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Biomedical subjects

K Wessel

Publications and source records attributed to K Wessel.

At least 37 records · Page 2Linked to original sources
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↗
PubMed1997

SCA2 trinucleotide expansion in German SCA patients.

Autosomal dominant spinocerebellar ataxias (SCA) are a group of clinically and genetically heterogeneous neurodegenerative disorders which lead to progressive cerebellar ataxia. A gene responsible for SCA type 2 has been mapped to human chromosome 12 and the disease causing mutation has been identified as an unstable and expanded (CAG)n trinucleotide repeat. We investigated the (CAG)n repeat length of the SCA2 gene in 842 patients with sporadic ataxia and in 96 German families with dominantly inherited SCA which do not harbor the SCA1 or MJD1/SCA3 mutation, respectively. The SCA2 (CAG)n expansion was identified in 71 patients from 54 families. The (CAG)n stretch of the affected allele varied between 36 and 64 trinucleotide units. Significant repeat expansions occurred most commonly during paternal transmission. Analysis of the (CAG)n repeat lengths with the age of onset in 41 patients revealed an inverse correlation. Two hundred and forty-one apparently healthy octogenerians carried alleles between 16 and 31 repeats. One 50-year old, healthy individual had 34 repeats; she had transmitted an expanded allele to her child. The small difference between 'normal' and disease alleles makes it necessary to define the extreme values of their ranges. With one exception, the trinucleotide expansion was not observed in 842 ataxia patients without a family history of the disease. The SCA2 mutation causes the disease in nearly 14% of autosomal dominant SCA in Germany.

Adolescent↗
PubMed1997

Diminished production of type-I interferons and interleukin-2 in patients with multiple sclerosis.

Several lines of evidence have supported the role of immunological mechanisms in the pathogenesis of multiple sclerosis (MS) and new immunomodulatory strategies for its treatment, e.g. subcutaneous application of interferon (IFN)-beta, have emerged. We investigated the ability of peripheral blood mononuclear cells (PBMC) in 21 consecutive patients with clinically definite MS to produce interferons and lymphokines in response to viral or mitogenic stimulation. Ten patients showed clinical signs of disease activity (acute relapse) and 11 patients were in a stable condition. Additionally, white blood count, leukocyte differentiation and lymphocyte subtyping were performed. A group of age-related healthy blood donors served as control (n=20). There was no difference between patients and controls in the production of IFN-gamma, tumor necrosis factor (TNF)-alpha and soluble interleukin (IL)-2 receptor. IFN-alpha and IFN-beta responsiveness, however, was significantly lower in patients with stable disease than in patients with active disease and controls (p<0.001). Furthermore, secretion of IL-2 after stimulation was significantly diminished in both patient groups as compared to the control group (p<0.01). Analysis of T-cell subsets revealed a significantly lower amount of CD8+ T-cells in patients with stable disease, leading to a significantly higher CD4/CD8 ratio in this group as compared to patients with active disease. Our study depicted an IL-2 deficiency in MS patients which is shared with other autoimmune diseases. In addition, our findings suggest that the ability to produce type-I IFNs, IFN-alpha and IFN-beta, is primarily impaired in MS patients and changes in correlation to the course of disease activity.

Adult↗
PubMed1997

Lipoic acid reduces glycemia and increases muscle GLUT4 content in streptozotocin-diabetic rats.

Alpha lipoic acid (lipoate [LA]), a cofactor of alpha-ketodehydrogenase, exhibits unique antioxidant properties. Recent studies suggest a direct effect of LA on glucose metabolism in both human and experimental diabetes. This study examines the possibility that LA positively affects glucose homeostasis in streptozotocin (STZ)-induced diabetic rats by altering skeletal muscle glucose utilization. Blood glucose concentration in STZ-diabetic rats following 10 days of intraperitoneal (i.p.) injection of LA 30 mg/kg was reduced compared with that in vehicle-treated diabetic rats (495 +/- 131 v 641 +/- 125 mg/dL in fed state, P = .003, and 189 +/- 48 v 341 +/- 36 mg/dL after 12-hour fast, P = .001). No effect of LA on plasma insulin was observed. Gastrocnemius muscle crude membrane GLUT4 protein was elevated both in control and in diabetic rats treated with LA by 1.5- and 2.8-fold, respectively, without significant changes in GLUT4 mRNA levels. Gastrocnemius lactic acid was increased in diabetic rats (19.9 +/- 5.5 v 10.4 +/- 2.8 mumol/g muscle, P < .05 v nondiabetic rats), and was normal in LA-treated diabetic rats (9.1 +/- 5.0 mumol/g muscle). Insulin-stimulated 2-deoxyglucose (2 DG) uptake into isolated soleus muscle was reduced in diabetic rats compared with the control group (474 +/- 15 v 568 +/- 52 pmol/mg muscle 30 min, respectively, P = .05). LA treatment prevented this reduction, resulting in insulin-stimulated glucose uptake comparable to that of nondiabetic animals. These results suggest that daily LA treatment may reduce blood glucose concentrations in STZ-diabetic rats by enhancing muscle GLUT4 protein content and by increasing muscle glucose utilization.

Animals↗
PubMed1997

Cerebellar somatotopic representation and cerebro-cerebellar interconnections in ataxic patients.

Different methods of functional neuroimaging were used for studying somatotopic encoding of function in the cerebellum and for investigating cerebro-cerebellar interconnections in patients with cerebellar degeneration. fMRI showed, that the center of activation for hand function was located in the intermediate hemispheric portion of Larsell lobules H IV-V. Foot movements activated areas medial and anterior to the corresponding hand areas within Larsell lobules II-III. Changed function in motor cortices could be demonstrated in patients with cerebellar degeneration as compared to normal controls by recording movement-related cortical potentials (BP). In patients the motor potential was almost lacking and transcranial magnetic stimulation demonstrated enhancement of inhibitory mechanisms (prolonged postexcitatory inhibition) in the motor cortex. PET-findings suggested, that both effects are correlated to increased activity of inhibitory interneurons. Cerebellar patients showed increased activation in relation to movements in the SMA and basal ganglia and reduced activation in the cerebellum and lateral premotor areas. It could be speculated, that compensatory mechanisms are the reason for a stronger activation of the medial premotor system, including SMA, in patients with cerebellar degeneration. On the basis of our results it appears, that the cerebellum facilitates the lateral premotor system areas much more than it does the medial areas.

Adult↗
PubMed1997

Neuroprotection by the metabolic antioxidant alpha-lipoic acid.

Reactive oxygen species are thought to be involved in a number of types of acute and chronic pathologic conditions in the brain and neural tissue. The metabolic antioxidant alpha-lipoate (thioctic acid, 1, 2-dithiolane-3-pentanoic acid; 1, 2-dithiolane-3 valeric acid; and 6, 8-dithiooctanoic acid) is a low molecular weight substance that is absorbed from the diet and crosses the blood-brain barrier. alpha-Lipoate is taken up and reduced in cells and tissues to dihydrolipoate, which is also exported to the extracellular medium; hence, protection is afforded to both intracellular and extracellular environments. Both alpha-lipoate and especially dihydrolipoate have been shown to be potent antioxidants, to regenerate through redox cycling other antioxidants like vitamin C and vitamin E, and to raise intracellular glutathione levels. Thus, it would seem an ideal substance in the treatment of oxidative brain and neural disorders involving free radical processes. Examination of current research reveals protective effects of these compounds in cerebral ischemia-reperfusion, excitotoxic amino acid brain injury, mitochondrial dysfunction, diabetes and diabetic neuropathy, inborn errors of metabolism, and other causes of acute or chronic damage to brain or neural tissue. Very few neuropharmacological intervention strategies are currently available for the treatment of stroke and numerous other brain disorders involving free radical injury. We propose that the various metabolic antioxidant properties of alpha-lipoate relate to its possible therapeutic roles in a variety of brain and neuronal tissue pathologies: thiols are central to antioxidant defense in brain and other tissues. The most important thiol antioxidant, glutathione, cannot be directly administered, whereas alpha-lipoic acid can. In vitro, animal, and preliminary human studies indicate that alpha-lipoate may be effective in numerous neurodegenerative disorders.

Animals↗