[Interest of the ketogenic diet in a refractory status epilepticus in adults]. / Intérêt du régime cétogène dans le traitement d'un état de mal épileptique résistant de l'adulte.

INTRODUCTION: Ketogenic diets have been employed for the treatment of intractable epilepsy in children since 1921, although underlying mechanism remains unknown. OBSERVATION: We report the case of a 54-year-old man with partial refractory status epilepticus who exhibited a favourable outcome about seven days after introduction of a ketogenic diet in association with antiepileptic drugs. DISCUSSION: Although its efficiency was largely demonstrated in children, little is known about the impact of a ketogenic diet in adults with refractory epilepsy. CONCLUSION: Introduction of a ketogenic diet requires a multidisciplinary approach. Its usefulness in adult intractable epilepsy and/or refractory status epilepticus merits further study into its efficacy in reducing the frequency of seizures and a possible prolonged effect.

[A case of neuropathy mimicking Guillain-Barré syndrome after arsenic intoxication]. / Un cas de neuropathie mimant un syndrome de Guillain-Barré après une intoxication à l'arsenic.

INTRODUCTION: Chronic arsenic toxicity is a global health problem affecting millions of people. Acute arsenic poisoning is less frequent and it is most often lethal. Therefore, its consequences are not well known, more precisely its neurological consequences. OBSERVATION: We report a case of Guillain-Barré-like syndrome and encephalopathy after acute arsenical poisoning in a 50 year-old man. After 4 month follow-up, the improvement was slow and limited with persistent motor and proprioceptive deficits. DISCUSSION: The most frequent neurological complication induced by acute arsenical poisoning is a distal, symmetrical, sensory, axonal polyneuropathy. Yet the clinical course and the electrophysiological findings may also suggest a Guillain-Barré like syndrome. Moreover, the chelating is not very effective on the neurological complications. CONCLUSION: Any discrepancies in the clinical course of a Guillain-Barré syndrome shall lead to reconsider the diagnosis. The association of gastro-intestinal disorders, skin lesions, and encephalopathy and mood disorders leads to discuss intoxication with heavy metal and more precisely with arsenic. Moreover, the chelating is not very effective on the neurological complications.

Clinical and economic results of bilateral subthalamic nucleus stimulation in Parkinson's disease.

BACKGROUND: High frequency stimulation of the subthalamic nucleus (STN) is an alternative but expensive neurosurgical treatment for parkinsonian patients with levodopa induced motor complications. OBJECTIVE: To assess the safety, clinical effects, quality of life, and economic cost of STN stimulation. METHODS: We conducted a prospective multicentre study in 95 consecutive Parkinson's disease (PD) patients receiving bilateral STN stimulation and assessed its effects over 12 months. A double blind randomised motor evaluation was carried out at 3 month follow up, and quality of life, self care ability, and predictive factors of outcome following surgery were assessed. The cost of PD was estimated over 6 months before and after surgery. RESULTS: The Unified Parkinson's Disease Rating Scale (UPDRS) motor score improved by 57% (p<0.0001) and activities of daily living improved by 48% (p<0.0001) at 12 month follow up. Double blind motor scoring improved by 51% at 3 month follow up (p<0.0001). The total PD Quality of Life Questionnaire (PDQL-37) score improved by 28% (p<0.001). The better the preoperative motor score after a levodopa challenge, the better the outcome after STN stimulation. Five patients developed an intracerebral haematoma during electrode implantation with permanent after effects in two. The 6 month costs of PD decreased from 10,087 euros before surgery to 1673 euros after surgery (p<0.0001) mainly because of the decrease in medication. These savings allowed a return on the procedure investment, estimated at 36,904 euros over 2.2 years. CONCLUSIONS: STN stimulation has good outcomes with relatively low risk and little cost burden in PD patients with levodopa induced motor complications.

Stimulation of the subthalamic nucleus in Parkinson's disease: cognitive and affective changes are not linked to the motor outcome.

BACKGROUND: Subthalamic nucleus deep brain stimulation (STN0 DBS) is a widely performed surgical treatment in PD. However, the relationship between motor results and cognitive/behavioural modifications is unclear. OBJECTIVE: This study investigated the correlation patterns of the motor, cognitive and behavioural consequences of STN DBS with respect to positioning of the active contact. METHODS: Fifty-eight consecutive PD patients having undergone STN DBS were assessed pre-operatively and 12 months after surgery. RESULTS: Motor, cognitive and behavioural results were neither correlated to each other nor linked to the position of the active contact. Three patients with a history of pre-operative, dopaminergic psychosis or post-surgical confusion became demented. Age and a distant history of depression were associated with the occurrence of post-surgical depression. CONCLUSION: Correct screening of patients for STN DBS remains an important issue, since the current implantation procedure is not able to take account of potential functional heterogeneity within the target.

Disturbance of sensory filtering in dementia with Lewy bodies: comparison with Parkinson's disease dementia and Alzheimer's disease.

INTRODUCTION: Prepulse inhibition (PPI) is considered to mirror an organism's ability to filter out irrelevant sensory or cognitive information. The disruption of PPI has never been studied in individuals suffering from dementia with Lewy bodies (DLB). As attention deficits largely contribute to cognitive impairment in DLB, an investigation with a PPI paradigm is useful for differential diagnosis of DLB versus Alzheimer's disease (AD) and Parkinson's disease dementia (PDD). OBJECTIVE AND METHODS: PPI of the N1/P2 component of auditory evoked potentials was used to investigate the early stages of attention selectivity in 10 DLB, 10 AD, and 10 PDD patients, as well as in 10 healthy controls. The PPI paradigm consisted of the presentation of sound pulses (40 ms, 115 dB) preceded by a prepulse (40 ms, 80 dB). Sound stimuli were presented in a total of 80 trials in a pseudo-random order. RESULTS: Non-parametric analyses of variance revealed a significant group effect on the 120 ms lead interval. Retrospective analyses revealed that PPI was significantly reduced in DLB compared to healthy controls and AD. In the PDD group, the disturbance was of intermediate intensity. CONCLUSION: The present study revealed a severe disturbance of PPI in DLB patients. The DLB patients displayed a specific disruption profile in terms of magnitude as well as time course.

[Differences in anticipatory postural adjustments between self-generated and triggered gait initiation in 20 healthy subjects]. / Caractérisation des ajustements posturaux lors d'une initiation de la marche déclenchée par un stimulus sonore et autocommandée chez 20 sujets sains.

OBJECTIVE: Preparation of upper-limb movements differs between self-paced and triggered conditions. This study analyzed the anticipatory postural adjustments (APAs) of gait initiation in normal subjects in 2 conditions: self-generated and triggered by a "beep" sound. METHODS: We recorded kinematic, spatiotemporal parameters of the first two steps by means of video motion analysis (6 infrared cameras), and kinetic parameters (using a force platform and the optoelectronic system) in 20 normal subjects. Two conditions: 1) self-generated initiation; and 2) initiation triggered by a "beep" sound were studied to evaluate the APA phase, by recording kinetic data (duration of the APAs, trajectory of the center of pressure, speed and trajectory of the center of mass). Kinematic data (first and second step speed, length and duration) were also recorded. RESULTS: First step speed and length were increased in self-paced gait initiation compared to triggered gait initiation in controls. We found no difference between the 2 conditions in terms of second step kinematic data. It was caused by a significant difference between the 2 conditions for the temporal characteristics of anticipatory postural adjustments (APAs) in the initiation of the first step, which was longer when normal subjects performed self-generated gait initiation. The trajectory of center of pressure and center of mass remained the same in the 2 conditions. CONCLUSION: APAs of gait initiation process are delayed under self-paced condition, although they do not differ qualitatively between reaction time and self-paced condition. Neuphysiological support of self-generated movement could explain these differences.

Effects of bilateral subthalamic stimulation on sleep in Parkinson's disease.

OBJECTIVE: Sleep disturbances are frequently observed in Parkinson's disease (PD). Bilateral chronic subthalamic nucleus (STN) stimulation is an alternative treatment for advanced PD. Improvements in motor disturbances after STN stimulation are well documented and seem to be associated with better sleep quality, even though the objective effect on sleep structure remains unclear. We have therefore studied the sleep/wakefulness cycle before and after surgical treatment in 10 consecutive parkinsonian patients. METHODS: Subjective sleep quality and sleep recordings were evaluated one month before and three months after initiation of STN stimulation. After surgery, the recordings were performed under two conditions: with stimulation (the "on" condition) and-if patients had given their consent-in the absence of stimulation (the "off" condition). RESULTS: With STN stimulation, subjective and objective sleep qualities were improved. Total sleep time, sleep efficiency and the durations of deep slow wave sleep and paradoxical sleep increased significantly. When stimulation was absent, sleep disturbances were similar to those observed before surgery. CONCLUSION: Chronic STN stimulation is associated with a sleep improvement, which can be explained in part by the concomitant decrease in motor disturbances but also by the reduction in dosages of antiparkinsonian medication. However, we can not exclude a direct effect of STN stimulation on sleep regulatory centres.

Subthalamic nucleus stimulation induces deficits in decoding emotional facial expressions in Parkinson's disease.

BACKGROUND: Bilateral subthalamic nucleus (STN) stimulation is recognised as a treatment for parkinsonian patients with severe levodopa related motor complications. Although adverse effects are infrequent, some behavioural disturbances have been reported. OBJECTIVE: To investigate the consequences of STN stimulation on emotional information processing in Parkinson's disease by assessing the performance of an emotional facial expression (EFE) decoding task in a group of patients before and after surgery. METHODS: 12 non-demented patients with Parkinson's disease were studied. They were assessed one month before surgery and three months after. Their ability to decode EFEs was assessed using a standardised quantitative task. Overall cognitive function, executive function, visuospatial perception, depression, and anxiety were also measured. Twelve healthy controls were matched for age, sex, and duration of education. RESULTS: Before surgery, the patients showed no impairment in EFE decoding compared with the controls. Their overall cognitive status was preserved but they had a moderate dysexecutive syndrome. Three months after surgery, they had significant impairment of EFE decoding. This was not related to their overall cognitive status or to depression/anxiety scores. Visuospatial perception was not impaired. There was no change in the extent of the dysexecutive syndrome except for a reduction in phonemic word fluency. CONCLUSIONS: Bilateral STN stimulation disturbs negative emotional information processing in Parkinson's disease. The impairment appears specific and unrelated to certain secondary variables. This behavioural complication of STN may have implications for the patient's social life.

Subthalamic nucleus stimulation modulates motor cortex oscillatory activity in Parkinson's disease.

In Parkinson's disease, impaired motor preparation has been related to an increased latency in the appearance of movement-related desynchronization (MRD) throughout the contralateral primary sensorimotor (PSM) cortex. Internal globus pallidus (GPi) stimulation improved movement desynchronization over the PSM cortex during movement execution but failed to improve impaired motor preparation. PET studies indicate that subthalamic nucleus (STN) stimulation partly reverses the abnormal premotor pattern of brain activation during movement. By monitoring MRD, we aimed to assess changes in premotor and PSM cortex oscillatory activity induced by bilateral STN stimulation and to compare these changes with those induced by l-dopa. Ten Parkinson's disease patients and a group of healthy, age-matched controls performed self-paced wrist flexions in each of four conditions: without either stimulation or l-dopa (the 'off' condition), with stimulation and without l-dopa (On Stim), with l-dopa and without stimulation ('on drug'), and with both stimulation and l-dopa (On Both). Compared with the Off condition, in both the On Stim and the On Drug condition the Unified Parkinson's Disease Rating Scale (UPDRS) III score decreased by about 60% and in the On Both condition it decreased by 80%. The desynchronization latency over central regions contralateral to movement and the movement desynchronization over bilateral central regions were significantly increased by stimulation and by l-dopa, with a maximal effect when the two were associated. Furthermore, desynchronization latency significantly decreased over bilateral frontocentral regions in the three treatment conditions compared with the Off condition. In Parkinson's disease, STN stimulation may induce a change in abnormal cortical oscillatory activity patterns (similar to that produced by l-dopa) by decreasing the abnormal spreading of desynchronization over frontocentral regions and increasing PSM cortex activity during movement preparation and execution, with a correlated improvement in bradykinesia. Parkinsonians under treatment displayed a desynchronization pattern close to that seen in healthy, age-matched controls, although central latencies remained shorter. The study indicates that it is possible to influence cortical reactivity related to the planning and execution of voluntary movement through the basal ganglia, and furthermore that the oscillatory activity of the PSM cortex (in addition to that of premotor areas) could be of major importance in the control of movement-associated, neural activity in Parkinson's disease.

Influence of chronic bilateral stimulation of the subthalamic nucleus on cognitive function in Parkinson's disease.

BACKGROUND: The clinical efficacy of chronic deep brain stimulation in the treatment of parkinsonian patients with severe levodopa-related motor adverse effects has been repeatedly shown. Bilateral subthalamic nucleus (STN) stimulation has been shown to present an advantage over pallidal stimulation as it induces a higher antiakinetic effect and has positive effects on all parkinsonian symptoms. The morbidity of such surgery is usually considered to be very low. However, few studies have extensively examined the effects of chronic STN stimulation on cognitive function. OBJECTIVE: The aim of the present study was to assess the effects of chronic bilateral STN stimulation on performance in an extensive battery of neuropsychological tests, three months and one year after surgery. METHODS: Nine patients with Parkinson's disease were selected for STN electrodes implantation. They underwent a neuropsychological evaluation at one month before and at three months after surgery. Six of them were examined again at one year after surgery. RESULTS: Before surgery, no patient showed cognitive decline. At three months after surgery, no modification was observed for most tasks. The information processing speed tended to improve. There was a significant reduction of the performance in a delayed free recall test and a trend toward a significant reduction of categorial word fluency. At one year after surgery, most task measures did not change. Slight impairment was observed for tasks evaluating executive function. Examination of individual results showed that some patients (30% at 3 months after surgery) showed an overall cognitive decline. Behavioural changes were also observed in 4 patients with overall cognitive decline in one of them. CONCLUSION: In general, STN deep brain stimulation can be considered as a significant contribution to the treatment of severe Parkinson's disease However, in some patients it can induce overall cognitive decline or behavioural changes.

Chronic bilateral pallidal stimulation and levodopa do not improve gait in the same way in Parkinson's disease: a study using a video motion analysis system.

Chronic bilateral internal globus pallidus (GPi) stimulation allows control of levodopa induced dyskinesias (LID) and motor symptoms in severe Parkinson's disease (PD). The effect on gait has not been clearly established. Different results have been reported, mostly consisting of clinical data. The aim of this study was to evaluate, by means of a video motion analysis system (optoelectronic VICON system), the influence of bilateral GPi stimulation on gait in PD. Five patients underwent bilateral GPi stimulation. The preoperative and postoperative (3 months after surgery) clinical gait disturbances (items 29 and 30 of the motor UPDRS), as well as spatial and temporal gait measurements (namely cadence, velocity, stride and step times, single and double limb support times, stride and step lengths) were analysed in off condition (the patient had received no treatment for 12 hours or merely the lowest dose of levodopa allowing him to walk for the gait analysis) and in the on drug condition (after administration of 200 mg of levodopa). The gait analysis was performed with the VICON system. In off condition, there was a statistically significant improvement after surgery for UPDRS III and gait (clinically assessed). In on drug condition, there was a significant improvement for LID whereas UPDRS III and clinical assessment of gait were unchanged. The VICON system also showed that surgery improved gait especially in off condition, but also in on drug condition. Our method allowed exact quantification of the influence of surgery on gait characteristics. As compared with levodopa treatment, the effect of stimulation seems to be different. Indeed, the results suggest only limited effects of pallidal stimulation on the control of stride length and rather point to compensatory additional mechanisms.

[Chronic electric stimulation of the internal globus pallidus and subthalamic nucleus in Parkinson disease]. / Stimulation électrique chronique du pallidum interne et du noyau subthalamique dans la maladie de Parkinson.

PATHOPHYSIOLOGY: In Parkinson's disease, the neurodegenerative process of the nigrostriatal dopaminergic pathways induces an increase in activity of the subthalamic nucleus and the medial globus pallidus, which cause inhibition of thalamo-cortical outputs explaining parkinsonism. HIGH-FREQUENCY DEEP BRAIN STIMULATION: The adverse effects induced by lesions of subcortical structures (thalamotomy, pallidotomy) have increased interest in chronic electrical stimulation proposed as a new therapy in Parkinson's disease. This technique is reversible and can be modulated with less adverse effects. TWO TARGETS: Two targets may be proposed in case of severe motor fluctuations: the medial globus pallidus and the subthalamic nucleus. Pallidial stimulation improves dramatically levodopa-induced dyskinesia and, with a variable degree, the parkinsonian triad. Subthalamic stimulation rapidly reverses akinesia, rigidity and tremor and also dyskinesias which progressively tend to diminish after decreasing L-dopa dosage. LONG-TERM EFFICACY: A follow-up period of a few years has confirmed that the beneficial effect is maintained. However, stimulation dose not prevent the development of certain symptoms (postural impairment, cognitive decline). LIMITED INDICATIONS: Chronic electrical stimulation of medial globus pallidus and subthalamic nucleus may be proposed for parkinsonian patients with severe motor fluctuations associated with abnormal involuntary movements which are not controlled by different medical therapies. Parkinsonian symptoms must still be levodopa responsive and cause severe clinical disability severely limiting daily living activities. Cognitive impairment and other severe pathologies are contraindications.

Thalamic tremor: correlations with three-dimensional magnetic resonance imaging data and pathophysiological mechanisms.

Tremor associated with a single focal thalamic lesion has rarely been reported. Furthermore, the exact localization of the lesions is difficult to determine because of the imprecision of "conventional" radiology (computed tomography scan and/or "standard" magnetic resonance imaging). The aim of this study was to identify which thalamic structures are involved in tremor associated with a single focal thalamic lesion. We selected two patients who presented with unilateral postural and kinetic tremor of the upper limb related to a localized thalamic infarction. Three-dimensional T1-weighted magnetic resonance imaging sequence (MP-RAGE sequence) was used to determine the precise topography of the lesions by stereotactic analysis using the atlas of Hassler. The lesions were located within the pulvinar, the sensory nuclei, the mediodorsal nucleus, and the ventral lateral posterior nucleus (according to the classification of Hirai and Jones), the latter including the ventral intermediate nucleus (Vim according to the classification of Hassler). However, the Vim was spared. The subthalamic area, which can induce tremor, was not involved. After having compared the topography of the lesions with the clinical findings, we suggest that thalamic tremors may result from the interruption of the cerebellar outflow tract to the Vim within the thalamus.

A case of severe dysexecutive syndrome consecutive to chronic bilateral pallidal stimulation.

In treatment for severe Parkinson's disease (PD), a recent procedure was developed which consists of implanting electrodes in the internal Globus Pallidus (GPi) for chronic electrical stimulation. The consequences on cognitive function of such an intervention are quite variable. Although most group studies observed no significant post-operative change, individual cases of post-operative cognitive impairment were reported. The present study reports the case of a PD patient who underwent bilateral implantation of deep brain stimulation electrodes in the GPi and who, after surgery, suffered from a severe dysexecutive syndrome. An extensive neuropsychological examination showed a selective negative effect of pallidal stimulation on tests assessing executive function. When the stimulation was turned off, the impairment was partly reversible. This observation emphasizes the role of the GPi in executive function.

Dystonia after striatopallidal and thalamic stroke: clinicoradiological correlations and pathophysiological mechanisms.

OBJECTIVE: To establish the pathophysiological mechanisms of striatopallidal and thalamic dystonia. METHODS: Five patients from among 26 who presented (between March 1987 and July 1996) with focal dystonia, segmental dystonia, or hemidystonia caused by a single localised vascular lesion, were selected. Patients with lesions with indefinite boundaries, and diffuse, or multiple, or large brain lesions were excluded. Three dimensional T1 weighted MRI (1.5 tesla) was performed to determine the topography of the lesions. The atlas of Hassler allowed the stereotactic localisation of the lesions to be specified exactly. RESULTS: Three patients had dystonic spasms associated with striatopallidal lesions and one with a thalamic and striatopallidal lesion. One other patient presented with a myoclonic dystonia related to a thalamic lesion. The striatopallidal lesions were located in the sensorimotor area with a somatotopical distribution. The pure thalamic lesion involved the centromedian nucleus, the sensory nuclei, and the pulvinar whereas the thalamic and striatopallidal lesion was located in the pallidonigral thalamic territory, which receives pallidonigral inputs. CONCLUSION: The striatopallidal dystonia might be the consequence of the interruption of the cortico-striato-pallido-thalamo-cortical loop induced by lesions located within the sensorimotor part of the striatopallidal complex. By contrast, it is suggested that thalamic dystonia might be caused by lesions located in the centro-median or the ventral intermediate nuclei, outside the pallidonigral territory, but leading also to a dysfunction of the cortico-striato-pallido-thalamo-cortical loop.

Effect of thalamic stimulation on gait in Parkinson disease.

OBJECTIVE: To assess the influence of ventral intermediate thalamic nucleus stimulation on gait in idiopathic Parkinson disease. DESIGN: Clinical and physiological assessments were compared in patients with and without ventral intermediate thalamic nucleus stimulation. SETTING: The research clinic of a university department of gait analysis. PATIENTS: Seven patients with idiopathic Parkinson disease who had long-term monopolar stimulation of the ventral intermediate thalamic nucleus to control a large-amplitude tremor. MAIN OUTCOME MEASURES: Gait kinematic parameters were autonomically recorded using the Vicon optoelectric system for movement analysis. Measures of locomotor displacement (cadence, walking speed, stride and step times, single and double support times, and stride and step lengths) were computed successfully during 2 conditions: stimulation on and off. Traces of ankle joint position were also analyzed for the left and right lower limbs and for the affected and unaffected lower limbs. RESULTS: No difference in mean values was observed between the 2 conditions. CONCLUSION: This study seems to confirm that ventral intermediate thalamic nucleus stimulation, effective in reducing tremor, does not modify gait parameters in idiopathic Parkinson disease.