Multiple genome-wide expression studies of bipolar disorder have been published. However, a unifi... more Multiple genome-wide expression studies of bipolar disorder have been published. However, a unified picture of the genomic basis for the disease has not yet emerged. Genes identified in one study often fail to be identified in other studies, prompting the question of whether microarray studies in the brain are inherently unreliable. To answer this question, we performed a meta-analysis of 12 microarray studies of bipolar disorder. These studies included >500 individual array samples, on a range of microarray platforms and brain regions. Although we confirmed that individual studies showed some differences in results, clear and striking regulation patterns emerged across the studies. These patterns were found at the individual gene level, at the functional level, and at the broader pathway level. The patterns were generally found to be reproducible across platform and region, and were highly statistically significant. We show that the seeming discordance between the studies was primarily a result of the following factors, which are also typical for other brain array studies: (1) Sample sizes were, in retrospect, too small; (2) criteria were at once too restrictive (generally focusing on fold changes >1.5) and too broad (generally using p < 0.05 or p < 0.01 as criteria for significance); and (3) statistical adjustments were not consistently applied for confounders. In addition to these general conclusions, we also summarize the primary biological findings of the meta-analysis, focusing on areas that confirm previous research and also on novel findings.
memo - Magazine of European Medical Oncology, 2010
... Cancer, 110(9): 20352041, 2007. [8] Brandes AA, Ermani M, Amista P, Basso U, Vastola F, Gard... more ... Cancer, 110(9): 20352041, 2007. [8] Brandes AA, Ermani M, Amista P, Basso U, Vastola F, Gardiman M, Iuzzolino P, Turazzi S ... [11] Durando X, Thivat E, Gilliot O, Irthum B, Verelle P, Vincent C, Bay JO. Temozolomide treatment of an adult with a relapsing medulloblas-toma. ...
Creutzfeldt-Jakob disease (CJD) belongs to the group of transmissible human spongiform encephalop... more Creutzfeldt-Jakob disease (CJD) belongs to the group of transmissible human spongiform encephalopathies. It is a very rare neurodegenerative disease of the brain, which occurs in humans as genetic, transmitted or sporadic form. Mutations in the prion protein gene are ...
Expression of the telomerase reverse transcriptase (TERT) might be altered by activating mutation... more Expression of the telomerase reverse transcriptase (TERT) might be altered by activating mutations of the rs2853669 polymorphism within the promoter region. Here we investigate the impact of these genomic alterations on telomerase activation and dissect their prognostic potential in glioblastoma (GBM). The respective TERT promoter region was sequenced in 126 GBM tissues and compared with clinical parameters and glioma biomarkers MGMT promoter methylation and IDH1 mutation. TERT mRNA expression, telomerase activity, and telomere lengths were determined by reverse transcriptase PCR, TRAP assay, and real-time PCR, respectively. Seventy-three percent of GBM patients harbored TERT promoter mutations associated with enhanced telomerase activity and TERT mRNA expression but reduced telomere lengths (P < .001 for all). Patients with mutated tumors exhibited significantly shorter overall survival in the entire cohort (11.5 vs 23.1 months; P < .0001) and in the primary GBM patient subgr...
Drug abuse represents a significant forensic issue worldwide. The major substances abused include... more Drug abuse represents a significant forensic issue worldwide. The major substances abused include cannabis, opiates, cocaine, amphetamine, methamphetamine, and “ecstasy.” Besides cardiovascular complications, psychiatric and neurologic symptoms are the most common manifestations of drug toxicity. A broad spectrum of changes affecting the central nervous system is seen in drug abusers. The major findings result from the consequences of cerebral ischemia and cerebrovascular diseases. Especially persons with underlying arteriovenous malformation or aneurysm are at higher risk for such events. So far, except for a few instances of vasculitis, the etiology of these cerebrovascular events is not completely understood. Besides pharmacologically induced vasospasm, impaired hemostasis, platelet dysfunction, and decreased cerebral blood flow have been proposed. Based on animal experiments, the abuse of amphetamine, methamphetamine, and 3,4-methylenedioxymethamphetamine (MDMA) has been related to neurotoxicity in human long-term abusers and to the risk of developing Parkinson’s disease. However, whether such neurotoxicity occurs remains to be established. A major focus of research in the neurobiology of addiction has been put on the drug-induced adaptations within the brain reward system. Alterations of the intracellular messenger pathways, transcription factors, and immediate early genes in these reward circuits seem to be fundamentally important for the development of addiction and chronic drug abuse.
Background: Human prion diseases are a group of rare fatal neurodegenerative conditions with well... more Background: Human prion diseases are a group of rare fatal neurodegenerative conditions with well-developed clinical and neuropathological diagnostic criteria. Recent observations have expanded the spectrum of prion diseases beyond the classically recognized forms. Results: In the present study we report six patients with a novel, apparently sporadic disease characterised by thalamic degeneration and rapidly progressive dementia (duration of illness 2-12 months; age at death: 55-81 years). Light and electron microscopic immunostaining for the prion protein (PrP) revealed a peculiar intraneuritic distribution in neocortical regions. Proteinase K resistant PrP (PrP res) was undetectable by Western blotting in frontal cortex from the three cases with frozen tissue, even after enrichment for PrP res by centrifugation or by phosphotungstic acid precipitation. Conformation-dependent immunoassay analysis using a range of PK digestion conditions (and no PK digestion) produced only very limited evidence of meaningful D-N (denatured/native) values, indicative of the presence of disease-associated PrP (PrP Sc) in these cases, when the results were compared with appropriate negative control groups. Conclusions: Our observation expands the spectrum of conditions associated with rapidly progressive dementia and may have implications for the understanding of the pathogenesis of prion diseases.
Increased concentrations of kynurenine pathway metabolites have been reported by several groups f... more Increased concentrations of kynurenine pathway metabolites have been reported by several groups for disorders involving psychosis, including schizophrenia and bipolar disorder. To identify components of the pathway that may be relevant as biomarkers or may underlie the etiology of psychosis, it is essential to characterize the extent of kynurenine pathway activation and to investigate known regulators of one of the key kynurenine-producing enzymes, tryptophan 2,3-dioxygenase (TDO2), previously shown in this laboratory to be increased commensurate with kynurenine in postmortem anterior cingulate brain tissue from individuals with schizophrenia. Using this same anterior cingulate sample set from individuals with schizophrenia, bipolar disorder, depression and controls (N = 12-14 per group), we measured the precursor of kynurenine and two downstream products. The precursor, tryptophan, was significantly increased only in the schizophrenia group (1.54-fold the mean control value, p = 0.02), and through substrate-induced activation, may be one cause of the increased kynurenine and kynurenine metabolites. This finding for tryptophan differs from some, but not all, previous reports and methodological reasons for the discrepancies are discussed. A product of kynurenine metabolism, 3-OH-anthranilic acid was also significantly increased only in the schizophrenia group (1.68-fold the mean control value, p = 0.03). 3-OH-anthranilic acid is a reactive species with cytotoxic properties, although the threshold for such effects is not known for neurons. Analysis of major pre-and post-mortem variables showed that none were confounding for these between-group experimental comparisons. Nicotinamide, a pathway end product, did not differ between groups but was associated with cause of death (suicide) within the bipolar group (p = 0.03).
The goal of this article is to present the clinical and histopathological features of two rare ca... more The goal of this article is to present the clinical and histopathological features of two rare cases of ganglioglioma occurring in the cervicothoracic and thoracolumbar spinal cord. A 4-year-old female patient presented with tetraparesis, whereas a 54-year-old woman showed paraparesis of both feet. Both tumors could be removed totally by microsurgical techniques. Light microscopically, the tumors in both cases showed basically identical histological features and were diagnosed as benign gangliogliomas. Postoperatively, the two patients did not show improvement. Tumor recurrence was not noted at follow-up examinations within 11 and 24 months after surgery, respectively. Ganglioglioma must be considered in the differential diagnosis of tumors affecting the spinal cord. In cases of suspected spinal ganglioglioma showing no sharp delineation from the surrounding tissue, a subtotal tumor removal should be considered to prevent severe neurological deficits.
GABA(B) receptors are widely expressed in the CNS. The distribution of the recently cloned GABA(B... more GABA(B) receptors are widely expressed in the CNS. The distribution of the recently cloned GABA(B1) receptor is highly concordant with GABA(B) ligand binding sites, but experiments with transfected cell lines indicate that GABA(B1) has to heterodimerize with GABA(B2) to gain the functionality of a native GABA(B) receptor. Using in situ hybridization we investigated the expression of GABA(B1) and GABA(B2) mRNAs in the human brain. Both transcripts were detectable in prefrontal cortex, hippocampus and cerebellum with no apparent mismatch. A distinct expression of GABA(B1) was detected in putative Bergmann glia. In the human striatum GABA(B1) mRNA was expressed in moderate amounts, whereas the GABA(B2) mRNA signal was not clearly above background. According to our data, the current concept on GABA(B) receptor composition needs re-evaluation, at least for certain brain structures.
Unusual glial cells, inconspicuous in routine histological sections, were demonstrated in the glo... more Unusual glial cells, inconspicuous in routine histological sections, were demonstrated in the globus pallidus using immunohistochemistry for anti–ubiquitin and a modified NOR–silver impregnation technique. These cells were identified as astrocytes and showed the following unusual features: (i) presence of intracytoplasmic vacuoles; (ii) immunoreactivity for ubiquitin; (iii) positive staining with a modified NOR–silver impregnation technique; and (iv) topographical location restricted to the globus pallidus. Quantitative analyses showed the numerical density of these cells to be significantly increased with normal ageing, whereas the presence of the cells was not related to pathological ageing or any other disease process. The data suggest that, not only in neurons but also in glial cells, accumulations of altered proteins can be found, which is probably due to a decline in the proteolytic activity of the cell.
Cocaine abuse represents a worldwide significant forensic issue as it is becoming widely recogniz... more Cocaine abuse represents a worldwide significant forensic issue as it is becoming widely recognized as one of the most dangerous illicit drugs in common use today. Besides cardiovascular complications, psychiatric and neurologic symptoms are the most common manifestations of cocaine toxicity. The latter include seizures, movement disorders and cerebrovascular complications. In chronic cocaine abusers morphological, physiological, and neurochemical abnormalities have been demonstrated by using neuroradiological techniques such as computed tomography, magnetic resonance imaging, positron emission tomography or single photon emission computed tomography. The spectrum of neuropathologic changes encountered in the brains of cocaine abusers is broad, but the major findings consist of ischemic and hemorrhagic stroke, subarachnoid and intracerebral hemorrhages and cerebral ischemia. Especially persons with underlying arteriovenous malformation or aneurysm are at risk for such events. Except for a few instances of vasculitis, the etiology of cocaine-related cerebrovascular accidents is still unclear. Besides pharmacologically-induced vasospasm, impaired hemostasis and platelet function and decreased cerebral blood flow have been proposed. At the cellular level, abnormalities in the expression of transcription factors and changes of brain neurotransmitter systems have been reported.
✓ Epidural cavernous hemangiomas are increasingly identified as a cause of acute or chronic progr... more ✓ Epidural cavernous hemangiomas are increasingly identified as a cause of acute or chronic progressive spinal cord syndrome and local back pain or radiculopathy. The authors present three cases of spinal epidural cavernous hemangiomas manifesting as spinal cord syndrome, thoracic radiculopathy, and lumbar radiculopathy. Based on the imaging characteristics of these three cases and a review of the literature, the clinical signs and symptoms and their implications, the role of preoperative neuroradiological diagnosis, and the need for complete surgical resection are discussed. Epidural cavernous hemangiomas display consistent magnetic resonance imaging properties: T1-weighted images most commonly show a homogeneous signal intensity similar to those of spinal cord and muscle, and contrast enhancement is homogeneous or slightly heterogeneous. On T2-weighted images the signal of the lesion is consistently high and slightly less intense than that of cerebrospinal fluid. Frequently, the l...
✓ Colloid cysts are rare intracerebral lesions that are preferentially encountered within the thi... more ✓ Colloid cysts are rare intracerebral lesions that are preferentially encountered within the third ventricle. There are only a few reports in which colloid cysts are described in other locations such as the fourth ventricle.A symptomatic intracerebellar colloid cyst in a 45-year-old woman is described. The patient presented with headache, gait disturbance, and nausea. Neuroradiological imaging revealed compression of the fourth ventricle, hydrocephalus, and an intracerebellar cystic lesion measuring 4 × 5 cm that had a small peripheral solid portion. The cyst was successfully removed via a paramedian suboccipital approach. Postoperatively, the patient recovered quickly.The findings in the present report represent an additonal example of the broad spectrum of cystic lesions encountered in the cerebellum.
The shift in cellular energy production from oxidative phosphorylation (OXPHOS) to glycolysis, ev... more The shift in cellular energy production from oxidative phosphorylation (OXPHOS) to glycolysis, even under aerobic conditions, called the Warburg effect, is a feature of most solid tumors. The activity levels of OXPHOS complexes and citrate synthase were determined in astrocytomas. A gradual decrease of citrate synthase and OXPHOS complexes was observed depending on tumor grade. In low‐grade astrocytomas (WHO grade II), enzyme activities of citrate synthase, complex I, and complex V were comparable to those of normal brain tissue. A trend to reduced activities was observed for complexes II–IV. In glioblastoma (WHO grade IV), activities of citrate synthase and complexes I–IV were decreased by 56–92% as compared with normal brain. Immunohistochemical staining for porin revealed that the tumorpil of low‐grade astrocytomas displays characteristics of the mitochondria‐rich neuropil of normal brain tissue. In high‐grade tumors (WHO grades III and IV), the tumorpil was characterized by seve...
Primary central nervous system lymphoma (PCNSL) is a rare tumor with a rising incidence in immuno... more Primary central nervous system lymphoma (PCNSL) is a rare tumor with a rising incidence in immunocompetent elderly and immunocompromised patients. The early diagnosis is important for quick initiation of appropriate treatment, although the clinical and radiological findings are frequently misleading. With the present case we show the usefulness of combining conventional magnetic resonance imaging (MRI) with magnetic resonance spectroscopy (1 H MRS) for the confirmation of the diagnosis in an immunocompetent patient; in the absence of a "gold standard criteria for the diagnosis" both procedures are necessary and complementary investigations.
To acquire normative data of the hippocampus and its postnatal growth in SO children (age, 1 mont... more To acquire normative data of the hippocampus and its postnatal growth in SO children (age, 1 month to IS years) without epilepsy. Methods: Morphometry of the hippocampus was carried out by using a spoiled FLASH 3D sequence (sagittal orientation), whereas the volume of the brain was assessed with a TIweighted spin-echo sequence (transverse orientation). The volume of the hippocampus and the brain was determined by following Cavalieri's principle. Growth curves of the brain and hippocampus were fitted to a nonlinear Boltzmann sigmoidal equation. Results: lntra-tinterobserver coefficient of variation was 2.01 4.9% for hippocampal volume measurements and 2.0/2. I % for brain volumetry. A significant difference in volume was noted
Multiple genome-wide expression studies of bipolar disorder have been published. However, a unifi... more Multiple genome-wide expression studies of bipolar disorder have been published. However, a unified picture of the genomic basis for the disease has not yet emerged. Genes identified in one study often fail to be identified in other studies, prompting the question of whether microarray studies in the brain are inherently unreliable. To answer this question, we performed a meta-analysis of 12 microarray studies of bipolar disorder. These studies included >500 individual array samples, on a range of microarray platforms and brain regions. Although we confirmed that individual studies showed some differences in results, clear and striking regulation patterns emerged across the studies. These patterns were found at the individual gene level, at the functional level, and at the broader pathway level. The patterns were generally found to be reproducible across platform and region, and were highly statistically significant. We show that the seeming discordance between the studies was primarily a result of the following factors, which are also typical for other brain array studies: (1) Sample sizes were, in retrospect, too small; (2) criteria were at once too restrictive (generally focusing on fold changes >1.5) and too broad (generally using p < 0.05 or p < 0.01 as criteria for significance); and (3) statistical adjustments were not consistently applied for confounders. In addition to these general conclusions, we also summarize the primary biological findings of the meta-analysis, focusing on areas that confirm previous research and also on novel findings.
memo - Magazine of European Medical Oncology, 2010
... Cancer, 110(9): 20352041, 2007. [8] Brandes AA, Ermani M, Amista P, Basso U, Vastola F, Gard... more ... Cancer, 110(9): 20352041, 2007. [8] Brandes AA, Ermani M, Amista P, Basso U, Vastola F, Gardiman M, Iuzzolino P, Turazzi S ... [11] Durando X, Thivat E, Gilliot O, Irthum B, Verelle P, Vincent C, Bay JO. Temozolomide treatment of an adult with a relapsing medulloblas-toma. ...
Creutzfeldt-Jakob disease (CJD) belongs to the group of transmissible human spongiform encephalop... more Creutzfeldt-Jakob disease (CJD) belongs to the group of transmissible human spongiform encephalopathies. It is a very rare neurodegenerative disease of the brain, which occurs in humans as genetic, transmitted or sporadic form. Mutations in the prion protein gene are ...
Expression of the telomerase reverse transcriptase (TERT) might be altered by activating mutation... more Expression of the telomerase reverse transcriptase (TERT) might be altered by activating mutations of the rs2853669 polymorphism within the promoter region. Here we investigate the impact of these genomic alterations on telomerase activation and dissect their prognostic potential in glioblastoma (GBM). The respective TERT promoter region was sequenced in 126 GBM tissues and compared with clinical parameters and glioma biomarkers MGMT promoter methylation and IDH1 mutation. TERT mRNA expression, telomerase activity, and telomere lengths were determined by reverse transcriptase PCR, TRAP assay, and real-time PCR, respectively. Seventy-three percent of GBM patients harbored TERT promoter mutations associated with enhanced telomerase activity and TERT mRNA expression but reduced telomere lengths (P < .001 for all). Patients with mutated tumors exhibited significantly shorter overall survival in the entire cohort (11.5 vs 23.1 months; P < .0001) and in the primary GBM patient subgr...
Drug abuse represents a significant forensic issue worldwide. The major substances abused include... more Drug abuse represents a significant forensic issue worldwide. The major substances abused include cannabis, opiates, cocaine, amphetamine, methamphetamine, and “ecstasy.” Besides cardiovascular complications, psychiatric and neurologic symptoms are the most common manifestations of drug toxicity. A broad spectrum of changes affecting the central nervous system is seen in drug abusers. The major findings result from the consequences of cerebral ischemia and cerebrovascular diseases. Especially persons with underlying arteriovenous malformation or aneurysm are at higher risk for such events. So far, except for a few instances of vasculitis, the etiology of these cerebrovascular events is not completely understood. Besides pharmacologically induced vasospasm, impaired hemostasis, platelet dysfunction, and decreased cerebral blood flow have been proposed. Based on animal experiments, the abuse of amphetamine, methamphetamine, and 3,4-methylenedioxymethamphetamine (MDMA) has been related to neurotoxicity in human long-term abusers and to the risk of developing Parkinson’s disease. However, whether such neurotoxicity occurs remains to be established. A major focus of research in the neurobiology of addiction has been put on the drug-induced adaptations within the brain reward system. Alterations of the intracellular messenger pathways, transcription factors, and immediate early genes in these reward circuits seem to be fundamentally important for the development of addiction and chronic drug abuse.
Background: Human prion diseases are a group of rare fatal neurodegenerative conditions with well... more Background: Human prion diseases are a group of rare fatal neurodegenerative conditions with well-developed clinical and neuropathological diagnostic criteria. Recent observations have expanded the spectrum of prion diseases beyond the classically recognized forms. Results: In the present study we report six patients with a novel, apparently sporadic disease characterised by thalamic degeneration and rapidly progressive dementia (duration of illness 2-12 months; age at death: 55-81 years). Light and electron microscopic immunostaining for the prion protein (PrP) revealed a peculiar intraneuritic distribution in neocortical regions. Proteinase K resistant PrP (PrP res) was undetectable by Western blotting in frontal cortex from the three cases with frozen tissue, even after enrichment for PrP res by centrifugation or by phosphotungstic acid precipitation. Conformation-dependent immunoassay analysis using a range of PK digestion conditions (and no PK digestion) produced only very limited evidence of meaningful D-N (denatured/native) values, indicative of the presence of disease-associated PrP (PrP Sc) in these cases, when the results were compared with appropriate negative control groups. Conclusions: Our observation expands the spectrum of conditions associated with rapidly progressive dementia and may have implications for the understanding of the pathogenesis of prion diseases.
Increased concentrations of kynurenine pathway metabolites have been reported by several groups f... more Increased concentrations of kynurenine pathway metabolites have been reported by several groups for disorders involving psychosis, including schizophrenia and bipolar disorder. To identify components of the pathway that may be relevant as biomarkers or may underlie the etiology of psychosis, it is essential to characterize the extent of kynurenine pathway activation and to investigate known regulators of one of the key kynurenine-producing enzymes, tryptophan 2,3-dioxygenase (TDO2), previously shown in this laboratory to be increased commensurate with kynurenine in postmortem anterior cingulate brain tissue from individuals with schizophrenia. Using this same anterior cingulate sample set from individuals with schizophrenia, bipolar disorder, depression and controls (N = 12-14 per group), we measured the precursor of kynurenine and two downstream products. The precursor, tryptophan, was significantly increased only in the schizophrenia group (1.54-fold the mean control value, p = 0.02), and through substrate-induced activation, may be one cause of the increased kynurenine and kynurenine metabolites. This finding for tryptophan differs from some, but not all, previous reports and methodological reasons for the discrepancies are discussed. A product of kynurenine metabolism, 3-OH-anthranilic acid was also significantly increased only in the schizophrenia group (1.68-fold the mean control value, p = 0.03). 3-OH-anthranilic acid is a reactive species with cytotoxic properties, although the threshold for such effects is not known for neurons. Analysis of major pre-and post-mortem variables showed that none were confounding for these between-group experimental comparisons. Nicotinamide, a pathway end product, did not differ between groups but was associated with cause of death (suicide) within the bipolar group (p = 0.03).
The goal of this article is to present the clinical and histopathological features of two rare ca... more The goal of this article is to present the clinical and histopathological features of two rare cases of ganglioglioma occurring in the cervicothoracic and thoracolumbar spinal cord. A 4-year-old female patient presented with tetraparesis, whereas a 54-year-old woman showed paraparesis of both feet. Both tumors could be removed totally by microsurgical techniques. Light microscopically, the tumors in both cases showed basically identical histological features and were diagnosed as benign gangliogliomas. Postoperatively, the two patients did not show improvement. Tumor recurrence was not noted at follow-up examinations within 11 and 24 months after surgery, respectively. Ganglioglioma must be considered in the differential diagnosis of tumors affecting the spinal cord. In cases of suspected spinal ganglioglioma showing no sharp delineation from the surrounding tissue, a subtotal tumor removal should be considered to prevent severe neurological deficits.
GABA(B) receptors are widely expressed in the CNS. The distribution of the recently cloned GABA(B... more GABA(B) receptors are widely expressed in the CNS. The distribution of the recently cloned GABA(B1) receptor is highly concordant with GABA(B) ligand binding sites, but experiments with transfected cell lines indicate that GABA(B1) has to heterodimerize with GABA(B2) to gain the functionality of a native GABA(B) receptor. Using in situ hybridization we investigated the expression of GABA(B1) and GABA(B2) mRNAs in the human brain. Both transcripts were detectable in prefrontal cortex, hippocampus and cerebellum with no apparent mismatch. A distinct expression of GABA(B1) was detected in putative Bergmann glia. In the human striatum GABA(B1) mRNA was expressed in moderate amounts, whereas the GABA(B2) mRNA signal was not clearly above background. According to our data, the current concept on GABA(B) receptor composition needs re-evaluation, at least for certain brain structures.
Unusual glial cells, inconspicuous in routine histological sections, were demonstrated in the glo... more Unusual glial cells, inconspicuous in routine histological sections, were demonstrated in the globus pallidus using immunohistochemistry for anti–ubiquitin and a modified NOR–silver impregnation technique. These cells were identified as astrocytes and showed the following unusual features: (i) presence of intracytoplasmic vacuoles; (ii) immunoreactivity for ubiquitin; (iii) positive staining with a modified NOR–silver impregnation technique; and (iv) topographical location restricted to the globus pallidus. Quantitative analyses showed the numerical density of these cells to be significantly increased with normal ageing, whereas the presence of the cells was not related to pathological ageing or any other disease process. The data suggest that, not only in neurons but also in glial cells, accumulations of altered proteins can be found, which is probably due to a decline in the proteolytic activity of the cell.
Cocaine abuse represents a worldwide significant forensic issue as it is becoming widely recogniz... more Cocaine abuse represents a worldwide significant forensic issue as it is becoming widely recognized as one of the most dangerous illicit drugs in common use today. Besides cardiovascular complications, psychiatric and neurologic symptoms are the most common manifestations of cocaine toxicity. The latter include seizures, movement disorders and cerebrovascular complications. In chronic cocaine abusers morphological, physiological, and neurochemical abnormalities have been demonstrated by using neuroradiological techniques such as computed tomography, magnetic resonance imaging, positron emission tomography or single photon emission computed tomography. The spectrum of neuropathologic changes encountered in the brains of cocaine abusers is broad, but the major findings consist of ischemic and hemorrhagic stroke, subarachnoid and intracerebral hemorrhages and cerebral ischemia. Especially persons with underlying arteriovenous malformation or aneurysm are at risk for such events. Except for a few instances of vasculitis, the etiology of cocaine-related cerebrovascular accidents is still unclear. Besides pharmacologically-induced vasospasm, impaired hemostasis and platelet function and decreased cerebral blood flow have been proposed. At the cellular level, abnormalities in the expression of transcription factors and changes of brain neurotransmitter systems have been reported.
✓ Epidural cavernous hemangiomas are increasingly identified as a cause of acute or chronic progr... more ✓ Epidural cavernous hemangiomas are increasingly identified as a cause of acute or chronic progressive spinal cord syndrome and local back pain or radiculopathy. The authors present three cases of spinal epidural cavernous hemangiomas manifesting as spinal cord syndrome, thoracic radiculopathy, and lumbar radiculopathy. Based on the imaging characteristics of these three cases and a review of the literature, the clinical signs and symptoms and their implications, the role of preoperative neuroradiological diagnosis, and the need for complete surgical resection are discussed. Epidural cavernous hemangiomas display consistent magnetic resonance imaging properties: T1-weighted images most commonly show a homogeneous signal intensity similar to those of spinal cord and muscle, and contrast enhancement is homogeneous or slightly heterogeneous. On T2-weighted images the signal of the lesion is consistently high and slightly less intense than that of cerebrospinal fluid. Frequently, the l...
✓ Colloid cysts are rare intracerebral lesions that are preferentially encountered within the thi... more ✓ Colloid cysts are rare intracerebral lesions that are preferentially encountered within the third ventricle. There are only a few reports in which colloid cysts are described in other locations such as the fourth ventricle.A symptomatic intracerebellar colloid cyst in a 45-year-old woman is described. The patient presented with headache, gait disturbance, and nausea. Neuroradiological imaging revealed compression of the fourth ventricle, hydrocephalus, and an intracerebellar cystic lesion measuring 4 × 5 cm that had a small peripheral solid portion. The cyst was successfully removed via a paramedian suboccipital approach. Postoperatively, the patient recovered quickly.The findings in the present report represent an additonal example of the broad spectrum of cystic lesions encountered in the cerebellum.
The shift in cellular energy production from oxidative phosphorylation (OXPHOS) to glycolysis, ev... more The shift in cellular energy production from oxidative phosphorylation (OXPHOS) to glycolysis, even under aerobic conditions, called the Warburg effect, is a feature of most solid tumors. The activity levels of OXPHOS complexes and citrate synthase were determined in astrocytomas. A gradual decrease of citrate synthase and OXPHOS complexes was observed depending on tumor grade. In low‐grade astrocytomas (WHO grade II), enzyme activities of citrate synthase, complex I, and complex V were comparable to those of normal brain tissue. A trend to reduced activities was observed for complexes II–IV. In glioblastoma (WHO grade IV), activities of citrate synthase and complexes I–IV were decreased by 56–92% as compared with normal brain. Immunohistochemical staining for porin revealed that the tumorpil of low‐grade astrocytomas displays characteristics of the mitochondria‐rich neuropil of normal brain tissue. In high‐grade tumors (WHO grades III and IV), the tumorpil was characterized by seve...
Primary central nervous system lymphoma (PCNSL) is a rare tumor with a rising incidence in immuno... more Primary central nervous system lymphoma (PCNSL) is a rare tumor with a rising incidence in immunocompetent elderly and immunocompromised patients. The early diagnosis is important for quick initiation of appropriate treatment, although the clinical and radiological findings are frequently misleading. With the present case we show the usefulness of combining conventional magnetic resonance imaging (MRI) with magnetic resonance spectroscopy (1 H MRS) for the confirmation of the diagnosis in an immunocompetent patient; in the absence of a "gold standard criteria for the diagnosis" both procedures are necessary and complementary investigations.
To acquire normative data of the hippocampus and its postnatal growth in SO children (age, 1 mont... more To acquire normative data of the hippocampus and its postnatal growth in SO children (age, 1 month to IS years) without epilepsy. Methods: Morphometry of the hippocampus was carried out by using a spoiled FLASH 3D sequence (sagittal orientation), whereas the volume of the brain was assessed with a TIweighted spin-echo sequence (transverse orientation). The volume of the hippocampus and the brain was determined by following Cavalieri's principle. Growth curves of the brain and hippocampus were fitted to a nonlinear Boltzmann sigmoidal equation. Results: lntra-tinterobserver coefficient of variation was 2.01 4.9% for hippocampal volume measurements and 2.0/2. I % for brain volumetry. A significant difference in volume was noted
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Papers by Serge Weis