Brain And Behavior 2011- Neuropathies And Myopathies

Front 1

causes of sensory neuropathy

Back 1

rare: toxins (B6/pyridoxine), anti-Hu (ANNA-1) abs due to paraneoplastic syndrome associated with small cell lung carcinoma, Sjogren's

Front 2

EMG denervation signs

Back 2

Motor unit APs are larger and longer, but fewer MUs present because of renervation using the few remaining LMN due to sprouting; also see fibrillation (small AP of single fiber)

Front 3

ALS

Back 3

common (increases with age); progressive loss of motor neurons (both LMN and UMN) w/o sensory involvement; begins in bulbar muscles (speech, chewing, swallowing), arms, or legs; usually idiopathic (10% inherited)

Front 4

SMA

Back 4

progressive loss of motor neurons w/o sensory involvement; caused by loss of SMN1 gene (replaced by SMN2); severity depends on type but is genetic so affects children from birth (SMA 1) to after 1 yr (SMA3) and adults after 30 yr (SMA 4 only)

Front 5

SMN1/2 gene

Back 5

SMN protein needed to prevent motor neuron loss; SMN1 gene produces stable full length protein while 90% SMN2 produces truncated protein; in SMA SMN2 replaced by SMN1 and thus instead of 110% of SMN protein we get 20%

Front 6

radiculopathies most common causes

Back 6

very common, usually due to compression of nerve root by herniated disks, boney overgrowth, or mass; most common in cervical (C5-8 and most common C7) and lumbosacral (L4-S1 and most common L5)

Front 7

PMP22

Back 7

duplication (i.e. 3 copies) leads to Charcot-Marie-Tooth disease (CMT1A) and deletion (i.e. 1 copy) leads to herid neuropathy with liability to pressure palsies (HNPP) -> these two diseases are thos emost common inherited demyelinating neuropathies, and in this case caused by too little or too much PMP22 in the myelin sheath

Front 8

presynaptic NMJ diseases

Back 8

Lambert-Eaton, botulusm

Front 9

postsynaptic NMJ diseases

Back 9

myasthenia gravis

Front 10

repetitive stimulation used to diagnose what?

Back 10

NMJ disorders -> presynaptic defects will see increased CMAP amplitude with repetitive stimulus (small at rest, rises as more ACh enters cleft); postsynaptic defects will see decreased CMAP amplitude with repetitive stimulus (normal at rest, drops as axon terminal runs low on AcH); normal will see no change in amplitude because of large safety factor

Front 11

congenital myopathies vs muscular dystrophies

Back 11

congenital myopathies have no active muscle breakdown and regeneration -> may show improvement or stable course rather than decline seen in MD

Front 12

classic congenital myopathies (4)

Back 12

nemaline myopathy, centronuclear/myotubular myopathy, central core disease, multi/minicore myopathy -> each describes a histological finding, not a cause (each disease is genetically heterogeneous)

Front 13

nemaline myopathy

Back 13

disease of thin filaments (often nemalin or actin mutations), cause nemaline rods composed of Z-line material in sarcoplasm regions of interrupted sarcomere structure (looks like red rods on trichrome)

Front 14

muscular dystrophy histology (3)

Back 14

degeneration, regeneration, connective and fatty tissue infiltration

Front 15

Duchenne muscular dystrophy: time course (3), symptoms (3), complications (3)

Back 15

onset 2-4 yrs (not floppy baby) and wheelchair in under 12 yrs, can live until 30s; proximal progressive weakness, pseudohypertrophy, elevated CK; complications: cardiomyopathy, respiratory insufficiency, scoliosis

Front 16

Gower's maneuver

Back 16

child on back can't get up immediately because of proximal muscle weakness -> must roll over and walk forward on hands to stand

Front 17

Trendelenburg sign

Back 17

hip abductor weakness due to proximal muscle weakness brought out by climbing stairs -> excessive hip swing

Front 18

Becker muscular dystrophy: demographics, time course (4), lab values (1), complication (1)

Back 18

10x less common than DMD (1:30,000 in Becker vs 1: 3500 in DMD); variable onset with wheelchair in more than 15 yrs and severity and lifespan variable; CK elevated; complication: cardiomyopathy, even while still ambulant -> usually looks similar to DMD in proximal progressive weakness and pseudohypertrophy b/c it's a MD after all!

Front 19

muscular dystrophy causes

Back 19

mutations in dystrophin (v. large protein that is important in binding proteins on sarcolemma); 65-70% mutations are deletions of exons (majority around exon 45-53) and 30% mutations de nova (common because large?); deletions that lead to disruption of reading frame (more common) leads to DMD (worse prognosis) while preservation of reading frame leads to BMD (less common, better prognosis) -> poss tx of forcing exon 51 skipping in DMD to lead to frame restoration and BMD

Front 20

"girls with DMD" have what?

Back 20

sarcoglycanopathy (limb-girdle MD due to mutation of sarcoglycan, a protein in complex with dystrophin) -> AR disease

Front 21

sarcoglycanopathy

Back 21

AR disease (aka both sexes!) that looks like DMD -> limb-girdle MD due to mutation of sarcoglycan, a protein in complex with dystrophin

Front 22

facioscapulohumeral dystophy (FSHD): demographics, inheritance, onset, symptoms, cause

Back 22

3rd most common dystrophy (after DMD and myotonic -> 1-5:100,000); AD or de nova (30%); onset variable but usually young adult (depends on deletion size); asymmetric weakness in face, scapula, biceps, distal leg (foot drop); caused by loss of repeat elements (DUX4) on the A version of 4qter (more deletions = more severe/earlier onset disease but lose all = no disease) -> this is because deletions allow the chromatin structure to relax and DUX4 to be polyadenylated (pLAM only on A 4q) and thus expressed = toxic