Myoclonic Epilepsy Beginning in Infancy or Early Childhood

Myoclonic Epilepsy Beginning in Infancy or Early Childhood

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Myoclonic seizures are characterized by rapid, jerklike movements that can affect the face, limbs, or axial musculature. Most families are familiar with hypnic jerks; that is, a sudden jerk that jolts one awake while falling asleep. In contrast to sleep-related myoclonus, myoclonic seizures occur during wakefulness and are associated with abnormal cortical discharges on EEG. Myoclonic seizures can occur in isolation or as part of a mixed-generalized epilepsy syndrome. Myoclonic epilepsies with onset in infancy and childhood are clinically and etiologically heterogeneous but, as a group, may be refractory to treatment.

The overall prognosis associated with myoclonic epilepsy in childhood depends on the underlying etiology. Identification of a distinct epilepsy syndrome may enable more accurate prognostication (see Etiology).

Clinical features can aid in the differentiation of myoclonic epilepsies from other forms of epilepsy and paroxysmal movements of childhood (see Clinical).

EEG is required to distinguish myoclonic seizures from nonictal causes of myoclonus, which can arise from lesions of the cortex, brainstem, spinal cord, or even peripheral nerve (see Workup).

The mainstays of therapy for myoclonic seizures are valproic acid (sodium valproate) and benzodiazepines (see Treatment). Some anticonvulsants may precipitate myoclonic seizures in predisposed individuals.

Myoclonic seizures are generally the product of hypersynchronous, generalized cortical discharges. These discharges arise from hyperexcitable neuronal networks.

Seizures associated with early myoclonic encephalopathy can be due to a number of etiologies. The International League Against Epilepsy (ILAE) revised concepts and terminology related to the classification and description of seizures in 2010. [1] This report emphasized that concepts related to the characterization of seizures, their etiologies, and meaningful electroclinical syndromes are evolving. Practically speaking, myoclonic seizures can be grouped into the following categories (myoclonic absences, myoclonic tonic seizures, and myoclonic clonic seizure types are not discussed here):

Early infantile epileptic encephalopathies [2] – This includes early myoclonic encephalopathy (EME) and early infantile epileptic encephalopathy (EIEE). These are severe disorders with a grave prognosis. Causes of early infantile epileptic encephalopathies include brain malformations, inborn errors of metabolism, and neurogenetic disorders.

Myoclonic epilepsy occurring as part of a mixed generalized epilepsy syndrome – This includes Doose syndrome (myoclonic-atonic epilepsy), [3] Dravet syndrome (severe myoclonic epilepsy of infancy), [4] and Lennox-Gastaut syndrome, [5] as well as other syndromes that feature several kinds of generalized seizures. Progressive spasticity is frequently seen in older children and adolescents with Dravet syndrome, often associated with the development of crouch gait. [6] Causes may include cortical malformation and ion channel mutations, such as SCN1A mutations.

Nonprogressive myoclonic epilepsies – This group of disorders overall has a more favorable prognosis and includes benign neonatal myoclonic epilepsy, familial myoclonic epilepsy, and autosomal dominant cortical myoclonus and epilepsy, among others. However, nonprogressive myoclonic encephalopathies may also occur, with a more guarded prognosis. These disorders are usually genetically determined conditions.

Progressive myoclonic epilepsies [7] – In this class of myoclonic epilepsies, seizures occur in the context of an underlying neurodegenerative disorder. Representative diseases include Unverricht-Lundborg disease, Lafora body disease, myoclonic epilepsy with ragged red fibers (MERRF), the neuronal ceroid lipofuscinoses, sialidosis, and dentate-rubral-pallidoluysian atrophy (DRPLA). Myoclonus occurring in the context of these disorders may be stimulus-sensitive or action-induced.

Some children may not be readily classifiable in any of the above categories.

Across subtypes of childhood myoclonic epilepsy, many patients have an underlying genetic cause for their seizures. In some cases, myoclonic seizures may be a prominent feature of a syndrome with wider central nervous system and systemic manifestations, such as is seen in mitochondrial diseases (ie, MERRF or Alper syndrome [POLG1 mutations]). However, despite advances in identifying causes of epilepsy, for most cases of infantile and early childhood myoclonic epilepsy, no clear etiology will be found despite an appropriate workup.

The incidence of myoclonic epilepsy is approximately 1 case in 40,000 children. Typically, the onset of these disorders is during the first 3 years of life. There are no known racial or sexual differences in the overall frequency of myoclonic epilepsies, although there may be differences in prevalence among specific populations for certain forms of myoclonic epilepsy (ie, Baltic epilepsy).

The prognosis depends heavily on the underlying etiology and the epilepsy syndrome. Patients with a benign syndrome typically respond well to medication and may outgrow their epilepsy. In other myoclonic epilepsy syndromes, the prognosis is usually less favorable.

Death in patients with myoclonic epilepsy may be related to the underlying disorder but is unlikely to be due to the myoclonic seizures themselves. Aspiration pneumonia is more common in this population and may result in frequent hospitalizations.

For patient education information, see the Brain and Nervous System Center, as well as Epilepsy.

Berg AT, Berkovic SF, Brodie MJ, et al. Revised terminology and concepts for organization of seizures and epilepsies: report of the ILAE Commission on Classification and Terminology, 2005-2009. Epilepsia. 2010 Apr. 51(4):676-85. [Medline].

Djukic A, Lado FA, Shinnar S, Moshé SL. Are early myoclonic encephalopathy (EME) and the Ohtahara syndrome (EIEE) independent of each other?. Epilepsy Res. 2006 Aug. 70 Suppl 1:S68-76. [Medline].

Kelley SA, Kossoff EH. Doose syndrome (myoclonic-astatic epilepsy): 40 years of progress. Dev Med Child Neurol. 2010 Nov. 52(11):988-93. [Medline].

Dravet C. The core Dravet syndrome phenotype. Epilepsia. 2011 Apr. 52 Suppl 2:3-9. [Medline].

Michoulas A, Farrell K. Medical management of Lennox-Gastaut syndrome. CNS Drugs. 2010 May 1. 24(5):363-74. [Medline].

Rodda JM, Scheffer IE, McMahon JM, Berkovic SF, Graham HK. Progressive Gait Deterioration in Adolescents With Dravet Syndrome. Arch Neurol. 2012 Mar 12. [Medline].

Shahwan A, Farrell M, Delanty N. Progressive myoclonic epilepsies: a review of genetic and therapeutic aspects. Lancet Neurol. 2005 Apr. 4(4):239-48. [Medline].

Cohen BH, Chinnery PF, Copeland WC. POLG-Related Disorders. Pagon RA, Bird TD, Dolan CR, Stephens K, eds. GeneReviews [Internet]. University of Washington, Seattle; 1993-2010 Mar 16.

Crompton DE, Berkovic SF. The borderland of epilepsy: clinical and molecular features of phenomena that mimic epileptic seizures. Lancet Neurol. 2009 Apr. 8(4):370-81. [Medline].

Korff CM, Nordli DR Jr. Epilepsy syndromes in infancy. Pediatr Neurol. 2006 Apr. 34(4):253-63. [Medline].

Wallace SJ. Myoclonus and epilepsy in childhood: a review of treatment with valproate, ethosuximide, lamotrigine and zonisamide. Epilepsy Res. 1998 Jan. 29(2):147-54. [Medline].

Andrade DM, Hamani C, Minassian BA. Treatment options for epileptic myoclonus and epilepsy syndromes associated with myoclonus. Expert Opin Pharmacother. 2009 Jul. 10(10):1549-60. [Medline].

Wilmshurst JM, Gaillard WD, Vinayan KP, Tsuchida TN, Plouin P, Van Bogaert P, et al. Summary of recommendations for the management of infantile seizures: Task Force Report for the ILAE Commission of Pediatrics. Epilepsia. 2015 Aug. 56 (8):1185-97. [Medline].

Wallace A, Wirrell E, Kenney-Jung DL. Pharmacotherapy for Dravet Syndrome. Paediatr Drugs. 2016 Mar 10. [Medline].

Devinsky O, Patel AD, Cross JH, Villanueva V, Wirrell EC, Privitera M, et al. Effect of Cannabidiol on Drop Seizures in the Lennox-Gastaut Syndrome. N Engl J Med. 2018 May 17. 378 (20):1888-1897. [Medline].

Thiele EA, Marsh ED, French JA, Mazurkiewicz-Beldzinska M, Benbadis SR, Joshi C, et al. Cannabidiol in patients with seizures associated with Lennox-Gastaut syndrome (GWPCARE4): a randomised, double-blind, placebo-controlled phase 3 trial. Lancet. 2018 Mar 17. 391 (10125):1085-1096. [Medline].

Wheless JW, Sankar R. Treatment strategies for myoclonic seizures and epilepsy syndromes with myoclonic seizures. Epilepsia. 2003. 44 Suppl 11:27-37. [Medline].

Hirschler, B. Cannabis drug succeeds in epilepsy, doubling value of GW Pharma. Reuters. March 14, 2016. Available at http://www.reuters.com/article/us-gw-pharma-cannabis-idUSKCN0WG16Z.

Michael C Kruer, MD Director, Neurogenetics and Pediatric Movement Disorders Programs, Barrow Neurological Institute, Phoenix Children’s Hospital; Associate Professor, Departments of Child Health and Neurology, Graduate Interdisciplinary Program in Genetics, University of Arizona College of Medicine in Phoenix

Michael C Kruer, MD is a member of the following medical societies: American Academy for Cerebral Palsy and Developmental Medicine, American Academy of Neurology, American Academy of Pediatrics, American Neurological Association, American Physician Scientists Association, American Society for Cell Biology, American Society of Human Genetics, Child Neurology Society, International Child Neurology Association, Mitochondrial Medicine Society, Movement Disorder Society

Disclosure: Nothing to disclose.

Raj D Sheth, MD Chief, Division of Pediatric Neurology, Nemours Children’s Clinic; Professor of Neurology, Mayo College of Medicine; Professor of Pediatrics, University of Florida College of Medicine

Raj D Sheth, MD is a member of the following medical societies: American Academy of Neurology, American Academy of Pediatrics, American Epilepsy Society, American Neurological Association, Child Neurology Society

Disclosure: Nothing to disclose.

Amy Kao, MD Attending Neurologist, Children’s National Medical Center

Amy Kao, MD is a member of the following medical societies: American Academy of Neurology, American Epilepsy Society, Child Neurology Society

Disclosure: Have stock (managed by a financial services company) in healthcare companies including AbbVie, Allergan, Celgene, Cellectar Biosciences, Danaher Corp, Mckesson.

James J Riviello Jr, MD George Peterkin Endowed Chair in Pediatrics, Professor of Pediatrics, Section of Neurology and Developmental Neuroscience, Professor of Neurology, Peter Kellaway Section of Neurophysiology, Baylor College of Medicine; Chief of Neurophysiology, Director of the Epilepsy and Neurophysiology Program, Texas Children’s Hospital

James J Riviello Jr, MD is a member of the following medical societies: American Academy of Pediatrics

Disclosure: Up To Date Royalty Section Editor

Francisco Talavera, PharmD, PhD, Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Medscape Reference Salary Employment

Myoclonic Epilepsy Beginning in Infancy or Early Childhood

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