H. Holger Capelle

Long-Term Clinical Outcome in Meige Syndrome Treated with Internal Pallidum Deep Brain Stimulation

Deep brain stimulation of the globus pallidus internus (GPi DBS) is effective in the treatment of primary segmental and generalized dystonia. Although limb, neck, or truncal dystonia are markedly improved, orofacial dystonia is ameliorated to a lesser extent. Nevertheless, several case reports and small cohort studies have described favorable short‐term results of GPi DBS in patients with severe Meige syndrome. Here, we extend this preliminary experience by reporting long‐term outcome in a multicenter case series, following 12 patients (6 women, 6 men) with Meige syndrome for up to 78 months after bilateral GPi DBS. We retrospectively assessed dystonia severity based on preoperative and postoperative video documentation. Mean age of patients at surgery was 64.5 ± 4.4 years, and mean disease duration 8.3 ± 4.4 years. Dystonia severity as assessed by the Burke–Fahn–Marsden Dystonia Rating Scale showed a mean improvement of 45% at short‐term follow‐up (4.4 ± 1.5 months; P < 0.001) and of 53% at long‐term follow‐up (38.8 ± 21.7 months; P < 0.001). Subscores for eyes were improved by 38% (P = 0.004) and 47% (P < 0.001), for mouth by 50% (P < 0.001) and 56% (P < 0.001), and for speech/swallowing by 44% (P = 0.058) and 64% (P = 0.004). Mean improvements were 25% (P = 0.006) and 38% (P < 0.001) on the Blepharospasm Movement Scale and 44% (P < 0.001) and 49% (P < 0.001) on the Abnormal Involuntary Movement Scale. This series, which is the first to demonstrate a long‐term follow‐up in a large number of patients, shows that GPi DBS is a safe and highly effective therapy for Meige syndrome. The benefit is preserved for up to 6 years.

Increased beta activity in dystonia patients after drug-induced dopamine deficiency.

Several studies have confirmed that subthalamic and pallidal local field potential activity in the beta frequency band (13-30 Hz) is exaggerated in untreated patients with Parkinsons disease (PD) and is suppressed by dopaminergic treatment. This particular spectral pattern differs from that in patients with dystonia in whom pallidal activity is prominent at low frequencies (<12 Hz). Here we demonstrate that tetrabenazine induced monoamine depletion and dopamine blockade is associated with increased activity in the low beta band (13-20 Hz) in the internal pallidum of patients with dystonia. Beta activity was elevated in six patients treated with tetrabenazine compared to six patients in whom this drug was not used. Our findings suggest that beta activity is enhanced in the chronically dopamine-depleted and blocked state irrespective of the underlying pathology, consistent with the idea that excessive synchrony in the beta band is directly related to dopaminergic hypofunction, rather than some degenerative disease-specific attribute of Parkinsons disease.

Effects of Pedunculopontine Area and Pallidal DBS on Gait Ignition in Parkinson's Disease

BACKGROUND Freezing of gait is a disabling feature of Parkinsons disease, and so far no established treatment exists. Deep brain stimulation of the pedunculopontine area has been proposed to treat refractory gait disorders, yet data on measurable effects, especially in combination with stimulation of other targets, are scarce. METHODS Acute effects of either low frequency pedunculopontine stimulation or high frequency stimulation of the posteroventral lateral globus pallidus internus and a combination of both in a 66-year-old man with advanced Parkinsons disease were assessed. Four weeks after the intervention, the gait was examined with patient blinded in each condition using computerized gait analysis. RESULTS Isolated pedunculopontine or pallidal stimulation had a mild impact on gait ignition and freezing of gait, but combined stimulation had a marked effect. CONCLUSIONS Combined multifocal stimulation may be a promising option for gait ignition and freezing of gait in advanced Parkinsons disease.

Effect of deep brain stimulation on levodopa-induced dyskinesias and striatal oscillatory local field potentials in a rat model of Parkinson's disease.

BACKGROUND In Parkinsons disease (PD) dyskinesias appear after long-term dopaminergic treatment. Deep brain stimulation (DBS) of the subthalamic nucleus (STN) or the globus pallidus internus (GPi) is a well-established treatment option for both PD symptoms and complications of medication. OBJECTIVE To elucidate physiological mechanisms of the effect of DBS on levodopa-induced dyskinesias (LID) we investigated both DBS in the GPi and the centromedian-parafascicular complex (CM-Pf), which are part of an internal basal ganglia loop connecting with the dorsolateral striatum. In particular, we focused on changes of oscillatory activity in the dorsolateral striatum, which also presents the entrance region of the basal ganglia (BG). METHODS 6-Hydroxydopamine (6-OHDA) hemiparkinsonian (HP) rats and 6-OHDA lesioned HP rats with LID (HP-LID) were used to compare the effect of DBS in the entopeduncular nucleus (EPN, the equivalent to the human GPi) and the thalamic parafascicular nucleus (Pf, the equivalent of the human CM-Pf) on dyskinesias and neuronal oscillatory activity of selected frequency bands in the dorsolateral striatum on and off levodopa. RESULTS In HP-LID rats the relative beta and gamma power was lower, while relative theta power was higher as compared to HP rats. Chronic DBS of either the EPN or the Pf improved dyskinesia scores in HP-LID rats, and no differences in oscillatory activity were observed between groups. CONCLUSIONS Stimulation of the Pf has a specific impact on dyskinesias, which is similar to that found after EPN stimulation, and which is accompanied by changes of oscillatory activity.

Cavernous hemangioma of the cavernous sinus, skin, and retina: hemodynamic changes after treatment: case report.

OBJECTIVEThere are several reports concerning cavernous hemangiomas of the skin and central nervous system. Additional retinal involvement has also been reported. CLINICAL PRESENTATIONThe authors report a 69-year-old woman with a giant extra-axial cavernous hemangioma of the right cavernous sinus involving the supra- and parasellar region, retina, and skin. INTERVENTIONShrinkage of its cutaneous part lead to subsequent increase of the volume of the intracranial part. Owing to compression of the optic and the oculomotor nerves, oculomotor disturbances, ptosis, and visual impairment to 0.2 occurred. Via a pterional approach microsurgical removal of the tumor except for a remnant of the intracavernous part was performed. CONCLUSIONHemodynamic connection between cutaneous, retinal, and intracranial hemangiomas should be considered.

Effect of Deep Brain Stimulation on Regional Cerebral Blood Flow in Patients with Medically Refractory Tourette Syndrome

In this study, alterations in brain perfusion have been investigated in patients with Tourette syndrome (TS) compared with control subjects. In addition, we investigated the effects of deep brain stimulation (DBS) in both globus pallidus internus (GPi) and centromedian-parafascicular/ventralis oralis internus nuclei of the thalamus (CM/Voi) and sham (SHAM) stimulation on cerebral blood flow. In a prospective controlled, randomized, double-blind setting, five severely affected adult patients with TS with predominant motor or vocal tics (mean total tic score on the Yale Global Tic Severity Scale: 39) underwent serial brain perfusion single photon emission computed tomography with 99mTc-ECD. Results were compared with data from six age-matched control subjects. All patients were investigated at four different time points: once before DBS implantation (preOP) and three times postoperatively. Postoperative scans were performed in a randomized order, each after 3 months of either GPi, CM/Voi, or SHAM stimulation. At each investigation, patients were injected at rest while awake, but scanned during anesthesia. This procedure ensured that neither anesthesia nor movement artifacts influenced our results. Control subjects were investigated only once at baseline (without DBS or anesthesia). At baseline, cerebral blood flow was significantly reduced in patients with TS (preOP) compared with controls in the central region, frontal, and parietal lobe, specifically in Brodmann areas 1, 4–9, 30, 31, and 40. Significantly increased perfusion was found in the cerebellum. When comparing SHAM stimulation to preOP condition, we found significantly decreased perfusion in basal ganglia and thalamus, but increased perfusion in different parts of the frontal cortex. Compared with SHAM condition both GPi and thalamic stimulation resulted in a significant decrease in cerebral blood flow in basal ganglia and cerebellum, while perfusion in the frontal cortex was significantly increased. Our results provide substantial evidence that, in TS, brain perfusion is altered in the frontal cortex and the cerebellum and that these changes can be reversed by both GPi and CM/Voi DBS.

Bilateral trochlear nerve palsy subsequent to ventriculoperitoneal shunting of normal pressure hydrocephalus

Abstract Misplacement of the ventricular catheters of shunt systems may result in shunt dysfunction or a variety of neurological symptoms. Bilateral fourth nerve palsy has not been reported thus far after shunting. Here, we describe the occurrence of this unusual neurological deficit in a patient who underwent shunting for normal pressure hydrocephalus, and demonstrate its pathoanatomical correlate.

Transient Global Amnesia Associated with Accidental High-Frequency Stimulation of the Right Hippocampus in Deep Brain Stimulation for Segmental Dystonia

We report on a 66-year-old woman with segmental dystonia treated with chronic bilateral deep brain stimulation of the globus pallidus internus, in whom accidental high-voltage, high-frequency stimulation induced an episode of transient global amnesia (TGA) via an electrode contact which was misplaced in the right hippocampus. A possible mechanism underlying this TGA episode may have been the inhibition of local neuronal activity or fiber activation by high current density via direct electrical stimulation of hippocampal structures. While a unifying etiology of TGA has not been proven so far, our case demonstrates a possible link between focal electrical stimulation of hippocampal structures and the full clinical picture of the syndrome.

Cervical Myelopathy due to an Epidural Cervical Mass after Chronic Cervical Spinal Cord Stimulation

Background: Spinal cord stimulation (SCS) is an established treatment for neuropathic pain. Severe long-term complications are rare. Only recently secondary mass lesions associated with chronic stimulation were noted to occur. Objectives: To report the rare occurrence of cervical myelopathy secondary to an epidural cervical spinal mass after chronic cervical SCS. Methods: Implantation of a paddle electrode at C2-C4 for chronic neuropathic pain resulted in improvement of pain for several years but it lost its efficacy after 8 years. Myelography and postmyelographic CT detected an epidural mass surrounding the electrode and compressing the spinal cord when cervical myelopathy had developed 17 years after electrode implantation. Results: The mass which consisted of dense fibrous scar tissue was removed via hemilaminectomy. At postoperative follow-up at 8 months there was no further progression of gait disorder. Conclusion: Long-term cervical SCS in a rare case may lead to fibrous epidural mass lesions which may not only cause loss of efficacy but which may also result in new neurological deficits.

Akinetic mutism and parkinsonism due to subdural and intraventricular tension pneumocephalus.

Pneumocephalus may occur after intracranial surgery and is most often asymptomatic. It is usually associated with posterior fossa surgery. Here, we present a 56-year-old man who developed akinetic mutism and parkinsonism caused by subdural and intraventricular tension pneumocephalus associated with decompression of a chronic subdural hygroma. As an emergency treatment, air was exchanged with saline via the drainage, which then was removed and a subduro-peritoneal shunt was implanted. The condition described here requires immediate attention and appropriate treatment.