An atypical case of <i>KMT2B</i>‐related dystonia manifesting asterixis and effect of deep brain stimulation of the globus pallidus

Miyata, Yohane; Hamanaka, Kohei; Kumada, Satoko; Uchino, Shumpei; Yokochi, Fusako; Taniguchi, Makoto; Miyatake, Satoko; Matsumoto, Naomichi

doi:10.1111/ncn3.12334

Cited by 4 publications

(8 citation statements)

References 7 publications

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“…In total, 52 patients (23 in the study cohort and 29 patients in the published cohort) had GPiDBS inserted for medically intractable dystonia (Tables 1, 4 and Supplementary Table 8) (Coubes et al, 1999;Zech et al, 2016;Meyer et al, 2017;Zech et al, 2017;Zhao et al, 2018;Kawarai et al, 2018;Nerrant et al, 2018;Carecchio et al, 2019;Dafsari et al, 2019;Miyata et al, 2019;Mun et al, 2020). In our focused DBS cohort, the median postoperative follow-up was 2.0 years, with the longest follow-up of 22.0 years.…”

Section: Discussionmentioning

confidence: 99%

“…Within the published cohort, eight publications reported a total of 31 subjects treated with DBS for KMT2B-dystonia (Zech et al, 2016;Meyer et al, 2017;Zech et al, 2017;Kawarai et al, 2018;Carecchio et al, 2019;Miyata et al, 2019;Cao et al, 2020;Mun et al, 2020) Overall, results were expressed mostly as "good or very good responses" and BFMDRS-M score changes were reported in 13 cases. (Supplementary Table 8)…”

Section: (F) Extended Kmt2b Cohort Analysismentioning

confidence: 99%

“…In many patients, additional clinical features have also been reported, including dysmorphism, short stature, intellectual disability (ID), eye movement abnormalities and psychiatric comorbidities. Although KMT2B was only recently identified, more than 80 patients are already published (Zech et al, 2016;Lange et al, 2017;Meyer et al, 2017;Reuter et al, 2017;Zech et al, 2017;Zech et al, 2017;Baizabal-Carvallo and Alonso-Juarez, 2018;Zhao et al, 2018;Faundes et al, 2018;Hackenberg et al, 2018;Kawarai et al, 2018;Brás et al, 2019;Dai et al, 2019;Dai et al, 2019;Ma et al, 2019;Miyata et al, 2019;Zhou et al, 2019;Carecchio et al, 2019;Dafsari et al, 2019;Klein et al, 2019;Mun et al, 2020;Cao et al, 2020) rendering KMT2B-dystonia an emerging key player in childhood-onset genetic dystonia, accounting for an estimated 21.5% of cases (Carecchio et al, 2019).…”

Section: Introductionmentioning

confidence: 99%

“…With the advance of next generation sequencing technologies and the identification of distinct genetic dystonia syndromes, accurate DBS prognostication is increasingly possible based on underlying aetiology (Coubes et al, 2000;Cif et al, 2010;Gruber et al, 2010;Timmermann et al, 2010;Panov et al, 2012;Krause et al, 2015;Koy et al, 2018). However, little is known about the long-term outcome with DBS in KMT2B-dystonia, though short-term benefit has been reported (Zech et al, 2016;Meyer et al, 2017;Zech et al, 2017;Kawarai et al, 2018;Carecchio et al, 2019;Dafsari et al, 2019;Miyata et al, 2019;Cao et al, 2020;Mun et al, 2020).…”

Section: Introductionmentioning

confidence: 99%

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KMT2B-related disorders: expansion of the phenotypic spectrum and long-term efficacy of deep brain stimulation

Cif¹,

Demailly²,

Lin³

et al. 2020

Brain

121

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Heterozygous mutations in KMT2B are associated with an early-onset, progressive and often complex dystonia (DYT28). Key characteristics of typical disease include focal motor features at disease presentation, evolving through a caudocranial pattern into generalized dystonia, with prominent oromandibular, laryngeal and cervical involvement. Although KMT2B-related disease is emerging as one of the most common causes of early-onset genetic dystonia, much remains to be understood about the full spectrum of the disease. We describe a cohort of 53 patients with KMT2B mutations, with detailed delineation of their clinical phenotype and molecular genetic features. We report new disease presentations, including atypical patterns of dystonia evolution and a subgroup of patients with a non-dystonic neurodevelopmental phenotype. In addition to the previously reported systemic features, our study has identified co-morbidities, including the risk of status dystonicus, intrauterine growth retardation, and endocrinopathies. Analysis of this study cohort (n = 53) in tandem with published cases (n = 80) revealed that patients with chromosomal deletions and protein truncating variants had a significantly higher burden of systemic disease (with earlier onset of dystonia) than those with missense variants. Eighteen individuals had detailed longitudinal data available after insertion of deep brain stimulation for medically refractory dystonia. Median age at deep brain stimulation was 11.5 years (range: 4.5–37.0 years). Follow-up after deep brain stimulation ranged from 0.25 to 22 years. Significant improvement of motor function and disability (as assessed by the Burke Fahn Marsden’s Dystonia Rating Scales, BFMDRS-M and BFMDRS-D) was evident at 6 months, 1 year and last follow-up (motor, P = 0.001, P = 0.004, and P = 0.012; disability, P = 0.009, P = 0.002 and P = 0.012). At 1 year post-deep brain stimulation, >50% of subjects showed BFMDRS-M and BFMDRS-D improvements of >30%. In the long-term deep brain stimulation cohort (deep brain stimulation inserted for >5 years, n = 8), improvement of >30% was maintained in 5/8 and 3/8 subjects for the BFMDRS-M and BFMDRS-D, respectively. The greatest BFMDRS-M improvements were observed for trunk (53.2%) and cervical (50.5%) dystonia, with less clinical impact on laryngeal dystonia. Improvements in gait dystonia decreased from 20.9% at 1 year to 16.2% at last assessment; no patient maintained a fully independent gait. Reduction of BFMDRS-D was maintained for swallowing (52.9%). Five patients developed mild parkinsonism following deep brain stimulation. KMT2B-related disease comprises an expanding continuum from infancy to adulthood, with early evidence of genotype-phenotype correlations. Except for laryngeal dysphonia, deep brain stimulation provides a significant improvement in quality of life and function with sustained clinical benefit depending on symptoms distribution.

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Section: Discussionmentioning

confidence: 99%

Section: (F) Extended Kmt2b Cohort Analysismentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

KMT2B-related disorders: expansion of the phenotypic spectrum and long-term efficacy of deep brain stimulation

Cif¹,

Demailly²,

Lin³

et al. 2020

Brain

121

View full text Add to dashboard Cite

show abstract

“…Although it is suggested that DBS should be considered as a treatment approach in pharmacoresistent DYT-THAP1 early in childhood to prevent more severe symptoms, such as disabling motor development and quality of life decline, including emotional and social aspects, the results are missing. Additionally, bilateral GPi-DBS has been reported as a valuable therapeutic option for DYT-KMT2B, especially for regaining motor function and mobility, but less so for speech if significant speech difficulties are developed (5,(22)(23)(24)(25)(26)(27)(28)(29)(30)(31)(32)(33)(34)(35)(36)(37).…”

Section: Introductionmentioning

confidence: 99%

GPi DBS treatment outcome in children with monogenic dystonia: a case series and review of the literature

et al. 2023

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IntroductionDystonia is the third most common pediatric movement disorder and is often difficult to treat. Deep brain stimulation (DBS) of the internal pallidum (GPi) has been demonstrated as a safe and effective treatment for genetic dystonia in adolescents and adults. The results of DBS in children are limited to individual cases or case series, although it has been proven to be an effective procedure in carefully selected pediatric cohorts. The aim of our study was to present the treatment outcome for 7- to 9-year-old pediatric patients with disabling monogenic isolated generalized DYT-THAP1 and DYT-KMT2B dystonia after bilateral GPi-DBS.Patients and resultsWe present three boys aged <10 years; two siblings with disabling generalized DYT-THAP1 dystonia and a boy with monogenic-complex DYT-KMT2B. Dystonia onset occurred between the ages of 3 and 6. Significantly disabled children were mostly dependent on their parents. Pharmacotherapy was inefficient and patients underwent bilateral GPi-DBS. Clinical signs of dystonia improved significantly in the first month after the implantation and continued to maintain improved motor functions, which were found to have improved further at follow-up. These patients were ambulant without support and included in everyday activities. All patients had significantly lower Burke–Fahn–Marsden Dystonia Rating Scale (BFMDRS) values, indicating >25% improvement over the first 15 months. However, there was a decline in speech and upper limb function, manifesting with bradylalia, bradykinesia, and dysphonia, which decreased after treatment with trihexyphenidyl.ConclusionAlthough reports of patients with monogenic dystonia, particularly DYT-THAP1, treated with DBS are still scarce, DBS should be considered as an efficient treatment approach in children with pharmacoresistent dystonia, especially with generalized monogenic dystonia and to prevent severe and disabling symptoms that reduce the quality of life, including emotional and social aspects. Patients require an individual approach and parents should be properly informed about expectations and possible outcomes, including relapses and impairments, in addition to DBS responsiveness and related improvements. Furthermore, early genetic diagnosis and the provision of appropriate treatments, including DBS, are mandatory for preventing severe neurologic impairments.

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Flapping Tremor: Unraveling Asterixis—A Narrative Review

Rissardo,

Muhammad,

Yatakarla

et al. 2024

Medicina

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Asterixis is a subtype of negative myoclonus characterized by brief, arrhythmic lapses of sustained posture due to involuntary pauses in muscle contraction. We performed a narrative review to characterize further asterixis regarding nomenclature, historical aspects, etiology, pathophysiology, classification, diagnosis, and treatment. Asterixis has been classically used as a synonym for negative myoclonus across the literature and in previous articles. However, it is important to distinguish asterixis from other subtypes of negative myoclonus, for example, epileptic negative myoclonus, because management could change. Asterixis is not specific to any pathophysiological process, but it is more commonly reported in hepatic encephalopathy, renal and respiratory failure, cerebrovascular diseases, as well as associated with drugs that could potentially lead to hyperammonemia, such as valproic acid, carbamazepine, and phenytoin. Asterixis is usually asymptomatic and not spontaneously reported by patients. This highlights the importance of actively searching for this sign in the physical exam of encephalopathic patients because it could indicate an underlying toxic or metabolic cause. Asterixis is usually reversible upon treatment of the underlying cause.

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An atypical case of KMT2B‐related dystonia manifesting asterixis and effect of deep brain stimulation of the globus pallidus

Cited by 4 publications

References 7 publications

KMT2B-related disorders: expansion of the phenotypic spectrum and long-term efficacy of deep brain stimulation

KMT2B-related disorders: expansion of the phenotypic spectrum and long-term efficacy of deep brain stimulation

GPi DBS treatment outcome in children with monogenic dystonia: a case series and review of the literature

Flapping Tremor: Unraveling Asterixis—A Narrative Review

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