Neuromuscular Disease Flashcards
Wallarian degeneration
Nerve is cut or crushed and the nerve segments distal to the lesion lose communication from the cell body and degenerate.
Damage to the nerve leads to axon swelling, schwann cells lose myelin sheath and proliferate, axon breaks down and is digested by macrophages and schwann cells.
Neurorpraxia
Sustained pressure to a nerve leads to transient conduction block of motor or sensory function without nerve degeneration. It is a mild form of peripheral nerve injury and completley reversible.
Steps of axon regeneration
Nerve regeneration may take several months; only occurs in cases where the axon is damaged but the surrounding connective tissue remains intact.
- Regeneration of soma and formation of Nissl structure
- Schwann cells eliminate myelin sheaths and arrange in cords along the length of the basal lamina of the endoneurial tube
- If the axon is severed, the Schwann cells form a number of cords (“band fibers”) to bridge the gap
- Macrophages recruited to remove debris
- Wallerian degeneration occurs at distal end of axon
- The ECM between Schwann cells provides a conduit for axon growth and trophic support to injured neurons
- The proximal end of the axon gives rise to numerous fine filaments (sprouts) which advance distally to reach the end organ
- Numerous axon sprouts begin, but only one will persist to reinnervate the end organ
- Once the axon reaches end-organ, Schwann cells begin to make myelin
Neuroma
Axonal sprouts escape from the epineural sheath and enter surrounding tissue forming a tangled mass
Jaw-Winking
Misdirected motor neurons to the wrong effector organ still function. Motor axons destined for jaw muscles are misdirected to muscles that close the eyelids.
Crocodile Tears Syndrome
Regenerating parasympathetic fibers from the facial nerve (Cranial Nerve VII) normally innervate the parotid salivary gland are directed to the lacrimal gland instead. Thus the gustolacrimal reflex is formed causing patients to shed tears when eating or drinking.
Neurorpraxia vs. Axonotmesis vs. Neurotmesis
Neuropraxia - a temporary interference with nerve function with no degeneration.
Axonotmesis - a nerve lesion in which the axons are damaged but the connective tissue sheath and Schwann cells surrounding the nerve remain intact.
Neurotmesis - a complete severance of a nerve. In addition to axons, myelin and connective sheaths are disrupted or transected. Regeneration cannot occur in the absence of surgical intervention.
Signs and types of neuropathy
Neuropathy is mixed motor and sensory loss with weakness
- Symptoms: weakness, sensory loss, dysesthesias (supersensitive skin, needles-like sensation)
- Signs: atrophy, LMN signs, loss of tendon reflexes
Pathology can be axonal (NCS loss of amplitude) or demyelinating (NCS slowed conduction and prlonged latency, chronic results in onion bulb formation)
Signs and symptoms of myopathic conditions
Signs
- Atrophy/pseudoatrophy
- Contractures
- Myotonia
Symptoms
- Weakness (typically of proximal muscles)
- Pain
- Muscles fatigue fast
Significance of creatine kinase and myoglobinuria
Elevated creatine kinase leves indicate muscle tissue damage or inflammation (muscle destruction)
Myoglobinuria indicates muscle destruction (can also bee high with vigorous exercize)
Neurogenic atrophy
Loss of innervaatino leading to atrophy of muscle
Over time may resulut in fiber-type switching or larger motor units due to denervation and then reinnervation
MUAPs for neurogenic versus myopathic conditions
Myasthenia gravis vs. Lambert-Eaton myasthenic syndrome
Myasthenia gravis
- Cause by auto-antibodies for AchR leading to degredation and depletion of receptors
- Symptoms are ptosis (drooping eyelids), diplopia, slow repetitive use of muscles makes weakness more severe
- Can use ice pack test for testing ptosis mimics effects of Ach-esterase inhibitor
- Strongly associated with thymic dysfunction
Lambert-Eaton
- Caused by auto-antibodies that inhibit function of the presynaptic calcium channels at neuromuscular junction
- Paraneoplastic disorder (>80%)
- Proximal muscle weakness without atrophy, ptosis
- Patients experience improvement in muscle strength with fast repetitive stimulation (buildup of calcium to facilitate neurotransmission)
Function of dystrophin protein and associated diseases
Links actin cytoskeleton of myofibrils in muscle cells with transmembrane poteins in the sarolemma of the muscle cell which is needed to stabilize the cell
Duchenne: mutation leading to complete absence of gene (look for internal nuclei on histology)
Becker: mutation leading to abnormal version of gene retaining some function
Both diseases X-linked, more common in men
Gowers sign shows weakness of proximal muscles (having to walk up own body to get up)
Charcot-Marie-Tooth disease (sensory and motor types)
A type of hereditary demyelinating neuropathy
Clinical presentation
- Peroneal atrophy
- High arch
- Claw toes
Autosomal dominant
- Duplication of gene leading to abnormal myelination
Myotonic dystrophy
- Most common adult muscular dystrophy
- Progressive trinucleotide repeat expansion of myotonin kinase
- Autosomal dominant inheritance
- Myotonia, progressive weakness and muscle wasting (facial and sternomastoid muscles), and cataracts
McArdle’s vs Pompe’s disease
McArdle’s: glycogen phosphorylase deficiency
- Recessive, onset < 15 years
- Exercise intolerance –> crampign and muscle swelling
- May cause myoglobinuria
- Accumulation of glycogen in sub-sarcolemma compartment
Pompe’s: acid maltase deficiency (still glycogen storage problem)
- Recessive, three distinct syndromes (depending on mutation) infant, childhood, or adult onset (decreasing severity)
- Glycogen accumulates in membrane bound lysosomes/vacuoles
Carnitine palmitoyl transferase II (CPTII) deficiency
- Most common lipid storage myopathy
- Usually in neonates, often fatal (rarely mild form in adults)
- Accumulation of large lipid droplets
Clinical and histopathologic findings of mitochondial myopathies
Clinical findings
- Present in young adulthood
- Proximal muscle weakness
Histopathologic findings
- Ragged red fibers (mitochondia accumulate in the peripheral of myofiber)
- Electron microscopy shows “parking lot” inclusions in mitochondia
Sometimes classified as mitochondrial encephalomyopathies because weakness can be accompanied by brain dysfunction (epilepsy or strokes)
Mode of inheritance of myoclonic epilepsy with ragged red fibers (MERRF), mitochondrial encephalopathy with lactic acidosis and stroke-like episodes and (MELAS), and Kearns-Sayre syndrome
- MERRF: maternally inherited mutation in mitochondrial genome
- MELAS: maternally inherited mutation in mitochondrial genome
- Kearns-Sayre syndrome: generally, not inherited
- Occurs by spontaneous somatic mutations in cells after you are born
Dermomyositis
Clinical presentation
- Heliotrope rash, gottron’s papules (pink scaley rash on knuckles), v-neck rash
- Proximal symmetric muscle weakness
- Associated with increased risk for malignancy
- Juvinile and adult forms
Responsive to steroids
Histopathologic findings include perifasicular atrophy
Polymyositis
Clinical presentation
- Insidious onset
- Weakness in pelvic and pectoral girdle muscles
- Adult onset, preference for females
Responsive to steroids
Histopathologic findings inclode scattered atrophy and andomysial infiltrates
Inclusion body myositis
Clinical presentation
- Weakness of more distal muscles than polymyositis
- Atrophy
- Onset over 50, preference for males
Not responsive to steroids
Histopathological findings include rimmed vacuoles and amyloid-containing inclusions
Chronic steroid myopathy
Characterized by type II fiber atrophy
Secondary iatrogenic myopathy due to corticosteroids (endogenous or exogenous)
