An Atlas of Infectious and Parasitic Diseases of the Central Nervous System. A Cooperative Study of SILAN (Sociedad Iberolatinoamericana de Neurorradiologia).

Infectious diseases of the central nervous system vary in frequency in different locations in America and Europe. What is common in Brazil can be a sporadic presentation in Europe. Cooperative work gathering experiences from neuroradiologists working in various places can be achieved and will help to identify uncommon cases that can present in our daily practice.

Beta-catenin transcriptional activity is inhibited downstream of nuclear localisation and is not influenced by IGF signalling in oesophageal cancer cells.

Aberrant expression/localisation of beta-catenin has been implicated in the progression of oesophageal cancer. As a member of the Wnt-signalling pathway, activated beta-catenin translocates into the nucleus and drives gene transcription. Insulin-like growth factors (IGFs) have been implicated in modulation of beta-catenin localisation and transcriptional activity. We have demonstrated that beta-catenin is abundantly expressed by oesophageal cancer cells, and is both cytoplasmic and nuclear in location. beta-catenin was transcriptionally inactive in 4 of 5 cell lines. All cells expressed the IGF-1 receptor. Addition of exogenous IGFs activated the PI-3 kinase pathway but did not enhance beta-catenin/T-cell factor- (TCF) mediated transcription. Activation of Wnt signalling by lithium induced beta-catenin stabilisation in 2 cell lines but this did not increase transcriptional activity. In contrast 2 cell lines without lithium-enhanced stabilisation or re-distribution of beta-catenin did exhibit beta-catenin/TCF-mediated transcriptional activity. This study shows that beta-catenin accumulation and nuclear localisation is not indicative of transcriptional activity, and therefore is not supportive of a major role in these oesophageal cancer cells. It also questions the value of immunohistochemical studies that examine only expression. Co-operative signalling from other growth factors or adhesive molecules is likely to be required to relieve nuclear inhibition of transcriptional activity, and the nature of this is currently unknown.

Stereotactic radiosurgery in the management of angiographically occult vascular malformations.

PURPOSE: To evaluate the role of stereotactic radiosurgery in the treatment of angiographically occult vascular malformations (AOVMs). METHODS AND MATERIALS: From 1987 to 1996, 21 patients, 10 males and 11 females, median age of 41 years (range: 7-75 years), with an intracerebral AOVM underwent stereotactic radiosurgery at our institution. All were considered at high risk for surgical intervention. The vascular lesions were located in the brainstem (17 patients), basal ganglia (2), occipital lobe (1), and cerebellum (1). Diagnosis was based on high-resolution magnetic resonance imaging (MRI). Clinical presentation at onset included previous intracerebral hemorrhage (20 patients) and epilepsy (1). All patients were treated with a linac-based radiosurgical technique. The median dose delivered was 25 Gy (range 13-50 Gy), typically prescribed to the 80-90% isodose surface (range 50-90%), which corresponded to the periphery of the vascular malformation. Patients were followed by clinical neurologic assessment and by MRI on a regular interval basis. RESULTS: Follow-up was obtained in 20 patients; clinical or MRI information was not available for 1 patient, and this patient was excluded from our analysis. At a median follow-up of 77 months (range: 4-141 months), follow-up MRIs postradiosurgery do not demonstrate any changes in the appearance of the AOVM. Four patients developed an intracranial bleed at 4, 8, 35, and 57 months postradiosurgery. Annual hemorrhage rates were considerably higher in the observation period preradiosurgery than postradiosurgery (30% vs. 3.2%, p < 0.001). Complications postradiosurgery were observed in 4 patients. Three patients developed mild to moderate edema surrounding the radiosurgical target, expressed at 5, 8, and 24 months, respectively. In all cases, the edema was transient and resolved completely on subsequent MRIs. One of the 4 patients developed radiation necrosis 8 months after radiosurgery. CONCLUSION: The use of stereotactic radiosurgery in the treatment of AOVM continues to be controversial. Our results appear to show a reduction in the risk of symptomatic hemorrhage post treatment. Patients with previous history of hemorrhage or progressive neurologic deficit and small, well circumscribed lesions may benefit from a trial of stereotactic radiosurgery.

Cyclosporine-associated thrombotic microangiopathy in renal allografts.

BACKGROUND: The association between cyclosporine (CsA) and thrombotic microangiopathy (TMA) in renal allografts is well documented. However, predisposing factors and therapy guidelines are not adequately characterized. METHODS: We reviewed 188 patients with kidney or kidney-pancreas transplants who were treated between January 1994 and December 1996 with prednisone, CsA, or tacrolimus, and azathioprine or mycophenolate. We analyzed 50 patients who had graft biopsies: 26 with TMA and 24 with no TMA, as well as 19 patients with well-functioning grafts who never required biopsy. RESULTS: TMA was observed in 26 of 188 renal graft recipients (14%). TMA was confined to the allograft kidney without any systemic evidence in 24 of the 26 patients. At the time of the diagnosis of TMA, 24 of the patients were on CsA, with 19 on the microemulsion form. Conversely, 5 of 18 control patients with no graft dysfunction were on the microemulsion form of CsA (P = 0.0026). Graft loss was seen in 8 of 26 patients with TMA. Conversion from CsA to tacrolimus resulted in a one-year salvage of graft function in 13 of 16 (81%) patients. CONCLUSIONS: TMA was the cause of renal graft dysfunction in 14% of renal graft recipients and was associated with the use of the microemulsion form of CsA. Systemic signs of TMA were rare, underscoring the importance of the graft biopsy in making the diagnosis. The most successful strategy was switching from CsA to tacrolimus, with good graft function in 81% of the recipients one year after the TMA episode.

Persistent lupus activity in end-stage renal disease.

Clinical and serological activity of systemic lupus erythematosus (SLE) has been reported to dramatically improve in patients who develop end-stage renal disease (ESRD). At Tulane University Medical Center, most patients with SLE and ESRD continue to have evidence of disease activity. A retrospective study of lupus activity was therefore performed in 19 patients with SLE, who were either undergoing dialysis or had undergone transplantation between 1988 and 1994, to determine disease activity before and a mean follow-up of 3 years after ESRD. There were seven hemodialysis patients, five peritoneal dialysis patients, and seven transplant recipients in the study population. Clinical events recorded to evaluate disease activity as indicators of serological activity were malar rash, ulcers, alopecia, arthritis, myositis, pleuritis, pericarditis, fever, cerebritis, and vasculitis. The following studies were recorded as measures of serological activity: leukocyte count, platelet count, serum complement 3 level, and anti-double-stranded DNA level. Disease activity was measured by using the SLE Disease Activity Index and the requirement for immunosuppressive medications. Clinical event rates for alopecia, arthritis, myositis, pleuritis, pericarditis, fever, and vasculitis were greater after ESRD but not to statistical significance. Serological studies showed little change in the dialysis patients before and after ESRD; however, there was a tendency for lupus serological results to improve after transplantation. When all event rates were combined, there was a statistically significant greater incidence of lupus activity after both hemodialysis and peritoneal dialysis (P < 0.01) but not after renal transplantation. Fifty-eight percent of the patients undergoing dialysis died, either during the study period or within a 5-year follow-up, all of whom had clinically active lupus. This study therefore shows that lupus activity may persist in patients with ESRD. It is speculated that the study population, 84% of whom were black women, may represent a subgroup of patients with lupus in whom the disease remains active, even after they have developed ESRD.

Exophytic primitive neuroectodermal tumor of the spinal cord.

We present a case of an exophytic spinal primitive neuroectodermal tumor that, radiologically, simulated an extramedullary nerve sheath tumor, meningioma, or metastatic tumor deposit. MR imaging provided discrete anatomic localization of the tumor, enabling exclusion of multicentricity in the brain and spinal cord.

Gliomatosis cerebri.

PURPOSE: To characterize gliomatosis cerebri on computed tomographic (CT) and magnetic resonance (MR) images. MATERIALS AND METHODS: MR and CT studies of 22 patients with cerebral gliomatosis were reviewed retrospectively. Tumor was confirmed with autopsy (n=5) or biopsy. Distribution and extent of disease were assessed, and disease progression was followed. RESULTS: Tumor involved at least two lobes of the brain in all patients, with extension to the corpus callosum in 12, basal ganglia and thalamus in 17, brain stem in three, and cerebellum in two patients. Widespread invasion with hyperintensity was noted on proton-density- and T2-weighted MR images. At CT, areas of hypo- or isoattenuation were noted, and no contrast enhancement occurred. Extent of tumor was greater on MR images than on concurrent CT scans in all patients. The MR findings closely correlated with the autopsy findings. CONCLUSION: Gliomatosis cerebri is best detected with MR imaging. The pattern is infiltrative with enlargement of cerebral structures.

Left atrial myxoma presenting as Gerstmann syndrome.

The authors describe a 29-year-old woman who presented with Gerstmann syndrome secondary to underlying left atrial myxoma. The clinicoradiologic features of atrial myxoma, as well as its neurologic manifestations, are reviewed.

Donor race does not affect cadaver kidney transplant survival--a single center experience.

Black kidney transplant recipients have worse graft survival than white recipients. Speculation regarding etiology has focused on differences in human lymphocyte antigens (HLA). Some suggest that improvements in graft survival would be obtained if donor and recipient race were matched. We reviewed 236 cadaver transplants performed over 9 years at a single center using an HLA-match-driven allocation system and a uniform immunosuppressive protocol to determine the impact of donor race on graft survival. A multivariate analysis of graft survival using patient race, sex, age, transplant number, current and maximum plasma renin activity, donor race, cold ischemia time and HLA mismatch, the need for dialysis, and the presence of rejection as independent variables. Sixty percent of recipients were black, and 82% were primary transplants; 28 kidneys (12%) were from black donors. The 112 patients with the same race donor had identical 5-year graft survival as the 124 who had a different race donor (40%; P = 0.1726). The 5-year survival of the 88 white recipients of white donor organs was better than that of the 120 black recipients of white donor organs (54% vs. 42%, respectively; P = 0.0398). Black recipients (t1/2 = 37 months) did worse than white recipients (t1/2 = 60 months) regardless of organ source (P = 0.023). In the multivariate analysis, neither donor nor recipient race were an independent variable in predicting graft survival. Rejection (RR = 2.9) and the need for dialysis on the transplant admission (RR = 4.1) were the only factors that predicted poor survival. Black recipients had more rejection (P = 0.04) but not more need for dialysis posttransplant regardless of donor race. Donor race did not affect graft survival in this series. The effect of recipient race on graft survival was due to an increased incidence of rejection episodes in black recipients, which was independent of HLA mismatch. These data suggest that improvements in immunosuppression, not changes in allocation, are needed to improve graft survival.

Effect of myeloma light chains on phosphate and glucose transport in renal proximal tubule cells.

Primary cultures of cells derived from the rat proximal tubule were exposed to up to 200 microM lambda- or kappa-light chain obtained from myeloma patients. Light chains inhibited the uptake of both phosphate and glucose by the cells while albumin had no effect. The half-maximal inhibitory concentration (IC50) of both the lambda- and kappa-light chains on phosphate transport were similar, 34 and 35 microM respectively. The IC50 of the kappa-light chain on glucose transport was 360 microM. The inhibitory effect of light chains was dose-dependent (r = 0.90, p < 0.01 for the lambda-light chain and r = 0.93, p < 0.001 for the kappa-light chain, on phosphate transport; and r = 0.93, p < 0.001 for glucose transport). Dixon and Line-weaver-Burk plot analyses were characteristic for noncompetitive inhibition. The inhibition constant 89 microM for phosphate uptake derived from the Dixon plot was similar to the IC50 calculated from the dose-response curves. These findings indicate that light chains, at concentrations found in the tubule fluid of a typical myeloma patient, are potent inhibitors of phosphate and glucose transport in proximal tubular cells, and that direct cell toxicity is a major mechanism of light chain nephrotoxicity.

Parathyroid hormone transport effects and hormonal processing in primary cultured rat proximal tubular cells.

The development of satisfactory cell culture models for the study of parathyroid hormone (PTH)-induced inhibition of Pi transport has proven difficult. Using subcellular fractionation techniques we investigated the response of primary cultures of rat proximal tubular cells to PTH-(1-34). Specific binding of 125I-bPTH-(1-34) occurred at 2 degrees C. After 5 min of rewarming, trypsin-releasable radioactivity decreased from 90 to 50%, indicating internalization of the ligand. Cell disruption, followed by density centrifugation with 17% Percoll either directly after binding at 2 degrees C or post-rewarming for 20 min, showed a shift of 125I label from the plasma membrane (5'-nucleotidase) to lysosomal fractions (beta-D-glucosaminidase), confirming the sequential occurrence of cell surface binding, internalization and transport to lysosomes of 125I-bPTH-(1-34). Reculture at 37 degrees C revealed steady accumulation of trichloroacetic acid-soluble radioactivity in the medium, indicating degradation of 125I-bPTH-(1-34). Phosphate transport in the absence of sodium was minimal. Incubation of the cells with bPTH-(1-34) resulted in up to 50% inhibition of sodium-dependent phosphate transport. Prior phosphate depletion abrogated the response to PTH.

Magnetic resonance imaging in the diagnosis of dominantly inherited cerebello-olivary atrophy: a clinicopathologic study.

To facilitate the study of cerebellar degenerative disorders, improved clinical diagnosis is needed. Cerebello-olivary atrophy is pathologically distinct, but until now its diagnosis has been thought to require postmortem examination. This condition was considered as a possible diagnosis in two patients from different families with dominantly inherited ataxia. The affected members of each family demonstrated a stereotyped, progressive, "pure" cerebellar syndrome, which began with gait ataxia followed years later by dysarthria and limb ataxia. The autopsy findings for the first patient's father revealed paleocerebellar and olivary atrophy, characteristic of cerebello-olivary atrophy. Magnetic resonance imaging (MRI) of the brain of both patients revealed medullary, vermian and, to a lesser extent, cerebellar hemispheric atrophy but a normal pons. Dominantly inherited cerebello-olivary atrophy was diagnosed in both patients. Characteristic clinical and MRI features thus permit a confident clinical diagnosis of dominantly inherited cerebello-olivary atrophy. Recognition of this entity during life should advance the classification of cerebellar degenerative disorders.

Diuretics in the therapy of hypertension: current status.

Diuretics were the first effective oral agents for treating hypertension. They have proven to be safe and effective. Recently, they have been scrutinized as possibly being responsible for certain side effects that may increase risk for cardiovascular morbidity and mortality. A careful review of the literature suggests this class of agents warrants continued use as first-line therapy of hypertension, especially in certain demographic groups. However, monitoring of potential baleful effects and a general reduction in dosage are appropriate. Furthermore, selection of other (alternative) agents for monotherapy is advised in certain clinical circumstances.

Subarachnoid hemorrhage resulting from methanol intoxication: demonstration by computed tomography.

Subarachnoid hemorrhage developed in a patient intoxicated with methanol. Computed tomography performed at the time of admission suggested this complication. The hemorrhage was definite and extensive by the 5th day after admission and was accompanied by left caudate and pontine hemorrhage, as well as severe cerebral edema. The authors are unaware of any previous reports of subarachnoid hemorrhage associated with ingestion of methanol.

MRI diagnosis of brainstem cavernous angiomas presenting as tumours.

We report experience with 11 patients misdiagnosed for years, on the basis of computed tomography (CT) and angiography, as harbouring brainstem tumours in whom magnetic resonance imaging (MRI) demonstrated cavernous angiomas. Seven had undergone external irradiation, 2 had a ventriculo-peritoneal shunt, 2 developed aseptic femur necrosis following corticosteroid treatment, 1 had undergone a biopsy with a pathological diagnosis of glioma. CT had depicted ill-defined, hyperdense, faintly enhancing lesions. Angiography was normal, or showed an avascular mass or subtle venous pooling. MRI delineated discrete lesions, typical of cavernous angiomas, with a mixed hyperintense, reticulated, central core surrounded by a hypointense rim. Six patients subsequently underwent stereotactic radiosurgery without changes in clinical status or lesion. Although hemorrhagic neoplasms may mimic the clinical course and MRI appearance of cavernous angiomas, MRI is useful in the diagnosis of brainstem cavernous angiomas and should be performed in patients with suspected brainstem tumours.

Bilateral thalamic glioma: review of eight cases with personality change and mental deterioration.

PURPOSE: To describe the clinical, radiographic, and neuropathologic features of bilateral thalamic glioma. METHODS: We searched our hospital records (1963 to present) to identify patients diagnosed as having the disease. RESULTS: Our search revealed eight patients, ranging in age from 8-63 years, with bithalamic tumor diagnosed by angiography, CT, and/or MR. All patients displayed personality changes and/or mental deterioration, including memory loss, inattention, confusion, hallucination, hyperphagia, or slow mentation. Unilateral motor weakness was also noted in six cases. The tumor always involved the medial aspect of the left and right thalami, but was often more extensive. The pathology was determined to be grades I-IV astrocytoma, confirmed by stereotactic biopsy or autopsy in six. Mild to moderate hydrocephaly occurred in some cases and was considered to be a contributing factor to mental deterioration. No correlation was found between age and type of tumor. CONCLUSIONS: Bilateral glioma of the dorsomedial and intralaminar nuclei of the thalamus can be a primary cause of dementia that has not been well-recognized in the past. CT and particularly MR should be considered for patients presenting with personality change or dementia, because of the possible presence of this unusual but devastating disease.

Renal transplantation in patients 65 years old or older.

Between January 1982 and August 1989, cadaveric renal transplantation was performed in 22 patients 65 years old or older. Mean recipient age was 68 years (range 65 to 73 years). There were 17 men and 5 women. Additional risk factors included retransplantation (3 patients), high (greater than 30%) panel reactive antibody (4) and diabetes (1). All patients received cyclosporine as part of the immunosuppressive regimen. The 3-year actuarial patient and allograft survival rates were 89% and 71%, respectively. There were 6 graft losses due to chronic rejection (2 patients), renal vein thrombosis (1), myocardial infarction (1), withdrawal of immunosuppression because of sepsis (1) and primary nonfunction (1). Of the 16 patients with a functioning graft 12 currently have a serum creatinine of less than 2.0 mg./dl. These results suggest that cadaveric renal transplantation is an acceptable form of treatment for patients older than 65 years with end stage renal disease.