1.ActualityThe major functions of the nervous system are to detect,analyze, and transmit information. Information is gatheredby sensory systems, integrated by the brain, and used togenerate signals to motor and autonomic pathways forcontrol of movement and of visceral and endocrinefunctions.Understanding the causes of neurologic diseases requiresknowledge of molecular and biochemical mechanisms.Discoveries in the fields of molecular biology and geneticshave made available important information about themechanisms of several disease states.Several neurologic disorders in which some of themolecular mechanisms of pathogenesis are known arediscussed later in this chapter including motor neurondisease, Parkinsons disease, myasthenia gravis, epilepsy,Alzheimers disease, and stroke.Exciting advances in our understanding and overlap ofthese diseases are leading to new therapeutic targets andthe hope of better treating these devastating diseases.

2. ContentContent Disorders of integrative function of CNS.Disorders of integrative function of CNS. Brain centres and their disorderBrain centres and their disorder.. Anxiety DisordersAnxiety Disorders Mood DisordersMood Disorders SchizophreniaSchizophrenia Acute and chronic disturbances of brainAcute and chronic disturbances of braincirculation. Strokecirculation. Stroke Cerebral infarction and cerebral hemorrhage.Cerebral infarction and cerebral hemorrhage. Seizure disorders.EpilepsySeizure disorders.Epilepsy Sleep DisordersSleep Disorders AphasiasAphasias Disorders of Memory. Alzheimers Disease.Disorders of Memory. Alzheimers Disease.CreutzfeldtJakob diseaseCreutzfeldtJakob disease 3. Brain centres and theirBrain centres and theirdisorderdisorder The brain is conventionally considered in sixThe brain is conventionally considered in six main anatomicalmain anatomicaland functional areas:and functional areas:1. Cerebrum1. Cerebrum two hemispheres of cerebral two hemispheres of cerebral cortex, containingcortex, containingthe limbic system andthe limbic system and basal ganglia.basal ganglia.2. Diencephalon2. Diencephalon, containing the hypothalamus, containing the hypothalamus and thalamus.and thalamus.3. Midbrain.3. Midbrain.4. Pons.4. Pons.5. Medulla oblongata.5. Medulla oblongata.6. Cerebellum.6. Cerebellum. Alternatively, the brain may be subdividedAlternatively, the brain may be subdivided into distinct regions:into distinct regions: TheThe forebrainforebrain, which includes areas 1 and 2., which includes areas 1 and 2. TheThe hindbrainhindbrain, which includes areas 4, 5, which includes areas 4, 5 and 6.and 6. TheThe brainstembrainstem, which includes the midbrain,, which includes the midbrain, medulla and pons.medulla and pons. Interconnections between these areas areInterconnections between these areas are manifold andmanifold andcomplex, accounting for the richnesscomplex, accounting for the richness and diversity of humanand diversity of humanactivity, experienceactivity, experience and achievement.and achievement. 4. Principal anatomical centres ofPrincipal anatomical centres ofbrain functionbrain functionFunctionFunction CentreCentreInputInput PerceptionPerception Sensory cortex, thalamus,Sensory cortex, thalamus,reticular formationreticular formationProcessingProcessing Cognitive (intellectual)Cognitive (intellectual)EmotionalEmotionalCerebral cortexCerebral cortexLimbic systemLimbic systemOutputOutput MotorMotorHomeostasisHomeostasisMotor cortex, cerebellum,Motor cortex, cerebellum,basal gangliabasal gangliaMedulla, hypothalamus,Medulla, hypothalamus,pituitarypituitary 5. Cerebral cortexCerebral cortex The cerebral cortex is, in evolutionary terms, the youngest centre. It isthe principal distinguishing feature of higher mammals. Notablydeveloped in man, where it contains 90% of the total brainneurones, the cerebral cortex is the location of: It functions like afunctions like a computercomputer,providing an objective, logical assessment of the environment asperceived via the senses, and then producing a plan for action depending on past experienceand biological goals. Specific areas of the cortex are dedicated to subsidiary functions,such as the speech centre and the visual, auditory and motorcortexes. Anatomically, the cerebral cortex is subdivided into various lobes, i.e.abstract thought judgementreasoningmemoryinterpretation ofsensory inputcreativityfrontal temporalparietaloccipital 6. Cortical disordersCortical disorders Cortical disorders usually have a profoundCortical disorders usually have a profound effect on alleffect on allCNS function. They are commonlyCNS function. They are commonly manifested asmanifested asdisorders ofdisorders of intellectintellect, e.g., e.g. MentalMental handicaphandicap,, dementiadementia oror AlzheimersAlzheimers disease, ordisease, orofof movementmovement, e.g., e.g. epilepsyepilepsy.. StrokesStrokes are caused byare caused by obstruction of blood flowobstruction of blood flowusually to discreteusually to discrete cortical areas.cortical areas. TheThe thought disorderthought disorder characteristiccharacteristic ofof schizophreniaschizophreniais partly cortical, but disorderedis partly cortical, but disordered limbic or thalamiclimbic or thalamicinfluences on theinfluences on the ortex are probably more important.ortex are probably more important. Most proven and putative neurotransmittersMost proven and putative neurotransmitters are foundare foundin the cortex. Many of the morein the cortex. Many of the more recently discoveredrecently discoveredmediators, such as themediators, such as the endorphinsendorphins and peptidesand peptides, have, haveyet to be definitelyyet to be definitely linked with specific CNS functions,linked with specific CNS functions,disorders ordisorders or drug actions. They may modulate thedrug actions. They may modulate theaction ofaction of the traditional transmitters.the traditional transmitters. 7. Limbic systemLimbic system This interesting evolutionaryThis interesting evolutionarydevelopment ofdevelopment of the higher mammalsthe higher mammalsprovidesprovides mental activitymental activity with anwith anemotional dimensionemotional dimension .. TheThe limbiclimbic systemsystem is responsibleis responsibleforfor feelingsfeelings rather thanrather than objectiveobjectivereasoningreasoning and is perceivedand is perceivedconsciouslyconsciously as anas an emotionalemotionaloverlayoverlay, i.e. the, i.e. the affect or moodaffect or mood,,which can modify the decisionswhich can modify the decisionstaken by thetaken by the cortex.cortex. The system mayThe system may mediate rage,mediate rage,fear, pleasurefear, pleasure and loveand love and, byand, byits influence on corticalits influence on cortical function, isfunction, isresponsible for beliefs as opposedresponsible for beliefs as opposedtoto rational thoughtrational thought .. A materialistic interpretationA materialistic interpretation of oneof oneof the objectives of some Easternof the objectives of some Easternphilosophies,philosophies, especiallyespeciallymeditationmeditation, would be that it, would be that itattempts to achieve control or evenattempts to achieve control or eveneliminationelimination of limbic influencesof limbic influences (the(theself, desire)self, desire) on theon the cortex.cortex. 8. Limbic systemLimbic system The contrast betweenThe contrast between limbiclimbic andand cortical functionscortical functions isisillustrated by our response to beingillustrated by our response to being caught for a motoringcaught for a motoringoffence.offence. One part of usOne part of us ourour limbic system is angrylimbic system is angry,, fearfulfearful ororashamedashamed (depending on our personality):(depending on our personality): at the sameat the same time, ourtime, ourcortexcortex is calculating the effect on ouris calculating the effect on our insurance premium,insurance premium, thethemost effective way tomost effective way to appease the policeman, or perhapsappease the policeman, or perhapseven how toeven how to manage without a driving licencemanage without a driving licence.. TheThe limbic systemlimbic system has evolved from a structurehas evolved from a structure in lowerin lowermammals concerned withmammals concerned with olfactionolfaction (sense of smell),(sense of smell), andandindeed it retains this functionindeed it retains this function in humans.in humans. Possibly this accountsPossibly this accountsfor thefor the emotional power that smells have on humans.emotional power that smells have on humans. TheThe limbic systemlimbic system is also involved inis also involved in memorymemory,, and we are alland we are allfamiliar with how strongly smellsfamiliar with how strongly smells can evoke evencan evoke even distantdistantmemoriesmemories.. The system isThe system is structurally complex with many componentstructurally complex with many component nucleinucleiand important connections with theand important connections with the frontalfrontal andand temporal lobestemporal lobesof the cortexof the cortex, with, with thethe reticular systemreticular system and with theand with thehypothalamushypothalamus (all of which are sometimes considered as(all of which are sometimes considered aspartially within the limbic system).partially within the limbic system). DopamineDopamine isis an importantan importanttransmitter, as aretransmitter, as are noradrenalinenoradrenaline (NA, norepinephrine) and(NA, norepinephrine) and 5-5-hydroxytryptaminehydroxytryptamine (5-HT, serotonin).(5-HT, serotonin). Gamma-aminobutyricGamma-aminobutyricacidacid ((GABA) is an inhibitory transmitter here.GABA) is an inhibitory transmitter here. 9. Disorders of theDisorders of the LLimbicimbic SSystemystem Disorders of the limbic systemDisorders of the limbic system are likely toare likely tocause inappropriate emotions, such ascause inappropriate emotions, such as:: depression,depression, mania ormania or excessive anxiety.excessive anxiety. DelusionsDelusions ((inappropriate beliefs) may arise ininappropriate beliefs) may arise inthe limbicthe limbic system. The now discreditedsystem. The now discreditedprefrontalprefrontal lobotomy (leucotomy), an operation tolobotomy (leucotomy), an operation tosever thesever the links between the limbic system andlinks between the limbic system andthe cortexthe cortex in severe psychiatric disorders,in severe psychiatric disorders,resulted in theresulted in the patient becoming emotionally flat.patient becoming emotionally flat. A similarA similar phenomenon is sometimes seen inphenomenon is sometimes seen inpatients onpatients on long-term antipsychoticslong-term antipsychotics.. 10. Psychological DisordersPsychological Disorders Its mental processes and/or behavior patterns that cause emotionalIts mental processes and/or behavior patterns that cause emotionaldistress and/or substantial impairment in functioningdistress and/or substantial impairment in functioning The presence of a constellation of symptoms that create significantThe presence of a constellation of symptoms that create significantdistress; impair work, school, family, relationships, or daily living; ordistress; impair work, school, family, relationships, or daily living; orlead to significant risk or harmlead to significant risk or harm SymptomsSymptoms CognitiveCognitive EmotionalEmotional BehavioralBehavioral What criteria can be used to determine whether behavior isWhat criteria can be used to determine whether behavior isabnormal?abnormal? Behavior may be considered abnormal ifBehavior may be considered abnormal if It is considered strange within a persons own cultureIt is considered strange within a persons own culture It causes personal distressIt causes personal distress It is maladaptiveIt is maladaptive It is a danger to the self or othersIt is a danger to the self or others A person is not legally responsible for his or her actsA person is not legally responsible for his or her acts 11. Types/CategoriesTypes/Categories Organic Brain Syndromes (Caused by Damage)Organic Brain Syndromes (Caused by Damage) Developmental Disorders (autism, retardation)Developmental Disorders (autism, retardation) Psychoses Schizophrenia, Mood Disorders (Bipolar)Psychoses Schizophrenia, Mood Disorders (Bipolar) Neuroses Anxiety Disorders (Phobias, OCD, PTSD)Neuroses Anxiety Disorders (Phobias, OCD, PTSD) Somatoform Disorders (Ulcers)Somatoform Disorders (Ulcers) Dissociative Disorders D.I.D.Dissociative Disorders D.I.D. Personality Disorders Antisocial Personality Disorder,Personality Disorders Antisocial Personality Disorder,Substances Abuse (problems with relationships)Substances Abuse (problems with relationships) Behavioral Disorders Sleep Disorders, TurretsBehavioral Disorders Sleep Disorders, Turrets General ProblemsGeneral Problems Seek Counseling (relationships)Seek Counseling (relationships) 12. General Adaptation SyndromeThree stages:1. Alarm stage- Emergency reaction (fight-or-flight)2. Resistance stage- Coping and adaptation3. Exhaustion stage- Termination of stress response and onset ofstress pathology StressStress refers to a number of biological changesthat can be triggered by any disturbance to ournormal physiology. Stress is neutral Stress is neutral the body responds the sameto positive or negative stressors. 13. Anxiety Disorders Components of Anxiety Responses 14. Phobic DisordersPhobic Disorders PhobiaPhobia an intense an intenseand irrational fear ofand irrational fear ofparticular object orparticular object orsituationsituationPsychological DisorderPsychological Disorder InsanityInsanity is a legal term. Insanity is beingis a legal term. Insanity is being unableunable to appreciate theto appreciate thenature and quality of the wrongfulness of his or her acts, because ofnature and quality of the wrongfulness of his or her acts, because ofmental disease or defect.mental disease or defect. AbnormalityAbnormality is a condition or behavior that deviates from the usualis a condition or behavior that deviates from the usualphysical or psychological state. Culture and context are important inphysical or psychological state. Culture and context are important indefining abnormality. Talking to the dead is normal in some cultures.defining abnormality. Talking to the dead is normal in some cultures. 15. Anxiety DisordersAnxiety Disorders PhobiasPhobias - strong and irrational fears- strong and irrational fearsof certain objects or situationsof certain objects or situations AgoraphobiaAgoraphobia: fear of open and: fear of open andpublic spaces from which escapepublic spaces from which escapewould be difficultwould be difficult Social phobiasSocial phobias: fear of situations in: fear of situations inwhich evaluation might occurwhich evaluation might occur Lifetime prevalence 13%Lifetime prevalence 13% Specific phobiasSpecific phobias: fear of specific: fear of specificobjects such as animals orobjects such as animals orsituationssituations Animal fearsAnimal fears Blood-injection-injury fearsBlood-injection-injury fears Natural environment fearsNatural environment fears Situation fearsSituation fears Miscellaneous fearsMiscellaneous fears Lifetime prevalence 10%Lifetime prevalence 10% 16. Anxiety DisordersAnxiety Disorders Panic DisorderPanic Disorder an extreme anxiety that manifestsan extreme anxiety that manifestsitself in the form of panic attacksitself in the form of panic attacks Panic occurs suddenly and unpredictablyPanic occurs suddenly and unpredictably Much more intense than typical anxietyMuch more intense than typical anxiety Panic attackPanic attack An episode of overwhelming anxiety, fear, or terrorAn episode of overwhelming anxiety, fear, or terror The brains of panic-attack sufferers respond to normal changes in the body as if they were lifeThe brains of panic-attack sufferers respond to normal changes in the body as if they were lifethreateningthreatening 17. Anxiety DisordersAnxiety Disorders Obsessive-Compulsive DisorderObsessive-Compulsive Disorder ObsessionsObsessions Repetitive and unwelcome thoughts, images, or impulsesRepetitive and unwelcome thoughts, images, or impulses CompulsionsCompulsions Repetitive behavioral responsesRepetitive behavioral responses CheckingChecking WashingWashing OrderingOrdering Lifetime prevalence 2-3%Lifetime prevalence 2-3% Caudate nucleusCaudate nucleus Obsession Obsession Constantly on your mindConstantly on your mind Compulsions Compulsions Keep repeating behaviorKeep repeating behavior 18. Posttraumatic StressPosttraumatic StressDisorderDisorder Severe anxiety disorderSevere anxiety disorder Can occur in people exposed to extreme traumaCan occur in people exposed to extreme trauma PTSD disorder in which victims of traumaticPTSD disorder in which victims of traumaticevents experience the original event in the formevents experience the original event in the formof dreams or flashbacksof dreams or flashbacks SymptomsSymptoms Re-experience eventRe-experience event Avoidance and emotionalAvoidance and emotionalnumbingnumbing Heightened arousalHeightened arousal Lifetime prevalence 8% (among Americans)Lifetime prevalence 8% (among Americans) Genetic predispositionGenetic predisposition 19. Somatoform DisordersSomatoform Disorders Used to be called hysteria by FreudUsed to be called hysteria by Freud Physical symptoms for which there is noPhysical symptoms for which there is noapparent physical causeapparent physical cause Two general typesTwo general types1.1. Conversion DisordersConversion Disorders2.2. HypochondriasisHypochondriasis 20. Conversion DisordersConversion Disorders Changing emotional difficulties into a lossChanging emotional difficulties into a lossof specific voluntary body functionof specific voluntary body function Subconsciously doneSubconsciously done Reinforced by increased attentionReinforced by increased attention Motor Deficits or Sensory DeficitsMotor Deficits or Sensory Deficits RareRare 21. HypochondriasisHypochondriasis Good health but intense worry about smallGood health but intense worry about smallproblems being really bigproblems being really big Extensive doctor visits, second opinions, selfExtensive doctor visits, second opinions, selfdiagnosisdiagnosis From repressed emotions?From repressed emotions? Get more reinforcement (positive attention)Get more reinforcement (positive attention) 22. Mood Disorders 23. Mood DisordersMood Disorders Long-lasting, severeLong-lasting, severe not just really sadnot just really sad BereavementBereavement not necessarily depressionnot necessarily depressionTypes:Types: Major Depressive DisorderMajor Depressive Disorder Bipolar DisorderBipolar Disorder Season Affective DisorderSeason Affective Disorder DysthymiaDysthymia Lifetime prevalence 6%Lifetime prevalence 6% SuicideSuicide Attempted by 30% of depressed peopleAttempted by 30% of depressed people 24. Major Depressive DisorderMajor Depressive Disorder Severe form of lowered mood, feelings ofSevere form of lowered mood, feelings ofworthlessness, apathy, disinterested inworthlessness, apathy, disinterested inpleasurable activities, intense sadness,pleasurable activities, intense sadness,hopelessnesshopelessness 2+ weeks, cant be due to bereavement2+ weeks, cant be due to bereavement(grieving)(grieving) Need 4 of following symptoms (consistently andNeed 4 of following symptoms (consistently andhigher in intensity) problems eating, sleeping,higher in intensity) problems eating, sleeping,thinking, focusing, making decisions, low energy,thinking, focusing, making decisions, low energy,suicidal thoughts, feel worthless/guilty, lack ofsuicidal thoughts, feel worthless/guilty, lack ofinterest in enjoyable activitiesinterest in enjoyable activities 25. Bipolar Disorder (Manic Depression)Bipolar Disorder (Manic Depression) Individual alternates between feelings of mania andIndividual alternates between feelings of mania anddepressiondepressionManiaMania little sleep, elation, confusion, delusions, little sleep, elation, confusion, delusions,distractibility, racing thoughts, overly optimisticdistractibility, racing thoughts, overly optimisticDepressiveDepressive feel worthless, sinful, despair, failure, feel worthless, sinful, despair, failure,lethargy, unresponsivenesslethargy, unresponsiveness 26. Seasonal Affective DisorderSeasonal Affective Disorder Depression during certain seasons,Depression during certain seasons, increase sleep, eatingincrease sleep, eatingCausesCauses Melatonin?Melatonin? Vitamin D?Vitamin D? Conditioning?Conditioning? Social Learning?Social Learning? 27. What is SchizophreniaWhat is Schizophrenia Disorders characterized by confused andDisorders characterized by confused anddisconnected thoughts, emotions,disconnected thoughts, emotions,perceptionsperceptions Considered by many to be most severeConsidered by many to be most severedisorderdisorder Often a variety of symptoms presentOften a variety of symptoms present Includes positive and negative symptomsIncludes positive and negative symptoms Positive add Negative take awayPositive add Negative take away Type IType I mostly positive symptomsmostly positive symptoms-delusions, hallucinations, disorders of thoughts and behavior-delusions, hallucinations, disorders of thoughts and behavior Type IIType II mostly negative symptomsmostly negative symptoms-flat affect (emotions), avolition (motivation), alogia (speech)-flat affect (emotions), avolition (motivation), alogia (speech) 28. Types of SchizophreniaTypes of SchizophreniaEtiologyEtiologyBiological Influences 1% in population, 10% in familiesBiological Influences 1% in population, 10% in familiesBiochemistry imbalance in neurotransmitters (dopamine/serotonin)Biochemistry imbalance in neurotransmitters (dopamine/serotonin)Family/interactionsFamily/interactionsDiathesis-stress model biological, needs stress triggersDiathesis-stress model biological, needs stress triggersCatatonic motor disturbancesCatatonic motor disturbancesParanoid preoccupied withParanoid preoccupied withdelusions, people out to get themdelusions, people out to get themDisorganized incoherentDisorganized incoherentlanguage, inappropriate emotion,language, inappropriate emotion,delusions, hallucinationsdelusions, hallucinationsUndifferentiated manyUndifferentiated manysymptomssymptomsRemission no current symptomsRemission no current symptoms 29. StrokeStroke StrokeStroke is a clinical syndromeis a clinical syndromecharacterized by thecharacterized by the suddensudden onset of aonset of afocal neurologic deficit that persists forfocal neurologic deficit that persists forat least 24 hoursat least 24 hours and is due to anand is due to anabnormality of the cerebral circulationabnormality of the cerebral circulation.. TheThe incidence ofincidence of strokestroke increasesincreasesand isand is higherhigher Significant risk factors includeSignificant risk factors include::hypercholesterolemiahypercholesterolemiadiabetesdiabetesoral contraceptiveoral contraceptiveuseuseheavy alcoholheavy alcoholconsumptionconsumptionhypertensionhypertensionin men than in womenin men than in womenwithagesmokingsmoking 30. PathophysiologyPathophysiology The focal symptoms and signs that resultThe focal symptoms and signs that resultfrom stroke correlate with the area of brainfrom stroke correlate with the area of brainsupplied by the affected blood vessel.supplied by the affected blood vessel. Strokes may be classified into two majorStrokes may be classified into two majorcategories based on pathogenesis:categories based on pathogenesis:hemorrhagehemorrhageischemicischemicIn ischemic stroke,vascular occlusioninterrupts blood flow to aspecific brain region,producing a fairlycharacteristic pattern ofneurologic deficitsresulting from loss offunctions controlled bythat region.The pattern of deficits resultingfrom hemorrhage is lesspredictable because it dependson the location of the bleed andalso on factors that affect thefunction of brain regions distantfrom the hemorrhage (eg,increased intracranial pressure,brain edema, compression ofneighboring brain tissue, andrupture of blood into ventriclesor subarachnoid space). 31. Classification of StrokeClassification of StrokeIschemic strokeLarge vessels(major cerebralarteries)Small vessels(lacunar stroke)Venous occlusionCardioembolicArtery toarteryThromboticocclusionEmbolicHemorrhageEpiduralhemorrhageHemorrhagic ischemicinfarctionSubduralhemorrhageSubarachnoidhemorrhageIntraparenchymalhemorrhage 32. Common Stroke SymptomsCommon Stroke Symptoms Weakness or paralysisWeakness or paralysis Numbness, tingling,Numbness, tingling,decreased sensationdecreased sensation Vision changesVision changes Speech problemsSpeech problems Swallowing difficulties orSwallowing difficulties ordroolingdrooling Loss of memoryLoss of memory Vertigo (spinningVertigo (spinningsensation)sensation) Loss of balance andLoss of balance andcoordinationcoordination Personality changesPersonality changes Mood changesMood changes(depression, apathy)(depression, apathy) Drowsiness, lethargy, orDrowsiness, lethargy, orloss of consciousnessloss of consciousness Uncontrollable eyeUncontrollable eyemovements or eyelidmovements or eyeliddroopingdrooping 33. Major Effects of Stroke Hemiplegia - most common result ofCVA Paralysis of one side of the body May affect other functions, such ashearing, general sensation and circulation The degree of impairment depends on thepart of the brain affected Stages: Flaccid numbness and weakness of affectedside Spastic muscles contracted and tense,movement hard Recovery therapy and rehab methodssuccessful 34. Aphasia and Dysphasia Brain Damage extent of brain damagedetermines chances of recovery Hemianopsia blindness in half of thevisual field of one or both eyes Pain usually very little; injection of localanesthetic provides temporary relief Autonomic Disturbances Such as perspiration or goose flesh above thelevel of paralysis May have dilated pupils, high or low BP orheadache Treated with atropine-like drugs Personality Changes either functional ororganic 35. Ischemic Stroke Ischemic strokes result from thrombotic orembolic occlusion of cerebral vessels. Neurologic deficits caused by occlusion of largearteries result from focal ischemia to the area ofbrain supplied by the affected vessel and producerecognizable clinical syndromes (next slide). Not all signs are present in every patient, becausethe extent of the deficit depends on the presenceof collateral blood flow, individual variations invascular anatomy, blood pressure, and exactlocation of the occlusion. Thrombosis usually involves the internalcarotid, middle cerebral, or basilar arteries. Symptoms typically evolve over several minutesand may be preceded by brief episodes ofreversible focal deficits known as transientischemic attacks. Emboli from the heart, aortic arch, or carotidarteries usually occlude the middle cerebralartery, because it carries more than 80% of bloodflow to the cerebral hemisphere. Emboli that travel in the vertebral and basilararteries commonly lodge at the apex of thebasilar artery or in one or both posteriorcerebral arteries. 36. Vascular Territories and Clinical Features in Ischemic StrokeVascular Territories and Clinical Features in Ischemic StrokeArtery Territory Symptoms and SignsAnteriorcerebralMedial frontal and parietalcortex, anterior corpuscallosumParesis and sensory loss of contralateral legand footMiddle cerebralLateral frontal, parietal,occipital, and temporal cortexand adjacent white matter,caudate, putamen, internalcapsuleAphasia (dominant hemisphere), neglect(nondominant hemisphere), contralateralhemisensory loss, homonymoushemianopia, hemiparesisVertebral(posterior inferiorcerebellar)Medulla, lower cerebellum Ipsilateral cerebellar ataxia, Hornerssyndrome, crossed sensory loss, nystagmus,vertigo, hiccup, dysarthria, dysphagiaBasilar (includinganterior inferiorcerebellar,superiorcerebellar)Lower midbrain, pons, upperand mid cerebellumNystagmus, vertigo, diplopia, skew deviation,gaze palsies, hemi- or crossed sensory loss,dysarthria, hemi- or quadriparesis, ipsilateralcerebellar ataxia, Horners syndrome, comaPosterior cerebralDistal territory: medialoccipital and temporal cortexand underlying white matter,posterior corpus callosumContralateral homonymous hemianopia,dyslexia without agraphia, visual hallucinationsand distortions, memory defect, corticalblindness (bilateral occlusion)Proximal territory: uppermidbrain, thalamusSensory loss, ataxia, third nerve palsy,contralateral hemiparesis, vertical gaze palsy,skew deviation, hemiballismus, choreoathetosis,impaired consciousness 37. Conditions Associated withFocal Cerebral Ischemia.Vascular disordersFibromuscular dysplasiaVasculitisAtherosclerosisSystemic (polyarteritis nodosa,lupus, giant cell, Wegners,Takayasus)Primary CNSMeningitis (syphilis, tuberculosis,fungal, bacterial, herpes zoster)Drug induced (cocaine,amphetamines)Carotid or vertebral artery dissectionLacunar infarctionMigraineMultiple progressive intracranialocclusions (moyamoya syndrome)Venous or sinus thrombosisCardiac disordersHematologic disordersRheumatic heart diseaseMural thrombusArrhythmiasEndocarditisMitral valve prolapseParadoxic embolusAtrial myxomaProsthetic heart valvesThrombocytosisPolycythemia Sickle cell diseaseLeukocytosisHypercoagulable states(homocysteinemia, protein Sdeficiency, antiphospholipidsyndrome, sickle cell disease) 38. HemorrhageHemorrhage StrokeStroke EpiduralEpidural andand subdural hematomassubdural hematomastypically occur as sequelae of head injury.typically occur as sequelae of head injury. Epidural hematomasEpidural hematomas arise from damagearise from damageto an artery, typically the middleto an artery, typically the middlemeningeal artery, which can be rupturedmeningeal artery, which can be rupturedby a blow to the temporal bone. Bloodby a blow to the temporal bone. Blooddissects the dura from the skull anddissects the dura from the skull andcompresses the hemisphere lying below.compresses the hemisphere lying below.Initial loss of consciousness from theInitial loss of consciousness from theinjury is due to concussion and may beinjury is due to concussion and may betransient.transient. Neurologic symptomsNeurologic symptoms then return a fewthen return a fewhours later as the hematoma exerts ahours later as the hematoma exerts amass effect that may be severe enough tomass effect that may be severe enough tocause brain herniation.cause brain herniation. Subdural hematomasSubdural hematomas usually arise fromusually arise fromvenous blood that leaks from torn corticalvenous blood that leaks from torn corticalveins bridging the subdural space. Theseveins bridging the subdural space. Thesemay be ruptured by relatively minormay be ruptured by relatively minortrauma, particularly in the elderly. Thetrauma, particularly in the elderly. Theblood is under low pressure, andblood is under low pressure, andsymptoms resulting from mass effect maysymptoms resulting from mass effect maynot appear for several days.not appear for several days. 39. Hemorrhage Stroke The most common cause of spontaneous (nontraumatic) subarachnoidhemorrhage is rupture of a berry aneurysm, which is thought to arise from acongenital weakness in the walls of large vessels at the base of the brain. The aneurysms become symptomatic in adulthood, usually after the thirddecade. Rupture suddenly elevates intracranial pressure, which caninterrupt cerebral blood flow and cause a generalized concussive injury. Thisresults in loss of consciousness in about half of patients. With very large hemorrhages, global cerebral ischemia can cause severebrain damage and prolonged coma. Focal ischemia may later result from vasospasm of arteries at or near the siteof rupture. Recurrence of hemorrhage within the first few days is a commonand often fatal complication. Subarachnoid hemorrhage may occur- from head trauma,- extension of blood from anothercompartment into the subarachnoid space,- or rupture of an arterial aneurysm. Cerebral dysfunction occurs because ofincreased intracranial pressure and frompoorly understood toxic effects ofsubarachnoid blood on brain tissue andcerebral vessels. 40. HemorrhageHemorrhage StrokeStroke Intraparenchymal hemorrhageIntraparenchymal hemorrhage may result from acute elevations inmay result from acute elevations inblood pressure or from a variety of disorders that weaken vessels. Theblood pressure or from a variety of disorders that weaken vessels. Theresultant hematomaresultant hematoma causes acauses a focal neurologic deficit by compressingfocal neurologic deficit by compressingadjacent structuresadjacent structures. In addition, metabolic effects of extravasated blood. In addition, metabolic effects of extravasated blooddisturb the function of surrounding brain tissuedisturb the function of surrounding brain tissue, and, and nearby vessels arenearby vessels arecompressedcompressed, causing, causing local ischemialocal ischemia.. Chronic hypertensionChronic hypertension is theis themost common predisposingmost common predisposingfactor. In hypertensive patients,factor. In hypertensive patients,smallsmall Charcot-BouchardCharcot-Bouchardaneurysmsaneurysms appear in theappear in thewalls of small penetratingwalls of small penetratingarteries and are thought to bearteries and are thought to bethe major sites of rupture. Mostthe major sites of rupture. Mostvulnerable are the smallvulnerable are the smallvessels that are also involvedvessels that are also involvedin lacunar infarction.in lacunar infarction.Hypertensive hemorrhagesHypertensive hemorrhagesoccur mainly in the basaloccur mainly in the basalganglia, thalamus, pons, andganglia, thalamus, pons, andcerebellum and less commonlycerebellum and less commonlyin subcortical white matter.in subcortical white matter. 41. Intraparenchymal hemorrhageIntraparenchymal hemorrhageOther causes of intraparenchymal hemorrhage includeOther causes of intraparenchymal hemorrhage include vascularvascularmalformations,malformations, which contain abnormally fragile vesselswhich contain abnormally fragile vesselssusceptible to rupture at normal arterial pressures, and certainsusceptible to rupture at normal arterial pressures, and certainbrain tumors,brain tumors, such as glioblastoma multiforme, which inducesuch as glioblastoma multiforme, which induceproliferation of fragile vessels within the tumor.proliferation of fragile vessels within the tumor.CertainCertain plateletplatelet andand coagulation disorderscoagulation disorders may predispose tomay predispose tointracerebral hemorrhage by inhibiting coagulation.intracerebral hemorrhage by inhibiting coagulation.CocaineCocaine andand amphetaminesamphetamines causecause rapidrapidelevation of blood pressureelevation of blood pressure and are commonand are commoncauses ofcauses of intraparenchymal hemorrhageintraparenchymal hemorrhage ininyoung adults.young adults. HemorrhageHemorrhage may be relatedmay be relatedto spontaneous bleeding from the acuteto spontaneous bleeding from the acuteelevation in blood pressure, rupture of anelevation in blood pressure, rupture of anoccult vascular abnormality, or drug-inducedoccult vascular abnormality, or drug-inducedvasculitis.vasculitis.Cerebral amyloid angiopathyCerebral amyloid angiopathy is a disorderis a disorderthat occurs mainly in the elderly and may bethat occurs mainly in the elderly and may beassociated withassociated with Alzheimers diseaseAlzheimers disease..Deposition of amyloid weakens the walls ofDeposition of amyloid weakens the walls ofsmall cortical vessels and causes lobarsmall cortical vessels and causes lobarhemorrhage, often at several sites.hemorrhage, often at several sites. 42. Seizure disordersSeizure disordersSeizureSeizure is and abnormal discharge ofis and abnormal discharge ofelectrical activity within the brain. It is aelectrical activity within the brain. It is arapidly evolving disturbance of brainrapidly evolving disturbance of brainfunction that may produce impairedfunction that may produce impairedconsciousness, abnormalities of sensationconsciousness, abnormalities of sensationor mental function or convulsiveor mental function or convulsivemovements.movements.ConvulsionsConvulsions are episodes of widespreadare episodes of widespreadand intense motor activityand intense motor activity 43. Epilepsy An epileptic seizure(epileptic attack, epilepticfit) is triggered by aspontaneous,synchronized, massiveexcitation of a largenumber of neurons,resulting in localized orgeneralized activation ofmotor (fits or seizures),sensory (sensoryimpressions), autonomic(e.g., salivation), orcomplex (cognitive,emotional) functions. 44. EpilepsySigns and symptoms vary:Signs and symptoms vary:petit mal almost imperceptible alterations in almost imperceptible alterations inconsciousnessconsciousnessgrand mal generalized generalized tonic-clonic seizurestonic-clonic seizures dramatic loss of consciousness, falling, generalizeddramatic loss of consciousness, falling, generalizedtonic-clonic convulsionstonic-clonic convulsions of all extremities,of all extremities,incontinence, and amnesia for the event.incontinence, and amnesia for the event. Some attacks are proceeded by aSome attacks are proceeded by a prodrome a set a setof symptoms that warn of a seizureof symptoms that warn of a seizure As the seizure begins, the patient may experienceAs the seizure begins, the patient may experienceanan aura mental, sensory or motor phenomenamental, sensory or motor phenomena Others have no warningOthers have no warning 45. Phases of a grand mal seizurePhases of a grand mal seizure1.1. Tonic phaseTonic phase ( 10 -20 seconds) muscle( 10 -20 seconds) musclecontractioncontractionEpileptic cryEpileptic cry respiration stops respiration stops2.2. Clonic phaseClonic phase (1/2 -2 minutes) muscle (1/2 -2 minutes) musclespasms; respiration is ineffective;spasms; respiration is ineffective;autonomic nervous system activeautonomic nervous system active3.3. Terminal phaseTerminal phase (about 5 minutes) (about 5 minutes) limp and quiet, EEG flat lineslimp and quiet, EEG flat lines 46. Sleep Disorders Normal sleep requires theinterplay of several cerebralstructures, among them the lociceruleus and subceruleus(norepinephrine being thetransmitter), the raphe nucleus(serotonin as transmitter), tractussolitarius nucleus, and neurons inthe hypothalamus. A lesion in the subceruleus nucleus results in rapid eye movement(REM) insomnia (see below); lesions in the raphe nuclei or the anteriorhypothalamus lead to (transient) insomnia; lesions in the posteriorhypothalamus cause narcolepsy. Excitation of the tractus solitariusnucleus (e.g., by gastric distension) causes fatigue. Sleep is also verydependent on the circadian rhythm, in that destruction of the centralrhythm generator, the suprachiasmatic nucleus (SCN) leads to irregularperiods of falling asleep and of difficulty in awakening. The latter ismediated by the ascending reticular activating system (ARAS), aconnection between the reticular formation via intralaminar nuclei of thethalamus to large areas of the brain. Destruction of the intralaminarthalamic nuclei (e.g., by ischemia) leads to somnolence.Desynchronization between subcortical activity and cortical sleep may bethe cause of sleepwalking (somnambulism). 47. Sleep Disorders Disorders of the regulation of breathing during sleephave been held responsible for the sudden infantdeath syndrome (SIDS) and sleep apnea in adults. Metabolic alkalosis is thought to favor sleep apnea. Inaddition, decreased muscle tone during sleeppromotes the collapse of the airways, apnea, andhypoxia. Normally one passes through several phases ofvarying depth during sleep. During one night there are typically about 5 phases ofrapid eye movement (REM) sleep, during whichbursts of excitation from the brain stem producetwitches in the otherwise hypotonic musculature. Several phases of non-REM (NREM) sleep must bepassed through before REM sleep is reached, wherebyincreasing depth of sleep correlates with decreasingfrequency of the EEG waves. Chronic use of sleeping pills leads tolighter NREM sleep and only occasional 48. ConsciousnessConsciousness We become conscious of only a fractionWe become conscious of only a fractionof the information reaching our brain.of the information reaching our brain.The conscious contents are stored inThe conscious contents are stored inassociative cortical areas that specializeassociative cortical areas that specializein this task.in this task. Conscious awareness requires not onlyConscious awareness requires not onlythat the specific afferents have beenthat the specific afferents have beentransmitted to the cerebral cortex, buttransmitted to the cerebral cortex, butalso nonspecific activation by thealso nonspecific activation by theascending reticular activating systemascending reticular activating system(ARAS)(ARAS) through which neurons from thethrough which neurons from thereticular formation activate wide areas ofreticular formation activate wide areas ofthe cerebral cortex via intralaminarthe cerebral cortex via intralaminarneurons of the thalamus.neurons of the thalamus. 49. Loss of ConsciousnessLoss of Consciousness Damage toDamage to large areas of the cortexlarge areas of the cortex and/or breakdown of theand/or breakdown of the ascendingascendingreticular activating system (ARAS)reticular activating system (ARAS) brings aboutbrings about loss of consciousnessloss of consciousness.. In addition, there may be primary causes influencing neuronal excitability in theIn addition, there may be primary causes influencing neuronal excitability in theabove-mentioned neuronal structures.above-mentioned neuronal structures. IschemiaIschemia (e.g., atherosclerotic vascular occlusion) or(e.g., atherosclerotic vascular occlusion) or hypoxiahypoxia (e.g., suffocation)(e.g., suffocation)impair excitability directly or byimpair excitability directly or by cell swellingcell swelling.. Swelling of glial cellsSwelling of glial cells impairs, among other functions, their capacity toimpairs, among other functions, their capacity to take up K+take up K+and thus to keep down the concentration of extracellular K+. This has an indirectand thus to keep down the concentration of extracellular K+. This has an indirecteffect oneffect on neuronal excitabilityneuronal excitability.. Part of the effect of tumors, abscesses, or bleeding is also exerted via ischemia orPart of the effect of tumors, abscesses, or bleeding is also exerted via ischemia orhypoxia in that they raise the cerebral pressure and thus impair cerebral perfusionhypoxia in that they raise the cerebral pressure and thus impair cerebral perfusionby narrowing the blood vessels.by narrowing the blood vessels. HypoglycemiaHypoglycemia also modifies excitability, partly via cellular swelling.also modifies excitability, partly via cellular swelling. HyponatremiaHyponatremia andand ammoniaammonia (NH4+) also act via this mechanism. The(NH4+) also act via this mechanism. The rise inrise inNH4NH4+ in+ in hepatic encephalopathyhepatic encephalopathy causes the formation of glutamine fromcauses the formation of glutamine from --ketoglutarate andketoglutarate and glutamate in glial cellsglutamate in glial cells; the accumulation of glutamine causes; the accumulation of glutamine causesthem to swell.them to swell. AtAt firstfirst this swelling is counteracted by thethis swelling is counteracted by the removal of osmolytesremoval of osmolytes, seen in magnetic, seen in magneticresonance imaging as a decrease in the cerebral concentration of inositol. Whenresonance imaging as a decrease in the cerebral concentration of inositol. Whenthis compensatory mechanism is exhausted,this compensatory mechanism is exhausted, consciousness is lostconsciousness is lost.. 50. Aphasias Speech and language comprehension aretasks that engage a large part of thecerebral cortex. For this reason, lesions invarious parts of the cortex may lead to animpairment of speech and of languagecomprehension. Simply put, spoken language is firstperceived in the primary auditory cortex (7)and then in the sensory speech center(Wernickes area, marked in light blue).Written words are transmitted via theprimary (gray-blue) and secondary (darkblue) visual cortex to area 39, whereacoustic, optical, and sensory perceptionsare integrated. When writing, the premotorcortex is activated via the arcuatefasciculus of the premotor cortex that, inturn, activates the motor cortex via thebasal ganglia and the thalamus. In right-handed people the structures involved arepredominantly localized in the lefthemisphere, and speech disorders(aphasia) are almost always the result oflesions in the left hemisphere. Each of the above-mentioned structurescan cease functioning, for example, due totraumatic or ischemic damage. Dependingon which cerebral area is affected,abnormalities characteristic for each willdevelop. 51. Brocas aphasiaBrocas aphasia Brocas aphasia is caused by a lesion of themotor speech center in area 44 and theneighboring areas 9, 46, and 47. Spontaneous speech (verbal output) isgrammatically incorrect and the patient typicallycommunicates by using single words and isincapable of repeating someone elses words(impaired repitition ability). Language comphrehension is not, or lessmarkedly, impaired. As a rule patients cannotwrite normally. However, if the lesion is limited toarea 44, the ability to write is preserved (a raredisorder, called aphemia). 52. Wernickes aphasiaWernickes aphasia Wernickes aphasiaWernickes aphasia results from a lesion in theresults from a lesion in the sensorysensoryspeech regionspeech region, i.e., in the, i.e., in the posterior portion of the temporalposterior portion of the temporalgyrusgyrus of theof the auditory association cortexauditory association cortex (area 22) and/or the(area 22) and/or thesupramarginal gyrussupramarginal gyrus (area 40).(area 40). Language comprehensionLanguage comprehension isisimpaired in these patients.impaired in these patients.At the same time they alsoAt the same time they alsolose the ability to repeatlose the ability to repeatwords spoken by somebodywords spoken by somebodyelse.else. Spontaneous speechSpontaneous speech isisfluent; sometimes patientsfluent; sometimes patientsspeak all the timespeak all the time((logorrhealogorrhea). However, in). However, indoing so they may makedoing so they may makeoccasional phonetic (spilloccasional phonetic (spillinstead of spin) orinstead of spin) orsemantic errors (mothersemantic errors (motherinstead of womaninstead of woman[[paraphasiaparaphasia]) or create new]) or create newwords (words (neologismsneologisms).). 53. Aphasia In conductive aphasia the connection between sensory andmotor speech center (arcuate fasciculus) is interrupted.Speech is fluent (although sometimes paraphasic) andcomprehension is good. However, their repetition ability isgreatly impaired. They are also unable to read aloud, eventhough they understand the text they read. In global aphasia (damage to both the sensory and the motorcenters, e.g., by occlusion of the medial cerebral artery) bothspontaneous speech and comprehension are impaired. Anomic aphasia is the result of a lesion in the temporal lobein the region of the medial and inferior gyrus. Patientsspeech is largely normal but it is difficult for them to find theright word for certain objects. In achromatic aphasia (lesion at the left inferior temporallobe close to temporal-occipital border) the person cannotname a color (even though it is correctly recognized andobjects can normally be sorted by color). 54. Aphasia Transcortical motor aphasia is caused by a lesion in theanterior inferior frontal lobe near the Broca speech center.Spontaneous speech is markedly impaired, while repetitionand comprehension are normal. Transcortical sensory aphasia occurs after a lesion in theparietaltemporal association cortex near the Wernickespeech center or area 39. The patient can speak fluentlyand repetition is normal. However, there is a problemunderstanding words and finding the right word; reading andwriting are impossible. Subcortical aphasia is due to lesions in the region of thebasal ganglia (especially the caudate nucleus) and thethalamus. There are transient disorders of comprehensionand finding of words. 55. Disorders of Memory It is needed, forexample, inorder to be ableto recognizecertain things(apples,animals, faces).Procedural,implicit memorydoes not requireconsciousactivation forstorage andrecall. It isrequired, e.g.for learning toplay the piano. Two forms of memory are distinguished: Declarative, explicitmemory (semantic or episodic) stores memory that can only berecalled consciously. 56. Disorders of Memory To form declarative memory the information firstof all reaches the corresponding associationcortex (e.g., the secondary visual cortex) via theparticular primary sensory cortical area (e.g., theprimary visual cortex). From here, via theentorhinal cortex (area 28), the informationreaches the hippocampus, which is essential forlong-term storage of declarative memory. With mediation from structures in thediencephalon, basal forebrain, and prefrontalcortex the item is again stored in the asssociationcortex. In this way the information is first takenup, via the sensory memory, by the short-termmemory, which can hold on to the content foronly a few seconds to minutes. The information can be transferred to the long-term memory, for example, through beingrehearsed. Such rehearsal is not an essentialprecondition for the formation of long-termmemory, however.` 57. AmnesiaAmnesia Lesions in the hippocampus or its connections result inanterograde amnesia. The affected patients will from thatmoment on no longer be able to form any new declarativememory. They will remember events prior to the lesion butnone subsequent to it. Retrograde amnesia, i.e., the loss of already storedinformation, occurs in disorders in the relevant associativecortical fields. Depending on the extent and localization ofthe disorder, the loss can be reversible or irreversible. In theformer case the patient will lose items of memory, but theycan be retrieved. In irreversible loss the particular items arepermanently lost. Transitory bilateral functional disturbance of the hippocampuscan cause anterograde and retrograde (days to years)amnesia (transient global amnesia). In Korsakoffssyndrome (frequent in chronic alcoholics) both anterogradeand retrograde amnesia can occur. Patients thus affectedoften try to cover up gaps in memory by means ofconfabulations. 58. Disorders of Memory The procedural (implicit) memory is not impaired inlesions of the hippocampus. It allows imprinting, learningof skills, sensitization, habituation, and conditioning. Depending on the task, cerebellum, basal ganglia,amygdala and cortical areas are involved. Both the cerebellum and basal ganglia play an importantrole when learning skills. Relevant afferent impulses reach the cerebellum viaolivary and pontine nuclei. The storage capacity of thecerebellum can be lost by, for example, toxic damage,degenerative diseases, and trauma. Dopaminergic projections of the substantia nigra also playa part in the formation of procedural memory. 59. Disorders of MemoryDisorders of MemoryTheThe amygdalaamygdala is important inis important inconditioningconditioning anxiety reactionsanxiety reactions. It. Itreceives its information from thereceives its information from thecortexcortex andand thalamusthalamus andand influencesinfluencesmotor and autonomic functionsmotor and autonomic functions(e.g., muscle tone, palpitations(e.g., muscle tone, palpitations[awareness of tachycardias], goose-[awareness of tachycardias], goose-pimples)pimples) via the reticular formationvia the reticular formationand hypothalamusand hypothalamus..Removal of the amygdalaRemoval of the amygdala (e.g.,(e.g.,by trauma or opiates)by trauma or opiates) cancelscancelsconditioned anxiety reactionsconditioned anxiety reactions..Bilateral removal of the amygdalaBilateral removal of the amygdalawith portions of the hippocampuswith portions of the hippocampusand temporal lobe results inand temporal lobe results inamnesia and disinhibited behavioramnesia and disinhibited behavior((KlverBucy syndromeKlverBucy syndrome).). 60. Clinical Features of DementiaClinical Features of Dementia DementiaDementia is anis an acquiredacquired decline in intellectual functiondecline in intellectual function resulting inresulting inloss of social independenceloss of social independence.. There isThere is impairment of memoryimpairment of memory and at least one other area ofand at least one other area of corticalcorticalfunctionfunction, such as, such as language, calculation, spatial orientation,language, calculation, spatial orientation,decision making, judgment, and abstract reasoningdecision making, judgment, and abstract reasoning .. InIn contrast to patients withcontrast to patients with confusional statesconfusional states,, symptoms progress oversymptoms progress overmonths to yearsmonths to years, and alertness is preserved until the, and alertness is preserved until the very late stages ofvery late stages ofdiseasedisease.. DementiaDementia affects 520% of persons over age 65affects 520% of persons over age 65, and, although not, and, although notpart of normal aging, its incidence increases with age.part of normal aging, its incidence increases with age. The most common causes, which are listed inThe most common causes, which are listed in ttableable on the next slideon the next slide,,account for almostaccount for almost 90% of cases90% of cases.. Treatable causesTreatable causes are important to recognize and includeare important to recognize and includehypothyroidism, vitamin B12 deficiency, neurosyphilis, brain tumor,hypothyroidism, vitamin B12 deficiency, neurosyphilis, brain tumor,normal pressure (communicating) hydrocephalus, and chronic subduralnormal pressure (communicating) hydrocephalus, and chronic subduralhematomahematoma.. In addition,In addition, although not curable, dementiaalthough not curable, dementia associated withassociated with HIVHIVinfection may be slowed byinfection may be slowed by antiretroviral treatmentantiretroviral treatment.. AboutAbout 1015%1015% of patients referred for evaluation of dementia sufferof patients referred for evaluation of dementia sufferfrom depression (from depression ("pseudodementia""pseudodementia" ), which may also respond to), which may also respond totreatment.treatment. 61. Dementia withLewy bodiesMultiplecerebral infarctsAlzheimers disease(> 50% of cases)Deficiency of vitaminsB12, B6, B1, or niacinHIV infectionHuntingtonsHuntingtonsdiseasediseasePicksdiseasePrion diseases (eg,Creutzfeldt-Jakobdisease)ParkinsonsParkinsonsdiseasediseaseSubduralhematomaFrontotemporaldementiaAlcoholismNormal pressurehydrocephalusPrimary or metastaticCNS neoplasmsNeurosyphilisChronicmeningitisHypothyroidismMajor Causesof Dementia 62. Alzheimers Disease The defective gene on chromosome 19,for example, codes for apolipoprotein E(ApoE 4), the relevant gene onchromosome 21 for a protein (-amyloid precursor) that can be brokendown to small amyloid peptides. Thesecan on their own bunch themselvestogether into protein fibrils 710nm long.These amyloid fibrils can then formaggregates, 10 m to several hundredm in diameter (senile plaques), thatare frequently found in the brain ofpatients with Alzheimers disease. Inaddition to extracellular amyloid, theseplaques contain distorted dendrites andaxons with abnormal intracellularneurofibrils. The formation of theseatypical elements of the cytoskeletonapparently precedes the death of theneurons. The occurrence of Alzheimers disease, the most common cause of (senile) dementia(about 70%), is favored by a genetic disposition. However, the disease is not genetically uniform. An especially severe form of thedisease has an autosomal dominant inheritance. Defects on chromosomes 1, 12, 14, 19, or 21 were found in families with Alzheimersdisease. 63. A consequence of the degenerativechanges is an increased loss ofcerebral functions. The disease typically beginsinsidiously with subtle deficits ofmemory, neglect of appearanceand body hygiene, phases ofconfusion, and taking wrongdecisions. As the disease progresses,anterograde amnesia will befollowed by impairment of pastmemories as well as proceduralmemory. Lesions in the limbic systemexpress themselves alternatelythrough restlessness and lethargy. Motor deficits (speech disorders,abnormal muscle tone, ataxia,hyperkinesia, myoclonus) occurrelatively late.Alzheimers Disease 64. CreutzfeldtJakobdisease, possiblycaused by prions(proteinaceousinfectious particles), isa neurodegenerativedisease that, inaddition to motor (e.g.,ataxia) andpsychogenicdisorders, also leadsto dementia.CreutzfeldtJakob disease 65. Literature:Literature:1.1. General and clinical pathophysiology / Edited by Anatoliy V. 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