Somatosensory evoked potentials recorded from DBS electrodes: the origin of subcortical N18.

The different peaks of somatosensory-evoked potentials (SEP) originate from a variety of anatomical sites in the central nervous system. The origin of the median nerve subcortical N18 SEP has been studied under various conditions, but the exact site of its generation is still unclear. While it has been claimed to be located in the thalamic region, other studies indicated its possible origin below the pontomedullary junction. Here, we scrutinized and compared SEP recordings from median nerve stimulation through deep brain stimulation (DBS) electrodes implanted in various subcortical targets. We studied 24 patients with dystonia, Parkinson's disease, and chronic pain who underwent quadripolar electrode implantation for chronic DBS and recorded median nerve SEPs from globus pallidus internus (GPi), subthalamic nucleus (STN), thalamic ventral intermediate nucleus (Vim), and ventral posterolateral nucleus (VPL) and the centromedian-parafascicular complex (CM-Pf). The largest amplitude of the triphasic potential of the N18 complex was recorded in Vim. Bipolar recordings confirmed the origin to be close to Vim electrodes (and VPL/CM-Pf) and less close to STN electrodes. GPi recorded only far-field potentials in unipolar derivation. Recordings from DBS electrodes located in different subcortical areas allow determining the origin of certain subcortical SEP waves more precisely. The subcortical N18 of the median nerve SEP-to its largest extent-is generated ventral to the Vim in the region of the prelemniscal radiation/ zona incerta.

What Do Medical Students Know about Deep Brain Stimulation?

BACKGROUND: Deep brain stimulation (DBS) is an established therapy for movement disorders. It is currently under investigation in neuropsychiatric disorders. Neurophobia is a common phenomenon that might have a negative impact in medical education. Little is known about medical students' knowledge about DBS when they enter university and what they learn about it during their medical formation. METHODS: A 10-item questionnaire was designed. Questions addressed indications for DBS, costs of DBS, complications, the percentage of Parkinson disease (PD) patients who might profit from DBS, etc. Students at Hannover Medical School were asked to complete the questionnaire in the preclinical study period and in the last year of the study. RESULTS: Comparing the "early group" (204 students) and the "advanced group" (162 students), there was a significant gain of knowledge. More common disorders such as PD and tremor were known to be indications for DBS. Knowledge about the impact of DBS on specific symptoms in PD and about DBS targets was limited in both groups. CONCLUSIONS: DBS is partly known among medical students in the preclinical phase with a gain of knowledge during further study. Future studies on this topic addressing general practitioners as neurologists are needed to better understand why knowledge on DBS is still limited.

Subtle Sensory Abnormalities Detected by Quantitative Sensory Testing in Patients with Trigeminal Neuralgia.

BACKGROUND: Trigeminal neuralgia (TN) is characterized by paroxysmal pain attacks affecting the somatosensory distributions of the trigeminal nerve. It is thought to be associated with a neurovascular conflict most frequently, but pathomechanisms have not been fully elucidated. In general, no sensory deficit is found in routine clinical examination. There is limited data available, however, showing subtle subclinical sensory deficits upon extensive testing. OBJECTIVE: We used quantitative sensory testing (QST) to detect abnormalities in sensory processing in patients with TN by comparing the affected and non-affected nerve branches with their contralateral counterparts and by comparing the results of the patients with those of controls. STUDY DESIGN: Observational study. SETTING: University Hospital, Departments of Neurosurgery, Institute for Cognitive and Clinical Neuroscience. METHODS: QST was conducted on 48 patients with idiopathic TN and 27 controls matched for age and gender using the standardized protocol of the German Neuropathic Pain Network. Stimulations were performed bilaterally in the distribution of the trigeminal branches. The patients had no prior invasive treatment, and medications at the time of examination were noted. RESULTS: In patients with TN deficits in warm and cold sensory detection thresholds in the affected and also the non-affected nerve branches were found. Tactile sensation thresholds were elevated in the involved nerve branches compared to the contralateral side. LIMITATIONS: More data are needed on the correlation of such findings with the length of history of TN and with changes of the morphology of the trigeminal nerve. CONCLUSIONS: QST shows subtle sensory abnormalities in patients with TN despite not being detected in routine clinical examination. Our data may provide a basis for further research on the development of TN and also on improvement after treatment. KEY WORDS: Quantitative sensory testing, trigeminal neuralgia, facial pain, neuropathic pain, microvascular decompression, cranial nerve.

Event-related cortical processing in neuropathic pain under long-term spinal cord stimulation.

BACKGROUND: Several mechanisms were suggested in the past to explain the beneficial effect of spinal cord stimulation (SCS) in patients suffering from neuropathic pain. Little is known about potential supraspinal mechanisms. OBJECTIVE: In this study cortical signaling of patients with neuropathic pain and successful long-term treatment with SCS was analyzed. STUDY DESIGN: Observational study. SETTING: University hospital, neurosurgical department, outpatient clinic for movement disorders and pain, institute for cognitive and clinical neuroscience. METHODS: Nine patients with neuropathic pain of a lower extremity with a lasting response to chronic SCS were included. Cortical activity was analyzed using event-related potentials of the electroencephalogram after non-painful and painful stimulation. Each patient was tested under the effect of long-term SCS and 24 hours after cessation of SCS. Cortical areas involved in the peaks of evoked potentials were localized using a source localization method based on a fixed dipole model. RESULTS: Detection threshold and intensity of non-painful stimulation did not differ significantly on both sides. Pain threshold was significantly lower on the neuropathic side under the effect of SCS (P = 0.03). Bilateral pain thresholds were significantly lower (P = 0.03 healthy side, P = 0.003 neuropathic side) in 5 patients with increased pain after cessation of SCS. Under the effect of SCS cortical negativities (N1, N2, N3) and positivities (P1) demonstrated bilaterally comparable amplitudes. After cessation of SCS, decreased threshold for peripheral stimulation resulted in lowered negativities on both sides. The positivity P1 was differentially regulated and was reduced more contralateral to the unaffected side. N2 was localized at the sensory representation of the leg within the homunculus. The main vector of P1 was localized within the cingular cortex (CC) and moved more anteriorly under the effect of SCS. LIMITATIONS: The exact time span that SCS continues to have an effect is not known. However, due to patient discomfort discontinuation of SCS therapy was not prolonged over a 24 hour period. Further limitations were the low number of patients who agreed to discontinue SCS therapy for research purposes. CONCLUSIONS: Long-term SCS for treatment of neuropathic pain influenced both pain thresholds and cortical signalling. Source localization of P1 suggests involvement of regions involved in cognitive/associative processing of pain.

Comparative characterization of single cell activity in the globus pallidus internus of patients with dystonia or Tourette syndrome.

Altered processing in the basal ganglia has been described both in dystonia and Tourette's syndrome (TS). Deep brain stimulation (DBS) of the globus pallidus internus (GPi) has become a recognized treatment for dystonia and has been used successfully to alleviate tics in TS. This study evaluates possible differences of GPi linear and nonlinear neuronal discharge characteristics between patients with dystonia and TS. Nine patients with primary dystonia and six patients with TS were studied during functional stereotactic neurosurgical operations for implantation of DBS electrodes under general anesthesia. Six patients with primary dystonia under local anesthesia served as non-anesthetized controls. Single-unit activity recordings in the GPi were obtained during routine microelectrode recording and mapping to delineate nuclear borders and to identify the sensorimotor subregions. Anesthesia profoundly decreased neuronal activity in patients with dystonia. Dystonia patients showed marginally higher mean firing rates in the GPi compared to TS patients (P = 0.06). Although the average total number of bursts and the mean peak frequency in bursts did not differ between groups, the mean spikes in bursts were higher in dystonia patients (P < 0.05). Nonlinear time series analysis metrics, measured as complexity of Lempel-Ziv and maximum approximate entropy, revealed higher randomness in TS compared to dystonia patients (P < 0.05). The percentage of oscillating neurons in spike trains was higher in dystonia compared to TS (P < 0.05). Our data provide evidence for differences of the neuronal dynamic complexity, randomness and oscillatory modulation of spike trains in the GPi between dystonia and TS. Such differences, although subtle, might contribute to the specific clinical phenomenology secondary to disordered neuronal basal ganglia processing.

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.

Effects of pedunculopontine area and pallidal DBS on gait ignition in Parkinson's disease.

BACKGROUND: Freezing of gait is a disabling feature of Parkinson's 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 Parkinson's 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 Parkinson's disease.

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.

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

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.

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 Parkinson's 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 Parkinson's disease.

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

OBJECTIVE: There are several reports concerning cavernous hemangiomas of the skin and central nervous system. Additional retinal involvement has also been reported. CLINICAL PRESENTATION: The 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. INTERVENTION: Shrinkage 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. CONCLUSION: Hemodynamic connection between cutaneous, retinal, and intracranial hemangiomas should be considered.

Chronic stimulation of the globus pallidus internus for treatment of non-dYT1 generalized dystonia and choreoathetosis: 2-year follow up.

OBJECT: The authors studied the long-term efficacy of deep brain stimulation (DBS) of the posteroventral lateral globus pallidus internus up to 2 years postoperatively in patients with primary non-DYT1 generalized dystonia or choreoathetosis. The results are briefly compared with those reported for DBS in DYT1 dystonia (Oppenheim dystonia), which is caused by the DYT1 gene. METHODS: Enrollment in this prospective expanded pilot study was limited to adult patients with severely disabling, medically refractory non-DYT1 generalized dystonia or choreoathetosis. Six consecutive patients underwent follow-up examinations at defined intervals of 3 months, 1 year, and 2 years postsurgery. There were five women and one man, and their mean age at surgery was 45.5 years. Formal assessments included both the Burke-Fahn-Marsden dystonia scale and the recently developed Unified Dystonia Rating Scale. Two patients had primary generalized non-DYT1 dystonia, and four suffered from choreoathetosis secondary to infantile cerebral palsy. Bilateral quadripolar DBS electrodes were implanted in all instances, except in one patient with markedly asymmetrical symptoms. There were no adverse events related to surgery. The Burke-Fahn-Marsden scores in the two patients with generalized dystonia improved by 78 and 71% at 3 months, by 82 and 69% at 1 year, and by 78 and 70% at 2 years postoperatively. This was paralleled by marked amelioration of disability scores. The mean improvement in Burke-Fahn-Marsden scores in patients with choreoathetosis was 12% at 3 months, 29% at 1 year, and 23% at 2 years postoperatively, which was not significant. Two of these patients thought that they had achieved marked improvement at 2 years postoperatively, although results of objective evaluations were less impressive. In these two patients there was a minor but stable improvement in disability scores. All patients had an improvement in pain scores at the 2-year follow-up review. Medication was tapered off in both patients with generalized dystonia and reduced in two of the patients with choreoathetosis. All stimulation-induced side effects were reversible on adjustment of the DBS settings. Energy consumption of the batteries was considerably higher than in patients with Parkinson disease. CONCLUSIONS: Chronic pallidal DBS is a safe and effective procedure in generalized non-DYT1 dystonia, and it may become the procedure of choice in patients with medically refractory dystonia. Postoperative improvement of choreoathetosis is more modest and varied, and subjective ratings of outcome may exceed objective evaluations.