Andreas Stevens

Inflammatory infiltrates and natural killer cell presence in human brain tumors.

Immunohistochemical analysis of subpopulations of inflammatory cells in 81 primary and secondary human brain tumors was done. Natural killer (NK) cells, representing non‐major histocompatibility complex‐restricted, spontaneous cytotoxicity and monocytic cells are virtually absent in infiltrates of gliomas and account only for a minor percentage of inflammatory cells in brain metastases of carcinoma and in craniopharyngeomas. Infiltrates in gliomas consist almost exclusively of T‐cells of the suppressor/cytotoxic type whereas infiltrates in carcinoma metastases and craniopharyngeomas contain considerable numbers of T‐helper/inducer cells and B‐cells. From this the authors conclude (1) that NK cells do not play a major role in tumor rejection, and (2) that the kind of inflammatory reaction does not depend upon the tumor site but more likely on the tumor type. No correlation between tumor differentiation and infiltrate composition is evident.

Comparative analysis of cytokine patterns in immunological, infectious, and oncological neurological disorders

Interleukins (IL) 1, 2, 4, 6 and soluble IL-2 receptor (sIL-2R), interferon-gamma (IFN-gamma), and tumor necrosis factor-alpha (TNF-alpha) were measured in CSF and serum from patients with relapsing-remitting and chronic multiple sclerosis, Guillain-Barré syndrome, chronic inflammatory demyelinating polyradiculoneuropathy, HIV infection, bacterial meningitis, viral encephalitis, meningeal carcinomatosis, hematologic meningeal malignancies, and disseminated melanoma. Our findings suggest that monitoring of disease activity in neuroimmunologic disorders by means of IL-1 beta, IL-2, sIL-2R, or IL-4 determination will not prove useful. IL-6, on the other hand, indicates relapse in multiple sclerosis and active disease in Guillain-Barré syndrome and meningeal carcinomatosis. High CSF TNF-alpha in metastatic melanoma and frequent detection in CSF of the multifunctional B-cell growth factor, IL-6 (27/30) and oligoclonal immunoglobulin bands (33%) in meningeal carcinomatosis confirm an intrathecal immune response in disseminated leptomeningeal neoplasia which might be amenable to therapeutic immunomodulation.

Borderline personality disorder: impaired visual perception and working memory

The neurobiology of borderline personality disorder (BPD) is still elusive. There are a few studies on neuropsychological performance in BPD, which report a broad spectrum of abnormalities. The present study evaluates perception and working memory as instances of basic cognitive functions. Female subjects diagnosed with DSM-IV borderline personality disorder (n=22) were compared with age- and education-matched controls (n=25). Perception speed was assessed by a backward masking paradigm. Working memory was tested by a series of delayed matching-to-sample paradigms involving varying subsidiary functions like mental rotation, retrieval from memory, ignoring distracters, and cross-modal performance. In backward masking, BPD subjects required significantly longer stimulus onset asynchrony (SOA) than controls to identify the visual target, and there was an additional slowing of the motor response. Working memory accuracy was impaired in BPD subjects, but did not worsen when the cognitive load was increased. With increasing task difficulty, they traded off speed for accuracy similarly as the controls. Impulsivity and dissociation ratings were not correlated with performance. It is concluded that perceptional speed and working memory are impaired in BPD, but that the deficits are not augmented by increasing cognitive load.

Implicit and explicit learning in schizophrenics treated with olanzapine and with classic neuroleptics.

Abstract.Objective: Novel and classic neuroleptics differ in their effects on limbic striatal/nucleus accumbens (NA) and prefrontal cortex (PFC) dopamine turnover, suggesting differential effects on implicit and explicit learning as well as on anhedonia. The present study investigates whether such differences can be demonstrated in a naturalistic sample of schizophrenic patients. Methods: Twenty-five inpatients diagnosed with DSM-IV schizophrenic psychosis and treated for at least 14 days with the novel neuroleptic olanzapine were compared with 25 schizophrenics taking classic neuroleptics and with 25 healthy controls, matched by age and education level. PFC/NA-dependent implicit learning was assessed by a serial reaction time task (SRTT) and compared with cerebellum-mediated classical eye-blink conditioning and explicit visuospatial memory. Anhedonia was measured with the Snaith-Hamilton-Pleasure Scale (SHAPS). Results: Implicit (SRTT) and psychomotor speed, but not explicit (visuospatial) learning were superior in the olanzapine-treated group as compared to the patients on classic neuroleptics. Compared to healthy controls, olanzapine-treated schizophrenics showed similar implicit learning, but reduced explicit (visuospatial) memory performance. Acquisition of eyeblink conditioning was not different between the three groups. There was no difference with regard to anhedonia and SANS scores between the patients. Conclusion: Olanzapine seems to interfere less with unattended learning and motor speed than classical neuroleptics. In daily life, this may translate into better adaptation to a rapidly changing environment. The effects seem specific, as in explicit learning and eyeblink conditioning no difference to classic NL was found.

Dynamic regulation of EEG power and coherence is lost early and globally in probable DAT

Abstract Electroencephalographic (EEG) findings in dementia of Alzheimer type (DAT) include slowing of alpha frequency, loss of alpha band power, increased theta and delta power and reduced coherence. Here it is evaluated whether a) EEG acquisition during different functional states facilitates the detection of DAT-associated EEG changes, and b) EEG changes in mild DAT are topographically confined or global. Power spectra and coherence of EEGs from 29 patients with mild probable DAT and 28 age- and sex-matched controls were compared during three cognitive states. Group differences in power spectra and coherence were largest during resting with eyes open, yielding a 77 % correct classification result. Already in early stages of probable DAT, EEG changes were topographically wide-spread. The task-related up- and down-regulation of power and coherence was impaired already in mild probable DAT. We propose to augment clinical EEG assessment by including a quantitative analysis of the dynamic power and coherence changes from rest, eyes closed to eyes open in suspected DAT.

Both pain and EEG response to cold pressor stimulation occurs faster in fibromyalgia patients than in control subjects.

Pain-evoked brain potentials elicited by laser stimulation have been repeatedly shown to be abnormal in fibromyalgia syndrome. However, to our knowledge this is the first study assessing enduring (cold pressor) pain and correlated EEG changes in fibromyalgia. EEG power and subjective pain ratings during the cold pressor test were analyzed and contrasted with tasks not involving sensory stimulation (rest, mental arithmetic and pain imagery) in 20 patients with fibromyalgia and 21 healthy control subjects. Fibromyalgia patients both perceived pain and judged pain as intolerable earlier than control subjects, while pain intensity ratings and EEG power changes during subjective awareness of pain were similar in both groups. In patients and control subjects, pain was correlated with a rise in delta, theta and beta power. EEG power spectra during pain imagery and mental arithmetic were significantly different from those observed during the cold pressor test. In conclusion, fibromyalgia patients seem to process painful stimuli abnormally in a quantitative sense, thus producing both the sensation of pain, as well as the associated EEG patterns, much earlier than control subjects. However, the quality of the pain-associated EEG changes seems similar.

CSF and serum ganglioside antibody patterns in MS

The authors determined CSF and serum IgG and IgM antibodies to seven gangliosides in 48 patients with multiple sclerosis. Differing ganglioside antibody patterns in CSF but not serum allowed to reclassify 93% of MS patients correctly when compared to patients with Guillain‐Barré syndrome or neuroborreliosis. This suggest that the antibody patterns are neither random nor alike in inflammatory diseases of the nervous system. CSF ganglioside antibody titres were found to be different for patients with relapsing remitting (RRMS; n = 35) and chronic progressive (CPMS; n = 13) multiple sclerosis. Our study reveals characteristic ganglioside antibody patterns in MS and confirms previous evidence of disturbed immunoregulation in MS.

A statistical model for length of psychiatric in-patient treatment and an analysis of contributing factors.

Objective: Direct illness costs in psychiatry are strongly related to the length of in‐patient stay (LOS). Prior studies have shown that LOS depends upon many factors; however, there is no systematic work on their interrelation and relative contribution.

Localized in vivo 1H spectroscopy of human skeletal muscle: Normal and pathologic findings

To obtain high signal to noise ratio in small volume elements (8 cm3), in vivo 1H NMR spectroscopy of normal and diseased human skeletal muscle was performed using a double spin-echo localization method on a 1.5-T whole body system. High resolved spectra of normal calf muscle show the well known resonances of lipids (methyl, methylene, olefinic, and other fatty acid resonances), creatine/phosphocreatine, choline/carnitine, taurine, and histidine with good intraindividual reproducibility. Pronounced intraindividual differences in the lipid range were found between different upper thigh muscle groups. On pathologic conditions like myopathy, myositis or irradiation damage the spectral lipid content was increased. Three months after local irradiation of the medial vastus muscle (50 Gy), the localized 1H NMR spectrum showed a complete loss of the choline and creatine signals. In a case of M. Behçet with muscular involvement the relative reduction of the choline signal may provide an insight in the pathobiochemistry. The results of our investigations in nine healthy volunteers and three patients are presented in detail including relaxation times of the metabolites.

COGNITIVE DECLINE UNLIKE NORMAL AGING IS ASSOCIATED WITH ALTERATIONS OF EEG TEMPORO-SPATIAL CHARACTERISTICS

Abstract The diagnosis of beginning dementia is based mainly on neuropsychological testing. Several measures of EEG spectral composition, coherence and complexity (correlation dimension) have been shown to correspond to cognitive function. Only a few studies have evaluated EEG changes in normal aging, and no quantitative study has addressed changes in EEG during cognitive tasks in demented elderly. In this study the quantitative descriptors of EEGs from 31 demented or cognitively impaired elderly persons, 30 healthy elderly (mean age 69 years) and 35 young controls (mean age 31 years) were compared. The EEGs were recorded during two resting conditions (eyes closed and eyes opened) and two tasks (mental arithmetics and a lexical decision). The goal of the study was to evaluate which temporal and spatial EEG descriptors change with cognitive decline and with normal aging, respectively. Cognitive categories (unimpaired, impaired, demented) were based on Structured Interview for the Diagnosis of Dementia of Alzheimer Type (SIDAM) scores. The EEGs were analysed using adaptive segmentation of continuous EEG, which quantifies the succession of distinct stable topographic voltage patterns (EEG microstates). The main findings were a significant increase in the number of ultra-short EEG microstates and, independently, a reduction in the average duration of EEG microstates in the cognitively impaired and demented patients. In addition, cognitive impairment was associated with a reduction or loss of EEG reactivity normally observed when the resting states with closed and with opened eyes are compared. No alterations in temporal or spatial EEG descriptors were found in normal aging. Cognitive tasks did not add to information already obtained during the resting states. The reduction in EEG microstate duration correlated with loss of cognitive function. Temporo-spatial analysis of EEG therefore is a useful indicator of cortical dysfunction in dementia, correlating with the degree of cognitive impairment. Normal aging seems not to be accompanied by changes in temporo-spatial EEG patterns. The data suggest that fragmentation of the electrophysiological processes underlies cognitive dysfunction in Alzheimer’s disease.