Letters to Editor
mucolipin‑1, a member of the transient receptor potential cation channel family. [5] Alterations in mucolipin leads to accumulation of heterogenous lipids and proteins in the cytosol vacuoles derived from lysosomes. EM examination of skin biopsies is a useful and relatively inexpensive method to screen for lysosomal storage diseases and for diagnosis of conditions for which there are no specific molecular or genetic tests. EM studies of biopsy specimens taken from skin, conjunctiva, peripheral nerve, muscle, and liver show two types of inclusions in ML-IV, membrane‑bound vesicles filled with granular material and concentric lamellar bodies.[5] The skin biopsy findings in our patient were consistent with those previously reported. The various forms of late infantile, juvenile, and adult onset neuronal ceroid lipofuscinoses are characterized by inclusion of either curvilinear and/or finger print bodies as opposed to membrane cytoplasmic or zebra bodies as seen in ML‑IV.[5] Phospholipids, mucopolysaccharides and gangliosides are found in these inclusion bodies. [6] Interestingly, these abnormalities are similar to those seen in cells of patients with GM2‑gangliosidosis Type I or Tay‑Sachs disease, fucosidosis, galactosialidosis or sialidosis.[5] The morphology, however, of the storage material in skin biopsies of ML‑IV patients is unique, enabling biopsies to be used for diagnostic purposes.
Ramshekhar N. Menon, Sujith Jagtap, Ravindra Thakkar1, Gayathri Narayanappa1, Muralidharan Nair Department of Neurology, Sree Chitra Tirunal Institute for Medical Sciences and Technology, Trivandrum, Kerala, 1 Department of Neuropathology, National Institute for Mental Health and Neurological Sciences, Bengaluru, Karnataka, India E‑mail: [email protected]
References 1. Altarescu G, Sun M, Moore DF, Smith JA, Wiggs EA, Solomon BI, et al. The neurogenetics of mucolipidosis type IV. Neurology 2002;59:306‑13. 2. Bonavita S, Virta A, Jeffries N, Goldin E, Tedeschi G, Schiffmann R. Diffuse neuroaxonal involvement in mucolipidosis IV as assessed by proton magnetic resonance spectroscopic imaging. J Child Neurol 2003;18:443‑9. 3. Chitayat D, Meunier CM, Hodgkinson KA, Silver K, Flanders M, Anderson IJ, et al. Mucolipidosis type IV: Clinical manifestations and natural history. Am J Med Genet 1991;41:313‑8. 4. Bindu PS, Gayathri N, Yasha TC, Kovoor JM, Subasree R, Rao S, et al. A variant form of mucolipidosis IV: Report on 4 patients from the Indian subcontinent. J Child Neurol 2008;23:1443‑6. 5. Alroy J, Ucci AA. Skin biopsy: A useful tool in the diagnosis of lysosomal storage diseases. Ultrastruct Pathol 2006;30:489‑503. 6. Wakabayashi K, Gustafson AM, Sidransky E, Goldin E. Mucolipidosis type IV: An update. Mol Genet Metab 2011;104:206‑13.
Neurology India | Sep-Oct 2013 | Vol 61 | Issue 5
Access this article online Quick Response Code:
Website: www.neurologyindia.com PMID: *** DOI: 10.4103/0028-3886.121943
Received: 13‑08‑2013 Review completed: 16‑08‑2013 Accepted: 20‑10‑2013
Bilateral symmetrical globus pallidus lesions following disulfiram ingestion Sir, Disulfiram is known to have central and peripheral neurotoxicity. We report a case of disulfiram encephalopathy with bilateral symmetrical globus pallidus lesions. A 35‑year‑old male with history of daily alcohol intake of 250‑750 mL for more than 18 years started self‑medication with disulfiram. He did not stop taking alcohol while on the drug. Within few days, he became irritable and aggressive would tear his clothes, undress in front of others and wander naked. He developed tremulousness and stiffness of all extremities with short step gait. By day‑7, he became incontinent and kept lying in soiled clothes without showing any concern, by day‑11 he became hypophonic and bed ridden with severe bradykinesia and rigidity and by day‑15 he presented with altered mental status. Metabolic profile including serum electrolytes, liver functions, blood urea, and serum creatinine was normal. Brain computed tomography showed bilateral hypodensities involving globus pallidus and subcortical white matter [Figure 1a]. Brain magnetic resonance imaging (MRI) showed T2 hyperintense and T1 hypointense lesions in bilateral globus pallidus which did not enhance with gadolinium [Figure 1b and c] and also diffuse T2 hyperintense and T1 hypointense lesions in bilateral subcortical white matter. Disulfiram is reported to be neurotoxic with and without alcohol intake. Disulfiram metabolizes into diethyldithiocarbamate and subsequently carbon disulfide. [1] Diethyldithiocarbamate impairs brain dopamine beta decarboxylase resulting in depletion of presynaptic norepinephrine and accumulation
539
Letters to Editor
a
b
c
Figure 1: (a) Computed tomography scan head showing bilateral globus pallidus hypodensities (b) magnetic resonance imaging (MRI) brain (gadolinium enhanced) showing nonenhancing T1 hypointensity in bilateral pallidal regions and subcortical paraventricular white matter (c) MRI brain showing T2 hyperintensities in bilateral pallidal regions and subcortical paraventricular white matter
Table 1: Conditions presenting with bilateral symmetrical globus pallidus lesions Carbon monoxide poisoning Cyanide poisoning Heroin/3.4 methylenedioxy‑N‑ methylamphetamine (MDMA; Ecstasy) Kernicterus Neurodegeneration with brain iron accumulation Pantothenate kinase associated Hepatic encephalopathy degeneration Methylmalonic academia Neurofibromatosis type‑1
of dopamine. Carbon disulfide induces severe microangiopathy and lesions of basal ganglia particularly pallidoputamen.[2] In the acute phase, enhancement of pallidal lesions has been reported. The gadolinium enhancement disappears later due to restoration of blood brain barrier.[1,3] Extensive signal changes in bilateral subcortical white matter observed in our patient have not been typically reported in literature. There are reports of delayed onset disulfiram‑related toxicity with clinical and radiological manifestations developing as late as 30 years after disulfiram treatment.[4] Our patient did not show signal changes in substantia nigra on MRI as reported in some earlier studies.[5] There is resurgence of interest in disulfiram after its’ reported value in treating cocaine and other stimulant dependence.[6] Disulfiram neurotoxicity should be considered in patients presenting with acute encephalopathy and parkinsonism. While symmetrical T2 basal ganglia hyperintensities are observed in other conditions as well [Table 1], pallidoputaminal lesions with greater involvement of globus pallidus on MRI brain indicates disulfiram toxicity in appropriate clinical setting.
Bhupender Kumar Bajaj, Anand Singh Department of Neurology, Post Graduate Institute of Medical Education and Research and Dr. Ram Manohar Lohia Hospital, New Delhi, India E‑mail: [email protected] 540
References 1. Lemoyne S, Raemakers J, Daems J, Heytens L. Delayed and prolonged coma after acute disulfiram overdose. Acta Neurol Belg 2009;109:231‑4. 2. Chuang WL, Huang CC, Chen CJ, Hsieh YC, Kuo HC, Shih TS. Carbon disulfide encephalopathy: Cerebral microangiopathy. Neurotoxicology 2007;28:387‑93. 3. Boukriche Y, Weisser I, Aubert P, Massoon C. MRI findings in a case of late onset disulfiram induced neurotoxicity. J Neurol 2000;247:714‑5. 4. Borrett D, Ashby P, Bilbao J, Carlen P. Reversible late onset disulfiram‑induced neuropathy and encephalopathy. Ann Neurol 1985;17:396‑9. 5. Park JW, Chung SW, Lee SJ, Lee KS, Kim BS. Selective vulnerability of nigrostriatopallidal dopaminergic pathway after disulfiram intoxication: Two cases with clinical and magnetic resonance study. Eur J Radiol Extra 2003;46:1‑5. 6. Kosten TR, Wu G, Huang W, Harding MJ, Hamon SC, Lappalainen J, Nielsen DA. Pharmacogenetic randomized trial for cocaine abuse: Disulfiram and dopamine beta hydroxylase. Biol Psychiatry 2013;73:219‑24. Access this article online Quick Response Code:
Website: www.neurologyindia.com PMID: *** DOI: 10.4103/0028-3886.121944
Received: 29‑08‑2013 Review completed: 03‑09‑2013 Accepted: 13‑10‑2013
Facial pain in carcinoma colon Sir, A 26‑year‑male, operated case of adenocarcinoma transverse colon, presented with left facial pain and Neurology India | Sep-Oct 2013 | Vol 61 | Issue 5
Copyright of Neurology India is the property of Medknow Publications & Media Pvt. Ltd. and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use.
mucolipin‑1, a member of the transient receptor potential cation channel family. [5] Alterations in mucolipin leads to accumulation of heterogenous lipids and proteins in the cytosol vacuoles derived from lysosomes. EM examination of skin biopsies is a useful and relatively inexpensive method to screen for lysosomal storage diseases and for diagnosis of conditions for which there are no specific molecular or genetic tests. EM studies of biopsy specimens taken from skin, conjunctiva, peripheral nerve, muscle, and liver show two types of inclusions in ML-IV, membrane‑bound vesicles filled with granular material and concentric lamellar bodies.[5] The skin biopsy findings in our patient were consistent with those previously reported. The various forms of late infantile, juvenile, and adult onset neuronal ceroid lipofuscinoses are characterized by inclusion of either curvilinear and/or finger print bodies as opposed to membrane cytoplasmic or zebra bodies as seen in ML‑IV.[5] Phospholipids, mucopolysaccharides and gangliosides are found in these inclusion bodies. [6] Interestingly, these abnormalities are similar to those seen in cells of patients with GM2‑gangliosidosis Type I or Tay‑Sachs disease, fucosidosis, galactosialidosis or sialidosis.[5] The morphology, however, of the storage material in skin biopsies of ML‑IV patients is unique, enabling biopsies to be used for diagnostic purposes.
Ramshekhar N. Menon, Sujith Jagtap, Ravindra Thakkar1, Gayathri Narayanappa1, Muralidharan Nair Department of Neurology, Sree Chitra Tirunal Institute for Medical Sciences and Technology, Trivandrum, Kerala, 1 Department of Neuropathology, National Institute for Mental Health and Neurological Sciences, Bengaluru, Karnataka, India E‑mail: [email protected]
References 1. Altarescu G, Sun M, Moore DF, Smith JA, Wiggs EA, Solomon BI, et al. The neurogenetics of mucolipidosis type IV. Neurology 2002;59:306‑13. 2. Bonavita S, Virta A, Jeffries N, Goldin E, Tedeschi G, Schiffmann R. Diffuse neuroaxonal involvement in mucolipidosis IV as assessed by proton magnetic resonance spectroscopic imaging. J Child Neurol 2003;18:443‑9. 3. Chitayat D, Meunier CM, Hodgkinson KA, Silver K, Flanders M, Anderson IJ, et al. Mucolipidosis type IV: Clinical manifestations and natural history. Am J Med Genet 1991;41:313‑8. 4. Bindu PS, Gayathri N, Yasha TC, Kovoor JM, Subasree R, Rao S, et al. A variant form of mucolipidosis IV: Report on 4 patients from the Indian subcontinent. J Child Neurol 2008;23:1443‑6. 5. Alroy J, Ucci AA. Skin biopsy: A useful tool in the diagnosis of lysosomal storage diseases. Ultrastruct Pathol 2006;30:489‑503. 6. Wakabayashi K, Gustafson AM, Sidransky E, Goldin E. Mucolipidosis type IV: An update. Mol Genet Metab 2011;104:206‑13.
Neurology India | Sep-Oct 2013 | Vol 61 | Issue 5
Access this article online Quick Response Code:
Website: www.neurologyindia.com PMID: *** DOI: 10.4103/0028-3886.121943
Received: 13‑08‑2013 Review completed: 16‑08‑2013 Accepted: 20‑10‑2013
Bilateral symmetrical globus pallidus lesions following disulfiram ingestion Sir, Disulfiram is known to have central and peripheral neurotoxicity. We report a case of disulfiram encephalopathy with bilateral symmetrical globus pallidus lesions. A 35‑year‑old male with history of daily alcohol intake of 250‑750 mL for more than 18 years started self‑medication with disulfiram. He did not stop taking alcohol while on the drug. Within few days, he became irritable and aggressive would tear his clothes, undress in front of others and wander naked. He developed tremulousness and stiffness of all extremities with short step gait. By day‑7, he became incontinent and kept lying in soiled clothes without showing any concern, by day‑11 he became hypophonic and bed ridden with severe bradykinesia and rigidity and by day‑15 he presented with altered mental status. Metabolic profile including serum electrolytes, liver functions, blood urea, and serum creatinine was normal. Brain computed tomography showed bilateral hypodensities involving globus pallidus and subcortical white matter [Figure 1a]. Brain magnetic resonance imaging (MRI) showed T2 hyperintense and T1 hypointense lesions in bilateral globus pallidus which did not enhance with gadolinium [Figure 1b and c] and also diffuse T2 hyperintense and T1 hypointense lesions in bilateral subcortical white matter. Disulfiram is reported to be neurotoxic with and without alcohol intake. Disulfiram metabolizes into diethyldithiocarbamate and subsequently carbon disulfide. [1] Diethyldithiocarbamate impairs brain dopamine beta decarboxylase resulting in depletion of presynaptic norepinephrine and accumulation
539
Letters to Editor
a
b
c
Figure 1: (a) Computed tomography scan head showing bilateral globus pallidus hypodensities (b) magnetic resonance imaging (MRI) brain (gadolinium enhanced) showing nonenhancing T1 hypointensity in bilateral pallidal regions and subcortical paraventricular white matter (c) MRI brain showing T2 hyperintensities in bilateral pallidal regions and subcortical paraventricular white matter
Table 1: Conditions presenting with bilateral symmetrical globus pallidus lesions Carbon monoxide poisoning Cyanide poisoning Heroin/3.4 methylenedioxy‑N‑ methylamphetamine (MDMA; Ecstasy) Kernicterus Neurodegeneration with brain iron accumulation Pantothenate kinase associated Hepatic encephalopathy degeneration Methylmalonic academia Neurofibromatosis type‑1
of dopamine. Carbon disulfide induces severe microangiopathy and lesions of basal ganglia particularly pallidoputamen.[2] In the acute phase, enhancement of pallidal lesions has been reported. The gadolinium enhancement disappears later due to restoration of blood brain barrier.[1,3] Extensive signal changes in bilateral subcortical white matter observed in our patient have not been typically reported in literature. There are reports of delayed onset disulfiram‑related toxicity with clinical and radiological manifestations developing as late as 30 years after disulfiram treatment.[4] Our patient did not show signal changes in substantia nigra on MRI as reported in some earlier studies.[5] There is resurgence of interest in disulfiram after its’ reported value in treating cocaine and other stimulant dependence.[6] Disulfiram neurotoxicity should be considered in patients presenting with acute encephalopathy and parkinsonism. While symmetrical T2 basal ganglia hyperintensities are observed in other conditions as well [Table 1], pallidoputaminal lesions with greater involvement of globus pallidus on MRI brain indicates disulfiram toxicity in appropriate clinical setting.
Bhupender Kumar Bajaj, Anand Singh Department of Neurology, Post Graduate Institute of Medical Education and Research and Dr. Ram Manohar Lohia Hospital, New Delhi, India E‑mail: [email protected] 540
References 1. Lemoyne S, Raemakers J, Daems J, Heytens L. Delayed and prolonged coma after acute disulfiram overdose. Acta Neurol Belg 2009;109:231‑4. 2. Chuang WL, Huang CC, Chen CJ, Hsieh YC, Kuo HC, Shih TS. Carbon disulfide encephalopathy: Cerebral microangiopathy. Neurotoxicology 2007;28:387‑93. 3. Boukriche Y, Weisser I, Aubert P, Massoon C. MRI findings in a case of late onset disulfiram induced neurotoxicity. J Neurol 2000;247:714‑5. 4. Borrett D, Ashby P, Bilbao J, Carlen P. Reversible late onset disulfiram‑induced neuropathy and encephalopathy. Ann Neurol 1985;17:396‑9. 5. Park JW, Chung SW, Lee SJ, Lee KS, Kim BS. Selective vulnerability of nigrostriatopallidal dopaminergic pathway after disulfiram intoxication: Two cases with clinical and magnetic resonance study. Eur J Radiol Extra 2003;46:1‑5. 6. Kosten TR, Wu G, Huang W, Harding MJ, Hamon SC, Lappalainen J, Nielsen DA. Pharmacogenetic randomized trial for cocaine abuse: Disulfiram and dopamine beta hydroxylase. Biol Psychiatry 2013;73:219‑24. Access this article online Quick Response Code:
Website: www.neurologyindia.com PMID: *** DOI: 10.4103/0028-3886.121944
Received: 29‑08‑2013 Review completed: 03‑09‑2013 Accepted: 13‑10‑2013
Facial pain in carcinoma colon Sir, A 26‑year‑male, operated case of adenocarcinoma transverse colon, presented with left facial pain and Neurology India | Sep-Oct 2013 | Vol 61 | Issue 5
Copyright of Neurology India is the property of Medknow Publications & Media Pvt. Ltd. and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use.
