NUPY 4_Muscle weakness

Question 1

ALS is an example of which type of cellular adaptation

Answer 1

denervation atrophy

Question 2

Diagnosis?

1. atrophic weakness of the hands and forearms, fasciculations
2. slight spasticity of the arms or legs, and generalized hyperreflexia
3. absence of sensory changes

Answer 2

Amyotrophic lateral sclerosis

UMN+ LMN signs

Question 3

Mutation in ALS

Answer 3

SOD1–>protein misfolding–>aggregates–> axonal disruption, mitochondrial dysfunction–> cell injury

SOD1 gain-of-function mutation encoding copper-zinc superoxide dismutase

Question 4

A common complication/ cause of death in individuals with ALS

Answer 4

respiratory failure due to diaphragmatic atrophy

Question 5

Morphologic features of ALS

Answer 5

Thinning of anterior roots of spinal cord
degeneration of corticospinal tracts, neurogenic atrophy of skeletal muscle fibers
Bunina bodies - PAS + cytoplasmic inclusions

Question 6

Pathogenic basis of spinal muscular atrophy

Answer 6

SMN1 mutation–>defective assembly of small nuclear ribonucleoproteins (snrps)–>impaired spliceosome function

Question 7

Diagnosis?

1 year old infant
unable to lift head up
hypotonia
depressed tendon reflexes
SMN1 mutation

Answer 7

Spinal muscular atrophy

Question 8

Diagnosis?

Male adolescent
Unsteadiness
impaired joint position and vibration sense
Romberg sign +
Extensor plantar repsonse
dysarthria
autosomal recessive condition

Answer 8

Friedreich Ataxia

Degeneration of posterior columns,corticospinal, spinocerebellar tracts

Question 9

Cardiac involvement in Friedrich ataxia

Answer 9

Hypertrophic cardiomyopathy

Question 10

Characteristic foot deformity in Friedrich ataxia

Answer 10

Pes cavus =high plantar arch with retraction of the toes at the metatarsophalangeal joints and flexion at the interphalangeal joints (hammertoes).

Question 11

Pathogenic basis of Friedrich ataxia

Answer 11

GAA trinucleotide repeat expansion –>decreased mitochondrial oxidative phosphorylation+ increased free iron–> oxidative stress

Question 12

Pathogenic mechanism of multiple sclerosis

Answer 12

autoimmune response directed against components of the myelin sheath

Question 13

main physiologic effect of demyelination

Answer 13

impedes saltatory electrical conduction of nerve impulses from one node of Ranvier to the other –>failure of electrical transmission.

Question 14

Cause for visual loss in multiple sclerosis

Answer 14

Optic neuritis

Question 15

Cause for diplopia in multiple sclerosis

Answer 15

internuclear ophthalmoplegia

Question 16

Why does internuclear ophthalmoplegia occur in multiple sclerosis?

Answer 16

demyelination of the medial longitudinal fasciculi

Question 17

Most likely type of internuclear ophthalmoplegia in multiple sclerosis- unilateral or bilateral?

Answer 17

Bilateral

Virtually diagnostic of MS when bilateral

Question 18

appearance of the eye in internuclear ophthalmoplegia

Answer 18

paresis of the medial rectus on attempted lateral gaze, with a coarse nystagmus in the abducting eye

Question 19

visual defect associated with development of optic neuritis (apart from eventual visual loss)

Answer 19

relative afferent pupillary defect (RAPD)

Marcus Gunn pupil - swinging flashlight test

Question 20

Key finding on CSF electrophoresis in multiple sclerosis

Answer 20

oligoclonal bands in the gamma region

Question 21

Why do individuals with MS develop blurring of vision when exposed to heat?

Answer 21

extreme sensitivity of conduction in demyelinated nerve fibers to an elevation in temperature

Uhthoff phenomenon

Question 22

Diagnosis?

35 year old woman
blurring of vision with painful eye exacerbated by eye movements
tingling of extremities
spasticity of upper limbs
ataxia
see radiologic image findings

Answer 22

Multiple sclerosis

Image 1- hyperintense MS plaque; Image 2 - Dawson fingers

Question 23

Gross morphology of multiple sclerosis

Answer 23

well circumscribed, gray-tan, irregularly shaped plaques - adjacent to the lateral ventricles, in other area sof white matter within the CNS

Question 24

Microscopic morphology of multiple sclerosis in an active demyelinating plaque

Answer 24

abundant foamy macrophages with lymphocytes present as perivascular cuffs

Question 25

Alcoholic admitted with seizures and altered mental status --> received sodium infusion --> subsequently developed quadriplegia

Answer 25

central pontine myelinolysis

Question 26

radiologic feature of central pontine myelinolysis (osmotic demyelination syndrome)

Answer 26

**Trident sign **due to osmotic stress affecting transverse pontine fibers with relative sparing of the compact motor and sensory tract

Question 27

Most likely condition in an individual presenting with symptoms involving demyelination the tracts indicated in the image

Answer 27

Subacute combined degeneration of the spinal cord - B12 deficiency | Posterior and lateral columns

Question 28

Basis for neurologic symptoms in Vitamin B12 deficiency

Answer 28

Accumulated propionyl-CoA displaces succinyl-CoA, which is the usual primer for the synthesis of even-chain fatty acids; this results in the anomalous insertion of odd-chain fatty acids into membrane lipids, such as are found in myelin sheaths.

Question 29

2 biochemical substrates that accumulate in B12 deficiency

Answer 29

Methylmalonic acid, homocysteine

Question 30

# Diagnosis and most likely organism? * Gastrointestinal infection * 1-3 weeks later lower limb weakness, paresthesias, followed by upper limb weakness and respiratory difficulties

Answer 30

Guillain Barre syndrome *Campylobacter jejuni*

Question 31

CSF findings in Guillain Barre syndrome

Answer 31

albuminocytologic dissociation | i.e. elevated protein and no or few white blood cells

Question 32

# Type of nerve fibers involved? * Diabetes- 20 year duration * pain on bedsheets touching the feet (allodynia),paresthesias, hyperalgesia,diminished pain and temperature sensation in affected areas

Answer 32

small fiber injury | allodynia (pain response to a nonpainful stimulus)

Question 33

# Type of nerve fibers involved? * Diabetes- 20 year duration * loss of vibration, proprioception, positive Romberg sign.

Answer 33

Distal axons of** Large** sensory fibers

Question 34

Pathogenesis of diabetic neuropathy

Answer 34

* accumulation of advanced glycosylation end products (AGEs), sorbitol -->oxidative stress injury * diabetic microangiopathy affecting the endoneurial vessels --> nerve ischemia

Question 35

Is diabetic neuropathy an axonal neuropathy or a demyelinating neuropathy?

Answer 35

Axonal neuropathy | most common- distal symmetric sensorimotor type

Question 36

# Is this critical illness myopathy or critical illness polyneuropathy? * Sepsis followed by diffuse symmetric extremity weakness * difficulty weaning off ventilator * sensory impairment + * reflexes absent * creatine kinase levels normal * Sensory nerve action potentials diminished * EMG shows decreased motor action potential due to axon loss

Answer 36

Critical illness polyneuropathy

Question 37

Differentiate Lambert Eaton syndrome from Myasthenia gravis

Answer 37

Question 38

# Diagnosis x-linked recessive delayed walking – an inability to lift the trunk without using the hands and arms to brace and push calf pseudohypertrophy

Answer 38

Duchenne muscular dystrophy

Question 39

Most common causes of death in Duchenne muscular dystrophy

Answer 39

respiratory insufficiency due to muscle weakness or cardiac arrhythmia due to myocardial involvement (dilated cardiomyopathy)

Question 40

Why does myofiber degeneration occur in Duchenne muscular dystrophy?

Answer 40

Dystrophin provides mechanical stability to the myofiber and its cell membrane during muscle contraction--> absence of dystrophin-->small membrane tears that permit influx of calcium, triggering events that result in myofiber degeneration

Question 41

Pathogenic basis for Duchenne dystrophy

Answer 41

total absence of dystrophin due to deletion of frameshift mutations

Question 42

What is pseudohypertrophy?

Answer 42

enlargement of a muscle when muscle fibers are replaced by fibroadipose tissue

Question 43

Key morphology of late, progressive Duchenne muscular dystrophy?

Answer 43

* fatty replacement * endomysial fibrosis * variation in myofiber size

Question 44

**What's the pathogenesis of the condition described?** Myotonia (prolonged muscle contractions) Cataracts Frontal balding Testicular atrophy Elevated creatine kinase Glucose intolerance

Answer 44

**expansions of CTG triplet repeats** in the 3′-noncoding region of the myotonic dystrophy protein kinase (DMPK) gene on chromosome 19

Question 45

**Dermatomyositis OR Polymyositis?** infiltrate rich in **_CD4+ T-helper cell_**s and the deposition of C5b-9 in capillary vessels of skeletal muscle

Answer 45

Dermatomyositis

Question 46

Morphologic finding in dermatomyositis

Answer 46

Perimysial inflammation with perifascicular atrophy

Question 47

**Dermatomyositis OR Polymyositis?** scaling erythematous eruption or dusky red patches over the knuckles, elbows, and knees proximal muscle weakness difficulty getting up from a chair anti Mi-2 antibodies

Answer 47

Dermatomyositis

Question 48

**1. What's your diagnosis?** proximal muscle weakness No cutaneous manifestations ↑↑Creatine kinase, aldolase, myoglobin ↑Anti–Jo-1 ↑ESR/CRP **2. What's the assoc morphologic finding?**

Answer 48

1. Polymyositis 2. endomysial inflammation with CD8+ T cells.

Question 49

**What is the basis for the condition described?** Exposure to a halogenated inhalational anesthetic leading to : Tachycardia Tachypnea Muscle spasms Hyperpyrexia Rhabdomyolysis

Answer 49

The condition described is malignant hyperthermia caused by **Mutations in the RYR1 gene** that disrupts the function of the **ryanodine receptor**

Question 50

# Diagnosis? * 58 year old female * slowly progressive muscle weakness - most severe in the knee extensors and the finger flexors * Muscle biopsy - rimmed vacuoles * Antibodies to 5’-nucleotidase 1A (cN1A)

Answer 50

Inclusion body myositis