Deep Brain Stimulation for Generalized Dystonia from Secondary Carnitine Deficiency: A Case Report and Literature Review.

BACKGROUND: Carnitine deficiencies result from a metabolic disorder of fatty acid β-oxidation and may lead to organic acidemia, which are thought to be associated with dystonia, epilepsy, autism and developmental delay. Pharmacotherapy has been the dominant therapy, while many refractory patients still require other treatment. Deep brain stimulation (DBS) of the globus pallidus internus (GPi) has been found to be effective for medically refractory primary dystonia and now it has been proposed to be used for secondary dystonia from mitochondrial metabolic disorder. OBJECTIVE: To investigate the efficacy and safety of DBS treatment in secondary dystonia from organic acid metabolic disorder. METHODS: We present a patient born with secondary carnitine deficiency who had the onset of generalized seizures at age 4.5 months and developed torsion dystonia at age 14. Multiple medical therapies failed to adequately control her symptoms, therefore she received GPi DBS at age 26 years. In addition, we performed a literature review of this therapy in the treatment of organic acid metabolic disorder. RESULTS: Our patient’s dystonia resolved without side effects post-DBS surgery, but intermittent spastic symptoms along with severe pain in her lower extremity persist. Concerning the 8 cases from our literature review, 7 received GPi DBS, and had improvement in motor symptoms. Overall, DBS efficacy was lower than in treatment of primary dystonia. One patient with methylmalonic acidemia received STN DBS and had marked improvement in dystonia and reduction in pain afterwards. CONCLUSION: DBS has become an effective therapy in refractory secondary dystonia from organic acid metabolic disorder. More prospective studies are needed to determine the eligibility and efficacy of this surgical therapy in these cases.

Status Dystonicus in Children with Secondary Dystonia: Reporting 3 Cases of Cerebral Palsy, Leigh Disease and Molybodynum Co Factor Deficiency

Objective: Patients with primary and secondary dystonic syndromes occasionally develop severe episodes of generalized dystonia and rigidity which is known as status dystonicus (SD) or dystonic storm. This is a frightening hyperkinetic movement disorder and it is an emergency. Marked, rapid exacerbation of dystonia requires prompt intervention and admission in the hospital. It is critical to recognize early and differentiate dystonic storm from other hyperkinetic movement disorder as it may lead to metabolic complications such as rhabdomyolysis, leading to acute renal failure. This paper has been written to describe three cases of SD, all having secondary dystonia with different etiologies to highlight the mode of presentation, diagnosis, treatment and outcome. Methodology: We report 3 cases of severe secondary dystonia culminating in SD necessitating management in hospital setting. All the three cases were admitted in a tertiary care hospital and evaluated. Results: One patient was treated in intensive care unit. In brief 1st case was a 5 year boy with dyskinetic CP who was treated with trihexiphenidyl (THP), baclofen and midazolam infusion. Second case was a 15 month old boy, diagnosed case of mitochondrial encephalopathy (Leigh disease) who was treated with THP, baclofen, haloperidol, clonazepam and infusion midazolam. The third case was a 13 month old boy, diagnosed case of Molybdenum Cofactor deficiency who was treated with THP, tizanidine but they refused to take midazolam. Conclusion: In this case series, three cases with SD with different etiology have been described with clinical features, modalities of treatment and outcome.

Evoked Potentials During Peripheral Stimulation Confirm Electrode Location in Thalamic Subnuclei in Children With Secondary Dystonia

Deep brain stimulation is an elective surgical intervention that improves the function and quality of life in children with dystonia and other movement disorders. Both basal ganglia and thalamic nuclei have been found to be relevant targets for treatment of dystonia in children, including the ventral intermediate nucleus of the thalamus, in which stimulation can control dystonic spasms. Electrophysiological confirmation of correct electrode location within the ventralis intermediate nucleus is thus important for the success of the surgical outcome. The present work shows the evoked potentials response during contralateral median-nerve stimulation at the wrist at low frequency (9 Hz) provides physiological evidence of the electrode’s localization within the thalamus. We show the correlation between evoked potentials and magnetic resonance imaging (MRI) and computed tomography (CT) in 14 children undergoing implantation of deep brain stimulation electrodes for secondary dystonia. High fidelity and reproducibility of our results provides a new approach to ensure the electrode localization in the thalamic subnuclei.

EMG-based vibro-tactile biofeedback training: effective learning accelerator for children and adolescents with dystonia? A pilot crossover trial

Background This study is aimed at better understanding the role of a wearable and silent ElectroMyoGraphy-based biofeedback on motor learning in children and adolescents with primary and secondary dystonia. Methods A crossover study with a wash-out period of at least 1 week was designed; the device provides the patient with a vibration proportional to the activation of an impaired target muscle. The protocol consisted of two 5-day blocks during which subjects were trained and tested on a figure-8 writing task: their performances (at different levels of difficulty) were evaluated in terms of both kinematics and muscular activations on day 1 and day 5, while the other 3 days were purely used as training sessions. The training was performed with and without using the biofeedback device: the week of use was randomized. Data were collected on 14 subjects with primary and secondary (acquired) dystonia (age: 6–19 years). Results Results comparing kinematic-based and EMG-based outcome measures pre- and post-training showed learning due to practice for both subjects with primary and secondary dystonia. On top of said learning, an improvement in terms of inter-joint coordination and muscular pattern functionality was recorded only for secondary dystonia subjects, when trained with the aid of the EMG-based biofeedback device. Conclusions Our results support the hypothesis that children and adolescents with primary dystonia in which there is intact sensory processing do not benefit from feedback augmentation, whereas children with secondary dystonia, in which sensory deficits are often present, exhibit a higher learning capacity when augmented movement-related sensory information is provided. This study represents a fundamental investigation to address the scarcity of noninvasive therapeutic interventions for young subjects with dystonia.

Clinical phenotypes associated with outcomes following deep brain stimulation for childhood dystonia

OBJECTIVEAlthough deep brain stimulation (DBS) is an accepted treatment for childhood dystonia, there is significant heterogeneity in treatment response and few data are available to identify ideal surgical candidates.METHODSData were derived from a systematic review and individual patient data meta-analysis of DBS for dystonia in children that was previously published. Outcomes were assessed using the Burke-Fahn-Marsden Dystonia Rating Scale for movement (BFMDRS-M) and for disability (BFMDRS-D). The authors used partial least squares, bootstrapping, and permutation statistics to extract patterns of contributions of specific preoperative characteristics to relationship with distinct outcomes, in all patients and in patients with primary and secondary dystonia separately.RESULTSOf 301 children undergoing DBS for dystonia, 167 had primary dystonia, 125 secondary dystonia, and 9 myoclonus dystonia. Three dissociable preoperative phenotypes (latent variables) were identified and associated with the following: 1) BFMDRS-M at last follow-up; 2) relative change in BFMDRS-M score; and 3) relative change in BFMDRS-D score. The phenotype of patients with secondary dystonia, with a high BFMDRS-M score and truncal involvement, undergoing DBS at a younger age, was associated with a worse postoperative BFMDRS-M score. Children with primary dystonia involving the trunk had greater improvement in BFMDRS-M and -D scores. Those with primary dystonia of shorter duration and proportion of life with disease, undergoing globus pallidus DBS, had greater improvements in BFMDRS-D scores at long-term follow-up.CONCLUSIONSIn a comprehensive, data-driven, multivariate analysis of DBS for childhood dystonia, the authors identified novel and dissociable patient phenotypes associated with distinct outcomes. The findings of this report may inform surgical candidacy for DBS.

Nucleus ventralis oralis anterior a potential target in deep brain stimulation for post anoxic dystonia?

Deep brain stimulation (DBS) effectiveness in secondary dystonia is still debated. Different targets have been utilized, thalamic (Vim), zona incerta, sub thalamic nucleus (STN), and globus pallidus internus (GPi) with generally disappointing clinical results. Structural lesions of the GPi, the target of choice in Dystonia, are found in some cases of secondary dystonia and prevent us from treating these patients with DBS implantation. We report the third published case of a patient with severe generalized post anoxic dystonia, associated with bilateral necrosis of the GPi, who showed significant improvement after DBS procedure in the thalamic Ventralis oralis anterior (Voa). The Ventral oralis anterior nucleus; pallidal receiving area in the thalamic nuclei could be an alternative target.