3-Step didactic white matter dissection of human cerebellum: Micro-neuroanatomical training.

OBJECTIVES: A thorough understanding of cerebellum anatomy is essential in 4th ventricle approaches (more frequent in pediatric neurosurgery), avoiding relevant complications such as cerebellar mutism. The aim of the present work is to show the feasibility of a didactic dissection of human cerebellum focusing on cerebellar peduncles and dentate nucleus (DN), which are structures at high risk during these surgical procedures. MATERIAL AND METHODS: The cerebellum was dissected according to the Klingler method for white matter, using standard and specific microsurgery tools. Surgical microscope magnification (×6-×40) provided by a D.F. Vasconcellos M900 was required. A Canon EOS T7 18-55 mm digital camera was used and Adobe Lightroom Classic CC and Keynote were selected as photo enhancing software. Special methods such as LED light endoscopic transillumination were used for photographical reasons. RESULTS: DN dissection was successfully achieved and the relations between these nucleus and the cerebellar peduncles, inferior vermis and medullary velums were described. Through this three steps dissection guide (1. tentorial surface; 2. suboccipital surface; 3. 4th ventricle structures), the most relevant anatomical structures were shown and its implications in different 4th ventricle approaches were characterised. CONCLUSION: 3 D perspective provided by real specimen anatomical dissection is critical for learning neuroanatomy. LED transillumination was shown as a useful technique for the 4th ventricle structures photographic documentation which improves spatial recognition. This benefit can be applied for the study of the relations between the medullary velums and the rhomboid fossa foramina, which are permeable to light. The proposed three-steps dissection guide helps to a better understanding of human cerebellum and to gain self-confidence, allowing safer practice for neurosurgeons in all stages of their career.

Case report: A third variant in the 5' UTR of TWIST1 creates a novel upstream translation initiation site in a child with Saethre-Chotzen syndrome.

Introduction: Saethre-Chotzen syndrome, a craniosynostosis syndrome characterized by the premature closure of the coronal sutures, dysmorphic facial features and limb anomalies, is caused by haploinsufficiency of TWIST1. Although the majority of variants localize in the coding region of the gene, two variants in the 5' UTR have been recently reported to generate novel upstream initiation codons. Methods: Skeletal dysplasia Next-generation sequencing (NGS) panel was used for genetic analysis in a patient with bicoronal synostosis, facial dysmorphisms and limb anomalies. The variant pathogenicity was assessed by a luciferase reporter promoter assay. Results: Here, we describe the identification of a third ATG-creating de novo variant, c.-18C>T, in the 5' UTR of TWIST1 in the patient with a clinical diagnosis of Saethre-Chotzen syndrome. It was predicted to create an out-of-frame new upstream translation initiation codon resulting in a 40 amino acid larger functionally inactive protein. We performed luciferase reporter promoter assays to demonstrate that the variant does indeed reduce translation from the main open reading frame. Conclusion: This is the third variant identified in this region and confirms the introduction of upstream ATGs in the 5' UTR of TWIST1 as a pathogenic mechanism in Saethre-Chotzen syndrome. This case report shows the necessity for performing functional characterization of variants of unknown significance within national health services.

The hippocampus as the switchboard between perception and memory.

Adaptive memory recall requires a rapid and flexible switch from external perceptual reminders to internal mnemonic representations. However, owing to the limited temporal or spatial resolution of brain imaging modalities used in isolation, the hippocampal-cortical dynamics supporting this process remain unknown. We thus employed an object-scene cued recall paradigm across two studies, including intracranial electroencephalography (iEEG) and high-density scalp EEG. First, a sustained increase in hippocampal high gamma power (55 to 110 Hz) emerged 500 ms after cue onset and distinguished successful vs. unsuccessful recall. This increase in gamma power for successful recall was followed by a decrease in hippocampal alpha power (8 to 12 Hz). Intriguingly, the hippocampal gamma power increase marked the moment at which extrahippocampal activation patterns shifted from perceptual cue toward mnemonic target representations. In parallel, source-localized EEG alpha power revealed that the recall signal progresses from hippocampus to posterior parietal cortex and then to medial prefrontal cortex. Together, these results identify the hippocampus as the switchboard between perception and memory and elucidate the ensuing hippocampal-cortical dynamics supporting the recall process.

3-Step didactic white matter dissection of human cerebellum: Micro-neuroanatomical training. / Disección didáctica de fibra blanca en cerebelo humano en tres pasos: entrenamiento microneuroanatómico.

OBJECTIVES: A thorough understanding of cerebellum anatomy is essential in 4th ventricle approaches (more frequent in pediatric neurosurgery), avoiding relevant complications such as cerebellar mutism. The aim of the present work is to show the feasibility of a didactic dissection of human cerebellum focusing on cerebellar peduncles and dentate nucleus (DN), which are structures at high risk during these surgical procedures. MATERIAL AND METHODS: The cerebellum was dissected according to the Klingler method for white matter, using standard and specific microsurgery tools. Surgical microscope magnification (x6-x40) provided by a D.F. Vasconcellos M900 was required. A Canon EOS T7 18-55 mm digital camera was used and Adobe Lightroom Classic CC and Keynote were selected as photo enhancing software. Special methods such as LED light endoscopic transillumination were used for photographical reasons. RESULTS: DN dissection was successfully achieved and the relations between these nucleus and the cerebellar peduncles, inferior vermis and medullary velums were described. Through this three steps dissection guide (1. tentorial surface; 2. suboccipital surface; 3. 4th ventricle structures), the most relevant anatomical structures were shown and its implications in different 4th ventricle approaches were characterised. CONCLUSION: 3 D perspective provided by real specimen anatomical dissection is critical for learning neuroanatomy. LED transillumination was shown as a useful technique for the 4th ventricle structures photographic documentation which improves spatial recognition. This benefit can be applied for the study of the relations between the medullary velums and the rhomboid fossa foramina, which are permeable to light. The proposed three-steps dissection guide helps to a better understanding of human cerebellum and to gain self-confidence, allowing safer practice for neurosurgeons in all stages of their career.

Diffuse leptomeningeal glioneuronal tumour: where to biopsy? Case report and literature review.

PURPOSE: Diffuse leptomeningeal glioneuronal tumour (DLGT) is an infrequent entity. Diagnosis is made with biopsy but with so few cases described management, prognosis remains undefined. There are not currently any articles regarding most effective place to biopsy. METHODS: Current literature review and introduction of the case of a 3-year-old male presenting at the emergency room with irritability, vomiting and nuchal rigidity. A head CT was made showing tetraventricular enlargement and a posterior fossa cyst. RESULTS: Patient underwent urgent ventriculoperitoneal shunting surgery with complete symptomp resolution. Brain MRI showed diffuse leptomeningeal enhancing, predominantly in basal cisterns, and multiple cystic-solid lesions along the neural axis. After ruling other conditions, a biopsy among intraoperative samples, was obtained of a PET positive gadolinium spinal enhancing lesion at D8 level, with the final diagnosis of DLGT. CONCLUSION: DLGT can present as acute hydrocephalus. Biopsy stablishes the diagnosis but the place to take the sample can be difficult to select. Our experience suggests that PET-CT and intraoperative biopsy analysis can improve the effectivity of a representative sample.

Risk factors associated with conversion of an Ommaya reservoir to a permanent cerebrospinal fluid shunt in preterm posthemorrhagic hydrocephalus.

OBJECTIVE: A considerable percentage of preterm infants with posthemorrhagic hydrocephalus initially managed with an Ommaya reservoir require a permanent CSF shunt. The objective of the study was to analyze possible risk factors associated with the need for converting an Ommaya reservoir to a permanent shunt. METHODS: The authors retrospectively reviewed the clinical records of premature infants weighing 1500 g or less with posthemorrhagic hydrocephalus (Papile grades III and IV) managed with an Ommaya reservoir at their institution between 2002 and 2017. RESULTS: Forty-six patients received an Ommaya reservoir. Five patients (10.9%) were excluded due to intraventricular infection during management with an Ommaya reservoir. Average gestational age and weight for the remaining 41 patients was 27 ± 1.8 weeks and 987 ± 209 grams, respectively. Thirty patients required a permanent shunt and 11 patients did not require a permanent shunt. The conversion rate from an Ommaya reservoir to a permanent shunt was 76.1%. Symptomatic persistent ductus arteriosus (PDA) was more frequent in the nonpermanent shunt group than in the shunt group (88.9% vs 50%, p = 0.04). The need for extraction of more than 10 ml/kg per day of CSF through the Ommaya reservoir was lower in the nonpermanent shunt group than in the shunt group (9.1% vs 51.7%, p = 0.015). CSF lactate was lower in the nonpermanent group than in the shunt group (mean 2.48 mg/dl vs 3.19 mg/dl; p = 0.004). A cutoff value of ≥ 2.8 mg/dl CSF lactate predicted the need for a permanent shunt with sensitivity and specificity of 82.4% and 80%, respectively. There were no significant differences in gestational age, sex, weight, Papile grade, ventricular index, or other biochemical markers. After the multivariate analysis, only CSF lactate ≥ 2.8 mg/dl was associated with a higher conversion rate to a permanent shunt. CONCLUSIONS: This study showed that a high level of CSF lactate, absence of symptomatic PDA, and a higher CSF extraction requirement were associated with a higher likelihood of implanting a permanent CSF shunt. The authors believe these findings should be considered in future studies.

Atypical clinical presentation and long-term survival in a patient with optic nerve medulloepithelioma: a case report.

INTRODUCTION: Medulloepithelioma is a rare congenital tumor of the primitive medullary neuroepithelium. A significant proportion of patients with medulloepithelioma arising from the optic nerve die from intracranial spread or cerebral metastasis. Because it has no known distinct clinical features and because of its low frequency, this tumor presents within the first two to six years of life and is usually misdiagnosed clinically as a different type of optic nerve tumor. Here, we describe a new and atypical case of medulloepithelioma of the optic nerve in a 12-year-old boy. To the best of our knowledge, he is the oldest reported patient to present with this disease and, now as an adult, has the longest documented period of disease-free survival. CASE PRESENTATION: A 12-year-old Caucasian boy with headache and unilateral amaurosis was referred for a presumed optic nerve glioma to our hospital. A computed tomography scan showed optic nerve enlargement, and fundoscopy showed a whitish mass at the optic disc. Our patient had been followed at his local hospital for four years for an 'optic disc cyst' with no change or progression. He experienced mild progressive visual impairment during that period. He was admitted for resection, and a histopathological analysis revealed a medulloepithelioma of the optic nerve. Supplemental orbital radiotherapy was performed. He remained disease-free for 25 years. CONCLUSIONS: Medulloepithelioma of the optic nerve can clinically mimic more common pediatric tumors, such as optic glioma, meningioma, or retinoblastoma. Thus, medulloepithelioma should be included in the differential diagnoses of pediatric optic nerve lesions. Fundoscopy in these patients may provide relevant information for diagnosis. Anterior optic nerve medulloepitheliomas may behave differently from and have a better prognosis than medulloepitheliomas that have a more posterior location. Our case report illustrates that long-term survival can be achieved in patients with this malignant tumor.

[Primary prophylaxis of early seizures after surgery of cerebral supratentorial tumors: Group for the Study of Functional-Sterotactic Neurosurgery of The Spain Society of Neurosurgery recommendations]. / Control de las crisis epilépticas durante el postoperatorio inmediato de los tumores cerebrales supratentoriales: recomendaciones del Grupo de Neurocirugía Funcional y Estereotáctica de la Sociedad Española de Neurocirugía.

Our review of the literature is basically focused on the primary prophylaxis of early seizures after surgery of cerebral supratentorial tumors, with the aim of suggesting several recommendations in medical antiepileptic treatment to avoid this kind of seizures which occur immediately after surgery. In conclusion, it is recommended to provide criteria for prophylaxis of early seizures after surgery of cerebral supratentorial tumors. It́s recommended a one week treatment with antiepileptic drugs in patients who didnt have seizures jet, starting immediately after the surgical treatment. If seizures appear during progress of the disease, a large period treatment will be needed. Preferred antiepileptic treatment is intravenous and with a low interactions profile. Levetiracetam, followed by valproic acid seem to be most appropriated drugs due to their properties and protective effects, particularly for our patients requirements. These recommendations are considered a general proposal to effective clinical management of early seizures after surgery, not taking into account the single circumstances of our patients. Always, clinical features of the patients could modify even significantly these guides in the benefit of each patient.

Control de las crisis epilépticas durante el postoperatorio inmediato de los tumores cerebrales supratentoriales: recomendaciones del Grupo de Neurocirugía Funcional y Estereotáctica de la Sociedad Española de Neurocirugía / Primary prophylaxis of early seizures after surgery of cerebral supratentorial tumors: Group for the Study of Functional-Sterotactic Neurosurgery of The Spain Society of Neurosurgery recommendations

Con la finalidad de proponer una serie de recomendaciones del tratamiento médico antiepiléptico, en el perioperatorio de los tumores cerebrales supratentoriales, se realiza una revisión de la literatura enfocada sobre todo a la profilaxis primaria de las crisis epilépticas precoces acaecidas en el postoperatorio inmediato. Se concluye que es recomendable pautar profilaxis primaria antiepiléptica poscirugía durante una semana en los pacientes con tumor cerebral supratentorial que no han presentado crisis epilépticas. Si las crisis aparecen durante la evolución de la enfermedad, es necesario pautar un tratamiento a largo plazo. Dadas las características de estos pacientes, se recomienda usar un fármaco antiepiléptico con presentación por vía intravenosa y un perfil bajo de interacciones. El levetiracetam, seguido del valproato, parecen ser los más adecuados. Dichas recomendaciones deben considerarse como una guía general de manejo, pudiendo ser modificadas, incluso de manera significativa, por las circunstancias propias de cada caso clínico (AU)

Our review of the literature is basically focused on the primary prophylaxis of early seizures after surgery of cerebral supratentorial tumors, with the aim of suggesting several recommendations in medical antiepileptic treatment to avoid this kind of seizures which occur immediately after surgery. In conclusion, it is recommended to provide criteria for prophylaxis of early seizures after surgery of cerebral supratentorial tumors. It's recommended a one week treatment with antiepileptic drugs in patients who didn't have seizures jet, starting immediately after the surgical treatment. If seizures appear during progress of the disease, a large period treatment will be needed. Preferred antiepileptic treatment is intravenous and with a low interactions profile. Levetiracetam, followed by valproic acid seem to be most appropriated drugs due to their properties and protective effects, particularly for our patients requirements. These recommendations are considered a general proposal to effective clinical management of early seizures after surgery, not taking into account the single circumstances of our patients. Always, clinical features of the patients could modify even significantly these guides in the benefit of each patient (AU)

[Cerebral hemisphere tumours in neurofibromatosis type 1 during childhood]. / Tumores de los hemisferios cerebrales en la neurofibromatosis tipo 1 durante la infancia.

AIM: To present seven tumors of the cerebral hemispheres in 6 children with neurofibromatosis type 1 (NF1). PATIENTS AND METHODS: Six patients (three males and three females) of 600 cases of a series with NF1 showed features of cerebral hemispheres tumor (seizures, headache and hemiparesis). They were studied neurologically, by EEG and by image (MR and/or spectroscopic-MR) because of these features or simply because having NF1. RESULTS: All the patients had the two diagnostic criteria of the NF1. Six patients had seven tumors (it was because one of them had one tumor in every frontal lobe, both with the same image characteristics), but they did not were removed and they were not studied histologically. The histological study was made to the other five patients and showed that the histological nature corresponded to pilocytic astrocytoma in one patient, neuroepitelial dysembryoplastic tumor in one, polymorphe xanthoastrocytoma in one, neuroectodermic hamartoma in one, and inflammatory chronic non-granulomatose lesion in one. CONCLUSION: The prevalence of the tumors in the cerebral hemispheres is very low (1%) in the patients with NF1. The tumors commonly are histologically benign, and they can be found in peripheral or deep region of the cerebral hemispheres. Identity of the tumors by MR study commonly is easy and the treatment is surgical in most cases. However, urgent treatment very seldom is necessary in these tumors, and most frequently is possible to take the attitude of 'wait and see' before to decide the definite treatment.

Tumores de los hemisferios cerebrales en la neurofibromatosis tipo 1 durante la infancia / Cerebral hemisphere tumours in neurofibromatosis type 1 during childhood

Objetivo. Presentar siete tumores en los hemisferios cerebrales en seis niños con neurofibromatosis tipo 1 (NF1). Pacientes y métodos. Seis pacientes (tres mujeres y tres varones) entre 600 casos con NF1 presentaban síntomas de tumor de los hemisferios cerebrales (crisis epilépticas, cefaleas y hemiparesia). Fueron estudiados por estos hechos o simplemente por la NF1 desde el punto de vista neurológico, mediante electroencefalograma e imagen (resonancia magnética o resonancia magnética espectroscópica). Resultados. Todos los pacientes presentaban los dos criterios diagnósticos de la NF1. Seis pacientes presentaban siete tumores (una paciente tenía un tumor en cada lóbulo frontal; las imágenes radiológicas de ambos fueron de similares características, pero no se extirparon y no se realizó el estudio histológico). El estudio histológico de los tumores extirpados se realizó a los otros cinco pacientes, y mostró que correspondía a astrocitoma pilocítico en el primero, tumor neuroepitelial disembrioplásico en el segundo, hamartoma neuroectodérmico en el tercero, xantoastrocitoma polimorfo en el cuarto y lesión inflamatoria crónica no granulomatosa en el quinto. Conclusión. La prevalencia de los tumores de los hemisferios cerebrales es muy baja (1%) en los pacientes con NF1. Los tumores son generalmente de naturaleza histológica benigna y pueden localizarse en zonas periféricas o centrales de los hemisferios cerebrales. La identificación tumoral mediante resonancia magnética es comúnmente fácil y el tratamiento es quirúrgico en la mayoría de los casos. En pocas ocasiones hay que actuar con urgencia en estos tumores, y la mayoría de las veces se puede adoptar la actitud prudente de ‘esperar y ver’ hasta tomar la decisión definitiva (AU)

Aim. To present seven tumors of the cerebral hemispheres in 6 children with neurofibromatosis type 1 (NF1). Patients and methods. Six patients (three males and three females) of 600 cases of a series with NF1 showed features of cerebral hemispheres tumor (seizures, headache and hemiparesis). They were studied neurologically, by EEG and by image (MR and/or spectroscopic-MR) because of these features or simply because having NF1. Results. All the patients had the two diagnostic criteria of the NF1. Six patients had seven tumors (it was because one of them had one tumor in every frontal lobe, both with the same image characteristics), but they did not were removed and they were not studied histologically. The histological study was made to the other five patients and showed that the histological nature corresponded to pilocytic astrocytoma in one patient, neuroepitelial dysembryoplastic tumor in one, polymorphe xanthoastrocytoma in one, neuroectodermic hamartoma in one, and inflammatory chronic nongranulomatose lesion in one. Conclusion. The prevalence of the tumors in the cerebral hemispheres is very low (1%) in the patients with NF1. The tumors commonly are histologically benign, and they can be found in peripheral or deep region of the cerebral hemispheres. Identity of the tumors by MR study commonly is easy and the treatment is surgical in most cases. However, urgent treatment very seldom is necessary in these tumors, and most frequently is possible to take the attitude of ‘wait and see’ before to decide the definite treatment (AU)