Nervous System Diseases & DisordersIntroduction to Human Diseases

Nervous System AnatomyDivisions of the nervous system:Central Nervous SystemBrain and spinal cordPeripheral Nervous SystemPeripheral nervesAutonomic Nervous SystemSymphathetic nervous systemParasympathetic nervous system

CNS anatomyMajor parts of the brainCerebrumCognitive center (thought, memory)Level of consciousnessCerebellumCenter of balance & coordinationBrain stemCenter of automatic functionsBlood pressure, respiration, etc.

How Microbes Enter the Nervous SystemSkull or backbone fracturesMedical proceduresAlong peripheral nervesBlood or lymph

The Nervous SystemFigure 22.1

Microbial Diseases of the Nervous SystemBacteria can grow in the cerebrospinal fluid in the subarachnoid space of the CNS.The blood brain barrier (capillaries) prevents passage of some materials (such as antimicrobial drugs) into the CNS.Meningitis: Inflammation of meninges.Encephalitis: Inflammation of the brain.

The Meninges and Cerebrospinal FluidFigure 22.2

Bacterial MeningitisFever, headache, and stiff neckFollowed by nausea and vomitingMay progress to convulsions and comaDiagnosis by Gram stain or latex agglutination of CSFTreated with cephalosporins

Bacterial MeningitisFigure 22.3

Haemophilus influenzae MeningitisOccurs mostly in children (6 months to 4 years).Gram-negative aerobic bacteria, normal throat microbiotaCapsule antigen type bPrevented by Hib vaccine

Neisseria Meningitis, Meningococcal MeningitisN. meningitidisGram-negative aerobic cocci, capsule10% of people are healthy nasopharyngeal carriersBegins as throat infection, rashSerotype B is most common in the United StatesVaccination recommended for college students.

Neisseria Meningitis, Meningococcal MeningitisFigure 22.4

Streptococcus pneumoniae Meningitis, Pneumococcal MeningitisGram-positive diplococci70% of people are healthy nasopharyngeal carriersMost common in children (1 month to 4 years)Mortality: 30% in children, 80% in elderlyPrevented by vaccination

ListeriosisListeria monocytogenesGram-negative aerobic rodUsually foodborne; it can be transmitted to fetus.Reproduce in phagocytes.Figure 22.5

TetanusClostridium tetaniGram-positive, endospore-forming, obligate anaerobeGrows in deep wounds.Tetanospasmin released from dead cells blocks relaxation pathway in muscles.Prevention by vaccination with tetanus toxoid (DTP) and booster (dT).Treatment with tetanus immune globulin.

TetanusFigure 22.6

BotulismClostridium botulinum Gram-positive, endospore-forming, obligate anaerobeIntoxication comes from ingesting botulinal toxin.Botulinal toxin blocks release of neurotransmitter causing flaccid paralysis.PreventionProper canningNitrites prevent endospore germination in sausages.

BotulismTreatment: Supportive care and antitoxin.Infant botulism results from C. botulinum growing in intestines.Wound botulism results from growth of C. botulinum in wounds.

BotulismType A60-70% fatalityFound in CA, WA, CO, OR, NM.Type B25% fatalityEurope and eastern United StatesType EFound in marine and lake sedimentsPacific Northwest, Alaska, Great Lakes area

LeprosyMycobacterium lepraeAcid-fast rod that grows best at 30C.Grows in peripheral nerves and skin cells.Transmission requires prolonged contact with an infected person.Tuberculoid (neural) form: Loss of sensation in skin areas; positive lepromin testLepromatous (progressive) form: Disfiguring nodules over body; negative lepromin test

LeprosyFigure 22.9

PoliomyelitisPoliovirusTransmitted by ingestion.Initial symptoms: Sore throat and nauseaViremia may occur; if persistent, virus can enter the CNS; destruction of motor cells and paralysis occurs in

PoliomyelitisFirst vaccine made in Canada by Connaught Medical Research Laboratories

PoliomyelitisFigure 22.11

Rabies Virus (Rhabdovirus)Transmitted by animal bite.Virus multiplies in skeletal muscles, then brain cells causing encephalitis.Initial symptoms may include muscle spasms of the mouth and pharynx and hydrophobia.Furious rabies: Animals are restless then highly excitable.Paralytic rabies: Animals seem unaware of surroundings.Preexposure prophylaxis: Infection of human diploid cells vaccine.Postexposure treatment: Vaccine plus immune globulin.

Rabies Virus (Rhabdovirus)Figure 22.12

Rabies Virus (Rhabdovirus)Figure 22.12

Rabies Virus (Rhabdovirus)Figure 22.12

Rabies Virus (Rhabdovirus)Figure 22.12

Rabies Virus (Rhabdovirus)Figure 22.12

Rabies Virus (Rhabdovirus)Figure 22.12

Rabies Virus (Rhabdovirus)Figure 22.12Negri Bodies in Neurons of Brain

Rabies Virus (Rhabdovirus)Figure 22.13

Arboviral EncephalitisArboviruses are arthropod-borne viruses that belong to several families.Prevention is by controlling mosquitoes.Figure 22.14

Arboviral Encephalitis

EncephalitisReservoirMosquito vectorU.S. distributionWestern equineBirds, horsesCulex

Eastern equineBirds, horsesAedes, Culiseta

St. LouisBirdsCulex

CaliforniaSmall mammalsAedesWest NileBirds, mammalsCulex, Aedes

Cryptococcus Neoformans Meningitis (Cryptococcosis)Figure 22.15

Cryptococcus Neoformans Meningitis (Cryptococcosis)Soil fungus associated with pigeon and chicken droppings.Transmitted by the respiratory route; spreads through blood to the CNS.Mortality up to 30%.Treatment: Amphotericin B and flucytosine.

African TrypanosomiasisTrypanosoma brucei gambiense infection is chronic (2 to 4 years).T. b. rhodesiense infection is more acute (few months).Transmitted from animals to humans by tsetse fly.Prevention: Elimination of the vector.Treatment: Eflornithine blocks an enzyme necessary for the parasite.Parasite evades the antibodies through antigenic variation.

African TrypanosomiasisFigure 22.16

Naegleria fowleriProtozoan infects nasal mucosa from swimming water.Figure 22.17

Transmissible Spongiform EncephalopathiesCaused by prionsSheep scrapieCreutzfeldt-Jakob diseaseKuruBovine spongiform encephalopathyTransmitted by ingestion or transplant or inherited.Chronic and fatal

Transmissible Spongiform EncephalopathiesFigure 22.18

MeningesDuraOutermost layerThick, fibrousArachnoidThin, filmy like a spiderwebPiaThin, vascular layer of loose connective tissue, inseparable from the outer brain surface

HeadachesDue to irritation, inflammation of any pain-sensitive structureBrain itself is not a source of headacheDiagnostic procedures and testing:Physical exam (PE), CT scan, LP (lumbar puncture or spinal tap), EEG, routine x-rays, MRA, MRI and more

Migraine HeadacheRecurrent, usually severe headache of vascular originMore common in females (3 to 1)Family history in 70-80%Onset common in adolescence or early adulthood80% have first migraine by 30YOAUsually become less frequent with age

Migraine Headache10-20% US population have migraines2nd most common cause of HA in USMuscle tension HA is #1S/S:Intense throbbing headache, uni-or bilateralNausea, vomiting, dizziness, tinnitusVisual disturbancesWith or without aura (classical vs. common)Duration from 4-72 hours

Migraine HeadacheEtiology:Vasoactive chemicals (peptides) in brain (serotonin and dopamine)Stimulate inflammatory cascadeThis causes vasodilationSerotonin appears to be most important factor

Subarachnoid HeadacheDue to a subarachnoid hemorrhage80% SAH due to ruptured intracranial aneurysmBerry aneurysm, saccular, acquired due to hemodynamic stress at bifurcationsAbout 28,000 SAH/yr in USMean age is 50 YOAAccounts for 6-8% strokes in US

Subarachnoid HeadacheMost common etiology of non-traumatic intracranial hemorrhagesS/S: worst headache of my lifeRapid onset, neck stiffness (nuchal rigidity), low back pain, photophobia, nausea & vomiting, seizures in 10-25%10% mortality immediatelyUp to 60% mortality in 1st month

Head Trauma#1 cause of trauma deaths in USMany possible mechanisms of injury:FallsMotor vehicle crashesAssaults

Shaken Baby SyndromeVigorous episode of shaking the baby by the arms, torso, or chest Most victims less than 3 years of ageProduces characteristic injury pattern:Neurological injury Mental retardation, seizures, hearing lossIntracranial hemorrhage or edema, comaRetinal hemorrhages

Shaken Baby SyndromeOne version of child abuseFirst described in 1946Part of overall pattern of child abuse:Multiple fracturesBruises in all stages of healing, often axialOften abuse from non-biological parent or caregiver

Shaken Baby SyndromeBrain injuries:Hemorrhage (SDH)Cerebral edema & raised pressureMore commonPrognosis:1/3rd mortality1/3rd with permanent neurological disabilities

Epidural and Subdural HematomasEpidural HematomaHemorrhage above the dura layerArterial bleedingParietal skull fx, middle meningeal arterylucid intervalSubdural HematomaBelow the duraVenous bleedingMore common

EDH & SDHS/S:Altered level of consciousness (coma or lethargy), headacheHemiparesis (right or left)Unilateral dilated pupilTreatment:Neurosurgical drainage of the hematoma

Cerebral ConcussionDisruption of brain function without actual physical brain injuryTypically follows a blow to the headOften, not always, has loss of consciousnessS/S: headache, nausea, dizziness, amnesias, disorientation, vertigo, photophobia

ConcussionTesting is done to rule out other injuriesTreatment: supportive, observation

Cerebral ContusionBruising of the brain tissueCerebral edema around the contusion is commonMechanism: a blow to the head, usually localized forceS/S: headache, variable loss of consciousness, variation from concussion-like symptoms to coma with hemiparesis

Cerebral ContusionTesting: CT scan to examine extent of brain injury & possible brain herniationTreatment: variableMonitoring of ICP, meds to decrease brain swelling, usually surgery is not helpful, other supportive care in ICU

Disorders that cause paralysisHemiplegiaLoss of muscle control & sensation on one side of the body (L or R)ParaplegiaLoss of muscle control & sensation on the lower part of the trunk and lower extremitiesQuadriplegiaParalysis of all four extremities

HemiplegiaEtiology: most frequently strokeAlso intracranial tumor or hemorrhageOther S/S: weakness of half of the face, aphasia, agnosia, apraxia, agraphia, alexia, etc.

Paraplegia & QuadriplegiaEtiology: most commonly spinal cord injuries due to traumaOther S/S: loss of bowel & bladder control, sexual dysfunctionS/S of quadriplegia also include:Low blood pressure and pulseVariable loss of respiratory control

CNS InfectionsAcute Bacterial MeningitisAcute inflammation & infection of the CSF & the meningesEtiology: bacterial, viral, or fungalSource may be spread from blood or nasopharynxMost severe type = bacterialMost common bacteria involved are Strep pneumoniae & Neisseria meningitidis

Acute Bacterial MeningitisS/S: Headache, nausea, vomiting, fever, seizure, nuchal rigidity, drowsiness, comaTesting: lumbar puncture makes the diagnosisCharacteristic rash with Neisseria m.Treatment: antibiotics or antifungals and supportive care

Brain AbscessesLocalized collection of pusMost commonly in:CerebellumFrontal or temporal lobes of cerebrumEtiology: spread from some other nearby or distant infection

Brain abscessesS/S: depending on location, may resemble hemorrhage or CVA Treatment:AntibioticsSurgical drainage of the abscess

Peripheral Nerve DiseasesPeripheral neuritis (peripheral neuropathy)Noninflammatory degenerative disease of nerve supplying the distal extremitiesCommonly males, 30-50 YOAEtiology: numerous, including alcohol, heavy metal, drug, poisons, TB & infections, diabetes, lupus, nutritional, etc

Peripheral neuropathyS/S: muscle weakness, paresthesias, pain, tenderness, atrophy, loss of reflexesGradual in onset usuallyDiagnostics: EMGTreatment: varies with cause

Bells PalsyDisorder of the facial nerve (cranial nerve VII)Unilateral paralysis/paresis of the facial musclesUsually transientTypically in patients 20-60 YOA

Bells PalsyEtiology: idiopathic technicallyViral etiology is strongly suspectedAutoimmune, ischemic, etcS/S: facial asymmetry, drooping mouth, drooling, incomplete closure of eye (Bells phenomenon)Treatment: antiviral drugs and steroids usually

Cerebrovascular Accident (CVA)Focal neurological impairment due to lack of blood supply to an area of the brain lasting more than 24 hoursClinical condition is called stroke2 types of stroke:Ischemic: embolic or thrombotic, 75% CVAsHemorrhagic: 25% CVAs

CVARisk factors: same as for cardiovascular disease, smoking, HTN, hyperlipidemia, diabetes, etc. TIAs, oral contraceptivesS/S: hemiplegia or hemiparesis, dysphagia, speech impairment, diplopia & loss of visual fields, lack of coordination, confusion, sensory impairment

CVADiagnostics: CT scan to rule out hemorrhage or tumorTreatment:Thrombolytic medicines Clot busters if stroke symptoms of 3 hrs or lessSupportive care, nutritional, PT & OT

Transient Ischemic Attacks (TIA)Focal neurological impairment due to transient lack of blood supply to an area of the brain, lasting less than 24 hrs.TIAs indicate increased risk of CVA in the futureResolve completelyOften 20-40 minutes in duration

Transient Ischemic AttacksSymptoms: most commonly upper extremity clumsiness, weakness, paresthesias, visual field cuts (curtain-like)Treatment: surgery for carotid plaque, anticoagulants

EpilepsyChronic brain disorder characterized by seizures (abnormal, rapid, intense neuronal discharge)Types of seizures:Generalized (gran mal)Involve entire body, unconsciousPartial: part of the body is involve, consciousPetit mal: momentary, frequent unconscious episodes

EpilepsyEtiology: mostly idiopathicTrauma, tumors, CNS infection, drugs & toxins, etcS/S: in classic generalized seizureAura, tonic, clonic, post-ictal phasesRespiratory insufficiency & cyanosisIncontinence of bowel & bladder

EpilepsyTreatment: acute and long-term anticonvulsant meds

Degenerative Neurological DiseasesAlzheimers DiseaseFatal, long-term disease of the brainCharacterized by neurofibrillary tangles and senile plaquesGradual & permanent deterioration of memory, judgment, cognitive and verbal skillsGeriatric disorder in general

Alzheimers DiseaseEtiology: unknownS/S: previous section, end-stage is complete inattention to selfDiagnosis of exclusionTreatment: some meds slow progression, supportive care of patient and family

Parkinsons DiseaseMovement disorder characterized by muscle rigidity & tremorsUsually males over 65 YOAEtiology: unknown, related to dopamine deficiency in brain

Parkinsons DiseaseS/S: bradykinesia, involuntary tremors, muscular rigidityTreatment: dopamine replacement meds, PT, supportive

Multiple Sclerosis (MS)Chronic, progressive, demyelinating autoimmune disorderMakes antibodies to myelinFemales (2:1)Occurs during adult years, not geriatricAbout 25,000 new cases/yr in US

MSS/S: variable, may last hours to weeksClassically: eye symptoms, paresthesias, paralysis, mood swings, balance problems, often sudden onset with relapsesTreatment: beta-interferon products, corticosteroids, glatiramen acetate (synthetic myelin protein)Usual cause of death is due to chronic disability issues

Amyotrophic Lateral Sclerosis (ALS)Adult-onset motor neuron diseaseProgressive degeneration & loss of motor functionCalled Lou Gehrigs Disease (1941)Males between 50-60 YOAAbout 6/100,000 adult population in US25,000-30,000 cases total in US

ALSS/S: progressive muscle weakness, atrophy, and fasciculations (twitching)Eventual involvement of mouth, respiratory muscles, end-stage is complete paralysis75-80% begin with limb involvementSlurred speech, hoarseness, dysphagia, tripping & stumbling, trouble with usual daily activities

ALSSporadic form (nonhereditary) 90-95% casesInherited version is autosomal dominantMean time till ventilator dependent or death: 2-4 yearsMay survive 5-10 years on ventilator

Cancers of the CNSPrimary brain tumorsBenign or malignantMost pediatric brain tumors are primaryExamples are astrocytoma, glioblastomaSecondary brain tumorsMetastases from other sitesMost common tumors of the brain