Term
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Definition
| 1 anterior horn cell, its axon and all muscle fibers innervated by that axon. problems w/the anterior horn cell: motor neuron disease, problems w/the peripheral nerve: peripheral neuropathy, and problems w/skeletal muscle: myopathy |
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Term
| what does the lab evaluation of peripheral neuropathy consist of? |
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Definition
| muscle enzymes, myoglobinuria, electrodiagnosis, and muscle biopsy |
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Term
| what serum muscle enzymes are used in dx of peripheral neuropathy/myopathy? |
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Definition
| *CPK (MM fraction: skeletal/MB fraction: cardiac [5-6%]), which is released in high amounts during muscle damage (rhabdomyolysis: CPK of ~1000 or 5x normal) or in lower amounts during vigorous exercise. *aldolase is also a very specific enzyme to skeletal muscle but it is not very sensitive. |
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Term
| does steroid muscle atrophy affect CPK? |
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Definition
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Term
| does motor neuron disease increase CPK? |
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Definition
| yes, but not as high as myopathy: CPK range of 5-600 |
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Term
| how is myoglobinuria diagnosed? why does it warrant immediate tx? |
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Definition
| ask pt if they have dark discoloration of urine and if they do, there is a quick and dirty way of confirming myoglobinuria: look microscopically for RBCs and if none - myoglobinuria is likely. any disease which causes acute rhabdomyolysis can cause myoglobinuria. if myoglobinuria is untreated = high incidence of renal failure (need to make sure pts are vigorously hydrate). |
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Term
| what is electrodiagnosis? |
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Definition
| a 2 part assessment involving: 1) nerve conduction studies (NCS - nerve conduction velocity which is usually abnormal in neuropathy/motor neuron disease). 2) electromyography (EMG - needle in motor unit) which when performed on pts w/neuropathy: amplitude is increased, duration is increased, and recruitment is decreased [axons are lost, each remaining axon increases signal]. when performed on pts w/myopathy: amplitude is decreased, duration is normal/decreased, and recruitment is early [muscle fibers are lost and amplitude decreases, b/c innervation to dead muscle is lost]. |
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Term
| what are the types of muscle fiber? |
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Definition
| type 1: oxidative, aerobic, sustained activity, ATPase (light staining), NADH (dark staining) and red. type 2: glycolytic, ischemic, burst activity, ATPase (dark staining), NADH (light staining), and white. every muscle has a mix of the 2 types (in calf: gastrocnemius has more type 1 fibers [postural] and soleus has more type 2 fibers [jumping]). the 2 different types have different anterior horn nuclei. |
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Term
| how are the different types of muscle fiber evaluated? |
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Definition
| via muscle bx. NADH stains dark in type I and light in type II. ATPase stains light in type I and dark in type II. on stains of healthy muscle, there is a checkerboard pattern of fiber distribution. |
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Term
| how does a muscle bx of neuropathy appear? |
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Definition
| fiber type grouping appears (vs normal checkerboard pattern) b/c axons die (fibers that used to be type 1 change to type 2 - vice versa). there may be a degree of atrophy as well. |
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Term
| how does a muscle bx of myopathy appear? |
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Definition
| increased degeneration of individual muscle fibers, atrophy, increased endomysial connective tissue (+inflammation), and increased internal nuclei |
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Term
| what characterizes motor neuron disease? |
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Definition
| degeneration of anterior horn cells and corresponding motor units - which produces weakness, atrophy and fasciculations. however in most motor neuron disease, there is simultaneous UMN involvement = mixture of hyperreflexia and spasticity (like ALS). |
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Term
| what are the classifications of spinal muscular atrophy (neuropathy)? |
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Definition
| infantile (werdnig-hoffman), intermediate, and mild (kugleberg-wielander) |
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Term
| what characterizes werdnig-hoffman disease (infantile spinal muscular atrophy)? |
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Definition
| early onset (may be detectable in utero as decreased fetal activity), **floppy infant w/poor control, respiratory distress due to bulbar weakness/intercostal muscle involvement, usually death occurs during infancy. tx: tube feeding and ventilation. |
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Term
| what characterizes intermediate spinal muscular atrophy? |
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Definition
| symmetrical proximal weakness, fasciculation, tongue atrophy, contractures, scoliosis, prognosis is determined by degree of respiratory involvement: may survive into early adulthood. *bulbar function, speech and swallowing usually spared* tx: aggressive respiratory care, prevention of deformities, physical therapy, and bracing for scoliosis. |
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Term
| what is kugleberg-wielander disease? |
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Definition
| the most mild form of spinal muscular atrophy, consisting of proximal muscle weakness (= waddling, lordotic gait which resembles muscular dystrophy), minimal respiratory involvement and a good prognosis. tx involves promotion of ambulation |
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Term
| what is the most important thing to promote in neuromuscular disease pts? |
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Definition
| promotion of ambulation (may lead to irreversible muscle deconditioning) and aggressive respiratory care |
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Term
| what generally characterizes motor system disease? what are the different kinds? |
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Definition
| progressive degeneration of UMN/LMN neurons in the spinal cord, brainstem and motor cortex. the sensory system is spared. primary lateral sclerosis: spinal UMN dz. pseudobulbar palsy: bulbar UMN dz. spinal muscular atrophy: spinal LMN dz. progressive bulbar palsy: bulbar LMN dz. ALS: all of the above. |
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Term
| what characterizes pts w/ALS? |
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Definition
| death of both upper and lower motor neurons in the motor cortex of the brain, the brain stem, and the spinal cord. pts usually present w/unilateral weakness of 1 limb (60% w/limb involvement/40% w/bulbar involvement) |
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Term
| what is the clinical presentation of ALS? |
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Definition
| asymmetric weakness and atrophy (40% arms, 40% legs, 20% bulbar). prominent fasciculations (esp tongue), dysphagia and tongue atrophy. on PE: UMN (increased DTRs, jaw jerk, and pseudo-bulbar palsy), LMN (atrophy, fasciculations), and bulbar signs (dysarthria) |
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Term
| if an ALS pt has progressive upper extremity atrophy and b/l lower extremity spasticity, where should imaging first be directed? |
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Definition
| the cervical cord - if nothing comes back of a dramatic nature, this **makes the diagnosis of ALS much more likely. |
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Term
| what characterizes the lab exam of ALS? |
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Definition
| NCS: normal sensory studies, EMG: denervation (fibrillations - spontaneous activity due to muscles losing their nerve supply), fasciculations, and large amplitude motor units (motor neurons are lost at a rapid rate and those surviving spread out broadly too re-innervate the remaining muscle fibers = motor units become giant in size). CPK: usually normal or mildly elevated. |
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Term
| what characterizes the pathology associated w/ALS? |
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Definition
| neuronal loss is seen in the *anterior horn and *motor nuclei of the brainstem along w/sclerosis of the lateral columns |
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Term
| what is the pathogenesis for ALS? is there a hereditary component? |
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Definition
| a defect in superoxide dismutase (free radical scavenger) leading to glutamate accumulation in motor neurons. 15% of pts w/ALS have a family hx. |
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Term
| what is the prognosis for ALS? |
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Definition
| 5 yr survival: 40%. (spinal: 46%, bulbar: 20%). prognosis depends largely on the pt's own aggressiveness (if they want feeding tubes/ventilator). most pts have a 3-10 yr survival. |
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Term
| what is myasthenia gravis (neuropathy)? |
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Definition
| a disorder of the neuromuscular junction w/the clinical manifestations of: *fatigable weakness (speech may be normal, but towards the end of the day becomes dysarthric), 40-50% diplopia/ptosis, 20% w/bulbar weakness (difficulty swallowing), and 20-30% w/weakness of extremities. DTR's are normal and atrophy is rare unless particularly severe. |
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Term
| what does the neuromuscular junction look like in myasthenia gravis? |
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Definition
| less postsynaptic ACh receptors and more ACh-esterase (can be inhibited by rx) |
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Term
| how is myasthenia gravis diagnosed? |
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Definition
| ACh receptor Ab (85%), tensilon (edrophonium) test (rapidly blocks the action of acetylcholinesterase), and EMG/NCS w/repetitive stimulation (observe decrease in amplitude of response) |
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Term
| what is tx for myasthenia gravis? |
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Definition
| anticholinesterases (mestinon and pyridostigmine - may produce cramps/diarrhea/increased salivation/sweating), corticosteroids (indicated for generalized form, 75% respond), immunosuppressive tx, and thymectomy |
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Term
| what is eaton lambert syndrome? |
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Definition
| a presynaptic disease of the neuromuscular junction, involving reduced release of ACh. 70% of pts have an associated malignancy (oat cell), pts will also exhibit proximal weakness (not bulbar as w/myasthenia gravis) and decreased DTRs (increased w/exercise, due to more ACh). NCS: low amplitude response which increases w/repetition (get more ACh). |
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Term
| what is botulism (neuropathy)? |
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Definition
| a toxin which binds to nerve endings and blocks ACh = decreased NM transmission. in adults: toxin ingested in non-acidic canned food -> opthalmoplegia, bulbar difficulty, and descending paralysis. infants: toxin produced in GI tract (c. botulini) -> constipation, lethargy, hypotonia, weakness [need to know for pediatrics: spores from new housing developments, honey, and karo corn syrup]. |
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Term
| what is ciguatera intoxication (neuropathy)? |
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Definition
| the most common (reef) fish borne toxin - causes a very pure and painful sensory neuropathy. |
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Term
| what generally characterizes myopathies? |
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Definition
| progressive proximal weakness (usually painless), normal sensory function, normal/reduced DTRs, proximal atrophy, and CPK (markedly increased in necrotic, inflammatory myopathies and mild-moderately increased in atrophic myopathies [steroid myopathy]) |
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Term
| what characterizes the lab findings for atrophic myopathy? |
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Definition
| CPK: normal, EMG: normal/myopathic, bx: fiber atrophy |
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Term
| what characterizes the lab findings for necrotic myopathy? |
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Definition
| CPK: mod/markedly increased, EMG: myopathic irritable, bx: necrosis inflammation |
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Term
| what characterizes the lab findings for degenerative myopathy? |
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Definition
| CPK: normal/mild increase, EMG: myopathic irritable, bx: vascular degeneration |
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Term
| what characterizes the lab findings for infiltrative myopathy (like sarcoidosis)? |
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Definition
| CPK: normal, EMG: normal/myopathic, bx: interstitial inflammation |
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Term
| what is polymyositis-dermatomyositis? |
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Definition
| a myopathy affecting primarily middle aged women or children who present w/progressive proximal muscle weakness primarily in the hips and less in the shoulders. *muscle pain is not uncommon. a small percent of pts will have speech/swallowing difficulties. another small portion of pts will have a dermatomyositis (heliotrope rash [circular around eyes or on extensor finger surfaces]). |
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Term
| what is the theorized pathophysiology for polymyositis- dermatomyositis? |
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Definition
| complement-mediated damage of microscopic vessels with muscle atrophy and lymphocytic inflammation secondary to tissue ischemia |
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Term
| what characterizes the spectrum of polymyositis- dermatomyositis? |
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Definition
| *polymyositis: heterogenous, only 4% w/CA (breast), associated w/CVD and maybe mild. *dermatomyositis: more homogeneous, high CA incidence (*breast), little association w/CVD and greater severity. |
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Term
| what are the groups for dermatomyositis-polymyositis dx? how are is the dx made? |
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Definition
| 1)skin lesions [heliotrope rash around eyes, groton's sign - erythema on dorsum/extensor finger surfaces, and erythema on extremity extensors] 2)proximal muscle weakness 3) increased aldolase/CPK 4) muscle pain on spontaneous grasping 5) myogenic EMG 6) anti-Jo Ab, nondestructive arthrotis/arthralgia 7) systemic inflammatory signs (increased sedimentation rate 8) C reactive protein, fever 9) inflammatory myositis on muscle bx. dermatomyositis: 1 from group 1 and 4 from groups 2-9. polymyositis: 4 from groups 2-9. |
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Term
| how does polymyositis-dermatomyositis appear on lab work? |
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Definition
| elevated CPK: often > 10x upper normal limits |
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Term
| what is tx for polymyositis- dermatomyositis? |
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Definition
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Term
| what does a muscle be for polymyositis- dermatomyositis show? |
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Definition
| perivascular infiltration, high levels of inflammation+inflammatory cells, fiber type variability, interstitial fibrosis, and w/dermatomyositis - a lot of *perifascicular atrophy (perhaps due to ischemia - possible associated vasculitis) |
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Term
| what are the clinical features of inclusion body myositis? |
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Definition
| age of onset > 30 y/o, duration > 6 mos, and weakness of proximal AND distal arm and leg muscles. the finger flexors are more involved than extensors (hand appears like a stop sign). CPK < 12x normal and EMG shows inflammatory changes. bx: inflammatory changes and vacuolated muscle fibers. (2nd most common myopathy) |
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Term
| what is the tx for inclusion body myositis? |
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Definition
| steroids/immunosuppressants, IV, IgG - however generally resistant to all therapies. |
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Term
| what is steroid myopathy? |
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Definition
the myopathic features of cushing's syndrome and chronic corticosteroid therapy are almost identical. any pt on corticosteroids will have reduction in muscle bulk, but a small percentage will develop a distinct myopathic weakness which may be more common w/longer acting (fluorinated) corticosteroids. this rarely begins before 3 mos of steroid therapy but will progress until dosage is reduced. to avoid this effect: put pts on an alternate day regimen.
(most common myopathy) |
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Term
| what are the clinical manifestations of steroid myopathy? labwork? tx? |
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Definition
| clinical manifestations: weakness beginning in proximal muscles (esp pelvic) which may progress to trunk, neck, and arms. labs: normal CPK and normal EMG. tx: switch to shorting acting preparation and/or alternate day therapy. |
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Term
| what is acute hypokalemic myopathy? prognosis? |
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Definition
| anything which can cause hypokalemia can cause a myopathy (diuretics/vomiting/diarrhea). K+ < 3.5: weakness, fatigue, myalgia. K+ < 2.5: moderate proximal weakness, CPK may increase. K+ < 2: proximal limb weakness, muscle pain. prognosis: improves w/in days after K+ replacement. |
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Term
| what are the hereditary muscular dystrophies? |
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Definition
| duchenne's, myotonic dystrophy, mytonia congenita and facioscapulohumeral dystrophy |
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Term
| what characterizes duchenne's muscular dystrophy (DMD) clinically? |
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Definition
| delayed motor milestones (seemingly normal at birth, then don't walk), clumsiness -> progressive weakness (beings in pelvifemoral muscles -> shoulder girdle -> distal/intercostal muscles). pts are wheelchair bound by age 7-10, death by 20. pts present w/pseudohypertrophy of their calves, mild mental retardation and cardiac involvement (common cause of death in these pts is from a cardiomyopathy). |
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Term
| what is gower's sign as seen in duchenne's (however this is seen w/anything that causes significant proximal muscle weakness)? |
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Definition
| if the child is put in a crosslegged position they will not be able to straighten their quadriceps/glutei so they inch their way up gradually up using their hands or calves. |
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Term
| what is the etiology linked to duchenne's? |
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Definition
| sex linked recessive (occurs only in boys - even though the gene is carried by the mother) on short arm of the X chromosome which codes for dystrophin. this normal enzyme is missing in DMD pts. |
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Term
| what is seen on lab work for DMD? |
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Definition
| massively elevated CPKs (>1000x upper limit of normal) - and the stronger the child is/less clinical involvement they have - the higher the serum CPK is. CPK starts to fall as muscle mass decreases and the disease enhances. CPK is never normal at birth or preclinical stages (detectable in utero via amniocentesis). |
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Term
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Definition
| interstitial inflammation, adipose tissue, fibrosis |
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Term
|
Definition
| genetic counseling (ID female carriers) and maintenance of ambulation |
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Term
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Definition
| muscle stiffness - not cramping, but difficulty w/relaxation. EMG shows "divebomber" discharge - high to low and back to high. |
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Term
| what is myotonic dystrophy? |
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Definition
| the most common myotonic disorder, autosomal dominant, commonly presenting around 20-25 and characterized by weakness primarily in the *distal (hands and distal lower extremities) *bulbar (dysarthria, dysphagia, ptosis), and a "hatchet face" (temporalis atrophy) |
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Term
| what is the systemic involvement associated w/myotonic dystrophy? |
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Definition
| smooth muscle: pharynx, esophagus, uterus. cardiac: conduction defects, arrhythmias. brain: decreased IQ. endocrine: testicular atrophy, DM, gynecomastia. eye: cataracts. skin: frontal balding. |
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Term
| what pathology is associated w/myotonic dystrophy? |
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Definition
| increased internal nuclei and ring fibers |
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Term
| what is myotonia congenita? |
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Definition
| the distinguishing factor between MD and MC is both of them have myotonia, however, MC pts have no significant skeletal muscle weakness and don’t have any other systemic involvement. clinically myotonia congenita pts have marked muscular hypertrophy. genetically, myotonia congenita is autosomal dominant or recessive. |
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Term
| what is facioscapulohumeral dystrophy? |
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Definition
| an autosomal dominant musculoskeletal disease characterized clinically by: variable facial weakness, difficulty w/eye closure, scapular winging, "popeye arm" (weakness/atrophy of biceps/triceps w/deltoid spared), anterior tibial weakness, and CPK usually 2-3x normal (minimal). |
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Term
| what generally characterizes DMD? |
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Definition
| x-linked recessive, onset @ 2-10, rapid progression, hips/shoulders/quads/calves/trunk, and heart/CNS effects. |
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Term
| what generally characterizes myotonic dystrophy? |
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Definition
| autosomal dominant, onset @ 2-50, slow progression, face/bulbar/hands affected, and heart/GI/GU/skin/eyes/endo/CNS affected |
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Term
| what generally characterizes FSH? |
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Definition
| autosomal dominant, onset @ 10-40, slow progression, and face/shoulders/biceps/triceps affected |
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