10.11.1 Basic Neuropathology Of Peripheral Nervous System & Muscle Flashcards
Muscle weakness VS Hypotonia
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
Clinical assessment of pt with neuromuscular disease
- 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)
Biochemistry - Creatine kinase (CK)
Elevated CK = muscle damage
1.Normal or mild elevation (2-5 X normal):
- Nemaline myopathy
- Core myopathies
- Centronuclear myopathies
- Mitochondrial myopathies
- Moderate elevation (5-10 X normal)
- Inflammatory myopathies
- Myotonic dystrophy
- Somecongenitalmuscular dystrophies
- Myofibrillar myopathies - Marked elevation (50-200 X normal)
- Duchenne and Becker muscular dystrophies
- Some limb-girdle muscular dystrophies
- Pompe disease
- Some congenital dystrophies
Electrophysiology
Nerve conduction velocity
Electromyography
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”
Define disorders of peripheral nerve
- Radiculopathy
- Mononeuropathy
- Mononeuropathy multiplex (myelin digesting chambers; neurofilament)
- Polyneuropathy
Polyneuropathy
Two types
1. Axonal polyneuropathies
- diabetic neuropathy
- alcoholic neuropathy etc.
2. Demyelinating polyneuropathies
- Acute: Guillain-Barré syndrome
- Chronic: CIDP, Charcot-Marie-Tooth disease (HMSN)
Clinical correlation of Axonal
- Sensory changes early, weakness later
- Glove-stocking sensory loss (mainly pain & temperature)
- Distal atrophy, weakness and reflex loss
- Slow distal to proximal progression
Clinical correlation of demyelinating
- 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
Leprosy
- Lepromatous (multi-bacillary) macrophages
- Tuberculoid (pauci-bacillary) granulomas
- Intermediate forms
Clinical correlation of myasthenia gravis
- Proximal > distal weakness
- Ocular weakness
- Bulbar weakness
- Fatiguability
Name examples of Muscular dystrophies
- Dystrophinopaties ( Duchenne / Becker)
- Limb girdle muscular dytrophies (LGMD) – dominant & recessive
- Congenital muscular dystrophies
Duchenne dystrophy
- 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
Congenital myopathies
- 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
Central core disease
- 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
Myotubular / centronuclear myopathy
- Large central nuclei in some fibres
- Accumulation of NADH in the centre of the fibre with pale peripheral halos
Metabolic myopathies
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
Idiopathic inflammatory myopathies
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
