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We reported previously that Go-deficient mice develop severe neurological defects that include hyperalgesia, a generalized tremor, lack of coordination, and a turning syndrome somewhat reminiscent of unilateral lesions of the dopaminergic nigro-striatal pathway. By using frozen coronal sections of serially sectioned brains of normal and Go-deficient mice, we studied the ability of several G protein coupled receptors to promote binding of GTPgammaS to G proteins and the ability of GTP to promote a shift in the affinity of D2 dopamine receptor for its physiologic agonist dopamine. We found a generalized, but not abolished reduction in agonist-stimulated binding of GTPgammaS to frozen brain sections, with no significant left-right differences. Unexpectedly, the ability of GTP to regulate the binding affinity of dopamine to D2 receptors (as seen in in situ [(35)S]sulpiride displacement curves) that was robust in control mice, was absent in Go-deficient mice. The data suggest that most of the effects of the Gi/Go-coupled D2 receptors in the central nervous system are mediated by Go instead of Gi1, Gi2, or Gi3. In agreement with this, the effect of GTP on dopamine binding to D2 receptors in double Gi1 plus Gi2- and Gi1 plus Gi3-deficient mice was essentially unaffected.

1. The authors investigated the prevalence of qualitatively rated structural brain abnormalities in schizophrenic probands and their first-degree relatives from families multiply affected with schizophrenia. 2. Magnetic resonance imaging was used to evaluate brain morphology in 33 schizophrenic probands, 54 of their non-schizophrenic first-degree relatives (including 11 presumed obligate carriers) and 37 unrelated control subjects. Structural images were examined by a neuroradiologist who was blind to diagnostic and family status. 3. 52% of the schizophrenic subjects were rated as showing abnormalities compared with 27% of presumed obligate carriers, 16% of their non-schizophrenic relatives and 11% of unrelated controls. 4. Brain abnormalities were more frequent in schizophrenic subjects from multiplex families than in their first-degree relatives and controls. Abnormalities were also found in unaffected relatives particularly those who appear to be transmitting the disorder.

The presence of focal signal hyperintensities on MRI images of the brain was compared in 48 schizophrenic patients, 26 patients with bipolar disorder and 34 healthy controls. Significantly larger areas of brain were affected by focal signal hyperintensities, particularly in the frontal lobes, in the schizophrenic group compared to the bipolar group and the controls. Although the bipolar group had more such foci than controls, this difference did not reach statistical significance.

In this study we assessed the subclinical disease activity in 45 patients with primary progressive, secondary progressive or relapsing-remitting multiple sclerosis (MS). The patients had gadolinium-enhanced brain MRI scans, which were analysed using a semiquantitative method both for lesion load and for degree of enhancement. At the same time cerebrospinal fluid (CSF) and serum samples were collected and, from these, cytokine levels were measured in most cases by enzyme-linked immunoassay using commercially available kits. Enhancing lesions on MRI were found in 73% of the patients. The sensitivity of this test was greatly increased by our method of analysis as far as the primary progressive patients are concerned (70% vs 40% for conventional evaluation). CSF interleukin-1 beta (IL-1 beta) levels were above the normal range in 22% and IL-6 levels in 13% of patients, while tumour necrosis factor alpha (TNF-alpha) was undetectable or below the upper normal limits in all the samples tested. Serum IL-1 beta was above the normal limits in 40%, IL-6 in 42% and TNF-alpha in 7% of patients. No significant differences in cytokine profiles were found between the clinical subgroups. This study confirms the high sensitivity of gadolinium-enhanced MRI in detecting MS activity, which was further increased by our method of analysis. Longitudinal studies performed with more sensitive immunological techniques are needed to define better the relationship between cytokine, clinical and MRI data in MS patients.

The MRI scans of 48 schizophrenic patients, fulfilling RDC criteria, were compared to those of 34 healthy controls matched for age, ethnicity and parental social class. The volume of the frontal and anterior parietal lobes was significantly reduced in the schizophrenic group as a result of a selective decrease in cortical volume, with a corresponding increase in the volume of sulcal fluid. Reduction in the volume of the temporal grey matter was more marked on the right, but was not in excess of the loss of volume observed in other areas of the cortex. MRI abnormalities correlated poorly with clinical parameters, although both unemployment and poor pre-morbid adjustment predicted reduced cerebral volume and increased sulcal volume. These results question whether the medial temporal lobes are the only site of structural pathology in schizophrenia.

Ten patients with multiple sclerosis (MS) and psychosis were assessed using the Present State Examination, and matched retrospectively with respect to age, disability, duration of symptoms, and disease type with 10 MS patients without psychosis. Both groups underwent MRI of the brain. There was a trend for the psychotic group to have a higher total lesion score, particularly around the periventricular areas. This reached statistical significance in the areas around the temporal horn. In all cases, neurological symptoms preceded the onset of psychosis. The psychotic group also had a later age of onset of psychosis than psychotic patients without brain disease. These results point to an aetiological association between the pathological process of MS and psychosis.

The ability to visualise multiple sclerosis lesions in vivo with magnetic resonance imaging suggests an important role in monitoring the course of the disease. In order to help the long-term assessment of prospective treatments, a semi-automated technique for measuring lesion volume has been developed to provide a quantitative index of disease progression. Results are presented from a preliminary study with a single patient and compared to measurements taken from lesion outlines traced by a neuroradiologist, two neurologists and a technician. The semi-automated technique achieved a precision of 6% compared to a range of 12-33% for the manual tracing method. It also reduced the human interaction time from at least 60 min to 15 min.

In 31 patients with definite or suspected multiple sclerosis (MS) presenting with a cervical cord syndrome, somatosensory evoked potentials (SEPs) were recorded to median and posterior tibial nerve stimulation, using cephalic and noncephalic reference electrodes. Magnetic resonance imaging (MRI) of the brain and cervical spinal cord was performed, the latter in sagittal and axial views. SEPs were abnormal in 67.7% of patients, whereas MRI showed cervical cord lesions in 74.2% and intracranial lesions possibly involving the somatosensory pathways in 64.5% of cases. A significant correlation was found between abnormalities of cervical (N13) and cortical (N20) potentials following median nerve stimulation with Fz reference and MRI abnormalities involving the ipsilateral or posterior half of the cervical cord, but not the contralateral or anterior half. The N13 potential, recorded from the low cervical region to a supraglottal reference, was most frequently abnormal in patients with MRI lesions at C6 or C7, whereas P14, recorded from the scalp to a clavicle reference, was most often affected by lesions at Cl or the cervicomedullary junction. Abnormalities of the cortical P40 to tibial nerve stimulation were less significantly correlated with cervical MRI lesions. The latency of N20 measured from N9 at the clavicle and the absolute latency of P40 were significantly correlated with the length of MRI abnormalities in the ipsilateral cervical cord. No significant correlation was observed between SEP abnormalities and brain MRI lesions, which it was considered might possibly involve the intracranial somatosensory pathways. It was concluded that (1) the morphological lesions seen in MRI of the cervical cord usually give rise to appropriate electrophysiological deficits, but the occasional finding of a widespread MRI lesion with normal SEP suggests that myelin damage is not the only or the major factor responsible for abnormal MRI signal; and (2) 'clinically silent' lesions apparently involving the radiations and other sensory structures of the brain appear not to give rise to detectable SEP abnormalities, using the methods of the present study.

The cerebral blood flow, oxygen extraction and oxygen utilization has been measured regionally in 22 dements, and 14 aged normal volunteers. Ten demented patients were studied twice at a six-month interval from initial measurements. The use of a steady-state 15O technique and positron tomography for measuring regional cerebral blood flow, regional oxygen extraction fraction and mean cerebral oxygen utilization is discussed. The limitations of measurements are reviewed in the light of the present results and the current state of technological development in positron emission tomography is discussed. A decline in cerebral blood flow and mean cerebral oxygen utilization was correlated with increasing severity of dementia in both degenerative and vascular dements. The decline was coupled, both for the cerebral hemisphere as a whole and regionally. There was no increase in oxygen extraction ratio globally, and therefore no evidence to support the existence of a chronic ischaemic brain syndrome. Focal abnormalities in oxygen utilization were observed for both vascular and degenerative groups. In the vascular group, parietal defects were the most pronounced. Individual derangements of the regional pattern varied, reflecting the different unique patterns of ischaemic damage in these patients. In the degenerative group, parietal and temporal defects were seen in the less severe group, but a profound depression in the frontal regions with relative sparing of occipital area characterized the severe degenerative dements.

Tinofedrine, a new derivative of l-norephedrine, was examined for cerebral vasodilator activity in man. Ten patients with reduced cerebral blood flow (CBF) and multi-infarct dementia were given the drug intravenously. Cerebral blood flow increased significantly by 28% from a mean of 43.3 to 55.5 ml/100 g/min.

Computerized axial tomography using the EMI scanner as a new method of using x-rays in diagnosis. The technique displays intracranial and orbital structures in the transverse plane. The appearances of normal EMI Scans are described and correlated with cerebral and orbital anatomy seen in transverse section.

A computerized subtraction technique has been described to measure regional cerebral blood volume (rCBV) using the EMI-Scanner in a group of 13 patients. Sodium iothalamte was injected intravenously (1-75 ml./kg) to increase the absorption of X rays in the cerebral circulation. Significant regional differences in CBV were shown, values in the frontal and temporal regions being lower than the mean hemisphere value (4-9 +/- 0-7) and higher in the occipital region. The left hemisphere showed a significantly higher CBV when compared with the right. Measurements of CBV in the cortex showed no regional variation, but the mean cortical value of 6-0 +/- 1-8 was significantly higher than the hemisphere mean.

Regional cerebral blood volume (rCBV) was measured in 14 patients with normal CT scans. An EMI CT 1010 scanner was used in combination with a computer subtraction technique. The mean CBV in the cortex was 5.0 ml/100 ml of tissue and 2.2 in the white matter. Regional differences were not significant and no difference was found between the right and left hemispheres.

Twenty-four cases have been operated upon using a prototype Brown-Roberts-Wells, CT-guided stereotactic neurosurgical system. This device has proved to be practical and flexible in clinical use. No CT scanner modifications were required, a fact which simplified its use in more than one hospital. Multiple targets can be biopsied with ease and relative safety. Drainage and other therapeutic procedures can be carried out with minimal hazard. Future applications of this system may include its use with NMR and PET images. [ABSTRACT FROM AUTHOR]