PSYC 415--Notes for Causes of Human Brain Damage

1. meningiomas (20% of primary brain tumors) - tumors forming in or between the meninges
   1. all are encapsulated - grow within their own membrane
   2. easily identified on scans
   3. most are benign and slow growing
      1. easily removed surgically
      2. little danger of metastasizing - spreading to other tissues
   4. in the brain even benign tumors are dangerous because they grow
      1. limited space for expansion inside the cranium
      2. function of tissue impaired due to compression - impairment might be far from the tumor
2. gliomas (60% of primary brain tumors) - tumors of glia
   1. generally diffuse or infiltrating - ie., not encapsulated by a membrane but growing diffusely through surrounding tissue, therefore, difficult to identify on a scan
   2. generally malignant - not easily removed and prone to metastasizing
   3. metastatic (spreading) tumors may also develop on blood vessels or other tissues in the brain, but rarely develop from neurons (which are no longer undergoing cell division)
   4. treated with chemotherapy and radiation
3. about 10% of tumors in the brain are not primary to the brain but are metastases from other organs - breast and lung cancers are esp. likely to metastasize to the brain
   1. tumor cells are carried in the blood supply or lymph and are, therefore, most likely to settle in organs with rich blood supplies (lungs, kidney, liver, and brain)
4. signs - headache, vomiting, edema of the optic disk (due to increased intracranial pressure), seizures and focal signs (due to irritation or compression of tissue)

1. strokes (cerebrovascular accidents or CVAs, at one time called apoplexy) - loss of blood supply to an area of brain tissue due to:
   1. cerebral hemorrhage (hemorrhage = bleeding)
      1. bursting blood vessels, perhaps due to an aneurysm (a ballooning out of a defective blood vessel wall)
   2. cerebral ischemia - interruption of blood flow due to a blockage
      1. thrombosis - blockage that forms "on the spot" (the "thrombus") due to a blood clot, tumor cells, fatty deposits, etc.
      2. embolism - blockage ("embolus") that is carried into a smaller blood vessel from a larger blood vessel (air bubbles, tumor cells, fat deposits that have broken loose from vessel walls, etc.)
      3. arteriosclerosis - "hardening of the arteries" or thickening of blood vessel walls due to fat deposits, eventually (perhaps) resulting in embolism or even thrombosis
   3. brain damage in a stroke may be partially or mainly due to release of glutamate due to disinhibition of excitatory neurons - it may be possible to prevent this with NMDA-blocking drugs (which are not the clot busting drugs currently used to treat many strokes)
      1. excitotoxicity
2. signs of a stroke - mainly focal signs
3. recovery - depends upon extent of tissue damage, how rapidly treatment is obtained, and ability to pay for physical therapy

1. contusions - damage to blood vessels causes bleeding and hematoma (hemato = blood, oma = tumor or mass), or bruising
   1. contusions result when the brain slams against the inside of the skull
   2. often there are contre coup injuries
   3. subdural hematomas - most common
   4. epidural or extradural hematomas
2. concussions - temporary impairment in consciousness due to a blow to the head, but with no evidence of bleeding or other structural damage (but punch-drunk syndrome resulting from repeated concussions suggests there is some damage to the brain in a concussion; there is probably some swelling, for example, and perhaps also scarring)

1. gunshot wounds
2. the case of Phineas Gage (1823-1860)
   1. most of what you've read cannot actually be verified - accounts even in "credible" sources are often greatly exaggerated
   2. the "American Crowbar Case" - first case to suggest that brain damage could alter personality and complex behavior
   3. Sept. 13, 1848, about 4:30 PM, near Cavendish, Vermont
   4. a tamping rod about 1.25 inches in diameter and 3.5 ft. in length was blown through his head and landed about 80 ft. away
   5. Gage spoke almost immediately, and sat upright on the trip to the doctor's office - when the doctor first saw him, he was telling bystanders what had happened to him!
   6. his primary problem at first seemed to be exhaustion from loss of blood
   7. he eventually became "semi-comatose" (stuporous), but within a month of the accident was walking again
   8. later worked in a livery stable and as a stage driver
   9. began to experience seizures in early 1860 and died May 21st (in San Francisco)
   10. his doctor (John Harlow) did not publish details of Gage's mental changes until 1868 - described him as fitful, irreverent, profane, impatient, obstinate, and capricious (and the most often quoted phrase that he was "no longer Gage")

1. bacterial infections
   1. meningitis - infection of the meninges (may be bacterial or viral)
      1. fever, malaise, headache, stiff neck resulting from protective reflex
      2. college students living in a dorm are especially at risk: CDC warning
      3. streptococcal meningitis
   2. encephalitis - infection of the brain tissue (may be bacterial or viral)
      1. mosquito-borne diseases
      2. encephalitis lethargica ("sleeping sickness")
         • not African sleeping sickness, which is carried by tsetse flies (link to Wikipedia)
         • Wikipedia article on encephalitis lethargica
         • this is the disease portrayed in the movie Awakenings
      3. syphilis - after many years (10-20) the bacteria can attack the CNS (but mental signs can also appear much sooner)
         1. tabes dorsalis - sensory and motor problems resulting from infection attacking the spinal cord
         2. general paresis - insanity and dementia resulting from infection attacking the brain
      4. tuberculosis
2. viral infections
   1. neurotropic infections - viral infections that specifically target neural tissue
      1. poliomyelitis ("polio") - virus attacks the motor areas of the spinal cord and brainstem resulting in paralysis, muscle wasting, and death
      2. rabies - description from ciba (Netter)
   2. pantropic infections - viral infections that do not specifically target neural tissue but which may travel there eventually
      1. mumps
      2. herpes
      3. AIDS
3. prion diseases - spongiform encephalopathies
   1. scrapie - in sheep (may have been the source of BSE)
   2. mad cow disease (bovine spongiform encephalopathy or BSE)
   3. chronic wasting disease - seen in members of the deer family
   4. feline and mink spongiform encephalopathies
   5. Creutzfeldt-Jakob disease (CJD) - in humans (first described 1920)
      1. rare, degenerative (1 per million per year--about 200 cases per year in U.S.), always fatal
      2. occurs mostly in the elderly and progresses rapidly (almost all die within a year)
      3. memory failure, behavioral and personality changes, visual disturbances and hallucinations
      4. later - motor symptoms, weakness, blindness, dementia, coma
      5. types
         • sporatic - appears in persons with no known risk factors (idiopathic) - 85% in U.S.
         • hereditary - appears in persons with a family history and who test positive for a certain genetic mutation - 5-10%
         • acquired - through exposure to brain or nervous tissue, e.g., dura mater grafts, transplanted corneas, contaminated growth hormone (iatrogenic)
         • (new) variant - CJD in humans due to eating infected beef - only 3 known cases in U.S.
      6. there is no cure and no treatment
      7. normal sterilization procedures to not destroy prions
   6. fatal familial insomnia
4. fungal, protozoan, metazoan infections

1. enlargement of the ventricles due to accumulation of CSF - normal flow is blocked
2. can happen in infants, children, or adults - in infants it causes cranial enlargement
3. the danger is compression of surrounding brain tissue

1. heavy metal poisoning (mercury, lead) can affect the CNS causing toxic psychosis
2. medications and other drugs
3. carbon monoxide - deprives the brain of oxygen
4. MPTP - later!
5. alcohol
   • Fetal Alcohol Syndrome, effect on the brains of children
   • alcoholism and the adult human brain (Science)

1. PKU (phenylketonuria) - a metabolic disorder inherited from both parents via an autosomal recessive allele
2. Down syndrome - a congenital (but not inherited) disorder in which chromosome 21 is tripled rather than paired

1. causes
   1. irritation from a tumor, dead tissue, a foreign object, etc.
   2. infections
   3. neurotoxins
   4. genes - over 70 different genes have been linked to it (Pinel)
   5. biochemical abnormalities - possible loss of GABA inhibition
   6. idiopathic - nobody knows! (about 1% of the population is diagnosed with epilepsy at some time during their lives, and most of these cases are idiopathic epilepsy)
   7. seizures secondary to some other illness or use of medication are not labeled epilepsy (so the diagnosis can be tricky)
2. seizures - a seizure is an abnormal burst of high-amplitude EEG spikes lasting from seconds to minutes
   1. seizure recordings
      • complex partial seizure
      • EEG showing spike-dome discharge ("spike-and-wave")
   2. if the seizure begins in a sensory area of the brain (for example), the person may experience an epileptic aura (a bad smell or some other sensation or feeling that forebodes the full blown seizure/convulsion)
   3. if the seizure occurs in a motor area of the brain, the person will experience a convulsion
      1. clonus - trembling or shaking of the body
      2. tonus - rigidity due to muscle contraction
      3. loss of balance, coordination, and often consciousness
   4. grand mal seizures - loss of consciousness and violent tonic-clonic convulsions accompanied by hypoxia (oxygen deficiency) and cyanosis (turning blue due to the pooling of unoxygenated blood in the tissues)
   5. petit mal seizures - absences, staring, lip-smacking, fluttering eyelids, 3 Hz spike-dome discharge in EEG
   6. generalized seizures - involve the "entire brain" although may originate from a specific focus and spread (grand mal and petit mal are examples)
   7. partial seizures - do not involve the "entire brain", hence resulting in a focal epilepsy (such as temporal lobe epilepsy)
      1. simple partial seizures - sensory or motor or both ("Jacksonian")
      2. complex partial seizures - in more "complicated" areas of the brain, resulting in more bizarre auras and signs (temporal lobe epilepsy)

1. Parkinson's disease - will be discussed in more detail under motor disorders
   1. unknown origin, probably environmental
   2. motor impairment (primarily)
      1. tremor and rigidity
      2. masklike face
      3. shuffling gait
2. Huntington's disease
   1. genetic in origin - autosomal dominant
   2. severe motor impairment and dementia with onset in middle age (fidgetiness evolving into choreiform movements and progressive dementia) with a fatal outcome
   3. finding in the brain - extensive degeneration, esp. in the cortex and basal ganglia
3. multiple sclerosis - a demyelinating disease (already discussed)
   • areas of sclerosis
4. Alzheimer's disease (or "senile dementia")
   1. most common cause of dementia in the elderly - 70-80% of dementias of the elderly
   2. there has been discussion of the fact that Alzheimer's behaves like a prion disease
      1. this is an UNPROVEN speculation!
      2. CJD is sometimes mistaken for Alzheimer's
   3. there is no definitive test for this disease, and there is no treatment (yet)
   4. usually strikes in people over 70, but there is also an early onset form that may occur as young as 40 and is probably genetic in origin
   5. a history of strokes (as well as other forms of brain damage) increases the risk
   6. aluminum is NOT a cause of Alzheimer's
   7. progressive degenerative disease progressing generally as follows:
      1. depression
      2. cognitive decline, esp. memory
      3. deterioration of speech
      4. personality changes
      5. motor impairment
      6. death
   8. findings in the brain
      1. neurofibrillary tangles - little knots and tangles of protein found in the cytoplasm of neurons and resulting from the degeneration of the microtubules
      2. amyloid plaques - clumps of scar tissue created by degenerating neurons and amyloid protein (not unique to Alzheimer's disease but much more prevalent)
      3. general cell loss throughout the cortex - up to 1/3 of total brain weight can be lost!
      4. these findings tend to be most severe in the temporal lobes and prefrontal cortex (although they occur to some degree throughout the cortex)
      5. an early marker is atrophy of the hippocampus

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