Ramsay hunt syndrome: Clinical characterization of progressive myoclonus ataxia caused by <i>GOSR2</i> mutation

Egmond, Martje E van; Verschuuren‐Bemelmans, Corien C.; Nibbeling, Esther; Elting, Jan Willem J.; Sival, Deborah A; Brouwer, Oebele F.; Vries, Jeroen J de; Kremer, H.P.H.; Sinke, Richard J.; Tijssen, Marina A. J.; Koning, Tom J. de

doi:10.1002/mds.25704

Cited by 52 publications

(55 citation statements)

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“…Worldwide only 21 NSPME patients have been described [1–3]. In this observational prospective study, we evaluated the efficacy of the MAD in four NSPME patients, with HRQL as our primary outcome measure.…”

Section: Discussionmentioning

confidence: 99%

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The efficacy of the modified Atkins diet in North Sea Progressive Myoclonus Epilepsy: an observational prospective open-label study

Egmond

Weijenberg

Rijn

et al. 2017

Orphanet J Rare Dis

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BackgroundNorth Sea Progressive Myoclonus Epilepsy is a rare and severe disorder caused by mutations in the GOSR2 gene. It is clinically characterized by progressive myoclonus, seizures, early-onset ataxia and areflexia. As in other progressive myoclonus epilepsies, the efficacy of antiepileptic drugs is disappointingly limited in North Sea Progressive Myoclonus Epilepsy. The ketogenic diet and the less restrictive modified Atkins diet have been proven to be effective in other drug-resistant epilepsy syndromes, including those with myoclonic seizures. Our aim was to evaluate the efficacy of the modified Atkins diet in patients with North Sea Progressive Myoclonus Epilepsy.ResultsFour North Sea Progressive Myoclonus Epilepsy patients (aged 7–20 years) participated in an observational, prospective, open-label study on the efficacy of the modified Atkins diet. Several clinical parameters were assessed at baseline and again after participants had been on the diet for 3 months. The primary outcome measure was health-related quality of life, with seizure frequency and blinded rated myoclonus severity as secondary outcome measures.Ketosis was achieved within 2 weeks and all patients completed the 3 months on the modified Atkins diet. The diet was well tolerated by all four patients. Health-related quality of life improved considerably in one patient and showed sustained improvement during long-term follow-up, despite the progressive nature of the disorder. Health-related quality of life remained broadly unchanged in the other three patients and they did not continue the diet. Seizure frequency remained stable and blinded rating of their myoclonus showed improvement, albeit modest, in all patients.ConclusionsThis observational, prospective study shows that some North Sea Progressive Myoclonus Epilepsy patients may benefit from the modified Atkins diet with sustained health-related quality of life improvement. Not all our patients continued on the diet, but nonetheless we show that the modified Atkins diet might be considered as a possible treatment in this devastating disorder.

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Section: Discussionmentioning

confidence: 99%

“…The clinical picture of NSPME is dominated by spontaneous and action-induced myoclonic jerks and ataxia, which have a severe impact on daily functioning [3]. Most NSPME patients also have generalized tonic or tonic-clonic seizures, albeit that the seizures are relatively mild compared to the myoclonic jerks.…”

Section: Introductionmentioning

confidence: 99%

The efficacy of the modified Atkins diet in North Sea Progressive Myoclonus Epilepsy: an observational prospective open-label study

Egmond

Weijenberg

Rijn

et al. 2017

Orphanet J Rare Dis

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“…One explanation for this heterogeneity could be that children with EOA often present with mixed ataxic phenotypes. [11][12][13] This can be understood by the interactions between the cerebellum and basal ganglia. 20,21 For instance, there are interacting neurons projecting from the subthalamic nucleus to the pontine nuclei (influencing the input to the cerebellar cortex), and there are interacting neurons projecting from the dentate nucleus (an output stage of the cerebellum) via the thalamus to the striatum (influencing the input to the basal ganglia).…”

Section: Discussionmentioning

confidence: 99%

“…The mixed phenotypic appearance may be understood by the longitudinal GOSR2 disease course, involving progressive myoclonic features by the age of 6 years and older. 12,26 Since all included GOSR2 patients were 6 years and older, assignment to the mixed ataxic subgroup appears comprehensive. Similarly, it is also known that ataxia with vitamin E deficiency phenotypes may change with age and/or treatment conditions.…”

Section: Discussionmentioning

confidence: 99%

“…In young children, it is wellknown that the physiological maturation of the nervous system can cause a phenotypic 'overlap' between immature motor behaviour and initiating signs of ataxia. [8][9][10] Furthermore, in young children, EOA concurs frequently with features of other movement disorders, [11][12][13] resulting in 'mixed' ataxic phenotypes. Finally, the EOA concept involves a large range in the age at onset, implicating the presence of heterogeneous underlying aetiologies, which are likely to differ between young children and adults.…”

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Reliability of phenotypic early‐onset ataxia assessment: a pilot study

Lawerman

Brandsma

Geffen

et al. 2015

Develop Med Child Neuro

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AIM To investigate the interobserver agreement on phenotypic early-onset ataxia (EOA) assessment and to explore whether the Scale for Assessment and Rating of Ataxia (SARA) could provide a supportive marker.METHOD Seven movement disorder specialists provided independent phenotypic assessments of potentially ataxic motor behaviour in 40 patients (mean age 15y [range 5-34]; data derived from University Medical Center Groningen medical records 1998-2012). We determined interobserver agreement by Fleiss' kappa. Furthermore, we compared percentage SARA subscores ([subscore/total score]9100%) between 'indisputable' (primary ataxia recognition by at least six observers) and 'mixed' (ataxia recognition, unfulfilling 'indisputable' criteria) EOA phenotypes.RESULTS Agreement on phenotypic EOA assessment was statistically significant (p<0.001), but of moderate strength (Fleiss' kappa=0.45; 95% CI 0.38-0.51). During mild disease progression, percentage SARA gait subscores discriminated between 'indisputable' and 'mixed' EOA phenotypes. In patients with percentage SARA gait subscores >30%, primary ataxia was more frequently present than in those with subscores <30% (p=0.001).INTERPRETATION Among movement-disorder professionals from different disciplines, interobserver agreement on phenotypic EOA recognition is of limited strength. SARA gait subscores can provide a supportive discriminative marker between EOA phenotypes. Hopefully, future phenotypic insight will contribute to the inclusion of uniform, high-quality data in international EOA databases.Ataxia is described by an impairment of the smooth performance of goal-directed movements, 1 resulting in impaired 'unconscious' decision making about balance, speed, force, and direction of intended movements. [2][3][4] Intentional motor behaviour may thus be affected by ataxic limb movements (intention and action tremor, dysdiadochokinesis, rebound, hypermetria), trunk movements (with staggering, swaying, and titubation), eye movements (nystagmus, saccades, overand undershoot), and speech (dysarthria, dysrhythmia). The underlying neuropathology involves abnormal spinal afferent input and/or cerebellar dysfunction, hampering multisensory fine-tuning and timing of motor output. In the literature, the concept of 'early-onset ataxia' (EOA) is used to define the initiation of ataxia before the 25th year of life. 5,6 The estimated EOA prevalence is about 14.6 per 100 000.7 As implicated by the large range in the age at onset, there is an enormous variety in underlying (genetic and metabolic) disorders. In this perspective, international EOA databases aim to (1) provide insight in the longitudinal disease course, (2) identify new genes, (3) design new treatment strategies, and (4) characterize uniform and transparent markers for disease monitoring. In the absence of a criterion standard, EOA patient inclusion will depend on subjective phenotypic recognition of ataxia. This process is complex for several reasons. In young children, it is wellknown that the physiological maturation of th...

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Myoclonus epilepsy and ataxia due to KCNC1 mutation: Analysis of 20 cases and K⁺ channel properties

Oliver

Franceschetti

Milligan

et al. 2017

Annals of Neurology

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MEAK has a relatively homogeneous presentation, resembling Unverricht-Lundborg disease, despite the genetic and biological basis being quite different. A remarkable improvement with fever may be explained by the temperature-dependent leftward shift in activation of wild-type K 3.1 subunit-containing channels, which would counter the loss of function observed for mutant channels, highlighting KCNC1 as a potential target for precision therapeutics. Ann Neurol 2017;81:677-689.

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Ramsay hunt syndrome: Clinical characterization of progressive myoclonus ataxia caused by GOSR2 mutation

Abstract: Based on the presented phenotype, we would advise movement disorder specialists to consider mutation analysis of GOSR2 in patients with Ramsay Hunt syndrome, especially when they also have areflexia.

Cited by 52 publications

References 6 publications

The efficacy of the modified Atkins diet in North Sea Progressive Myoclonus Epilepsy: an observational prospective open-label study

The efficacy of the modified Atkins diet in North Sea Progressive Myoclonus Epilepsy: an observational prospective open-label study

Reliability of phenotypic early‐onset ataxia assessment: a pilot study

Myoclonus epilepsy and ataxia due to KCNC1 mutation: Analysis of 20 cases and K⁺ channel properties

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Ramsay hunt syndrome: Clinical characterization of progressive myoclonus ataxia caused by GOSR2 mutation

Abstract: Based on the presented phenotype, we would advise movement disorder specialists to consider mutation analysis of GOSR2 in patients with Ramsay Hunt syndrome, especially when they also have areflexia.

Cited by 52 publications

References 6 publications

The efficacy of the modified Atkins diet in North Sea Progressive Myoclonus Epilepsy: an observational prospective open-label study

The efficacy of the modified Atkins diet in North Sea Progressive Myoclonus Epilepsy: an observational prospective open-label study

Reliability of phenotypic early‐onset ataxia assessment: a pilot study

Myoclonus epilepsy and ataxia due to KCNC1 mutation: Analysis of 20 cases and K+ channel properties

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Myoclonus epilepsy and ataxia due to KCNC1 mutation: Analysis of 20 cases and K⁺ channel properties