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Evidence from recent functional magnetic resonance imaging studies suggests that adaptive cortical changes (‘plasticity’) could participate in the maintenance of function in multiple sclerosis (MS). Here, we addressed the impact of brain atrophy on the pattern of cerebral activation in an MS patient with a relapsing-remitting course. This patient showed mildly disabling hemiparesis of the left side (EDSS 2.0), and corresponding brain hemiatrophy (15% volume reduction) of the right hemisphere. The clinical syndrome was considered to result from a lesion in the corona radiata involving corticospinal fibers. Motor-evoked potential recordings confirmed substantial axonal damage to the pyramidal tract arising from that hemisphere. Irrespective of these asymmetries, normal brain activation was found for hand and foot movements for both brain sides. This demonstrates that brain atrophy itself does not necessarily induce cortical adaptive changes, even if mild disability is present. On the other hand, significantly disabling distinct clinical syndromes e.g. arising from spinal cord lesions may evoke cortical changes irrespective of brain atrophy. This issue has to be studied in longitudinal investigations.

This article reviews possible clinical applications of positron emission tomography (PET) in brain tumor patients. PET allows quantitative assessment of brain tumor pathophysiology and biochemistry. It therefore provides different information about tumors when compared to histological or neuroradiological methods. Common clinical indications for PET comprise tumor delineation and identification of the metabolically most active tumor regions (target for biopsy, differentiation of viable tumor from necrosis). Further, the spatial relation between brain activated e.g., by speech, and the tumor bulk can be explored by activation studies. PET could also aid in the prediction of treatment response by measurement of tumor perfusion or hypoxia. Moreover, PET tracers could identify treatment targets e.g., gene products. The latter topic has not been systematically evaluated in human patients.

5-bromodeoxyuridine (BUdR) provides in vitro measures of tumor cell proliferation. We used positron emission tomography to study tissue and plasma kinetics of [76Br]BUdR in tumor-bearing animals. In order to account for the slow washout of the major plasma metabolite, [76Br]bromide, a mathematical correction for the distribution volume of [76Br]bromide was applied. However, following correction specific tumor tracer retention was low or even zero and did not correlate with independent measures of proliferation. The kinetic characteristics of [76Br]BUdR make this tracer unsuitable for proliferation imaging.

This article reviews possible clinical applications of positron emission tomography (PET) in patients with CNS lymphomas. PET allows quantitative assessment of brain tumor pathophysiology and biochemistry in vivo. Therefore, it provides different information about tumors when compared to histological or neuroradiological methods. In a diagnostic setting, PET cannot differentiate between primary lymphomas of the CNS, brain secondaries, or malignant gliomas, since various brain tumors share biochemical alterations. In HIV patients with contrast-enhancing brain tumors, however, data from the literature suggest that PET with the tracer F-18 fluoro-deoxyglucose may help to discriminate neoplastic (CNS lymphoma) from inflammatory (e.g. toxoplasmosis) lesions. Assuming that tumor biochemistry is highly abnormal in the most malignant parts of tumors, PET may also assist in defining targets for stereotactic biopsy. With regard to treatment evaluation, the prediction of individual treatment response is among the most challenging clinical applications of PET. On the one hand, this could be achieved on the basis of measures like tumor perfusion, oxygen consumption, or hypoxia. On the other hand, PET tracer methods may allow to quantify the expression of gene products following gene therapy. However, in CNS lymphoma patients these topics have yet not been addressed with PET.

Im folgenden wird die Wertigkeit von PET anhand von Fragen, wie sie immer wieder im neuroonkologischen Alltag auftreten, diskutiert.

Cerebral gliomas may cause a reduction of glucose metabolism in the cerebellum contralateral to the tumor side (crossed cerebellar diaschisis, CCD). We investigated whether CCD is related to tumor localization, histological grade, size and tumor biochemistry. Cerebellar glucose metabolism was measured in 44 glioma patients and 15 healthy subjects using positron emission tomography and [18F]fluorodeoxyglucose (FDG). CCD was determined by calculating an asymmetry index of cerebellar glucose metabolism. Further, the tumor uptake of FDG and [11C]methionine (MET) was also assessed, and was expressed as ratio of normalized tracer uptake in tumor over contralateral cortex (T/C). Frontal lobe tumors were associated with highest CCD values. For these tumors, CCD was higher in malignant (-11.8+/-9.9%) than in low-grade (-4.3+/-4.1%) gliomas (P=0.010). In addition, frontal lobe tumors showed increasing CCD values with increasing size. In tumors of the parietal or temporal lobe, CCD was less marked or absent. T/C ratios of tumor tracer uptake were higher in malignant than in low-grade gliomas, but were not correlated with CCD. Our data indicate that the magnitude of CCD is mainly determined by tumor localization and size, the latter being associated with tumor grade. These findings raise the question whether CCD provides a measure of expansion or progression particularly in low-grade tumors of the frontal lobe.

We studied a patient with juvenile pilocytic astrocytoma (JPA) using positron emission tomography (PET), 18F-fluorodeoxyglucose (FDG), 11C-methionine (MET), and 82Rubidium (RUB). Non-linear fitting and multiple time graphical plotting of the dynamic PET data revealed values for tumor plasma volume, blood-brain barrier transport rate constants and tracer distribution volume in the range of glioblastomas and meningiomas, or higher. Likewise, the steady-state accumulation of MET and FDG was increased. With regard to the known vascular composition of JPA, our data suggest that increased transport and distribution considerably contribute to the high net tracer uptake observed in this tumor.

The age distribution and incidence of loss of heterozygosity (LOH) of 1p and 19q was analyzed in 85 oligodendroglial tumors WHO II and III. The peak of tumor manifestation was in the age group of 35 to 55 years. There was no association between age at diagnosis and LOH incidence. We conclude that the prognostic effect of age on survival is not mediated by LOH 1p/19q.

From a series of 10 patients undergoing PET studies of brain metabolism with 18Fluo-ro-Desoxy-Glucose (FDG) between 18 days and 62 months after a major head injury 3 chronic cases examined 25, 33 and 62 months after the accident are presented to illustrate some neuroradiologic aspects. Cortical defects are easily recognised on PET as zones of decreased metabolism after brain laceration corresponding to the residual neurologic deficits. A crossed cerebellar diaschisis is present, reflecting the deafferentation of the cerebellum. In the patient studied 62 months after a left frontotemporal trauma with subdural hematoma and brain swelling, a good correlation between CT, MR, SPECT and PET was found. In the third patient with diffuse axonal injury and predominantly left frontal subdural hygroma 33 months before, the brain perfusion looked normal on SPECT and the cerebral metabolism was only mildly reduced in the right frontal and left parieto-occipital regions on PET. These findings reflect only partially the neuropsychologic sequelae, making the patient unable to work more than 30%. In case of diffuse white matter (and brain stem) injury, the cortical abnormalities shown by PET may not reflect enough the severity of the remaining disability. Finally two materials used for cranioplasty (Palacos® and BOP®) were tested in vitro before the two patients underwent PET examination. There was no significant attenuation of the radiation in vitro and no distinguishable anomalies over the corresponding hemisphere, like in a third patient without bone flap.

Genetic alterations of brain tumors were first detected in bilateral schwannomas (central neurofibromatosis Type II, NF 2) and sporadic vestibular schwannomas (acoustic neuromas). These hereditary tumors, which produce similar clinical syndromes due to the manifestation at the cerebellopontine angle, can be clearly distinguished by their different patterns of genetic changes [1-3]. At a later stage, the investigation of genetic alterations focussed upon neuroepithelial tumors. In particular, the controversial issue whether glioblastomas arise from either previously low grade astrocytomas, or de novo, or whether exist other developmental pathways, was assessed using different histological grades of astrocytic tumors as putative models for malignant tumor progression. In the following, investigations of brain tumor related genes, which provided several insights into modes of tumorigenesis and progression, are briefly reviewed. The importance of gene mapping is demonstrated by giving examples of advances that resulted from the knowledge of chromosome location of the genes involved.

We present a case report of Cogan's syndrome and a review of the literature. Cogan's syndrome is most likely due to autoimmune disease primarily affecting the vestibulocochlear organ and cornea and secondarily resulting in systemic disease. 40% of patients develop bilateral complete deafness and 70% show signs of systemic disease mostly in the form of cardiovascular symptoms. The mortality rate of 10% is mainly due to vasculitis. It is important to consider Cogan's syndrome in the differential diagnosis of sudden hearing loss accompanied by ocular signs in young patients, as high morbidity and mortality rates are effectively lowered by early immunosuppressive treatment.

To investigate the pathophysiology of fatigue in MS, we assessed cerebral glucose metabolism (CMR-Glu) in 47 MS patients using PET and 18F-fluorodeoxyglucose. Applying the Fatigue Seventy Scale (FSS), we first compared MS patients with severe fatigue (MS-FAT, n = 19, FSS > 4.9) and MS patients without fatigue (MS-NOF, n = 16, FSS < 3.7) on a pixel-by-pixel basis using Statistical Parametric Mapping (SPM95). Second, we compared FSS values of all 47 patients covering the whole range of this scale with CMRGlu using an analysis of covariance (SPM95). In addition, we determined global CMRGlu by region-of-interest analysis. Sixteen healthy subjects served as control subjects (CON). Global CMRGlu was significantly lower in both MS groups compared with CON (CON 43.3 ± 6.9 μmol/100 mL/min, MS-FAT 34.7 ± 4.4, MS-NOF 35.4 ± 4.5) but was not related to fatigue severity. Comparing the two MS groups, SPM95 analysis revealed predominant CMRGlu reductions bilaterally in a prefrontal area involving the lateral and medial prefrontal cortex and adjacent white matter, in the premotor cortex, putamen, and in the right supplementary motor area of MS-FAT. In addition, there were CMRGlu reductions in the white matter extending from the rostral putamen toward the lateral head of the caudate nucleus. FSS values were inversely related to CMRGlu in the right prefrontal cortex. CMRGlu in the cerebellar vermis and anterior cingulate was relatively higher in MS-FAT than in MS-NOF patients. CMRGlu of both regions showed positive correlations with FSS values. Our data suggest that fatigue in MS is associated with frontal cortex and basal ganglia dysfunction that could result from demyelination of the frontal white matter.

Objectives-To assess the effect of a transverse spinal cord lesion on cerebral energy metabolism in view of sensorimotor reorganisation. Methods-PET and F-18-fluorodeoxyglucose were used to study resting cerebral glucose metabolism in 11 patients with complete paraplegia or tetraplegia after spinal cord injury and 12 healthy subjects. Regions of interest analysis was performed to determine global glucose metabolism (CMRGlu). Statistical parametric mapping was applied to compare both groups on a pixel by pixel basis (significance level P = 0 . 001). Results-Global absolute CMRGlu was lower in spinal cord injury (33 . 6 (6 . 6) mu mol/100 ml/min (mean (SD)) than in controls (45 . 6 (6 . 2), Mann-Whitney P = 0 . 0026). Statistical parametric mapping analysis disclosed relatively increased glucose metabolism particularly in the supplementary motor area, anterior cingulate, and putamen. Relatively reduced glucose metabolism in patients with spinal cord injury was found in the mid-brain, cerebellar hemispheres, and temporal cortex. Conclusions-It is assumed that cerebral deafferentiation due to reduction or loss of sensorimotor function results in the low level of absolute global CMRGlu found in patients with spinal cord injury. Relatively increased glucose metabolism in brain regions involved in attention and initiation of movement may be related to secondary disinhibition of these regions.

This article aims at drawing attention to the peculiar association of intense exposure to sunlight and subacute development of sensory neuropathy which was seen in 7 psychiatric patients treated with the phenothiazine derivative, perazine. Three patients additionally developed bilateral VII nerve palsy. Symptoms followed a monophasic course with almost complete remission. Routine neurophysiology suggested axonal neuropathy confirmed by sural nerve biopsy in 1 patient. A toxic origin of neuropathy is supposed, possibly induced by phenothiazine photoproducts, which may cause cell damage via lipid peroxidation.

Polymyalgia rheumatica (PMR) and giant cell (temporal) arteritis (GCA) are overlapping disease entities that show a variety of nonspecific symptoms and may lead to neurologic complications.1 Here we describe a patient who developed aseptic meningoradiculitis during prednisone treatment for PMR/GCA. A 63-year-old man first presented with myalgia and fever. Masticatory claudication developed, and a tender temporal artery was found. The erythrocyte sedimentation rate was 70 mm/h. Temporal artery biopsy confirmed GCA. He initially responded well to prednisone (60 mg/d), which was slowly tapered. Six months later (prednisone 25 mg/d) headache, neck stiffness, and bilateral seventh nerve palsy occurred. The neurologic examination was otherwise unremarkable; visual acuity and a brain MR scan were normal. CSF showed 42 cells/μL (31 mononuclear); the glucose level was 4.1 mmol/L; and the total protein was 0.65 g/L (normal limit 0.45). Extensive diagnostic workup excluded infectious, rheumatic, or neoplastic disease and sarcoidosis. Increasing prednisone to 50 mg/d resolved headache nearly completely. Every attempt …

In 14 patients with brain tumors uptake of 11C methionine and 82Rb into the tumor tissue showed a significant correlation. This suggests that methionine uptake mainly reflects transport alteration from blood into tumor.

86Rubidium influx and Na — K-cotransport have been investigated in erythrocytes of mild essential hypertensives and normotensives devoid of familial hypertension.

A 65-year-old female presented with Bannwarth's syndrome. Symptoms initially responded to antibiotics but soon progressed despite further adequate antibiotic treatment. Consistently absent antibody titres to Borrelia burgdorferi, repeated CSF examinations combined with an extensive search for tumour, revealed leukaemic meningitis secondary to uterine centrocytic-centroblastic lymphoma. The diagnostic steps required to elucidate the aetiology of meningopolyradiculitis, especially when chronic and progressive, are described.