Subthalamic nucleus deep brain stimulation in primary Meige syndrome: motor and non-motor outcomes.

BACKGROUND AND PURPOSE: Deep brain stimulation (DBS) has emerged as a promising treatment for movement disorders. This prospective study aims to evaluate the effects of bilateral subthalamic nucleus DBS (STN-DBS) on motor and non-motor symptoms in patients with primary Meige syndrome. METHODS: Thirty patients who underwent bilateral STN-DBS between April 2017 and June 2020 were included. Standardized and validated scales were utilized to assess the severity of dystonia, health-related quality of life, sleep, cognitive function and mental status at baseline and at 1 year and 3 years after neurostimulation. RESULTS: The Burke-Fahn-Marsden Dystonia Rating Scale movement scores showed a mean improvement of 63.0% and 66.8% at 1 year and 3 years, respectively, after neurostimulation. Similarly, the Burke-Fahn-Marsden Dystonia Rating Scale disability scores improved by 60.8% and 63.3% at the same time points. Postoperative quality of life demonstrated a significant and sustained improvement throughout the follow-up period. However, cognitive function, mental status, sleep quality and other neuropsychological functions did not change after 3 years of neurostimulation. Eight adverse events occurred in six patients, but no deaths or permanent sequelae were reported. CONCLUSIONS: Bilateral STN-DBS is a safe and effective alternative treatment for primary Meige syndrome, leading to improvements in motor function and quality of life. Nevertheless, it did not yield significant amelioration in cognitive, mental, sleep status and other neuropsychological functions after 3 years of neurostimulation.

Deep brain stimulation for the abernethy malformation related tremor.

Deep brain stimulation (DBS) is introduced for the surgical treatment of movement disorders such as Parkinson's disease, tremor, dystonia, and tics. Electrostimulation of the ventral thalamus or subthalamic area has been found effective in different types of tremors that have different etiologies. Abernethy malformation is a rare congenital abnormality characterized by the presence of a congenital extrahepatic portosystemic shunt between the portal vein and systemic circulation. In this report, we present as a case of Abernethy malformation that caused hyperammonemia congenitally and presented as action and resting tremor in the hands and, treated with DBS.

Harnessing cognitive strategy use for functional problems and proposed underlying mechanisms in childhood-onset dystonia.

BACKGROUND: There is a significant gap in knowledge about rehabilitation techniques and strategies that can help children and young people with hyperkinetic movement disorders (HMD) including dystonia to successfully perform daily activities and improve overall participation. A promising approach to support skill acquisition is the Cognitive Orientation to daily Occupational Performance (CO-OP) intervention. CO-OP uses cognitive strategies to help patients generate their own solutions to overcome self-identified problems encountered in everyday living. PURPOSE: 1. To identify and categorize strategies used by children with HMD to support skill acquisition during CO-OP; 2. To review the possible underlying mechanisms that might contribute to the cognitive strategies, in order to facilitate further studies for developing focused rehabilitation approaches. METHODS: A secondary analysis was performed on video-recorded data from a previous study exploring the efficacy of CO-OP for childhood onset HMD, in which CO-OP therapy sessions were delivered by a single occupational therapist. For the purpose of this study, we reviewed a total of 40 randomly selected hours of video footage of CO-OP sessions delivered to six participants (age 6-19 years) over ten intervention sessions. An observational recording sheet was applied to identify systematically the participants' or therapist's verbalizations of cognitive strategies during the therapy. The strategies were classified into six categories in line with published literature. RESULTS: Strategies used by HMD participants included distraction, externally focussed attention, internally focussed attention, emotion self-regulation, motor imagery and mental self-guidance. We postulate different underlying working mechanisms for these strategies, which have implications for the therapeutic management of children and young people with HMD including dystonia. CONCLUSIONS: Cognitive strategy training can fundamentally change and improve motor performance. On-going work will address both the underlying neural mechanisms of therapeutic change and the mediators and moderators that influence how change unfolds.

Dystonia, chorea, hemiballismus and other dyskinesias.

Hyperkinesias are heterogeneous involuntary movements that significantly differ in terms of clinical and semeiological manifestations, including rhythm, regularity, speed, duration, and other factors that determine their appearance or suppression. Hyperkinesias are due to complex, variable, and largely undefined pathophysiological mechanisms that may involve different brain areas. In this chapter, we specifically focus on dystonia, chorea and hemiballismus, and other dyskinesias, specifically, levodopa-induced, tardive, and cranial dyskinesia. We address the role of neurophysiological studies aimed at explaining the pathophysiology of these conditions. We mainly refer to human studies using surface and invasive in-depth recordings, as well as spinal, brainstem, and transcortical reflexology and non-invasive brain stimulation techniques. We discuss the extent to which the neurophysiological abnormalities observed in hyperkinesias may be explained by pathophysiological models. We highlight the most relevant issues that deserve future research efforts. The potential role of neurophysiological assessment in the clinical context of hyperkinesia is also discussed.

Globus Pallidus Interna and Ventral Intermediate Nucleus of the Thalamus Deep Brain Stimulation for Adductor Laryngeal Dystonia: a Case Report of Blinded Analyses of Objective Voice Outcomes in 2 Patients.

BACKGROUND: Adductor laryngeal dystonia (ADLD) is a substantially debilitating focal progressive neurological voice disorder. Current standard of care is symptomatic treatment with repeated injections of botulinum toxin into specific intrinsic laryngeal muscles with extremely variable and temporary benefits. We report the use of bilateral deep brain stimulation (DBS) of globus pallidus (GPi) for long-term improvement of ADLD voice symptoms. OBJECTIVE: To investigate the effects of bilateral DBS of the GPi and ventral intermediate nucleus (VIM) of the thalamus on vocal function in 2 patients with ADLD associated with voice and hand tremor. METHODS: Blinded objective and quantitative analyses of voice were conducted before and after treatment in 2 female patients (70 and 69 years). Paired t-tests were conducted to compare voice measurements pre-GPi and post-GPi and VIM-DBS. A 2-way analysis of variance was conducted to determine the interaction between target (GPi/VIM) and time (pre/post) for each voice measure. RESULTS: Although the follow-up period differed between patients, the GPi-DBS implanted patient had notable improvement in vowel voicing (%), extent of tremor intensity (%), and overall speech intelligibility (%), compared with preoperative status. GPi-DBS also resulted in significant improvement in cepstral peak prominence (dB). VIM-DBS resulted in a significantly greater change in the tremor rate (Hz). CONCLUSION: Changes in phonatory function provide preliminary support for the use of bilateral GPi-DBS for treatment of ADLD and bilateral VIM-DBS for vocal tremor predominant ADLD. Future studies with larger sample sizes and standardized follow-up periods are needed to better assess the role of DBS for ADLD.

Thalamic deep brain stimulation for acquired dystonia in children and young adults: a phase 1 clinical trial.

OBJECTIVE: The aim of this study was to evaluate the feasibility and preliminary efficacy and safety of combined bilateral ventralis oralis posterior/ventralis intermedius (Vop/Vim) deep brain stimulation (DBS) for the treatment of acquired dystonia in children and young adults. Pallidal DBS is efficacious for severe, medication-refractory isolated dystonia, providing 50%-60% long-term improvement. Unfortunately, pallidal stimulation response rates in acquired dystonia are modest and unpredictable, with frequent nonresponders. Acquired dystonia, most commonly caused by cerebral palsy, is more common than isolated dystonia in pediatric populations and is more recalcitrant to standard treatments. Given the limitations of pallidal DBS in acquired dystonia, there is a need to explore alternative brain targets. Preliminary evidence has suggested that thalamic stimulation may be efficacious for acquired dystonia. METHODS: Four participants, 3 with perinatal brain injuries and 1 with postencephalitic symptomatic dystonia, underwent bilateral Vop/Vim DBS and bimonthly evaluations for 12 months. The primary efficacy outcome was the change in Burke-Fahn-Marsden Dystonia Rating Scale (BFMDRS) and Barry-Albright Dystonia Scale (BADS) scores between the baseline and 12-month assessments. Video documentation was used for blinded ratings. Secondary outcomes included evaluation of spasticity (Modified Ashworth Scale score), quality of life (Pediatric Quality of Life Inventory [PedsQL] and modified Unified Parkinson's Disease Rating Scale Part II [UPDRS-II] scores), and neuropsychological assessments. Adverse events were monitored for safety. RESULTS: All participants tolerated the procedure well, and there were no safety concerns or serious adverse events. There was an average improvement of 21.5% in the BFMDRS motor subscale score, but the improvement was only 1.6% according to the BADS score. Following blinded video review, dystonia severity ratings were even more modest. Secondary outcomes, however, were more encouraging, with the BFMDRS disability subscale score improving by 15.7%, the PedsQL total score by 27%, and the modified UPDRS-II score by 19.3%. Neuropsychological assessment findings were unchanged 1 year after surgery. CONCLUSIONS: Bilateral thalamic neuromodulation by DBS for severe, medication-refractory acquired dystonia was well tolerated. Primary and secondary outcomes showed highly variable treatment effect sizes comparable to those of pallidal stimulation in this population. As previously described, improvements in quality of life and disability were not reflected in dystonia severity scales, suggesting a need for the development of scales specifically for acquired dystonia.Clinical trial registration no.: NCT03078816 (clinicaltrials.gov).

Treatment of Dystonia: Medications, Neurotoxins, Neuromodulation, and Rehabilitation.

Dystonia is a complex disorder with numerous presentations occurring in isolation or in combination with other neurologic symptoms. Its treatment has been significantly improved with the advent of botulinum toxin and deep brain stimulation in recent years, though additional investigation is needed to further refine these interventions. Medications are of critical importance in forms of dopa-responsive dystonia but can be beneficial in other forms of dystonia as well. Many different rehabilitative paradigms have been studied with variable benefit. There is growing interest in noninvasive stimulation as a potential treatment, but with limited long-term benefit shown to date, and additional research is needed. This article reviews existing evidence for treatments from each of these categories. To date, there are many examples of incomplete response to available treatments, and improved therapies are needed.

Individualized Homeopathic Therapy in a Case of Obesity, Dysfunctional Uterine Bleeding, and Autonomic Dystonia.

BACKGROUND Obesity is one of the leading causes of morbidity and mortality globally and challenging to treat because of the multifactorial etiology and presentation. Individualized homeopathy takes into account factors that led to a patient's health condition and hence may have a role in the treatment of obesity and related co-morbidities; co-morbidities that may arising from the same etiology may respond as a whole to homeopathy treatment. CASE REPORT A 39-year-old Russian female who developed multiple problems after severe emotional stress was treated with individualized classical homeopathic therapy. Obesity, dysfunctional uterine bleeding, and dysautonomia were pathologies that showed improvement. CONCLUSIONS The response in this patient's case, supports the need for further investigation on the relevance of individualized homeopathy in these related conditions.

Hyperbaric oxygen for late sequelae of carbon monoxide poisoning enhances neurological recovery: case report.

Neuropsychiatric sequelae have been reported in 15%-45% of survivors of carbon monoxide (CO) poisoning. Hyperbaric oxygen (HBO2) therapy reduces the incidence of cognitive and neurological a dysfunction. The efficacy of providing HBO2 beyond the first one to two days after initial insult is unknown. However, some evidence exists for the benefit of this treatment. We report on treating a patient 14 months after CO injury, who responded with markedly improved neurologic status. A 27-year-old scholar was found comatose due to CO poisoning (carboxyhemoglobin = 31.7%). He received five acute HBO2 treatments. After discharge, he developed chorea, Parkinsonism, dystonia, memory loss, slowed processing speed and verbal fluency, leaving him disabled. After the patient reached a clinical plateau, HBO2 was tried again at 90 minutes at 2.4 ATA plus air breaks. Neuropsychological testing was performed at baseline and after each 20 HBO2 cycles, five of which were performed during the period from 14-22 months after CO exposure. After the first 20 treatments, Parkinsonism and dystonia improved. After 40 sessions, further improvements were seen on mental speed, verbal fluency, and fine motor movements. The outcome following 100 treatments was that the patient regained independence, including the ability to drive and to become gainfully employed. Our case calls into question the concept that HBO2 therapy has no role during the chronic phase of CO brain injury. Randomized clinical trials should be considered to evaluate the therapeutic efficacy of HBO2 in patients with neurological sequelae following CO injury.

Neurostimulation Devices for the Treatment of Neurologic Disorders.

Rapid advancements in neurostimulation technologies are providing relief to an unprecedented number of patients affected by debilitating neurologic and psychiatric disorders. Neurostimulation therapies include invasive and noninvasive approaches that involve the application of electrical stimulation to drive neural function within a circuit. This review focuses on established invasive electrical stimulation systems used clinically to induce therapeutic neuromodulation of dysfunctional neural circuitry. These implantable neurostimulation systems target specific deep subcortical, cortical, spinal, cranial, and peripheral nerve structures to modulate neuronal activity, providing therapeutic effects for a myriad of neuropsychiatric disorders. Recent advances in neurotechnologies and neuroimaging, along with an increased understanding of neurocircuitry, are factors contributing to the rapid rise in the use of neurostimulation therapies to treat an increasingly wide range of neurologic and psychiatric disorders. Electrical stimulation technologies are evolving after remaining fairly stagnant for the past 30 years, moving toward potential closed-loop therapeutic control systems with the ability to deliver stimulation with higher spatial resolution to provide continuous customized neuromodulation for optimal clinical outcomes. Even so, there is still much to be learned about disease pathogenesis of these neurodegenerative and psychiatric disorders and the latent mechanisms of neurostimulation that provide therapeutic relief. This review provides an overview of the increasingly common stimulation systems, their clinical indications, and enabling technologies.

The role of the pallidothalamic fibre tracts in deep brain stimulation for dystonia: A diffusion MRI tractography study.

BACKGROUND: Deep Brain Stimulation (DBS) of the Globus pallidus internus (GPi) is gold standard treatment in medically refractory dystonia. Recent evidence indicates that stimulation effects are also due to axonal modulation and affection of a fibre network. For the GPi, the pallidothalamic tracts are known to be the major motor efferent pathways. The aim of this study is to explore the anatomic vicinity of these tracts and DBS electrodes in dystonia applying diffusion tractography. METHODS: Diffusion MRI was acquired in ten patients presenting for DBS for dystonia. We applied both a conventionally used probabilistic tractography algorithm (FSL) as well as a probabilistic streamline tracking approach, based on constrained spherical deconvolution and particle filtering with anatomic priors, to the datasets. DBS electrodes were coregistered to the diffusion datasets. RESULTS: We were able to delineate the pallidothalamic tracts in all patients. Using the streamline approach, we were able to distinguish between the two sub-components of the tracts, the ansa lenticularis and the fasciculus lenticularis. Clinically efficient DBS electrodes displayed a close anatomic vicinity pathway of the pallidothalamic tracts, and their course was consistent with previous tracer labelling studies. Although we present only anatomic data, we interpret these findings as evidence of the possible involvement of fibre tracts to the clinical effect in DBS. Electrophysiological intraoperative recordings would be needed to complement our findings. In the future, a clear and individual delineation of the pallidothalamic tracts could optimize the stereotactic process of optimal electrode localization. Hum Brain Mapp 38:1224-1232, 2017. © 2016 Wiley Periodicals, Inc.

Combined cognitive-behavioural and mindfulness programme for people living with dystonia: a proof-of-concept study.

OBJECTIVES: To design and test the delivery of an intervention targeting the non-motor symptoms of dystonia and pilot key health and well-being questionnaires in this population. DESIGN: A proof-of-concept study to test the delivery, acceptability, relevance, structure and content for a 3-day group residential programme for the management of dystonia. SETTING: Participants were recruited from a single botulinum toxin clinic. The intervention was delivered in the community. PARTICIPANTS: 14 participants consented to take part (2 withdrew prior to the starting of intervention). The average age was 60 years (range 44-77), 8 of whom were female. After drop-out, 9 participants completed the 3-day programme. INTERVENTION: A 3-day group residential programme. PRIMARY AND SECONDARY OUTCOME MEASURES: Process evaluation and interviews were carried out before and after the intervention to explore participant's views and expectations, as well as experiences of the intervention. Select questionnaires were completed at baseline, 1-month and 3-month follow-up. RESULTS: Although participants were not sure what to expect from the programme, they found it informative and for many this together with being in a group with other people with dystonia legitimised their condition. Mindfulness was accepted and adopted as a coping strategy. This was reflected in the 1-month follow-up. CONCLUSIONS: We successfully delivered a 3-day residential programme to help those living with dystonia manage their condition. Further improvements are suggested. The quantitative outcome measures were acceptable to this group of patients with dystonia.

Current and emerging strategies for treatment of childhood dystonia.

Childhood dystonia is a movement disorder characterized by involuntary sustained or intermittent muscle contractions causing twisting and repetitive movements, abnormal postures, or both (Sanger et al, 2003). Dystonia is a devastating neurological condition that prevents the acquisition of normal motor skills during critical periods of development in children. Moreover, it is particularly debilitating in children when dystonia affects the upper extremities such that learning and consolidation of common daily motor actions are impeded. Thus, the treatment and rehabilitation of dystonia is a challenge that continuously requires exploration of novel interventions. This review will initially describe the underlying neurophysiological mechanisms of the motor impairments found in childhood dystonia followed by the clinical measurement tools that are available to document the presence and severity of symptoms. Finally, we will discuss the state-of-the-art of therapeutic options for childhood dystonia, with particular emphasis on emergent and innovative strategies.

Deep brain stimulation for movement disorders.

Deep brain stimulation (DBS) is an implanted electrical device that modulates specific targets in the brain resulting in symptomatic improvement in a particular neurologic disease, most commonly a movement disorder. It is preferred over previously used lesioning procedures due to its reversibility, adjustability, and ability to be used bilaterally with a good safety profile. Risks of DBS include intracranial bleeding, infection, malposition, and hardware issues, such migration, disconnection, or malfunction, but the risk of each of these complications is low--generally ≤ 5% at experienced, large-volume centers. It has been used widely in essential tremor, Parkinson's disease, and dystonia when medical treatment becomes ineffective, intolerable owing to side effects, or causes motor complications. Brain targets implanted include the thalamus (most commonly for essential tremor), subthalamic nucleus (most commonly for Parkinson's disease), and globus pallidus (Parkinson's disease and dystonia), although new targets are currently being explored. Future developments include brain electrodes that can steer current directionally and systems capable of "closed loop" stimulation, with systems that can record and interpret regional brain activity and modify stimulation parameters in a clinically meaningful way. New, image-guided implantation techniques may have advantages over traditional DBS surgery.

The neurosurgical treatment of patients in dystonic state - overview of the literature.

Treatment options for patients in dystonic state include sedation, artificial ventilation, intrathecal baclofen infusions and stereotactic procedures. The main aim of this overview is the presentation and assessment of stereotactic procedures applied for treating patients in severe dystonic state. We performed literature overview starting from 1998 to 2012 with case reports regarding all patients treated by stereotactic procedures for dystonic state. We were able to find 15 articles describing 22 patients. Ablative procedures were described in 5 articles (3 thalamotomies, 3 pallidotomies) and were done in 6 patients. In the remaining 10 articles, globus pallidus internus stimulation was utilized in another 16 patients. We can conclude that bilateral pallidal deep brain stimulation seems to be the best stereotactic target for patients in dystonic state.

Shorter pulse generator longevity and more frequent stimulator adjustments with pallidal DBS for dystonia versus other movement disorders.

BACKGROUND: Deep brain stimulation has become a routine therapy for movement disorders, but it is relatively invasive and costly. Although stimulation intensity relates to battery longevity, less is known about how diagnosis and stimulation target contribute to this clinical outcome. Here we evaluate battery longevity in movement disorders patients who were treated at a tertiary referral center. OBJECTIVE: To compare single channel pulse generator longevity in patients with movement disorders. METHODS: With Institutional Review Board approval, we evaluated 470 consecutive Soletra implants for routine care. Battery longevity was estimated with Kaplan-Meier analyses, and group comparisons were performed with the log rank mean test. The frequency of clinic encounters for ongoing care was evaluated across diagnoses with analysis of variance (ANOVA). RESULTS: The mean pulse generator longevity was 44.9 ± 1.4 months. Pallidal DBS for dystonia was associated with shorter battery longevity than subthalamic and thalamic DBS for Parkinson's disease and essential tremor (28.1 ± 2.1 versus 47.1 ± 1.8 and 47.8 ± 2.6 months, respectively, mean ± standard error, P < 0.001), and dystonia patients required more frequent clinic visits for routine care (F = 6.0, P = 0.003). Pallidal DBS for Parkinson's disease and thalamic DBS for cerebellar outflow tremor were associated with shorter battery longevity, as well (35.3 ± 4.6 and 26.4 ± 4.3 months, respectively). CONCLUSIONS: Pallidal DBS for dystonia was associated with shorter battery longevity and more frequent stimulator adjustments versus DBS for Parkinson's disease and essential tremor. Characteristics of the stimulation target and disease pathophysiology both likely contribute to battery longevity in patients with movement disorders.

[Neuromuscular electric stimulation therapy in otorhinolaryngology]. / Neuromuskuläre Elektrostimulationsverfahren in der HNO-Heilkunde.

BACKGROUND: Animal experiments have shown that after specific nerve traumatization, neuromuscular electrostimulation (NMES) can promote nerve regeneration and reduce synkinesia without negatively interfering with normal regeneration processes. NMES is used routinely in physical rehabilitation medicine. METHODS: This systematic literature search in the Cochrane Central Register of Controlled Trials, the Cochrane Database of Systematic Reviews, the DAHTA database, the Health Technology Assessment Database and MEDLINE or PubMed considered studies on the use of NMES in otorhinolaryngology that have been published in German or English. RESULTS: The search identified 180 studies. These were evaluated and relevant studies were included in the further evaluation. DISCUSSION: In the fields of otorhinolaryngology and phoniatry/paediatric audiology, clinical studies investigating the effects of NMES on facial and laryngeal paresis, as well as dysphonia and dysphagia have been carried out. The evidence collected to date is encouraging; particularly for the treatment of certain forms of dysphagia and laryngeal paresis.