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Dystonia is a debilitating disease with few treatment options. One effective option is deep brain stimulation (DBS) to the internal pallidum. While cervical and generalized forms of isolated dystonia have been targeted with a common approach to the posterior third of the nucleus, large-scale investigations regarding optimal stimulation sites and potential network effects have not been carried out. Here, we retrospectively studied clinical results following DBS for cervical and generalized dystonia in a multicenter cohort of 80 patients. We model DBS electrode placement based on pre- and postoperative imaging and introduce an approach to map optimal stimulation sites to anatomical space. Second, we investigate which tracts account for optimal clinical improvements, when modulated. Third, we investigate distributed stimulation effects on a whole-brain functional connectome level. Our results show marked differences of optimal stimulation sites that map to the somatotopic structure of the internal pallidum. While modulation of the striatopallidofugal axis of the basal ganglia accounted for optimal treatment of cervical dystonia, modulation of pallidothalamic bundles did so in generalized dystonia. Finally, we show a common multisynaptic network substrate for both phenotypes in the form of connectivity to the cerebellum and somatomotor cortex. Our results suggest a brief divergence of optimal stimulation networks for cervical vs. generalized dystonia within the pallidothalamic loop that merge again on a thalamo-cortical level and share a common whole-brain network.

Severe forms of primary dystonia are difficult to manage medically. We assessed the safety and efficacy of pallidal neurostimulation in patients with primary generalised or segmental dystonia prospectively followed up for 5 years in a controlled multicentre trial. In the parent trial, 40 patients were randomly assigned to either sham neurostimulation or neurostimulation of the internal globus pallidus for a period of 3 months and thereafter all patients completed 6 months of active neurostimulation. 38 patients agreed to be followed up annually after the activation of neurostimulation, including assessments of dystonia severity, pain, disability, and quality of life. The primary endpoint of the 5-year follow-up study extension was the change in dystonia severity at 3 years and 5 years as assessed by open-label ratings of the Burke–Fahn–Marsden dystonia rating scale (BFMDRS) motor score compared with the preoperative baseline and the 6-month visit. The primary endpoint was analysed on an intention-to-treat basis. The original trial is registered with ClinicalTrials.gov (NCT00142259). An intention-to-treat analysis including all patients from the parent trial showed significant improvements in dystonia severity at 3 years and 5 years compared with baseline, which corresponded to −20·8 points (SD 17·1; −47·9%; n=40) at 6 months; −26·5 points (19·7; −61·1%; n=31) at 3 years; and −25·1 points (21·3; −57·8%; n=32). The improvement from 6 months to 3 years (–5·7 points [SD 8·4]; −34%) was significant and sustained at the 5-year follow-up (–4·3 [10·4]). 49 new adverse events occurred between 6 months and 5 years. Dysarthria and transient worsening of dystonia were the most common non-serious adverse events. 21 adverse events were rated serious and were almost exclusively device related. One patient attempted suicide shortly after the 6-month visit during a depressive episode. All serious adverse events resolved without permanent sequelae. 3 years and 5 years after surgery, pallidal neurostimulation continues to be an effective and relatively safe treatment option for patients with severe idiopathic dystonia. This long-term observation provides further evidence in favour of pallidal neurostimulation as a first-line treatment for patients with medically intractable, segmental, or generalised dystonia. Medtronic.

In this sham-controlled trial of neurostimulation of the internal globus pallidus for primary dystonia, neurostimulation improved movement, disability, and quality-of-life scores. Adverse events were common; 18% of patients had infections at the stimulator site, seroma, or lead breakage or dislodgment, and 12% had dysarthria. In patients with primary dystonia, neurostimulation of the internal globus pallidus improved movement, disability, and quality-of-life scores. Adverse events were common. Primary dystonia comprises a group of idiopathic, incurable movement disorders that vary with respect to age at onset, body distribution, and genetic association. 1 All these disorders are characterized by twisting, repetitive movements or abnormal postures caused by involuntary muscle contractions. 2 The mainstay of treatment for focal or segmental dystonia is the injection of botulinum toxin to denervate the affected muscles. 3 When this approach fails (because too many muscles are involved, the movement pattern is too complex, or neutralizing antibodies develop 4 ), the management of dystonia becomes difficult. Drug therapy is often unsatisfactory, 5 which leaves many patients with a profound incapacity . . .

Human retinal pigment epithelial (RPE) cells produce levodopa and their transplantation into the striatum might improve continuity of administration compared with that achieved with oral levodopa. We aimed to assess the safety, tolerability, and efficacy of transplantation of microcarrier-bound human RPE cells versus a sham surgery control in patients with advanced Parkinson's disease. In this randomised, double-blind study eligible patients were aged 36–70 years, had been symptomatic for at least 5 years, were in Hoehn and Yahr stage 3–4 and had unified Parkinson's disease rating scale (UPDRS) motor scores of 38–70 when off medication (off state), and had symptoms that responded to oral levodopa but were insufficiently controlled by optimised pharmacotherapy. Randomisation was done in a 1:1 ratio. Only the neurosurgical team was aware of treatment assignments. During stereotactic transplantation around 325 000 cells per side were injected into the postcommissural putamen; sham surgery patients received partial burr holes. The primary efficacy endpoint was change in UPDRS off-state motor score at 12 months. This study is registered with ClinicalTrials.gov, number NCT00206687. Of 71 enrolled patients, 35 underwent cell transplantation and 36 sham surgery. Change in mean motor scores did not differ significantly between groups (−10·5 [SD 10·26] for transplantation vs −10·1 [SD 12·26] for sham surgery, p=0·9). The overall rate of adverse events was similar in the two study groups, although the number attributable to surgery or RPE cells (mostly neurological or psychiatric) was higher in transplant recipients. Two and seven patients died in the sham surgery and transplantation group, respectively; one death in the latter group was possibly related to surgery or RPE cells. Transplantation of human RPE cells provided no antiparkinsonian benefits compared with sham surgery. Bayer HealthCare AG.

Dystonia is a neurological movement disorder characterised by abnormal involuntary movements and postures, particularly affecting the head and neck. However, current clinical assessment methods for dystonia rely on simplified rating scales which lack the ability to capture the intricate spatiotemporal features of dystonic phenomena, hindering clinical management and limiting understanding of the underlying neurobiology. To address this, we developed a visual perceptive deep learning framework that utilizes standard clinical videos to comprehensively evaluate and quantify disease states and the impact of therapeutic interventions, specifically deep brain stimulation. This framework overcomes the limitations of traditional rating scales and offers an efficient and accurate method that is rater-independent for evaluating and monitoring dystonia patients. To evaluate the framework, we leveraged semi-standardized clinical video data collected in three retrospective, longitudinal cohort studies across seven academic centres. We extracted static head angle excursions for clinical validation and derived kinematic variables reflecting naturalistic head dynamics to predict dystonia severity, subtype, and neuromodulation effects. The framework was also applied to a fully independent cohort of generalised dystonia patients for comparison between dystonia sub-types. Computer vision-derived measurements of head angle excursions showed a strong correlation with clinically assigned scores. Across comparisons, we identified consistent kinematic features from full video assessments encoding information critical to disease severity, subtype, and effects of neural circuit interventions, independent of static head angle deviations used in scoring. Our visual perceptive machine learning framework reveals kinematic pathosignatures of dystonia, potentially augmenting clinical management, facilitating scientific translation, and informing personalized precision neurology approaches.

Objective Cranial nerves (CNs) crossing between the brainstem and skull base at the level of the tentorial hiatus may be at risk in temporomesial surgery involving subpial dissection and/or tumorous growth leading to distorted anatomy. We aimed to identify the surgical steps most likely to result in CN damage in this type of surgery. Methods Electromyographic responses obtained with standard neuromonitoring techniques and a continuous free-running EMG were graded as either contact activity or pathological spontaneous activity (PSA) during subpial resection of temporomesial structures in 16 selective amygdalohippocampectomy cases. Integrity of peripheral motor axons was tested by transpial/transarachnoidal electrical stimulation while recording compound muscle action potentials from distal muscle(s). Results Continuous EMG showed pathological activity in five (31.2%) patients. Nine events with PSA (slight activity, n = 8; strong temporary activity, n = 1) were recorded. The oculomotor nerve was involved three times, the trochlear nerve twice, the facial nerve once, and all monitored nerves on three occasions. Surgical maneuvers associated with PSA were the resection of deep parts of the hippocampus and parahippocampal gyrus (CN IV, twice; CN III, once), lining with or removing cotton patties from the resection cavity (III, twice; all channels, once) and indirect exertion of tension on the intact pia/arachnoid of the uncal region while mobilizing the hippocampus and parahippocampal gyrus en bloc (all channels, once; III, once). CMAPs were observed at 0.3 mA in two patients and at 0.6 mA in one patient, and without registering the exact amount of intensity in three patients. Conclusion The most dangerous steps leading to cranial nerve damage during mesial temporal lobe surgery are the final stages of the intervention while the resection is being completed in the deep posterior part and the resection cavity is being lined with patties. Distant traction may act on nerves crossing the tentorial hiatus via the intact arachnoid.

Programming deep brain stimulation in dystonia is difficult because of the delayed benefits and absence of evidence-based guidelines. Therefore, we evaluated the efficacy of a programming algorithm applied in a double-blind, sham-controlled multicenter study of pallidal deep brain stimulation in dystonia. A standardized monopolar review to identify the contact with the best acute antidystonic effect was applied in 40 patients, who were then programmed 0.5 V below the adverse effect threshold and maintained on these settings for at least 3 months, if tolerated. If no acute effects were observed, contact selection was based on adverse effects or anatomical criteria. Three-year follow-up data was available for 31 patients, and five-year data for 32 patients. The efficacy of the algorithm was based on changes in motor scores, adverse events, and the need for reprogramming. The mean (±standard deviation) dystonia motor score decreased by 73 ± 24% at 3 years and 63 ± 38% at 5 years for contacts that exhibited acute improvement of dystonia (  = 17) during the monopolar review. Contacts without acute benefit improved by 58 ± 30% at 3 years (  = 63) and 53 ± 31% at 5 years (  = 59). Interestingly, acute worsening or induction of dystonia/dyskinesia (  = 9) correlated significantly with improvement after 3 years, but not 5 years. Monopolar review helped to detect the best therapeutic contact in approximately 30% of patients exhibiting acute modulation of dystonic symptoms. Acute improvement, as well as worsening of dystonia, predicted a good long-term outcome, while induction of phosphenes did not correlate with outcome. ClinicalTrials.gov NCT00142259.

The purpose of this study was to investigate the fMRI response of the sensorimotor cortex to a vibration paradigm produced by a novel vibrotactile stimulator. Fifteen contiguous slices covering the sensorimotor cortex parallel to the anterior (AC) and posterior commissure (PC) line were obtained with echoplanar magnetic resonance imaging at 1.5T. Cortical activity in ten healthy subjects (20–45 years) was investigated during vibration (50 Hz) of the palm of the right hand and compared to a finger-to-thumb tapping paradigm. For the vibration paradigm a mechanically driven vibration head was mounted on the palm of the right hand. The new vibration device produces vibration frequencies (1–130 Hz) and displacement amplitudes (0.5–4 mm) suitable to elicit the tonic vibratory reflex. The fMRI measurement during vibratory stimulation revealed activation in the pre- and postcentral gyrus in all subjects. These activations were comparable to the finger-to-thumb tapping paradigm. The advantages of the new MR compatible vibration device include effective transmission of the stimulus and controlled vibration frequencies and intensities. These preliminary fMRI results indicate that vibration can be an alternative paradigm for the evaluation of sensory and motor functions in patients unable to perform active motor paradigms.

Zusammenfassung Funktionsstörungen der Hand umfassen Bewegungsstörungen und Schmerzen. Die Ursache kann lokal in der Hand, im Arm, im Thoraxbereich, in der Halswirbelsäule, im Hirnstamm oder im Gehirn liegen. Speziell bei Schmerzen der Hand kann bei diagnostischem Unverstand viel Schaden angerichtet werden, wie die sinnlose Amputation einer schmerzenden Hand, wenn der Schmerz eine zentrale Ursache hat. Die Neuromodulation ist in der Lage, schwere und schwerste Schmerzzustände und Bewegungsstörungen effektiv, sicher und nachhaltig zu beeinflussen.

Zusammenfassung Ziel der manuellen Medizin ist es, die Patienten von ihren Beschwerden zu befreien. Allerdings gibt es Schmerzen, die sich mit der manuellen Medizin nicht behandeln lassen. Daher werden im vorliegenden Beitrag nichtmanuelle Behandlungsverfahren und ihre Wirkungsweise dargestellt. Dabei ist zwischen nozizeptivem und neuropathischem Schmerz zu unterscheiden. Bei den Verfahren handelt es sich einerseits um pharmakologische Ansätze, die auf Empfehlungen der WHO und aktuellen Behandlungsrichtlinien basieren, andererseits um invasive Therapien, wie z. B. die Neuromodulation. Somit kann eine Brücke über beide schmerzmedizinische Herangehensweisen zum Wohle der Patienten geschlagen werden.