Marek Moll

Perilesional pathological oscillatory activity in the magnetoencephalogram of patients with cortical brain lesions.

In the surrounding of focal ischemic brain lesions dysfunctional neuronal zones emerge often resulting in pathological oscillatory activity. Using whole-head magnetoencephalography we recorded brain activity during rest in 23 patients with ischemic cortical lesions to find out whether we can localise and characterise low-frequency oscillatory activity. We measured patients at different times after stroke and partly in a follow-up approach to determine the time course of slow-wave activity. Using the analysis tool Dynamic Imaging of Coherent Sources we computed tomographic maps of oscillatory power in the delta-band (0.5-3 Hz). Fifteen of 23 patients with cortical strokes showed delta-activity, which was localised in an area not more than 2 cm away from the lesion. We found this perilesional low-frequency activity in the acute as well as in the chronic stage of stroke. Follow-up measurements of individual patients revealed persistence of perilesional low-frequency activity for months and even years. No consistent relation between perilesional activity and clinical symptoms was observed. Our results indicate that perilesional delta activity is common after ischemic cortical stroke. However, the functional significance remains to be elucidated.

Rapid mapping of finger representations in human primary somatosensory cortex applying neuromagnetic steady-state responses

We analyzed somatosensory evoked steady-state fields in order to localize finger representations in the hand area of the primary somatosensory cortex (S1). Using a 122-channel whole-head neuromagnetometer we recorded in six healthy subjects neuromagnetic responses to high frequency electrical stimuli delivered simultaneously to digit I, II, III and V at 22, 24, 27 and 30 Hz, respectively, and to transient stimulation of each single digit with a frequency of 3 Hz. Responses were averaged separately for each digit and were modeled by single equivalent current dipoles. Both conditions yielded the typical somatotopic finger representations within S1 hand area. Dipole locations did not differ significantly between the transient and the steady-state stimulation. Therefore, simultaneous high-frequency stimulation of the digits seems to be a reliable method for rapid and detailed mapping of the S1 hand area. This procedure has potential advantages over recording of transient responses. With simultaneous steady-state stimulation the measurement times are reduced to 2 min for mapping the whole hand area. Because of this our method probably increases spatial accuracy and permits repeated short interval recordings, e.g. in experiments studying short term plasticity.

Partial rescue of the perfusion deficit area by thrombolysis.

To investigate the evolution of the perfusion deficit area following systemic thrombolysis with recombinant tissue plasminogen activator (rtPA) in a clinical study on acute cerebral ischemia.

Prospective analysis of neutralising antibody titres in secondary non-responders under continuous treatment with a botulinumtoxin type A preparation free of complexing proteins—a single cohort 4-year follow-up study

Objectives In long-term botulinum neurotoxin treatment, loss of therapeutic efficacy may occur due to neutralising antibody formation. Preliminary results with incobotulinumtoxinA, a preparation free of complexing/accessory proteins, have indicated a low antigenicity. We hypothesised that continuous treatment with this botulinum neurotoxin preparation would not result in an increase in neutralising antibody titres (NABTs) in patients with pre-existing NABTs. Design Prospective, blinded cohort study. Setting Single centre in Germany. Participants Thirty-seven cervical dystonia patients with NABTs and partial secondary non-responsiveness to their previous botulinum neurotoxin type A treatment. Intervention Three-monthly intramuscular injections of incobotulinumtoxinA with a constant dose of 200 MU per injection during the first year; thereafter up to 500 MU for the next 36 months. Outcome measures Primary outcome measure: number of patients in whom NABTs declined below the initial titre after 48 months of incobotulinumtoxinA treatment or in whom titres had become negative within the 48 months. Secondary outcome measure: steepness of changes in NABT. NABTs were determined by mouse hemidiaphragm assay. Findings were compared to long-term data from 24 cervical dystonia patients who had developed NABTs and in whom treatment had been discontinued. Results Following a transient increase in the first 24 months under incobotulinumtoxinA treatment in some patients, NABTs declined well below the initial titre in the majority of patients. Test assay results were negative in most of the patients followed for more than 36 months. NABTs seemed to decline into the negative detection range as rapidly under incobotulinumtoxinA treatment as after cessation of botulinum neurotoxin therapy. Conclusions The reduction of NABTs despite continuous treatment with incobotulinumtoxinA indicates low antigenicity of incobotulinumtoxinA. This might have implications on restrictions such as minimum injection intervals of ≥10 weeks currently in place for maintaining successful long-term application of botulinum neurotoxin.

High Botulinum Toxin‐Neutralizing Antibody Prevalence Under Long‐Term Cervical Dystonia Treatment

The aim of this study was to determine the prevalence of neutralizing antibodies in a large cohort of long‐term treated patients with cervical dystonia (CD) still responding to repetitive injections with botulinum toxin (BoNT).