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Biomedical subjects

K Wessel

Publications and source records attributed to K Wessel.

At least 19 recordsLinked to original sources
PubMed2000

Association between clinical disease activity and Epstein-Barr virus reactivation in MS.

OBJECTIVE: To assess the potential significance of Epstein-Barr virus (EBV) reactivation in disease activity in MS patients. METHODS: The prevalence of antibodies against herpes simplex virus type 1 (HSV-1), HSV-2, EBV, and cytomegalovirus was determined in a group of 108 MS patients and in 163 healthy control subjects. Sera were analyzed using combinations of novel assay systems employing highly purified viral and recombinant antigens. In addition, PCR for the detection of EBV DNA was performed in serial samples. RESULTS: In contrast to the control populations, antibodies against EBV were present in 100% of MS patients. Among the tested human herpesviruses, this high extent of seropositivity was only found for EBV. Primary infection was found exclusively in the control group (3.7%), whereas serologic evidence of EBV reactivation was seen in MS patients (13. 9%) as well as control subjects (17.2%). There was no temporal coincidence between EBV reactivation and disease activity in MS patients. However, in 19 patients followed monthly for 1 year, active viral replication as measured by increased immunoglobulin (Ig) M and IgA responses to EBV early antigens (p54 + p138) and positive serum DNA was seen in 72.7% of patients with exacerbations during the study period and in none of the patients with clinically stable disease. CONCLUSIONS: The results demonstrate an association between EBV reactivation and disease activity in MS patients over time, and suggest that EBV might play an indirect role in MS as an activator of the underlying disease process.

Adult↗
PubMed2000

CNV and temporal uncertainty with 'ageing' and 'non-ageing' S1-S2 intervals.

OBJECTIVES: Uncertainty about the timing of a known external event is an everyday phenomenon but has been rarely investigated with electrophysiological methods. We studied how the amplitude of the contingent negative variation (CNV) is affected by temporal variation of S2 presentation. Competing hypotheses about the development of CNV during the foreperiod until S2 presentation were that CNV either would follow a monotonic trend, be it increasing or decreasing, or alternatively that the time-course of CNV would be affected by the probability with which S2 was presented at each time-point in a given task. METHODS: The interval between cueing stimulus and imperative stimulus was randomly chosen from 3 different values between 1.3 and 2.6 s, using 3 different probability distributions in separate blocks: an 'ageing', a 'non-ageing' and a 'Gaussian' distribution. RESULTS: As previously shown, reaction times were determined by the probability of the imperative stimulus at the given length of the foreperiod. The same was found for CNV amplitude: the effects of temporal uncertainty on CNV mainly depended on the particular distribution of temporal probabilities used in a block. The relevant parameter was the a posteriori probability of event occurrence, very similar to the effects of this parameter on response times. In fact, the major part of the effect of a posteriori probability on CNV was common variation of CNV and response times. CONCLUSIONS: Thus, under temporal uncertainty the amplitude of CNV reflects the subjective expectancies for the occurrence of a given event, with this variation being related to variations in response times.

Adult↗
PubMed1999

Consequences of altered cerebellar input for the cortical regulation of motor coordination, as reflected in EEG potentials.

The cerebellum is certainly involved in fine coordination of movements, but has no efferences of its own to the muscles. Thus, it can exert its influence only via other cerebral areas that have those efferences. This study investigated in patients with cerebellar atrophy how cortical motor areas are affected by dysfunction of the cerebellum. The main question was whether the patients' slow cortical electroencephalogram (EEG) potentials during key-press preparation and execution would be generally altered or would be specifically altered when fine coordination was needed. In the coordination task, right- and left-hand keys had to be pressed simultaneously with different forces, under visual feedback. Control tasks were to press with both hands equally or with one hand only. The patients indeed had a performance deficit in the coordination task. Their cortical EEG potentials were already drastically reduced in the simple tasks, but were enhanced by the same amount as in healthy subjects when more coordination was needed. These results suggest that the cerebellum is not exclusively active in fine coordination, but is generally involved in any kind of preparatory and executive activity, whereas the motor cortex becomes more active with fine coordination. The role of the cerebellum might be to provide the motor cortex with information needed for coordinating movements. In cerebellar atrophy, this altered input may be sufficient for the motor cortex in controlling simple tasks, but not for complex ones.

Adult↗
PubMed1999

Clinical and molecular findings in multiple sclerosis patients with type 1 diabetes mellitus.

The clinical and molecular findings in three patients with multiple sclerosis (MS) and additional type 1 diabetes mellitus are described. These patients all presented with a severe and progressive disease course of MS. Molecular testing for HLA class II genes demonstrated the presence of the haplotype DRB1*0401, DQB1*0302 in all patients. This haplotype is closely linked to type 1 diabetes mellitus and is increased among patients with the primary progressive subtype of MS. We conclude that the immunogenetic background in patients with diabetes mellitus may determine the severity and clinical course of MS in these individuals. Copyright 1999 Harcourt Publishers Ltd.

Journal Article↗
PubMed1998

Risk factors for idiopathic cerebellar ataxia of late onset.

In an attempt to identify risk factors for the development of idiopathic cerebellar ataxia (IDCA) we performed a case-control study of 59 IDCA patients. Hypertension and medicine intake were less frequent in IDCA than in neurological controls. Multiple logistic regression yielded an odds ratio (OR) for hypertension of 0.13 (95% confidence interval: 0.00-1.02, P=0.0527) and medicine intake of 0.10 (95% confidence interval: 0.00-0.72, P=0.0157). In contrast, we did not identify an association of IDCA with a number of medical diseases, head trauma, smoking, alcohol intake, rural living and well-water drinking. Some of these factors have been previously shown to be associated with other neurodegenerative diseases. In addition, serum antibody titers against neurotropic viruses were not elevated in IDCA.

Age Factors↗
PubMed1998

Lack of evidence for Marek's disease virus genomic sequences in leukocyte DNA from multiple sclerosis patients in Germany.

Herpes viruses have repeatedly been associated with the etiology of multiple sclerosis (MS). In the course of investigations on a cluster of MS patients in Key West, Florida, it was suggested that Marek's disease virus (MDV), a cell-associated avian herpes virus, might be involved in the pathogenesis of the disease. The aim of our study was to investigate 107 well-defined MS patients with regard to latent MDV infection. Using a highly-sensitive polymerase chain reaction technique, we did not find MDV-related sequences in leukocyte DNA of any of the patients. The results of our study do not suggest an implication of MDV in the pathogenesis of MS.

DNA, Viral↗
PubMed1998

Oculomotor testing in the differential diagnosis of degenerative ataxic disorders.

BACKGROUND: Oculomotor abnormalities have been reported in patients with degenerative ataxic disorders. OBJECTIVE: To assess the diagnostic sensitivity and specificity of oculomotor deficits in patients with Friedreich ataxia (FA), cerebellar atrophy (CA), and olivopontocerebellar atrophy (OPCA). SETTING: Neurology clinic at a university hospital in Lübeck, Germany. PATIENTS: Seven patients with FA, 9 with CA, and 10 with OPCA were studied. These patients were selected from an ongoing follow-up study. MAIN OUTCOME MEASURES: Eye movements were recorded by electro-oculography; an extensive battery of quantitative tests was used. RESULTS: A proven CAG repeat expansion on chromosome 6 or 14 was significantly associated with reduced saccadic eye velocity and vertical gaze palsy (P<.001, Mann-Whitney U test). All 6 patients with OPCA and slow saccades had an autosomal-dominant inheritance; 4 of them were proved to have spinocerebellar atrophy type 1. In 9 of these patients (4 with FA, 1 with CA, and 4 with OPCA), the genetic defect could not be identified. Saccadic dysmetria, impairment of smooth pursuit and optokinetic nystagmus, deficient suppression of the vestibulo-ocular reflex by either visual or otolith input, and pathological nystagmus were attributed to degenerative lesions in different parts of the cerebellum. However, these symptoms failed to clearly distinguish between the different groups of patients, whereas decreased vestibulo-ocular reflex gain, slow saccades, and vertical gaze palsy pointed to an extracerebellar manifestation of the degenerative disease, occurring only in patients with OPCA and FA. CONCLUSIONS: In this prospective study, oculomotor disturbances were mainly related to cerebellar dysfunction. Only a few of them were caused by extracerebellar manifestations of the disease, such as slowing of saccades, which was characteristic for patients with OPCA of autosomal-dominant inheritance.

Adult↗
PubMed1998

Preoperative functional magnetic resonance imaging (fMRI) of the motor system in patients with tumours in the parietal lobe.

Intracranial lesions may compromise structures critical for motor performance, and mapping of the cortex, especially of the motor hand area, is important to reduce postoperative morbidity. We investigated nine patients with parietal lobe tumours and used functional MRI sensitized to changes in blood oxygenation to define the different motor areas, especially the primary sensorimotor cortex, in relation to the localization of the tumour. Activation was determined by pixel-by-pixel correlation of the signal intensity time course with a reference waveform equivalent to the stimulus protocol. All subjects showed significant activation of the primary sensorimotor cortex while performing a finger opposition task with the affected and unaffected side. In five patients the finger opposition task additionally activated the ipsilateral sensorimotor cortex and the supplementary motor area (SMA). Extension and flexion of the foot, additionally performed in two patients, also activated the sensorimotor cortex, in one case within the perifocal oedema of the tumour. Tumour localization near the central sulcus induced displacement of the sensorimotor cortex as compared to the unaffected side in all patients with a relevant mass effect. The results of our study demonstrate that functional MRI at 1.5 T with a clinically used tomograph can reproducibly localize critical brain regions in patients with intracranial lesions.

Adult↗
PubMed1998

Reduced intracortical facilitation in patients with cerebellar degeneration.

OBJECTIVES: Transcranial magnetic stimulation (TMS) was used to study intracortical inhibitory and excitatory phenomena in patients with cerebellar ataxia. METHODS: Motor evoked potentials (MEP) following single and paired TMS were recorded from the first dorsal interosseus muscle (FDI) in 15 patients with autosomal-dominant or idiopathic cerebellar ataxia and 15 age matched normal controls. RESULTS: MEP amplitudes after paired TMS with short interstimulus intervals (1-4 ms) showing intracortical inhibition in the control group were not significantly different in the patient group. In contrast, with longer interstimulus intervals (8-20 ms) mean MEP amplitudes were significantly reduced in the patient group, indicating a decrease of intracortical facilitation. The mean postexcitatory inhibition after TMS was also significantly prolonged in the patient group. CONCLUSION: Our findings support the idea that the cerebellum physiologically exerts a facilitatory influence on the motor cortex which is decreased in patients with a cerebellar degeneration.

Action Potentials↗
PubMed1998

Effect of high-dose methylprednisolone administration on immune functions in multiple sclerosis patients.

OBJECTIVES: To investigate the in vivo effect of corticosteroid pulse therapy on immunocompetent cells in 18 patients given methylprednisolone to treat an acute episode of MS. MATERIAL AND METHODS: Blood was sampled before and after 3 days of methylprednisolone administration at doses of 1 g/day. Lymphocyte subtyping was performed and whole blood cell cultures were used to measure the cytokine producing capacity for interleukin-1 (IL-1), interleukin-2 (IL-2), interferon-gamma (IFN-gamma), tumor necrosis factor-alpha (TNF-alpha) and interferon-alpha (IFN-alpha). In addition, serum levels of the immunoglobulin classes IgG, IgA and IgM were determined. RESULTS: Before treatment, production of IL-1 was significantly increased in MS patients as compared to healthy controls. After therapy, production of all cytokines was significantly decreased, whereas there were significant increases in the numbers of monocytes, neutrophils and T and B lymphocytes. Treatment had no effect on serum immunoglobulin levels. CONCLUSION: An important mechanism for the antiinflammatory effect of corticosteroids in MS results from a suppression of the activation of the peripheral immune compartment through inhibition of cytokine production and lymphocyte endothelial adhesiveness.

Adult↗
PubMed1998

Activation of the cerebellum by sensory finger stimulation and by finger opposition movements. A functional magnetic resonance imaging study.

Activation of the ipsilateral anterior lobe of the cerebellum by means of hand movements by humans is a well-known phenomenon, but the cerebellar encoding of sensory information has not been well established. The authors delineated the representation of sensory stimulation of fingers in the anterior lobe of the cerebellum using functional magnetic resonance imaging sensitized to changes in blood oxygenation and compared these areas to the regions activated by means of finger opposition movements. Activation was determined by means of pixel-by-pixel correlation of the signal intensity time course with a reference waveform equivalent to the stimulus protocol. All subjects showed significant activation of the anterior lobe of the cerebellum, mainly located in the ipsilateral Larsell lobules IV-V and less consistent in the vermis in relation to sensory finger stimulation. Among some subjects the authors also found activation in the anterior lobe on the contralateral side. The finger movements activated regions that overlapped with the areas activated by sensory finger stimulation but showing a larger and more intense activation pattern.

Adult↗
PubMed1997

International Cooperative Ataxia Rating Scale for pharmacological assessment of the cerebellar syndrome. The Ataxia Neuropharmacology Committee of the World Federation of Neurology.

Despite the involvement of cerebellar ataxia in a large variety of conditions and its frequent association with other neurological symptoms, the quantification of the specific core of the cerebellar syndrome is possible and useful in Neurology. Recent studies have shown that cerebellar ataxia might be sensitive to various types of pharmacological agents, but the scales used for assessment were all different. With the long-term goal of double-blind controlled trials-multicentric and international-an ad hoc Committee of the World Federation of Neurology has worked to propose a one-hundred-point semi-quantitative International Cooperative Ataxia Rating Scale (ICARS). The scale proposed involves a compartimentalized quantification of postural and stance disorders, limb ataxia, dysarthria and oculomotor disorders, in order that a subscore concerning these symptoms may be separately studied. The weight of each symptomatologic compartment has been carefully designed. The members of the Committee agreed upon precise definitions of the tests, to minimize interobserver variations. The validation of this scale is in progress.

Cerebellar Ataxia↗
PubMed1997

Double-blind crossover study with physostigmine in patients with degenerative cerebellar diseases.

OBJECTIVE: To determine whether treatment with physostigmine can improve the conditions of patients with ataxia. DESIGN: A double-blind crossover study with physostigmine was performed in 19 patients with degenerative cerebellar diseases. SETTING: Patients were selected from an ongoing prospective follow-up study at the university hospital in Lübeck, Germany. PATIENTS: Eleven patients with autosomal dominant cerebellar ataxia and 8 patients with idiopathic cerebellar ataxia. INTERVENTION: Physostigmine was administered by using a transdermal system (patch) containing 30 mg of physostigmine as a base, of which about 6 mg is released during 24 hours along a diffusion gradient. Each treatment phase with the physostigmine patch or the placebo lasted 4 weeks, after which the treatment of patients was crossed over to the other phase. MAIN OUTCOME MEASURES: Ataxia was documented and quantified by using a clinical score and posturographic measures. RESULTS: Physostigmine patches had no significant effect on cerebellar symptoms. CONCLUSION: Treatment with physostigmine does not improve the conditions of patients with ataxia.

Cerebellar Ataxia↗
PubMed1997

Slow saccades and other eye movement disorders in spinocerebellar atrophy type 1.

In order to study the relation between genotype and phenotype, a detailed study of the course of oculomotor deficits was performed in three patients with autosomal-dominant cerebellar ataxia, subtype spinocerebellar atrophy type 1 (SCA 1) using clinical testing and electrooculography. DNA analysis revealed a CAG repeat expansion of 65 in the SCA 1 gene on chromosome 6p in all patients. A progressive disorder of the saccadic system became obvious, leading to a marked slowing of saccadic eye movements and loss of pathological and physiological nystagmus. An upward gaze palsy developed early, followed by horizontal and downward gaze palsy at a later state of the disease. Smooth pursuit eye movements were disturbed to a lesser extent; the vestibulo-ocular reflex was reduced. As an additional feature, severe loss of visual acuity developed due to progressive optic nerve atrophy. The oculomotor deficits can be explained by progressive damage to the brain stem rather than to the cerebellum. Each combination of oculomotor deficits with or without optic atrophy may occur irrespective of the gene locus of the disease, making a correlation between clinical signs and genetic findings difficult.

Adult↗
PubMed1997

CAG repeat analyses in frozen and formalin-fixed tissues following primer extension preamplification for evaluation of mitotic instability of expanded SCA1 alleles.

Neurodegenerative disorders, including spin-ocerebellar ataxias (SCA), Huntington disease (HD) and dentatorubral-pallidoluysian atrophy (DRPLA), are associated with unstable CAG repeats. To investigate the mitotic stability of the repetitive element in the genes for SCA1, SCA3, HD, and DRPLA we extracted DNA from up to 13 tissue samples from four deceased individuals with progressive neurological disorders and neuropathological signs. Due to the formalin fixation of some tissues the genomic DNA was highly degraded and unsuitable for amplification of fragments longer than 150 bp. After size selection and primer extension preamplification, specific analyses could be performed even for expanded alleles. In all four patients the SCA1 mutation could be demonstrated, in one case with remarkable somatic heterogeneity of the elongated allele, whereas alleles of the normal range were stable in all tissues examined.

Adult↗