Serge Blond

Bilateral, pallidal, deep-brain stimulation in primary generalised dystonia: a prospective 3 year follow-up study

BACKGROUND We have previously reported the efficacy and safety of bilateral pallidal stimulation for primary generalised dystonia in a prospective, controlled, multicentre study with 1 year of follow-up. Although long-term results have been reported by other groups, no controlled assessment of motor and non-motor results is available. In this prospective multicentre 3 year follow-up study, involving the same patients as those enrolled in the 1 year follow-up study, we assessed the effect of bilateral pallidal stimulation on motor impairment, disability, quality of life, cognitive performance, and mood. METHODS We studied 22 patients with primary generalised dystonia after 3 years of bilateral pallidal stimulation. We compared outcome at 3 years with their status preoperatively and after 1 year of treatment. Standardised video recordings were scored by an independent expert. Data were analysed on an intention-to-treat basis. FINDINGS Motor improvement observed at 1 year (51%) was maintained at 3 years (58%). The improvement in quality of life (SF-36 questionnaire) was similar to that observed at 1 year. Relative to baseline and to the 1 year assessment, cognition and mood were unchanged 3 years after surgery, but slight improvements were noted in concept formation, reasoning, and executive functions. Pallidal stimulation was stopped bilaterally in three patients because of lack of improvement, technical dysfunction, and infection, and unilaterally in two patients because of electrode breakage and stimulation-induced contracture. No permanent adverse effects were observed. INTERPRETATION Bilateral pallidal stimulation provides sustained motor benefit after 3 years. Mild long-term improvements in quality of life and attention were also observed.

Bilateral pallidal deep brain stimulation for the treatment of patients with dystonia-choreoathetosis cerebral palsy: a prospective pilot study

BACKGROUND Cerebral palsy (CP) with dystonia-choreoathetosis is a common cause of disability in children and in adults, and responds poorly to medical treatment. Bilateral pallidal deep brain stimulation (BP-DBS) of the globus pallidus internus (GPi) is an effective treatment for primary dystonia, but the effect of this reversible surgical procedure on dystonia-choreoathetosis CP, which is a subtype of secondary dystonia, is unknown. Our aim was to test the effectiveness of BP-DBS in adults with dystonia-choreoathetosis CP. METHODS We did a multicentre prospective pilot study of BP-DBS in 13 adults with dystonia-choreoathetosis CP who had no cognitive impairment, little spasticity, and only slight abnormalities of the basal ganglia on MRI. The primary endpoint was change in the severity of dystonia-choreoathetosis after 1 year of neurostimulation, as assessed with the Burke-Fahn-Marsden dystonia rating scale. The accuracy of surgical targeting to the GPi was assessed masked to the results of neurostimulation. Analysis was by intention to treat. FINDINGS The mean Burke-Fahn-Marsden dystonia rating scale movement score improved from 44.2 (SD 21.1) before surgery to 34.7 (21.9) at 1 year post-operatively (p=0.009; mean improvement 24.4 [21.1]%, 95% CI 11.6-37.1). Functional disability, pain, and mental health-related quality of life were significantly improved. There was no worsening of cognition or mood. Adverse events were related to stimulation (arrest of the stimulator in one patient, and an adjustment to the current intensity in four patients). The optimum therapeutic target was the posterolateroventral region of the GPi. Little improvement was seen when the neurostimulation diffused to adjacent structures (mainly to the globus pallidus externus [GPe]). INTERPRETATION Bilateral pallidal neurostimulation could be an effective treatment option for patients with dystonia-choreoathetosis CP. However, given the heterogeneity of motor outcomes and the small sample size, results should be interpreted with caution. The optimum placement of the leads seemed to be a crucial, but not exclusive, factor that could affect a good outcome. FUNDING National PHRC; Cerebral Palsy Foundation: Fondation Motrice/APETREIMC; French INSERM Dystonia National Network; Medtronic.

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 Parkinsons 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 Parkinsons disease However, in some patients it can induce overall cognitive decline or behavioural changes.

Safety and efficacy of deep brain stimulation in refractory cluster headache: a randomized placebo-controlled double-blind trial followed by a 1-year open extension

Chronic cluster headache (CCH) is a disabling primary headache, considering the severity and frequency of pain attacks. Deep brain stimulation (DBS) has been used to treat severe refractory CCH, but assessment of its efficacy has been limited to open studies. We performed a prospective crossover, double-blind, multicenter study assessing the efficacy and safety of unilateral hypothalamic DBS in 11 patients with severe refractory CCH. The randomized phase compared active and sham stimulation during 1-month periods, and was followed by a 1-year open phase. The severity of CCH was assessed by the weekly attacks frequency (primary outcome), pain intensity, sumatriptan injections, emotional impact (HAD) and quality of life (SF12). Tolerance was assessed by active surveillance of behavior, homeostatic and hormonal functions. During the randomized phase, no significant change in primary and secondary outcome measures was observed between active and sham stimulation. At the end of the open phase, 6/11 responded to the chronic stimulation (weekly frequency of attacks decrease >50%), including three pain-free patients. There were three serious adverse events, including subcutaneous infection, transient loss of consciousness and micturition syncopes. No significant change in hormonal functions or electrolytic balance was observed. Randomized phase findings of this study did not support the efficacy of DBS in refractory CCH, but open phase findings suggested long-term efficacy in more than 50% patients, confirming previous data, without high morbidity. Discrepancy between these findings justifies additional controlled studies (clinicaltrials.gov number NCT00662935).

Chronic thalamic stimulation improves tremor and levodopa induced dyskinesias in Parkinson's disease.

Chronic thalamic stimulation was performed in 10 Parkinsonian patients with disabling tremor and poor response to drug therapy. During the stereotactic procedure, an electrode was introduced in the ventralis intermediate nucleus of the thalamus. Test stimulation was performed during the intra-operative procedure and a few days after surgery using an external stimulator. When tremor was obviously reduced by thalamic stimulation, an internal stimulator was implanted under the clavicle. Tremor was initially suppressed in all cases and reappeared whenever stimulation was stopped. Patients were followed for 22 to 34 months. Tremor was controlled in eight cases but reappeared after three months in two cases. Levodopa induced dyskinesias were observed before electrode implantation in 5 cases. They consisted of peak-dose choreic or ballistic dyskinesias in 4 cases and biphasic dystonic dyskinesias in 3 cases. Peak-dose dyskinesias were greatly improved or suppressed in all cases. Biphasic dyskinesias were improved in 2 cases. Thalamic stimulation was well tolerated. Mild dystonic hand posture related to the deep brain stimulation was observed in one case. No neuropsychological side-effects were noted. Thalamic stimulation could prove to be an adequate treatment for resistant tremor and levodopa induced dyskinesias.

Improvement of levodopa induced dyskinesias by thalamic deep brain stimulation is related to slight variation in electrode placement: possible involvement of the centre median and parafascicularis complex

OBJECTIVE To define the reason why two teams using the same procedure and the same target for deep brain stimulation (DBS) obtained different results on levodopa induced dyskinesias, whereas in both, parkinsonian tremor was improved or totally suppressed. METHODS Deep brain stimulation can replace lesions in the surgical treatment of abnormal movements. After 10 years of experience with DBS in Parkinson’s disease, a comparison of results between the teams of Lille (A) and Grenoble (B) was carried out, for as long as they used intraoperative ventriculography. Both teams aimed at the same target, the ventralis intermedius nucleus of the thalamus (VIM), but team A found a clear improvement of choreic peak dose dyskinesias, whereas team B did not consistently. Therefore all teleradioanatomical data of both teams were re-examined and compared with the therapeutic effects. Location of 99 monopolar electrodes of thalamic stimulation applied to treat parkinsonian tremor has been retrospectively measured (team A included 21 patients, 22 electrodes; team B included 52 patients, 74 electrodes). Peak dose levodopa dyskinesias were suppressed by DBS in all nine patients of team A, four of which were severely disabling. Only eight out of 32 patients from team B experienced a moderate (four) or clear (four) improvement of dyskinesias, whereas in the remaining 24 patients, dyskinesias were unchanged with stimulation. RESULTS The mean centre of team A’s electrodes was on average 2.9 mm deeper, more posterior and medial than team B’s (t=8.05; p<0.0001). This does not correspond to the coordinates of the VIM, but seems to be closer to those of the centre median and parafascicularis complex (CM-Pf), according to stereotaxic atlases. Considering only the dyskinetic patients, significant differences were found in the electrode position according to the therapeutic effects on levodopa dyskinesias, but they were not related to the team membership. Improvement in levodopa dyskinesias was significantly associated with deeper and more medial placement of electrodes. CONCLUSION The retrospective analysis of patients treated with DBS using comparable methodologies provides important information concerning electrode position and therapeutic outcome. The position of the electrode is related to the therapeutic effects of DBS. The results support the hypothesis that patients experiencing an improvement of dyskinesias under DBS are actually stimulated in a structure which is more posterior, more internal, and deeper than the VIM, very close to the CM-Pf. These results are consistent with neuroanatomical and neurophysiological data showing that the CM-Pf is included in the motor circuits of the basal ganglia system and receives an important input from the internal pallidum. This suggests that the CM-Pf could be involved specifically in the pathophysiology of levodopa peak dose dyskinesias.

Prognosis factors of survival time in patients with glioblastoma multiforme: a multivariate analysis of 340 patients.

SummaryBackground. The prognosis of glioblastoma multiforme remains poor despite recent therapeutic advances. Several clinical and therapeutic factors as well as tumour characteristics have been reported as significant to survival. A more efficient determination of the prognostic factors is required to optimize individual therapeutic management. The aim of our study was to evaluate by univariate then multivariate analysis the factors that influence prognosis and particularly survival. Methods. Data of 340 patients with newly-diagnosed GBM were retrospectively analyzed. Univariate analysis of prognosis factors of survival time was performed. Factors that seemed determinant were evaluated by Kaplan–Meier survival curves. Finally, the significant factors found in univariate analysis were tested in multivariate analysis using the COX regression method. Findings. Using multivariate analysis, the following factors were found to influence survival: radiotherapy was the predominant factor followed by radical surgery, tumour location, age and chemotherapy. Patients treated with temozolomide had a markedly better survival rate than patients treated with other chemotherapies (Log-rank test P < 0.005). The values of GBM type (de novo or secondary), as well as repeated surgery and partial surgery (vs. simple biopsy) were suggested by univariate analysis but not confirmed by the COX regression method. After radical surgery, progression-free survival was correlated to overall survival (r = 0.87, P < 10e-5). Conclusions. The influence of radiotherapy on survival was greater than the influence of age, an argument supporting the proposition of radiotherapy for patients until at least age 70. In the case of recurrence, the correlation between overall survival and progression-free survival is an important factor when considering the therapeutic options. Initial radical surgery and repeated procedures dramatically influence survival. The benefit of partial surgery remains difficult to evaluate. Partial surgery could be used to decrease intracranial pressure and to minimize residual tumours in order to enable treatment by chemotherapy and radiotherapy. The value of temozolomide treatment was confirmed.

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.

Exhaustive, one-year follow-up of subthalamic nucleus deep brain stimulation in a large, single-center cohort of parkinsonian patients.

OBJECTIVE To prospectively assess the impact of subthalamic nucleus (STN) deep brain stimulation (DBS) at 12 months after surgery in a series of 100 consecutive patients treated in a single center. The primary objective was to describe the clinical outcome in terms of efficacy and tolerance in STN-DBS patients. A secondary objective was to discuss presurgery clinical characteristics a posteriori as a function of outcome. METHODS One hundred and three consecutive patients with severe Parkinsons disease received bilateral STN-DBS in our clinic between May 1998 and March 2003. Clinical assessment was performed before and 12 months after surgery and was based on the Unified Parkinsons Disease Rating Scale, Parts II, III, and IV A; the Schwab and England Scale; and cognitive evaluation. Patient-rated overall improvement was also evaluated. RESULTS Twelve months after surgery, the Unified Parkinsons Disease Rating Scale Part III score decreased by 43%, the Unified Parkinsons Disease Rating Scale Part II score (activities of daily living) fell by 34%, and the severity of dyskinesia-related disability decreased by 61%. The main surgical complications after STN-DBS were as follows: infection (n = 7), intracerebral hematoma (n = 5), electrode fracture (n = 4), and incorrect lead placement (n = 8). We observed cognitive decline and depression in 7.7 and 18% of the patients, respectively. The mean patient-rated overall improvement score was 70.7%. CONCLUSION The efficacy and safety of STN-DBS in our centers large cohort of Parkinsonian patients are generally similar to the results obtained by other groups, albeit at the lower limit of the range of reported values. In contrast to efficacy, the occurrence of adverse events cannot be predicted. Younger patients with Parkinsons disease (i.e., those younger than 60 yr) often show an excellent response to levodopa. However, in view of our data on overall patient satisfaction and the occurrence of adverse events, we suggest that older patients (but not those older than 70 yr) and less dopa-sensitive patients (but not those with a response <50%) should still be offered the option of STN-DBS.

Cerebral arteriovenous malformations in children: report on 62 cases

A series of 62 children with cerebral arteriovenous malformations admitted to our department in the course of 17 years (1975–1992) was reviewed in a retrospective study. In 54 cases hemorrhagic stroke was the first presenting symptom, followed by epilepsy in five cases. On admission 26 children presented with a neurological deficit, and 21 were admitted with a grade 3 status according to Botterell. Fifty-one malformations were supratentorial (41 hemispheric, 10 deep-seated) while 11 were infratentorial. According to Moris criteria, 28 lesions were small, 19 medium, and 15 large. Fifty-two children were operated on, with total excision of the malformation achieved in 47 cases. In two children the malformation recurred. The evolution of neurological disorders has been studied with a mean follow-up of 8.5 years. Fifty patients had a satisfactory outcome on the Glasgow Outcome Scale. Four children died. These results were compared with those reported elsewhere in the pediatric literature.