Mkgrady8 Neuro 3 Myopathies

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what are myopathies

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neuromuscular disorders in which the primary symptom is muscle weakness due to dysfunction of muscle fiber; can either be due to destruction of muscle fibers (muscular dystrophies, metabolism myopathies, or inflammatory myopathies) or due to a functional deficit (myotonic disorders or periodic paralysis)

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signs of symptoms of myopathy

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chief complaint is weakness (paresis); paresis refers to insufficient force development whereas fatigue refers to inability to maintain force; paresthesias are absent (sensation intact); myalgia (muscle pain) may be present but abnormal sensations (e.g. pins and needles, burning, numbness) are absent; there may be muscle waisting (atrophy) aka flaccid paralysis due to muscle fiber necrosis; muscle tone will either be slightly decrease (hypotonia) or normal; DTRs will be normal unless muscle is severely weakened; fibrillations present with active myonecrosis; fasciculations absent in myopathy, rare in peripheral neuropathy (more common in axonpathies than in demyelinating diease), important in dx of lower motor neuron disease

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diagnostic algorithm for myopathy

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pt with weakness? yes then paresthesia? yes then neuropathy involving sensory neurons, no then creatinine kinase levels? less than 5 times upper limit of normal (ULN) then selected myopathies, motor neuropathy, NMJ disorders, motor neuron disease, greater than 5 times UNL then myopathic EMG to confirm and characterize myopathy? no then selected myopathies, motor neuropathy, NMJ disorders, motor neuron disease, yes then if myopathy confirmed may need muscle biopsy and/or genetic testing

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creatine kinase levels

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leaks into the blood after damage to muscles BUT it is not specific; CK can be elevated in neurogenic diseases such as motor neuron disease and guillain barre syndrome, following vigorous exercise or other forms of muscle trauma; CK may be normal in metabolic myopathies and outside the acute phase of chronic slowly progressive myopathies

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needle EMG results

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myopathic changes= variable spontaneous (fibrillation) and/or insertional activity, motor unit potentials (MUPs)= smaller amplitude, short duration, polyphasic, rapid recruitment of small MUPs

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muscle biopsy results

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reduction in muscle fiber number; muscle fibers replaced by fat or fibrosis; inflammatory infiltrate in inflammatory myopathies; histochemical measures of protein abundance or activity

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DNA analysis results

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ID gene mutations to confirm dx

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A 5 yo boy presented to our clinic with ahistory of progressive muscle weakness, especially of his shoulder and pelvismuscles and loss of motor milestones. PEidentified Gower sign and calf pseudohypertrophy. DTRs are present. No fasciculations are detected. Serum creatine kinase levels are 10 to 100times UNL. Needle EMG of the ptsshoulder muscles shows motor unit potentials (MUPs) of decreased amplitude andduration. Nerve conduction studies are normal. Muscle biopsy showed absence ofdystrophin. What is your dx?a. McArdle’s diseaseb. Duchenne muscular dystrophy (DMD)c. Hyperkalemic periodic paralysis (hyperPP)d. Amylotrophic lateral sclerosis (ALS)e. Spinal muscular atrophy (SMA)

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B

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what are muscular dystrophies

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a group of hereditary progressive diseases affecting the muscles; Duchenne muscular dystrophy is the most common muscular dystrophy; always inheritable but not always inherited= 1/3 of DMD cases occur as a result of spontaneous new mutations, the large size of the dystrophin gene allows mistakes in protein synthesis to occur at multiple sites

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gower's sign

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classical sign of DMD; indicates proximal limb weakness > distal limb weakness; involves the use of distal limb muscles to brace and lift oneself from sitting to standing position; not pathognomonic because also seen in spinal muscle atrophy (SMA which is a motor neuron disease)

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pseudohypertrophy

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commonly associated with DMD; pseudohypertrophy of a person's calf muscle is an increase in muscle diameter due to fibrous tissue and fat replacement

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muscle biopsy staining and DMD

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dystrophin is absent

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summary DMD

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distribution of weakness= proximal limb weakness > distal limb weakness; CK-MM is 10-200 times UNL; needle EMG shows myopathic changes; muscle biopsy shows myofiber necrosis, histochemical absence of dystrophin; DNA testing shows mutations in the gene that encodes the cytoskeletal protein dystrophin

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a 35 yo male with history of HTN,cardiomyopathy, scoliosis, and obesity presents with slowly progressingdifficulty jogging and lately, trouble getting out of bed with using hisarms. He has noticed his calves areenlarged. PE revelas deep tendonreflexes are 1+ throughout, strength decreased in lower extremity more thanupper extremity. Lab studies demonstratemoderately elevated CK. Muscle biopsystaining shows dystrophin to be fragmented an patchy. What is your dx?a. Duchenne muscular dystrophyb. Becker muscular dystrophy

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B

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metabolic myopathies: what are they, symptoms

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heterogeneous group of disorders that share the common feature of inadequate production of cellular energy in the muscle; notable for exertional related symptoms= transient exercise induced fatigue, exertional myalgia, cramping, rhabdomyolysis and myoglobinuria during times of high energy demand due to exercise, illness, or fasting

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A 22 yo male presented to the neuromuscular clinic with recurrent myoglobinuria associated with red tinged urine. Symptoms were associated with intensephysical exertion. There was no weaknessat rest and no fasciculations. Lab examrevealed an elevated CK after exercise. Muscle histo showed subsarcolemmal glycogen particles. EMG demonstrated mild myopathic changes. What is your DX?a. McArdle diseaseb. Duchenne muscular dystrophy (DMD)c. Hyperkalemic periodic paralysis (hyperPP)d. Amylotrophic lateral sclerosis (ALS)e. Spinal muscular atrophy (SMA)

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A

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what is McArdles's disease: cause, symptoms

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an inherited metabolic myopathy, a form of glycogen storage disease due to muscle phosphorylase deficiency; the pathophysiological mechanism is a defect in the gene that encodes glycogen phosphorylase which breaks glycogen down into glucose units (glucose 1 phosphatase) in muscles; a person with a metabolic myopathy may tolerate light to moderate exercise but intense physical exertion usually will bring on symptoms quickly including transient exercise induced weakness, cramping, and rhabdomyolysis; confirm DX with DNA analysis for a mutation in the gene encoding for glycogen phosphorylase

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A 10 yo boy has frequent muscle cramps and red tinged urine (myoglobinuria) with exercise. He also experiences a second wind phenomenon in which the first 15 mins of exercise is associated with progressive fatigue followed by exercise without difficulty. Suspecting McArdle disease, the physician performs an ischemic forearm exercise test. In this test an intravenous line is placed inthe median vein. The subject is asked to clench and unclench the hand rapidly while the blood supply is occluded, during which time a sample of venous blood is taken, and samples are also taken after the occlusion is stopped. When compared to a healthy pt, lactate levels in venous blood drawn from the occluded forearm of a pt with McArdle disease should be: a. low b. normal c. elevated

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A

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the ischemic forearm exercise test

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stimulates anaerobic generation of ATP; the anaerobic generation of ATP proceeds from glycogen --> increase in glucose --> increase in pyruvate --> increase in lactate; in the glycogen phosphorylase deficiency of McArdle disease glycogen breakdown is impaired so that muscle glycogen levels remain high and muscle glucose and lactate levels do not rise to expected levels with exercise

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McArdle disease 'second wind'

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an increase in CO increases muscle blood flow in order to supply exercising muscle with substrates that can substitute for muscle glycogen (free fatty acids (FFA), bloodborne glucose); changes in the metabolic pathways that promote the use of FFAs and bloodborne glucose to play a major role in energy supply at an earlier stage in exercise than in control subjects; an increased recruitment of motor units to compensate for a failure of force generation in the muscle fibers

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summary: McArdle disease of myophosphorylase deficiency

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distribution of weakness= 1/3 of pts develop fixed weakness with proximal limb weakness --> distal limb weakness; CK MM level is rarely normal even at rest it is 5-40 times UNL; needle EMG shows mild myopathic changes especially with activity; muscle biopsy shows elevated glycogen histo shows absence of myophosphorylase; DNA testing shows loss of function mutations in the PYGM gene encoding the muscle isoform of glycogen phosphorylase *myophosphorylase)

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what are channelopathies?: caused by what, symptoms, 2 forms

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caused by mutations in ion channel genes; characterized by episodic failure of motor activity due to muscle weakness (paralysis) or stiffness (myotonia); there are 2 forms of periodic paralysis based on changes in serum K levels during the attacks= familial HYPERKALEMIC PERIODIC PARALYSIS (hyperPP) which is due to mutations in the Na channel gene, and familial HYPOKALEMIC PERIODIC PARALYSIS (hypoPP) which is due to mutations in the Ca channel gene

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An 8 yo pt present with episodes of transient paralysis triggered during rest after exercise and, in some cases, by K rich foods, Muscle strength improves between attacks. Serum creatine kinase (CK)levels are slightly elevated. Myopathic changes are apparent with needle AMG. Sensation is normal, no fasciculations are visible. What is your DX? a. McArdle disease b. Duchenne muscular dystrophy (DMD) c. Hyperkalemic periodic paralysis (hyperPP) d. Amylotrophic lateral sclerosis (ALS) e. Spinal muscular atrophy (SMA)

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C

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explanation for paralytic attacks in hyperkalemic periodic paralysis

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increased [K+] intake of exercise followed by rest --> increased extracellular [K+] --> slight membrane depolarization --> opening of Na channels but also switch to abnormal Na channels to non inactivating mode --> persitent inward Na current --> sustained depolarization --> inactivation of normal Na channels --> block of action potentials --> paralytic attacks

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A 32 yo man sees his physician after collapsing suddenly without any other physical stress. Lab results demonstrate an elevated serum concentration of K and he is diagnosed with a hyperkalemic periodic paralysis (hyperPP). Which of the following is most likely to cause muscle weakness as a result of increased extracellular K concentration? a. hyperpolarization of muscle cells b. inactivation of Na channels in muscle cellsc. increased release of neurotransmitters from alpha motoneurons d. decreased K conductance in muscle cells e. increased duration of action potentials produced by alpha motoneurons

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B

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summary: hyperkalemic periodic paralysis (hyperPP)

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distribution of weakness= pts experience attacks of either focal or generalized muscle weakness often after exercise; permanent mild or moderate weakness that persists between bouts usually proximal and symmetric; CK MM is normal or mildly elevated; needle EMG shows moderate myopathic changes; muscle biopsy shows typical myopathic features myonecrosis; DNA testing shows mutations in Na channel (SCN4A) alpha subunit