Cortical structural involvement and cognitive dysfunction in early Parkinson's disease.

Magnetic resonance imaging (MRI) studies in early Parkinson's disease (PD) have shown promise in the detection of disease-related brain changes in the white and deep grey matter. We set out to establish whether intrinsic cortical involvement in early PD can be detected with quantitative MRI. We collected a rich, multi-modal dataset, including diffusion MRI, T1 relaxometry and cortical morphometry, in 20 patients with early PD (disease duration, 1.9 ± 0.97 years, Hoehn & Yahr 1-2) and in 19 matched controls. The cortex was reconstructed using FreeSurfer. Data analysis employed linked independent component analysis (ICA), a novel data-driven technique that allows for data fusion and extraction of multi-modal components before further analysis. For comparison, we performed standard uni-modal analysis with a general linear model (GLM). Linked ICA detected multi-modal cortical changes in early PD (p = 0.015). These comprised fractional anisotropy reduction in dorsolateral prefrontal, cingulate and premotor cortex and the superior parietal lobule, mean diffusivity increase in the mesolimbic, somatosensory and superior parietal cortex, sparse diffusivity decrease in lateral parietal and right prefrontal cortex, and sparse changes to the cortex area. In PD, the amount of cortical dysintegrity correlated with diminished cognitive performance. Importantly, uni-modal analysis detected no significant group difference on any imaging modality. We detected microstructural cortical pathology in early PD using a data-driven, multi-modal approach. This pathology is correlated with diminished cognitive performance. Our results indicate that early degenerative processes leave an MRI signature in the cortex of patients with early PD. The cortical imaging findings are behaviourally meaningful and provide a link between cognitive status and microstructural cortical pathology in patients with early PD.

Apathy in rapid eye movement sleep behaviour disorder is common and under-recognized.

BACKGROUND AND PURPOSE: Apathy is an important neuropsychiatric feature of Parkinson's disease (PD), which often emerges before the onset of motor symptoms. Patients with rapid eye movement sleep behaviour disorder (RBD) have a high probability of developing PD in future. Neuropsychiatric problems are common in RBD, but apathy has not previously been detailed in this key prodromal population. METHODS: Eighty-eight patients with polysomnographically proven RBD, 65 patients with PD and 33 controls were assessed for apathy using the Lille Apathy Rating Scale. Cognition and depression were also quantified. The sensitivity of the Unified Parkinson's Disease Rating Scale screening questions for apathy and depression was calculated. RESULTS: A total of 46% of patients with RBD were apathetic, compared with 31% of patients with PD in our sample. Most patients with RBD with depression were apathetic but more than half of apathetic patients were not depressed. The sensitivity of the single Unified Parkinson's Disease Rating Scale screening question was only 33% for mild apathy and 50% for severe apathy. CONCLUSIONS: Apathy is common in RBD and is underestimated by a single self-report question. Recognition of apathy as a distinct neuropsychiatric feature in RBD could aid targeted treatment interventions and might contribute to the understanding of prodromal PD.

Mortality from Listeria monocytogenes meningoencephalitis following escalation to alemtuzumab therapy for relapsing-remitting Multiple Sclerosis.

We report the case of a patient who died from the rare complication of Listeriosis in the immediate phase following alemtuzumab administration one month after discontinuing dimethyl fumarate (DMF). There is considerable overlap with typical post-infusion symptoms therefore high surveillance and low threshold for empirical or possible prophylactic antibiotic therapy is advocated.