Over the years there has been an appreciation of the dimensions of the disease. In an analysis of 34 cases of diffuse Lewy body disease, acquired when the syndrome was being defined, Burkhardt and colleagues found that the most characteristic syndrome was one of progressive dementia in an elderly patient with the additional late onset of parkinsonism in many cases. In Lennox’s summary of 75 cases, parkinsonism, particularly with limb and axial rigidity, was a prominent feature in 90 percent once the illness was fully developed, and almost half had tremor of the parkinsonian type (this is somewhat different from other series). Byrne and associates, as have many others, pointed out that episodic confusion, hallucinations, and paranoid delusions were features of Lewy body dementia; such psychotic aspects are generally uncharacteristic of Alzheimer and lobar dementias and only then, in advanced stages. In Lennox’s review, one-third of patients had these swings in behavior, but as the illness advanced, amnesia, dyscalculia, visuospatial disorientation, aphasia, and apraxia differed little from those of Alzheimer disease. In the cases reported by Fearnley and coworkers, there was a supranuclear gaze palsy simulating that of progressive supranuclear palsy. These overlapping clinical features make diagnosis difficult unless the specific feature of episodic hallucinations is evident. Difficulty in diagnosis also arises because the parkinsonian disorder may be either mild or prominent and may occur as an early or a late manifestation.
The parkinsonian features can respond favorably to l-dopa, but only for a limited time and sometimes at the expense of causing an agitated delirium or hallucinations that would be uncharacteristic of early Parkinson disease (Hely et al); in others, the response to l-dopa is inconsistent or inapparent. Some patients also have orthostatic hypotension corresponding to cell loss and Lewy bodies in the intermediolateral cell column of the spinal cord or in the sympathetic ganglia, thereby simulating multiple system atrophy-P (striatonigral degeneration, or Shy-Drager syndrome [see further on]). Many authors have commented on an extreme sensitivity of such patients to neuroleptic drugs, including increased confusion and greatly worsening parkinsonism or the development of the neuroleptic malignant syndrome.
In our experience with Lewy body disease, the parkinsonian symptoms have been more prominent than they are in progressive supranuclear palsy, and the most characteristic feature besides the movement disorder and a slowly advancing dementia has been a vacuous, anxious state with intermittent psychotic or delirious behavior. The burden on family and other caregivers for this disease have impressed us as being unusually high.
With regard to diagnostic testing, SPECT scans with radiolabeled dopamine transporter or dopamine receptor tracers show reductions in lenticular nuclei and caudate (striatal) activity, usually asymmetrically, compared to controls, as also seen with Parkinson’s disease but unlike Alzheimer disease. Increased avidity with FDG PET in these same structures is also an abnormal and characteristic finding in both Lewy body and Parkinson diseases. With radiolabeled dopamine ligands, PET in Lewy body disease shows reduced avidity in these regions. Therefore, these studies can be used to distinguish Lewy body (and
Parkinson’s disease) from normal individuals and those with other dementias, including Alzheimer disease but are not used to distinguish the two parkinsonian disorders from each other. There has been increased interest in detecting phosphorylated alpha-synuclein in the small (presumably autonomic) nerves in the skin and it has been found that this test can distinguish Lewy body from other dementias (Donadio et al). Whether it differentiates this from Parkinson disease is not clear.