Motor Neuron Disorders Flashcards

1
Q

Anterior Horn Cell diseases affect primarily the motor neurons in the spinal cord. Such diseases include, for example:

A

Familial Spinal Muscular Atrophy and poliomyelitis.

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2
Q

T or F. In Amyotrophic Lateral Sclerosis (ALS) the upper motor neurons and the lower motor neurons are affected.

A

T. These disorders cause weakness with muscle atrophy and are usually accompanied by muscles fasciculations and signs of denervation on the EMG.

The reflexes are usually depressed except in Amyotrophic Lateral Sclerosis in which they could be increased because of involvement of the upper motor neurons. There are no sensory deficits because the sensory axons are not affected. Anterior Horn Cell diseases may be hereditary or sporadic, and usually they have no cure.

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3
Q

This diagram shows the different areas affected in neuromuscular diseases.

In motor neuron diseases the motor neurons, their motor axons, and secondarily the muscle fibers they innervated are affected (the motor unit).

A
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4
Q

What are the major anterior horn cell diseases?

A

INFANTILE SPINAL MUSCULAR ATROPHY: Werdnig-Hoffman

JUVENILE PROXIMAL CHRONIC SPINAL MUSCULAR ATROPHY: Wolfart-Kugelberg-Welander

ADULT ONSET SPINAL MUSCULAR ATROPHY

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5
Q

Describe INFANTILE SPINAL MUSCULAR ATROPHY: Werdnig-Hoffman

A

This is a fatal AR disease marked by:

  • hypotonicity and hyporeflexia
  • tongue fasciculations
  • poor suck reflex
  • abdominal respirations
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6
Q

Describe JUVENILE PROXIMAL CHRONIC SPINAL MUSCULAR ATROPHY: Wolfart-Kugelberg-Welande

A

This is a AR disease marked by:

slowly progressive proximal weakness that resembles myopathy and fasciculations

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7
Q

Descrive ADULT ONSET SPINAL MUSCULAR ATROPHY

A

This is a sporadic (some familial) syndrome marked by:

hypotonicity, hyporeflexia and

proximal and distal wekaness

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8
Q

Here is a baby with the most severe motor neuron disease manifesting at birth with weakness , hypotonia, (floppy baby), areflexia, muscle atrophy, difficulty breathing and swallowing. They usually die early of respiratory failure.

A

Note the “frog leg posture” with the hips abducted do to weakness. The disease is called Werdnig-Hoffman Disease.

The EMG will show signs of denervation and fasciculations. The muscle biopsy will show group fiber atrophy.

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9
Q

What causes infantile spinal muscular atrophy?

A

This is an autosomal recessive disease from mutations of the ‘survival motor neuron gene’ on chromosome 5q.

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10
Q

this is a patient with juvenile spinal muscular atrophy. This disease manifests in childhood and clinically resembles a muscular dystrophy.

Note the atrophy of the pectoralis and thigh muscles. Unlike myopathies, the EMG and biopsy show denervation changes, and the serum CK is usually normal.

A
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11
Q

What causes juvenile spinal muscular atrophy?

A

This disease is also caused by mutation of the ‘survival motor neuron gene’. The survival motor neuron gene has two copies, SMN1 and SMN2. SNM1 is absent in spinal muscular atrophy, and the size of SMN2 determines if the patients has the neonatal or the juvenile form (larger in the later). This disease is called Kugelberg Welander Disease.

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12
Q

How does PROGRESIVE BULBAR PALSY present?

A

Sporadic, Fasciculations, Bulbar muscles weakness, Rapidly progressive, Tongue atrophy (adult onset)

Progressive bulbar palsy affects primarily the muscles innervated by the medulla (form bulb or medulla in French) neurons , causing tongue and palate weakness. Patients with Progressive Bulbar Palsy may later develop classical ALS.

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13
Q

How does ALS present?

A

Mostly sporadic, Some familial cases, Hyperreflexia, Spasticity, Muscle atrophy, Fasciculations, Tongue atrophy, Rapidly progressive (adult onset)

ALS manifests with upper and lower motor neuron symptoms and findings as well as “bulbar” weakness.

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14
Q

How does progressive lateral sclerosis present?

A

Sporadic, Involves only the upper motor neurons, Spasticity, Hyperreflexia, More benign course

Progressive lateral sclerosis affects primarily the upper motor neurons with little atrophy or signs of denervation. Although these patients could later develop signs of classical ALS, progression of symptoms is slower as this appears to be a more benign form of the disease.

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15
Q

How does PROGRESSIVE SPINAL MUSCULAR ATROPHY present?

A

Mostly sporadic, Progressive weakness, Muscle atrophy, Fasciculations, Areflexia (adult onset)

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16
Q

What are some signs/symptoms of motor neuron diseases?

A
  • Symmetrical or asymmetrical weakness
  • Atrophy

Increased or decreased reflexes- dependent upon corticospinal tract involvement (ALS)

  • Fasciculations
  • Normal sensation
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17
Q

Lab findings of motor neuron diseases

A
  • Normal nerve conduction velocities
  • Denervation on EMG
  • Decreased # of motor units
  • Muscle biopsy shows atrophic fibers & fiber grouping
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18
Q

ALS is caused by degeneration of the upper and lower motor neurons. It is progressive and lethal. Patients present how?

A

They are weak, have atrophic muscles fasciculations, hyperreflexia and spasticity, but normal sensation. Characteristically patients develop difficulty swallowing and breathing.

Most cases are sporadic but about 10% of cases are hereditary.

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19
Q
A

This woman with ALS shows early atrophy and weakness of the distal muscles.

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20
Q

This woman has a more advanced case of ALS with difficulty closing her mouth. She is wheelchair bound and has hyperreflexia, bilateral Babinski signs, fasciculations, atrophy, and normal sensation.

A
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21
Q

The differential diagnosis of ALS is large. One should always search for a more benign disorder or a treatable one. What should be included?

A
  • Multisystem atrophy, spinocerebellar degeneration (Hereditary cerebellar degenerations could present with difficult swallowing but they have ataxia.)
  • Craniocervical junction disorders
  • Cervical spondylosis
  • Post polio syndrome
  • Polyglucosan body disease
  • Hexoaminidase A deficiency
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22
Q

What is Multisystem atrophy?

A

A late onset degenerative disease that could affect the lower motor neurons, autonomic neurons and also cerebellar neurons. This is also a progressive disorders, but slower than ALS.

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23
Q

Note about craniocervical jucntion disorders being on the Ddx for ALS:

Tumors of the craniocervical junction could present with arm weakness and difficulty swallowing , thus patients with these symptoms should always have a MRI before diagnosing ALS

A

Cervical canal disease such as spondylosis, with degenerative disc disease, could present with arm , hand atrophy, weakness, and spasticity from compression of the pyramidal tracts. Sensory deficits could be absent or minimal. MRI of the spine is thus very important.

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24
Q

More on the Ddx of ALS

A

Patients with a history of poliomyelitis in childhood, later may develop a progressive lower motor neuron disease. The cause is unclear and it is not from infection , but likely do to age-related degeneration of the surviving motor neurons. The previous history of polio is paramount in making this diagnosis.

Milder phenotypes of Tay Sachs disease present like ALS in younger individuals. They also usually have intellectual deterioration and ataxia

25
Q

What is polyglucosan body disease?

A

A glycogen storage disorder that presents in younger individuals with a lower motor neuron type of weakness. The muscle or nerve biopsy show the characteristic polyglucosan inclusions.

26
Q

MRI of a patient with cervical spondylosis. Note several protruding discs pressing the spinal cord. Patients with cervical spondylosis may present with lower motor neuron signs in the upper extremities secondary to nerve root compression and upper motor neuron signs in the lower extremities secondary to compression of the spinal cord and corticospinal tracts.

A
27
Q

What else should be on the Ddx for ALS?

A
  • Hyperparathyroidism (Patients with hyperparathyroidism may present with progressive muscle weakness resembling ALS. An elevated serum calcium and parathyroid hormone level are diagnostic)
  • Heavy metal (lead) intoxication- Lead poisoning rarely causes lower motor neuron degeneration resembling the lower motor neuron type of ALS.
  • Bulbo-spinal muscular atrophy (Kennedy’s disease) and other motor neuron disorders

Other benign variants of motor neuron disorders such as benign focal amyotrophy and benign cramp fasciculation syndrome

28
Q

What is Kennedy disease?

A

Kennedy disease is a more benign disorder than ALS that may present without a family history. The disease is caused by mutations of the androgen receptor gene on the X chromosome.

29
Q

The classical phenotype of Kennedy disease includes:

A

gynecomastia and testicular atrophy, lower motor neuron syndrome, i.e., atrophy , fasciculations , signs of denervation in limbs and tongue, and they may have a mild neuropathy.

The serum CPK may be elevated. DNA testing is diagnostic.

30
Q

There are patients that have more benign motor neuron syndromes such as a non progressive unilateral limb weakness and atrophy. The etiology of this syndrome is unclear, but could be caused by chronic dural compression of the cord. There are some families that present with a benign syndrome of fasciculations and cramps.

A
31
Q

Rarely patients with Myasthenia Gravis or Eaton-Lambert Syndrome may resemble ALS, especially when they do not have eye muscle weakness. Their diagnosis is established by EMG testing.

A

Myopathies should also be considered in the differential diagnosis of ALS. The serum CPK, EMG and muscle biopsy help in the diagnosis.

32
Q

This patient has Kennedy’s disease. Despite the gene defect in the androgen receptor he had children, no testicular atrophy and did not show gynecomastia. He did have mild, generalized weakness

A
33
Q

This is a spinal cord section from a patient that died from ALS. Note the lack of myelin stain (pale) in the corticospinal tracts. There was also a loss of the anterior horn neurons.

A

Bunina eosinophilic inclusions may be seen in anterior horn cell neurons. These are ubiquitin accumulations. (ALS)

34
Q

Although most cases of ALS are sporadic, some are familial. What are some possible causes?

A
  • SOD (superoxide dismutase-cause an toxic gain of function of this enzyme) gene mutations in chromosome 21 in AD familial ALS
  • Juvenile ALS: in chromosome 2q33 (also in gene 9q34, 15q15, 8q21), and also ALS associated with mutation of 9q21, XP, others
  • ALS associated with other diseases such as chromosome 17-linked fronto-temporal dementia (FTD)
35
Q

What is the most common cause of familial ALS with or without FTD?

A

An expanded section of DNA on chromosome 9 in the gene C90RF72

36
Q
A
37
Q

How is ALS tx?

A
  • Glutamate antagonists, such as riluzole is helpful.
  • Experimental: Creatine and antioxidants such as carotene, coenzyme Q10, vitamins C and E could be of benefit, COX 2 inhibitors?, Nerve growth factors?.
  • Physical therapy
38
Q

These are some of the treatments that help relief symptoms of ALS. Local Botox injections in the salivary glands are used to decrease excessive salivation do to poor swallowing. Botox injections in muscles are also used to relief spasticity.

Physical bracing is used for foot drop. Feeding gastrostomy is used for feedings in those with difficulty swallowing and risk of aspiration. Finally non-invasive, continuous pressure, external mask ventilation, or invasive thru tracheostomy, ventilation prolong survival.

A
39
Q

Proximal myopathy- proximal weakness, Gower sign, difficult ascending stairs, etc.

A

Neuropathies are often marked by distal weakness and cause sensory loss (while in motor neuron disease there is only weakness)

40
Q

In ALS there are increased reflexes and wasting but no sensory loss

A

With contraction, motor units are recruited 1 by 1

41
Q

Normally, muscles are mixed with type 1 and 2 fibers

A

Denervation causes muscle fiber atrophy

42
Q

After denervation, other motor neurons take over and cover more fibers leading to a larger action potential

A

In myopathies you dont have decreased motor units (but the fibers are damaged leading to small APs) but you do in neuropathies

43
Q

Myopathies have decreased numbers of muscle fibers, not motor units

A
44
Q
A
45
Q
A
46
Q

hypereflexia= UMN disease

A

Sensory is normal in ALS

47
Q

1 (and possibly 3) and probably an EMG

A

5.

48
Q

4.

A

4.

49
Q

1 and 2

A
50
Q

Probably Kennedy Disease

A
51
Q
A
  1. Peripheral nerves
52
Q

4.

A
53
Q

Note the inheritance

A

D. Spinal muscular atrophy

Could be cerebral palsy but usually reflexes are present

54
Q

A and C

A
55
Q

Probably a primary myopathy (proximal weakness) or juvenile spinal muscular atrophy

Cerebral palsy= usually have reflexes

A

A (CPK is not high with spinal atrophy, only myopathy) and C

56
Q

suggests spinal muscular atrophy (anterior horn disease)

A

Muscle biopsy may show angular or grouping (dont need)

Answer: D. DNA testing

57
Q
A

Inflammatory myopathy doesnt usually cause facial weakness

Progressive bulbar palsy usually shows tongue fasciculations (could be though)

Answer: C Myasthenia gravis

58
Q

D. All of the above

A
59
Q

C.

A