This is a timely paper given ongoing questions about nomenclature in Parkinsons. Previously, people who developed dementia and then problems with movement were classified as having dementia with lewy bodies, whereas those who developed dementia after their initial movement problems were given a diagnosis of Parkinson's Disease dementia. For those who develop both problems around the same time, the diagnostic label can feel quite arbitrary. The MDS guidelines in 2015 challenged this paradigm by allowing for a diagnosis of Parkinson's disease in the context of dementia - suggesting the term PD (dementia with Lewy bodies subtype).
But more recently the DLB consortium brought out specific guidelines for diagnosis of DLB - suggesting we still use this diagnostic term where dementia occurs before or concurrently with parkinsonism. They do acknowledge that "in practice the term that is most appropriate to the clinical situation should be used and generic terms such as lewy body disease may be helpful".
Classifying both diseases along the same continuum is largely in keeping with their underlying pathophysiology. Both are characterised by lewy body inclusions of alpha-synuclein protein in the brain - and are likely to be different outward manifestations of the same underlying process. A further line of evidence for this is that rapid eye movement sleep behaviour disorder, which confers increased risk of both diseases, is also now recognised to be characterised by lewy body pathology.
In this paper in JNNP, authors from Bologna aimed to look at the validity of guidelines for diagnosis of DLB, performing a systematic review and meta-analysis of papers in which the authors had corroborated the clinical diagnosis with pathological assessment of brain tissue. They included studies with over 1500 patients and looked at diagnostic criteria over time, finding overall that with revised criteria over time, the sensitivity (likelihood of correct diagnosis) increased but specificity (likelihood of not having the disease after being given the diagnosis) declined. We seem to be picking up more of the people who truly have the disease but also diagnosing more people with the disease who don't have it.
Part of the problem is overlap of clinical symptoms - some patients with Alzheimer's disease present similarly to those with dementia with lewy bodies. But the study also underlines the issues with our classification, some of those 'misdiagnosed' had Parkinson's Disease. If we start to consider both as part of a spectrum of lewy body diseases Parkinson's wouldn't be a misdiagnosis - which challenges both our conceptions of disease (clinical vs pathological entity) and diagnosis. What do you think?
-Anna
But more recently the DLB consortium brought out specific guidelines for diagnosis of DLB - suggesting we still use this diagnostic term where dementia occurs before or concurrently with parkinsonism. They do acknowledge that "in practice the term that is most appropriate to the clinical situation should be used and generic terms such as lewy body disease may be helpful".
Classifying both diseases along the same continuum is largely in keeping with their underlying pathophysiology. Both are characterised by lewy body inclusions of alpha-synuclein protein in the brain - and are likely to be different outward manifestations of the same underlying process. A further line of evidence for this is that rapid eye movement sleep behaviour disorder, which confers increased risk of both diseases, is also now recognised to be characterised by lewy body pathology.
In this paper in JNNP, authors from Bologna aimed to look at the validity of guidelines for diagnosis of DLB, performing a systematic review and meta-analysis of papers in which the authors had corroborated the clinical diagnosis with pathological assessment of brain tissue. They included studies with over 1500 patients and looked at diagnostic criteria over time, finding overall that with revised criteria over time, the sensitivity (likelihood of correct diagnosis) increased but specificity (likelihood of not having the disease after being given the diagnosis) declined. We seem to be picking up more of the people who truly have the disease but also diagnosing more people with the disease who don't have it.
Part of the problem is overlap of clinical symptoms - some patients with Alzheimer's disease present similarly to those with dementia with lewy bodies. But the study also underlines the issues with our classification, some of those 'misdiagnosed' had Parkinson's Disease. If we start to consider both as part of a spectrum of lewy body diseases Parkinson's wouldn't be a misdiagnosis - which challenges both our conceptions of disease (clinical vs pathological entity) and diagnosis. What do you think?
-Anna
Accuracy of clinical diagnosis of dementia with Lewy bodies: a systematic review and meta-analysis
Giovanni Rizzo, Simona Arcuti, Massimiliano Copetti, Maria Alessandria, Rodolfo Savica, Andrea Fontana, Rocco Liguori, Giancarlo Logroscino
Background
The diagnosis of dementia with Lewy bodies (DLB) is based on diagnostic clinical criteria, which were updated over the years.
Objective
To evaluate, through a systematic review, accuracy of the diagnostic criteria, testing a possible improvement over time.
Methods
We searched on MEDLINE and SCOPUS databases for studies reporting diagnostic parameters regarding the clinical diagnosis of DLB until October 2016. We performed meta-analysis, using a Bayesian approach, on those using pathological examination as gold standard, subclassified based on the different diagnostic criteria used.
Results
We selected 22 studies on 1585 patients. Pooled sensitivity, specificity and accuracy were 60.2%, 93.8%, 79.7%, respectively, for criteria antecedents to McKeith 1996. For McKeith 1996-possible, pooled sensitivity, specificity and accuracy were 65.6%, 80.6%, 77.9% in early stages and 72.3%, 64.3%, 66% in late stages, respectively. For McKeith 1996-probable, pooled sensitivity, specificity and accuracy were 19.4%, 95.1%, 77.7% in early stages and 48.6%, 88%, 79.2% in late stages, respectively. McKeith criteria 2005 were evaluated only in late stages: pooled sensitivity, specificity and accuracy were 91.3%, 66.7% and 81.6%, respectively, for possible diagnosis (only one study) and 88.3%, 80.8%, 90.7% for probable diagnosis, decreasing to 85.6%, 77.1% and 81.7% if only considering clinical settings focused on dementia diagnosis and care.
Conclusions and relevance
Diagnostic criteria have become more sensitive and less specific over time, without substantial change in the accuracy. Based on current data, about 20% of DLB diagnosis are incorrect. Future studies are needed to evaluate if the recently released revised consensus criteria will improve the diagnostic accuracy of DLB.
Hello,
ReplyDeletein the near future, we will surely be able to create homogenate groups of patients with 3 kinds of parameters:
1. What kind of abnormal misfolded protein is accumulating? Lumbar puncture, specific PET imaging and genetics will help.
2. Where are the problems? Wich network? Wich nuclei are impaired?
With anatomic MRI (with special sequences), functional MRI...
3. What are the modifying factors? Genetics? Treatments received? Gut microbiota?
Using those 3 factors, it will surely be possible to define precisely what we today call Parkinson's disease or Lewy body dementia on clinical grounds. But, it will also be possible to understand what happens with the patients that don't fit the usual definitions. Don't you think so?
Thanks a lot for this insightful blog!
felix Pottecher, neurologist
I guess the question is whether these factors will cluster together with our current clinical diagnoses or whether the heterogeneity at different levels will make this a difficult fit. I think it is plausible to imagine a multi-tiered approach to diagnosis e.g.
ReplyDelete1. lewy body disease
2. nigro-strial degeneration
3. parkinson's phenotype
Thanks for the comment.
Anna