Prospective evaluation of Globus pallidus internus deep brain stimulation in Huntington's disease.

INTRODUCTION: Pharmacological treatment of chorea in Huntington's disease (HD) is often limited by poor efficacy or side effects. Pallidal deep brain stimulation (DBS) has been considered in these patients but experience is so far limited. METHODS: We prospectively evaluated the effects of bilateral DBS of the Globus pallidus internus (GPi) over one year in six severely affected HD patients with treatment refractory chorea in an advanced stage of the disease. Primary endpoint of the study was improvement in chorea. Additionally, we evaluated the effects of GPi DBS on the motor part of the Unified Huntington's Disease Rating Scale (UHDRS), bradykinesia, dystonia, functional impairment, psychiatric and cognitive symptoms. Side effects were systematically assessed. RESULTS: The chorea subscore was significantly reduced postoperatively (-47% six months, -40% twelve months postoperatively). The UHDRS total motor score was significantly reduced at six months postoperatively (- 17%) but the effect was not sustained twelve months after the operation (- 5%). Pallidal DBS did not improve other motor symptoms or functional impairment. There was no effect on psychiatric symptoms or cognition. A number of side effects were noted, especially spasticity in three of the patients. CONCLUSIONS: Pallidal DBS is a treatment option for HD patients with severe pharmacologically refractory chorea. Further studies are needed to define optimal candidates for this procedure.

Biochemical mechanisms of pallidal deep brain stimulation in X-linked dystonia parkinsonism.

OBJECTIVE: Invasive techniques such as in-vivo microdialysis provide the opportunity to directly assess neurotransmitter levels in subcortical brain areas. METHODS: Five male Filipino patients (mean age 42.4, range 34-52 years) with severe X-linked dystonia-parkinsonism underwent bilateral implantation of deep brain leads into the internal part of the globus pallidus (GPi). Intraoperative microdialysis and measurement of gamma aminobutyric acid and glutamate was performed in the GPi in three patients and globus pallidus externus (GPe) in two patients at baseline for 25/30 min and during 25/30 min of high-frequency GPi stimulation. RESULTS: While the gamma-aminobutyric acid concentration increased in the GPi during high frequency stimulation (231 ± 102% in comparison to baseline values), a decrease was observed in the GPe (22 ± 10%). Extracellular glutamate levels largely remained unchanged. CONCLUSIONS: Pallidal microdialysis is a promising intraoperative monitoring tool to better understand pathophysiological implications in movement disorders and therapeutic mechanisms of high frequency stimulation. The increased inhibitory tone of GPi neurons and the subsequent thalamic inhibition could be one of the key mechanisms of GPi deep brain stimulation in dystonia. Such a mechanism may explain how competing (dystonic) movements can be suppressed in GPi/thalamic circuits in favour of desired motor programs.

Epidural and subdural stimulation.

Cortical stimulation, either transcranial or by means of electrodes implanted epidurally or subdurally, is used increasingly to treat neuropsychiatric diseases. In cases where transcranial stimulation gives only short-term success, implanted electrodes can yield results that are similar but long-term. Epidural stimulation is used widely to treat chronic neuropathic pain, whereas newer fields are in movement disorders, tinnitus, depression, and functional rehabilitation after stroke. For epidural stimulation, computational models explain the geometry of stimulation parameters (anodal, cathodal, and bifocal) and are used for targeting to yield the best clinical results. Nevertheless, the role of the cerebrospinal fluid layer also has to be taken into consideration. Subdural or intrasulcal stimulation allows a more focused stimulation with lower current intensities. This advantage, however, is counterbalanced by a higher complication rate with regard to epileptic seizures, subdural or intracerebral hemorrhages, and wound infections.

[Experience in treatment of patients with neuropathic facial pain using ziconotide]. / Erfahrungen mit intrathekaler First-line-Therapie mit Ziconotide bei Patienten mit Neuropathischen Gesichtsschmerzen.

We report on the intrathecal use of ziconotide in three patients with idiopathic facial pain after surgery of the mouth, jaw or face and one patient with neuropathic pain after damage of the lingual nerve. The therapy was successful in three patients but one patient with idiopathic facial pain had pain relief only during the test phase of ziconotide with an external pump and not after implanting the Synchromed® pump. With intrathecal morphine therapy this patient achieved good pain relief. We recommend that patients with neuropathic facial pain should be treated with ziconotide after implementation of guideline-based therapy. In the test phase the ziconotide dose should be increased by 0.6 µg/day per week after an initial dose of 0.6-1.2 µg/day to avoid side-effects.

[Subcutaneous peripheral stimulation of the greater occipital nerve for the treatment of chronic headache syndromes]. / Subkutane periphere Stimulation des N. occipitalis major zur Behandlung chronischer Kopfschmerzsyndrome.

Medical treatment for certain chronic headache syndromes such as hemicrania continua (HC), chronic migraine (CM) or chronic cluster headache (CCH) is challenging and in many cases does not lead to sufficient pain relief or is limited by severe side effects. In the last few years neuromodulatory treatments such as subcutaneous stimulation of the greater occipital nerve or deep brain stimulation (DBS) in the hypothalamus have evolved. This report focuses on current knowledge and the results of peripheral subcutaneous nerve stimulation (SPNS) in the literature of the described headache syndromes and presents our own long-term results in ten patients. Technical details of implantation and possible complications are reported. The results between the two different stimulation types are compared. In summary, peripheral nerve stimulation of the greater occipital nerve is less invasive but also less effective in comparison to hypothalamic stimulation. However, the severity and frequency of pain attacks is significantly reduced. For other intractable headache syndromes SPNS of the greater occipital nerve offers a reasonable addition to medical treatment.

[Neuroablative procedures in pain therapy]. / Neurodestruktive Verfahren in der Schmerztherapie.

Although surgical ablative procedures can be effective in the management of chronic pain of malignant and non-malignant origin, they are often disregarded as treatment options due to the fact that in the past these procedures were associated with high complication rates. The complications include the development of new neurological deficits and in cases of long-term follow-up, the occurrence of the old or new pain syndromes by deafferentation. On the other hand there exist many less invasive, e.g. neuromodulatory procedures or non-invasive measures (systemic oral or transdermal opioids) which are able to considerably reduce chronic pain. Nevertheless, there remain certain very restricted indications for the use of neuroablative procedures for the treatment of chronic pain even today.

Hypothalamic deep brain stimulation for cluster headache: experience from a new multicase series.

Deep brain stimulation (DBS) of the posterior hypothalamus was found to be effective in the treatment of drug-resistant chronic cluster headache. We report the results of a multicentre case series of six patients with chronic cluster headache in whom a DBS in the posterior hypothalamus was performed. Electrodes were implanted stereotactically in the ipsilateral posterior hypothalamus according to published coordinates 2 mm lateral, 3 mm posterior and 5 mm inferior referenced to the mid-AC-PC line. Microelectrode recordings at the target revealed single unit activity with a mean discharge rate of 17 Hz (range 13-35 Hz, n = 4). Out of six patients, four showed a profound decrease of their attack frequency and pain intensity on the visual analogue scale during the first 6 months. Of these, one patient was attack free for 6 months under neurostimulation before returning to the baseline which led to abortion of the DBS. Two patients had experienced only a marginal, non-significant decrease within the first weeks under neurostimulation before returning to their former attack frequency. After a mean follow-up of 17 months, three patients are almost completely attack free, whereas three patients can be considered as treatment failures. The stimulation was well tolerated and stimulation-related side-effects were not observed on long term. DBS of the posterior inferior hypothalamus is an effective therapeutic option in a subset of patients. Future controlled multicentre trials will need to confirm this open-label experience and should help to better define predictive factors for non-responders.

[Neuromodulation in cluster headache. Clinical follow-up after deep brain stimulation in the posterior hypothalamus for chronic cluster headache, case report--Part II]. / Neuromodulation bei Clusterkopfschmerz. Klinische Verlaufsbeobachtung nach Tiefenhirnstimulation im posterioren Hypothalamus zur Behandlung des chronischen Clusterkopfschmerzes, Fallbericht--Teil II.

Deep brain stimulation (DBS) of the posterior hypothalamic area is a new treatment option for patients with refractory chronic cluster headache (CCH). A review of the literature reveals that studies based on large numbers of patients, long-term observations and controlled randomised trials are still lacking. In 2006 a case report of the first patient in Germany to be operated on to allow DBS was published, and we now present a report of this patient's course in the first 6 months after the operation; in addition, a current literature review is discussed. In July 2005 a DBS lead was placed in the left posterior hypothalamic area of this 39-year-old woman with CCH. Stimulation on demand achieved complete suppression of the cluster attacks, and the patient no longer needed medication. After about 8 months a decreasing effect of the stimulation, with only about 50% reduction of cluster attacks, and stimulation-induced side effects were observed. Neither reprogramming of the stimulation parameters nor pharmacological therapy with on-demand and long-term medication reduced the frequency or severity of CCH attacks to the level experienced in the early postoperative stage. Because of intolerable subjective side effects and tension-related pain at the site of the connection cable, in September 2006 the whole system was explanted at the patient's request.DBS in the posterior hypothalamic area is an invasive treatment option for use in cases with CCH that is refractory to any pharmacological therapy. As demonstrated by this case report, it is not possible to give a prognosis concerning its long-term efficacy: despite the initial excellent benefit there can be a reduction and even a loss of the effect of stimulation. The clinical results and long-term follow-up observations of the few cases published so far need to be evaluated in a larger multicentre trial with a double-blind study design.

Loss of anisotropy in trigeminal neuralgia revealed by diffusion tensor imaging.

We studied the trigeminal nerve in seven healthy volunteers and six patients with trigeminal neuralgia using the diffusion tensor imaging derived parameter fractional anisotropy (FA). While controls did not show a difference between both sides, there was a reduction of FA in the affected nerve in three of six patients with accompanying nerve-vessel conflict and atrophy. Reversibility of abnormally low FA values was demonstrated in one patient successfully treated with microvascular decompression.

Functional magnetic resonance imaging for cranial neuronavigation: methods for automated and standardized data processing and management. A technical note.

Preoperative fMRI is one of the best established clinical fMRI applications. Due to the difficulties in recording and coregistration of functional image data, we present methods to standardize and automate these procedures. We used a self-made interactive software package (AFI - Automated Functional Imaging) to automate the time consuming and complex analysis of fMRI data. AFI controls the BrainVoyager program, a postprocessing software package, and furthermore facilitates data management, anonymization of patient data, storage, documentation, data export to neuronavigation systems and the opportunity of spatial transformation of image data for use in group studies. By the end of 2006 we have used this method on 123 patients with brain tumors and 47 patients with trigeminal neuralgia. The fundamental basis of multimodal neuronavigation is precise coregistration. EPI images contain spatial distortions of 5-15 mm. We were able to reduce the misregistration of EPI and FLASH images in a selectable region of interest to 1-2 mm. Furthermore AFI reduces the average evaluation time for a standard clinical fMRI study (four functional measurements, one anatomical data set) by approx. 50% from 140 minutes to about 70 minutes in comparison to manual evaluation by an expert. More importantly, the personal attendance time required for the evaluation decreases by 84% to 23 minutes as the remainder of the program runs automatically. In comparison to currently available online postprocessing software tools which are more limited in use, BrainVoyager can be used for coregistration, data export to neuronavigation systems and spatial transformation.

[Trigeminal neuralgia: how often are trigeminal nerve-vessel contacts found by MRI in normal volunteers]. / Trigeminusneuralgie: Wie häufig gibt es einen Gefäss-Nerven-Kontakt bei schmerzfreien Probanden?

PURPOSE: To assess prospectively how often contacts are found between the trigeminal nerve and arteries or veins in the perimesencephalic cistern via MRI in normal volunteers. MATERIALS AND METHODS: 48 volunteers without a history of trigeminal neuralgia were examined prospectively (MRI at 1.5 T; T2-CISS sequence, coronal orientation, 0.9 mm slice thickness). Two radiologists decided by consensus whether there was a nerve-vessel contact in the perimesencephalic cistern. RESULTS: In 27 % of the volunteers, no contact was found between the trigeminal nerve and regional vessels, while in 73 %, such a contact was present. In 61 % of the cases, the offending vessel was an artery, in 39 %, it was a vein. In 2 volunteers, a deformation of the nerve was noted. CONCLUSION: Contrary to what has been suggested by retrospective studies, the majority of normal volunteers, if studied prospectively, do show a contact between the trigeminal nerve and local vessels. A close proximity between the nerve and regional vessels is thus normal and is not necessarily proof of a pathological nerve-vessel conflict.

[Deep brain stimulation in the posterior hypothalamus for chronic cluster headache. Case report and review of the literature]. / Tiefenhirnstimulation im posterioren Hypothalamus zur Behandlung des chronischen Clusterkopfschmerzes. Fallbericht und Literaturübersicht.

Primary chronic cluster headache (CCH) is a rare but severe pain syndrome and pathophysiological explanations are still missing. PET studies revealed activation in the hypothalamus and therefore it became a target for therapeutic deep brain stimulation (DBS). A case of a 39-year-old woman and a literature review are presented. The patient suffered from left-sided primary CCH for 14 months. The headache was resistant to any pharmacological therapy or treatment was limited by major drug side effects. Using a stereotactic approach a quadripolar lead was inserted in the left posterior hypothalamus. A test trial was performed and attack frequency, intensity, and adverse events were noted. Intraoperative test stimulation evoked typical side effects like tachycardia, diplopia and panic attacks. During the trial test a marked reduction in frequency and intensity of CCH was recorded. After 7 days the stimulation device was implanted subcutaneously. DBS with implantation of a lead in the ipsilateral inferior posterior hypothalamus is an experimental treatment option and should be offered to selected patients in a prospective controlled clinical trial. Data concerning the long-term follow-up need to be collected.

Behr syndrome variant with tremor treated by VIM stimulation.

Behr syndrome was first described in 1909 as a syndrome of heredofamilial optic atrophy, visual disturbances, nystagmus, and variable pyramidal tract signs. The syndrome has been reported in both sexes. So far, tremor has not been reported to be part of Behr Syndrome. We present the case of a 51-year-old man with a rare complicated dominant inherited cerebellar ataxia with accompanying visual loss and tremor (CICALVT) resembling a Behr Syndrome variant who suffered from advanced visual deterioration since childhood and progressive spastic paraparesis for 15 years. Furthermore, the patient presented increasing tremor of both hands for 5 years. The successful treatment of the tremor using deep brain stimulation (DBS) of the ventral intermediate thalamic nucleus (VIM) is reported. Our case indicates that deep brain stimulation of the ventral intermediate nucleus is an adequate operative intervention that can help to reduce tremor even in patients with complicated movement disorders.

[Spinal cord stimulation in Failed-Back-Surgery-Syndrome. Preliminary study for the evaluation of therapy by functional magnetic resonance imaging (fMRI)]. / Epidurale Rückenmarkstimulation bei Postnukleotomiesyndrom. Pilotstudie zur Therapieevaluation mit der funktionellen Magnetresonanztomographie (fMRT).

BACKGROUND: Spinal cord stimulation (SCS) is an effective alternative treatment in patients with chronic neuropathic pain and mainly radicular distribution. The aim of this prospective study was to investigate changes in BOLD signal with fMRI during active SCS and to correlate the results with the clinical pain intensity, measured with a visual analogue scale (VAS). PATIENTS AND METHODS: Three patients with failed back surgery syndrome were tested during the clinical trial of SCS. A first fMRI was performed with marked pain and a high VAS score. Before the second fMRI a therapeutic stimulation phase with pain reduction was carried out. RESULTS: With high pain levels SCS activated the cingulate gyrus, thalamus, prefrontal cortex, supplementary motor area and postcentral gyrus. After pain reduction, SCS did not elicit these activations in the second fMRI, using the same stimulation parameters. CONCLUSIONS: In patients with chronic neuropathic pain and high VAS levels, SCS elicited BOLD activation in the cingulate gyrus, thalamus, prefrontal cortex, and primary and secondary somatosensory area. Pain reduction by SCS resulted in a reduction of functional activity in these areas as revealed by follow-up fMRI.

Acute posttraumatic paraplegia associated with asymptomatic thoracic meningioma.

A case of a patient with acute paraparesis after compression fracture of the twelfth vertebra with progressive neurological deterioration is reported. The occurrence of clinical asymptomatic thoracic meningioma and coincidence with posttraumatic compression fracture of the vertebra at the same level resulting in acute paraparesis is extremely rare.

Treatment of trigeminal neuralgia associated with multiple sclerosis: case report.

The incidence of trigeminal neuralgia (TN) in patients with multiple sclerosis is higher than in the general population. If pharmacologic therapy fails, invasive procedures in the gasserian ganglion are usually offered. Microvascular decompression is not routinely performed. The authors report a patient with persistent TN after repetitive trigeminal radiofrequency rhizotomy and finally successful microvascular decompression after demonstration of neurovascular compression with high-resolution MRI.

[MR volumetry of the trigeminal nerve in patients with unilateral facial pain]. / MR-Volumetrie des N. trigeminus bei Patienten mit einseitigen Gesichtsschmerzen.

PURPOSE: To assess whether MRI can detect atrophy of the trigeminal nerve in patients with trigeminal neuralgia. MATERIALS AND METHODS: A prospective MRI study was conducted in 39 patients (trigeminal neuralgia, trigeminal neuropathy, or atypical facial pain) and 25 volunteers. Using a coronal orientation (T1 Flash 3D; T2 CISS 3D), regions of interest were delineated in the cisternal part of the trigeminal nerve along the border of the nerve to calculate the volume of the nerve. The volume of the nerve was compared side-by-side in each patient (t-test, p < 0.05) and the volume difference compared between patients and volunteers. RESULTS: The volume of the compromised trigeminal nerve in patients with trigeminal neuralgia was lower than on the contralateral healthy side, with the difference between healthy and compromised side statistically significant (p < 0.05). In all other patients and in all volunteers, no significant difference was found between the volume of the healthy and compromised nerve. The volume difference between the healthy and compromised side in patients with trigeminal neuralgia was significantly higher (p < 0.05) than in all other patients and volunteers. CONCLUSION: Atrophy of the trigeminal nerve caused by a nerve-vessel conflict can be detected by MRI. Only patients with trigeminal neuralgia show this unilateral atrophy. Therefore, it is possible to demonstrate the result of the nerve-vessel conflict and to determine the consequences of such a conflict.

[Neurosurgical therapy of facial neuralgias]. / Neurochirurgische Therapie der Gesichtsneuralgien.

INTRODUCTION: Neuralgias of the face, especially trigeminal neuralgia and glossopharyngeal neuralgia are indications for surgical interventions after failed medical therapy. In contrast to other forms of headache or atypical facial pain, where surgical measures are considered to be contraindicated, percutaneous procedures or microvascular decompression are able to produce immediate and longstanding pain relief. Careful preoperative evaluation is essential to confirm the clinical diagnosis and to rule out other causes as multiple sclerosis or tumors afflicting the cranial nerves. The following study will summarize the common surgical techniques and their role considering a mechanism-based therapy as well as document long-term results of these measures. METHODS: Between 1977 and 1997 316 thermo-controlled radiofrequency trigeminal rhizotomies (TK) and 379 microvascular decompressions (MVD) were performed in our hospital to treat trigeminal neuralgia; additional 6 MVDs for glossopharyngeal neuralgia and one MVD of the intermediate facial nerve were carried out. Questionnaires were sent out to all patients still living in 1981, 1982, 1992 and 1998. For all other patients, interviews with relatives or the general practitioners were conducted. A retrospective analysis of postoperative pain relief was performed using Kaplan-Meier curves at the latest follow-up. Additionally 80 patients underwent careful quantitative sensory testing with Von-Frey-hairs. RESULTS: 225 patients who underwent microvascular decompression and 206 with radiofrequency trigeminal rhizotomies were further analyzed. There was a 50% risk for pain recurrence two years after radiofrequency rhizotomy. On the other hand 64% of patients who underwent microvascular decompression remained painfree 20 years postoperatively. Patients with microvascular decompression without sensory deficit were painfree significantly longer than patients with postoperative hypesthesia. DISCUSSION: Etiology and pathogenesis of facial neuralgias are far from understood despite several hypotheses. Based on current models there is no explanation for the immediate pain relief especially after microvascular decompression. Some authors even discuss surgical trauma as the only cause for postoperative pain relief.

Treatment of idiopathic trigeminal neuralgia: comparison of long-term outcome after radiofrequency rhizotomy and microvascular decompression.

OBJECTIVE: To evaluate the long-term outcome of patients after either percutaneous trigeminal rhizotomy or microvascular decompression (MVD) for idiopathic trigeminal neuralgia at a single institution. METHODS: From 1977 to 1997, 316 radiofrequency lesion procedures and 378 MVDs were performed. Questionnaires were sent to all patients who were alive in 1981, 1982, 1992, and 1998. For all other patients, interviews were conducted with their relatives and general practitioners. A retrospective comparative analysis was performed with Kaplan-Meier probability curves as of the latest follow-up date. In addition, 80 patients who underwent MVD were examined postoperatively with quantitative sensory measurements by use of von Frey hairs. RESULTS: Two hundred twenty-five patients who underwent MVD and 206 patients who underwent radiofrequency could be analyzed retrospectively in detail. Overall, there was a 50% risk for recurrence of pain 2 years after percutaneous radiofrequency rhizotomy. Conversely, 64% of patients who underwent MVD remained completely pain free 20 years postoperatively. Patients without sensory impairment after MVD were pain free significantly longer than patients who experienced postoperative hypesthesia or partial rhizotomy. CONCLUSION: Because it is curative and nondestructive, MVD is considered the treatment of choice for trigeminal neuralgia in otherwise healthy people. In our study, it proved to be a more effective and long-lasting procedure for patients with typical trigeminal neuralgia than radiofrequency rhizotomy. Patients without postoperative sensory deficit remained pain free significantly longer, which is a strong argument against the "trauma" hypothesis of this procedure.