Chapter 14

1. Chapter 14 Neurological Disorders

2. Neurological Disorders • Neurological disorders can originate from multiple causes • By studying individuals’ behaviors we have learned a lot about the functions of the brain and about neurological disorders that produce deficits in these behaviors. • Tumors are one cause of neurological disorders • They result from uncontrolled growth of non-nervous cells and serve no useful function • Tumors can be Malignant or Benign

3. Neurological Disorders Cont’d. • Malignant tumors have no distinct borders, or is not encapsulated • It grows by infiltrating surrounding tissue • Attempts to remove malignant tumors usually leave some cells which will produce a new tumor • Additionally, malignant tumors often give rise to metastases • A shedding of cells which travel through the vascular system, lodge in capillaries and form the seeds for new tumors • Benign tumors have distinct borders or are encapsulated • When surgically removed there is a good chance of getting it all

4. Neurological Disorders Cont’d. • Tumors produce brain damage by compression or by infiltration • The most serious types of tumors are metastases and Gliomas which are usually very malignant and grow very fast • Seizures are one of the results of tumors • They are periodic episodes of abnormal brain electrical activity • Seizures can be Partial or Generalized; Simple or Complex

5. Neurological Disorders Cont’d. • Partial seizures are localized and begin with a focus or source of irritation • The focus is typically a scarred region produced/caused by an injury or tumor • Partial seizures usually begin with an aura • A sensory experience or change in mood • Simple Partial seizures do not produce profound changes in consciousness- they do not produce unconsciousness • Complex Partial seizures usually produce unconsciousness

6. Neurological Disorders Cont’d. • Generalized seizures may or may not have a single focus • Generalized seizures usually involve most of the brain • Some seizures involve motor areas of the brain and thus involve motor activity • The most severe seizure is Grand Mal and it is a generalized seizure • Grand Mal seizures include the motor system and is thus accompanied by convulsions

7. Neurological Disorders Cont’d. • Grand Mal seizures are usually preceded by warnings • Change in mood • Sudden muscular jerks upon awakening • An aura- resulting from neuronal excitation around the focus • Grand Mal begins with a tonic phase- a few seconds of rigidity • This is followed by a clonic phase- rhythmic jerking • After about 30 seconds the muscles relax, breathing begins again, and stuporous unresponsive sleep follows for about 15 minutes • The patient may awaken briefly after 15 minutes, but usually sleeps for a few hours (an exhausted sleep)

8. Neurological Disorders Cont’d. • Children are particularly susceptible to seizures • Absence seizures (Petit Mal) are commonly seen in children • They are marked by periods of inattention and temporary loss of awareness • Seizures can also be produced by drugs and infections that cause high fever or withdrawal from alcohol and barbiturates

9. Neurological Disorders Cont’d. • Alcohol withdrawal seizures seems to be caused by hyperexicitability of NMDA receptors (N-methyl-D-asparate) • Because such seizures can be prevented in mice by drugs that block NMDA receptors (Lijequist, 1991) • Seizures are treated with anticonvulsant drugs which increase the effectiveness of inhibitory synapses (agonists) • Another source of Neurological Disorders is Cerebrovascular accidents which damage sections of the brain by obstruction or rupturing of the blood vessels and cause ischemia (loss of blood flow to a region)

10. Neurological Disorders Cont’d. • There are two major types of vascular accidents • Hemorrhagic strokes- caused by a rupture of the vessels • Caused by malformed vessels or hypertension weakened vessels • Obstructive strokes- caused by blocking of vessels • Obstructive strokes are caused by thrombi or emboli where walls are already weak • They sometimes completely block blood flow by causing strokes

11. Neurological Disorders Cont’d. • Emboli- caused by debris carried through vessels and lodged in artery • Emboli can result from infection in chambers of heart and consist of dislodged thrombi or portions of thrombi • The resulting brain damage seems to result from overstimulation of NMDA receptors and not lack of oxygen • Overstimulation of NMDA receptors cause excessive amounts of calcium to enter cells and cause a massive release of glutamate

12. Neurological Disorders Cont’d. • Developmental disorders and Inherited Metabolic Disorders can result in brain damage that can produce mental retardation (Congenital) • A common cause of mental retardation is the presence of toxins like alcohol and other chemicals produced by some viruses during pregnancy. (FAS/ Rubella) • Alcohol interferes with neural adhesion protein that helps guide growth of neurons in developing brain

13. Neurological Disorders Cont’d. • Brain impairment can also be produced by inherited metabolic disorders • There are at least 10 metabolic disorders that can affect brain development • The most common and best known is PKU • PKU is caused by lack of an enzyme that converts phenylalanine into tyrosine (build up phenylalanine is toxic) • Feeding the baby a diet low in phenylalanine can avert brain damage • Early diagnosis is therefore essential

14. Neurological Disorders Cont’d. • Other inherited metabolic brain disorders include: • Pyridoxine dependency- produces damage to cerebral white matter, to thalamus, and cerebellum • Treatable with large doses of B6 • Pyridoxine is a metabolic disorder in which infant requires large amounts of pyridoxine (vitamin B6) to avoid neurological symptoms • Galactosemia- inability to metabolize galactose, a sugar in milk • Untreated it causes damage to cerebral white matter and to cerebellum • Treatable with milk substitute that is galactose free

15. Neurological Disorders Cont’d. • Tay-Sachs- inability of cells to destroy waste products within lysosomes. This causes cells to swell and die. • Brain damages self against inside walls because of swelling • Occurs mainly in Jewish Eastern European children • Untreatable, symptoms first appear at 4 months, include listlessness, irritability, spasticity, seizures, dementia, exaggerated startle response to sound and eventual death • Down’s Syndrome- produced by extra 21st chromosome • Brain development is abnormal • After 30 years brain develops abnormal microscopic structures- Neurofibrillary tangles and begins to degenerate • This degeneration resembles that seen in Alzheimer’s disease

16. Neurological Disorders Cont’d. • Parkinson’s Disease- this disease is caused by degeneration of dopaminergic neurons that project from Substantia Nigra to Basal Ganglia • Recent research suggests that Parkinson’s may be caused by an environmental toxin • An MAO inhibitor, Deprenyl, has been found to retard neural degeneration seen in Parkinson’s disease

17. Neurological Disorders Cont’d. • Alzheimer’s Disease- A degenerative disease that leads to dementia • It is more widespread than Parkinsons, affecting about 5% of the population • It leads to eventual destruction of most of the hippocampus and cortical gray matter • It is associated with memory loss similar to the anterograde amnesia of Korsakoff’s syndrome • Acetylcholinergic neurons are the first to be destroyed in the basal forebrain which accounts for the memory deficits • However, there is hippocampal damage as well suggesting that the memory deficit is not due solely to ACh neuron destruction • Alzheimer’s patients show substantial loss of cortical tissue in hippocampus, and frontal and temporal association cortex (see 14.9 & 14.10)

18. Neurological Disorders Cont’d. • Multiple Sclerosis- This is a degenerative demyelinating disease • It is an autoimmune disease in which myelin sheathes in CNS are attacked by the immune system • This results in patches of debris called Sclerotic Plaques • It is marked by periodic attacks of neurological symptoms followed by periods of remission • It affects women slightly more often than men and attacks individuals in late 20’s and 30’s • More frequent in people who grow up in places far from the equator • Also in people who are born in late winter and early spring

19. Neurological Disorders Cont’d. • Brain damage can also be produced by infectious diseases • Encephalitis is one of the most common • It is caused by a virus that affects the entire brain • Most common cause is mosquito which transmits the virus from birds, horses, or rodents • Encephalitis can also be caused by herpes simplex virus • This virus infects the 5th (trigeminal) nerve ganglia, proliferates periodically travelling down the nerve to cause sores in mucus membrane • Occasionally it travels upward and infects the brain, frontal and temporal lobes

20. Neurological Disorders Cont’d. • Poliomyelitis is a virus that attacks motor neurons in the brain and spinal cord • This results in motor impairment and paralysis • The virus attacks the primary motor cortex, thalamic motor nuclei, hypothalamus, brainstem, cerebellum, and ventral horns gray • It is seldom seen in developed countries since the development of the vaccine • Rabies is a virus acquired from animal bite carried in saliva • It travels through PNS to CNS where it causes damage • It attacks cells in the cerebellum and hippocampus especially • During its inception period (may be several months) individuals can be immunized

21. Neurological Disorders Cont’d. • AIDS, although it does not directly infect the brain can cause brain damage • 75% of AIDS patients show brain damage which results from the disease, AIDS dementia complex • It is believed the damage results from calcium channels being opened and allowing lethal doses of calcium to enter the cells (Glutamic Acid to overstimulate) • Meningitis is an infection of the meninges • It is caused by a virus or bacteria • The most common, viral forms, does not produce severe brain damage • The bacterial forms usually produce serious brain damage • The usual causes are spread of middle-ear infection; infection through head injury; emboli from bacterial infection in heart; and unclean hypodermic needles • The bacterial forms of meningitis can be treated with antibiotics- early diagnosis is essential