Drug Prescribing for Patients with Chronic Kidney Disease in General Practice: a Cross-Sectional Study

Coherent oscillations of neurons in the primary motor cortex (M1) have been shown to be involved in the corticospinal control of muscle activity. This interaction between M1 and muscle can be measured by the analysis of corticomuscular coherence in the β‐frequency range (β‐CMCoh; 14–30 Hz). Largely based on magnetoencephalographic (MEG) source‐modeling data, it is widely assumed that β‐CMCoh reflects direct coupling between M1 and muscle. Deafferentation is capable of modulating β‐CMCoh, however, and therefore the influence of reafferent somatosensory signaling and corresponding neuronal activity in the somatosensory cortex (S1) has been unclear. We present transcranial magnetic stimulation (TMS) and MEG data from three adult patients suffering from congenital hemiparesis due to pre‐ and perinatally acquired lesions of the pyramidal tract. In these patients, interhemispheric reorganization had resulted in relocation of M1 to the contralesional hemisphere, ipsilateral to the paretic hand, whereas S1 had remained in the lesioned hemisphere. This topographic dichotomy allowed for an unequivocal topographic differentiation of M1 and S1 with MEG (which is not possible if M1 and S1 are directly adjacent within one hemisphere). In all patients, β‐CMCoh originated from the contralesional M1, in accordance with the TMS‐evoked motor responses, and in contrast to the somatosensory evoked fields (SEFs) for which the sources (N20m) were localized in S1 of the lesioned hemisphere. These data provide direct evidence for the concept that β‐CMCoh reflects the motorcortical efferent drive from M1 to the spinal motoneuron pool and muscle. No evidence was found for a relevant contribution of neuronal activity in S1 to β‐CMCoh. Hum Brain Mapp, 2006. © 2006 Wiley‐Liss, Inc.

The authors administered procarbazine, 1-(2-chloroethyl)-3-cyclohexyl-1-nitrosourea (CCNU, lomustine), and vincristine (PCV) to 86 patients with recurrent glioblastoma. There were three partial responses, but no complete responses. Median progression-free survival was 17.1 weeks and progression-free survival at 6 months was 38.4%. World Health Organization grade III/IV hematologic toxicity was common (25.6%), but nonhematologic toxicity was mild.

Adult medulloblastoma is a rare tumor with few retrospective studies published so far. The role of adjuvant chemotherapy or chemotherapy at relapse is unclear. This study reports therapy and outcome in all adult (≥ 16 years old) medulloblastoma (n = 34) and supratentorial primitive neuroectodermal tumor (PNET) patients (n = 2) treated in 2 neuro–oncological centers between 1976 and 2002. The median age was 24.5 years (range 16–76). After resection, 16 patients were treated with craniospinal radiotherapy alone, 20 patients also received adjuvant chemotherapy (8 vincristine, CCNU, cisplatin; 7 methotrexate alone or methotrexate/vincristine–based polychemotherapy; 5 other protocols). Median survival in the whole cohort was 126 months (2+ – 200+ months). Five–year and 10–year survival rates were 79 % and 56%. Adjuvant chemotherapy was associated with a non–significant trend to prolonged survival (relative risk (RR) 1.89; p = 0.068). The median progression–free survival (PFS) after primary therapy was 83 months. At relapse, 10 of 12 evaluable patients achieved a complete response upon second–line therapy. The median survival times from first (n = 17) and second relapse (n = 9) were 21 months (0–67+ months; 5/17 without second relapse) and 20 months (1–29 months). Cox regression analysis revealed the infiltration of the floor of the 4 th ventricle at diagnosis as the only therapy–independent prognostic factor (RR 0.48; p = 0.03). In conclusion, adjuvant chemotherapy may prolong survival in adult medulloblastoma patients. Moreover, second–line therapy may be beneficial for these patients. As in pediatric medulloblastoma patients, primary infiltration of the floor of the 4 th ventricle indicates a poor prognosis.

A 74-year-old man with right-sided amaurosis fugax had an ultrasound examination revealing right internal carotid artery (ICA) stenosis (figure 1, A and B). Angiography (figure 2A) showed a proximal ICA stenosis of approximately 90% according to NASCET criteria1 and a distal thrombus. The patient was anticoagulated with heparin. Invasive treatment options were discussed, but …

Central nervous system infectious diseases mimicking multiple sclerosis: recognizing distinguishable features using MRI,

BACKGROUND It is unknown whether multiple system atrophy of the cerebellar type (MSA-C) and idiopathic cerebellar ataxia with extracerebellar presentation (IDCA-P) represent distinct entities. OBJECTIVE To investigate the discriminative validity of magnetic resonance imaging in sporadic cerebellar ataxia. DESIGN Basal ganglia and infratentorial structures were screened for signal abnormalities and atrophic changes. Magnetic resonance imaging raters were masked to the clinical diagnosis. SETTING Outpatient clinic of a university hospital. PATIENTS Forty-one individuals were diagnosed as having MSA-C (n = 30) or IDCA-P (n = 11) based on their clinical features. RESULTS Shrinkage of the cerebellar vermis and hemispheres was found in both groups. Atrophy of the brainstem and middle cerebellar peduncles was significantly more frequent in patients with MSA-C (P<.001). Hyperintensities of infratentorial structures were common in patients with MSA-C (middle cerebellar peduncles: 87%; pons: 97%) but were absent in patients with IDCA-P. Hypointensities or hyperintensities of basal ganglia structures did not reliably differentiate the groups. CONCLUSIONS Patients with MSA-C were characterized by a higher frequency and severity of magnetic resonance imaging abnormalities (atrophic changes and additional hyperintense signal changes) of the middle cerebellar peduncles and pons. The presence of these magnetic resonance imaging features points to the diagnosis of MSA-C and helps differentiate MSA-C from other types of sporadic cerebellar ataxia with extracerebellar features.

Tuberous sclerosis complex (TSC) is a common neurological autosomal‐dominant syndrome caused by mutations in the TSC1 or TSC2 genes. TSC starts in early childhood and is characterized by cerebral hamartomas (benign tumours), severe epilepsy and cognitive deficits such as mental retardation and autism. The hamartomas are characterized by loss of the remaining wild‐type TSC allele, and clinical data implicate cerebral hamartomas in the generation of epileptic seizures, which may play a significant role in the development of mental retardation. The TSC2 mutation predicts alterations in mitogen‐associated protein kinase (MAPK) and, together with the TSC1 mutation, in mammalian target of rapamycin (mTOR) signalling pathways. Both pathways are involved in neuronal plasticity. We therefore hypothesized that the heterozygous mutation itself, besides cerebral hamartomas, contributes to the pathogenesis of cognitive deficits and possibly also epilepsy. Here, we show that young adult TSC2+/– rats, which are virtually free of cerebral hamartomas, exhibit enhanced episodic‐like memory and enhanced responses to chemically‐induced kindling. The activation of cyclic adenosine monophosphate (cAMP) in the hippocampus results in stronger induction of phospho‐p42‐MAPK in TSC2+/– rats than in wild‐type animals. Thus, the cognitive phenotype and, possibly, epilepsy in TSC patients may result not only from the focal hamartomatous lesions but also, from altered neuronal plasticity in the heterozygous tissue.

Adult medulloblastoma is a rare tumor with few retrospective studies published so far. The role of adjuvant chemotherapy or chemotherapy at relapse is unclear. This study reports therapy and outcome in all adult (>or=16 years old) medulloblastoma (n=34) and supratentorial primitive neuroectodermal tumor (PNET) patients (n=2) treated in 2 neuro-oncological centers between 1976 and 2002. The median age was 24.5 years (range 16-76). After resection, 16 patients were treated with craniospinal radiotherapy alone, 20 patients also received adjuvant chemotherapy (8 vincristine, CCNU, cisplatin; 7 methotrexate alone or methotrexate/vincristine-based polychemotherapy; 5 other protocols). Median survival in the whole cohort was 126 months (2+ - 200+months). Five-year and 10-year survival rates were 79 % and 56%. Adjuvant chemotherapy was associated with a non-significant trend to prolonged survival (relative risk (RR) 1.89; p=0.068). The median progression-free survival (PFS) after primary therapy was 83 months. At relapse, 10 of 12 evaluable patients achieved a complete response upon second-line therapy. The median survival times from first (n=17) and second relapse (n=9) were 21 months (0-67+ months; 5/17 without second relapse) and 20 months (1-29 months). Cox regression analysis revealed the infiltration of the floor of the 4(th) ventricle at diagnosis as the only therapy-independent prognostic factor (RR 0.48; p=0.03). In conclusion, adjuvant chemotherapy may prolong survival in adult medulloblastoma patients. Moreover, second-line therapy may be beneficial for these patients. As in pediatric medulloblastoma patients, primary infiltration of the floor of the 4(th) ventricle indicates a poor prognosis.

Glioblastoma is a highly angiogenic tumor with a dismal prognosis. Continuous oral low-dose chemotherapy with methotrexate (MTX) and cyclophosphamide (CPM) has modest activity in heavily pretreated patients with breast cancer. We explored the efficacy of 100 mg CPM daily and 5 mg MTX twice weekly in relapsed glioblastoma. Ten patients, 22–59 years old, with a Karnofsky score of 50% or higher who had failed at least two chemotherapies were accrued. No toxicity was observed. No patient showed a complete or partial response. Five of 10 patients progressed within 2 months of therapy. Another five patients progressed after 3–4.5 months. The median time to progression was 2.5 months. The median overall survival after start of MTX/CPM was 6.9 months (range 0.5–18.8 months). Since the progression-free survival rate at 6 months was 0%, the trial was prematurely closed.

Twenty-one patients with recurrent or progressive glioblastoma were enrolled in a prospective phase II trial to determine the safety and efficacy of a 1-week on/1-week off regimen of temozolomide administered at 150 mg/m2 on days 1 to 7 and days 15 to 21 of 28-day treatment cycles. Two patients achieved a partial response (10%), and 17 patients (81%) had stable disease. The median progression-free survival was 5 months. The progression-free survival at 6 months was 48%.

Infarction is a rare cause of spinal cord dysfunction. Whereas diffusion-weighted (DW) MRI has been established as a highly sensitive technique for assessing acute cerebral ischemia, its role in spinal cord infarction remains to be determined. The purpose of this study is to present the signal characteristics of acute spinal cord ischemia using DWMRI within the first two days and after one week. MRI including DW imaging (DWI) was performed in three patients with acute spinal cord dysfunction 8, 12 and 30 hours after the onset of symptoms and repeated after one week in two patients. Two initial scans included EPI DW sequences in transverse and sagittal orientation. The remaining examinations were performed with an optimised high-spatial resolution DWI sequence in the transverse plane. The diagnosis of spinal cord ischemia was established by imaging, clinical history and CSF analysis. T2 signal abnormality and restricted diffusion was demonstrated in all initial examinations. Transverse DW sequences had the highest sensitivity. The spinal infarctions were mainly located in the centre of the spinal cord and the grey matter. Contrast enhancement was absent. After one week, the restricted diffusion had normalised (pseudo normalisation) whereas the T2 signal changes had become more prominent. Restricted diffusion in the course of spinal cord ischemic infarction can be demonstrated using DW-MRI. Whereas a diffusion abnormality can be found after few hours, it does not last for longer than one week. At this time, the establishment of the diagnosis has to rely mainly on T2-weighted images with additional post contrast T1-weighted images being useful.

Successful motor skill learning requires repetitive training interrupted by rest periods. In humans, improvement occurs within and between training sessions reflecting fast and slow components of motor learning [Karni A, Meyer G, Rey-Hipolito C, Jezzard P, Adams MM, Turner R, et al. The acquisition of skilled motor performance: fast and slow experience-driven changes in primary motor cortex. Proc Natl Acad Sci USA 1998;95:861–8]. Here, these components are characterized in male and female rats using a model of skilled forelimb reaching and are compared to time scales of instrumental learning. Twenty female and 14 male adult Long–Evans rats were pre-trained to operate a motorized door (via a sensor in the opposite cage wall) to access a food pellet by tongue. Latencies between pellet removal and door opening were recorded as measures of instrumental learning. After criterion performance was achieved, skilled forelimb reaching was requested by increasing the pellet–window distance to 1.5 cm. Reaching success was recorded per trial. Mean latencies decreased exponentially over sessions and no improvement within-session was found. Skill learning over eight training sessions followed an exponential course in females and a sigmoid course in males. Females acquired the skill significantly faster than males starting at higher baseline levels (P < 0.001) but reaching similar plateaus. Within-session improvement was found during the sessions 1–3 in females and 1–4 in males. Performance at the end of session 1 was not carried over to session 2. Learning curves of individual animals were highly variable. These findings confirm in rat that motor skill learning has fast and slow components. No within-session improvement is seen in instrumental learning.

The authors report a German family with autosomal dominant cerebellar ataxia tightly linked to the spinocerebellar ataxia type 5 (SCA5) locus (multipoint lod score 5.76). The phenotype is characterized by a purely cerebellar syndrome with a downbeat nystagmus occurring prior to the development of other features. Imaging studies demonstrated cortical cerebellar atrophy. Progression is slow even in patients with a disease onset during the second decade. The age at onset varies from 15 to 50 years.

This study examined the diagnostic and prognostic value of vascular endothelial growth factor (VEGF) levels in the cerebrospinal fluid (CSF) of 39 patients with leptomeningeal metastasis (LM). Vascular endothelial growth factor levels at diagnosis were significantly higher in patients with LM (median 359 pg ml −1 ) than in patients with other neurological diseases (median <25 pg ml −1 ). The specificity of VEGF levels above 250 pg ml −1 for LM was high (98.3%), while the sensitivity was low (51.4%; 73% for VEGF values above 100 pg ml −1 ). In 49% of the LM patients, particularly with lymphoma or medulloblastoma, VEGF levels were below 250 pg ml −1 and thus in the range of VEGF levels in other neurological diseases. Vascular endothelial growth factor levels correlated significantly with CSF lactate and albumin. Vascular endothelial growth factor levels mirrored the clinical course with a marked reduction in response to therapy and an increase at relapse in some patients who had serial CSF samples available. Multivariate Cox regression analysis showed VEGF below 100 pg ml −1 (relative risk (RR)=4.24, P =0.0002) and age below 60 years (RR=2.5, P =0.004) to be associated with longer survival in LM. In conclusion, CSF VEGF levels in LM vary considerably. High VEGF levels have a very high specifity for LM and may help to establish the diagnosis. The role of VEGF as a predictor of outcome should be substantiated in prospective studies.