Severe myoclonic epilepsy syndromes progressive myoclonic epilepsies pmes anoxia head trauma tumors uremia and other metabolic encephalopathies degenerative central nervous system disease stroke viral infections fig. Bespalova, 1steve adkins, michael pranzatelli,2 and margit burmeister1,3 1mental health research institute, department of human genetics, university of michigan, ann arbor, michigan 2national pediatric myoclonus center, washington, d. These diseases share certain features, including a worsening of symptoms over time and the presence of both muscle contractions myoclonus and seizures epilepsy. The progressive myoclonic epilepsies pmes are a group of symptomatic generalised epilepsies caused by rare disorders, most of which have a genetic component, a debilitating course, and a poor outcome. Affected individuals usually begin showing signs and symptoms of the disorder between the ages of 6 and 15. Lafora disease is a severe, autosomal recessive, progressive myoclonus epilepsy. Vagus nerve progressive myoclonus epilepsy electrical stimulation epilepsy seizure. Progressive myoclonic epilepsy medigoo health tests. In contrast, patients with north sea progressive myoclonus epilepsy experienced a period of rapid progression between the ages of 610 years of age, followed by a slow and progressive decline. Myoclonus consists of sudden, irregular muscle jerks unassociated with loss of consciousness. Unverrichtlundborg disease is a rare inherited form of epilepsy.
People with pme have a decline in motor skills, balance and cognitive function over time. Lafora progressive myoclonus epilepsy is a brain disorder characterized by recurrent seizures epilepsy and a decline in intellectual function. Longterm efficacy and safety of piracetam in the treatment. Epm1 is caused by lossoffunction mutations in the cystatin b cstb gene 2, 3, which. The progressive myoclonus epilepsies are characterised by severe myoclonus, grand mal seizures, and varying neurological deteriora tion. Progressive myoclonic epilepsy pme is a syndrome complex characterized by progressive myoclonus, cognitive impairment, ataxia, and other neurologic deficits. Progressive myoclonus epilepsy definition of progressive. Progressive myoclonus epilepsy of unverrichtlundborg type epm1, omim 254800 is an autosomal recessively inherited neurodegenerative disorder with onset from 6 to 16 years of age and characterized by actionactivated and highly incapacitating myoclonus, tonicclonic epileptic seizures, and ataxia. People with this disorder experience episodes of involuntary muscle jerking or. Progressive myoclonus epilepsy with lafora inclusion bodies. Action myoclonus renal failure amrf syndromealso called progressive myoclonic epilepsy type 4 epm4is a distinctive form of progressive myoclonus epilepsy associated with renal dysfunction. The progressive myoclonic epilepsies practical neurology.
Progressive myoclonic epilepsy medigoo health tests and. Lafora disease is a progressive myoclonus epilepsy with polyglucosan accumulations and a peculiar neurodegeneration with generalised organellar disintegration. Progressive myoclonus epilepsy pme is a rare epilepsy syndrome caused by a variety of genetic disorders. Progressive myoclonic epilepsies pmes include phenotypes arising from various causes but all leading to myoclonic jerks i. Progressive myoclonic epilepsy 7 is a neurologic disorder characterized by onset of severe progressive myoclonus and infrequent tonicclonic seizures in the first or second decades of life. Lafora progressive myoclonus epilepsy genetics home. Progressive myoclonic epilepsies pmes are characterised by myoclonic seizures, tonicclonic seizures.
The signs and symptoms of the disorder usually appear in late childhood or adolescence and worsen with time. Progressive myoclonic epilepsies pme are a group of more than 10 rare types of epilepsy that are progressive. Piracetam relieves symptoms in progressive myoclonus. Feb 04, 2014 progressive myoclonic epilepsies pmes include phenotypes arising from various causes but all leading to myoclonic jerks i. Myoclonus starts at 510 years with a mean at 7 years. Gosr2related progressive myoclonus ataxia genetic and. Piracetam relieves symptoms in progressive myoclonus epilepsy. Unverrichtlundborg disease uld, or epilepsy progressive myoclonus type 1, is an autosomalrecessive disorder that was described by unverricht2 in 1891. Novel cystatin b mutation and diagnostic pcr assay in an. Mutations in the cystatin b gene cstb underlie epm1.
Only comments seeking to improve the quality and accuracy of information on the orphanet website are accepted. Pubmed is a searchable database of medical literature and lists journal articles that discuss gosr2related progressive myoclonus ataxia. Progressive myoclonus epilepsy pme may develop in adult life. As in other progressive myoclonus epilepsies, the efficacy of antiepileptic drugs is disappointingly limited in north sea. Arriving at the correct epilepsy syndrome andor etiology allows better decisionmaking about treatment and improves patient care. The diagnosis of laforas syndrome, progressive myoclonus epilepsy and intracytoplasmic periodic acidschiffpositive inclusions lafora bodies, was made by skin biopsy in a 16yearold girl at the depts of pathology and dermatology, university of texas medical branch, galveston, tx. Myoclonus epilepsy and ragged red fibers the clinical presentation of myoclonus epilepsy and ragged red fibers merrf is variable, but cerebellar ataxia and myoclonus are the most characteristic features. We present two patients with pme appearing around the age of 30 years in whom the disorder represented a manifestation of alzheimers disease. Each of these progressive myoclonic epilepsy syndromes produces a collection of signs and symptoms as well as a characteristic progression and prognosis. Lafora disease ld is an autosomal recessive disease that strikes previously healthy young teenagers, initially with progressive headaches, insidious decline in school performance, myoclonus, perhaps some visual hallucinations, and then a convulsive seizure.
We describe clinical and molecular genetic data on a family from the united states in which four of five sibs are affected with progressive myoclonus epilepsy of unverrichtlundborg type. However, advances in molecular genetics have enabled better understanding of the pathogenesis of these diseases, bringing hope for improved treatment options in the future. Myoclonus is a term used to describe episodes of sudden, involuntary muscle jerking or. This form of progressive myoclonus epilepsy has a more precipitous disease course than classical unverrictlundborg disease. One lafora disease gene, epm2a, has been identified on chromosome 6q24. However, despite extensive evaluation, the cause of progressive myoclonus epilepsy may remain unknown in some patients. People with this disorder experience episodes of involuntary muscle jerking or twitching myoclonus that increase in frequency and. These genes provide instructions for making proteins called laforin and malin, respectively.
Pdf progressive myoclonus epilepsy in a beagle hanne. Neurology a heterogeneous group of disorders that share clinical features, and thus generically termed pme syndrome clinical prominent sensitivity of myoclonus to all stimulieg, passive movement of a limb might evoke a generalized convulsions etiology unverrichtlundborgs disease, lafora body disease, neuronal. Age at disease and myoclonus onset in patients with undetermined progressive myoclonic epilepsies belonging to clusters 1 and 2 figure 3a highlights the fact that clinical characteristics differ between the clusters. Progressive myoclonic epilepsy satishchandra p, sinha s. Background piracetam has been proven to be effective and well tolerated in the treatment of myoclonus in shortterm studies objective to assess its longterm clinical efficacy, 11 patients with disabling myoclonus due to progressive myoclonus epilepsy were treated with piracetam in an openlabel study. Progressive myoclonus epilepsy of unverricht lundborg type pmeul is a rare, autosomal recessive disorder characterized by spontaneous, stimulus sensitive, and action myoclonus, tonicclonic seizures. Over the last two decades, considerable developments have occurred in. They all have several features in common, including multiple seizure types, difficulttocontrol seizures, and lifelong learning, developmental, and physical impairment. Jun 26, 2010 progressive myoclonic epilepsy pme is a syndrome complex characterized by progressive myoclonus, cognitive impairment, ataxia, and other neurologic deficits. Loss of lysosomal association of cystatin b proteins. Pdf progressive myoclonic epilepsy pme is a syndrome complex encompassing different diagnostic entities and often cause problems in. Ultimately, patients become wheelchairbound and experience early death.
Laforin and malin play a critical role in the survival of nerve cells neurons in the brain studies suggest that laforin and malin work together and may have several functions. Myoclonus that is refractory to trials of appropriate antiseizure medication. Progressive myoclonic epilepsy7 is a neurologic disorder characterized by onset of severe progressive myoclonus and infrequent tonicclonic seizures in the first or second decades of life. The efficacy of the modified atkins diet in north sea. The syndrome includes myoclonic seizures and tonicclonic seizures together with progressive neurological decline. The gene for this disorder epm1 has previously been mapped to the distal region of chromosome 21. Progressive myoclonus ataxia pma is a rare disorder and defined in the literature as progressive ataxia and myoclonus, without prominent decline in cognitive functions, and with or without infrequent epileptic seizures. They are characterized clinically by a progressive neurological disorder starting in childhood with myoclonus and epilepsy kalviainen.
As in other progressive myoclonus epilepsies, the efficacy of antiepileptic drugs is disappointingly limited in north sea progressive myoclonus epilepsy. Myoclonus indicates frequent muscle jerks, both spontaneous and often stimulus induced. Merrf may also be associated with dementia, tonicclonic seizures, deafness, optic atrophy, neuropathy, dys. It causes severe seizures, leading to dementia and eventually death in early adulthood. Effects of vagus nerve stimulation on progressive myoclonus. Progressive myoclonic epilepsies epilepsy foundation.
North sea progressive myoclonus epilepsy is exacerbated by. Progressive myoclonus epilepsy with lafora inclusion. Unverrichtlundborg disease is classified as a type of progressive myoclonus epilepsy. Brain inflammation is accompanied by peripheral inflammation. Progressive myoclonic epilepsy pme is a disease complex and is. Nov 28, 2016 progressive myoclonus epilepsy of unverrichtlundborg type epm1 is an autosomal recessively inherited childhoodonset neurodegenerative disorder, characterized by myoclonus, seizures, and ataxia. Challenges with pme arise from difficulty with diagnosis, especially in the early stages of the illness, and further problems of management and drug treatment. Jan 12, 2017 autosomalrecessive progressive myoclonus epilepsyataxia syndrome age of onset with ataxia at 45 years. Myoclonus epilepsy an overview sciencedirect topics. They are grouped together on pathologic grounds due to the common presence of neuronal and extraneuralautofluorescent pigment accumulations. The progressive myoclonic epilepsies pme are a rare group of inherited neurodegenerative diseases with debilitating evolution, resistance to treatment and poor prognosis. Progressive myoclonus epilepsies are a heterogeneous group of inherited disorders defined by the association of myoclonus, epilepsy and progressive neurological deterioration. Lafora progressive myoclonus epilepsy can be caused by mutations in either the epm2a gene or the nhlrc1 gene. People with this disorder experience episodes of involuntary muscle jerking or twitching myoclonus that increase in frequency.
Progressive myoclonic epilepsy linkedin slideshare. Novel cystatin b mutation and diagnostic pcr assay in an unverrichtlundborg progressive myoclonus epilepsy patient irina n. The syndrome was not recognized prior to the advent of dialysis and renal transplantation because of its rapidly fatal course if renal failure is untreated. Progressive myoclonus epilepsy nord national organization. Progressive myoclonic epilepsies are a group of disorders characterised by a relentlessly progressive disease course until death. The progressive myoclonic epilepsies pmes are a devastating group of rare disorders1 that manifest with increasing action myoclonus, which is also present at rest but activates with stimuli such as noise, light, or touch. To compare the efficacy, tolerability, and safety of three daily dosage regimens of oral piracetam in patients with progressive myoclonus epilepsy.
S154 postmodern therapeutic approaches for progressive myoclonus epilepsy. Pdf piracetam relieves symptoms in progressive myoclonus. Neurologic signs that frequently but not reliably coexist include other seizure types particularly. Genetic mapping of a new lafora progressive myoclonus. Ncls the ncls are pmes, because they affect previously normal children, are progressive, and include worsening myoclonus during these childrens short lives.
Locus heterogeneity led us to search for a second gene. May 19, 2011 progressive myoclonus epilepsy pme refers to a group of inherited conditions involving the central nervous system and representing more than a dozen different diseases. The international league against epilepsy ilae diagnostic manuals goal is to assist clinicians who look after people with epilepsy to diagnose the epilepsy syndrome and if possible the etiology of the epilepsy. Twenty patients 12 men, eight women, aged 1743 years, with classical unverrichtlundborg disease. Please help improve this section by adding citations to reliable sources. Omim 254800 is an autosomal recessive disorder characterized by the age of onset at. Many metabolic and genetic causes of progressive myoclonus epilepsy exist, and specific etiologies often present at certain ages. Death within four to ten years has been the inevitable outcome in all reported cases. Progressive myoclonus epilepsy is a group of conditions involving the cns central nervous system and representing more than a dozen different diseases. Autosomalrecessive progressive myoclonus epilepsyataxia syndrome age of onset with ataxia at 45 years. Unverrichtlundborg disease genetics home reference nih. Caused by a missense mutation in the prickle1 gene.
Progressive myoclonic epilepsies pmes form a group of rare diseases of different genetic aetiologies kalviainen. Progressive myoclonus epilepsy of unverrichtlundborg type epm1. Progressive myoclonus epilepsy pme is a group of conditions involving the central nervous system and representing more than a dozen different diseases. Progressive myoclonic epilepsy due to kctd7 deficiency. His different types of epileptic seizures were classified as atypical absence seizures, multifocal cortical myoclonus, and generalised tonicclonic seizures. Progressive myoclonic epilepsy satishchandra p, sinha s neurol. The disease usually manifests in previously healthy adolescents, and death commonly occurs within 10 years of. It encompasses several diagnostic entities and often causes diagnostic problems leading to nosological confusion. It is clinically characterized by progressive myoclonus, seizures, earlyonset ataxia and areflexia. The progressive myoclonic epilepsies pmes are a devastating group of rare disorders1 that manifest with increasing action myoclonus, which. Merrf may also be associated with dementia, tonicclonic. Progressive myoclonic epilepsy genetic and rare diseases.
Clinical signs included mental depression and paroxysmal jerks of the head and forelimbs, apparently elicited by changes in light, noise or. North sea progressive myoclonus epilepsy is a rare and severe disorder caused by mutations in the gosr2 gene. This manuscript is an overview of the clinical and. Vagus nerveprogressive myoclonus epilepsyelectrical stimulationepilepsyseizure. These diseases share certain features, including a worsening of symptoms over time and the presence of both muscle contractions and seizures. Action myoclonusrenal failure syndrome amrf, omim 254900 is a rare form of progressive myoclonus epilepsy associated with severe renal dysfunction. Progressive myoclonus epilepsy type 1 epm1 of the unverrichtlundborg type is an autosomal recessive neurodegenerativedisorder thathasthehighest incidenceamong the progressive myoclonus epilepsies worldwide. Progressive myoclonus epilepsy in a beagle article pdf available in journal of small animal practice 4411. Progressive myoclonus epilepsy pme refers to a group of inherited conditions involving the central nervous system and representing more than a dozen different diseases. The intellect is usually preserved an neuroimaging studies are normal. Laforas aforas disease is a rare form of myoclonus epilepsy. Progressive myoclonus epilepsy epm1 is an autosomal recessive disorder, characterized by severe, stimulussensitive myoclonus and tonicclonic seizures. Mutations in the golgi snap receptor 2 gene gosr2 cause a particular. This diagnosis must be considered in addition to possible kufs disease or myoclonic epilepsy with ragged red fibers merrf when pme develops in young adults.
Molecular genetic results suggest that the disease gene in this family is linked to the same region of. Myoclonus with or without generalized seizures and progressive cognitive decline were universally present in all the patients. In its fully developed form, the syndrome consists of myoclonic jerks, tonicclonic seizures, mental retardation, and ataxia. A nineyearold, neutered female beagle was presented with a history of progressive myoclonic jerks. We report a consanguineous family with 2 affected individuals whose clinical symptoms closely resembled merrf myoclonus epilepsy with ragged red fibers syndrome including severe myoclonic epilepsy, progressive spastic tetraparesis, progressive impairment of vision and hearing, as well as progressive cognitive decline. Identification of mutations in cystatin b, the gene. Click on the link to view a sample search on this topic.
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