IMPORTANCE Atypical parkinsonian syndromes (APS), including progressive supranuclear palsy (PSP), corticobasal syndrome (CBS), and multiple system atrophy (MSA), may be difficult to distinguish in early stages and are often misdiagnosed as Parkinson disease (PD). The diagnostic criteria for PSP have been updated to encompass a range of clinical subtypes but have not been prospectively studied. OBJECTIVE To define the distinguishing features of PSP and CBS subtypes and to assess their usefulness in facilitating early diagnosis and separation from PD.

Autonomic and somatic denervation is well established in Parkinson's disease (PD).Objectives(1) To determine whether corneal confocal microscopy (CCM) can non-invasively demonstrate small nerve fiber damage in PD. (2) To identify relationships between corneal nerve parameters, intraepidermal nerve fiber density (IENFD) and clinical features of PD.MethodsTwenty-six PD patients and 26 controls underwent CCM of both eyes. 24/26 PD patients and 10/26 controls underwent skin biopsies from the dorsa of both feet. PD patients underwent assessment of parasympathetic function [deep breathing heart rate variability (DB-HRV)], autonomic symptoms [scale for outcomes in Parkinson's disease – autonomic symptoms (SCOPA-AUT)], motor symptoms [UPDRS-III “ON”] and cumulative Levodopa dose.ResultsPD patients had significantly reduced corneal nerve fiber density (CNFD) with increased corneal nerve branch density (CNBD) and corneal nerve fiber length (CNFL) compared to controls. CNBD and CNFL but not CNFD correlated inversely with UPDRS-III and SCOPA-AUT. All CCM parameters correlated strongly with DB-HRV. There was no correlation between CCM parameters and disease duration, cumulative Levodopa dose or pain. IENFD was significantly reduced in PD compared to controls and correlated with CNFD and UPDRS-III. However, unlike CCM measures, IENFD correlated with disease duration and cumulative Levodopa dose but not with autonomic dysfunction.ConclusionCCM identifies corneal nerve fiber pathology, which correlates with autonomic symptoms, parasympathetic deficits and motor scores in patients with PD. IENFD is also reduced and correlates with CNFD and motor symptoms but not parasympathetic deficits, indicating it detects different aspects of peripheral nerve pathology in PD.

Pain in early/moderate PD cannot be explained by peripheral factors. Central causes may play a much more important role than previously considered. These results should lead to a major shift in the investigation and management of this common and disabling symptom.

Semantic dementia, a circumscribed disorder of semantic knowledge, provides a unique model for understanding the neural basis for semantic representation. The study addressed areas of contention: the relative roles of the left and right temporal lobe, the contribution of anterior versus posterior temporal cortex and the status of the anterior temporal lobes as amodal hub. Naming and word comprehension was examined in 41 semantic dementia patients, 31 with left-predominant and 10 right-predominant atrophy. In keeping with expectation, naming and comprehension were significantly poorer in left-predominant patients. Structural magnetic resonance image analysis, using a visual rating scale, showed strong inverse correlations between naming scores and severity of both left anterior and posterior temporal lobe atrophy. By contrast, comprehension performance was more strongly correlated with left posterior temporal atrophy. Analysis of naming errors revealed a correlation between anterior temporal atrophy and associative/functional descriptive responses, implying availability of semantic information. By contrast, 'don't know' responses, indicative of loss of semantic knowledge, were linked to left posterior temporal lobe atrophy. Semantic errors, the hallmark of semantic dementia, were linked to right hemisphere atrophy, especially the right posterior temporal lobe. Matched visual-verbal tasks (famous face and name identification, Pyramids and Palm trees pictures and words, animal knowledge from 3-D models and animal names) administered to nine patients elicited variable correspondence between performance on nonverbal and verbal versions of the task. Marked performance dissociations were demonstrated in some patients: poorer understanding of names/words in left-predominant patients and of faces/pictures/models in right-predominant cases. The findings are compatible with the notion of the anterior temporal lobes as areas of convergence, but are less easily accommodated within the framework of amodal conceptual representation. The data, which reconcile some apparent contradictions in the literature, are discussed in the light of the nature and distribution of degenerative change in semantic dementia.

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L-Dopa-induced dyskinesia in patients with Parkinson's disease can be alleviated by amantadine, an antagonist at N-methyl-D-aspartate glutamate receptors. The antiepileptic drug topiramate, which blocks α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptors, has also been shown to reduce dyskinesia. The purpose of this study was to examine the behavioral pharmacology of topiramate alone and in combination with amantadine in animal models of PD and L-dopa-induced dyskinesia. The effects of topiramate (5-20 mg/kg) and amantadine (5-20 mg/kg) on abnormal involuntary movements (the rat homologue of dyskinesia) and Rotarod performance were assessed alone and in combination in the 6-hydroxydopamine-lesioned rat following chronic L-dopa treatment. Dyskinesia, parkinsonian disability, and "on-time" were assessed in the MPTP-lesioned nonhuman primate following administration of topiramate (5-20 mg/kg) and amantadine (0.1-1.0 mg/kg) alone and in combination. Topiramate and amantadine dose-dependently reduced dyskinesia in the 6-hydroxydopamine-lesioned rat, whereas topiramate reduced Rotarod performance; there was no effect on parkinsonian disability in the MPTP-lesioned nonhuman primate, in which both drugs reduced dyskinesia. Topiramate and amantadine exhibited differential antidyskinetic effects on dyskinesia elicited by the dopamine D1 receptor agonist SKF 38393 (2 mg/kg). Subthreshold doses of both drugs in combination had a synergistic effect on dyskinesia in the 6-hydroxydopamine-lesioned rat, with no worsening of motor performance; this effect was confirmed in the MPTP-lesioned nonhuman primate, with a selective reduction in "bad on-time." These data confirm the antidyskinetic potential of topiramate and suggest that combination with low-dose amantadine may allow better reduction of dyskinesia with no adverse motor effects.

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