The most common disorder in a patient presenting to a movement disorder clinic will be parkinsonism. The challenge is to provide the patient with the most accurate diagnosis and prognosis possible. The assumption at the time of initial presentation of the clinical diagnosis of Parkinson's disease is often wrong (20-25%). Waiting to see the pattern of progression, and response to medication provides invaluable additional information. This manuscript summarizes the clinical manifestations of Parkinson's disease and the main akinetic-rigid syndromes (progressive supranuclear palsy, multiple system atrophy, cortical-basal ganglionic degeneration, and dementia with Lewy bodies) that make up the differential diagnosis.

Absence seizures may be seen in a variety of epileptic syndromes in childhood. Identification of the specific syndrome is important to determine medical prognosis. With childhood absence epilepsy, approximately two thirds of children can be expected to enter long-term remission, while in juvenile absence epilepsy, seizure control is often achieved, however, lifelong treatment is usually required. Other absence syndromes have a poorer prognosis, with lower rates of seizure control and remission. Psychosocial outcome is often poor, even in patients with more benign forms of absence epilepsy. Remission of epilepsy does not preclude psychosocial morbidity.

There is still no medical cure for epilepsy. Clinical epileptology is in need of a “paradigm shift” when it comes to the continuing development of therapeutics. An important first step in this conceptual evolution is differentiating between the notions of ictogenesis and epileptogenesis. All traditional therapeutics are anti-ictogenic, not antiepileptogenic. The future of antiepileptic drug development lies in the discovery of antiepileptogenics. Just as aspirin is not the drug of choice for meningitis, an anticonvulsant is not the drug of choice for epilepsy. Drug design for epilepsy needs to discover a penicillin, not more aspirins.

Les adaptations de l'organisme à l'exercice sont permises par l'ajustement de l'activité des neurones centraux qui est en partie régulée par l'activité des afférences I et II (mécanosensibles), par la mise en jeu des afférences III et IV (métabosensibles) et par les modifications du métabolisme musculaire au cours de l'exercice. Le rôle des afférences métabosensibles apparaît comme fondamental dans les mécanismes adaptatifs à l'exercice et dans la tolérance à la fatigue. Néanmoins, de nombreuses interrogations demeurent. Cette revue fait le bilan des connaissances concernant l'implication de ces afférences dans les boucles de rétrocontrôle sensori-motrices et les mécanismes d'adaptation neuromusculaire. Il semble désormais établi que l'activation des afférences métabosensibles soit à l'origine de l'adaptation cardiovasculaire et respiratoire à l'exercice. De plus, ces afférences seraient à l'origine d'un mécanisme de protection du muscle contre la fatigue en modulant la commande motrice centrale au niveau spinal et supraspinal.

There is growing recognition that Parkinson's disease (PD) is likely to arise from the combined effects of genetic predisposition as well as largely unidentified environmental factors. The relative contribution of each varies from one individual to another. Even in situations where more than one family member is affected, the predominant influence may be environmental. Although responsible for only a small minority of cases of PD, recently identified genetic mutations have provided tremendous insights into the basis for neurodegeneration and have led to growing recognition of the importance of abnormal protein handling in Parkinson's as well as other neurodegenerative disorders. Abnormal protein handling may increase susceptibility to oxidative stress; conversely, numerous other factors, including oxidative stress and impaired mitochondrial function can lead to impaired protein degradation. A limited number of environmental factors are known to be toxic to the substantia nigra; in contrast, some factors such as caffeine intake and cigarette smoking may protect against the development of PD, although the mechanisms are not established. We review the various genetic and environmental factors thought to be involved in PD, as well as the mechanisms that contribute to selective nigral cell death.

Oculopharyngeal muscular dystrophy (OPMD) is an adult-onset disorder characterized by progressive eyelid drooping (ptosis), swallowing difficulties (dysphagia), and proximal limb weakness. The autosomal dominant form of this disease is caused by expansions of a (GCG)6 repeat to (GCG)8-13 in the PABPN1 gene. These mutations lead to the expansion of a polyalanine stretch from 10 to 12-17 alanines in the N-terminal domain of PABPN1. Mutated PABPN1 (mPABPN1) induces the formation of muscle intranuclear inclusions that are thought to be the hallmark of this disease. In this review, we discuss: 1) OPMD genetics and PABPN1 function studies; 2) diseases caused by polyalanine expansions and cellular polyalanine toxicity; 3) mPABPN1-induced intranuclear inclusion toxicity; 4) role of oligomerization of mPABPN1 in the formation and toxicity of OPMD intranuclear inclusions and; 5) recruitment of subcellular components to the OPMD inclusions. We present a potential molecular mechanism for OPMD pathogenesis that accounts for these observations.

Although levodopa-related motor response complications remain challenging from a pathophysiological and therapeutic standpoint, major advances have been made in the last decade, supporting the development of several promising drugs. Eventually, these drugs may help us to prevent, alleviate, or even “deprime” these frequent and disabling complications. Knowledge of the basic mechanisms and hypotheses underlying this fascinating conversion in the parkinsonian brain allows neurologists to understand the rationale behind emerging treatment strategies.