Diseases of Nerve, Muscle and

Neuromuscular Junction
 Peripheral nerves
• Structure: cell body, dendrites, axons, myelin
sheath
• Neurons are specialized cells that display the
physiologic properties of excitability/irritability,
conduction and secretion
• Due to this cellular and functional specialization,
most neurons lose the ability to mitotically
devide, they therefore must last a lifetime
 Diseases P. Nerves: Terminology:
• Diseases of the peripheral nerves can affect
any part of the nerve:
- Cell body (ganglionopathy)
- The axons (axonopathy)
- The encasing myelin sheaths/schwann cells
(myelinopathy)
• Most peripheral nerves are mixed and contain
sensory, motor and autonomic fibers
 DS of P. Nerves: Terminology
• Dss of P.N can impair sensory, motor, or
autonomic function, either singly or in
combination
• Dss of PN can target either:
- The nerve roots (radiculopathy)
- A nerve plexuses (plexopathy)
- The individual nerves themselves
(neuropathy)
 DS of P. Nerves
• Progression: Dss of peripheral nerves can be acute
or chronic
• Ds of PN can be:
- Focal (affecting a single nerve: mononeuropathy)
- Generalised (polyneuropathy)
- Multifocal (several single nerves: mononeuropathy
multiplex)
• Cranial nerves 3-12 share the same tissue
characteristics as peripheral nerves elsewhere and
are subject to the same range of diseases
 P. Nerve disorders: etiology
1. Inherited ( genetic): charcot- marie –tooth,
Friedreichs ataxia, Refsum syndrome etc)

2. Acquired causes of P. neuropathies

 P.Nerve disorders: Etiology
Acquired causes of P.N:
1. Metabolic
2. Drugs
3. Toxins
4. Inflammatory
5. Deficiency states
6. Malignancy associated
7. Infections
8. Others: critical illness associated P.N
Causes of peripheral neuropathies

Metabolic Deficiency states

1. Diabetes mellitus 1. Cobalamine ( B12)
2. Hypothyroidism 2. Pyridoxine( B6)
3. Chronic renal failure 3. Thiamine
4. Chronic liver failure 4. Folate
5. Unusual causes: 5. Vitamin A, E
amyloidosis, porphyrias,
cryoglobulinemias
Causes of peripheral neuropathies

Inflammatory Toxins
1. Alcohol
1. Acute: GullainBarre 2. Heavy metals: lead, mercury,
Syndrome 3. Arsenic,
2. Chronic demyelinating 4. Gold
polyneuropathy( CIDPN) 5. Organophosphates
3. Connective tissue diseases: Drugs
SLE, Sjogrens syndrome 6. Isoniazid
7. Phenytoin
Scleroderma, Rheumatoid
8. Metronidazole
arthritis 9. Dapsone,
4. Sarcoidosis 10. hydroxychloroquine
11. Chemotherapeutic agents: vincristine,
cisplatin, taxanes
 Causes of peripheral neuropathies

Infections Malignancy associated

HIV 1. Nerve compression
2. Nerve t infiltration by
Herpes zooster virus
tumour
Ebstein barr virus( EBV) 3. Paraneoplastic syndrome
CMV(cytomegalovirus) 4. Immunosupression by
Hepatistis B, C malignancy/treatment
5. A/E of chemotherapeutic
agents
 P. neuropathies: clinical presentation
o Distal paraesthesias: feet then hands( distal
ends of the longest nerves)
o Proximal progression
o Sensory loss in a glove and stocking
distribution
o Distal weakness
o Reduced or absent reflexes
o Autonomic disturbance ( bladder)
 P.neuropathies: History and P/E
1. What systems are involved?
– Motor, sensory, autonomic, or combinations
2. What is the distribution of weakness?
– Only distal versus proximal and distal
– Focal/asymmetric versus symmetric
3. What is the nature of the sensory involvement?
– Temperature loss or burning or stabbing pain (e.g., small
fiber)
– Vibratory or proprioceptive loss (e.g., large fiber)
4. Motor deficit: LMN/UMN?
 P. neuropathies: HX/PE
5. What is the temporal evolution?
– Acute (days to 4 weeks)
– Subacute (4 to 8 weeks)
– Chronic (>8 weeks)
6. Is there evidence for a hereditary neuropathy?
– Family history of neuropathy

7. Are there any associated medical conditions?

– Cancer, diabetes mellitus, connective tissue disease or other autoimmune
diseases, infection e.g., HIV
– Medications including over-the-counter drugs that may cause a toxic
neuropathy
– Preceding events, drugs, toxins
 P. neuropathies: investigations
Nerve conduction studies (NCS)
NCS confirm the presence of a neuropathy and whether its
axonal or demyelinating
Biochemistrty:
Kidney function/liver fuction
Blood sugar
Thyroid function
Toxicology screen
Vitamin assays
Mono clonal proteins; urine Bence Jones proteins
 P. neuropathies: investigations
Haematolgy: CBC, ESR
B12, folate levels
Immunological tests
VDRL
Serum auto-antibodies: ANA, Ds DNA, antineuronal
antibodies
Nerve biopsy
Investigations to exclude malignacies: PSA, etc
Infectious screen: HIV tests
 P. neuropathies: Treatment
• In upto 1/3, a treatable cause is identified
from HX, P/E, Investigations
• 1/3: cause is identified but is not treatable
• 1/3: No cause is identified
 P. neuropathies: RX
1. Treat or eliminate the cause
2. Correct deficiency states
3. Inflammatory neuropathies: may respond to
steroids, immunosupressive agents,
intravenous immunoglobulins,
plasmapharesis
4. Physiotherapy/ occupational therapy
 Gullain Barre Syndrome
The acute immune-mediated polyneuropathies are
classified under the eponym Guillain-Barré
syndrome (GBS), after the authors of early
descriptions of the disease.
GBS is an acute monophasic paralyzing illness
usually provoked by a preceding infection
= Acute inflammatory polyneuropathy
=Acute post infectious demyelinating
polyneuropathy
 GBS: Pathophysiology:

• Immunologically mediated Demyelination of

spinal roots, peripheral nerves
• Upto 70% of cases develop after a respiratory
infection /diarrhoea
• The immunologic association with bacterial/viral
infections is complex and not clearly understood.
- Autoantibodies ?
- Molecular mimicry immunologic response to an
infectious cause?
 GBS: clinical PX
• Distal paraesthesias/pain Followed by the
Characteristic rapidly progressive weakness
often ascending from lower to upper limbs
and more marked distally than proximal
• May progress to involve respiratory muscles,
cranial nerves, bulbar weakness
• Neurological Exam findings: LMN weakness:
flaccid, absent or reduced reflexes
 GBS: subtypes/Variants
• It now is recognized GBS is a heterogeneous
syndrome with several variant forms.
• Each form of GBS has distinguishing clinical,
pathophysiologic, and pathologic features.
 GBS: variants
1. Acute inflammatory demyelinating
polyradiculoneuropathy (AIDP)
- Is the most common form (85 to 90% of cases).
- Inflammatory demyelination that start at the
level of the nerve roots leading to a
progressive, fairly symmetric muscle weakness
accompanied by absent or depressed deep
tendon reflexes
 GBS: variants
2. Miller Fisher syndrome (MFS) (occurs in 5%)
• The typical presentation of MFS is that of
ophthalmoplegia with ataxia and areflexia
• About one-quarter of patients who present with
MFS will develop some extremity weakness,
• Antibodies against GQ1b (a ganglioside
component of nerve) are present in 85 to 90 %
of patients with MFS
 GBS: variants
3. Acute motor axonal neuropathy (AMAN)
- An acute axonal form of GBS.
- Most cases are preceded by Campylobacter
jejuni infection
- Deep tendon reflexes are occasionally
preserved in patients with AMAN
- Sensory nerves are not affected
 GBS: variants
4. Acute sensori-motor axonal neuropathy
(AMSAN ) 
AMSAN is a more severe form of AMAN, in which
both sensory and motor fibers are affected with
marked axonal degeneration
5. Several other rare variants:
Pharyngeal-cervical-brachial,
Acute pan- dysautonomia,
Pure sensory GBS etc
 GBS: Diagnosis
1. Nerve conduction studies (NCS) electromyography (EMG)
for confirming the diagnosis of GBS.
2. Cerebrospinal fluid analysis: 
 Typically reveals an elevated CSF protein with a normal CSF
white blood cell (WBC) count.
This finding, known as albumin-cytologic dissociation, is
present in 80 to 90% of patients with GBS one week after
the onset of symptoms
The elevated protein may be due to increased permeability of
the blood-nerve-barrier at the level of the proximal nerve
roots
 GBS: diagnosis
3. Antibodies
e.g Antibodies against GQ1b, a ganglioside
component of nerve, are present in the vast
majority of patients with Miller Fisher
syndrome (MFS).
4. Other Investigations are often to R/O other
causes of peripheral neuropathies (as guided
by History and clinical finding)
 GBS: diagnosis
• The following features make the diagnosis of GBS doubtful:
- Sensory level on neurologic examination
- Marked, persistent asymmetry of weakness
- Severe and persistent bowel and bladder dysfunction
- More than 50 white cells in the CSF
Differential diagnosis of GBS: 

- other acute polyneuropathies

- Diseases of the spinal cord: Transverse myelitis
- chronic inflammatory demyelinating polyneuropathy (CIDPN)
- Diseases of the neuromuscular junctionand muscle
 GBS: RX

Supportive treatment:
- Regular monitoring of respiratory function: clinically,
lung function tests e.g vital capacity, regular blood gases
- Intubation and ventilatory support in severe if
involvement of respiratory/ bulbar muscles
- DVT prophylaxis

- Prevention of pressure sores

- Physiotherapy
 GBS: treatment: steroids, IV Ig, plasma
exchange
1. Steroids : No evidence that they are effective or reduce
mortality/ slow progreesion / improve neurological deficts
2. Plasma exchange
3. Intravenous immunoglobulin therapy:
2 and 3 : Are indicated in patients with rapid progression of
neurological deficits or respiratory/bulbar muscle
involvement:
- Treatment must be started within 14 days of onset of
symptoms:
- Equally effective, no advantage in combining the 2
- Has been shown to shorten the duration of mechanical
ventilation and improve prognosis
 GBS: prognosis
- 80% recover completely within 3-6months
- 4% die
- The rest suffer residual neurological disability,
sometimes severe
Idiopathic facial nerve palsy: Bell’s palsy
• common condition affecting all ages and both sexes
• The lesion is within the facial canal
Clinical PX:
Symptoms usually develop subacutely over a few hours
- pain around the ear
- unilateral facial weakness
- Patients often describe the face as 'numb'
- Loss of taste sense of taste, May be Hyperacusis, diminished salivation
and tear secretion
- Examination reveals an ipsilateral lower motor neuron facial nerve palsy
- Vesicles in the ear or on the palate indicate that the facial palsy is due
to herpes zoster rather than Bell's palsy: Ramsy hunt syndrome
 Bell’s palsy : RX
• Prednisolone 40-60 mg daily for a week
speeds recovery if started within 72 hours.
• Artificial tears and ointment prevent exposure
keratitis and the eye should be taped shut
overnight.
• Prognosis: About 80% of patients recover
spontaneously within 12 weeks
 Further reading
1. Peripheral neuropathies in HIV
2. Chronic inflamatory demyelinating
polyneuropathies( CIDPN)
3. Clonic ( hemifacial) spasms
BREAK
Diseases of the neuromuscular junction

Diseases that present with muscle weakness

due to impaired transmission across the
neuromuscular junction
1. Myesthena Gravis( MG)
2. Lambert Eaton myesthenia syndrome( LEMS)
 Myesthenia Gravis
• It is a condition characterized by progressive
inability to sustain a maintained or repeated
contraction of striated muscle (progressive
fatigable weakness)
• Mostly affects the ocular, neck, facial and
bulbar muscles
 MG: Pathophysiology
• Commonly caused by autoantibodies to acetylcholine
receptors in the post-junctional membrane of the
neuromuscular junction
• These antibodies initiate a complement-mediated
inflammatory response which reduces the number of
acetylcholine receptors and damages the end plate thus
blocking neuromuscular transmission
• other autoantibodies : e.g autoantibodies to a muscle-
specific kinase (MuSK), a receptor which is involved in the
regulation and maintenance of the acetylcholine receptors
 MG
• Majority of patients with MG have a
thymoma/thymic hyperplasia
• Drugs e.g: aminoglycosides, ciprofloxacin( long
list) may exacerbate the blockade: avoid
 MG: clinical
• Ages: 15-50 yrs
• Males vs females : More common in females
• Runs a relapsing /remitting cause
• Earliest symptoms: intermittent ptosis
• Characteristic fatigable weakness: worsening of weakness
towards the end of the day or after exercise
• Progresses to difficulty in: chewing, swallowing, speaking,
limb movements especially the shoulder muscles: difficult
combing hair/ takes frequent rests
• May have sudden weakness with respiratory involvement
requiring ventilation support: cholinergic/ myesthenia crisis
 Diagnosis
1. Clinical suspicion
2. Tensilon test: injection of the short acting anticholinesterase
endrophonium: positive test: improvemnet in muscle power
within seconds , lasts abt 2-3minutes
3. Autoantibodies:
- Immunologic assay to detect the presence of circulating
acetylcholine receptor antibodies (AChR-Ab)( found in 80% of
pts)
- Other antibodies: autoantibodies to a muscle-specific kinase
(MuSK)
 MG: Diagnosis
4. Electromyography (EMG) may show changes
in muscle conduction
5. CT scan chest to screen for thymoma
6. Test to R/O other autoimmune diseases eg.
Autoimmune thyroid disease
 MG: treatment
• Goal:
1. Maximise the activity of acetycholine at the
remaining receptors in the neuromuscular
junction
2. Limit/eliminate the immunologic attack at
the motor endplate
 MG: treatment
1. Pyridostigmine: acetycholinesterase inhibitor
- 3-0120mg 6 hrly
2. Immunologic treatment:
- corticosteroids
- Azathioprine
- IV Ig( intravenous immunoglobulin) or plasma
exchange in severe cases or
cholinergic/myesthenic crisis
- Removal of thymoma( thymectomy)
Lambert EatonMyesthenia syndrome( LEMS)

Pathophysiology:
• Impaired transmission due to antibodies to
voltage gated calcium channels
 Diseases of muscle( Myopathies)
1. Inherited
2. Metabolic
3. Endocrine
4. Inflammatory
5. Toxic
 Inherited myopathies
Muscular dystrophies
1. Duchenne’s MD- proximal legs/arms
generalised)
2. limb girdle MD- weakness of shoulder girdle, or
pelvic girdle or both
3. Fascioscapulohumeral- facial weakness, shoulder
4. Dystrophia myotonica -face, neck nmuscles, limbs
Inherited disrders of muscle metabolism:
e.g phosphofructokinase deficiency
 Metabolic/ endocrine myopathies
1. Hypo/hyperkalemia
2. Hypo/hypercalcemia
3. Hypo/Hyperthyroidism
4. Cushing’s syndrome
5. Adrenal insufficiency

Clinical: Acute weakness, muscle pains

 Toxic myopathies
Drugs:
Thiazide diuretics
Steroids
Toxins:
Alcohol : mild myopathy to severe muscle
necrosis i.e Rhabdomyolysis
 Clinical presentation
Clinical:
Progressive degeneration of muscle groups without involvement of the nervous
system
- Weakness, muscle wasting, s often symmetrical
- No sensory loss
- No fasciculations
- Tendon reflexes are spared until late stages of the ds
Diagnosis:
- Suggestive history: alcohol, drugs, family history etc
- electromyography
- muscle biopsy
- Creatinine kinase elevation
- Biochemsitry
- Thyroid funtion