Cerebellar cortical vein thrombosis mimicking a vermian tumor: case report.

Cortical vein thrombosis is an uncommon cause of stroke and generally occurs in the supratentorial compartment. Spontaneous venous thrombosis with infarction in the posterior fossa usually occurs in association with either dural sinus thrombosis and/or thrombosis of the petrosal vein, usually with venous infarction of the cerebellar hemisphere. Our goal is to present the case of a patient with thrombosis of cerebellar cortical veins, without sinus involvement, which mimicked a vermian cerebellar tumor.

The cellular state determines the effect of melatonin on the survival of mixed cerebellar cell culture.

The constitutive activation of nuclear factor-κB (NF-κB), a key transcription factor involved in neuroinflammation, is essential for the survival of neurons in situ and of cerebellar granule cells in culture. Melatonin is known to inhibit the activation of NF-κB and has a cytoprotective function. In this study, we evaluated whether the cytoprotective effect of melatonin depends on the state of activation of a mixed cerebellar culture that is composed predominantly of granule cells; we tested the effect of melatonin on cultured rat cerebellar cells stimulated or not with lipopolysaccharide (LPS). The addition of melatonin (0.1 nM-1 µM) reduced the survival of naïve cells while inhibiting LPS-induced cell death. Melatonin (100 nM) transiently (15 min) inhibited the nuclear translocation of both NF-κB dimers (p50/p50, p50/RelA) and, after 60 min, increased the activation of p50/RelA. Melatonin-induced p50/RelA activity in naïve cells resulted in the transcription of inducible nitric oxide synthase (iNOS) and the production of NO. Otherwise, in cultures treated with LPS, melatonin blocked the LPS-induced activation of p50/RelA and the reduction in p50/p50 levels and inhibited iNOS expression and NO synthesis. Therefore, melatonin in vehicle-treated cells induces cell death, while it protects against LPS-induced cytotoxicity. In summary, we confirmed that melatonin is a neuroprotective drug when cerebellar cells are challenged; however, melatonin can also lead to cell death when the normal balance of the NF-κB pathway is disturbed. Our data provide a mechanistic basis for understanding the influence of cell context on the final output response of melatonin.

Spontaneous poisoning by Solanum subinerme Jack as a cause of cerebellar cortical degeneration in cattle.

The present work reports cerebellar degeneration in cattle associated with the ingestion of Solanum subinerme in northern Brazil. The main clinical signs were periodic crises with loss of balance, falls, opisthotonus, and nystagmus. The histological lesions consisted of diffuse vacuolation of the perikaryon of the Purkinje neurons, followed by the loss of these cells and their substitution by Bergman glia. It is concluded that S. subinerme is another species of Solanum that causes cerebellar degeneration in cattle.

Gray matter volume in left rostral middle frontal and left cerebellar cortices predicts frontal executive performance in alcoholic subjects.

BACKGROUND: Alcoholic subjects manifest important deficits in frontal executive function, yet maintain cognitive mental status within normal range. METHODS: This study searched for volumetric measurements of segmented brain structures obtained from magnetic resonance imaging (MRI) that would predict executive functions and cognitive mental status in alcoholic subjects. The frontal assessment battery (FAB) and the Mini-Mental State Examination (MMSE) were applied to alcoholic subjects who underwent MRI. Cortical and subcortical segmentation and corrections were performed using FreeSurfer. Multiple linear regressions analyses having volumetric measures of segmented brain structures as predictors for FAB or MMSE scores as dependent measures were conducted. Sixty alcoholic subjects, 52 males, mean age of 47.2 ± SD 10.4 years, with heavy use of alcohol (mean 284.4 ± SD 275.9 g of alcohol/d) over a long time (mean 32.4 ± SD 11.1 years), showed FAB 11.1 ± SD 3.2 and MMSE of 25.2 ± SD 4.1. RESULTS: Multiple regression analyses having left and right side of each segment as predictors showed that gray matter volumes of rostral middle frontal cortex and cerebellar cortex (p < 0.001), in which only the left side of these structures showed significant partial effects in the full model (p < 0.05), showed to predict FAB performance. They were even more predictive when considered together (p < 0.001), in which both left rostral middle frontal cortex (p < 0.05) and left cerebellar cortex (p < 0.01) predictors had significant partial effects in the full model. None of brain structures was predictive of MMSE performance. CONCLUSIONS: We have concluded that volumetric measurements of left rostral middle frontal and cerebellar cortices seem to be able to predict the frontal executive performance but not the cognitive mental status in alcoholic subjects.

A combined voxel-based morphometry and 1H-MRS study in patients with Friedreich's ataxia.

Friedreich's ataxia (FA) is the most frequent autosomal recessive ataxia and essentially considered a disease of the dorsal root ganglia and spinal cord. It is caused by homozygous GAA expansions in the Frataxin gene in most cases. Although only a few studies have addressed cerebral involvement in FA, cognitive symptoms have lately been emphasized. To evaluate brain damage in vivo, we employed whole-brain VBM and analysis of pre-defined regions of interest (ROIs) over the cerebellum to compare 24 patients with 24 age-and-sex-matched normal controls. (1)H-MRS of deep cerebral white matter (WM) was subsequently performed. Mean age of patients was 28 years (range 14-45), mean duration of disease was 14 years (range 5-28) and 11 were men. Mean length of shorter (GAA1) and longer (GAA2) alleles were 735 and 863, respectively. VBM analysis identified WM atrophy in the posterior cyngulate gyrus, paracentral lobule and middle frontal gyrus. ROIs over the infero-medial cerebellar hemispheres and dorsal brainstem presented gray matter atrophy, which correlated with duration of disease (r = -0.4). NAA/Cr ratios were smaller among patients (P = 0.006), but not Cho/Cr (P = 0.08). Our results provide evidence of axonal damage in the cerebellum, brainstem and subcortical WM in FA. This suggests that neuronal dysfunction is more widespread than previously thought in FA.

Long-lasting effects of neonatal ionizing radiation exposure on spatial memory and anxiety-like behavior.

Neonatal ionizing radiation exposure has been shown to induce a cerebellar cytoarchitecture disarrangement. Since cerebellar abnormalities have been linked to an impairment of behavioral functions, the aim of the present work was to investigate whether exposure of developing rats to ionizing radiations can produce behavioral deficits in the adult. Male Wistar rats were X-irradiated with 5Gy within 48h after birth and were tested in a radial maze and in an open field at 30 and 90 days post irradiation. Irradiated rats showed significative changes in spatial, exploratory, and procedural parameters in the radial maze, as well as a significative decrease in anxiety-like behavior, assessed in the open field. These results suggest that ionizing radiations can induce long-lasting spatial memory and anxiety-related changes. A relationship with radiation-induced cerebellar cytoarchitecture abnormalities supports the hypothesis that cerebellar integrity seems to be critical to achieve spatial performance and emotional behavior establishment.

Imatinib therapy blocks cerebellar apoptosis and improves neurological symptoms in a mouse model of Niemann-Pick type C disease.

Niemann-Pick type C (NPC) disease is a fatal autosomal recessive disorder characterized by the accumulation of free cholesterol and glycosphingolipids in the endosomal-lysosomal system. Patients with NPC disease have markedly progressive neuronal loss, mainly of cerebellar Purkinje neurons. There is strong evidence indicating that cholesterol accumulation and trafficking defects activate apoptosis in NPC brains. The purpose of this study was to analyze the relevance of apoptosis and particularly the proapoptotic c-Abl/p73 system in cerebellar neuron degeneration in NPC disease. We used the NPC1 mouse model to evaluate c-Abl/p73 expression and activation in the cerebellum and the effect of therapy with the c-Abl-specific inhibitor imatinib. The proapoptotic c-Abl/p73 system and the p73 target genes are expressed in the cerebellums of NPC mice. Furthermore, inhibition of c-Abl with imatinib preserved Purkinje neurons and reduced general cell apoptosis in the cerebellum, improved neurological symptoms, and increased the survival of NPC mice. Moreover, this prosurvival effect correlated with reduced mRNA levels of p73 proapoptotic target genes. Our results suggest that the c-Abl/p73 pathway is involved in NPC neurodegeneration and show that treatment with c-Abl inhibitors is useful in delaying progressive neurodegeneration, supporting the use of imatinib for clinical treatment of patients with NPC disease.

Congenital cerebellar cortical degeneration in Holstein cattle in Southern Brazil.

A congenital progressive cerebellar disorder is described in Holstein calves. The clinical signs were progressive and were characterized by ataxia, hypermetria, a wide stance and fine head tremors. When the affected cattle were forced to run, the signs were exacerbated, leading to epileptiform attacks. Histological lesions consisted of a very selective cerebellar cortical degeneration, almost exclusively affecting the Purkinje cells. The disease affected 6 out of 200 Holstein calves from the same bull. However, results of mating tests of the bull with his daughters and granddaughters suggested that it was not hereditary (p = 0.0062) although an environmental-genetic interaction could not be ruled out.

A tryptophan-deficient corn-based diet induces plastic responses in cerebellar cortex cells of rat offspring.

Sprague-Dawley male rats, fed with a tryptophan-deficient and 8% protein corn-based diet were compared with a group of animals fed with 8% protein alone, and with a group fed with Chow Purina containing 23% protein. Retardation of Bergmann glial cell maturation and a concomitant retardation in granule cell migration were observed in the corn-fed group at 21 days. At 30 days of age, the dendrites of granule cells of both hypoproteic and corn-fed groups were larger than those of the Chow-fed animals. At 60 days of age, dendritic arborization of Purkinje cells was more profuse in both the hypoproteic and corn-fed rats compared with the Chow-fed group. This retardation in granule cell migration could be partially due to Bergmann glial cell immaturity. Consequently, several plastic and maybe compensatory events in both granule and Purkinje cells could have occurred, due to tryptophan deficiency resulting from the corn-based diet.

GM1 ganglioside treatment protects against long-term neurotoxic effects of neonatal X-irradiation on cerebellar cortex cytoarchitecture and motor function.

Exposure of neonatal rats to a 5 Gy dose of X-irradiation induces permanent abnormalities in cerebellar cortex cytoarchitecture (disarrangement of Purkinje cells, reduction of thickness of granular cortex) and neurochemistry (late increase in noradrenaline levels), and motor function (ataxic gait). The neuroprotective effects of gangliosides have been demonstrated using a variety of CNS injuries, including mechanical, electrolytic, neurotoxic, ischemic, and surgical lesions. Here, we evaluated whether systemically administered GM1 ganglioside protects against the long-term CNS abnormalities induced by a single exposure to ionizing radiation in the early post-natal period. Thus, neonatal rats were exposed to 5 Gy X-irradiation, and subcutaneously injected with one dose (30 mg/kg weight) of GM1 on h after exposure followed by three daily doses. Both at post-natal days 30 and 90, gait and cerebellar cytoarchitecture in X-irradiated rats were significantly impaired when compared to age-matched controls. By contrast, both at post-natal days 30 and 90, gait in X-irradiated rats that were treated with GM1 was not significantly different from that in non-irradiated animals. Furthermore, at post-natal day 90, cerebellar cytoarchitecture was still well preserved in GM1-treated, X-irradiated animals. GM1 failed to modify the radiation-induced increase in cerebellar noradrenaline levels. Present data indicate that exogenous GM1, repeatedly administered after neonatal X-irradiation, produces a long-term radioprotection, demonstrated at both cytoarchitectural and motor levels.

Lysosomal storage disease caused by Sida carpinifolia poisoning in goats.

A neurologic disease characterized by ataxia, hypermetria, hyperesthesia, and muscle tremors of the head and neck was observed for 2 years in a flock of 28 Anglo-Nubian and Saanen goats on a farm with 5 ha of pasture. Six newborns died during the first week of life, and five abortions were recorded. The predominant plant in the pasture was Sida carpinifolia. The disease was reproduced experimentally in two goats by administration of this plant. Three goats with spontaneous disease and the two experimental animals were euthanatized and necropsied. No significant gross lesions were observed. Fragments of several organs, including the central nervous system, were processed for histopathology. Small fragments of the cerebellar cortex, liver, and pancreas of two spontaneously poisoned goats and two experimentally poisoned goats were processed for electron microscopy. Multiple cytoplasm vacuoles in hepatocytes, acinar pancreatic cells, and neurons, especially Purkinje cells, were the most striking microscopic lesions in the five animals. Ultrastructural changes included membrane-bound vacuoles in hepatocytes, Kupffer cells, acinar pancreatic cells, Purkinje cells, and the small neurons of the granular cell layer of the cerebellum. Paraffin-embedded sections of the cerebellum and pancreas were submitted for lectin histochemical analysis. The vacuoles in different cerebellar and acinar pancreatic cells reacted strongly to the following lectins: Concanavalia ensiformis, Triticum vulgaris, and succinylated Triticum vulgaris. The pattern of staining, analyzed in Purkinje cells and acinar pancreatic cells coincides with results reported for both swainsonine toxicosis and inherited mannosidosis.

Motor abnormalities and changes in the noradrenaline content and the cytoarchitecture of developing cerebellum following X-irradiation at birth.

We have studied the developmental time-course of changes in the noradrenaline (NA) content of cerebellum (CE), cytoarchitecture of the cerebellar cortex, and motor abnormalities induced by the exposure of the cephalic end of rats to a single dose (5 Gy) of X-irradiation immediately after birth. At all ages examined, i.e., from postnatal (PN) d 5 to 90, CE from exposed animals show a marked atrophy, with an agranular cortex that has lost its layered structure. Purkinje cells are scattered at all depths in the cortex, and their primary dendrite is randomly oriented. The motor syndrome includes dystonia-like movements, a fine tremor, and an ataxic gait. Being progressive, the abnormal movements are evident from PN d 10, and fully developed by d 30. On the other hand, no differences in cerebellar NA content between X-irradiated rats and age-matched nonirradiated controls were detected from PN d 5 to 60. However, at PN d 90 a significant increase in NA content of CE from exposed animals is found when compared to either age-matched controls (+36%, p < 0.01), or data from irradiated rats obtained at PN d 5 to 60 (p < 0.01). These results indicate a temporal dissociation between the motor and cytoarchitectural abnormalities and the increase in cerebellar NA content produced by a single dose of X-rays at birth. The late increase in cerebellar NA content might represent a compensatory response of noradrenergic terminals to an altered information flow out of the cerebellar cortex induced by the ionizing noxa.

[Cytologic aspects of intracranial and spinal canal tumors]. / Aspecto citológico de tumores intracranianos e do canal vertebral.

We present the cytologic aspects of 137 tumors operated by neurosurgeons, including 12 astrocytomas, 4 anaplastic astrocytomas, 26 glioblastomas, 7 oligodendrogliomas, 5 medulloblastomas, 8 schwannomas, 17 meningiomas, 13 pituitary adenomas, 20 metastatic tumors and 18 assorted tumors and nonneoplastic lesions. We have also analysed cytologically samples of normal nervous tissue obtained from autopsies, aiming at its recognition and distinction from the neoplastic tissue in biopsies. The tumors were analysed in smears which were subsequently compared with the histological sections. Although it is important to observe cytological details in the tumor, occasionally cells are arranged in such a way, that an overview of the smear practically allows the diagnosis of the tumor.

Aspecto citológico de tumores intracranianos e do canal vertebral / Cytologic aspects of intracranial and spinal canal tumors

We present the cytologic aspects of 137 tumors operated by neurosurgeons, including 12 astrocytomas, 4 anaplastic astrocytomas, 26 glioblastomas, 7 oligodendrogliomas, 5 medulloblastomas, 8 schwannomas, 17 meningiomas, 13 pituitary adenomas, 20 metastatic tumors and 18 assorted tumors and nonneoplastic lesions. We have also analysed cytologically samples of normal nervous tissue obtained from autopsies, aiming at its recognition and distinction from the neoplastic tissue in biopsies. The tumors were analysed in smears which were subsequently compared with the histological sections. Although it is important to observe cytological details in the tumor, occasionally cells are arranged in such a way, that an overview of the smear practically allows the diagnosis of the tumor.

[Creutzfeldt-Jakob disease. The first case with histopathological study in Panama]. / Enfermedad de Creutzfeldt-Jakob. Primer caso con estudio histopatológico en Panamá.

We studied the clinical and histopathology findings of the first proved case of Creutzfeldt-Jakob disease in Panama. A sixty-five-years-old female patient referred from Santiago de Veraguas was admitted to Santo Tomás Hospital with a progressive clinical picture of dementia, incoordination and generalized myoclonia. The electroencephalogram showed periodic paroxysmal activity. The patient died eight months after initiated the disease. The cerebral histopathologic study was characteristic of Creutzfeldt-Jakob disease: status spongiform, neuronal loss and non-inflammatory gliosis was found.

Nota sobre as alteraçöes dos córtices cerebral e cerebelar no alcoolismo crônico / Cerebral and cerebellar cortices changes in chronic alcoholism

O estudo dos córtices cerebral cerebelar de 23 pacientes alcoólatras crônicos reveleu, no cérebro, macroscopicamente, atrofia cortical com adelgaçamento dos giros e largamento dos sulcos, notadamente no córtice frontal. Presente hidrocefalia interna do tipo "exvacuo" nos prolongamentos dos ventrículos laterais. No cerebelo ocorreru o desnudamento do pedúnculo cerebelar médio. Nunca constatamos atrofia do vermis cerebelar, macroscopicamente visível. O corpo caloso e a ponte do cérebro eram aparentemente normais. O estudo microscópico do córtice cerebral revelou importante perda da populaçäo neuronal e no cerebelar constatou-se a degeneraçäo dos grânulos e das células de Purkinje. Estas alteraçöes, macro e microscópicas, näo eram encontradiças em todos os casos. Estabeleceu-se a sua etiologia como alcoólica pela näo existência de outras patologias que pudessem explicá-las

[Dysplastic gangliocytoma of the cerebellum or Lhermittee-Duclos disease]. / Gangliocitoma displásico de cerebelo o enfermedad de Lhermittee-Duclos.

Lhermitte-Duclós disease is an infrequent condition of which there are only 37 cases described in the literature. Although presently considered as a displasic process, its clinical presentation is of a typical posterior fossa tumour and should be treated as such. Even though it is a benign growth there are only 7 cases described with postoperative survival. The uniform pathological anatomy in all the cases presented makes the definitive diagnosis. The authors present a new case with postoperative survival and discuss its clinical presentation, treatment and origin of the disease.

[Extensive cerebellar necrosis in sickle cell anemia. Report of a case]. / Necrose cerebelar extensa na anemia falciforme. Relato de um caso.

A 6 month-old mulatto boy was admitted on account of acute gastroenteritis, malnutrition and dehydration. In the hospital, the child developed septicemia, and temperature reached up to 38.6 degrees C. Despite intensive antibiotic treatment the patient died 12 days after admission. Necropsy disclosed bilateral bronchopneumonia, bilateral fronto-parietal subarachnoid hemorrhage, and extensive necrosis of the inferior half of both cerebellar hemispheres. On histopathological examination of the necrotic cerebellar cortex, numerous sickled erythrocytes were observed in petechial hemorrhages, and, in lesser quantities, inside capillaries. Lesions of the central nervous system in sickle cell anemia most often involve the cerebral cortex, and a single extensive cerebellar infarction as present in this case seems extremely rare. The pathogenetic mechanism of the necrosis is unclear, since thrombosis was not observed either in large blood vessels or in capillaries. Possible contributory factors were the infectious condition (septicemia), fever, and anoxia caused by the extensive bronchopneumonia.

Massive intracerebellar hemorrhage in low-birth-weight infants.

The clinical and pathologic observations of massive intracerebellar hemorrhage (destruction of at least one-third of cerebellar tissue) are described in six low-birth-weight infants. In all infants, severe progressive apnea associated with a falling hematocrit were the prominent clinical features. Four infants were asphyxiated at birth. Some degree of cerebellar hemorrhage (macroscopic or microscopic) was observed in 21% of 157 newborn brains examined at autopsy. The cause of massive intracerebellar hemorrhage is unknown, but may result from deforming pressures on the skull secondary to perinatal trauma. A close follow-up of cerebellar function in low-birth-weight infants is important.