Michelle Silva Zeny

Hospital Erasto Gaertner

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Daniel Almeida do Valle

Hospital Erasto Gaertner

Mara Lúcia Schmitz Ferreira Santos

Hospital Erasto Gaertner

Giulia Vilela Silva

Hospital Erasto Gaertner

Mara L. Cordeiro

University of California, Los Angeles

Josiane Souza

Hospital Erasto Gaertner

Tiago Bara

Instituto de Tecnologia do Paraná

Elisabete Coelho Auersvald

Hospital Erasto Gaertner

Rui Carlos Silva

Hospital Erasto Gaertner

Julia Vilela Rezende

I. Marques

Association for Innovation and Biomedical Research on Light and Image

Cooperative Institutions

Hospital Erasto Gaertner

Universidade de São Paulo

University of Genoa

Ospedale Policlinico San Martino

Universidade Federal do Rio Grande do Sul

Universidade Federal de São Paulo

Hospital de Clínicas de Porto Alegre

Nationwide Children's Hospital

UCSF Benioff Children's Hospital

National Institute on Population Medical Genetics

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Characteristics of Opsoclonus-Myoclonus Syndrome in Patients of the Largest Pediatric Hospital in Latin America

Pediatric Neurology (2024)

Michelle Silva Zeny Daniel Almeida do Valle Mara Lúcia Schmitz Ferreira Santos Tiago Bara Mara L. Cordeiro

BackgroundOpsoclonus–myoclonus syndrome (OMS) is a rare neuroinflammatory disorder characterized by ataxia, opsoclonus, and myoclonus. Clinical diagnosis of OMS has been challenging; therefore, we sought to determine the clinical and treatment profiles of patients with OMS at the largest pediatric hospital in Latin America.MethodsWe analyzed the data of patients diagnosed with OMS between 2010 and 2020 at Pequeno Principe Hospital (Brazil) to determine the corresponding clinical profile more accurately.ResultsOf the approximately 50,000 visitors to our pediatric neurology department from 2010 to 2020, 10 patients with OMS were observed. Five non-tumor cases included three parainfectious and two idiopathic cases. The median time from symptom onset to diagnosis was 34 days. All patients with diagnostic OMS criteria in the idiopathic, non-tumor group underwent whole-exome sequencing, with potentially pathogenic mutations identified in two cases. Nine patients were treated with methylprednisolone pulse, followed by oral steroids; eight received one or more intravenous immunoglobulin treatments; and six received azathioprine and cyclophosphamide. Complete symptomatic recovery was observed in only one patient.ConclusionOMS diagnosis remains challenging. Diagnostic suspicion is necessary to improve the management of these patients and allow early immunosuppressive treatment. The paraneoplastic etiology is the most prevalent. In idiopathic patients who do not respond to immunosuppressive treatment, tests, such as whole-exome sequencing, may reveal a differential diagnosis. Genetic alterations that increase the risk of tumors may be an important clue to the pathophysiology of OMS.

Etiology

10.1016/j.pediatrneurol.2023.12.028

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Characterization of patients treated at a rare disease referral service: a descriptive study, 2016-2021

Epidemiologia e Serviços de Saúde (2024)

Endrigo Antônio de Carvalho Roberto Del Claro Hopker Gustavo Henrique Pedroso Leonardo Silva de Almeida José Alfredo Trevisan Pacher

Abstract Objective: To analyze the first referral service for rare diseases accredited by the Brazilian Ministry of Health, focusing on referral from the primary healthcare network through to diagnosis. Methods: This is a descriptive study with patients treated between 2016 and 2021 at a referral hospital service located in Curitiba, Paraná, Brazil. Clinical and epidemiological data were obtained from medical records, as were the results of genetic tests at the hospital’s clinical analysis laboratory. Qualitative data were expressed as absolute and relative frequencies, while quantitative data were expressed as medians and interquartile ranges and compared using the Kruskal-Wallis test. Results: The study included 1,751 cases, 34.1% were diagnosed with rare diseases, with average time until diagnosis being 3.0 years, whereby mucopolysaccharidosis type II (4.0%) and tuberous sclerosis (3.9%) were the most common. Greater length of time for obtaining diagnosis (p-value 0.004) and receiving specialized care (p-value<0.001) was found in patients from the interior region of Paraná state, compared to those residing in Curitiba city and its metropolitan region. Conclusion: Diagnosis of rare diseases occurred in approximately one third of cases. The average time until diagnosis suggests a possible positive impact of implementing the referral service. The longer time until diagnosis and specialized care found among patients from the interior region of Paraná represent challenges regarding adequate referral to specialized services.

Curitiba

Interquartile range

Christian ministry

10.1590/s2237-96222024v33e20240204.en

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Table of Contents

Pediatric Neurology (2024)

Michelle Silva Zeny Daniel Almeida do Valle Mara Schmitz Ferreira Santos Tiago Bara

Table (database)

10.1016/s0887-8994(24)00111-5

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Clinical, genotypic, and neuropsychological profile in a series of cases of patients with Niemann-Pick type C disease

Research Square (Research Square) (2024)

Rita Mendes Daniel Almeida do Valle Tiago Bara Vanessa Furlin Michelle Silva Zeny

Abstract Background Niemann-Pick type C (NPC) disease is a rare neurodegenerative disorder with a wide spectrum of clinical manifestations and genetic variability. This cross-sectional study aimed to comprehensively describe the neuropsychological impact of NPC and investigate its correlation with specific genotypes. Results Eight patients from six unrelated families were included in this study. The age at symptom onset ranged from 2–16 years, with all patients presenting with ataxia, dysarthria, and cognitive impairment. Following the initiation of miglustat treatment, five patients showed a decrease in the Scale for the Assessment and Rating of Ataxia (SARA) score, whereas two demonstrated subsequent increases. Brain magnetic resonance imaging scans were performed in five patients, revealing white matter abnormalities and/or brain volumetric reduction in three cases. Despite the small sample size, the overall cognitive performance of the cohort was significantly below average. The Family Environmental Scale highlighted positive structural patterns, particularly regarding Personal Growth and System Maintenance. Genetic analysis identified five mutations in the NPC1 gene, correlating with the severity of impairments and clinical outcomes. Conclusions This study highlighted a consistent association between cognitive and behavioral impairments, with severity correlating with age and specific genetic variants. Notably, a subgroup showed a higher prevalence of psychotic and behavioral symptoms, suggesting a potential link with specific genetic variants.

10.21203/rs.3.rs-4177612/v1

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Rare disease reported in a pediatric patient: Pearson syndrome

Residência Pediátrica (2024)

Lorena Rezende Mara Lúcia Schmitz Ferreira Santos Michelle Silva Zeny Marian Vallim Rui Medeiros

Pearson Syndrome (PS) is a congenital multisystem disorder caused by mitochondrial DNA deletions. The main clinical manifestations are: Sideroblastic anemia, neutropenia, thrombocytopenia and exocrine pancreatic insufficiency. Organs such as the heart, kidneys, eyes, ears and brain are the most affected due to the greater energy demand they need. Diagnosis is often challenging due to phenotypic heterogeneity and should always be suspected in multisystemic manifestations. It is confirmed by genetic testing, through mitochondrial DNA sequencing. It is a disease that has no cure, however, there is treatment with co-factors that reduce the signs and symptoms, in addition to ongoing research in gene therapy. Supportive measures aim to avoid physiological stressors. It is a syndrome that is usually fatal in childhood, and those who survive develop signs and symptoms of Kearns-Sayre Syndrome. This case report aims to guide and favor the diagnosis of similar clinical conditions, since PS is probably underdiagnosed, as few physicians are aware of the existence of the disease, much less of its signs and symptoms.

10.25060/residpediatr-2024.v14n3-1110

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Follow-up younger patient with anti-NMDA-R encephalitis

Arquivos de Neuro-Psiquiatria (2023)

Lisandra Coneglian Farias Rigoldi Rui Carlos Silva Giulia Vilela Silva Lorena Vilela Rezende Ana Paula Resende Silva

Case presentation: Male, 8 months old, previously healthy, initiated with fever, inappetence, dystonia and axial hypotonia. Initial examination presented cerebrospinal fluid (CSF) with lymphomononuclear leukocytosis and proteinorrachia. Electroencephalogram (EEG) with slowed base activity. Other infectious screening tests with viral serology, rheumatological, neoplastic diseases, nuclear magnetic resonance (NMR) imaging of the brain were standard. After exclusion of main causes of encephalitis, antibodies against N-methyl-D-aspartate receptor (NMDA-R) were identified in the CSF. It evolved with worsening motor and respiratory, and regression of neuropsychomotor development (NPMD), he needed tracheostomy (TQT) and gastrostomy (G-tube). Treatment, besides a front line with steroids and Human Immunoglobulin, were six cyclophosphamide cycles and starting azathioprine, remaining hospitalized for four months. Following up, at five years of age, he is still using azathioprine, in weaning. He presents NPMD milestones appropriate for his chronological age. There is no need for tracheostomy (TQT) and gastrostomy (G-tube).

Leukocytosis

Aspiration Pneumonia

10.1055/s-0043-1774630

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Scholar patient with autoimmune encephalitis after being infected with SARSCov2

Arquivos de Neuro-Psiquiatria (2023)

Robison Antônio Coelho Júnior Giulia Vilela Silva Lorena Vilela Rezende Mariah Pereira de Andrade Vallim Izabela Cristina Macedo Marques

Case presentation: B,F,D, 6 years, female, previously healthy, initiated SARSCov2 symptoms with infection, fever, asthenia and recurrent vomiting, signals of extrapyramidal release, ataxia, dysarthria and paraplegia. These symptoms evolved to metabolic acidosis, flaccid quadriplegia and hospitalization at intensive care unit (ICU). When investigating, serology's and CSF with no alteration. Electrophysiological studies were made with EEG and electroneuromyography, and the results were normal. Nuclear magnetic resonance (NMR) image and angio-NMR of normal cranium. NMR from vertebral column without significantly changes. Received methylprednisolone 30(mg/kg/day) for 5 and 7 days of human immunoglobulin (IgH), gradually recovering from lower members and cervical tone. Keeping broca's aphasia and PCR positive SARSCov2 for seven more days. Was discharged and initially following: Recovering from member's mobilization, strength and cognition. Dystonia got worse after three months and new development regression. With good recovering from the signals and symptoms after IgH, fulfilling criteria for autoimmune encephalitis possibility. Being opted for monthly replacement from IgH with gain maintenance from neuropsychomotor development.

10.1055/s-0043-1774633

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Caracterização de pacientes atendidos em serviço de referência em doenças raras: estudo descritivo, 2016-2021

Epidemiologia e Serviços de Saúde (2024)

Endrigo Antônio de Carvalho Roberto Del Claro Hopker Gustavo Henrique Pedroso Leonardo Silva de Almeida José Alfredo Trevisan Pacher

Resumo Objetivo: Analisar o primeiro serviço de referência em doenças raras credenciado pelo Ministério da Saúde, com foco no encaminhamento desde a rede primária até o diagnóstico. Métodos: Trata-se de um estudo descritivo com pacientes atendimentos entre 2016 e 2021 em serviço hospitalar de referência localizado de Curitiba. Dados clínicos e epidemiológicos foram obtidos de registros médicos e os resultados de exames genéticos do laboratório de análises clínicas do hospital. Dados qualitativos foram expressos como frequência absoluta e relativa, e os quantitativos por mediana e intervalo interquartil e comparados pelo teste Kruskal-Wallis. Resultados: Foram incluídos 1.751 pacientes, 34,1% obtiveram diagnóstico de doenças raras, com tempo médio de 3,0 anos, sendo a mucopolissacaridose tipo II (4,0%) e esclerose tuberal (3,9%) as mais frequentes. Maior tempo até obter diagnóstico (p-valor 0,004) e atendimento especializado (p-valor<0,001) foram observados em pacientes do interior do Paraná, em comparação com aqueles que residem em Curitiba e região metropolitana. Conclusão: O diagnóstico de doenças raras ocorreu em cerca de um terço dos casos. O tempo médio até o diagnóstico sugere possível impacto positivo da implementação do serviço de referência. Maior tempo até o diagnóstico e atendimento especializado observado em pacientes do interior do Paraná representam desafios no encaminhamento adequado para unidades especializadas.

10.1590/s2237-96222024v33e20240204.pt

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Phenotypic/Genotypic Profile of Children with Neuronal Ceroid Lipofuscinosis in Southern Brazil

Neuropediatrics (2024)

Berkmis Viana Santos Josiane Souza Michelle Silva Zeny Mara Lúcia Schmitz Ferreira Santos Daniel Almeida do Valle

Abstract Introduction Neuronal ceroid lipofuscinoses (CLNs) are a group of lysosomal storage disorders of genetic origin, characterized by progressive neurodegeneration and intracellular accumulation of autofluorescent lipopigment. Thirteen genes related to CLNs are currently described, showing genetic and allelic heterogeneity, most of them with an autosomal recessive pattern. Due to the few descriptions of cases related to CLNs in Brazil, it is necessary to describe the phenotypic and genotypic characteristics of these patients. This study aims to evaluate the genotypic profile and correlate it with the phenotypic characteristics of patients with CLN in a children's hospital. Methods This study was performed as a descriptive cross-sectional study with analysis of medical records, imaging, and laboratory tests of patients who had a confirmed molecular diagnosis of CLN. Results The sample consisted of 11 patients from nine families with different subtypes of CLNs (CLN2, 5, 6, 7, and 8), with CLN2 being the most prevalent in the study. A total of 16 mutation variants were identified in genes associated with the five CLNs described in this study, with typical and atypical clinical phenotypes depending on the subtype and its variants. Conclusion Novel mutations identified in the patients in this study showed phenotypes of rapid and severe progression in the CLN2 patient and similar characteristics in CLN6 and CLN7 patients, as previously described in the literature.

Neuronal ceroid lipofuscinosis

10.1055/s-0044-1787706

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Encephalomyelitis by adenovirus

Arquivos de Neuro-Psiquiatria (2023)

I. Marques Rui Carlos Silva Giulia Vilela Silva Nildo Vilacorte de Araújo Júnior Daniel Almeida do Valle

Case presentation: Three-year-old male admitted with aphasia and mental confusion that last 48 hours. Report a fever peak of 38°C. Vomiting and hyaline rhinorrhea resolved four days ago. Plus diarrheal symptoms three weeks prior to hospitalization. He did not recognize his mother and other family members, he was frightened by environmental stimuli, he could not walk, he fell if placed standing and did not sit without support. Previously healthy. History of febrile seizures at 1 year of age on sodium valproate. Proper motor development, but with speech delay. Son of a healthy couple non-consanguineous from Manaus, attended day care with good socialization. On examination he was awake but disoriented, cranial nerves unaltered. He presented traction of the lower limbs with flexion of the thigh to painful stimuli and spontaneous elevation of the lower limbs against gravity, without signs of pyramidal release with bilateral patellar areflexia. Lumbar puncture showed cellularity of 27 and predominance of lymphocytes, protein 19, glucose 51and lactate 1.4. Normal metabolic tests and cranial tomography. Started acyclovir and requested panel for viral meningitis in the cerebrospinal fluid (CSF). The following day, he progressed with worsening, dysphagia and loss of head support, he maintained the lower limb areflexia, being referred to the ICU where he received immunoglobulin. He was discharged from the ICU after 48 hours with improvement. Ophthalmologic evaluation and EEG were normal. Neuroaxis MRI showed bilateral and symmetrical signal alteration in the posterior region of the brainstem, more evident in the bulb pontine region with insinuation to the dentate nucleus of the cerebellar hemispheres, without anomalous contrast impregnation, suggesting viral or autoimmune etiology. Therefore, it was chosen to repeat the lumbar puncture with normal CSF (4 cells). The patient evolved with recovery of consciousness and neurotendinous reflexes. The CSF panel showed positive PCR for adenovirus. The patient was discharged asymptomatic, and acyclovir was discontinued.

10.1055/s-0043-1774629

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