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LRRK2 is one of the most important genetic contributors to Parkinson's disease (PD). Point mutations in this gene cause an autosomal dominant form of PD, but to date no cellular phenotype has been consistently linked with mutations in each of the functional domains (ROC, COR and Kinase) of the protein product of this gene. In this study, primary fibroblasts from individuals carrying pathogenic mutations in the three central domains of LRRK2 were assessed for alterations in the autophagy/lysosomal pathway using a combination of biochemical and cellular approaches. Mutations in all three domains resulted in alterations in markers for autophagy/lysosomal function compared to wild type cells. These data highlight the autophagy and lysosomal pathways as read outs for pathogenic LRRK2 function and as a marker for disease, and provide insight into the mechanisms linking LRRK2 function and mutations., (Copyright © 2013 The Authors. Published by Elsevier Inc. All rights reserved.)

Somatosensory evoked potentials (SEPs) were recorded in 41 patients with focal brain lesions recognized by computerized tomography. 21 patients presented damage of the primary sensorimotor area (PSMA), and their SEPs were reduced in amplitude and increased in latency for the two early components (N-22 and N-39), in accordance with previous evidence. The other 20 patients pesented lesions remote from the PSMA, 15 (71%) showing abnormal SEPs mainly characterized by increment in amplitude and duration of N-22 and N-39. Abnormalities of the N-70 and later waves were not specific for any type of lesion. SEPs appeared more sensitive than the EEG for detecting brain dysfunction. The physiopathological and clinical importance of these findings are discussed.

The latencies of evoked potentials recorded at different levels of the peripheral and central nervous system by median nerve stimulation were measured before and after dialysis, and compared with similar recordings in normal volunteers. Abnormally slow conduction velocity was more often found in proximal rather than in distal segments of the peripheral pathway in patients with chronic renal failure. This abnormality was not correlated with the presence of clinical signs of neuropathy or low values of motor conduction velocity, neither was it affected by dialysis. These findings support the hypothesis of peripheral nerve dysfunction secondary to metabolic derangement in uraemic patients.