Thy: Neuromuscular Flashcards

Front 1

What % of ALS is familial?

Back 1

5%

Front 2

What is the associated genetic mutation for ALS

Back 2

in 20% of the familial cases; chromosome 21 superoxide dismutase gene

Front 3

What is the pathology in the anterior horn cells in ALS

Back 3

Bunina bodies; intracytoplasmic, eosinophilic inclusions in anterior horn cells

Front 4

What are Bunina Bodies

Back 4

intracytoplasmic, eosinophilic inclusions in anterior horn cells

Front 5

What is Mills Variant ALS?

Back 5

Disease primarily starts on one side of the body, hemiplegic variant

Front 6

What is the action of Riluzole?

Back 6

glutamate presynaptic inh, prolongs survival in ALS pt. by 2-3 months; more marked in bulbar onset disease

Front 7

Spinal muscular atrophy 1
Werdnig Hofmman clinical sx

Back 7

never sit, floppy baby, poor suck, respiratory distress
85% die by 2 years

Front 8

What is the survival for Werdnig Hoffman?

Back 8

85% die by 2 years

Front 9

SMA type 2 clinical sx

Back 9

onset 6 mos. to 1 year, may survive past 2 years

Front 10

Kugelberg Welander clinical sx

Back 10

late childhood or adolescence, slowly progressive gait disorder, bulbar muscles usually spared

Front 11

Fazio Londe clinical sx

Back 11

childhood bulbar muscular atrophy
late childhood to adolescence onset, dysarthria, dysphagia, facial diplegia, tongue wasting with fibrillations

Front 12

Kennedy's Disease clinical sx

Back 12

X linked recessive trinucleotide repeat disorder CAG repeat androgen receptor protein; gynecomastia, bulbar weakness

Front 13

Primary lateral sclerosis

Back 13

rare, <5% of all motor neuron disease, onset after 40, slowly progressive spastic gait that stabilizes , rarely lose the ability to walk with a cane or some other assistance, sphincter is preserved

Front 14

West Nile Virus Poliomyelitis clinical symptoms

Back 14

flavivirus, causes a menigoencephalitus as well as lower motor neuron poliomyelitic syndrme,

Front 15

What is the genetic abnormalitiy for Duchenne's muscular dystrophy

Back 15

X linked recessive, deletion or duplication in Xp21, female carrier

Front 16

What is the pathophysiology for Duchenne's muscular dystrophy?

Back 16

Dystrophin is a cytoskeletal protein which usually acts to stabilize the membrane, abnormality causes the sarcolemma to become unstable allowing influx of calcium

Front 17

Duchenne's Muscular Dystrophy clinical symptoms

Back 17

difficulty walking, gower maneuver, calf hypertrophy common, rare weakness of face, rapid progression, 12 wheelchair bound, 20 respiratory dependent , heart involved late

Front 18

Fascioscapulohumeral dystrophy chromosome

Back 18

chromosome 4

Front 19

Fascioscapulohumeral dystrophy clinical sx

Back 19

involves face/trapezius muscles first, lower ext are affected later; assoc. mr, deafness, oropharyngeal disturbances

Front 20

Limb Girdle MD

Back 20

usually onset 20s to 30s with pelvic involvement spreads to involve shoulders, increased cpks, pseudohhypertrophy, nl lifespan

Front 21

The path shows long rows of central sarcolemmal nuclei

Back 21

Myotonic Dystrophy

Front 22

What is the chromosome, mechanism and product of Myotonic Dystrophy

Back 22

Chr. 19
>40 CTG repeats (triplet repeat)
myotonin

Front 23

What are the clinical sx of MD?

Back 23

facial weakness
hatchet face, ptosis, thin scm, frontal balding, cataracts, testicular atrophy, mr, cardiac conduction abnormality, respiratory muscle weakness, percussion myotonia, milkmaid grip

Front 24

What is the defect of myotonia congenita thought to be due to?

Back 24

abnormal chloride conductance

Front 25

Oculopharyngeal muscular dystrophy chromosome, mechanism, gene product

Back 25

Triplet Repeat disorder
GCG in French Canadians & New Mexico Hispanics
GCA in Louisiana Cajuns
Chromosome 14
poly adenylate binding protein, adds the polyA tail to mRNA, abnormal, causes misfolding and filaments to build up intranuclear

Front 26

OPMD clinical symptoms

Back 26

progressive asymmetric ptosis usually 50s, opthalmoplegia, distal symmetric weakness, dysphagia

Front 27

The pathology shows tubulofilamentous inclusions in a 50 year old woman Louisiana Cajun with progressive ptosis, opthalmoplegia and dysphagia

Back 27

Oculopharyngeal muscular Dystrophy

Front 28

Emery Dreifuss Syndrome Clinical SX

Back 28

X linked recessive d/o;
humeroperoneal weakness, early contracts, neck flexion and elbow flexion constriction, cardiac abnormalities in >95% of patients with a fib and slow ventricular rate; onset usuall teens

Front 29

Emery Dreifuss Syndrome hereditary and pathophysiology

Back 29

X linked dominant or recessive,
abnormality in emerin or lamin A or B

Front 30

What are the clinical features of Trichinella myopathy?

Back 30

cranial nerves involved EOM, dysphagia, dysarthria
trichinella myocarditis can cause emboli

Front 31

What tests are used for the diagnosis of trichinella myopathy?

Back 31

eosinophilia
bentonate flocculation assay
muscle biopsy

Front 32

What is the treatment for trichinella myopathy?

Back 32

thiobendazole

Front 33

The Gomori Trichrome stained muscle biopsy shows red rod-like inclusion near the sarcolemma

Back 33

Nemaline Rod Myopathy

Front 34

What type of endocrine problems do patients with myotonic dystrophy get?

Back 34

Hyperinsulinemia, rare frank diabetes
Infertility in women
testicular atrophy

Front 35

Myotonia Congenita Thomsen's Disease chromosome, inheritance

Back 35

Autosomal Dominant
Chromosome 7
Abnormal Chloride Channel Conductance

Front 36

Myotonia Congenita Clinical Symptoms

Back 36

Myotonia often severe lower limbs> upper limbs, gait abnL
without the systemic sx of MD (cataracts, MR, testicular atrophy, endocrine, cardiac, no muscle weakness ) ;
provoked by cold, "warming up
phenomenon" with exercise,myotonia improves; Mini-Hercules apperance

Front 37

Paramyotonia Congenita chromosome, inheritance

Back 37

Autosomal dominant, Sodium Channel; mostly chromosome 17

Front 38

Paramyotonia Congenita clinical symptoms

Back 38

Similar to hyperkalemic periodic paralysis; begins in childhood, myotonia intensifies with exercie, cold cause stiffnes of bulbar and limb muscles

Front 39

How to distinguish paramyotonia congenita from myotonia congenita

Back 39

Paramyotonia congenita worsens with exercise, both provoked by cold, may have high potassium during an attack for paramyotonia congenita

Front 40

How to distinguish myotonic dystrophy from myotonia congenita

Back 40

lack of systemic symptoms such as endocrinopathy, cataracts, cardiac, mr, muscle weakness. Myotonia congenita patients also have mini-Herculues appearance

Front 41

What are the clinical symptoms of Nemaline rod myopathy

Back 41

AD, childhood acquired, nonprogressive myopathy, often infantile hypotonia, dysmorphic features such as high-arch palate, club feet, kyphoscoliosis, high arched feet, elongated face, elevated CPK

Front 42

What is the distribution of weakness for myotonic dystrophy?

Back 42

Distal involvement: finger flexors and foot drop, bulbar

Front 43

What is the distribution of weakness for emery dreifuss myopathy

Back 43

humeroperoneal (rare limb girdle)

Front 44

What is the distribution of weakness for infectious myopathies?

Back 44

proximal symmetric

Front 45

What is the pattern of weakness for nemaline myopathy

Back 45

scapuloperoneal

Front 46

What is the pattern of weakness for Fazio Londe?

Back 46

Bulbar

Front 47

What is the pattern of weakness for LEMs?

Back 47

generally spares ocular muscles

Front 48

What is the pattern of weakness for centronuclear myopathy?

Back 48

facial weakness, extraocular muscle palsy at birth, can also affect proximal/distal muscle

Front 49

What is the inheritance of Centronuclear or Myotubular Myopathy?

Back 49

Fetal myocytes
X linked recessive

Front 50

Centronuclear Myopathy Clinical features

Back 50

Facial weakness infant some proximal and distal limb weakness

Front 51

Central Core myopathy inheritance

Back 51

autosomal dominant chromosome 19, ryanodine receptor

Front 52

Central Core myopathy features

Back 52

myopathy and can be assoc. with malignant hyperthermia; hypotonia, proximal weakness, dev. delay, hip dislocations, skeletal deformities such as kyphoscoliosis

Front 53

Cytoplasmic Body myopathy

Back 53

desmin accumulation; proximal weakness, face, neck, respiratory and spinal muscles

Front 54

Hyperkalemic Periodic Paralysis chromosome, inheritance, defect

Back 54

Chromosome 17
Sodium Channel AD with almost complete penetrance

Front 55

Hyperkalemic periodic paralysis clinical sx

Back 55

episodes of paralysis less severe than hypokalemic periodic paralysis; hours to days; induced by cold, triggered by hunger,potassium worse with exercise; mild myotonia either on EMG or clinically

Front 56

Hyperkalemic periodic paralysis treatment

Back 56

Calcium Gluconate Insulin

Front 57

HYpokalemic periodic paralysis inheritance, chrosome, gene

Back 57

autosomal dominant,
chromosome 1, L type calcium channel

Front 58

Hypokalemic periodic paralysis clinical symptoms

Back 58

triggers: rest, cold, insulin, carb-heavy meal time: night or early morning severity: severe hours to weeks no myotonia

Front 59

Hypokalemic periodic paralysis treatment

Back 59

diamox prevents >90% attacks
Potassium IV acute treatment

Front 60

Polymyositis clinical sx

Back 60

proximal myopathy
no muscle tenderness
elevated CPK
cell mediated
30% assoc. with malignancy

Front 61

Polymyositis pathology

Back 61

infiltration around muscle cells by CD8 T cells, necrosis

Front 62

Dermatomyositis clinical sx

Back 62

mechanic's hands, gottron's papules, heliotrope rash, shawl sign
proximal myopathy
elevated CPK
humoral mediated
assoc. with SLE, sjogrens, PAn

Front 63

dermatomyositis pathology

Back 63

perifascicular atrophy

Front 64

Inclusion Body myositis clinical sx

Back 64

age usually > 50, male predominance
distal finger flexors + proximal hip flexor weakness

Front 65

inclusion body myositis pathology

Back 65

rimmed vacuoles

Front 66

polymyositis treatment

Back 66

prednisone, immunosuppressant, search for neoplasm

Front 67

dermatomyositis treatment

Back 67

prednisone, immunosuppresant

Front 68

ibm treatment

Back 68

poor response to steroids, trials of IVIG, no proven benefit to treatments

Front 69

This patient has noticed dryness on the extensor surface of the MCPs along with difficulty climbing stairs and brushing hair

Back 69

Gottron's papules
Dermatomyositis

Front 70

Patient noticed discoloration around the eyes. Recently diagnosed with Lupus

Back 70

Heliotrope rash, dermatomyositis

Front 71

Patient's husband noted discoloration around her shoulder along with proximal weakness

Back 71

Shawl sign, dermatomyositis

Front 72

60 year old man who has noticed progressive difficulty with buttoning clothes and arising from a chair.

Back 72

IBM, rimmed vacuoles on congo red stain

Front 73

In addition to weakness, this patient noticed some changes around their nails.

Back 73

Periungual erythema
Dermatomyositis

Front 74

This patient was recently diagnosed with lung cancer. He comes in presenting with symmetric proximal weakness

Back 74

CD8 cell infiltration around the muscle and necrosis. Non-specific. Polymyositis is a possibility.

Front 75

This patient was recently diagnosed with lung cancer. He comes in presenting with symmetric proximal weakness

Back 75

CD8 cell infiltration around the muscle and necrosis. Non-specific. Polymyositis is a possibility.

Front 76

6 month old with hypotonia since birth, developmental delay and recent hip dislocation.

Back 76

Central core myopathy
chromosome 19
assoc with malignant hyperthermia

Front 77

3 month old boy with weakness with ptosis, eom palsy and facial weakness noted since birth. Mild progression with involvement of the proximal and distal muscles as well.

Back 77

Centronuclear myopathy on H&E stain, normal nuclei are at the sides of the muscle

Front 78

Patient presented with proximal weakness. Muscle biopsy shown with H&E stain

Back 78

Perifascicular atrophy
Dermatomyositis
Capillary ischemia thought to cause this pathognomonic path finding

Front 79

What is the missing enzyme in Pompe's disease Type 2 Glycogenosis

Back 79

acid maltase deficiency

Front 80

Pompe's Dz clinical sx

Back 80

Limb-girdle weakness, childhood or late adolescent onset, hepatomegaly, enlarged tongue, cardiac abnL, propensity for respiratory failure

Front 81

Pompe's Dz Diagnosis

Back 81

Autosomal recessive
muscle biopsy with vacuoles

Front 82

What is the enzyme affected in McArdle's Disease Type 5 Glycogenosis

Back 82

myophosphorylase which usually acts to convert glycogen to glucose during exercise

Front 83

McArdle's Disease Clinical symptoms

Back 83

painful cramping during exercise, myoglobinuria, cramps, mild proximal weakness between episodes; exercise intolerance

Front 84

McArdle's Diseae Diagnosis

Back 84

Autosomal recessive (rare AD)
ischemic exercise test with abnormal rise in serum lactate
biopsy with a necrotic myopathy

Front 85

Tarui's Disease enzyme affected

Back 85

Muscle Phosphofructokinase. conversion of F-6-phosphate to 1-6 diphosphate

Front 86

How to differentiate Tarui's disease from McArdle's?

Back 86

Assay for phosphofructokinase on muscle biopsy

Front 87

How to differentiate Pompe's Disease from Limb Girdle?

Back 87

tongue enlarged for Pompe's disease

Front 88

Explain the 2nd wind phenomena in relation to McArdle's Disease

Back 88

Repetitive contraction causes cramping but this can improve if the pt. slows down and rests due to release of free fatty acid as the 2nd energy source

Front 89

Tarui's disease clinical symptoms

Back 89

limb weakness, seizures, cortical blindness and corneal opacities can occur . exercise intolerance, cramping, myoglobinuria

Front 90

How do you do the ischemic exercise test?

Back 90

Take a pre-exercise blood sample. Then inflate a blood pressure cuff to 50 mm HG more than systolic pressure. Then exercise the arm by pumping the first for 1 minute. Then deflate the cuff and take a 1 minute sample, 2 minute sample and 4 minute sample. Patients with McArdle's or Tarui disease will not have normal rise in lactate.

Front 91

What is the pathophysiology of carnitine deficiency resulting in myopathy?

Back 91

Lipids serve as muscle energy source during rest and prolonged low intensity exercise. Carnitine couples to the FFA and then they enter the mitochondria. Carnitine dficiency results when there is decreased ability to uptake the carnitine.

Front 92

Carnitine deficiency clinical symptoms

Back 92

limb-girdle weakness, episodic hepatic insufficiency; congenital slowly progressive myopathy

Front 93

Carnitine deficiency diagnosis

Back 93

muscle biopsy with lipid droplets in type 1 fibers,

Front 94

Carnitine palmitoyl transferease deficiency pathophysiology

Back 94

Carnitine palmitoyl genearlly catalyze the binding of carnitine to FFA. The lipids cannot move into the mitochondria because of the lack of carnitine

Front 95

Carnitine palmitoyl transferase deficiency clinical sx

Back 95

painful cramps on exercise or fasting, recurrent myoglobinuria, strong muscle between attacks, cramping with exercise

Front 96

What is the most common mitochondrial myopathy?

Back 96

Kearns-Sayre Disease

Front 97

Kearns Sayre Disease diagnosis

Back 97

Triad: 1) age < 2 2)progressive opthalmoplegia 3)pigmentary retinopathy + 1 of following:
- MRI/CT leukoencephalopathy
-CSF protein >100
- cerebellar dysfunction
- HEART BLOCK

biopsy: ragged red fibers

Front 98

Kearns Sayre Disease clinical symptoms

Back 98

progressive opthalmoplegia, progressive weakness, conduction block, endocrine abnomallity, sensorineural deafness, pigmentary retinopathy, ataxia, dementia, lactic acidosis

Front 99

Myoclonic Epilepsy Ragged Red Fibers genetics

Back 99

point mutation 8344 or 8356 for mitochondrial DNA for transfer RNA

Front 100

MERRF clinical symptoms

Back 100

Triad: 1) myoclonus 2) myoclonic epilepsy 3) cerebellar dysfunction with common features: short stature, ataxia, dementia, lactic acidosis, progressive weakness

Front 101

Mitochondrial encephalopathy, lactic acidosis and stroke like episodes genetics

Back 101

point mutation 3243 gene for transfer RNA for leucine

Front 102

MELAS clinical sx
age 3-65 years

Back 102

multiple strokes not conforming to a vascular territory, recurrent headaches, DIABETES, short stature, SEIZURES dementia, lactic acidosis, age less than 40

Front 103

Leigh disease defect

Back 103

pyruvate dehydrogenase or cytochrome oxidase in respiratory chain

Front 104

Leigh disease clinical sx

Back 104

age onset < 2 years, floppy baby, seizures, respiratory difficulty, lactic acidosis, CSF elevated lactate, hypotonia, weakness, ataxia, developmental delay, opthalmoplegia

Front 105

Isaac's Syndrome Neuromyotonia clinical symptoms

Back 105

Myotonia, Myokymia/Stiffness that persists during sleep/anesthesia, hyperhidrosis assoc; no weakness, occasionally assoc. with paraneoplastic, can lead to posturing

Front 106

Stiff Person syndrome pathophysiology

Back 106

assoc with anti-glutamic acid decarboxylase enzyme which is the rate limiting step for GABA production

Front 107

Stiff Person syndrome Clinical Sx

Back 107

stiffness that improves with sleep, painful muscle contraction, usually affects the trunk, 80% female, occasionally paraneopalstic

Front 108

What is the treatment for stiff peron syndrome

Back 108

benzodiazepines, baclofen, vigabatrine, immunomodulation such as IVIG

Front 109

What cortex layer does the pyramidal cells of Betz arise from?

Back 109

Layer 5

Front 110

Why does pseudobulbar emotional lability occur in ALS?

Back 110

Limbic motor control arises from the periaqueductal gray and nucleus retroambiguens and projects to CN for pharyngeal, soft palate, intercostal, diaphragm, abd and laryngeal muscle

Front 111

What is thought to be the etiology of cerbebellar cognitive affective syndrome?

Back 111

Cerbellar connections between cerebral association and limbic regions are disconnected by structural lesions, leading to loss of emotional control

Front 112

Define spasticity

Back 112

caused by abnormal balance between excitatory and inhibitory input into motor, there is a resistive catch during passive movement

Front 113

What is the proposed pathophysiology of primary lateral sclerosis?

Back 113

loss of layer 5 pyramidal cells of betz in the frontal and prefrontal motor cortex

Front 114

What is the clinical symptomatology of PLS?

Back 114

spastic gait disorder that starts to involve the upper limbs, generally spares/late involvement of bladder dysfunction, generally spares/late involvement of muscle atrophy, purely motor UMN, some reports describe change to ALS as long as 27 years -> need reexamination; age 50s younger than ALS patients

Front 115

What is the genetics, protein cellular mechanism proposed for hereditary spastic paraplegia?

Back 115

autosomal dominant 40% spastin, plays a role in axonal transport

Front 116

What are the clinical symptoms of hereditary spastic paraplegia

Back 116

Pure HSP would be bilateral lower extremity spasticity, varying weakness, usually presents 20-40, generally with a variable family history (difficult if spontaneous mutation)

complicated HSP: ataxia, ichthyosis, deafness, optic neuropathy, peripheral neuropathy, amyotrophy, dementia, mr, bladder dysfunction, evan's syndrome (AIHA/Thrombocytopenia)

Front 117

What are the endemic regions for Human T-Lymphotropic virus Type 1?

Back 117

Caribbean, Africa, South Africa, Japan, (some Asia, central America, South America)

Front 118

What is the clinical symptomatology for HTLV-1 associated myelopathy and tropical spastic paraparesis?

Back 118

HAM-(Japan)/TSP(Caribbean) slowly progressive paraparesis, presents in 30s, bladder dysfunction, hyperreflexia, sensory neuropathy, can have optic neuropathy (some assoc. with sjogrens)

Front 119

How should the diagnosis of HTLV-1 associated myelopathy/TSP be made?

Back 119

CSF for HTLV-1 DNA PCR and HTLV-1 antibody with elevated IgG index, serum for HTLV-1

Front 120

Does HTLV-2 cause neurological disease?

Back 120

Previously thought no, but now there is a spastic paraparesis, bladder dysfunction, hyperreflexia related to HTLV 2 without HTLV 1, consider in IV drug users

Front 121

What is the gene, protein, and abnormality in Adrenomyeloneuropathy?

Back 121

Xq28, ABCD1 gene, atp-binding cassette transporter protein, abnl peroxisomal beta oxidation, accumulation of VLCFA in cells

Front 122

Diagnostic test for Adrenomyeloneuropathy?

Back 122

VLCFA in plasma, red blood cells, skin fibroblasts

Front 123

Clinical symptoms of adrenomyeloneuropathy?

Back 123

X-linked primarily men although carriers can have a slowly progressive myelopathy as well; +/- bladder dysfunction +/- sensory neuropathy +/-adrenal insufficency

Front 124

What is lathyrism?

Back 124

UMN only d/o attributed to consumption of chickling pea flour. Spastic paraparesis, +/- sensory d/o and bladder dysfxn, irreversible; excitotoxin which increased reactive oxidative stress

Front 125

What is konzo?

Back 125

spastic paraparesis attributed to consumption of kassava roots not properly soaked; excitotoxcin stimulates AMPA glutamate receptor

Front 126

What is thought to be the agent of ALS-Parkinsonism-Dementia complex of guam

Back 126

cycad seed consumption through flying fox with cyanobacteria toxin

Front 127

What is the pathophysiology of spinal muscular atrophy?

Back 127

Autosomal recessive. Deletion in SMN gene on chromosome 5. SMN gene plays a role in spliceosome for nuclear RNPs. Also check the SMN 2 gene, because more SMN 2 better prognosis

Front 128

What is SMA 5?

Back 128

SMA 5 is a distal presentation myopathy (unclear if distinct from HMN 5 CMT variant) newly described

Front 129

What is the genetics for SMA 5?

Back 129

AD/AR/Sporadic
GARS (glycyl t-RNA synthetase

Front 130

What is benign focal amyotrophy?

Back 130

ALS variant, monomelic (1 limb, can be brachiocephalic) focal, benign course, LMN predominant, rarely can spread to opposite limb or progress to ALS

Front 131

What is Hirayama's disease?

Back 131

Benign focal amyotrophy first described by Hirayama who originally thought it was due to mechanical impingment

Front 132

What is the clinical course of benign focal amyotrophy?

Back 132

idiopathic slowly progressive, painless (2-3 years, stable by 5 years) focal amyotrophy, 75% upper ext. sometimes hypesthesia

Front 133

What percentage of ALS patients present with bulbar onset?

Back 133

25%

Front 134

What % of ALS patients present with respiratory weakness?

Back 134

1-2 %

Front 135

What disease is minipolymyoclonus a heralding sign for?

Back 135

spinal muscular atrophy

Front 136

What facial muscle is always preserved in SMA?

Back 136

Extraocular muscle is always spared

Front 137

How to distinguish limb-girdle myopathy from adult onset SMA?

Back 137

In limb girdle the triceps is stronger than biceps; in SMA the biceps is stronger than the triceps (much)

Front 138

What are the clinical charactertistics of Kennedy's disease (bulbospinal neuronopathy)?

Back 138

gynecomastia, testicular atrophy
bulbar onset weakness pt. in 50s; tremor, sensory sx, calf pseudohypertrophy

Front 139

What important group of muscles does Kennedy's disease tend to spare?

Back 139

respiratory

Front 140

What is the genetics, moa of Kennedy's?

Back 140

CAG trinucleotide repeat >40, androgen receptor protein, X linked recessive;
polyglutamine causes abnormal aggregates which impair tubulin-mediated cellular transport

Front 141

In Kennedy's disease, what clinical symptoms do female carriers display?

Back 141

Some have been reported to have late onset bulbar dysfunction

Front 142

What are the chances of a female sibiling of a Kennedy's disease patient carrying the disease?

Back 142

50% due to X chromosome inactivation

Front 143

What is the clinical symptomatology of progressive muscular atrophy?

Back 143

Considered a variant of ALS with longer survival, LMN primarily, need to be reexamined X 3 years to evaluate for progression to UMN/ALS, younger age of set 55-65

Front 144

What are some of the proposed mechanisms for ALS?

Back 144

free radicals, cellular transport, immunologic, mitochondrial abnormality, excitotoxicity

Front 145

What are some of the variants of ALS?

Back 145

monomelic 1 limb
flail/barrier both upper limbs
mills hemiplegic
bulbar onset
respiratory onset

Front 146

When should a PEG be placed in ALS patients according to ALS practice parameters?

Back 146

Before the FVC falls to less than 50%

Front 147

What percentage of ALS patients also have FTD

Back 147

30-50%

Front 148

What is the mean survival of ALS?

Back 148

3 years

Front 149

What is the mean survival for bulbar onset ALS?

Back 149

12-24 months

Front 150

What prognostic factors indicate a poor prognosis for ALS?

Back 150

aggressive course, poor nutrition, depression, bulbar onset, dyspnea at onset, age more than 65

Front 151

What percentage of anterior horn cells have to be lost before pt. start exhibiting symptoms of ALS?

Back 151

patients do not exhibit symptoms until they have less than 30% of normal anterior horn cells

Front 152

What is the usual age of presentation for ALS patients?

Back 152

65 to 74

Front 153

What is the genetic abnormality in Machado Joseph disease or spinocerebellar ataxia type 3?

Back 153

CAG triplet repeat, ataxin 3 gene, chromosome 14, aggregates that interfere with cellular proteosome

Front 154

What are the clinical symptoms in Machado Joseph disease and compare to ALS?

Back 154

spasticity, fasciculations, prominent cerebellar ataxia, opthalmoplegia, extrapyramidal sx such as dystonia or rigidity; protuberant eyes

Front 155

What is allgrove's syndrome or Four-A syndrome?

Back 155

1) Alacrima
2) Achalasia
3) Adrenocorticotrophic insufficiency
4) amyotrophy

Front 156

What is post-polio syndrome?

Back 156

many years after surviving polio people can get dysarthria, dyphagia, depression, muscle fatigue, pain, sleep disturbances, cold intolerance

Front 157

What is adult polyglucosan body disease?

Back 157

rare late-onset UMN & LMN & cognitive decline, sensory loss, bowel & bladder dysfunction; diagnosis by skin/nerve biopsy showing polyglucosan bodies,

Front 158

What is the prognosis for paraneoplastic motor neuron isease

Back 158

generally do not respond well to treatment of the tumor per Bradley

Front 159

How does the clinical course and natural history of HIV Type 1 associated motor neuron disorder differ from ALS?

Back 159

HIV motor neuron d/o age of onset younger, responds to HAART and is reversible

Front 160

What is the target of antibodies for dermatomyositis?

Back 160

endothelial cell capillaries via complement-mediated lysis, membrane attack complex

Front 161

Why does perifascicular atrophy happen?

Back 161

Capillary ischemia

Front 162

What is the sensitivity of binding, blocking & modulating antibodies?

Back 162

93, 88, 71

Front 163

What percentage of patients that are seronegative for AchR antibodies have MUSK antibodies?

Back 163

38-50%

Front 164

What percentage of patients are seronegative?

Back 164

6-12%

Front 165

What percentage of patients with striational antibodies have thymoma?

Back 165

80% from the age of 20-50
**after 50 the false positive rate goes up to 50%
**below 20 thymoma is rare

Front 166

What is the sensitivity of repetitive nerve stimulation for diagnosing MG?

Back 166

88%
use 2 to 3 HZ stimulation
decrement of 10% in the CMAP is diagnostic for myasthenia gravis
jitter is nonspecific

Front 167

When should the ice pack test be used?

Back 167

In cases of overt ptosis there is an 80% sensitivity. However, EOM weakness & muscular weakness are too unreliable to have positive predictive value.

Front 168

When should the tensilon test be used?

Back 168

It can be used at the bedside with a crash cart, has a 30-45 second onset of action and duration of 5 minutes

Front 169

What is the duration of action of pyridostigmine?

Back 169

3-4 hours

Front 170

How to treat the cholinergic side effects of pyridostigmine?

Back 170

You could give medications such as glycopyrollate with anti-cholinergic activity that has little to no effect on the nicotinic receptors

Front 171

What are the benefits to thymectomy in patients WITHOUT THYMOMA under the age of 60?

Back 171

Complicated issue:
1) 1.5 times more likely to become asymptomatic with thymectomy
2) 2 times more likely to have medication-free remission
3) the beneficial effect of thymectomy is delayed and takes several years to accrue

Front 172

What is a typical starting dose for pyridostigmine treatment in MG?

Back 172

Pyridostigmine 30 mg TID

Front 173

What percentage of patients presents with ocular symptoms?

Back 173

50% and half of those patients will become generalized, half will remain purely ocular

Front 174

What percentage of ocular MG patients are seronegative for achR antibody?

Back 174

only 40 to 50% have binding, blocking, modulating antib; musk antibody is also rare

Front 175

What percentage of myasthenic patients experience a crisis?

Back 175

15-20%

Front 176

When does the myasthenic crisis usually occur?

Back 176

in the first 2 years after diagnosis in 74% of patients

Front 177

What is Hirayama disease?

Back 177

juvenile segmental muscular atrophy, focal weakness and atrophy of the muscles of the hand and forearm initially progressive then stops. Usually unilateral but can be bilateral.

Front 178

Why is it important to obtain anterior flexion MRI Cspine on patients with distal weakness/atrophy?

Back 178

Important because on anterior flexion patients with hirayama disease can develop anterior displacement of the dural sac and posterior epidural venous gorging for hirayama disease

Front 179

what is characteristically seen on cervical mri in patients with hirayama disease?

Back 179

cervical spinal cord atrophy

Front 180

What finding can be found on EMG of acid maltase deficiency?

Back 180

increased insertional activity, fibrillations and particularly clinical myotonia in the paraspinal muscles

Front 181

What is the gene involved in myotonic dystrophy?

Back 181

dystrophia myotonia protein kinase (DMPK) gene

Front 182

What is the gene, protein, chromosome and abnormality in DM2?

Back 182

zinc finger protein
tetranucleotide CCTG expansion

Front 183

What is the differential diagnosis of myoglobinuria?

Back 183

Inflammatory myopathies (rare), limb-girdle muscular dystrophy 2C-2F (sarcoglycanopathies), metabolic myopathies, lipid d/o, carnitine palmitoyltransferase deficiency, myophosphorylase deficiency, malignant hyperthermia, duchenne muscular dystrophy, central core myopathy

Front 184

What is affected in limb girdle dystrophy 2C-2f?

Back 184

sarcoglycanopathies

Front 185

How should you distinguish myotonia from paramyotonia or pseudomyotonia?

Back 185

myotonia should improve with exercise and paramyotonia worsens with exercise

Front 186

Which myopathies may present with respiratory failure?

Back 186

myotonic dystrophy, centronuclear myopathy, nemaline myopathy, or acid maltase deficiency

Front 187

Which myopathies can affect the cardiac muscle?

Back 187

Duchenne
Becker
Limb girdle (sarcoglycan, fukutin, laminopathy, telthoninopathy)
Emery dreifuss
Andersen

Front 188

Which myopathies may have hepatomegaly?

Back 188

pompe's disease or acid maltase deficiency and carnitine deficiency

Front 189

Which myopathies develop early contractures?

Back 189

emery dreifuss, lgmd, bethlem myopathy

Front 190

Which myopathies are associated with prominent scapular winging?

Back 190

FSH, LGMD 1B (laminopathy), LGMD2A (calpainopathy) and LGMD2c-2f (sarcoglycanopathes)

Front 191

What are 6 criteria for the diagnosis of myotonia fluctuans?

Back 191

1) eyelid paramyotonia
2) warm up phenomenon in limbs
3) no weakness or episodic weakness
4) not provoked by cold
5) exacerbated by exercise
6) fluctuating myotonia of varying severity

Front 192

What is myotonia permanens?

Back 192

a severe form of myotonia fluctuans characterized by dyspnea, hypoxia, acidosis secondary to respiratory muscle myotonia and less fluctuations than myotonia congenita

Front 193

What are the characteristics of acetazolamide responsive myotonia

Back 193

this is a myopathy characterized by stifness, action myotonia, percussion myotonia. Worse with exercise, cold, potassium. Eased with carbohydroate load. Secondary to sodium channel. No WEAKNESS

Front 194

What age does hyperkalemic periodic paralysis generally present.

Back 194

1st decade of life; after 30s less likely to be hyperkalemic periodic paralysis

Front 195

What is the most common mutation causing hypokalemic periodic paralysis ?

Back 195

calcium channel
chromosome 1

Front 196

What are some features that distinguish between hyperkalemic periodic paralysis and hypokalemic periodic paralysis.

Back 196

No episodic weakness in hypo, no myotonia in hypo (rarely eyelids), triggers hypo tends to be carbohydrate meals and rest after exercise, hypo is more likely to present after the 3rd decade, hyperkalemic periodic paralysis rarely causes generalized weakness, usually focal

Front 197

What is the triad associated with Andersen Twail syndrome?

Back 197

ventricular dysrhythmia, weakness, dysmorphism (hypertelorism, short stature, high palate)

Front 198

What are the 3 types of GSD II or acid maltase deficiency?

Back 198

1) infantile "Pompe's" macroglossia, cardiomegaly, hepatomegaly- death by 2 yrs b/c resp failure
2) juvenile- 1st decade of life proximal > distal weakness
less cardiomegaly/hepatomegaly/macroglossia; death by 30
3) adult- no cardiomegaly/hepatomegaly/macroglossia; rare scapuloperoneal, proximal > distal weakness

Front 199

What is the deficient enzyme in Pompe's disease?

Back 199

lysosomal alpha glucosidase

Front 200

What is the deficient enzyme in Cori-Forbes disease?

Back 200

debrancher enzyme GSD III, makes up 25% of all GSD

Front 201

What are the features of Cori-Forbes disease?

Back 201

IIIa- liver only
IIIb- muscle & liver
hepatomegaly, cirrhosis, hypoglycemia
static myopathy 3rd decade with progressive weakness and predilection for resp. muscles

Front 202

How do you diagnose cori-forbes disease?

Back 202

lymphocytes and muscle fibroblasts biochemical assay for debranching enzyme; can also be diagnosed prenatally

Front 203

What is Glycogen storage disease type IV characterized by in adult presentations?

Back 203

umn/lmn signs, sensory neuropathy, cerebellar ataxia, neurogenic bladder and dementia a.k.a. polyglucosan body disease

Front 204

How can you distinguish clinically between DMD and BMD?

Back 204

age of wheelchair confinement.
Wheelchair <13->DMD
wheelchair >16-> BMD
13-16 "Outliers"

Front 205

What are some features that differentiate DMD & BMD?

Back 205

BMD tends to develop later 5-15 years old; less MR and no GI symptoms (gastric obstruction/intestinal hypomotility can be present in DMD)

Front 206

What is the usual starting dose of prednisone in DMD?

Back 206

0.75 mg/kg/day for 3 months then can decrease to 0.5 mg/kg/day

Front 207

What is the evidence for benefit of steroids in DMD?

Back 207

prolongs ambulation by 2 years

Front 208

What is considered the therapeutic age window for steroid treatment for dystrophinopathies?

Back 208

5 to 15 years, steroids are considered treatment of choice

Front 209

What is the mode of inheritance in Emery Dreifuss muscular dystrophy?

Back 209

depends on the gene involved
emerin- x linked recessive
lamin a/c- ad or ar

Front 210

What is the pattern of muscular involvement in EDMD?

Back 210

humeroperoneal- biceps/triceps first than peroneal muscles such as dorsiflexion; mild facial involvement, significant cardiac involvement (50% with sudden cardiac death) and usually not severe respiratory involvement

Front 211

What are some subtypes of dystrophinopathies?

Back 211

carriers with mild weakness
XLDCM
myoglobinuria & cramps sans weakness
isolated quadriceps myopathy

Front 212

What is the treatment for myotonic dystrophy?

Back 212

mexilitine which is a sodium channel blocker/antiarrhythmic, can treat myotonia

Front 213

What is the genetics, protein, mode of inheritance for Myotonic Dystrophy DM1?

Back 213

autosomal dominant, myotonin protein kinase, triplet repeat disorder usually more than 80

Front 214

Differentiate between PROMM/DM2 and myotonic dystrophy/DM1

Back 214

mod

Front 215

What are the clinical features of Cori-Forbes or GSD III?

Back 215

deficient debrancher enzyme, progressive proximal myopathy, distal weakness UMN/LMN, some with sensory neuropathy

Front 216

What is the deficient enzyme in Cori-Forbes?

Back 216

Debrancher enzyme

Front 217

What is the out of wind phenomenon?

Back 217

Tarui's disease, cannot use glucose so giving glucose pre-exercise causes worsening exercise intolerance b/c of dec ffa & ketones

Front 218

What are 2 x linked metabolic myopathies?

Back 218

phosphorylase beta kinase deficiency (AR-> neuromusc)
phosphoglycerate kinase deficiency (PGK)

Front 219

What is a distinguishing feature of LDH deficiency?

Back 219

uterine stiffness requiring c-sxn and genearlized scaly rash during summer

Front 220

Summarize the clinical features of PGK, PBK and LDH deficiency?

Back 220

dynamic myopathy
no weakness b/t attacks
myoglobinuria
exercise intolerance

Front 221

What metabolic myopathy would you suspect if the patient had an abnormal rise in ammonia & normal lactate rise ?

Back 221

myoadenolate deaminase deficiency

Front 222

What is the most common lipid metabolic myopathy?

Back 222

carnitine deficiency

Front 223

What is the most common of frequent recurrent myoglobinuria in adults?

Back 223

CPT deficiency

Front 224

What age do patients with Myoadenylate deaminase deficiency present?

Back 224

late adolescence to middle age

Front 225

What is the mechanism of genetic inheritance of myotonia congenita?

Back 225

autosomal dominant
point mutation in a chloride channel 7q35

Front 226

Why should you avoid muscles that were recently needled by EMg?

Back 226

needle insertion can cause artifacts

Front 227

What is the genetic basis for thyrotoxic periodic paralysis?

Back 227

unknown

Front 228

What is the usual course of natural history of hypokalemic periodic paralysis without treatment?

Back 228

Decreasing severity of attacks with age

Front 229

What is the MOA of Azathioprine?

Back 229

T and B cell synthesis, blocks purine

Front 230

How long does it take for AZA to take effect in MG?

Back 230

up to 1 year

Front 231

What is the MOA of cellcept or mycofenolate mofetil?

Back 231

blocks iminosine monophosophate purine de novo synthesis pathway, takes up to 6 months to take effect

Front 232

What percentage of patients will experience a GI like viral illness characterized by nausea, vomiting, fevers?

Back 232

10%, harati rechallenges and if still with the current symptoms he will not try again

Front 233

What is the most common childhood neuromuscular disorder?

Back 233

Duchenne's muscular dystrophy

Front 234

What percentage of patients with dystrophinopathies are missed by PCR-genetic testing?

Back 234

30%

Front 235

What percentage of patients with dystrophinopathies have autism or mr?

Back 235

30-50%

Front 236

What is the age of presentation of Becker's muscular dystrophy?

Back 236

8 to 50+

Front 237

What is the clinical phenotype of Beckers?

Back 237

proximal hip more than shoulder girdle weakness, isolated quadriceps wasting, +/- calf pseudohypertrophy

Front 238

What percentage of dystrophinopathy patients may have no relatives with symptoms?

Back 238

up to 1/3

Front 239

What is the clinical difference between Duchenne MD and Becker MD?

Back 239

BMD patients are ambulatory past age of 16

Front 240

What is the rare dilated cardiomyopathy only form of DMD called?

Back 240

X-linked DMD associated dilated cardiomyopathy

Front 241

What is the mode of inheritance for SDH?

Back 241

pure nuclear

Front 242

What is the mode of inheritance for COX?

Back 242

both nuclear and mitochondrial

Front 243

What is the mode of inheritance for NADH?

Back 243

pure mitochondrial

Front 244

Which muscle type is primarily oxidative?

Back 244

type 1

Front 245

What muscle types is predominantly dependent on glycogen?

Back 245

type 2

Front 246

What is dystrophin?

Back 246

cytoskeletal protein mantains the integrity of the muscle, "scaffolding"

Front 247

What is emerin?

Back 247

nuclear envelope protein, emerin absent- look at nuclei

Front 248

What are some features of interdisciplinary care required in dystrophinopathy patients (6)

Back 248

1) GI- decreased smooth muscle, gastroparesis, watch out for obstruction- bowel regimen
2) cardiac- echo annually from age 10
3) lungs- PFTs annually, initiating bipap
4) End of life issues
5) Pain- myalgias
6) Spine- referral to spine doctor for scoliosis to improve lung mechanics

Front 249

What percentage of female patients with dystrophin mutations will exhibit symptoms?

Back 249

10%

Front 250

What is one thing to be cautious of before calling a muscle biopsy inflammatory?

Back 250

Dystrophinopathies which are necrotic may look inflammatory, but be physiologic inflammation, if evidence can be found of inflammatory cells devouring a normal muscle this suggests pathologic inflammation

Front 251

What are the current AAN recommendations regarding steroid treatment in DMD?

Back 251

prednisone 0.75 mg/kg/day initiated between age 5-15 has shown benefit in 7 class I studies. Benefit: scoliosis prevention, pulmonary function and a decreased cardiac dysfunction

Front 252

What percentage of female carriers with DMD may have normal CK?

Back 252

up to 30%

Front 253

What should you ask for in history of patients with DMD or BMD?

Back 253

they can have associated adverse reactions to anesthesia

Front 254

What is the PWP of Fragile X syndrome?

Back 254

Prader Willi phenotype characterized by a deletion in 15q with hyperphagia, hoarding, obesity, and developmental delay/ puberty delay

Front 255

What is the inheritance of NADH?

Back 255

pure mitochondrial

Front 256

What is the inheritance of SDH?

Back 256

pure nuclear

Front 257

What is the inheritance of COX?

Back 257

both

Front 258

What pattern is indicated by random atrophy and hypertrophy of both fiber types?

Back 258

myopathic

Front 259

What pattern is indicated by type 1 hypertrophy, fiber type grouping and atrophy of type 1 and type 2?

Back 259

neurogenic (ALS)
SMA- type 1 hypertrophy

Front 260

What does non-specific esterase help with?

Back 260

Overall-denervation appears dark (lysosomes, macrophages)

Front 261

What do nuclear clumps indicate?

Back 261

neurogenic atrophy

Front 262

Which group of LGMD are AD inheritance

Back 262

Group 1, calveolin, lamin a/c, myotilin

Front 263

Which grop of LGMD are AR inheritance

Back 263

Group 2; dysferlin, sarcoglycans and calpain, fukutin related protein

Front 264

What is the etiology of neurotoxicity in acute intermittent porphyria?

Back 264

aminolevulinic acid accumulation

Front 265

What neurologic symptoms are assoc. with acute intermittent porphyria?

Back 265

primarily motor neuropathy
hyporeflexia with preserved achilles reflex
encephalopathy-sz, siadh (rare focal)
abd sx, autonomic dysfunction