Bechir Jarraya

Functional Recovery in a Primate Model of Parkinson's Disease following Motor Cortex Stimulation

A concept in Parkinsons disease postulates that motor cortex may pattern abnormal rhythmic activities in the basal ganglia, underlying the genesis of observed motor symptoms. We conducted a preclinical study of electrical interference in the primary motor cortex using a chronic MPTP primate model in which dopamine depletion was progressive and regularly documented using 18F-DOPA positron tomography. High-frequency motor cortex stimulation significantly reduced akinesia and bradykinesia. This behavioral benefit was associated with an increased metabolic activity in the supplementary motor area as assessed with 18-F-deoxyglucose PET, a normalization of mean firing rate in the internal globus pallidus (GPi) and the subthalamic nucleus (STN), and a reduction of synchronized oscillatory neuronal activities in these two structures. Motor cortex stimulation is a simple and safe procedure to modulate subthalamo-pallido-cortical loop and alleviate parkinsonian symptoms without requiring deep brain stereotactic surgery.

Long-term results of the neuroendoscopic management of colloid cysts of the third ventricle: a series of 90 cases.

BACKGROUND:The endoscopic removal of third ventricular colloid cysts has been developed as an alternative to microsurgical transcortical-transventricular and transcallosal approaches. OBJECTIVE:To examine the value of endoscopic technique by reviewing the large number of endoscopically treated patients with long-term follow-up in 2 neurosurgical centers. METHODS:A retrospective chart review was conducted for all patients admitted for resection of a third ventricular colloid cyst to the Radboud University Nijmegen Medical Centre (Nijmegen, the Netherlands) and the Hôpital Henri Mondor (Paris, France) between 1994 and 2007. Both clinical and radiological symptoms and operative results were evaluated. RESULTS:Postdischarge clinical follow-up was available for 85 patients over a mean period of 4 years 3 months. Permanent morbidity occurred in 1 patient (persisting preoperative memory deficit). Follow-up imaging of 80 evaluable patients showed that total or nearly total cyst removal was possible in 46 individuals (57.5%). Residual cyst was present in 34 patients (42.5%), and 6 required repeated endoscopic surgery for symptomatic regrowth. Recurrent cysts were mainly seen within the first 2 years after surgery. CONCLUSION:It is debatable whether the higher numbers of recurrent or residual cysts can be justified by the slightly lower complication rates achieved with endoscopic removal. However, results have been improving over the years. Moreover, the modifications observed on control magnetic resonance images justify the need for regular control imaging for at least the first 2 years postoperatively.

Spinal cord stimulation for chronic pain improved motor function in a patient with Parkinson's disease.

Spinal cord stimulation (SCS) is a validated therapy for various chronic pain syndromes [1] that was recently shown to improve locomotor behaviour in rodent model of Parkinson’s disease (PD) [2]. We report herein the antiparkinsonian effect of SCS in a patient implanted for lower limb neuropathic painwho later developed PD. A 74-year oldmanwas successfully treated since the age of 61 by SCS implanted at T9-T10 level for a failed back surgery syndrome. Parameters of stimulation were as follows: 70–100 Hz frequency, 410 ms pulse width, 3.5 V (Symmix quadripolar electrode and Itrel-3 pulse generator, Medtronic, Inc., Minneapolis, USA). At the age of 69, the patient developed a tremor-dominant type of PD predominating on right side. A [123-I]FP-CIT dopamine transporter SPECT imaging showed asymmetric striatal loss of binding consistent with PD. Tremor was partially controlled by levodopa (1200 mg/day). We assessed the effect of SCS on motor PD symptoms in four sessions (two to five weeks apart) after overnight dopaminergic medication withdrawal. In sessions 1, 2, and 4, the patient was successively evaluated in offand on-stimulation conditions, while he remained off-drug. In session 3, offand onstimulation conditions were tested before and after (off-/on-drug) the administration of a single suprathreshold dose of levodopa/carbidopa (350/35 mg). SCS frequency was set at 130 Hz (the highest frequency allowed by the generator) during the sessions, but was left at 100 Hz between the sessions, except between sessions 3 and 4 where SCS frequency was maintained at 130 Hz for five weeks. All examinations were performed while SCS was switched on or off for 30–60 min. Outcome measures were the motor score of the Unified Parkinson’s Disease Rating Scale (UPDRS-III), time to walk 7 m, turn, and walk back, and pain level in the lower limbs scored on a 0–10 visual analogue scale. In session 3, tremor was assessed using surface EMG recordings. All motor features, with the exception of rigidity, were videotaped and independently rated by two blinded neurologists who had to agree on the final score. Rigidity was rated by consensus between the two neurologists who performed the tests. Double-blind evaluationwas not feasible, since the patient felt paresthesiae and pain relief in the lower limbs when the stimulator was on. The study was approved by the local ethics committee.

Disruption of cigarette smoking addiction after posterior cingulate damage

The authors describe the case of a 35-year-old woman with a history of an addiction to cigarette smoking who presented with an intracerebral hemorrhage from a ruptured arteriovenous malformation. The patient reported an immediate and complete disruption of her addiction to cigarette smoking following her stroke. Structural MR imaging revealed a lesion of the posterior cingulate cortex. Neuropsychological tests showed intact cognitive functioning. This observation suggests that the posterior cingulate cortex may play a role in the addiction to cigarette smoking.

Using the Accelerometers Integrated in Smartphones to Evaluate Essential Tremor

Background/Aims: Evaluation of tremor constitutes a crucial step from the diagnosis to the initial treatment and follow-up of patients with essential tremor. The severity of tremor can be evaluated using clinical rating scales, accelerometry, or electrophysiology. Clinical scores are subjectively given, may be affected by intra- and interevaluator variations due to different experience, delays between consultations, and subtle changes in tremor severity. Existing medical devices are not routinely used: they are expensive, time-consuming, not easily accessible. We aimed at showing that a smartphone application using the accelerometers embedded in smartphones is effective for quantifying the tremor of patients presenting with essential tremor. Methods: We developed a free iPhone/iPod application, Itremor, and evaluated different parameters on 8 patients receiving deep brain stimulation of the ventral intermediate nucleus of the thalamus: average and maximum accelerations, time above 1 g of acceleration, peak frequency, typical magnitude of tremor, for postural and action tremors, on and off stimulation. Results: We demonstrated good correlations between the parameters measured with Itremor and clinical score in all conditions. Itremor evaluation enabled higher discriminatory power and degree of reproducibility than clinical scores. Conclusion: Itremor can be used for routine objective evaluation of essential tremor, and may facilitate adjustment of the treatment.

Chronic systemic treatment with a high-dose proteasome inhibitor in mice produces akinesia unrelated to nigrostriatal degeneration

Supporting the hypothesis that proteasome dysfunction is involved in Parkinsons disease (PD), McNaught et al. (2004) reported that the systemic administration of the proteasome inhibitor Z-Ile-Glu(OtBu)-Ala-Leu-aldehyde (PSI) in rats led to the degeneration of the nigrostriatal pathway. However, several groups could not reproduce this finding. We herein attempted to improve the reliability of the PSI model by chronically delivering the inhibitor using osmotic minipumps in aged mice. We also tested whether PSI co-administered with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) could act synergistically to induce toxicity. We found that PSI produced a significant reduction in locomotor activity that was mildly exacerbated by MPTP. However, PSI alone produced no sign of degeneration of the nigrostriatal dopaminergic pathway and did not exacerbate MPTP toxicity. To conclude, PSI administration does not provide a reliable phenotypic model of PD.