Progressive myoclonic epilepsy: A clinical, electrophysiological and pathological study from South India

• Published in: Journal of the neurological sciences Vol. 252; no. 1; pp. 16 - 23
• Main Authors: Sinha, S, Satishchandra, P, Gayathri, N, Yasha, T.C, Shankar, S.K
• Format: Journal Article
• Language: English
• Published: Shannon Elsevier B.V 15.01.2007; Elsevier Science
• Subjects: Adolescent; Adult; Age of Onset; Biological and medical sciences; Child; Child, Preschool; Degenerative and inherited degenerative diseases of the nervous system. Leukodystrophies. Prion diseases; Electroencephalography; Electrophysiology; Evoked Potentials, Visual - physiology; Female; Headache. Facial pains. Syncopes. Epilepsia. Intracranial hypertension. Brain oedema. Cerebral palsy; Humans; Immunohistochemistry; India - epidemiology; Indoles; Infant; Lafora body disease; Male; Medical sciences; MERRF; Middle Aged; Myoclonic Epilepsies, Progressive - classification; Myoclonic Epilepsies, Progressive - epidemiology; Myoclonic Epilepsies, Progressive - pathology; Myoclonic Epilepsies, Progressive - physiopathology; Nervous system (semeiology, syndromes); Neurology; Neuronal ceroid lipofuscinoses; Photic Stimulation - methods; Photosensitivity; Progressive myoclonic epilepsy; Retrospective Studies; Ubiquitin - metabolism; Unverricht–Lundborg disease; Asia; India; Lafora body disease; Photosensitivity; MERRF; Unverricht–Lundborg disease; Progressive myoclonic epilepsy; Neuronal ceroid lipofuscinoses; Skin disease; Nervous system diseases; Lafora body; South; Progressive myoclonus epilepsy; Cerebral disorder; Unverricht-Lundborg disease; Central nervous system disease; Degenerative disease; Lafora disease
• ISSN: 0022-510X; 1878-5883
• DOI: 10.1016/j.jns.2006.09.021

Abstract Progressive myoclonic epilepsy (PME) is a syndrome complex encompassing different diagnostic entities and often cause problems in diagnosis. We describe the clinical, electrophysiological and pathological features of 97 patients with the diagnosis of PME evaluated over 25 years. Case records of confirmed patients of Neuronal ceroid lipofuscinosis (NCL = 40), Lafora body disease (LBD = 38), Myoclonic epilepsy with ragged red fibers (MERRF = 10), and probable Unverricht–Lundberg disease (ULD = 9) were reviewed. The mean age at onset in patients with NCL ( n = 40) was 5.9 ± 9.1 years (M:F:: 28:12). Subtypes of NCL were: late infantile ( n = 19), infantile ( n = 8), juvenile ( n = 11) and adult ( n = 2) NCL. EEG ( n = 37) showed varying degree of diffuse slowing of background activity in 94.6% and epileptiform discharges in 81.1% of patients. Slow frequency photic stimulation evoked photo-convulsive response in 5 patients only. Giant SSEP was demonstrated in 7 and VEP study revealed a prolonged P100 (2) and absent waveform (7). Electrophysiological features of neuropathy were present in 3 patients. Presence of PAS and Luxol Fast Blue (LFB) positive, auto fluorescent (AF) ceroid material in brain tissue ( n = 12) and electron microscopy of brain ( n = 5), skin ( n = 28) and muscle ( n = 1) samples showing curvilinear and lamellar bodies established the diagnosis. Patients of LBD (mean age of onset at 14.4 ± 3.9 years, M:F:: 24:14) with triad of PME symptoms were evaluated. EEG ( n = 37) showed variable slowing of background activity in 94.6% and epileptiform discharges in 97.4%. Photosensitivity with fast frequency was observed only in 5 patients. CT ( n = 32) and MRI ( n = 4) revealed diffuse cortical atrophy. Giant SSEP was demonstrated in 24 patients of LBD while VEP study revealed a prolonged P100 (4) and absent waveform (8). Electrophysiological features of neuropathy were present in one patient. Diagnosis was established by the presence of PAS positive diastase resistant, Lugol's Iodine labeled inclusions in sweat glands of axillary skin ( n = 35), brain ( n = 2) and liver ( n = 1). Ten patients with MERRF (mean age at onset: 14.6 ± 5.8 years; M: F:: 3:2) had triad of PME symptoms. Muscle biopsy revealed oxidative reaction product and classical ragged red fibers. In nine patients of PME without cognitive decline, probable diagnosis of ULD (mean age at onset: 13.8 ± 9.5 years) was considered after biopsy of skin and/or muscle excluded other forms of PMEs. Neuronal ceroid lipofuscinosis and Lafora body diseases were the common causes of PME in the series from south India. This is one of the largest series from the Indian subcontinent to the best of our knowledge. Photosensitivity is notably less common in LBD/NCL in this series distinctly different from those reported in the literature. Further exploration is required to determine whether different genotype is responsible. Morphological changes were helpful in diagnosis and could be confirmed by biopsy of peripheral tissues like skin and muscle in majority (60%). Electron microscopy was helpful in the diagnosis NCL and MERRF.