Adult Neuromuscular Disorders

Question 1

Amyotrophic Lateral Sclerosis (ALS) or Lou Gehrig’s disease

Answer 1

Most common motor neuron disease.
Degeneration of motor neurons in spinal cord and brainstem (LMN) and cerebral cortex and corticospinal tract (UMN).
Most are limb onset versus bulbar onset.
Death 3-5 years after diagnosis, usually due to respiratory muscle failure.
4/100,000
Age peak: 55-75
M:F 2:1
10% familial.

Question 2

Clinical Symptoms of ALS:

Answer 2

Both UMN and LMN signs:
UMN: hyper-reflexia, spasticity, Babinski
LMN: weakness, atrophy, fasciculations.
30-50% get cognitive dysfunction

Question 3

Diagnosis of ALS:

Answer 3

History and exam.

EMG is helpful.

Question 4

Management of ALS:

Answer 4

Supportive: biPAP, feeding tub, communication devices.

Meds for drooling, spasticity, muscle cramps.

Question 5

Diabetic Polyneuropathy epidemiology:

Answer 5

65-80% of DM.

Mean time 8 years after onset of DM. (Type 1 tend to have longer). Type 2 may develop polyneuropathy before DM.

Question 6

Clinical features of diabetic polyneuropathy:

Answer 6

Longest nerves first affected - paresthesias and numbness in toes and then up. Stocking-glove pattern.
Can have burning pain and hypersensitivity in feet and hands (small unmeylinated fibers)
Impaired propriocepton and vibratory sense, unsteady gait (large myelinated fibers).
Toe flexion weakness, foot drop, hand weakness can occur.

Question 7

Treatment of DM polyneuropathy:

Answer 7

• blood gluc control
• CV exercise, weight loss
• symptomatic (for pain and paresthesias): gabapentin, amitriptyline, pregabalin

Question 8

Guillain-Barre Syndrome (GBS)

epidemiology and pathogenesis:

Answer 8

1. Acute, progressive polyradiculoneuropathy that results in sensory loss and weakness
2. 2/3 after infection: campylobacter jejuni, haemophilus influenzae, EBV, CMV
3. Molecular mimicry of antibodies against Schwann cells. Usually only myelin loss but axonal loss can occur and is worse.
4. 1/100,000

Question 9

Clinical features of GBS/l

Answer 9

1. Progressive motor weakness usually starting in the feet and moving proximally into the legs and arms
2. Severe cases may include difficulties with speech/swallowing/breathing necessitating feeding tube and/or mechanical ventilation, facial weakness, ophthalmoplegia
3. Areflexia or significantly diminished reflexes is an expected finding
4. Diminished sensation and paresthesias (may be the only symptoms in mild cases)
5. Autonomic dysfunction—heart rate and blood pressure variability, urinary retention, ileus

Question 10

Diagnostic testing for GBS:

Answer 10

1. Nerve conduction studies reveal a demyelinating pattern
2. Cerebrospinal fluid studies—elevated total protein and no or few white blood cells; if there are many white blood cells, an infectious etiology such as HIV or Lyme disease should be considered

Question 11

Treatment of GBS:

Answer 11

1. Admit to the hospital to monitor closely for respiratory failure and autonomic dysfunction
2. The natural course of GBS is to improve over time (months – year); patients with mild disease may not require further treatment
3. For those with difficulty walking, using their arms, or respiratory failure, IVIG or plasmapheresis can be initiated to lessen disease duration

Question 12

Prognosis of GBS:

Answer 12

1. Symptoms usually progress over 2-4 weeks, may or may not plateau for a few weeks, and then start to slowly improve (monophasic)
2. Most patients recover almost completely over months
3. 5-10% of patients have permanent disabling weakness, imbalance, or sensory loss (often due to axonal loss)
4. Mild neuropathic signs (paresthesias, numbness) persist in 50%

Question 13

Chronic Inflammatory Demyelinating Polyneuropathy (CIDP)

Answer 13

1. Similar in symptomatology and diagnostic testing results as GBS but has a relapsing-remitting course and often requires long-term treatment
2. Treatments include serial IVIG, corticosteroids, and for more severe symptoms plasmapheresis

Question 14

Most common NMJ disorder:

Answer 14

Myasthenia Gravis - a post synaptic disorder (abnorm on muscle membrane)
-it is autoimmune: autoAbs attack nicotinic ACh receptors on muscle mebrane –> reduces AP –> muscle weakens.

Question 15

Epidemiology of MG:

Answer 15

1. Prevalence—50 – 400 cases per million
2. Disease onset—bimodal distribution:
   a. Between 15 – 30 years—female predominance:
   b. Between 60 – 75 years—more males

Question 16

Clinical features of MG:

Answer 16

Hallmark is fatiguable weakness (muscles are strong initially but become weak with continued use and improve with rest)

• Diplopia, ptosis, bulbar symptoms (nasal dysarthria, dysphagia), diaphragmatic weakness, facial weakness, neck weakness, limb weakness
• Rarely, respiratory failure may be the initial symptom (prior to modern-day therapies, 20-30% mortality due to respiratory failure)
• symptoms can get worse with stresses like infection, trauma, surg, sleep deprivation.

Question 17

Majority of patients with MG present with:

Answer 17

Diplopia and Ptosis (extraocular and palpebral muscles) as their initial symptoms.
If symptoms involve eyes only = Ocular MG.

Question 18

Diagnostic tests for MG:

Answer 18

1. Blood tests—ACh Abs.
2. Cholinesterase Inhibitors—
   a. Intravenous (Tensilon) or intramuscular (Prostigmine) cholinesterase inhibitor is administered
   b. Weakness should transiently improve (i.e. severe ptosis –> eyelid raises)
3. Slow rate repetitive nerve stimulation—decrement

Question 19

Treatments for MG:

Answer 19

1. Symptomatic—cholinesterase inhibitors
   a. Allow more acetylcholine in the synaptic cleft to be available for the receptors
   b. Does not change the course of the disease
   c. Most commonly used—Pyridostigmine (Mestinon)
2. Immunosuppression
   a. Prednisone– mainstay of treatment, but due to side effects, patients should not stay on high doses long-term
   b. Steroid-sparing medications
   i. Azathioprine– suppress delayed hypersensitivity and cellular cytotoxicity
   ii. Mycophenolate mofetil– inhibits T and B lymphocytes
3. IVIG, plasmapheresis– used for crisis and severe symptoms
4. Thymectomy - Most patients continue to require treatment; some go into remission

Question 20

A rare presynaptic NMJ disorder:

Answer 20

Lambert-Eaton Myasthenic Syndrome: abnormality occurs at the nerve terminal, rare

Question 21

Pathogenesis of Lambert-Eaton Myasthenic Syndrome:

Answer 21

Abs attack the voltage-gated Ca2+ channels on the cholinergic nerve terminals –>reduced Ca2+ uptake –> reduced release of ACh into the synaptic cleft –> less ACh available for the ACh receptors on the post-synaptic membrane–> reduction in AP production of the muscle –>weakness

Question 22

Clinical symptoms of Lambert-Eaton Myasthenic Syndrome:

Answer 22

Fatiguing proximal weakness (may seem strong on exam but not able to function well due to severe fatiguing), Dry mouth and erectile dysfunction (antibodies also affect cholinergic nerve terminals of the autonomic nervous system)

Question 23

What is Lambert-Eaton Myasthenic Syndrome associated with?

Answer 23

50% of cases may be associated with an underlying malignancy (paraneoplastic syndrome), most commonly small-cell carcinoma of the lung

Question 24

Diagnostic tests for Lambert-Eaton Myasthenic Syndrome:

Answer 24

1. Blood test—P/Q type voltage-gated calcium channel antibodies
2. High rate repetitive nerve stimulation—increment
3. Chest CT to evaluate for lung cancer

Question 25

Treatment for Lambert-Eaton Myasthenic Syndrome:

Answer 25

1. Treat underlying cancer if present
2. Symptomatic treatment—pyridostigmine, 3,4-diaminopyridine
3. Immunosuppressive therapy if necessary (similar to myasthenia treatments)

Question 26

A pre-synaptic NMJ disorder from a toxin:

Answer 26

Botulism - after eating botulinum toxin.

Question 27

Pathogenesis of Botulism:

Answer 27

Botulinum toxin prevents ACh release from the pre-synaptic membrane of the motor nerve causing weakness and results in dysautonomia by blocking muscarinic autonomic cholinergic function

Question 28

Symptoms of Botulism:

Answer 28

Progress over 12 – 48 hours, initially—diplopia, ptosis, blurred vision, dysarthria, dysphagia, followed by limb weakness; severe cases cause respiratory failure

Question 29

Diagnostic testing for Botulism:

Answer 29

Stool and serum evaluation for toxin at CDC or state labs.

Question 30

Management of Botulism:

Answer 30

1. Supportive—admission to intensive care units, mechanical ventilation and feeding tube if necessary
2. Antitoxin (most readily available contains types A, B, E)—does not reverse current symptoms but hopefully prevents progression, only available through state health departments or CDC

Question 31

Inflammatory myopathies:

Answer 31

1. Polymyositis
2. Dermatomyositis
3. Inclusion Body Myositis (IBM)

Question 32

Polymyositis:

Answer 32

1. Usually presents greater than age 20 years
2. Symmetric proximal arm and leg weakness developing over several weeks – months
3. Difficulty with rising from chairs, shampooing hair
4. Myalgias
5. May have dysphagi

Question 33

Diagnostic testing for polymyositis:

Answer 33

1. CK levels elevated, can be as high as 50X

2. Muscle biopsy - invasion of T cells into muscle fibers

Question 34

Treatment of polymyositis:

Answer 34

High-dose prednisone followed by a slow taper (once strength has returned) over 6 months or so

Question 35

Dermatomyositis:

Answer 35

1. May present at any age, including childhood
2. Subacute weakness affecting neck flexion, pectoral, and pelvic girdle muscles
3. Rashes (heliotrope rash—purple discoloration of the eyelids, erythematous rash of face, neck, chest, extensor surfaces of elbows, knees, malleoli) may accompany or precede muscle weakness
4. 5. May have dysphagia

Question 36

Dermatomyositis may be associated with?

Answer 36

underlying malignancies such as lung, breast, colon, ovarian

Question 37

Diagnostic testing for dermatomyositis:

Answer 37

1. CK levels elevated, can be as high as 50X

2. Muscle biopsy - perivascular inflammatory infiltrates, perifasciular atrophy is pathonomonic.

Question 38

Treatment of dermatomyositis:

Answer 38

Similar to polymyositis; if prednisone does not work, additional immunosuppressive treatments (azathioprine, methotrexate, IVIG) can be used

Question 39

Inclusion Body Myositis (IBM)

Answer 39

1. Occurs in adults > age 50 years, most common acquired muscle disease in older adults
2. Insidious onset of slowly progressive asymmetrical weakness
3. Clinical hallmark is early weakness and atrophy of quadriceps and forearm muscles (wrist and finger flexors) and foot drop

Question 40

Diagnostic testing for IBM:

Answer 40

1. CK levels can be normal or elevated 10-fold
2. Muscle biopsy—endomysial inflammation, basophilic granular inclusions around the edges of vacuoles (rimmed vacuoles); rimmed vacuoles may not be present on the biopsy, thus, the clinical presentation is important to determine the diagnosis of IBM

Question 41

Most common inherited neuromuscular disease in adults:

Inheritence pattern?

Answer 41

Myotonic dystrophy.
Autosomal dominant.
Type 1: CTG repeat - more common, mutation of myotonin protein kinase (DMPK) - many places in body.
Type 2: CCTG repeat - mutation of zinc finger protein 9 (ZNF9) - mostly in heart and skeletal m.

Question 42

Clinical features of myotonic dystrophy:

Answer 42

1. Skeletal Muscle
   a. Type 1—usually distal weakness (hand weakness, foot drop)
   b. Type 2—usually proximal weakness (hip flexion, upper arms)
   c. Myotoinia—delay of muscle relaxation after contraction due to chloride channel abnormality, can occur with hand grip or eye closure, elicited by percussion of the thenar eminence
   d. Temporal muscle wasting
   e. Eventual diaphragmatic weakness and dysphagia
2. Early onset cataracts
3. Cardiac arrhythmias—require routine monitoring with cardiology
4. Endocrinopathies—hypogonadism, insulin resistance
5. Hypersomnia
6. Frontal balding
7. May have mild mental retardation or apathy; avoidant personality

Question 43

Diagnostic testing and treatment for myotonic dystrophy:

Answer 43

1. Electromyography—myotonic discharges
2. Genetic testing
   Treatment is symptomatic.