Unverricht‐Lundborg Disease, a Condition with Self‐limited Progression: Long‐term Follow‐up of 20 Patients

Magaudda, Adriana; Ferlazzo, Edoardo; Nguyen, Vi-Hong; Genton, Pierre

doi:10.1111/j.1528-1167.2006.00553.x

Cited by 96 publications

(85 citation statements)

References 25 publications

(30 reference statements)

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“…Patients with ULD typically live into adulthood and the life expectancy may be normal. [52] From India there no reports of genetically proven cases of ILD. However, we have reported the probable cases.…”

Section: Myoclonic Epilepsy With Ragged-red Fibersmentioning

confidence: 98%

Progressive myoclonic epilepsy

Satishchandra

Sinha

2010

Neurol India

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Progressive myoclonic epilepsy (PME) is a disease complex and is characterized by the development of relentlessly progressive myoclonus, cognitive impairment, ataxia, and other neurologic deficits. It encompasses different diagnostic entities and the common causes include Lafora body disease, neuronal ceroid lipofuscinoses, Unverricht-Lundborg disease, myoclonic epilepsy with ragged-red fiber (MERRF) syndrome, sialidoses, dentato-rubro-pallidal atrophy, storage diseases, and some of the inborn errors of metabolism, among others. Recent advances in this area have clarified molecular genetic basis, biological basis, and natural history, and also provided a rational approach to the diagnosis. Most of the large studies related to PME are from south India from a single center, National Institute of Mental Health and Neurological Sciences (NIMHANS), Bangalore. However, there are a few case reports and small series about Lafora body disease, neuronal ceroid lipofuscinoses and MERRF from India. We review the clinical and research experience of a cohort of PME patients evaluated at NIMHANS over the last two decades, especially the phenotypic, electrophysiologic, pathologic, and genetic aspects.

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Section: Myoclonic Epilepsy With Ragged-red Fibersmentioning

confidence: 98%

Progressive myoclonic epilepsy

Satishchandra

Sinha

2010

Neurol India

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“…VPA is recommended as the first drug of choice. Benzodiazepines, piracetam, chloral hydrate, LEV, TPM, and ZNS were reported to have some therapeutic effect, either on myoclonia alone or on the frequency of generalized tonic-clonic seizures (Genton & Guerrini, 1990;Paulus et al, 1991;Pranzatelli & Tate, 2001;Conry, 2004;Crest et al, 2004;Aykutlu et al, 2005;Magaudda et al, 2006;Mancuso et al, 2006;Kalviainen et al, 2008).…”

Section: Discussionmentioning

confidence: 99%

Chronic high-frequency deep-brain stimulation in progressive myoclonic epilepsy in adulthood-Report of five cases

et al. 2011

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SUMMARYPurpose: To assess the efficacy and tolerability of chronic high-frequency deep brain stimulation (DBS) in adult patients with progressive myoclonic epilepsy (PME) syndromes. Methods: Five adult patients (four male, 28-39 years) with PME underwent chronic high-frequency DBS according to a study protocol that had been approved by the local ethics committee. Electrodes were implanted in the substantia nigra pars reticulata (SNr)/subthalamic nucleus (STN) region in the first patient and additionally in the ventral intermediate nucleus (VIM) bilaterally in the following four cases. Follow-up took place in intervals of 3 months and DBS effects were compared with baseline frequency of passive and activation-induced myoclonic jerks and daily life performance 8 weeks prior to implantation. Key Findings: Follow-up periods ranged from 12-42 months (median 24 months). The best clinical effects were seen with SNr/STN DBS in all patients. VIM stimulation failed to achieve acute therapeutic effects and revealed low side-effect thresholds and even triggering of myoclonia. In all patients the reduction of myoclonic seizures was observed and ranged between 30% and 100% as quantified by a standardized video protocol. All patients reported clinically relevant improvements of various capabilities such as free standing and walking or improved fine motor skills. In one patient with an excellent initial response generalized tonic-clonic seizures increased after 3 months of stimulation following extensive traumarelated surgery. The best effect was seen in the least impaired patient. Significance: DBS of the SNr/STN may be an effective treatment option for patients with PME. Less impaired patients may benefit more markedly. KEY WORDS: Myoclonic epilepsy, Surgery, Deep brain stimulation, Stereotaxy.According to the Proposal of the International League Against Epilepsy (ILAE) (Commission on Classification and Terminology of the International League Against Epilepsy, 1989), progressive myoclonic epilepsy (PME) syndromes are classified as relatively well-defined entities such as Unverricht-Lundborg disease or Lafora's disease. In many instances though, a more specified classification is lacking, although recent developments in molecular genetics have helped to achieve a better understanding of PME (Shahwan et al., 2005). Patients with PME usually develop highly drug-resistant and often trigger-dependent myoclonic jerks and generalized tonic-clonic seizures. The stimulus sensitivity, the severity, the frequent association with additional ataxia and fine motor skills impairment and the correlation with sleeplessness regularly lead to dramatic impairment of personal quality of life with the necessity to use helmets or wheelchairs. In addition, the course of the diseases usually progresses, so that some disorders like Lafora's disease are characterized by a very rapid deterioration with fatal prognosis, whereas other forms such as UnverrichtLundborg disease often show a slow progression with severe impairment of the patients over decades...

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“…Moreover, patients carrying such a mutation are more likely to have a severer form of the disease resulting in severer myoclonus and treatment-resistant epileptic seizures. It has previously been reported that in EPM1, the epileptic seizures have a positive response to antiepileptic drug treatment [16] and tend to decrease in frequency or cease completely within 10-15 years from the onset of the disease [2,17] . We found that 3 of the compound heterozygous patients, with a disease duration of over 10 years, were still suffering from tonicclonic seizures despite extensive antiepileptic drug treatment.…”

Section: Discussionmentioning

confidence: 99%

Severer Phenotype in Unverricht-Lundborg Disease (EPM1) Patients Compound Heterozygous for the Dodecamer Repeat Expansion and the c.202C>T Mutation in the <i>CSTB</i> Gene

et al. 2011

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Background/Aims: Unverricht-Lundborg disease (EPM1) is caused by mutations in the cystatin B (CSTB) gene. Most patients are homozygous for the expanded dodecamer repeat mutation alleles, but 9 other EPM1-associated mutations have also been identified. We describe the clinical, cognitive and imaging characteristics of 5 Finnish EPM1 patients who are compound heterozygous for the dodecamer repeat expansion and the c.202C>T mutations. Methods: Five compound heterozygous patients and 21 patients homozygous for the expansion mutation, participating in an ongoing nationwide clinical and molecular genetics study, were evaluated using the Unified Myoclonus Rating Scale test and comprehensive neuropsychological testing. All patients underwent MR imaging. The MR data were also compared with those of 24 healthy control subjects. Results: Age at onset of symptoms was significantly lower in the compound heterozygotes than in the homozygous EPM1 patients. They also had severer myoclonus and drug-resistant tonic-clonic seizures. Moreover, they had lower cognitive performance. In MRI a voxel-based morphometry analysis of primary and premotor cortex, supplementary motor cortex and thalami revealed gray matter volume loss when compared with the healthy controls, similar to patients homozygous for the expansion mutation. Conclusion: Patients compound heterozygous for the dodecamer repeat expansion and the c.202C>T mutations seem to have a severer form of EPM1 than patients homozygous for the expansion mutation. These findings have implications for counseling of EPM1 patients with different genetic defects.

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Unverricht‐Lundborg Disease, a Condition with Self‐limited Progression: Long‐term Follow‐up of 20 Patients

Cited by 96 publications

References 25 publications

Progressive myoclonic epilepsy

Progressive myoclonic epilepsy

Chronic high-frequency deep-brain stimulation in progressive myoclonic epilepsy in adulthood-Report of five cases

Severer Phenotype in Unverricht-Lundborg Disease (EPM1) Patients Compound Heterozygous for the Dodecamer Repeat Expansion and the c.202C>T Mutation in the <i>CSTB</i> Gene

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