RESUMO
Guillain-Barre syndrome (GBS) is an immune-mediated acute polyradiculoneuropathy and commonly occurs after a preceding infection or immunization sequalae. Following the severe acute respiratory syndrome-coronavirus-2 virus pandemic with co-introduction of massive vaccinations, several GBS cases associated with coronavirus disease 2019 (COVID-19) infection per se or after vaccination for COVID-19 were reported internationally. Herein, we report two cases of Korean GBS presenting with tetraplegia after two different COVID-19 vaccinations (42-year old man by AstraZeneca and 48-year woman by Pfizer vaccines) within four weeks after vaccination. The patients were diagnosed with clinical examination, serial electromyography, and compatible laboratory results and improved after comprehensive rehabilitative treatment and intravenous immunoglobulin therapy. Furthermore, we performed an electrodiagnostic follow-up study of each case to examine their unique characteristics.
Assuntos
Vacina BNT162/efeitos adversos , ChAdOx1 nCoV-19/efeitos adversos , Síndrome de Guillain-Barré/patologia , Quadriplegia/patologia , Vacinação/efeitos adversos , Adulto , Vacina BNT162/imunologia , COVID-19/prevenção & controle , ChAdOx1 nCoV-19/imunologia , Eletromiografia , Feminino , Síndrome de Guillain-Barré/reabilitação , Síndrome de Guillain-Barré/terapia , Humanos , Imunoglobulinas Intravenosas/uso terapêutico , Masculino , Pessoa de Meia-Idade , Quadriplegia/reabilitação , Quadriplegia/terapia , SARS-CoV-2/imunologiaRESUMO
CASE: A 55-year-old man undergoes posterior cervical decompression and instrumentation for progressive cervical myelopathy and develops white cord syndrome (WCS) postoperatively with acute tetraplegia. CONCLUSION: WCS is a rare complication of spinal surgery that is thought to be due to reperfusion injury. We diagnosed WCS in our patient through postoperative examination consisting of acute tetraplegia and magnetic resonance imaging revealing increased signal in the cord. In this case, we used intravenous dexamethasone and mean arterial pressure above 90 mm Hg resulting in markedly improved clinical examination.
Assuntos
Vértebras Cervicais , Doenças da Medula Espinal , Vértebras Cervicais/diagnóstico por imagem , Vértebras Cervicais/cirurgia , Descompressão/efeitos adversos , Humanos , Imageamento por Ressonância Magnética/métodos , Masculino , Pessoa de Meia-Idade , Quadriplegia/etiologia , Quadriplegia/patologiaRESUMO
The genetic etiology of intellectual disability remains elusive in almost half of all affected individuals. Within the Solve-RD consortium, systematic re-analysis of whole exome sequencing (WES) data from unresolved cases with (syndromic) intellectual disability (n = 1,472 probands) was performed. This re-analysis included variant calling of mitochondrial DNA (mtDNA) variants, although mtDNA is not specifically targeted in WES. We identified a functionally relevant mtDNA variant in MT-TL1 (NC_012920.1:m.3291T > C; NC_012920.1:n.62T > C), at a heteroplasmy level of 22% in whole blood, in a 23-year-old male with severe intellectual disability, epilepsy, episodic headaches with emesis, spastic tetraparesis, brain abnormalities, and feeding difficulties. Targeted validation in blood and urine supported pathogenicity, with heteroplasmy levels of 23% and 58% in index, and 4% and 17% in mother, respectively. Interestingly, not all phenotypic features observed in the index have been previously linked to this MT-TL1 variant, suggesting either broadening of the m.3291T > C-associated phenotype, or presence of a co-occurring disorder. Hence, our case highlights the importance of underappreciated mtDNA variants identifiable from WES data, especially for cases with atypical mitochondrial phenotypes and their relatives in the maternal line.
Assuntos
Epilepsia/genética , Deficiência Intelectual/genética , Quadriplegia/genética , RNA de Transferência de Leucina/genética , Epilepsia/patologia , Humanos , Deficiência Intelectual/patologia , Masculino , Mutação , Quadriplegia/patologia , Sequenciamento do Exoma , Adulto JovemRESUMO
Pathogenic variants in GEMIN4 contribute to a hereditary disorder characterized by neurodevelopmental features, microcephaly, cataracts, and renal abnormalities (known as NEDMCR). To date, only two homoallelic variations have been linked to the disease. Moreover, clinical features associated with the variants have not been fully elucidated yet. Here, we identified a novel variant in GEMIN4 (NM_015721:exon2:c.440A>G:p.His147Arg) in two siblings from a consanguineous Saudi family by using whole exome sequencing followed by Sanger sequence verification. We comprehensively investigated the patients' clinical features, including brain imaging and electroencephalogram findings, and compared their phenotypic characteristics with those of previously reported cases. In silico prediction and structural modeling support that the p.His147Arg variant is pathogenic.
Assuntos
Consanguinidade , Antígenos de Histocompatibilidade Menor/genética , Mutação , Transtornos do Neurodesenvolvimento/patologia , Fenótipo , Ribonucleoproteínas Nucleares Pequenas/genética , Catarata/complicações , Catarata/genética , Catarata/patologia , Criança , Epilepsia/complicações , Epilepsia/genética , Epilepsia/patologia , Feminino , Humanos , Lactente , Recém-Nascido , Masculino , Microcefalia/complicações , Microcefalia/genética , Microcefalia/patologia , Transtornos do Neurodesenvolvimento/complicações , Transtornos do Neurodesenvolvimento/genética , Linhagem , Quadriplegia/complicações , Quadriplegia/genética , Quadriplegia/patologia , Irmãos , Sequenciamento do ExomaRESUMO
Mutations in adaptor protein complex-4 (AP-4) genes have first been identified in 2009, causing a phenotype termed as AP-4 deficiency syndrome. Since then several patients with overlapping phenotypes, comprised of intellectual disability (ID) and spastic tetraplegia have been reported. To delineate the genotype-phenotype correlation of the AP-4 deficiency syndrome, we add the data from 30 affected individuals from 12 out of 640 Iranian families with ID in whom we detected disease-causing variants in AP-4 complex subunits, using next-generation sequencing. Furthermore, by comparing genotype-phenotype findings of those affected individuals with previously reported patients, we further refine the genotype-phenotype correlation in this syndrome. The most frequent reported clinical findings in the 101 cases consist of ID and/or global developmental delay (97%), speech disorders (92.1%), inability to walk (90.1%), spasticity (77.2%), and microcephaly (75.2%). Spastic tetraplegia has been reported in 72.3% of the investigated patients. The major brain imaging findings are abnormal corpus callosum morphology (63.4%) followed by ventriculomegaly (44.5%). Our result might suggest the AP-4 deficiency syndrome as a major differential diagnostic for unknown hereditary neurodegenerative disorders.
Assuntos
Complexo 4 de Proteínas Adaptadoras/genética , Estudos de Associação Genética , Deficiência Intelectual/genética , Quadriplegia/genética , Complexo 4 de Proteínas Adaptadoras/deficiência , Adolescente , Encéfalo/metabolismo , Encéfalo/patologia , Criança , Pré-Escolar , Estudos de Coortes , Corpo Caloso/diagnóstico por imagem , Corpo Caloso/patologia , Feminino , Humanos , Deficiência Intelectual/diagnóstico por imagem , Deficiência Intelectual/patologia , Irã (Geográfico)/epidemiologia , Masculino , Mutação/genética , Linhagem , Fenótipo , Quadriplegia/diagnóstico por imagem , Quadriplegia/patologiaRESUMO
INTRODUCTION: It is difficult to diagnose an acute abdomen condition in people with spinal cord injury due to abnormal sensation below the injured level and multiple co-morbidities. These issues can mislead the exact diagnosis and delay proper treatment. CASE PRESENTATION: A 57-year-old male with C4 AIS C tetraplegia developed nausea and vomiting, abdominal distension and feeding intolerance. Serum electrolytes indicated severe hyponatremia. A provisional diagnosis of pseudo-gut obstruction was made. After the failure of 48 h of conservative treatment with a nasogastric and rectal tube, abdominal CT was performed and revealed sigmoid volvulus. CONCLUSIONS: Due to the inconclusive clinical features and lack of subjective complaints, early use of CT scan or MRI is preferable in people with SCI who are suspected of an emergency intra-abdominal condition.
Assuntos
Colo Sigmoide/patologia , Volvo Intestinal/patologia , Quadriplegia/patologia , Doença Aguda/terapia , Colo Sigmoide/diagnóstico por imagem , Humanos , Volvo Intestinal/diagnóstico , Masculino , Pessoa de Meia-Idade , Tomografia Computadorizada por Raios X/métodosRESUMO
Context: GRASSP Version 1 (GV1) was developed in 2010, is an upper extremity measure specifically designed to assess recovery after traumatic tetraplegia. A second version was developed to reduce length of the test and refine instructions/standardization. The purpose of this post hoc analysis was to calculate psychometric properties of GRASSP Version 2 (GV2). Design/Setting: A post-hoc analysis of datasets for the GRASSP cross-sectional (n = 72 chronic,) and longitudinal (n = 127 acute) studies was conducted. Reliability, validity and MDD were calculated from the chronic sample and responsiveness was re-calculated from the longitudinal sample. Both studies were observational. Participants: A chronic sample (n = 72) and acute longitudinal sample (n = 127) of individuals with traumatic tetraplegia (AIS A to D, NLI C2 to C8) were studied. Outcome Measures: GV1, the Spinal Cord Independence Measure III (SCIM), International Standards of Neurological Classification of Spinal Cord Injury (ISNCSCI) were administered in both studies at all centers and the Capabilities of the Upper Extremity Questionnaire (CUE-Q) was administered in North American sites only. GRASSP-Palmar Sensation, GRASSP-Prehension Performance subtest items included in GV2 were re-analyzed for reliability; validity, MDD and responsiveness. Results: Inter-rater and test-retest reliability for all subtests ranged between 0.849-0.971 and 0.950-0.971 respectively. Concurrent validity between domains of GV2 were positively and moderately (0.530-0.830, P < 0.0001) correlated to SCIM, SCIM self-care subscore (SS) and CUE-Q. MDD values were 4 and 3 points for sensation and prehension performance (single side). Responsiveness values were .84-.88 for GR-Sens and .93-1.22 for GR-PP respectively. Conclusions: GV2 retains excellent psychometric properties as does GV1.
Assuntos
Força Muscular , Exame Neurológico/normas , Quadriplegia/reabilitação , Traumatismos da Medula Espinal/reabilitação , Adolescente , Adulto , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Avaliação de Resultados em Cuidados de Saúde/normas , Psicometria/normas , Quadriplegia/patologia , Recuperação de Função Fisiológica , Reprodutibilidade dos Testes , Traumatismos da Medula Espinal/patologia , Extremidade Superior/fisiopatologiaRESUMO
Purpose To investigate metabolic changes in chronic spinal cord injury (SCI) by applying MR spectroscopy in the cervical spinal cord. Materials and Methods Single-voxel short-echo spectroscopic data in study participants with chronic SCI and healthy control subjects were prospectively acquired in the cervical spinal cord at C2 above the level of injury between March 2016 and January 2017 and were compared between groups. Concentrations of total N-acetylaspartate (tNAA), myo-inositol (mI), total choline-containing compounds (tCho), creatine, and glutamine and glutamate complex were estimated from the acquired spectra. Participants were assessed with a comprehensive clinical evaluation investigating sensory and motor deficits. Correlation analysis was applied to investigate relationships between observed metabolic differences, lesion severity, and clinical outcome. Results There were 18 male study participants with chronic SCI (median age, 51 years; range, 30-68 years) and 11 male healthy control subjects (median age, 45 years; range, 30-67 years). At cervical level C2, tNAA/mI and tCho/mI ratios were lower in participants with SCI (tNAA/mI: -26%, P = .003; tCho/mI: -18%; P = .04) than in healthy control subjects. The magnitude of difference was greater with the severity of cord atrophy (tNAA/mI: R2 = 0.44, P = .003; tCho/mI: R2 = 0.166, P = .09). Smaller tissue bridges at the lesion site correlated with lower ratios of tNAA/mI (R2 = 0.69, P = .006) and tCho/mI (R2 = 0.51, P = .03) at the C2 level. Lower tNAA/mI and tCho/mI ratios were associated with worse sensory and motor outcomes (P < .05). Conclusion Supralesional metabolic alterations are observed in chronic spinal cord injury, likely reflecting neurodegeneration, demyelination, and astrocytic gliosis in the injured cervical cord. Lesion severity and greater clinical impairment are both linked to the biochemical changes in the atrophied cervical cord after spinal cord injury. © RSNA, 2019 Online supplemental material is available for this article. See also the editorial by Lin in this issue.
Assuntos
Vértebras Cervicais/patologia , Espectroscopia de Ressonância Magnética/métodos , Traumatismos da Medula Espinal/patologia , Adulto , Idoso , Atrofia/patologia , Estudos de Casos e Controles , Doença Crônica , Humanos , Espectroscopia de Ressonância Magnética/normas , Masculino , Pessoa de Meia-Idade , Paraplegia/patologia , Quadriplegia/patologiaRESUMO
Anatomical studies of spinal cord injury (SCI) using magnetic resonance imaging (MRI) report diverging observations, from "no changes" to "tissue atrophy in motor and non-motor regions." These discrepancies among studies can be attributed to heterogeneity in extent, level, and post-injury duration observed within the SCI population. But, no studies have investigated structural changes associated with different levels of injury (paraplegia vs. tetraplegia). High-resolution MRI images were processed using a voxel-based morphometry technique to compare regional gray matter volume (GMV) between 16 complete paraplegia and 7 complete tetraplegia SCI subjects scanned within 2 years of injury when compared to 22 age-matched healthy controls using one-way analysis of covariance (ANCOVA). A post-hoc analysis using a region of interest-based approach was utilized to quantify GMV differences between healthy controls and subgroups of SCI. A voxel-wise one-sample t-test was also performed to evaluate the mean effect of post-injury duration on GMV of the SCI group. ANCOVA resulted in altered GMV in inferior frontal gyrus, bilateral mid orbital gyrus extending to rectal gyrus, and anterior cingulate cortex. Post-hoc analysis, in general, indicated GM atrophy after SCI, but tetraplegia showed a greater decrease in GMV when compared to paraplegia and healthy controls. Further, the GMV of the middle frontal gyrus, superior frontal gyrus, inferior frontal gyrus, insula, mid-orbital gyrus, and middle temporal gyrus was positively correlated with post-injury duration in both paraplegia and tetraplegia groups. GM atrophy after SCI is affected by level of cord injury, with higher levels of injury resulting in greater loss of GMV. Magnitude of GMV loss in the frontal cortex after SCI also appears to be dynamic within the first 2 years of injury. Understanding the effect of injury level and injury duration on structural changes after SCI can help to better understand the mechanisms leading to positive and negative clinical outcome in SCI patients.
Assuntos
Córtex Cerebral/diagnóstico por imagem , Substância Cinzenta/diagnóstico por imagem , Imageamento por Ressonância Magnética/tendências , Paraplegia/diagnóstico por imagem , Quadriplegia/diagnóstico por imagem , Traumatismos da Medula Espinal/diagnóstico por imagem , Adulto , Atrofia , Córtex Cerebral/patologia , Feminino , Substância Cinzenta/patologia , Humanos , Masculino , Pessoa de Meia-Idade , Paraplegia/patologia , Quadriplegia/patologia , Traumatismos da Medula Espinal/patologiaRESUMO
OBJECTIVE/BACKGROUND: To assess frequency domain heart rate variability (HRV) parameters at rest and in response to postural autonomic provocations in individuals with spinal cord injury (SCI) and investigate the autonomic influences on the heart of different physical activities. DESIGN: Cross-sectional study. METHODS: Ten subjects with complete cervical SCI and fourteen subjects with complete low thoracic SCI were prospectively recruited from the community and further divided in sedentary and physically active groups, the latter defined as regular weekly 4 hour physical activity for the preceding 3 months. Sixteen healthy individuals matched for sex and age were recruited to participate in the control group. The Low Frequency (LF), High Frequency (HF) powers and the LF/HF ratio of HRV were measured from continuous electrocardiogram (ECG) recordings at rest and after sitting using a fast Fourier transformation. OUTCOME MEASURES: The LF,HF, and the LF/HF ratio at rest and after sitting. RESULTS: A significant decrease in all HRV parameters in patients with SCI was found compared to controls. The change in HF, LF and LF/HF following sitting maneuver was significantly greater in controls as compared with the SCI group and greater in subjects with paraplegia as compared to subjects with tetraplegia. Better HRV values and enhanced vagal activity appears to be related to the type of physical activity in active subjects with paraplegia. CONCLUSION: In this cohort of subjects spectral parameters of HRV were associated with the level of the injury. Passive standing was associated with higher HRV values in subjects with paraplegia.
Assuntos
Sistema Nervoso Autônomo/fisiopatologia , Exercício Físico/fisiologia , Frequência Cardíaca/fisiologia , Paraplegia/fisiopatologia , Quadriplegia/fisiopatologia , Traumatismos da Medula Espinal/fisiopatologia , Vértebras Torácicas/lesões , Adolescente , Adulto , Estudos Transversais , Eletrocardiografia , Humanos , Masculino , Pessoa de Meia-Idade , Paraplegia/etiologia , Paraplegia/patologia , Quadriplegia/etiologia , Quadriplegia/patologia , Traumatismos da Medula Espinal/complicações , Traumatismos da Medula Espinal/patologia , Adulto JovemRESUMO
STUDY DESIGN: Cross-sectional OBJECTIVE: To investigate the association between skeletal muscle mass and spasticity in people with spinal cord injury (SCI). SETTING: Tertiary level hospital in Seoul, Korea METHODS: Spasticity was evaluated in 69 participants with SCI using the spasticity sum score (SSS), Penn Spasm Frequency Scale (PSFS), and Spinal Cord Assessment Tool for Spastic Reflexes (SCATS). Skeletal muscle mass was measured using a dual-energy X-ray absorptiometry scanner, and skeletal muscle index was calculated by dividing skeletal muscle mass by height squared. Laboratory parameters including hemoglobin, albumin, creatinine, fasting glucose, and cholesterol were measured. Spearman's correlation analysis was performed to assess the association between the skeletal muscle mass and spasticity scales. Multiple linear regression analysis was used to present the independent association between them. RESULTS: The participants' mean age was 41.8 years; 54 (78.3%) were male, and 46 (66.7%) were tetraplegic. Skeletal muscle index of lower extremities was significantly correlated with all spasticity scales. Spearman's correlation coefficients were 0.468, 0.467, 0.555, 0.506, and 0.474 for SSS, PSFS, SCATS clonus, SCATS flexor, and SCATS extensor with p-values < 0.001, respectively. After adjustment for age, sex, level of injury, body mass index, and serum creatinine, all spasticity scales were significantly associated with skeletal muscle index of lower extremities in multiple regression analysis. Standardized coefficients were 0.228, 0.274, 0.294, 0.210, and 0.227 for SSS, PSFS, SCATS clonus, SCATS flexor, and SCATS extensor. CONCLUSIONS: Spasticity was significantly correlated with the skeletal muscle mass even after adjusting for possible confounders. Spasticity may need to be considered as an influencing factor in interventions such as electrical stimulation to preserve skeletal muscle mass.
Assuntos
Espasticidade Muscular/complicações , Espasticidade Muscular/diagnóstico por imagem , Músculo Esquelético/diagnóstico por imagem , Traumatismos da Medula Espinal/complicações , Traumatismos da Medula Espinal/diagnóstico por imagem , Adulto , Estudos Transversais , Feminino , Humanos , Extremidade Inferior/diagnóstico por imagem , Extremidade Inferior/patologia , Masculino , Espasticidade Muscular/patologia , Espasticidade Muscular/fisiopatologia , Músculo Esquelético/patologia , Tamanho do Órgão , Paraplegia/diagnóstico por imagem , Paraplegia/etiologia , Paraplegia/patologia , Paraplegia/fisiopatologia , Quadriplegia/diagnóstico por imagem , Quadriplegia/etiologia , Quadriplegia/patologia , Quadriplegia/fisiopatologia , Índice de Gravidade de Doença , Traumatismos da Medula Espinal/patologia , Traumatismos da Medula Espinal/fisiopatologiaRESUMO
Angiostrongylus cantonensis is the most common cause of eosinophilic meningitis worldwide. Infection typically occurs through ingestion of undercooked molluscs or vegetables contaminated by infective larvae. Endemic regions were previously limited to southeast Asia and the Pacific basin; however, this parasite is seeing an alarming increase in global distribution with reported cases in more than 30 countries, including several states in the USA. Although infection typically results in meningitis, a broad spectrum of CNS involvement and severity is emerging as diagnostic methods (such as real-time PCR) continue to improve diagnosis. In this Grand Round, we report a case of a 20-year-old active duty US marine serving in Okinawa, Japan, afflicted with severe CNS angiostrongyliasis marked by radiculomyelitis with quadriparesis, hyperaesthesia, and urinary retention. We present this case to highlight that no clear guidelines exist for the treatment of severe CNS angiostrongyliasis and provide our consensus recommendation that treatment algorithms include use of dual corticosteroids plus anthelmintics when radicular symptoms are present. In this Grand Round we review the clinical features, epidemiology, advances to diagnostic techniques, and available data on current treatment options for CNS angiostrongyliasis. This diagnosis should be highly considered in the differential diagnosis of a patient presenting with meningeal symptoms, paraesthesia or hyperaesthesia, and CSF eosinophilia so that treatment can be started early, which is particularly important in children, because of their increased risk of severe disease and mortality. We recommend combined therapy with albendazole and prednisolone, with consideration for increased steroid dosing in severe cases.
Assuntos
Eosinofilia/diagnóstico , Hiperestesia/diagnóstico , Meningite/diagnóstico , Quadriplegia/diagnóstico , Infecções por Strongylida/diagnóstico , Retenção Urinária/diagnóstico , Corticosteroides/uso terapêutico , Albendazol/uso terapêutico , Angiostrongylus cantonensis/efeitos dos fármacos , Angiostrongylus cantonensis/patogenicidade , Angiostrongylus cantonensis/fisiologia , Animais , Anti-Helmínticos/uso terapêutico , Diagnóstico Diferencial , Eosinofilia/tratamento farmacológico , Eosinofilia/parasitologia , Eosinofilia/patologia , Humanos , Hiperestesia/tratamento farmacológico , Hiperestesia/parasitologia , Hiperestesia/patologia , Imageamento por Ressonância Magnética , Masculino , Meningite/tratamento farmacológico , Meningite/parasitologia , Meningite/patologia , Prednisolona/uso terapêutico , Quadriplegia/tratamento farmacológico , Quadriplegia/parasitologia , Quadriplegia/patologia , Índice de Gravidade de Doença , Infecções por Strongylida/tratamento farmacológico , Infecções por Strongylida/parasitologia , Infecções por Strongylida/patologia , Retenção Urinária/tratamento farmacológico , Retenção Urinária/parasitologia , Retenção Urinária/patologia , Adulto JovemRESUMO
Mutations in the WWOX gene have been reported in a number of patients with various neurological disorders including spino-cerebellar ataxia, intellectual disability, epilepsy, and epileptic encephalopathy. We aimed to study the clinical, electrographic, and imaging features of two new cases with WWOX mutations and compare them to previously reported cases with WWOX mutations. We assessed two unrelated children from two consanguineous families who had severe neurological disorder including early-onset spastic quadriplegia, profound developmental delay, epilepsy, and West syndrome. Based on whole-exome sequencing, we identified homozygous null mutations in WWOX in both children, and further addressed the genotype-phenotype correlation. In addition, we provide a detailed review of the previously reported cases of WWOX-related neurological disorders and compare them to the children in this report. The findings in this report expand the clinical phenotype associated with WWOX mutations and confirm a well characterised severe central nervous system disorder in association with biallelic null mutations in WWOX. This syndrome consists of profound psychomotor delay, early-onset spastic quadriplegia, and refractory epilepsy including epileptic encephalopathy, acquired microcephaly, and growth restriction. This can be associated with progressive brain atrophy, suggestive of neurodegeneration. Identification of this phenotype by clinicians may help with early diagnosis and appropriate genetic counselling.
Assuntos
Deficiências do Desenvolvimento , Mutação/genética , Quadriplegia , Proteínas Supressoras de Tumor/genética , Oxidorredutase com Domínios WW/genética , Pré-Escolar , Consanguinidade , Deficiências do Desenvolvimento/genética , Deficiências do Desenvolvimento/patologia , Deficiências do Desenvolvimento/fisiopatologia , Humanos , Lactente , Masculino , Quadriplegia/genética , Quadriplegia/patologia , Quadriplegia/fisiopatologia , Espasmos Infantis/genética , Espasmos Infantis/patologia , Espasmos Infantis/fisiopatologiaRESUMO
The advancement in genomic sequencing has greatly improved the diagnostic yield for neurodevelopmental disorders and led to the discovery of large number of novel genes associated with these disorders. WDR45B has been identified as a potential intellectual disability gene through genomic sequencing of 2 large cohorts of affected individuals. In this report we present 6 individuals from 3 unrelated families with homozygous pathogenic variants in WDR45B: c.799C>T (p.Q267*) in 1 family and c.673C>T (p.R225*) in 2 families. These individuals shared a similar phenotype including profound development delay, early-onset refractory epilepsy, progressive spastic quadriplegia and contractures, and brain malformations. Neuroimaging showed ventriculomegaly, reduced cerebral white matter volume, and thinning of cerebral gray matter. The consistency in the phenotype strongly supports that WDR45B is associated with this disease.
Assuntos
Proteínas Adaptadoras de Transdução de Sinal/genética , Predisposição Genética para Doença , Deficiência Intelectual/genética , Transtornos do Neurodesenvolvimento/genética , Adolescente , Criança , Pré-Escolar , Epilepsia/genética , Epilepsia/patologia , Feminino , Homozigoto , Humanos , Lactente , Deficiência Intelectual/patologia , Masculino , Mutação , Transtornos do Neurodesenvolvimento/patologia , Quadriplegia/genética , Quadriplegia/patologiaRESUMO
We ascertained two unrelated consanguineous families with two affected children each having microcephaly, refractory seizures, intellectual disability, and spastic quadriparesis. Magnetic resonance imaging showed atrophy of cerebrum, cerebellum and spinal cord, prominent cisterna magna, symmetric T2 hypo-intensities in the bilateral basal ganglia and thinning of corpus callosum. Whole-exome sequencing of three affected individuals revealed c.105C>A [p.(Tyr35Ter)] variant in AIMP2. The variant lies in a common homozygous region of 940 kb on chromosome 7 and is likely to have been inherited from a common ancestor. The phenotype noted in our subjects' shares marked similarity with that of hypomyelinating leukodystrophy-3 caused by mutations in closely related gene AIMP1. We hereby report the first human disease associated with deleterious mutations in AIMP2.
Assuntos
Códon sem Sentido , Doenças Genéticas Inatas/genética , Homozigoto , Microcefalia/genética , Transtornos do Neurodesenvolvimento/genética , Proteínas Nucleares/genética , Quadriplegia/genética , Convulsões/genética , Criança , Cromossomos Humanos Par 7/genética , Exoma , Feminino , Doenças Genéticas Inatas/patologia , Humanos , Microcefalia/patologia , Transtornos do Neurodesenvolvimento/patologia , Quadriplegia/patologia , Convulsões/patologiaRESUMO
Mutations in human MPV17 have been reported in patients with severe mitochondrial DNA (mtDNA) depletion manifesting as early childhood onset failure to thrive, hypoglycemia, encephalopathy and progressive liver failure. We describe an 11 year old girl, born to consanguineous parents, who presented with rapidly progressive weakness of all 4 limbs with symmetrical proximal and distal weakness, gastrointestinal disease and leukoencephalopathy. Genetic analysis of the patient revealed a homozygous pathogenic mutation c.121C>T (p.R41W) in the MPV17 gene. Further, screening for this mutation in the parents revealed the presence of heterozygous mutation in both the parents, suggesting the recessive nature of the disease.
Assuntos
Proteínas de Membrana/genética , Doenças Mitocondriais/diagnóstico por imagem , Doenças Mitocondriais/patologia , Proteínas Mitocondriais/genética , Quadriplegia/etiologia , Quadriplegia/patologia , Criança , Feminino , Gastroenteropatias/etiologia , Gastroenteropatias/patologia , Humanos , Leucoencefalopatias/etiologia , Leucoencefalopatias/patologia , Proteínas Mutantes/genética , Mutação PuntualRESUMO
We describe the clinical and whole genome sequencing (WGS) study of a non-consanguineous Italian family in which two siblings, a boy and a girl, manifesting a severe epileptic encephalopathy (EE) with skeletal abnormalities, carried novel SLC35A3 compound heterozygous mutations. Both siblings exhibited infantile spasms, associated with focal, and tonic vibratory seizures from early infancy. EEG recordings showed a suppression-burst (SB) pattern and multifocal paroxysmal activity in both. In addition both had quadriplegia, acquired microcephaly, and severe intellectual disability. General examination showed distal arthrogryposis predominant in the hands in both siblings and severe left dorso-lumbar convex scoliosis in one. WGS of the siblings-parents quartet identified novel compound heterozygous mutations in SLC35A3 in both children. SLC35A3 encodes the major Golgi uridine diphosphate N-acetylglucosamine transporter. With this study, we add SLC35A3 to the gene list of epilepsies. Neurological symptoms and skeletal abnormalities might result from impaired glycosylation of proteins involved in normal development and function of the central nervous system and skeletal apparatus.
Assuntos
Artrogripose/genética , Deficiência Intelectual/genética , Microcefalia/genética , Mutação , Proteínas de Transporte de Nucleotídeos/genética , Quadriplegia/genética , Espasmos Infantis/genética , Artrogripose/diagnóstico , Artrogripose/patologia , Osso e Ossos/anormalidades , Criança , Eletroencefalografia , Feminino , Expressão Gênica , Glicosilação , Heterozigoto , Humanos , Deficiência Intelectual/diagnóstico , Deficiência Intelectual/patologia , Masculino , Microcefalia/diagnóstico , Microcefalia/patologia , Quadriplegia/diagnóstico , Quadriplegia/patologia , Irmãos , Espasmos Infantis/diagnóstico , Espasmos Infantis/patologiaRESUMO
CONTEXT: Patients with complete quadriplegia after high cervical spinal cord injury are fully dependent with activities of daily living. Assistive technology can improve their quality of life. We examined the use of a hybrid assistive limb for single joints (HAL-SJ) in a 19-year-old man with complete C4 quadriplegia due to chronic spinal cord injury to restore function of active elbow flexion. This is the first report on the use of the HAL-SJ in a patient with spinal cord injury. FINDINGS: The HAL-SJ intervention for each elbow was administered in 10 sessions. Clinical assessment using surface EMG was conducted to evaluate muscle activity of the trapezius, biceps brachii, infraspinatus, and triceps brachii muscle before, and during the 2nd, 3rd, 6th, and 9th interventions. Surface electromyography (EMG) before intervention showed no contraction in the upper arms, but in the bilateral trapezius. The HAL-SJ used motion intention from the right trapezius for activation. After the 6th and 7th session, respectively, biceps EMG showed that voluntary contraction and right elbow flexion could be performed by motion intention from the right biceps. After the 10th session, voluntary bicep contraction was possible. HAL-SJ treatment on the left elbow was performed using the same protocol with a similar outcome. After completing treatment on both upper extremities, both biceps contracted voluntarily, and he could operate a standard wheelchair for a short distance independently. CONCLUSION: HAL-SJ intervention is feasible and effective in restoring elbow flexor function in a patient with C4 chronic spinal cord injury and complete quadriplegia.
Assuntos
Cotovelo/fisiopatologia , Terapia Passiva Contínua de Movimento/instrumentação , Contração Muscular , Reabilitação Neurológica/instrumentação , Quadriplegia/reabilitação , Humanos , Masculino , Terapia Passiva Contínua de Movimento/métodos , Músculo Esquelético/fisiopatologia , Reabilitação Neurológica/métodos , Quadriplegia/patologia , Quadriplegia/terapia , Adulto JovemRESUMO
Chikungunya virus (CHIKV) is a mosquito-borne alphavirus which presents with symptoms of fever, rash, arthralgia, and occasional neurologic disease. While outbreaks have been earlier reported from India and other parts of the world, the recent outbreak in India witnessed more than 1000 cases. Various systemic and rarely neurological complications have been reported with CHIKV. We report two cases of Guillain-Barré syndrome (GBS) with CHIKV. GBS is a rare neurological complication which may occur after subsidence of fever and constitutional symptoms by several neurotropic viruses. We describe two cases of severe GBS which presented with rapidly progressive flaccid quadriparesis progressing to difficulty in swallowing and breathing. Both required mechanical ventilation and improved partly with plasmapharesis. The cases emphasize on (1) description of the rare complication in a setting of outbreak with CHIKV, (2) acute axonal as well as demyelinating neuropathy may occur with CHIKV, (3) accurate identification of this entity during outbreaks with dengue, both of which are vector borne and may present with similar complications.