Neuroscience Week 3: Congenital Malformations and Perinatal Brain Injury

Question 1

Polio Description

Answer 1

Poliovirus is an enterovirus that most often causes subclinical or mild gastroenteritis; in a small fraction of cases, it secondarily invades the nervous system and damages motor neurons in the spinal cord and brain stem (paralytic poliomyelitis).

Question 2

Polio Clinical Presentation

Answer 2

The loss of motor neurons results in a flaccid paralysis with muscle wasting and hyporeflexia in the corresponding region of the body. In the acute disease, death can occur from paralysis of respiratory muscles.

Long after the infection has resolved, typically 25 to 35 years after the initial illness, a poorly understood post-polio syndrome of progressive weakness associated with decreased muscle bulk and pain may appear. The re-emergent weakness has the same distribution as the prior polio infection.

Question 3

Vitamin B₁₂ Deficiency Description

Answer 3

In addition to causing anemia, deficiency of vitamin B₁₂ may lead to neurologic deficits associated with changes in the spinal cord, resulting in a syndrome called subacute combined degeneration of the spinal cord.

Question 4

Vitamin B₁₂ Deficiency Pathopysiology

Answer 4

subacute combined degeneration of the spinal cord. As the name implies, both ascending and descending tracts of the spinal cord are affected.

Question 5

Vitamin B₁₂ Deficiency Clinical Presentation

Answer 5

Symptoms develop over weeks. Early clinical signs often include mild ataxia and lower-extremity numbness and tingling, which can progress to spastic weakness of the lower extremities; sometimes, complete paraplegia ensues.

Question 6

Vitamin B₁₂ Deficiency Treatment

Answer 6

Prompt vitamin replacement therapy produces clinical improvement; however, if paraplegia has developed, recovery is poor.

Question 7

Amyotrophic Lateral Sclerosis Description

Answer 7

results from the death of lower motor neurons in the spinal cord and brain stem as well as upper motor neurons (Betz cells) in the motor cortex

Question 8

Amyotrophic Lateral Sclerosis Pathogenesis

Answer 8

While most cases are sporadic, about 10% are familial, mostly with autosomal dominant inheritance. The familial disease begins earlier in life than a sporadic disease, but once symptoms appear, the clinical course is similar in both forms. Mutations in the superoxide dismutase gene, SOD1, on chromosome 21 were the first identified genetic cause of ALS and account for about 20% of the familial forms. These mutations are thought to generate abnormal misfolded forms of the SOD1 protein, which may trigger the unfolded protein response and cause apoptotic death of neurons.

A number of other genetic loci have been identified as associated with ALS. The most common cause of familial ALS is hexanucleotide repeat expansion in a gene with the rather cumbersome name C9orf72 , which is also frequently expanded in frontotemporal lobar degeneration. The protein encoded by C9orf72 associates with RNA binding proteins; notably, two other genes that when mutated may cause ALS, TDP43 (also associated with FTLD) and FUS, encode RNA binding proteins. This convergence suggests that an abnormality of RNA processing directly or indirectly contributes to the pathogenesis of ALS, but it is uncertain how mutations in SOD1 fit into this picture, and much remains to be discovered. As expected from the genetic overlap, there is some clinical overlap between ALS and FTLD, such as cognitive impairment.

Question 9

Amyotrophic Lateral Sclerosis Pathophysiology

Answer 9

The most striking gross changes are found in anterior roots of the spinal cord, which are thin and gray. In especially severe cases, the precentral gyrus (motor cortex) is mildly atrophic due to the death of upper motor neurons. Microscopic examination demonstrates a reduction in the number of anterior horn cell neuronsthroughout the spinal cord associated with reactive gliosis and loss of anterior root myelinated fibers. Similar findings are found with involvement of motor cranial nerve nuclei except those supplying the extraocular muscles, which are spared in all but a few long term survivors. Cytoplasmic inclusions that contain TDP43 may be seen in a subset of cases. With the loss of innervation from the death of anterior horn cells, skeletal muscles show neurogenic atrophy.

Question 10

Amyotrophic Lateral Sclerosis Epidemiology

Answer 10

The disease affects men slightly more frequently than women and becomes clinically manifest in the fifth decade or later.

Question 11

Amyotrophic Lateral Sclerosis Clinical Presentation

Answer 11

It usually begins with subtle asymmetric distal extremity weakness. As the disease progresses, muscle strength and bulk diminish, and involuntary contractions of individual motor units, termed fasciculations, occur.

The disease eventually involves the respiratory muscles, leading to recurrent bouts of pulmonary infection, which is the usual cause of death. The balance between upper and lower motor neuron involvement can vary, although most patients exhibit involvement of both.

In some patients, degeneration of the lower brain stem cranial motor nuclei occurs early and progresses rapidly, a pattern of disease referred to as bulbar amyotrophic lateral sclerosis. With this disease pattern, abnormalities of swallowing and speaking dominate.

Question 12

bulbar amyotrophic lateral sclerosis

Answer 12

degeneration of the lower brain stem cranial motor nuclei occurs early and progresses rapidly

With this disease pattern, abnormalities of swallowing and speaking dominate.