Multiple Sclerosis Flashcards

Vocabulary flashcards about Multiple Sclerosis

Multiple Sclerosis (MS)

The most prevalent inflammatory disease of the CNS, affecting over 2 million people worldwide and currently incurable.

Initial Manifestation of MS

Episodes of neurologic disability that are fully or partially reversible, but progress to worsening disability after 10-20 years.

Epidemiology of MS

Higher in females than males (3:1), with a mean age at onset of 20-30 years, mostly in North America and Europe.

Environmental Causes of MS

Vitamin D deficiency, cigarette smoking, diet, obesity early in life, late infection with Epstein-Barr virus, and microbiota dysbiosis.

Genetic Causes of MS

Polymorphisms in genes involved with Ag presentation like HLA DR2, HLA DRB1*15:01, IL2RA and IL7RA

Mechanism of MS Development

Autoreactive T cells escaping central tolerance and being released into the periphery due to T reg cell defects.

Clinical Manifestations of MS

Cognitive impairment, Sensory or motor deficits, Affective disturbances, Visual loss, Tremor, Ataxia, Diplopia, Vertigo, Weakness, Spasticity, Urinary incontinence, Erectile dysfunction, Pain, Fatigue, Heat sensitivity

MRI Findings in MS

Focal inflammations visible in the spinal cord parenchyma, with recent lesions enhancing after contrast injection.

CSF Analysis in MS

Presence of many antibodies in the cerebrospinal fluid, indicating a neurological autoimmune disease.

Treatment Mechanisms for MS

Primarily involve diminishing neuroinflammation; some may slow the underlying neurodegenerative process.

BTK (Bruton’s tyrosine kinase)

Bruton’s tyrosine kinase, interacts with intracellular kinase, activating the Fcy receptor of Ig and inducing phosphorylation of the NFKB pathway.

MS Animal Models

Isoallergic encephalomyelitis and radiculitis, Rapid production of acute disseminated encephalomyelitis, Experimental disseminated encephalomyelitis, Experimental autoimmune encephalomyelitis

Experimental Autoimmune Encephalomyelitis (EAE) Types

Myelin basic protein, Myelin oligodendrocyte glycoprotein, Proteolipid protein, Encephalitogen peptides

Active EAE

Myelin peptides are injected in the skin to develop inflammatory disease in the animal model due to induced phenotypes.

Active Transfer EAE

Injecting blood (containing active T CD4 cells) from an active EAE mice.

EAE scoring system

Score 1: tail paralysis only Score 2: hind legs weakness Score 3: complete paralysis of hind legs Score 4: complete hind leg and partial front leg paralysis Score 5: death due to paralysis

Chronic EAE (CREAE)

Characterized by relapses and remissions during disease progression, induced by different peptides.

Limitations of EAE Models

EAE has a known and induced start, we don't know when multiple sclerosis starts, neither the cause. This is why many therapies do not perform as well in humans.

Field of Interest

IL17 affects synaptic plasticity and cognition in an experimental model of MS.