Immunohistochemical expression of cyclin D1 is higher in supratentorial ependymomas and predicts relapses in gross total resection cases.

Ependymomas are tumors of the CNS. Although cyclin D1 overexpression has been related to several cancers, its prognostic value in ependymomas has not yet been fully established. We evaluated cyclin D1 expression by an immunohistochemistry analysis of 149 samples of ependymomas, including some relapses, corresponding to 121 patients. Eighty-one patients were adults, 60 were intracranial cases and 92 tumors were grade II. Gross total resection (GTR) was achieved in 62% of cases, and relapse was confirmed in 41.4% of cases. Cyclin D1 protein expression was analyzed by immunohistochemistry and scored with a labeling index (LI) calculated as the percentage of positively stained cells by intensity. We also analyzed expression of CCND1 and NOTCH1 in 33 samples of ependymoma by quantitative real-time PCR. A correlation between cyclin D1 LI score and anaplastic cases (P < 0.001), supratentorial location (P < 0.001) and age (P = 0.001) were observed. A stratified analysis demonstrated that cyclin D1 protein expression was strong in tumors with a supratentorial location, independent of the histological grade or age. Relapse was more frequent in cases with a higher cyclin D1 LI score (P = 0.046), and correlation with progression-free survival was observed in cases with GTR (P = 0.002). Only spinal canal tumor location and GTR were suggestive markers of PFS in multivarite analyses. Higher expression levels were observed in anaplastic cases for CCND1 (P = 0.002), in supratentorial cases for CCND1 (P = 0.008) and NOTCH1 (P = 0.011). There were correlations between the cyclin D1 mRNA and protein expression levels (P < 0.0001) and between CCND1 and NOTCH1 expression levels (P = 0.003). Higher cyclin D1 LI was predominant in supratentorial location and predict relapse in GTR cases. Cyclin D1 could be used as an immunohistochemical marker to guide follow-up and treatment in these cases.

Angiogenesis and expression of PDGF-C, VEGF, CD105 and HIF-1α in human glioblastoma.

Glioblastoma (GBM), the most frequent and aggressive brain tumor, is characterized by marked angiogenesis directly related to invasiveness and poor prognosis. Hypoxia is considered to be an important stimulus for angiogenesis by inducing hypoxia-inducible factor 1-alpha (HIF-1α) overexpression that activates platelet-derived growth factor (PDGF) and VEGF. The aim of this study is to analyze the expression of PDGF-C, VEGF in endothelial and tumor cells of GBM and their relation to HIF-1α expression. Two hundred and eight GBM cases were studied by tissue microarray immunohistochemical preparation. Expression of HIF-1α, VEGF and PDGF-C was observed in 184 (88.5%), 131 (63%) and 160 (76.9%) tumor cases, respectively. The numbers of vessels were quantified by CD34, PDGF-C, VEGF and CD105 staining, and were in median 20, 16, 5 and 6, respectively. The GBMs that showed positive or negative expression for HIF-1α showed a median vascular density of 30 and 14, respectively, for CD34 (P < 0.015). Positive expression for HIF-1α was correlated with VEGF and PDGF-C expression in tumors (P < 0.001). There was a significant correlation between VEGF and PDGF-C expression in the cytoplasm of GBM tumor cells (P < 0.0001). We showed that VEGF expression in tumor cells was correlated with its expression in blood vessels (P < 0.0001). Endothelial cells with PDGF-C and VEGF positive expression were also positive for CD105 and their nuclei for Ki-67, confirming the neoangiogenic and proliferative influence of VEGF and PDGF-C. VEGF nuclear staining in tumor cells (P = 0.002) as well as nuclear staining for HIF-1α and VEGF (P = 0.005) correlated with survival. In summary, our present findings of the concomitant upregulation of PDGF-C with VEGF in GBM tumor cells and vessels further reinforce the benefit of using combined anti-angiogenic approaches to potentially improve the therapeutic response for GBM.

Long-term epilepsy associated-tumors (LEATs): what is new?

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.

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.

Neuropathology of yellow fever autopsy cases.

BACKGROUND: Yellow fever is a viral hemorrhagic fever caused by yellow fever virus, a mosquito-borne flavivirus. Despite an effective vaccine, major outbreaks continue to occur around the world. Even though it is not a proven neurotropic virus, neurological symptoms in more severe clinical forms are frequent. The understanding of this apparent paradox is still rarely addressed in literature. METHODS: The brains of thirty-eight patients with yellow fever confirmed by RT-PCR, who underwent autopsy, were analyzed morphologically to identify and characterize neuropathological changes. The data were compared with brains collected from individuals without the disease, as a control group. Both cases and controls were subdivided according to the presence or absence of co-concurrent septic shock, to exclude changes of the sepsis associated encephalopathy. To verify possible morphological differences between the yellow fever cases groups, between the control groups, and between the cases and the controls, we applied the statistical tests Fisher's exact test and chi-square, with p values < 0.05 considered statistically significant. RESULTS: All cases and controls presented, at least focally, neuropathological changes, which included edema, meningeal and parenchymal inflammatory infiltrate and hemorrhages, and perivascular inflammatory infiltrate. We did not find an unequivocal aspect of encephalitis. The only parameter that, after statistical analysis, can be attributed to yellow fever was the perivascular inflammatory infiltrate. CONCLUSIONS: The neuropathological findings are sufficient to justify the multiple clinical neurologic disturbances detected in the YF cases. Since most of the parameters evaluated did not show statistically significant difference between cases and controls, an explanation for most of the neuropathological findings may be the vascular changes, consequent to shock induced endotheliopathy, associated with stimulation of the immune system inherent to systemic infectious processes. The statistical difference obtained in yellow fever cases regarding perivascular infiltrate can be can be explained by the immune activation inherent to the condition.

Cushing disease due to a somatic USP8 mutation in a patient with evolving pituitary hormone deficiencies due to a germline GH1 splicing variant.

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.

Clinical and molecular characterization of a large cohort of childhood onset hereditary spastic paraplegias.

The present study aimed to characterize clinical and molecular data of a large cohort of subjects with childhood-onset hereditary spastic paraplegias (HSPs). A multicenter historical cohort was performed at five centers in Brazil, in which probands and affected relatives' data from consecutive families with childhood-onset HSP (onset < 12 years-old) were reviewed from 2011 to 2020. One hundred and six individuals (83 families) with suspicion of childhood-onset HSP were evaluated, being 68 (50 families) with solved genetic diagnosis, 6 (5 families) with candidate variants in HSP-related genes and 32 (28 families) with unsolved genetic diagnosis. The most common childhood-onset subtype was SPG4, 11/50 (22%) families with solved genetic diagnosis; followed by SPG3A, 8/50 (16%). Missense pathogenic variants in SPAST were found in 54.5% of probands, favoring the association of this type of variant to childhood-onset SPG4. Survival curves to major handicap and cross-sectional Spastic Paraplegia Rating Scale progressions confirmed the slow neurological deterioration in SPG4 and SPG3A. Most common complicating features and twenty variants not previously described in HSP-related genes were reported. These results are fundamental to understand the molecular and clinical epidemiology of childhood-onset HSP, which might help on differential diagnosis, patient care and guiding future collaborative trials for these rare diseases.

Clinical and biochemical study of 29 Brazilian patients with metachromatic leukodystrophy.

Metachromatic leukodystrophy (MLD) is a lysosomal disorder caused by arylsulfatase A (ARSA) deficiency. It is classified into three forms according to the age of onset of symptoms (late infantile, juvenile, and adult). We carried out a cross-sectional and retrospective study, which aimed to determine the epidemiological, clinical, and biochemical profile of MLD patients from a national reference center for Inborn Errors of Metabolism in Brazil. Twenty-nine patients (male, 17) agreed to participate in the study (late infantile form: 22; juvenile form: 4; adult form: 1; asymptomatic: 2). Mean ages at onset of symptoms and at biochemical diagnosis were, respectively, 19 and 39 months for late infantile form and 84.7 and 161.2 months for juvenile form. The most frequently reported first clinical symptom/sign of the disease was gait disturbance and other motor abnormalities (72.7%) for late infantile form and behavioral and cognitive alterations (50%) for juvenile form. Leukocyte ARSA activity level did not present significant correlation with the age of onset of symptoms (r = -0.09, p = 0.67). Occipital white matter and basal nuclei abnormalities were not found in patients with the late infantile MLD. Our results suggest that there is a considerable delay between the age of onset of signs and symptoms and the diagnosis of MLD in Brazil. Correlation between ARSA activity and MLD clinical form was not found. Further studies on the epidemiology and natural history of this disease with larger samples are needed, especially now when specific treatments should be available in the near future.

Hereditary spastic paraplegia: a clinical and epidemiological study of a Brazilian pediatric population.

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.

Multiphasic disseminated encephalomyelitis associated with herpes virus infection in a patient with TLR3 deficiency.

We report a case of a 14-year-old girl that presented headache, amaurosis, drowsiness, fever, vomiting and diffuse reduction of muscle strength. She had been diagnosed with ADEM one year before and had a previous diagnosis of Toll-Like 3 receptor deficiency. Cerebrospinal fluid analysis revealed pleocytosis (28/mm3, 12/mm3 red blood cells, 70% lymphocytes cells, 2% monocytes cells, 28% neutrophils), normal total protein (38 pg/mL) and normal glucose level (53/mm3). Studies for CSF oligoclonal bands and serum anti-MOG were negative but polymerase chain reaction (PCR) testing was positive for herpes virus 1. In the first ADEM episode, PCR for herpes virus was also positive. Magnetic resonance imaging (MRI) of the brain revealed disseminated hyperintense lesions on T2-weighted and FLAIR images in the white matter of frontal, parietal and temporal lobes, corresponding to extensive asymmetric areas of demyelination that produced mass effect and gadolinium enhancement. Electroencephalography demonstrated irregular diffuse and generalized slow-wave activity with predominance in frontal region. The diagnosis of multiphasic disseminated encephalomyelitis (MDEM) triggered by herpes simplex virus was made. Herpes virus is a neurotropic virus that can cause a wide variety of neurological infection-triggered autoimmune disorders and that is particularly damaging to the central nervous system in situations of impaired immune system. TLR3 is expressed in astrocytes and dendritic cells of the central nervous system and is essential for natural immunity to herpes simplex. TLR3-deficient patients have already been described with herpes simplex encephalitis. TLR3 deficiency may predispose and explain autoimmune and demyelinating manifestations induced by herpes virus. The association of multiphasic disseminated encephalomyelitis triggered by herpes virus in a patient with TLR3 deficiency has not been previously reported in the literature.

Cancer-testis (CT) antigen expression in medulloblastoma.

Medulloblastoma is the most common childhood malignant tumor of the central nervous system. Treatment of medulloblastoma requires harmful therapy and nevertheless carries a poor prognosis. Due to their presence in various cancers and their limited expression in normal tissues, CT antigens are ideal vaccine targets for tumor immunotherapy. CT antigens, such as MAGE and NY-ESO-1, have been employed in clinical trials in various malignancies but little is known about their presence in medulloblastoma. We analyzed 25 medulloblastomas for the expression of a panel of CT antigens by RT-PCR and immunohistochemistry. Messenger RNA expression in the samples was as follows: GAGE 64%, MAGEA3/6 56%, SYCP1 44%, SLCO6A1 32%, MAGEC1 28%, MAGEC2 28%, MAGEA4 28%, NY-ESO-1 20%, MAGEA1 16%, and TPTE 0%. All cases except one (96%) were positive for mRNA expression of at least one CT gene. However, CT antigen expression was scarce on a protein level. Immunoreaction to monoclonal antibody E978 (NY-ESO-1) was negative in all cases; MA454 (MAGEA1), 57B (MAGEA4), M3H67 (MAGEA3/6), CT10#5 (MAGEC2) and #23 (GAGE) were each positive in 1 case, while the highest incidence of positive immunostaining, albeit heterogeneous, was seen with CT7-33 (MAGEC1) in 3 out of the 25 cases. The absence of correlation between mRNA and protein expression in medulloblastoma has not been observed in other tumors and further studies addressing the biology of CT antigens are necessary to investigate the present discrepant results.

Good surgical outcome in discordant ictal EEG-MRI unilateral mesial temporal sclerosis patients.

PURPOSE: Video electroencephalography (vEEG) monitoring of patients with unilateral mesial temporal sclerosis (uMTS) may show concordant or discordant seizure onset in relation to magnetic resonance imaging (MRI) evidence of MTS. Contralateral seizure usually leads to an indication of invasive monitoring. Contralateral seizure onset on invasive monitoring may contraindicate surgery. We evaluated long-term outcome after anteromesial temporal lobectomy (AMTL) in a consecutive series of uMTS patients with concordant and discordant vEEG findings, uniformly submitted to AMTL on the MRI evidence of MTS side without invasive monitoring. METHODS: We compared surgical outcome of all uMTS patients undergoing vEEG monitoring between January 1999 and April 2005 in our service. Discordant cases were defined by at least one seizure onset contralateral to the MRI evidence of MTS. Good surgical outcome was considered as Engel's class I. We also evaluated ictal SPECT concordance to ictal EEG and surgical outcome. RESULTS: Fifty-four patients had concordant (C) and 22 had discordant (D) scalp EEG and MRI. Surgical outcome was similar in both groups (C = 74% versus D = 86%). Duration of follow-up was comparable in both groups: C = 56.1 +/- 20.7 months versus D = 59.8 +/- 21.2 months (p = 0.83, nonsignificant). Discordant single-photon emission computed tomography (SPECT) results did not influence surgical outcome. DISCUSSION: Surgical outcome was not influenced by contralateral vEEG seizure onset or contralateral increased flow on ictal SPECT. Although vEEG monitoring should still be performed in these patients, to rule out psychogenic seizures and extratemporal seizure onset, a potentially risky procedure such as invasive monitoring may not only not be indicated in this patient population, but may also lead to patients erroneously being denied surgery.

Peritumoral brain edema in benign meningiomas: correlation with clinical, radiologic, and surgical factors and possible role on recurrence.

BACKGROUND: Approximately 60% of meningiomas are associated with peritumoral edema. Various causative factors have been discussed in the literature. The objective of this study was to investigate the correlation of PTBE with clinical, radiologic, and surgical aspects and recurrence of meningiomas. METHODS: Sixty-one patients with benign meningiomas were chosen for surgical treatment by the Group of Brain Tumors and Metastasis of the Department of Neurosurgery. All patients underwent complete surgical resection (Simpson grades 1 and 2), and those with atypical and malignant histopathologic grades were excluded. Tumors located in the cavernous sinus, tuberculum sellae, foramen magnum, ventricles, and petroclival region were excluded. RESULTS: Edema extension had a positive correlation with the higher recurrence rates (P = .042) and with the presence of irregular margins (P < .011) on bivariate analysis. Meningiomas with larger edema sizes also showed correlation with large meningiomas (P = .035), and the ones with smaller edema sizes correlated with the tentorial location (P = .032). Multivariate analysis showed an association between PTBE and the presence of seizures (odds ratio, 3.469), large meningiomas (odds ratio, 15.977), and for each cubic centimeter added to its size, the risk of edema increased 1.082 times (odds ratio). CONCLUSION: Peritumoral brain edema may be related to the invading potential of meningiomas and may play a role in the recurrence potential of the tumor. As a consequence, it is reasonable to consider the presence of edema as an additional factor to be taken into account when mapping out strategies for the treatment of meningiomas.

Long-term epilepsy associated-tumors (LEATs): what is new? / Tumores associados a epilepsia de longa duração: o que há de novo?

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.

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.

Wilson's disease with myoclonus and white matter lesions.

White matter lesions (WML) and epilepsy have been occasionally seen in Wilson's disease. No cases of generalized myoclonus have been reported so far. We present a patient with psychiatric symptoms starting at age 16, followed by tremor, generalized dystonia and severe generalized myoclonus. In addition to classical findings, the MRI showed also extensive WML in temporal, parietal and frontal regions, preserving interhemispheric fibers. Necropsy revealed marked alterations of white matter, cortex and basal ganglia. We subsequently review the literature concerning WML and myoclonus in Wilson's disease.

Ganglioneuroblastoma of the cerebellum: neuroimaging and pathological features of a case.

OBJECTIVE: To report a case of ganglioneuroblastoma of cerebellum, with emphasis to the neuroimaging and pathological findings. CASE REPORT: A one year and eight-month-old girl presented with a two-month history of hypoactivity and tremor in the legs. The MRI showed an enhancing cerebellar mass hypointense on T1 and hyperintense on T2-weighted images. The patient underwent a craniotomy with resection of the lesion. The histological and immunohistochemical studies defined the diagnosis of ganglioneuroblastoma. CONCLUSION: The MRI findings of our case showed no features which could help in the differentiation between ganglioneuroblastoma and the other common types of posterior fossa neoplasms in the pediatric population.

[Subependymal giant cell astrocytoma in patients with tuberous sclerosis: magnetic resonance imaging findings in ten cases]. / Astrocitoma subependimário de células gigantes em pacientes com esclerose tuberosa: achados em ressonância magnética de dez casos.

OBJECTIVE: To report the magnetic resonance imaging (MRI) findings in 10 patients with subependimal giant cell astrocytoma (SGCA) and tuberous sclerosis (TS). METHOD: Ten patients were retrospectively studied, presenting TS and histologically proven SGCA. Four patients were male and six female, with mean age 15.7 years. All patients underwent MRI, which was analyzed by two radiologists, final diagnosis was reached by consensus. The following findings were studied: topography, size, signal intensity on T1/T2-weighted images, contrast enhancement and associated findings. RESULTS: All patients presented a single lesion suggestive of SGCA, measuring between 1.5 cm and 8 cm in the largest diameter. Eight lesions were found near the foramen of Monro and two in the body of the lateral ventricles. The tumors showed preferentially intermediate signal on T1 (70%), high signal on T2-weighted images (100%), with intense enhancement after contrast administration (100%). CONCLUSION: SGCA in patients with TS usually presents as a single lesion near the foramen of Monro, with intermediate signal on T1, high signal on T2-weighted images and intense contrast enhancement.

Intracranial meningiomas: magnetic resonance imaging findings in 78 cases.

OBJECTIVE: To present the magnetic resonance (MR) imaging findings of 78 patients with meningiomas diagnosed in a single institution. METHOD: 78 patients with histological proven intracranial meningioma were studied. There were 52 female and 26 male patients (median=56 years). All MR imaging examinations were performed with 1.5-T MR imaging unit with standard protocol. The images were studied by two neuroradiologists, who reached the decisions regarding the findings by consensus. RESULTS: Most of the tumors showed low signal on T1- (60%) and high signal on T2- (68%) and FLAIR (69%) weighted images. Also, the lesions showed heterogeneous signal on T1 (60%), T2 (68%) and FLAIR (64%) sequences. After contrast administration, 83% (n=65) of the tumors presented accentuated and 17% (n=13) showed moderate enhancement. The tumors were located in the frontal lobe in 44% of the cases, in the parietal lobe in 35%, the occipital lobe in 19% and the temporal lobe in 12% of the patients. Areas of vasogenic edema around the tumors were seen in 90% of the cases. Twenty six per cent of the cases showed bone infiltration, and the dural tail sign was seen in 59% of the tumors. CONCLUSION: Intracranial meningiomas usually show heterogeneous low signal on T1- and high signal on T2-weighted and FLAIR images, with intense enhancement after contrast administration. The frontal and parietal lobes are commonly affected. In addition, brain edema, dural tail sign and bone infiltration are the most frequent associated findings.

Brain tumors in the first three years of life: a review of twenty cases.

OBJECTIVE AND METHOD: To review the clinical and neuropathological findings as well as the type of therapy and outcome in 20 infants under 3 years-old with central nervous system (CNS) tumor. They were treated at the Department of Neurology, "Hospital das Clínicas" University of São Paulo Medical School, from January 1997 to May 2001. RESULTS: Astrocytoma was the most common histological type (n=7), followed by ependymoma (n=3), medulloblastoma (n=2), craniopharyngioma (n=2) and desmoplastic ganglioglioma (n=2). The location of the tumor was predominantly supratentorial. Mean follow-up time was 20.2 months with recurrence in 7 cases. For each type of tumor we have emphasized the treatment currently recommended. CONCLUSION: Although follow-up time is not sufficient for analyzing survival, a trend of improvement in prognosis was noted, compared to another series of cases from our Institution that had been evaluated before 1990.

Dementia pugilistica with clinical features of Alzheimer's disease.

A 61-year-old ex-boxer presented with a three-year history of progressive memory decline. During a seven-year follow-up period, there was a continuous cognitive decline, very similar to that usually observed in Alzheimer's disease. Parkinsonian, pyramidal or cerebellar signs were conspicuously absent. Neuropathological examination revealed the typical features of dementia pugilistica: cavum septi pellucidi with multiple fenestrations, numerous neurofibrillary tangles in the cerebral isocortex and hippocampus (and rare senile plaques). Immunohistochemistry disclosed a high number of tau protein deposits and scarce beta-amyloid staining. This case shows that dementia pugilistica may present with clinical features practically undistinguishable from Alzheimer's disease.

High phenotypic variability in Gerstmann-Sträussler-Scheinker disease.

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.