Stimulation of the globus pallidus internus in the treatment of Parkinson's disease: Long-term results of a monocentric cohort.

BACKGROUND: Pallidal deep brain stimulation (DBS) has shown to be beneficial in patients with advanced levodopa-responsive Parkinson's disease (PD) in several short-term studies. However, reported long-term outcomes of pallidal DBS for PD are limited and contradictory. METHODS: Eighteen consecutive PD patients were treated with unilateral or bilateral stimulation of the internal part of the globus pallidus (GPi). Assessments were carried out before and six months after neurosurgery, and annually thereafter for up to 16 years (mean follow-up time: 6 years). Primary outcomes included motor signs (Unified PD Rating Scale [UPDRS]-III), activities of daily living (ADL, UPDRS-II), and levodopa-induced motor complications (UPDRS-IV). RESULTS: The results show that GPi stimulation improves levodopa-responsive PD motor signs (UPDRS-III), levodopa-induced motor complications (UPDRS-IV), and ADL (UPDRS-II) in advanced PD. Among motor signs, tremor showed the best response to pallidal stimulation. Levodopa-induced motor complications and tremor showed improvements for more than 10 years after neurosurgery. CONCLUSIONS: The overall findings in our cohort demonstrate that pallidal stimulation is effective in reducing parkinsonian motor signs (UPDRS-III), particularly in the 'off'-medication state. Although the beneficial effects on bradykinesia, rigidity and ADL may be limited to 5-6 years, the follow up results indicate that the improvements of levodopa-induced motor complications (UPDRS-IV) and tremor can be sustained for more than 10 years.

Factors associated with quality of life in facial melasma: a cross-sectional study.

BACKGROUND: Melasma is a common chronic focal hypermelanosis that affects photexposed areas as face, mainly in women at fertile age. It inflicts a significant impact in quality of life; nevertheless, quality of life scores (e.g. MELASQoL) are not strongly correlated with clinical severity (e.g. MASI) in facial melasma, suggesting that different factors can influence the perception of disease beyond the clinical extension or the intensity of pigmentation. OBJECTIVES: To explore clinical and socio-demographic aspects that influences MELASQoL scores. METHODS: Cross-sectional study enrolling 155 adults (>18 y.o.) with facial melasma. MELASQoL, MASI, clinical and demographic information were assessed. The associations among factors were explored by multivariable methods. RESULTS: The mean (SD) age of the participants was 39 (8) years, and 134 (86%) were females. The correlation (Spearman's rho) between MELASQoL and MASI was 0.35 (P < 0.05). In a multivariate regression, MELASQoL score was associated (P ≤ 0.05) to MASI score (ß = 0.6), lower income (ß = 6.8), be single (ß = 4.2) and low education level (ß = 5.0). At multiple correspondence analysis, MASI, sex, marriage, education and income were associated with MELASQoL, as well as MASI was associated to skin phototypes, income and education level. CONCLUSION: The perception of life quality impairment in melasma is influenced by low scholarly, low family income, single marital status and greater clinical severity.

Combination of MRI and dynamic FET PET for initial glioma grading.

AIM: MRI and PET with 18F-fluoro-ethyl-tyrosine (FET) have been increasingly used to evaluate patients with gliomas. Our purpose was to assess the additive value of MR spectroscopy (MRS), diffusion imaging and dynamic FET-PET for glioma grading. PATIENTS, METHODS: 38 patients (42 ± 15 aged, F/M: 0.46) with untreated histologically proven brain gliomas were included. All underwent conventional MRI, MRS, diffusion sequences, and FET-PET within 3±4 weeks. Performances of tumour FET time-activity-curve, early-to-middle SUVmax ratio, choline / creatine ratio and ADC histogram distribution pattern for gliomas grading were assessed, as compared to histology. Combination of these parameters and respective odds were also evaluated. RESULTS: Tumour time-activity-curve reached the best accuracy (67%) when taken alone to distinguish between low and high-grade gliomas, followed by ADC histogram analysis (65%). Combination of time-activity-curve and ADC histogram analysis improved the sensitivity from 67% to 86% and the specificity from 63-67% to 100% (p < 0.008). On multivariate logistic regression analysis, negative slope of the tumour FET time-activity-curve however remains the best predictor of high-grade glioma (odds 7.6, SE 6.8, p = 0.022). CONCLUSION: Combination of dynamic FET-PET and diffusion MRI reached good performance for gliomas grading. The use of FET-PET/MR may be highly relevant in the initial assessment of primary brain tumours.

Effects of amygdala-hippocampal stimulation on synchronization.

Changes in EEG synchronization, i.e., spatio-temporal correlation, with amygdala-hippocampal stimulation were studied in patients with temporal lobe epilepsy. Synchronization was evaluated for high frequency, 130 Hz, pseudo-monophasic or biphasic charge-balanced pulses. Desynchronization was most frequently induced by stimulation. There was no correlation between the changes in synchronization and the changes in interictal epileptiform discharge rates. Changes in synchronization do not appear yet to be a marker of stimulation efficiency in reducing seizures.

Effects of amygdala-hippocampal stimulation on interictal epileptic discharges.

Deep brain stimulation (DBS) of different nuclei is being evaluated as a treatment for epilepsy. While encouraging results have been reported, the effects of changes in stimulation parameters have been poorly studied. Here the effects of changes of pulse waveform in high frequency DBS (130 Hz) of the amygdala-hippocampal complex (AH) are presented. These effects were studied on interictal epileptic discharge rates (IEDRs). AH-DBS was implemented with biphasic versus pseudo monophasic charge balanced pulses, in two groups of patients: six with temporal lobe epilepsy (TLE) associated with hippocampal sclerosis (HS) and six with non lesional (NLES) temporal epilepsy. In patients with HS, IEDRs were significantly reduced with AH-DBS applied with biphasic pulses in comparison with monophasic pulse. IEDRs were significantly reduced in only two patients with NLES independently to stimulus waveform. Comparison to long-term seizure outcome suggests that IEDRs could be used as a neurophysiological marker of chronic AH-DBS and they suggest that the waveform of the electrical stimuli can play a major role in DBS. We concluded that biphasic stimuli are more efficient than pseudo monophasic pulses in AH-DBS in patients with HS. In patients with NLES epilepsy, other parameters relevant for efficacy of DBS remain to be determined.

[Epilepsy surgery: the curative approach]. / Chirurgie de l'épiepsie: l'approche curative.

Epilepsy surgery is possible in specific cases of localisation-related pharmaco-resistant epilepsy and can often lead to seizure-freedom condition. A presurgical diagnostic workup is necessary to localise the epileptic focus and assess the risks of post-operative neurological or cognitive deficits. Even when the brain MRI does not reveal any lesion, other imaging techniques and in some cases intracranial EEG recordings can lead to successful surgery. All patients suffering from pharmaco-resistant epilepsy should be referred to an expert centre to confirm the diagnosis and evaluate the possibility of epilepsy surgery. In children, early epilepsy surgery can allow better continuation of cognitive development and education.

["Palliative" surgical procedures in refractory epilepsy]. / Approches chirurgicales "palliatives" de l'épilepsie.

In some patients with refractory epilepsy, no resective surgery of the epileptogenic zone can be offered. This is the case when for instance the epileptogenic zone is located in an eloquent region (motor, language or visual) or when there are several epileptogenic zones. When disabling seizures persist despite the medical treatment, several surgical procedures can be proposed with the aim of decreasing the seizure frequency. Among these procedures, we review briefly here vagus nerve stimulation, the various brain stimulations procedures, multiples subpial transsections, and the corpus callosotomy. For each procedure, we will discuss its indication and outcome.

[Periinsular hemispherotomy: surgical technique, intraoperative EEG monitoring and results on seizure outcome]. / L'hémisphérotomie péri-insulaire: technique chirurgicale, monitoring EEG intraopératoire et résultats sur le contrôle de l'épilepsie.

Peri-insular hemispherotomy is a surgical technique used in the treatment of drug-resistant epilepsy of hemispheric origin. It is based on the exposure of insula and semi-circular sulci, providing access to the lateral ventricle through a supra- and infra-insular window. From inside the ventricle, a parasagittal callosotomy is performed. The basal and medial portion of the frontal lobe is isolated. Projections to the anterior commissure are interrupted at the time of amygdala resection. The hippocampal tail and fimbria-fornix are disrupted posteriorly. We report our experience of 18 cases treated with this approach. More than half of them presented with congenital epilepsy. Neuronavigation was useful in precisely determining the center and extent of the craniotomy, as well as the direction of tractotomies and callosotomy, allowing minimal exposure and blood loss. Intra-operative monitoring by scalp EEG on the contralateral hemisphere was used to follow the progression of the number of interictal spikes during the disconnection procedure. Approximately 90% of patients were in Engel's Class I. We observed one case who presented with transient postoperative neurological deterioration probably due to CSF overdrainage and documented one case of incomplete disconnection in a patient presenting with hemimegalencephaly who needed a second operation. We observed a good correlation between a significant decrease in the number of spikes at the end of the procedure and seizure outcome. Peri-insular hemispherotomy provides a functional disconnection of the hemisphere with minimal resection of cerebral tissue. It is an efficient technique with a low complication rate. Intra-operative EEG monitoring might be used as a predictive factor of completeness of the disconnection and consequently, seizure outcome.

Sub-acute delayed failure of subthalamic DBS in Parkinson's disease: the role of micro-lesion effect.

OBJECTIVE: To study delayed failure after subthalamic nucleus (STN) deep brain stimulation in Parkinson's disease (PD) patients. METHODS: Out of 56 consecutive bilaterally STN-implanted PD patients, we selected subjects who, after initial clinical improvement (1 month after surgery), lost benefit (delayed failure, DF). RESULTS: Five patients developed sub-acutely severe gait disorders (DF). In 4/5 DF patients, a micro-lesion effect, defined as improvement without stimulation, was observed; immediate post-operative MRI demonstrated electrode located above or behind to the STN. CONCLUSIONS: Patients presenting micro-lesion effect should be carefully monitored, as this phenomenon can mask electrodes misplacement and evolution in DF.

Long-term outcome of 50 consecutive Parkinson's disease patients treated with subthalamic deep brain stimulation.

OBJECTIVE: To describe the long-term outcome in 50 consecutive advanced Parkinson's disease (PD) patients treated with subthalamic nucleus deep brain stimulation (STN-DBS). METHOD: Assessments were carried out at baseline, 6 months, 2 years, and 5 years postoperatively. RESULTS: Compared to baseline scores without medication, we found a highly significant improvement of UPDRS III with stimulation, maintained at 5 years (p<0.001). This improvement, however, tended to diminish over time. Dyskinesia and off periods were also improved (p<0.0001 for both). Seventeen patients died during follow-up, who tended to be older at surgery (p<0.01). CONCLUSIONS: STN-DBS is an effective treatment for advanced PD patients, and the beneficial effect is maintained at 5 years. However, worsening occurs over time due to disease progression.

Rationale, mechanisms of efficacy, anatomical targets and future prospects of electrical deep brain stimulation for epilepsy.

Electrical stimulation of deep brain structures is a promising new technology for the treatment of medically intractable seizures. Performed in vitro and on animal models of epilepsy, electrical stimulation has shown to reduce seizure frequency. Preliminary results on humans are encouraging. However, such improvements emerge despite a lack of understanding of the precise mechanisms underlying electrical stimulation either delivered directly on the epileptogenic zone (direct control) or through an anatomical relay of cortico-subcortical networks (remote control). Anatomical targets such as the thalamus (centromedian nucleus, anterior thalamus, mamillary body and mamillothalamic tracts), the subthalamic nucleus, the caudate nucleus and direct stimulation of the hippocampal formation have been successfully investigated. Although randomized controlled studies are still missing, deep brain stimulation is a promising treatment option for a subgroup of carefully selected patients with intractable epilepsy who are not candidates for resective surgery. The effectiveness, the optimal anatomic targets, the ideal stimulation parameters and devices, as well as patient selection criteria are still to be defined.

Dense deformation field estimation for atlas-based segmentation of pathological MR brain images.

Atlas registration is a recognized paradigm for the automatic segmentation of normal MR brain images. Unfortunately, atlas-based segmentation has been of limited use in presence of large space-occupying lesions. In fact, brain deformations induced by such lesions are added to normal anatomical variability and they may dramatically shift and deform anatomically or functionally important brain structures. In this work, we chose to focus on the problem of inter-subject registration of MR images with large tumors, inducing a significant shift of surrounding anatomical structures. First, a brief survey of the existing methods that have been proposed to deal with this problem is presented. This introduces the discussion about the requirements and desirable properties that we consider necessary to be fulfilled by a registration method in this context: To have a dense and smooth deformation field and a model of lesion growth, to model different deformability for some structures, to introduce more prior knowledge, and to use voxel-based features with a similarity measure robust to intensity differences. In a second part of this work, we propose a new approach that overcomes some of the main limitations of the existing techniques while complying with most of the desired requirements above. Our algorithm combines the mathematical framework for computing a variational flow proposed by Hermosillo et al. [G. Hermosillo, C. Chefd'Hotel, O. Faugeras, A variational approach to multi-modal image matching, Tech. Rep., INRIA (February 2001).] with the radial lesion growth pattern presented by Bach et al. [M. Bach Cuadra, C. Pollo, A. Bardera, O. Cuisenaire, J.-G. Villemure, J.-Ph. Thiran, Atlas-based segmentation of pathological MR brain images using a model of lesion growth, IEEE Trans. Med. Imag. 23 (10) (2004) 1301-1314.]. Results on patients with a meningioma are visually assessed and compared to those obtained with the most similar method from the state-of-the-art.

Electrophysiological characteristics of limbic and motor globus pallidus internus (GPI) neurons in two cases of Lesch-Nyhan syndrome.

OBJECTIVE: Lesch-Nyhan syndrome is a rare and debilitating condition characterized by dystonia and self-mutilating behavior. In order to shed light on the pathophysiology of dystonia, we report the pallidal electrophysiological activity recorded in two patients during deep brain stimulation surgery (DBS). METHODS: Microrecordings were performed on 162 neurons along four tracks aimed at the right and left anterior (limbic) and posterior (motor) globus pallidus internus (GPI). RESULTS: Regardless of the anesthetic agent used (propofol or sevoflurane), both patients showed similar neurons firing rates in the four regions studied, namely the limbic and motor portions of the globus pallidus externus (GPE) or GPI. In both patients, firing rates were similar in the GPE (12.2+/-1.8 Hz, N=38) and GPI (13.2+/-1.0 Hz, N=83) portions of the limbic track, while the motor GPE fired at a higher frequency (23.8+/-2.7 Hz, N=18) than the motor GPI (12.5+/-1.4 Hz, N=23). CONCLUSIONS: These results demonstrate that light propofol or sevoflurane anesthesia influences pallidal activity in a similar way. Electrophysiological recordings suggest that Lesch-Nyhan syndrome might be characterized by analogous firing frequencies in the limbic GPE and GPI while motor GPE would tend to fire at higher rate than the motor GPI. It is therefore tempting to suggest that the symptoms that are observed in Lesch-Nyhan syndrome might result from motor GPI inhibition. SIGNIFICANCE: This observation may confirm the Albin and Delong's model of the basal nuclei in hypokinetic and hyperkinetic disorders.

Ruptured cerebral aneurysm in the early stage of life--a congenital origin?

We report the case of a large fusiform aneurysm of the anterior cerebral artery in a 3-month-old girl presenting with generalized seizures and complicated by a cardiorespiratory arrest needing resuscitation. The native cerebral CT scan revealed a diffuse subarachnoid hemorrhage (Fischer III grade); CT angiography showed an aneurysm of the distal A1 segment of the anterior cerebral artery (ACA). Successful treatment was achieved through surgical trapping of the aneurysm and sacrifice of the distal A1 segment. A histological study of the aneurysmal wall revealed the absence of elastic fibers in an otherwise fibromuscular media and showed no signs of previous hemorrhage. Intracranial aneurysms of the ACA are very rare in the early stage of life and their pathogenesis is not clear. This case is of interest as the location and shape of the aneurysm, the absence of relevant familial and medical history, and the histopathological findings raise the hypothesis of a congenital origin. It further describes the value of CT angiography for studying aneurysms in the very young.

[Resection of a retroperitoneal schwannoma by a combined approach]. / Résection d'un schwannome rétropéritonéal en sablier par abord combiné.

BACKGROUND AND PURPOSE: We report a remarkable case of retroperitoneal schwannoma with significant spinal growth illustrating the effectiveness of a combined surgical approach. METHODS: A 41-year-old man presented with a long history of back pain and unexplained weight loss. An abdominal mass was found in the right upper quadrant. The CT-scan revealed a partially cystic lesion located in the right psoas muscle. Spinal extension was noticed through the L1-L2 neural foramen. MRI better showed the wide rostro-caudal extension in the spinal canal. RESULTS: Bilateral L1 and L2 laminectomy was performed to remove the spinal portion of the tumor. It was extradural but attached to the dura. The roots were not infiltrated. The retroperitoneal mass was removed by an anterior transperitoneal approach. The histological examination did not reveal criteria of malignancy. CONCLUSIONS: Retroperitoneal schwannomas are rare and their preoperative diagnosis remains difficult. In case of significant spinal growth, a combined surgical exposure should be preferred to allow total removal of the lesion and control of the neurological structures.

Magnetic resonance artifact induced by the electrode Activa 3389: an in vitro and in vivo study.

BACKGROUND: The electrode Activa 3389 is widely implanted for deep brain stimulation (DBS) and MRI is often used to control the position of the electrode. However, induced distorsion artifacts may result in imprecise localization and may lead to misinterpretations of the clinical effects and mechanisms of DBS. METHODS: In vitro 3D MR study: the proximal and distal contacts of one electrode were spotted by two localizers. The maximal artifact height (MAH) and width (MAW: measured on distal contact), and the distances between the artifact and the localizers (proximal, distal and lateral) were measured on 2 transverse and sagittal MR sequences with 90 degrees rotation of frequency-encoded gradient and phase direction. In vivo 3D MR study: coronal and sagittal reconstructions along the main axis of the electrode were performed on 10 postoperative MR (20 electrodes) to measure MAH and MAW. A Student t test was used to compare in vitro and in vivo measurements. FINDINGS: In vitro study: A MAH of 10.35 mm (+/-0.23) and MAW of 3.6 mm (+/-0.2) were found. We measured symmetrical extensions of the artifact over the distal contact. In vivo study: A MAH of 10.36 mm (+/-0.44) and MAW of 3.56 mm (+/-0.30) were obtained. No significant different artifact dimensions were measured between in vitro and in vivo studies (p<0.0001). INTERPRETATION: Precise 3D localization of the electrode in implanted patients is provided by MR identification of the limits of the distal contact artifact. The position of the other contacts is deduced given the size of the contacts and the intercontact distance.

Spontaneous bilateral subdural haematomas in the posterior cranial fossa revealed by MRI.

A 52-year-old woman treated for acute myeloproliferative disease developed progressive stupor. CT showed obstructive hydrocephalus resulting from unexplained mass effect on the fourth ventricle. MRI revealed bilateral extra-axial collections in the posterior cranial fossa, giving high signal on T1- and T2-weighted images, suggesting subacute subdural haematomas. Subdural haematomas can be suspected on CT when there is unexplained mass effect. MRI may be essential to confirm the diagnosis and plan appropriate treatment.

Subthalamic DBS replaces levodopa in Parkinson's disease: two-year follow-up.

BACKGROUND: Subthalamic nucleus (STN) deep brain stimulation (DBS) of patients with PD allows reduction of antiparkinsonian medication but has only a mild direct effect on dyskinesia. Since antiparkinsonian medication has short- and long-term effects that may prevent an estimate of the maximal possible impact of STN DBS, such medication was used at the lowest possible dosage after DBS implantation. OBJECTIVE: To study the maximal and long-term effects of STN DBS using the lowest dose of medication. METHODS: Twenty consecutive patients with PD with motor fluctuations and dyskinesia underwent bilateral implantation under stereotactic guidance, microrecording, and clinical control. All medications were stopped before implantation and reintroduced, at the lowest dosage needed, only if the postoperative motor score did not reach the baseline level. Unified PD Rating Scale (UPDRS) motor (subscale III) scores were measured at baseline and after 3, 6, 12, and 24 months. RESULTS: After 21 plus minus 8 months, the UPDRS III "off-medication" score was decreased by 45% and was similar to the preoperative UPDRS III "on" score. Overall, medication was reduced by 79%, being completely withdrawn in 10 patients. Fluctuations and dyskinesia showed an overall reduction of >90%, disappearing completely in patients without medication. These improvements were maintained for 2 years. CONCLUSIONS: These results show that STN DBS could replace levodopa and allowed all antiparkinsonian medication to be discontinued in 50% of patients with PD. Fluctuations and dyskinesia disappeared completely in these patients but persisted in those still on medication. These improvements were maintained for 2 years.

Postanoxic generalized dystonia improved by bilateral Voa thalamic deep brain stimulation.

A patient with severe postanoxic dystonia and bilateral necrosis of the basal ganglia, who was confined to a wheelchair, underwent bilateral ventralis oralis anterior deep brain stimulation (Voa-DBS) after 6 weeks of unsuccessful bilateral pallidal DBS (GPi-DBS). After 4 months of high intensity Voa-DBS, cognitively unimpaired, he showed major improvement in dystonia, became ambulant, but committed suicide. Brain examination confirmed the correct location of the electrodes in GPi and Voa on both sides.