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Purpose: Predicting seizure control after epilepsy surgery is difficult. The objectives of this work are: (a) to estimate the value of surgical procedure, presence of neuroimaging abnormalities, need for intracranial recordings, resection lobe, pathology, durations of epilepsy and follow-up period to predict postsurgical seizure control after epilepsy surgery and (b) to provide empirical estimates of successful outcome after different combinations of the above factors in order to aid clinicians in advising patients presurgically about the likelihood of success under their patients' individual circumstances., Methods: We report postsurgical seizure control from all 243 patients who underwent resective surgery for epilepsy at King's College Hospital between 1999 and 2011. Among the 243 patients, 233 had lobar or sub-lobar resections, 8 had multilobar resections and 2 had excision of a hypothalamic hamartoma. We examined the relation between postsurgical seizure control and type of surgical procedure, presence of neuroimaging abnormalities, pathology, resection lobe and the need of intra-cranial electrodes to identify seizure onset., Results: Among the 243 patients, 126 (52%) enjoyed outcome grade I, 40 (16%) had grade II, 51 (21%) had grade III and 26 (11%) had grade IV (mean follow-up 41.1 months). Normal neuroimaging or need for intracranial recordings was not associated with poorer outcome. Patients undergoing temporal resections showed better outcome than those with frontal resections, due to the poor outcome seen in frontal patients with normal neuroimaging. Among temporal resections, there was no difference in outcome between patients with and without neuroimaging abnormalities. Among patients with lesions on imaging, temporal and frontal resections showed similar outcomes. Likelihood of favourable outcome under the patient's individual circumstances was estimated by the tables provided. There was an 8-9% decrease in the percentage of grade I between follow-up at 12 and >36 months., Conclusion: Overall, nearly 70% of patients undergoing resective surgery enjoy favourable post-surgical seizure control. Normal neuroimaging should not discourage surgery in temporal patients but is a negative prognostic sign in normal MRI frontal patients. There were no statistical differences in outcome between patients with neuroimaging lesions in frontal or temporal lobes., (Copyright © 2013 British Epilepsy Association. Published by Elsevier Ltd. All rights reserved.)

Background: Gliomas exhibit high glycolytic rates, and monocarboxylate transporters (MCTs) play a major role in the maintenance of the glycolytic metabolism through the proton-linked transmembrane transport of lactate. However, their role in gliomas is poorly studied. Thus, we aimed to characterize the expression of MCT1, MCT4, and their chaperone CD147 and to assess the therapeutic impact of MCT inhibition in gliomas., Methods: MCTs and CD147 expressions were characterized by immunohistochemistry in nonneoplastic brain and glioma samples. The effect of CHC (MCT inhibitor) and MCT1 silencing was assessed in in vitro and in vivo glioblastoma models., Results: MCT1, MCT4, and CD147 were overexpressed in the plasma membrane of glioblastomas, compared with diffuse astrocytomas and nonneoplastic brain. CHC decreased glycolytic metabolism, migration, and invasion and induced cell death in U251 cells (more glycolytic) but only affected proliferation in SW1088 (more oxidative). The effectiveness of CHC in glioma cells appears to be dependent on MCT membrane expression. MCT1 downregulation showed similar effects on different glioma cells, supporting CHC as an MCT1 inhibitor. There was a synergistic effect when combining CHC with temozolomide treatment in U251 cells. In the CAM in vivo model, CHC decreased the size of tumors and the number of blood vessels formed., Conclusions: This is the most comprehensive study reporting the expression of MCTs and CD147 in gliomas. The MCT1 inhibitor CHC exhibited anti-tumoral and anti-angiogenic activity in gliomas and, of importance, enhanced the effect of temozolomide. Thus, our results suggest that development of therapeutic approaches targeting MCT1 may be a promising strategy in glioblastoma treatment.

MGMT downregulation in high-grade gliomas (HGG) has been mostly attributed to aberrant promoter methylation and is associated with increased sensitivity to alkylating agent-based chemotherapy. However, HGG harboring 10q deletions also benefit from treatment with alkylating agents. Because the MGMT gene is mapped at 10q26, we hypothesized that both epigenetic and genetic alterations might affect its expression and predict response to chemotherapy. To test this hypothesis, promoter methylation and mRNA levels of MGMT were determined by quantitative methylation-specific PCR (qMSP) or methylation-specific multiplex ligation dependent probe amplification (MS-MLPA) and quantitative RT-PCR, respectively, in a retrospective series of 61 HGG. MGMT/chromosome 10 copy number variations were determined by FISH or MS-MLPA analysis. Molecular findings were correlated with clinical parameters to assess their predictive value. Overall, MGMT methylation ratios assessed by qMSP and MS-MLPA were inversely correlated with mRNA expression levels (best coefficient value obtained with MS-MLPA). By FISH analysis in 68.3% of the cases there was loss of 10q26.1 and in 15% of the cases polysomy was demonstrated; the latter displayed the highest levels of transcript. When genetic and epigenetic data were combined, cases with MGMT promoter methylation and MGMT loss depicted the lowest transcript levels, although an impact in response to alkylating agent chemotherapy was not apparent. Cooperation between epigenetic (promoter methylation) and genetic (monosomy, locus deletion) changes affecting MGMT in HGG is required for effective MGMT silencing. Hence, evaluation of copy number alterations might add relevant prognostic and predictive information concerning response to alkylating agent-based chemotherapy.

The gene encoding protein kinase WNK2 was recently identified to be silenced by promoter hypermethylation in gliomas and meningiomas, suggesting a tumour-suppressor role in these brain tumours. Following experimental depletion in cell lines, WNK2 was further found to control GTP-loading of Rac1, a signalling guanosine triphosphatase involved in cell migration and motility. Here we show that WNK2 promoter methylation also occurs in 17.5% (29 out of 166) of adult gliomas, whereas it is infrequent in its paediatric forms (1.6%; 1 out of 66). Re-expression of WNK2 in glioblastoma cells presenting WNK2 gene silencing reduced cell proliferation in vitro, tumour growth in vivo and also cell migration and invasion, an effect correlated with reduced activation of Rac1. In contrast, when endogenous WNK2 was depleted from glioblastoma cells with unmethylated WNK2 promoter, changes in cell morphology, an increase in invasion and activation of Rac1 were observed. Together, these results validate the WNK2 gene as a recurrent target for epigenetic silencing in glia-derived brain tumours and provide first mechanistic evidence for a tumour-suppressing role of WNK2 that is related to Rac1 signalling and tumour cell invasion and proliferation.

Malignant gliomas are highly infiltrative and invasive tumors, which precludes the few treatment options available. Therefore, there is an urgent need to elucidate the molecular mechanisms underlying gliomas aggressive phenotype and poor prognosis. The Raf Kinase Inhibitory protein (RKIP), besides regulating important intracellular signaling cascades, was described to be associated with progression, metastasis and prognosis in several human neoplasms. Its role in the prognosis and tumourigenesis of gliomas remains unclear. In the present study, we found that RKIP protein is absent in a low frequency (10%, 20/193) of glioma tumors. Nevertheless, the absence of RKIP expression was an independent prognostic marker in glioma. Additionally, by in vitro downregulation of RKIP, we found that RKIP inhibition induces a higher viability and migration of the cells, having no effect on cellular proliferation and angiogenesis, as assessed by in vivo CAM assay. In conclusion, this is the largest series studied so far evaluating the expression levels of this important cancer suppressor protein in glioma tumors. Our results suggest that in a subset of tumors, the absence of RKIP associates with highly malignant behavior and poor survival of patients, which may be a useful biomarker for tailored treatment of glioma patients.

The authors present the case of a 41-year-old woman with nasal and laryngeal involvement by sarcoidosis, review the literature and discuss the otolaryngologic manifestations, the diagnostic evaluation, treatment and prognostic of this entity.

Glioblastoma (GBM) is the most common and aggressive primary brain tumor. The identification of novel molecular prognostic markers of GBM has recently been an area of great interest in neuro-oncology. The methylation status of the MGMT gene promoter is currently a promising molecular prognostic marker, but some controversial data have precluded its clinical use. We analyzed MGMT methylation by methylation-specific PCR in 90 GBM patients from four Portuguese hospitals, uniformly treated with radiotherapy combined with concomitant and adjuvant temozolomide (Stupp protocol). The Kaplan-Meier method was used to construct survival curves, and the log-rank test and a Cox-regression model were used to analyze patient survival. The methylation status of MGMT was successfully determined in 89% (80/90) of the tumors. The frequency of tumoral MGMT promoter methylation was 47.5%. The median overall survivals (OSs) were 16 months (95% CI 12.2-19.8) and 13 months (95% CI 13.3-18.7) for patients whose tumors had a methylated or unmethylated MGMT, respectively. Univariate and multivariate analyses did not show any statistically significant association between MGMT methylation status and patient OS (P=0.583 by the log-rank test; P=0.617 by the Cox-regression test) or progression-free survival (P=0.775 by the log-rank test; P=0.691 by the Cox-regression test). None of the patient clinical features were significantly correlated with survival. This is the first study to report the frequency of MGMT methylation among Portuguese GBM patients. Our data did not show statistically significant associations between MGMT promoter methylation and the outcome of GBM patients treated with temozolomide. Additional robust prospective studies are warranted to clarify whether the MGMT status should be used in clinical decisions.

Evidence from brain imaging studies indicates that white matter volume, density and fractional anisotropy may be altered in individuals with schizophrenia and bipolar disorder. However, the molecular correlates of these deficits remain unknown. In this study we performed a cytoarchitectural assessment of the white matter adjacent to the planum temporale (PT), an auditory association region located within the superior temporal gyrus, in subjects with schizophrenia, bipolar disorder, major depressive disorder and controls (15 subjects per group). Using two-dimensional measures, we recorded the cell density, distribution and size of all neurons and glial nuclei within this region. Glial density was lower in the schizophrenia group, relative to the control group. Neuronal density, neuronal size, and glial nuclear size did not differ between groups. No significant differences in neuronal clustering were observed in the patient groups. Further studies are required to examine whether the observed decrease in glial density within the superior temporal white matter in schizophrenia reflects a deficit in any individual glial cell population.

Osteoblastoma is an uncommon benign bone tumor that accounts for 1% of all primary bone tumors. Well documented in the spine and long bones, it is rarely found in the skull, namely in the sphenoid bone, with only five cases reported in the literature. We report a case of an 11-year-old girl with a histologically confirmed benign osteoblastoma in an unusual location and an atypical aspect on the imaging studies.

Dieulafoy's lesions are rare and usually present in the stomach. There are only 18 cases of jejunal Dieulafoy's lesion reported. It can present as a massive gastrointestinal bleed and a high grade of suspicion is necessary for a quick and effective approach. The authors present the case of a 14-year-old adolescent with a sudden onset of hematochezia and shock. The high and low endoscopies as well as the arteriography were all inconclusive. An exploratory laparotomy was undertaken in the first 24 h of hospital admission. A review of the small bowel by advancing soft bowel clamps in a sequential manner revealed a bleeding lesion in the jejunum. The histological exam showed a Dieulafoy's lesion.

Objective: Rosette-forming glioneuronal tumor is a newly described mixed glial and neuronal tumor. We describe two cases and review the literature to better characterize this entity., Methods: Patients were surgically treated, and tumors were diagnosed by light microscopy and immunohistochemistry using the avidin-biotin complex method. PubMed was searched for previously reported cases., Results: Patient 1 was a 38-year-old woman who presented with headaches and no neurological abnormality. Magnetic resonance imaging showed a solid mass in the fourth ventricle. Subtotal excision of the mass caused transient gait ataxia. Patient 2 was a 51-year-old woman with dizziness who fell and sustained head trauma. Magnetic resonance imaging revealed a right paramedian cerebellar cystic and nodular mass and a separate nodule in the vermis, which were excised gross totally with no morbidity. Microscopic examination showed neuroepithelial tumors composed of neurocytic cells focally forming well-defined rosettes that were immunopositive for neuronal markers and of elongated, glial fibrillary acidic protein-immunoreactive astrocytes. No histological anaplasia was present. Both patients were well 18 and 8 months after surgery, respectively. Eighteen rosette-forming glioneuronal tumors were identified with the literature search., Conclusion: These are tumors of young adulthood (range, 12-59 yr) usually in or close to the fourth ventricle. Histologically, they are low-grade, although multiple foci or local extension may prevent total excision and account for some recurrences. On imaging, they are cystic, solid, or both, with minimal perilesional edema or mass effect. They are composed of neurocytic and glial elements, probably arising from a common progenitor in the subependymal plate, and need to be differentiated from a variety of glioneuronal tumors.

An intra-conical histologically malignant solitary fibrous tumor of the orbit presented in a 28 year-old female with intact vision and exophthalmos. Total resection was achieved by means of a frontal craniotomy and orbital roof osteotomy. Evidence of a beneficial role for adjuvant treatments in this particular tumor is controversial and vision impairment is a possible side effect. Therefore they were not employed. The patient is well after two years of follow-up.

Objective: To determine whether it is worth pursuing surgery for the treatment of epilepsy in patients with normal neuroimaging., Methods: Two patient populations were studied: (1) 136 consecutive patients who were surgically treated; (2) 105 consecutive patients assessed with chronically implanted intracranial electrodes within the same period. Sixty patients belonged to both groups, and included all 21 patients who had normal neuroimaging., Results: There were no differences in the proportion of patients with favourable outcome between those with normal and those with abnormal neuroimaging, irrespective of whether intracranial recordings were required. Among the 19 operated patients with normal neuroimaging, 74% had a favourable outcome (Engel's seizure outcome grades I and II), and among the 93 patients with abnormal neuroimaging, 73% had favourable outcome (p = 0.96). In patients with temporal resections, 92% of the 13 patients with normal neuroimaging had a favourable outcome, whereas among the 70 patients with abnormal neuroimaging, 80% had a favourable outcome (p = 0.44). In patients with extratemporal resections, two of the six patients with normal neuroimaging had a favourable outcome, while 12 of the 23 patients with abnormal neuroimaging had a favourable outcome (p = 0.65). Among the 105 patients studied with intracranial electrodes, five suffered transitory deficits as a result of implantation, and two suffered permanent deficits (one hemiplegia caused by haematoma and one mild dysphasia resulting from haemorrhage)., Conclusions: It is worth pursuing surgery in patients with normal neuroimaging because it results in good seizure control and the incidence of permanent deficits associated with intracranial studies is low.

A cavernous malformation involving the Gasserian ganglion, 2nd and 3rd divisions of the trigeminal nerve on the left side was resected via an extradural route in a 54 year old male. Cavernous malformations of the cranial nerves are rare. Specific origin from the trigeminal nerve has not been previously reported.

Background: Abnormal late responses to single pulse electrical stimulation (SPES) in patients with intracranial recordings can identify epileptogenic cortex. We aimed to investigate the presence of neuropathological abnormalities in abnormal SPES areas and to establish if removal of these areas improved postsurgical seizure control., Methods: We studied abnormal responses to SPES during chronic intracranial recordings in 40 consecutive patients who were thereafter operated on because of refractory epilepsy and had a follow-up period of at least 12 months., Findings: 22 patients had abnormal responses to SPES exclusively located in resected regions (96% with favourable outcome), seven had abnormal responses to SPES located in resected and non-resected regions (71% with favourable outcome), three had abnormal responses to SPES exclusively outside the resected region (none with favourable outcome), and eight did not have abnormal responses to SPES (62.5% with favourable outcome). Surgical outcome was significantly better when areas with abnormal responses to SPES were completely resected compared with partial or no removal of abnormal SPES areas (p=0.006). Neuropathological examination showed structural abnormalities in the abnormal SPES areas in 26 of the 29 patients in whom these regions were resected, despite the absence of clear MRI abnormalities in nine patients., Interpretation: Abnormal responses to SPES are functional markers of epileptogenic structural abnormalities, and can identify epileptogenic cortex and predict surgical outcome, especially when a frontal or temporal focus is suspected.

Reductions in neuronal size and glial cell density have been described in the frontal cortex in major psychiatric disorders. In this investigation, we performed a cytoarchitectural assessment within the planum temporale (PT), an auditory association region located within the superior temporal gyrus, using two-dimensional (2D) measures of cell size and density and spatial point pattern analysis. In sections of the PT from subjects with schizophrenia, bipolar disorder, major depressive disorder and controls (15 subjects per group), the laminar distribution and size of all neurons and glial cell nuclei was recorded. Spatial point pattern investigation demonstrated reduced neuronal clustering in bipolar disorder (p=0.033) and schizophrenia (p=0.027) compared with controls. Statistical analyses comparing each of the patient groups with the control group failed to identify differences in neuronal density between groups. Neuronal size was reduced in cortical layer 3 (p=0.02) and glial cell density reduced in cortical layer 6 (p=0.05) in bipolar disorder relative to controls but these findings did not remain significant after adjusting for six layer-wise comparisons. We propose that alterations in cortical cytoarchitecture within this region are subtle and involve reduced clustering of neurons, which may be due to altered neuronal organisation within cortical mini-columns or within cortical layers.

A case of conventional intramedullary osteosarcoma (epithelioid subtype) with 10 years of evolution and another of high grade surface osteosarcoma of the chondroblastic type, both in the skull, gave rise to several diagnostic and therapeutic difficulties. Key points concerning the definition, classification, imaging, clinical series data and treatment options available for skull osteosarcoma are highlighted.

Six cases of cavernous abducens nerve schwannoma have been reported. A new case of a 39 year old female with abducens nerve paresis, exophtalmos, chemosis and headache due to a 1,36 x 2,58 cm cystic right cavernous abducens nerve schwannoma is presented and discussed. The cavernous sinus was opened between the trochlear and ophthalmic nerves. A portion of the tumor capsule adherent to the internal carotid artery was not resected. No deficits were added by surgery. After 30 months of follow up there is no evidence of relapse and only abducens nerve paresis persists.

Objective: Description of the demographic, clinical and neuropathological features of 11 cases of Creutzfeldt-Jakob disease (CJD)., Method: Review of the clinical and neuropathological features of patients with CJD diagnosed in hospitals in the North of Portugal between 1993 and 2002., Results: Eleven patients were identified, 4 females: mean age of onset of symptoms--64 years, mean duration of disease--8 months. All presented with a syndrome of progressive dementia with myoclonus, with four patients presenting with cerebellar signs. Neuropathological examination of brain at autopsy showed spongiosis and reactive gliosis associated with neuronal loss. In eight cases immunocytochemistry for prion protein (PrP) was carried out and was positive., Conclusion: The group of patients described represents the heterogeneity of the clinical phenotypes possible in CJD. Neuropathological examination is still indispensable to make the definitive diagnosis of the disease.

Solitary fibrous tumour is a well defined pathological entity originally described as a tumour of the pleura, but the occurrence of this neoplasm has increasingly been described at other sites. At present the development of these tumours is recognized as possible in virtually all anatomical sites. The rarity of this type of pathology has not allowed up to the present time clarification of the histogenesis, clinical behaviour, treatment and prognosis of these tumours. Differential diagnosis becomes important, especially in extra-thoracic sites so as not to mistake them for much more aggressive mesenquimal tumours. Two additional cases of this neoplasm are presented, one of them responsible for obstructive uropathy, accidentally found in a patient suffering renal trauma. The second tumour was located in the spermatic cord. A review of the theme is presented based on the available literature.

C cell hyperplasia is associated with medullary carcinoma of the thyroid in the inherited MEN2 syndromes, in which the great majority of cases have been shown to be due to a mutation in the RET oncogene. We report a study of a family with C cell hyperplasia and hypercalcitoninemia in which no cases of medullary carcinoma have yet occurred and which lacked an identifiable causative RET mutation. Four of the family members showed hypercalcitoninemia, and marked C cell hyperplasia was present in each of the three in whom thyroidectomy has been performed. We investigated the possible involvement of the SDHD gene, because somatic and germline mutations in this gene have been found in a variety of tumors of neural crest-derived tissue. A germline mutation in exon 2 of the SDHD gene (c149 A-G, His 50 Arg) was found in six members of the family; all the four available members with hypercalcitoninemia possessed the mutation. One of the five available members without hypercalcitoninemia, an 18-yr-old female, also showed the mutation. We conclude that we have identified a new syndrome, characterized by familial non-RET C cell hyperplasia. Our studies suggest that a mutation in SDHD may be causative. These observations have implications for apparently incidental cases of hypercalcitoninemia or C cell hyperplasia.

Purpose: Hamartomas of the hypothalamus (HH) cause an uncommon and unusual epilepsy syndrome. The condition is recognized to affect children, but the presentation in adults is not well understood. We present 19 children and adult patients with HH, including three patients whose epilepsy began in adult life. The patterns of clinical presentation, evolution of the epilepsy from childhood to adult life, and electroclinical diagnostic features are presented., Methods: Nineteen patients, both children and adults with HH and epilepsy, were evaluated clinically, with EEG, video-EEG, and magnetic resonance imaging (MRI) scanning. Seven patients underwent surgical resection of the hamartoma. Stereotactic thermocoagulation of the hamartoma was performed in two patients., Results: Gelastic seizures occurred at onset of epilepsy in 15 of 16 early-onset cases. Subsequently, multiple seizures types occurred, which then evolved to mainly partial epilepsy with tonic or complex partial seizures (five of eight adults), or became entrenched symptomatic generalized epilepsy with atypical absences, drop attacks, and secondarily generalized seizures, and cognitive impairment (three of eight adults). In the adult-onset patients, gelastic seizures were not prominent, the epilepsy was milder, and they functioned normally. Stereotactic thermocoagulation of the hamartoma resulted in improvement in seizure control in two patients., Conclusions: Gelastic seizures are not a prominent feature of epilepsy in adult patients with HH. The epilepsy associated with HH, although severe at onset, can evolve into a milder syndrome in later life. For less severely affected patients, minimally invasive alternatives to the traditionally difficult open surgical treatment should be considered.

Inverted papillomas are rare tumours representing about 2.2% of all urothelial tumours (benign or malignant). Inverted papillomas are predominantly seen in the bladder but these tumours have also been described in other locations, all over the urinary tract. The authors report six additional cases of such tumours describing the individual characteristics of each case, presenting symptoms, treatment employed and follow up available. A review of the literature relative to aetiology, clinical signs and symptoms, diagnostic criteria, treatment options and outcome has also been carried out.

One case of intradiploic meningioma, causing partial occlusion of the superior longitudinal sinus, with subsequent visual trouble and another of lipomatous meningioma with great fat content and very calcified, that was found in a LCR fistula study of the cranial anterior stage, are described by the authors as atypical meningiomas.

Determination of neuroglial cell fate and neural tube development during embryogenesis is influenced by the Notch/Wnt signalling pathway. We have studied the localisation of several proteins in the Wnt pathway in focal cortical dysplasia (FCD). This disorder, thought to be due to abnormalities of neuronal migration and differentiation, contains regions of morphologically normal neocortex interrupted by areas of neuronal laminar disorganisation, heterotopic white matter neurons, abnormal large neurons and balloon cells of uncertain histogenesis. We found that the subcellular distribution of several proteins involved in the Wnt pathway differed in regions of FCD from normal cortex, and that within the areas of FCD, the pattern varied with cellular phenotype. Thus, in balloon cells, elevated cytoplasmic levels of dishevelled (Dvl-1) protein were accompanied by an absence of Notch-1, increased adenomatous poliposis coli (APC), altered cytoplasmic beta-catenin, and reduced nuclear expression of beta-catenin. A contrasting pattern of expression was found in abnormal large neurons, which demonstrated elevated levels of Notch-1, and glycogen synthase kinase-3beta (GSK-3beta), and normal levels of APC. Our results are consistent with the notion that Wnt/Notch signalling influences neuroglial cell fate, and suggest that a perturbation of Wnt/Notch signalling may contribute to the neuropathology of FCD.

Objective: To describe the various patterns of neurophysiological abnormalities which may complicate prolonged critical illness and identify possible aetiological factors., Design: Prospective case series of neurophysiological studies, severity of illness scores, organ failures, drug therapy and hospital outcome. Some patients also had muscle biopsies., Setting: General intensive care unit (ICU) in a University Hospital., Patients: Forty-four patients requiring intensive care unit stay of more than 7 days. The median age was 60 (range 27-84 years), APACHE II score 19 (range 8-33), organ failures 3 (range 1-6), and mortality was 23%., Results: Seven patients had normal neurophysiology (group I), 4 had a predominantly sensory axonal neuropathy (group II), 11 had motor syndromes characterised by markedly reduced compound muscle action potentials and sensory action potentials in the normal range (group III) and 19 had combinations of motor and sensory abnormalities (group IV). Three patients had abnormal studies but could not be classified into the above groups (group V). All patients had normal nerve conduction velocities. Electromyography revealed evidence of denervation in five patients in group III and five in group IV. There was no obvious relationship between the pattern of neurophysiological abnormality and the APACHE II score, organ failure score, the presence of sepsis or the administration of muscle relaxants and steroids. A wide range of histological abnormalities was seen in the 24 patients who had a muscle biopsy; there was no clear relationship between these changes and the neurophysiological abnormalities, although histologically normal muscle was only found in patients with normal neurophysiology. Only three of the eight patients from group III in whom muscle biopsy was performed had histological changes compatible with myopathy., Conclusions: Neurophysiological abnormalities complicating critical illness can be broadly divided into three types -- sensory abnormalities alone, a pure motor syndrome and a mixed motor and sensory disturbance. The motor syndrome could be explained by an abnormality in the most distal portion of the motor axon, at the neuromuscular junction or the motor end plate and, in some cases, by inexcitable muscle membranes or extreme loss of muscle bulk. The mixed motor and sensory disturbance which is characteristic of 'critical illness polyneuropathy' could be explained by a combination of the pure motor syndrome and the mild sensory neuropathy. More precise identification of the various neurophysiological abnormalities and aetiological factors may lead to further insights into the causes of neuromuscular weakness in the critically ill and ultimately to measures for their prevention and treatment.

Gliosarcomas are rare tumors of the central nervous system with a poor prognosis. Histologically these tumors are characterized by an admixture of neoplastic glial cells and sarcomatous elements. Due to the scarcity of data in literature, the diagnosis is often missed and treatment is difficult. The authors report three cases of cerebral gliosarcomas and review the literature on this subject.

HIV infection can cause extensive neuronal loss and clinically a severe dementia. The cause of the neurotoxicity remains unclear as neurons are not infected, but disturbance of glutamate-linked calcium entry has been implicated. In this study, we have shown a decrease in HIV-infected brain of the expression of mRNA and protein of the GluR-A flop subtype of alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA) glutamate receptor in cerebellar Purkinje cells. Although Purkinje cells are relatively resistant to loss, the observed disturbance of AMPA receptors may contribute to the neurotoxic process in other vulnerable brain regions and clinically to the development of dementia.

Activity of the enzyme which synthesizes acetylcholine, choline acetyltransferase, was estimated in the neocortex of three series of control and demented cases. Clinically demented cases were divided into those with the classical neuropathological features of Alzheimer's disease (numerous neocortical plaques and tangles) and those with Lewy bodies in the brain stem and cortex (together with plaques and variable neurofibrillary pathology). In the Lewy body cases neocortical choline acetyltransferase was consistently lower than in the classical Alzheimer-type cases. Two of the Lewy body cases with extremely low cholinergic activity were responders in therapeutic trials of the cholinesterase inhibitor, tacrine, and the combined data suggest that cholinergic therapy may be particularly relevant to patients with Lewy body type dementia.

Thirty-one patients with a mean age of 18.9 years (range 3 to 53 years) who underwent temporal lobe surgery for tumor-related epilepsy over a 14-year period are presented. All had suffered chronic drug-resistant temporal lobe seizures (mean age at onset 6.9 years, range 0 to 30 years; mean duration of condition 11.9 years, range 3 to 39 years). Preoperative interictal scalp electroencephalography tracings indicated unilateral localized epileptic foci in 90% of patients, and computerized tomography scans showed abnormalities within the temporal lobe in 87%. All patients underwent en bloc temporal lobectomy. No patient received adjuvant radiotherapy or chemotherapy. Review of the histological material showed dysembryoplastic neuroepithelial tumor in 27 (87%) of the specimens and microscopic evidence of incomplete removal of tumor in 22 (71%). At long-term follow-up evaluation (mean duration 5.8 years, range 1 to 14 years), 81% of patients were completely free of seizures (Engel grade I) and 10% were almost seizure free (Engel grade II) with no deaths reported in either early or late follow-up review. Only one patient in the series failed to benefit from the surgery. Four patients suffered permanent neurological deficit causing a mild disability. Psychological assessment showed no significant fall in verbal or performance intelligent quotient for the group, but a mild memory impairment was evident in 32%. Behavioral and social aspects improved in nearly all (94%) cases. Relief of seizures could not be predicted by intraoperative electrocorticography, and outcome was independent of the completeness of tumor resection. Postoperative electroencephalographic findings identified epileptiform potentials in 65% of patients, which were associated with a worse seizure-control outcome grade.

A patient with von Recklinghausen neurofibromatosis (NF-1) developed spinal cord compression from atlanto-axial subluxation caused by a neurofibroma involving the odontoid peg. His case is discussed and the relevant literature reviewed.

The ultrastructure of the cells and capillaries of the frontal cortex and hippocampus was studied in marmosets to assess age-related changes. The appearances in the brains of four marmosets, more than 12 years of age, were compared with those of two young marmosets aged 26 and 21 months. There was widespread accumulation of lipofuscin in neurons, glial cells, perivascular macrophages and pericytes, but not in endothelial cells. Many of the nerve cell nuclei showed marked membrane infolding, alteration of nuclear morphology and occasional inclusions. A few degenerated and dystrophic axons containing abnormal organelles were seen. The capillaries displayed irregularly thickened and split basal laminae. No neurofibrillary tangles, neuritic plaques, amyloid deposits or granulovacuoles were present. These changes are compared to those occurring in other animal species and in man during ageing.

To find out whether the diagnosis of dementia agreed with findings at necropsy a detailed assessment of 27 elderly patients (mean age 82 (range 70-94] presenting with dementia was conducted at a combined department of geriatric medicine and psychiatry for the elderly. On the basis of the results the cause of the dementia was diagnosed clinically. Neuropathological examinations were performed after death. The clinical diagnosis made during life was not supported by the findings at necropsy in 11 cases. Alzheimer's disease was overdiagnosed in life (13 cases, of which only six were confirmed at necropsy). Although the clinical investigation was limited by availability of resources, neither cranial computed tomography nor the Hachinski score helped to distinguish between multi-infarct dementia and Alzheimer's disease in this age group. This study confirms the value of neuropathological studies in the precise diagnosis of dementia.