Pathophysiological mechanisms implicated by high-frequency stimulation in Parkinson's disease: the restoration of high and low frequency oscillatory systems

INTRODUCTION: Increased neuronal activity in the internal pallidum (GPi) and the subthalamic nucleus (STN) has been clearly demonstrated in Parkinsonian models, and the two structures have thus been selected as therapeutic targets for functional neurosurgery. High-frequency electrical stimulation of the GPi or the STN improves the parkinsonian symptoms but also dyskinesias directly by GPi stimulation or indirectly by reduction of L-Dopa associated with STN stimulation. According to Alexander's model of the organisation of the basal ganglia, electrical stimulation of GPi or STN should have led to uncontrolled hyperkinesia. This apparent paradox could be explained on one hand by the involvement of different anatomo-functional areas within these structures and on the other by spatial and temporal changes in neuronal discharge patterns in the basal ganglia which in turn produce variations in synchronisation. RESULTS: Event-related (de)synchronisation (ERD) has enabled us to study variations in subcortico-cortical oscillatory activity: it has been shown that high-frequency electrical stimulation of the GPi/STN increases desynchronisation of low frequency rhythms (mu and beta,<30 Hz) during movement preparation and execution and augments post-movement synchronisation. Stimulation also decreases the abnormal frontocentral spreading of desynchronisation during movement preparation. CONCLUSIONS: In accordance with previous coherence analyses, electrical stimulation of STN is likely to restore the activity of high-frequency and low-frequency systems, as evidenced by a decrease in the hypersynchronisation of low-frequency rhythms at rest and restoral of a high-frequency rhythm during movement. Stimulation may improve spatial selectivity by activating the selected programs in conjunction with the primary sensorimotor cortex, whilst inhibiting competitive programs represented by abnormal spreading outside the primary sensorimotor cortex.     

Investigation of set-shifting ability in patients with Parkinson's disease: influence of task sequence type

INTRODUCTION: The aim of the present study was to investigate the origin of set-shifting deficits observed in Parkinson's disease (PD). METHODS: Seventeen patients diagnosed as having idiopathic PD were compared with 15 control subjects. We used a task-switching paradigm, including two tasks (task A and task B) so that subjects were required to switch either immediately after a switch-trial (i.e. alternating switch or ABA task sequence) or following one or two non-switch trials (ABBA or ABBBA task sequences). RESULTS: In both groups, switch cost (SC) in ABA task sequence was larger than SC in ABBA task sequence (p<0.05) and SC was larger in ABBA than ABBBA task sequence (p<0.05). PD patients demonstrated an increased SC compared to controls for alternating switch trials (p<0.01). Alternatively, when required to switch to a task abandoned two or three trials earlier (i.e. ABBA and ABBBA tasks sequences), patients did not demonstrate increased SC compared to controls. DISCUSSION AND CONCLUSION: The fact that SC associated with alternating switch trials was exacerbated in PD patients may reflect difficulties for switching to a recently inhibited task-set. In conclusion, our results indicate that set-shifting deficits in PD patients may depend of the type of task sequence.     

Advantages and limitations in the assessment of neuroprotective treatment of Parkinson's disease by functional imaging

INTRODUCTION: The development of neuroprotective strategies is a crucial issue for Parkinson's disease, since up to now only symptomatic therapies are available. The clinical evaluation of neuroprotective drugs is difficult considering the long-term effect of anti-Parkinsonian medication that nearly make impossible accurate measurement of the "true" clinical stage of the disease in the early years of progression. BACKGROUND: Two recent functional imaging studies (CALM-PD and REAL-PET) using positron emission tomography (PET) or single photon emission computed tomography (SPECT), suggest that dopamine agonist may have a neuroprotective effect compared to L-Dopa. CONCLUSION: These results are still controversial, notably because of the lack of clinical-imaging correlations, the absence of a placebo group and some important methodological considerations. Nevertheless, these studies are encouraging and give some arguments for the potential neuroprotective role of dopamine agonists. The aim of this work is first to present the pros and cons of these studies and second to propose guidelines in order to improve the design and methodology for future studies designed to assess the neuroprotective properties of new drugs in Parkinson's disease.     

Behçet's disease associated with peripheral neuropathy

INTRODUCTION: The involvement of the peripheral nervous system in Beh?et's disease is very rare. CASE REPORT: We report a case of a 47-year-old man with a six-year history of Beh?et's disease and a two-year history of peripheral nervous system involvement. This patient presented with paraesthesia and weakness of the upper and lower limbs, diarrhea and erectile dysfunction. The electromyogram showed evidence of an axonal sensorimotor neuropathy and the nerve biopsy showed an axonal neuropathy. Routine blood tests were normal, there was no increase of serum creatine kinase, aspartate aminotransfease or lactate dehydrogenase and no signs of hyperthyroidism. Fibroscopy and colonoscopy showed no signs of entero-Beh?et. The patient was treated with prednisone, cyclophosphamide and carbamazepine with an improvement of paraesthesia. CONCLUSION: The mechanism of the peripheral neuropathy in Beh?et's disease is still unknown, it might be due to vasculitis of the vasa nervorum or to the side effects of colchicine. Our report is particular by the association of sensorimotor and autonomic involvement of peripheral neuropathy in a patient with Beh?et's disease.     

Systemic lupus erythematosus presenting with a choreo-athetosic syndrome associated with antiphospholipid antibodies

INTRODUCTION: Chorea is a rare manifestation of systemic lupus erythematosus (1-4 percent), commonly affecting young woman. Chorea is revealing lupic disease in 50 percent, in the other cases it occurs early in the course of the disease. OBSERVATION: A 33-year-old woman was hospitalized for choreo-athetosic movements prevailing on the left leg and arm accompanied by behavioral and general state deterioration. The biological assessment consolidated the diagnosis of lupic disease associated antiphospholipides antibody (aPL). Cerebral magnetic resonance imaging (MRI) was normal except for cortical and subcortical atrophy. The patient was treated by corticosteroids (1mg/kg/day) and then was lost to follow-up. CONCLUSION: We review data in the literature on the pathophysiological mechanisms of lupic chorea focusing particularly on role of aPL.     

Behcet disease: uncommon cause of myocardial infarction

A 25-year-old man who was known to have Beh?et's syndrome and who has no coronary risk factors suffered an acute anterior wall myocardial infarction which was complicated by a ventricular fibrillation. The diagnosis of Beh?et's syndrome was based on recurrent thrombophlebitis, genital and oral aphtoses, posterior uveitis, positive pathergy test and HLAB51. About 20 cases of myocardial infarction were reported in the literature but the etiopathogeny, the causal relationship and the treatment are yet unknown.     

Symptom variations in ADHD: importance of context, development and comorbidity

Attention-deficit hyperactivity (ADHD) is a common disorder in school-aged children and is associated with significant impairment in social and academic functioning. Its recognition is based on congruent information from different sources, because most ADHD children and adolescents are not completely aware of impairments caused by inattention and/or hyperactivity/impulsivity. Fluctuations in symptom expression may complicate the diagnosis: during clinical examination or tests sessions, ADHD symptoms may be less severe than usual or completely absent. This review examines variations in ADHD symptoms due to environmental context, internal state, circadian factors, development, psychiatric comorbidity and discusses their clinical relevance. Generally, ADHD symptoms are pervasive and identified in different areas of functioning. Despite their chronicity, they show a relative context-dependency. An unfamiliar environment or situation may lessen symptoms. The same happens in dual relations or in calm settings, when the child receives attention and positive reinforcement from the adult. On the contrary, the classroom situation with its high stimulation level (noise, visual distractors, large class size) is likely to reveal or accentuate instability, impulsivity and inattention. Independently from objective symptom fluctuations, the impact of ADHD symptoms, and their consequences on self-esteem may also vary with the degree of environmental mismatch. Recent research in experimental psychology also draws attention to the motivational state of ADHD children: preference for immediate gratification and delay aversion may explain why most of them show satisfactory attentional capacities in certain activities (for instance video games or TV), while showing impairment in school work or in other effortful tasks. The diagnosis of the full ADHD syndrome requires significant impact on functioning in at least two areas. Some children with "situational" ADHD are impaired either in school setting or exclusively at home. Manuzza et al. report long-term outcome of "situational" versus "pervasive" ADHD. School-ADHD, in opposition to home-ADHD shows similarities with the full blown syndrome, as regards proportion of anti-social personality disorder, psycho-social functioning and academic/professional achievements. Moderate seasonal variations have also been identified with less ADHD symptoms in August. This result is likely to reflect a better fit between individual characteristics and environmental demands during school holidays rather than neurobiological changes, as there are no convincing arguments for seasonal fluctuations of serotoninergic tone in ADHD. Another cause for variations in ADHD symptom expression may be the co-occurrence of a mood disorder. Relationships between early-onset mania and ADHD are discussed. The appropriate definition of prepubertal mania is still in debate; its recognition is hindered by symptom overlap and high level of comorbid conditions. Chronic emotional dysregulation with irritability and frequent temper tantrums, sometimes viewed as characteristics of early-onset mania, might reflect a--possibly severe--sub-type of ADHD rather than a prodrome of bipolarity. A marked cyclicity of symptoms, with periodic accentuation of ADHD and mood symptoms, requires careful monitoring and systematic analysis of comorbid conditions. Clarification of the complex interrelations between ADHD and bipolar disorder will be obtained from long-term studies.