Neurological System Disorders

Neurological System Disorders
Pathophysiology

A & P Review of Nervous System
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

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

Diencephalon (literally means between the brain)
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

vasculature located at base of brain
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

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 parasympathetic
1. origin of thoracic & upper lumbar mid-brain & medulla in first neuron part of spinal cord brain stem ; sacral cord 2. ganglia location 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: (see next slide) preganglionic ACH ACH postganglionic * Nor - Epinephrine ACH * Dopamine is : 1. a neurotransmitter 2. a precursor of norepinephrine 3. works as an antagonist to acetylcholine

ANS Receptors Sympathetic Alpha Parasympathetic muscarinic Beta
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

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 Papilledema Increased intracranial pressure & possible herniations

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

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

Cerebral Vascular Accident
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 Encephalitis 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 * Irritability 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 see next slide 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 Cerebral Contusion
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 Basilar 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 C neck mobility T12 to L 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 * May get Hypothermia Only in Neurogenic Shock
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 degenerative disorders
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

* dopamine = decreases muscle tone and activity Clinical Picture
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 % 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 Depression 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

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