Mitochondrial DNA variations and evidence of haplogroups in Indian Friedreich's ataxia (FRDA) patients

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Abstracts / Journal of the Neurological Sciences 333 (2013) e679–e727

Findings: The majority of participants are female (51.1%). The mean age is 21.6 ± 2.3. The mean PSQI score of the students is 8.3 ± 2.9. Only 14.9% of the student PSQI scores are 5 or under. The sixth year students' sleep quality is the worst (9.3 ± 3.2), however the 4th year students' sleep quality is the best (7.0 ± 2.2) (p b 0.001). Sleep quality was the worst in those their mothers' educational level was less than high school (9.0 ± 3.0) (p = 0.017). People with chronic disease (9.8 ± 3.5) and smokers (9.9 ± 3.2) were also with poor sleep quality. Conclusions: Significant numbers of medical students have poor sleep quality. Interventions to improve sleep quality should be planned in the light of the findings of the studies on this issue. doi:10.1016/j.jns.2013.07.2443

Abstract — WCN 2013 No: 3038 Topic: 36 — Other Topic Is it post-malaria neurological syndrome or viral encephalitis? A. Caetanoa, M. Mendonçaa, M. Pintoa, N. Ferreirab, L. Alvesa. a Neurology, Hospital Egas Moniz (Centro Hospitalar de Lisboa Ocidental), Portugal; bInternal Medicine, Hospital São Francisco Xavier (Centro Hospitalar de Lisboa Ocidental), Lisbon, Portugal Introduction: Post-malaria neurological syndrome (PMNS) is a rare selflimited clinical syndrome in which patients develop neurological and/or psychiatric symptoms within 2 months of a severe falciparum malaria infection, after the parasites have cleared from the peripheral blood. Case report: A 60-year-old Caucasian man presented with a confusional state associated with ataxia that had started 3 days earlier. On admission, he had a generalized seizure. He had recently returned from Angola, where he had been treated with quinine in an intensive care unit for a severe malaria infection, and later discharged, following full recovery and clearance of parasitemia. He had had no fever during the previous 15 days. CSF analysis revealed lymphocytic pleocytosis (123 cel/μL) and hyperproteinorrhachia (188 mg/dL). Brain MRI showed no abnormalities. The EEG detected slightly slowed fronto-temporal activity. No evidence of central nervous system (CNS) infection was found, with negative CSF polymerase chain reaction (PCR) testing for common neurotropic viruses and negative CSF and blood cultures. The patient was empirically treated with ceftriaxone and acyclovir, with full symptomatic recovery following the first day of treatment. Conclusion: We report the case of a patient who had fully recovered from a severe malaria infection and later developed a diffuse encephalopathy. PMNS, usually a self limited entity, should be considered in the differential diagnosis, taking into account the patient's recent history. Nevertheless, the lack of relevant changes on brain MRI and EEG, along with a clinical picture suggestive of viral encephalitis means we shouldn't exclude a false negative CSF PCR viral encephalitis. doi:10.1016/j.jns.2013.07.2444

Abstract — WCN 2013 No: 2734 Topic: 36 — Other Topic Different clinical presentations with similar reversible splenial lesions V. Cruz e Silvaa, L. Alvesb,c, J. Graçaa, C. Jordãoa, M. Mendonçab, A. Tralhãod, R. Serranob, S. Caladob,c, M. Viana-Baptistab,c. a Neuroradiology, Hospital Egas Moniz (Centro Hospitalar de Lisboa Ocidental), Portugal; bNeurology, Hospital Egas Moniz (Centro Hospitalar de Lisboa Ocidental), Portugal; cCEDOC, Faculdade de Ciências Médicas, Universidade Nova de Lisboa, Portugal; dCardiology, Hospital Santa Cruz (Centro Hospitalar de Lisboa Ocidental), Lisbon, Portugal

Background: Mild encephalopathy with reversible isolated splenial lesion (MERS) is an occasionally reported clinicoradiological entity. It has been associated with anti-epileptic drugs, viral encephalitis, metabolic disturbances, pre-eclampsia and posterior reversible encephalopathy syndrome. Magnetic Resonance Imaging (MRI) shows restricted diffusion in the splenium of the corpus callosum (SCC), along with hyperintensity on T2/T2-FLAIR weighted imaging, iso/hypointensity on T1 and non-enhancement after gadolinium injection. It is totally reversible, usually disappearing in days to weeks. Rarely, it involves the whole corpus callosum and bilateral white matter. Prognosis is mostly related to the etiology. Few clinical reports describe this imaging finding after cardiac arrest or metronidazole administration. Objective: Comparison of two cases of reversible isolated restricted diffusion in the SCC with different etiologies and clinical presentations. Patients and methods: Description of the clinical picture, initial and follow-up brain MRIs of two patients; one presenting with mild encephalopathy after metronidazole administration and another with coma after cardiac arrest. Results: Both presented reversible restricted diffusion in the SCC. Complete clinical resolution and transient bilateral augmented ADC value on the dentate nucleus were found in one, compatible with metronidazole-induced encephalopathy. The follow-up MRI showed hypoxic– ischemic brain lesions in another with persistent vegetative state. Conclusion: Restricted diffusion in the SCC seems to be unreliable for prognostic purposes. It can be observed not only in the setting of a mild encephalopathy, but also in the acute stage of a more aggressive brain insult. Only follow-up MRI can identify such an entity as being reversible. doi:10.1016/j.jns.2013.07.2445

Abstract — WCN 2013 No: 1666 Topic: 36 — Other Topic Mitochondrial DNA variations and evidence of haplogroups in Indian Friedreich's ataxia (FRDA) patients I. Mudilaa, F. Mohammedb, A. Srivastavaa. aNeurology, All India Institute of Medical Sciences, India; bFunctional Genomics Unit, Institute of Genomics and Integrative Biology, New Delhi, India Objective: This study is aimed to evaluate FRDA patients for mtDNA sequence variations and identify related haplogroup in FRDA patients from Indian population. Background: FRDA is an early onset autosomal recessive disorder, caused by loss of function of the frataxin protein. Frataxin is required for the biogenesis of the iron–sulphur-cluster (ISC) which is vital for the synthesis of the respiratory chain complexes I–III enzymes and aconitase in mitochondria. Methods: Considering D loop, NADH dehydrogenase and ATP region as hotspots for the mitochondrial pathogenic mutations in neurodegenerative diseases, these regions were sequenced by direct sequencing method for 30 FRDA patients and 63 ethnically and age matched controls. The FRDA patients were genetically confirmed with southern blot and TP PCR protocols. Results: 185 variations were observed in all 30 patients. 101 variations were in coding region (ND genes and ATP) while non-coding (D Loop) had 84 variations. Variations at positions 16519, 4883 and 5178 were found significantly associated with patients (P b 0.05). Haplogroup analysis using D loop results had revealed that 57% of patients belong to haplogroup M, while control constitutes only 18.6%. Variations at positions 489 and 195 were found in 100% of patients belonging to the M group, while control at theses locus were under represented. Conclusions: Variations at positions 16519, 4883 and 5178 suggest that these variations may act as modifier for the disease. Significant association of haplogroup M with patients suggests possible impact of

Abstracts / Journal of the Neurological Sciences 333 (2013) e679–e727

haplogroup M encompassing inherited mitochondrial DNA variations on predisposition to FRDA patients of Indian ethnicity. doi:10.1016/j.jns.2013.07.2446

Abstract — WCN 2013 No: 3022 Topic: 36 — Other Topic Neuroimaging study in 210 Iranian neurometabolic patients B. Shalbafan, O. Aryani, M. Houshmand. Special Medical Center, Tehran, Iran Inborn error of metabolism (IEM) involving CNS encompasses a wide spectrum of inherited disorders. We present and discuss imaging features of the more common and important IEMs involving CNS that diagnosed molecularly in Iran. Our pattern approach for neuroimaging classification of Common Metabolic Disorders was according to anatomic evaluation: White matter (WM) – Primarily affecting periventricular – Primarily affecting subcortical Gray matter (GM) – Primarily affecting cortical – Primarily affecting deep Disorders involving WM and GM During 3 past years, we studied systematically neuroimages of our patients and finally we classified our cases pre- and post-molecular diagnosis as below: Initially affecting periventricular WM Metachromatic leukodystrophy (12 cases) Krabbe disease (4 cases) X-linked adrenoleukodystrophy (6 cases) Phenylketonuria (21 cases) Maple syrup urine disease (18 cases) Homocystinuria (7 cases) Merosin-deficient congenital muscular dystrophy (10 cases) Initially affecting subcortical WM Canavan disease (8 cases) Alexander disease (5 cases) Lack of myelination Pelizaeus–Merzbacher disease (5 cases) Cortical gray matter Neuronal ceroid lipofuscinoses (9 cases) Mucolipidosis type I (5 case) Deep gray matter Leigh disease (13 cases) Organic acidopathies (31 cases) Cortical gray matter only – – – – –

Cortical dysplasia: Walker-Warburg syndrome (1 case) Muscle-eye-brain disease (1 case) No cortical dysplasia Menkes disease (4 cases)

Deep gray matter involvement – – – –

Primarily affecting thalamus: Krabbe disease (8 cases) GM1 or GM2 gangliosidoses (18 cases) Wilson disease (6 cases)

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Deep gray matter involvement – – – – – – – – – –

Primarily affecting globus pallidus: Canavan disease (2 cases) Kearn–Sayre disease-subcortical U fiber (4 cases) Methylmalonic acidemia-deep WM (8 cases) Maple syrup urine disease-dorsal brainstem (18 cases) Primarily affecting striatum: Leigh disease (13 cases) MELAS (10 cases) Glutaric aciduria type I (6 cases) Wilson disease (6 cases)

doi:10.1016/j.jns.2013.07.2447

Abstract — WCN 2013 No: 1479 Topic: 36 — Other Topic Levodopa-responsive parkinsonism and autonomic (small fiber) dysfunction in patients with Wilson's disease (WD) F.D.A.A. Gondima, Í.S. Oliveirab, D.F. Araújob, A.P. Melob, L.C. Alvesb, I.T. Araújob, O.C. Valea. aInternal Medicine-Neurology Division, Brazil; b Universidade Federal do Ceará, Fortaleza, Brazil Background: Autonomic dysfunction has been rarely described in WD patients. Objective: To describe a series of patients with WD, levodoparesponsive parkinsonism and autonomic dysfunction. Methods: After IRB approval, we evaluated 4 patients with WD and parkinsonism for the presence of neuromuscular dysfunction and performed water-induced skin wrinkling test — SWT (Teoh, JNNP 2008;79:835). Results: Patient 1: A 37 year old female presented with cirrhosis at age 33 was diagnosed with WD and treated with ZnSO4, penicillamine and piridoxine/complex B vitamins. Since age 35 she developed pramipexole and levodopa-responsive parkinsonism, with burning and numbness in arms and genital area and urinary incontinence. NCS/EMG was normal. Water-induced SWT revealed small fiber dysfunction (mean 4-digit wrinkling of 1). Patient 2: A 23 year old male was diagnosed with WD at age 14 and was treated with penicillamine + piridoxine. Since age 21, he developed levodopa-responsive parkinsonism, with resting tremor, weight loss, dysphagia and dysphonia. NCS/ EMG was normal but water-induced SWT was abnormal (mean wrinkling of 0.25). Patient 3: A 34 year old male presented with psychosis, behavioral dysfunction, levodopa-responsive parkinsonism and episodes of loss of consciousness. He was treated with penicillamine and complex B vitamins. NCS/EMG and water-induced SWT were normal (mean wrinkling of 4). Patient 4: A 38 year old female presented with liver dysfunction, behavior changes and parkinsonism at age 24. She was diagnosed with WD and treated with penicillamine and biperiden. Parkinsonism almost completely subsided with penicillamine. SWT was normal (mean wrinkling of 3.6). Conclusions: A subset of WD patients with levodopa-responsive parkinsonism also exhibits abnormalities on SWT (autonomic dysfunction). doi:10.1016/j.jns.2013.07.2448