Abstract Long-term epilepsy-associated tumors (LEATs) include a series of neoplasms that commonly occur in children, adolescents, or young adults, have an astrocytic or glioneuronal lineage, are histologically benign (WHO grade1) with a neocortical localization predominantly situated in the temporal lobes. Clinically, chronic refractory epilepsy is usually the unique symptom. Gangliogliomas (GG) and dysembryoplastic neuroepithelial tumors (DNT) are the most common representative entities besides pilocytic astrocytomas (PA) and angiocentric gliomas (AG). Recent molecular studies have defined new clinicopathological entities, which are recognized by the WHO 2021 classification of brain tumors. Some of them such as diffuse astrocytoma MIB or MYBL1 altered, polymorphous low-grade neuroepithelial tumor of the young (PLNTY), and multilocular and vacuolating neuronal tumor (MVNT) are currently considered LEATs. The relationship between LEATs and epilepsy is still a matter of debate, and there is a general agreement about the beneficial effects of an early neurosurgical intervention on the clinical outcome. Longterm Long term epilepsyassociated associated (LEATs children adolescents adults lineage grade1 grade lobes Clinically symptom GG (GG DNT (DNT PA (PA AG. AG . (AG) 202 MYBL altered lowgrade low PLNTY, PLNTY , (PLNTY) MVNT (MVNT debate outcome (AG 20 (PLNTY 2

Resumo Tumores associados a epilepsia de longa duração constituem uma série de neoplasias asatrocitárias ou glioneuronais que comumente incidem em crianças, adolescentes e jovens adultos e que são histologicamente benignos (OMS grau 1), de localização neocortical e predominantemente situados nos lobos temporais. Clinicamente, a epilepsia crônica refratária é, de modo geral, o único sintoma. Gangliogliomas (GG) e tumores neuroepiteliais disembrioplásticos (DNT) são as entidades mais representativas associadas a astrocitomas pilocíticos (AP) e gliomas angiocêntricos (GA). Estudos moleculares recentes permitiram a definição de novas entidades clínico-patológicas reconhecidas pela classificação de tumores cerebrais da OMS 2021. Algumas delas, como o astrocitoma difuso MIB ou MIBL1 alterados, o tumor neuroepitelial polimorfo do jovem (PLNTY) e o tumor neuronal multilocular e vacuolizado (MVNT) são atualmente considerados tumores associados a epilepsia de longa duração. A relação entre este grupo de tumores e epilepsia é ainda debatida e há um consenso geral sobre o benefício prognóstico de intervenção cirúrgica precoce. crianças 1, 1 , 1) temporais Clinicamente sintoma GG (GG DNT (DNT AP (AP GA. GA . (GA) clínicopatológicas clínico patológicas 2021 delas MIBL alterados PLNTY (PLNTY MVNT (MVNT precoce (GA 202 20 2

SUMMARY We present the unique case of an adult Brazilian woman with severe short stature due to growth hormone deficiency with a heterozygous G to T substitution in the donor splice site of intron 3 of the growth hormone 1 (GH1) gene (c.291+1G>T). In this autosomal dominant form of growth hormone deficiency (type II), exon 3 skipping results in expression of the 17.5 kDa isoform of growth hormone, which has a dominant negative effect over the bioactive isoform, is retained in the endoplasmic reticulum, disrupts the Golgi apparatus, and impairs the secretion of other pituitary hormones in addition to growth hormone deficiency. This mechanism led to the progression of central hypothyroidism in the same patient. After 5 years of growth and thyroid hormone replacement, at the age of 33, laboratory evaluation for increased weight gain revealed high serum and urine cortisol concentrations, which could not be suppressed with dexamethasone. Magnetic resonance imaging of the sella turcica detected a pituitary macroadenoma, which was surgically removed. Histological examination confirmed an adrenocorticotropic hormone (ACTH)-secreting pituitary macroadenoma. A ubiquitin-specific peptidase 8 (USP8) somatic pathogenic variant (c.2159C>G/p.Pro720Arg) was found in the tumor. In conclusion, we report progression of isolated growth hormone deficiency due to a germline GH1 variant to combined pituitary hormone deficiency followed by hypercortisolism due to an ACTH-secreting macroadenoma with a somatic variant in USP8 in the same patient. Genetic studies allowed etiologic diagnosis and prognosis of this unique case.

RESUMO Objetivo: Investigar paraplegia espástica hereditária (PEH) em uma amostra brasileira de pacientes pediátricos. Métodos: Foram colhidos dados clínicos, epidemiológicos, radiológicos e laboratoriais de 35 pacientes. Resultados: Doze pacientes foram classificados como PEH simples (PEH-S), e 23 como PEH complicada (PEH-C). A média de idade de início dos sintomas foi de 2,9 anos na PEH-S e 1,6 anos na PEH-C (p = 0,023). A doença foi mais grave na PEH-C. Não houve diferença de sexo, etnia e histórico familial entre os dois grupos. Deficiência intelectual foi a associação clínica mais frequente na PEH-C. Neuropatia periférica axonal foi encontrada em três pacientes. A RM foi normal em 13 casos de PEH-C. Anormalidades de RM incluiram alterações inespecíficas da substância branca, atrofia de cerebelo, afilamento de corpo caloso e o “sinal da orelha de lince”. Conclusões: PEH deve ser considerada em crianças com paraparesia espástica sempre que descartadas condições patológicas similares, principalmente paralisia cerebral.

ABSTRACT Aims: To investigate hereditary spastic paraplegia (HSP) in a pediatric Brazilian sample. Methods: Epidemiological, clinical, radiological and laboratory data were analyzed in 35 patients. Results: Simple HSP (HSP-S) was detected in 12 patients, and complicated HSP (HSP-C) was detected in 23 patients. The mean age of onset of symptoms was 2.9 years in HSP-S and 1.6 years in HSP-C (p = 0.023). The disease was more severe in HSP-C. There were no differences in sex, ethnic background, or family history between groups. Intellectual disability was the most frequent finding associated with HSP-C. Peripheral axonal neuropathy was found in three patients. In the HSP-C group, MRI was abnormal in 13 patients. The MRI abnormalities included nonspecific white matter lesions, cerebellar atrophy, thinning of the corpus callosum and the “ear of the lynx sign”. Conclusions: In children with spastic paraplegia, HSP must be considered whenever similar pathologies, mainly diplegic cerebral palsy, are ruled out.

RESUMO A doença de Gerstmann-Sträussler-Scheinker é uma doença priônica genética, cuja mutação mais frequente é p.Pro102Leu. Descrevem-se dados clínicos, moleculares e neuropatológicos de sete indivíduos em duas famílias não relacionadas com p.Pro102Leu. Diferenças notáveis entre os pacientes em relação à idade de início, duração da doença e apresentação clínica foram encontradas. Na primeira família, dois pacientes apresentaram demência rapidamente progressiva e três apresentaram fenótipo de ataxia com idade variáveis de início e duração da doença. Nesta família, a idade de início entre mãe e filha diferiu em 39 anos. Na segunda família, fenótipos diferentes foram observados e idades precoces de início dos sintomas foram associadas à heterozigose no códon 129. Não houve diferença em relação ao genótipo do gene da apoE. O genótipo do códon 129 não foi responsável pela variabilidade clínica; heterozigose no códon 129 esteve associada ao início precoce da doença. O exame neuropatológico em dois pacientes confirmou presença de placas típicas e imunohistoquímica para PrPsc.

ABSTRACT Gerstmann-Sträussler-Scheinker is a genetic prion disease and the most common mutation is p.Pro102Leu. We report clinical, molecular and neuropathological data of seven individuals, belonging to two unrelated Brazilian kindreds, carrying the p.Pro102Leu. Marked differences among patients were observed regarding age at onset, disease duration and clinical presentation. In the first kindred, two patients had rapidly progressive dementia and three exhibited predominantly ataxic phenotypes with variable ages of onset and disease duration. In this family, age at disease onset in the mother and daughter differed by 39 years. In the second kindred, different phenotypes were also reported and earlier ages of onset were associated with 129 heterozygosis. No differences were associated with apoE genotype. In these kindreds, the codon 129 polymorphism could not explain the clinical variability and 129 heterozygosis was associated with earlier disease onset. Neuropathological examination in two patients confirmed the presence of typical plaques and PrPsc immunopositivity.

Introduction: Endovascular repair of aortic aneurysm emerges as a less invasive option for patients with high operative risk, constituting a feasible and safe treatment due to technical advances. For this reason, our institution considers endovascular treatment as the "first line therapy" in patients with very high operative risk, as those with ruptured abdominal aortic aneurysm. Objective: The goal of this study is to report the experience with our surgical treatment protocol of patients with ruptured abdominal aortic aneurysm. Methods: Seventeen patients were treated based on the protocol "endovascular approach first". The population was classified according to systolic blood pressure (SBP) at admission in: hemodynamically stable (SBP = 80 mm Hg) or hemodynamically unstable (SBP < 80 mm Hg during > 10 minutes). The outcomes included mortality at 30 days and during follow-up and complications after the procedure. The statistical analysis was performed using Fisher's test. Results: Mortality at 30 days was 23.5%. Technical success was achieved in 94.1% of patients. Despite both groups had similar comorbidities, mortality in stable patients, operated on under local anesthesia, was 7.7% (p < 0.02). Conclusion: Endovascular treatment of ruptured abdominal aortic aneurysm, following a strict clinical and surgical treatment, is feasible and safe, particularly in stable patients under local anesthesia.

Introducción: El tratamiento endovascular del aneurisma de la aorta surge esencialmente como una alternativa menos invasiva para pacientes de riesgo quirúrgico alto, que con los avances tecnológicos se ha hecho factible y segura. Ello ha llevado a nuestra Institución a brindar el abordaje endovascular como "primera opción de tratamiento" en pacientes de riesgo quirúrgico más alto aún, como son los pacientes con aneurismas de la aorta abdominal rotos. Objetivo: Presentar la experiencia con nuestro protocolo quirúrgico de tratamiento del paciente con aneurisma de la aorta abdominal roto. Material y métodos: Diecisiete pacientes fueron tratados bajo el protocolo de "abordaje endovascular primero". La población se clasificó en función de la presión arterial sistólica (PAS) de ingreso: hemodinámicamente estables (PAS = 80 mm Hg) e inestables (PAS < 80 mm Hg durante > 10 minutos). Los resultados incluyeron la mortalidad a los 30 días y en el seguimiento y las complicaciones posprocedimiento. El análisis estadístico se realizó con la prueba de Fisher. Resultados: La mortalidad a los 30 días fue del 23,5%. El éxito técnico se logró en el 94,1%. Si bien ambos grupos tuvieron comorbilidades similares, los pacientes estables, operados bajo anestesia local, presentaron una tasa de mortalidad del 7,7% (p < 0,02). Conclusión: El tratamiento endovascular del aneurisma de la aorta abdominal roto, siguiendo un manejo clínico-quirúrgico estricto, es factible y seguro, especialmente en pacientes estables bajo anestesia local.

RESUMO OBJETIVO: Determinar a prevalência de mutações no DNA mitocondrial (DNAmt) em casos com achados compatíveis com o diagnóstico de síndrome de Leigh em um Servicro de Neurologia brasileiro, e comparar essas descobertas entre os pacientes que apresentam ou não essas mutações. MÉTODO: Seis pontos de mutações do DNAmt (T8993G, T8993C, T8851C, G1644T, T9176C e T3308C) foram analisados por PCR e digestão com endonuclease em 32 pacientes com diagnóstico presuntivo de síndrome de Leigh, de acordo com a distribuição em diferentes faixas etárias. RESULTADOS: Dois pacientes no subgrupo abaixo de 4 anos de idade apresentaram as mutações T8993G e T8993C do DNAmt. Os sintomas clínicos e os achados de neuroimagens destes dois pacientes foram similares aos dos casos sem mutações detectadas. CONCLUSÃO: Como a confirmaçãoo molecular é fundamental tanto para o aconselhamento genético como para a orientação terapêutica, enfatizamos o benefício da pesquisa de mutações no DNAmt em pacientes com fenótipo de Síndrome de Liegh abaixo de 4 anos de idade. O sequenciamento em larga escala do genoma mitocondrial e do exoma completo por tecnologia de sequenciamento de nova geração poderá ser uma alternativa futura no estabelecimento do diagnóstico molecular nesta síndrome genética extensamente heterogênea.

OBJECTIVE: To determine the prevalence of mitochondrial DNA (mtDNA) mutations in cases with findings compatible with the diagnosis of Leigh syndrome in a Brazilian Neurological Service, and to compare those findings between the patients presenting or not these mutations. METHOD: We analyzed six mtDNA point mutations (T8993G, T8993C, T8851C, G1644T, T9176C, and T3308C) by PCR and endonuclease digestion in 32 patients with presumptive diagnosis of Leigh syndrome, according to distribution across different age ranges. RESULTS: We found two patients, in the subgroup under 4 years of age, presenting T8993G and T8993C mutations. Their clinical symptoms and neuroimaging findings were similar when compared to those patients not harboring these mutations. CONCLUSION: As the molecular confirmation is pivotal for both the precise genetic counselling and therapeutic guidance, we emphasise the benefit of screening for mtDNA mutation in Leigh syndrome patients under 4 years old. Mitochondrial whole genome and whole exome analysis by next-generation sequencing technology maybe a future alternative for molecular diagnosis of this extensive genetic heterogeneous syndrome.

Germinomas intracranianos (GE) são neoplasias malignas comumente na região suprasselar, podendo causar deficiência hormonal da hipófise anterior, em particular da hipófise posterior, com diabetes insípido central (DI). Entre os diagnósticos diferenciais do espessamento de haste hipofisária, incluem-se doenças granulomatosas, inflamatórias, infecciosas e neoplásicas. Embora as avaliações clínica, laboratorial e a ressonância magnética selar sugiram o diagnóstico, a biópsia transesfenoidal está indicada para confirmação, visto que o diagnóstico correto direciona o tratamento.

Intracranial germinomas (GE) are malignant neoplasms most commonly found in the suprasellar region, which may cause anterior and particularly posterior pituitary hormone deficits with central diabetes insipidus (DI). Differential diagnosis of pituitary stalk thickening includes granulomatous, inflammatory, infectious, and neoplastic lesions. Although careful analysis of clinical, laboratory, and imaging findings may facilitate the diagnosis, transsphenoidal biopsy is indicated to confirm the disease, as the correct diagnosis directs the appropriate treatment.

OBJECTIVES: We investigated four components of the Wnt signaling pathway in medulloblastomas. Medulloblastoma is the most common type of malignant pediatric brain tumor, and the Wnt signaling pathway has been shown to be activated in this type of tumor. METHODS: Sixty-one medulloblastoma cases were analyzed for β-catenin gene (CTNNB1) mutations, β-catenin protein expression via immunostaining and Wnt signaling pathway-related gene expression. All data were correlated with histological subtypes and patient clinical information. RESULTS: CTNNB1 sequencing analysis revealed that 11 out of 61 medulloblastomas harbored missense mutations in residues 32, 33, 34 and 37, which are located in exon 3. These mutations alter the glycogen synthase kinase-3β phosphorylation sites, which participate in β-catenin degradation. No significant differences were observed between mutation status and histological medulloblastoma type, patient age and overall or progression-free survival times. Nuclear β-catenin accumulation, which was observed in 27.9% of the cases, was not associated with the histological type, CTNNB1 mutation status or tumor cell dissemination. The relative expression levels of genes that code for proteins involved in the Wnt signaling pathway (CTNNB1, APC, AXIN1 and WNT1) were also analyzed, but no significant correlations were found. In addition, large-cell variant medulloblastomas presented lower relative CTNNB1 expression as compared to the other tumor variants. CONCLUSIONS: A small subset of medulloblastomas carry CTNNB1 mutations with consequent nuclear accumulation of β-catenin. The Wnt signaling pathway plays a role in classic, desmoplastic and extensive nodularity medulloblastoma variants but not in large-cell medulloblastomas.

RESUMO A região parietooccipital é mais frequente e gravemente acometida na panencefalite esclerosante subaguda (PEESA). Os gânglios da base, cerebelo e corpo caloso são menos envolvidos. Descrevemos um paciente com PEESA confirmada por neuropatologia com imagens de ressonância magnética (RNM) evidenciando acometimento extenso dos gânglios da base sem envolvimento de outras estruturas corticais. Embora raramente descritas nesta doença, deve-se ficar atento para tal acometimento e PEESA deve ser lembrada quando alterações de sinal nos gânglios da base são vistas na RNM com ou sem acometimento de outras regiões do cérebro a fim de evitar outros diagnósticos etiológicos errôneos de patologias que cursam com demência rapidamente progressiva.

ABSTRACT The parieto-occipital region of the brain is the most frequently and severely affected in subacute sclerosing panencephalitis (SSPE). The basal ganglia, cerebellum and corpus callosum are less commonly involved. We describe a patient with SSPE confirmed by neuropathology based on brain magnetic resonance imaging showing extensive basal ganglia involvement and no significant involvement of other cortical structures. Though rarely described in SSPE, clinicians should be aware of this involvement. SSPE should be kept in mind when changes in basal ganglia signal are seen on brain magnetic resonance imaging with or without involvement of other regions of the human brain to avoid erroneous etiological diagnosis of other pathologies causing rapidly progressive dementia.

Endovascular Repair of Type IV Thoracoabdominal Aneurysms Type IV thoracoabdominal aortic aneurysms are characterized by involvement of the visceral aortic segment which determines the lack of a proximal aortic neck suitable for the implantation conventional stents. Fenestrated stents have been specially developed for these cases. We describe the experience of a surgical center using fenestrated stents in six patients. All the stents were successfully implanted, respecting 20 visceral vessels. This approach is a valid alternative for patients who are at high risk for conventional surgery.

Los pacientes con aneurismas toracoabdominales tipo IV se caracterizan anatómicamente por la presencia de una dilatación aórtica visceral que determina la falta de un cuello proximal aórtico adecuado para el anclaje de las endoprótesis convencionales. Para tal fin existen injertos especialmente diseñados con fenestraciones. En esta comunicación se describe la experiencia de un grupo quirúrgico en la utilización de endoprótesis fenestradas. Fueron tratados seis pacientes. Todas las endoprótesis fueron implantadas con éxito, respetando 20 vasos viscerales. Este abordaje constituye hoy una alternativa válida para el tratamiento de este grupo de pacientes candidatos a cirugía convencional de alto riesgo.

O astrocitoma pilomixoide, entidade descrita como variante histológica do astrocitoma pilocítico, é um raro tumor primário do sistema nervoso central. Geralmente, localiza-se em topografia hipotálamo-quiasmática, acomentendo crianças com idade média de 10 meses. Apresenta alta taxa de recorrência e disseminação liquórica, podendo se apresentar ao longo de todo o neuroeixo. Dada sua topografia, pode se apresentar com atraso do desenvolvimento na infância e síndrome diencefálica, caracterizada por emagrecimento extremo, ausência de acúmulo de tecido adiposo, hiperatividade motora, euforia e estado de alerta. A ressonância magnética possui um papel importante para o diagnóstico, estadiamento e seguimento do astrocitoma pilomixoide. No entanto, para o diagnóstico definitivo, o estudo anatomopatológico é fundamental, principalmente na diferenciação com o astrocitoma pilocítico. Além disso, em alguns casos, como o aqui apresentado, evidencia-se a apresentação simultânea de características histológicas do astrocitoma pilomixoide e pilocítico, constituindo um grupo denominado astrocitoma pilomixoide intermediário. A cirurgia é a melhor opção de tratamento e geralmente há necessidade de tratamento adjuvante.

Pilomyxoid astrocytoma, an entity described as a histological variant of pilocytic astrocytoma, is a rare primary tumor of the central nervous system. It is usually located in the hypothalamic-chiasmatic area, affecting children with a mean age of 10 months. It has a high rate of recurrence and cerebrospinal fluid dissemination, which may be present throughout the neuroaxis. Due to its topography, it may present developmental delay in childhood and diencephalic syndrome, characterized by extreme weight loss, lack of fat accumulation, hyperactivity, euphoria and alertness. Magnetic resonance imaging has an important role in its diagnosis, staging and follow-up of pilomyxoid astrocytoma. However, for a definitive diagnosis, anatomopathology is particularly important to differentiate it from pilocytic astrocytoma. Some cases, as in this present one, have simultaneous histological features of pilocytic and pilomyxoid astrocytomas, constituting a group called intermediate pilomyxoid astrocytoma. Surgery is the best treatment option and it usually requires adjuvant therapy.

In patients with juxtarenal abdominal aortic aneurysm, the segment of the infrarenal aorta that is necessary to achieve an adequate fixation of a stent graft is insufficient or absent. Thus, the use of traditional stent grafts does not provide sealing or exclusion of the aneurysm. For this reason, implantation of fenestrated devices (with orifices) that preserve blood flow to visceral and renal arteries has been used as a valid and less invasive therapeutic option. We describe the first case of a juxtarenal aortic aneurysm treated in our country using a fenestrated stent graft. The patient had high surgical risk due to the presence of comorbidities. Under regional anesthesia, a fenestrated stent graft was implanted to preserve blood flow to the celiac trunk, superior mesenteric artery and both renal arteries. The procedure was successful and the aneurysm was excluded. Aneurysm exclusion with adequate patency of the visceral arteries was demonstrated during the first postoperative control.

En los pacientes con un aneurisma de la aorta abdominal yuxtarrenal, el segmento normal de aorta infrarrenal necesario para lograr el anclaje proximal de una endoprótesis es insuficiente o inexistente, por lo que con las endoprótesis tradicionales no existe la posibilidad de sellar o excluir el aneurisma. Por este motivo, en los últimos años se han utilizado endoprótesis con fenestraciones (orificios) para la preservación de los ramos viscerales y renales como alternativa válida y menos invasiva. En esta presentación se describe el primer caso de un aneurisma aórtico yuxtarrenal tratado en nuestro país mediante la colocación de una endoprótesis con múltiples fenestraciones. Se trata de un paciente de alto riesgo quirúrgico por comorbilidades clínicas, al cual con empleo de anestesia regional se le colocó una endoprótesis con fenestraciones para preservar la irrigación del tronco celíaco, la arteria mesentérica superior y ambas arterias renales. El procedimiento fue exitoso, lográndose la exclusión del aneurisma. El primer control posoperatorio demostró la exclusión del aneurisma con permeabilidad adecuada de los ramos viscerales.