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Introduction: Diencephalic-mesencephalic junction dysplasia syndrome is a rare neurogenetic disorder reported to be caused by variants in several genes. Phenotypic presentation is characterized by clinical findings including developmental delay, hypotonia, spasticity, and dyskinetic movements in combination with distinctive imaging features on brain magnetic resonance imaging (MRI). Methods: Whole exome sequencing was conducted to unveil the molecular etiology of patients presenting with neurological manifestations from two unrelated families. Results: To the best of our knowledge, here we report the third family affected with diencephalic-mesencephalic junction dysplasia caused by a novel variant in GSX2 and two siblings with a PCDH12 variant exhibiting a less severe phenotype. The siblings with a PCDH12 variant were positioned at the milder end of the phenotypic spectrum. Although both exhibited a clinical phenotype resembling cerebral palsy, one showed partial fusion of the hypothalamus and mesencephalon, whereas MRI was unremarkable in the other. Biallelic GSX2 variants have been implicated in basal ganglia agenesis, and similarly, our patients had basal ganglia hypoplasia along with hypothalamic-mesencephalic fusion. Conclusion: Identifying variants associated with the syndrome in different genes will contribute to genotype-phenotype correlation.
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OBJECTIVE: Horizontal gaze palsy with progressive scoliosis (HGPPS) is a rare, autosomal recessive disorder resulting from axonal midline crossing defect due to variants in ROBO3. METHODS: We retrospectively evaluated demographics, clinical phenotype, course of spinal deformities, and neuroimaging findings of six Turkish patients with HGPPS. We performed targeted gene testing by next-generation sequencing. RESULTS: The median age at symptom onset and diagnosis was 1.5 years (0.5-4), and 11 years (2-16), respectively. Oculomotor signs were the most common presenting symptom (n = 4), followed by scoliosis (n = 2). The course of scoliosis was progressive and accompanied by kyphosis, showed intrafamilial variability, and was corrected surgically in three of the patients. Intellectual disability (n = 4), hypergonadotropic hypogonadism (n = 2), hearing loss (n = 2), and tranisent movement disorders (n = 1) were additional features. Targeted gene sequencing revealed five distinct homozygous variants. Of the four novel variants, two of them were located in the acceptor site of the noncoding region of the gene, remaining two were missense and frameshift variants, located in immunoglobulin-like domain-2, and cytoplasmic signaling motif 2, respectively. Structural magnetic resonance imaging (MRI) and diffusion tensor imaging (DTI) showed the absence of decussation of superior cerebellar peduncle and dorsal transverse pontine fibers. INTERPRETATION: Spectrum of HGPPS is further expanded with novel variants in the ROBO3 with clinical and radiological fingerprints. Spinal deformities require close orthopedic screening and individualized approach. Intellectual disability and hearing loss emerge as additional features. Hypogonadism and transient subtle movement disorders require further attention and confirmation from other series.
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Receptores de Superfície Celular , Escoliose , Humanos , Escoliose/genética , Escoliose/diagnóstico por imagem , Masculino , Feminino , Criança , Adolescente , Pré-Escolar , Estudos Retrospectivos , Receptores de Superfície Celular/genética , Oftalmoplegia Externa Progressiva Crônica/genética , Receptores Imunológicos/genética , Lactente , Fenótipo , Transtornos Congênitos de Denervação Craniana , Proteínas RoundaboutRESUMO
Proline-5-carboxylate reductase 2, encoded by PYCR2 gene, is an enzyme that catalyzes the last step of proline synthesis from pyrroline-5-carboxylate synthetase to proline. PYCR2 gene defect causes hypomyelinating leukodystrophy 10. Up until now, to our knowledge around 38 patients with PYCR2 defect have been reported. Herein, we describe clinical, neuroradiological, biochemical findings, and metabolomic profiling of three new genetically related cases of PYCR2 defects from a large family. Cerebrospinal fluid (CSF) amino acid levels were measured and untargeted metabolomic profiling of plasma and CSF were conducted and evaluated together with the clinical findings in the patients. While plasma and CSF proline levels were found to be totally normal, untargeted metabolomic profiling revealed mild increases of glutamate, alpha-ketoglutarate, and l-glutamate semialdehyde and marked increases of inosine and xanthine. Our findings and all the previous reports suggest that proline auxotrophy is not the central disease mechanism. Untargeted metabolomics point to mild changes in proline pathway and also in purine/pyrimidine pathway.
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Doenças Desmielinizantes Hereditárias do Sistema Nervoso Central , Metabolômica , Prolina , Pirrolina Carboxilato Redutases , Criança , Feminino , Humanos , Masculino , delta-1-Pirrolina-5-Carboxilato Redutase , Ácido Glutâmico/metabolismo , Doenças Desmielinizantes Hereditárias do Sistema Nervoso Central/genética , Doenças Desmielinizantes Hereditárias do Sistema Nervoso Central/patologia , Doenças Desmielinizantes Hereditárias do Sistema Nervoso Central/diagnóstico , Ácidos Cetoglutáricos/metabolismo , Ácidos Cetoglutáricos/sangue , Imageamento por Ressonância Magnética , Redes e Vias Metabólicas/genética , Metaboloma/genética , Metabolômica/métodos , Mutação/genética , Linhagem , Prolina/líquido cefalorraquidiano , Purinas/metabolismo , Pirimidinas , Pirrolina Carboxilato Redutases/genética , Pirrolina Carboxilato Redutases/deficiência , Xantina/sangue , LactenteRESUMO
ADPRHL2 is involved in posttranslational modification and is known to have a role in physiological functions such as cell signaling, DNA repair, gene control, cell death, and response to stress. Recently, a group of neurological disorders due to ADPRHL2 variants is described, characterized by childhood-onset, stress-induced variable movement disorders, neuropathy, seizures, and neurodegenerative course. We present the diagnostic pathway of two pediatric patients with episodic dystonia and ataxia, who later had a neurodegenerative course complicated by central hypoventilation syndrome due to the same homozygous ADPRHL2 variant. We conducted a systematic literature search and data extraction procedure following the Preferred Reporting Items for Systematic Review and Meta-Analysis 2020 statement in terms of patients with ADPRHL2 variants, from 2018 up to 3 February, 2023. In total, 12 articles describing 47 patients were included in the final analysis. Median age at symptom onset was 2 (0.7-25) years, with the most common presenting symptoms being gait problems (n = 19, 40.4%), seizures (n = 16, 34%), ataxia (n = 13, 27.6%), and weakness (n = 10, 21.2%). Triggering factors (28/47; 59.5%) and regression (28/43; 60.4%), axonal polyneuropathy (9/23; 39.1%), and cerebral and cerebellar atrophy with white matter changes (28/36; 77.7%) were the other clues. The fatality rate and median age of death were 44.6% (n = 21) and 7 (2-34) years, respectively. ADPRHL2 variants should be considered in the context of episodic, stress-induced pediatric and adult-onset movement disorders and seizures.
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Ataxia , Humanos , Masculino , Criança , Feminino , Pré-Escolar , Adolescente , Adulto Jovem , Ataxia/genética , Ataxia/fisiopatologia , Adulto , Lactente , Hipoventilação/genética , Hipoventilação/diagnósticoRESUMO
OBJECTIVE: To evaluate clinical characteristics and long-term outcomes in patients with guanidinoacetate methyltransferase (GAMT) deficiency with a special emphasis on seizures and electroencephalography (EEG) findings. METHODS: We retrospectively analyzed the clinical and molecular characteristics, seizure types, EEG findings, neuroimaging features, clinical severity scores, and treatment outcomes in six patients diagnosed with GAMT deficiency. RESULTS: Median age at presentation and diagnosis were 11.5 months (8-12 months) and 63 months (18 months -11 years), respectively. Median duration of follow-up was 14 years. Global developmental delay (6/6) and seizures (5/6) were the most common symptoms. Four patients presented with febrile seizures. The age at seizure-onset ranged between 8 months and 4 years. Most common seizure types were generalized tonic seizures (n = 4) and motor seizures resulting in drop attacks (n = 3). Slow background activity (n = 5) and generalized irregular sharp and slow waves (n = 3) were the most common EEG findings. Burst-suppression and electrical status epilepticus during slow-wave sleep (ESES) pattern was present in one patient. Three of six patients had drug-resistant epilepsy. Post-treatment clinical severity scores showed improvement regarding movement disorders and epilepsy. All patients were seizure-free in the follow-up. CONCLUSIONS: Epilepsy is one of the main symptoms in GAMT deficiency with various seizure types and non-specific EEG findings. Early diagnosis and initiation of treatment are crucial for better seizure and cognitive outcomes. This long-term follow up study highlights to include cerebral creatine deficiency syndromes in the differential diagnosis of patients with global developmental delay and epilepsy and describes the course under treatment.
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Eletroencefalografia , Guanidinoacetato N-Metiltransferase/deficiência , Transtornos do Desenvolvimento da Linguagem , Transtornos dos Movimentos/congênito , Humanos , Masculino , Feminino , Pré-Escolar , Lactente , Criança , Estudos Retrospectivos , Convulsões/diagnóstico , Convulsões/fisiopatologia , Convulsões/etiologia , Convulsões/tratamento farmacológico , Transtornos dos Movimentos/diagnóstico , Seguimentos , Deficiências do Desenvolvimento/etiologiaRESUMO
The importance of Carotid Artery Perivascular Adipose Tissue Density (CAPATd), a parameter that can be readily evaluated on emergency computed tomographic angiography (CTA), in acute stroke has not been adequately clarified. We created exploratory logistic regression models to detect the interaction between the effect of CAPATd and intravenous (IV) tissue plasminogen activator (tPA) in 174 patients (mean age 71 ± 14 years, 94 women) with acute ischemic stroke treated with IV-tPA alone. The CAPATd-average mean (-60.6 ± 18.7 vs -89.8 ± 25.3 Hounsfield units (HU), P = .002) and CAPATd-maximum (14.8 ± 68.9 vs -20.5 ± 39.8 HU, P = .020) values were higher on the ipsilateral side of carotid artery stenosis >60%. CAPATd-maximum ipsilateral emerged as an independent predictor for both modified Rankin's Score 0-2 (52%) [exp(ß) = .984] and mRS 0-1 outcome (32%) [exp(ß) = .828] in addition to admission National Institutes of Health Stroke Scale, age and carotid plaque burden. CAPATd-maximum ipsilateral was acceptably accurate (Area under the Receiver operating characteristic Curve was .607, P = .0109 for mRS 0-2 and .613, P = .0102 for mRS 0-1). Ipsilateral CAPATd ≥ -25 HU predicted both mRS >3 and mRS >2 with usable sensitivity (59.8% and 66.07%) and specificity (63.6% and 59.68%). In conclusion, higher maximum CAPATd measured on emergency CTA indicates poorer functional prognosis in acute stroke patients treated with IV-tPA.
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Isquemia Encefálica , AVC Isquêmico , Acidente Vascular Cerebral , Humanos , Feminino , Pessoa de Meia-Idade , Idoso , Idoso de 80 Anos ou mais , Ativador de Plasminogênio Tecidual/uso terapêutico , Fibrinolíticos/uso terapêutico , Resultado do Tratamento , Acidente Vascular Cerebral/diagnóstico por imagem , Acidente Vascular Cerebral/tratamento farmacológico , Artérias Carótidas , Estudos Retrospectivos , Isquemia Encefálica/diagnóstico por imagem , Isquemia Encefálica/tratamento farmacológicoRESUMO
Sarcoidosis is a granulomatous inflammatory disease of uncertain cause. It occurs most commonly in young and middle-aged adults and less frequently in children; therefore, few data on pediatric sarcoidosis exist in the literature. The diagnosis and management of sarcoidosis remain challenging because of diverse and often nonspecific clinical and imaging findings. In addition, the clinical picture varies widely by age. Prepubertal and adolescent patients often present with adult-like pulmonary disease; however, early-onset sarcoidosis is typically characterized by the triad of arthritis, uveitis, and skin rash. Sarcoidosis is mostly a diagnosis of exclusion made by demonstrating noncaseating granulomas at histopathologic examination in patients with compatible clinical and radiologic findings. Although sarcoidosis often affects the lungs and thoracic lymph nodes, it can involve almost any organ in the body. The most common radiologic manifestation is pulmonary involvement, characterized by mediastinal and bilateral symmetric hilar lymphadenopathies with perilymphatic micronodules. Abdominal involvement is also common in children and often manifests as hepatomegaly, splenomegaly, and abdominal lymph node enlargement. Although neurosarcoidosis and cardiac sarcoidosis are rare, imaging is essential to the diagnosis of central nervous system and cardiac involvement because of the risky biopsy procedure and its low diagnostic yield due to focal involvement. Being familiar with the spectrum of imaging findings of sarcoidosis may aid in appropriate diagnosis and management. ©RSNA, 2023 Test Your Knowledge questions are available in the supplemental material.
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Sarcoidose , Adulto , Pessoa de Meia-Idade , Adolescente , Humanos , Criança , Sarcoidose/diagnóstico por imagem , Sarcoidose/patologia , Granuloma/patologia , Biópsia , Pulmão , Tomografia Computadorizada por Raios X/métodosRESUMO
OBJECTIVES: The aim of this study was to examine whether cervical stabilization exercises (CSEs) change the effects of conventional exercises (CEs) in patients with PD. METHODS: Twenty-five patients with PD were randomized into two groups. While the experimental group (EG) received CSEs in addition to CEs, the control group (CG) received only CEs. Both programs lasted 8 weeks. Eighteen participants were able to complete the study. The outcomes were the changes in posture, cervical joint position sense (JPS), balance assessment, 10-m walking tests (10MWT), and the Timed Up & Go (TUG) test. RESULTS: At the end of the study, significant improvement was observed in both groups in terms of trunk rotation angle and pelvic asymmetry, the time parameter of TUG, and the 10MWT (p < 0.05). In the EG, greater improvement was detected in the Berg Balance Scale, static posturography, postural alignment, JPS, and the cadence parameter of TUG (p < 0.05). DISCUSSION: CEs and CSEs could improve walking speed and posture in patients with PD, but if CSEs are added to CEs, greater improvements could be achieved in JPS and postural control.(Clinical Trials ID: NCT03854747).
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Doença de Parkinson , Humanos , Doença de Parkinson/terapia , Terapia por Exercício , Exercício Físico , Equilíbrio Postural , PosturaRESUMO
OBJECTIVE: Our understanding of IgG4-RD and pachymeningitis has grown substantially, but the optimal approach for diagnosis, management, and long-term outcomes is still an area of uncertainty. METHODS: HUVAC is a database for IgG4-RD patients, this database was retrospectively evaluated for pachymeningeal disease. Demographic, clinical, serological, imaging, histopathological data, and treatment details were re-interpreted in patients with pachymeningitis. RESULTS: Among 97 patients with IgG4-RD, 6 (6.2%) had pachymeningitis. None of these patients had extracranial features, and also, in most of the patients, serum IgG4 levels were normal. Tentorium cerebelli and transverse sinus dura were the most commonly involved in the posterior fossa. During 18 months of median follow-up on steroid+-rituximab, none of them relapsed as pachymeningitis. CONCLUSION: Our patients were mainly older males with sole neurological involvement. Non-specific headache was the most common manifestation, and serum IgG4 levels were not useful for diagnosis. Typical radiology and tentorial thickening should suggest IgG4-RD and prompt an early biopsy. Moreover, accompanying hypophysitis could also be a clue. With steroids+ rituximab treatment, no relapse related to meningeal involvement was seen in long-term follow-up.
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Doença Relacionada a Imunoglobulina G4 , Meningite , Masculino , Humanos , Imunoglobulina G , Doença Relacionada a Imunoglobulina G4/diagnóstico , Doença Relacionada a Imunoglobulina G4/tratamento farmacológico , Doença Relacionada a Imunoglobulina G4/patologia , Seguimentos , Rituximab/uso terapêutico , Estudos Retrospectivos , Meningite/diagnóstico por imagem , Meningite/tratamento farmacológicoRESUMO
INTRODUCTION: Bevacizumab is a monoclonal antibody for the vascular endothelial growth factor receptor and is utilized in the treatment of various tumors. Gastrointestinal perforation/fistula, heart failure, hemorrhage, hypertension, proteinuria/nephrotic syndrome, thromboembolism, posterior reversible encephalopathy syndrome, and necrotizing fasciitis are serious side effects of bevacizumab. Bevacizumab associated de novo brain arterio-venous malformation formation has not been documented in the literature. CASE REPORT: Here, we presented a 35-year-old female patient with recurrent high-grade glial tumor who developed multiple supra- and infratentorial de novo arterio-venous malformations after receiving the last dose of bevacizumab. MANAGEMENT & OUTCOME: Intervention options for the adverse effect were limited. In fact, there was no chance of intervention because the patient died for another reason. DISCUSSION: Based on this experience, it can be hypothesized that bevacizumab may induce de novo arterio-venous malformations in the brain as a result of arterial and venous thrombotic effects. Additional studies should be done to clarify the causal relationship between bevacizumab and arterio-venous malformations in primary brain tumors.
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BACKGROUND: Leukocyte and platelet integrin function defects are present in leukocyte adhesion deficiency type III (LAD-III) due to mutations in FERMT3. Additionally, osteoclast/osteoblast dysfunction develops in LAD-III. AIM: To discuss the distinguishing clinical, radiological, and laboratory features of LAD-III. METHODS: This study included the clinical, radiological, and laboratory characteristics of twelve LAD-III patients. RESULTS: The male/female ratio was 8/4. The parental consanguinity ratio was 100%. Half of the patients had a family history of patients with similar findings. The median age at presentation and diagnosis was 18 (1-60) days and 6 (1-20) months, respectively. The median leukocyte count on admission was 43,150 (30,900-75,700)/µL. The absolute eosinophil count was tested in 8/12 patients, and eosinophilia was found in 6/8 (75%). All patients had a history of sepsis. Other severe infections were pneumonia (66.6%), omphalitis (25%), osteomyelitis (16.6%), gingivitis/periodontitis (16%), chorioretinitis (8.3%), otitis media (8.3%), diarrhea (8.3%), and palpebral conjunctiva infection (8.3%). Four patients (33.3%) received hematopoietic stem cell transplantation (HSCT) from HLA-matched-related donors, and one deceased after HSCT. At initial presentation, 4 (33.3%) patients were diagnosed with other hematologic disorders, three patients (P5, P7, and P8) with juvenile myelomonocytic leukemia (JMML), and one (P2) with myelodysplastic syndrome (MDS). CONCLUSION: In LAD-III, leukocytosis, eosinophilia, and bone marrow findings may mimic pathologies such as JMML and MDS. In addition to non-purulent infection susceptibility, patients with LAD-III exhibit Glanzmann-type bleeding disorder. In LAD-III, absent integrin activation due to kindlin-3 deficiency disrupts osteoclast actin cytoskeleton organization. This results in defective bone resorption and osteopetrosis-like radiological changes. These are distinctive features compared to other LAD types.
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Síndrome da Aderência Leucocítica Deficitária , Osteopetrose , Humanos , Masculino , Feminino , Osteopetrose/diagnóstico , Osteopetrose/genética , Síndrome da Aderência Leucocítica Deficitária/diagnóstico , Síndrome da Aderência Leucocítica Deficitária/genética , Integrinas/fisiologia , Leucócitos/metabolismo , Leucócitos/patologiaRESUMO
OBJECTIVE: The nature of neurovascular involvement in cases of familial Mediterranean fever (FMF) has not been adequately clarified. METHODS AND PATIENTS: Clinical features, infarct topography, vascular status, and stroke etiology were prospectively determined in 35 acute neurovascular events that occurred in 23 FMF patients. Clinicoradiological features were compared with an age- and gender-matched control group of 115 acute stroke patients. Characteristics of additional FMF and acute stroke cases (6 episodes in 6 patients) identified from a systematic literature review (PROSPERO registration no: CRD420212264820) were also analyzed. RESULTS: There were 27 acute ischemic stroke episodes in 19 patients, 7 transient ischemic attack episodes in 3 patients, and 1 patient with a single episode of parietal hematoma in our cohort. Twenty (74%) ischemic stroke episodes in 12 patients were cryptogenic. Ten of these 12 cases had a previous FMF diagnosis and were taking colchicine. There was no significant difference in the FMF group in terms of the presence of vascular risk factors and angiography-documented disease in comparison to controls. Cerebral distal artery involvement was significantly prevalent in FMF (78% vs 45%, P = .002). Especially, midbrain central deep perforating territory involvement was higher (30% vs 1%, P < .001). The long-term prognosis (median 8.5 years) under antiplatelet agents and colchicine is favorable. DISCUSSION: The acute stroke phenotype in FMF cases is herein described for the first time. Several clinicoradiological features such as thrombotic lacunar infarcts located in the central mesencephalon seem so typical that we recommend searching for FMF mutations in geographic regions where FMF is common.
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Febre Familiar do Mediterrâneo , AVC Isquêmico , Acidente Vascular Cerebral , Humanos , Febre Familiar do Mediterrâneo/complicações , Febre Familiar do Mediterrâneo/diagnóstico , Febre Familiar do Mediterrâneo/tratamento farmacológico , Colchicina/uso terapêutico , Fatores de Risco , Acidente Vascular Cerebral/diagnóstico , Acidente Vascular Cerebral/epidemiologia , Acidente Vascular Cerebral/etiologiaRESUMO
Cogan's syndrome (CS) is a rare inflammatory disease characterized by interstitial keratitis or uveitis, vestibular impairment, and progressive hearing loss, commonly bilateral. Although glucocorticoids are fundamental treatment options, in most cases, hearing loss gradually worsens. Herein we report 2 pediatric cases of CS who were treated with corticosteroids and methotrexate. One patient had a cochlear implant, and the hearing of the other patient improved with treatment. Also, a systematic literature review was conducted for articles including pediatric CS patients. In the literature, 34 articles describing 44 pediatric patients with CS were identified. Sudden hearing loss (95.3%) and ocular symptoms (92.5%) were the most common manifestations in these patients. Also, aortic involvement was present in 19.5% of patients in the literature. Otorhinolaryngologists, ophthalmologists, and pediatricians should collaborate to diagnose and manage CS to prevent progressive hearing loss and eye involvement.
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Síndrome de Cogan , Perda Auditiva Neurossensorial , Ceratite , Humanos , Criança , Perda Auditiva Neurossensorial/diagnóstico , Síndrome , Ceratite/diagnósticoRESUMO
Tumor necrosis factor (TNF) antagonists have made significant progress in treating autoimmune diseases like inflammatory bowel disease. Adalimumab, a human anti-TNF monoclonal antibody, may be a treatment option for patients with moderate to severe Crohn's disease for whom conventional treatments have not been effective. Central nervous system (CNS) and peripheral nervous system (PNS) demyelination may rarely develop during treatment. However, it is unclear whether CNS and PNS demyelination occurs as a coincidence or consequence. This report presents a 45-year-old male patient who developed multiple sclerosis-like demyelinating lesions at the seventh month of TNF alpha-blocker treatment. We discontinued anti-TNF therapy and initiated azathioprine. In the approximately eighteen-month follow-up, he did not show any neurological or radiological deterioration. When the autoimmune disease develops during anti-TNF blocker therapy, it would be a safe approach to choose a different group of biologic agents for disease control. The potential risk of developing neurological side effects requires closely follow-up of patients.
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SUMMARY: Anatomy education has gathered together a great many of many new modalities and was modified from classical lecture-based and laboratory practice system to the blended modules. In the scope of the present study, we develop a new, practical, cost- effective and efficient three dimensional (3D) educational model, which aimed to be helpful for the detection and better understanding of basic neuroanatomy education. Tractographic imaging, fiber dissection, microscopic anatomy and plastination techniques were applied to the white matter regions of the two brains. After the photographs that were taken were converted to 3D images, the specimens were plastinated. By way of establishing an educational model as a whole, we applied it to 202 second-year medical students. The students were separated into two groups when they attended to the theoretical lecture. Group 1 took the classical laboratory education; on the other hand, Group 2 received the newly designed educational model. Pre and post-tests were introduced to each group before and after laboratory sessions, respectively. The success scores were put to comparison. The average achievement scores of each group showed increase significantly (p<0.05) after the laboratory sessions, besides the increase in the post-test results of Group 2 was more statistically significant (p<0.05). Consequently, this new educational model enriched by newly designed unified methods could be regarded as useful for grasping and improving the basic neuroanatomy knowledge.
La educación en anatomía ha reunido una gran cantidad de nuevas modalidades, modificándose el sistema clásico de la práctica del laboratorio y de las clases basadas en conferencias, hacia los módulos combinados. En el ámbito del presente estudio, desarrollamos un modelo educativo tridimensional (3D) nuevo, práctico, rentable y eficiente, que pretendía ser útil para la detección y una mejor comprensión de la educación básica en neuroanatomía. Se tomaron imágenes tractográficas, disección de fibras, anatomía microscópica y técnicas de plastinación en los cerebros. Después de convertir las fotografías que se tomaron en imágenes 3D, se plastinaron los especímenes. A modo de establecer un modelo educativo en su conjunto, lo aplicamos a 202 estudiantes de segundo año de medicina. Los estudiantes fueron separados en dos grupos cuando asistieron a la clase teórica. El Grupo 1 tomó la educación clásica de laboratorio; por su parte, el Grupo 2 recibió el nuevo modelo educativo diseñado para el estudio. Se introdujeron pruebas previas y posteriores a cada grupo, antes y después de las sesiones de laboratorio. Se compararon las puntuaciones. Los puntajes promedio de rendimiento de cada grupo mostraron un aumento significativo (p<0,05) después de las sesiones de laboratorio. Además, se obtuvo un aumento en los resultados positivos, posteriores a la prueba del Grupo 2, siendo estadísticamente significativo (p<0,05). En consecuencia, este modelo educativo, enriquecido por métodos unificados de nuevo diseño, podría considerarse útil para captar y mejorar los conocimientos básicos de neuroanatomía.
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Humanos , Modelos Educacionais , Educação Médica/métodos , Neuroanatomia/educação , Dissecação , Cérebro/anatomia & histologia , Imagem de Tensor de Difusão , Substância Branca/anatomia & histologia , Plastinação , Microscopia , Fibras NervosasRESUMO
Cytotoxic T-lymphocyte antigen-4 (CTLA-4) haploinsufficiency is the defect of one of the checkpoint inhibitory molecules and defined as a primary immunodeficiency characterized by immune dysregulation. A 26-year-old female with a history of autoimmune hemolytic anemia, autoimmune thrombocytopenia, and hypogammaglobulinemia was admitted with an inability to walk, urinary hesitancy, and bowel incontinence. Neurological examination revealed mild weakness, pyramidal, and deep sensorial involvement of the left lower extremity. Brain MRI revealed periventricular, juxtacortical, and cerebellar inflammatory lesions. Thoracic spinal MRI showed a longitudinaly extensive cord lesion. Additionally, thoracal CT showed parenchymal opacities and bilateral hilar lymph nodes. The biopsy from mediastinal lymph nodes and lung parenchyma demonstrated a low-grade lymphoproliferation and grade 1 "Lymphomatoid granulomatosis". Detailed laboratory analyses indicated the diagnosis of ''common variable immunodeficiency''. Next-generation sequencing with primary immunodeficiency panel revealed a heterozygous mutation in CTLA-4 (c.436G>A(p.G146R)(p.Gly146Arg)). After molecular diagnosis, abatacept therapy was started as a targeted therapeutic approach with subcutaneous immunoglobulin therapy.
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Spondylo-epi-metaphyseal dysplasias with joint laxity, type 3 (SEMDJL3) is a genetic skeletal disorder characterized by multiple joint dislocations, caused by biallelic pathogenic variants in the EXOC6B gene. Only four individuals from two families have been reported to have this condition to date. The molecular pathogenesis related to primary ciliogenesis has not been enumerated in subjects with SEMDJL3. In this study, we report two additional affected individuals from unrelated families with biallelic pathogenic variants, c.2122+15447_2197-59588del and c.401T>G in EXOC6B identified by exome sequencing. One of the affected individuals had an intellectual disability and central nervous system anomalies, including hydrocephalus, hypoplastic mesencephalon, and thin corpus callosum. Using the fibroblast cell lines, we demonstrate the primary evidence for the abrogation of exocytosis in an individual with SEMDLJ3 leading to impaired primary ciliogenesis. Osteogenesis differentiation and pathways related to the extracellular matrix were also found to be reduced. Additionally, we provide a review of the clinical and molecular profile of all the mutation-proven patients reported hitherto, thereby further characterizing SEMDJL3. SEMDJL3 with biallelic pathogenic variants in EXOC6B might represent yet another ciliopathy with central nervous system involvement and joint dislocations.