acid-phosphatase and Epilepsy

Focal cortical dysplasia (FCD) is a localized malformation of cortical development and is the commonest cause of severe childhood epilepsy in surgical practice. Children with FCD are severely disabled by their epilepsy, presenting with frequent seizures early in life. The commonest form of FCD in children is characterized by the presence of an abnormal population of cells, known as balloon cells. Similar pathological changes are seen in the cortical malformations that characterize patients with tuberous sclerosis complex (TSC). However, the cellular and molecular mechanisms that underlie the malformations of FCD and TSC are not well understood. We provide evidence for a defect in autophagy in FCD and TSC. We have found that balloon cells contain vacuoles that include components of the autophagy pathway. Specifically, we show that balloon cells contain prominent lysosomes by electron microscopy, immunohistochemistry for LAMP1 and LAMP2, LysoTracker labelling and enzyme histochemistry for acid phosphatase. Furthermore, we found that balloon cells contain components of the ATG pathway and that there is cytoplasmic accumulation of the regulator of autophagy, DOR. Most importantly we found that there is abnormal accumulation of the autophagy cargo protein, p62. We show that this defect in autophagy can be, in part, reversed in vitro by inhibition of the mammalian target of rapamycin (mTOR) suggesting that abnormal activation of mTOR may contribute directly to a defect in autophagy in FCD and TSC.

Topics: Acid Phosphatase; Adaptor Proteins, Signal Transducing; Autophagy; Brain; Brain Diseases; Cells, Cultured; Child; Cytoplasm; Epilepsy; Humans; Immunohistochemistry; Lysosomal Membrane Proteins; Lysosomal-Associated Membrane Protein 2; Lysosomes; Malformations of Cortical Development; Malformations of Cortical Development, Group I; Sequestosome-1 Protein; Tissue Banks; TOR Serine-Threonine Kinases; Tuberous Sclerosis

Topics: Acid Phosphatase; Animals; Cobalt; Epilepsy; Lysosomes; Male; Rats

A family is described in which adult-onset Gaucher's disease developed, followed years later by atypical psychotic disorders with neurologic and electroencephalographic abnormalities. A biochemical investigation of primary and secondary enzyme alterations in the index case was performed in an attempt to identify a pattern that might be specific to this clinical profile. The literature pertaining to CNS involvement in adult patients with Gaucher's disease is also reviewed. An etiologic link may exist between the inherited metabolic disorder and associated neuropsychiatric impairment. The biochemical basis of this hypothesized association remains unclear, however, and further enzymatic and pathologic investigations are warranted.

Topics: Acid Phosphatase; Adult; Basal Ganglia Diseases; Epilepsy; Female; Gaucher Disease; Glucosidases; Glucosylceramidase; Glucosylceramides; Humans; Leukocytes; Male; Middle Aged; Neurocognitive Disorders

The purpose of the investigation presented was to study whether the lymphocytes from patients with Spielmeyer-Vogt-Batten's syndrome deviate from normal with respect to acid phosphatase activity. The distribution of the activity seems to show that the patients with Spielmeyer-Vogt-Batten's syndrome can be divided into two groups, viz. one in which the values are concentrated around the normal level, and another with increased values.

Topics: Acid Phosphatase; Adolescent; Adult; Child; Epilepsy; Female; Humans; Lymphocytes; Male; Neutrophils; Pigmentation Disorders; Syndrome

Topics: Acid Phosphatase; Adult; Autopsy; Biopsy; Chromatography, Paper; Colorimetry; Epilepsy; Female; Glucosidases; Glycogen; Histocytochemistry; Humans; Maltose; Molecular Weight; Muscles; Myoclonus; Myofibrils; Phosphorylases; Polysaccharides; Staining and Labeling

Topics: Acetylcholinesterase; Acid Phosphatase; Adenosine Triphosphatases; Alkaline Phosphatase; Animals; Cholinesterases; Epilepsy; Esterases; Histocytochemistry; Hypothalamus; Rats; Thiamine; Transferases; Water

Topics: Acid Phosphatase; Adult; Brain Neoplasms; Central Nervous System Diseases; Cerebrospinal Fluid; Child, Preschool; Epilepsy; Female; Glioblastoma; Humans; Hypersensitivity; Inflammation; Lymphoma, Large B-Cell, Diffuse; Lysosomes; Male; Mental Disorders; Neurotic Disorders; Peptide Hydrolases; Psychotic Disorders; Vascular Diseases

Topics: Acid Phosphatase; Alkaline Phosphatase; Barbiturates; Biochemical Phenomena; Biochemistry; Blood Chemical Analysis; Epilepsy; Humans; Kidney Tubules; Urea

Topics: Acid Phosphatase; Blood; Cerebrospinal Fluid; Epilepsy; Humans