Long-term outcome of deep brain stimulation in generalised dystonia: a series of 60 cases.

BACKGROUND: There is solid evidence of the long term efficacy of deep brain stimulation of the globus pallidus pars interna in the treatment of generalised dystonia. However there are conflicting reports concerning whether certain subgroups gain more benefit from treatment than others. We analysed the results of a series of 60 cases to evaluate the effects of previously proposed prognostic factors including dystonia aetiology, dystonia phenotype, age at onset of dystonia, and duration of dystonia prior to treatment. METHODS: 60 patients with medically intractable primary or secondary generalised dystonia were treated with deep brain stimulation of the globus pallidus pars interna during the period 1999-2010 at the Department of Neurosurgery in Oxford, UK. Patients were assessed using the Burke-Fahn-Marsden (BFM) Dystonia Rating Scale prior to surgery, 6 months after implantation and thereafter at 1 year, 2 years and 5 years follow-up. RESULTS: The group showed mean improvements in the BFM severity and disability scores of 43% and 27%, respectively, by 6 months, and this was sustained. The results in 11 patients with DYT gene mutations were significantly better than in non-genetic primary cases. The results in 12 patients with secondary dystonia were not as good as those seen in non-genetic primary cases but there remained a significant beneficial effect. Age of onset of dystonia, duration of disease prior to surgery, and myoclonic versus torsional disease phenotype had no significant effect on outcome. CONCLUSIONS: The aetiology of dystonia was the sole factor predicting a better or poorer outcome from globus pallidus pars interna stimulation in this series of patients with generalised dystonia. However even the secondary cases that responded the least well had a substantial reduction in BFM scores compared with preoperative clinical assessments, and these patients should still be considered for deep brain stimulation.

Deep brain stimulation for tremor resulting from acquired brain injury.

OBJECTIVES: To evaluate the efficacy of deep brain stimulation (DBS) in the treatment of tremor resulting from acquired brain injury (ABI). METHODS: A series of eight consecutive patients with post-ABI tremor were treated with DBS of the ventro-oralis posterior (VOP)/zona incerta (ZI) region, and subsequently underwent blinded assessments using Bain's tremor severity scale. RESULTS: VOP/ZI DBS produced a mean reduction in tremor severity of 80.75% based on Bain's tremor severity scale, with significant reductions in all five component tremor subscores: rest, postural, kinetic, proximal and distal. No adverse neurological complications were reported, although one patient experienced exacerbation of pre-existing gait ataxia. CONCLUSION: VOP/ZI stimulation is demonstrated here to be an effective and safe approach for the treatment of post-ABI tremor in the largest series published at the time of writing.

Diagnostic and prognostic markers in gliomas - an update.

Gliomas are the most common primary central nervous system tumour seen in adults. There have been many advances over the last two decades as we widen our search for a molecular basis of gliomagenesis. Many biomarkers have been discovered to be important in the management of gliomas, including 1p19q co-deletion, MGMT promoter methylation, BRAF and IDH1 mutations. In this review, we attempt to summarise the available literature on these biomarkers and their use in the diagnosis and management of gliomas. We pay special attention to the recently discovered IDH1 mutation, which is already proving to be a valuable new marker for favourable prognosis and may also indicate a greater response to therapy. 1p19q co-deletions have been shown to delineate a clinically distinct tumour type and are now routinely tested for in certain situations and can help direct treatment. MGMT promoter methylation is one of the most commonly studied biomarkers in gliomas. It has been shown to be a strong positive prognostic marker in gliomas, with positive tumours being more sensitive to chemotherapy. However, a lack of alternatives means that it is not yet a routine mutation tested for clinically. BRAF mutations are new markers found in pilocytic astrocytomas. Although the prognostic value of such mutations is not yet known, they may play a significant role in the diagnosis and treatment of such tumours. IDH1 mutations are 'the new kid on the block' and seem to play a central role in the pathogenesis of gliomas. They represent an independent and favourable prognostic marker and are a new molecular marker for disease diagnosis. Its role in determining response to chemotherapy is still controversial but with further study, IDH1 mutations may prove to be an invaluable marker in the management of gliomas.

Deep brain stimulation of the pedunculopontine nucleus in Parkinson's disease. Preliminary experience at Oxford.

Deep brain stimulation (DBS) of the pedunculopontine nucleus (PPN) is a novel neurosurgical therapy developed to address symptoms of gait freezing and postural instability in Parkinson's disease and related disorders. Here, we summarize our non-human primate and neuroimaging research of relevance to our surgical targeting of the PPN. We also describe our clinical experience of PPN DBS with greatest motor improvements achieved by stimulation at low frequencies.

Proposals for the management of gastrointestinal stromal tumours of the stomach.

BACKGROUND AND AIMS: It has been reported that gastric gastrointestinal stromal tumours (GIST) are aggressive, rare and difficult to treat. Some have advocated radical resection as the only potential cure. We present data to support treatment of gastric GISTs with a limited surgical approach and minimal morbidity. Furthermore, we propose that surveillance for recurrence is unnecessary based upon the follow-up of a cohort of patients with gastric GISTs. METHODS: Database and case notes analysis of 20 patients diagnosed with gastric GIST (1998-2004) and managed by one surgeon in a single centre over seven years. Main outcome measures were inpatient adverse events, positive resection margins and symptom free survival. OUTCOMES: Three cases have been managed with surveillance only. Successful resection was performed in 17 patients without mortality. No patient had positive margins on histological assessment. Fifteen out of seventeen samples were positive for the c-Kit proto-oncogene (CD117) and 14117 positive for CD34. Only two patients required en-bloc resections due to the tumour size and involvement of adjacent structures. One patient developed metastatic disease during follow-up of 19-86 months. CONCLUSIONS: We recommend local excision of gastric GISTs to allow macroscopically clear margins. This policy then allows symptomatic follow-up due to the indolent nature of the majority of the tumours resected. A tailored follow-up with endoscopy and radiological imaging has been advocated by others but appears unnecessary in most cases. Imatinib (anti c-Kit) can now be offered to patients presenting with recurrent GIST, if further surgery is deemed inappropriate.

Using magnetoencephalography to investigate brain activity during high frequency deep brain stimulation in a cluster headache patient.

PURPOSE: Treatment-resistant cluster headache can be successfully alleviated with deep brain stimulation (DBS) of the posterior hypothalamus [1]. Magnetoencephalography (MEG) is a non-invasive functional imaging technique with both high temporal and high spatial resolution. However, it is not known whether the inherent electromagnetic (EM) noise produced by high frequency DBS is compatible with MEG. MATERIALS AND METHODS: We used MEG to record brain activity in an asymptomatic cluster headache patient with a DBS implanted in the right posterior hypothalamus while he made small movements during periods of no stimulation, 7 Hz stimulation and 180 Hz stimulation. RESULTS: We were able to measure brain activity successfully both during low and high frequency stimulation. Analysis of the MEG recordings showed similar activation in motor areas in during the patient's movements as expected. We also observed similar activations in cortical and subcortical areas that have previously been reported to be associated with pain when the patient's stimulator was turned on or off [2,3]. CONCLUSION: These results show that MEG can be used to measure brain activity regardless of the presence of high frequency deep brain stimulation.

Dose-related effect of sevoflurane sedation on higher control of eye movements and decision making.

BACKGROUND: Saccadic latency may provide an objective method to assess sedative doses of anaesthetic on cortical oculomotor mechanisms and decision making. METHODS: We tested the effects of random doses of 0, 0.1, 0.2 and 0.3 MAC sevoflurane in six subjects, in a double-blind study using two measures of behavioural impairment: saccadic latency and stop signal reaction time (SSRT) in a countermanding task. RESULTS: Saccadic latency and SSRT both increased with increasing doses of sevoflurane. In both measures, reciprocal reaction time was linearly related to dose in each subject: all but two of the twelve regression coefficients were statistically significant (P<0.05). In one subject, SSRT was significantly more sensitive than simple latency (P<0.05); for the others there was no significant difference. CONCLUSION: Measurements of this kind could potentially provide estimates of cortical effects of sevoflurane sedation, and give a clinically useful measure of cognitive fitness.