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Chapter 15

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McGill University
PSYC 211
Yogita Chudasama

Chapter 15: Neurological Disorders Notes taken by: Ashley Brown Contact for mistakes: [email protected] These notes probably suck (esp. near the end) and a lot of the time are essentially copied straight from the book (10 edition btw) because I kind of just stare and take notes at the same time, so they contain not the most brief of statements but yeah… I still feel like I owe docuum a set of notes for saving my butt every exam. Enjoy, happy studying, and hope these help! Tumours The major categories of neuropathological conditions that the brain can sustain are: tumours, seizure disorders, cerebrovascular accidents, disorders of development, degenerative disorders, and disorders caused by infectious diseases Tumour: a mass of cells whose growth is uncontrolled and that serves no useful function - malignant tumour: a cancerous tumour, it lacks a distinct border and may metastasize - benign tumour: a noncancerous tumour, it has a distinct border and cannot metastasize - the major difference between the two is whether the tumour is encapsulated or has a distinct border between the mass of tumour cells and surrounding tissue Metastasis: the processes by which cells break off tumours, travel through the vascular system, and grow elsewhere in the body Tumours damage brain tissue by two means: compression and infiltration - both benign and malignant tumours can cause damage by compression because they occupy space and push against the brain either destroying brain tissue or indirectly blocking the flow of cerebrospinal fluid and causing hydrocephalus - malignant tumours also infiltrate by invading the surrounding region and destroying cells in its path - some are sensitive to radiation and can be destroyed by a beam of radiation focussed on them o in the brain they remove as much as possible and then target the remaining cells with radiation Tumours don’t arise from nerve cells (b/c they can’t divide) so they come other cells in the brain or from metastasis. For types see TABLE 15.1 PAGE 522 - most serious types are metastases and the gliomas, which are usually very malignant/fast growing Glioma: a cancerous brain tumour composed of one of several types of glial cells - glioblastoma multiformae: poorly differentiated glial cells - Astrocytoma: from astrocytes - ependymoma: from ependymal cells that line the ventricle - medulloblastoma: from cells in the roof of the fourth ventricle - oligodendrocytoma: from oligodendrocytes Meningioma: a benign brain tumour composed of the cells that constitute the meninges - tend originate in either the part of the dura mater b/t the two cerebral hemispheres or along the tentorium (the sheet of dura mater b/t the occipital lobe and cerebellum) Seizure Disorders Physicians use the term seizure disorder for epilepsy due to negative connotations acquired in the past - second most important category of neurological disorders (after strokes) - see TABLE 15.2 PAGE 524 for categories A seizure is a period of sudden, excessive activity of cerebral neurons - if neurons that make up the motor system are involved it can cause a convulsion o a violent sequence of uncontrolled muscular movements caused by a seizure o most seizures do not cause these Two important distinctions in seizure disorders: (1) partial vs. generalized seizures and (2) simple vs. complex - Partial seizures: a seizure that begins at a focus and remains localized, not generalizing to the rest of the brain o Definite focus or source of irritation (typically a scarred region from an injury or a developmental abnormality such as a malformed blood vessel) o Neurons involved remained restricted to a small area - Generalized seizures: a seizure that involves most of the brain, not just a localized area o Usually grow from a cous Partial seizures can be simple or complex - simple partial seizures: starts from a focus, remains localized, and doesn’t lose consciousness o involves changes in consciousness - complex partial seizures start from a focus, remain localized but produce loss of consciousness Grand mal (or tonic-clonic seizures): a generalized seizure which is the most severe and accompanied by convulsions - often before it starts they have warning symptoms like changes in moods or a few sudden jerks upon awakening - a few seconds before it occurs the person can experience an aura which is a sensation whose nature depends on the location of its focus o effects having to do with what the area the focus does like if the temporal lobe is where the focus is (which is in control of emotion) they could suddenly feel angry or euphoric - tonic phase: the first phase of the grand mal seizure in which all of the patient’s skeletal muscles contract o sometimes there is an involuntary scream from muscles around the lung contracting o holds a rigid posture for about 15 seconds before entering the next phase - clonic phase: the second phase in which the patient shows rhythmic jerking movements o literally means “agitated phase” o muscles are trembling then jerking convulsively, quickly at first then more and more slowly o eyes roll, face is contorted with violent grimaces, tongue may be biten o intense activity of ANS results in sweating and salivation o after 30 seconds the patients muscles relax and then breathing begins again - after clonic phase they fall into an unresponsive sleep for about 15 minutes then may awake briefly only to fall back into an exhaustive sleep for a few hours Neural activity of a grand mal seizure: - firing beigns in the focus at the time of the aura then spreads first to around the focus then to the contralateral side through the corpus callosum - then to the basal ganglia, the thalamus, and various nuclei of the brain stem reticular formation o the symptoms begin here - the excited subcortical feed back more excitation to the cortex which amplifies the activity there - neurons in the motor cortex fire continuously  tonic phase - diencephalic structures try to quench the seizure by sending inhibitory msg to the cortex o at first comes in brief burst  jerking of the clonic phase (as they relax and contract again) o burst of inhibition become more and more prolonged  jerking of clonic phase occurs more slowly o finally inhibition wins and they completely relax Partial seizures involve smaller portions of the brain so their symptoms can include sensory changes, motor activity, or both. - a seizure that begins in the occipital lobe may produce visual symptoms such as spots of colors, flashes of lights or temporary blindness - in the parietal region it can evoke somatosensations such as feelings of pins and needles or heat and cold Absence (or petit mal seizures): a type of generalized seizure often seen in children; characterized by periods of inattention, which are not subsequently remembered - stop what they’re doing then stare off in the distance often blinking repeatedly - unresponsive and normally don’t notice their attacks - can occur up to several hundred times a day - can go unnoticed - can stop occurring when they reach adolescence Seizures can cause brain damage, particularly the hippocampus. Damage is correlated with the number and severity of seizures - status epilepticus (a condition in which a patient undergoes a series of seizures without regain consciousness) causes significant hippocampal damage o apparently damage caused by excessive release of glutamate during the seizure (like an excitotoxic lesion) Causes: - most common is scarring (from an injury, stroke, developmental abnormality, or irritating effect of a growing tumour) o most often seizures from injuries occur much after the injury itself(like several months) - various drugs and infections that cause a high fever can also produce seizures o high fevers in children particularly o alcoholics or barbiturate addicts who suddenly stop using  sudden lack of inhibition that they’re used to caused hyperactivity that can cause the seizure  NMDA receptor involved in seizures from alcohol withdrawal  long-term suppression of NMDA (alcohol blocks the receptor) causes supersensitivity (up-regulation) and without alcohol the receptors suddenly rebound and are super active and over fire - Genetic factors most involving ion channels - Most are caused by nongenetic factors or idiopathic (literally one’s own suffering) o Small brain abnormalities Normally treated with anticonvulsant drugs, which work by increasing effectiveness of inhibitory synapses. If the foci is super irritable, brain surgery is required. Interesting because it is found sometimes after removing parts of the brain to eliminate the seizure their neuropsychological functioning usually improves rather than exhibiting behavioural deficits - this can be explained because the regions surrounding the focus are constantly trying to inhibit seizures a phenomenon referred to as interictal inhibition (when the excitation wins over this inhibition is when a seizure occurs) o this also suppresses normal functioning so when the foci is removed it can stop inhibiting and therefore they function better Many patients with seizures find relief in a ketogenic diet which is high in fats, moderate in proteins, and low in carbs so the brain has less glucose but needs to rely on ketones (compounds from broken down fats when blood glucose levels are low) Cerebrovascular Accidents Cerebrovascular accidents or strokes can produce impairments in perception, emotional recognition and expression, memory, and language. Likelihood of strokes is relative to age  probably doubles ever decade after 45 years. Two major types: hemorrhagic and obstructive - Hemorrhagic stroke: a cerebrovascular accident caused by the rupture of a cerebral blood vessel o Bleeding comes from a malformed blood vessel or one weakened from high blood pressure) o blood accumulates and puts pressure on surrounding brain tissue, damaging it - Obstructive stroke: a cerebrovascular accident caused by occlusion of a blood vessel o Ischemia: the interruption of the blood supply to a region of the body o Caused by thrombi or emboli  Thrombus: a blood clot that forms within a blood vessel, which may occlude it  Forms especially in blood vessels with previously damaged walls  If especially susceptible to formation people take aspirin which helps prevent clot formation  Embolus: a piece of matter (such as a blood clot, fat, or bacterial debris) that dislodges from its site of origin and occludes an artery o Or caused by arteriosclerosis which is thickening of the arterial wall Strokes cause permanent brain damage, depending on the size of the affected blood vessel varying from negligible to massive. Actions taken after strokes - hemorrhagic stroke from high blood pressure  medication to reduce it - hemorrhagic stroke from weak/malformed blood vessels  brain surgery that seals off the faulty vessel to prevent further strokes - obstructive by thrombus  anticoagulant drugs that make blood less likely to clot - obstructive by embolus from bacterial infection  antibiotics We expect that the neurons die because they have been starved to death after being cut off from oxygen and glucose but research shows that it is the presence of excessive amounts of glutamate that kill the cells (as with excitotoxic lesions) - sodium-potassium transporters that regulate the balance of ions in and out of the cell stop functioning from lack of fuel - the membrane depolarises and causes excessive release of glu+amate 2+ - this excessive glutamate triggers excessive influx of Na and Ca ions into by way of NMDA receptors which is toxic to the cell o intracellular sodium causes the cell to absorb water and swell o inflammation attracts white blood cells which obstruct capillary walls - damaged mitochondria produce free radicals (molecules with unpaired electrons that act as powerful oxidizing agents) which are extremely toxic to cells, destroying nucleic acids, proteins, and fatty acids Ways to minimize the amount of brain damage caused by strokes: - administer drugs that dissolve blood clots in attempt to re-establish circulation to an ischemic brain region o some success  tPA (tissue plasminogen activator – a clot-dissolving drug) administration after the onset of a stroke has clear benefits if given within 3 hours of stroke  this enzyme works by converting plasminogen (a protein in blood) to plasmin which dissolves fibrin (a protein involved in clot formation)  research shows it has toxi effects in the CNS o with Desmodus rotundus plasminogen activator (DPSA) or desmoteplase is an anticoagulant that appears to have no excitotoxic injuries and can restore blood flow and reduce clinical symptoms if given up to nine hours after onset of stroke Prevention  reducing risk factors by taking medication or changing lifestyle to reduce risk from high blood pressure, cigarette smoking, diabetes, and high blood levels of cholesterol Atherosclerosis is a precursor to stokes and heart attacks - linings of arteries develop a layer of plaque which consist of deposits of cholesterol, fats, calcium, and cellular waste - makes arteries more vulnerable to being blocked, and greatly increase the risk of massive strokes - the internal carotid artery is sensitive to this o may need carotid endarterectomy which removes the plaque by cutting a hole in the neck and such o or placing a stent in the artery which doesn’t involve cutting open the neck they insert it using a catheter (a flexible plastic tube) and string its way from an artery in the groin then expand the stent when its in place, opening the narrowed artery Depending on the location of brain damage, people with strokes receive physical therapy and sometimes speech therapy to help recover - forcing patients to use impaired arm by putting other in a sling, which is a procedure called constraint-induced movement therapy, causes long term improvement in using the affected arm o causes changes in the connections of the primary motor cortex Disorders of Development Brain development can be aversely affected by presence of toxic chemicals during pregnancy and by genetic abnormalities (both hereditary and nonhereditary) which can result in mental retardation Toxic Chemicals A common cause of mental retardation is the presence of toxins that impair fetal development during pregnancy. - ex: if during pregnancy the mother contracts rubella or German measles, toxic chemicals released from the virus interfere with the chemical signals that control normal development of the brain - various drugs adversely affect fetal development Fetal alcohol syndrome: a birth defect caused by ingestion of alcohol by a pregnant woman; includes characteristic facial anomalies and faulty brain development - women don’t need to be alcoholics to cause this, a single alcoholic beverage during a critical period can cause it Alcohol disrupts normal brain development by interfering with a neural adhesion protein which plays a role in brain development by helping to guide the growth of neurons Prenatal exposure to alcohol also appears to have direct effects on neural plasticity Inherited Metabolic Disorders Errors of metabolism refer to genetic abnormalities in which an enzymes instructions are messed up so it can’t be synthesized Phenylketonuria (PKU): a hereditary disorder caused by the absence of an enzyme that converts the amino acid phenylalanine into tyrosine. The accumulation of phenylalanine causes brain damage unless a special diet is implemented soon after birth - most common and best know of the metabolism disorders - a lot of phenylalanine in the blood interferes with the myelinisation of neurons in the CNS and because this myelination take place after birth and so if infants with PKU consume food containing phenylalanine they’ll develop severe mental retardation (an average IQ of 20 at age 6) - if a mother has PKU she must follow a strict diet or her baby will have severe brain damage (because her brain is fine now but it’ll hurt her baby) - new bourns are tested for this immediately Pyridoxine dependency: a metabolic disorder in which an infant requires larger-than- normal amounts of pyridoxine (vitamin B ) to 6void neurological symptoms - untreated results in damage to cerebral white matter, to the thalamus, and to the cerebellum Galactosemia: an inherited metabolic disorder in which galactose (milk sugar) cannot easily be metabolized - untreated causes damage to the cerebral white matter and to the cerebellum - treatment involves use of a milk substitute that does not contain galactose - don’t confuse with lactose intolerance which is caused by insufficient production of lactase so they can’t break down lactose, causing digestive problems not brain damage Tay-Sachs disease: a heritable, fatal, metabolic storage disorder; lack of enzymes in lysosomes causes accumulation of waste products and swelling of cells of the brain - lysosomes gets larger as they accumulate waste causing eventual swelling of the brain Down Syndrome Down syndrome is a congenital disorder (present at birth) caused by the presence of an extra twenty-first chromosome, characterized by moderate-to-severe mental retardation and often by physical abnormalities - closely associated with the mother’s age  something goes wrong with ova resulting in presence of 2 rather than one 21 chromosome (with dad’s there is now 3) - extra chromosome causes biochemical changes that impair normal brain development o can be detected by amniocentesis Distinguishing features: - round heads, thick protruding tongues that tend to keep mouth open much of the time, stubby hands, short statue, low-set ears, somewhat slanting eyelids - slow to learn to talk but most do by 5 years old - brains are approx. 10 percent lighter, convolutions are simpler and smaller - frontal lobes are small and superior temporal gyrus (Wernicke’s area) is thinner After age 30 brain begins degenerating similar to Alzheimer’s disease Some study found that injects of drugs that serve as GABA antagonists it increased both LTP and performance on declarative learning task on some mice with downs. Degenerative Disorders Many disease processes cause degeneration of the cells of the brain Transmissible Spongiform Encephalopathies Transmissible spongiform encephalopathy (TSE): a contagious brain disease who degenerative process gives the brain a spongelike appearance; caused by the accumulation of misfolded prion protein - Different forms: o Bovine Spongiform encephalopathy (BSE) or mad cow disease o Creutzfeldt-Jakob disease – which is transmitted to humans from cows o Fatal familial insomnia o Kuru – affects humans only  Transmitted through cannibalism o Scrapie – affects mainly sheep (no humans) - Transferred by prions rather than microorganisms like other transmissible diseases
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