA should be performed to test for Lyme disease if this is suspected.[64]
Inflammatory markers
• If patients present with painful neuropathy, especially mononeuritis multiplex, vasculitis markers
should be measured. ANA, extractable nuclear antigens, anti-double-stranded DNA, antineutrophil
cytoplasmic antibody, serum cryoglobulins, serum complement, and rheumatoid factor are useful
markers of the underlying vasculitides.[33] The C-reactive protein (CRP) is often highly elevated. An
FBC shows eosinophilia in Churg-Strauss syndrome, or a normocytic anaemia with leukocytosis and
thrombocytosis in granulomatosis with polyangiitis (formerly known as Wegener's granulomatosis).
• Anti-60 kDa Ro (SSA), anti-La (SSB) antibodies, and Schirmer's test should be performed in patients
with suspected Sjogren's syndrome. Additional confirmatory tests include quantitative sweat and
sensory testing, which show sensory and sympathetic nerve dysfunction and Rose-Bengal staining of
the eye, showing a severe dry eye.
DIAGNOSIS
• A diagnosis of sarcoidosis usually requires confirmation by tissue biopsy, and is usually already
established in most patients. Angiotensin converting enzyme (ACE) levels and calcium may be high.
Chest x-ray reveals hilar adenopathy or widening of the mediastinum. Tuberculin skin test should be
negative.
Other laboratory tests
• Patients with CIDP (diagnosed by clinical findings and LP) should have tests for anti-myelin-associated
protein and anti-ganglioside antibodies (specifically anti-GM1). Serum protein electrophoresis with
immunofixation identifies the subtype.
• Serum and urine electrophoresis with immunofixation should be performed if monoclonal protein
production is suspected. If positive, further tests for the specific underlying disease should be
undertaken and include serum amyloid free light chains (positive in amyloidosis), serum cryoglobulins
and hepatitis C antibodies (positive in cryoglobulinaemia), and serum beta-2 microglobulin (increased
in Waldenstrom's macroglobulinaemia).
• Inherited neuropathies should be suspected if there is a strong family history, an insidious onset of
painless symptoms, or associated deformities such as hammer-toe deformity or pes cavus, or if an
25
acquired cause is not identified. Genetic testing identifies the underlying causative mutation. A clinical
picture screen can be used to identify patients with inborn errors of metabolism.[65]
• In distal symmetric polyneuropathy, additional testing is determined by the suspected underlying
aetiologies, since several conditions may cause it, including hereditary, infectious, toxic, nutritional,
and inflammatory conditions.[13] [12]
Peripheral vascular perfusion studies
• If peripheral vascular disease is suspected as the cause, patients require an assessment of peripheral
vascular perfusion that includes ankle brachial index ≤0.90 with a gradient of >20 mmHg between
adjacent segments on segmental pressure examination; duplex ultrasound showing a peak systolic
velocity ratio >2.0, and subsequent angiography revealing stenosis of the affected artery.
Electromyography and nerve conduction studies
• Diabetic neuropathy, hypocalcaemia, vitamin deficiencies, drug toxicity, and minor infections such
as shingles or HSV can usually be diagnosed clinically or with laboratory testing. All other peripheral
neuropathies require EMG with nerve conduction studies to confirm and characterise the neuropathy.
• EMG includes nerve conduction studies and needle examination of selected muscles and should be
directed at nerves and muscles whose involvement is suspected based on the clinical examination.
EMG is able to characterise the type of peripheral nerve abnormality by its electrophysiological
features (e.g., an axonal or demyelinating neuropathy). It provides a definitive diagnosis of nerve
entrapment syndromes and can also identify more proximal lesions such as radiculopathies or
plexopathies.
DIAGNOSIS
Nerve conduction testing of the lower leg

Created by the BMJ Group
• EMG helps distinguish AIDP and CIDP from CISP. AIDP and CIDP produce sensori-motor peripheral
neuropathy, whereas the EMG in CISP is normal.
• Small-fibre sensory neuropathy (which typically produces burning paraesthesias) cannot be excluded
by standard EMG and must be investigated using quantitative sensory or sudomotor testing, or skin
biopsy to quantify intra-epidermal nerve fibre densities.
Further investigations
• May be considered based on the associated symptoms and EMG findings.

• Patients with nerve entrapment syndromes may require further imaging to identify the site of the
compression, identify causative lesions, and assess the patient prior to surgery. Imaging modalities
used include ultrasound of the wrist or elbow and magnetic resonance imaging (MRI) of the elbow,
knee, or ankle.
• Patients with suspected CISP (clinical features, albuminocytological dissociation, normal EMG) require
somatosensory-evoked potentials from the upper and lower extremities that show delayed conduction
of potentials through the spinal cord due to demyelination of the dorsal sensory roots. An MRI of the
spine, done with and without contrast administration, may help to confirm the site of the lesion by
virtue of enlarged or enhancing dorsal roots, or both.
• Paraneoplastic antibodies (particularly anti-Hu) can be tested in patients with high levels of suspicion.
If patients have positive paraneoplastic antibodies, thorough investigation is required to identify
the source of the primary tumour. This includes a mammogram in female patients; a computed
tomographic (CT) scan of the chest, abdomen, and pelvis; and a whole-body PET scan. If the initial
CT scan is negative, it should be repeated every 3 to 6 months until a cause is found for at least the
first 2 years after diagnosis. Whole-body PET scan should be repeated annually if other screening
tests for cancer are negative.
• If patients have autonomic symptoms, including orthostatic dizziness and sweating abnormalities,
specific autonomic function testing is helpful. This may be considered in patients with possible
inherited sensory and autonomic neuropathy, in patients with paraesthesias and autonomic
dysfunction in Sjogren's syndrome, or in those with distal symmetric polyneuropathy, or
polyneuropathy after bariatric surgery.[35]
DIAGNOSIS
• Peripheral nerve biopsy is reserved for patients with peripheral neuropathy that is suspected to be
due to an inflammatory cause such as vasculitis, monoclonal protein deposition, sarcoidosis, distal
symmetric polyneuropathy, polyneuropathy after bariatric surgery, or if the aetiology is not readily
determined by non-invasive methods.[29] [54] [66] [67] [13] [12] The nerve biopsy should be done in
a nerve that is involved in the disease process. Usually the sural nerve is biopsied just proximal to
the ankle, but other cutaneous nerves can be used.[67] The risks of the procedure are very small,
but include bleeding, infection, poor wound healing, and neuroma formation at the site of the biopsy.
Almost all patients experience neuropathic pain at the site of the biopsy, which typically persists for a
few days to a few weeks, and permanent numbness in the distribution of the biopsied nerve distal to
the biopsy site.
• In distal symmetric polyneuropathy, a skin biopsy to determine epidermal nerve fibre density may be
an alternative to peripheral nerve biopsy in selected cases.[13] [12]
Plexopathy or radiculopathy
Plexopathy
27
• An MRI of the plexus with contrast is important to confirm possible nerve compression by a mass
lesion (such as an invading malignancy) or a patchy inflammatory process.
Radiculopathy or ganglionopathy
• MRI with contrast of the suspected spinal level (cervical, thoracic, lumbosacral) is required to search
for evidence of disc herniation, facet arthropathy, spondylosis, spinal canal stenosis, or neuroforaminal
stenosis. Anatomical lesions identified by imaging should correlate with the dermatomal distribution
of the paraesthesias. The MRI may also show abnormal enhancement or enlargement of nerve roots,
which may occur in CISP or lymphomatous infiltration of the nerve roots in the spinal canal. If the
nerve roots are enhancing or enlarged, LP with CSF examination should be performed and reveals
abnormal cytology in lymphoma or albuminocytological dissociation in CISP.
DIAGNOSIS
A single level of spinal cord compression with T2 changes, on cervical sagittal T2

sequence in the presence of symptomatic cervical spondylotic myelopathy (CSM)
From the collection of Professor Dennis Turner, Duke University Medical Center; used with permission
Axial T2-weighted MRI with broad-based lumbar disc herniation predominantly towards the right side
From the collection of Alexios G. Carayannopoulos, Lahey Clinic; used with permission
Spinal cord involvement

MRI of total spine with contrast
• This is the image modality of choice in most patients. May show disc displacement, epidural
enhancement, a mass effect, or a T2 cord signal if spinal cord compression is present. MRI may also
reveal characteristic lesions of multiple sclerosis or transverse myelitis. Enlargement and abnormal
enhancement of spinal nerve roots may be present in patients with sarcoidosis.
DIAGNOSIS
29
DIAGNOSIS Assessment of paraesthesias Diagnosis
Sagittal T2-weighted MRI showing MS-related myelitis lesion

From the collection of Dean M. Wingerchuk, Mayo Clinic; used with permission
Spine x-ray
• This is the first test if there is a history of trauma or a compression fracture is suspected. May reveal
decreased disc space height (disc compression), loss of bony detail (tumour, infection), misalignment
of vertebral elements (trauma), or loss of endplate definition (infection).
Lumbar puncture
• CSF examination should be performed to exclude infection and demonstrate characteristic findings of
multiple sclerosis and transverse myelitis (elevated protein and oligoclonal bands, and increased CSF
IgG index).
Infective markers
• If infectious causes are suspected, testing for syphilis (tabes dorsalis) or HIV (HIV myelopathy) should
be performed.
Brainstem or brain involvement

Brain imaging
• CT brain should be considered in patients with an acute onset of numbness in the face or extremities
and clinical features suggestive of a stroke to exclude haemorrhage. This should be followed with an
MRI to identify ischaemic stroke. An MR angiogram of the Circle of Willis and neck may demonstrate
focal stenosis of medium- to-large-diameter vessels, suggesting a possible source of emboli.
• An MRI brain should be considered in patients with suspected multiple sclerosis or acute
demyelinating encephalomyelitis, and may reveal characteristic demyelinating lesions. In acute
demyelinating encephalomyelitis, the lesions are multi-focal and may contain haemorrhages.
Sagittal FLAIR images with typical MS lesions

From the collection of Lael A. Stone, Cleveland Clinic Foundation; used with permission
Lumbar puncture
DIAGNOSIS
• CSF examination reveals the characteristic features of elevated protein and oligoclonal bands and
increased CSF IgG index in patients with multiple sclerosis or acute demyelinating encephalomyelitis,
and should be performed if these conditions are suspected.
Visual-evoked potentials
• May show delayed conduction in patients with multiple sclerosis associated with optic neuritis.
Electroencephalogram (EEG)
• Should be considered in patients with a focal or partial sensory seizure to look for interictal
epileptogenic discharges in the suspected area of origin in the cortex.
31
Differentials overview
Common
Carpal tunnel syndrome
Ulnar neuropathy at elbow (UNE)
Fibular (peroneal) neuropathy
Meralgia paraesthetica
Cervical radiculopathy
Thoracic radiculopathy
Lumbosacral radiculopathy
Multiple sclerosis
Distal symmetric polyneuropathy (DSP)
Diabetes mellitus
Hypothyroidism
DIAGNOSIS
Vitamin B1 deficiency
Vitamin B6 deficiency or excess
Vitamin B12 deficiency
Vitamin E deficiency
Drug toxicity
Alcoholic neuropathy
Stroke/transient ischaemic attack
Migraine with aura
Peripheral vascular disease
Common
Panic attack with hyperventilation
Charcot-Marie-Tooth disease
Hereditary sensory and autonomic neuropathy (HSAN)
Hereditary neuropathy with liability to pressure palsy (HNPP)
Uncommon
Brachial plexopathy
Lumbosacral plexopathy
Tibial neuropathy
Trigeminal neuropathy
Acute demyelinating encephalomyelitis
Acute inflammatory demyelinating polyneuropathy (AIDP)
Chronic inflammatory demyelinating polyneuropathy (CIDP)
Chronic inflammatory demyelinating sensory polyradiculopathy (CISP)
Uraemia
DIAGNOSIS
Hypocalcaemia
Copper deficiency
Heavy metal poisoning
Radiation
Hexane
Ciguatera or saxitoxin poisoning
HIV neuropathy
Leprosy
33
Uncommon
Herpes simplex infection
Neurosyphilis
Herpes zoster infection (shingles)
Lyme disease
Conversion and somatisation disorders
Inborn errors of metabolism
Rheumatoid arthritis
Systemic lupus erythaematosus
Churg-Strauss syndrome
Granulomatosis with polyangiitis (formerly known as Wegener's granulomatosis)
Polyarteritis nodosa
Microscopic polyangiitis
Sjogren's syndrome
Sarcoidosis
DIAGNOSIS
Monoclonal protein production
Partial epilepsy
Paraneoplastic sensory neuropathy or ganglionopathy
Intravascular lymphoma
Neuro-Behcet's disease
Wartenberg's migrant sensory neuritis
Numb chin syndrome
Peripheral neuropathy after bariatric surgery
Uncommon
Notalgia paraesthetica
Neuromyelitis optica spectrum disorder (Devic's disease)
Anti-myelin-associated glycoproteins (MAG) peripheral neuropathy
Hypertriglyceridaemia
Human T-lymphotropic virus (HTLV)
DIAGNOSIS
35
Differentials
Common
◊ Carpal tunnel syndrome
History Exam 1st Test Other tests
paraesthesias in weakness in median- »Electromyography »ultrasound of wrist:

first three digits of innervated hand (EMG) and nerve enlargement of the
affected hand; grip muscles; decreased conduction studies: median nerve in the
weakness; pain in pinprick sensation slowed conduction carpal tunnel
wrist or hand possibly on palmar aspect velocity in median
extending into forearm, of first three digits; sensory responses
elbow, or shoulder; positive carpal tunnel across the wrist with
symptoms worse at compression tests: prolonged distal motor
night (awakening paraesthesias elicited latency
patient from sleep) by Tinel's manoeuvre Amplitudes may be
and exacerbated (lightly percussing low, indicating axonal
by prolonged wrist the nerve), Phalen's
extension such as manoeuvre (maximum loss, in which case
driving, typing on a passive flexion of the carpal tunnel syndrome
keyboard, or reading a wrist for 1 minute), is severe. Combined
newspaper or reverse Phalen's motor and sensory
manoeuvre (hand in a
fist with maximum wrist abnormalities indicate
extension and pressure moderately severe
applied to carpal tunnel disease; isolated
for 1 minute) sensory abnormalities
indicate mild disease.
◊ Ulnar neuropathy at elbow (UNE)

DIAGNOSIS
paraesthesias involving weakness in interossei; »EMG and nerve »ultrasound of

fourth and fifth digits weak flexion with wrist conduction studies: elbow: may show
of affected hand; in ulnar deviation; slowed conduction enlargement of nerve at
weakness in hand grip; weak flexion of distal velocity, with or site of compression or
possible elbow pain; joint of fourth and without block (drop in tendinous impingement
history of prolonged fifth digits; loss or amplitude from distal »MRI of elbow:
or repetitive flexion of relative reduction of to proximal stimulus focal enlargement or
elbow or leaning on pinprick sensation sites from neuropraxia) enhancement of the
elbow on palmar and dorsal across the elbow in the ulnar nerve at the site
aspect of fourth and ulnar motor nerve of compression or a
fifth digits of affected There may be distal mass lesion or tendon
hand; palpation of amplitude loss in the compressing the nerve
the ulnar nerve in
motor and sensory Required to further
olecranon groove elicits
paraesthesias ulnar nerves indicating localise the nerve
more severe pathology. lesion if surgery is
EMG may also show being considered.
Common
◊ Ulnar neuropathy at elbow (UNE)

denervation in ulnar
innervated muscles.
◊ Fibular (peroneal) neuropathy
history of weight loss; weakness in ankle »EMG and nerve »MRI or ultrasound
trauma or surgery dorsiflexion and toe conduction studies: of knee and
involving lateral aspect extension, eversion of conduction velocity proximal leg:
of affected knee; the ankle, decreased slowing across the enlargement or
history of repetitive pinprick sensation fibular head, with or enhancement of the
crossing of knees or on lateral leg and without conduction fibular (peroneal)
prolonged kneeling, dorsal foot and ankle, block (drop in nerve at the site of
crouching, or squatting palpation of the fibular amplitude from distal to compression; vascular
prior to onset of (peroneal) nerve at the proximal stimulus sites abnormality or mass
symptoms; pain at fibular head just distal from neuropraxia) in the lesion compressing the
knee; paraesthesias in to the knee joint elicits fibular motor nerve nerve
lateral leg and dorsal paraesthesias Sensory and motor Imaging should be
foot; foot drop amplitudes may done if there is no
be reduced distally compatible history for
indicating more severe a cause of lesion or if
pathology. surgical intervention is
planned.
◊ Meralgia paraesthetica
DIAGNOSIS
acute or subacute allodynia or »EMG: normal with »nerve conduction

onset of burning hypersensitivity to no evidence of lumbar studies: reduced
paraesthesias in the touch, with sensory radiculopathy amplitude in lateral
anterolateral thigh loss, in distribution cutaneous nerve of the
region with increased of the lateral femoral thigh
sensitivity to touch or cutaneous nerve of the
pressure thigh, either unilaterally
or bilaterally, preserved
quadriceps deep
tendon reflex, no motor
weakness
37
Common
◊ Cervical radiculopathy
neck pain with pain with palpation of »MRI or CT

radiation into upper the spine or range-of- myelogram of
extremity, possibly motion testing, reduced cervical spine:
in a dermatomal pinprick sensation focal disc herniation
pattern; paraesthesias in dermatomal or protrusion
in affected arm distribution, muscle impinging on affected
and/or hand; weakness in myotomal roots; spinal canal
muscle weakness distribution, loss or stenosis; spondylosis,
in corresponding reduction of deep facet arthropathy,
myotomes tendon reflexes in neuroforaminal stenosis
affected limb compared »EMG and nerve
with the unaffected side conduction studies:
needle examination
shows signs of
denervation in limb
or trunk muscles
innervated by same
nerve root and in
the corresponding
paraspinal muscles;
normal sensory nerve
conduction
◊ Thoracic radiculopathy

DIAGNOSIS
pain, burning, pain with palpation of »MRI or CT

numbness on trunk the spine or range-of- myelogram of
or chest wall in a motion testing, reduced thoracic spine:
dermatomal pattern, pinprick sensation focal disc herniation
muscle weakness in dermatomal or protrusion
in corresponding distribution, muscle impinging on affected
myotomes weakness in myotomal roots; spinal canal
distribution stenosis; spondylosis,
facet arthropathy,
neuroforaminal stenosis
»EMG and nerve
conduction studies:
needle examination
shows signs of
denervation in limb
or trunk muscles
innervated by same
nerve root and in
the corresponding
paraspinal muscles;
Common
◊ Thoracic radiculopathy

conduction
◊ Lumbosacral radiculopathy
low back pain with pain with palpation of »MRI or CT

radiation into the the spine or range-of- myelogram of
leg in a dermatomal motion testing, reduced lumbar spine:
pattern, paraesthesias pinprick sensation focal disc herniation
in dermatomal pattern, in dermatomal or protrusion
muscle weakness distribution, muscle impinging on affected
in corresponding weakness in myotomal roots; spinal canal
myotomes distribution, loss or stenosis; spondylosis,
reduction of deep facet arthropathy,
tendon reflexes in neuroforaminal stenosis
affected limb compared »EMG and nerve
with the unaffected conduction studies:
side, hip range-of- needle examination
motion testing and shows signs of
straight leg raising denervation in limb
reproduces symptoms or trunk muscles
radiating from the lower innervated by same
back into the leg nerve root and in
the corresponding
paraspinal muscles;
DIAGNOSIS
conduction
back pain; bowel and brisk deep tendon »MRI of total spine »CT myelography:
bladder incontinence; reflexes; ankle clonus; with contrast: disc classical hour-glass
difficulty walking due upgoing toes to displacement, epidural constriction shape of
to spasticity; muscle plantar stimulation; enhancement, mass the dye column
weakness in the sensory loss and motor effect, T2 cord signal Performed if MRI is
lower extremities; weakness caudal to the unavailable or cannot
»spine x-ray:
paraesthesias in the spinal level affected decreased disc be used.
extremities; intermittent space height (disc
paraesthesias in compression), loss of
the body associated bony detail (tumour,
with neck flexion infection), misalignment
(Lhermitte’s sign) of vertebral elements
(trauma), loss of
endplate definition
39
Common

(infection), atlanto-
axial subluxation
(rheumatoid arthritis)
◊ Multiple sclerosis
acute onset of loss of sensation in »MRI of brain and »visual-evoked

paraesthesias, the extremities or face, total spine: hyper- potentials: delayed
weakness, pupillary abnormalities intensities in the conduction of potentials
incoordination, visual and visual loss, periventricular white from one or both eyes if
changes developing muscle weakness matter, most sensitive prior optic neuritis
at different times that and spasticity, images are sagittal »somatosensory-
may or may not resolve incoordination, fluid-attenuated evoked potentials:
after being present for abnormal gait inversion recovery; delayed conduction of
a few days to months; demyelinating lesions potentials from upper
bowel and bladder in the spinal cord, or lower extremities
incontinence, bladder particularly the cervical through brain or spinal
retention, or bladder spinal cord cord levels that have
spasms »lumbar puncture demyelinating lesions
with cerebrospinal May be used to support
fluid (CSF) clinical diagnosis if
examination and
culture: unique MRI is equivocal or not
oligoclonal bands; possible.
increased IgG
index; increased
DIAGNOSIS
myelin basic protein;

mild lymphocytic
pleocytosis; testing for
infectious agents is
negative
◊ Distal symmetric polyneuropathy (DSP)
acute, sub-acute, initially distally reduced »EMG and nerve »autonomic

or insidious onset or loss of sensation conduction studies: reflex function
of distally and (light touch, pinprick, may be normal if testing (especially
symmetrically temperature, vibratory, only small diameter, quantitative sweat
distributed symptoms joint position sense), unmyelinated sensory testing): confirms
of paraesthesias with a gradient of return nerve fibres are involvement of small
(usually tingling to normal sensation affected; decreased diameter, unmyelinated
paraesthesias with moving from distal to sensory nerve nerve fibres if a
or without associated proximal regions of the action potential and small fibre sensory
asleep- or dead-type lower limbs; if primarily compound muscle neuropathy is present
numbness in the same small diameter sensory action potential
Common

areas) and usually later nerve fibres involved, amplitudes if primarily »quantitative
muscle weakness; may be dissociation axonal degeneration, sweat testing:
progressive symptoms between abnormal slowed conduction may demonstrate a
from onset, may be findings when testing velocities and length-dependent,
intermittently present for spinothalamic prolonged distal or distal reduction or
initially, then become (pinprick, temperature) sensory and motor loss of sweat output
more constant, and and dorsal column latencies if primarily volumes comparing
begin in the toes and (vibratory, joint position nerve demyelination, proximal (upper limb)
extend proximally sense) pathways, with or a combination and distal (proximal
in both legs to the the former showing of both findings if a leg and dorsal foot)
level of the knees, reduced or absent mixed axonal and test sites; a length-
at which point the sensation distally demyelinating process dependent decrease
distal fingertips of both in the limbs; if only is occurring; lower in sweat output may
hands typically become small diameter, extremity nerve correlate with a
involved; if small unmyelinated sensory conduction studies length-dependent, or
sensory nerve fibres nerve fibres involved, abnormal initially, but distally predominant,
are affected, burning the neurological exam with progression of polyneuropathy
pains and allodynia may be completely DSP the abnormal involving small
(painful sensations normal, with findings findings in the lower diameter, unmyelinated
elicited by normally developing over time limbs become more nerve fibres
non-noxious stimuli, as the polyneuropathy severe and first »quantitative
such as light touch) are progressively worsens sensory, then motor sensory testing: may
usually reported by the and larger diameter nerve conduction show increased cooling
patient sensory nerves studies in the distal and vibratory detection
become affected by upper extremities will thresholds; heat
the disease process; also become abnormal; detection threshold
sensory ataxia and findings should be may be increased
positive Romberg essentially symmetric or decreased, the
sign may be present in distribution, by latter in the case of
DIAGNOSIS
if there is significant definition allodynia with small
impairment of joint sensory nerve fibre
position sensation; dysfunction; these
distal motor weakness quantitative sensory
in the same distribution abnormalities should
as the sensory loss, be distally predominant
when present; reduced in terms of severity
or absent deep tendon and distribution,
reflexes, worse in when comparing
the lower limbs, test results from the
and symmetric in foot and the hand;
distribution distally predominant
abnormalities
may be seen in
distal symmetric
polyneuropathy,
involving large
diameter, myelinated
and/or small diameter,
thinly myelinated or
unmyelinated nerve
41
Common

fibres, depending on
the test results
»peripheral
cutaneous nerve
biopsy: examines
nerve morphology and
interstitial pathology,
as may be seen in
such conditions as
sarcoidosis, vasculitis,
amyloidosis, or tumour;
may be appropriate in
selected cases[12] [13]
»skin biopsy:
determines epidermal
nerve fibre density,
specifically small
unmyelinated or thinly
myelinated nerve fibres;
may be of value in
terms of quantifying
loss of these fibres
at any given location,
and if proximal and
distal locations are
selected in a limb for
biopsies, such as the
leg, a proximal-to-distal
DIAGNOSIS
gradient reduction in
epidermal nerve fibre
density may help to
demonstrate a length-
dependent neuropathic
process involving this
nerve fibre population;
may be appropriate in
selected cases[12] [13]
»additional tests:
additional testing is
determined by the
suspected underlying
aetiologies, since
several conditions may
cause distal symmetric
polyneuropathy[68]
Common
◊ Diabetes mellitus
history of diabetes distal loss of sensation »none: clinical »EMG and nerve
mellitus; history of other affecting lower more diagnosis conduction studies:
end-organ disease than upper extremities, mixed axonal and
from diabetes mellitus, reduced deep tendon demyelinating sensori-
such as retinopathy reflexes (especially motor polyneuropathy
or nephropathy; distal Achilles reflexes), or polyradiculopathy
paraesthesias or possible muscle »HbA1c: elevated, >53
burning pains; painless weakness and atrophy mmol/mol (>7%)
and occult injuries to
the feet due to lack of
protective sensation;
possible muscle
weakness or abnormal
gait
◊ Hypothyroidism
cold intolerance, weight loss of sensation in »EMG and nerve

gain, fatigue, brittle hair the distal extremities conduction studies:
or nails; distal extremity or in the distribution of distal sensori-motor
paraesthesias, possible individual peripheral peripheral neuropathy,
motor weakness nerves, such as median mixed axonal and
nerve in the hand; demyelinating;
possible muscle may have focal
weakness in the superimposed
distal extremities and mononeuropathies
DIAGNOSIS
decreased or delayed such as median
deep tendon reflexes neuropathy at the wrist
»thyroid function
tests: increased TSH
and low free T4 in
primary hypothyroidism;
low or normal
TSH and low free
T4 in secondary
hypothyroidism
◊ Vitamin B1 deficiency
vomiting, encephalopathy; »therapeutic »EMG and nerve

encephalopathy, decreased deep tendon trial of thiamine conduction studies:
burning feet, shooting reflexes, distal muscle supplementation: sensori-motor
pains, calf cramps; weakness affecting symptoms resolve in peripheral neuropathy
lower more than upper vitamin B1 deficiency
43
Common

heart failure symptoms extremities, hoarseness »24-hour urine »transketolase
in infants from laryngeal nerve thiamine excretion: activity in whole
palsy reduced in vitamin B1 blood or red blood
deficiency cell: enzyme activity
increases after addition
»serum thiamine
of thiamine in vitamin
level: reduced in
B1 deficiency
vitamin B1 deficiency
»serum pyruvate:
increased in vitamin B1
deficiency
◊ Vitamin B6 deficiency or excess
paraesthesias in loss of sensation in the »serum vitamin »EMG and nerve

the extremities, distal lower extremities, B6 level: reduced in conduction studies:
gait unsteadiness, distribution of sensory vitamin B6 deficiency; may demonstrate a
seborrhoeic dermatitis, loss may be patchy, elevated with excess sensory peripheral
atrophic glossitis with decreased deep tendon neuropathy greater
ulceration, angular reflexes than motor peripheral
cheilosis neuropathy

DIAGNOSIS
history of peptic ulcer loss of deep »serum vitamin B12 »EMG and nerve
disease or other tendon reflexes, level: <221 picomol/L conduction studies:
upper gastrointestinal decreased vibratory (<300 picogram/mL) sensori-motor
condition or surgery and joint position peripheral neuropathy
»serum
that may reduce sensation initially with methylmalonic acid: »MRI of spinal
absorption of paraesthesias, may elevated cord: may show
vitamin B12, ataxia, have gait ataxia increased signal on
paraesthesias may be »serum
T2-weighted images in
transient and migratory homocysteine level:
the dorsal and lateral
elevated
columns of the spinal
cord in cases with
sub-acute combined
degeneration[69]
Common
◊ Vitamin E deficiency
history of gait ataxia; absent »serum vitamin E: »EMG and nerve

malabsorption due or decreased deep <0.5 mg/dL conduction studies:
to cirrhosis, cystic tendon reflexes; loss may show sensory
fibrosis, coeliac of proprioceptive and neuropathy, worse in
disease, Crohn's vibratory sensation the lower extremities
disease, cholestatic May be normal.
liver disease; gait
unsteadiness and »somatosensory-
paraesthesias in the evoked potentials:
lower extremities may show slowing of
conduction of evoked
potentials at the spinal
cord level
◊ Drug toxicity
history of exposure to distal loss of sensation »trial of

chemotherapy agents in the extremities; discontinuation
(cisplatin, vincristine, possible muscle of causative
cytosine arabinoside, weakness medication:
thalidomide, symptoms resolve
paclitaxel), antibiotics
(metronidazole,
nitrofurantoin),
antiretroviral
DIAGNOSIS
agents (zidovudine,
stavudine, lamivudine),
antiepileptics
(phenytoin), or vitamin
B6 overdose; slowly
progressive distal
paraesthesias
◊ Alcoholic neuropathy
history of alcohol loss of sensation and »EMG and nerve »liver function
abuse, gait instability, deep tendon reflexes in conduction studies: tests (LFTs):
paraesthesias in the the lower extremities, axonal sensori-motor normal or elevated
distal lower extremities sensory ataxia, positive peripheral neuropathy gamma-GT, aspartate
progressing proximally, Romberg's sign; aminotransferase
paraesthesias of the signs of alcoholic (AST), and alanine
fingers and hands liver disease: ascites, aminotransferase (ALT;
appear once symptoms splenomegaly, AST>ALT)
cutaneous
45
Common
◊ Alcoholic neuropathy

extend above ankle telangiectasias, palmar
level erythaema, finger
clubbing, Dupuytren's
contractures
Stroke/transient ischaemic at tack
sudden onset of loss of sensation »CT scan of head: »MR angiogram of

numbness in the face in the face or the may appear normal Circle of Willis and
or extremities (more extremities either on initially or show acute neck: focal stenosis
likely to be loss of the same side of the intraparenchymal of medium- to large-
sensation reported by body (hemisensory) ischaemic infarct diameter intracranial
the patient than pain or or on opposite sides (hypodensity) or and extra-cranial
tingling paraesthesias), for the face and body, haemorrhagic infarct blood vessels; acute
may or may not be depending on the (hyperdensity) dissection of arterial
unilateral and may or location of the infarct walls (internal carotid,
»MRI of brain:
may not involve motor acute infarction vertebral) in head and
weakness, slurred neck can produce
(haemorrhagic or
speech, change in thrombi that may block
ischaemic) in one or
vision; history of risk blood flow and cause
more cerebrovascular
factors for stroke, an acute ischaemic
territories
including tobacco intraparenchymal
abuse, diabetes infarct or transient
mellitus, hypertension, cerebral ischaemia;
history of prior stroke acute dissection may
occur spontaneously
DIAGNOSIS
or following minor
head/neck trauma or
repositioning, and neck/
head pain may or may
not be present;[70]
proceed with 4-vessel
cerebral arteriography
(or CT angiogram) if
there is high suspicion
for a vascular aetiology
for a cerebral infarct
or transient cerebral
ischaemia, and initial
imaging is negative;
fibromuscular dysplasia
of the carotid or
vertebral arteries may
also cause ischaemic
stroke in young adults,
and may be diagnosed
using one of these
techniques[71]
Common
Stroke/transient ischaemic at tack

»CT angiogram
of head and neck:
to detect arterial
dissection when
cerebral arteriography
is not readily
available, or there are
contraindications to
cerebral angiogram
(contrast dye allergy,
renal insufficiency)
◊ Migraine with aura
acute onset of may be normal »none: clinical »MRI brain: may be

paraesthesias as paraesthesias diagnosis normal or demonstrate
spreading over several may be transient, mild sub-cortical
minutes in association may demonstrate white matter changes
with severe, throbbing, sensory loss in face or (chronic), if history
usually unilateral extremities if examined of prior migraine
headache; may during the episode headache
have nausea and
vomiting, photophobia,
phonophobia; sensory
symptoms may start
in the hand and then
DIAGNOSIS
progress to involve
ipsilateral arm, face,
and tongue; sensory
symptoms typically last
<1 hour from the onset
of the headache
◊ Peripheral vascular disease
history of reduced or absent »ankle brachial »segmental pressure

smoking, diabetes, peripheral pulses, pallor index: ≤0.90 examination: gradient
hyperlipidaemia, and cold of affected of >20 mmHg between
coronary artery disease limb, non-healing leg adjacent segments
or cerebrovascular wounds or ulcers, »duplex ultrasound:
disease, claudication, muscle atrophy, loss of peak systolic velocity
pain and paraesthesias hair over the dorsum of ratio >2.0
worse in one leg the foot, shiny or scaly
skin, thickened toe nails »angiography: artery
stenosis
47
Common
◊ Panic at tack with hyperventilation
hyperventilation, may be normal; patient »none: clinical »trial of

associated symptoms visibly hyperventilating, diagnosis hyperventilation
of anxiety or panic carpopaedal spasm for 1 to 2 minutes:
including overwhelming reproduces symptoms
sense of impending »EMG and nerve
doom, chest pain, conduction studies:
palpitations and normal
shortness of breath,
perioral and bilateral
paraesthesias in
hands and feet with
associated carpopaedal
spasm
◊ Charcot-Marie-Tooth disease
abnormal or clumsy length-dependent, »EMG and nerve »sural nerve

gait due to foot drop; symmetric, 'glove and conduction studies: biopsy: type 1: onion
toe-walking as a child; stocking' distribution varies depending bulb formation and
paraesthesias are of sensory and motor on type; type 1: demyelination; type
minimal abnormalities, distal severe demyelinating 2: chronic axonal
muscle atrophy; neuropathy with degeneration
inverted 'champagne conduction velocities
bottle' legs, pes cavus, in the 10 to 20 m/
and hammer-toe second range (cut-off
deformities 38 m/second); type 2:
DIAGNOSIS
relatively preserved
conduction velocities
(cut-off 38 m/second)
but low sensory and
motor nerve amplitudes
»genetic testing:
identification of
causative mutations;
type 1: duplication
of PMP 22 gene on
chromosome 17p11.2,
MPZ, connexin 32 or
mutations P0; type
2: mitofusin 2, RAB7
mutations
Common
◊ Hereditary sensory and autonomic neuropathy (HSAN)
positive family history, length-dependent »EMG with nerve »autonomic

painless injuries to the sensory greater than conduction studies: function testing:
extremities, severe motor peripheral sensori-motor generalised autonomic
burning pain in the feet, neuropathy, dry peripheral neuropathy failure including
possible dysautonomia skin, pes cavus, with predominant sudomotor, cardiovagal,
and hammer-toe sensory component and adrenergic
deformities; may have dysfunction
orthostatic hypotension »genetic testing:
identified mutation in
HSAN type 1 (most
common) in serine
palmitoyltransferase
(SPTLC1) at
chromosome 9q221-
q22.3[72]
◊ Hereditary neuropathy with liability to pressure palsy (HNPP)
multiple entrapment pes cavus and »EMG and nerve »sural nerve
neuropathies in the hammer-toe conduction studies: biopsy: tomacula or
extremities in the deformities; focal generalised, mild, reduplication of myelin
setting of minimal motor weakness demyelinating sensori- around axons and
compression; positional and numbness in motor peripheral demyelination
paraesthesias in the distribution of individual neuropathy with
extremities peripheral nerves; superimposed focal
DIAGNOSIS
positive Tinel's or mononeuropathies
Phalen's sign at common sites of
compression
»genetic testing:
deletion of
chromosome 17p11.2
Uncommon
Brachial plexopathy
history of injury, acute loss of sensation and »EMG and nerve »chest x-ray: elevated
onset of unilateral weakness in affected conduction hemidiaphragm on side
shoulder or arm pain limb involving more studies: asymmetric of affected limb
(if inflammatory) than a single peripheral abnormalities in Indicated in patients
followed by numbness nerve territory; possible sensory and motor who present with
and weakness in the loss of reflexes nerve conduction
affected arm after the studies in the affected shortness of breath.
49
Uncommon
Brachial plexopathy

pain has resolved, limb; no involvement »peripheral nerve
shortness of breath of corresponding biopsy: perivascular
due to diaphragmatic paraspinal muscles inflammation; may also
involvement if cervical show perineurioma
»MRI of the
roots involved or lymphomatous
brachial plexus
or carcinomatous
or lumbosacral
infiltration
plexus (pelvis
and hip): increased
signal and abnormal
enhancement in a
patchy pattern; possible
mass lesion (tumour
or retroperitoneal
haematoma) impinging
on plexus
Lumbosacral plexopathy
history of injury, pelvic loss of sensation and »EMG and nerve »peripheral nerve
mass, surgical, or weakness in affected conduction biopsy: perivascular
vascular procedure, limb involving more studies: asymmetric inflammation; may also
painless onset of than a single peripheral abnormalities in show perineurioma
numbness and nerve territory; possible sensory and motor or lymphomatous
paraesthesias and loss of reflexes nerve conduction or carcinomatous
weakness in affected studies in the affected infiltration
DIAGNOSIS
leg limb; no involvement

of corresponding
paraspinal muscles
»MRI of the
brachial plexus
or lumbosacral
plexus (pelvis
and hip): increased
signal and abnormal
enhancement in a
patchy pattern; possible
mass lesion (tumour
or retroperitoneal
haematoma) impinging
on plexus
Uncommon
◊ Tibial neuropathy
pain and paraesthesias loss of sensation on »EMG and nerve »MRI of ankle joint:
in the medial aspect the sole of the affected conduction studies: often normal; may
and sole of the foot, foot, weakness with toe asymmetry between show enlargement of
medial ankle pain, foot flexion, compression the affected and tibial nerve in the tarsal
weakness of the tibial nerve in unaffected leg with tunnel or increased
the tarsal tunnel just tibial motor nerve signal in adjacent
proximal to the medial conduction studies connective tissue
malleolus reproduces with recording from suggestive of localised
paraesthesias, normal the abductor hallucis inflammation
Achilles deep tendon and the abductor Used to exclude focal
reflex digiti quinti minimi mass lesion if planning
muscles; prolonged
distal latencies and/ surgery.
or reduced or absent
medial and lateral
plantar sensory
potentials on the
affected foot
◊ Trigeminal neuropathy
acute or subacute loss of sensation in »MRI brain with and »EMG and nerve
onset of hemifacial pain the hemiface or in without contrast: conduction studies:
and paraesthesias the distribution of abnormal signal or decreased trigeminal
individual branches of contrast enhancement nerve function detected
the trigeminal nerve; of ipsilateral trigeminal by blink reflex testing
DIAGNOSIS
corneal reflex absent or nerve or its ganglia on affected and
reduced on the affected unaffected sides
side
acute or subacute loss of sensation in »MRI brain and

onset of headache, the extremities; mental spinal cord, with and
cognitive changes, status changes; may without contrast:
paraesthesias in the have muscle weakness multi-focal deep sub-
extremities, weakness, and spasticity in the cortical white matter
gait difficulty, fever, extremities lesions with increased
meningismus, typically signal intensity on T2-
occurs 1 to 2 weeks weighted and fluid-
after a viral illness or attenuated inversion
vaccination recovery sequences;
may enhance with
contrast administration
51
Uncommon

or contain haemorrhage
in acute setting
»lumbar puncture
with cerebrospinal
fluid examination:
pleocytosis, increased
protein level, abnormal
immunoglobulin
production (IgG index)
and presence of
oligoclonal bands
initially acute onset absence of deep »lumbar puncture

of paraesthesias tendon reflexes, flaccid with cerebrospinal
in the toes, with paralysis, and loss of fluid examination:
rapidly ascending sensation involving albuminocytological
paraesthesias and proximal and distal limb dissociation (elevated
motor weakness; may segments (upper and cerebrospinal fluid
involve respiratory lower extremities) protein with normal
and bulbar muscles WBC and red blood cell
and lead to acute counts)
respiratory failure; May be normal within
progression may first few days of illness;
DIAGNOSIS
proceed over hours

to a couple of days; repeat after first week
symptoms may develop to confirm diagnosis.
after recent (within
2 weeks) upper »EMG and nerve
respiratory or GI viral conduction studies:
infection or vaccination demyelinating sensori-
motor peripheral
neuropathy with
prolonged F-wave
and distal sensory
and motor latencies;
relative preservation
of sensory and motor
nerve amplitudes
Important to document
peripheral neuropathy
as cause of the
symptoms; also
provides information
regarding severity of
Uncommon

disease; may evolve
over the first 2 weeks of
illness.
◊ Chronic inflammatory demyelinating polyneuropathy (CIDP)
progressive numbness proximal and distal »EMG and nerve »anti-myelin-

and weakness of symmetric extremity conduction studies: associated protein
the extremities with muscle weakness, loss demyelinating sensori- antibody: may have
symmetric involvement of sensation distally in motor peripheral positive or elevated
the extremities, loss of neuropathy with titres in serum with
deep tendon reflexes prolonged distal certain subtypes of
latencies and slowed CIDP
conduction velocities; »anti-GM1 antibody:
relative preservation of may have positive or
amplitudes elevated titres in serum
»lumbar puncture with certain subtypes of
with cerebrospinal CIDP
fluid examination: »serum protein
albuminocytological electrophoresis with
dissociation (elevated immunofixation:
cerebrospinal fluid monoclonal protein
protein with normal spike with certain
WBC and red blood cell subtypes of CIDP
counts)
DIAGNOSIS
◊ Chronic inflammatory demyelinating sensory polyradiculopathy
(CISP)
progressive loss of sensation in the »MRI of spine, »lumbar puncture

paraesthesias and gait extremities and loss of with and without with cerebrospinal
instability deep tendon reflexes, contrast: diffuse fluid examination:
motor examination is enlargement and albuminocytological
relatively preserved, abnormally increased dissociation (elevated
sensory gait ataxia signal and contrast cerebrospinal fluid
enhancement of protein with normal
multiple dorsal nerve WBC and red blood cell
roots counts)
»EMG and nerve
conduction studies:
usually normal
53
Uncommon
◊ Chronic inflammatory demyelinating sensory polyradiculopathy

(CISP)

»somatosensory-
evoked potentials
from the upper and
lower extremities:
delayed conduction
of potentials through
the spinal cord;
demonstrates the site
of the pathology, which
is the dorsal sensory
root
◊ Uraemia
history of renal failure, impaired vibratory »serum creatinine: »EMG and nerve
paraesthesias of distal sensation, absent deep elevated conduction studies:
extremities progressing tendon reflexes axonal sensori-motor
»creatinine
proximally and followed polyneuropathy
clearance: <10 mL/
by motor weakness; min
associated vomiting,
fatigue, anorexia,
weight loss, muscle
cramps, pruritus,
mental status changes,
visual disturbances,
DIAGNOSIS
increased thirst;
possible superimposed
compression
neuropathy
◊ Hypocalcaemia
history of thyroid positive Chvostek's or »serum calcium:

surgery or Trousseau's sign reduced
hypoparathyroidism, »serum vitamin D:
lethargy, muscle reduced in vitamin D
cramps, twitches, deficiency
spasms, or tetany
»serum parathyroid
hormone: reduced in
hypoparathyroidism;
elevated in pseudo-
hypoparathyroidism
Uncommon
◊ Hypocalcaemia

»serum magnesium:
may be reduced
◊ Copper deficiency
history of zinc spasticity in the lower »serum copper: »somatosensory-

exposure or toxicity, extremities, loss of decreased evoked potentials:
paraesthesias, vibratory and joint delay of conduction of
»serum zinc:
abnormal gait position sense nerve potentials at the
increased in zinc
toxicity level of the spinal cord
»EMG and nerve

conduction studies:
may show sensory
neuropathy
Heavy metal poisoning
history of heavy distal sensory loss and »EMG and nerve »hair and fingernail
metal exposure (use weakness in the distal conduction studies: arsenic level: positive
of treated lumber, extremities, loss of axonal sensori-motor in arsenic exposure
consumption of well deep tendon reflexes, polyneuropathy
water, use of fertilisers Mee lines on fingernail »whole blood lead
DIAGNOSIS
or insecticides beds, hyperkeratosis level: elevated in lead
containing arsenic), of the skin of palms exposure
acute exposure may and soles, alopecia in
have GI symptoms thallium toxicity »24-hour urine test
including nausea and for arsenic, mercury,
vomiting, abdominal thallium: elevation of
pain and diarrhoea; relevant heavy metal
paraesthesias and
weakness in the
distal extremities
that progress
proximally; mercury
poisoning: patients
also have circumoral
paraesthesias with
slurred speech,
tremors, and psychiatric
manifestations; lead
toxicity may cause lead
encephalopathy
55
Uncommon
◊ Radiation
history of radiotherapy loss of sensation and »EMG and nerve »chest x-ray: elevated
to axilla, groin, or weakness in affected conduction hemidiaphragm on
pelvis; brachial limb involving more studies: asymmetric side of affected limb in
plexopathy: acute than a single peripheral abnormalities in brachial plexopathy
onset of unilateral nerve territory; possible sensory and motor Indicated in patients
shoulder and/or arm loss of reflexes nerve conduction who present with
pain (if inflammatory), studies in the affected
followed by numbness limb; no involvement shortness of breath.
and weakness in the of corresponding
»peripheral nerve
affected arm after the paraspinal muscles;
biopsy: perivascular
pain has resolved, myokymia (localised
inflammation
shortness of breath muscle quivering)
due to diaphragmatic on needle EMG
involvement if examination of muscles
cervical roots in affected extremity
involved; lumbosacral »MRI of the
plexopathy: history brachial plexus or
of pelvic mass, lumbosacral plexus
surgical or vascular (pelvis and hip):
procedure, painless increased signal and
onset of numbness
abnormal enhancement
and paraesthesias, and in a patchy pattern
weakness in affected
leg
Hexane

DIAGNOSIS
history of glue- loss of sensation and »EMG and nerve

sniffing behaviour or deep tendon reflexes in conduction studies:
industrial exposure, the lower extremities, axonal sensori-motor
paraesthesias in the sensory ataxia, positive peripheral neuropathy
distal lower extremities Romberg's sign »urine hexanediol
progressing proximally, and hexenol level:
paraesthesias of the elevated
fingers and hands
appear once symptoms
extend above ankle
level
history of ingestion loss of sensation in »EMG and nerve

of fish that are the extremities, loss of conduction studies:
known to contain deep tendon reflexes,
Uncommon

neurotoxins, acute motor weakness, or axonal sensori-motor
or subacute onset of paralysis depending peripheral neuropathy
distal paraesthesias on the severity of the »testing for serum
and circumoral poisoning ciguatera toxin or
paraesthesias and saxitoxin: positive if
paralysis, acute GI ingested
symptoms within
hours after ingestion,
myalgias
◊ HIV neuropathy
history of long- distal sensory loss in »HIV antibody:

standing HIV infection, the extremities with positive
distal extremity or without muscle »EMG and nerve
sensory symptoms weakness conduction studies:
(paraesthesias) and distal axonal sensori-
motor weakness motor peripheral
neuropathy
◊ Leprosy
DIAGNOSIS
residency or travel to distal sensory changes »skin smear: isolation »sural cutaneous
endemic area; close and later motor of Mycobacterium nerve biopsy: may
contact with infected weakness; may be leprae show mixture of axonal
person; skin macules, confined to distribution Typically found on and demyelinating
papules, or nodules; of individual peripheral cooler portions of head abnormalities;
distal sensory followed nerves infectious organism
by motor loss and extremities. may be found within
Schwann cells
May not be necessary if
diagnosis is determined
by skin biopsy and
follows typical pattern.
»EMG and nerve

conduction studies:
may show distal
sensori-motor
with superimposed
mononeuropathies
57
Uncommon
◊ Leprosy

(ulnar, median, fibular
[peroneal], tibial)
◊ Herpes simplex infection
dysuria, prodrome fever, »viral culture: virus

of localised tingling lymphadenopathy, detected
sensation prior to the normal neurological »herpes simplex
appearance of genital examination virus (HSV)
or oral ulcers polymerase chain
reaction (PCR):
positive
»serum anti
HSV-1 and HSV-2
antibodies: positive
for causative virus
◊ Neurosyphilis
history of syphilis, tabes dorsalis: loss »EMG and nerve »lumbar puncture
progressive gait of proprioceptive conduction studies: with CSF
unsteadiness, and vibratory sensory peripheral examination: normal
DIAGNOSIS
lancinating pains, and sensation in the neuropathy greater or may show mildly

paraesthesias in the distal extremities, gait than motor peripheral elevated protein and
extremities ataxia, reduced deep neuropathy mild pleocytosis
tendon reflexes, Argyll- »serum rapid »CSF VDRL: positive
Robertson pupils; plasma reagin (RPR) Can be used to
polyradiculopathy: test: positive confirm the diagnosis if
sensory, and loss and
weakness in the distal »serum Venereal serology is negative.
extremities Disease Research
Laboratory (VDRL)
test: positive
◊ Herpes zoster infection (shingles)
burning or stabbing erythaematous »none: clinical »PCR of lesions:

followed by a vesicular maculopapular diagnosis positive for varicella
rash in the affected rash, followed by zoster virus
dermatome the appearance
of clear vesicles,
Uncommon
◊ Herpes zoster infection (shingles)

in a dermatomal
distribution; corneal
ulceration may be
present if the trigeminal
nerve is affected
◊ Lyme disease
history of tick bite with distal sensory loss »serum »EMG and nerve
erythaema migrans; and motor weakness, enzyme-linked conduction
residence in or travel lymphadenopathy immunosorbent studies: may
to endemic area, assay (ELISA): show distal sensori-
painful paraesthesias in positive motor peripheral
upper more than lower May be difficult to neuropathy, multiple
extremities; possible confirm in late disease. mononeuropathies, or
associated arthritis, stiff radiculoneuropathy
neck and photophobia »lumbar puncture
(due to meningitis), with CSF
cranial neuropathies, examination: may
fatigue, fevers show elevated protein
or mild lymphocytosis;
positive Lyme antibody
titres
◊ Conversion and somatisation disorders
DIAGNOSIS
history of psychological normal »EMG and nerve

or physical trauma; conduction studies:
paraesthesias normal
associated with other
neurological and
psychiatric symptoms
◊ Inborn errors of metabolism
positive family history; sensory loss in the »clinical picture »MRI brain:
painful paraesthesias distal extremities, and screen for hyperintense confluent
in the extremities; other specific features appropriate inborn white matter lesions
associated sphincter depending on the error of metabolism: in both hemispheres
dysfunction, gait cause identification of in adult polyglucosan
abnormalities, underlying condition body disease
dementia, and other
59
Uncommon
◊ Inborn errors of metabolism

specific features »EMG and nerve »genetic testing:
depending on the conduction studies: identification of
cause sensory neuropathy; causative mutations
pattern depends on
underlying cause
Rheumatoid arthritis
acute onset of pain, joint deformities, loss of »EMG and nerve »cervical spine x-
then paraesthesias deep tendon reflexes, conduction ray: may show atlanto-
and weakness in the loss of sensation studies: multiple axial subluxation
distribution of single and weakness and mononeuropathies causing cervical spinal
or multiple peripheral muscle atrophy in with axonal features or cord compression
nerves (mononeuritis distribution of individual axonal sensori-motor »sural nerve biopsy:
multiplex); associated peripheral nerves or polyneuropathy vasculitis
arthralgias in distal extremities; »serum rheumatoid Vasculitis may be non-
joint deformities and factor: positive systemic or limited
tenderness to palpation
to peripheral nerve
only, in the setting of
rheumatoid arthritis.
Systemic lupus erythaematosus

DIAGNOSIS
arthralgias; joint tenderness to »EMG and nerve »anti-double-

photosensitive malar palpation and joint conduction studies: stranded DNA:
(butterfly), generalised, swelling in multiple distal sensori-motor elevated titres
or discoid rash; fatigue, joints; distal sensory peripheral neuropathy
weight loss, painful and motor deficits »antinuclear
sensory symptoms, on neurological antibody: elevated
or paraesthesias or examination; titres, >1:80
sensory loss lymphadenopathy;
alopecia, oral ulcers,
lymphadenopathy
fever, weight loss, palpable purpura, »EMG and nerve »biopsy of skin
fatigue, allergic rhinitis, loss of sensation or conduction studies: lesions: inflammation
asthma, cardiovascular weakness in distal axonal polyneuropathy
Uncommon

disease; numbness extremities or in or multiple with increased
or weakness in the individual nerve mononeuropathies eosinophils
distal extremities distributions »FBC with »sural nerve biopsy:
(polyneuropathy), differential: epineurial vasculitis in
or in individual eosinophilia, more than nerve with increased
nerve distributions 10% eosinophils and CD8
(mononeuritis multiplex) and CD4 lymphocytes
Granulomatosis with polyangiitis (formerly known as Wegener's

granulomatosis)
sinus disease; oral loss of sensation or »EMG and nerve »FBC with
or nasal ulcers; weakness in distribution conduction differential:
parenchymal nodules of individual peripheral studies: multiple normocytic anaemia;
in lung or upper nerves mononeuropathies with may have leukocytosis
respiratory tract; axonal loss and thrombocytosis
polyarthralgias; »antineutrophil »erythrocyte
myalgias; purpura; cytoplasmic sedimentation rate
acute onset of pain; antibodies: positive; (ESR): highly elevated
paraesthesias; motor sub-components PR3
weakness in distribution »CRP: highly elevated
or MP0 also positive
of individual peripheral »biopsy of affected
nerves (mononeuritis tissue: vasculitis of
multiplex) medium and large
vessels
DIAGNOSIS
Polyarteritis nodosa
pain, numbness, and loss of sensation and »EMG and nerve

paraesthesias, and muscle weakness in conduction
possibly weakness, in distribution of single studies: multiple
the distribution of single or multiple peripheral mononeuropathies with
or multiple peripheral nerves axonal features
nerves (mononeuritis »peripheral nerve
multiplex) biopsy: vasculitis
involving large-sized
more than medium-
sized blood vessels
61
Uncommon
Microscopic polyangiitis
acute onset of pain, loss of sensation and »EMG and nerve »ESR: normal or
numbness, and weakness in distribution conduction elevated
weakness in the of single or multiple studies: multiple »CRP: normal or
distribution of single peripheral nerves mononeuropathies in elevated
or multiple peripheral the extremities with
nerves (mononeuritis axonal features[25]
multiplex) »peripheral nerve
biopsy: perivascular
inflammation in
the epineurium or
endoneurium
Important to document
pathological features of
vasculitis.
◊ Sjogren's syndrome
dry eyes tonic pupils, severe »EMG and nerve »quantitative sweat
(xerophthalmia) and dry eye and dry conduction testing: patchy or
dry mouth (xerostomia), mouth, patchy sensory studies: patchy length-dependent post-
patchy burning pains, loss greater than sensory peripheral ganglionic sympathetic
paraesthesias that motor involvement; neuropathy greater sudomotor nerve fibre
may be migratory may have excessive than motor peripheral dysfunction
and involve cranial (hyperhidrosis) neuropathy is the »quantitative
DIAGNOSIS
nerve distributions, or decreased most common pattern; sensory testing:

autonomic symptoms (hypohidrosis or may also have elevated vibratory
such as orthostatic anhidrosis) sweating, ganglionopathy or and cooling detection
intolerance and orthostatic hypotension, sensory neuronopathy thresholds; may have
sweating abnormalities, or tachycardia with absence of lowered heat-pain
associated arthralgias, sensory nerve detection threshold
other rheumatological responses and normal and/or hypersensitivity
symptoms motor nerve conduction to heat-pain testing if
studies primarily small-fibre
»Schirmer's test: sensory neuropathy
severe dry eye »Rose-Bengal
»serum anti- staining of eye:
Sjögren's-syndrome- severe dry eye and
related antigen A reduced tear formation
(SSA) and Sjögren's »minor salivary
syndrome type B gland lip biopsy:
(SSB) antibodies perivascular or
positive: positive periductal mononuclear
cell infiltrates
Uncommon
◊ Sjogren's syndrome

A focus score is
assigned, which is
defined as the number
of foci containing ≥50
mononuclear cells
per high power field/4
mm². A score of ≥1 is
diagnostic.
◊ Sarcoidosis
pain, numbness, decreased or absent »EMG and nerve »sural nerve biopsy:
and weakness of the sensation in the distal conduction studies: multi-nucleated giant
extremities; history of extremities, possibly axonal sensori-motor cells; granuloma
shortness of breath or also in a dermatomal peripheral neuropathy; with inflammatory
pulmonary symptoms; pattern also in the pattern may be multiple perivascular
skin lesions; ocular trunk or extremities mononeuropathies, infiltrates and axonal
problems (radiculopathy); muscle polyneuropathy, loss; negative for
weakness in distal radiculopathy, or cranial tuberculosis
extremities; loss of or neuropathy »tissue biopsy:
diminished deep tendon granuloma
reflexes; may have
cranial neuropathies »MRI of total
spine: may show
DIAGNOSIS
enlargement and
abnormal enhancement
of spinal nerve roots if
radiculopathy is present
»chest x-ray: hilar
adenopathy or widening
of the mediastinum
»tuberculin skin
test with cutaneous
anergy panel:
negative
◊ Monoclonal protein production
cranial neuropathies, distal symmetric »EMG and nerve »serum amyloid free
distal paraesthesias, sensory loss and conduction studies: light chains: increase
and motor weakness; motor weakness, demyelinating sensori- in free light chain
may also have decreased sensation motor peripheral
63
Uncommon
◊ Monoclonal protein production

numbness and and weakness in neuropathy or multiple (kappa and lambda)
weakness in the distribution of mononeuropathies ratios in amyloidosis
the territories of multiple peripheral »serum protein »serum
multiple individual and/or cranial nerves, electrophoresis with cryoglobulins:
peripheral nerves; decrease or loss of immunofixation: positive in
cryoglobulinaemia: deep tendon reflexes, monoclonal or biclonal cryoglobulinaemia;
history of hepatitis C; purpuric skin lesions IgM protein spike pattern of monoclonal
episodic purpura in the protein determines type
lower extremities or »urine protein
trunk electrophoresis with »hepatitis C
immunofixation: antibodies: IgG
free light chain (Bence- or IgM titres may
Jones) proteins or be positive in
monoclonal proteins cryoglobulinaemia
»beta-2-
microglobulin:
increased in
Waldenstrom's
macroglobulinaemia
»sural nerve biopsy:
demyelination with
IgM deposits and
myelin lamellae
in Waldenstrom's
macroglobulinaemia;
amyloid deposits
surrounding
endoneurial blood
vessels in patients
DIAGNOSIS
with amyloidosis;
cryoglobulinaemia
may produce vasculitis
affecting small-
calibre blood vessels
in epineurium or
endoneurium
Partial epilepsy
stereotyped pattern and normal; may be »electroencephalogram»MRI brain, with and

distribution of sensory abnormal, with focal (EEG): interictal without contrast
symptoms evolving findings, if seizures are epileptiform discharges administration:
over a few seconds; due to intracranial mass over the contralateral may show evidence of
automatisms or altered lesion parietal lobe cortical-based lesion or
level of consciousness scar, such as tumour or
or responsiveness stroke
indicates complex
Uncommon
Partial epilepsy

partial seizure with
focal onset involving
somatosensory cortex
◊ Paraneoplastic sensory neuropathy or ganglionopathy
ataxia, paraesthesias, severe sensory loss, »serum anti-Hu and »mammogram:

and sensory loss; ataxia; may have anti CV-2 antibodies: identification of breast
history of cancer or cerebellar signs, loss of negative or positive cancer lesion
cancer risk factors, deep tendon reflexes, »EMG and nerve »CT scan of chest/
weight loss, or specific or pseudoathetosis; conduction studies: abdomen/pelvis:
symptoms of underlying specific signs of ganglionopathy identification of
cancer underlying cancer produces absence of underlying malignancy
sensory nerve action If negative with initial
potential responses screening, should
diffusely; sensory
neuropathy produces repeat every 3 to 6
reduced sensory nerve months for surveillance
amplitudes for at least the first 2
years after diagnosis.
»whole-body PET
scan: identification of
underlying malignancy
Should be done
DIAGNOSIS
annually if other
screening tests for
cancer are negative.
paraesthesias, muscle sensory and motor »MRI brain: ischaemic »brain biopsy:
weakness, speech neuropathies, foci histopathological
difficulties (production hemiparesis, Neuroimaging only evidence of lymphoma
and understanding), meningoradiculitis, detects cerebrospinal Diagnosis of
seizures, transient dysarthria, aphasia, intravascular
visual loss, vertigo, impaired cognitive fluid involvement in
and impaired cognitive function[24] half of patients with lymphoma requires
function[24] neurological symptoms histopathological
because there are confirmation. Biopsy
no pathognomonic is indicated in patients
neuroradiological with progressive
65
Uncommon

signs in intravascular neurological
lymphoma. As deterioration and
ischaemic foci are unclear abnormalities
the most common on MRI of the brain.[24]
finding, vasculitis
is a differential
diagnosis.[24]
Neuro-Behcet's disease
rarely presents with weakness and sensory »MRI spinal

paraesthesias and deficits in extremities cord: inflammatory
weakness in the lesions[37]
extremities;[37] »MRI brain with
cerebrospinal fluid magnetic resonance
involvement leads to angiography: findings
variable symptoms can be similar to those
including headaches, in multiple sclerosis,
mental status changes, or distinct white matter
hemiparesis, dizziness, changes commonly
loss of balance, or involving mid-brain
coma
◊ Wartenberg's migrant sensory neuritis

DIAGNOSIS
sudden-onset painful sensory deficits in »none: clinical »nerve conduction

paraesthesias in distribution of affected diagnosis studies: sensory
distribution of one or nerve; normal motor There are no nerve action potential
multiple cutaneous or function[39] conclusive diagnostic (SNAP) amplitude
sensory nerves (most low in affected nerve
commonly peripheral tests for Wartenberg's or <50% of that on
limb nerves, but also migrant sensory unaffected side; motor
trigeminal nerve and neuritis.[39] nerve conduction
truncal branches), studies normal[39]
either sequentially »nerve biopsy:
or simultaneously; variable and non-
paraesthesia can be specific changes
preceded by painful ranging from perineural
sensations (stabbing, inflammatory changes,
burning, tingling) in the changes more
same area; stretching suggestive of non-
of affected nerve systemic vasculitic
(e.g., by kneeling)
Uncommon
◊ Wartenberg's migrant sensory neuritis

may precipitate neuropathy, to axonal
symptoms[38] [39] degeneration as seen
in ischaemic neuronal
lesions[38] [39]
As Wartenberg's
migrant sensory
neuritis has a mild
and often remitting
course, and due
to the associated
risks of nerve biopsy
without significant
therapeutic benefit, in
patients with a clinical
history, a neurological
examination, and
electrophysiological
findings consistent with
the condition, a nerve
biopsy can reasonably
be omitted from the
diagnostic work-up.[39]
Numb chin syndrome
DIAGNOSIS
unilateral paraesthesias unilateral sensory »MRI of brain and »lumbar puncture

or anaesthesia of deficit on chin total spine: multiple with CSF
chin; possible history sclerosis shows examination and
of dental or oral hyperintensities in culture: multiple
surgery; may be the periventricular sclerosis shows
initial manifestation of white matter; most unique oligoclonal
multiple sclerosis or sensitive images are bands; increased
occult malignancy[11] sagittal fluid-attenuated IgG index; increased
[53] inversion recovery, and myelin basic protein;
demyelinating lesions mild lymphocytic
in the spinal cord, pleocytosis; testing for
particularly the cervical infectious agents is
spinal cord negative
»mammogram: »whole-body PET
identification of breast scan: identification of
cancer lesion underlying malignancy
»CT scan of chest/
abdomen/pelvis:
67
Uncommon
Numb chin syndrome

identification of Should be done
underlying malignancy annually if other
If negative with initial
screening tests for
screening, should
cancer are negative.
repeat every 3 to 6
months for surveillance
for at least the first 2
years after diagnosis.
◊ Peripheral neuropathy after bariatric surgery
history of bariatric loss or reduction of »EMG and nerve »serum vitamin B12:
surgery within sensation (light touch, conduction studies: CSFmay show B12
prior 12-24 month pinprick, temperature, reduced or absent deficiency
period, especially vibratory, joint position sensory nerve »serum folate: may
in association with sensations) in distal action potential and show folate deficiency
rapid loss of a large lower more than compound muscle
amount of body weight; upper extremities, in action potential »serum thiamine:
symmetric sensory a symmetric pattern; amplitudes in the may show thiamine
symptoms of asleep- or some muscle weakness lower extremities, deficiency
dead-type numbness possible in the distal with upper extremity »serum vitamin
and paraesthesias in lower extremities, nerves affected B6: may show B6
the hands and feet, including foot drop; as polyneuropathy deficiency
occasionally with some reduced or absent progresses proximally
»cerebrospinal fluid
DIAGNOSIS
muscle weakness in deep tendon reflexes in the limbs; findings

these same regions; in the lower more than are symmetric in examination: with
insidious more often the upper extremities, distribution; less likely increased protein but
than acute or sub-acute also symmetric in prolongation of distal normal WBC counts
onset of symptoms; distribution; may have latencies or slowing of »ESR: may be elevated
aching, sharp, or sensory ataxia and conduction velocities,
»quantitative
burning pains in hands positive Romberg but if present, also in
sensory testing:
and feet sign if sensory loss is a distal pattern; may
may show elevated
severe and involving be normal if only small
vibratory, cooling,
the large myelinated diameter sensory nerve
and heat detection
nerve fibres (dorsal fibres involved clinically
thresholds; heat
column pathway); may
detection threshold may
have small diameter,
be reduced in patients
unmyelinated sensory
with small fibre sensory
nerve fibre impairment
neuropathy who have
only, in which case
allodynia
the neurological exam
may be normal or have »autonomic
abnormal findings only reflex function
in terms of reduced testing (especially
or absent pinprick quantitative sweat
and/or temperature testing): may show
Uncommon
◊ Peripheral neuropathy after bariatric surgery

sensation in a distal distal loss or reduction
pattern involving the of sweat output, if small
hands and feet diameter, unmyelinated
nerve fibres are
affected
»thermoregulatory
sweat testing: may be
abnormal in the distal
extremities, showing
reduced sweating
»peripheral
cutaneous nerve
biopsy: may show
active or chronic
axonal degeneration;
pathological evidence
of an immune process
with perivascular
inflammatory
mononuclear cell
deposits
◊ Notalgia paraesthetica
itching or pruritus in a skin changes resulting »none: clinical »spinal MRI:
DIAGNOSIS
unilateral, dermatomal from persistent diagnosis consider if additional
(T2-T6) distribution scratching of the neurological symptoms
in the upper back, affected area; may are present or current
below the scapula; may have decreased (or symptoms are
also be accompanied increased) light touch, progressive
by localised pain, temperature or pinprick »skin biopsy:
tingling numbness, or sensation in the may show focal
increased sensitivity in affected dermatomes inflammatory changes
the same area[63] posteriorly in affected skin[63]
◊ Neuromyelitis optica spectrum disorder (Devic's disease)
acute often bilateral afferent pupillary »MRI of brain »serum AQP4

visual loss and eye defect, visual field loss and spinal antibodies (NMO-
pain (worse with and hyperaemia and cord: classically IgG): positive
movements of eye); swelling of the optic show gadolinium Has 91% sensitivity and
may be nausea, disc; sensory level, enhancement and 100% specificity.
vomiting and hiccups weakness in myotomal oedema of the optic
and/or leg and arm distributions, initial nerves, and a central
69
Uncommon
◊ Neuromyelitis optica spectrum disorder (Devic's disease)

weakness, bowel and reduction in reflexes cord lesion extending »Lumbar puncture
bladder dysfunction and (due to spinal shock) over three or more with cerebrospinal
sensory loss; typically then hyperreflexia segments acutely; later fluid examination:
follows a relapsing stages have atrophy often shows a
pattern over weeks or and cavitation pleocytosis and
months elevated protein levels
◊ Anti-myelin-associated glycoproteins (MAG) peripheral

neuropathy
distal acquired sensory loss in hands »EMG and nerve »serum protein
demyelinating, and feet especially conduction studies: electrophoresis with
symmetric neuropathy to vibration; ataxic demyelinating immunofixation: may
(DADS) with numbness gait and tremor in sensorimotor peripheral show a monoclonal
and tingling in hands hands; reflexes usually neuropathy with spike
and feet with difficulty reduced or absent prolonged distal »serum IgM
walking due to poor latencies and slowed antibodies to MAG:
balance; muscle conduction velocities; positive
weakness in legs relative preservation of
and hands, often amplitudes
with involuntary hand »lumbar puncture
‘shaking’ (tremor); most with cerebrospinal
patients are male fluid examination:
elevated protein
with normal cells
DIAGNOSIS
and glucose
albuminocytological
dissociation (elevated
cerebrospinal fluid
protein with normal
WBC and red blood cell
counts)
◊ Hypertriglyceridaemia
chronic pain, decreased pin »electrodiagnostic »serum lipid profile:

numbness, tingling in sensation in feet with studies: may be high triglyceride levels
feet normal vibration and normal or show mild
normal strength; absent decrease in sensory
ankle reflexes amplitudes distally
Uncommon
◊ Human T-lymphotropic virus (HTLV)
weakness, stiffness, hyperreflexia with »MRI of spine: normal »ELISA assay:

and numbness in legs clonus and spasticity in To rule out other positive
associated with urinary the legs; numbness and causes of spinal cord A positive result should
incontinence and often weakness in legs be confirmed with a
severe back pain compression.
Western blot.
»Western blot:
positive
Confirmatory test if
ELISA is positive.
Types HTLV as I or II.
DIAGNOSIS
71
Assessment of paraesthesias Guidelines
Guidelines
North America
Quality improvement in neurology: distal symmetric polyneuropathy quality

measures (ht tps://www.aan.com/policy-and-guidelines/quality/quality-
measures2/quality-measures/other/)
Published by: American Academy of Neurology

Last published: 2014
Practice parameter: evaluation of distal symmetric polyneuropathy - role

of laboratory and genetic testing (ht tps://www.aan.com/Guidelines/home/
ByTopic?topicId=19)
GUIDELINES
Published by: American Academy of Neurology; American Association of Neuromuscular and

Electrodiagnostic Medicine; American Academy of Physical Medicine and Rehabilitation
Practice parameter: evaluation of distal symmetric polyneuropathy - role

of autonomic testing, nerve biopsy, and skin biopsy (ht tps://www.aan.com/
Guidelines/home/ByTopic?topicId=19)
Published by: American Academy of Neurology; American Association of Neuromuscular and

Electrodiagnostic Medicine; American Academy of Physical Medicine and Rehabilitation
Assessment of paraesthesias References
Key articles
• England JD, Gronseth GS, Franklin G, et al. Evaluation of distal symmetric polyneuropathy: the role
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of laboratory and genetic testing (an evidence-based review). Muscle Nerve. 2009 Jan;39(1):116-25.
Abstract
• England JD, Gronseth GS, Franklin G, et al. Evaluation of distal symmetric polyneuropathy: the role
of autonomic testing, nerve biopsy, and skin biopsy (an evidence-based review). Muscle Nerve. 2009
Jan;39(1):106-15. Abstract
• Kumar N. Nutritional neuropathies. Neurol Clin. 2007 Feb;25(1):209-55. Abstract
• Windebank AJ. Metal neuropathy. In: Dyck PJ, Thomas PK, eds. Peripheral neuropathy. 3rd ed. St.
Louis, MO: Elsevier Saunders; 2005:2527-51.
• Masi AT, Hunder GG, Lie JT, et al. The American College of Rheumatology 1990 criteria for the
classification of Churg-Strauss syndrome (allergic granulomatosis and angiitis). Arthritis Rheum. 1990
Aug;33(8):1094-100. Abstract
• Dyck PJ. The clinical heterogeneity of immune sensory and autonomic neuropathies with (or
without) sicca. Brain. 2005 Nov;128(Pt 11):2480-2. Full text (http://brain.oxfordjournals.org/cgi/
reprint/128/11/2480) Abstract
• Sonneville R, Klein I, de Broucker T, et al. Post-infectious encephalitis in adults: diagnosis and

management. J Infect. 2009 May;58(5):321-8. Abstract
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79
Assessment of paraesthesias Images
Images
IMAGES
Figure 1: Differential diagnoses of paraesthesias based on the chronicity of symptom onset

IMAGES
Figure 2: Peripheral nervous system causes of paraesthesias according to the pattern and level of the lesion
81
IMAGES Assessment of paraesthesias Images
Figure 3: Central nervous system and non-neurological causes of paraesthesias according to the pattern and
level of the lesion
IMAGES
Figure 4: Nerve conduction testing of the lower leg
Created by the BMJ Group
83
Figure 5: A single level of spinal cord compression with T2 changes, on cervical sagittal T2 sequence in the
presence of symptomatic cervical spondylotic myelopathy (CSM)
From the collection of Professor Dennis Turner, Duke University Medical Center; used with permission
Figure 6: Axial T2-weighted MRI with broad-based lumbar disc herniation predominantly towards the right
side
From the collection of Alexios G. Carayannopoulos, Lahey Clinic; used with permission
IMAGES
85
Figure 7: Sagittal T2-weighted MRI showing MS-related myelitis lesion

From the collection of Dean M. Wingerchuk, Mayo Clinic; used with permission
Figure 8: Sagittal FLAIR images with typical MS lesions
IMAGES
From the collection of Lael A. Stone, Cleveland Clinic Foundation; used with permission
87
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Contributors:
// Authors:
Nigel Ashworth, MBChB, MSc, FRCP(Can)

Professor
Division of Physical Medicine & Rehabilitation, Faculty of Medicine & Dentistry, University of Alberta,
Edmonton, Canada
DISCLOSURES: NA declares that he has no competing interests.
// Acknowledgements:
We would like to gratefully acknowledge the late Dr Caroline M. Klein for her contribution to this topic. CMK
authored a number of references cited in this topic.
// Peer Reviewers:
Annabel Wang, MD
Director
Neuromuscular Diagnostic Laboratory, Associate Professor, Department of Neurology, ALS and
Neuromuscular Center, University of California, Irvine, CA
DISCLOSURES: AW declares that she has no competing interests.
Richard W. Orrell, BSc, MD, FRCP

Senior Lecturer and Consultant Neurologist
Department of Clinical Neuroscience, UCL Institute of Neurology, London, UK
DISCLOSURES: RWO declares that he has no competing interests.

Assessment of Paraesthesias

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Assessment of Paraesthesias

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Assessment of

Straight to the point of care

Last updated: Nov 01, 2018

The somatosensory pathway

Nerve compression or injury

• Median neuropathy at the wrist (carpal tunnel syndrome)

Nerve demyelination and/or axonal degeneration

• The most commonly encountered variant of Guillain-Barré syndrome. A demyelinating polyneuropathy

• An acquired, demyelinating, peripheral neuropathy of presumed autoimmune aetiology. The course is

• A length-dependent or distally predominant peripheral neuropathy, which is symmetric in distribution,

Endocrine or metabolic disease

• Vitamin B12 is critical in the production of S-adenosylmethionine, which is thought to be important

Vitamin B6 deficiency or excess[15]

• Thiamine is an important co-factor in carbohydrate metabolism. Deficiency produces symptoms

• Vitamin E is an important lipid-soluble antioxidant nutrient. Deficiency produces nerve damage.

Drug or toxin exposure

panic symptoms and hyperventilation. An extremely common cause of paraesthesias.

Vasculitic or inflammatory disease

• Vasculitis associated with connective-tissue diseases such as systemic lupus erythematosus

Guillain-Barré syndrome, acute inflammatory demyelinating

Spinal cord compression

Acute disseminated encephalomyelitis

Characteristics of the paraesthesias

Differential diagnoses of paraesthesias based on the chronicity of symptom onset

• The location of the symptoms indicates the level of the lesion.

General medical history

• A history of malnutrition or adherence to a specialised diet, such as a low-protein, vegetarian, or vegan

• A history of smoking should raise suspicion of a paraneoplastic syndrome. A history of occupational,

• May reveal diabetic retinopathy in a diabetic patient.

• Sensory loss in the distribution of a single peripheral nerve indicates a peripheral

Peripheral nerve involvement

Metabolic or endocrine tests

Nerve conduction testing of the lower leg

• May be considered based on the associated symptoms and EMG findings.

A single level of spinal cord compression with T2 changes, on cervical sagittal T2

Spinal cord involvement

Sagittal T2-weighted MRI showing MS-related myelitis lesion

Brainstem or brain involvement

Sagittal FLAIR images with typical MS lesions

Carpal tunnel syndrome

Ulnar neuropathy at elbow (UNE)

Fibular (peroneal) neuropathy

Spinal cord compression

Distal symmetric polyneuropathy (DSP)

Vitamin B6 deficiency or excess

Vitamin B12 deficiency

Stroke/transient ischaemic attack

Migraine with aura

Peripheral vascular disease

Panic attack with hyperventilation

Hereditary sensory and autonomic neuropathy (HSAN)

Hereditary neuropathy with liability to pressure palsy (HNPP)

Acute demyelinating encephalomyelitis

Acute inflammatory demyelinating polyneuropathy (AIDP)

Chronic inflammatory demyelinating polyneuropathy (CIDP)

Chronic inflammatory demyelinating sensory polyradiculopathy (CISP)

Heavy metal poisoning

Ciguatera or saxitoxin poisoning

Herpes simplex infection

Herpes zoster infection (shingles)

Conversion and somatisation disorders

Inborn errors of metabolism

Systemic lupus erythaematosus