Rethinking status dystonicus

Status dystonicus is a movement disorder emergency that has been a source of controversy in terms of terminology, phenomenology, and management since it was first described in 1982. Here we argue that the current use of the term status dystonicus falls well short of the precision needed for either clinical or academic use. We performed a critical review on this topic, describing possible pathophysiological mechanisms and areas of uncertainties. This review also addresses the problems derived by the extreme clinical heterogeneity of this condition, as the lack of an objective criterion useful for the definition, or the fact that status dystonicus may present not only in the context of a known dystonic syndrome. We propose a new possible definition that includes not only dystonia but also other hyperkinetic movements in the wide range of movement disorders that can be seen during an episode. The new definition keeps the term status dystonicus and highlights the fact that this is a medical emergency based on the impairment of bulbar and/or respiratory function requiring hospital admission as the principal feature. Furthermore, the new definition should not consider as necessary unspecific features as patient's condition at baseline, the distribution of dystonia, occurrence of systemic symptoms such as fever or laboratory findings. We hope that this proposal will stimulate the debate on this subject among our peers, further developing a clinical and pathophysiological understanding of status dystonicus. © 2017 International Parkinson and Movement Disorder Society     

Patients' perceptions of life shift after deep brain stimulation for primary dystonia—A qualitative study

Studies of deep brain stimulation for dystonia have shown significant motor improvement. However, patients' perceptions of surgery and its effects have been less studied. We aimed to explore perceptions of changes in life in patients with primary dystonia after deep brain stimulation. Thirteen patients underwent thematic interviews 8–60 months after pallidal deep brain stimulation. Interviews were transcribed verbatim and analyzed with grounded theory. Patients described a profound impact of dystonia on daily life. After surgery, physical changes with a more upright posture and fewer spasms translated into an easier, more satisfying life with greater confidence. Notwithstanding this positive outcome, the transition from a limited life before surgery to opportunities for a better life exhibited obstacles: The “new life” after deep brain stimulation was stressful, including concern about being dependent on the stimulator as well as having to deal with interfering side effects from deep brain stimulation. The whole coping process meant that patients had to quickly shift focus from struggling to adapt to a slowly progressive disorder to adjustment to a life with possibilities, but also with new challenges. In this demanding transition process, patients wished to be offered better professional guidance and support. Even though deep brain stimulation provides people with primary dystonia with a potential for better mobility and more confidence, patients experienced new challenges and expressed the need for support and counseling after surgery. Grounded theory is a useful method to highlight patients' own experience and contributes to a deeper understanding of the impact of deep brain stimulation on patients with dystonia. © 2011 Movement Disorder Society     

Management of status dystonicus: our experience and review of the literature.

Status dystonicus (SD) is a life threatening disorder that develops in patients with both primary and secondary dystonia, characterized by acute worsening of symptoms with generalized and severe muscle contractions. To date, no information is available on the best way to treat this disorder. We review the previously described cases of SD and two new cases are reported, one of which occurring in a child with static encephalopathy, and the other one in a patient with pantothenate kinase-associated neurodegeneration. Both patients were admitted to an intensive care unit and treated with midazolam and propofol. This approach proved to be useful in the former while the progressive nature of the dystonia of the second patient required the combination of intrathecal baclofen infusion and bilateral pallidal deep brain stimulation. We believe that a rapid and aggressive approach is justified to avoid the great morbidity and mortality which characterize SD. Our experience, combined with the data available in the literature, might permit to establish the best strategies in managing this rare and severe condition.     

Deep brain stimulation for dystonia: outcome at long-term follow-up

OBJECTIVE: Deep brain stimulation (DBS) has emerged as a useful therapeutic option for patients with insufficient benefit from conservative treatment. METHODS: Nine patients with chronic DBS who suffered from cervical dystonia (4), generalized dystonia (2), hemidystonia (1), paroxysmal dystonia (1) and Meige syndrome (1) were available for formal follow-up at three years postoperatively, and beyond up to 10 years. All patients had undergone pallidal stimulation except one patient with paroxysmal dystonia who underwent thalamic stimulation. RESULTS: Maintained improvement was seen in all patients with pallidal stimulation up to 10 years after surgery except in one patient who had a relative loss of benefit in dystonia ratings but continued to have improved disability scores. After nine years of chronic thalamic stimulation there was a mild loss of efficacy which was regained when the target was changed to the pallidum in the patient with paroxysmal dystonia. There were no major complications related to surgery or to chronic stimulation. Pacemakers had to be replaced within 1.5 to 2 years, in general. CONCLUSION: DBS maintains marked long-term symptomatic and functional improvement in the majority of patients with dystonia.     

Long‐term clinical outcome in meige syndrome treated with internal pallidum deep brain stimulation

Deep brain stimulation of the globus pallidus internus (GPi DBS) is effective in the treatment of primary segmental and generalized dystonia. Although limb, neck, or truncal dystonia are markedly improved, orofacial dystonia is ameliorated to a lesser extent. Nevertheless, several case reports and small cohort studies have described favorable short‐term results of GPi DBS in patients with severe Meige syndrome. Here, we extend this preliminary experience by reporting long‐term outcome in a multicenter case series, following 12 patients (6 women, 6 men) with Meige syndrome for up to 78 months after bilateral GPi DBS. We retrospectively assessed dystonia severity based on preoperative and postoperative video documentation. Mean age of patients at surgery was 64.5 ± 4.4 years, and mean disease duration 8.3 ± 4.4 years. Dystonia severity as assessed by the Burke–Fahn–Marsden Dystonia Rating Scale showed a mean improvement of 45% at short‐term follow‐up (4.4 ± 1.5 months; P < 0.001) and of 53% at long‐term follow‐up (38.8 ± 21.7 months; P < 0.001). Subscores for eyes were improved by 38% (P = 0.004) and 47% (P < 0.001), for mouth by 50% (P < 0.001) and 56% (P < 0.001), and for speech/swallowing by 44% (P = 0.058) and 64% (P = 0.004). Mean improvements were 25% (P = 0.006) and 38% (P < 0.001) on the Blepharospasm Movement Scale and 44% (P < 0.001) and 49% (P < 0.001) on the Abnormal Involuntary Movement Scale. This series, which is the first to demonstrate a long‐term follow‐up in a large number of patients, shows that GPi DBS is a safe and highly effective therapy for Meige syndrome. The benefit is preserved for up to 6 years. © 2011 Movement Disorder Society     

Factors predicting improvement in primary generalized dystonia treated by pallidal deep brain stimulation

Despite the beneficial effects of Globus Pallidus internus (GPi) deep brain stimulation (DBS) in patients with primary generalized dystonia (PGD), the degree of improvement varies from one patient to another. The objective of this study was to examine the effects of clinical, anatomical (volume of the GPi), and electrical variables on the postoperative Burke‐Fahn‐Marsden Dystonia rating scale (BFMDRS) motor score to identify which factors may be predictive of the degree of improvement. We reviewed retrospectively the clinical records of 40 steady‐state patients with PGD who had been treated by bilateral GPi lead implantation. The follow‐up period was 2 to 8 years. The correlation between the electrical parameters (voltage, impedance, and current) and the clinical outcome was studied. An analysis of covariance was performed to identify factors predictive of the magnitude of improvement. The most influential factors according to the model are as follows: the preoperative BFMDRS score (P < 0.0001); age at surgery (P < 0.0001); the right GPi volume (P = 0.002); the left stimulated GPi volume (P = 0.005). No significant correlation was found between the electrical parameters used and the mean motor scores in steady state. © 2009 Movement Disorder Society     

Focal childhood‐onset,action induced primary hip dystonia treated with pallidal deep brain stimulation

Focal proximal lower limb dystonias are rare. Unlike the adult form, focal lower limb dystonias in children usually become generalized. The condition is often unrecognized and the patient often receives orthopedic or psychiatric treatment for years before the diagnosis eventually made. Previously reported cases of isolated lower limb dystonias have been managed nonsurgically. We present a case of a childhood‐onset action‐induced primary hip dystonia that has remained focal even in adulthood and which responded successfully to pallidal deep brain stimulation. Additionally, our results suggest that neurons representing the leg lie within the most ventral aspect of the globus pallidus interna. © 2008 Movement Disorder Society     

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     

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     

Deep brain stimulation in dystonia: Sonographic monitoring of electrode placement into the globus pallidus internus

Deep brain stimulation (DBS) of the globus pallidus internus (GPi) is an effective treatment in primary dystonia. Its success depends on the implantation accuracy of the DBS electrode into the targeted GPi. Discrepancies of up to 4 mm between the initial target, selected on preoperative MRI, and the final DBS lead location are caused mainly by caudal brain shift that occurs once the cranium is open. Nowadays, transcranial sonography (TCS) can display echogenic deep brain structures with higher image resolution compared to MRI under clinical conditions. Here, we demonstrate for the first time the use of a contemporary clinical high‐end TCS system for intraoperative monitoring of DBS electrode position. Herewith, a high‐resolution real‐time imaging of closely located microelectrodes and of the DBS lead through the intact skull is feasible. Simultaneous color‐coded sonographic imaging of arteries near the anatomical target allows further intraoperative refinement of DBS lead positioning, simultaneously preventing hemorrhages. © 2009 Movement Disorder Society     

Deep brain stimulation of the anterior nucleus of the thalamus in a patient with super-refractory convulsive status epilepticus

We report the first patient to die from refractory convulsive status epilepticus (SE) after the removal of a stimulator. The removal occurred after a two-year period of successful control of super-refractory convulsive SE with deep brain stimulation of the bilateral anterior nucleus of the thalamus (ANT-DBS). The female patient, born in 1990, suffered from high fever and seizures, and was diagnosed with viral encephalitis in 2005. After four weeks of medical treatment, she recovered with no neurological disabilities, but suffered from monthly seizures. Ten years later, the patient presented with convulsive SE, while four months pregnant in February of 2015. Her SE remained super-refractory to drugs despite the termination of pregnancy. Therefore, ANT-DBS was performed in March of 2015. The patient became SE-free following activation of an ANT-DBS stimulator. However, the stimulation treatment was terminated according to the family's request when a tremor developed two years after the treatment had begun. Subsequently, four SE episodes occurred and the tremor did not improve. The stimulator and electrodes were removed in August of 2017. The patient died of an uncontrolled SE two months later. This case demonstrates the effectiveness of ANT-DBS for emergency super-refractory convulsive SE with both positive and negative outcomes.     

Globus pallidus deep brain stimulation in dystonia.

Globus pallidus deep brain stimulation (GPi-DBS) is a useful alternative in the treatment of dystonia. Patients selected for GPi-DBS were prospectively rated with the Unified Dystonia Rating Scale (UDRS). Also, "blinded" videotape assessments were performed. Eleven patients were identified. Compared with pre-DBS scores, there were improvements in mean total UDRS score (15.3%) and in the following subscores: neck (18.18%), trunk (32.9%), arm (17.9%), and leg (19.9%). One patient developed a skin infection and erosion requiring surgical debridement. GPi-DBS is a safe and effective treatment for generalized dystonia in patients who remained impaired, despite optimal medical therapy.     

Deep brain stimulation to treat hyperkinetic symptoms of Cockayne syndrome.

Cockayne syndrome manifests a spectrum of neurological dysfunction that includes medically intractable movement disorders. Deep brain stimulation has not been well studied in such rare neurodegenerative conditions. In this case, stimulation of the ventral intermediate nucleus of the thalamus was used to manage severe motor symptoms in a young man with Cockayne syndrome. There was a marked and progressive response to thalamic stimulation within weeks of surgery. These results suggest that patients with Cockayne syndrome should be considered for deep brain stimulation to treat refractory movement disorders.