10.11.1 Basic Neuropathology Of Peripheral Nervous System & Muscle

Question 1

Muscle weakness VS Hypotonia

Answer 1

Muscle weakness: Reduction in the maximum power that can be generated against resistance or gravity

Hypotonia: Decreased resting tone (tension) and decreased resistance to passive movement

Question 2

Clinical assessment of pt with neuromuscular disease

Answer 2

• Differentiating weakness from hypotonia
• Presence and distribution of contractures
• Distribution of weakness (proximal versus distal/facial/ocular/bulbar)
• Presence of muscle wasting or hypertrophy
• Fluctuation of muscle weakness during the course of the day or with exercise
• Involvement of other systems (heart, CNS, eye, skin)

Question 3

Biochemistry - Creatine kinase (CK)

Answer 3

Elevated CK = muscle damage

1.Normal or mild elevation (2-5 X normal):
- Nemaline myopathy
- Core myopathies
- Centronuclear myopathies
- Mitochondrial myopathies

2. Moderate elevation (5-10 X normal)
   - Inflammatory myopathies
   - Myotonic dystrophy
   - Somecongenitalmuscular dystrophies
   - Myofibrillar myopathies
3. Marked elevation (50-200 X normal)
   - Duchenne and Becker muscular dystrophies
   - Some limb-girdle muscular dystrophies
   - Pompe disease
   - Some congenital dystrophies

Question 4

Electrophysiology
Nerve conduction velocity
Electromyography

Answer 4

Nerve conduction velocity: differentiate between a demyelinating neuropathy and axonal neuropathy BUT does not inform about the underlying cause

Electromyography:
determines if the muscle is normal or abnormal, and whether the pattern is “myopathic” or “neuropathic”

Question 5

Define disorders of peripheral nerve

Answer 5

• Radiculopathy
• Mononeuropathy
• Mononeuropathy multiplex (myelin digesting chambers; neurofilament)
• Polyneuropathy

Question 6

Polyneuropathy
Two types

Answer 6

1. Axonal polyneuropathies
- diabetic neuropathy
- alcoholic neuropathy etc.

2. Demyelinating polyneuropathies
- Acute: Guillain-Barré syndrome
- Chronic: CIDP, Charcot-Marie-Tooth disease (HMSN)

Question 7

Clinical correlation of Axonal

Answer 7

• Sensory changes early, weakness later
• Glove-stocking sensory loss (mainly pain & temperature)
• Distal atrophy, weakness and reflex loss
• Slow distal to proximal progression

Question 8

Clinical correlation of demyelinating

Answer 8

• Weakness early and most prominent
• No or vague distal sensory symptoms (often proprioception & vibration sense)
• Global weakness and reflex loss, atrophy variable
• Rapid or slow progression

Question 9

Leprosy

Answer 9

• Lepromatous (multi-bacillary) macrophages
• Tuberculoid (pauci-bacillary) granulomas
• Intermediate forms

Question 10

Clinical correlation of myasthenia gravis

Answer 10

• Proximal > distal weakness
• Ocular weakness
• Bulbar weakness
• Fatiguability

Question 11

Name examples of Muscular dystrophies

Answer 11

• Dystrophinopaties ( Duchenne / Becker)
• Limb girdle muscular dytrophies (LGMD) – dominant & recessive
• Congenital muscular dystrophies

Question 12

Duchenne dystrophy

Answer 12

• genetically determined (X-linked)
• deficiency of dystrophin (normally in muscle cell membrane) - raised CPK
• presents in males 2-4 years
• weakness
• pseudo-hypertrophy of calves
• usually die by age 20 years

Question 13

Congenital myopathies

Answer 13

• Uncommon, inherited disorders
• Hypotonia & floppiness in infancy (hypotonia has OTHER causes as well)
• Reflect abnormal maturation of muscle fibres
• Often only slowly progressive
• Muscle biopsy ESSENTIAL

Question 14

Central core disease

Answer 14

• The most common congenital myopathy
• Characteristic: MRI of the muscles shows a pattern of selective
  involvement (ex affected quads with sparing of rectus femoris)
• Gene involved: RYR1 – association with malignant hyperthermia

Question 15

Myotubular / centronuclear myopathy

Answer 15

• Large central nuclei in some fibres
• Accumulation of NADH in the centre of the fibre with pale peripheral halos

Question 16

Metabolic myopathies

Answer 16

1. Glycogenoses
- Type 0 to type 15
- Vacuolar myopathy – accumulation of glycogen
- Characteristic: muscle symptoms occur after physical exercise (cramps and fatigue)

2. Lipid related disorders

3. Mitochondrial myopathies
- Heterogenous and complex group of neuromuscular disorders
- Caused by defective oxidative phosphorylation
- Nuclear and/or mitochondrial gene mutations
- Diagnosis: mitochondrial studies / muscle biopsy not necessary

Question 17

Idiopathic inflammatory myopathies

Answer 17

Dermatomyositis
- Proximal muscle weakness
- Dysphagia / Skin changes
- In 15% of adult cases associated with visceral cancer
- Most common idiopathic inflammatory myopathy in children
- Biopsy essential for diagnosis
- CD4 T lymphocytes

Polymyositis
- Clinical similar to dermatomyositis without skin changes
- Diagnosis of exclusion – no unique clinical features
- Histology:
➡️CD8+ T cell mediated and MHC class 1 restricted autoimmune myopathy
➡️Inflammatory cells characteristically invade normal (non-necrotic fibres)

Inclusion body myositis (myopathy)
- Affects men over age of 50 years
- Characteristically affects the quads and the fingers flexors • No response to corticosteroids
- Histology:
➡️Rimmed vacuoles and eosinophilic inclusions
➡️Immunohistochemistry: accumulation of BetaA4 amyloid, TAU protein, TDP-43 protein – similar to neurodegenerative conditions

Antisynthetase syndrome
- Histology: Perifascicular necrosis with regeneration
- Autoantibodies in the anti-tRNA group (Jo-1, PL-7, PL-12, OJ,
EJ…..)
- Clinically: Interstitial lung disease, hyperkeratotic rash on fingers – “mechanic’s hands”
- No associated malignancy
- New group: Immune mediated myopathies with perimysial pathology