Polyneuropathy

for internist
Monton Wongwandee, MD
Division of Neurology
Department of Medicine
Srinakharinwirot University
 Classification of Neuropathy
• Clinical distribution
1. Mononeuropathy
2. Polyneuropathy
• Symmetrical polyneuropathy
• Asymmetrical polyneuropathy/ multifocal neuropathy /
multiple mononeuropathy/ mononeuritis multiplex
 Mononeuropathy
• Compression
• Injury
• Ischemia
 Multiple mononeuropathy
• Vasculitis
• Leprosy
• Lymphoma
• Demyelination
 Classification of Neuropathy
• Pathology
– Axonal neuropathy
– Demyelinating neuropathy
 Peripheral nervous system
Ia

Aα

Large myelinated fiber   Aα
Small myelinated fiber    Peripheral nerve
Aδ,B
Unmyelinated fiber       C
 Clinical manifestations
• Motor
• Sensory
• Autonomic
• Etc.
– Abnormal movement & balance
– Musculoskeletal
 Clinical manifestations
• Autonomic dysfunction
– Cardiovascular system: orthostatic hypotension
– GI: diarrhea, constipation
– GU: urinary retention/ incontinence, erectile dysfunction
– Sudomotor: anhydrosis
– Secretomotor: dry eye, dry mouth
– Pupil abnormality: anisocoria
 Clinical characteristics of
symmetrical polyneuropathy
• “Glove & stocking” pattern sensory loss
• Symmetrical distal or proximal weakness
• Hyporeflexia or areflexia
 Axonopathy VS Demyelination

Axonopathy Demyelination
Length dependence Non-length dependence
Sensory loss
Pain & Temperature Proprioception
Weakness Distal Proximal or distal
 Symmetrical axonal polyneuropathy
• Acute (days-weeks)
– Toxic: As
– Axonal GBS
– Porphyria
• Subacute (weeks to months)
– Endocrine: DM, hypothyroid •Chronic (months to years)
– Toxic: chemotherapy, drug, alcoholic •Hereditary: HMSN II, HSAN
•DM
– Nutritional deficiency: B1, B12
•Paraproteinemia
– Infection: HIV
– Paraneoplastic: SCLC, thymoma
– Paraproteinemia
– Systemic disease: uremia, critical illness
neuropathy
– Idiopathic
 Symmetrical demyelinating polyneuropathy
• Acute (<1 mo)
– GBS (AIDP)
– Diphtheria
• Subacute (1-2 mo) Immune 
– SIDP process
• Chronic (>2 mo)
– CIDP
– Paraproteinemia
– Hereditary: HMSN I
Approach to polyneuropathy
 Approach
1. Diagnosis of polyneuropathy
2. Clinical assessment
3. Investigation
 Clinical assessment
• Symmetrical / asymmetrical
• Axonal / demyelination
• Acute / subacute / chronic
• Motor / sensory / autonomic predominate
• Clinical clues
• Others: systemic disease, multiorgan involve, FH, drug,
toxic history
 Painful small fiber polyneuropathy
• DM
• Amyloidosis
• HIV
• Toxic: ARV, thallium
• Sjogren’s syndrome
• HSAN
• Idiopathic
 Painless sensory polyneuropathy
associated feet injury
• DM
• Amyloidosis
• HSN
 Motor predominate polyneuropathy
• Immune mediated
– GBS, CIDP
• Porphyric neuropathy
• Lead intoxication
• Hereditary: HMSN
Autonomic predominate polyneuropathy
• DM
• Amyloidosis
• GBS
• Porphyria
• Sjogren’s syndrome
• Toxic: vincristine
• HSAN
 Clinical clues
Clinical Cause
Gum lead line Lead neuropathy
Mee’s line, Skin hyperkeratosis Arsenic neuropathy
Palpable purpura Vasculitic neuropathy
Skin bruise, shoulder fat pad sign, Amyloidosis
organomegaly
Charcot’s joint DM, Leprosy
Palpable thick nerves Leprosy, CIDP
Abdominal pain, psychiatric symptom Porphyric neuropathy
Anemia B12 def, Lead
Lead or Burton’s lines
 Mee’s or Beau’s lines

The Lancet 2008 372, DOI: (10.1016/S0140-6736(08)61587-1)

Copyright © 2008 Elsevier Ltd Terms and Conditions
 Pinch purpura

http://www.clevelandclinicmeded.com/medicalpubs/diseasemanagement/dermatology/dermatologic-signs-of-systemic-disease/
 Investigation
• Neurophysiology
– NCS, EMG
– QST (quantitative sensory testing)
– SSR (sympathetic skin response)
• Blood, urine
• CSF
• Imaging
• Pathology (nerve, skin)
• Genetic
 Blood test
Basic
• CBC, ESR
• FBS, BUN, Cr, e’lyte, LFT
• TFT
• (B1, B12)
Special
• HIV, HBV/HCV, VDRL
• Serum protein electrophoresis, immunofixation
• Immunology: ANA, RF, ANCA, anti-SSA/SSB, cryoglobulin
• Paraneoplastic: anti-Hu
• Urine porphyrin
• Toxic screening: As, Pb
 Imaging
• CXR
• Bone survey
• Nerve root enhancement: CIDP
 Pathology (biopsy)
• Nerve biopsy
– Vasculitis
– Amyloidosis
– Tumor infiltration
– Sarcoidosis
– HMSN I,III
– CIDP
– Anti-MAG neuropathy
Polyneuropathy example
 Drug induced polyneuropathy
• Axonal polyneuropathy
• Drug
– Antibiotics: INH, ethambutol, metronidazole, linezolid, dapsone
– Chemotherapy: platinum, taxane, vincristine, bortezomib, etoposide
– ARV: ddC, ddI, d4T
– Amiodarone, hydralazine
– Colchicine, chloroquine, hydroxychloroquine
– Dapsone (motor predominate)
– Phenytoin
– Statin
– Etc.
 Thiamine deficiency
• Acute to subacute sensory or sensori-motor polyneuropathy
• Distal > proximal weakness
• Large & small fiber sensory loss
• Extraocular paresis
• Wet beri-beri, Wernicke’s encephalopathy
• Risk
– Alcoholism
– Severe malnutrition
– Postbariatic surgery with severe vomitting
– Worker in stressful environment
• Dx: ETKA with TPP effect
• Rx
– Acute: thiamine 100mg iv before glucose then 100mg im 3-5 days
– Chronic: thiamine: 50mg im for 2 weeks then 50mg/d oral
• Response: extraocular paresis- early, dementia, neuropathy – less well
 Cobalamin deficiency
• Subacute combined degeneration
– Severe proprioceptive dysfunction (posterior column)
– Spasticity of legs (corticospinal tract)
• Symmetrical sensory polyneuropathy
• Dementia
• Megaloblastic anemia
• Risk
– Gastrectomy
– Pernicious anemia
– Strict vegetarian
– Corrosive agent ingestion
• Dx: blood B12 level
• Rx: B12 iv 1000mg/wk…3mo then q 3mo
 GBS
• Demyelination
– AIDP (acute inflammatory demyelinating polyneuropathy)
– MFS (Miller Fisher syndrome)
– Acute oropharyngeal neuropathy
• Axonal
– AMAN (acute motor axonal neuropathy)
– AMSAN (acute motor sensory axonal neuropathy)
AIDP
 Clinical manifestations
• Acute symmetrical weakness (proximal > distal)
• Ascending paralysis (legs > arms)
• Tingling sensation with little sensory loss
• Pain: denervated muscle, back
• Areflexia
• Facial diparesis 50%
• Dysphagia
• Respiratory failure 30%
• Autonomic failure: rare
 Facial diplegia
• GBS (AIDP)
• HIV
• Porphyria
• Tumor infiltration
• Lyme disease
• Sarcoidosis
• Others: FSHD, myotonic dystrophy, MG
 Antecedent infection
• 75% of GBS
• 1-3 weeks before clinical onset
• Organism
– C. jejuni
– M. pneumoniae
– CMV, EBV
– Influenza
• Vaccination: influenza, rabies
 CSF
• Albuminocytologic dissociation
• High protein
• No pleocytosis (WBC < 10/mm3)
– Pleocytosis ddx: HIV infection
• Normal CSF 1/3 in 1st week
 Treatment
• Disease modifying treatment
• Supportive care
 Disease modifying treatment (AAN)
• Plasma exchange or IVIG hastens recovery
• IVIG = PE
• Combining the two treatments is not beneficial
• Steroid treatment alone is not beneficial
• Indication
– Nonambulation
– Onset < 4 weeks
 Prognosis
• Recovery initiates at 4th week after onset (70%)
• Disease modifying rx can shorten the recovery time
about 50%.
– One grade muscle power improvement at 20 days
– Walking unaided at 50 days
 CIDP
• Variations in clinical & distribution
• Typical CIDP
– Chronic progressive or relapsing symmetrical distal & proximal motor
dysfunction with sensory involvement
– Large > small sensory fiber involvement
– Hyporeflexia or areflexia
– High CSF protein without pleocytosis (WBC < 10/mm3)
– Electrodiagnostic criteria
– Rx: steroid = IVIG = PE
 Disease associated CIDP
• Paraproteinemia: MM, amyloidosis
• Endocrine
– DM, thyrotoxicosis
• Infection
– HIV, HBV, HCV
• Autimmune disease
– SLE, IBD
• Nephrotic syndrome
• Organ transplantation