First occurrence of Arnold Chiari type II malformation and associated abnormalities in a Gir calf produced in vitro from Brazil - case report / [Primeira ocorrência de malformação de Arnold Chiari tipo II e anormalidades associadas em uma bezerra Gir de produção in vitro no Brasil - relato de caso]

This study characterized the clinical, radiological, ultrasound, and necroscopic findings of a case of Arnold-Chiari type II malformation in a Gir breed calf from Brazil. The animal was hospitalized at sixty days of age, in permanent sternal recumbency, cutaneous appendix at the 4th lumbar vertebra and kyphoscoliosis of the caudal and lumbosacral thoracic spine. Radiographic examination of the spine and skull revealed spina bifida and suspected occipital hypoplasia. Upon examination of myelography with an injection of lumbar and atlantooccipital contrast, it was possible to visualize the meningocele at the 4th lumbar vertebra region and findings at the rhombencephalon level of increased regional pressure with failure to fill the contrast in the posterior fossa, in the presence of clear demarcation of the circumvolutions of the cerebral cortex and the subarachnoid space of the cervical spinal cord. Ultrasonographic examination of the cerebellum showed an insinuation of the cerebellar worm through the foramen magnum. The animal did not show changes in complete blood count, biochemical series, and cerebrospinal fluid and was negative for Pestivirus. There was a worsening of the clinical conditions and the animal died. This malformation of unknown etiology must be studied as a differential diagnosis of the nervous system disorders.(AU)

Este estudo caracterizou os achados clínicos, radiológicos, ultrassonográficos e necroscópicos de um caso de malformação de Arnold-Chiari tipo II em uma bezerra Gir no Brasil. O animal foi hospilatizado aos 60 dias de idade, apresentando decúbito esternal permanente, apêndice cutâneo na altura da quarta vértebra lombar e cifoescoliose da coluna vertebral torácica caudal e lombossacra. Ao exame radiográfico da coluna e do crânio, foram observadas espinha bífida e suspeita de hipoplasia occipital. Ao exame de mielografia com injeção de contraste lombar e atlanto-occipital, foi possivel visualizar a meningocele na altura da quarta vértebra lombar e achados em nível rombencefálico de aumento da pressão regional com falha de preenchimento do contraste na fossa posterior, na presença de nítida demarcação das circunvoluções do córtex cerebral e do espaço subaracnoide da medula espinhal cervical. Ao exame ultrassonográfico do cerebelo, foi observada insinuação do verme cerebelar através do forame magno. O animal não apresentou alterações em hemograma completo, série bioquímica e fluido cérebro-espinhal e foi negativo para Pestivirus. Houve uma piora do quadro clínico e o animal morreu. Essa malformação de etiologia desconhecida deve ser estudada como um diagnóstico diferencial.(AU)

Isolated hemorrhage in the cerebellar vermis with vertigo and body lateropulsion to the contralesional side / 영남의대학술지

There have been several reports of patients with isolated lesions of the cerebellar vermis presenting with clinical features similar to those of peripheral vestibulopathy. We report a case of small, isolated hematoma in the cerebellar vermis in a patient who presented with vertigo, ipsilesional nystagmus, and body lateropulsion to the contralesional side without the usual signs or symptoms of cerebellar dysfunction. Although they present with symptoms that mimic those of peripheral vestibulopathy, and brain computed tomography shows no abnormality, as there may be a small, isolated hematoma or infarction in the cerebellar vermis. Thus, brain magnetic resonance imaging should be performed in elderly patients with vascular risk factors.

Systemic injection of an H4 receptor agonist induces a decrease in CREB and pCREB levels in the cerebellar vermis and prefrontal cortex in mice

Studies have shown that an injection with the histamine H4 receptor agonist VUF-8430 modulates emotional memory processes. In the present study, the aim was to verify if intraperitoneal (ip) injection of VUF-8430 (500 ng/kg) in mice affects the synthesis of proteins required for memory consolidation processes by activating the phosphorylation of CREB (pCREB) in classical structures linked to emotional memory (prefrontal cortex, amygdala, and hippocampus) and the cerebellar vermis, a structure that has also been recently implicated in emotional memory. The results obtained using western blot analysis demonstrated that VUF-8430 induced a decrease in CREB and pCREB levels in the cerebellar vermis and prefrontal cortex, suggesting that this dose impaired the activation of cell signaling pathways in these structures. There was no change in protein expression in the amygdala and hippocampus. Our results are preliminary, and further investigations are needed to investigate the role of the H4 receptors in the central nervous system.

Treadmill Exercise Improves Motor Function by Suppressing Purkinje Cell Loss in Parkinson Disease Rats / 대한배뇨장애요실금학회지

PURPOSE: Rotenone is the most widely used neurotoxin for the making Parkinson disease (PD) animal model. The neurodegenerative disorder PD shows symptoms, such as slowness of movements, tremor at resting, rigidity, disturbance of gait, and instability of posture. We investigated whether treadmill running improves motor ability using rotenone-caused PD rats. The effect of treadmill running on PD was also assessed in relation with apoptosis of cerebellar Purkinje cells. METHODS: Treadmill running was applied to the rats in the exercise groups for 30 minutes once a day for 4 weeks, starting 4 weeks after birth. We used rota-rod test for the determination of motor coordination and balance. In this experiment, terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) staining, immunohistochemistry for calbindin, glial fibrillary acidic protein (GFAP), Iba-1, and western blot analysis for Bax and Bcl-2 were performed. RESULTS: Treadmill running enhanced motor balance and coordination by preventing the loss of Purkinje cells in the cerebellar vermis. Treadmill running suppressed PD-induced expression of GFAP-positive reactive astrocytes and Iba-1-positive microglia, showing that treadmill running suppressed reactive astrogliosis and microglia activation. Treadmill running suppressed TUNEL-positive cell number and Bax expression and enhanced Bcl-2 expression, demonstrating that treadmill running inhibited the progress of apoptosis in the cerebellum of rotenone-induced PD rats. CONCLUSIONS: Treadmill running improved motor ability of the rotenone-induced PD rats by inhibiting apoptosis in the cerebellum. Apoptosis suppressing effect of treadmill running on rotenone-induced PD was achieved via suppression of reactive astrocyte and inhibition of microglial activation.

Intermediate Pilomyxoid Astrocytoma in the Cerebellum of a 5-Year-Old Boy

Intermediate pilomyxoid tumors (IPTs) were defined by the presence of some features typical of pilomyxoid astrocytoma (PMA) in combination with features that could be considered more consistent with pilocytic astrocytoma (PA). PMA is rare in the cerebellum. And, IPT in the cerebellum is rarer than PMA. To our knowledge, only 2 reports have described IPT in the cerebellum. A 5-year-old boy had nausea and vomiting. Computed tomography revealed a large, round, low-density tumor in the cerebellar vermis area. On enhanced magnetic resonance imaging (MRI), the tumor showed inhomogeneous diffuse enhancement; the central portion showed homogenous enhancement, while the peripheral portion showed inhomogeneous enhancement. The patient underwent a midline suboccipital craniotomy, and gross total resection was performed. The tumor was gray-colored, rubbery hard, and severely hemorrhagic with a clear boundary. On pathologic examination, the combined features of both PA and PMA were retrospectively indicative of an IPT. The patient was symptom-free for 18 months, with no evidence of tumor recurrence on MRI. More observation and further studies on PMA and IPT are required to determine the most appropriate treatment for these tumors.

Whole Exome Sequencing in a Korean Child with Joubert Syndrome-related Disorders

Joubert syndrome and Joubert syndrome-related disorders (JSRDs) are rare autosomal recessive or X-linked disorders characterized by cerebellar vermis hypoplasia and a brain stem malformation, which presents as the “molar tooth sign” in magnetic resonance imaging (MRI). JSRDs are a group of clinically heterogeneous conditions that exhibit neurological manifestations and multiple organ involvement. JSRDs are also genetically heterogeneous, and approximately 20 causative genes that account for 45% of JSRDs have been identified. A 7-yr-old boy visited Wonkwang University Sanbon Hospital with the following presentations: no ocular fixation, ataxia, growth retardation, and hypotonia. Physical examination revealed facial dysmorphism, spindle shaped fingers, and height (99 cm) and weight (13 kg) below the third percentile. Ophthalmic examination revealed retinal dystrophy. A diagnosis of JSRDs was made based on clinical and brain MRI findings. We found two heterozygous variants c.2945 G>T; p.Arg982Met (G>T) and c.2216dupA; p.Phe740Valfs*2 (dupA) in AHI1, and a heterozygous c.3973C>T; p.Arg1325Trp (C>T) variant in KIF7 by whole exome sequencing (WES). Genetic analysis on the proband's father revealed that he had both AHI1 variants, but did not have the KIF7 variant, which was inconsistent with autosomal recessive inheritance. Therefore, the G>T variant and C>T variant were presumed to be of “uncertain significance.” Furthermore, one novel dupA variant was interpreted as “pathogenic,” while the second allele was not detected. Caution should be exercised while interpreting the significance of variants detected by WES. In addition, the involvement of genes other than the 20 known ones will require further investigation to elucidate the pathogenesis of JSRDs.

Down syndrome with asymptomatic neuroglial cyst: A case report and review of the literature

Down syndrome (DS, trisomy 21) is associated with neuroanatomical abnormalities, including choroid plexus cysts and various types of brain tumors. Trisomy 21 is associated with oncogenic factor, especially in brain tumor. The brain of DS patients had a smaller volume of gray and white matter and an unbalanced cerebellum volume, indicating a smaller volume overall than normal. We report a case of a DS male patient who had an incidentally discovered neuroglial cyst in left cerebellar vermis. He visited our hospital with gait disturbance and fatigue. But, the neurologic exam was normal. To the best of our knowledge, this is the first reported case of a neuroglial cyst in a trisomy 21 patient. As the developmental mechanisms of a cyst and the choroid plexus are related, more research is needed.

Wernicke Encephalopathy Associated with Acute Wet Beriberi

Wernicke encephalopathy is usually accompanied with peripheral neuropathy, known as dry beriberi. In contrast, wet beriberi presenting as cardiovascular symptoms rarely occurs. The acute type of wet beriberi can be fatal, if untreated quickly. It is reported that the cerebellar vermis has a role of the coordination and control of cardiovascular and autonomic reflex activities. We report a 58-year-old man showing acute wet beriberi in Wernicke encephalopathy with cerebellar vermis lesion.

A neonate with Joubert syndrome presenting with symptoms of Horner syndrome / 소아과

Joubert syndrome (JS) is characterized by the “molar tooth sign” (MTS) with cerebellar vermis agenesis, episodic hyperpnea, abnormal eye movements, and hypotonia. Ocular and oculomotor abnormalities have been observed; however, Horner syndrome (HS) has not been documented in children with JS. We present the case of a 2-month-old boy having ocular abnormalities with bilateral nystagmus, left-dominant bilateral ptosis, and unilateral miosis and enophthalmos of the left eye, which were compatible with HS. Brain magnetic resonance imaging (MRI) revealed the presence of the MTS. Neck MRI showed no definite lesion or mass around the cervical sympathetic chain. His global development was delayed. He underwent ophthalmologic surgery, and showed some improvement in his ptosis. To the best of our knowledge, the association of HS with JS has not yet been described. We suggest that early neuroimaging should be considered for neonates or young infants with diverse eye abnormalities to evaluate the underlying etiology.

Isolated Infarction of Anterior Cerebellar Vermis / 대한평형의학회지

The anterior cerebellar vermis has been known to act in coordination of gait and postural adjustment of the trunk and legs. However, oculomotor abnormalities in an isolated anterior vermian lesion have not been described in the literature. A 59-year-old man presented with acute non-rotatory dizziness and disequilibrium. Neuro-ophthalmologic examination found impaired smooth pursuit and hypometric saccades in the contralesional direction, and disconjugate ipsiversive ocular torsion, but without spontaneous or gaze-evoked nystagmus. Imaging study showed an infarction restricted to the rostral end of right cerebellar vermis involving the lingual and central lobules. The anterior cerebellar vermis participates in the maintenance of axial posture and gait, and also in the control of ocular motor and vestibular systems.

Estudio neuropsicológico pre y posquirúrgico en dos niños de 8 años de edad con tumor en fosa posterior / Neuropsychological study pre and post surgical in two children aged 8 years with posterior fossa tumor

Objetivo: Identificar y describir las diferencias neuropsicológicas antes y después de resecar el tumor en 2 pacientes de 8 años de edad con una neoplasia en la fosa posterior. Metodología: Se realizó evaluación neuropsicológica pre y posquirúrgica a 2 pacientes de 8 años de edad del Instituto Nacional de Pediatría, uno femenino con quiste aracnoideo en cisterna paravermiana y otro masculino con meduloblastoma en vermis y se compararon los datos obtenidos antes de extirpación de tumor y después de ella. Para la obtención del IQ se aplicó el WISC-IV y para las otras funciones, la Evaluación Neuropsicológica Infantil (ENI), para niños de 5 a 16 años, obteniéndose sus valores en percentiles que se igualaron con la clasificación cualitativa. Resultados: Los 2 pacientes presentaron deficiencias en el IQ, en Funciones Cognitivas, en las Habilidades de Rendimiento Académico, así como en sus Funciones Ejecutivas. A pesar de que no se aplicó quimioterapia ni radioterapia, tanto antes de la cirugía, como después de la extirpación del tumor, empeorando dichas funciones después de la extirpación. Conclusiones: Los tumores en Fosa Posterior originan diversas alteraciones neuropsicológicas similares a las observadas con lesiones en la corteza cerebral, dichas alteraciones se hacen más severas después de la extirpación del tumor; esta evolución puede presentar un dilema a la luz de la Bioética: ¿Se prolonga la vida a expensas de mayor deterioro neurocognitivo al quitar el tumor, o no se opera para evitar mayor deterioro en la calidad de vida y se reduce el tiempo de vida?.

Aim: Identify and describe the neuropsychological differences before and after surgery in 2 patients 8 years of age with a tumor in the posterior fossa. Methodology: Neuropsychological assessment was performed before and after surgery to 2 patients (8 years of age), one female with arachnoid cyst in paravermian cyst and another male with medulloblastoma in vermis and we compared the data obtained before removal of tumor and after. We use the following Neuropsychological Tests: WISC-IV was applied to assess IQ and Child Neuropsychological Assessment (ENI) was to evaluate cognitive functions. Results: The 2 patients had deficits in IQ, cognitive functions, the academic performance skills and his executive skills, even without chemotherapy or radiotherapy, both before surgery and after removal of the tumor. These functions worsened after surgery. Conclusions: Posterior fossa tumors originate many various neuropsychological similar to those observed in cerebral cortex, these changes are most evident after removal of the tumor, this evolution can present a dilemma in light of Bioethics: Is justified to prolong the life at expense of neurocognitive impairment, after removing a big tumor, or not to operate preventing further deterioration in the quality of life and reducing the lifetime?.

Effect of histamine H1 and H2 receptor antagonists, microinjected into cerebellar vermis, on emotional memory consolidation in mice

This study investigated the effects of histamine H1 or H2 receptor antagonists on emotional memory consolidation in mice submitted to the elevated plus maze (EPM). The cerebellar vermis of male mice (Swiss albino) was implanted using a cannula guide. Three days after recovery, behavioral tests were performed in the EPM on 2 consecutive days (T1 and T2). Immediately after exposure to the EPM (T1), animals received a microinjection of saline (SAL) or the H1 antagonist chlorpheniramine (CPA; 0.016, 0.052, or 0.16 nmol/0.1 µL) in Experiment 1, and SAL or the H2 antagonist ranitidine (RA; 0.57, 2.85, or 5.7 nmol/0.1 µL) in Experiment 2. Twenty-four hours later, mice were reexposed to the EPM (T2) under the same experimental conditions but they did not receive any injection. Data were analyzed using one-way ANOVA and the Duncan test. In Experiment 1, mice microinjected with SAL and with CPA entered the open arms less often (%OAE) and spent less time in the open arms (%OAT) in T2, and there was no difference among groups. The results of Experiment 2 demonstrated that the values of %OAE and %OAT in T2 were lower compared to T1 for the groups that were microinjected with SAL and 2.85 nmol/0.1 µL RA. However, when animals were microinjected with 5.7 nmol/0.1 µL RA, they did not show a reduction in %OAE and %OAT. These results demonstrate that CPA did not affect behavior at the doses used in this study, while 5.7 nmol/0.1 µL RA induced impairment of memory consolidation in the EPM.

Joubert Syndrome.

Joubert syndrome is a very rare condition seen in our country. Herein, we report a case of Joubert syndrome in a one year four months old, male baby from a consanguineous marriage presenting with delayed developmental milestone, hypotonia, abnormal respiratory pattern and nystagmus . Cranial MRI shows ‘‘Molar Tooth Sign’’.

Papel de la adrenomedulina cerebelosa en la regulación de la presión arterial / Role of cerebelar adrenomedullin in blood pressure regulation

La adrenomedulina (AM) es un péptido ubicuo de 52 residuos de aminoácidos que cumple funciones importantes en la regulación de la función cardiovascular (CDV). La AM ejerce sus acciones a través de su unión con tres subtipos de receptores, el receptor del péptido relacionado al gen de la calcitonina tipo 1 (CGRP1), el receptor de AM tipo 1 (AM1) y tipo 2 (AM2). El CGRP1 está formado por el receptor similar al receptor de calcitonina (CRLR) y la proteína que modifica la actividad del receptor tipo 1 (RAMP1). El AM1 por el CRLR+RAMP2 y el AM2 por el CRLR+RAMP3. A nivel del sistema nervioso central, la AM y sus receptores se localizan en diversas regiones, incluyendo el cerebelo. Se ha demostrado marcados incrementos en la densidad de los sitios de unión para la AM en el cerebelo durante la hipertensión, lo que sugiere un papel del sistema adrenomedulinérgico cerebeloso en la regulación de la presión arterial (PA). En el presente estudio se evaluó la participación de la AM cerebelosa en la regulación de la PA. Nuestros hallazgos muestran la existencia de desregulación de los componentes del sistema AM cerebeloso durante la hipertensión, ya que se encontró una reducida expresión de CRLR, RAMP1 y RAMP3 y una incrementada expresión de la AM y RAMP2 en el vermis de cerebelo de ratas hipertensas (SHR), cuando se comparó con las ratas controles, Wistar Kyoto (WKY), de 8 y 16 semanas de edad. La reducción de la PA mediante el tratamiento crónico con valsartán (60mg/Kg/día,p.o.) revirtió las desregulación de la AM y los componentes de su receptor, observados en las ratas SHR. El papel de las especies reactivas de oxígeno (EROS) en la acción de la AM cerebelosa quedó evidenciado, ya que la AM fue capaz de reducir la actividad de las tres enzimas antioxidantes, superóxiodo dismutasa (SOD), catalasa (CAT) y glutatión peroxidasa (GPx), en las ratas WKY y Sprague - Dawley (SD). Aún mas, nuestros hallazgos mostraron claramente el efecto antagónico entre la AM y la ANG II sobre la actividad de las enzimas antioxidantes inducida por la ANG II. El efecto de la AM sobre las enzimas antioxidantes no se manifestó en la ratas hipertensas, sin embargo el mismo fue restaurado mediante la disminución de la presión arterial con la administración crónica de dos antihipertensivos de mecanismo de acción distintos como la amlodipina (5mg/Kg/día,p.o) o el valsartán (60mg/Kg/día,p.o), lo que sugiere una relación entre la hipertensión y ausencia del efecto de AM en la ratas SHR. Al evaluar la posible vía de señalización que media la acción de la AM y el antagonismo con la ANG II sobre la actividad de las enzimas antioxidantes, demostramos que no existe una vía final común para dicho antagonismo, siendo la proteína quinasa A (PKA) y los 3 subtipos de receptores CGRP1, AM1 y AM2 los que median la acción de la AM, mientras que la acción de la ANG II se encuentra mediada a través de una vía que involucra la PKC/NAD(P)H oxidasa. Los hallazgos demuestran el antagonismo entre la AM y la ANG II en la regulación del estrés oxidativo en el cerebelo y ratifican la desregulación de la señalización de la AM mediada por EROs durante la hipertensión. Al evaluar las vías de señalización intracelular que median la acción de la AM en el cerebelo, demostramos que la AM es capaz de activar a las ERK, la producción de GMPc y NO a través de la estimulación del receptor AM1, y del AMPc a través de los tres subtipos de receptores de AM, lo que apoya que en el cerebelo la AM ejerce acciones a través de diversas vías de señalización como lo son NO/GMPc, AC/AMPc/PKA y/o ERK. El posible papel funcional de la AM in vivo fue inequívoco, ya que se demostró que la microinyección de AM en el vermis cerebeloso produjo una respuesta hipotensora profunda en las ratas SHR pero no en las normotensas. El hecho que la microinyección de AM en el vermis cerebelar en las ratas SD, WKY y SHR disminuyó significativamente la respuesta presora frente al estrés simpatoadrenal inducido por el estímulo eléctrico plantar, sugiere que la acción hipotensora está mediada a través de la regulación del eflujo simpático e indica un posible papel de la AM en la regulación de la respuesta CDV frente al estrés. En conjunto, nuestros resultados demuestran la existencia de un sistema adrenomedulinérgico funcional en el cerebelo, e indican por primera vez, que la AM cumple un papel importante en la regulación de la PA durante la hipertensión y el estrés.

A case of Arnold-Chiari malformation / 영남의대학술지

The Arnold-Chiari malformation (ACM) is an anomaly of the hindbrain consisting of two components: a variable displacement of a tongue of tissue derived from the inferior cerebellar vermis in the upper cervical canal and a similar caudal dislocation of the medulla and fourth ventricle. Hydrocephalus and meningomyelocele are another abnormalities that associated frequently. We present a case of Arnold-Chiari malformation with hydrocephalus and meningomyeolcele and a brief review of the literatures was added.