Tuesday, 6 October 2015


The Proximus trial of neuroprotective drug on top of a DMT has had serious problems recruiting.


a) Have you been full of hot air when it comes to the willingness to have a lumbar puncture?

In the surveys you said yes not problem, but the reality has been somewhat different.

(b) There was also a big problem that was due to us. This was the level of neurofilament to be in spinal fluid needed to be included into the study. 

The good news is that the reality has been that the level of neurofilament has been lower than anticipated the bad news means we turned a lot of willing people away and also we we had to go through ethics and back to the regulators and sponsors for protocol amendments to change the eligibility. This too way too long. 

However, we are back on track. So if you are eligible please, please sign up. 

You may say I want to wait until after Saturday for news from ECTRIMS to determine if anti-CD20 halts progression. That is fine, however, my guess is that it won't. So there will still be a need for neuroprotection on top of what a DMT can do in many people with progressive MS.

This is going to be one of the quickest routes to be able to get a potential neuroprotective drug and we not asking you to stop your current DMT, infact we want you to stay on them.

Need a brain boost?

Case Rep Neurol Med. 2015;2015:251829. doi: 10.1155/2015/251829. Epub 2015 Sep 2.

Modulation of the Left Prefrontal Cortex with High Frequency Repetitive Transcranial Magnetic Stimulation Facilitates Gait in Multiple Sclerosis.


Multiple Sclerosis (MS) is a chronic central nervous system (CNS) demyelinating disease. Gait abnormalities are common and disabling in patients with MS with limited treatment options available. Emerging evidence suggests a role of prefrontal attention networks in modulating gait. High-frequency repetitive transcranial magnetic stimulation (rTMS) is known to enhance cortical excitability in stimulated cortex and its correlates. We investigated the effect of high-frequency left prefrontal rTMS on gait parameters in a 51-year-old Caucasian male with chronic relapsing/remitting MS with residual disabling attention and gait symptoms. Patient received 6 Hz, rTMS at 90% motor threshold using figure of eight coil centered on F 3 location (using 10-20 electroencephalography (EEG) lead localization system). GAITRite gait analysis system was used to collect objective gait measures before and after one session and in another occasion three consecutive daily sessions of rTMS. Two-tailed within subject repeated measure t-test showed significant enhancement in ambulation time, gait velocity, and cadence after three consecutive daily sessions of rTMS. Modulating left prefrontal cortex excitability using rTMS resulted in significant change in gait parameters after three sessions. To our knowledge, this is the first report that demonstrates the effect of rTMS applied to the prefrontal cortex on gait in MS patients.

Figure: Transcranial magnetic stimulation uses a coil magnetic field generator which induces electrical currents in the area of brain underneath.
Repetitive transcranial magnetic stimulation (rTMS) is not a new thing and has been utilized in neurological conditions to demonstrate disruption in the brain circuitry e.g. in stroke and in MS, but also as a therapeutic option in the treatment of resistant depression and spasticity in MS.
Here the authors report a potential use in improving walking in MS; in particular, on measures of walking time, speed and the flow of walking (see figure below). rTMS was applied to the prefrontal cortex of the brain, which is believed to modulate the caudate nucleus deeper within the brain that is involved in controlling the movement of our bodies. Interestingly, the function of the caudate nucleus is affected in Parkinson's disease and rTMS also appears to boost dopamine release which is perturbed in this condition.
Although, the results are only in one person and a proper clinical trial needs to be carried out, it is a promising therapeutic option in MS. Falls risk is a leading cause of morbidity in MS patients and if this therapy can help improve this by improving gait, then rTMS should be a licensed therapy in MS. The authors demonstrate an improvement in walking speed in the range of 10m/sec after three sessions, which is a huge achievement.
The drawbacks of therapy are that it can have transient negative effects on mood, memory loss, hearing loss, and rarely can induce seizures.

Figure: Mean data showing ambulation time, velocity, and cadence at baseline, after one rTMS session, at baseline 2 (three days after one rTMS session), and after three consecutive daily rTMS sessions. Ambulation time was significantly shorter and velocity was significantly faster only after 3 rTMS sessions while cadence was significantly higher after both 1 and 3 rTMS sessions.