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At least 19 recordsLinked to original sources
PubMed2023

Retinal Phenotyping of a Murine Model of Lafora Disease.

Lafora disease (LD) is a progressive neurologic disorder caused by biallelic pathogenic variants in EPM2A or EPM2B, leading to tissue accumulation of polyglucosan aggregates termed Lafora bodies (LBs). This study aimed to characterize the retinal phenotype in Epm2a-/- mice by examining knockout (KO; Epm2a-/-) and control (WT) littermates at two time points (10 and 14 months, respectively). In vivo exams included electroretinogram (ERG) testing, optical coherence tomography (OCT) and retinal photography. Ex vivo retinal testing included Periodic acid Schiff Diastase (PASD) staining, followed by imaging to assess and quantify LB deposition. There was no significant difference in any dark-adapted or light-adapted ERG parameters between KO and WT mice. The total retinal thickness was comparable between the groups and the retinal appearance was normal in both groups. On PASD staining, LBs were observed in KO mice within the inner and outer plexiform layers and in the inner nuclear layer. The average number of LBs within the inner plexiform layer in KO mice were 1743 ± 533 and 2615 ± 915 per mm2, at 10 and 14 months, respectively. This is the first study to characterize the retinal phenotype in an Epm2a-/- mouse model, demonstrating significant LB deposition in the bipolar cell nuclear layer and its synapses. This finding may be used to monitor the efficacy of experimental treatments in mouse models.

Mice↗
PubMed1978

Electroretinographic responses in Lafora disease.

In 3 patients with Lafora disease specific ERGs were observed resembling closely those seen in the Schubert-Bronschein type of night blindness. In contrast to essential hemeralopia, where the b-wave is completely lacking a gradual recovery of the b-wave was recorded in Lafora disease. The recovery occurred within about 15 min of dark adaptation. ERG examinations may have diagnostic significance in patients with myoclonic epilepsy.

Adolescent↗
PubMed1975

Biochemical studies on tissues from a patient with Lafora disease.

Tissues from the cerebral cortex, liver and myocardium of a patient with Lafora disease were obtained at autopsy and were studied biochemically. 1. Glucose content in the myocardium and liver was almost nil while that in the controls was 0.66 mg/g wet weight in the former and 8.80 mg/g wet weight in the latter. Glycogen content in the cerebral cortex and myocardium was about 10 and 3 times more than in controls. 2. Polyglucosan extracted from the cerebral cortex, liver and myocardium had a longer exterior glucose chain than that in the liver of the control but a normal, alpha or beta 1,4-glucosidic linkage was observed. 3. The activities of glucose-6-phosphatase and amylo-1,6-glucosidase in the cerebral cortex, liver and myocardium were well preserved. The activities of acid maltase in the three organs mentioned above and of neutral maltase in the myocardium were elevated twice and one and half times more than the control. Phosphorylase levels in the myocardium were extremely small, while in the cerebral cortex and liver normal activities were observed. In light of these findings, glycogen metabolism in Lafora disease is discussed.

Adult↗
PubMedDate not supplied

[2 familial cases of Lafora disease. Clinical, electroencephalographic and pathologic study].

Three children born of consanguineous parents had Lafora's disease and two of them had been studied clinically, pathologically and biochemically. The autosomal recessive transmission of the disease is confirmed by the familial study and the parents present no phenotypic anomaly of the disease. Electroclinical data are discussed with regard to the early differential diagnosis between this entity and idiopathic generalised epilepsy and myoclonic epilepsy without Lafora's bodies. Iodine spectrum of the cerebral and hepatic abnormal deposits suggest that Lafora's bodies mainly consist of long chains glycogen similar to amylopectin.

Brain↗
PubMed1979

[Recent data on Lafora disease. Apropos of 17 cases].

This study reviews 99 anatomically verified case of Lafora body disease (82 from the literature and 17 personal cases). The clinical symptoms of the disease are characterised by the triad; epilepsy, myoclonus and dementia. An anatomical and histochemical study has been undertaken and as a result emphasis is given to recent hypotheses that suggest there are similarities with Type IV glycogen storage disease (Andersen's disease) which, although clinically distinct, has the same enzyme defect.

Adolescent↗
PubMedDate not supplied

[Lafora disease (author's transl)].

On the basis of 21 personal observations as well as those (82) from the litterature, it is concluded that the progressive myoclonic epilepsy with Lafora bodies (P.M.E.) constitutes a disease on its own. The clinical features are those described in the litterature observations and completed by some characteristics; the high frequency of visual symptoms (47 p. 100 personal cases); the relatively less bad evolution of epilepsy, perhaps in relation with use of modern drugs; the relatively moderate intensity of myoclonus which becomes complete only at the end of the evolution. From E.E.G. point of view, we can distinguish three periods: an initial one at the very onset of disease, who will show the same features as observated in primary generalized epilepsy, i.e. a well preserved background activity with superimposed generalized fast spikes and waves facilitated by the I.L.S. Then follows a period of evolutive E.E.G. (1-2 years after the onset of the disease) characterized by progressive slowing of the posterior background, enlargement of posterior slow activity and appearance of diffuse theta and delta activity. Simultaneously spikes and waves are taking less typical and bisynchronous aspect. Finally after 3 to 5 years from the onset there is a diffusely slow E.E.G. with superimposed fast multiple spikes. The E.E.G. findings in litterature usually refer only to this last period (stationary or terminal period). Occipital independent multiple spikes are frequently observed and could correlate with the visual symptoms observated in the Lafora disease. Some elements of differential diagnosis are given with respect to primary generalized epilepsy at the onset of the disease and later on with respect to dyssynergia cerebellaris myoclonica and to the progressive myoclonic epilepsy without Lafora bodies.

Adolescent↗
PubMed1979

Tendency to periodic recurrence of EEG changes in Lafora's disease. Case report.

A young male patient affected with Lafora's disease and concomitant mental deterioration, myoclonic jerks and epileptic seizures is reported. A cerebral biopsy showed round PAS-positive myoclonus bodies in nerve cells and neuropile. A tendency to periodic recurrence of paroxysmal activity in the EEG tracings, an unusual finding in Lafora's disease, is briefly discussed.

Adolescent↗
PubMed2023

Laforin targets malin to glycogen in Lafora progressive myoclonus epilepsy.

Glycogen is the largest cytosolic macromolecule and is kept in solution through a regular system of short branches allowing hydration. This structure was thought to solely require balanced glycogen synthase and branching enzyme activities. Deposition of overlong branched glycogen in the fatal epilepsy Lafora disease (LD) indicated involvement of the LD gene products laforin and the E3 ubiquitin ligase malin in regulating glycogen structure. Laforin binds glycogen, and LD-causing mutations disrupt this binding, laforin-malin interactions and malin's ligase activity, all indicating a critical role for malin. Neither malin's endogenous function nor location had previously been studied due to lack of suitable antibodies. Here, we generated a mouse in which the native malin gene is tagged with the FLAG sequence. We show that the tagged gene expresses physiologically, malin localizes to glycogen, laforin and malin indeed interact, at glycogen, and malin's presence at glycogen depends on laforin. These results, and mice, open the way to understanding unknown mechanisms of glycogen synthesis critical to LD and potentially other much more common diseases due to incompletely understood defects in glycogen metabolism.

Animals↗
PubMed1979

Progressive myoclonus epilepsy: genetic and nosological aspects with special reference to 107 Finnish patients.

In 107 Finnish patients with progressive myoclonus epilepsy (PME), belonging to 74 families, autosomal recessive inheritance was evident. The sex ratio was 48:51, the corrected proportion of affected sibs being 0.260. Of 68 marriages 15, or 22%, were consanguineous; several of the parents were related and the geographical distribution was of the uneven type typical of young, isolated populations in Finland. The incidence in Finland was estimated to exceed 1:20,000. The clinical picture in the Finnish PME patients was uniform, being identical with that of Unverricht's and Lundborg's patients, but clearly distinct from Lafora disease. The following classification of PME is proposed: (1) PME, Lafora type: onset of grand mal attacks and/or myoclonus around the 15th year of life; rapid and severe mental deterioration, often with psychotic symptoms; short survival; histological finding of Lafora bodies; autosomal recessive inheritance. (2) PME, Unverricht-Lundborg type: onset around the 10th year of life; severity variable, progressive invalidity from myoclonic features associated with mild mental symptoms, time of survival variable, "degenerative" histological changes; autosomal recessive inheritance. (3) Autosomal dominant or otherwise atypical cases of PME. The importance of accurate diagnosis is stressed.

Adolescent↗
PubMed1979

Lafora-like bodies in a cat. Case report suggestive of glycogen metabolism disturbances.

Lafora-like bodies in an 8-year-old cat were studied light and electron microscopically and histochemically. In addition ot Lafora-like bodies composed of branching filaments, glycogen granules and electron-dense materaisl, abnormal accumulations of glycogen granules attracted attention. The most remarkable features were the developmental processes of the branching filaments originating directly from glycogen granules. Lafora-like bodies in the present study showed ultrastructural, histochemical, and enzymatic similarities to those described in the previous reports in Lafora's disease, glycogenosm is considered to be probably related to the productive mechanism of Lafora-like bodies.

Animals↗
PubMed1978

Lafora-like inclusion bodies in the CNS of aged dogs.

Forty randomly selected dogs, arranged into three groups according to age, were examined light and electron microscopically. Lafora-like inclusion bodies were found in all cases of aged dogs without neurological signs. They appeared as PAS positive, round bodies measuring up to 15 mu in diameter. Typically they had central cores and radiating peripheral lines. Electronmicroscopically, the inclusions consisted of irregularly clustered, short branching filaments measuring about 80--120 A in diameter or of electron-dense homogeneous or granular central cores with filamentous peripheral areas and located both in the perikarya and neuronal processes. The inclusions were disseminated all over the brain and spinal cord. The thalamic nuclei, a circumscribed area dorsal to the aqueduct, and the molecular layer of the superior colliculus were the most severely affected. The frequency of the inclusions showed age-dependency; the inclusions were not found in dogs younger than 2 years, but were extensive in all dogs of more than 8 years of age. The occurrence of the inclusions may therefore represent an age-dependent phenomenon. The relationship between the present findings and Lafora's disease is discussed.

Aging↗
PubMed1979

Liver cell injury (bodies similar to Lafora's) in alcoholics treated with disulfiram (Antabuse).

Inclusions, structurally similar to Lafora's bodies, are described in the liver cells of three chronic alcoholic patients who stopped drinking after disulfiram treatment. The inclusions were strongly positive with PAS and methenamine silver stains. Shikata stain for HBsAg was negative. On electron microscopy the inclusions are not membrane-bound and contain glycogen beta-granules, secondary lysosomes containing lamellar structures, lipid droplets and filaments; the SER was almost completely lost. In the patient least affected, the cells bearing inclusions were predominantly periportal in location, as is usual in Lafora's disease. In the two other patients the change involved the whole lobule. The possibility of an induced carbohydrate metabolic disorder, which could be due to the disulfiram, a drug that interferes with the activity of several hepatic enzymes is discussed. The presence of appearances suggestive of SER breakdown could also be interpreted as a manifestation of 'disuse atrophy' due to alcohol withdrawal.

Adult↗