Authors: Carles Gaig MD1,2, Francesc Valldeoriola MD, PhD1,*, Ellen Gelpi MD, PhD2, Mario Ezquerra PhD1, Sara Llufriu MD1, Mariateresa Buongiorno MD1, Maria Jesús Rey MD, PhD2, Maria Jose Martí MD, PhD1, Francesc Graus MD, PhD1,2, Eduardo Tolosa MD, PhD1
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Lewy body syndromes (mainly Parkinson's disease and dementia with Lewy bodies) share many clinical features and usually have a slowly progressive course. Some patients may show rapid symptoms progression.
To evaluate clinical and neuropathological features of patients with a rapidly progressive diffuse Lewy Body disease.
Review clinical records and pathological findings of 6 cases with diffuse Lewy Body disease and rapid disease progression (less than 18 months before death).
Mean age at disease onset was 72.5 years, and mean disease duration was 9 months. Onset consisted of delirium in 3 patients and rapidly progressive dementia in the other three. All cases presented visual hallucinations and delusions; cognitive symptoms were fluctuating in two, parkinsonism occurred in four, and myoclonus in three. Brain MRI did not show cortical or basal ganglia hyperintensities. Periodic sharp waves were absent on EEG. 14.3.3 protein in CSF was negative. Myocardial 123I-metaiodo-benzyl-guanidine SPECT showed marked reduction in tracer uptake in the 2 patients tested. Neuropathological studies did not identify any particular feature that could differentiate rapidly progressive diffuse Lewy body disease from classical diffuse Lewy body disease.
Diffuse Lewy body disease is a possible cause of rapidly progressive dementia and should be included in the differential diagnosis of confusional states of undetermined cause. In patients with rapidly progressive dementia, the presence of fluctuating cognition, parkinsonism, hallucinations, delusions, or severe dysautonomia, should raise the suspicion of diffuse Lewy body disease. Neuroimaging studies such as 123I-metaiodo-benzyl-guanidine myocardial scintigraphy may support the clinical diagnosis of diffuse Lewy body disease.
© 2011 Movement Disorder Society
Summary and review by David J. Burn, MD, FRCP, Acting Director, Institute for Ageing and Health, Newcastle University, Newcastle upon Tyne, UK
The Lewy body dementias comprise dementia associated with Parkinson's disease (PDD) and dementia with Lewy bodies (DLB). The two disorders are separately rather arbitrarily by a so-called "12 month" rule. Other than age at onset, temporal course and possibly levodopa responsiveness, no major differences between PDD and DLB have been identified, including cognitive profile, attentional performance, sleep disorders, autonomic dysfunction, extrapyramidal features and response to cholinesterase inhibitors. Although parkinsonism is a frequent accompaniment of DLB, it is by no means inevitable, while recent reports have documented REM sleep behaviour disorder, autonomic failure and mild cognitive impairment preceding the onset of a DLB diagnosis, sometimes by many years. Once a diagnosis of DLB is made the reported "typical" disease duration is 5-8 years.In some cases, however, DLB may present acutely with delirium and display such a rapid disease progression that alternative diagnoses, such as Creutzfeldt-Jakob disease (CJD), may need to be considered.
The paper by Gaig and colleagues describes six such cases, defined on a neuropathological basis as having "diffuse Lewy body disease" and with disease duration from onset of symptoms to death of 18 months or less. The shortest disease duration reported was only three months. Four of the six cases were male and mean age at disease onset was 72.5 years (range 71-75). In three cases the initial presentation was of an acute confusional state (although "slight" cognitive and behavioural symptoms predated this in two of the cases). All six cases presented with well-formed visual hallucinations and three had action and spontaneous myoclonus. Three of the cases (but not 100% congruent with those displaying myoclonus) were diagnosed antemortem with CJD, even though MRI, EEG and CSF studies did not lend support to a prion disorder. The authors prudently tested for alpha-synuclein gene multiplications and progranulin gene mutations, but this was negative. Interestingly, myocardial 123I-meta-iodo-benzyl-guanidine (MIBG) SPECT was abnormal (i.e. suggestive of post-ganglionic sympathetic denervation) in both of the cases where it was used.
The retrospective nature of this report, and one or clinical features reported in the histories (for example, REM sleep behaviour disorder present for three years in case 1 prior to presentation) suggests that the disease duration may have been longer than originally suspected in some of the patients. Nevertheless, the rapid and fulminant clinical course is evidently atypical from that usually observed in DLB.
So what should we learn from this report? First, patients with DLB may present with delirium. Second, parkinsonism is not essential for the diagnosis of DLB (it was absent in two of the cases and only mild in three others). Third, a prion disorder may sometimes be suspected clinically but appropriate testing with MRI, EEG and CSF studies that have good sensitivity and specificity for the diagnosis of CJD are helpful in the differential, as is the absence of ataxia. Finally, if available, MIBG SPECT may be useful to support the diagnosis of DLB. Ultimately, autopsy is the "final arbitrator" and requesting permission for this is an important (but often neglected) aspect of patient and carer management.
About Prof. David Burn, MD, FRCP
David Burn is Professor of Movement Disorder Neurology at Newcastle University and Honorary Consultant Neurologist for Newcastle upon Tyne Hospitals Foundation Trust. He is also Director of the Clinical Ageing Research Unit, located on the newly established Campus for Ageing and Vitality. He qualified from Oxford University and Newcastle upon Tyne Medical School in 1985.
His MD was in the functional imaging of parkinsonism. He runs the Movement Disorders service in Newcastle upon Tyne and his research programme is conducted through Newcastle University's Institute for Ageing and Health. Research interests include dementia associated with Parkinson's disease and progressive supranuclear palsy. He was the Royal College of Physicians' representative on the NICE National Guidelines writing group for Parkinson's disease (2004-2006) is currently a member of the Medical Advisory Panels for the Progressive Supranuclear Palsy (Europe) Association, Sarah Matheson Trust and Parkinson's Disease Society. He has been the Association of British Neurologists' representative on Parkinson's Disease Subsection of British Geriatric Society since 2003. He was a member of the Special Interest Committee Task Force of the International Movement Disorder Society for Diagnostic Criteria for Parkinsonian Disorders (2002-3) and the Parkinson's Disease Dementia Task Force (2004-6).
He has been Chair of the PD Clinical Study Group of UK DeNDRoN since May 2008 and Clinical Reviews Editor for the Movement Disorder Journal since January 2007. He has published over 150 articles on movement disorders in peer reviewed journals. In his spare time, he runs for Heaton Harriers.