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.

Objective and Clinically Feasible Analysis of Diffusion MRI Data can Help Predict Dystonia After Neonatal Brain Injury.

BACKGROUND: Dystonia in cerebral palsy is debilitating but underdiagnosed precluding targeted treatment that is most effective if instituted early. Deep gray matter injury is associated with dystonic cerebral palsy but is difficult to quantify. Objective and clinically feasible identification of injury preceding dystonia could help determine the children at the highest risk for developing dystonia and thus facilitate early dystonia detection. METHODS: We examined brain magnetic resonance images from four- to five-day-old neonates after therapeutic hypothermia for hypoxic-ischemic encephalopathy at a tertiary care center. Apparent diffusion coefficient values in the striatum and thalamus were determined using a web-based viewer integrated with the electronic medical record (IBM iConnect Access). The notes of specialists in neonatal neurology, pediatric movement disorders, and pediatric cerebral palsy (physicians most familiar with motor phenotyping after neonatal brain injury) were screened for all subjects through age of five years for motor phenotype documentation. RESULTS: Striatal and thalamic apparent diffusion coefficient values significantly predicted dystonia with receiver operator characteristic areas under the curve of 0.862 (P = 0.0004) and 0.838 (P = 0.001), respectively (n = 50 subjects). Striatal apparent diffusion coefficient values less than 1.014 × 10-3 mm2/s provided 100% specificity and 70% sensitivity for dystonia. Thalamic apparent diffusion coefficient values less than 0.973 × 10-3 mm2/s provided 100% specificity and 80% sensitivity for dystonia. CONCLUSIONS: Lower striatal and thalamic apparent diffusion coefficient values predicted dystonia in four- to five-day-old neonates who underwent therapeutic hypothermia for hypoxic ischemic encephalopathy. Objective and clinically feasible neonatal brain imaging assessment could help increase vigilance for dystonia in cerebral palsy.

Hyperbaric oxygen therapy for hypoxic-ischemic encephalopathy in non-fatal drowning.

Paroxysmal autonomic instability syndrome with dystonia (PAISD) is a possible complication that worsens the prognosis of hypoxic-ischemic encephalopathy related to non-fatal drowning. There are case reports of hyperbaric oxygen (HBO2) therapy enhancing recovery in such cases. We report a case of a 5-year-old boy admitted to the Pediatric Intensive Care Unit after a non-fatal drowning. He was transferred under mechanical ventilation and sedation, with hemodynamic instability and hypothermia. On admission he had a Glasgow Coma Score of 6. On the fifth day of admission he presented episodes of dystonia with decerebration posture, diaphoresis, tachycardia and hypertension, sometimes with identified triggers, suggesting PAISD. The episodes were difficult to control; multiple drugs were needed. Electroencephalography showed diffuse slow wave activity, and cranioencephalic magnetic resonance imaging showed hypoxia-related lesions, suggesting hypoxic-ischemic encephalopathy. Early after admission the patient started physiotherapy combined with normobaric oxygen therapy. Subsequently he started HBO2 therapy at 2 atmospheres, with a total of 66 sessions. Dystonia progressively subsided, with gradual discontinuation of therapy. He also showed improvement in spasticity, non-verbal communication and cephalic control. This case highlights the diagnostic and therapeutic challenges of PAISD and the potential benefit of HBO2 therapy, even in the subacute phase, in recovery of hypoxic-ischemic encephalopathy.

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).

Dystonia as complication of thalamic neurosurgery.

BACKGROUND: Thalamotomy and deep brain stimulation of the ventralis intermedius nucleus are effective symptomatic treatments for tremor, irrespective of the underlying diagnosis. METHODS AND RESULTS: Herein we describe six tremor patients (2 Parkinson's disease, 1 dystonic tremor, 2 Essential tremor plus dystonia, 1 Essential tremor plus ataxia) who underwent thalamic neurosurgery and acutely or sub-acutely developed dystonia that was permanent in three cases and could not be managed with any adjustments in the stimulation settings. Tremor response was excellent. We argue that thalamic procedures disrupted either or both the cerebello-thalamic and the cortico-striato-pallido-thalamo-cortical loop resulting in an increase of the thalamo-cortical outflow and subsequent change in the clinical picture from tremor to dystonia. CONCLUSION: Thalamic neurosurgery might be rarely complicated by dystonia. Why some patients are more prone to develop this adverse event is still unknown and possibly related to intrinsic factors, which certainly need further studies.

[Acute Generalized Chorea, Dystonia and Brain Calcifications: A Case Report]. / Coreia Aguda Generalizada, Distonia e Calcificações Cerebrais: A Propósito de um Caso Clínico.

Pathological basal ganglia calcification, or Fahr's Syndrome, can be secondary to a variety of diseases, namely parathyroid disturbances. Movement disorders are common clinical features, in which chorea is seen in less than 20% of cases and dystonia just in 8%. We report the clinical case of a 49-year-old male with a history of thyroidectomy, who was admitted in Emergency Service with acute generalized chorea and focal painful feet dystonia. Laboratory analysis showed hypocalcemia and rhabdomyolysis, and computed tomography scan revealed parenchymal calcification with basal ganglia involvement. After complementary studies we established a Fahr's Syndrome diagnosis secondary to an iatrogenic hypoparathyroidism. Clinical management has been successful with stabilized calcium levels, with no more neurologic symptoms. Hypocalcemia should be readily investigated and treated after a thyroidectomy, given the irreversibility of intracerebral calcifications and potential neurological or systemic consequences.

A calcificação dos núcleos da base, ou síndrome de Fahr, pode ser secundária a variadas doenças, nomeadamente as que cursam com envolvimento da paratiróide. Distúrbios do movimento são achados clínicos comuns, mas a coreia é observada em menos de 20% dos casos e a distonia apenas em 8%. Apresentamos o caso de um homem de 49 anos com antecedentes de tiroidectomia, admitido no serviço de urgência com coreia aguda generalizada e distonia focal dolorosa dos pés, cujo estudo laboratorial revelava hipocalcémia e rabdomiólise e a tomografia computorizada crânio-encefálica mostrava calcificações parenquimatosas extensas com envolvimento dos núcleos da base. A alargada investigação complementar permitiu fazer o diagnóstico de síndrome de Fahr secundária a hipoparatiroidismo iatrogénico. Após estabilização da calcémia, a evolução clínica foi favorável com resolução dos sintomasneurológicos. A hipocalcémia deve ser investigada e corrigida depois de tiroidectomias, dada a irreversibilidade das calcificações intracerebrais e as potenciais consequências neurológicas e sistémicas.

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.

Secondary paroxysmal dyskinesia in multiple sclerosis: Clinical-radiological features and treatment. Case report of seven patients.

Secondary paroxysmal dyskinesias (SPDs) are short, episodic, and recurrent movement disorders, classically related to multiple sclerosis (MS). Carbamazepine is effective, but with risk of adverse reactions. We identified 7 patients with SPD among 457 MS patients (1.53%). SPD occurred in face ( n = 1), leg ( n = 2), or arm +leg ( n = 4) several times during the day. Magnetic resonance imaging (MRI) showed new or enhancing lesions in thalamus ( n = 1), mesencephalic tegmentum ( n = 1), and cerebellar peduncles ( n = 5). Patients were treated with clonazepam and then acetazolamide ( n = 1), acetazolamide ( n = 5), or levetiracetam ( n = 1) with response within hours (acetazolamide) to days (levetiracetam). No recurrences or adverse events were reported after a median follow-up of 33 months.

Status Dystonicus in a Child with Familial Idiopathic Hypoparathyroidism.

Hypoparathyroidism leading to status dystonicus is rarely reported in literature. The authors present an 8-y-old girl with idiopathic familial hypoparathyroidism who presented with status dystonicus. She was managed successfully with midazolam infusion, calcium and vitamin D supplementation, and oral anti-dystonia drugs.

Historical developments in children's deep brain stimulation.

BACKGROUND: Heterogeneous by the underlying pathobiology and clinical presentation, childhood onset dystonia is most frequently progressive, with related disability and limitations in functions of daily living. Consequently, there is an obvious need for efficient symptomatic therapies. METHODS AND RESULTS: Following lesional surgery to basal ganglia (BG) and thalamus, deep brain stimulation (DBS) is a more conservative and adjustable intervention to and validated for internal segment of the globus pallidus (GPi), highly efficient in treating isolated "primary" dystonia and associated symptoms such as subcortical myoclonus. The role of DBS in acquired, neurometabolic and degenerative disorders with dystonia deserves further exploration to confirm as an efficient and lasting therapy. However, the pathobiological background with distribution of the sequellae over the central nervous system and related clinical features, will limit DBS efficacy in these conditions. Cumulative arguments propose DBS in severe life threatening dystonic conditions called status dystonicus as first line therapy, irrespective of the underlying cause. There are no currently available validated selection criteria for DBS in pediatric dystonia. Concurrent targets such as subthalamic nucleus (STN) and several motor nuclei of the thalamus are under exploration and only little information is available in children. DBS programming in paediatric population was adopted from experience in adults. The choice of neuromodulatory DBS parameters could influence not only the initial therapeutic outcome of dystonic symptoms but also its maintenance over time and potentially the occurrence of DBS related side effects. CONCLUSION: DBS allows efficient symptomatic treatment of severe dystonia in children and advances pathophysiological knowledge about local and distributed abnormal neural activity over the motor cortical-subcortical networks in dystonia and other movement disorders.

Clinical patterns of dystonia and choreoathetosis in participants with dyskinetic cerebral palsy.

AIM: The aim of the study was to map clinical patterns of dystonia and choreoathetosis and to assess the relation between functional classifications and basal ganglia and thalamus lesions in participants with dyskinetic cerebral palsy (CP). METHODS: In this cross-sectional study, 55 participants with dyskinetic CP (mean age 14y 6mo, SD 4y 1mo; range 6-22y) were assessed with the Dyskinesia Impairment Scale and classified with the Gross Motor Function Classification System (GMFCS), Manual Ability Classification System (MACS), and Communication Function Classification System (CFCS). RESULTS: Dystonia and choreoathetosis are simultaneously present. Median levels of dystonia (70.2%) were significantly higher than levels of choreoathetosis (26.7%) and both were significantly higher during activity than at rest (both p<0.01). High correlations were found between dystonia levels and GMFCS level (Spearman's rank correlation coefficient, rS =0.70; 95% confidence interval [CI] 0.53-0.81; p<0.01) and MACS (rS =0.65; 95% CI 0.47-0.81; p<0.01), and fair correlation with CFCS (rs =0.36; 95% CI=0.11-0.57; p<0.05). No significant correlation was found between choreoathetosis levels and motor classifications. Finally, higher choreoathetosis levels were found in participants with pure thalamus and basal ganglia lesions (p=0.03) than mixed lesions, but not for dystonia (p=0.41). INTERPRETATION: Dystonia and choreoathetosis increase during activity. However, dystonia predominates and seems to have a larger impact on functional abilities. Our findings further suggest that choreoathetosis seems to be more linked to pure thalamus and basal ganglia lesions than dystonia.

Manganese transport disorder: novel SLC30A10 mutations and early phenotypes.

BACKGROUND: SLC30A10 mutations cause an autosomal recessive disorder, characterized by hypermanganesaemia, polycythemia, early-onset dystonia, paraparesis, or late-onset parkinsonism, and chronic liver disease. This is the first identified inborn error of Mn metabolism in humans, reported in 10 families thus far. METHODS: Methods for this study consisted of clinical examination, neuroimaging studies (MRI), serum dosages, and SLC30A10 genetic analysis. RESULTS: We describe early disease manifestations (including videos) in 5 previously unreported Indian children, carrying novel homozygous SLC30A10 mutations. Gait and speech disturbances, falls, dystonias, and central hypotonia were the presenting neurological features, starting within the first 5 years of life. All children also had severe hypermanganesemia, polycythemia, variable degree of liver disease, and marked brain MRI T1 hyperintensities. CONCLUSIONS: Our findings expand the mutational and clinical spectra of this recently recognized disorder. An early diagnosis is warranted, because treatment with manganese-chelating agents, iron supplementation, or their combination might improve symptoms and prevent progression of this otherwise potentially fatal disease. © 2015 International Parkinson and Movement Disorder Society.

Dystonia and tremor secondary to thalamic infarction successfully treated with thalamotomy of the ventralis intermedius nucleus.

BACKGROUND: Focal thalamic lesions have been associated with a variety of involuntary movements such as tremor, dystonia, and chorea-ballism. METHODS: We describe a patient with severe hyperkinesias of the right arm secondary to a thalamic infarction in the left postero-ventral region of the thalamus. RESULTS: The dystonia and tremor of the right upper limb were subsequently controlled with another surgical lesion of the ventralis intermedius nucleus of the thalamus. CONCLUSION: This observation suggests that ablative surgery might be applied to treat a movement disorder induced by the lesion of the same nucleus, which in addition lead to interesting pathophysiological conjectures.

Impact of paroxysmal sympathetic hyperactivity on nutrition management after brain injury: a case series.

OBJECTIVE: To review the nutritional requirements of all new inpatient brain injury admissions presenting with Paroxysmal Sympathetic Hyperactivity (PSH) in the rehabilitation setting. METHODS: RABIU is a 25-bed Regional facility in Northern Ireland which opened in 2006. All records of patients with a single episode non-progressive acquired brain injury admitted to RABIU from 2006 until the present were reviewed for evidence of PSH. Dietetic assessment and management was examined and recorded. RESULTS: Four patients with persisting paroxysmal sympathetic hyperactivity were identified. All patients displayed dystonia and posturing and had clinically important percentage weight loss. All had nutrition and/or hydration requirements markedly above their estimated requirement for slow weight gain, despite adjustment for brain injury. All four had posture-related complications of their dystonia and nutrition. CONCLUSION: Careful monitoring of nutrition, hydration and mineral supplementation is paramount in patients presenting with paroxysmal sympathetic hyperactivity after brain injury. It is argued that morbidity may be reduced by aggressive and expert nutrition management.

Motor cortex stimulation does not improve dystonia secondary to a focal basal ganglia lesion.

OBJECTIVE: To assess the efficacy of epidural motor cortex stimulation (MCS) on dystonia, spasticity, pain, and quality of life in patients with dystonia secondary to a focal basal ganglia (BG) lesion. METHODS: In this double-blind, crossover, multicenter study, 5 patients with dystonia secondary to a focal BG lesion were included. Two quadripolar leads were implanted epidurally over the primary motor (M1) and premotor cortices, contralateral to the most dystonic side. The leads were placed parallel to the central sulcus. Only the posterior lead over M1 was activated in this study. The most lateral or medial contact of the lead (depending on whether the dystonia predominated in the upper or lower limb) was selected as the anode, and the other 3 as cathodes. One month postoperatively, patients were randomly assigned to on- or off-stimulation for 3 months each, with a 1-month washout between the 2 conditions. Voltage, frequency, and pulse width were fixed at 3.8 V, 40 Hz, and 60 µs, respectively. Evaluations of dystonia (Burke-Fahn-Marsden Scale), spasticity (Ashworth score), pain intensity (visual analog scale), and quality of life (36-Item Short Form Health Survey) were performed before surgery and after each period of stimulation. RESULTS: Burke-Fahn-Marsden Scale, Ashworth score, pain intensity, and quality of life were not statistically significantly modified by MCS. CONCLUSIONS: Bipolar epidural MCS failed to improve any clinical feature in dystonia secondary to a focal BG lesion. CLASSIFICATION OF EVIDENCE: This study provides Class I evidence that bipolar epidural MCS with the anode placed over the motor representation of the most affected limb failed to improve any clinical feature in dystonia secondary to a focal BG lesion.

Cathodal transcranial direct current stimulation in children with dystonia: a sham-controlled study.

Increased motor cortex excitability is a common finding in dystonia, and transcranial direct current stimulation can reduce motor cortex excitability. In an earlier study, we found that cathodal direct-current stimulation decreased motor overflow for some children with dystonia. To investigate this observation further, we performed a sham-controlled, double-blind, crossover study of 14 children with dystonia. We found a significant reduction in overflow following real stimulation, when participants performed the experimental task with the hand contralateral to the cathode. While these results suggest that cathodal stimulation may help some children to reduce involuntary overflow, the size of the effect is small. Further research will need to investigate ways to increase the magnitude of the effect of cathodal transcranial direct current stimulation.

Management of spasticity and dystonia in children with acquired brain injury with rehabilitation and botulinum toxin A.

OBJECTIVE: To investigate the effect of a combination of botulinum toxin A (BTX-A) and rehabilitation on spasticity, pain and motor functioning in children with acquired brain injury (ABI). METHODS: All children and adolescents with ABI, aged 2-20 years, consecutively treated in the department over a 22-month period, were prospectively followed-up and clinically assessed pre- and post-treatment. They had spasticity and/or dystonia leading to impairment in activities of daily living, orthopaedic deformations and/or pain. Injections were performed using electro-stimulation. Doses of BTX-A (Botox) were administered using recent recommendations. RESULTS: Twenty-five children (mean age 6.3 years) participated in the study (51 injection sessions). All patients received BTX-A injections, followed with physical and/or occupational therapy. Significant improvement was achieved for spasticity reduction (p < 0.0001), command on antagonist muscles (p = 0.03 for the tibialis anterior) and goniometry assessment (p < 0.05). Pain relief was achieved in patients in a minimally responsive state. Functional goals were achieved, such as improving transfers or gait, grasping and releasing abilities, with significant transfer in activities of daily living (p < 0.0001). CONCLUSION: A combination of BTX-A injection with rehabilitation is an interesting option for treatment of muscle tone disorders in children with ABI.