Narcolepsy and IVIg

Intravenous immunoglobulin (IVIg) is a blood product that is given via a tube into a vein, just like a blood transfusion. However with IVIg rather than deliver blood it delivers a blood product called IgG (immunoglobulin (antibody) G) which is extracted from the blood plasma of at least a thousand blood donors, which makes it both expensive and rare. Intravenous immunoglobulin is designed to treat conditions such as acute infections, immune deficiencies and auto immune diseases.

If narcolepsy is an auto-immune disorder (which seems to be the case) it was thought that IVIg or other immune suppressing drugs might stop the auto immune response and allow the patient with narcolepsy to lead a normal life. The first report published was in 2003 by a group led by Dr Hecht who tried prednisone on an 8 year old boy (sleep 2003); the results were promising enough for others to try. The Bassetti team were the first to report on IVIg use (Journal of Sleep Research 2003) and this was quickly followed by the most famous report by Professor Tafti and Dauvilliers (Journal of Sleep research 2004) who were able to give IVIg to two young patients with what appeared to be good recovery in one of them. While several other groups tried to replicate these findings few were able to see any significant changes in the patients. This led to Dr Mignot and his team at Stanford to produce a paper in 2004 (Journal of Sleep Research) that suggested IVIg responses were variable, the reports too subjective and even in those patients that showed improvements a persistent low level of hypocretin/orexin was seen in the spinal fluid. When reviewing novel new methods of narcolepsy therapy in 2005 for the Journal Sleep, Dr Mignot and Dr Nishino again raised these problems.

However to many researchers and doctors it looked to be a promising area of research and remained the only possible “cure” for narcolepsy. The major problems seemed to be finding enough patients to study and also getting them quickly enough – certainly before the hypothalamus had been significantly attacked to the level where hypocretin was no longer detectable in spinal fluid. It was very difficult to find narcolepsy patients so quickly until the onset of Pandemrix vaccinations in 2010. The history of Pandemrix is well covered in other articles on this website and while a disaster for the families involved it has allowed significant new research to go on that might in the future help the entire narcolepsy community.

One of these areas is the use of IVIg; with medical centres and doctors more aware of the problems of narcolepsy we did start to see quicker diagnosis and referral. This would allow IVIg to be tried again. The first report of IVIg use on post Pandemrix narcolepsy patients happened at the Neurological Conference in Budapest on September 10th 2011. Dr Stine Knudson from Denmark reported on a 21 year old patient who had Pandemrix in late October 2010. By January he was suffering from narcolepsy with cataplexy and on February 15th had the first of two doses of IVIg. Unfortunately the treatment didn’t appear to work and the patient did not improve his hypocretin in spinal fluid or his sleep latency tests.

At the crossover meeting of the BSS and Narcolepsy UK in September 2011, Birmingham Children Hospital also reported on a patient that had been diagnosed with narcolepsy with cataplexy within weeks of problems beginning and he too was tried on IVIg; once again with no positive results. To move forward to 2012, on June 10th at the latest European Neurological Society meeting the Bassetti group reported on a 15 year old girl who was tried with IVIg after developing Pandemrix narcolepsy. This time there was a delay of nine months before the first of three doses of IVIg was delivered. The results were not positive, though this could be due to the late onset of the treatment. The very latest report on IVIg is in this month’s edition of Neurology (July 2012) and includes reports of therapy carried out on a patient 19 days after an abrupt onset of narcolepsy. Once again the patient had no positive reaction to IVIg and the general feeling of the report (whose authors include Dr Mignot) is that the value of IVIg is limited, if it exists at all.

Some are suggesting that the mechanism of the Pandemrix narcolepsy could be different to spontaneous narcolepsy and as such IVIg might not be as successful on this type of narcolepsy. While possible that would suggest that spontaneous narcolepsy was caused by a different type of pathogenesis (mechanism) and no report has yet suggested this. Add to that the questions on the success of IVIg on traditional or spontaneous narcolepsy in the first place (which was limited at best)and it does seem that all that is happening here is the same that happened in the majority of other trials – limited or no effect at all.

It was almost ten years ago that the Tafti and Dauvilliers report suggested a possible cure for narcolepsy by the early use of IVIg. While it certainly makes sense that you could control and perhaps reverse an auto immune disease by quickly providing doses of immune suppressing drugs the facts suggest, with narcolepsy at least, that is not the case. For those of you that might see this as another “one step forward followed by two back” report on research do remember that at times a negative report is as important as a positive one. In this case it could lead to further research and answers on if Pandemrix narcolepsy is a separate form of the disease. It must also start to make researchers look at other regimes for suppressing auto immune diseases and also reviewing the theory of narcolepsy as an auto immune condition. It is however disappointing that the first possible cure for narcolepsy, a possibility that energised many campaigners and people with the disease, has been shown not to be as effective as hoped and it is “back to the drawing board” once again.

 John Cherry

(Added to website 17th July 2012)