Degenerative conditions affecting the nervous system

preferential destruction of myelin sheath around axon Relative preservation of axons themselves disease of myelin or oligodendrocyte/Schwann cell

• oligodendrocytes - disruption of electrical conductivity within the CNS

Primary (MS) Secondary (central pontine myelinolysis, progressive multifocal leucoencephalopathy, sub-acute sclerosing pan encephalitis, AIDS, axonal degeneration) Metabolic Toxic (cyanide, CO, solvents)

• episodes of neurological deficit separated by time, brain and spinal cord lesions disseminated in both time and space, ned to have different areas involved • relapsing and remitting with flare-up episodes -Visual disturbance, parasthesia, spasticity of one or more of the extremities, speech disturbance, gait abnormalities. May develop cognitive impairment -environmental, genetic (HLA gene), immune -areas of demyelination, myelinated areas in brain are normally dark tends to radiate out from the corpus colossum in patches -external- appears normal cut- see multiple areas of demyelination termed plaques As white matter disease well-demarcated plaques (acute the soft and pink) non anatomical distribution, optic nerve, periventricular white matter, corpus callosum, brain stem and spinal cord might act as a SOL (rarely)

acute active plaques (ongoing myelin breakdown, abundant macrophages, inflammatory cells including both lymphocytes and monocytes, mostly as perivascular cuffs. small active lesions often entered around veins.) Chronic inactive plaques (centre of an inactive plaque contains little or no myelin astrocytic proliferation and gliosis are prominent) Chronic active plaques relapse on the same part of the brain as has been previously affected Shadow plaques border between normal and affected white matter is not clearly defined. some abnormally thinned out myelin sheaths can be identified, especially at the outer edges -Acute demyelinated plaques are yellow/brown with an ill defined edge which blends into surrounding white matter chronic well demarcated grey/brown lesions in white matter, classically situated around lateral ventricles -demyelination inflammation Gliosis

• Nuerodegenerative disorder: an impairment of previously acquired occupational or social functioning due to development of acquired and persistent memory impairment associated with impairment of intellectual function in the presence of normal consciousness • nooope, always pathological -Primary dementias Alzheimers disease (most common), diffuse Lewy body disease, Huntington's disease, Pick's disease Secondary dementias other disorders resulting in secondary changes in the CNS resulting in dementia such as; vascular, metabolic, infection and trauma

• over 60s • sporadic occurrence, slight familial tendency • amyloid precursor protein (APP) gene found on chromosome 21, presenilin 1 gene on chromosome 14 and presenilin 2 gene on chromosome 8. -insidious impairment of higher intellectual function, with alterations in mood and behaviour Later- progressive disorientation, memory loss and aphasia = severe cortical dysfunction can eventually result in profound disability, muteness and immobility -decreased size and weight of brain widening of sulci narrowing of gyri compensatory dilatation ventricles and secondary hydrocephalus frontal, temporal and parietal lobes affected brainstem and cerebellum normal -Intracytoplasmic neurofibrillary tangles AB amyloid plaques (extracellular or neuritic plaques) amyloid angiopathy extensive neuronal loss with astrocytosis • sulk wider, gyri narrower, increased space between brain and cranium

-bundles of filaments in the cytoplasm of the neurons that displace or encircle the nucleus. Major component is tau protein, a micro-tubule associated protein, which is abnormally phosphorylated in Alzheimer’s disease. use silver stains to see -focal, spherical collections of dilated, tortuous, neuritic processes surrounding a central amyloid core. Often surrounded by peripheral reactive astrocytes and microglia. Occur most frequently in hippocampus, cerebral cortex and deep grey matter. CONGO RED!! – perivascular amyloid deposition, derived from abnormally cleavage of APP.

-progressive, hallucination and fluctuating levels of attention can develop features of parkinson disease Fluctuation of severity of condition day to day -degeneratin of the substance nigra remaining nerve cells contain lewy bodies degeneration of the cortical areas of the brain as seen in Alzheimers formation of cortical lewy bodies -by immunochemical staining for the protein ubiquitin

• neuropsychiatric dosorder, onset between 35-50 • autosomal dominant (huntington gene of chromosome 4p) • emotional, cognitive and motor disturbance -chorea, myoclonus, clumsiness, slurred speech, depression, irritability, apathy dementia develops later -loss of neurones in caudate nucleus and cerebral cortex accompanies by reactive fibrillary gliosis

• progressive dementia, characterised by slowly progressing changes in character and social deterioration leading to impairment of intellect, memory and language • 50-60 -extreme atrophy of cerebral cortex in frontal and temporal lobes neuronal loss and astrocytosis -Pick’s cells (swollen neurones) and intracytoplasmic filamentous inclusions known as Pick’s bodies -personality and behavioural change speech and communication problems Changes in eating habits reduced attention span rapidly progressive, mean length 7 years

• deterioration in mental functioning due to changes or damage to the brain tissue from hypoxia or anoxia as a result of multiple blood clots within vessels supplying the brain • after age 60, also in middle aged hypertensives • depression and anxiety, as sufferers aware of mental deficits -abrupt onset stepwise progression Hx hypertension/stroke evidence to stroke on CT or MRI