Multiple Sclerosis Multidisciplinary Care: A National Survey and Lessons for the Global Community.

BACKGROUND: Access to, standardization and reimbursement of multidisciplinary care for people with MS (PwMS) is lacking in many countries. Therefore, this study aims to describe the current multidisciplinary care for people with MS (PwMS) in Belgium and identify benefits, needs and future perspectives METHODS: A survey for PwMS questioned various aspects of MS and viewpoints on care. For MS nurses (MSN) and neurologists, employment, education, job-content, care organization and perspectives were inquired. Descriptive and univariate statistics were performed RESULTS: The PwMS survey comprised 916 respondents with a mean age of 46±12.7 years and 75,4 % of the respondents being female. The majority of the participants had relapsing remitting MS (60.8 %) and the mean patient determined disease steps (PDDS) was 2.0 (IQR=3). 65.3 % and 60.4 % of the PwMS reported having access to a multidisciplinary team (MDT) or MSN. Access to an MSN was associated with more frequent disease modifying treatment (p=.015), spasticity (p=.042) and gait treatment (p=.035), but also more physiotherapy (p=.004), driver's license adjustment (p<.001) and a higher employment rate (p=.004). MDT access was associated with more frequent symptomatic bladder treatment (p=.047), higher physiotherapy rate (p<.001), higher work- (p=.002), insurance- (p<.001) and home support measures (p=.019). PwMS without an available MDT more often indicated that MS care needs improvement (p<.001). MSN's (n = 22) were mainly funded through various budgets, including hospital and neurology practice budgets. Finally, 69 % and 75 % neurologists (n = 62) working without an MSN or MDT stated a need of such support and 61 % agreed that MDT's should be organized at hospital-network level CONCLUSION: MDT and MSN availability may enhance medical and socio-economic support for PwMS. Guidelines, alignment and reimbursement are needed.

Metaplastic effect of apamin on LTP and paired-pulse facilitation.

In area CA1 of hippocampal slices, a single 1-sec train of 100-Hz stimulation generally triggers a short-lasting long-term potentiation (S-LTP) of 1-2 h. Here, we found that when such a train was applied 45 min after application of the small conductance Ca(2+)-activated K(+ )(SK) channel blocker apamin, it induced a long-lasting LTP (L-LTP) of several hours, instead of an S-LTP. Apamin-induced SK channel blockage is known to resist washing. Nevertheless, the aforementioned effect is not a mere delayed effect; it is metaplastic. Indeed, when a single train was delivered to the Schaffer's collaterals during apamin application, it induced an S-LTP, like in the control situation. At the moment of this LTP induction (15th min of apamin application), the SK channel blockage was nevertheless complete. Indeed, at that time, under the influence of apamin, the amplitude of the series of field excitatory postsynaptic potentials (fEPSPs) triggered by a stimulation train was increased. We found that the metaplastic effect of apamin on LTP was crucially dependent on the NO-synthase pathway, whereas the efficacy of the NMDA receptors was not modified at the time of its occurrence. We also found that apamin produced an increase in paired-pulse facilitation not during, but after, the application of the drug. Finally, we found that the induction of each of these two metaplastic phenomena was mediated by NMDA receptors. A speculative unitary hypothesis to explain these phenomena is proposed.

Tyrosine phosphorylation of rabphilin during long-lasting long-term potentiation.

Long-term potentiation (LTP) is a persistent increase in the strength of synaptic transmission triggered by neuronal activity. Here, we submitted hippocampal slices to a perfusion of forskolin and IBMX, which induces a long-lasting LTP (>4 h) (L-LTP). We separated the proteins of the CA1 region by two-dimensional gel electrophoresis (2-DE). We then immunoblotted them using an anti-p-Tyr antibody. We found a protein whose tyrosine phosphorylation was unchanged 10 min after LTP induction but was dramatically increased after 1h, dropping back to its baseline after 4 h. This protein was identified as rabphilin using matrix-assisted laser desorption ionisation-time of flight mass spectrometry (MALDI-TOF MS). We also demonstrated that genistein, an inhibitor of tyrosine phosphorylation, prevented the development of the late phase of electrically-induced L-LTP. Our results suggest that rabphilin, a protein present in presynaptic terminals, could play a role in the late phase of L-LTP.

The characteristics of LTP induced in hippocampal slices are dependent on slice-recovery conditions.

In area CA1 of hippocampal slices which are allowed to recover from slicing "in interface" and where recordings are carried out in interface, a single 1-sec train of 100-Hz stimulation triggers a short-lasting long-term potentiation (S-LTP), which lasts 1-2 h, whereas multiple 1-sec trains induce a long-lasting LTP (L-LTP), which lasts several hours. Moreover, the threshold and the features of these LTP depend on the history of the neurons, a phenomenon known as metaplasticity. Here, where all recordings were performed in interface, we found that allowing the slices to recover "in submersion" had dramatic metaplastic effects. In these conditions, a single 1-sec train at 100 Hz induced an L-LTP which lasted at least 4 h and was dependent on protein synthesis. Interestingly, this type of metaplasticity was observed when the concentration of Mg(++) used was 1.0 mM but not when it was 1.3 mM. The LTP induced by four 1-sec trains at 100 Hz was similar whatever the incubation method. However, the signaling cascades recruited to achieve that pattern were different. In the interface-interface paradigm (recovery and recording both in interface) the four-train induced LTP recruited the PKA signaling pathway but not that of the p42/44MAPK. On the contrary, in the submersion-interface paradigm the four-train induced LTP recruited the p42/44MAPK signaling pathway but not that of the PKA. To our knowledge this is the first example of metaplasticity involving the recruitment of signaling cascades in LTP.

Labyrinthectomy changes T-type calcium channels in vestibular neurones of the guinea pig.

In the vestibular nuclei of the awake guinea pig, all neurones are spontaneously active. After unilateral labyrinthectomy, this activity virtually disappears on the ipsilateral side, but is completely restored one week later. In a recent study, we observed that the restoration of spontaneous activity was correlated with an increase in pacemaker activity. In the current study, we found that the ratio of medial vestibular nucleus (MVN) neurones endowed with one of the currents known to play a role in pacemaker activity (i.e. low-threshold calcium current; LTCC) increased from 29% in control guinea pigs to 65% in animals labyrinthectomised on the ipsilateral side one week earlier. Yet this change was not correlated with a modification of the ratio of neurones expressing any of the three related protein-channels (alpha1G, alpha1H and alpha1I).