Questions and Answers from the TM Meeting In Glasgow 17th October 2007 with Professor Doug Kerr

Q. What test can you have to investigate whether you have had a recurrent attack of TM or not?
The serologic NMO-IgG blood test checks for antibodies which can indicate if you at an increased risk of experiencing multiple attacks of TM. In 100 patients with diagnosed RTM this test is positive for only 66/100 therefore there are 33% who remain negative in the testing period who have RTM, therefore in patients who have TM/RTM you must note that further deliberation is needed after these tests as they are not wholly accurate for every test subject.

Q. Is there a link between TM and autoimmune diseases like Sjogren’s Syndrome and diseases like Chronic Obstructive Pulmonary Disease (COPD)?
.I think they ARE linked.  I think that recurrent TM and Sjogren’s or recurrent TM and lupus (SLE) or recurrent TM and sarcoidosis are linked together.  That is, these systemic rheumatologic disorders can cause TM and by extension, treating them helps to treat the TM.  We still don’t know the extent of the overlap.  For example, patients with TM and SS-A (an autoantibody test in the blood that is associated with Sjogren’s syndrome) are more likely to have recurrent disease and they don’t necessarily have to have the full Sjogren’s disease.  So, my take is that anybody with TM and especially recurrent TM should be looked at for whether they have one of these systemic rheumatologic diseases. ).
COPD is not an autoimmune condition and there is no link to COPD and TM.

 

Q. What do I ask my neurologist when I see him in the initial contact after a first or recurring attack of TM, especially considering the appointments are few and far between and last for only a short time?
In the first visit after an acute attack you need to define the risk of your inflammation and occurrence, most recurrent attacks occur in the first 2 yrs after the initial onset/attack and so there is a crucial need to diagnose the problem and identify the most appropriate treatment plan to be deployed initially after onset and during this time of heightened risk. It is best to be as fit and healthy and full of vigour as possible to receive therapy in the most optimum condition.
SLEEP, EXERCISE, NUTRITION, POSITIVE THINKING, STRESS/ANXIETY REDUCTION are all vital to maintaining the most optimal health and to boosting your immune system.
If feeling poorly, enhancing one of these factors will do some good to helping your immediate and future health.

Q. I’ve recurrent TM, if a severe episode occurred what drugs should I ask for or use to help myself, assuming it was right after an attack/onset?
(See the drug therapy algorithm chart established by JHU and written by Doug Kerr, coming as a dossier from Doug very soon)
See attached new treatment algorithm. 
Prednisolone or IV steroids- available and almost all we have, proven effectivness, an essential.
Intravenous cyclophosphamide (IV/CP) - is a chemotherapy drug that works by slowing or stopping cell growth. It also works by decreasing the immune system's response to various diseases. It is the best drug we have and the most rapid in action. IV/C-VAMP (Intravenous cyclophosphamide, vincristine, Adriamycin & the steroid methylprednisolone) is a chemotherapeutic and steroidal compound drug with similar applications but more specific uses.
Plasma Exchange (plasmapheresis-not possible yet in the UK but there is lots of data upon its effectiveness), where the rapid removal of disease-causing autoantibodies from the circulation is required in addition to slower medical therapy. It is important to note that plasma exchange therapy in and of itself is useful to temper the disease process, where simultaneous medical and imunosuppressive therapy is required for long term management. Plasma exchange offers the quickest short-term answer to removing harmful autoantibodies; however, the production of autoantibodies by the immune system must also be stopped, usually by the use of medications that suppress the immune system, such as prednisone, cyclophosphamide, cyclosporine, mycophenilate mofetil, and/or rituximab/rituxan. The 2nd best drug we have and the second most rapid.
Intravenous Immunoglobulin (IV/IG)- is a blood product administered intravenously. It contains the pooled IgG immunoglobulins (antibodies extracted from the plasma of over a thousand blood donors). IVIG's effects last between 2 weeks and 3 months. It is used primarily to modulate the immune system and to prevent against harmful inflammation. No data.
Thalidomide- a potent anti-inflammatory with useful other actions usually used with IV/IG or all the above. Data available from JHU but not elsewhere.

After 5 years reduction of medication is needed, it is unspecified how patients will react when taken off the drugs even gradually and regular tests and monitoring will most likely be needed, consultations at this point are vital.

Q. If Oligioclonal Bands are positive in tests do they suggest MS only?
7-8% of people with Monophasic TM will be positive for the test, whereas 84% of people with MS will be positive for the test. Therefore if the test is possible it suggests you more than likely have MS but not necessarily you could have Monophasic TM but the chances are less likely. If the test is false or negative you more than likely don’t have MS but you will require further tests to rule out TM.

Q. What are the most effective treatments for the management of pain in TM?
Neurontin (Gabapentin) max 4800mg-6000mg daily once at 4200mg/day you should be considering how much more effective it is too take more as t this high a dose its hard to withdraw easily and side effects are more prominent.
Lyrica (Pregabalin) up to 600 mg/day
Amytryptaline- 10-100mg/day but beware of dry eyes, dry mouth, constipation, sedation and maybe some cardiac abnormalities.  It’s a really good medicine for some, but gotta be a bit cautious here. 
Nortrypaline-  same here.  Same doses. Less of some of the side effects
Methadone-could work for chronic pain. 
Marinol/Sativex- Cannabinoid therapy currently only approved for MS patients in the UK for neurological conditions.

Q. Following my ADEM attack, my memory esp. Short Term Memory was badly affected. Can you elaborate on the symptoms of cerebral attacks?
In most TM & related conditions multitasking and cognitive processing and concentration is affected. In ADEM too, sometimes equally and sometimes more or less. Cognitive adaptation requires the brain to learn over time how to cope by meeting new processes (assuming no recurring attacks). Inflammation in the brain, spinal fluid and sometimes to a lesser extend drugs causes these effects. Animal models speculate that in relation to Cognitive processing it may take up to 1-4 yrs after an attack for optimal cognitive function to be restored.

Q. What is the link between Depression and TM?
As a result of TM or its cousins, chemical imbalances occur producing depression. This depression is markedly different that the depression you may associate with someone who experiences “depression” after losing a job, a spouse, a child, it is chemical and unrelated although at times exacerbated by issues like poor motor/sensory function, poor cognitive function. For more information see Adam Kaplan’s literature on Depression in TM, this provides a more comprehensive answer and a greater support to those who wish to understand more about this complex relationship. Adam is my colleague and a inspired psychiatrist as well as neurologist who specialises in depression in these instances.  Exactly right.

Q. When should steroids be given?
After an acute attack of TM, ADEM, NMO a short pulse of IV steroids 1-3 days every time!!!
In relation to MS- unsure?
For further information upon this see Ben Greenberg Literature upon the JHU TM website and refer to the Up to date Treatment plan Algorithm set out by Doug Kerr and others.

Q. What are the current thoughts on prognosis of infants and children with TM and recurrent TM?
I’ve never seen or heard of a recurrence, adults often plateau in the treatment after 1-18mnths, children often continue to improve much further beyond this. Rehab is especially crucial for children and is much more critical; children will always plateau at a lower point where physiotherapy/exercise are not maintained. Everyday do physiotherapy, even if it is only passive and even if it has to be done by you or a neighbour, it’s a prophylactic, it helps to make children’s future progressively better.  And active physiotherapy when possible (water therapy, trying to get the legs to move) or functional electrical stimulation. 

Q. Can a Spinal Trauma/Injury increase the likelihood of getting TM even if it is 2months-20 years later?
No evidence for this. Speculation is there. Sensibly any trauma especially a serious one can impair and affect nerve health and blood supply health. TM may develop years later after something like this, its plausible but not proven.

Q. Post-stem cell therapy should there be an improvement in treatment and prognosis of TM?
Unsure, lots of uncertainty involving how stem cells repair and how they behave, its early days for this issue but it will be the subject of much debate, hope and deliberation in the future I’m sure.

Q. Hyperbaric Chambers and TM (or its cousins) what are your thoughts?
Acute phase- No it could exacerbate or worsen.
Chronic Phase- unsure, research into this is not a priority.

Q. In non-recurrent TM what is the long term prognosis?
In the absence of new attacks the condition is progressive and will worsen over time, perhaps by a great deal or perhaps not by much, usually not dramatically to the point of lack of all mobility, but certainly it makes it more difficult to exercise.

Q. Is recurrent TM still recurrent TM after occurring 2 or 3 times in different Spinal locations?
Yes, if untreated Recurrent TM can reoccur without prophylaxis (see info on Immunosuppressant drugs for Prophylaxis of Recurrent TM). It is not necessarily MS, they present different both clinically and pathophysiologically. If it has reoccurred there is a greater likelihood it will reoccur again and again and the more frequent the reoccurrences the less time there is likely to be between each attack. i.e. if you had 3 attacks in 10yrs, during the next 10yrs it would be likely that without prophylaxis (i.e. immunosuppressant therapy) you would have more than 3 attacks.

Q. During neuropathic pain attacks should I push through the pain or relax?
If during therapy, be it receiving drugs or going to physiotherapy, you should follow your body, paying attention and caution as to when you are exerting yourself, being overly active or not feeling your usual average day to day well-being. Any energy spent over exerting or pushing beyond one’s limits in these circumstances may be detrimental as they may have a counterproductive effect.
If at rest, during the night or at times when you are feeling your usual daily sense of well-being, breaking through the pain barrier or stretching through the pain may actually lessen severe pain in the long term by building greater tolerance or by simply having mindfulness over how to detract your attention and heightened awareness to such pain.
Exercise and Positive thinking are crucial to helping the body release its own form of painkillers and mood enhancers (endorphins & morphoids), both exercise and positive thinking help to reduce pain, increased sensory input (i.e. anything that keeps you active or upbeat) will help to reduce the pain.

Q. 4AP Fampardine is this a useful drug to use in TM ?
This drug has been available for 15 yrs, it has been experimentally used in small clinical trials for patients with Spinal Injury, the trials criteria did not mean the standards of the FDA (American Food and Drug Administration) however with greater follow up it is hoped to be approved for MS by 2008-9 after further and more rigourous trials have been completed (new trials are currently underway but not complete).
4-aminopyridine (also known as 4-AP and Fampridine) is a drug that blocks the potassium channels in neurons. This effectively improves the transmission of nerve impulses down damaged axons. It does not replace damaged myelin but users of 4-AP report dramatic improvement in a number of symptoms especially paraesthesia (numbness/pins and needles). Its benefits can affect all functions including Motor, Sensory, Pain Perception, Autonomic (Bladder, Renal & Sexual), 30% of people feel significant benefits to one or more of these functions and the rest may feel benefits which are functionally irrelevant but are positive nonetheless.
The side effects are that it can cause seizure esp in doses above 50-60mg and at this does it can also increase pain in 10% or less of patients due to increasing nerve impulses. Dosages should be carefully regulated as potassium is a chemical that is used extensively in other parts of the body including heart functions.
It may be useful if you can access this drug to take 10mg for a period of 1 week, taking 20mg the 2nd week, 30mg for a 3rd week and 40mg the 4th, 5th and 6th week, after the 6 weeks, a self-assessment could be made on whether the drugs effects were none, marginal, detrimental or beneficial and further treatment or cessation would be decided.

Q. Is TM hereditary?
There is a very low risk, almost minimal that TM is hereditary it would be exceptional for such a case to occur, it is more likely in MS but it still tends to be only a risk to a specific individual and not all children or grandchildren if one or both parents are affected or if one parent and grandparent is affected. The risk in MS is higher perhaps 1:10 whereas in TM it is much, much more rare.

Q. What are your hopes in 10years time for the treatment, management and care of those with TM?
Realistically, the hopes are to have better acute therapies, given across the board (i.e. more than just IV steroids), to be at the point of identifying people at a high risk of TM genetically but perhaps otherwise too e. g. those who may be at a greater risk due to non-genetic factors.
Stem cells Treatment/Clinical Trials will be a reality and be more prevalent, acceptable and easier funded…..this wont be the be all and end all but it will certainly provide a part to play in the treatment plan and strategy of management for all TM patients
IV (Intravenous)/C-VAMP (cyclophosphamide, vincristine, Adriamycin & the steroid methylprednisolone) or IV/CP (cyclophosphamide) as a single dose chemotherapy treatment to suppress the immune system may be more prevalent and easier to access as a TM therapy where at the moment such medication would not be considered for TM as there is no license to use it for this condition in the UK at present. Currently, trials in the JHU show that all acute patients benefit from this treatment, that 66.6% of patients display no symptoms after treatment post rehabilitation, with the other 33.4% of patients have mixed results.
SUSTAINED REMISSION IS A POSSIBILITY!!!!