Selective deep brain stimulation in the substantia nigra reduces myoclonus in progressive myoclonic epilepsy: a novel observation and short review of the literature

We report the case of a patient suffering from pharmacotherapy‐resistant bilateral progressive myoclonic epilepsy (PME) showing a beneficial response upon selective deep brain stimulation (DBS) of the substantia nigra pars reticulata. As an individual experimental therapeutic approach, we implanted DBS electrodes in the transitional zone between the subthalamic nucleus (STN) and the substantia nigra pars reticulata (SNr). Electrode placement allowed for a selective stimulation of either the STN, SNr, or both targets. Postoperatively, we observed a moderate subjective and objective improvement in positive and negative myoclonus by high‐frequency DBS of the STN/SNr transitional zone. However, a systematic exploration of different stimulation settings revealed that monopolar stimulation of the substantia nigra alone was more effective than high‐frequency monopolar DBS of either the motor STN (monopolar) or stimulation of both targets (STN/SNr). This observation confirms earlier findings showing that patients with PME benefit from high‐frequency DBS. However, in contrast to previous reports stimulating the STN/SNr transitional zone, our patient showed the most significant effect upon selective stimulation of the SNr. We propose that in patients undergoing DBS for myoclonus, at least one electrode contact should be placed in the SNr allowing for selective monopolar stimulation of this target.     

Frequency matters: beta‐band subthalamic nucleus deep‐brain stimulation induces Parkinsonian‐like blink abnormalities in normal rats

The synchronized beta‐band oscillations in the basal ganglia‐cortical networks in Parkinson's disease (PD) may be responsible for PD motor symptoms or an epiphenomenon of dopamine loss. We investigated the causal role of beta‐band activity in PD motor symptoms by testing the effects of beta‐frequency subthalamic nucleus deep‐brain stimulation (STN DBS) on the blink reflex excitability, amplitude, and plasticity in normal rats. Delivering 16 Hz STN DBS produced the same increase in blink reflex excitability and impairment in blink reflex plasticity in normal rats as occurs in rats with 6‐hydroxydopamine lesions and patients with PD. These deficits were not an artifact of STN DBS because, when these normal rats received 130 Hz STN DBS, their blink characteristics were the same as without STN DBS. To demonstrate that the blink reflex disturbances with 16 Hz STN DBS were frequency specific, we tested the same rats with 7 Hz STN DBS, a theta‐band frequency typical of dystonia. In contrast to beta stimulation, 7 Hz STN DBS exaggerated the blink reflex plasticity as occurs in focal dystonia. Thus, without destroying dopamine neurons or blocking dopamine receptors, frequency‐specific STN DBS can be used to create PD‐like or dystonic‐like symptoms in a normal rat.     

Bilateral subthalamic nucleus deep brain stimulation in a patient with cervical dystonia and essential tremor.

The role of subthalamic nucleus (STN) deep brain stimulation (DBS) is well established in Parkinson's disease, but experience with STN DBS in other movement disorders is limited. We report on a patient with medically refractory cervical dystonia and essential tremor resulting in dystonic head tremor and action tremor of the hands who obtained complete tremor suppression and near resolution of her cervical dystonia with bilateral STN stimulation. The results in this case demonstrate that STN DBS can dramatically improve dystonia and tremor in nonparkinsonian movement disorders.     

Evaluation of the efficacy of deep brain stimulation in the surgical treatment of cervical dystonia

ObjectiveDeep brain stimulation (DBS) of the globus pallidus internus (GPi) is a promising therapeutic option for patients with medically refractory dystonia. We present the results after 1 year of DBS of the GPi in 4 patients with cervical dystonia.Materials and methodsFour patients with medically refractory cervical dystonia who underwent stereotactic pallidal DBS surgery between June 2010 and November 2011 were included in this retrospective study. Preoperative and postoperative evaluations at 3, 6 and 12 months after surgery were performed using the Toronto Western Spasmodic Torticollis Rating Scale (TWSTRS).ResultsThe 4 patients experienced a sustained improvement, with a mean TWSTRS reduction of 74.25%, at 12 months follow-up. Disability improved by 80.5% (mean) at 1 year follow-up. No stimulation-related side effects were reported.ConclusionPallidal DBS is a valid and effective second-line treatment for patients with cervical focal dystonia. Our results support its use in patients with an insufficient response to medical treatment.     

Deep Brain Stimulation in Movement Disorders: From Experimental Surgery to Evidence‐Based Therapy

Deep brain stimulation (DBS) of 3 different targets is the most important therapeutic innovation of the past 30 years for patients with fluctuating Parkinson's disease (PD), disabling dystonia, tremors, and refractory Gilles de la Tourette syndrome. When compared with medical treatment alone, controlled studies have shown better motor, nonmotor, and particularly quality‐of‐life outcomes with large effect sizes for advanced complicated PD that cannot be improved with medication, and also for PD patients with only early fluctuations. Class 1 studies have also shown superiority over medical treatment for generalized, segmental, and botulinum‐toxin refractory focal cervical dystonia. Long‐term efficacy is established for all indications with open studies. For tremors, open studies have shown that DBS is remarkably effective on PD and essential tremor, but efficacy on severe essential tremor and cerebellar tremors is limited by a tendency for tolerance/habituation, including concerns about long‐term efficacy. Open studies of disabling Gilles de la Tourette syndrome show an improvement in tics. New developments hold a promise for further improvement. New hardware with directional stimulation and new stimulation paradigms are further areas of research. The targets of DBS are refined with new imaging processing that will help to diversify the surgical targets. New indications are being explored. Closed‐loop DBS using brain or peripheral sensor signals have shown favorable clinical short‐term results. Long‐term data are lacking, and it is hoped that similar approaches for other movement or behavioral disorders may be developed. Exciting new developments carry the hope for a more pathophysiology‐based approach for DBS for various brain circuit disorders. © 2019 International Parkinson and Movement Disorder Society     

Good long-term efficacy of pallidal stimulation in cervical dystonia: a prospective, observer-blinded study

Background and purpose: Deep brain stimulation of the internal globus pallidus (GPi‐DBS) is established as an effective treatment of primary generalised dystonia in controlled studies. In cervical dystonia (CD), only one previous study has reported observer‐blinded outcome assessment of long‐term GPi‐DBS, with 1‐year follow‐up. Methods: In this prospective, single‐centre study, eight patients with CD (7 women:1 man, 4 focal:4 segmental) treated with bilateral GPi‐DBS for median (range) 30 (12–48) months, were evaluated by the Toronto Western Spasmodic Torticollis Rating Scale (TWSTRS; Severity, Disability and Pain scores), the Short‐Form Health Survey‐36 (SF‐36), and the Becks Depression Index in an open design. In addition, a blinded rater assessed the TWSTRS Severity score from videos obtained preoperatively and at the last follow‐up. Results: In the blinded evaluation, median (range) TWSTRS Severity score improved from 25 (19–30) to 8 (4–23) (P = 0.028), thus a 70% (23–82) score reduction. In the open evaluation, median Severity score improvement at the last follow‐up was 73%, representing a significant further improvement from 50% at 6 months. The Disability and Pain scores improved by median 91% and 92%, respectively, and the SF‐36 subdomain scores improved significantly. A reversible right hemiparesis and aphasia occured in one patient 4 days postoperatively, because of reversible oedema around the left electrode. No other serious adverse effects and no permanent morbidity were observed. Conclusions: This single‐blinded study shows good long‐term efficacy of GPi‐DBS in CD patients and supports using this treatment in those who have insufficient response to medical treatment.     

Pallidal and thalamic deep brain stimulation in myoclonus‐dystonia

Deep brain stimulation (DBS) of the internal globus pallidus (GPi) and ventral intermediate thalamic nucleus (VIM) are established treatment options in primary dystonia and tremor syndromes and have been reported anecdotally to be efficacious in myoclonus‐dystonia (MD). We investigated short‐ and long‐term effects on motor function, cognition, affective state, and quality of life (QoL) of GPi‐ and VIM‐DBS in MD. Ten MD‐patients (nine ε‐sarcoglycan‐mutation‐positive) were evaluated pre‐ and post‐surgically following continuous bilateral GPi‐ and VIM‐DBS at four time points: presurgical, 6, 12, and as a last follow‐up at a mean of 62.3 months postsurgically, and in OFF‐, GPi‐, VIM‐, and GPi‐VIM‐DBS conditions by validated motor [unified myoclonus rating scale (UMRS), TSUI Score, Burke‐Fahn‐Marsden dystonia rating scale (BFMDRS)], cognitive, affective, and QoL‐scores. MD‐symptoms significantly improved at 6 months post‐surgery (UMRS: 61.5%, TSUI Score: 36.5%, BFMDRS: 47.3%). Beneficial effects were sustained at long‐term evaluation post‐surgery (UMRS: 65.5%, TSUI Score: 35.1%, BFMDRS: 48.2%). QoL was significantly ameliorated; affective status and cognition remained unchanged postsurgically irrespective of the stimulation conditions. No serious long‐lasting stimulation‐related adverse events (AEs) were observed. Both GPi‐ and VIM‐DBS offer equally effective and safe treatment options for MD. With respect to fewer adverse, stimulation‐induced events of GPi‐DBS in comparison with VIM‐DBS, GPi‐DBS seems to be preferable. Combined GPi‐VIM‐DBS can be useful in cases of incapaciting myoclonus, refractory to GPi‐DBS alone. © 2010 Movement Disorder Society     

Long Disease Duration Interferes With Therapeutic Effect of Globus Pallidus Internus Pallidal Stimulation in Primary Cervical Dystonia

Objectives: We retrospectively investigated the correlation between disease duration and the therapeutic effect of globus pallidus internus (GPi) stimulation in patients with primary cervical dystonia (CD). Materials and Methods: Eight patients with CD unresponsive to medical treatments underwent bilateral GPi deep brain stimulation (DBS). They were followed for 63.5 ± 38.2 months (mean ± standard deviation) and were assessed before and at 1, 12, 24, and 36 months after surgery and at their final visit to our outpatient clinic using the Toronto Western Spasmodic Torticollis Rating Scale (TWSTRS). Univariate analysis was performed to identify factors that affected their postoperative TWSTRS score. Results: At last follow‐up, disease severity and the degree of disability and pain on the TWSTRS were significantly improved by 70.2%, 76.1%, and 87.1%, respectively (p < 0.05, Wilcoxon signed‐rank test). Neither age nor preoperative CD severity was predictive of postoperative improvement; however, the disease duration affected their reduction rate of TWSTRS severity score at each time point investigated (p < 0.05). Conclusions: Bilateral GPi‐DBS is an effective long‐term therapy in patients with CD. The delivery of GPi stimulation in the earlier course of CD may yield greater postoperative improvement.     

Sustained quality‐of‐life improvements over 10 years after deep brain stimulation for dystonia

Background : Little is known about the quality of life of people with dystonia and DBS beyond 5 years. The objectives of this study were (1) to examine the long‐term quality‐of‐life outcomes in a large cohort of people with dystonia and DBS, (2) to determine the incidence of stimulation‐induced parkinsonism, and (3) to elucidate the potential long‐term cognitive impact of DBS in this cohort. Methods : Fifty‐four subjects with dystonia and DBS for more than 5 years were contacted via social media and were offered to complete a quality‐of‐life survey comparing current‐day life and life prior to DBS. The primary study outcomes were the Short Form survey, a parkinsonian symptoms questionnaire, the Telephone Montreal Cognitive Assessment, and the Measurement of Every Day Cognition. Results : Thirty‐seven of 54 subjects consented to the study. Average age was 39.7 ± 16.6 years, 16 were female, and 23 were DYT1+. Average time from implantation was 10.5 years. Average total Short Form survey scores improved, from 43.7 pre‐DBS to 69.5 current day (P < 0.0005). Mean total self‐reported parkinsonian symptom score was 13.8 ± 14.7, with worsening balance and hypophonia the most common. Average Telephone Montreal Cognitive Assessment was 20.1 ± 1.6, with 3 of 29 scores (10.3%) in the impaired range (score of 18 or less). Average total Every Day Cognition score was 1.25 ± 0.35, with 3 subjects (10.3%) scoring in the range of impaired cognition (>1.81). Conclusions : DBS for dystonia results in long‐term quality‐of‐life improvements that persist on average 10 years or more after surgery. The prevalence of stimulation‐induced parkinsonism and cognitive impairment is low. © 2018 International Parkinson and Movement Disorder Society     

Long‐term results of a multicenter study on subthalamic and pallidal stimulation in Parkinson's disease

We report the 5 to 6 year follow‐up of a multicenter study of bilateral subthalamic nucleus (STN) and globus pallidus internus (GPi) deep brain stimulation (DBS) in advanced Parkinson's disease (PD) patients. Thirty‐five STN patients and 16 GPi patients were assessed at 5 to 6 years after DBS surgery. Primary outcome measure was the stimulation effect on the motor Unified Parkinson's Disease Rating Scale (UPDRS) assessed with a prospective cross‐over double‐blind assessment without medications (stimulation was randomly switched on or off). Secondary outcomes were motor UPDRS changes with unblinded assessments in off‐ and on‐medication states with and without stimulation, activities of daily living (ADL), anti‐PD medications, and dyskinesias. In double‐blind assessment, both STN and GPi DBS were significantly effective in improving the motor UPDRS scores (STN, P < 0.0001, 45.4%; GPi, P = 0.008, 20.0%) compared with off‐stimulation, regardless of the sequence of stimulation. In open assessment, both STN‐ and GPi‐DBS significantly improved the off‐medication motor UPDRS when compared with before surgery (STN, P < 0.001, 50.5%; GPi, P = 0.002, 35.6%). Dyskinesias and ADL were significantly improved in both groups. Anti‐PD medications were significantly reduced only in the STN group. Adverse events were more frequent in the STN group. These results confirm the long‐term efficacy of STN and GPi DBS in advanced PD. Although the surgical targets were not randomized, there was a trend to a better outcome of motor signs in the STN‐DBS patients and fewer adverse events in the GPi‐DBS group. © 2010 Movement Disorder Society     

Long-term outcome of bilateral pallidal deep brain stimulation for primary cervical dystonia

Ten patients with severe cervical dystonia (CD) unresponsive to medical treatment underwent bilateral globus pallidus internus (GPi) deep brain stimulation (DBS) and were followed for 31.9 +/- 20.9 months. At last follow-up, the Toronto Western Spasmodic Torticollis Rating Scale (TWSTRS) severity score improved by 54.8%, the TWSTRS disability score improved by 59.1%, and the TWSTRS pain score improved by 50.4%. Bilateral GPi DBS is an effective long-term therapy in patients with CD.     

Chronic high-frequency deep-brain stimulation in progressive myoclonic epilepsy in adulthood--report of five cases

Purpose: To assess the efficacy and tolerability of chronic high‐frequency deep brain stimulation (DBS) in adult patients with progressive myoclonic epilepsy (PME) syndromes. Methods: Five adult patients (four male, 28–39 years) with PME underwent chronic high‐frequency DBS according to a study protocol that had been approved by the local ethics committee. Electrodes were implanted in the substantia nigra pars reticulata (SNr)/subthalamic nucleus (STN) region in the first patient and additionally in the ventral intermediate nucleus (VIM) bilaterally in the following four cases. Follow‐up took place in intervals of 3 months and DBS effects were compared with baseline frequency of passive and activation‐induced myoclonic jerks and daily life performance 8 weeks prior to implantation. Key Findings: Follow‐up periods ranged from 12–42 months (median 24 months). The best clinical effects were seen with SNr/STN DBS in all patients. VIM stimulation failed to achieve acute therapeutic effects and revealed low side‐effect thresholds and even triggering of myoclonia. In all patients the reduction of myoclonic seizures was observed and ranged between 30% and 100% as quantified by a standardized video protocol. All patients reported clinically relevant improvements of various capabilities such as free standing and walking or improved fine motor skills. In one patient with an excellent initial response generalized tonic–clonic seizures increased after 3 months of stimulation following extensive trauma‐related surgery. The best effect was seen in the least impaired patient. Significance: DBS of the SNr/STN may be an effective treatment option for patients with PME. Less impaired patients may benefit more markedly.     

Bilateral pallidal stimulation improves cervical dystonia for more than a decade

IntroductionDeep brain stimulation (DBS) is an effective treatment in medically resistant cervical dystonia (CD) with a documented therapeutic effect. Long term outcome beyond a decade, however, has not been studied systematically.MethodsTo investigate the impact of pallidal DBS beyond 10 years in CD we followed a series of five consecutive patients with severe medication-resistant CD. Severity of head and neck deviation, disability, and pain related to dystonia were assessed by the Toronto Western Spasmodic Torticollis Rating Scale (TWSTRS) in the frame of a prospective study. The primary endpoint of this study was a change in the TWSTRS total score. Secondary endpoints were changes in the subscores of the TWSTRS.ResultsThe mean follow-up time was 11.5 years (range 10–12.8). Comparing baseline and the last follow-up, CD improved by 53% on the total TWSTRS score, by 54.1% on the severity score, and by 70.1% on the disability score, while pain did not improve significantly. Improvement was stable over time. Patients with a tonic pattern of CD responded less to DBS than patients with a phasic pattern. DBS had no significant effect on mood and cognition. Two patients underwent electrode revisions. One patient had an infection of the proximal cable two years after surgery.ConclusionsChronic bilateral pallidal stimulation improves severity of dystonia and disability over more than a decade in treatment resistant CD. Results may vary among individual patients.     

Biochemical and electrophysiological changes of substantia nigra pars reticulata driven by subthalamic stimulation in patients with Parkinson's disease

To understand the events underlying the clinical efficacy of deep brain stimulation (DBS) of the subthalamic nucleus (STN), electrophysiological recordings and microdialysis evaluations were carried out in the substantia nigra pars reticulata (SNr), one of the two basal ganglia (BG) nuclei targeted by STN output, in patients with Parkinson's disease (PD). Clinically effective STN-DBS caused a significant increase of the SNr firing rate. The poststimulus histogram (PSTH) showed an excitation peak at 1.92-3.85 ms after the STN stimulus. The spontaneous discharge of SNr neurons was driven at the frequency of the stimulation (130 Hz), as shown in the autocorrelograms (AutoCrl). The fast Fourier transform (FFT) analysis showed a peak at 130 Hz, and a less pronounced second one at 260 Hz. Accordingly, in the distribution of the interspike intervals (ISIs), the mode was earlier, and skewness more asymmetric. Biochemically, the increased excitatory driving from the STN was reflected by a clear-cut increase in cyclic guanosine 3',5'-monophosphate (cGMP) levels in the SNr. These results indicate that the beneficial effect of DBS in PD patients is paralleled with a stimulus-synchronized activation of the STN target, SNr. Our findings suggest that, during STN-DBS, a critical change towards a high-frequency oscillatory discharge occurs.     

Long‐term plasticity of glutamatergic input from the subthalamic nucleus to the entopeduncular nucleus

The hyperdirect pathway of the basal ganglia bypasses the striatum, and delivers cortical information directly to the subthalamic nucleus (STN). In rodents, the STN excites the two output nuclei of the basal ganglia, the entopeduncular nucleus (EP) and the substantia nigra reticulata (SNr). Thus, during hyperdirect pathway activation, the STN drives EP firing inhibiting the thalamus. We hypothesized that STN activity could induce long‐term changes to the STN‐>EP synapse. To test this hypothesis, we recorded in the whole‐cell mode from neurons in the EP in acute brain slices from rats while electrically stimulating the STN. Repetitive pre‐synaptic stimulation generated modest long‐term depression (LTD) in the STN‐>EP synapse. However, pairing EP firing with STN stimulation generated robust LTD that manifested for pre‐before post‐as well as for post‐ before pre‐synaptic pairing. This LTD was highly sensitive to the time difference and was not detected at a time delay of 10 ms. To investigate whether post‐synaptic calcium levels were important for LTD induction, we made dendritic recordings from EP neurons that revealed action potential back‐propagation and dendritic calcium transients. Buffering the dendritic calcium concentration in the EP neurons with EGTA generated long term potentiation instead of LTD. Finally, mild LTD could be induced by post‐synaptic activity alone that was blocked by an endocannabinoid 1 (CB1) receptor blocker. These results thus suggest there may be an adaptive mechanism for buffering the impact of the hyperdirect pathway on basal ganglia output which could contribute to the de‐correlation of STN and EP firing.     

Deep brain stimulation and cognitive functions in Parkinson's disease: A three‐year controlled study

There is debate over the cognitive and behavioral effects of deep brain stimulation (DBS) of the subthalamic nucleus (STN) in advanced Parkinson's disease (PD). To evaluate these effects, we performed a prospective, naturalistic controlled, 3‐year follow‐up study. A total of 65 PD patients were enrolled, of whom 32 underwent STN‐DBS (PD‐DBS) and 33, even though eligible for this treatment, declined surgery and chose other therapeutic procedures (PD‐control). Motor and neuropsychological functions were assessed in all the subjects at baseline (T0) and 36 months (T36). The PD‐DBS patients were also evaluated at 1, 6, 12, and 24 months after surgery (T1, T6, T12, and T24). At T1, compared with T0, the PD‐DBS patients recorded worse logical executive function task and verbal fluency (FAS) scores, whereas their performance of memory tasks remained stable. At T12, their cognitive profile had returned within the pre‐DBS range, thereafter remaining stable until T36. FAS scores at T36 were significantly worse in the PD‐DBS compared with the PD‐control patients. This is the first long‐term naturalistic controlled study of cognitive functions in PD patients submitted to STN‐DBS. Our results confirm previous reports of a worsening of verbal fluency after DBS, but show that STN‐DBS seems to be relatively safe from a cognitive standpoint, as the short‐term worsening of frontal‐executive functions was found to be transient. © 2009 Movement Disorder Society     

High‐frequency stimulation of the subthalamic nucleus restores neural and behavioral functions during reaction time task in a rat model of Parkinson's disease

Deep brain stimulation (DBS) has been used in the clinic to treat Parkinson's disease (PD) and other neuropsychiatric disorders. Our previous work has shown that DBS in the subthalamic nucleus (STN) can improve major motor deficits, and induce a variety of neural responses in rats with unilateral dopamine (DA) lesions. In the present study, we examined the effect of STN DBS on reaction time (RT) performance and parallel changes in neural activity in the cortico‐basal ganglia regions of partially bilateral DA‐ lesioned rats. We recorded neural activity with a multiple‐channel single‐unit electrode system in the primary motor cortex (MI), the STN, and the substantia nigra pars reticulata (SNr) during RT test. RT performance was severely impaired following bilateral injection of 6‐OHDA into the dorsolateral part of the striatum. In parallel with such behavioral impairments, the number of responsive neurons to different behavioral events was remarkably decreased after DA lesion. Bilateral STN DBS improved RT performance in 6‐OHDA lesioned rats, and restored operational behavior‐related neural responses in cortico‐basal ganglia regions. These behavioral and electrophysiological effects of DBS lasted nearly an hour after DBS termination. These results demonstrate that a partial DA lesion‐induced impairment of RT performance is associated with changes in neural activity in the cortico‐basal ganglia circuit. Furthermore, STN DBS can reverse changes in behavior and neural activity caused by partial DA depletion. The observed long‐lasting beneficial effect of STN DBS suggests the involvement of the mechanism of neural plasticity in modulating cortico‐basal ganglia circuits. © 2009 Wiley‐Liss, Inc.     

Neuromodulation in Dystonia: Current Aspects of Deep Brain Stimulation

Among the surgical treatment options for patients with medically refractory dystonia chronic deep brain stimulation (DBS) of different targets in the basal ganglia circuitry has become one of the most important tools. The globus pallidus internus nowadays is the target of choice, while there is only limited experience with other targets. At this time, patients with primary (genetic or sporadic) generalized and segmental dystonia, and patients with (complex) cervical dystonia are thought to be the best candidates for pallidal DBS. Advantages of DBS are its reversibility, its adjustability, and the continuous access to modify the target in the basal ganglia. The present review gives an account on the development of surgical neuromodulation therapy for dystonia, surgical approaches, hardware‐related problems, DBS programming and patient management, and clinical outcome. Studies conducted according to the practices of evidence‐based medicine confirm the results of early pilot studies. The wide majority of patients achieve beneficial lasting outcome at a relatively low rate of manageable side‐effects. Along with improvement of the movement disorder, studies report on amelioration of quality‐of‐life surrogates. We also provide an overview on DBS surgery in less common dystonic syndromes, such as craniofacial dystonia, status dystonicus, task‐specific dystonia, paroxysmal dystonia, camptocormia, and secondary dystonias, including choreoathetosis, hemidystonia, tardive dystonia, and pantothenate kinase‐associated neurodegeneration. Furthermore, we discuss the implications of intra‐operative microelectrode recordings and pallidal field potentials for the pathophysiology of dystonia and the particular possible mechanisms of DBS in dystonia. Finally, future perspectives are outlined.     

Pallidal deep brain stimulation in patients with cranial-cervical dystonia (Meige syndrome).

Idiopathic cranial-cervical dystonia (ICCD) is an adult-onset dystonia syndrome affecting orbicularis oculi, facial, oromandibular, and cervical musculature. ICCD is frequently difficult to treat medically. Deep brain stimulation (DBS) of the globus pallidus internus (GPi) is a highly effective treatment for idiopathic generalized dystonia, however less is known about the effect of GPi DBS on ICCD. In this article, we present the results from a pilot study assessing the effect of GPi DBS in a series of patients with ICCD. Six patients underwent bilateral stereotactic implantation of DBS leads into the sensorimotor GPi. Patients were evaluated with the Burke-Fahn-Marsden dystonia rating scale (BFMDRS) and Toronto western spamodic torticollis rating scale (TWSTRS) before surgery and 6 months postoperatively. At 6 months, patients showed a 72% mean improvement in the BFMDRS total movement score (P < 0.028, Wilcoxin signed rank test). The mean BFMDRS disability score showed a trend toward improvement (P < 0.06). The total TWSTRS score improved 54% (P < 0.043). Despite improvement in dystonia, mild worsening of motor function was reported in previously nondystonic body regions with stimulation in 4 patients. Although GPi DBS was effective in these patients, the influence of GPi DBS on nondystonic body regions deserves further investigation.     

Effect of high‐frequency subthalamic neurostimulation on gait and freezing of gait in Parkinson's disease: a systematic review and meta‐analysis

The aim of this meta‐analysis was to summarize the short‐ and long‐term effects of bilateral deep brain stimulation of the subthalamic nucleus (STN‐DBS) on gait and freezing of gait (FOG) in Parkinson's disease and to detect predictors of post‐stimulation outcome. A comprehensive review of the literature was conducted up to October 2015 using Medline Ovid databases for studies analyzing the effect of bilateral STN‐DBS on FOG and/or gait. Sixteen studies with available data for the gait item (no. 29) of the Unified Parkinson's Disease Rating Scale (UPDRS) and six studies with the FOG item (no. 14) were included. Data were summarized for the following follow‐up periods: 6–15, 24–48 and >48 months. For the medication (Med)‐Off/stimulation(Stim)‐On condition compared with baseline Med‐Off, STN‐DBS significantly improved gait on average from 2.43 to 0.96, 2.53 to 1.31 and 2.56 to 1.40 points at 6–15, 24–48 and >48 months, respectively (P < 0.05). Pre‐operative levodopa responsiveness of UPDRS‐III and Med‐Off severity of gait were the predictors of this beneficial effect. STN‐DBS significantly improved FOG for the Med‐Off/Stim‐On condition compared with baseline on average from 2.26 to 0.82, 2.43 to 1.13 and 2.48 to 1.38 points at 6–15, 24–48 and >48 months, respectively (P < 0.05). There was no significant effect in the Med‐On/Stim‐On condition. This meta‐analysis showed a robust improvement of gait and FOG by STN‐DBS for more than 4 years in the Med‐Off/Stim‐On condition. No beneficial effect was found for the On state of medication. Pre‐operative levodopa responsiveness of global motor performance (UPDRS‐III) is the strongest predictor of the effect of deep brain stimulation on gait.