KMT2B-Related Dystonia: Challenges in Diagnosis and Treatment

2021 ◽  
pp. 1-6
Author(s):  
Ayşe Aksoy ◽  
Özlem Yayıcı Köken ◽  
Ahmet Cevdet Ceylan ◽  
Özge Toptaş Dedeoğlu
Keyword(s):  
Clinical Status ◽  
Childhood Onset ◽  
Generalized Dystonia ◽  
Basic Functions ◽  
Turkish Case ◽  
The Right ◽  
Hereditary Dystonia ◽  
Climbing Stairs ◽  
Deep Brain

In this study, we report the first known Turkish case of a novel nonsense mutation c.2453dupT (p.M818fs*28) in the <i>KMT2B</i> (NM_014727.2) gene diagnosed in a male patient with <i>KMT2B</i>-related dystonia (DYT-<i>KMT2B</i>, DYT-28, Dystonia*-28), which is a complex, childhood-onset, progressive, hereditary dystonia. The patient, who is followed up from 9 to 13 years of age, had dysmorphic features, developmental delay, short stature, and microcephaly, in addition to focal dystonia and hemichorea (in the right and left lower extremities). Generalized dystonia involving bulbar and cervical muscles, in addition to dystonic cramps, myoclonus, and hemiballismus, were also observed during the course of the follow-up. While he was able to perform basic functions like eating, climbing stairs, walking, and writing with the aid of levodopa and trihexyphenidyl treatment, his clinical status gradually deteriorated secondary to progressive generalized dystonia in the 4-year follow-up. Deep brain stimulation has been shown to be effective in several patients which could be the next preferred treatment for the patient.

Disease Stabilization of DYT1-Positive Primary Generalized Dystonia With Deep Brain Stimulation of the Globus Pallidus Interna: A 15-Year Follow-up

2017 ◽  
Vol 14 (5) ◽  
pp. E53-E57 ◽  
Author(s):  
Derrick A Dupre ◽  
Raj Nangunoori ◽  
Sravanthi Koduri ◽  
Cindy Angle ◽  
Diane Cantella ◽  
...  
Keyword(s):  
Deep Brain Stimulation ◽  
Globus Pallidus ◽  
Brain Stimulation ◽  
Disease Stabilization ◽  
Long Term Follow Up ◽  
Generalized Dystonia ◽  
The Right ◽  
Deep Brain

Abstract BACKGROUND AND IMPORTANCE Primary generalized dystonia (PGD) is a genetic form of dystonia that frequently displays pharmacological resistance and progresses quickly after onset. Deep brain stimulation (DBS) has been used successfully to treat refractory dystonia, specifically globus pallidus interna (GPi) DBS for DYT1-positive PGD patients. Long-term follow-up of the safety and efficacy falls short of the longevity seen in other diseases treated with DBS. CASE PRESENTATION A male patient presented for neurosurgical evaluation with scapular winging, hand contractures, and violent truncal spasms, which forced him to be bedridden. After failing conservative therapy, the 18-yr-old patient was implanted with bilateral GPi-DBS. DBS parameter adjustments were made primarily within the first 3 yr after implantation, with nominal changes thereafter. Initial settings were contact of 3 + 0−, amplitude of 4.9 V, frequency of 185 Hz, and pulse width of 270 μsec on the left and 3 + 0−, 2.8 V, 185 Hz, and 120 μsec on the right. Current settings are 3 + 2 + 1−, 5.2 V, 130 Hz, 330 μsec on the left and 3 + 0−, 3.5 V, 185 Hz, and 180 μsec on the right and have been relatively unchanged in the past 4 yr. Unified dystonia rating scale scores reveal a significant decrease in dystonic symptoms. CONCLUSION While prior reports have shown that GPi-DBS is effective for dystonia, this is the first with 15 yr of long-term follow-up showing disease stabilization, suggesting that stimulation is efficacious and can potentially prevent disease progression. This report reaffirms previous reports that recommend early surgical intervention before the onset of permanent musculoskeletal deficits.

Secondary chronic cluster headache treated by posterior hypothalamic deep brain stimulation: First reported case

Cephalalgia ◽  
2012 ◽  
Vol 33 (2) ◽  
pp. 136-138 ◽  
Author(s):  
Giuseppe Messina ◽  
Michele Rizzi ◽  
Roberto Cordella ◽  
Augusto Caraceni ◽  
Ernesto Zecca ◽  
...  
Keyword(s):  
Deep Brain Stimulation ◽  
Cluster Headache ◽  
Brain Stimulation ◽  
Soft Tissues ◽  
Chronic Cluster Headache ◽  
Successful Outcome ◽  
The Right ◽  
Fondazione Irccs ◽  
Deep Brain

Introduction Deep brain stimulation (DBS) of the posterior hypothalamus (pHyp) has been reported as an effective treatment for primary, drug-refractory and chronic cluster headache (CCH). We here describe the use of such a procedure for the treatment of secondary CCH due to a neoplasm affecting the soft tissues of the right hemiface. Methods A 27-year-old man affected by infiltrating angiomyolipoma of the right hemiface who subsequently developed drug refractory homolateral CCH underwent DBS of the right pHyp region at the Fondazione IRCCS Istituto Nazionale Neurologico Carlo Besta. Results After surgery, the patient presented a significant reduction in frequency of pain bouts. However, because of a subsequent infection, the entire system was removed. After re-implantation of the system, successful outcome was observed at 2 years follow-up. Discussion This brief report shows the feasibility of pHyp DBS in secondary drug-refractory CCH syndromes; future reports are needed in order to confirm our positive result.

scholarly journals Deep brain stimulation in children and young adults with secondary dystonia: the Children's Hospital Los Angeles experience

2013 ◽  
Vol 35 (5) ◽  
pp. E7 ◽  
Author(s):  
Joffre E. Olaya ◽  
Eisha Christian ◽  
Diana Ferman ◽  
Quyen Luc ◽  
Mark D. Krieger ◽  
...  
Keyword(s):  
Young Adults ◽  
Deep Brain Stimulation ◽  
Brain Stimulation ◽  
Secondary Dystonia ◽  
Benefit Evaluation ◽  
Generalized Dystonia ◽  
Children And Young Adults ◽  
The Mean ◽  
Deep Brain

Background Dystonia is a movement disorder in which involuntary sustained or intermittent muscle contractions cause twisting and repetitive movements, abnormal postures, or both. It can be classified as primary or secondary. There is no cure for dystonia and the goal of treatment is to provide a better quality of life for the patient. Surgical intervention is considered for patients in whom an adequate trial of medical treatment has failed. Deep brain stimulation (DBS), specifically of the globus pallidus interna (GPi), has been shown to be extremely effective in primary generalized dystonia. There is much less evidence for the use of DBS in patients with secondary dystonia. However, given the large number of patients with secondary dystonia, the significant burden on the patients and their families, and the potential for DBS to improve their functional status and comfort level, it is important to continue to investigate the use of DBS in the realm of secondary dystonia. Object The objective of this study is to review a series of cases involving patients with secondary dystonia who have been treated with pallidal DBS. Methods A retrospective review of 9 patients with secondary dystonia who received treatment with DBS between February 2011 and February 2013 was performed. Preoperative and postoperative videos were scored using the Barry-Albright Dystonia Scale (BADS) and Burke-Fahn-Marsden Dystonia Rating Scale (BFMDRS) by a neurologist specializing in movement disorders. In addition, the patients' families completed a subjective questionnaire to assess the perceived benefit of DBS. Results The average age at DBS unit implantation was 15.1 years (range 6–20 years). The average time to follow-up for the BADS evaluation from battery implantation was 3.8 months (median 3 months). The average time to follow-up for the subjective benefit evaluation was 10.6 months (median 9.5 months). The mean BADS scores improved by 9% from 26.5 to 24 (p = 0.04), and the mean BFMDRS scores improved by 9.3% (p = 0.055). Of note, even in patients with minimal functional improvement, there seemed to be decreased contractures and spasms leading to improved comfort. There were no complications such as infections or hematoma in this case series. In the subjective benefit evaluation, 3 patients' families reported “good” benefit, 4 reported “minimal” benefit, and 1 reported no benefit. Conclusions These early results of GPi stimulation in a series of 9 patients suggest that DBS is useful in the treatment of secondary generalized dystonia in children and young adults. Objective improvements in BADS and BFMDRS scores are demonstrated in some patients with generalized secondary dystonia but not in others. Larger follow-up studies of DBS for secondary dystonia, focusing on patient age, history, etiology, and patterns of dystonia, are needed to learn which patients will respond best to DBS.

scholarly journals Short circuit in deep brain stimulation

2012 ◽  
Vol 117 (5) ◽  
pp. 955-961 ◽  
Author(s):  
Kazuhiro Samura ◽  
Yasushi Miyagi ◽  
Tsuyoshi Okamoto ◽  
Takehito Hayami ◽  
Junji Kishimoto ◽  
...  
Keyword(s):  
Deep Brain Stimulation ◽  
Brain Stimulation ◽  
Short Circuit ◽  
Open Circuit ◽  
Symptom Improvement ◽  
Generalized Dystonia ◽  
Short Circuits ◽  
Insidious Development ◽  
Deep Brain

Object The authors undertook this study to investigate the incidence, cause, and clinical influence of short circuits in patients treated with deep brain stimulation (DBS). Methods After the incidental identification of a short circuit during routine follow-up, the authors initiated a policy at their institution of routinely evaluating both therapeutic impedance and system impendence at every outpatient DBS follow-up visit, irrespective of the presence of symptoms suggesting possible system malfunction. This study represents a report of their findings after 1 year of this policy. Results Implanted DBS leads exhibiting short circuits were identified in 7 patients (8.9% of the patients seen for outpatient follow-up examinations during the 12-month study period). The mean duration from DBS lead implantation to the discovery of the short circuit was 64.7 months. The symptoms revealing short circuits included the wearing off of therapeutic effect, apraxia of eyelid opening, or dysarthria in 6 patients with Parkinson disease (PD), and dystonia deterioration in 1 patient with generalized dystonia. All DBS leads with short circuits had been anchored to the cranium using titanium miniplates. Altering electrode settings resulted in clinical improvement in the 2 PD cases in which patients had specific symptoms of short circuits (2.5%) but not in the other 4 cases. The patient with dystonia underwent repositioning and replacement of a lead because the previous lead was located too anteriorly, but did not experience symptom improvement. Conclusions In contrast to the sudden loss of clinical efficacy of DBS caused by an open circuit, short circuits may arise due to a gradual decrease in impedance, causing the insidious development of neurological symptoms via limited or extended potential fields as well as shortened battery longevity. The incidence of short circuits in DBS may be higher than previously thought, especially in cases in which DBS leads are anchored with miniplates. The circuit impedance of DBS should be routinely checked, even after a long history of DBS therapy, especially in cases of miniplate anchoring.

scholarly journals Management of a rare case of adrenergic myocarditis complicated with cardiogenic shock

10.3823/2609 ◽  
2019 ◽  
Vol 12 ◽  
Author(s):  
Liviu Macovei ◽  
Robert Magopet ◽  
Larisa Anghel ◽  
Mircea Ovanez Balasanian ◽  
Cezara Raileanu ◽  
...  
Keyword(s):  
Cardiogenic Shock ◽  
Clinical Status ◽  
Myocardial Edema ◽  
Abdominal Ultrasound ◽  
Left Ventricular ◽  
Cardiac Enzymes ◽  
Severe Left Ventricular Dysfunction ◽  
Progressive Dyspnea ◽  
The Right

A 41-year-old female was referred to our clinic with progressive dyspnea and a syncope, preceded by angina. On admission she was in cardiogenic shock. ECG showed diffuse repolarization changes and cardiac enzymes were elevated. The echocardiogram revealed severe left ventricular dysfunction with basal and medium walls hypokinesia. After stabilizing the patient, a coronary angiography was performed which revealed normal epicardial arteries. In the next days her clinical status was marked by severe hypertensive episodes with flash pulmonary edema and low responsiveness to therapy. Cardiovascular magnetic resonance showed myocardial edema and intramyocardial late gadolinium enhancement. An abdominal ultrasound raised suspicion of a pheochromocytoma due to an abnormal mass with cystic areas found on the right suprarenal gland. Elevated urinary free catecholamines and fractionated metanephrines confirmed the diagnosis. Further on, a CT scan better identified the heterogeneous tumor and the patient was referred for a right laparoscopic adrenalectomy. Follow-up at 1 month reported full recovery of the sistolic function. The particularity of the case is represented by the difficulty of diagnosis of adrenergic myocarditis, as well as the management of cardiogenic shock induced by it.

scholarly journals Successful Pallidal Deep Brain Stimulation Treatment in a Case of Generalized Dystonia due to a Novel ANO3 Mutation

2019 ◽  
Vol 2019 ◽  
pp. 1-2 ◽  
Author(s):  
Lizl Lasky ◽  
Lindsay Bliss ◽  
Christos Sidiropoulos
Keyword(s):  
Deep Brain Stimulation ◽  
Brain Stimulation ◽  
Case Series ◽  
Long Term Outcomes ◽  
Pallidal Stimulation ◽  
Generalized Dystonia ◽  
Pallidal Deep Brain Stimulation ◽  
Deep Brain

Background. Dystonia is a ubiquitous syndrome, with a growing number of genes being continually identified. Mutations in the anoctamin-3 gene have been described to cause dystonia but the management and long-term outcomes are still largely unknown. Methods. We present here a long term, longitudinal follow up of a patient with generalized dystonia, who was treated with bilateral pallidal deep brain stimulation and was found to harbor a mutation in the anoctamin-3 gene. Results. Ongoing adjustment of stimulation settings and medications led to good and sustained dystonia control; however the patient did suffer short term relapses, manifested as dystonic crisis, which necessitated inpatient admission. Conclusion. This only the second patient to be reported with pallidal stimulation and an anoctamin-3 gene mutation. Long term outcomes seem to be favorable but larger case series are needed to confirm our findings.

Pallidal Stimulation for Dystonia

Neurosurgery ◽  
2004 ◽  
Vol 55 (6) ◽  
pp. 1361-1370 ◽  
Author(s):  
Martin Krause ◽  
Wolfgang Fogel ◽  
Manja Kloss ◽  
Dirk Rasche ◽  
Jens Volkmann ◽  
...  
Keyword(s):  
Deep Brain Stimulation ◽  
Treatment Option ◽  
High Frequency ◽  
Dystonic Tremor ◽  
Tardive Dystonia ◽  
Pallidal Stimulation ◽  
Generalized Dystonia ◽  
Promising Treatment ◽  
Deep Brain

Abstract OBJECTIVE: High-frequency deep brain stimulation (DBS) of the globus pallidus internus (GPi) is a new and promising treatment option for severe dystonia. Yet only few studies have been published to date regarding this treatment. We present the results of DBS of the GPi in 17 patients with severe dystonia of different causes. METHODS: In our study, we included 10 patients with primary generalized dystonia, six patients with secondary generalized dystonia, and one patient with a severe dystonic cervical tremor. In all patients, DBS electrodes were implanted bilaterally within the GPi. Mean follow-up time was 36 months (range, 12–66 mo). Preoperative and postoperative evaluations (at least annually) were performed using the Burk-Fahn-Marsden scale. RESULTS: The best improvement was achieved in patients with DYT1-positive dystonia. Patients with DYT1-negative generalized dystonia showed inhomogeneous results. There was no significant change in patients with tardive dystonia. One case of Hallervorden-Spatz disease improved dramatically within the first 2 years. The improvement in the cervical dystonic tremor was disappointing, however. Three years after DBS implantation, we found a secondary worsening of symptoms in one patient with a DYT1-positive dystonia and in the patient with Hallervorden-Spatz disease. CONCLUSION: DBS of the GPi is a new and promising treatment option for dystonia. Secondary worsening may limit this therapy.

Stimulation of the globus pallidus internus in a patient with DYT1-positive primary generalized dystonia: a 10-year follow-up

2010 ◽  
Vol 29 (2) ◽  
pp. E16 ◽  
Author(s):  
Dunbar Alcindor ◽  
Michael Y. Oh ◽  
Susan Baser ◽  
Cindy Angle ◽  
Boyle C. Cheng ◽  
...  
Keyword(s):  
Deep Brain Stimulation ◽  
Globus Pallidus ◽  
Brain Stimulation ◽  
Surgical Intervention ◽  
Efficacy And Safety ◽  
Generalized Dystonia ◽  
Early Surgical Intervention ◽  
Deep Brain ◽  
Stimulation Of

The authors report the case of DYT1-positive primary generalized dystonia refractory to medical management that was successfully treated with continuous deep brain stimulation of the internal segment of the globus pallidus. Prior studies have shown that neuromusculoskeletal deficits can remain permanent if early surgical intervention is not undertaken. The authors report prolonged efficacy and safety over a 10-year period in a 28-year-old man.

Sign in / Sign up

Export Citation Format

Share Document