PSYC 415--Study Points for Causes of Human Brain Damage (revised 26 Aug 2020) I. brain tumors (neoplasms or "new growth"; i.e., cancer) - uncontrolled growth (cell division) of a tissue mass that serves no useful purpose A. 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 ("harmless", not cancerous) and slow growing a. easily removed surgically b. little danger of metastasizing - spreading to other tissues 4. in the brain even benign tumors are dangerous because they grow a. there is limited space for expansion inside the cranium b. function of tissue impaired due to compression - impairment might be far from the tumor B. gliomas (60% of primary brain tumors) - tumors of glial cells 1. generally diffuse or infiltrating - i.e., 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 a. metastatic - spreading from one place to another b. usually through the blood or lymphatic system 3. astrocytoma - cancer of astrocytes (includes glioblastoma) C. 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) D. 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 2. therefore, most likely to settle in organs with rich blood supplies (lungs, kidney, liver, and brain) E. signs (vs. symptoms) - headache, vomiting, edema of the optic disk (due to increased intracranial pressure), seizures and focal signs (due to irritation or compression of tissue) F. treatments: surgery, radiation, chemotherapy G. best source of info: http://www.cancer.gov/cancertopics/types/brain II. epilepsy (seizure disorders) A. seizures - a seizure is an abnormal burst of high-amplitude EEG spikes lasting from seconds to minutes 1. 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) 2. if the seizure occurs in a motor area of the brain, the person will experience a convulsion a. tonus - rigidity due to muscle contraction b. clonus - trembling or shaking of the body c. loss of balance, coordination, and often consciousness B. types of seizures 1. generalized seizures - involve the "entire brain" although may originate from a specific focus and spread (grand mal and petit mal are examples) a. 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) b. petit mal seizures - absences, staring, lip-smacking, fluttering eyelids, 3 Hz spike-dome discharge in EEG 2. partial seizures - do not involve the "entire brain", hence resulting in a focal epilepsy (such as temporal lobe epilepsy) a. simple partial seizures - sensory or motor or both b. complex partial seizures - in more "complicated" areas of the brain, resulting in more bizarre auras and signs (temporal lobe epilepsy) C. 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 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. birth hypoxia or ischemia (tissues deprived of oxygen) 8. hippocampal sclerosis (scarring) 9. seizures secondary to some other illness or use of medication are not labeled epilepsy (so the diagnosis can be tricky) III. cerebrovascular disorders (cerebrovascular accidents) A. 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) a. bursting blood vessels, perhaps due to an aneurysm i. aneurysm - abnormal widening or ballooning of an artery or blood vessel due to weakness in the artery wall ii. commonly form at branch points of blood vessels iii. surgical treatment - aneurysm clip ligation b. hemorrhagic stroke 2. cerebral ischemia - interruption of blood flow due to a blockage a. thrombosis - blockage that forms "on the spot" (the "thrombus") due to a blood clot, tumor cells, fatty deposits, etc. b. 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.) c. arteriosclerosis - "hardening of the arteries" or thickening of blood vessel walls due to fat deposits, eventually (perhaps) resulting in embolism or even thrombosis d. ischemic (obstructive) stroke B. signs of a stroke - mainly focal signs (sudden numbness, weakness, dizziness, slurring of speech, headache, visual or sensory disturbances) C. recovery - depends upon extent of tissue damage, how rapidly treatment is obtained, and ability to pay for physical therapy IV. closed-head injuries (in which the skull is not fractured or opened - traumatic brain injury part 1)) A. 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 (can be acute or chronic) a. "roaring" headache b. usually no vomiting (burst aneurysm results in "thunderclap" headache and projectile vomiting) 4. epidural or extradural hematomas B. 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) C. chronic traumatic encephalopathy (CTE) 1. can result from multiple concussive or sub-concussive episodes 2. degeneration of the brain similar to that which occurs in Alzheimer's 3. accumulation of tangled tau protein (although in a somewhat different pattern from Alzheimer's) 4. most likely to occur in athletes in contact sports (football, boxing, etc.), victims of domestic abuse, military veterns of combat duty V. open-head injuries (traumatic brain injury part 2) A. skull fractures, gunshot wounds, etc. 1. linear skull fractions 2. depressed skull fractures 3. basal skull fractures - bleeding from the nose and ears, raccoon eyes B. 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, Gage 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") VI. neurotoxins and developmental disorders A. heavy metal poisoning (mercury, lead, arsenic) can affect the CNS causing brain and nerve damage, mental retardation, convulsions, coma, and death 1. symptoms of lead poisoning: abdominal pain, constipation, headache, irritability, memory problems, sterility 2. mechanisms of lead poisoning a. interferes with calcium, iron, and zinc in the body b. creates free radicals that damage membranes and DNA c. demyelination of neurons d. etc. e. gets into the brain and neurons by hijacking calcium transporters B. carbon monoxide - deprives the brain of oxygen C. MPTP - an injested neurotoxin, converted in the brain to MPP+ (by MAO), taken up by dopamine neurons, and then kills them by oxidative stress, resulting in a profound Parkinsonian-like state that comes on overnight D. alcohol 1. Fetal Alcohol Syndrome, effect on the brains of children 2. alcoholism and the adult human brain (Science) 3. heavy drinking in college students E. summary of neurotoxins 1. ion channel inhibitors - tetrodotoxin, conotoxins, various toxins derived from algae and bacteria 2. inhibitors of neurotransmitter release - botulinum toxin, tetanus 3. neurotransmitter receptor blockers - bungarotoxin (from snake venom), curare (from a S. American plant) 4. irreversible actions on neurotransmitters - black widow spider venom, anatoxin ("Very Fast Death Factor") produced by cyanobacteria 5. substances that attack the cytoskeleton - arsenic 6. substances that interfere with calcium transport - lead 7. blood-brain barrier inhibitors - aluminum, mercury 8. substances with multiple effects - alcohol F. developmental disorders 1. toxins that damage the brain, such as alcohol and heavy metals 2. effects of neglect 3. genetic diseases a. PKU (phenylketonuria) - a metabolic disorder inherited from both parents via an autosomal recessive allele (one of 100 or more metabolic disorders that can effect brain development) b. Tay-Sachs disease - due to a mutation of teh HEXA gene on chromosome 15; autosomal recessive; most common in isolated populations such as Ashkenazi Jews; cherry red spot on retina is diagnositc; symptoms appear after 6 months of normal development and include abnormal startle, listlessness, muscle stiffness and progressing to blindness, deafness, paralysis, and death by age 4; there is no treatment; due to an inability to biodegrade waste gangliosides b. Down syndrome - a congenital (but not inherited) disorder in which chromosome 21 is tripled rather than paired, resulting in abnormal brain development, and in adults a degenerative disorder similar to that which occurs in Alzheimer's disease VII. degenerative disorders A. spongiform encephalopathies (prion diseases) - see the Mad Cow video handout B. Parkinson's disease 1. one of the most common neurodegenerative diseases, esp. in the elderly (with Alzheimer's disease) 2. caused by degeneration in the nigrostriatal dopamine system - originates in the substantia nigra of the midbrain and terminates in the striatum (caudate nuc. and putamen) of the telencephalon 3. most cases are of unknown origin (idiopathic), probably environmental 4. symptoms - motor impairment (primarily) a. tremor and rigidity - tremor in the hands with "pill rolling" b. masklike face c. stooped posture, with short, shuffling gait, freezing up d. difficulty initiating voluntary movements 5. standard treatment is with l-dopa, precursor of dopamine 6. various surgical procedures have also been tried, most notably placing lesions in the globus pallidus C. 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 4. most famous case - Woodie Guthrie (folk singer) a. first signs in 1940s (when he was in his 30s) b. diagnosed as alcoholism and schizophrenia c. eventually (1952) recognized as HD - inherited from his mother d. hospitalized last 10 years of his life; died 1967 D. multiple sclerosis - an autoimmune demyelinating disease (already discussed), usually considered a motor disorder but also has sensory signs; most common neurological disorder north of 45 degrees N latitude! E. amyotrophic lateral sclerosis (ALS) 1. Lou Gehrig's disease (most famous case, 1903-1941, 1st baseman NY Yankees) 2. strikes motor neurons in the spinal cord and cranial nerves 3. leading to spasticity, exaggerated stretch reflexes, progressive muscle weakness, muscle atrophy, fasciculations, and death (within 5-10 years; Lou Gehrig died just 2 yrs. after diagnosis) 4. there is generally limited or no cognitive impairment 5. 10% of cases are genetic, the remainder sporatic (idiopathic) F. Alzheimer's disease (or "senile dementia") 1. most common cause of dementia in the elderly - 70-80% of dementias of the elderly 2. occurs in 10% of people over age 65 and 50% over age 85 3. there has been discussion of the fact that Alzheimer's behaves like a prion disease a. you CANNOT get Alzheimer's disease from an afflicted relative b. CJD is sometimes mistaken for Alzheimer's 4. there is no definitive test for this disease, and there is no treatment (yet) 5. 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 6. a history of strokes (as well as other forms of brain damage such as concussions) is the leading risk factor 7. aluminum is NOT a cause of Alzheimer's 8. progressive degenerative disease progressing generally as follows: a. depression b. cognitive decline, esp. memory c. deterioration of speech d. personality changes e. motor impairment f. death 9. findings in the brain a. neurofibrillary tangles - little knots and tangles of protein found in the cytoplasm of neurons and resulting from the degeneration of the microtubules resulting in tangled clumps of tau protein b. amyloid plaques - clumps of scar tissue created by degenerating neurons and amyloid protein (not unique to Alzheimer's disease but much more prevalent) c. general cell loss throughout the cortex - up to 1/3 of total brain weight can be lost! d. these findings tend to be most severe in the temporal lobes and prefrontal cortex (although they occur to some degree throughout the cortex) e. an early marker is atrophy of the hippocampus 10. myths a. not fatal (it's always fatal if the patient doesn't die of something else first) b. only old people get it - there is an early onset form c. drinking out of aluminum cans can cause it - 1970s nonsense d. aspartame can cause it - no credible evidence of this e. flu shots increase the risk - reseawrch suggests just the opposite f. silver dental fillings increase the risk - no credible evidence g. progression can be stopped - not at this time G. other dementias 1. Lewy body dementia - associated with abnormal deposits of a protein called alpha-synuclein (Lewy bodies) 2. Parkinson's disease dementia - appears to be associated with Lewy body dementia 3. fronto-temporal dementia VIII. infections of the brain A. meningitis - infection of the meninges (may be bacterial or viral) 1. college students living in a dorm are especially at risk: CDC warning 2. fever, malaise, headache, stiff neck resulting from protective reflex, convulsions, loss of consciousness, death 3. viral meningitis - usually not as serious as... 4. bacterial meningitis a. streptococcal meningitis b. may result from: a middle ear infection that spreads to the brain, bacterial that enter an open head injury, an embolis of bacterial debris that arrives in the brain from elsewhere (perhaps resulting from use of infected hypodermic needles) B. encephalitis - infection of the brain tissue (may be bacterial or viral, but is more commonly viral) 1. mosquito-borne diseases 2. pantropic infections - viral infections that do not specifically target neural tissue but which may travel there eventually a. mumps b. herpes simplex - lives in the trigeminal nerve ganglia and occasionally causes cold sores, but also can result in a viral infeciton of the frontal and temporal lobes c. AIDS - 75% of people who die of AIDS show accompanying brain damage (1989 study) 1. neurotropic infections - viral infections that specifically target neural tissue a. poliomyelitis ("polio") - virus attacks the motor areas of the spinal cord and brainstem resulting in paralysis, muscle wasting, and death b. rabies - description from ciba (Netter) C. an example of a bacterial encephalitis 1. syphilis - after many years (10-20) the bacteria can attack the CNS (but mental signs can also appear much sooner) a. tabes dorsalis - sensory and motor problems resulting from infection attacking the spinal cord, particularly the dorsal columns b. general paresis - insanity and dementia resulting from infection attacking the brain (Argyll Robertson pupils that constrict when person focuses on a near object but not in response to light are considered diagnostic of neurosyphilis) D. fungal, protozoan, metazoan infections