Impulsive and compulsive behaviors in Parkinson's disease.

Impulsive-compulsive behaviors (ICBs) in Parkinson's disease (PD) are a common and devastating side effect of dopamine replacement therapy. In this review we describe the phenomenology, prevalence, and risk factors of patients with PD. Results of behavioral studies assessing the neuropsychological profile of patients with PD emphasize that the ICBs, which are behavioral addictions, are not hedonically motivated. Rather, other factors such as the inability to cope with uncertainty may be triggering ICBs. New insights from functional imaging studies, strengthening the incentive salience hypothesis, are discussed, and therapeutic guidelines for the management of ICBs in PD are given.

Altered expression of voltage-dependent calcium channel alpha(1) subunits in temporal lobe epilepsy with Ammon's horn sclerosis.

Voltage-dependent calcium channels, the initial components in the calcium signalling cascade, are increasingly being recognised as relevant factors in the pathology of epilepsy. To further characterise their role in temporal lobe epilepsy associated with Ammon's horn sclerosis, we investigated the immunohistochemical distribution of five different voltage-dependent calcium channel alpha(1) subunits (alpha(1A), alpha(1B), alpha(1C), alpha(1D), alpha(1E)) in 14 hippocampal specimens of patients with Ammon's horn sclerosis in comparison with eight autopsy control cases. In epilepsy specimens an increased immunoreactivity was observed for alpha(1A), alpha(1B), alpha(1D) and alpha(1E) in the neuropil of the dentate gyrus molecular layer. Dentate gyrus granule cells and residual CA3 pyramidal neurones showed enhanced immunoreactivity for alpha(1A), while labelling of these neurones was decreased for alpha(1C). Astrocytes in Ammon's horn sclerosis specimens were strongly immunoreactive for the alpha(1C) subunit contrasting with an absent astrocytic alpha(1C) labelling in controls. Our results suggest that the expression of calcium channels in neurones and glial cells is dynamically regulated in temporal lobe epilepsy, supporting the relevance of calcium signalling pathways for this disease.

Distribution of a calcium channel subunit in dystrophic axons in multiple sclerosis and experimental autoimmune encephalomyelitis.

Multiple sclerosis and experimental autoimmune encephalomyelitis (EAE) are immune-mediated diseases of the CNS. They are characterized by widespread inflammation, demyelination and a variable degree of axonal loss. Recent magnetic resonance spectroscopy studies have indicated that axonal damage and loss are a reliable correlate of permanent clinical disability. Accordingly, neuropathological studies have confirmed the presence and timing of axonal injury in multiple sclerosis lesions. The mechanisms of axonal degeneration, however, are unclear. Since calcium influx may mediate axonal damage, we have studied the distribution of the pore-forming subunit of neuronal (N)-type voltage-gated calcium channels in the lesions of multiple sclerosis and EAE. We found that alpha(1B), the pore-forming subunit of N-type calcium channels, was accumulated within axons and axonal spheroids of actively demyelinating lesions. The axonal staining pattern of alpha(1B) was comparable with that of beta-amyloid precursor protein, which is an early and sensitive marker for disturbance of axonal transport. Importantly, within these injured axons, alpha(1B) was not only accumulated, but also integrated in the axoplasmic membrane, as shown by immune electron microscopy on the EAE material. This ectopic distribution of calcium channels in the axonal membrane may result in increased calcium influx, contributing to axonal degeneration, possibly via the activation of neutral proteases. Our data suggest that calcium influx through voltage-dependent calcium channels is one possible candidate mechanism for axonal degeneration in inflammatory demyelinating disorders.

An autosomal dominant early adult-onset distal muscular dystrophy.

In this study we describe an autosomal dominant distal muscular dystrophy in a small Austrian family. The myopathy started in early adulthood with a slowly progressive weakness of the muscles of the anterior tibial compartment, followed by the long finger extensors and sternocleidomastoids in some family members. Other muscles were spared. Histopathology showed fiber size variation and autophagic vacuoles. This disease pattern is similar to Laing distal myopathy, which has been described previously in only one other family.