Hans-Holger Capelle

Effect of Nicardipine Prolonged-Release Implants on Cerebral Vasospasm and Clinical Outcome After Severe Aneurysmal Subarachnoid Hemorrhage A Prospective, Randomized, Double-Blind Phase IIa Study

Background and Purpose— The purpose of this study was to investigate the effect of nicardipine prolonged-release implants (NPRIs) on cerebral vasospasm and clinical outcome after severe subarachnoid hemorrhage. Methods— Thirty-two patients with severe subarachnoid hemorrhage and undergoing aneurysm clipping were included into this single center, randomized, double-blind trial. Sixteen patients received NPRIs implanted into the basal cisterns in direct contact to the exposed proximal blood vessels; in 16 control patients, the basal cisterns were opened and washed out only without leaving implants. Angiography was performed preoperatively and at day 8±1. Computed tomography imaging was analyzed for the incidence of territorial infarcts unrelated to surgery. Patient outcome was assessed using the modified Rankin and National Institute of Health Stroke scales. Results— The incidence of angiographic vasospasm in proximal vessel segments was significantly reduced after implantation of NPRIs (73% control versus 7% NPRIs). Significant differences occurred also for the majority of distal vessel segments. Computed tomography scans revealed a lower incidence of delayed ischemic lesions (47% control versus 14% NPRIs). The NPRI group demonstrated more favorable modified Rankin and National Institute of Health Stroke scales as well as a significantly lower incidence of deaths (38% control versus 6% NPRIs). Conclusions— Implantation of NPRIs reduces the incidence of cerebral vasospasm and delayed ischemic deficits and improves clinical outcome after severe subarachnoid hemorrhage.

Bilateral pallidal stimulation for blepharospasm–oromandibular dystonia (Meige syndrome)

Deep brain stimulation (DBS) of the globus pallidus internus (GPi) is performed for treatment of medically intractable dystonia, including primary generalized dystonia, myoclonic dystonia, and cervical dystonia.1-3⇓⇓ There is little experience, however, with other focal dystonias. We present long-term follow-up of chronic pallidal DBS in blepharospasm–oromandibular dystonia (Meige syndrome). A 60-year-old woman with medically refractory Meige syndrome had an unremarkable medical history with no exposure to neuroleptic drugs. At age 55, she noted mild spasms of her tongue. She then developed blepharospasm and involuntary contractions of her lower facial muscles. Dystonia improved after local injections of botulinum toxin (BTX) A, which were repeated over 3 years. Then, a gradual loss of efficacy was noted. Medical treatment did not yield satisfactory improvement or was limited by side effects. When seen in our office she presented with blepharospasm–oromandibular dystonia, involuntary movements of her tongue, and difficulty swallowing. She complained about pain of her temporo-mandibular joints. Medication included trihexyphenidyl, tiapride, tetrazepam, zopiclon, and zolpidem. Her sleep quality was poor, …

GPi-DBS may induce a hypokinetic gait disorder with freezing of gait in patients with dystonia

Objectives: Stimulation-induced hypokinetic gait disorders with freezing of gait (FOG) have been reported only recently as adverse effects of deep brain stimulation (DBS) of the globus pallidus internus (GPi) in patients with dystonia. The aim of this work was to determine the frequency and the nature of this GPi-DBS–induced phenomenon. Methods: We retrospectively screened our database of patients with dystonia who underwent DBS. Patients with focal, segmental, or generalized dystonia of primary or tardive origin and no gait disorder due to lower limb dystonia before DBS, bilateral pallidal stimulation, and a follow-up for more than 6 months were included. Reports of adverse events were analyzed, and gait abnormalities were scored by comparing preoperative and postoperative video recordings using Movement Disorder Society–sponsored revision of the Unified Parkinsons Disease Rating Scale (MDS-UPDRS) items 3.10 (gait) and 3.11 (FOG). To assess the role of GPi-DBS in gait abnormalities, DBS was paused for 24 hours. Gait and FOG were assessed 30 minutes, 2 hours, and 24 hours after restarting DBS. Finally, a standardized adjustment algorithm was performed trying to eliminate the gait disorder. Results: Of a collective of 71 patients with dystonia, 6 presented with a new gait disorder (8.5%; 2 men, 4 women, mean age 61.3 years [48–69 years], 2 craniocervical, 1 DYT-1 segmental, 1 truncal, 2 tardive dystonia). GPi-DBS improved Burke-Fahn-Marsden Dystonia Rating Scale motor score by 54% and disability score by 52%. MDS-UPDRS item 3.10 worsened from 0.5 (±0.8) to 2.0 (±0.9) and item 3.11 from 0 to 2.5 (±0.5). The gait disorder displayed shuffling steps and difficulties with gait initiation and turning. Increasing voltages improved dystonia but triggered FOG, sometimes worsening over a period of a few hours. It vanished within minutes after ceasing DBS. Electrode misplacement was ruled out. In all but one patient, no optimal configuration was found despite extensive testing of settings (monopolar, bipolar, pulse width 60–210 μs, frequency 60–180 Hz). Nevertheless, a compromise between optimal stimulation for dystonia and eliciting FOG was achieved in each case. Conclusions: A hypokinetic gait disorder with FOG can be a complication of GPi-DBS.

Chronic Deep Brain Stimulation in Patients with Tardive Dystonia Without a History of Major Psychosis

Tardive dystonia usually occurs with a delay after neuroleptic exposure in patients with major psychosis. A subgroup of patients, however, is given such medication for “mild depression” or “neurasthenia.” Tardive dystonia, in general, may respond favorably to pallidal deep brain stimulation (DBS). Nevertheless, it remains unclear thus far whether or not similar beneficial outcome is achieved with pallidal DBS in different subgroups of patients with tardive dystonia. Four women (mean age 59 years at surgery) underwent stereotactic pallidal DBS in the frame of an observational study. Tardive dystonia occurred secondary to medication with fluspirilene and haloperidol, and injection of long‐acting depot neuroleptics prescribed for mild depression or “nervousness.” Assessment included the Burke‐Fahn‐Marsden (BFM) scale preoperatively and at 12 months follow‐up. Extended follow‐up was available at a mean of 27.3 months postoperatively (range 16–36 months). There were no surgically related complications. All 4 patients experienced sustained statistically significant benefit from pallidal DBS. Mean improvement at 12 months was 77% for the BFM motor score (range, 45–91%; P = 0.043), and 84% at the last available follow‐up (range, 70–91%; P = 0.03). This was paralleled by improvement of the BFM disability score. Chronic pallidal DBS in patients with tardive dystonia without a history of major psychosis provides sustained improvement which is similar to that in other subgroups of patients with tardive dystonia. This effect is stable on extended follow‐up for up to 3 years.

Chronic deep brain stimulation for segmental dystonia.

Fourteen consecutive patients with segmental dystonia underwent chronic deep brain stimulation (DBS) surgery in the frame of a prospective study protocol. Twelve patients received chronic pallidal stimulation, while 2 patients with prominent dystonic tremor received chronic thalamic ventrointermediate nucleus stimulation. Twelve patients had primary dystonia, and 2 patients secondary dystonia. The Burke-Fahn-Marsden dystonia rating scale (BFM motor) showed a mean relative improvement of 57.3% at the first follow-up (FU1, mean 7 months) and 57.8% at the second follow-up (FU2, mean 16 months). The mean BFM scores were 34.9 ± 17.7 preoperatively, 14.9 ± 11.7 at FU1, and 14.8 ± 10.3 at FU2. Scores of the disability subscale improved by 43% at FU1 and 36% at FU2. Improvement was comparatively less in those patients with secondary dystonia. Dysarthria was a limitation of DBS in 4 patients when using high voltage. Overall, chronic DBS is a very effective treatment option for medically refractory segmental dystonia.

Electromagnetic-guided neuronavigation for safe placement of intraventricular catheters in pediatric neurosurgery

OBJECT Ventricular catheter shunt malfunction is the most common reason for shunt revision. Optimal ventricular catheter placement can be exceedingly difficult in patients with small ventricles or abnormal ventricular anatomy. Particularly in children and in premature infants with small head size, satisfactory positioning of the ventricular catheter can be a challenge. Navigation with electromagnetic tracking technology is an attractive and innovative therapeutic option. In this study, the authors demonstrate the advantages of using this technology for shunt placement in children. METHODS Twenty-six children ranging in age from 4 days to 14 years (mean 3.8 years) with hydrocephalus and difficult ventricular anatomy or slit ventricles underwent electromagnetic-guided neuronavigated intraventricular catheter placement in a total of 29 procedures. RESULTS The single-coil technology allows one to use flexible instruments, in this case the ventricular catheter stylet, to be tracked at the tip. Head movement during the operative procedure is possible without loss of navigation precision. The intraoperative catheter placement documented by screenshots correlated exactly with the position on the postoperative CT scan. There was no need for repeated ventricular punctures. There were no operative complications. Postoperatively, all children had accurate shunt placement. The overall shunt failure rate in our group was 15%, including 3 shunt infections (after 1 month, 5 months, and 10 months) requiring operative revision and 1 distal shunt failure. There were no proximal shunt malfunctions during follow-up (mean 23.5 months). CONCLUSIONS The electromagnetic-guided neuronavigation system enables safe and optimal catheter placement, especially in children and premature infants, alleviating the need for repeated cannulation attempts for ventricular puncture. In contrast to stereotactic techniques and conventional neuronavigation, there is no need for sharp head fixation using a Mayfield clamp. This technique may present the possibility of reducing proximal shunt failure rates and costs for hydrocephalus treatment in this age cohort.

Micrographia induced by pallidal DBS for segmental dystonia: a subtle sign of hypokinesia?

Recently parkinsonism has been reported as a rare side effect of globus pallidus internus (GPi) deep brain stimulation (DBS) for dystonia. In the present systematic prospective study in 11 patients with segmental dystonia not affecting distal arm function, we could demonstrate significant changes in handwriting characterized by mild micrographia following GPi-DBS. We propose that this finding reflects GPi-DBS-induced disturbances of basal ganglia function in terms of a mild hypokinetic syndrome, as a result of outflow alterations in pallido-thalamo-cortical pathways.

Effects of the selective endothelin A (ET(A)) receptor antagonist Clazosentan on cerebral perfusion and cerebral oxygenation following severe subarachnoid hemorrhage - preliminary results from a randomized clinical series.

SummaryObjective. To study the effects of clazosentan, a new selective endothelin receptor subtype A antagonist, on cerebral perfusion and cerebral oxygenation following severe aneurysmal subarachnoid haemorrhage (aSAH). Methods. All 12 patients treated at our institution in the context of a phase IIa, multicenter, randomized trial on clazosentan’s safety and efficacy in reducing the incidence of angiographic cerebral vasospasm were included in this substudy. The phase IIa study (n = 34) consisted of two parts: a double-blind, randomized Part A (clazosentan 0.2 mg/kg/h versus placebo) and an open-label Part B (clazosentan 0.4 mg/kg/h for 12 h followed by 0.2 mg/kg/h) for patients with established vasospasm. In parallel to the phase IIa study protocol, which included assessment of vasospasm by angiography and transcranial Doppler sonography, we determined regional cerebral blood flow (rCBF), cerebrovascular resistance, and regional tissue oxygenation. Results. Cerebral perfusion was comparable between treatment groups during the early post-bleeding period (rCBF placebo, 22.6 ± 3.5 ml/100 g/min versus rCBF clazosentan, 23.9 ± 1.1 ml/100 g/min). By the time of control angiography (day 8 after aSAH), rCBF decreased by 50% in the placebo group (11.3 ± 6.7 ml/ 100 g/min) while it remained stable in the clazosentan group (23.5 ± 12.9 ml/100 g/min). During Part B of the study, all 3 patients who developed haemodynamically relevant vasospasm during placebo treatment, showed a sustained improvement in rCBF upon conversion to clazosentan. Conclusions. These preliminary data suggest that clazosentan reduces the extent of vasospasm-associated impairment of cerebral perfusion following aSAH. Furthermore, clazosentan may exert beneficial actions on overt vasospasm-associated hypoperfusion.

Risperidone-responsive segmental dystonia and pallidal deep brain stimulation

A 67-year-old man with risperidone-responsive segmental dystonia underwent bilateral deep brain stimulation (DBS) of the globus pallidus internus. Prospectively, the authors assessed the Burke–Fahn–Marsden Dystonia Rating Scale in medication (M) and stimulation (S) “on”/“off” states. With DBS at 9 months, the score improved by 86% to 8.5 in M-“on”/S-“on” and 12.5 in M-“off”/S-“on.” Studies of the effects of DBS and concomitant medication may be warranted in selected patients treated by DBS for dystonia.

Microvascular Decompression of the Anterior Inferior Cerebellar Artery for Intermediate Nerve Neuralgia

The authors present the case of a 63-year-old woman with a 5-year history of intractable paroxysmal ‘atypical’ otofacial pain. The patient’s pain attacks were not typical for either trigeminal or vagoglossopharyngeal neuralgia. Surgical exploration via a suboccipital retromastoid craniotomy showed vascular compression of the nervus intermedius by the anterior inferior cerebellar artery and the patient’s pain was successfully managed with microvascular decompression.