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Biotinidase deficiency is a treatable neurometabolic disorder. It usually presents during the first year of life with seizures, ataxia, hypotonia, vision and hearing disturbance, alopecia, and skin rashes. It can have various neuroimaging findings but demyelinating leukoencephalopathy is an unusual finding in children with biotinidase deficiency that can cause diagnostic challenge as it can radiologically mimic perinatal hypoxic-ischemic encephalopathy or other leukodystrophies. It reverses with early diagnosis and treatment with biotin supplementation and the outcome is rewarding.
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BACKGROUND: Disorders of tetrahydrobiopterin metabolism represent a rare group of inherited neurotransmitter disorders that manifests mainly in infancy or childhood with developmental delay, neuroregression, epilepsy, movement disorders, and autonomic symptoms. METHODOLOGY: A retrospective review of genetically confirmed cases of disorders of tetrahydrobiopterin metabolism over a period of three years (Jan 2018 to Jan 2021) was performed across two paediatric neurology centres from South India. RESULTS: A total of nine patients(M:F=4:5) fulfilled the eligibility criteria. The genetic variants detected include homozygous mutations in the QDPR(n=6), GCH1(n=2), and PTS(n=1) genes. The median age at onset of symptoms was 6-months(range 3-78 months), while that at diagnosis was 15-months (8-120 months), resulting in a median delay in diagnosis of 9-months. The main clinical manifestations included neuroregression (89%), developmental delay(78%), dystonia(78%) and seizures(55%). Management strategies included a phenylalanine restricted diet, levodopa/carbidopa, 5-Hydroxytryphtophan, and folinic acid. Only, Patient-2 afforded and received BH4 supplementation at a sub-optimal dose later in the disease course. We had a median duration of follow up of 15 months (range 2-48 months). Though the biochemical response has been marked; except for patients with GTPCH deficiency, only mild clinical improvement was noted with regards to developmental milestones, seizures, or dystonia in others. CONCLUSION: Tetrahydrobiopterin deficiencies represent a rare yet potentially treatable cause for non-phenylketonuria hyperphenylalaninemia with better outcomes when treated early in life. Screening for disorders of biopterin metabolism in patients with hyperphenylalaninemia prevents delayed diagnosis. This study expands the genotype-phenotype spectrum of patients with disorders of tetrahydrobiopterin metabolism from South India.
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Distonía , Fenilcetonurias , Biopterinas/análogos & derivados , Biopterinas/metabolismo , Biopterinas/uso terapéutico , Niño , Preescolar , Distonía/genética , Femenino , Humanos , Lactante , Masculino , Fenilalanina , Fenilcetonurias/diagnóstico , Fenilcetonurias/tratamiento farmacológico , Fenilcetonurias/genéticaAsunto(s)
Trastorno Depresivo Mayor , Meditación , Yoga , Ansiedad , Depresión , Trastorno Depresivo Mayor/tratamiento farmacológico , Humanos , RecreaciónRESUMEN
INTRODUCTION: Schizophrenia is one of the most severe mental disorders with a prevalence of about 1% and a leading cause of disability among young adults. Pharmacotherapy is the mainstay in the management of schizophrenia. However, even with the best of medication, several problems like refractoriness, negative symptoms, frequent relapses, and cognitive impairments persist. METHODS: This is a randomized-controlled clinical study including patients from an urban tertiary hospital and a semi-urban community center, with a between-group, repeated-measures, longitudinal design. This study will recruit 160 patients with DSM 5 diagnosis of schizophrenia who are on stable medication for a minimum of 6 weeks; they will be randomly assigned into 2 arms viz., yoga therapy (YT), and treatment-as-usual (TAU) with 80 patients in each arm. Participants will undergo Clinical, Laboratory, and Radiological assessments at baseline and at intervals of 1 month, 3 months, and 6 months from the baseline. It is hypothesized that yoga will improve psychopathology and emotion processing, increase serum brain derived neurotrophic factor (BDNF) and plasma oxytocin levels and effect changes in cerebral activation in areas of the brain associated with schizophrenia. DISCUSSION: This study aims to measure the efficacy of a Yoga-based intervention as an adjunct in patients with schizophrenia as well as the mechanisms of these effects. TRIAL REGISTRATION: Registered retrospectively with Clinical Trial Registry - India (CTRI) with registration number CTRI/2017/08/009219.
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Plasticidad Neuronal , Esquizofrenia/fisiopatología , Esquizofrenia/terapia , Psicología del Esquizofrénico , Yoga/psicología , Adolescente , Adulto , Femenino , Humanos , Estudios Longitudinales , Masculino , Persona de Mediana Edad , Ensayos Clínicos Controlados Aleatorios como Asunto , Método Simple Ciego , Resultado del Tratamiento , Población Urbana , Adulto JovenRESUMEN
Encephalopathy and Myopathy in children of varying ages can be due to variety of causes including Mitochondrial diseases, metabolic diseases like renal tubular acidosis, storage diseases as well as fatty acid oxidation (FAO) disorders. FAO related disorders have variable clinical presentation and manifest in different ages. They may present with hypoglycemia, effort intolerance, multi organ involvement with or without ketonuria. High degree of suspicion and appropriate investigations are mandatory for diagnosis. Here we describe an 11 Year old boy, born to non - consanguineous parents. Presented with exertion induced muscle pain and fatigue of 1year duration, which slowly progressed to severe weakness and vomiting. His reflexes were retained. Therefore metabolic vs inflammatory muscle diseases were considered. Patient had ketonuria with elevated blood levels of medium chain acyl carnitine and long chain acyl carnitine suggestive of MADD. Urine organic acid assessment showed elevated excretion of 2-hydroxyglutarate (2HG), adipate and arabitol. Muscle biopsy showed multiple fine vacuoles on Eosin- hematoxylin stained preparation. Modified Gomori - trichrome stain showed vacuolated fibers with red granular material consistent with ragged red fibers. Oil Red O stains showed vacuolated fibers with 'oil red O' positive material suggesting lipid storage. Above combination of features is consistent of MADD. Genetic evaluation is not done due to financial constraint. Patient was started on high dose riboflavin and carnitine, with which the child became near normal. Our patient is a case of MADD presenting as Reye's syndrome like features and showed excellent response to riboflavin, carnitine, dietary and life style changes. High degree of suspicion is lifesaving.
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CONTEXT AND AIMS: Impairment in cognition is well-known in patients with major depressive disorder. This study examined the effect of yoga therapy with or without antidepressants and antidepressants alone on certain neuropsychological functions in patients with depression. Correlation between changes in neuropsychological test performance and serum brain-derived neurotrophic factor (BDNF) levels was also explored. MATERIALS AND METHODS: Antidepressant-naïve/antidepressant-free outpatients with depression received antidepressant medication alone (n = 23) or yoga therapy with (n = 26) or without (n = 16) antidepressants. Depression was assessed using the Hamilton Depression Rating Scale. Neuropsychological tests included digit-span forward and backward, Rey Auditory Verbal Learning Test, and Trail Making Tests (TMT-A and B). These tests were administered before and 3 months after the treatment in patients, and once in healthy comparison subjects (n = 19). STATISTICAL ANALYSIS: Baseline differences were analyzed using independent sample t-test, Chi-square, and one-way ANOVA. Paired t-test was used to analyze the change from baseline to follow-up. Pearson's correlation was used to explore the association of change between 2 variables. RESULTS: Patients had impaired performance on most neuropsychological tests. After 3 months, there was significant improvement - patients' performance was comparable to that of healthy controls on majority of the tests. Significant inverse correlation was observed between increase in BDNF levels and improvement in TMT "A" duration in Yoga-alone group (r = -0.647; P = 0.009). CONCLUSIONS: To conclude that, Yoga therapy, alone or in combination with medications, is associated with improved neuropsychological functions and neuroplastic effects in patients with depression.
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BACKGROUND & AIMS: The debated vascular risk potential of total homocysteine (tHcy), due to failed clinical trials designed on B vitamin supplementation, raises many possible explanations like the higher risk potential of the deleterious, free form of homocysteine (fHcy) or, the unchecked confounding effects of B-vitamins in tHcy-based association studies. Additionally, the cardiovascular risk probability of altered status of the homocysteine precursor, methionine (tMet) could shed light on the causality of association between tHcy and cardiovascular diseases. Hence, we aimed to evaluate the risk associations of elevated plasma levels of tHcy, fHcy and low levels of tMet with premature, ischemic stroke. METHODS: We recruited 171 young, ischemic stroke patients (aged ≤45 years) and 249 age- and gender-matched healthy controls. Plasma levels of fHcy, tHcy, tMet and vitamin B6 were estimated using HPLC coupled with coulometric electrochemical detection. Plasma levels of vitamin B12 and folate were estimated by radioimmunoassay. RESULTS: Elevated fHcy (>2.9 µmol/L) was independently and strongly associated with the risk of premature, ischemic stroke (OR = 9.62, 95% CI = 3.51-26.40). On the contrary, association between premature ischemic stroke and elevated tHcy (>15.0 µmol/L) was found to attenuate when adjusted for vitamin B6 values (OR = 0.24, 95%, CI = 0.03-1.69). Interestingly, compromised B6-status (<59.2 nmol/l) was found to confer high risk of premature ischemic stroke (OR = 170.80, 95% CI = 58.22-501.06). We could not establish any significant correlation between fHcy and B-vitamin levels (P > 0.05). Low tMet (<13.86 µmol/L) was also not significantly associated with premature, ischemic stroke (OR = 2.53, 95% CI = 0.613-10.38). CONCLUSION: Our results indicate significant but not-correlated, independent associations of fHcy and vitamin B6 with risk of premature, ischemic stroke. However, the causality of these associations need prospective and large scale validations. Further, our findings highlight the crucial confounding effects of B-vitamins on risk association between tHcy and premature ischemic stroke.
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Homocisteína/sangre , Metionina/sangre , Accidente Cerebrovascular/sangre , Adolescente , Adulto , Estudios Transversales , Femenino , Ácido Fólico/sangre , Humanos , Masculino , Oportunidad Relativa , Factores de Riesgo , Vitamina B 12/sangre , Vitamina B 6/sangre , Adulto JovenRESUMEN
It has been found that reduction of posttraumatic stress symptoms is positively associated with the reduction of postconcussive symptoms. Cortisol is commonly used as a biomarker of stress. Understanding the role of posttraumatic stress and cortisol in symptom reduction has implication for neuropsychological rehabilitation particularly in the context of spontaneous recovery. OBJECTIVE: The aim of the research was to study the effectiveness of EEG neurofeedback training on clinical symptoms, perceived stress, and cortisol in traumatic brain injury (TBI) patients in the context of spontaneous recovery. METHODS: The design was an experimental longitudinal design with the pre-post comparison. The sample comprised 60 patients with the diagnosis of TBI-30 patients in the neurofeedback training (NFT) group and 30 patients in the treatment as usual group (TAU) group. Half of the patients were recruited within 6 months of injury to study the role of spontaneous recovery and the other half were recruited in the 12 to 18 months postinjury phase. Alpha-theta training was given to the NFT group over 20 sessions. Pre and post comparisons were made on clinical symptom rating, perceived stress, and serum cortisol levels. RESULTS: The results indicate significant differences in symptom reporting and perceived stress between the NFT and TAU groups. Significant differences were also seen in cortisol levels with implications for the acute recovery phase. CONCLUSION: Alpha-theta NFT has a beneficial effect on symptom reduction as well as perceived stress. It also has a beneficial effect on levels of serum cortisol, corroborating these findings.
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Lesiones Traumáticas del Encéfalo/terapia , Hidrocortisona/sangre , Neurorretroalimentación , Síndrome Posconmocional/terapia , Adolescente , Adulto , Lesiones Traumáticas del Encéfalo/fisiopatología , Electroencefalografía/métodos , Femenino , Humanos , Masculino , Persona de Mediana Edad , Neurorretroalimentación/métodos , Síndrome Posconmocional/fisiopatología , Trastornos por Estrés Postraumático/fisiopatología , Trastornos por Estrés Postraumático/terapia , Resultado del Tratamiento , Adulto JovenRESUMEN
Depression is associated with low serum Brain Derived Neurotrophic Factor (BDNF) and elevated levels of serum cortisol. Yoga practices have been associated with antidepressant effects, increase in serum BDNF, and reduction in serum cortisol. This study examined the association between serum BDNF and cortisol levels in drug-naïve patients with depression treated with antidepressants, yoga therapy, and both. Fifty-four drug-naïve consenting adult outpatients with Major Depression (32 males) received antidepressants only (n = 16), yoga therapy only (n = 19), or yoga with antidepressants (n = 19). Serum BDNF andcortisol levels were obtained before and after 3 months using a sandwich ELISA method. One-way ANOVA, Chi-square test, and Pearson's correlation tests were used for analysis. The groups were comparable at baseline on most parameters. Significant improvement in depression scores and serum BDNF levels, and reduction in serum cortisol in the yoga groups, have been described in previous reports. A significant negative correlation was observed between change in BDNF (pre-post) and cortisol (pre-post) levels in the yoga-only group (r = -0.59, p = 0.008). In conclusion, yoga may facilitate neuroplasticity through stress reduction in depressed patients. Further studies are needed to confirm the findings and delineate the pathways for these effects.
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Antidepresivos/farmacología , Factor Neurotrófico Derivado del Encéfalo/sangre , Trastorno Depresivo Mayor/sangre , Trastorno Depresivo Mayor/terapia , Hidrocortisona/sangre , Evaluación de Resultado en la Atención de Salud , Yoga , Adulto , Terapia Combinada , Trastorno Depresivo Mayor/tratamiento farmacológico , Femenino , Humanos , Masculino , Persona de Mediana EdadRESUMEN
Although serum autoantibodies directed against basal ganglia (BG) implicate autoimmunity in the pathogenesis of obsessive-compulsive disorder (OCD), it is unclear whether these antibodies can cross the blood-brain barrier to bind against BG or other components of the OCD circuit. It is also unclear how they might lead to hyperactivity in the OCD circuit. We examined this by investigating the presence of autoantibodies directed against the BG or thalamus in the serum as well as CSF of 23 OCD patients compared with 23 matched psychiatrically normal controls using western blot. We further investigated CSF amino acid (glutamate, GABA, taurine, and glycine) levels and also examined the extent to which these levels were related to the presence of autoantibodies. There was evidence of significantly more binding of CSF autoantibodies to homogenate of BG as well as to homogenate of thalamus among OCD patients compared with controls. There was no significant difference in binding between patient and control sera except for a trend toward more bands to BG and thalamic protein corresponding to 43 kD among OCD patients compared with controls. CSF glutamate and glycine levels were also significantly higher in OCD patients compared with controls, and further multivariate analysis of variance showed that CSF glycine levels were higher in those OCD patients who had autoantibodies compared with those without. The results of our study implicate autoimmune mechanisms in the pathogenesis of OCD and also provide preliminary evidence that autoantibodies against BG and thalamus may cause OCD by modulating excitatory neurotransmission.
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Autoanticuerpos/metabolismo , Ganglios Basales/inmunología , Neurotransmisores/metabolismo , Trastorno Obsesivo Compulsivo/inmunología , Trastorno Obsesivo Compulsivo/metabolismo , Tálamo/inmunología , Adulto , Anciano , Autoanticuerpos/sangre , Autoanticuerpos/líquido cefalorraquídeo , Femenino , Ácido Glutámico/líquido cefalorraquídeo , Glicina/líquido cefalorraquídeo , Humanos , Masculino , Persona de Mediana Edad , Análisis Multivariante , Neurotransmisores/líquido cefalorraquídeo , Taurina/líquido cefalorraquídeo , Adulto Joven , Ácido gamma-Aminobutírico/líquido cefalorraquídeoRESUMEN
BACKGROUND AND OBJECTIVE: Hyperhomocysteinemia (hyper-Hcy) is a known risk factor for venous thrombosis, but few studies document the risk in puerperal cerebral venous thrombosis (CVT). Nutritional folate and vitamin B(12) deficiency can cause hyper-Hcy and pregnancy may contribute to this deficiency. We studied the association of plasma total homocysteine (tHcy), folate and vitamin B(12) levels with puerperal CVT through a case-control study. METHODS: Sixty women with puerperal CVT and 64 healthy puerperal controls were recruited. Plasma fasting tHcy was estimated by high pressure liquid chromatography using coulometric electrochemical detection. Vitamin B(12) and folate were measured by radioimmunoassay. Risk of puerperal CVT was estimated for each of the three variables. RESULTS: Adjusted odds ratio for the risk of puerperal CVT with hyper-Hcy (>90th percentile) was 10.8 (95% CI: 4.0-29.4; adjusted for vitamin B(12) and folate levels). Low folate and vitamin B(12) levels (<10th percentile) did not increase the risk for puerperal CVT. There was a significant inverse correlation between folate and tHcy levels (rho=-0.471, p<0.001). CONCLUSIONS: Hyperhomocysteinemia is associated with an increased risk of puerperal CVT occurring in Indian women and low folate levels contribute significantly to hyper-Hcy. Regular antenatal folate and vitamin B(12) supplementation is likely to lower puerperal tHcy levels, but its clinical benefit needs to be tested by large therapeutic trials.
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Ácido Fólico/sangre , Homocisteína/sangre , Trombosis Intracraneal/sangre , Trastornos Puerperales/sangre , Trombosis de la Vena/sangre , Vitamina B 12/sangre , Adolescente , Adulto , Intervalos de Confianza , Femenino , Humanos , Trombosis Intracraneal/complicaciones , Trombosis Intracraneal/genética , Metilenotetrahidrofolato Reductasa (NADPH2)/genética , Mutación , Oportunidad Relativa , Protrombina/genética , Trastornos Puerperales/genética , Riesgo , Medición de Riesgo/métodos , Estadística como Asunto , Trombosis de la Vena/complicaciones , Trombosis de la Vena/genéticaRESUMEN
Two-thirds of stroke deaths worldwide occur in developing countries. The higher prevalence of undernutritional states and parasitic infestations in many of these countries could lead to vitamin B(12) and folate deficiencies. Hyperhomocysteinemia, a proxy measure for the nutritional status of B vitamins, has been reported in many developing countries and is found to be associated with nutrition-related low plasma folate and vitamin B(12). Several epidemiological observations have linked hyperhomocysteinemia to increased risk for stroke. The exact molecular mechanism by which homocysteine promotes atherothrombosis is not clear, although several possible roles have been suggested. Homocysteine is believed to cause atherogenesis and thrombogenesis via endothelial damage, focal vascular smooth muscle proliferation probably causing irregular vascular contraction, and coagulation abnormalities. Supplementation with the nutrient cofactors required for optimal functioning of the homocysteine metabolic pathways significantly impacts plasma homocysteine levels, and offers a new integrated possibility for prevention of stroke in the underdeveloped and rapidly developing countries.