Neurological System Disorders

1. Neurological System Disorders Pathophysiology

2. Divisions CNS = Brain & Spinal Cord Brain Divisions (in ascending order) Brain Stem * Medulla Oblongata * Pons * Midbrain Cerebellum Diencephalon * Hypothalamus * Thalamus Cerebrum PNS = Motor Nerves (efferent) & Sensory Nerves (afferent) Cranial Nerves = 12 pair Spinal Nerves = 31 pair ANS = Parasympathetic (Cholinergic) Sympathetic (Adrenergic) These primarily control involuntary muscles & glands A & P Review of Nervous System

3. Brain Stem has 3 parts (in ascending order) • Generally brain stem is white matter with some scattered gray matter • Medulla Oblongata • Regulates vital functions (cardiac, respiratory, & vasomotor) • Crossing over of corticospinal tracts (decussation) • Pons • Connects cerebellum to brain stem & relays sensory input to cerebellum & thalamus • Has nucleus to control respiration (medulla also has these) • Midbrain • Processes visual & auditory sensory input • Coordinating muscle motor movements • Maintains consciousness via reticular activating system(RAS) • RAS • Determines degree of arousal & awareness of cerebral cortex • Gatekeeper for incoming sensory impulses

4. Cerebellum • has gray matter (outer layer) & white matter (inner core) • Gray matter = nerve cell bodies ; white matter = myelinated axons • controls : coordination & balance (proprioception) • It coordinates between what the cerebral cortex wants how the PNS reacts • Diencephalon(literally means between the brain) • Has 2 major structures • Thalamus • “gatekeeper” for sensory input to cerebrum • e.g. to allow sleep it shuts down input to cortex • Relay station of motor impulses between cerebrum & subcortical motor centers • Hypothalamus • coordinates impulses between nervous system and endocrine system • Controls the ANS (coordinates voluntary & autonomic functions) • Controls emotions & behavior (e.g. hunger, pain, pleasure, sex, etc) • Connects limbic system with ANS (see n ext slide) • Controls homeostasis (e.g. regulates temperature) • It’s an endocrine gland (controls ant pit & is post pit)

5. Limbic System • Connected nuclei in cerebral hemispheres that encircle superior part of brain stem • Functions • Emotions& feelings • Drives ones behavior which is a result of emotions & feelings • Links cognitive intelligent thought from cerebral frontal lobes with emotions(derived from memory) Memory & memory retrieval • Reactions this process causes is done via hypothalamus • Example: • Think about exam • Memory of poor result in past • Get nervous (stress) • BP increases

6. Cerebrum • largest part of brain • 2 halves called “hemispheres” • Each hemisphere divided into 4 lobes *Frontal, Parietal, Temporal, & Occipital • Lobes into convolutions (gyri) & fissures (sulci) • Connected at lower mid-portion called corpus callosum • gray matter = outer layer; white matter = inner area • basal ganglia = areas of gray matter deep within white matter • They are part of extrapyramidal system which coordinates skeletal muscle activity • Controls proprioception (posture & involuntary skeletal muscle movements) • Connected to nuclei in mid brain & cerebellum • Functional areas(generally) ------- see next slide • Lobes • Frontal = motor, higher thought -Parietal= sensory • Temporal = hearing - Occipital = vision • Language center • Expressive area = Broca’s area = base of premotor area frontal lobe • Sensory area = Wernicke’s area = posterior temporal lobe

8. Blood supply to brain • Arterial supply via • Carotid –to--internal carotid– into-- circle of Willis • Subclavian --to– vertebral – into– circle of Willis • Venous return via dural sinuses into internal jugular • Circle of Willis • vasculature located at base of brain • Vertebral Arteries -to- Basilar -to- Posterior Cerebral -to- Post. Communicating • Internal Carotid -into- Middle Cerebral & Anterior Cerebral • Ant. Cerebral -to- Ant. Communicating • Anterior cerebral supplies frontal lobes • Middle cerebral supplies temporal & parietal lobes • Basilar artery supplies brainstem & cerebellum • Branch off vertebral to cerebellum • Posterior cerebral supplies occipital lobes

9. Meninges = layers of tissue that cover the CNS • 3 layers • Dura mater = tough outer layer • Brain has 2 dural layers which are fused together except in certain areas where they form dural sinuses • These collect blood from brain & direct it into internal jugular veins • Arachnoid = filmy middle layer • Arachnoid villi = CSF back into blood (into superior sagittal sinus • Pia mater = innermost layer Coverings & Fluid Compartments in CNS

10. Cerebrospinal fluid • Formed by choroid plexus located in roof of each ventricle • Made up of capillaries within pia & ependymal cells • Continuously circulating fluid • Avg amt to fill area = 150 cc; replaced every 8 hours • Outside the CNS – fluid in subarachnoid space of brain & cord • Inside the CNS: • 2 lateral ventricles connected via interventricular foramen • Third ventricle • Cerebral aqueduct – connects 3rd with 4th ventricle • Fourth ventricle between cerebellum & brain stem • From 4th ventricle fluid enters either subarachnoid space of brain or goes down central canal of cord • Lateral & medial apertures in wall of fourth ventricle allow fluid to enter subarachnoid space

11. Sympathetic Adrenergic system Use: stress or emergency 3 F’s– Fright flight, or fight agonists sympathomimetics adrenergics antagonists sympatholytics adrenergic blockers Parasympathetic Cholinergic system Use: normal everydaythings 2 R’s-- rest & rumination agonists parasympathomimetics cholinergics antagonists parasympatholytics anticholinergics Autonomic Nervous System

12. sympatheticparasympathetic 1. origin ofthoracic & upper lumbarmid-brain & medulla in first neuronpart of spinal cordbrain stem ; sacral cord 2.ganglia locationnear the spinal cord near the target organ Ganglia location produces different responses: Sympathetic ganglia stimulation = get whole system Parasympathetic ganglia = just effector organ stimulated 3.neurotransmitters: (see next slide) preganglionicACH ACH postganglionic *Nor - Epinephrine ACH *Dopamine is : 1. a neurotransmitter 2. a precursor of nor- epinephrine 3. works as an antagonist to acetylcholine

14. Sympathetic Alpha Alpha-1 mainly on smooth muscle of vessels - get constriction Alpha-2 Inhibitory; on preganglionic axon knob Beta Beta -1 on heart muscle-stimulates rate & strength In kidney for renin secretion Beta -2 on smooth muscle of organs -get relaxation On skeletal muscle Get vasodilation Parasympathetic muscarinic on cardiac & smooth muscle nicotinic I (Ng) on all preganglionic neurons of ANS nicotinic II (Nm) on skeletal muscle ANS Receptors

15. General effects of diseases of the nervoussystem Cranium • Supratentorial & infratentorial lesions • Reference = tentorium cerebelli • Supratentorial lesions in cerebral cortex • Infratentorial lesions in brain stem & cerebellum • Hemisphere lesions • Dominant hemisphere (usually left) --- logical thinking ability • Other hemisphere (usually right) ----art & behavior • Level of consciousness • Def of consciousness = aware of surroundings & oriented to time, place, & people • Dependent on RAS & cerebral cortex • Glasgow coma scale (15 points = normal) • 3 key things: • eye opening (4) points • motor response (6 points) • Verbal response (5 points)

16. Motor dysfunction Upper motor neuron = hyperreflexia Lower motor neuron = flaccidity, weakness,paralysis radiating pain Sensory dysfunction sensation problems (numbness) Peripheral spinal nerves = touch, pain temp, and position Cranial nerves = special senses problems Language disorders Aphasia = inability to comprehend or express language Expressive or motor aphasia (Broca’s) Receptive or sensory aphasia (Wernicke’s) Combination = “global aphasia” Alexia = impaired reading ability Agraphia = impaired writing ability General effects of diseases of the nervoussystem (cont)

17. General effects of diseases of the nervoussystem (cont) • Increased intracranial pressure • Causes : • Hemorrhage • Inflammatory exudate • Any mass (tumor) • Results if this increased pressure • Less blood entering brain • Compression of brain tissue • Dispersed pressure from local to general • Herniation of brain tissue • BP increased; P & RR decreases • headache, • N & V • Papilledema Increased intracranial pressure & possible herniations

18. Acute problems Tumors Vascular disorders TIA’s CVA’s Aneurysms Infections Head injuries Spinal injuries Spinal disc problems Chronic problems Congenital disorders Seizure disorders Chronic degenerative disorders MS Parkinson’s ALS Myasthenia gravis Huntington’s disease Dementia Peripheral nerve disorders Psychiatric disorders Neurological disordersGeneral overview

19. Tumors • Signs & symptoms of all tumors come from increased intracranial pressure • From the tumor itself • From inflammatory swelling • Primary Brain Tumors = arise from the connective tissue cells called “glia” or arise from the meninges • Glia Cells: (1) Astrocytes = fasten blood vessels to nerves (2) Microglia = brain macrophages (3) Oligodendroglia = form myelin in CNS • Tx & Px : Meningiomas = fair prognosis Glial Tumors = poor prognosis * astrocytoma * glioblastoma • Secondary Brain Tumors = more common

20. VascularDisorders Cerebral Vascular Accident • condition results from lack of blood supply; also called stroke • Pathophysiology = (1) Thrombus (2) Embolus (3) Hemorrhage • These can occur as a result of: • Systemic Disease ---------- diabetes, increase lipids, hypertension • Heart Disease -------------- valvular, arrhythmias • Trauma • Risk Factors = lifestyle, family history • Tx = anticoagulants; surgery; rehab • new : • treat as emergency • steroids to reduce edema * big danger = increase ICP • fibrinolytic agents

21. Transient Ischemic Attacks (TIA’s) • Also called “little strokes” • Results from temporary localized reduction of blood flow • Usually get recovery within 24 hours • etiol : • emboli ------ plaque , fibrin • arterial vascular spasm • May be warning sign of impending major CVA • New treatment modality = carotid stenting Cerebral Aneurysms • Localized dilation in an artery; frequent site = bifurcation in circle of Willis • Called “berry” aneurysms • Mortality = high; 35% die with the initial rupture

22. Infections Meningitis • def = inflammation of meninges • etiol = pathogens • HI-b ; Neisseria m.; Strept pneumonia (pneumococcal); E.Coli • N. meningococcus = can get asymptomatic carriers ( in nasopharynx) * seen in groups; associated with rash (meningococcemia) • In neonates E.Coli meningitis most common • HI-b most common in children --- vaccine available • Strept = most common in older people --- vaccine available • Sx = headache, nuchal rigidity, irritability Encephalitis • def = inflammation of brain tissue • etiol = usually viral (frequently transmitted by mosquito) • May be secondary to vaccinations • Sx = mental confusion is hallmark of symptoms

23. Guillain-Barre Syndrome • Def = Acute, rapidly progressing disease of spinal nerves beginning in feet/ legs & spreads upward rapidly (1-3 days) • also called postinfectious polyneuritis • It’s an inflammatory condition of peripheral nervous system • Frequently preceded by viral infection or immunization • Tx = usually complete recovery • About 30% get residual weakness Reye’s syndrome • Etiol: usually viral infection treated with aspirin • ? Abnormal immune response • Get brain & liver problems • Cerebral edema with increase intracranial pressure • Frequent early sx = change in behavior & personality • Liver progresses to acute failure • Mortality = 30% !!!

24. Head Trauma • Closed injuries = skull not fractured • Concussion • Contusion • Contrecoup injury • Open injuries = skull fractured • Linear fracture • Depressed fracture • Basilar fracture • With either type injury can get hematomas • Epidural • Subdural • Intracerebral

25. Head Trauma • Post concussive syndrome • Any physical trauma to head can give one this syndrome • Do not confuse with posttraumatic stress disorder • This secondary to terrifying trauma exposure • Approx 7% - 10% incidence • Gives person “painful recollections” * Irritability * Insomnia *Can’t respond to affection • Post concussive syndrome = 50% incidence • Sx: headache, somatic & psychologic complaints; cognitive impairments

26. Closed injury --- direct & contrecoupOpen injury ---- depressed fracture

27. Hematomas • 3 types • Epidural ----- between skull & dura • Usually temporal area trauma • Get symptoms within few hours • Loss od consciousness • Subdural ----- between dura & arachnoid • Acute (sx w/in 24 hours) • Subacute (sx w/in 1-2 weeks) • Intracerebral • May take several days to develop after injury • Sx = N&V, headache, loss of consciousness, coma, death, dilated pupil • etiol = trauma • Tx = surgery (craniotomy) see next slide

29. Cerebral Concussion • temporary disruption of brain’s electrical activity • Sx = loss of consciousness may also get amnesia (+/-) • usually lasts for less than 24 hours Cerebral Contusion • get bruising of brain tissue, thus more serious than concussion • often associated with skull fracture • Sx = loss of consciousness & lasts more than 24 hours, may go into coma • May get residual damage • High incidence of “post concussive syndrome” --- if blow severe

30. Depressed Skull Fracture • Sx = non-progressive, but static until pressure relieved • may get epilepsy • may get Posttraumatic Stress Disorder Basilar Skull Fracture • Occurs at base of skull • Area where circle of Willis is very close to subarachnoid space • Can get blood into cerebral spinal fluid • Can get leakage of CSF from ears & nose • Etiol: trauma to base of skull • Posterior fossa if occipital bone involved • Middle fossa if temporal bone involved • These hard to diagnose since fracture frequently occult • Get air in sinuses or intracranially = key to diagnosis

31. Spinal Cord Injuries • General trauma to vertebrae ---- get fracture or dislocation • Common areas of spine = mobility areas , not support areas • Cervical area C1 to C7 ------ neck mobility • T12 to L2 ------ movable area at junction of chest & abdomen • Examples: hyperflexion of head, hyperextension of head, compression fx • Penetration injuries occur to any area of spine see next slide

33. Spinal Cord Injuries • usually get paraplegia or quadriplegia === depending on injury level • Injuries above C3 usually result in death • Injury at C2 to C5 may damage phrenic nerve & diaphragm paralyzed • With acute injury may go into Neurogenic Shock (spinal shock) • Remember: * As BPdecreases,Pulse also decreases * May get HypothermiaOnly in Neurogenic Shock • Facts about Myelin Regeneration • In PNS -------------------Schwann Cells lay down myelin from their cell membrane ( Neurilemma) • In CNS -------------------Oligodendroglia lay down myelin; they don’t have neurilemma, thus do not regenerate myelin NOTE: Axons Only Grow Down Neurilemma of SchwannCell

34. Spinal Shock = major complication of severe injury • It’s the period immediately following injury • Level of injury determines symptoms • Get no function below injury (motor or sensory) • Major danger = malignant hypertension • Syndrome of autonomic dysreflexia • Sympathetic nervous system gets overactive • Higher center can’t correct this since blockage

35. Herniated intervertebral disc • Cartilaginous discs separate the vertebrae • Herniation of nucleus pulposus through annulus fibrosus • Common areas • L5/S1 • L4/L5 • C5 through C7 • Signs & symptoms depend on location • Usually unilateral

36. Chronic problems • Congenital disorders • Seizure disorders • Chronic degenerative disorders • MS • Parkinson’s • ALS • Myasthenia gravis • Huntington’s disease • Dementia • Peripheral nerve disorders • Psychiatric disorders

37. Congenital Neurologic Disorders Neural tube defects • When posterior portion of neural tube fails to close between 3 & 4 weeks of embryonic development • Etiology = unknown • Incidence = 1/ 1000 births • 90% occur in pregnancy where there is no definable risk • if you have had a child with NTD , your risk is increased 10 fold • second most common congenital defect ( first = Heart defects) • 5 types • Spina Bifida (overt or occult) • Meningocele • Myelomeningocele --- has neurological symptoms • Hydrocephalus • Anencephaly ---- incompatible with life • Diagnosis via early prenatal test ------ alpha-feto-protein • Treatment -------- surgery; use of shunts • Prevention = folic acid see next slide

39. Def: bilateral, non-progressive paralysis from damage to motor control areas of brain • occurs in prenatal period, perinatal period, and postnatal period • Most common crippling disease of children • Etiol: anoxia to brain • May or may not have related complications as: • Mental retardation • Seizures • Hearing/vision defects • Most common in premies & males • 3 basic types • Spastic = increase tone, reflexes & rigidity • Dyskinetic = no fine motor coordination • Ataxic = gait & stability problems Cerebral Palsy (CP)

40. Seizure Disorders • Outdated term = epilepsy ------- means recurrent seizures • Def: brain disorder where you get sudden episodes (paroxysmal) of intense brain activity with resultant seizures • Classification based on generalized or focal discharge of activity • Generalized = loss of consciousness • Focal (partial) = no loss of consciousness

41. Etiol: • Primary seizure disorder - - - etiology unknown • Secondary seizure disorder - - etiology known • fever • hypoglycemia • trauma ( including birth trauma) • tumors • electrolyte imbalances • Postictal state = time just after the seizure • Patient usually has confusion for a few moments

42. Classification: • Generalized --- lose consciousness; aura • Absence (petit mal) === no aura; brief (10 sec) • Myoclonic --- sudden jerking of one (or more) extremity & fall suddenly to ground; occur in clusters • Tonic --- whole body; infants & children • Tonic- clonic --- whole body; children & adults (2-5 minutes) • Partial --- no loss of consciousness • Simple --- slow repetitive jerking of body part • Complex (temporal lobe/ psychomotor) --- get automatisms • Exp = lip smacking, chewing, facial grimacing, swallowing • Status epilepticus • Clinically a generalized convulsion is described as a “Tonic-Clonic Seizure” • In Tonic Phase ----- get body stiffening • In Clonic Phase ---- get body jerking

43. Chronic degenerative disorders • MS ------------------------- multiple sclerosis; demyelination • Parkinson’s --------------- synaptic disease; no dopamine • ALS ------------------------- amyotrophic lateral sclerosis ; lateral motor tracts in spinal cord go bad • Myasthenia gravis -------- autoimmune lack of acetylcholine receptivity at synapse; usually facial & unilateral • Huntington’s disease ----- autosomal dominant genetic defect; in brain & basal ganglia get neurotransmitter deficiency of Ach & GABA Key = chronicity & progression

44. Multiple Sclerosis • Def: Inflammatory disease of the CNS where the myelin sheath is destroyed • Etiol: ? Autoimmune • General information: • Occurs between ages 20 – 40; women > men (1.5>1) • 2 main types • Exacerbation/remitting type • Get step-like progression • Chronic progressive type • Onset of first episode may be rapid • Can occur over a few hours • Symptoms • Transient weakness of limbs--- from demyelination of tracts in cord • Monoparesis, hemiparesis, paraparesis • Sudden loss of vision in one eye • Transient onset of cerebellar disease • Unsteady, vertigo, tremor of intention • Prognosis • Generally, average life span with the disease = 30 years

45. Parkinson’s disease • Pathophysiology • Get degeneration of cells in substancia nigra(gray matter in midbrain) . These cells produce dopamine • Substancia nigra interconnected to basal ganglia deep in cerebral cortex (thus brain’s control of movement out of sync • General features • Average age of onset = 60 • Avg life span with disease = 10 –15 years • Get • mild tremors • * pill-rolling • shuffling gait • muscle rigidity

46. This is really a disease of the synapse (i.e. no dopamine neurotransmitter) • Physiology: • acetylcholine & dopamine work in opposition to each other as skeletal muscle neurotransmitters * acetylcholine = increases muscle tone & activity * dopamine = decreases muscle tone and activity • Clinical Picture • Avg Age Onset = 60 ; Avg Life Span = 10 years • Early Symptoms = pill-rolling tremor, muscle rigidity, shuffling gait • Late Symptoms = behavioral changes, dementia(25%), mask-face • Treatment • Key = increase levels of dopamine; decrease levels of acetylcholine • Dopamine has problems crossing blood-brain barrier • Med = L-dopa • What’s new • New drugs to increase amount of dopamine that goes to brain • Electrical implants • Tissue implants

47. Amyotrophic Lateral Sclerosis (ALS) • Also called Lou Gehrig’s Disease • Usually appears between age 40 – 60 • Pathophysiology • Motor neuron degeneration without inflammation • One type is genetic (chromosome 21 defect) • get progressive destruction of upper & lower motor neurons by means of destruction of lateral corticospinal tracts with resultant muscle atrophy • Usually begins in hands & forearms (flaccidity) • Then affects upper motor neurons by ruining tract (axon) first (spasticity) • Remember -- Lower motor neurons gives flaccidity • Upper motor motor neurons give spasticity & hyperreflexia • get no sensory involvement & no cognitive impairment • Prognosis = death via respiratory failure in 2- 5 years

48. Myasthenia gravis • Pathophysiology: antibodies take out Ach receptors & eventually muscle won’t work • Occurs gradually • Get weakness (asthenia) & fatigue • Primarily face & eyes • May affect arm & trunk muscles • Etiol: autoimmune • Associated sometimes with thymoma • Women (avg age 30) > men (avg age 50) • Dx: Tensilon test (short acting anticholinesterase) • Complication: myasthenic crisis • Muscle weakness spreads to the respiratory muscles & get respiratory impairment • Treatment plan is to increase effect of Ach by using anticholinesterases • Future: ? Immunomodulators

49. Huntington’s chorea (disease) • Degenerative disease of cerebral cortex & basal ganglia • Neurons fail to secrete Ach & GABA (inhibitory) • Chorea = involuntary, ceaseless, purposeless movements • Etiol = genetic; autosomal dominant (on chromosome #4) • Pathophysiology = progressive atrophy of brain neurons especially in frontal cerebral cortex & basal ganglia • Key = progressive chorea & dementia • Onset of impairment begins in early adult life (25yrs – 35 yrs)

50. Dementia Alzheimer’s disease • Accounts for 50% of dementia cases • Incidence in people over 65 ----- 15% • Pathophysiology: (see next slide) • Cortical atrophy • Neurofibrillary tangles • Plaques of amyloid • Defect in neurotransmitter Ach in brain • Used to be called “presenile dementia” • Senile dementia = vascular dementia • Average age of onset ---- between age 65 – 75 • Clinically • First memory loss & lack concentration & lose emotional control • Loss of cognitive function & can’t do daily living activities • Survival up to 20 years, but average = 7