An old man with hallucination

Transcription

1 An old man with hallucination Inter-hospital Geriatric Meeting 30 March 2012 Speaker: Dr Siu Chun Yue Chairman: Dr Leung Chi Shing Caritas Medical Center

2 History Admission 4/ /M Premorbid: ADLI, walk unaided Live with old wife and a daughter Non smoker, Non drinker Retired constructive site worker Few years of basic education

3 History Admission 4/2011 PMH: Atrial filbrilation on warfarin Hypertension Hypercholesteralaemia Benign Prostate hypertrophy OA knee with Lt TKR 2006 Cataract FU in Geriatrics clinic

4 History Admission 4/2011 Medication Warfarin 2mg daily Amlodipine 5mg daily Prazosin 2mg BD Famotidine 20mg BD Simvastatin 10mg nocte

5 History Admission 4/2011 Admitted 4/2011 C/O acute confusion x two days Talking to door with nonsense According to relatives, he claimed that he is talking to someone at that time. However, patient deny any hallucination after admission Cannot recognize relatives Day-night disorientation

6 History - Admission 4/2011 No fever No limb weakness/slurring of speech No fall but increase gait unsteadiness.

7 Physical examination Alert, conscious, Orientated to time and person, but not to place BP 130/70, pulse 70 irregular Chest clear, HS dual no murmur, abdomen soft non tender, 4 limbs power full

8 Investigation WCC 12, Hb 11, R/LFT normal INR 2.1 CXR clear CT brain: periventricular ischaemia, old lacunar infarct over Lt corona radiata

9 Working diagnosis Delirium for investigation

10 Further history from relatives Premorbid he is able to regconize relatives Can go to restaurant alone with no history of missing way home Occasionally he got day-night disorientation in previous few months. Daughter thought that it may be due to patient s blurring of vision Occasionally got fluctuating conscious level with some incoherent speech for short limited period.

11 Further history from relatives History of suspecting visual hallucination in last year (2010) Claim occasional seeing devils at night time by patient. Actually patient was referred to psychiatry clinic and seen by psychiatrist in last year (2010)

12 Further history from relatives Patient strongly deny to have any hallucination during consultation. Only reported he had gradual onset of memory decline over the past few years. But functioning was not affected MMSE 23/30 Dx: Cognitive impairment could be related to normal aging Follow PRN Patient refuse to see psychiatry anymore

13 Progress MMSE 14 on admission Still incoherent speech few days after admission Click of fever notice after admission Lumbar puncture done: No evidence of CNS infection Culture results all negative

14 Progress Put on antibiotics, fever down Still incoherent speech but improving Gradually out of delirium with coherent speech. Repeated MMSE 19 (about 10days after last MMSE) (?out of delirium? Learning effect) TFT, syphilis serology, Vit B12 normal Walk unaided upon discharge EMS 18, BBS 56, BI 78

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17 Follow up in OPD 7/2011 During OPD follow up 7/2011 Increase frequency of visual hallucination Sometimes saw devil at night, even accused his daughter as devil occasionally. Also C/O increasing unsteady gait with few episodes of fall Poor memory

18 Follow up in OPD 7/2011 Physical Examination Mild rigidity with bradykinesia over bilateral upper limbs, no definite resting tremor DDx:?Dementia of lewy bodies?alzheimer s disease Rivastigmine 1.5mg BD started

19 Follow up in OPD 9/11 C/O poor sleep at night with confusion Haloperidol 0.5mg nocte added

20 Follow up in OPD 11/11 Still C/O poor sleep at night with nocturnal confusion Haloperidol stepped up to 1mg nocte

21 Admission 1/2012 C/o Frequent fall for one week Actually gradually decrease mobility since last year Condition continued to deteriorate in recent few months and fall everyday now. Increase rigidity of limbs Poor stability on walking

22 History - Admission 1/2012 Increase confusion Wife reported that he always seeing nonexisting object No auditory hallucination Often accused his relatives as devil. Shouting at night with confuse speech Fluctuating consciousness, with daytime sleepiness.

23 History - Admission 1/2012 His daughter commented that the drugs could not help and wondered haloperidol had worsened his confusion and gait. No fever

24 Physical examination Disorientated BP/P stable, afebrile Cardiovascular/Chest/Abdominal examination unremakable 4 limbs power full Limbs cogwheel rigidity with bradykinesia

25 Investigation Bl test CBC normal RFT Cr 120, LFT normal INR 2.2 TFT normal CT brain: Periventricular ischaemia

26 MMSE 10/30 Investigation

27 Progress Haloperidol stopped after admission Psychiatry consulted, suggested switch to quetiapine 25mg nocte for BPSD control Condition further complicated with fever/mild pneumonia after admission Settled with a course antibiotics Transfer to rehabilitation ward for convalescence and rehabilitation.

28 Progress History reviewed Cognitive impairment Parkinson feature Visual hallucination +/- fluctuation in consciousness level Worsening in mobility and cognition after haloperidol

29 Progress Dignosis: Dementia with Lewy bodies

30 Progress Decrease in confusion after fever down Rivastimine was stepped up to 3mg BD Quetiapine stepped down to 12.5mg nocte PRN

31 Progress Sinemet was started with caution, dosage started 0.5tab tds Good response to parkinsonism feature with decrease in rigidity and improving walking steadiness. No deteriorating in hallucination After the sepsis completely settled and a course of rehabilitation Repeat MMSE 14/30

32 Progress A course of rehabilitation continued EMS 4->10 BBS 8->24 BI 38->60 Walk with Frame + supervision Discharge to GDH for further mobility and ADL training

33 Dementia with lewy bodies

34 Introduction Dementia with lewy bodies (DLB) is thought to be the second most common type of degenerative dementia in elderly, account for 10-15% of all cases in autopsy.* It is sometimes difficult in recognizing DLB and under diagnosis it. *McKeith IG. Consensus guidelines for the clinical and pathology diagnosis of dementia with lewy bodies: report of the consortium on DLB internation workshop 1996

35 Introduction One local study in Hong Kong 2002 There were only three cases of dementia with Lewy bodies out of 102 dementia inpatients in year 2000, giving a prevalence rate of 2.9% over a two-year period. Chan SS. Prevalence of dementia with Lewy bodies in an inpatient psychogeriatric population in Hong Kong Chinese. Int J Geriatr Psychiatry 2002

36 Introduction More prevalent with aging, mean age at presentation is 75years.

37 Pathology DLB occupied part of a spectrum of clinical presentations that also includes parkinson s disease. Both syndrome are underpinned by similar pathological changes, including lewy bodies and lewy neurites formation.

38 Pathology Lewy bodies (LB) and Lewy neurites (LN) are pathological aggregations of alpha-synuclein. Alpha-synuclein is a normal synaptic protein that may have role in vesicle production. An aggregated and insoluble form of alphasynnuclein is a major component of LB. Mechanism underlying the accumulation of alphasynuclein is not well understood.

39 Pathology Lewy Neurites are degenerating neuronal process that stain positively for alphasynuclein.

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41 Pathology In DLB, significant lewy body formation occur in brain stem, paralimbic and neocortical structures, with extensive depletion of acetylcholine neurotransmission in neocortical areas occurs as a result of degeneration in the brain stem and basal forebrain cholinergic projection neurons.

42 Pathology The lewy neurites are seen in the hippocampal region, basal nucleus of Meynert, transentorhinal cortex, amygdala and other brainstem nuclei.

43 Pathology Neither severity nor duration of dementia is directly correlated with cortical LB density. Lewy neurites and neuotransmitter deficits are suggested as more likely to links with clinical symptoms.

44 Pathology Seems no significant cortical pathology that is associated with fluctuating cognition Increase number in the anterior and inferior temporal lobe may associate with presence and onset of well-formed visual hallucination. Parkinsonism is related to the degress of cell loss an pathology in nigrostriatal pathway..

45 Pathology Most DLB patients may also have Alzheimer s disease(ad) pathology, including cortical amyloid plaques and neurofibrillary tangles (relatively less). Presence of these neocortical neurobrillary tangle modifies the typical presentation of DLB to more closely resembling AD. DLB patient with few tangles show more core clinical feature of DLB whereas those with many tangles show a pattern more like AD. Pathological diagnostic criteria.

46 Clinical Presentation

47 Clinical presentation Generally, the onset of DLB tends to be insidious, although reports of a period of increase confusion, the onset of hallucinations or a significant fall, may give the impression of a sudden onset. The course of DLB is progressive, with cognitive test scores declining about 10% per annum (similar to AD).

48 Clinical Criteria Dementia with lewy bodies are clinically defined syndromes. Diagnostic criteria revised in 2005 Clinical diagnosis Pathological diagnosis Distinguish between DLB and parkinson disease with dementia.

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51 Clinical diagnostic criteria (McKeith Criteria) 1. Central feature -Essential for a diagnosis of probable or possible DLB Dementia 2. Core feature - Two core features are sufficient for a diagnosis of probable DLB or One for possible DLB Fluctuating cognition with pronounced variation in attention and alertness Recurrent visual hallucination Spontaneous feature of parkisonism

52 Clinical Diagnostic Criteria 3. Suggestive feature - One or more suggestive feature plus one ore more core feature=> Probable DLB or One or more suggestive feature=> Possible DLB REM sleep behavior disorder Severe neuroleptic sensitivity Low dopamine transporter uptake in basal ganglia demonstrated by SPECT or PET imaging.

53 Clinical diagnostic criteria 4. Supportive feature - Commonly present but not proven to have diagnostic specificity Repeated fall/syncope Transient, unexplained loss of consciousness Severe autonomic dysfunction Hallucination in other modality Systematized delusion

54 Clinical diagnostic criteria 4. Supportive feature (Con t) - Commonly present but not proven to have diagnostic specificity Depression Relative preservation of medial temporal lobe structure on MRI/CT scan Generalized low uptake on SPECT/PET perfusion scan with reduce occipital activity Abnormal (low uptake) MIBG myocardial scintigraphy Prominent slow wave activity on EEG with temporal lobe transient sharp waves.

55 Clinical diagnostic criteria 5. Diagnosis of DLB least likely 6. Temporal sequence of symptoms (DLB vs PDD)

56 Clinical diagnostic criteria 1. Central feature 2. Core feature 3. Suggestive feature 4. Supportive feature 5. Diagnosis of DLB least likely 6. Temporal sequence of symptoms (DLB vs PDD)

57 Central feature Essential for a diagnosis Dementia defined as sufficient to interfere with normal social or occupation function. Prominent or persistent memory impairment may not be necessarily occur in the early stages but is usually evident with progression. Deficits on tests of attention, executive function and visuospatial ability may be especially prominent

58 Central feature - Dementia Relative preservation of confrontation naming and short and medium term recall as well as recognition, and greater impairment on verbal fluency, visual perception and performance tasks Memory affected later in the course of disease. Patient with DLB perform better than those with AD on test of verbal memory, but less well on visuospatial performance tasks and test of attention.

59 Central feature - Dementia Bedside tests of cognitive function e.g MMSE may not reliable to differentiate among dementia types. Some people who meet criteria for DLB may score in the normal range. Early appearance of impaired figure copying(overlapping pentagons), clock drawing and serial sevens is more suggestive DLB, while AD patients show impaired short-term memory and orientated as earliest deficit on the MMSE.

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63 Central feature - Dementia DLB patient with prominent AD pathology (eg neurofibrillary tangle) may have a cognitive profile that is more characteristic of AD.

64 Clinical diagnostic criteria 1. Central feature 2. Core feature 3. Suggestive feature 4. Supportive feature 5. Diagnosis of DLB least likely 6. Temporal sequence of symptoms (DLB vs PDD)

65 Core feature Two core features are sufficient for a diagnosis of Probable DLB or One for Possible DLB Fluctuating cognition with pronounced variation in attention and alertness Recurrent visual hallucination Spontaneous feature of parkisonism feature

66 Core feature Two core features are sufficient for a diagnosis of Probable DLB or One for Possible DLB Fluctuating cognition with pronounced variation in attention and alertness Recurrent visual hallucination Spontaneous feature of parkisonism feature

67 Fluctuation Fluctuations in cognition and level of alertness may occur early in the course of DLB and are estimated to be a feature in 60-80% of cases. Caregivers often descried episodes in which patients appear to blank out or lose consciousness, become confused or behave in a bizarre manner, have speech or motor arrest or become excessively somnolent. Episode can last seconds to days and they can be interspersed with periods of near-normal function.

68 Fluctuation Difficult to evaluate the features. The question to elicit the history may be too general to obtain false positive response in patients with other forms of dementia. Some structure questionnaires (e.g clinical assessment of Fluctuation, one day fluctuation assessment scare) could be use to elicit the history.

69 Fluctuation Mayo Fluctuations Composite Scale The Study* results show four items significantly differentiate DLB from AD, including (1)daytime drowsiness and lethargy, (2) daytime sleep lasting more than two hours, (3)prolonged staring spells, (4)times when patient s flow of ideas seems disorganized, unclear. Presence of 3 or 4 features more likely to have DLB rather than AD Fluctuations in AD are more usually more vague, or often explained by external stressors, while DLB are more often spontaneous and episodic, have more impact on function ability *Ferman TJ, Specific features that reliably differentiate DLB from AD and normal aging Neurology 2004

70 Core feature Two core features are sufficient for a diagnosis of Probable DLB or One for Possible DLB Fluctuating cognition with pronounced variation in attention and alertness Visual hallucination Spontaneous feature of parkisonism

71 Visual hallucination Recurrent, complex visual hallucination (VH) is one of the most useful sign to clinical diagnosis of DLB. Occur in ~ 2/3 of patients with DLB These hallucinations consist of well formed, detailed and animate figures, proking emotional responses, usually with some insight into the unreality of the episode when it had finished.

72 Visual hallucination Patient with DLB with VH show more profound visuoperceptual dysfunction compared to those without hallucinations. Increased numbers of LB in the anterior and inferior temporal lobe and amygdala at autopsy are associated with the presence and onset of VH. VH are associated with greater deficits in cortical acetylcholine and their presence may predict a good response to cholinergic therapy.

73 Core feature Two core features are sufficient for a diagnosis of Probable DLB or One for Possible DLB Fluctuating cognition with pronounced variation in attention and alertness visual hallucination Spontaneous feature of parkisonism

74 Parkisonism 70-90% of patient with DLB The severity of extrapyramidal motor features in DLB is generally similar to that of age matched patients with PD with or without dementia. There is an axial tendency with greater postural instability, gait difficult, and facial immobility than in non demented patients with PD. Rest tremor is less common. Rate of motor deterioration is about 10% per year, similar to PD

75 Parkisonism Levodopa responsiveness in DLB is certainly less than in uncomplicated PD, possibly because of intrinsic striatal degeneration and that significant proportion of the parkinson symptoms may be non-dopaminergic in origin.

76 Clinical diagnostic criteria 1. Central feature 2. Core feature 3. Suggestive feature 4. Supportive feature 5. Diagnosis of DLB least likely 6. Temporal sequence of symptoms (DLB vs PDD)

77 Suggestive feature One or more suggestive feature plus one ore more core feature=> Probable DLB One or more suggestive feature=> Possible DLB REM sleep behavior disorder Severe neuroleptic sensitivity Low dopamine transporter uptake in basal ganglia demonstrated by SPECT or PET imaging.

78 Suggestive feature One or more suggestive feature plus one ore more core feature=> Probable DLB One or more suggestive feature=> Possible DLB REM sleep behavior disorder Severe neuroleptic sensitivity Low dopamine transporter uptake in basal ganglia demonstrated by SPECT or PET imaging.

79 REM sleep behavior disorder Rapid eye movement (REM) sleep behavior disorder is a parasomnia characterized by vivid dreams in REM sleep without the usual acompanying muscle atonia. Act out their dreams - vocalizing, moving limbs and moving around the bed sometimes violently. Can lead to injury to the patient or bed partner Rarely with other neurodegenerative disorders.

80 Suggestive feature One or more suggestive feature plus one ore more core feature=> Probable DLB One or more suggestive feature=> Possible DLB REM sleep behavior disorder Severe neuroleptic sensitivity Low dopamine transporter uptake in basal ganglia demonstrated by SPECT or PET imaging.

81 Clive ballard, Neuroleptic sensitivity in dementia with lewy bodies and alzheimer s disease Lancet 1998 Severe neuroleptic sensitivity 30-50% of DLB cases Reactions include severe sometimes irreversible parkisonism and impaired consciousness, neuroleptic malignant syndrome. Deliberate pharmacologic challenge with D2 receptor blocking agents should not be used as diagnostic strategy because of the increase in morbidity and mortality.* Not dose related

82 Severe neuroleptic sensitivity Approximately 50% of patients with DLB receiving typical or atypical antipsychotic agents do not react so adversely. Thus tolerance of neuroleptic cannot exclude a diagnosis of DLB. However, a positive history of severe neuroleptic sensitivity strongly suggestive of DLB.

83 Suggestive feature One or more suggestive feature plus one ore more core feature=> Probable DLB One or more suggestive feature=> Possible DLB REM sleep behavior disorder Severe neuroleptic sensitivity Low dopamine transporter uptake in basal ganglia demonstrated by SPECT or PET imaging.

84 Dopamine transporter imaging Dopamine transporter loss in caudate and putamen as consequence of nigrostriatal dompaminergic dengeneration., but not in AD Low dopamine transporter uptake in basal ganglia demonstrated by Single Photon Emission Computed Tomography(SPECT) or Positron-emission Tomography (PET) imaging. Useful in distinguishing between DLB/AD High sensitivity (78%) and specificity (90%) Not widely available for clinical use.

85 SPECT images of the dopamine transporter at the level of the striatum using IFP CIT show marked reduction of activity in dementia with Lewy bodies compared with activity in Alzheimer s disease and normal ageing.

86 Supportive feature Commonly present but not proven to have diagnostic specificity Repeated fall/syncope Transient, unexplained loss of consciousness Severe autonomic dysfunction Hallucination in other modality Systemtized delusion Depression Prominent slow wave activity on EEG with temporal lobe transient sharp waves.

87 Relative preservation of medial temporal lobe structure on MRI/CT scan Generalized low uptake on SPECT/PET perfusion scan with reduce occipital activity Abnormal (low uptake) MIBG myocardial scintigraphy (Radiological feature)

88 Radiological feature Preservation of hippocampal and medial temporal lobe volume in MRI c/w AD with greater degree of hippocampal atrophy Atrophy of putamen in MRI c/w AD. Occipital hypoperperfusion in SPECT and hypometabolism in PET, without occipital atrophy on MRI.

89 A B Thin section coronal T1 weighted images from a 61-year-old male with pathologically proven Dementia with Lewy bodies (A) and a 69- year-old male with Alzheimer disease (B). There is relative preservation of the medial temporal lobes and hippocampal structures in the DLB patient as compared with the AD patient.

90 Radiological feature 123-I-metaiodobenzylguanidine(MIBG) myocardial scintgraphy demonstrate low uptake in DLB, representing reduce postganglionic sympathetic cardiac innervation. Study in small series, appear to have high sensitivity and specificity for DLB especially when distinguishing it from AD

91 Exclusion features In the presence of cerebrovascular disease evident as focal neurologic signs or on brain imaging In the presence of any other physical illness or brain disorder sufficient to accounting part or in total for the clinical picture Parkisonism only appears for the first time at a stage of severe dementia

92 Dementia with Lewy Bodies vs Parkinson disease dementia DLB should be diagnosed when dementia occurs before or concurrently with parkisnonism. Parkinson disease dementia (PDD) should be used to describe dementia that occurs in the context of well established parkinsonism In research studies, distinction needs to be made between DLB and PDD, the existing 1year rule between the onset of dementia and parkinsonism DLB continues to be recommended. In other research setting, both clinical phenotypes may be considered collectively under categories such as LB disease or alpha-synucleinopathy.

93 DLB vs PDD 1 year rule is arbitrary to separate DLB from PDD Onset of dementia within 12 months of parkinsonism qualifies as DLB and more than 12 months of parkisonism before dementia as PDD. At autopsy, cases of both disorders have lewy bodies which are the characteristic pathological feature of lewy-body disease. No definite pathological criteria that separate the disorder or from parkinson s disease without dementia.

94 DLB vs PDD Lewy body disease was therefore as catchall term which brought together from typical idiopathic mother parkinson s disease, through cases with a mixture of parkinsonism and dementia to a few cases with dementia but no extrapyramidal mother feature??spectrum of disease.

95 Dementia with Lewy bodies (DLB) and Parkinson s disease with dementia (PDD) is a not infrequent late complication of PD. By the end stage DLB and PDD patients are often clinically indistinguishable with a combination of extrapyramidal motor features, cognitive impairment, psychiatric symptoms and autonomic dysfunction. End-stage neuropathology is also similar with diffusely distributed Lewy neurites (LN) and Lewy bodies (LB), with betaamyloid cortical plaques (BAP) also common but neocortical neurofibrillary tangles (NFT) only in a minority.

96 Prognosis Conflicting evidence from comparative studies with AD about both symptoms progression and survival in DLB Some reported that the rate of cognitive decline are similar for AD and DLB, and some report a faster rate of cognitive decline in DLB.

97 Management

98 Management Four stage approach has been described* Accurate diagnosis Identification of target symptoms with patient and carer Non pharmacological interventions Pharmacological *Barber R, Dementia with lewy bodies: diagnosis and management Int J Geriatr Psychiatry 2001

99 Non pharmacological Management Combination of cognitive, psychiatric motor and autonomic symptoms More impaired in their activities of daily living.

100 Non pharmacological Management Tailoring of interventions to patient, career and environment. Patient and carer education. Modifying stressor in the environment.

101 Pharmacological treatment Cholinesterase inhibitor Neuroleptics Medication for Parkisonism Others

102 Cholinesterase inhibitor It is suggested that cholinergic deficits are even greater in DLB than AD. Multiple studies suggest that cholinesterase inhibitors are efficacious in LB in cognition, fluctuation, psychotic symptoms

103 Cholinesterase inhibitor One Randomize control study for rivastigmine in DLB* 120 patients to Rivastigmine 6-12mg daily or placebo for 20 weeks. Significantly less apathetic and anxious, fewer delusion and hallucination than control. Better performance on a computerized battery of neuropsychological test. Drug tolerated well in overall After drug discontinuation, differences between rivastigmine and placebo tended to disappear. *I McKeith, Efficacy of rivastigmine in dementia with lewy bodies: a randomised, doubleblind, placebo-controlled international study Lancet 2000

104 Neuroleptics Potential for severe neuroleptic sensitivity reaction including exacerbation of parkinsonism, confusion, autonomic dysfunction. Typical antipsychotics should be avoided. Worsens parkisonism Neuroleptic sensitivity If antipsychotic therapy is required (AChEI fail), only atypical narcoleptics such as quetiapine, clozapine should be used.

105 Neuroleptics Atypical psychotics may still bring a risk of adverse effect. Prescribing neuroleptics in DLB should be in caution and start with a small dose.

106 Medication for Parkisonism Many patients have their parkinsonism treated with levadopa with some beneficial effect. Patient with DLB may be less responsive to levodopa therapy then those with parkinson s disease. About 1/3 to ½ of DLB patients show a useful treatment response.

107 Antiparkison medication Medication should introduce at low dose and increased slowly to minimum required to minimize disability without exacerbating psychiatric symptoms.

108 Memantine Other Medication A RCT has report benefit in Global clinical status and behavioral symptoms in DLB patients. Murat Emre, Memantine for patients with Parkinson s disease dementia or dementia with lewy bodies: a randomised, double blind, placebo-controlled trial Lancel Neuro 2010

109 Other Medication Low dose clonazepam or melatonin for REM sleep disorder SSRI for depression (Tricyclic agent should be avoid in view of anticholinergic properties) Fludrocortisone, midodrine to improve symptoms of orthostatic hypotension.

110 Timeline Our patient

111 2010?Vague visual hallucination MMSE 23/30 4/2011 Admitted x Increase visual hallucination +?fluctuation, MMSE 19/30 7/2011 Some Parkinson features, Unsteady gait, fall Start Rivastigmine 1.5mg BD 9/2011 Add Haloperidol 0.5mg nocte 11/2011 Step up Haloperidol 1mg nocte 1/2012 Admitted x Frequent fall + Increase confusion + decrease GC, MMSE 14 Stop Haloperidol, Add quetiapine 12.5mg PRN Step up Rivastigmine 3mg BD Start Sinemet 25/ mg tds

112 Our patient Probable Dementia with Lewy bodies?component of vascular dementia CT brain showed periventricular ischaemia Relatively rapid deterioration in MMSE

113 Summary DLB is one of a group of neurodegenerative disorder that has been characterised as alpha synucleinopathies. There is often under diagnosis of DLB. The Diagnosis of DLB if made by clinical criteria. Radiological features may aid in the diagnosis, but are not required. Cholinesterase inhibitor have a role on management Neuroleptics should be used in caution.

114 Thankyou