Sadaquate Khan

Bilateral stimulation of the caudal zona incerta nucleus for tremor control.

Introduction: The ventrolateral (VL) nucleus of the thalamus is the commonly chosen target for deep brain stimulation (DBS) to alleviate tremor. However, it has a poor efficacy in alleviating proximal tremor and patients may develop tolerance to the action component of tremor. We performed bilateral stimulation of the caudal or motor part of the zona incerta nucleus (cZI) to determine its safety and efficacy in alleviating tremor. Methods: 5 patients with parkinsonian tremor and 13 with a range of tremors (Holmes (HT), cerebellar (CT), essential (ET), multiple sclerosis (MS) and dystonic tremor (DT)) affecting both the proximal and distal body parts underwent MRI guided, bilateral cZI DBS. Tremor was assessed by the Fahn–Tolosa–Marin (FTM) tremor scale at baseline and at a mean follow-up of 12 months. Results: Resting PD tremor improved by 94.8% and postural tremor by 88.2%. The total tremor score improved by 75.9% in 6 patients with ET. HT improved by 70.2%, proximal CT by 60.4% and proximal MS tremor by 57.2% in the total tremor rating score. In the single patient with DT, there was improvement in both the dystonia and the tremor. Patients required low voltages of high-frequency stimulation and did not develop tolerance to it. Stimulation-related side effects were transient. Conclusion This prospective study shows that the cZI may be an alternative target for the treatment of tremor with DBS. In contrast to bilateral DBS of the VL nucleus, it improves all components of tremor affecting both the distal and proximal limbs as well as the axial musculature.

The impact of low-frequency stimulation of the pedunculopontine nucleus region on reaction time in parkinsonism

Objectives Attentional augmentation and enhanced motor function are potential mechanisms by which stimulation of the region of the pedunculopontine nucleus (PPN) may improve gait in parkinsonism. Here, the authors assess the impact of stimulation of this region on attentional and motor aspects of reaction task performance in patients with parkinsonism. Methods Eleven patients implanted with PPN stimulators underwent computerised assessment of simple, choice and digit vigilance reaction tasks. Patients were assessed ‘off medication’ during stimulation at different frequencies (0 Hz, 5 Hz, 10 Hz and ‘therapeutic’ 20–35 Hz). There were two primary endpoints: ‘Speed of Reaction’ (sum of the mean task reaction times) and ‘Accuracy of Reaction’ (reflecting omissions and percentage of correct responses). Baseline performance was compared with age- and sex-matched healthy controls. Clinical effects of stimulation were assessed using the Unified Parkinsons Disease Rating Scale and a falls frequency scale. Results Compared with healthy controls, subjects had significant deficits in ‘Speed of Reaction’ and in all mean task reaction times. ‘Accuracy of Reaction’ was not different from healthy controls and did not improve with stimulation. ‘Speed of Reaction’ significantly improved with stimulation at therapeutic frequencies (20–35 Hz). Of the individual tasks, only simple reaction time improved significantly. Simple reaction time distribution analysis revealed a general speeding of responses rather than a selective reduction in outliers. Acute PPN stimulation improved gait and balance but not akinesia scores. Chronic PPN stimulation significantly improved falls frequency. Falls score improvement significantly correlated with changes to simple reaction time with therapeutic stimulation. Conclusion The pattern of reaction time improvement with stimulation of the PPN area suggests a benefit on motor performance, rather than augmentation of attention.

Comparison of atlas- and magnetic-resonance-imaging-based stereotactic targeting of the subthalamic nucleus in the surgical treatment of Parkinson's disease.

Aims: To assess the variability of the subthalamic nucleus (STN) size, orientation and target coordinates from direct visualization on high-resolution magnetic resonance (MR) images in patients undergoing surgical intervention for Parkinson’s disease. Methods: Sixty-six patients with Parkinson’s disease were included in this study. The STN was visualized directly on high-resolution MR images, the size and orientation in both coronal and axial planes were recorded, as were the coordinates of the dorsolateral STN target in relation to the anterior-posterior commissural (AC-PC) line. The same STN target was defined in the Schaltenbrand atlas and atlas-based coordinates in proportion to the patient’s AC-PC dimension were calculated. MR-imaging-based STN target coordinates were compared with the corresponding atlas-based coordinates. Results: Marked variation of STN size and orientation was observed. A significant difference was demonstrated on comparing left- and right-sided x and y coordinates. The comparison between MR-imaging-based and atlas-derived target coordinates demonstrated a significant difference in all directions except the left y coordinate. Conclusions: This study demonstrates the substantial individual variability of STN size, orientation and target coordinates and a significant difference between target coordinates obtained by direct visual targeting on MR images and those obtained by indirect targeting based on atlases.

Outcomes from stimulation of the caudal zona incerta and pedunculopontine nucleus in patients with Parkinson's disease

Introduction. Axial symptoms including postural instability, falls and failure of gait initiation are some of the most disabling motor symptoms of Parkinsons disease (PD). We performed bilateral deep brain stimulation (DBS) of the pedunculopontine nucleus (PPN) in combination with the caudal zona incerta (cZi) in order to determine their efficacy in alleviating these symptoms. Methods. Seven patients with predominant axial symptoms in both the ‘on’ and ‘off’ medication states underwent bilateral cZi and PPN DBS. Motor outcomes were assessed using the motor component of the Unified Parkinsons Disease Rating Scale (UPDRS 3) and a composite axial subscore was derived from items 27, 28, 29 and 30 (arising from chair, posture, gait and postural stability). Quality of life was measured using the PDQ39. Comparisons were made between scores obtained at baseline and those at a mean follow-up of 12 months. Results. In both the off and on medication states, a statistically significant improvement in the UPDRS part 3 score was achieved by stimulation of the PPN, cZi and both in combination. In the off medication state, our composite axial subscore of the UPDRS part 3 improved with stimulation of the PPN, cZi and both in combination. The composite axial subscore, in the ‘on’ medication state, however, only showed a statistically significant improvement when a combination of cZi and PPN stimulation was used. Conclusions. This study provides evidence that a combination of PPN and cZi stimulation can achieve a significant improvement in the hitherto untreatable ‘on’ medication axial symptoms of PD.

Neuralgia of the glossopharyngeal and vagal nerves: long-term outcome following surgical treatment and literature review

This study describes our experience in the surgical treatment of neuralgia of the glossopharyngeal and vagal nerves. Over the last 19 years, 21 patients underwent surgery. Their case notes were reviewed to obtain demographic information, clinical presentation, surgical findings and early results. All patients were then contacted by telephone for long-term results and complications. Independent analysis of results was carried out by a Neurology team. Ten patients had microvascular decompression (MVD). Four patients had MVD and nerve section. In the remaining seven patients, the glossopharyngeal and first two rootlets of the vagal nerve were sectioned. Nineteen (90%) of 21 patients experienced complete relief of pain immediately after surgery. The remaining patients reported an improvement in their symptoms. There were no mortalities. Four patients experienced short-term complications, which resolved. Two patients were left with a persistent hoarse voice. At follow-up (mean duration of 4 years), there was no recurrence in symptoms. In our experience, surgery is safe and effective for the treatment of vago-glossopharyngeal neuralgia.

Deep brain stimulation relieves refractory hypertension

Increased activity of the sympathoadrenal system plays a major role in the pathogenesis of essential hypertension and end organ damage.1,2 Recent effective antihypertensive strategies have manipulated autonomic nervous control mechanisms including renal nerve ablation.1 Here, we present the first patient in whom refractory hypertension was controlled chronically with deep brain stimulation (DBS) of the ventrolateral periaqueductal gray (PAG)/periventricular gray (PVG) as a primary response and not secondary to associated pathologic changes. ### Level of evidence. This study provides Class IV evidence that chronic electrical stimulation of the PAG/PVG may provide effective treatment for controlling blood pressure in patients with drug-resistant hypertension. ### Case report. A 55-year-old man developed left-sided weakness, and an ischemic stroke affecting the internal capsule was diagnosed (figure e-1A on the Neurology ® Web site at www.neurology.org). At hospital admission, hypertension and hypercholesterolemia were diagnosed. In the peristroke period, blood pressure readings ranged from 265/96 to 153/89 mm Hg, and antihypertensive medication was prescribed: atenolol (50 mg), diltiazem (240 mg), perindopril (4 mg), and indapamide (1.25 mg). Aspirin (75 mg) and simvastatin (40 mg) were also prescribed. This medication regimen maintained his blood pressure at 145/69 mm Hg. Four months later, subsequent to multiple dose increases in the quadruple therapy, his blood pressure ranged from 153/87 to 134/72 mm Hg. Unfortunately, although his hemiplegia resolved, he developed a severe left-sided hemibody central pain syndrome that proved refractory to treatment over the following 3 years, leading to referral for DBS to treat his pain. With use of established protocols3 and a MRI-guided stereotactic technique, the PAG/PVG region was …

High frequency stimulation of the mamillothalamic tract for the treatment of resistant seizures associated with hypothalamic hamartoma

We investigate the clinical outcome from stimulation of the mamillothalamic tract in two patients with intractable epilepsy secondary to hypothalamic hamartomas. One patient has a left‐sided and the other a right‐sided tumor. Both patients presented with a history of gelastic and complex partial seizures resistant to multiple antiepileptic drugs. Both patients underwent insertion of a single deep brain‐stimulating electrode ipsilateral to the site of the tumor, lying adjacent to the mamillothalamic tract. Postoperatively they both had a significant reduction in seizure frequency, with one patient being seizure free for the last 10 months. An improvement in mood was reported by the patient’s primary carers and demonstrated on quality of life questionnaires.

Bilateral caudal zona incerta nucleus stimulation for essential tremor: outcome and quality of life

Background Over the past few years, bilateral stimulation of the caudal or motor part of the zona incerta nucleus (cZI) has been performed by the authors in patients with essential tremor (ET). Outcomes including quality of life data in 15 patients with a follow-up period of up to 84 months (mean 31.7±28.6 months) are presented. Methods 15 consecutive ET patients underwent MRI guided bilateral cZI deep brain stimulation implantation. Patients were assessed by applying the Fahn–Tolosa–Marin Tremor Rating Scale and the Short Form Health Survey-36 (SF-36) to assess quality of life. Results The total tremor score improved by 73.8% (p<0.0001). The part A score (items 1–9) improved by 86.6% (p<0.0001). Postural tremor improved by 88.2% (p<0.0001) and action tremor by 82.2% (p<0.0001). The part B score, which evaluates the functional activities of the upper limbs, improved by 60.1% (p<0.0001). Part C score, which evaluates the activities of daily living, improved by 80.0% (p<0.0001). The SF-36 physical component score improved by 23.7% (p<0.0001) and the mental component score by 22.4% (p<0.0001). There was one wound infection and three patients developed stimulation related transient dysarthria. None developed any disequilibrium or tolerance to stimulation. Conclusion Bilateral cZI stimulation is safe and effective in suppressing the postural and action component of ET. It is associated with a low incidence of stimulation related complications and patients do not develop tolerance to stimulation with maintained clinical benefit over a follow-up period of up to 7 years.

Clinical outcomes from bilateral versus unilateral stimulation of the pedunculopontine nucleus with and without concomitant caudal zona incerta region stimulation in Parkinson's disease

Abstract Introduction. The Pedunculopontine nucleus is a novel target for deep brain stimulation and this may improve postural instability and gait dysfunction in Parkinsons disease. If unilateral Pedunculopontine nucleus stimulation is as efficacious as bilateral stimulation this would lead to less surgical risk. Methods. 5 Parkinsons disease patients with bilateral caudal Zona Incerta region and Pedunculopontine nucleus electrodes were assessed using the motor component of the Unified Parkinsons Disease Rating Scale. Patients were assessed in the on-medication state to determine the optimal combination of stimulation setting for axial symptom control. Results. The on-medication composite axial-subscore only showed a statistically significant improvement when bilateral Pedunculopontine nucleus and caudal Zona Incerta region stimulation was used. Conclusions. In the on-medication state bilateral Pedunculopontine nucleus and caudal Zona Incerta region stimulation is required in order to produce a significant change in the motor Unified Parkinsons Disease Rating Scale axial-subscore from baseline.

Long-term effectiveness and tolerability of vagal nerve stimulation in adults with intractable epilepsy: a retrospective analysis of 100 patients

Abstract Data for 100 vagal nerve stimulation (VNS) patients were collected and analysed retrospectively. The mean seizure reduction was 17.86% (n = 67) at 6 months, 26.21% (n = 63) at 1 year, 30.43% (n = 53) at 2 years, 48.10% (n = 40) at 3 years, 49.44% (n = 32) at 4 years, 50.52% (n = 35) at 5 years, 45.85% (n = 31) at 6 years, 62.68% (n = 25) at 8 years, 76.41% (n = 9) at 10 years, 82.90% (n = 4) at 12 years. Evidence of statistical significance for mean seizure reduction over time was strong with all p values less than 0.05 except at 12 years (p = 0.125) where the sample size was small (n = 4). Mean seizure reduction was 49.04% and 51 (51%) patients were considered responders, defined as a 50% or more reduction in seizure frequency. Twenty-one (21%) patients suffered surgical complications. Of these 15 patients were self-limiting and 6 patients were irreversible or required a device revision. Fifty patients (50%) suffered from side-effects, while vagal stimulation cycled on (VNS on) post-operatively. However, of these, only one patient suffered from intolerable side effects requiring the device to be switched off temporarily. This study demonstrates the long-term efficacy in seizure reduction with the use of VNS. Complication rates and tolerability did not deviate greatly from that previously reported, indicating that VNS is a safe and effective treatment for seizure reduction in intractable epilepsy.