Op de trap van Erasmus: de vrijheid van neuronen

Afscheidsrede als Hoogleraar Neurologie, uitgesproken op 8 januari 201

Locomotion in the cat : a behavioural and neurophysiological study of interlimb coordination

The alternating periods of flexion and extension movements at the different joints farm the elements of the locomotor cycle, which may be adapted in force and timing to satisfy the requirements for support of the body, balance and direction of progression. These basic elements of movement are produced by the activities of interneurones and moteneurones lying in the respective spinal segments innervating each limb. In his study of narcosis progression in the cat Brown (20) suggested that the flexion and extension movernents were generated by groups of rieurones driving the respective motoneurons. These groups were organized into functional half eentres producing the signals necessary for the flexion and extension phases of stepping by virtue of mutual inhibition. The existence of half eentres received some confirmatien by Lundberg and hi.s collaborators in studies on the effects of L-DOPA on spinal cord reflexes (82). Thè actual mechanisms by which the groups of interneurones produce phases of flexor and extensor activity have not yet been defined, although Grillner (62) and Pearson (I 15) have suggested some possible models

Chronic motor neuropathies: response to interferon-beta1a after failure of conventional therapies

OBJECTIVES: The effect of interferon-beta1a (INF-beta1a; Rebif) was studied in patients with chronic motor neuropathies not improving after conventional treatments such as immunoglobulins, steroids, cyclophosphamide or plasma exchange. METHODS: A prospective open study was performed with a duration of 6-12 months. Three patients with a multifocal motor neuropathy and one patient with a pure motor form of chronic inflammatory demyelinating polyneuropathy were enrolled. Three patients had anti-GM1 antibodies. Treatment consisted of subcutaneous injections of IBF-beta1a (6 MIU), three times a week. Primary outcome was assessed at the level of disability using the nine hole peg test, the 10 metres walking test, and the modified Rankin scale. Secondary outcome was measured at the impairment level using a slightly modified MRC sumscore. RESULTS: All patients showed a significant improvement on the modified MRC sumscore. The time required to walk 10 metres and to fulfil the nine hole peg test was also significantly reduced in the first 3 months in most patients. However, the translation of these results to functional improvement on the modified Rankin was only seen in two patients. There were no severe adverse events. Motor conduction blocks were partially restored in one patient only. Anti-GM1 antibody titres did not change. CONCLUSION: These findings indicate that severely affected patients with chronic motor neuropathies not responding to conventional therapies may improve when treated with INF-beta1a. From this study it is suggested that INF-beta1a should be administered in patients with chronic motor neuropathies for a period of up to 3 months before deciding to cease treatment. A controlled trial is necessary to confirm these findings

Holter monitoring in patients with transient and focal ischemic attacks of the brain

The results of Holter monitoring in 100 patients with transient and focal cerebral ischemia were studied retrospectively. Atrial fibrillation (AF) was found in five patients compared with two from a group of 100 age and sex-matched control patients. Four of these had a previous history of AF or showed AF on the standard electrocardiogram. Episodic forms of sick sinus syndrome, which have also been related to cerebral embolism, were found in 32 of the TIA patients against 13 of the controls (p less than 0.0025). Sick sinus syndrome was of the bradyarrhythmia-tachyarrhythmia type in 14 of the TIA patients and in three of the controls (p less than 0.01). The relationship between TIAs and transient sinus node dysfunction could not be explained by concomitant heart disease. It is not yet clear whether the relationship is causal or indirect

Guillain-Barré syndrome:multifactorial mechanisms versus defined subgroups

The clinical spectrum of Guillain-Barré syndrome (GBS) is summarized in relation to antecedent infections and anti-ganglioside antibodies. Associations exist between a pure motor form of GBS, diarrhea, Campylobacter jejuni infection, and anti-GM1 antibodies; between cranial nerve involvement and Miller Fisher syndrome, C. jejuni infection, and anti-GQ1b antibodies; and between variants, such as severe sensory involvement and cytomegalovirus infection. These three clinical variants are suggested to form the extremes of a continuous spectrum; they are discussed in relation to the more pathologically defined patterns of acute motor axonal neuropathy and acute motor-sensory axonal neuropathy. In particular, patients with a clinically pure motor variant of GBS, diarrhea, anti-GM1 antibodies, or C. jejuni infection seem to respond better to early treatment with high-dose immunoglobulins than to plasma exchange.</p

Anti‐GM₁ IgG antibodies and <i>campylobacter </i>bacteria in Guillain‐Barré syndrome:Evidence of molecular mimicry

In Guillain‐Barré syndrome antibodies to GM1 and the presence of an antecedent Campylobacter jeJunei infection are correlated with a more severe course of the disease. From a group of 137 consecutive GBS patients, 11 sera had elevated titers of anti‐GM1 IgG antibodies during the acute stage of disease. Each serum sample was preincubated with three different Penner serotypes of whole C. jeJunei (PEN O:4/59, PEN O:41) and Campylobacter coli (PEN O:22) bacteria. The PEN O:4/59 serotype, isolated from the stools of a Guillain‐Barré syndrome patient, inhibited 63 to 93% of the anti‐GM1 activity in 6 of 11 patients. The PEN O:41 inhibited 63 to 100% of the anti‐GM1 antibody activity in 9 of 11 patients. The PEN O:22 inhibited anti‐GM1 antibody activity in only 2 of 11 patients (80 and 86%). Two Guillain‐Barré syndrome patients did not show antibody absorption by any of the Campylobacter serotypes tested, although this does not exclude the involvement of other serotypes. An Escherichia coli control strain did not significantly absorb anti‐GM1 antibodies. The results of this study indicate that anti‐GM1 IgG antibodies in Guillain‐Barré syndrome sera recognize surface epitopes on whole Campylobacter bacteria and that this recognition is strain‐specific. This provides evidence for molecular mimicry in the pathogenesis of Guillain‐Barré syndrome.</p

Self reported stressful life events and exacerbations in multiple sclerosis: prospective study

OBJECTIVE: To study the relation between self reported stressful life events not related to multiple sclerosis and the occurrence of exacerbations in relapsing-remitting multiple sclerosis. DESIGN: Longitudinal, prospective cohort study. SETTING: Outpatient clinic of department of neurology in the Netherlands. PARTICIPANTS: Patients aged 18-55 with relapsing-remitting multiple sclerosis, who could walk with a cane or better (score of 0-6.0 on the expanded disability status scale), and had had at least two exacerbations in 24 months before inclusion in the study. Patients with other serious conditions were excluded. MAIN OUTCOME MEASURE: The risk of increased disease activity as measured by the occurrence of exacerbations after weeks with stressful events. RESULTS: Seventy out of 73 included patients (96%) reported at least one stressful event. In total, 457 stressful life events were reported that were not related to multiple sclerosis. Average follow up time was 1.4 years. Throughout the study, 134 exacerbations occurred in 56 patients and 136 infections occurred in 57 patients. Cox regression analysis with time dependent variables showed that stress was associated with a doubling of the exacerbation rate (relative risk 2.2, 95% confidence interval 1.2 to 4.0, P = 0.014) during the subsequent four weeks. Infections were associated with a threefold increase in the risk of exacerbation, but this effect was found to be independent of experienced stress. CONCLUSION: Stressful events were associated with increased exacerbations in relapsing-remitting multiple sclerosis. This association was independent of the triggering effect of infections on exacerbations of multiple sclerosis

Indices from flow-volume curves in relation to cephalometric, ENT- and sleep-O2 saturation variables in snorers with and without obstructive sleep-apnoea

In a group of 37 heavy snorers with obstructive sleep apnoea (OSA, Group 1) and a group of 23 heavy snorers without OSA (Group 2) cephalometric indices, ENT indices related to upper airway collapsibility, and nocturnal O2 desaturation indices were related to variables from maximal expiratory and inspiratory flow-volume (MEFV and MIFV) curves. The cephalometric indices used were the length and diameter of the soft palate (spl and spd), the shortest distance between the mandibular plane and the hyoid bone (mph) and the posterior airway space (pas). Collapsibility of the upper airways was observed at the level of the tongue base and soft palate by fibroscopy during a Muller manoeuvre (mtb and msp) and ranked on a five point scale. Sleep indices measured were the mean number of oxygen desaturations of more than 3% per hour preceded by an apnoea or hypopnoea of more than 10 s (desaturation index), maximal sleep oxygen desaturation, baseline arterial oxygen saturation (Sa,O2) and, in the OSA group, percentage of sleep time with Sa,O2 < 90%. The variables obtained from the flow-volume curves were the forced vital capacity (FVC), forced expiratory and inspiratory volume in 1 s (FEV1 and FIV1), peak expiratory and peak inspiratory flows (PEF and PIF), and maximal flow after expiring 50% of the FVC (MEF50). The mean of the flow-volume variables, influenced by upper airway aperture (PEF, FIV1) was significantly greater than predicted.(ABSTRACT TRUNCATED AT 250 WORDS