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Primary mitochondrial DNA mutations and probable variants in Leber's hereditary optic neuropathy
Abstracts / Journal of the Neurological Sciences e629 (2013) e629–e678
Abstract — WCN 2013 No: 1517 Topic: 36 — Other topic A case report: 53-year old Filipino with polyneuropathy, organomegaly, endocrinopathy, monoclonal gammopathy, and skin changes (poems) or Crow-Fukase syndrome C.A.V. Inso, J.A.S. Vatanagul. Internal Medicine, Perpetual Succour Hospital, Cebu City, Philippines
RO
OF
Background: POEMS syndrome or Crow-Fukase syndrome is a rare multi-systemic disease caused by overproduction of vascular endothelial growth factor (VEGF), probably mediated by monoclonal proliferation of plasma cells. Most patients with POEMS syndrome commonly present with extremity weakness. The syndrome is also associated with monoclonal plasma proliferative disorder, along with organomegaly, endocrinopathy, and skin changes. The Mayo Clinic Experience identified only 170 patients to have POEMS syndrome. Clinical presentation: A 53 year-old man who complained of 18 months duration of progressive weakness and numbness of both upper and lower extremities associated with hyperpigmentation of the skin, hypertrichosis, and bipedal edema. Predominant distal muscle weakness and atrophy was noted. Multiple large non-tender, cervical lymph nodes were noted. EMG-NCV showed polyneuropathy, sensory and motor diffuse, axonopathic and demyelinating, with signs of acute denervation and chronic denervation changes. The distal sensory and motor nerves of both upper and lower limbs were severely axonopathic. Hypothyroidism and impaired fasting glucose was noted and β2 microglobulin determination was also elevated. MRI of the spine showed patchy areas of sclerosis involving the vertebral bodies of C3–C5, T2–T5 and T11. After treatment with cyclophosphamide and prednisone improvement of motor function and neuropathic pain was noted. On followup he was already ambulatory with assistance and less dependent for his activities of daily living. Recommendations: To our knowledge, there is only one published case of POEMS syndrome in the Philippines. Early recognition of POEMS syndrome is important to limit its morbidity, even if not all the features are present initially.
DP
Background: Nervous system in congenital heart diseases (CHD) has always attracted the attention of pediatricians, surgeons and neurologists. According to most researchers with cyanotic CHD type shows more diverse changes CNS than the evils of “white” type. Objective: To study the cognitive function in children with cyanotic heart disease before and after surgery in recovery. Material and methods: A total number of 97 children aged between 4 and 14 years with cyanotic congenital heart disease. To assess the level of intellectual development, D. Wechsler's children version was used, which consist of tests adapted for preschool (WPPSI) and school children (WISC) for the Uzbek-speaking children. Results: The study of cognitive function before surgery showed reduced performance on non-verbal intelligence subtests (65.6%), than on verbal subtests (82.4%). Children experienced some difficulty in carrying out the following tests “Labyrinth”, “Coding”, “Folding the figures,” “Finding similarities”, and “Sentences”. Thus, suffered more memory, attention, spatial analysis, and thought process that manifest with difficulty in performance of test “Cubes of Kohs” (59.4%). It should be noted that the decline of intelligence is prevalent among patients with seizures (44.9%). Conclusion: Hemodynamic findings in the brains of children with CHD lead to cognitive impairment, as a reduction in attention and memory, spatial analysis and cognitive functions. In the postoperative period after 1 month period was significant cognitive decline as a result of prolonged cardiopulmonary bypass and the impact of drugs for anesthesia.
e637
doi:10.1016/j.jns.2013.07.2211
TE
Abstract — WCN 2013 No: 1652 Topic: 36 — Other topic Primary mitochondrial DNA mutations and probable variants in Leber's hereditary optic neuropathy
EC
I. Bekri, H. Nahdi, F. Hentati, R. Amouri. National Institute of Neurology, Tunis, Tunisia
UN
CO
RR
Introduction: Leber's hereditary optic neuropathy (LHON) is one of the most common mitochondrial disorders, which mainly leads to vision loss in young males. Objective: To describe the clinical manifestations of Leber's hereditary optic neuropathy (LHON), and to determine the genetic mutations responsible for these phenotypes. Materials and methods: We report the cases of three patients suffering from progressive visual loss. In these patients we have performed genetic study searching for three primary mutations in mitochondrial DNA (m.11778G.A, m.3460G.A and m.14484 T.C). Results: Two men and one woman have been addressed for a visual loss with optic atrophy. The age varied between 29 and 32 years. The neurological examination was normal except visual disturbances. Visual evoked potentials showed a prolongation of P100 wave. Brain MRI was normal in all patients. We found the point mutation (m.14484 T.C) in a single patient. Discussion: One of three patients had a mutation. The other two may have other mitochondrial genes that are mutated and only reported in a minority of families. Conclusion: mtDNA is highly polymorphic in nature with very high mutation rate, 10–17 fold higher as compared to nuclear genome. Identification of new mtDNA sequence variations is necessary to establish a clean link with human disease.
doi:10.1016/j.jns.2013.07.2212
doi:10.1016/j.jns.2013.07.2213
Abstract — WCN 2013 No: 1653 Topic: 36 — Other topic Curcumin nanoparticulate based neuroprotective approach for management of cerebral malaria K. Jain, S. Sood, K. Gowthamarajan. Pharmaceutics, J.S.S College of Pharmacy, Udhagamandalam, India Background: Curcumin is a polyphenol derived from the dietary spice turmeric and possesses diverse biological and pharmacological activities. Objective: To investigate the potential of nanostructured lipid carriers (NLCs) loaded curcumin for management of cerebral malaria. Materials and methods: Curcumin loaded NLCs (C-NLC) were prepared using microemulsion technique. They were characterized for surface morphology, particle size, zeta potential and ex vivo release studies in sheep nasal mucosa. Toxicity assessment was carried out by SK-N-SH cell lines, hemolytic activity and histopathological studies. Antimalarial efficacy was carried out in Plasmodium berghei ANKA murine model of cerebral malaria. Results: The NLCs showed average particle size of 18–30 nm with zeta potential of −33.2 ± 0.75 mV. Transmission electron microscopy studies confirmed that NLCs were spherical in shape. In vitro hemolytic
Abstract — WCN 2013 No: 1517 Topic: 36 — Other topic A case report: 53-year old Filipino with polyneuropathy, organomegaly, endocrinopathy, monoclonal gammopathy, and skin changes (poems) or Crow-Fukase syndrome C.A.V. Inso, J.A.S. Vatanagul. Internal Medicine, Perpetual Succour Hospital, Cebu City, Philippines
RO
OF
Background: POEMS syndrome or Crow-Fukase syndrome is a rare multi-systemic disease caused by overproduction of vascular endothelial growth factor (VEGF), probably mediated by monoclonal proliferation of plasma cells. Most patients with POEMS syndrome commonly present with extremity weakness. The syndrome is also associated with monoclonal plasma proliferative disorder, along with organomegaly, endocrinopathy, and skin changes. The Mayo Clinic Experience identified only 170 patients to have POEMS syndrome. Clinical presentation: A 53 year-old man who complained of 18 months duration of progressive weakness and numbness of both upper and lower extremities associated with hyperpigmentation of the skin, hypertrichosis, and bipedal edema. Predominant distal muscle weakness and atrophy was noted. Multiple large non-tender, cervical lymph nodes were noted. EMG-NCV showed polyneuropathy, sensory and motor diffuse, axonopathic and demyelinating, with signs of acute denervation and chronic denervation changes. The distal sensory and motor nerves of both upper and lower limbs were severely axonopathic. Hypothyroidism and impaired fasting glucose was noted and β2 microglobulin determination was also elevated. MRI of the spine showed patchy areas of sclerosis involving the vertebral bodies of C3–C5, T2–T5 and T11. After treatment with cyclophosphamide and prednisone improvement of motor function and neuropathic pain was noted. On followup he was already ambulatory with assistance and less dependent for his activities of daily living. Recommendations: To our knowledge, there is only one published case of POEMS syndrome in the Philippines. Early recognition of POEMS syndrome is important to limit its morbidity, even if not all the features are present initially.
DP
Background: Nervous system in congenital heart diseases (CHD) has always attracted the attention of pediatricians, surgeons and neurologists. According to most researchers with cyanotic CHD type shows more diverse changes CNS than the evils of “white” type. Objective: To study the cognitive function in children with cyanotic heart disease before and after surgery in recovery. Material and methods: A total number of 97 children aged between 4 and 14 years with cyanotic congenital heart disease. To assess the level of intellectual development, D. Wechsler's children version was used, which consist of tests adapted for preschool (WPPSI) and school children (WISC) for the Uzbek-speaking children. Results: The study of cognitive function before surgery showed reduced performance on non-verbal intelligence subtests (65.6%), than on verbal subtests (82.4%). Children experienced some difficulty in carrying out the following tests “Labyrinth”, “Coding”, “Folding the figures,” “Finding similarities”, and “Sentences”. Thus, suffered more memory, attention, spatial analysis, and thought process that manifest with difficulty in performance of test “Cubes of Kohs” (59.4%). It should be noted that the decline of intelligence is prevalent among patients with seizures (44.9%). Conclusion: Hemodynamic findings in the brains of children with CHD lead to cognitive impairment, as a reduction in attention and memory, spatial analysis and cognitive functions. In the postoperative period after 1 month period was significant cognitive decline as a result of prolonged cardiopulmonary bypass and the impact of drugs for anesthesia.
e637
doi:10.1016/j.jns.2013.07.2211
TE
Abstract — WCN 2013 No: 1652 Topic: 36 — Other topic Primary mitochondrial DNA mutations and probable variants in Leber's hereditary optic neuropathy
EC
I. Bekri, H. Nahdi, F. Hentati, R. Amouri. National Institute of Neurology, Tunis, Tunisia
UN
CO
RR
Introduction: Leber's hereditary optic neuropathy (LHON) is one of the most common mitochondrial disorders, which mainly leads to vision loss in young males. Objective: To describe the clinical manifestations of Leber's hereditary optic neuropathy (LHON), and to determine the genetic mutations responsible for these phenotypes. Materials and methods: We report the cases of three patients suffering from progressive visual loss. In these patients we have performed genetic study searching for three primary mutations in mitochondrial DNA (m.11778G.A, m.3460G.A and m.14484 T.C). Results: Two men and one woman have been addressed for a visual loss with optic atrophy. The age varied between 29 and 32 years. The neurological examination was normal except visual disturbances. Visual evoked potentials showed a prolongation of P100 wave. Brain MRI was normal in all patients. We found the point mutation (m.14484 T.C) in a single patient. Discussion: One of three patients had a mutation. The other two may have other mitochondrial genes that are mutated and only reported in a minority of families. Conclusion: mtDNA is highly polymorphic in nature with very high mutation rate, 10–17 fold higher as compared to nuclear genome. Identification of new mtDNA sequence variations is necessary to establish a clean link with human disease.
doi:10.1016/j.jns.2013.07.2212
doi:10.1016/j.jns.2013.07.2213
Abstract — WCN 2013 No: 1653 Topic: 36 — Other topic Curcumin nanoparticulate based neuroprotective approach for management of cerebral malaria K. Jain, S. Sood, K. Gowthamarajan. Pharmaceutics, J.S.S College of Pharmacy, Udhagamandalam, India Background: Curcumin is a polyphenol derived from the dietary spice turmeric and possesses diverse biological and pharmacological activities. Objective: To investigate the potential of nanostructured lipid carriers (NLCs) loaded curcumin for management of cerebral malaria. Materials and methods: Curcumin loaded NLCs (C-NLC) were prepared using microemulsion technique. They were characterized for surface morphology, particle size, zeta potential and ex vivo release studies in sheep nasal mucosa. Toxicity assessment was carried out by SK-N-SH cell lines, hemolytic activity and histopathological studies. Antimalarial efficacy was carried out in Plasmodium berghei ANKA murine model of cerebral malaria. Results: The NLCs showed average particle size of 18–30 nm with zeta potential of −33.2 ± 0.75 mV. Transmission electron microscopy studies confirmed that NLCs were spherical in shape. In vitro hemolytic