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1、CASE PRESENTATION Dr.LU,QINCHIn nDEPARTMENT OF NEUROLOGYDEPARTMENT OF NEUROLOGY REN JI HOSPITAL REN JI HOSPITAL SHANGHAI JIAO TONG UNIVERSITY SHANGHAI JIAO TONG UNIVERSITY SCHOOL OF MEDICINE SCHOOL OF MEDICINEn nTel:58752345-3094 Email:2021/9/102021/9/101 1History A 68-year-old woman has been noted
2、by her daughter to have memory loss and confusion.The daughter states that her mother has been going“downhill”for the past several months.The mother has lived on her own for many years,but recently she has begun to become unable to take care of herself.2021/9/102021/9/102 2History The daughter state
3、s that her mother has become withdrawn and has lost interest in her usual activities,such as gardening and reading.Her mothers memory is poor,and she is often fatigued.The patient states that she sleeps well at night and that her appetite is good,although she has lost 10 lb over the past 6 months.Sh
4、e denies bowel and urinary incontinence.2021/9/102021/9/103 3History The patients past medical history is significant for hypertension for which she has been taking hydrochlorethiazide.The patient was last hospitalized 35 years ago when she underwent a total abdominal hysterectomy with bilateral sal
5、pingo-oophorectomy.The patient has enjoyed overall good health.She does not smoke or drink.2021/9/102021/9/104 4Physical Exam On examination,her blood pressure is 116/56 mmHg,her heart rate is 78 bpm,her temperature is 37.5。C,and her respiratory rate is 18 breaths per minute.She weighs 88 kg and her
6、 height is 1.62m.The patient is a well-developed white women with a flat affect.She is oriented to person,but she is not oriented to time and place.2021/9/102021/9/105 5Pyhsical&Neuro Exam Mini Mental Status ExaminationMini Mental Status Examination gives a score of gives a score of 18 out of 30.The
7、 head and neck and cardiovascular 18 out of 30.The head and neck and cardiovascular examination are unremarkable.Abdomen is benign examination are unremarkable.Abdomen is benign without hepatosplenomegaly.The extremities are without hepatosplenomegaly.The extremities are without edema,cyanosis,or cl
8、ubbing.The neurologic without edema,cyanosis,or clubbing.The neurologic examination reveals that the cranial nerves are intact,examination reveals that the cranial nerves are intact,and the motor and sensory exams are within normal and the motor and sensory exams are within normal limits.Cerebellum
9、examination is unremarkable and limits.Cerebellum examination is unremarkable and the gait is normal.the gait is normal.2021/9/102021/9/106 6Questionsn nWhat is the most likely diagnosis?n nWhat are the next diagnostic steps?n nWhat is the best treatment for this condition?2021/9/102021/9/107 7Summa
10、ry:A 68-year-old woman has memory loss,confusion,and fatigue,and is withdrawn.She had a flat affect.She is oriented to person,but she is not oriented to time and place.The remainder of the examination,including neurological examination,is normal except for a low score on the MMSE.2021/9/102021/9/108
11、 8Most likely diagnosis:Alzheimer dementia.2021/9/102021/9/109 9Next diagnostic step:Assess for depression and reversible causes of dementia.2021/9/102021/9/101010Probable treatment:Acetylcholinesterase inhibitor 2021/9/102021/9/101111 AnalysisAnalysis2021/9/102021/9/101212Objectivesn nKnow some of
12、the common causes of dementian nUnderstand the presentation and diagnosis of Alzheimer dementian nKnow the treatment for Alzheimer dementia is acetylcholinesterase inhibitor2021/9/102021/9/101313Considerations This is an elderly woman without any significant past medical history except for hypertens
13、ion who was brought to your office with a history of progressive functional decline and memory loss.The first step should be to rule out depression.Depression in the elderly may have a presentation very similar to that of dementia with withdrawal,apathy,irritability,memory impairment,and confusion.2
14、021/9/102021/9/101414Considerations The next step should be to rule out all the possible causes of reversible or arrestable dementia,such as multi-infarct dementia,hypothyroidism,drugs,B12 deficiency,normal pressure hydrocephalus,alcoholism,HIV,and syphilis.2021/9/102021/9/101515Considerations Labor
15、atory tests will help you to eliminate some of these common causes of reversible dementia:complete blood count(CBC),comprehensive metabolic panel,thyroid-stimulating hormone(TSH),urinalysis,serologic test for syphilis,and a head CT(see table 49-1).2021/9/102021/9/101616Table 49-1Table 49-1ABBREVIATE
16、D WORKUP FOR DEMENTIAABBREVIATED WORKUP FOR DEMENTIAComplete blood count and consider erythrocyte Complete blood count and consider erythrocyte sedimentation rate(ESR)sedimentation rate(ESR)Chemistry panel Chemistry panel Thyroid-stimulating hormone level Thyroid-stimulating hormone level Venereal D
17、isease Research Laboratory(VDRL)Venereal Disease Research Laboratory(VDRL)HIV assay HIV assay Urinalysis Urinalysis Serum vitamin B12 and folate levels Serum vitamin B12 and folate levels Chest radiographChest radiographElectrocardiogram Electrocardiogram CT or MRI imaging of the head CT or MRI imag
18、ing of the head 2021/9/102021/9/101717Considerations The possibility of HIV-induced dementia is not high on the differential in this case given the patients age,but it would certainly be a consideration in younger people.Possible infectious causes of reversible dementia include not only HIV but also
19、 neurosyphilis.Therefore,a serologic test for syphilis is indicated.2021/9/102021/9/101818Considerations Because our patient does not have a history of chronic alcoholism,we can rule out this condition.The CBC and mean cell volume(MCV)are normal,as is the TSH,eliminating the possibilities of vitamin
20、 B12 deficiency and of hypothyroidism.The patient is only taking hydrochlorothiazide,which is not associated with the described mental status changes.A CT head scan can assess for brain lesions,multiple infarcts,and hydrocephalus.2021/9/102021/9/101919Considerations Therefore,in this case we are lef
21、t with the possibility of multi-infarct dementia and Alzheimer disease.Multi-infarct dementia develops later in life and is caused by diffuse cerebrovascular disease.Most of the patients will have a history of transient ischemic attacks and strokes,and stepwise progression of dementia which our pati
22、ent does not report.In this particular case,Alzheimer dementia becomes the most likely diagnosis.2021/9/102021/9/102020 APPROACH APPROACH TO TO DEMENTIADEMENTIA2021/9/102021/9/102121Definitionsn nAlzheimer disease:The leading cause of dementia,accounting for half of the cases involving elderly indiv
23、iduals,correlating to brain atrophy with ventricular enlargement.n nDementia:Progressive and generalized decline of intellectual ability from a previously attained level,usually without alteration of consciousness.2021/9/102021/9/102222Definitionsn nMultiinfarct dementia:Numerous small cerebral Mult
24、iinfarct dementia:Numerous small cerebral vascular accidents,most commonly caused by vascular accidents,most commonly caused by atherosclerotic disease,leading to dementia.atherosclerotic disease,leading to dementia.n nNormal pressure hydrocephalus:Reversible form of Normal pressure hydrocephalus:Re
25、versible form of dementia where the cerebral ventricles slowly enlarge dementia where the cerebral ventricles slowly enlarge as a result of disturbances to cerebral spinal fluid as a result of disturbances to cerebral spinal fluid resorption.The classic triad is dementia,gait resorption.The classic
26、triad is dementia,gait disturbance,and urinary or bowel incontinence.disturbance,and urinary or bowel incontinence.2021/9/102021/9/102323Clinical Approach A patient who presents with memory and functional impairment should be approached from the perspective that many etiologies can be causative.A th
27、orough description of the patients cognitive,adaptive,memory,and behavioral ability over time is critical.Multiple family members are often needed to construct a complete and accurate picture.The time frame(months to years versus days to weeks)is important.2021/9/102021/9/102424Clinical Approach A h
28、istory of head trauma,neurological symptoms,a stepwise decline(multi-infarct dementia)versus a insidious gradual decline may be helpful.A record of all medications,habits,alcohol use(even remote),can potentially cause mental status changes in the elderly.A resting tremor of Parkinson disease,cold in
29、tolerance suggestive of hypothyroidism,or vitamin deficiencies may be helpful.2021/9/102021/9/102525Clinical Approach The other intracranial diseases that could cause a dementia-like picture include subdural hematoma and normal pressure hydrocephalus.Usually,a CAT(computed axial tomography)scan will
30、 allow you to rule out these disease processes.Also,remember,that normal pressure hydrocephalus is usually accompanied by gait disturbances and urinary incontinence which our patient does not have.2021/9/102021/9/102626Clinical Approach Parkinson disease is also associated with the development of de
31、mentia but patients with Parkinson disease have symptoms and physical findings that will alert you to the diagnosis.Table 49-2 lists the neurological diseases that impair cognitive ability.2021/9/102021/9/102727Table 49-2Table 49-2NEUROLOGICAL DISEASES IMPAIRING COGNITIVE ABILITYNEUROLOGICAL DISEASE
32、S IMPAIRING COGNITIVE ABILITYDISEASE DISEASE CLINICAL FEATURES CLINICAL FEATURES TREATMENT TREATMENT Alzheimer disease Alzheimer disease Slow decline in cognitive and Slow decline in cognitive and behavioral ability;pathology:behavioral ability;pathology:neurofibrillary tangles,enlarged neurofibrill
33、ary tangles,enlarged cerebral ventricles,and atrophy cerebral ventricles,and atrophy Cholinesterase inhibitors such Cholinesterase inhibitors such as donepezil or rivastigmine as donepezil or rivastigmine Normal-pressure Normal-pressure hydrocephalus hydrocephalus Gate disturbance,dementia,Gate dist
34、urbance,dementia,incontinence;enlarged ventricles incontinence;enlarged ventricles without atrophy without atrophy Ventricular shunting process Ventricular shunting process Multi-infarct Multi-infarct dementia dementia Focal deficits,stepwise loss of Focal deficits,stepwise loss of function;multiple
35、 areas of function;multiple areas of infarct usually subcortical infarct usually subcortical Address atherosclerotic risk Address atherosclerotic risk factors,identify and treat factors,identify and treat thrombus thrombus Parkinson disease Parkinson disease Extrapyramidal signs(tremor,Extrapyramida
36、l signs(tremor,rigidity),slow onset rigidity),slow onset Dopaminergic agents Dopaminergic agents 2021/9/102021/9/102828Table 49-2(cont)Table 49-2(cont)NEUROLOGICAL DISEASES IMPAIRING COGNITIVE ABILITYNEUROLOGICAL DISEASES IMPAIRING COGNITIVE ABILITYDISEASE DISEASE CLINICAL FEATURES CLINICAL FEATURES
37、 TREATMENT TREATMENT HIV defintion HIV defintion Systemic involvement;risk factors Systemic involvement;risk factors for acquisition;positive HIV for acquisition;positive HIV serology serology Treat specific infection Treat specific infection Neurosyphilis Neurosyphilis Optic atrophy,Argyll-Robertso
38、n Optic atrophy,Argyll-Robertson pupils,gait disturbance;positive pupils,gait disturbance;positive cerebro-spinal fluid serology cerebro-spinal fluid serology High dose intravenous High dose intravenous penicillinpenicillinMultiple sclerosis Multiple sclerosis Brainstem signs,optic atrophy,Brainstem
39、 signs,optic atrophy,long-standing disease with long-standing disease with exacerbations and remissions;exacerbations and remissions;MRI showing white matter MRI showing white matter abnormalities abnormalities Recombinant interferon,Recombinant interferon,corticosteroids corticosteroids Intracrania
40、l tumor Intracranial tumor Focal signs,papilledema,seizures Focal signs,papilledema,seizures Corticosteroids to reduce Corticosteroids to reduce intracranial pressure,treat intracranial pressure,treat the lesion the lesion 2021/9/102021/9/102929Clinical Approach The etiology of Alzheimer dementia is
41、 an unknown The etiology of Alzheimer dementia is an unknown but Alzheimer disease has a genetic component.The but Alzheimer disease has a genetic component.The risk of developing the disease for an individual in a risk of developing the disease for an individual in a family with Alzheimer disease i
42、ncreases by a factor family with Alzheimer disease increases by a factor of 3 or 4.The gene that codes for apoprotein E seems of 3 or 4.The gene that codes for apoprotein E seems to be associated with some prediction.The pathologic to be associated with some prediction.The pathologic changes in the
43、brains of Alzheimer disease patients changes in the brains of Alzheimer disease patients include neurofibrillary tangles with a deposition of include neurofibrillary tangles with a deposition of abnormal amyloid in the brain.abnormal amyloid in the brain.2021/9/102021/9/103030Amyloid Precursor Prote
44、inA-Neurofibrillary TanglesA-AggregationNeuron DeathBasal Forebrain and Brainstem NucleiNeurotransmitter DeficitsNeuritic PlaquesNeuron DeathCortexDemantia Syndrome2021/9/102021/9/103131Mutations and vulnerability genes associated Mutations and vulnerability genes associated with Alzheimers diseasew
45、ith Alzheimers disease2021/9/102021/9/103232Mutations and vulnerability genes associated with Mutations and vulnerability genes associated with Alzheimers diseaseAlzheimers disease2021/9/102021/9/103333Classical neuritic plaque(Bielschowsky silver stain)(Bielschowsky silver stain)2021/9/102021/9/103
46、434Neurofibrillary Tangles2021/9/102021/9/103535Neurofibrillary tangles(H&E stain)(H&E stain)2021/9/102021/9/103636Cerebral amyloid angiopathy(H&E stain)(H&E stain)2021/9/102021/9/103737Clinical Approach The disease onset can be very insidious and the average life expectancy after diagnosis is 7-10
47、years.The clinical course is characterized by the progressive decline of cognitive functions(memory,orientation,attention and concentration)and the development of psychological and behavioral symptoms(wandering,aggression,anxiety,depression and psychosis)(see Table 49-3)2021/9/102021/9/103838Table 4
48、9-3Table 49-3ALZHEIMER DISEASE CLINICAL COURSEALZHEIMER DISEASE CLINICAL COURSECLINICAL STAGECLINICAL STAGE MANIFESTATIONS MANIFESTATIONS Early Early Mild forgetfulness,poor concentration,fairly good Mild forgetfulness,poor concentration,fairly good function,denial,occasional disorientation function
49、,denial,occasional disorientation Intermediate Intermediate Drastic deficits for recent memory,can travel to Drastic deficits for recent memory,can travel to familiar locations,suspicious,anxious,aware of familiar locations,suspicious,anxious,aware of confusion confusion Late Late Cannot remember na
50、mes of family members or close Cannot remember names of family members or close friends;may have delusions or hallucinations,agitation,friends;may have delusions or hallucinations,agitation,aggression,wandering,disoriented to time and place,aggression,wandering,disoriented to time and place,need for