Rosalind Mitchell

Deep brain stimulation of the subthalamic nucleus for advanced Parkinson disease using general anesthesia: long-term results.

OBJECT The authors analyze long-term outcome in a substantial number of patients who underwent subthalamic nucleus (STN) deep brain stimulation (DBS) surgery under general anesthesia. METHODS Eighty-two patients underwent bilateral placement of DBS electrodes under general anesthesia for advanced Parkinson disease; the STN was the target in all cases. All patients underwent intraoperative microelectrode recording of the STN. No intraoperative macrostimulation was performed. Unified Parkinsons Disease Rating Scale (UPDRS) data were recorded in 28 patients. Assessment of outcome was performed using the UPDRS (in 28 cases), the electrophysiological recordings (in all 82 cases), medication reduction (in 78 cases), and complications (in 82 cases). RESULTS There was improvement in UPDRS scores across all measures following surgery. The total UPDRS score, off medication, improved from 68.78 (geometrical mean, 95% CI 61.76-76.60) preoperatively to 45.89 (geometrical mean, 95% CI 34.86-60.41) at 1 year postoperatively (p = 0.003, data available in 26 patients). Improvements were obtained in UPDRS Part II (Activities of Daily Living) off medication (p = 0.001) and also UPDRS Part III (Motor Examination) off medication (p < 0.001). Results for the on-medication and on-stimulation states also showed a statistically significant improvement for UPDRS Part III (p = 0.047). Good microelectrode recording of the STN was obtained under general anesthesia; the median first-track length was 4.0 mm, and the median number of tracks passed per patient was 3.0. The median reduction in levodopa medication was 58.1% (interquartile range 42.9%-73.3%). One patient had an intracerebral hemorrhage in the track of 1 electrode but did not require surgical evacuation. One patient had generalized convulsive seizures 24 hours postoperatively and was intubated for seizure control. Unified Parkinsons Disease Rating Scale scores were obtained in 26 patients at 1 year, 28 patients at 3 years, 17 at 5 years, and 7 at 7 years postoperatively. Up to 7 years postoperatively, there was sustained improvement in the total UPDRS score. The results in these patients showed minimal deterioration in the motor section of the UPDRS over time, up to 7 years following the operation. The authors found no evidence that the UPDRS Part II scores changed significantly over the period of 1-7 years after surgery (p = 0.671, comparison of mean scores at 1 and 7 years using generalized estimating equations). CONCLUSIONS Long-term outcomes confirm that it is both safe and effective to perform STN DBS under general anesthesia. As part of patient choice, this option should be offered to all DBS candidates with advanced Parkinson disease to enable more of these patients to undergo this beneficial surgery.

An approach to deep brain stimulation for severe treatment-refractory Tourette syndrome: the UK perspective

Deep brain stimulation (DBS) is an emerging therapeutic option for severe, treatment-resistant Tourette Syndrome (TS), with about 40 cases reported in the scientific literature over the last decade. Despite the production of clinical guidelines for this procedure from both European and USA centres, a number of unresolved issues still persist, mainly in relation to eligibility criteria and brain targets. The present article illustrates the UK perspective on DBS in TS and proposes consensus-based recommendations for double-blind controlled trials.

Deep brain stimulation improves survival in severe Parkinson's disease.

Objectives Levodopa and other dopaminergic treatments have not had the expected effect on survival in Parkinsons disease (PD). Bilateral subthalamic nucleus deep brain stimulation (STN-DBS) has been shown to improve motor function, motor fluctuations, health-related quality of life, and to reduce medication usage and drug-induced dyskinesia in patients with severe PD refractory to medical therapy. Little however, has been described on the impact of STN-DBS on the survival of these patients. We aim in this study to examine the impact of STN-DBS on the survival of patients with severe PD. Methods Patients who were eligible for STN-DBS were given the choice of undergoing surgery or continuing on medical treatment. Those who exercised patient choice and preferred to continue with medical treatment formed a control population. All eligible patients seen in a 10-year period are included in this study. Our primary outcome measure is a difference in mortality between the two groups with a secondary measure of admission rates to residential (nursing home) care. Results 106 patients underwent STN-DBS, and 41 patients exercised patient choice and declined the procedure. The two groups were matched for age, gender, ethnicity, duration of disease, rates of pre-existing depression and Levodopa equivalent doses of anti-Parkinsons medications taken. Patients undergoing STN-DBS had significantly longer survival and were significantly less likely to be admitted to a residential care home than those managed purely medically. The statistical significance of these findings persisted after adjusting for potential confounding factors (survival: p=0.002, HR 0.29 (0.13 to 0.64) (residential care home admission: OR: 0.1 (95% CI 0.0 to 0.3; p<0.001). Interpretation We show for the first time that there is a survival advantage of DBS surgery in advanced PD. The effect of potential bias factors is examined. The survival advantage may arise for several postulated reasons, ranging from improvement in axial functions, such as swallowing, to some as yet unrecognised benefit of reduction in dopaminergic medication. These findings are of great interest to both patients with PD and the health professionals considering the treatment options for patients with severe PD.

Percutaneous glycerol rhizotomy for trigeminal neuralgia: safety and efficacy of repeat procedures

Percutaneous glycerol rhizotomy (PGR) is an established technique to treat trigeminal neuralgia. Our aim was to establish how safe and efficacious repeat glycerol rhizotomies were on a study of 179 PGRs performed in our institution. There was an overall success rate of 92.1% in improvement of facial pain. Nine patients had reduced facial sensation post-operatively. There were no cases of anaesthesia dolorosa. The mean time to repeat injection was 22.9 months (1–108 months). Of those requiring repeat glycerol rhizotomies within 6 months, 23% had multiple sclerosis. There was no evidence that the number of repeat glycerol rhizotomies affects the probability of them having a complication (p = 0.87). Glycerol rhizotomy for trigeminal neuralgia is a safe and efficacious method of pain relief, which is particularly useful in the elderly. It can be repeated many times with no increase in morbidity and most importantly, in our practice, no anaesthesia dolorosa.

Haemorrhagic cerebellar fibrous histiocytoma: case report and literature review.

Malignant fibrous histiocytoma is uncommon within the central nervous system. It is a pleomorphic sarcoma originally found in soft tissue1 and there are few reported cases within the central nervous system, in particular the cerebellum. This tumour is difficult to diagnose and may be difficult to treat. We present a case of cerebellar malignant fibrous histiocytoma, its management and literature review.

Subthalamic nucleus microelectrode recordings (MER) can be reliably detected despite general anaesthesia and dopaminergic treatment.

Dear Editor, We would like to thank Dr. Israel for his interest in our paper, BThe effect of dopaminergic therapy on intraoperative microelectrode recordings for subthalamic deep brain stimulation under GA: can we operate on patients ‘on medications’?^ [1]. We would respectfully disagree with Dr. Israel’s opinions in the following regards. In particular, we would disagree that the adopted endpoints are inappropriate. In addition to examining two standard neurophysiological parameters, we have reported on significant clinical markers, including changes in a disability scale, the Boff^ phase duration, alteration in dyskinesia and changes in dopaminergic medication (LEDD), and have also reported on adverse clinical effects. It remains unclear as to which of these outcome measures Dr. Israel considers Binappropriate^. No literature has been cited to support this assertion. The number of tracks and the length of microelectrode recording (MER) are surrogates for the quality of intraoperative microelectrode recording, which Dr. Israel argues would be compromised by both general anaesthesia (GA) and the continuation of dopaminergic therapy. Whilst evidence is cited to support the former there is no literature cited to support the latter contention. Our group has shown good long-term outcomes in patients treated under GA [4, 9] and others have reported equally good outcomes, particularly using low-dose propofol infusions [5, 6]. Failure to obtain a satisfactory subthalamic nucleus (STN) MER for a minimum of 3 mm is (in our practice) an indication for inserting further recording electrodes. Multiple electrode penetrations is correlated with increased risk of intracerebral haemorrhage [2]. Hence, it is of particular significance to examine the effect of any change in practice using these standard quantifiable and reproducible endpoints that can be correlated to the procedure’s effectiveness and safety. Whilst we accept that the role of intraoperative neurophysiological mapping is debated by some functional neurosurgeons, we would disagree that BMost surgeons who have turned to using GA have done so in the realization that MER in their hands did not improve outcome and they could therefore rely on imaging alone^. We would welcome sight of the evidence that supports this statement. The current study demonstrates that the boundaries of the STN can be identified clearly (in our hands) under GA, even in patients on dopaminergic medications. Centres experienced in intraoperative MER for target refinement have been able to demonstrate significant target adjustment compared to anatomical localisation alone [3] and there are suggestions of a better clinical outcome compared with ‘pure’ anatomical localisation and intraoperative testing [8]. The correlation between beta-oscillations and pathological STN activity is a very interesting area. Whilst we acknowledge that there is some evidence suggesting that dopaminergic treatment modulates the STN electrical activity (reducing beta-oscillations), it must be highlighted that the electrical activity picked up by MER is not solely comprised of betaoscillations but includes other local field potentials of differing frequencies [7]. Indeed, the heart of our paper is that, theoretical considerations aside, we can obtain useful MER data to guide the electrode placement even in patients who continued dopaminergic treatment. Assuming that dopaminergic treatment might completely suppress the STN-specific electrical activity, one would expect patients who continued treatment and underwent STN DBS under GA not to have satisfactory STN MER intraoperatively, requiring multiple brain recording tracks and not * Mohammed Asha mohammedjamil80@yahoo.com

P.08 Low dose L-dopa induced dystonic dyskinesia in Parkinson's disease patients with deep brain stimulation

L-dopa given to Parkinsons disease (PD) patients for prolonged periods or at sustained high doses is known to produce disabling choreiform and dystonic dyskinesias. The production of dystonic dyskinesias at small doses in patients with deep brain stimulation surgery (DBS) has been poorly reported. We present a case series of 13 patients who tolerated high doses of l-dopa prior to DBS, who subsequently developed severe disabling dystonic dyskinesias on minimal doses of l-dopa after surgery. Of the 13 patients (7 male, 6 female), mean age was 54 (range 46–63), and mean disease duration was 10 years (range 6–17). 11 patients had presented with tremor as their first motor symptom of PD, and 10 had developed dyskinesias prior to surgery. At time of DBS the mean calculated L-dopa equivalent dose was 1073 mg (range 480–1566.7 mg) of which the mean l-dopa dose was 581 mg (range 300–1350 mg). The mean time from DBS to develop dystonic dyskinesias was 3 years (range 0.3–5 years), at which time the mean l-dopa equivalent dose was 366 mg (range 50–660 mg) and the mean l-dopa dose was 196 mg (range 50–600). Replacing l-dopa with a dopamine agonist either removed or largely relieved this motor complication. This case series highlights an important motor complication in the DBS PD patient and suggests one method to ameliorate it. It also raises important questions about the mechanism for reduction of dyskinesia threshold following DBS.

Battery Longevity Comparison of Two Commonly Available Dual Channel Implantable Pulse Generators Used for Subthalamic Nucleus Stimulation in Parkinson’s Disease

Objectives: Deep brain stimulation for Parkinson’s disease (PD) utilises an implantable pulse generator (IPG) whose finite lifespan in non-rechargeable systems necessitates their periodic replacement. We wish to determine if there is any significant difference in longevity of 2 commonly used IPG systems; the Medtronic Kinetra, and the Medtronic Activa Primary Cell (PC), which has come to replace it. Methods: All patients with bilateral Subthalamic Nucleus stimulators for PD performed in our centre were included. Battery life was then assessed using a Kaplan-Meier approach and comparisons between the Kinetra and Activa PC batteries were performed using log-rank tests. Results: Complete data was available for 183 patients. There was a significant difference in the average battery duration with an estimated median battery life in the Kinetra cohort of 6.6 years (95% CI 6.4–6.7), compared to 4.5 years (95% CI 4.4–4.5) in the Activa PC cohort (p < 0.001). Conclusion: The Activa PC IPG demonstrates a significantly reduced battery life of 2.1 years, with a median battery life of 4.5 years in comparison to 6.6 years in the Kinetra IPG. Future technology developments should therefore be focused on improving the battery life of the newer IPG systems.

SUBTHALAMIC NUCLEUS DEEP BRAIN STIMULATION AND APATHY IN PATIENTS WITH PARKINSON'S DISEASE

Objective Apathy has been reported as a possible adverse effect of deep brain stimulation of the subthalamic nucleus (STN-DBS). We investigated the prevalence and severity of apathy in 22 patients with Parkinsons disease (PD) who underwent STN-DBS and the effects on quality of life (QOL). Method All patients were assessed with the Lille Apathy Rating Scale (LARS), the Apathy Scale (AS) and the Parkinsons Disease Questionnaire and were compared to a control group of 38 patients on pharmacotherapy alone. The relationship between apathy and clinico-demographic variables was explored through correlation analysis. Results Apathy was reported by a similar proportion of patients in the two groups: 18.4% in the DBS group and 22.7% in the control group according to LARS ratings; 45.5% in the DBS group and 42.1% in the control group according to AS ratings. There was no significant difference in apathy or QOL ratings between the two groups. Significant correlations were observed between poorer QOL and degree of apathy, as measured by the LARS (p<0.001) and AS (p=0.021). PD-related disability also correlated with both apathy ratings (p><0.001 and p=0.017, respectively). Conclusion Our findings suggest that STN-DBS is not associated with changes in apathy in the PD population, as there was no difference in prevalence or severity of apathy between patients who had undergone STN-DBS and those on pharmacotherapy alone. More severe apathy was associated with a higher level of disability due to PD and worse QOL in PD but no other clinico-demographic characteristics.

P.07 The role of amantadine in motor complications after deep brain stimulation for Parkinson's disease

Subthalamic deep brain stimulation (STN DBS) for Parkinsons disease typically enables a 50% reduction in dopaminergic medication postoperatively. This reduction in medication is accompanied by a 60% reduction in dyskinesia and a reduction in off periods. However, there remains a subgroup of patients who have disabling dyskinesias despite optimisation of drug and stimulator setting. Amantadine is sometimes used for the medical management of drug-induced dyskinesias in Parkinsons disease. Its use in dyskinesias after DBS has not been formally assessed. We report a series of 8 cases who had bilateral STN DBS. These patients had similar characteristics to our local database of patients who have had DBS. However, these patients had disabling bradykinesia and/or dyskinesias despite attempts at optimisation of stimulator settings and dopaminergic medication. The addition of amantadine led to clear improvements in dsykinesias and/or mobility, without the need to increase the total dose of dopaminergic medication. Stopping amantadine caused worsening of symptoms. This case series suggests amantadine is an important additional medication in the small group of patients whose disease has not been stabilised after DBS. The outflow of the STN includes a glutamatergic pathway. The glutamate receptor blocking properties of amantadine provide a possible mechanism for the observed benefit. We plan to extend the results of this case series to include objective scoring in subsequent patients.