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Flashcards in Other Neuroimmunology Deck (16):

Whast is central pontine myelinolysis?

"Central pontine myelinolysis (CPM) is also known as the osmotic demyelination syndrome

CPM consists of demyelination in the base of the pons, with a relative sparing of the axons and the nerve cells. Myelinolysis in the pons is frequently associated with demyelination in other areas of the brain where the gray and the white matter are closely admixed. These extrapontine lesions are thought to coexist with CPM in 10% of the cases. The pathogenesis of CPM is unknown. It is hypothesized that in the chronic hyponatremic state, rapid treatment with hypertonic
saline solution creates an osmotic stress on the brain. This leads to an osmotic injury to the vascular endothelial cells resulting in the release of myelinotoxic factors or vasogenic edema. The brain dehydration may lead to the separation of the axons from its myelin sheath with resultant injury of oligodendrocytes. Neurological deterioration may often be preceded by a transient improvement paralleling the correction of electrolyte disturbance. Fluctuating levels of consciousness, convulsions, hypoventilation, or hypotension may herald the onset of this syndrome. Eventually pseudobulbar palsy and quariparesis develops.
Swallowing dysfunction and inability to speak may be dominant features. In severe cases, the patient may develop a ""locked-in syndrome"". Predisposing factors include severe underlying medical illness or nutritional deficiency. The disease may develop in patients undergoing liver transplantation, long term alcohol abuse and liver cirrhosis, due to uremia or as a complication of dialysis, and in patients with severe malnutrition."


What is the morphologic hallmark of Alexander disease? What is the genetic mutation?

Alexander disease is a leukodystrophy. Alexander disease classically presents in its infantile form with frontal lobe cystic changes, often severe.
Abundant Rosenthal fibers are typically found."

The morphologic hallmark of Alexander disease is the presence of profuse numbers of Rosenthal fibers. Rosenthal fibers are composed of densely compacted glial intermediate filaments made of glial fibrillary acidic protein (GFAP). Recent studies have demonstrated that a large percentage of Alexander disease cases are associated with a mutation in the GFAP gene."


Devic's Disease - Which ABx are involved? Which population is it more common in?

Demyelinating disorder of CNS characterised by optic neuritis and transverse myelitis

NMO less common than MS, significantly more common in women

Transverse myelitis is longitudinally extensive (more than 2 segments on MRI)

Autoimmune disorder associated with Aquaporin 4 ABs - serum +ve diagnostic

May be monophasic or relapsing remitting course:
Attack - IV methylpred or plasmapheresis

Chronic immunosuppression: rituximab, azathioprine, mycophenolate,

In neuromyelitis optica, women are affected up to four times more often than men and the clinical course of the disease is frequently rapidly progressive. Devic disease is much more common in Asia, with up to 8% of multiple sclerosis cases in Japan being of the Devic type. Oligoclonal bands are absent from the CSF in most cases. The presence of necrosis in spinal cord virtually defines the entity. The disease is now recognized to be related to antibodies to aquaporin 4 in the cell membranes of astrocytes which acts as a channel for the transport of water across the cell membrane. The aquaporin 4 membrane channel is concentrated on astrocyte foot processes.
Demyelinative lesions are not seen in other areas of the brain as would be more typical of multiple sclerosis."


In what diseases do you see Megalencephaly?

Megalencephaly is seen in a wide variety of conditions including some other inborn errors of metabolism, but among the choices the only correct answer would be Canavan disease. (need to add list)


What is adrenoleukodystrophy?

"Adrenoleukodystrophy is an X-linked disorder characterized by defective beta oxidation and accumulations of
very-long chain fatty acids. This metabolic defect is detectable in heterozygotes and prenatally. The adult-onset phenotype (progressive spastic paraparesis) is called adrenomyeloneuropathy."


What is Marburg's Disease?

"Marburg's disease, is another name for tumefactive MS (and for Balo concentric sclerosis or acute MS).

Tumefactive MS is an acute tumor-like MS variant in which some patients with demyelinating disease present with large (>2 cm) acute lesions, often associated with edema or ring enhancement. There may be mass effect, with compression of the lateral ventricle and shift across the midline. It can cause severe cerebral damage and render a
patient comatose within a few weeks. The patient does not go into remission and may die within weeks or months after onset of the demyelinating disorder."


What is Pelizaeus-Merzbacher disease?

"Pelizaeus-Merzbacher disease is an X-linked recessive disorder in which the gene codes for proteolipid protein,
the main membrane protein of myelin. The most frequent gene mutation leads to duplication of the PLP gene."


What is ADEM?

Acute disseminated encephalomyelitis. Monophasic demyelination:

Primarily affects children
May report antecedent infection
ABs to myelin basic protein

Sx: alterations in consciousness, seizures, focal weakness, numbness, visual field defects

Tretament: corticosteroids, IVIg, plasmapheresis

The disease usually affects children and young adults, presents abruptly with headaches and fever usually 2 to 12 days after an infection, and resolves rapidly within a week. Usually, there are no residual neurologic deficits, and most cases are now nonfatal. Historically, this monophasic acute demyelinating disorder
was associated with smallpox vaccinations and then later was identified after measles, mumps, rubella, varicella, or vaccinia infections. Today, usually the disorder follows a nonspecific upper respiratory illness."

The clinical features, coupled with the perivenular inflammatory and demyelinating features illustrated in the
images on the Luxol fast blue-periodic acid Schiff stain for myelin, are pathognomonic


What is Krabbe disease?

Krabbe disease is due to a deficiency of galactocerebroside-beta-galactosidase.


What is Metachromatic leukodystrophy?

Metachromatic leukodystrophy is due to a deficiency of arylsulfatase.


What is Canavan disease

Canavan disease is due to a deficiency of aspartoacylase.


What is CADASIL? Which gene is it associated with?

Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) results from missense mutations of the Notch 3 gene on chromosome 19. The small deep white matter vessels show replacement of the media by eosinophilic, periodic acid-Schiff positive, Congo red negative, granular material. Ultrastructurally, there is compact electrondense material known as granular osmophilic material surrounding myocytes in the arterial media. Although the predominant effects of CADASIL are on the central nervous system, it is a systemic vasculopathy that can be appreciated on skin or nerve biopsy. Vasculitis is not seen in CADASIL.


What is Leber hereditary optic neuropathy

LHON is a maternally inherited bilateral subacute optic neuropathy caused by mutations in the mitochondrial genome.

mtDNA point mutation

Typically produces severe permanent visual loss that predominantly affects males - onset late teens,

Classic features: telangiectatic microangiopathy, disk pseudoedema, vascular tortuosity


What are some of the neuroimmunological granulomatous disorders?

Sarcoidosis, chronic infections (TB, leprosy)



Systemic granulomatous disease of unknown etiology
Can affect any part of nervous system
Common presentation: bilateral facial palsy, other cranial neuropathies, mononeuritis multiplex, myopathy

Dx: typically requires biopsy demonstrating noncaseating granulomas
Hilar LN typically biopsied
Serum ACE can be elevated, but limited sensitivity and specificity
CSF - may show mononuclear cell pleocytosis, elevated protein, low glucose, elevated IgG, elevated ACE

Treatment: corticosteroids +/- other immunosuppressants


CNS vasculitis - presentation, pathology

wide range of sx and signs