Understanding Nervous System Diseases: A Comprehensive Overview

1. PATHOPHYSIOLOGY OF NERVOUS SYSTEM DISEASES Mehtap KAÇAR KOÇAK MD PhD Yeditepe University Medicine School

2. OVERWIEV • 1- Alterations in Cognitive Networks • 2- Seizures and Epilepsy • 3- Cerebrovascular Diseases (Ischemic stroke) • 4- Dementias (Alzheimer’s Disease) • 5- Movement Disorders (Parkinson’s Disease) • 6- Motor Neuron Diseases (ALS) • 7- Demyelinating Diseases (Multiple Sclerosis) • 8- Neuromuscular Junction Diseases (Myasthenia Gravis) • 9- Meningitis (Acute Bacterial Meningitis) • 10- Stress

3. Alterations in Cognitive Networks • Full consciousness: awareness of self and the environment • Arousal: state of awakeness • Mediated by the reticularactivatingsystem • Content of Thought: all cognitive functions • Awareness of self, environment and affective states (moods)

4. Alterations in Arousal • Causes: • Structural • Divided by location above or below tentorial plate • Metabolic • Psychogenic

5. Alterations in Arousal • Pathological processes • Infectious, vascular, neoplastic, traumatic, congenital, degenerative, polygenic • Metabolic • Hypoxia, electrolyte disturbances, hypoglycemia, drugs and toxins

6. Alterations in Arousal “range from slight drowsiness to coma” • Coma – produced by either • Bilateral cerebral hemisphere damage or suppression • Brain stem* lesions or metabolic derangement that damages and suppresses the reticular activating system • *midbrain, medulla, Pons

7. Alterations in Arousal • Clinical manifestations “extent of brain dysfunction” “index for identifying ↑ or ↓ CNS function” 1) Level of consciousness 2) Pattern of breathing - Post hyperventilation apnea (PHVA) - Cheyne–Stokes respiration (CSR) 3) Pupillary changes (size and reactivity) 4) Oculomotor response (position and reflexes) 5) Motor response (skeletal muscle)

9. Clinical Manifestations

10. Test for oculocephalic reflex response A:Normal response, B:Abnormal response C:Absent response

11. Clinical Manifestations Normal response Abnormal response Absent response Conjugate eye movementsdysconjugate eye movements no eye movements

12. A: Decorticate response: flexion of arms, wrists, and fingers with adduction in upper extremities. Extension, internal rotation, and plantar flexion in lower extremities. B: Decerebrate response: all four extremities in rigid extension, with hyperpronation of forearms and plantar extension of feet. C: Decorticate response on right side of body and Decerebrate response on left side of body.

13. Brain Death “never recover nor maintain internal homeostasis” • Brain stem death – criteria (5) • Completion of all appropriate and therapeutic procedures • Unresponsive coma (absence of motor and reflex responses) • No spontaneous respirations (apnea) • No ocular responses • Isoelectric EEG: 6 to 12 hours without hypothermia/depressant drugs

14. Cerebral Death “death exclusive of brain stem and cerebellum” • No behavioral or environmental responses • Brain continues to maintain internal homeostasis • Survivors • Coma • Vegetative state (“wakeful unconscious state”) • Minimal conscious state • Locked-in syndrome

15. SEIZURES AND EPILEPSY • Seizure is and abnormal discharge of electrical activity within the brain. • It is a rapidly evolving disturbance of brain function that may produce impaired consciousness, abnormalities of sensation or mental function or convulsive movements. • Convulsions are episodes of widespread and intense motor activity

16. Epilepsy, a recurrent disorder of cerebral function marked by sudden, brief attacks of altered consciousness, motor activity or sensory phenomenon. • Convulsive seizures are the most common form. • Using the definition of epilepsy as two or more unprovoked seizures the incidence of epilepsy is 0.3 to 0.5 % in different populations throughout the world. • Incidence increases with age, with 30% initially occurring before 4 years and 75 -80 % before 20 years.

18. great majority of cases are idiopathic. • Signs and symptoms vary: petit mal – almost imperceptible alterations in consciousness grand mal – generalized tonic-clonic seizures – dramatic loss of consciousness, falling, generalized tonic-clonic convulsions of all extremities, incontinence, and amnesia for the event.

19. Epileptogenic focus • Group of brain neurons susceptible to activation. • Plasma membranes may be more permeable to ion movement. • Firing of these neurons may be greater in frequency and amplitude. • Electrical activity can spread to other hemisphere and then to the spinal cord.

20. Eliciting stimuli: • Hypoglycemia • Fatigue • Emotional or physical stress • Fever • Hyperventilation • Environmental stimuli

21. MECHANISM OF SEIZURE INITIATION AND PROPAGATION • Partial seizure activity can begin in avery discrete region of cortex and then spread to neighboring regions; i.e. There are two phases: • 1- the seizure initiation phase • 2- the seizure propagation phase. • The seizure initiation phase is characterized by two concurrent events in an aggregate of neurons: • 1- high-frequency burst of action potentials, • 2- hypersynchronization.

22. The bursting activity is caused by a relatively long-lasting depolarization of the neuronal membrane due to influx of extracellular calcium. • The influx of extracellular calcium leads to • 1- the opening of voltage-dependent sodium channels, • 2- influx of sodium, • 3- Generation of repetetive action potentials. • This is followed by a hyperpolarizing afterpotential mediated by GABA receptors or potassium channels, depending on the cell type.

23. Repetitive discharges leads to the following: • 1- an increase in extracellular potassium which blunts hyperpolarization and depolarization and depolarizes neighboring neurons, • 2- accumulation of calcium in presynaptic terminals, leading to enhanced neurotransmitter release, • 3- depolarization-induced activation of the N-methyl-D-aspartate (NMDA) subtype of the excitatory aminoacid receptor, which causes calcium influx and neuronal activation.

24. The recruitment of a sufficient number of neurons leads to: • a loss of the surrounding inhibition and • propagation of seizure activity into contiguous areas via local cortical connections, • and to more distant areas via long commissural pathways such as corpus callosum.

25. Seizures • Partial (focal/local) • Simple, complex, secondary, generalized • Generalized (bilateral/symmetric) • Unclassified

27. CEREBROVASCULAR DISEASES • Most frequent of all neurological problems • Due to blood vessel pathology: • Lesions on walls of vessels leading to brain • Occlusions of vessel lumen by thrombus or embolus • Vessel rupture • Alterations of blood quality CV disease leads to two types of brain abnormalities : • Ischemia (with or without infarct) • Hemorrhage

28. Cerebrovascular Accident(Stroke) • Clinical expression of cerebrovascular disease: a sudden, nonconvulsive focal neurological deficit • Incidence: • third leading cause of death in U.S. – half a million people a year – one third will die from it • Highest risk > 65 years of age • But about 1/3 (28%) are < 65 years old • Tends to run in families • More often seen in females

29. Stroke • Classification based on underlying pathophysiologic findings; • 1- Oclussive stroke • (Ischemia – thrombotic and embolic) • 2- Hemorrhagic stroke

30. Major Types of Stroke

31. Risk Factors • Arterial hypertension • Heart disease • Myocardial infarction or endocarditis • Atrial fibrillation • Elevated plasma cholesterol • Diabetes mellitus • Oral contraceptives • Smoking • Polycythemia and thrombocythemia

32. Occlusive strokes • Occurs with blockage of blood vessel by a thrombus or embolus • Atherosclerosis is a major cause of stroke • Can lead to thrombus formation and contribute to emboli • May be temporary or permanent • Thrombotic stroke: • 3 clinical types: • TIAs • Stroke-in-evolution • Completed stroke

33. Sites for Atherosclerosis

34. Transient Ischemic Attacks • Last for only a few minutes, always less than 24 hours • All neurological deficits resolve • Symptom of developing thrombosis

35. Causes of TIA: • Thrombus formation • Atherosclerosis • Arteritis • Hypertension • Vasospasm • Other: • Hypotension • Anemia • Polycythemia

36. Symptoms depend on location • Ophthalmic branch of internal carotid artery – amaurosis fugax – fleeting blindness • Anterior or middle cerebral arteries – contralateral monoparesis, hemiparesis, localized, tingling numbness in one arm, loss of right or left visual field or aphasia

37. Stroke-in-evolution • Can have abrupt onset, but develop in a step-by-step fashion over minutes to hours, occasionally, from days to weeks • Characteristic of thrombotic stroke or slow hemorrhage

38. Thrombotic Stroke • Involves permanent damage to brain due to ischemia, hypoxia and necrosis of neurons • Most common form of CVA • Causes: • Atherosclerosis associated with hypertension • Diabetes mellitus, and vascular disease • Trauma

39. May take years to develop, often asymptomatic until major narrowing of arterial lumen • Anything that lowers systemic B.P. will exacerbate symptoms (60 % during sleep) • Area affected depends on artery and presence of anastomoses • Area affected initially is greater than damage due to edema • Infarcted tissue undergoes liquifaction necrosis

40. Embolic stroke • Second most common CVA • Fragments that break from a thrombus outside the brain, or occasionally air, fat, clumps of bacteria, or tumors • Impact is the same for thrombotic stroke • Rapid onset of symptoms • Often have a second stroke • Common causes: • Atrial fibrillation • Myocardial infarction • Endocarditis • Rheumatic heart disease and other defects

41. Hemorrhagic Stroke • Third most common, but most lethal • Bleeding into cerebrum or subarachnoid space • Common causes: • Ruptured aneurysms • Vascular malformations • Hypertension • Bleeding into tumors • Bleeding disorders • Head trauma

42. Often a history of physical or emotional exertion immediately prior to event • Causes infarction by interrupting blood flow to region downstream from hemorrhage • Further damage by hematoma or ICP • Onset less rapid than embolic CVA, evolving over an hour or two • Usually chronic hypertension, and B.P. may continue to rise • About half report severe headache • In about 70 % hematoma expands, destroying vital brain centers, shifts of brain tissue, and death

43. Pathophysiology of stroke • Brain requires continuous supply of O2 and glucose for neurons to function • If blood flow is interrupted • Neurologic metabolism is altered in 30 seconds • Metabolism stops in 2 minutes • Cell death occurs in 5 minutes

44. Around the core area of ischemia is a border zone of reduced blood flow where ischemia is potentially reversible • If adequate blood flow can be restored early (<3 hours) and the ischemic cascade can be interrupted • less brain damage and less neurologic function lost

45. Necrosis • Two kinds of ischemic insult • 1. Cell damage cell death (acute cell necrosis, • delayed cell degeneration) • 2. Vascular(endothelial) damage • (1) vasogenic edema  pressure effect • (2) reperfusion bleeding Pneumbra

48. Clinical Manifestations of Stroke • Affects many body functions • Motor activity • Elimination • Intellectual function • Spatial-perceptual alterations • Personality • Affect • Sensation • Communication

49. Manifestations of Right-Brain and Left-Brain Stroke

50. Neurodegenerative Disorders