Nervous System and Special Senses

Question 1

Fetal alcohol syndrome

Answer 1

*fetal alcohol syndrome lies at the most extreme end of fetal alcohol spectrum
*alcohol interferes with crest migration and results in craniofacial dysmorphology
*alcohol disrupts the Wnt signaling pathway involved in cytokine release necessary for neural growth
*the risk of effects is does-dependent in binge drinking
*higher risk lies within smoker females and those with low socioeconomic status
*the risk is decreased in women with efficient alcohol dehydrogenase enzyme
*The effects of maternal alcohol consumption can be
seen in craniofacial dysmorphology, central nervous system abnormalities, internal organ damage, development deficits, and growth retardation. Severe
malformations (e.g., Dandy-Walker) also occur. Facial characteristics include small chin, cleft lip/palate, low nasal bridge, hypoplastic maxillae, ptosis,
hypertelorism, prominent epicanthic fold, short nose/anteverted nostrils, short palpebral fissure, thin vermillion border of upper lip, and smooth philtrum
(with the last three bearing diagnostic importance)
*many cases are not diagnosed until school age due to phenotypic variability
*Dx: Key features in diagnostic criteria for FAS include the presence of CNS abnormalities, growth deficits, neurobehavioral impairment, and ≥2 facial abnormalities.
*morphological ft.s:
Microcephaly
Enlarged ventricles
Agenesis of the corpus callosum
Cerebellar hypoplasia
*DDx:
exposure to other teratogens including (hydantoin, valproate, toluene)
*pregnant women are advised to abstain from alcohol
*alcohol gets oxidized into acetaldehyde which crosses the placenta and then gets metabolized by acetaldehyde dehydrogenase which is present in negligible amounts in fetal liver. Ethanol is metabolized to a lesser extent by cytochrome p450 oxidizing system (specifically CYP2E1) which is upregulated by chronic alcohol use and increases at higher levels. This enzyme generates reactive oxygen species during its action

Question 2

subdural hematoma

Answer 2

*blood collects between the dura and the arachnoid
*the cortical bridging veins are involved
*trumatic injuries, especially those with rapid acceleration, also abuse injuries in children
*epidural and DAI might coexist with SDH
*chronic subdural hematoma is associated with brain atrophy in elderlies and minor traumas leading to blood accumulation in the subdural space over time
*clinically, acute SDH causes loss of conciousness, chronic SDH symptoms include headache, cognitive deficits, and other neurological manifestations
*Dx: imaging studies (CT, MRI), diagnostic features include:
-unilateral sundural blood over the temporoparietal region
-skull fractures are present in 50% of acute cases
-chronic subdural hematomas become organized over time, and might show evidence of rebleeding
DDx: epidural hematoma (lucid interval, middle meningeal artery)
Treatment:
-observation and repeated head imaging for small bleeds
-evacuation for large bleeds
-craniotomy or burr holes for chronic SDH with the instillation of tPA to prevent rebleeds (tPA induces local fibrinolysis)

Question 3

Gullian-Barrie syndrome

Answer 3

*immune-mediated demyelinating polyneuropathy
*infection might be precipitating, examples include C.jejuni, and viruses like (EBV, CMV, HIV, and Zika virus)
Clinical features: acroparesthesia, proximal muscle weakness of the lower extremities followed by ascending bilateral weakness, severe radicular back pain may occur, facial nerve involvement is common, ultimately respiration is compromised
*clinical disease categories:
Vignette 3 Table
*Diagnosis:
-LP: albuminocytoloic dissociation (elevated albumin, normal WBC count)
-EMG and NCS (might be normal early in the course of illness, can differentiate subtypes)
-Serology: anti-GQ1b antibodies in MFS
*Morphology: perivascular myelin loss accompanied by mononuclear infiltrate
*Ddx:
Diphtheria: paralysis that follows an initial pharyngeal infection, causing paralysis of the soft palate and oculomotor muscles before other muscle groups(descending paralysis), it is a toxin mediated disease caused by corynebacterium diphtheria, it causes segmental demyelination
Mysthenia Gravis, electrolyte abnormalities: no sensory involvement
DM: the commonest cause of polyneuropathy
Treatment and Outcomes:
-Supportive therapy: plasma exchange, IV immunoglobulin therapy, pain modulators, mechanical ventilation, anticoagulants, physical therapy and adaptive devices
-Half of patients experience prolonged disability but the majority recover
-Causes of death include infection, diffuse alveolar damage, and pulmonary embolism
-Physiology: loss of myelination decreases nerve conduction velocity
-Pharmacology: IVIG therapy side effects include immediate and late reactions, anaphylaxis in tose with IgA def., renal failure and enteritis

Question 4

Juvenile Huntigton’s disease: ( Westphal variant)

Answer 4

*AD, degeneration of the GABAneregic neurons of the caudate nucleus, the gene HTT is located on chr.4, it codes for huntigtin protein
*Mean age is 40, juvenile(<20 years) presenting with involuntary movements(chorea), mood/behavioral changes, dementia. Rigidity, hypokinesia, and cerebellar involvement (in juvenile cases), chorea maybe be absent, gait abnormalities and learning difficulties may present before seizures
Dx: PCR to amplify a portion of the Huntington disease gene, in order to count the number of triplet repeats of CAG (cytosine-adenine-guanine) MRI (preferred imaging study) shows caudate head atrophy with relative enlargement of frontal horns causing a boxcar configuration of the ventricles
Gross examination of the brain: bilateral atrophy of the caudate and
putamen with ventricular enlargement
Microscopy: neuronal loss and astrocytosis in the neostriatal nuclei
Ddx: temporal lobe seizures in chorea acanthocytosis
generalized seizures in McLeod syndrome.
Dentatorubralpallidoluysian atrophy (DPRLA), similar clinically, caused by CAG repeat mutation in ATN1 gene
Huntington disease-like 2 occurs in families with South African descent, no CAG expansion
*Treatment is palliative, death ensues within 14-15 years, while juvenile HD is more rapidly progressive with death in less than 10 years.
*Physiology of disease: degeneration of the GABAneregic neurons-which are inhibitory- in the corpus striatum will lead to uncontrolled movements
*Pharmacology: one of the ddopamine antagonists used is Tetrabenazine; it does not cause the usual tardive dyskinesia caused by other neuroleptics.

Question 5

Posterior cerebellar stroke

Answer 5

*occlusion of the basilar artery
*This subset of posterior circulation ischemia causes
symptoms that are not typical of stroke, and for that reason, neurologic workup is often delayed. Prodromal symptoms include vertigo, nausea, headache, and neck pain. These symptoms are followed by a latent period that precedes the development of signs that prompt a workup for stroke. The predominating stroke symptomology is determined by the location of occlusion. For example, “locked-in syndrome” occurs when the pons
becomes ischemic due to midbasilar occlusion; these patients are fully conscious but paralyzed. An infarct of the lower midbrain result in bilateral ataxia.
*Dx:
MRI is more sensitive, an early MRI however should not rule out stoke if symptoms persist
Cerebral angio. Is the gold standard

Ddx:

Question 6

CJ disease

Answer 6

• prion disease that results from misfolded cellular protein
• Classical vs. Variant
• most of the cases are sporadic, 10% is familial
• can be iatrogenic from contaminated neurosurgical instruments, but that’s rare
• the variant subtype results from foodborne exposure to bovine spongiform encephalopathy prion, or exposure due to blood transfusions from donors with subclinical vCJD

*clinical presentation: the latent phase lasts for decades.
the sporadic type typically presents at the age of 70 with rapid onset of cognitive decline, ataxia, and myoclonus, then akinetic mutism within weeks to a year.

• Familial CJD and vCJD present earlier in
  adulthood. Psychiatric symptoms often precede other manifestations in cases of vCJD
• Dx:
• in vCJD, the pulvinar sign is the finding of bilateral hyperintensities in the pulvinar (posterior) thalamic nuclei
• characteristic EEG findings are not always present; periodic sharp wave complexes are present in 50% of cases of sCJD but are not usually seen in vCJD
• presence of 14-3-3 protein in spinal fluid can also support the diagnosis
• pathologic examination of brain biopsy or autopsy material is required for definitive diagnosis

*morphology:
Spongiform change without inflammation in the cerebral cortex, putamen and thalamus
Amyloid plaques in vCJD

*DDx:
Alzheimer disease (in purely cognitive presentations)
In AD there is abnormal folding of Aβ peptide;
in CJD there is abnormal folding of PrPSC

*tr: palliative
*prognosis: disease is fatal within a year, vCJD survival is longer
*pharmacology:
There is an increased risk of liver failure due to valproic acid use in patients with mitochondrial disease due to POLG mutations, such as Alpers syndrome.

Question 7

meningioma

Answer 7

• arises from the arachnoid cap cells present in the arachnoid granulations, and also in the tela choroidea of the ventricles
• 90% are intracranial, 9% arise in the spine
• exposure to ionizing radiation has the greatest risk, there might be a genetic susceptibility to the exposure
• Type 2 neurofibromatosis is the most common genetic association; it should be suspected in pt.s<40 years old with meningioma (NF2 is caused by 22q deletion)
• clinical presentation:
• small, asymptomatic meningiomas are incidental
• non-specific findings of headache or paresis
• it is more common in middle-aged women
• can be multiple in cases that are radiation-induced, or in NF2
• Dx:
• MRI: