Peripheral Lesions

Myasthenia Gravis (MG)

 Nomenclature:
o Myasthenia – `Muscle weakness`
o Gravis – `Grave`
o Therefore, translates as `grave muscle weakness`
 Localisation:
o Nicotinic ACH receptors on post-synaptic membranes of skeletal muscle at
the neuromuscular junction
 Pathology:
o Progressive type II hypersensitivity autoimmune disease which causes
progressive skeletal muscle weakness and extraocular muscle weakness
leading to ptosis (dropping of eyelid) and diplopia (double vision)
o B cells inappropriately produce autoantibodies, known as anti-acetylcholine
receptor (AChR) antibodies that bind to nicotinic Ach receptors on post-
synaptic membranes of skeletal muscle at the neuromuscular junction, these
autoantibodies can also activate the classical complement pathway which
leads to inflammation and destruction of muscle cells.
 A minority portion of people affected by MG produce anti-muscle-
specific tyrosine kinase (MuSK) antibodies which attack proteins
inside the muscle cells, and similarly lead to the destruction of healthy
muscle cells.
o Therefore, Ach cannot bind, and calcium channels cannot open to cause
depolarisation of the post-synaptic membranes of skeletal muscle at the
neuromuscular junction and thus, these post-synaptic membranes do not
respond to “contract” signals from the CNS.
 Epidemiology & Aetiology:
o Generally unknown aetiology
o Associated in some cases with paraneoplastic syndromes caused by
thymoma, thymic carcinoma, as well as bronchogenic carcinoma which
induce immune responses which ultimately form autoantibodies.
o Has a bimodal distribution:
1) Commonly seen in young women 20 to 30s
2) Also commonly seen in older men 60s to 70s
 Symptoms:
o Weakness tends to spread from the ocular  facial  bulbar muscles (head
and neck)  truncal and limb muscles, typically more severe proximally
than distally and is typically asymmetrically distributed (one side > other)
o Observed pathology of extraocular muscles diplopia (double vision) and
ptosis (drooping of eyelid)
 Eye muscle weakness is often asymmetrical and variable
  Ptosis occurs initially in 50% of patients and occurs during the course
of illness in 90% of patients.
o Normally fine in the morning, but progressively skeletal muscles become
weaker and patient may feel fatigued at the end of the day, especially after
repetitive movements.
 Complications:
o MYASTHENIA CRISIS
 Life threatening manifestation of MG (unfavourable outcome) and is
medical emergency whereby admission to ICU, intubation and
ventilation are required with IV prednisone, IVIg & plasmapheresis.
 Typically characterised as extreme muscle weakness particularly of the
diaphragm and chest muscles, which causes breathing to become
shallow or ineffective and can result in respiratory failure This is an
emergency situation. Use of ventilators is required.
 Myasthenic crisis (respiratory failure) presents in about 15% to 20% of
patients with MG.
 Differential Diagnosis:
o Lambert-Eaton
o Botulism
o Guillain-Barre
 Ascending type of Landry’s paralysis (flaccid paralysis of respiratory
muscles and bulbar group of muscles of CN9, CN10, CN12)
o Multiple sclerosis
 Diagnostic Test:
o Serology (blood tests) – To look for autoantibodies titers for anti-AChR &
Anti-MuSK
o Electromyogram (EMG) – Measures the electrical activity of a muscle
o Nerve conduction studies (NCS) – rule out neurogenic causes
o Contrast-enhanced computed tomography (CT) > MRI of chest
 Check for thymoma/bronchogenic carcinoma
o Special tests:
1) Tensilon test – Improvement of weakness upon administration of
short-acting acetylcholinesterase inhibitor (edrophonium chloride)
2) The Ice Test in Myasthenia Gravis – ice pack is applied to the ptotic lid
for 2 minutes, and ptosis is measured with a ruler before and after
cooling; a rise of 2 mm is a positive result
 Prognosis:
o Tend to have average life expectancy with medical care and supervision.
o No cure of idiopathic form and thus is requires life-long medical treatment
and observation.
 Treatment: MACP IT
o Monoclonal antibody (eculizumab) – if positive for the antiacetylcholine
receptor (AchR) autoantibody
 o Anticholinesterase medicines – prolong Ach duration in synaptic cleft and
increase its concentration.
 Neostigmine
 Pyridostigmine
 Edrophonium
 Glycopyrrolate
o Immunosuppressants
 Azathioprine, mycophenolate mofetil & tacrolimus
 Corticosteroids – prednisone which reduces production of antibodies.
o Plasmapheresis – Removes abnormal antibodies from blood
o IV Immunoglobulin therapy (IVIg) – 1-2g/kg for 2-5 days
 If symptoms of myasthenia gravis are severe
o Thymectomy (removal of the thymus) or removal of bronchogenic neoplasm:
 The thymus produces Th-cells which assist B-cells in the formation of
autoantibodies and its removal often decreases the symptoms of MG,
this is even true when the patient does not have thymoma, in this
case its often removed to prevent progression and metastasis and
hopefully improve symptoms of MG or cure them all together.

Lambert-Eaton Myasthenic Syndrome (LEMS)

 Nomenclature:
 Lambert – refers to `Edward Lambert` 1 of 2 doctors who first described LEMS
 Eaton – refers to `Lealdes Eaton` 1 of 2 doctors who first described LEMS
 Myasthenic – refers to `Muscle Weakness`
 Localisation:
 Voltage gated Ca2+ channels on the pre-synaptic membrane of motor
neurons at the neuromuscular junction
 Pathology:
 Rare type II hypersensitivity autoimmune disease that attacks the voltage
gated Ca2+ channels on the presynaptic membrane of motor neurons at the
neuromuscular junction within the peripheral nervous system (PNS).
 Body produces B cells which produce P/Q type voltage gated calcium channel
(P/Q-type VGCC) autoantibodies (85% of cases, non-malignancy) or N-type
VGCC autoantibodies that are related to malignancy-associated LEMS
  These autoantibodies recognise and block voltage gated Ca2+ channels on
presynaptic membranes of motor neurons at the neuromuscular junction.
 This means inadequate Ca2+ influx occurs in the presynaptic membrane and
thus vesicles within the presynaptic membrane release insufficient Ach is
into synaptic cleft of the neuromuscular junction and thus no contraction or
weakness of muscle contraction as well as areflexia or hyporeflexia.
 Epidemiology:
 Commonly seen in those with small cell lung cancer (SCLC) due to
paraneoplastic syndrome.
 This is because small cell lung cancer cells express the same calcium
channels are found on presynaptic membranes of motor neurons at
the neuromuscular junction.
 Non-paraneoplastic syndrome causes are associated with autoimmune
diseases such as graves’ disease, Hashimoto’s thyroiditis & type 1 diabetes
mellitus.
 Symptoms:
 Symmetrical weakness of proximal muscles and fatigue
 Typically hips and thighs  shoulders  arms and legs  hands and
feet  Cranial nerves supplying head and neck are last to be affected.
 Lower limbs > upper limbs
 Upper arms and thighs may be painful
 Post-tetanic potentiation – normalized tendon reflex after strong muscular
contraction, due to increase in neurotransmitter after a brief, high-frequency
train of action potentials
 Post-exercise facilitation – muscle weakness Improved temporarily after
repeated use/movements of muscle
 Autonomic disturbances – dry mouth, sluggish pupillary responses, erectile
dysfunction, bladder and bowel changes
 Signs:
 Areflexia or Hyporeflexia
 Ptosis
 Associations:
1. Other autoimmune disorders such as graves’ disease, Hashimoto’s
thyroiditis & type 1 diabetes mellitus.
2. Small cell lung cancer (SCLC)
 The Voltage-gated Ca channel in lung cancer resemble Ca channels
on the presynaptic membrane, so while producing antibodies
against lung cancer Ca channel. Those will attack also the
neuromuscular junction channel.
 Differential Diagnosis:
 Myasthenia gravis
 Guillain-Barre Syndrome (GBS)
 Botulism
 Multiple Sclerosis
 Diagnostic Tests:
 Nerve conduction studies (NCS) with electromyogram (EMG)
 ↓ Amplitude initially with ↑ Amplitude with repetitive stimulation
(movement or electrical stimulation)
 Antibody titers – check for P/Q-type VGCC or N-type VGCC autoantibodies
 CT Chest – detect lung cancer
 Prognosis:
 Prognosis is more favourable than myasthenia gravis.
 If lung cancer progresses, outcome is less favourable.
 Treatment:
 Treatment of underlying cancer
 Acetylcholinesterase inhibitors – e.g., pyridostigmine for moderate
symptomology
o 30 to 120 mg every 3 to 6 hours
 Amifampridine (K+ blocker) for moderate symptomology
 Guanidine hydrochloride
o Initially 125mg and then increased to 35mg/kg
 Refractory/severe symptomology or weakness – Plasmapheresis, IVIG and
prednisone

Guillain-Barre Syndrome (GBS)

 Localisation:
o Degeneration of myelin sheath of many peripheral nerves (schwann cells)
 Pathology:
o Covers a group of monophasic acute inflammatory polyneuropathy of
autoimmune pathogenesis producing an acute inflammatory demyelinating
polyradiculoneuropathy.
 Acute inflammatory demyelinating polyneuropathy (AIDP) and
`polyradiculoneuropathy` version are synonymous with each other.
o Their onset is 1-4 weeks after a respiratory or gastrointestinal infection in
1/3rd of cases.
o The causative agent often cannot be identified, associated organisms include:
 Viruses (CMV, EBV, VZV, HIV)
 Bacteria (Campylobacter Jejuni, Mycoplasma pneumoniae)
 Campylobacter Jejuni is the most common cause, commonly
seen in undercooked poultry.
 Vaccines (rabies).
o Viral vector vaccines increase the risk of GBS.
o Organisms induce T-cell autoreactivity which induce antibodies produced by
B-cells can be detected in serum and may block impulse conduction (acute
paralysis) or activate compliment and macrophages (myelin lesions).
o Once inflammatory response has subsided, regenerative processes of axonal
growth and remyelination occur.
 o Recovery begins within 4 weeks after progression stops – sensitivity
improves first followed by motor function and then reflex disorders disappear.
 Epidemiology:
o More common in those with Hodgkins lymphoma.
o 1.2-3 per 100,000 inhabitants
o Military personnel > general population
o Men > women (1.5:1)
o Bimodal peak incidence in age, infants have the lowest risk of GBS.
a) First peak in young adulthood (15-35y)
b) Second peak, higher one in middle-aged and elderly persons (50-75y)
 Clinical forms of GBS:
1) Acute inflammatory demyelinating polyradiculoneuropathy (AIDP)
o Most common (classic presentation) and is about 85% of cases
o Primarily motor inflammatory demyelination +/- secondary axonal
damage
o Progression can continue for a maximum of 4 weeks
2) Acute motor axonal neuropathy (AMAN)
o Primary motor inflammatory axonal degeneration
o Often affects children and young adults
o ~75% of patients have +ve Campylobacter Jejuni serology  anti-GM1
& anti-GD1a antibodies
3) Acute sensory and motor axonal neuropathy (AMSAN)
o Primary inflammatory axonal degeneration with motor and sensory
involvement
o Severe course of respiratory and bulbar involvement
o Poor prognosis
4) Miller-Fisher syndrome
 5% of all cases – rare
 Characterized by ophthalmoplegia, sensory ataxia and areflexia, with
little muscle weakness
 96% of patients positive for anti-GQ1b antibodies
5) Acute pandysautonomic neuropathy
 Most rare form of GBS
 Widespread sympathetic and parasympathetic failure
 May be accompanied by encephalopathy
 Symptoms & Signs:
o Characterizable features of symptoms:
a) Symptoms on both sides
b) Symptoms appear quickly (days or weeks instead of months)
o Classic Presentation of AIDP:
1) Acute ascending rapidly progressive symmetrical bilateral weakness
of lower limbs.
 Sometimes progressively ascends to upper limbs and causes
respiratory muscle weakness  respiratory insufficiency
  This is known as “ascending type of Landry’s paralysis” which
causes flaccid paralysis of respiratory muscles and bulbar
group of muscles (CN 9, CN 10, CN12).
 Unfavourable prognosis
2) Areflexia or hyporeflexia
3) Relatively mild paraesthesia
4) Pain is not uncommon – due demyelination and axonal degeneration
 Shock like, tingling, aching or myalgia quality
 Often misattributed to disc herniation, flu or rheumatism
5) Cranial nerve defects normally always present
 Bilateral CN 7 peripheral palsy is most common
 Peripheral palsy of CN 4, CN 6, CN 9, CN 10 may also be seen.
o Complications of AIDP
1) Respiratory weakness leading to respiratory failure – Landry’s
paralysis
2) Autonomic dysfunction – bradycardia, tachycardia, hypotension,
hypertension, loss of bladder and bowel control
3) Abnormalities in fluid and electrolyte balance
4) Immobility and functional dependence during recovery
 Differential Diagnosis:
 Polyneuropathy
a) Diabetic neuropathy
b) Chronic inflammatory demyelinating polyradiculopathy (CIDP), differs
from GBS in that it is subacute and responds to immune suppression
(CCS, azathioprine, cyclophosphamide)
c) Neuropathy of infectious origin
d) Paraproteinemic polyneuropathy
 Botulism
 Spinal cord compression
 Acute disseminated encephalomyelitis (ADEM)
 Diagnostic Tests:
1) Electromyography (EMG) – records the electrical impulses that your muscles
produce
2) Nerve conduction studies (NCS) – measures the speed at which impulses
travel along a nerve
3) Lumbar puncture for CSF analysis // exclusion of alternative diagnoses & can
provide evidence of diagnosis
 Cytoalbuminologic dissociation – High protein levels with normal
white blood cell count
 IF Lymphocytosis is seen  inconsistent with GBS, need to consider
alterative diagnosis
4) Serology for autoantibodies
a) Anti-GM1 – frequently seen in AIDP & AMAN and closely associated
antecedent C Jejuni infections.
b) Anti-GQ1b – Miller-Fisher syndrome
c) Assays for antibodies for infectious agents
- C Jejuni
 - Cytomegalovirus (CMV)
- Epstein-Barr virus (EBV)
- Herpes simplex virus (HSV)
- HIV
- Mycoplasma pneumoniae
 Prognosis:
o Without Landry’s paralysis – favourable prognosis as most people fully
recover, recovery starts about 4 weeks after progression stops.
 80% patients with GBS walk independently at 6 months
 60% of patients attain full recovery of motor strength by 1 year
o With Landry’s paralysis – unfavourable prognosis, possible mortality, or
morbidity
 Recovery in approximately 5-10% of patients with GBS is prolonged,
with several months of ventilator dependency and a very delayed,
incomplete recovery.
 15-20% of patients have moderate residual deficits from GBS
 1-10% are left severely disabled
o Most cases of mortality (2-12%) are due to severe autonomic instability or
from the complications of prolonged intubation and paralysis
 Treatment: (AIDP)
 Urgent admittance to hopsitial (hospitalisation)
 Intubation & mechanical respiration if needed
 Intravenous immunoglobulin (IVIG)
 Plasmapheresis
 Corticosteroids (Dexamethasone) // ONLY FOR IVANE, research does not
support
 In clinical practice, have not been found to have a clinical benefit in
GBS

Poliomyelitis
 Localisation:
o Destruction of lower motor neurons of motor nuclei of brainstem and
anterior horns of spinal cord
 Pathology:
o Viral infectious disease caused by Poliovirus (RNA virus)
o Spread by the faecal-oral route and by aerosol droplets
 Epidemiology // NOT REQUIRED FOR IVANE
o Three antigenically distinct wild strains (type 1, type 2 and type 3) are known,
with type 1 accounting for 85% of cases of paralytic illnesses.
 Wild poliovirus type 2 was eradicated in 1999 from everywhere
EXCEPT from Nigeria where in 2022 alone, Nigeria reported 168 cases.
 Wild poliovirus type 3 was eradicated in 2020.
 As at 2022, endemic wild poliovirus type 1 remains in two countries:
Pakistan & Afghanistan
o Infection with one type does not protect from the other types; however,
immunity to each of the three strains is lifelong.
 Stages of Disease:
 Stage 1 – mild non-specific symptoms of viremia:
 Infectious prodrome symptoms of sore throat, fever, headache,
myalgia, malaise and fatigue
 May have GIT complaints: nausea and vomiting, abdominal cramps
and pain, and diarrhoea
 Stage 2 – pre-paralytic:
 Meningism (nuchal rigidity, +ve Kernig’s & Brodzinski sign) without
paralysis
 Stage 3 – paralytic stage:
 Meningism + profound asymmetrical muscle fasciculations, myalgia,
muscle atrophy, weakness and flaccid paralysis.
 Predominantly lower limb > upper limb // EXTERNAL SOURCE
 Bulbar signs – pharyngeal, laryngeal, lingual weakness
 Recovery phase (convalescent stage):
 Acute symptoms and muscle tenderness disappear, and the paralyzed
muscles begin to recover
 Stage lasts for up to 2 years after the onset of the disease – there is
gradual recovery of the muscles; the recovery is rapid in the first 6
months but is slower during the subsequent months
 Any remaining weakness >2 years `residual-paralysis stage` and no
further recovery occurs after this point.
 Post-polio Syndrome (PPS)
 History of documented acute paralytic poliomyelitis in childhood 
usually occurs 15-40 years after the infection and recovery
 Not contagious
 Result of a deterioration motor neurones over many years that leads
to the following:
a) Slow progressive loss of muscle strength
b) Atrophy
c) Paralysis
d) Fatigue
e) Pain from joint degeneration
f) Skeletal deformities
 Rarely life-threatening
a) May induce respiratory muscle weakness affecting daytime
functions and sleep
b) May result in dysphagia, increasing risk of pneumonia
 Complications:
o Transverse myelitis (very rare)
 Paraparesis, urinary retention, sensory symptoms and signs,
autonomic dysfunction (including hyperhidrosis or hypohidrosis), and
decreased limb temperature may occur
o Residual-paralysis stage – weakness and deformity
o Spinal and Joint deformity
o High-risk group for fracture
o Post-polio Syndrome (PPS)
 Differential Diagnosis:
 Spinal muscle atrophy
 ALS
 Meningitis
 Encephalitis
 Transverse myelitis
 Syringomyelia or Syringobulbia
 Diagnostic Tests:
 Identification of Acute Flaccid Paralysis (AFP) cases // gold standard for
surveillance for detecting polio cases
 Lumbar puncture & CSF Analyse:
 CSF findings: increased pressure, pleocytosis and increased protein
 PCR – detect poliovirus in throat, feces (stool), and occasionally CSF
 Treatment: (AAPPPS)
o Assisted walking devices
o Antispasmodics
o Pain relief
 Joint contractures – Joint capsular release or Tenotomy
 Deformities – Arthrodesis, Osteotomies, Limb lengthening (Ilizarov
techniques), Joint replacement
 Muscle transplantation of paralyzed muscle
 Stabilization of a relaxed or flail join – Tenodesis
o Prevention – prophylactic inactivated polio vaccine (IPV) in endemic
countries.
o Physiotherapy
o Surgery

Bulbar Palsy
 Localisation:
1) Bilateral impairment due to lower motor lesion at EITHER at the cranial
nerve fasciculi located at the base of the medulla or cranial nerve nuclei
located at the roof of the medulla
2) Bilateral lesions of CN 9, CN 10, CN 11 & CN 12 outside the brainstem
 Pathology:
o Bilateral motor lesion causing impairment of the cranial nerve fasciculi
located at the base of the medulla or cranial nerve nuclei at the roof of
medulla or bilateral lesions of the CN 9, CN 10, CN 11 & CN 12 outside the
brainstem
o All of these result in peripheral palsy of CN 9, CN 10, CN 11, CN 12 bilaterally
 Symptoms:
o Dysphagia (difficulty swallowing)
o Dysphonia (impaired temper/timbre of voice, due to CN 10)
o Dysarthria (impaired speech, due to CN 9 & CN 12)
o Anarthria (due to unable to move tongue from mouth)
o Nasal regurgitation (water comes out nose if given by mouth to pt)
 o Nasal and slurring speech
o Choking on liquids
 Signs:
o Weakness of soft palatal and uvular movement
o Tongue weakness (Glossoplegia), atrophic with fasciculations,
o Absent gag reflex
o Normal or absent jaw jerk reflex
o Dribbling of saliva (Sialorrhoea)
 Causes & Differential Diagnosis (pick 3 + main diagnosis of bulbar palsy) :
o Medullary infarction
o Syringobulbia
o Guillain-Barre
o Brainstem glioma
o Poliomyelitis
o Lyme Disease
o Botulism
 Diagnostic tests:
o Physical examination
o MRI
 Treatment:
o Treat underlying cause