DIFFUSE LEWY BODY DISEASE (DLBD)
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- Beryl Gilmore
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1 CASE #2 Mr. S is a 62 years old male who was hospitalized in the dept. of psychogeriatrics after a suicide attempt (tried to jump from his balcony on the second floor). After a few days it was clear that he was not depressed or psychotic, he said that all he wanted was his wife s attention and he promised he would never attempt to repeat this act; he was released home.
2 CASE #2 He was a highschool teacher of mathematics Married for over 30 years, 2 children (25, 36) A good husband for most of his life (wife) A demanding father (daughter) A beloved teacher
3 CASE #2 A week later readmitted in the ER for an other attempt! released home same story A third attempt two days later following a trial to cut his veins Admitted! Past history: urinary problems for 6 months catheter (ER story) Very obsessive about his catheter which he believes is blocked and begs to have it changed (OCD) A Hx of LBP
4 DIFFUSE LEWY BODY DISEASE (DLBD) DIANA PALEACU KERTESZ, MD NEUROLOGY SERVICE AND MEMORY CLINIC ABARBANEL MENTAL HEALTH CENTER, DEPARTMENT OF NEUROLOGY SACKLER SCHOOL OF MEDICINE, TEL AVIV UNIVERSITY
5 EPIDEMIOLOGY It is perhaps surprising that a common, clinically important illness could still be hiding under our noses in the 21st century, but such is the case with diffuse Lewy body disease. This entity, also called Lewy body dementia, is the second most common dementing illness found in autopsy studies--more common than vascular dementia and surpassed only by Alzheimer's disease Beck BJ. Neuropsychiatric manifestations of diffuse Lewy body disease. J Geriatr Psychiatry Neurol 1995;8(3):189-96
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8 Diffuse Lewy body disease was first described by the neuropathologist Kosaka and colleagues in 1984 intracytoplasmic inclusions composed of several proteins, including ubiquitin and α-synuclein
9 Diagnosis and management of dementia with Lewy bodies: third report of the DLB Consortium. McKeith IG, Dickson DW, Lowe J, Emre M, O'Brien JT, Feldman H, Cummings J, Duda JE, Lippa C, Perry EK, Aarsland D, Arai H, Ballard CG, Boeve B,Burn DJ, Costa D, Del Ser T, Dubois B, Galasko D, Gauthier S, Goetz CG, Gomez-Tortosa E, Halliday G, Hansen LA, Hardy J, Iwatsubo T, Kalaria RN,Kaufer D, Kenny RA, Korczyn A, Kosaka K, Lee VM, Lees A, Litvan I, Londos E, Lopez OL, Minoshima S, Mizuno Y, Molina JA, Mukaetova- Ladinska EB,Pasquier F, Perry RH, Schulz JB, Trojanowski JQ, Yamada M; Consortium on DLB. Neurology Dec 27;65(12): Epub 2005 Oct 19.
10 Abstract The dementia with Lewy bodies (DLB) Consortium has revised criteria for the clinical and pathologic diagnosis of DLB incorporating new information about the core clinical features and suggesting improaved methods to assess them. REM sleep behavior disorder, severe neuroleptic sensitivity, and reduced striatal dopamine transporter activity on functional neuroimaging are given greater diagnostic weighting as features suggestive of a DLB diagnosis. The 1-year rule distinguishing between DLB and Parkinson disease with dementia may be difficult to apply in clinical settings and in such cases the term most appropriate to each individual patient should be used. Generic terms such as Lewy body (LB) disease are often helpful. The authors propose a new scheme for the pathologic assessment of LBs and Lewy neurites (LN) using alpha-synuclein immunohistochemistry and semiquantitative grading of lesion density, with the pattern of regional involvement being more important than total LB count. The new criteria take into account both Lewy-related and Alzheimer disease (AD)-type pathology to allocate a probability that these are associated with the clinical DLB syndrome. Finally, the authors suggest patient management guidelines including the need for accurate diagnosis, a target symptom approach, and use of appropriate outcome measures. There is limited evidence about specific interventions but available data suggest only a partial response of motor symptoms to levodopa: severe sensitivity to typical and atypical antipsychotics in approximately 50%, and improvements in attention,.visual hallucinations, and sleep disorders with cholinesterase inhibitors
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12 Alzheimer's disease Cortical neuritic plaques, neurofibrillary tangles 50%-60% of all dementias Equally prevalent in men and women Often familial Some day-to-day variability Abrupt deterioration always indicates superimposed illness or drug reaction Parkinsonian features very rare, occur late in illness Diffuse Lewy body disease Cortical Lewy bodies 15%-20% of all dementias Twice as prevalent in men Rarely familial Prominent day-to-day variability Abrupt deterioration common, may be idiopathic ("pseudodelirium") Parkinsonian features obvious early in illness
13 Alzheimer's disease Autonomic dysfunction rare Incidence of hallucinations 20%, usually in moderately advanced disease Adverse reactions to antipsychotics often seen Diffuse Lewy body disease Autonomic dysfunction common Incidence of hallucinations 80%, usually early in illness Severe or life-threatening adverse reactions to antipsychotics usually occur
14 CLINICAL FEATURES Alzheimer's-like dementia Parkinsonian symptoms Psychotic symptoms Extreme sensitivity to antipsychotic agents RBD
15 DEMENTIA prominent memory loss aphasia apraxia initially executive deficits (eg, disinhibition, loss of initiative, incontinence) later. progress more rapidly than in Alzheimer's disease symptoms generally vary a great deal more from one day to the next 81% of patients with diffuse Lewy body disease have unexplained periods of markedly increased confusion that lasts days to weeks and closely mimics delirium "pseudodelirium" (not been explained)
16 PARKINSONIAN FEATURES IN DLBD mild to moderate usually start at about the same time as the dementia bradykinesia, rigidity, and falls are common, but resting tremor often is absent response to levodopa and carbidopa (Madopar, Sinemet) is not nearly as robust as in Parkinson's disease prominent symptoms of autonomic parkinsonism like orthostatic hypotension and constipation
17 Comparison of features of Parkinson's disease and diffuse Lewy body Parkinson's disease Diffuse Lewy body disease Midbrain Lewy bodies - Cortical Lewy bodies Executive dementia late in illness - Cortical dementia always early Resting tremor present - Resting tremor usually absent Autonomic dysfunction - Autonomic dysfunction very seen at times prominent Robust response to levodopa - Marginal response to levodopa Hallucinations only in response - Hallucinations common in absence antiparkinsonian drugs of antiparkinsonian drugs (80%)
18 HALLUCINATIONS These symptoms also occur much earlier in the course of the illness Purely visual hallucinations are by far the most common psychotic symptoms usually feature people or animals Most important and perhaps surprisingly, these hallucinations often are not particularly distressing to the patient (12), although the patient's family may be concerned.
19 HALLUCINATIONS These psychotic symptoms are generally well tolerated by patients, which is fortunate severe adverse reactions if treated with antipsychotic agents: Severe akinesia, dystonias, and neuroleptic malignant syndrome are common reactions to even very low doses of the older, typical antipsychotics life span is halved in patients treated with these drugs treatment with these antipsychotic agents doubles the rate of cognitive decline
20 In fact, an unexpected severe reaction to antipsychotics in an older patient should raise strong suspicion of diffuse Lewy body disease! Patients may tolerate low doses of atypical antipsychotic agents, although risperidone (Risperdal) often is not tolerated* *Ballard C, Grace J, McKeith I, et al. Neuroleptic sensitivity in dementia with Lewy bodies and Alzheimer's disease. Lancet 1998;351(9108):1032-3
21 OTHER COMMON SYMPTOMS unexplained loss of consciousness and falls (probably related in part, but not completely, to parkinsonism and orthostasis) occasional myoclonic jerks rapid eye movement (REM) behavior disorder (RBD), which is characterized by abnormal motor activity during REM sleep (vivid dreaming, with persistent dreams, purposeful or violent movements, and falling out of bed )
22 Cause a genetic link with the PARK11 gene has been described As with Alzheimer's disease and Parkinson's disease, most cases of DLB appear sporadically and DLB is not thought to have a strong hereditary link As with Alzheimer's disease, the LBD risk is heightened with inheritance of the ε4 allele of the apolipoprotein E (APOE In DLB, loss of cholinergic (acetylcholine-producing) neurons is thought to account for degeneration of cognitive function (similar to Alzheimer's), while the death of dopaminergic (dopamine-producing) neurons appears to be responsible for degeneration of motor control (similar to Parkinson's) in some ways, therefore, LBD resembles both disorders.
23 Diffuse reduced glucose uptake in the entire cortical region with relative sparing of the central region but including the occipital cortex was determined in all the patients Mirzaei S et al. BMC Nuclear Medicine 2003, 3:1
24 123I-METAIODOBENZYLGUANIDINE (MIBG) MYOCARDIAL SCINTIGRAPHY 123I-metaiodobenzylguanidine (123I-MIBG), a physiological analogue of noradrenaline, is actively transported into noradrenaline granules at sympathetic nerve terminals by a noradrenaline transporter and allows the quantification of cardiac sympathetic innervation in vivo combined examination of cerebral blood flow with 3D-SSP and SEE analysis, and cardiac sympathetic nerve function with 123 I-MIBG, would be a useful supporting diagnostic method in patients with DLB particularly, in possible DLB and when cerebral blood flow does not indicate occipital hypoperfusion.
25 MIBG MYOCARDIAL SCINTIGRAPHY I-MIBG images in early and delayed phase in 2 patients with probable DLB. Patient 1 shows low 123 I-MIBG uptake in both images (H/M ratio: early, 1.33; delayed, 1.14). In contrast, patient 10 shows normal uptake in both images (H/M ratio: early, 2.05; delayed, 2.04).
26 MANAGEMENT ISSUES First and foremost, patients with this disorder probably should never be given typical antipsychotic agents. This sensitivity should be considered tantamount to an allergy The patient's family and other caregivers (informal or professional) should be aware of this
27 HALLUCINATION TREATMENT Because the hallucinations often are not troublesome to the patient, the best initial management often is caregiver education and benign neglect Improving visual acuity and environmental lighting and increasing the number of people in the environment (eg, not living alone, participating in day care programs) also may be helpful for some patients for truly problematic psychotic symptoms: low doses quetiapine fumarate (Seroquel), 6.25 to 50 mg/day, or olanzapine (Zyprexa), 1.25 to 5 mg/day. psychotic symptoms usually do not completely abate with treatment, but the patient's emotional and behavioral reactions improve Again, risperidone generally is not well tolerated
28 DEMENTIA TREATMENT Cholinesterase inhibitors: donepezil hydrochloride [Aricept] rivastigmine tartrate [Exelon] galantamine hydrobromide [Reminyl]) are as effective as they are in Alzheimer's disease memantine B grade recommendation based upon 5.9 points improvement on NPI vs. placebo
29 EP SD. TREATMENT Parkinsonian symptoms in diffuse Lewy body disease generally respond modestly at best to levodopa/carbidopa or to dopamine agonists a trial may be reasonable if symptoms are disabling bear in mind that these agents can exacerbate visual hallucinations Anticholinergic agents (Artane, Dekinet) should be strictly avoided because they invariably lead to increased confusion and hallucinations. Generally, assistive devices and attention to environmental safety seem more useful than medication for these symptoms.
30 Other treatments ample dietary sodium, exercise, avoidance of prolonged bed rest, efforts to stand up slowly, and discontinuation of medications that contribute to orthostasis. medications such as fludrocortisone acetate (Florinef) or midodrine hydrochloride (Gutron) Constipation : Discontinuation of constipating medications and improvement of basic bowel hygiene (eg, with exercise, dietary fiber, adequate hydration) stool softeners or laxatives often are needed. REM behavior disorder: clonazepam (Clonex), 0.25 to 1 mg at bedtime
31 On August 11, 2014, Williams committed suicide by hanging at his home in Paradise Cay, California. His wife attributed his suicide to his struggle with Lewy body dementia. By Eva Rinaldi - Robin Williams, CC BY-SA 2.0,
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