Lewy Body Dementia (LDB)
Overview
- It's helpful to divide LDB into two main categories of symptoms: Dementia & Motor Features of Parkinsonism.
Dementia
- Visual hallucinations
- Delusions.
- Specifically, Capgras syndrome (aka imposter syndrome): patients are convinced their spouse (or caretaker) has been replaced by an imposter (we show a familiar face hidden behind an alien mask).
- Severe fluctuations in level of arousal with sudden sleep attacks.
- REM sleep behavior disorder, in which patients act out their dreams, due to dysregulation of muscle atonia during REM sleep.
Parkinsonism
- Symmetric rigidity, typically without tremor.
- Gait impairment: we show frequent falls, since this is often an important, presenting feature.
- These symptoms will have a limited response to dopamine (unlike in PD wherein they respond dramatically and are sustained).
- Patients with LDB have severe neuroleptic sensitivity, meaning these drugs profoundly worsen the parkinsonism and can even lead to neuroleptic malignant syndrome.
- Treat hallucinations with quetiapine or clozapine, instead (see: https://www.lbda.org/sites/default/files/treatment.pdf).
Histopatology
Cortical Lewy Body
- From a dementia standpoint, the pathological hallmark is the cortical Lewy body.
- We show a nucleus within a cortical neuron and a Lewy body inclusion, which lacks the concentric halo found in nigral Lewy bodies: rather, it has a more uniform density. As expected, cortical Lewy bodies stain for alpha-synuclein and ubiquitin via immunohistochemistry.
- Note that AD-type pathology: amyloid plaques and neurofibrillary tangles are also commonly seen.
- Be aware that cortical Lewy bodies are distinct from brainstem Lewy bodies.
Nigral Lewy Body
- From a parkinsonism standpoint, the pathological hallmark is the nigral Lewy body.
- We show a cell body from the substantia nigra (the key site of pathology in Parkinson’s disease).
- We recognize it as a nigral dopaminergic cell because of the neuromelanin pigment in the cell body.
- The nigral Lewy body is indistinguishable from those in Parkinson’s disease but has a slightly different appearance than cortical Lewy bodies.
- With alpha-synuclein staining, there is a central clearing with a peripheral halo of alpha-synuclein.
- On H&E staining, the Lewy body has an eosinophilic core with a peripheral halo.
References
- See the Non-Alzheimer's Dementia Tutorial