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Biomedical subjects

W Paulus

Publications and source records attributed to W Paulus.

At least 37 records · Page 2Linked to original sources

Why do restless legs occur at rest?--pathophysiology of neuronal structures in RLS. Neurophysiology of RLS (part 2).

Restless legs syndrome (RLS) is a heterogeneous disorder encompassing genetically caused types with early onset and acquired varieties occurring later in life. Genetic studies in the near future will most likely discover more than one causative gene. The acquired cases too have different etiologies ranging from idiopathic types to secondary forms with uremia, iron depletion, polyneuropathy and others. Here we aim to correlate typical RLS symptoms, such as the sensory symptoms at rest, the reduction of the complaint in response to movement or other physical stimuli, the dominant involvement of the legs, pain, circadian rhythm, and the responsiveness to dopaminergic drugs with neurophysiological features of the central nervous system. We outline the complexity of the neural structures involved and their connections. A diversity of hypothetical affections of different neuronal levels might lead to various combinations of RLS symptomatology. No single pathophysiological explanation has yet been developed that covers all clinical features.

Animals↗

MRI study of human brain exposed to weak direct current stimulation of the frontal cortex.

OBJECTIVE: To determine whether weak transcranial direct current stimulation (tDCS), which is an interesting new tool inducing prolonged cortical excitability shifts in humans, induces brain edema, disturbance of the blood-brain barrier or structural alterations of the brain detectable by magnetic resonance imaging (MRI). METHODS: In 10 healthy individuals, tDCS, which is known to alter cortical excitability for about 1 h, was applied over motor and pre-frontal cortices. contrast-enhanced t1-, t2-, and diffusion-weighted mri was performed immediately before, 30 and 60 min after tdcs. RESULTS: MRI performed 30 and 60 min after tDCS did not show pathological signal alterations in pre- and post-contrast-enhanced T1-weighted and diffusion-weighted MR sequences. CONCLUSIONS: tDCS protocols which are known to result in cortical excitability changes persisting for an hour after stimulation do not induce brain edema or alterations of the blood-brain barrier or cerebral tissue detectable by MRI. SIGNIFICANCE: These results deliver further evidence for the safety of the currently applied tDCS protocols in humans.

Adult↗

No evidence of hSNF5/INI1 point mutations in choroid plexus papilloma.

Choroid plexus carcinomas (CPC) have been shown to carry mutations in the hSNF5/INI1 gene on chromosomal arm 22q11.2. A recent study on choroid plexus papillomas (CPP) and CPC revealed frequent losses of chromosomal portions on the long arm of chromosome 22 (-22q). The region harbouring hSNF5/INI1 was affected in 47% of the CPP and 73% of the CPC, respectively. -22q occurred more frequently in adult than in infantile CPP suggesting different pathogenetic pathways for these tumours. These findings may indicate a potential tumour suppressor gene function of hSNF5/INI1 in a subset of choroid plexus tumours. In order to examine its potential role in the pathogenesis of choroid plexus tumours, we analysed exons 1-9 of hSNF5/INI1 by SSCP analysis in a series of 21 formalin-fixed and paraffin-embedded CPP. No alterations in migratory patterns were detected. These data indicate that somatic point mutations of hSNF5/INI1 do not play a role in the pathogenesis of CPP and that CPP and CPC may arise by two different molecular pathways.

Choroid Plexus Neoplasms↗

A close look at autoimmune muscle disorders: association of Lambert-Eaton myasthenic syndrome with dermatomyositis.

Dermatomyositis/polymyositis (DM/PM) and Lambert-Eaton myasthenic syndrome (LEMS) are two autoimmune disorders that have very rarely been reported to occur together in the same patient. We report on two patients with DM who were later diagnosed with concomitant LEMS, and point out diagnostic challenges in identifying LEMS in patients with DM/PM. As specific treatment for LEMS is available, it is important to identify those DM/PM patients who suffer from concomitant LEMS.

Comorbidity↗

The role of V5 (hMT+) in visually guided hand movements: an fMRI study.

Electrophysiological studies in animals suggest that visuomotor control of forelimb and eye movements involves reciprocal connections between several areas (striate, extrastriate, parietal, motor and premotor) related to movement performance and visuospatial coding of movement direction. The extrastriate area MT [V5 (hMT+) in humans] located in the "dorsal pathway" of the primate brain is specialized in the processing of visual motion information. The aim of our study was to investigate the functional role of V5 (hMT+) in the control of visually guided hand movements and to identify the corresponding cortex activation implicated in the visuomotor tasks using functional magnetic resonance imaging. Eight human subjects performed visually guided hand movements, either continuously tracking a horizontally moving target or performing ballistic tracking movements of a cursor to an eccentric stationary target while fixating a central fixation cross. The tracking movements were back-projected onto the screen using a cursor which was moved by an MRI-compatible joystick. Both conditions activated area V5 (hMT+), right more than left, particularly during continuous tracking. In addition, a large-scale sensorimotor circuit which included sensorimotor cortex, premotor cortex, striatum, thalamus and cerebellum as well as a number of cortical areas along the intraparietal sulcus in both hemispheres were activated. Because activity was increased in V5 (hMT+) during continuous tracking but not during ballistic tracking as compared to motion perception, it has a pivotal role during the visual control of forelimb movements as well.

Adult↗

Pharmacological modulation of cortical excitability shifts induced by transcranial direct current stimulation in humans.

Transcranial direct current stimulation (tDCS) of the human motor cortex results in polarity-specific shifts of cortical excitability during and after stimulation. Anodal tDCS enhances and cathodal stimulation reduces excitability. Animal experiments have demonstrated that the effect of anodal tDCS is caused by neuronal depolarisation, while cathodal tDCS hyperpolarises cortical neurones. However, not much is known about the ion channels and receptors involved in these effects. Thus, the impact of the sodium channel blocker carbamazepine, the calcium channel blocker flunarizine and the NMDA receptor antagonist dextromethorphane on tDCS-elicited motor cortical excitability changes of healthy human subjects were tested. tDCS-protocols inducing excitability alterations (1) only during tDCS and (2) eliciting long-lasting after-effects were applied after drug administration. Carbamazepine selectively eliminated the excitability enhancement induced by anodal stimulation during and after tDCS. Flunarizine resulted in similar changes. Antagonising NMDA receptors did not alter current-generated excitability changes during a short stimulation, which elicits no after-effects, but prevented the induction of long-lasting after-effects independent of their direction. These results suggest that, like in other animals, cortical excitability shifts induced during tDCS in humans also depend on membrane polarisation, thus modulating the conductance of sodium and calcium channels. Moreover, they suggest that the after-effects may be NMDA receptor dependent. Since NMDA receptors are involved in neuroplastic changes, the results suggest a possible application of tDCS in the modulation or induction of these processes in a clinical setting. The selective elimination of tDCS-driven excitability enhancements by carbamazepine proposes a role for this drug in focussing the effects of cathodal tDCS, which may have important future clinical applications.

Adult↗

[Therapy and prophylaxis of facial neuralgias and other forms of facial pain syndromes -- revised recommendations of the German Society of Migraine and Headache].

Trigeminal neuralgia and postherpetic neuralgia are the most relevant neuralgiform facial pain syndromes. Trigeminal neuralgia is characterized by lancinating intensive pain attacks of very short duration, triggered by external cues,whereas postherpetic neuralgia consists predominantly of long-lasting burning pain. Sodium channel blocking drugs are first choice in treatment of trigeminal neuralgia, operative procedures encompass microvascular decompression,thermocoagulation and percutaneous retrogasserian glycerol rhizotomy. In the acute stage postherpetic neuralgia is treated antivirally and analgesically, in the chronic stage by tricyclic antidepressive substances. Other pain syndromes described encompass the Tolosa-Hunt-syndrome, cervicogenic headache, craniomandibular dysfunction syndrome, atypical facial pain and rarer syndromes. Therapeutic recommendations are based on evidence based medicine criteria (EBM).

Facial Neuralgia↗

Transcranial direct current stimulation (tDCS).

tDCS appears to be a promising tool in neuroplasticity research with some tentative perspectives in clinical neurophysiology. The next steps to be carried out encompass better histological safety data. In order to preclude the possibility of neuronal damage, extending tDCS duration should be limited until more direct safety criteria are available than those derived from Agnew and McCreery (1987) (cf. Nitsche et al, this volume). Safe stimulation protocols have to be developed which allow an extension of the duration of after-effects towards a somewhat permanent state, supposing a beneficial effect can be found in neurological diseases or in neurorehabilitation.

Animals↗

AMOG/beta2 and glioma invasion: does loss of AMOG make tumour cells run amok?

The beta2 subunit of Na,K-ATPase, initially described as adhesion molecule on glia (AMOG), has been shown to mediate neurone-astrocyte adhesion as well as neural cell migration in vitro. We have investigated the expression of AMOG/beta2 in human gliomas and its effect on glioma cell adhesion and migration. Compared to normal astrocytes of human brain, AMOG/beta2 expression levels of neoplastic astrocytes were down-regulated in biopsy specimens and inversely related to the grade of malignancy. One rat and four human glioma cell lines showed complete loss of AMOG. To investigate the function of AMOG/beta2, its expression was re-established by transfecting an expression plasmid into AMOG/beta2-negative C6 rat glioma cells. In vitro assays revealed increased adhesion and decreased migration on matrigel of AMOG/beta2-positive cells as compared to their AMOG/beta2-negative counterparts. We conclude that increasing loss of AMOG/beta2 during malignant progression parallels and may underlie the extensive invasion pattern of malignant gliomas.

Adenosine Triphosphatases↗

Lack of chromosomal imbalances in adamantinomatous and papillary craniopharyngiomas.

Craniopharyngiomas are among the most common paediatric tumours and are thought to arise from embryonic remnants of Rathke's pouch. The molecular mechanisms involved in their formation remain elusive and little is known about chromosomal imbalances that could suggest the locations of tumour suppressor or proto-oncogenes involved in the pathogenesis. The paucity of published data on the molecular basis of such tumours prompted this investigation of 20 adamantinomatous and nine papillary craniopharyngiomas for genetic abnormalities by comparative genomic hybridisation (CGH). CGH revealed no DNA copy number changes in any of the 29 primary craniopharyngiomas, regardless of their histological subtype. These data suggest that chromosomal imbalances are a rare event in both adamantinomatous and papillary craniopharyngiomas.

Adolescent↗

No evidence of tumour cells in blood of patients with glioma.

BACKGROUND: Although clinically apparent systemic metastases of gliomas are very rare, reports of gliomas developing in recipient's transplanted organs have suggested that haematogenous spread might be more common. METHODS: This report describes a newly developed, sensitive real time quantitative reverse transcription polymerase chain reaction assay for the detection of mRNA encoding glial fibrillary acidic protein (GFAP). Blood from 10 patients with astrocytoma and 10 patients with glioblastoma was analysed. RESULTS: No GFAP mRNA was detected. CONCLUSIONS: These results suggest that even subclinical metastases are very rare and are probably restricted to distinct subsets of glioma.

Biomarkers, Tumor↗

[Modulation of cortical excitability by transcranial direct current stimulation].

Modulation of cerebral excitability is thought to be one mechanism underlying the pharmacological treatment of neuropsychiatric diseases such as epilepsy, depression, and dystonia. Repetitive transcranial magnetic stimulation (rTMS) has been tested for several years as a nonpharmacological, noninvasive method of directly influencing patients' cortical functions. We present an overview of the more easily performed transcranial direct current stimulation (tDCS) with weak current, which produces distinctly more pronounced changes in excitability than rTMS. The basic underlying mechanism is a shift in the resting membrane potential towards either hyper- or depolarisation, depending on stimulation polarity. This in turn leads to changes in the excitability of cortical neurons. Anodic stimulation increases cortical excitability, while cathodic stimulation decreases it. These changes persist after the end of stimulation if the stimulation lasts long enough, i.e., at least several minutes. The duration of this aftereffect can be controlled through the duration and intensity of the stimulation. Transcranial direct current stimulation essentially allows a focal, selective, reversible, pain-free, and noninvasive induction of changes in cortical excitability, the therapeutic potential of which must be evaluated in clinical studies, once possible risk factors have been assessed.

Animals↗

Mycotic cerebral vasculitis in a paediatric cardiac transplant patient excludes misadventure.

We present the case of a 10-year-old girl with cardiomyopathy who received a heart transplant. Due to organ rejection, the dosage of immunosuppressive agents was increased postoperatively. The patient complained of intermittent headaches in the following days and developed a haemorrhagic necrosis of the left thalamus. A week later, an oral dose of cyclosporin A was accidentally given intravenously, and 2 weeks later a recurrent subarachnoid haemorrhage of unknown origin was diagnosed. The clinical course was then characterised by progressive deterioration resulting in coma, fluctuating brain stem symptoms and the development of a massive cerebral oedema with subsequent brain death. A coroner's autopsy was instigated to investigate a claim of medical misadventure. Neuropathological investigations found a focal infiltration of fungal hyphae in the left posterior cerebral artery resulting in necrosis of the vascular wall and thus explaining the source of the recurrent subarachnoid haemorrhage which eventually resulted in the girl's death. Medical misadventure due to the administration of cyclosporin was not directly responsible for the death of this patient. This case illustrates that it is of paramount importance to copiously sample and investigate the basal cerebral arteries in cases of subarachnoid haemorrhage of unknown origin, in particular in a medico-legal context.

Aspergillosis↗

Intra- and interindividual variability of motor responses to repetitive transcranial magnetic stimulation.

OBJECTIVES: Repetitive transcranial magnetic stimulation (rTMS) can modify cortical excitability and is widely used for clinical and research purposes. We sought to determine the intra- and interindividual variability of its effects on motor cortex excitability, and whether repeated paired-pulses yield less variability than repeated single-pulses. METHODS: We investigated rTMS over the left motor cortex of 6 healthy subjects and recorded motor evoked potentials (MEPs) from the right abductor digiti minimi muscle. Eighty single suprathreshold stimuli or conditioning-test pairs of stimuli were delivered at 2Hz frequency. The pairs consisted of a subthreshold pulse followed by a suprathreshold pulse after 2, 5 or 10ms. In each subject we studied all types of rTMS 5 times on separate days. Single suprathreshold pulses at 0.17Hz preceded rTMS for baseline determination. RESULTS: The day-to-day variability of MEPs during either type of rTMS was small compared to the subject-to-subject variability. MEPs increased during all types of rTMS except for interstimulus interval (ISI) 2ms. Paired-pulses yielded less variability than single-pulse rTMS. CONCLUSIONS: Motor responses to rTMS show a high interindividual, but a low intraindividual variability. Repeated paired-pulses yield less variability than repeated single-pulses.

Adult↗