Carbapenem-Resistant Pseudomonas aeruginosa Spondylodiscitis Treated with Ceftazidime-Avibactam: A Case Report with Literature Review.

Pyogenic spondylodiscitis (PS) is a highly morbid and potentially fatal bacterial infection with an increasing incidence in recent decades. Its diagnosis and treatment are challenging, especially with the expansion of multidrug- or extensively drug-resistant bacteria. We report a rare case of PS caused by carbapenem-resistant Pseudomonas aeruginosa (CRPA) that was treated with ceftazidime-avibactam (C/A). The choice of C/A therapy was based on the patient's bacterial sensitivity profile and intolerance to the initial therapeutic regimen (polymyxin B and meropenem). The total antimicrobial treatment time was seven weeks. The evolution of the clinical course met the cure criteria, which was characterized by remission of signs and symptoms, normalization of inflammatory markers, and radiological improvement over 18 months of clinical follow-up. This is a rare case of CRPA spondylodiscitis that responded to C/A treatment.

Retrospective Study of 57 Patients Submitted to Dorsal Root Entry Zone Lesioning by Radiofrequency for Brachial Plexus Avulsion Pain.

BACKGROUND: Dorsal root entry zone (DREZ) lesioning may be used to treat neuropathic pain in patients with traumatic brachial plexus injuries. The clinical outcome after surgery is variable in the medical literature. We aimed to report the surgical outcome after DREZ lesioning by radiofrequency and to analyze prognostic factors such as the presence of a spinal cord injury identified before surgery. METHODS: We conducted a retrospective study that included 57 patients who had experienced traumatic brachial plexus injuries and exhibited neuropathic pain that did not respond to conservative treatment methods. They were submitted to DREZ lesioning. We defined the inclusion and exclusion criteria, collected sociodemographic and clinical characteristics, and identified and classified spinal cord lesions based on magnetic resonance imaging. We applied statistical tests to evaluate the association between pain intensity after surgery and the radiological profile and sociodemographic characteristics. RESULTS: Immediately after surgery, the pain outcome was considered good or excellent in 50 patients (89.28%). At the last follow-up, it was good or excellent in 39 patients (68.43%). There was no association (P > 0.05) between the pain outcome and the variables analyzed (time interval between trauma and DREZ lesioning, presence of spinal cord injury, age, the number of avulsed roots, and the type of pain). CONCLUSIONS: DREZ lesioning using radiofrequency represents a significant therapeutic approach for managing neuropathic pain after a traumatic brachial plexus injury. Importantly, we found that the presence of a spinal cord injury is not associated with the surgical outcome.

Clinical and epidemiological profiles from a case series of 26 Brazilian CADASIL patients.

BACKGROUND: Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is a genetic cause of ischemic stroke and the most common form of non-atherosclerotic stroke. Despite being the most prevalent vascular hereditary disease, clinical data regarding the Brazilian population are scarce. Considering that the Brazilian population has one of the most heterogeneous genetic constitutions in the world, knowledge about genetic and epidemiological profiles is mandatory. The present study aimed to elucidate the epidemiological and clinical features of CADASIL in Brazil. METHODS: We performed a case series study comprising 6 rehabilitation hospitals in Brazil and reported the clinical and epidemiological data from the medical records of patients admitted from 2002 to 2019 with genetic confirmation. RESULTS: We enrolled 26 (16 female) patients in whom mutations in exons 4 and 19 were the most common. The mean age at the onset of the disease was of 45 years. Ischemic stroke was the first cardinal symptom in 19 patients. Cognitive impairment, dementia, and psychiatric manifestations were detected in 17, 6, and 16 patients respectively. In total, 8 patients had recurrent migraines, with aura in 6 (75%) of them. White matter hyperintensities in the temporal lobe and the external capsule were found in 20 (91%) and 15 patients (68%) respectively. The median Fazekas score was of 2. Lacunar infarcts, microbleeds, and larger hemorrhages were observed in 18 (82%), 9, and 2 patients respectively. CONCLUSION: The present is the most extensive series of Brazilian CADASIL patients published to date, and we have reported the first case of microbleeds in the spinal cord of a CADASIL patient. Most of our clinical and epidemiological data are in accordance with European cohorts, except for microbleeds and hemorrhagic strokes, for which rates fall in between those of European and Asian cohorts.

ANTECEDENTES: Arteriopatia cerebral autossômica dominante com enfartes subcorticais e leucoencefalopatia (Cerebral Autosomal Dominant Arteriopathy with Subcortical Infarcts and Leukoencephalopathy, CADASIL, em inglês) é uma causa genética de acidente vascular cerebral (AVC) isquêmico e a forma mais comum de acidente vascular cerebral não aterosclerótico. Apesar de ser a doença vascular hereditária mais prevalente que há, os dados clínicos para a população brasileira são escassos. Considerando que o Brasil tem uma das constituições genéticas mais heterogêneas do mundo, o conhecimento sobre perfis genéticos e epidemiológicos é obrigatório. Este estudo teve como objetivo elucidar as características clínicas e epidemiológicas de pacientes com CADASIL no Brasil. MéTODOS: Apresentamos uma série de casos envolvendo 6 hospitais de reabilitação no Brasil, e relatamos dados clínicos e epidemiológicos de prontuários de pacientes admitidos entre 2002 e 2019 com confirmação genética. RESULTADOS: incluímos 26 pacientes (16 mulheres) em que as mutações nos éxons 4 e 19 eram as mais comuns. A idade média de início da doença foi de 45 anos. O AVC isquêmico foi o primeiro sintoma cardinal em 19 pacientes. Comprometimento cognitivo, demência e manifestações psiquiátricas foram detectados em 17, seis e 16 pacientes, respectivamente. Ao todo, 8 pacientes apresentavam enxaqueca, sendo com aura em 6 (75%) pacientes. Hiperintensidades de substância branca no polo temporal e na cápsula externa foram encontradas em 20 (91%) e 15 pacientes (68%), respectivamente. A pontuação mediana na escala de Fazekas foi de 2. Infartos lacunares, microssangramentos e macro-hemorragias foram observadas em 18 (82%), 9 (41%) e 2 (9%) pacientes, respectivamente. CONCLUSãO: O presente estudo representa a mais extensa série de pacientes brasileiros com CADASIL publicada até o momento, e relatamos o primeiro caso de micro-hemorragia na medula espinhal de um paciente com CADASIL. A maior parte dos nossos dados clínicos e epidemiológicos está de acordo com as coortes europeias, exceto para micro-hemorragias e macro-hemorragias, para as quais as taxas se enquadram entre as das coortes europeias e asiáticas.

Clinical and epidemiological profiles from a case series of 26 Brazilian CADASIL patients / Perfil clínico e epidemiológico de uma série de casos de 26 pacientes com diagnóstico de CADASIL

Abstract Background Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is a genetic cause of ischemic stroke and the most common form of non-atherosclerotic stroke. Despite being the most prevalent vascular hereditary disease, clinical data regarding the Brazilian population are scarce. Considering that the Brazilian population has one of the most heterogeneous genetic constitutions in the world, knowledge about genetic and epidemiological profiles is mandatory. The present study aimed to elucidate the epidemiological and clinical features of CADASIL in Brazil. Methods We performed a case series study comprising 6 rehabilitation hospitals in Brazil and reported the clinical and epidemiological data from the medical records of patients admitted from 2002 to 2019 with genetic confirmation. Results We enrolled 26 (16 female) patients in whom mutations in exons 4 and 19 were the most common. The mean age at the onset of the disease was of 45 years. Ischemic stroke was the first cardinal symptom in 19 patients. Cognitive impairment, dementia, and psychiatric manifestations were detected in 17, 6, and 16 patients respectively. In total, 8 patients had recurrent migraines, with aura in 6 (75%) of them. White matter hyperintensities in the temporal lobe and the external capsule were found in 20 (91%) and 15 patients (68%) respectively. The median Fazekas score was of 2. Lacunar infarcts, microbleeds, and larger hemorrhages were observed in 18 (82%), 9, and 2 patients respectively. Conclusion The present is the most extensive series of Brazilian CADASIL patients published to date, and we have reported the first case of microbleeds in the spinal cord of a CADASIL patient. Most of our clinical and epidemiological data are in accordance with European cohorts, except for microbleeds and hemorrhagic strokes, for which rates fall in between those of European and Asian cohorts.

Resumo Antecedentes Arteriopatia cerebral autossômica dominante com enfartes subcorticais e leucoencefalopatia (Cerebral Autosomal Dominant Arteriopathy with Subcortical Infarcts and Leukoencephalopathy, CADASIL, em inglês) é uma causa genética de acidente vascular cerebral (AVC) isquêmico e a forma mais comum de acidente vascular cerebral não aterosclerótico. Apesar de ser a doença vascular hereditária mais prevalente que há, os dados clínicos para a população brasileira são escassos. Considerando que o Brasil tem uma das constituições genéticas mais heterogêneas do mundo, o conhecimento sobre perfis genéticos e epidemiológicos é obrigatório. Este estudo teve como objetivo elucidar as características clínicas e epidemiológicas de pacientes com CADASIL no Brasil. Métodos Apresentamos uma série de casos envolvendo 6 hospitais de reabilitação no Brasil, e relatamos dados clínicos e epidemiológicos de prontuários de pacientes admitidos entre 2002 e 2019 com confirmação genética. Resultados incluímos 26 pacientes (16 mulheres) em que as mutações nos éxons 4 e 19 eram as mais comuns. A idade média de início da doença foi de 45 anos. O AVC isquêmico foi o primeiro sintoma cardinal em 19 pacientes. Comprometimento cognitivo, demência e manifestações psiquiátricas foram detectados em 17, seis e 16 pacientes, respectivamente. Ao todo, 8 pacientes apresentavam enxaqueca, sendo com aura em 6 (75%) pacientes. Hiperintensidades de substância branca no polo temporal e na cápsula externa foram encontradas em 20 (91%) e 15 pacientes (68%), respectivamente. A pontuação mediana na escala de Fazekas foi de 2. Infartos lacunares, microssangramentos e macro-hemorragias foram observadas em 18 (82%), 9 (41%) e 2 (9%) pacientes, respectivamente. Conclusão O presente estudo representa a mais extensa série de pacientes brasileiros com CADASIL publicada até o momento, e relatamos o primeiro caso de micro-hemorragia na medula espinhal de um paciente com CADASIL. A maior parte dos nossos dados clínicos e epidemiológicos está de acordo com as coortes europeias, exceto para micro-hemorragias e macro-hemorragias, para as quais as taxas se enquadram entre as das coortes europeias e asiáticas.

Variable Presentation and Reduced Penetrance in Autosomal Dominant Acute Necrotizing Encephalopathy Related to RANBP2 Variant.

Acute necrotizing encephalopathy (ANE) is clinically characterized by fever, acute alteration of consciousness, seizures, and rapid progression to coma within days of onset of a viral illness occurring in healthy children without evidence of central nervous system infection. Brain magnetic resonance imaging (MRI) shows multiple symmetrical lesions affecting primarily the thalami but also brain stem, putamina, periventricular white matter, and cerebellum. Most cases of ANE are sporadic and nonrecurrent. However, a missense variant in RANBP2 has been identified in some families with recurrent ANE (OMIM # 608033), also named autosomal dominant ANE (ADANE). Clinical manifestation, clinical course, and brain MRI imaging findings of six affected members of two distinct families with ADANE were described. Sequencing revealed heterozygous c.1754C > T variant in RANBP2 (p.Thr585Met) in affected and asymptomatic family members. Only few ADANE families have been reported and it is the first description in South America. Differential diagnosis of Leigh disease and acute disseminated encephalomyelitis is discussed. Our report reinforces incomplete penetrance of ADANE and intrafamilial phenotypic variability of outcome.

White matter hyperintensity presence, quantity, and location exhibits no association with motor and non-motor manifestations of PD.

INTRODUCTION: Nonspecific areas of brain white matter hyperintensity (WMH) are commonly found in the elderly. Some studies have shown that the presence, quantity, and location of WMHs may be associated with the development of cognitive and motor decline in patients with Parkinson's disease (PD), but the results remain controversial. This study aimed to evaluate the relationship of WMH to motor and non-motor symptoms, including dysautonomia and rapid eye movement sleep behavior disorder (RBD), in patients with PD. METHODS: Brain magnetic resonance images were acquired from 120 patients diagnosed with PD and analyzed for WMH classification and quantification. Motor symptoms were quantified using sub-scores of the Movement Disorder Society-Unified Parkinson Disease Rating Scale (MDS-UPDRS)-III. Dysautonomia was evaluated by autonomic reactivity tests, and polysomnography was used for the diagnosis of RBD. RESULTS: Age, total value of the MDS-UPDRS-III tremor sub-score, and the presence of dysautonomia were found to be linearly positively associated. Specifically, the duration of PD was positively associated with rigidity, bradykinesia, axial symptoms, prevalence of dysautonomia, and RBD sub-scores. However, in the multivariate analysis adjusted for variables of interest, no statistical significance was found for any of the models. CONCLUSION: The presence, quantity, and location of WMH were not associated with the analyzed motor and non-motor manifestations of PD.

Neuromuscular Choristoma: Report of Five Cases With CTNNB1 Sequencing.

Neuromuscular choristoma (NMC) are lesions of the peripheral nervous system characterized by an admixture of skeletal muscle fibers and nerves fascicles that are frequently associated with desmoid fibromatosis (DF). Mutations in CTNNB1, the gene for ß-catenin protein, are common in DF and related to its pathogenesis. They are restricted to exon 3, with 3 point mutations: T41A, S45F, and S45P. To understand the pathogenesis of NMC, we tested CTNNB1 status in 5 cases of NMC whether or not they were associated with DF. The screening of mutations in CTNNB1 gene was based on amplicon deep sequencing using the ION Proton platform. Three patients had the S45F mutation; in 2 the mutation was common to both lesions and in one the DF was wild type while the NMC had the S45F mutation. One patient had a T41A mutation in the NMC and no associated DF. In the last patient, the DF lesion had a T41A mutation; there was no lesion with the S45P mutation. The presence of similar CTNNB1 mutations in NMC/DF-associated lesions and sporadic DF reinforces the relationship between both lesions and points to a common pathogenic mechanism.

Escore de Cálcio Coronário e Estratificação do Risco de Doença Arterial Coronariana em Pacientes com Acidente Vascular Encefálico Isquêmico Aterosclerótico e não-Aterosclerótico / Coronary Calcium Score and Stratification of Coronary Artery Disease Risk in Patients with Atherosclerotic and Non-Atherosclerotic Ischemic Stroke

Resumo Fundamento O acidente vascular encefálico isquêmico (AVEi) e a doença arterial coronariana (DAC) coexistem frequentemente e compartilham fatores de risco para doença aterosclerótica. Segundo a American Heart Association , os subtipos de AVEi podem ser considerados equivalentes de risco para DAC, mas a evidência para o AVEi não-aterosclerótico não está bem definida. Além disso, o escore de cálcio coronário (CAC) é um marcador preciso para estimar o risco de DAC. Entretanto, a distribuição do CAC pelos subtipos de AVEi ainda não foi bem caracterizada. Objetivos Comparar o CAC entre os grupos de AVEi ateroscleróticos e não ateroscleróticos, e determinar quais covariáveis estão associadas a CAC alto no AVEi Métodos Em um estudo transversal, incluímos todos os pacientes com AVEi, com idades entre 45 a 70 anos no momento do acidente vascular, consecutivamente admitidos em um hospital de reabilitação entre agosto de 2014 e dezembro de 2016, sem DAC prevalente. Todos os pacientes passaram por tomografia computadorizada (TC), para medir o CAC. CAC≥100 foi considerado alto risco de DAC. O nível de significância foi p<0,05. Resultados Dos 244 pacientes estudados (média de idade de 58,4±6,8 anos; 49% do sexo feminino), 164 (67%) apresentavam etiologia não-aterosclerótica. As proporções de CAC≥100 foram semelhantes entre os grupos ateroscleróticos e não-ateroscleróticos (33% [n=26] x 29% [n=47]; p= 0,54). Entre todos os pacientes com AVEi, apenas os de idade ≥60 anos foram associados independentemente a CAC≥100 (RC 3,5; 95% IC 1,7-7,1), ajustado para hipertensão, dislipidemia, diabetes, sedentarismo, e histórico familiar de DAC. Conclusão O AVEi aterosclerótico não apresentou risco maior de DAC quando comparado ao AVEi não-aterosclerótico de acordo com o CAC. Apenas a faixa etária ≥60 anos - mas não a etiologia - foi associada independentemente a CAC≥100. (Arq Bras Cardiol. 2020; 115(6):1144-1151)

Abstract Background Ischemic Stroke (IS) and Coronary Artery Disease (CAD) frequently coexist and share atherosclerotic disease risk factors. According to the American Heart Association, IS subtypes may be considered CAD risk equivalents, but the evidence for non-atherosclerotic IS is uncertain. Additionally, the Coronary Calcium Score (CCS) is an accurate marker to address CAD risk; however, CCS distribution between IS subtypes is not well characterized. Objectives To compare the CCS between atherosclerotic and non-atherosclerotic IS groups; and to determine which covariates were associated with high CCS in IS. Methods This cross-sectional design included all patients with IS, 45 to 70 years of age at the time of the stroke, consecutively admitted to a rehabilitation hospital between August 2014 and December 2016, without prevalent CAD. All patients underwent CT scanning for CCS measurement. CCS≥100 was considered a high risk for CAD, with a significance level of p<0.05. Results From the 244 studied patients (mean age 58.4±6.8 years; 49% female), 164 (67%) had non-atherosclerotic etiology. The proportions of CCS≥100 were similar between the atherosclerotic and the non-atherosclerotic groups (33% [n=26] x 29% [n=47]; p= 0.54). Among all IS patients, only age ≥60 years was independently associated with CCS≥100 (OR 3.5; 95%CI 1.7-7.1), accounting for hypertension, dyslipidemia, diabetes, sedentarism, and family history of CAD. Conclusion Atherosclerotic IS did not present a greater risk of CAD when compared to non-atherosclerotic IS according to CCS. Only age ≥60 years, but not etiology, was independently associated with CCS≥100.

Coronary Calcium Score and Stratification of Coronary Artery Disease Risk in Patients with Atherosclerotic and Non-Atherosclerotic Ischemic Stroke. / Escore de Cálcio Coronário e Estratificação do Risco de Doença Arterial Coronariana em Pacientes com Acidente Vascular Encefálico Isquêmico Aterosclerótico e não-Aterosclerótico.

BACKGROUND: Ischemic Stroke (IS) and Coronary Artery Disease (CAD) frequently coexist and share atherosclerotic disease risk factors. According to the American Heart Association, IS subtypes may be considered CAD risk equivalents, but the evidence for non-atherosclerotic IS is uncertain. Additionally, the Coronary Calcium Score (CCS) is an accurate marker to address CAD risk; however, CCS distribution between IS subtypes is not well characterized. OBJECTIVES: To compare the CCS between atherosclerotic and non-atherosclerotic IS groups; and to determine which covariates were associated with high CCS in IS. METHODS: This cross-sectional design included all patients with IS, 45 to 70 years of age at the time of the stroke, consecutively admitted to a rehabilitation hospital between August 2014 and December 2016, without prevalent CAD. All patients underwent CT scanning for CCS measurement. CCS≥100 was considered a high risk for CAD, with a significance level of p<0.05. RESULTS: From the 244 studied patients (mean age 58.4±6.8 years; 49% female), 164 (67%) had non-atherosclerotic etiology. The proportions of CCS≥100 were similar between the atherosclerotic and the non-atherosclerotic groups (33% [n=26] x 29% [n=47]; p= 0.54). Among all IS patients, only age ≥60 years was independently associated with CCS≥100 (OR 3.5; 95%CI 1.7-7.1), accounting for hypertension, dyslipidemia, diabetes, sedentarism, and family history of CAD. CONCLUSION: Atherosclerotic IS did not present a greater risk of CAD when compared to non-atherosclerotic IS according to CCS. Only age ≥60 years, but not etiology, was independently associated with CCS≥100.

FUNDAMENTO: O acidente vascular encefálico isquêmico (AVEi) e a doença arterial coronariana (DAC) coexistem frequentemente e compartilham fatores de risco para doença aterosclerótica. Segundo a American Heart Association , os subtipos de AVEi podem ser considerados equivalentes de risco para DAC, mas a evidência para o AVEi não-aterosclerótico não está bem definida. Além disso, o escore de cálcio coronário (CAC) é um marcador preciso para estimar o risco de DAC. Entretanto, a distribuição do CAC pelos subtipos de AVEi ainda não foi bem caracterizada. OBJETIVOS: Comparar o CAC entre os grupos de AVEi ateroscleróticos e não ateroscleróticos, e determinar quais covariáveis estão associadas a CAC alto no AVEi. MÉTODOS: Em um estudo transversal, incluímos todos os pacientes com AVEi, com idades entre 45 a 70 anos no momento do acidente vascular, consecutivamente admitidos em um hospital de reabilitação entre agosto de 2014 e dezembro de 2016, sem DAC prevalente. Todos os pacientes passaram por tomografia computadorizada (TC), para medir o CAC. CAC≥100 foi considerado alto risco de DAC. O nível de significância foi p<0,05. RESULTADOS: Dos 244 pacientes estudados (média de idade de 58,4±6,8 anos; 49% do sexo feminino), 164 (67%) apresentavam etiologia não-aterosclerótica. As proporções de CAC≥100 foram semelhantes entre os grupos ateroscleróticos e não-ateroscleróticos (33% [n=26] x 29% [n=47]; p= 0,54). Entre todos os pacientes com AVEi, apenas os de idade ≥60 anos foram associados independentemente a CAC≥100 (RC 3,5; 95% IC 1,7-7,1), ajustado para hipertensão, dislipidemia, diabetes, sedentarismo, e histórico familiar de DAC. CONCLUSÃO: O AVEi aterosclerótico não apresentou risco maior de DAC quando comparado ao AVEi não-aterosclerótico de acordo com o CAC. Apenas a faixa etária ≥60 anos ­ mas não a etiologia - foi associada independentemente a CAC≥100. (Arq Bras Cardiol. 2020; 115(6):1144-1151).

Dantrolene e células-tronco mesenquimais promovem melhora funcional em ratos Wistar com trauma espinhal agudo / Dantrolene and mesenchymal stem cells promote functional improvement in Wistar rats with spinal cord injury

Objetivou-se avaliar o efeito do dantrolene (DAN) e das células-tronco mesenquimais (CTM) no trauma espinhal agudo (TEA). Sessenta ratos Wistar foram divididos nos grupos CTM, DAN + CTM, DAN, trauma e placebo (TP) e sem trauma e placebo (STP). Realizou-se laminectomia de T12 em todos os grupos, seguida de TEA contusivo ∕ compressivo, com exceção do grupo STP. Uma hora depois, os grupos DAN + CTM e DAN receberam 10mg/kg de DAN. Após sete dias os grupos CTM e DAN + CTM receberam 1x106 células, por via intravenosa. Testes comportamentais foram realizados para avaliar a recuperação funcional durante 28 dias. Os animais traumatizados apresentaram paraplegia. Houve melhora funcional significativa nos grupos tratados com CTM, DAN ou associação DAN + CTM em comparação ao grupo TP (p<0,05). Conclui-se que o DAN e as CTM para tratamento de TEA em ratos apresentam efeitos neuroprotetores e promovem melhora neurológica funcional.(AU)

This study aimed to evaluate the effects of dantrolene (DAN) and mesenchymal stem cells (MSCs) in acute spinal cord injury (SCI). Sixty Wistar rats were divided into groups MSCs, MSCs + DAN, DAN, trauma and placebo (TP) and no trauma and placebo (STP). Laminectomy was performed at T12 level in all animals, followed by a weight-drop model of SCI, except for the STP group. An hour later, the MSCs + DAN and DAN groups received 10mg/kg of DAN. After seven days, the MSCs and MSCs + DAN groups received 1x106 cells intravenously. Behavioral tests were performed to assess functional recovery for 28 days. Traumatized animals showed paraplegia. There was a significant improvement in groups MSCs, DAN and MSCs + DAN compared to TP (p<0.05). It was concluded that DAN and MSCs for the treatment of SCI in rats have neuroprotection effect and promote functional neurological improvement.(AU)

Additional features of Gillespie syndrome in two Brazilian siblings with a novel ITPR1 homozygous pathogenic variant.

Gillespie syndrome (GS) [MIM: 206700] is a very rare condition characterized by bilateral iris defect, congenital hypotonia, cerebellar ataxia and intellectual disability. The typical iris anomaly is considered necessary to the diagnosis of GS. Recently, variants in ITPR1 were described causing GS. Non-neurological features were reported in few patients. Here we describe two consanguineous siblings with GS and a novel homozygous ITPR1 pathogenic variant (p.N984fs). They also present a cardiac defect (pulmonary valve stenosis) and one sib had a genitourinary malformation (ureteropelvic junction obstruction). Our report reinforces ITPR1 as the cause of GS and suggests a possible role of ITPR1 in the development of other organs.

Association of riluzole and dantrolene improves significant recovery after acute spinal cord injury in rats.

BACKGROUND CONTEXT: Damage to the spinal cord can result in irreversible impairment or complete loss of motor, sensory, and autonomic functions. Riluzole and dantrolene have been shown to provide neuroprotection by reducing neuronal apoptosis after brain and spinal cord injury (SCI) in several animal models of neurologic disorders. As these drugs protect the injured spinal cord through different mechanisms, we investigated the cumulative effects of riluzole and dantrolene. PURPOSE: This study aimed to investigate the neuroprotective efficacy of the combined administration of riluzole and dantrolene in experimental thoracic SCI. STUDY DESIGN: Twenty-nine Wistar rats were laminectomized at T12 and divided in five groups. Rats in GI (n=6) underwent laminectomy alone and were treated with placebo. Rats in GII (n=6) underwent laminectomy followed by SCI and were treated with placebo. Rats in GIII (n=5) underwent laminectomy followed by SCI and were treated with riluzole and placebo 15 minutes and 1 hour after laminectomy, respectively. Rats in GIV (n=6) underwent laminectomy followed by SCI and were treated with placebo and dantrolene 15 minutes and 1 hour after laminectomy, respectively. Rats in GV (n=6) underwent laminectomy followed by SCI and were treated with riluzole and dantrolene 15 minutes and 1 hour after laminectomy, respectively. A compressive trauma was performed to induce SCI. METHODS: Behavioral testing of hind limb function was performed using the Basso Beattie Bresnahan locomotor rating scale, which revealed significant recovery in the group treated with the association of riluzole and dantrolene compared with other groups. After euthanasia, the spinal cord was evaluated using light microscopy and immunochemistry with anti-NeuN and transferase dUTP nick-end-labeling (TUNEL) staining. RESULTS: Animals treated with the association of riluzole and dantrolene showed a larger number of NeuN-positive neurons adjacent to the epicenter of injury (p≤.05). Furthermore, the TUNEL staining was similar between animals treated with riluzole and dantrolene and those that did not receive spinal cord trauma (p>.05). CONCLUSIONS: These results showed that riluzole and dantrolene have a synergistic effect in neuroprotection after traumatic SCI by decreasing apoptotic cell death.

Ischemia-reperfusion model in rat spinal cord: cell viability and apoptosis signaling study.

This work aimed at determining the ideal ischemia time in an in vitro ischemia-reperfusion model of spinal cord injury. Rat spinal cord slices were prepared and then exposed or not to oxygen deprivation and low glucose (ODLG) for 30, 45, 60, 75 and 90 minutes. Cell viability was assessed by triphenyltetrazolium (TTC), lactate dehydrogenase (LDH) release, and fluorochrome dyes specific for cell dead (ethidium homodimer) using the apotome system. Glutamate release was enzymatically measured by a fluorescent method. Gene expression of apoptotic factors was assessed by real time RT-PCR. Whereas spinal cord slices exposed to ODLG exhibited mild increase in fluorescence for 30 minutes after the insult, the 45, 60, 75 and 90 minutes caused a 2-fold increase. ODLG exposure for 45, 60, 75 or 90 minutes, glutamate and LDH release were significantly elevated. nNOS mRNA expression was overexpressed for 45 minutes and moderately increased for 60 minutes in ODLG groups. Bax/bcl-xl ratio, caspase 9 and caspase 3 mRNA expressions were significantly increased for 45 minutes of ODLG, but not for 30, 60, 75 and 90 minutes. Results showed that cell viability reduction in the spinal cord was dependent on ischemic time, resulting in glutamate and LDH release. ODLG for 45 minutes was adequate for gene expression evaluation of proteins and proteases involved in apoptosis pathways.

Symmetric bimanual phacofragmentation: a new approach for nucleus disassembly.

PURPOSE: To describe a new technique to split the lens nucleus inside the capsular bag, using a novel pair of instruments. METHODS: Two identical instruments are employed on the horizontal axis to promote nuclear splitting into 2 or more fragments. Each instrument has a portion that functions as a hook (H); an anterior edge, opposite to the hook, which acts as a knife (K); and a surface area located between the hook and knife, which functions as a cracker (C). RESULTS: Nuclei up to grade 4 nuclear sclerosis were successfully fractured employing this technique. CONCLUSIONS: Symmetric bimanual phacofragmentation with HKC instruments provides effective bimanual splitting of nuclei for phacoemulsification, also allowing depth adjustment of cleavage plane, and can be applied for a wide range of nuclear densities.

Omega-conotoxin MVIIC attenuates neuronal apoptosis in vitro and improves significant recovery after spinal cord injury in vivo in rats.

Excessive accumulation of intracellular calcium is the most critical step after spinal cord injury (SCI). Reducing the calcium influx should result in a better recovery from SCI. Calcium channel blockers have been shown a great potential in reducing brain and spinal cord injury. In this study, we first tested the neuroprotective effect of MVIIC on slices of spinal cord subjected to ischemia evaluating cell death and caspase-3 activation. Thereafter, we evaluated the efficacy of MVIIC in ameliorating damage following SCI in rats, for the first time in vivo. The spinal cord slices subjected a pretreatment with MVIIC showed a cell protection with a reduction of dead cells in 24.34% and of caspase-3-specific protease activation. In the in vivo experiment, Wistar rats were subjected to extradural compression of the spinal cord at the T12 vertebral level using a weigh of 70 g/cm, following intralesional treatment with either placebo or MVIIC in different doses (15, 30 and 60 pmol) five minutes after injury. Behavioral testing of hindlimb function was done using the Basso Beattie Bresnahan locomotor rating scale, and revealed significant recovery with 15 pmol (G15) compared to other trauma groups. Also, histological bladder structural revealed significant outcome in G15, with no morphological alterations, and anti-NeuN and TUNEL staining showed that G15 provided neuron preservation and indicated that this group had fewer neuron cell death, similar to sham. These results showed the neuroprotective effects of MVIIC in in vitro and in vivo model of SCI with neuronal integrity, bladder and behavioral improvements.

Brain MRI and magnetic resonance spectroscopy findings in patients with hyperargininemia.

BACKGROUND AND PURPOSE: Hyperargininemia (HA) is a rare autosomal recessive metabolic disorder and the neuroimaging features of this disease have seldom been reported. Hyperammonemic encephalopathy is uncommon in HA, and the clinical presentation of HA is distinct from other urea cycle disorders. This paper describes the brain MRI findings and a magnetic resonance spectroscopy (MRS) study of a series of Brazilian HA patients. METHODS: Brain MR images were obtained in eight male and two female patients with the classic HA phenotype. Six patients were evaluated twice. Single-voxel (1)H-MRS was also performed in six of the patients. RESULTS: Only 1 patient, with less severe neurological symptoms, had normal MRI images. A variable degree of cerebral atrophy was noted in the other patients, and 3 patients also presented mild symptoms of cerebellar atrophy. MRS indicated no metabolic abnormalities in any patient. CONCLUSIONS: We present the MRI and MRS findings of a large series of HA patients. Variable degrees of brain atrophy and mild cerebellar atrophy were observed, and these findings were not specific. No metabolic abnormality was observed using MRS in this series of patients.