|Year : 2019 | Volume
| Issue : 4 | Page : 420-422
Lafora body disease: A case of progressive myoclonic epilepsy in an adolescent male
Sushma Ramraje, Sameer Ansari, Ankita Nayak, Grace Costa
Department of Pathology, Grant Government Medical College, Mumbai, Maharashtra, India
|Date of Submission||02-Oct-2018|
|Date of Decision||05-Jun-2019|
|Date of Acceptance||22-Oct-2019|
|Date of Web Publication||16-Jul-2020|
Dr. Sushma Ramraje
2/15, Dhanwantari, Sir J J Hospital Campus, Byculla, Mumbai - 400 008, Maharashtra
Source of Support: None, Conflict of Interest: None
Progressive myoclonic epilepsy is defined as a neurological disorder manifesting classically as a trio of progressive myoclonic seizures, cognitive impairment, ataxia, and/or any other neurologic defects. Syndromic association is seen specifically with Unverricht–Lundborg disease, myoclonic epilepsy with ragged red fibers, neuronal ceroid lipofuscinoses, Lafora body disease (LBD), and sialidoses. LBD is characterized by an autosomal recessive inheritance. Adolescent-onset progressive myoclonic epilepsy is seen along with Lafora bodies in the brain, liver, and the ducts of the sweat glands in skin. We hereby present a case of a 17-year-old male, presenting with progressing myoclonus and Lafora bodies in axillary skin biopsy, thereby confirming the diagnosis of LBD.
Keywords: Cognitive impairment, lafora body, progressive myoclonic epilepsy
|How to cite this article:|
Ramraje S, Ansari S, Nayak A, Costa G. Lafora body disease: A case of progressive myoclonic epilepsy in an adolescent male. J Datta Meghe Inst Med Sci Univ 2019;14:420-2
|How to cite this URL:|
Ramraje S, Ansari S, Nayak A, Costa G. Lafora body disease: A case of progressive myoclonic epilepsy in an adolescent male. J Datta Meghe Inst Med Sci Univ [serial online] 2019 [cited 2020 Aug 14];14:420-2. Available from: http://www.journaldmims.com/text.asp?2019/14/4/420/289862
| Introduction|| |
Progressive myoclonic epilepsy is defined as a neurological disorder manifesting classically as a trio of progressive myoclonic seizures, cognitive impairment, ataxia, and/or any other neurologic defects. Syndromic association is seen specifically with Unverricht–Lundborg disease, myoclonic epilepsy with ragged red fibers, neuronal ceroid lipofuscinoses, Lafora body disease (LBD), and sialidoses.
LBD is characterized by an autosomal recessive inheritance. Adolescent-onset progressive myoclonic epilepsy is seen along with Lafora bodies in the brain, liver, and the ducts of the sweat glands in skin.
| Case Report|| |
A 17-year-old male patient, born of consanguineous marriage, presented with complaints of occasional, brief, sudden, jerky movements of the whole body, occipital lobe seizures with vivid aura, and progressive cognitive decline since 14 years of age.
Systemic examination was normal. No focal neurologic deficits or abnormal reflexes were noted. The patient had a positive family history of similar illness, with one female sibling and another male sibling dying around 19 years and 18 years of age, respectively.
On investigation, routine hematological, biochemical, and radiological tests were unremarkable. Electroencephalography was suggestive of frequent generalized spikes with diffuse low-voltage delta-waves. A diagnosis of LBD was suspected, and histopathological examination of axillary as well as forearm skin biopsies was done to confirm the presence of LBD.
Histopathological examination of hematoxylin- and eosin-stained sections of both axillary and forearm skin biopsies revealed epidermis, dermis, and subcutaneous tissue. The epidermis showed hyperkeratosis, mild acanthosis, and basal layer pigmentation. On examination of the axillary biopsy at higher magnification, few lightly basophilic inclusions were seen in the cytoplasm of the acinar cells of the sweat glands [Figure 1]. However, the biopsy from the forearm showed no atypia or any histopathological abnormalities. Periodic acid–Schiff (PAS) staining of both the biopsies from the axillary region and forearm was carried out to confirm the nature of these inclusions. PAS-positive and diastase-resistant eosinophilic inclusion bodies were seen in the acinar cells lining the eccrine glands in the dermis of the axillary skin biopsy only [Figure 2]. The forearm biopsy showed no such bodies in the dermal glands [Figure 3].
|Figure 1: Axillary biopsy – few lightly basophilic inclusions in the cytoplasm of the acinar cells of the sweat glands (H and E; ×400)|
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|Figure 2: Axillary biopsy – periodic acid–Schiff-positive and diastase-resistant eosinophilic Lafora bodies in the acinar cells (periodic acid–Schiff; ×400)|
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|Figure 3: Forearm biopsy – no Lafora bodies in the dermal glands (periodic acid–Schiff; ×400)|
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| Discussion|| |
Gonzalo Rodriguez Lafora, a Spanish neuropathologist, and Bernhard Glueck first described LBD way back in 1911. However, the proposal that skin biopsy can be a convenient method of diagnosing Lafora disease was put forward by Carpenter and Karpati in 1981 who successfully identified Lafora bodies within the eccrine ducts. Acharya et al. documented the first case from India.,
The patients present with progressive aggravation of symptoms between 12 and 17 years, despite a normal first decade (rarely, childhood febrile seizures may be present). Cognitive impairment and myoclonus may be present before the first seizure which is usually generalized in nature. Mental decline may be noted later. Kaufman et al. reported that epileptic seizures account for personality disintegration and mental decline.
The etiology is unknown, affecting both sexes equally. Despite global prevalence, ethnic isolates and regions with high consanguinity coupled with autosomal recessive inheritance or increased mutational frequency have a higher disease burden.
The common mutations seen in LBD are as follows: EPM2A (laforin) discovered in 1998 and EPM2B (malin) discovered in 2003., These proteins ubiquitinate the protein targeting to glycogen and glycogen synthase for proteasomal degradation. These lead to characteristic accumulation of polyglucosans. Pathologically, Lafora disease is characterized by increased glycogen content in tissues and the presence of malformed glycogen molecules called polyglucosans. The latter accumulates over time into masses called Lafora bodies.
Many studies favor examination of skin biopsies from axilla as well as other areas.
Andrade et al. favored skin biopsy outside the axilla as the apocrine glands are few or absent outside the axilla and genital regions. This helps to reduce the false-positive reports which may be due to apocrine contents., Doaei et al. found axillary skin biopsy to be more reliable to make a definitive diagnosis of LBD for its greater number of apocrine and eccrine glands. They found an abundance of Lafora bodies in the epithelial and myoepithelial cells of the ducts of the sweat, apocrine, and eccrine glands from the biopsy at axillary site. Despite advances in the genetics of Lafora disease, skin biopsy remains a convenient, least invasive, and a primary diagnostic modality. Skin biopsy taken from the axillary fold in our case showed PAS-positive intracytoplasmic inclusions in the acinar cells of both eccrine and apocrine glands.
Other than the skin biopsy, confirmation of diagnosis can also be obtained by demonstration of pathognomonic inclusion bodies in the heart, liver, skeletal muscle, brain, and spinal cord. In the brain, inclusions are seen in the perikarya and dendrites of neurons. In muscle, type IIB muscle fibers are primarily affected. Special stains such as PAS and Alcian blue are noted positive. However, they are diastase resistant and also stain variably metachromatic with methyl violet or toluidine blue. On electron microscopy, the inclusions are electron-lucent and contain glycogen-like granules and filamentous material. However, such inclusions can be seen as part of normal aging process (imitated by corpora amylacea) or in entities such as type IV glycogen storage disease, amyotrophic lateral sclerosis, or motor neuron disease. In polyglucosan diseases, they are located in axons and astrocytes.
Antiepileptic drugs such as sodium valproate help in the treatment of both myoclonic and generalized seizures. Psychological and social management is of equal importance. Death occurs 4–10 years after onset. The majority of cases die 6 years after the onset of symptoms. In our case, the siblings died at the ages of 18 and 19 years of age.
| Conclusion|| |
Despite advances in the genetics of Lafora disease, axillary skin biopsy being a more convenient, cost-effective, minimally invasive, and safer method remains a primary diagnostic modality. Axillary skin biopsy is diagnostic as it has more number of apocrine and eccrine glands.
Declaration of patient consent
The authors certify that they have obtained all appropriate patient consent forms. In the form the patient(s) has/have given his/her/their consent for his/her/their images and other clinical information to be reported in the journal. The patients understand that their names and initials will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed.
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
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[Figure 1], [Figure 2], [Figure 3]