CHAPTER 23 NERVOUS SYSTEM ! ASTROCYTOMAS: THE MOST COMMON CNS NEOPLASM.

. 3 forms o Astrocytes are cells that support the neurons in the CNS. o Primary neoplasms of the brain and of course metastases to the brain ! Invlvd in healing & forming scar-like tissue in brain injury - supportive cells o Even benign tumors can result in death when in CNS b/c no room for expansion o ASTROCYTOMA: well differentiated but infiltrative. Grows slowly & persons life span can be 5 - 10 years. Constitutes 20% of primary CNS neoplasms ! Well diff. tumor but tends to be very infiltrative (slow grwth but relentless) ! Unfortunately they tend to never go away ! Least aggressive of the 3 forms of astrocytoma; so long term survivability o ANAPLASTIC ASTROCYTOMA: mod diff & more aggr w/life expect. of 3 years ! More aggressive, still relatively well differentiated, or moderately differentiated " not as differentiated as astrocytoma ! Its life span prognosis is shorter, about 3 years o GLIOBLASTOMA MULTIFORME: poorly differentiated; most aggressive; life span 1-1.5 yrs. 40% of primary CNS neoplasms ! Most aggressive form of astrocytomas ! Life span is about a year or so (most poorly differentiated) ! MOST COMMON OF THE ASTROCYTOMAS ! NEOPLASMS METASTATIC TO BRAIN o Leukemia, lymphoma, carcinoma of lung & breast, melanoma in decr order ! PRIMARY DISEASES OF MYELIN o MULTIPLE SCLEROSIS: MOST COMMON DEMYELINATING DISEASE. Mostly in 2nd & 3rd decades of life. Less common in Blacks & Asians. Etiology unknown; strong immuno possibilities. Plaques (areas of demyelin.) in CNS only ! Clinical Features: blurred vision, diplopia, paresthesia, spasticity, slurred speech, and abnormal gait. Life span unpredictable ! MOST COMMON OF THE MYELIN FORMING DISEASES ! In MS, you are born with a normal CNS histology, function, and anatomy ! Probably b/c of immunologic processes, T cell mediated injuring myelin sheaths are destroyed focally in CNS, & therefore conduction of the axons is interrupted ! Key factoid of MS is idea of PLAQUE FORMATION. You see a slice of brain w/big red area " PLAQUE- AN AREA OF DEMYELINIZATION & THAT WHY ITS RED. This is the gross, visible abnormality of MS ! Unfortunately, this is a permanent situation.

! Some ppl have what is referred to as ACUTE MS. They die rather quickly usually due to respiratory failure or pneumonia, pulmonary problems that develop from of lack of control of diaphragm & normal respiration ! In other people there will be slow progression o LEUKODYSTROPHIES: A group of inherited problems that result in INABILITY TO FORM NORMAL MYELIN TO BEGIN WITH. Usually seen in childhood ! INABILITY TO FORM AND MAINTAIN NORMAL MYELIN TO BEGIN WITH o Important to say that these 2 conditions are DEMYELINATING DISEASES -one where myelin formation isnt maintained and with the leukodystrophies, myelin formation never really occurred properly to begin with ! DEGENERATIVE DISEASES: A group of disorders characterized by progressive degeneration of neurons in various parts of the CNS o Problems with NEURONS, NOT THE MYELIN o ALZHEIMER: Dementia is defined as the development of memory impairment and cognitive deficits in those with a normal level of consciousness ! Dementia means gradual dvlpmnt in older adults of memory impairment & other cognitive deficits in somebody who is of normal consciousness ! No CNS depression, not comatose ! MOST COMMON CAUSE OF DEMENTIA IN THE ELDERLY ! Most cases are sporatic ! Causation- 10% cases genetic. B-amyloid been shown toxic to neurons There are abnormalities of a neuronal intracell protein called TAU Aggregates of TAU proteins form NEUROFIBRILLARY TANGLES that, when combined with beta-amyloid, form SENILE PLAQUES that are the histologic hallmark of Alzheimers ! 2 microscopic findings in the brains of all Alzheimers NEUROFIBRILLARY TANGLES SENILE PLAQUES (Histologic hallmark) ! It appears the neurofibrillary tangles are made up of these TAU proteins. ! Couple neurofibriilary tangles + beta-amyloid " form senile plaques ! Clinical--- Brain shrinkage, progressive cognitive impairment, death from pneumonia and infection o PARKINSONISM: A motor function prblm (rarely w/dementia) causing abnormal tremors & loss of muscle coordination. Expressionless, unintentional tremors. Loss of dopamine secreting neurons in SUBSTANTIA NIGRA. Decreased responsiveness to and production of dopamine occurs. Slow, unremitting disease ! Degenerative NEURONAL problems ! Neurons in substantia nigra form prtn inclusions called LEWY BODIES

! The dopamine secreting neurons in this part of the brain quit forming DA. Theres decreased responsiveness to dopamine. AND Increased reduction of dopamine is occurring in substantia nigra part of brain ! Early in Parkinsons, L-dopa is administered & tends to ameliorate sympt for awhile, but people become unresponsive to that and symptoms return ! Progression is variable ! FACTOID: The neurons in the substantia nigra form protein inclusions called LEWY BODIES ! Most cases occur in 50s & 60s. Death may occur due to inf. & accidents ! Theres no particular predisposing factors that are generally identifiable o HUNTINGTON DISEASE: A hereditary, progressive motor function disorder that involves EXTRAPYRAMIDAL system characterized by uncontrolled spastic movements "chorea" and dementia. A TRINUCLEOTIDE REPEAT DISORDER on chromosome #4, transmitted by the father. The gene defect produces an abnormal protein called HUNTINGTIN. Not manifested until 30s or 40s. Suicide common cause of death ! Enormously spastic movements - They flail. Cases where arms and legs are totally out of control ! The gene on CHROMOSOME 4 produces an abnormal protein. That abnormal protein is called HUNTINGTIN, NOT -TON