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Progressive myoclonus epilepsies: description of a case of Lafora disease with autopsy

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Text of Progressive myoclonus epilepsies: description of a case of Lafora disease with autopsy

  • Neurologa. 2013;28(9):584593


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    Please cite this article as: Jimnez Caballero PE. Epilepsia mio-clnica progcon autopsia

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    accompanied by visual symptoms that persisted in spiteof treatment with several drug combinations. He lostfunctional abilities to the point of becoming completely dis-abled; nasogastric feeding was required since his frequent

    2173-5808/$resiva: Descripcin de un caso de enfermedad de Lafora. Neurologa. 2013;28:584586.

    palatal myoclonias provoked difculty swallowing. He pre-sented bladder and bowel incontinence and tetraparesis,

    see front matter 2012 Sociedad Espaola de Neurologa. Published by Elsevier Espaa, S.L. All rights reserved.ive myoclonus epilepsies:ion of a case of Lafora diseaseopsy

    mioclnica progresiva: Descripcinso de enfermedad de Lafora con


    progressive myoclonus epilepsy (PME) refers tof clinical entities with heterogeneous causes.characterised by different types of epilep-s (mainly myoclonic), intellectual impairment,

    clinical manifestations mainly involving the.1,2

    ent the case of a 15-year-old male whose gesta-rth were uneventful. Psychomotor developmentional level were also normal until the age of 11.ealthy brother 3 years older. Their parents wereguineous, although both were from the same vil-e 1000 of 12, the patient began to suffer episodestation lasting a few seconds, which were inter-absence seizures. During the following months,ed several generalised tonic-clonic seizures. Cra-ded normal results; EEG revealed overall slowingkground activity plus some diffuse spike-wave. Intermittent light stimulation generated a pho-al response at low frequencies. Epileptic activityrease during stages of drowsiness.

    initially diagnosed with juvenile myoclonusd treated with valproic acid (1500 mg per day)with clonazepam (40 mg per day). Given theponse to medication, doctors added phenobar-g per day) and ethosuximide (1000 mg per day) toeralised seizures and absence seizures, respec-

    he following 2 years, the patients epilepsy pro-favourably with increasingly frequent seizures.

    atypicand gedeclindecitties. Tmyoclo

    Genmata (spots. amnesnormafollowchangepresenbe incr(nger

    Anaand thantinetate leacid lestudy

    Bralar atr

    Thegeneraspike/that pstimulfrequestages

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    AxiPAS-poglandswere c

    Diseeralisesence seizures, multifocal cortical myoclonus,lised tonic-clonic seizures. Doctors also observedcademic performance with multiple cognitive

    ainly affecting visuospatial and literacy abili-patient was nally diagnosed with progressiveepilepsy based on the above symptoms.

    physical examination revealed no cutaneous stig-omatosis), visceromegalies, or retinal cherry-redrological examination revealed bradypsychia andecit for recent events. Cranial nerves werecept for horizontal nystagmus with quick phasehe direction of the gaze. There were no relevant

    the motor system or in sensitivity. The patienttruncal ataxia, tremor in both hands that couldd voluntarily, dysarthria, and bilateral dysmetriaose test).al tests, including a haemogram, renal, liver,

    proles, copper, ceruloplasmin, creatine kinase,al antibodies, and baseline and post-exercise lac-

    all yielded normal results. Blood and urine aminowere normal. Results from the lysosomal enzyme

    also unremarkable.I showed moderate overall cerebral and cerebel-.G showed slow background activity with

    epileptiform discharges manifesting asspike wave complexes of variable durationted throughout the reading. Intermittent light

    generated a photoparoxysmal response at lows. Epileptic activity did not increase duringrowsiness.

    muscle biopsy revealed no structural changes;eters were moderately variable. The basophilicrillar network was increased by multiples bresall round basophilic deposits, which were PAS-cording to enzymatic oxidation methods.

    skin biopsies (Fig. 1A) showed rounded intenselye formations in the epithelial cells of the apocrine

    in the ducts of the eccrine glands. Both biopsiesatible with Lafora disease.progression was aggressive, with multiple gen-onic-clonic, myoclonic, and partial seizures


    Figure 1 (A) Axillary skin biopsy (PAS stain, 2 400 magni-cation) showing round-shaped intensely PAS-positive formationsin the epithelial cells of the apocrine glands and in the ductsof the eccrine glands which correspond to Lafora bodies. (B)Heart (PAS stain, 1 200 magnication). Multiple Lafora bodiesin myocytes.

    and became conned to bed and armchair. He died of aspi-ration pneumonia 8 years after disease onset.

    Autopsy revealed typical Lafora bodies in several areasof the central nervous system (especially the thalamus andcerebellum), the liver, and the heart (Fig. 1B).

    The mocases are Uronal cerocytopathieMERRF) (Ta

    Dr Rodrease in 191disorder ofautosomal related diffEuropean c

    Lafora alised tonicdecline, asigns.4 It adolescencyears afteease is cauchromosom(laforin), aglycogen.5

    From a by the preorgans succially comminclude gluin an axilnomonic.

    Myoclonare resistaciated withcharacteristimes comdisease. Thdeteriorati

    On raretations macharacteriswave paroxslower andmittent ligbecome colow frequeepileptic astages of L

    Brain MRmediate staby cerebra

    In theoestablish a been detec

    In conclof Lafora dor adolesceataxia and structural changes in st frequent causes of PME affecting most of thenverricht-Lundborg disease, Lafora disease, neu-id lipofuscinoses, sialidosis, and mitochondrials (myoclonus epilepsy with ragged red bres,ble 1).guez Lafora was the rst to describe Lafora dis-1.3 It consists of a degenerative and progressive

    the central nervous system with a recessiveinheritance pattern. This disease presents no sex-erences and it is predominantly found in southernountries.disease is clinically characterised by gener--clonic seizures, myoclonias, progressive mentalnd pyramidal, extrapyramidal, and cerebellarappears at the end of childhood or duringe (6 to 20 years) and it leads to death 10r the onset of the rst symptoms. The dis-sed by a homozygous EPM2 mutation linked toe 6q23-25, which codies tyrosine phosphatase

    protein involved in the metabolic control of

    histological point of view, it is characterisedsence of intracytoplasmic inclusion bodies in

    h as the liver, heart, and brain. They are espe-on in biopsies of axillary skin.6 These bodies

    cose polymers (polyglucosan) and their presencelary skin biopsy is considered nearly pathog-

    ias become continuous during waking hours; theynt to antiepileptic medication and usually asso-

    occipital lobe seizure. Occipital seizures areed by simple visual hallucinations that are some-plex. These hallucinations are typical of Laforae onset of myoclonias coincides with progressiveon of cortical function and ataxia.

    occasions, electroencephalographic manifes-y appear prior to symptom onset. They areed by increasingly frequent spike- or polyspike-ysms. Subsequently, the baseline record becomes

    more disorganised. Paroxysms caused by inter-ht stimulation grow more frequent and graduallyntinuous; photoparoxysmal response is typical atncies.7 Unlike in juvenile myoclonus epilepsy,nomalies do not increase during sleep in initialafora disease.I shows no relevant changes in initial and inter-ges of the disease; nal stages are characterised

    l and cerebellar atrophy.8

    ry, doctors can offer genetic counselling andprenatal diagnosis when the genetic anomaly hasted in a family member.9

    usion, doctors should assign a suspected diagnosisisease when a young patient (in late childhoodnce) begins experiencing myoclonias followed byprogressive cognitive decline with no evidence ofchanges in neuroimaging tests and no metabolicthe analytical study.10


    Table 1 Differential diagnosis of progressive myoclonic epilepsies.

    Progressivemyoclonic epilepsy

    Inheritance Age at onset Indicative symptoms Pathological patterns Gene


    AR 615 Slow progression,

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