RESUMO
BACKGROUND: Vestibular system is critical for maintaining balance and learning complex tasks. This study aimed to determine the frequencies, types, and predictors of vestibular dysfunctions (VDs) in children with type 1 diabetes (T1D) using videonystagmography (VNG). PATIENTS AND METHODS: This study included 65 patients (children with T1D = 40; controls = 25). The patients underwent VNG. RESULTS: Patients (boys = 15; girls = 25) had a mean age of 14.05 ± 1.82 years and duration of illness of 6.30 ± 2.84 years. The majority had frequent attacks of diabetic ketoacidosis (DKA) (65%) and hypoglycemia (40%). Dizziness was reported in 20%. VNG abnormalities were reported in 70% (n = 28), of them 71.43 and 28.57% had central and peripheral VDs, respectively. Dizziness was associated with peripheral VD. Compared to patients without VDs, those with VDs were older and had earlier age at onset and longer duration of diabetes (>5 years), higher levels of HbA1c (>7%), higher frequencies of DKA and hypoglycemic attacks, comorbid medical conditions, and diabetic complications. Multiple logistic regression analysis showed that presence of VNG abnormalities (VDs) was independently correlated with diabetes duration >5 years (odds ratio [OR] = 4.52 [95% confidence interval [CI] = 3.55-7.04], p = 0.001), HbA1c% levels >7% (OR = 3.42 [95% CI = 2.84-5.75], p = 0.001), and presence of hypoglycemic attacks (OR = 4.65 [95% CI = 2.85-7.55]). CONCLUSIONS: -VDs are prevalent in children with T1D and correlated with the duration and severity of diabetes and the occurrence of hypoglycemic attacks. Therefore, optimizing glycemic control and prevention and treatment of diabetic complications and comorbidities are important. Multidisciplinary follow-ups are required for early detection and management of diabetic VDs.
Assuntos
Diabetes Mellitus Tipo 1 , Cetoacidose Diabética , Hipoglicemia , Adolescente , Criança , Diabetes Mellitus Tipo 1/complicações , Diabetes Mellitus Tipo 1/epidemiologia , Feminino , Humanos , Hipoglicemiantes , Masculino , VertigemRESUMO
BACKGROUND: Epilepsy is a chronic medical disease and is associated with comorbid adverse somatic conditions due to epilepsy itself or its long-term treatment. OBJECTIVES: This study evaluated cochlear function in patients with idiopathic epilepsy and treated with carbamazepine (CBZ). PATIENTS AND METHODS: Included were 47 patients (mean age = 34.56 ± 7.11 years and duration of illness = 17.84 ± 7.21 years) and 40 healthy subjects. They underwent pure-tone audiometry and transient evoked otoacoustic emission (TEOAE) analyses. RESULTS: Hearing loss (mainly bilateral mild) was reported in one third of patients. Compared to controls, patients had lower TEOAE amplitudes at 1.0-4.0 kHz particularly at high frequencies (3 and 4 kHz). Significant correlations were identified between TEOAE amplitudes with CBZ dose (at 3 kHz: r = -0.554, p = 0.008; at 4 kHz: r = -0.347, p = 0.01), its serum level (at 4 kHz: r = -0.280, p = 0.045) and duration of treatment (at 3 kHz: r = -0.392, p = 0.008; at 4 kHz: r = -0.542, p = 0.001). CONCLUSIONS: Long-term CBZ treatment may result in cochlear dysfunction and auditory deficits.
Assuntos
Anticonvulsivantes/efeitos adversos , Carbamazepina/efeitos adversos , Cóclea/fisiopatologia , Epilepsia/fisiopatologia , Doenças do Labirinto/induzido quimicamente , Adulto , Anticonvulsivantes/farmacologia , Anticonvulsivantes/uso terapêutico , Audiometria de Tons Puros , Limiar Auditivo/efeitos dos fármacos , Limiar Auditivo/fisiologia , Carbamazepina/farmacologia , Carbamazepina/uso terapêutico , Cóclea/efeitos dos fármacos , Epilepsia/tratamento farmacológico , Feminino , Humanos , Doenças do Labirinto/fisiopatologia , Masculino , Emissões Otoacústicas Espontâneas/efeitos dos fármacos , Emissões Otoacústicas Espontâneas/fisiologiaRESUMO
Aim: Frequent cyanotic breath holding spells cause fear and severe anxiety to parents. This study aimed to evaluate clinical, laboratory and treatment characteristics of children with cyanotic breath holding spells. Methods: Included were 180 children (mean age: 1.82 ± 0.53 years) with cyanotic breath holding spells. They were divided into three groups: with iron deficiency, with iron deficiency anemia and without iron deficiency. Blood hemoglobin (HB), ferritin and iron concentrations were measured at baseline and after 3 and 6 months of iron treatment. Results: The mean spell frequency was 24.57 ± 7.31/months, 83% had spells after the age of 1 year, 37% had daily spells, 16% had family history of spells, and 61% had Iron deficiency/Iron deficiency anemia (p = .001). No significant difference in the frequency of spells between children with iron deficiency and those with Iron deficiency anemia. Compared to patients without iron deficiency, there was significant reduction of spells frequency, increased hemoglobin, ferritin and iron levels after 3 and 6 months of iron therapy (p = .0001). Negative correlations were observed between spell frequency with hemoglobin (p = .001), ferritin (p = .0001) and iron (p = .001) levels. Conclusion: Not only Iron deficiency anemia but also iron deficiency alone without anemia is associated with a risk of high-frequency cyanotic breath holding spells. Iron therapy results in reduction in spells' frequency which was correlated with increasing ferritin and iron levels.
Assuntos
Anemia Ferropriva/tratamento farmacológico , Suspensão da Respiração , Cianose/etiologia , Ferro/uso terapêutico , Anemia Ferropriva/patologia , Pré-Escolar , Feminino , Humanos , Ferro/farmacologia , MasculinoRESUMO
The hereditary spastic paraplegias are a heterogeneous group of degenerative disorders that are clinically classified as either pure with predominant lower limb spasticity, or complex where spastic paraplegia is complicated with additional neurological features, and are inherited in autosomal dominant, autosomal recessive or X-linked patterns. Genetic defects have been identified in over 40 different genes, with more than 70 loci in total. Complex recessive spastic paraplegias have in the past been frequently associated with mutations in SPG11 (spatacsin), ZFYVE26/SPG15, SPG7 (paraplegin) and a handful of other rare genes, but many cases remain genetically undefined. The overlap with other neurodegenerative disorders has been implied in a small number of reports, but not in larger disease series. This deficiency has been largely due to the lack of suitable high throughput techniques to investigate the genetic basis of disease, but the recent availability of next generation sequencing can facilitate the identification of disease-causing mutations even in extremely heterogeneous disorders. We investigated a series of 97 index cases with complex spastic paraplegia referred to a tertiary referral neurology centre in London for diagnosis or management. The mean age of onset was 16 years (range 3 to 39). The SPG11 gene was first analysed, revealing homozygous or compound heterozygous mutations in 30/97 (30.9%) of probands, the largest SPG11 series reported to date, and by far the most common cause of complex spastic paraplegia in the UK, with severe and progressive clinical features and other neurological manifestations, linked with magnetic resonance imaging defects. Given the high frequency of SPG11 mutations, we studied the autophagic response to starvation in eight affected SPG11 cases and control fibroblast cell lines, but in our restricted study we did not observe correlations between disease status and autophagic or lysosomal markers. In the remaining cases, next generation sequencing was carried out revealing variants in a number of other known complex spastic paraplegia genes, including five in SPG7 (5/97), four in FA2H (also known as SPG35) (4/97) and two in ZFYVE26/SPG15 Variants were identified in genes usually associated with pure spastic paraplegia and also in the Parkinson's disease-associated gene ATP13A2, neuronal ceroid lipofuscinosis gene TPP1 and the hereditary motor and sensory neuropathy DNMT1 gene, highlighting the genetic heterogeneity of spastic paraplegia. No plausible genetic cause was identified in 51% of probands, likely indicating the existence of as yet unidentified genes.
Assuntos
Proteínas/genética , Paraplegia Espástica Hereditária/genética , Paraplegia Espástica Hereditária/fisiopatologia , Adolescente , Adulto , Linhagem Celular , Criança , Pré-Escolar , Estudos de Coortes , Feminino , Fibroblastos , Humanos , Masculino , Mutação , Linhagem , Fenótipo , Paraplegia Espástica Hereditária/diagnóstico por imagem , Tripeptidil-Peptidase 1 , Reino Unido , Adulto JovemRESUMO
Patients with epilepsy and on valproate (VPA) therapy may develop tremors as a common adverse effect; however, its exact mechanisms are unknown. We hypothesize that VPA-induced tremors may be related to the disturbances in dopamine (DA) and catecholamines (norepinephrine (NE) and epinephrine (E)) concentrations (which are also involved in VPA anticonvulsant effect). We aimed to determine the frequency and type of VPA-induced tremors and their risk factors and to investigate whether or not they are related to the plasma DA, NE and E concentrations. This study included 75 adults with primary epilepsy (mean age: 31.90 ± 5.62 years) and on VPA therapy for 10.57 ± 3.55 years and 40 matched healthy controls. Patients were divided according to the absence or presence of tremors. Blood samples were analyzed for DA, NE and E. Intermittent action tremors in both hands were reported in 31 (41.33%). Chronic standard VPA therapy, older age, longer treatment duration and higher serum concentrations of VPA are risk factors for tremors. None of the patients on controlled release VPA had tremors. Compared to controls, patients (without and with tremors) had lower DA (p = 0.0001) and NE (p = 0.01) concentrations. Compared to patients without tremors, patients with tremors had lower levels DA (p = 0.045) and NE (p = 0.01). Significant correlations were identified between DA with NE (r = 0.540, p = 0.001) concentrations and serum VPA with DA (r = -0.285, p = 0.045) and NE (r = -0.358, p = 0.01) plasma levels. We conclude that benign action tremors are common with standard VPA. Mechanisms underlying VPA-induced tremors may involve abnormalities of DA and NE neurotransmitters.
Assuntos
Anticonvulsivantes/efeitos adversos , Neurotransmissores/sangue , Convulsões/sangue , Tremor/induzido quimicamente , Ácido Valproico/efeitos adversos , Adulto , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Convulsões/tratamento farmacológico , Estatísticas não Paramétricas , Adulto JovemRESUMO
INTRODUCTION: The genetic causes of limb-girdle muscular dystrophy (LGMD) have been studied in numerous countries, but such investigations have been limited in Egypt. METHODS: A cohort of 30 families with suspected LGMD from Assiut, Egypt, was studied using immunohistochemistry, homozygosity mapping, Sanger sequencing, and whole exome sequencing. RESULTS: Six families were confirmed to have pathogenic mutations, 4 in SGCA and 2 in DMD. Of these, 3 families harbored a single nonsense mutation in SGCA, suggesting that this may be a common mutation in Assiut, Egypt, originating from a founder effect. CONCLUSIONS: The Assiut region in Egypt appears to share at least several of the common LGMD genes found in other parts of the world. It is notable that 4 of the 6 mutations were ascertained by means of whole exome sequencing, even though it was the last approach adopted. This illustrates the power of this technique for identifying causative mutations for muscular dystrophies. Muscle Nerve 54: 690-695, 2016.
Assuntos
Códon sem Sentido/genética , Homozigoto , Distrofia Muscular do Cíngulo dos Membros/epidemiologia , Distrofia Muscular do Cíngulo dos Membros/genética , Sarcoglicanas/genética , Egito/epidemiologia , Feminino , Humanos , Masculino , Distrofia Muscular do Cíngulo dos Membros/diagnóstico , LinhagemRESUMO
Evidence from epidemiological, longitudinal, prospective, double-blinded clinical trials as well as case reports documents age-accelerated atherosclerosis with increased carotid artery intima media thickness (CA-IMT) in patients with epilepsy. These findings raise concern regarding their implications for age-accelerated cognitive and behavioral changes in midlife and risk of later age-related cognitive disorders including neurodegenerative processes such as Alzheimer's disease (AD). Chronic epilepsy, cerebral atherosclerosis, and age-related cognitive disorders including AD share many clinical manifestations (e.g. characteristic cognitive deficits), risk factors, and structural and pathological brain abnormalities. These shared risk factors include increased CA-IMT, hyperhomocysteinemia (HHcy), lipid abnormalities, weight gain and obesity, insulin resistance (IR), and high levels of inflammatory and oxidative stresses. The resulting brain structural and pathological abnormalities include decreased volume of the hippocampus, increased cortical thinning of the frontal lobe, ventricular expansion and increased white matter ischemic disease, total brain atrophy, and ß-amyloid protein deposition in the brain. The knowledge that age-accelerated atherosclerosis may contribute to age-accelerated cognitive and behavioral abnormalities and structural brain pathologies in patients with chronic epilepsy represents an important research path to pursue future clinical and management considerations.
Assuntos
Aterosclerose/etiologia , Transtornos Cognitivos/etiologia , Comorbidade , Epilepsia/etiologia , Aterosclerose/epidemiologia , Transtornos Cognitivos/epidemiologia , Epilepsia/epidemiologia , HumanosRESUMO
OBJECTIVES: Obsessive-compulsive symptoms (OCSs) and disorder (OCD) are often underdiagnosed in the out-patient epilepsy clinic. This work aimed at determining the risks and comorbidities (psychopathological and neurobiological correlates) of OCSs in treated adults with idiopathic epilepsy recruited from a university hospital. METHODS: Psychiatric evaluation was done using DSM-IV (The Diagnostic and Statistical Manual of Mental Health Disorders). Obsessive-compulsive disorder was identified using the Mini International Neuropsychiatric Interview (MINI). The Beck Depression Inventory (BDI-II), Hamilton Anxiety Rating Scale (HAM-A), and Yale-Brown Obsessive Compulsive Scale (Y-BOCS) were used to determine the severity of the related psychiatric symptoms. RESULTS: Out of 474 patients screened, included in this study were 107 with no psychiatric symptoms and 188 with OCSs [classified as those with at least OCSs=93; mild OCSs=36; moderate, severe, and extreme OCSs=59]. A hundred healthy subjects were included as controls. Blood concentrations of serotonin, adrenaline, noradrenaline, and dopamine were measured. Compared with controls, patients with OCSs had higher frequencies of depression and anxiety. Low concentrations of serotonin, adrenaline, noradrenaline, and dopamine were reported regardless of the presence or the absence of psychiatric symptoms, OCS severities, and antiepileptic drug (AED)-related variables (dose and serum drug level). Significant correlations were identified between Y-BOCS, BDI-II, and HAM-A scores, age, age at onset, and concentrations of noradrenaline. CONCLUSION: This study indicates that a) OCSs are common in patients with epilepsy. Male sex, age, duration of illness, seizure focus, lateralization, and intractability to AEDs are its main risks; b) depression and anxiety are comorbid psychopathologies; and c) serotonin, catecholamines, and dopamine are linked to epilepsy-related variables and its comorbid psychopathies but not to its medications.
Assuntos
Monoaminas Biogênicas/sangue , Epilepsia/sangue , Epilepsia/epidemiologia , Transtorno Obsessivo-Compulsivo/sangue , Transtorno Obsessivo-Compulsivo/epidemiologia , Transtornos Psicóticos/epidemiologia , Adulto , Anticonvulsivantes/uso terapêutico , Comorbidade , Manual Diagnóstico e Estatístico de Transtornos Mentais , Ensaio de Imunoadsorção Enzimática , Epilepsia/complicações , Epilepsia/tratamento farmacológico , Feminino , Hospitais , Humanos , Masculino , Pessoa de Meia-Idade , Transtorno Obsessivo-Compulsivo/complicações , Transtorno Obsessivo-Compulsivo/tratamento farmacológico , Escalas de Graduação Psiquiátrica , Transtornos Psicóticos/sangue , Transtornos Psicóticos/diagnóstico , Inquéritos e Questionários , Adulto JovemRESUMO
This study was aimed to assess: (1) the additive diagnostic utility of diffusion-weighted imaging (DWI) and magnetic resonance angiography (MRA) over conventional MRI in detecting brain lesions in patients with acute primary neuropsychiatric systemic lupus erythematosus (NPSLE), and (2) the relevance of their findings to the associated NP manifestations. Included were 34 patients with acute NPSLE with mean age of 33.26 ± 10.14 years and duration of illness of 3.33 ± 1.71 years. Clinical interviewing and psychiatric and cognitive evaluations were performed by applying the criteria of the diagnostic and statistical manual of mental health disorders criteria (DSM-IV), Stanford Binet Subset Testing, Mini-Mental State Examination and Wechsler Memory Scale-Revised. Serologic tests included looking for antinuclear antibodies, anti-double strand DNA, anti-phospholipid antibodies. Radiologic evaluation included conventional MRI, DWI and MRA. One or more NP manifestations were diagnosed in 28 patients, in which cognitive deficits were reported with headache, psychosis and CVS. Anti-phospholipid antibodies were reported in patients with CVS. Twenty patients (71.43 %) with primary NPSLE (n = 28) had MRI abnormalities in which hyperintense signals at subcortical and periventricular white matter and at the junction between the gray and white matter represented 75 % (n = 15) and with headache (n = 6), psychosis (n = 6) and acute confusional state (n = 3) with and without cognitive deficits, respectively. Moderate-sized infarctions with restricted diffusion in the distribution of middle cerebral arteries were represented in 35 % (n = 7) and with CVS, of them, 71.43 % (n = 5) had beading and focal narrowing of carotid arteries were consistent with vasculitis. Brain atrophy represented 20 % (n = 4) and with psychosis. Compared to those with normal MRI, patients with MRI abnormalities were older (P < 0.050) and had longer duration of illness (P < 0.050). To conclude, although DWI and MRA are helping in more precise etiopathologic diagnosis compared to conventional MRI, but their relevance to the present NP manifestations is still limited.
Assuntos
Imagem de Difusão por Ressonância Magnética , Vasculite Associada ao Lúpus do Sistema Nervoso Central/diagnóstico , Angiografia por Ressonância Magnética , Doença Aguda , Adolescente , Adulto , Anticorpos Antinucleares/sangue , Anticorpos Antifosfolipídeos/sangue , Atenção , Biomarcadores/sangue , Distribuição de Qui-Quadrado , Cognição , Feminino , Humanos , Vasculite Associada ao Lúpus do Sistema Nervoso Central/sangue , Vasculite Associada ao Lúpus do Sistema Nervoso Central/imunologia , Vasculite Associada ao Lúpus do Sistema Nervoso Central/patologia , Vasculite Associada ao Lúpus do Sistema Nervoso Central/psicologia , Masculino , Memória , Pessoa de Meia-Idade , Testes Neuropsicológicos , Valor Preditivo dos Testes , Prognóstico , Desempenho Psicomotor , Adulto JovemRESUMO
The Human Variome Project (http://www.humanvariomeproject.org) is an international effort aiming to systematically collect and share information on all human genetic variation. The two main pillars of this effort are gene/disease-specific databases and a network of Human Variome Project Country Nodes. The latter are nationwide efforts to document the genomic variation reported within a specific population. The development and successful operation of the Human Variome Project Country Nodes are of utmost importance to the success of Human Variome Project's aims and goals because they not only allow the genetic burden of disease to be quantified in different countries, but also provide diagnosticians and researchers access to an up-to-date resource that will assist them in their daily clinical practice and biomedical research, respectively. Here, we report the discussions and recommendations that resulted from the inaugural meeting of the International Confederation of Countries Advisory Council, held on 12th December 2011, during the 2011 Human Variome Project Beijing Meeting. We discuss the steps necessary to maximize the impact of the Country Node effort for developing regional and country-specific clinical genetics resources and summarize a few well-coordinated genetic data collection initiatives that would serve as paradigms for similar projects.
Assuntos
Variação Genética , Genoma Humano , Projeto Genoma Humano , Guias como Assunto , Projeto Genoma Humano/economia , Projeto Genoma Humano/ética , Projeto Genoma Humano/legislação & jurisprudência , Humanos , Cooperação Internacional , Sistema de Registros , SoftwareRESUMO
The rate of DNA variation discovery has accelerated the need to collate, store and interpret the data in a standardised coherent way and is becoming a critical step in maximising the impact of discovery on the understanding and treatment of human disease. This particularly applies to the field of neurology as neurological function is impaired in many human disorders. Furthermore, the field of neurogenetics has been proven to show remarkably complex genotype-to-phenotype relationships. To facilitate the collection of DNA sequence variation pertaining to neurogenetic disorders, we have initiated the "Neurogenetics Consortium" under the umbrella of the Human Variome Project. The Consortium's founding group consisted of basic researchers, clinicians, informaticians and database creators. This report outlines the strategic aims established at the preliminary meetings of the Neurogenetics Consortium and calls for the involvement of the wider neurogenetic community in enabling the development of this important resource.
Assuntos
Bases de Dados Genéticas/normas , Variação Genética , Genética Médica/organização & administração , Cooperação Internacional , Sistema Nervoso/metabolismo , Algoritmos , Congressos como Assunto , Variação Genética/fisiologia , Genética Médica/normas , Projeto Genoma Humano/organização & administração , Humanos , Doenças do Sistema Nervoso/genética , Doenças do Sistema Nervoso/metabolismo , Relatório de PesquisaRESUMO
BACKGROUND: Abdominal migraine is a commonly described migraine variant in children and young adults, but associations with Alice in Wonderland syndrome and lilliputian hallucinations are exceptional. CASE PRESENTATION: A 20 years-old male experienced frequent and prolonged attacks of abdominal colic associated with autonomic manifestations started at the age of ten. At the age of 17, he additionally described prolonged attacks (>or= 7 days) of distortions of shape, size or position of objects or subjects. He said "Quite suddenly, objects appear small and distant (teliopsia) or large and close (peliopsia). I feel as I am getting shorter and smaller "shrinking" and also the size of persons are not longer than my index finger (a lilliputian proportion). Sometimes I see the blind in the window or the television getting up and down, or my leg or arm is swinging. I may hear the voices of people quite loud and close or faint and far. Occasionally, I experience attacks of migrainous headache associated with eye redness, flashes of lights and a feeling of giddiness. I am always conscious to the intangible changes in myself and my environment". There is a strong family history of common migraine. Clinical examination, brain-MRI and EEG were normal. Transcranial magnetic stimulation and evoked potentials revealed enhanced cortical excitability in multiple brain regions. Treatment with valproate resulted in marked improvement of all clinical and neurophysiological abnormalities. CONCLUSIONS: The association between the two migraine variants (abdominal migraine and Alice in Wonderland Syndrome) might have clinical, pathophysiological and management implications. I think this is the first description in the literature.
Assuntos
Cólica , Alucinações , Enteropatias , Transtornos de Enxaqueca , Encéfalo/efeitos dos fármacos , Encéfalo/patologia , Encéfalo/fisiopatologia , Cólica/tratamento farmacológico , Cólica/fisiopatologia , Eletroencefalografia , Potenciais Evocados/efeitos dos fármacos , Alucinações/tratamento farmacológico , Alucinações/fisiopatologia , Humanos , Enteropatias/tratamento farmacológico , Enteropatias/fisiopatologia , Imageamento por Ressonância Magnética , Masculino , Transtornos de Enxaqueca/tratamento farmacológico , Transtornos de Enxaqueca/fisiopatologia , Exame Neurológico , Psicotrópicos/uso terapêutico , Síndrome , Estimulação Magnética Transcraniana , Resultado do Tratamento , Ácido Valproico/uso terapêutico , Adulto JovemRESUMO
PURPOSE: The objective of this study is to provide evidence that primary hyperuricemia is associated with cochlear dysfunction as other metabolic diseases that interfere with cell metabolism. MATERIALS AND METHODS: Cochlear function was evaluated in 25 subjects with asymptomatic hyperuricemia using routine diagnostic audiometry along with transient evoked and distortion product otoacoustic emissions (TEOAE and DPOAE, respectively). To support the notion that vascular compromise was a significant underlying factor for such cochlear dysfunction, we assessed vascular anatomical and functional states through measuring the common carotid artery intima-media thickness and flow velocity of the basal intracranial vessels. RESULTS: Compared with control subjects, reduced response levels of TEOAEs (P < .01) and amplitudes of DPOAEs (P < .001) were detected at higher frequencies. The reduced DPOAE levels at 5 kHz and TEOAEs at 4 kHz correlated significantly with uric acid (P < .05; P < .01), patients' age (P < .06; P < .05), duration since diagnosis of hyperuricemia (P < .05; P < .001), common carotid artery intima-media thickness (P < .05), mean flow velocities of middle cerebral arteries (P < .05), and vertebral arteries (P < .01). Multivariate analysis showed that the abnormalities at higher frequencies were significantly correlated with the duration and degree of hyperuricemia. CONCLUSIONS: These data suggest that subclinical changes in cochlear function are associated with hyperuricemia. They support the usefulness of otoacoustic emissions in early detection of cochlear dysfunction. It is possible that hyperuricemia could be accompanied by increased stiffness and/or compromise of blood supply of the outer hair cells, which will impair their electromotile response.
Assuntos
Cóclea/fisiopatologia , Hiperuricemia/fisiopatologia , Emissões Otoacústicas Espontâneas/fisiologia , Estimulação Acústica , Adulto , Audiometria de Resposta Evocada , Audiometria de Tons Puros/métodos , Limiar Auditivo/fisiologia , Artérias Carótidas/diagnóstico por imagem , Estudos de Casos e Controles , Egito , Potenciais Evocados Auditivos , Hospitais Universitários , Humanos , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Ultrassonografia Doppler TranscranianaRESUMO
Recent studies indicated that migraine is associated with specific vascular risk profile. However, the functional and structural vascular abnormalities in migraine are rarely addressed. We evaluated the vascular risk factors, endothelial function, and carotid artery (CA)-intima-media thickness (IMT), segregators of preclinical atherosclerosis, in migraineurs. This preliminary study included 63 adults with headache (migraine with aura [n=14], migraine without aura [n=24], transformed migraine [n=6], and tension headache [n=19]) and 35 matched healthy subjects. The following vascular risks were assessed: body mass index (BMI), systolic blood pressure (SBP) and diastolic blood pressures (DBP), serum levels of C-reactive protein, fasting glucose, fasting insulin, total cholesterol, and triglycerides. Plasma endothelin (ET)-1, a vasoactive peptide produced by vascular smooth muscle cells and marker for endothelial injury and atherosclerosis, was measured. Endothelial-dependent vasoreactivity was assessed using brachial artery flow-mediated dilatation (FMD) in response to hyperemia. CA-IMT, structural marker of early atherosclerosis, was measured. Compared with control subjects, SBP, DBP, glucose, insulin, ET-1, and CA-IMT were elevated with migraine. FMD% was inversely correlated with SBP (P < .001), DBP (P < .01), glucose (P < .001), and insulin levels (P < .01). CA-IMT was correlated with BMI (P < .05), SBP (P < .01), total cholesterol (P < .01), triglycerides (P < .001), glucose (P < .001), insulin (P < .01), and FMD% (P < .05). In multivariate analysis, ET-1 was correlated with duration of illness, SBP, DBP, glucose, insulin, IMT, and FMD%. We conclude that endothelial injury, impaired endothelial vasoreactivity, and increased CA-IMT occur with migraine and are associated with vascular risk factors that strongly suggest that migraine could be a risk for atherosclerosis.
Assuntos
Doenças das Artérias Carótidas/epidemiologia , Doenças das Artérias Carótidas/fisiopatologia , Transtornos de Enxaqueca/epidemiologia , Transtornos de Enxaqueca/fisiopatologia , Adulto , Biomarcadores/análise , Biomarcadores/sangue , Glicemia/análise , Pressão Sanguínea/fisiologia , Índice de Massa Corporal , Proteína C-Reativa/análise , Proteína C-Reativa/metabolismo , Artérias Carótidas/patologia , Artérias Carótidas/fisiopatologia , Doenças das Artérias Carótidas/diagnóstico , Estudos de Casos e Controles , Colesterol/análise , Colesterol/sangue , Comorbidade , Complicações do Diabetes/epidemiologia , Complicações do Diabetes/fisiopatologia , Células Endoteliais/metabolismo , Endotelina-1/análise , Endotelina-1/sangue , Feminino , Humanos , Hipertensão/epidemiologia , Hipertensão/fisiopatologia , Masculino , Transtornos de Enxaqueca/diagnóstico , Análise Multivariada , Fatores de Risco , Triglicerídeos/análise , Triglicerídeos/sangue , Túnica Íntima/patologia , Túnica Íntima/fisiopatologia , Vasoconstrição/fisiologiaRESUMO
Cerebrovascular stroke caused by skull base meningioma has been rarely reported. A 30-year-old male presented (April 2015) with acute right-sided hemiplegia. His brain neuroimaging (computerized tomography and magnetic resonance imaging) showed left ischemic infarction in the territory of middle cerebral artery. Magnetic resonance imaging also showed a right parasellar solid lesion which extended to the right basisphenoid and cavernous sinus and attenuated the right internal carotid artery. It also had left smaller parasellar extension. The lesion enhanced uniformly and strongly following gadolinium injection. Digital subtraction angiography using selective catheterization of both common carotid and left vertebral arteries (07/13/2015) showed occlusion of both internal carotid arteries and faint visualization of left terminal internal carotid artery and its bifurcation. The right internal carotid artery and its branches were not visualized. Left vertebral injection showed prominent left vertebral and basilar arteries and filling of both internal carotid arteries through posterior communicating arteries. A faint blush of contrast was noticed at the parasellar region coinciding with meningioma. The patient received three treatment sessions of gamma knife radiosurgery as follow: 20 cc of the tumor was treated with 12 Gy (15 August 2015), 1.7 cc was treated with 10 Gy (31 January 2016), and 2.5 cc was treated with 11 Gy (13 August 2016) which resulted in complete clinical recovery and tumor size reduction. Compensation from the posterior communicating and external carotid arteries might explain the complete clinical recovery after tumor size reduction with gamma knife radiosurgery.
RESUMO
BACKGROUND: Cyanotic breath-holding spells (CBHS) are self-limited conditions among younger children. Frequent spells cause parents' fear and anxiety. Seizures, brain damage and sudden death have been rarely reported with BHS. Some reported spells' frequency reduction with iron or piracetam. We evaluated the effectiveness of valproic acid (VPA) to treat CBHS and predictors of improvement. METHODS: Participants were 90 children with CBHS (≥4/week) (age: 1.6±0.4yrs). They were treated with VPA (5 mg/kg/d). Follow-ups occurred after 3-≥6 months. Autonomic nervous system functions were evaluated. RESULTS: The majority (74.4%) had daily spells and 19% had ≥2 spells/d. Crying or anger provoked spells. Postural hypotension was found in 46.7%. They had normal electroencephalography and QT, QTc interval or QTd or QTcd and heart rate. Compared to controls, postural fall in systolic (>20mmHg) and diastolic (>10mmHg) blood pressures and mean arterial pressure (>10mmHg) were observed in 46.7%, 74.4% and 72.2% and miosis observed with 0.125% pilocarpine in 28.9% (P=0.001). Spells' frequency reduction (P=0.001) occurred within 3 months with VPA. The independent prdictors for spell' frequency reduction were reduction of anger and crying [OR=4.52(95%CI=2.35-6.04), P =0.01]. CONCLUSION: VPA therapy reduces CBHS' frequency. Mood improvement is a suggestive effective mechanism. CLINICAL TRIAL REGISTRATION: www.clinicaltrials.gov identifier is NCT04482764.
Assuntos
Anticonvulsivantes/uso terapêutico , Suspensão da Respiração/efeitos dos fármacos , Cianose/tratamento farmacológico , Ácido Valproico/uso terapêutico , Afeto/efeitos dos fármacos , Pré-Escolar , Cianose/etiologia , Eletroencefalografia , Feminino , Compostos Ferrosos/uso terapêutico , Seguimentos , Humanos , Lactente , Masculino , Projetos Piloto , Piracetam/uso terapêutico , Estudos ProspectivosRESUMO
Here we report biallelic mutations in the sorbitol dehydrogenase gene (SORD) as the most frequent recessive form of hereditary neuropathy. We identified 45 individuals from 38 families across multiple ancestries carrying the nonsense c.757delG (p.Ala253GlnfsTer27) variant in SORD, in either a homozygous or compound heterozygous state. SORD is an enzyme that converts sorbitol into fructose in the two-step polyol pathway previously implicated in diabetic neuropathy. In patient-derived fibroblasts, we found a complete loss of SORD protein and increased intracellular sorbitol. Furthermore, the serum fasting sorbitol levels in patients were dramatically increased. In Drosophila, loss of SORD orthologs caused synaptic degeneration and progressive motor impairment. Reducing the polyol influx by treatment with aldose reductase inhibitors normalized intracellular sorbitol levels in patient-derived fibroblasts and in Drosophila, and also dramatically ameliorated motor and eye phenotypes. Together, these findings establish a novel and potentially treatable cause of neuropathy and may contribute to a better understanding of the pathophysiology of diabetes.
RESUMO
An amendment to this paper has been published and can be accessed via a link at the top of the paper.
RESUMO
BACKGROUND: Bacterial meningitis is often associated with cerebral compromise which may be responsible for neurological sequelae in nearly half of the survivors. Little is known about the mechanisms of CNS involvement in bacterial meningitis. Several studies have provided substantial evidence for the key role of nitric oxide (NO) and reactive oxygen species in the complex pathophysiology of bacterial meningitis. METHODS: In the present study, serum and CSF levels of NO, lipid peroxide (LPO) (mediators for oxidative stress and lipid peroxidation); total thiol, superoxide dismutase (SOD) (antioxidant mediators) and S-100B protein (mediator of astrocytes activation and injury), were investigated in children with bacterial meningitis (n = 40). Albumin ratio (CSF/serum) is a marker of blood-CSF barriers integrity, while mediator index (mediator ratio/albumin ratio) is indicative of intrathecal synthesis. RESULTS: Compared to normal children (n = 20), patients had lower serum albumin but higher NO, LPO, total thiol, SOD and S-100B. The ratios and indices of NO and LPO indicate blood-CSF barriers dysfunction, while the ratio of S-100B indicates intrathecal synthesis. Changes were marked among patients with positive culture and those with neurological complications. Positive correlation was found between NO index with CSF WBCs (r = 0.319, p < 0.05); CSF-LPO with CSF-protein (r = 0.423, p < 0.01); total thiol with LPO indices (r = 0.725, p < 0.0001); S-100B and Pediatric Glasow Coma Scores (0.608, p < 0.0001); CSF-LPO with CSF-S-100B (r = 0.482, p < 0.002); serum-total thiol with serum S-100B (r = 0.423, p < 0.01). CONCLUSION: This study suggests that loss of integrity of brain-CSF barriers, oxidative stress and S-100B may contribute to the severity and neurological complications of bacterial meningitis.
Assuntos
Meningites Bacterianas/sangue , Meningites Bacterianas/líquido cefalorraquidiano , Fatores de Crescimento Neural/sangue , Estresse Oxidativo , Proteínas S100/sangue , Adolescente , Análise de Variância , Biomarcadores/sangue , Biomarcadores/líquido cefalorraquidiano , Criança , Pré-Escolar , Estudos Transversais , Ensaio de Imunoadsorção Enzimática , Feminino , Humanos , Masculino , Fatores de Crescimento Neural/líquido cefalorraquidiano , Exame Neurológico , Óxido Nítrico/sangue , Óxido Nítrico/líquido cefalorraquidiano , Seleção de Pacientes , Subunidade beta da Proteína Ligante de Cálcio S100 , Proteínas S100/líquido cefalorraquidiano , Albumina Sérica/metabolismo , Punção Espinal , Estatísticas não Paramétricas , Superóxido Dismutase/sangue , Superóxido Dismutase/líquido cefalorraquidianoRESUMO
Studies examined the neurological involvement of ankylosing spondylitis (AS) are limited. This study aimed to assess the frequency of myelopathy, radiculopathy and myopathy in AS correlating them to the clinical, radiological and laboratory parameters. Included were 24 patients with AS. Axial status was assessed using bath ankylosing spondylitis metrology index (BASMI). Patients underwent (a) standard cervical and lumbar spine and sacroiliac joint radiography, (b) somatosensory (SSEP) and magnetic motor (MEP) evoked potentials of upper and lower limbs, (c) electromyography (EMG) of trapezius and supraspinatus muscles. Patients' mean age and duration of illness were 36 and 5.99 years. Bath ankylosing spondylitis metrology index mean score was 4.6. Twenty-five percent (n = 6) of patients had neurological manifestations, 8.3% of them had myelopathy and 16.7% had radiculopathy. Ossification of the posterior (OPLL) and anterior (OALL) longitudinal ligaments were found in 8.3% (n = 2) and 4.2% (n = 1). About 70.8% (n = 17) had >or=1 neurophysiological test abnormalities. Twelve patients (50%) had SSEP abnormalities, seven had prolonged central conduction time (CCT) of median and/or ulnar nerves suggesting cervical myelopathy. Six had delayed peripheral or root latencies at Erb's or interpeak latency (Erb's-C5) suggesting radiculopathy. Motor evoked potentials was abnormal in 54% (n = 13). Twelve (50%) and five (20.8%) patients had abnormal MEP of upper limbs and lower limbs, respectively. About 50% (n = 12) had myopathic features of trapezius and supraspinatus muscles. Only 8.3% (n = 2) had neuropathic features. We concluded that subclinical neurological complications are frequent in AS compared to clinically manifest complications. Somatosensory evoked potential and MEP are useful to identify AS patients prone to develop neurological complications.