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Neurological System Disorders Pathophysiology A & P Review of Nervous System Divisions – CNS = Brain & Spinal Cord – Brain Divisions (in ascending order) – PNS = Motor Nerves (efferent) & » Brain Stem Sensory Nerves (afferent) * Medulla Oblongata » Cranial Nerves = 12 pair * Pons » Spinal Nerves = 31 pair * Midbrain » Cerebellum » Diencephalon – ANS = Parasympathetic (Cholinergic) * Hypothalamus * Thalamus » Cerebrum Sympathetic (Adrenergic) » These primarily control involuntary muscles & glands • – Brain Stem has 3 parts (in ascending order) Generally brain stem is white matter with some scattered gray matter • • Medulla Oblongata – – Pons – – • Regulates vital functions (cardiac, respiratory, & vasomotor) Crossing over of corticospinal tracts (decussation) 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 • 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) • 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 • 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 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 -toPosterior 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 Coverings & Fluid Compartments in CNS • 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 • 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 Autonomic Nervous System • 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 everyday things – 2 R’s-- rest & rumination – agonists • parasympathomimetics • cholinergics – antagonists • parasympatholytics • anticholinergics sympathetic 1. origin of first neuron 2. ganglia location parasympathetic thoracic & upper lumbar part of spinal cord mid-brain & medulla in brain stem ; sacral cord near 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: preganglionic postganglionic (see next slide) ACH * Nor - Epinephrine * Dopamine is : 1. a neurotransmitter 2. a precursor of nor- epinephrine 3. works as an antagonist to acetylcholine ACH ACH ANS Receptors • Sympathetic – Alpha • Alpha-1 – mainly on smooth muscle of vessels - get constriction • Alpha-2 – Inhibitory; on preganglionic axon knob • Parasympathetic – muscarinic • on cardiac & smooth muscle – nicotinic I (Ng) – Beta • Beta -1 – on heart musclestimulates rate & strength – In kidney for renin secretion • Beta -2 – on smooth muscle of organs -get relaxation – On skeletal muscle » Get vasodilation • on all preganglionic neurons of ANS – nicotinic II (Nm) • on skeletal muscle General effects of diseases of the nervous system 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) General effects of diseases of the nervous system (cont) • 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 nervous system (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 Increased intracranial pressure – Papilledema & possible herniations Neurological disorders General overview • 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 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 Vascular Disorders 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 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 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 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% !!! 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 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 Closed injury --- direct & contrecoup Open injury ---- depressed fracture 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 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 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 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 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 BP decreases, Pulse also decreases * May get Hypothermia Only 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 Schwann Cell 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 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 • Chronic problems – Congenital disorders – Seizure disorders – Chronic degenerative disorders • • • • • MS Parkinson’s ALS Myasthenia gravis Huntington’s disease – Dementia – Peripheral nerve disorders – Psychiatric disorders 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 Cerebral Palsy (CP) – – – – – – 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 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 • 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 • 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 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 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 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 – 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 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 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 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) 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 Dementia HIV (AIDS) – Virus is directly neuro-toxic especially in cerebral cortex – Seen in later stages of the disease – In congenital HIV infection, get frequent retardation Vascular dementia – Also called senile dementia --- an age related phenomenon – Patients generally older than 70 – Risk factor = hypertension Creutzfeldt – Jakob Disease – Etiol = prion (an altered protein particle) – Long incubation period – Get rapid destruction of neurons – Spongioform encephalopathy – Related to bovine spongioform encephalopathy – Mad cow disease – Transmissible Peripheral Nerve Disorders Peripheral Neuritis • Get degeneration of peripheral nerves (both Motor & Sensory) • Insidious Onset; Usually affects hands & feet • Etiol = (1) Toxins------ Alcohol, lead, Arsenic (2) renal failure --- uremic poisoning (3) Metabolic Diseases ------ diabetes, alcoholism (4) Dietary deficiencies ----- vitamin deficiency e.g. Beriberi (niacin deficiency) Trigeminal Neuralgia (Tic Douloureux) • pain in area of 5th cranial nerve – 3 branches: ophthalmic, maxillary, mandibular • Sx = Sudden Onset of Pain; Unilateral – can be set off by chewing, swallowing, or touching Bell’s Palsy • Sudden onset of motor paralysis of 7th cranial nerve ( FACIAL) • Sx = usually unilateral with drooping & drooling • Etiol = ?? , seen with viral illnesses, maybe seen in Lyme Disease Psychiatric disorders • 3 basic classes • Personality disorders » Tx: awareness & self improvement • Neurotic behavior » Tx: out-patient psychiatric care with good prognosis • Psychotic behavior » Tx: in-patient psychiatric care with poor prognosis Panic attack & panic disorder (anxiety disorder) – Panic attack sudden brief episode of discomfort & anxiety • Dx as personality disorder – Panic disorder = when panic attacks frequent & prolonged • Dx as neurotic disorder – Pathophysiology: • abnormal problems with neurotransmitters – Norepinephrine,serotonin, GABA • irritability of the limbic system – Memories evoke panic Schizophrenia – Psychotic disorder – Pathophysiology = dopamine excess; disorganized thought – Sx: • Positive group = delusions & bizarre behavior • Negative group = flat emotions & decreased speech – Clinically get pure groups or combinations Depression – Neurotic or psychotic – Types • Major unipolar depression • Bipolar disorder • Reactive (situational) depression – Pathophysiology = decreased activity in brain of excitatory neurotransmitters • These are norepinephrine & serotonin