Fibromyalgie : la (Grande-Bretagne) Pour ses lecteurs, Myalgies pouvoirs publics anglais, annonça "la est sur tous les fronts fibromyalgie est maintenant une entité avec ses correspondants. reconnue et les médecins qui persistent à Kathy Longley, journaliste dire que ce n'est qu'une vue de l'esprit, se anglaise au Family Magazine, moquent ironiquement de leur propre igno- vous propose, dans les pages rance». suivantes et dans sa langue Le message douloureux, sur la piste des ca- maternelle, le résumé de naux potassiques ou de l'hormone de crois- certaines des communications sance, les anomalies du système nerveux données à cette conférence. central, le syndrome de fatigue chronique, Plus de 300 participants, profession- furent quelques uns des sujets abordés au nels de santé et fibromyalgiques, ont pu en- cours de cette conférence d'Harrogate, étu- des que vous avez eu l'occasion de lire dans auteurs dont I.J.
Russell (San Antonio, qu'objets de tra- Texas-USA) et K. Lawson (Sheffield, Grande-Bretagne) qui Ainsi des équipes collaborent à la rédac- De gauche à droite : R. Bennett, IJ Russel, A. Teitelbaum tion de Myalgies Inter- savent se mobili- national, notre supplément scientifique. sent pour ce syndrome et une rédaction plu- Le point d'orgue de cette rencontre fut sans ridisciplinaire s'efforce de se trouver tou-doute lorsque le Pr Mansel Aylward chargé jours là où a lieu l'événement pour vous ren-du dossier "Fibromyalgie" à présenter aux dre compte. n Michèle Iltis Medical highlights
From the Fibromyalgia Conference 2002
By Kathy Longley BSc (HONS) These highlights are simply transmitters involved are called glutamate and sub- stance P. Levels of substance P have been shown to a sample of the inspiring be three times higher in the spinal cord fluid of fi- and informative talks bromyalgia patients. Also, constant incoming pain signals cause large amounts of glutamate to be re- given at the conference. leased activating specialised receptors called There were many others NMDA receptors, which normally remain silent during general pain transmission. Activation of I don't have room these receptors together with the abnormal levels of to write about. substance P greatly enhances the intensity of the I am sure you would pain signal transmitted. Another nerve descending from the brain down to all like to join with me the spinal cord acts to interrupt the transmission of in thanking all the speakers the pain signal, either dampening it down or filter- ing it out completely before it reaches the brain. who gave up their valuable This descending nerve pathway uses the neurotrans- time to come and talk to us mitters serotonin, GABA, and the body's natural painkillers called endorphins. Due to a deficiency and of course in these neurotransmitters the dampening down to Pam and Bob Stewart process is ineffective allowing more intense and in- creased numbers of pain signals to reach the brain. for all their hard work These alterations in the nerve pathways involved in in organising the conference. the transmission of pain lead to a state of hypersen- sitisation where pain is felt at a much lower thresh- old referred to as "central sensitisation". Under- standing these altered mechanisms in fibromyalgia Dr Robert Bennett.n Altered Pain Pathways has led to the use of specific drugs targeted at the
pain transmission sites in the spinal cord. Dr Robert Bennett is a highly acclaimed professor (To read about the alterations of the pain pathways of medicine at the Oregon Health Sciences Univer- in fibromyalgia and the drugs used in more detail sity in Portland, Oregon USA. He has been in- please refer to the articles entitled "Ouch don't volved in fibromyalgia research since 1979 and has touch me!" part 1 and 2 to be found in ) published countless original studies. In his first talk he proceeded to explain the concept of "central sen- Dr Kim Lawson.n A link between Fi-
sitisation". In fibromyalgia the pain pathways have bromyalgia and Potassium Channels ?
become highly sensitised to pain, with pain mes- Dr Kim Lawson, a Senior Lecturer in Pharmacology sages being amplified at the level of the spinal cord. at Sheffield Hallam University, presented the hy- When a pain message reaches the spinal cord it has pothesis of dysfunctional potassium (K+) channels to be transmitted to an ascending nerve, which con- being the root cause for the symptoms of fibromyal- ducts the signal up to the brain. This is achieved by gia. K+ channels are involved in fundamental cell using special chemicals called neurotransmitters processes and maintain electrical stability across the stored at the nerve terminal. The neurotransmitters cellular membrane. When a cell is activated, for are released into the gap between the two nerves example a nerve cell, specific ions enter into the cell and transmit the signal by opening channels in the and alter the electric charge across the cellular membrane of the ascending nerve. The main neuro- membrane, causing the cell to become excited and therefore active. K+ ions, stored within the cell, are in the CSF of 84% of fibromyalgia patients com-responsible for calming the cell down again and re- pared to controls, while the other found a twofold storing it to its resting state. They achieve this by increase. This significant increase in substance P moving out of the cell through the K+ channels in was found to be specific to the central nervous sys-the cell membrane to readjust the electric charge to tem rather than the peripheral nervous system indi-its resting potential. cating that the drugs used to treat fibromyalgia need Malfunctions in K+ channels have been implicated to target the central nervous system. It was also in a range of diseases. The malfunctions are gener- found that substance P remains high and can even ally believed to be due to mutations in the genes en- increase over time. Another chemical involved in coding for the proteins that make up the channels in pain pathways is called nerve growth factor (NGF) the cell membrane. If these proteins are not formed and has been found to be four-times higher in the properly the K+ ions may not be able to move CSF of fibromyalgia patients compared to controls. across the cellular membrane effectively, leaving This significant rise in NGF appears to be a distin-the cell in an activated and excited state for a longer guishing feature of fibromyalgia and could be re-period of time. These mutations could be either in- sponsible for the increased levels of substance P. herited or acquired, possibly as a result of trauma. Decreased levels of serotonin and tryptophan have There are many different types of K+ channels dis- also been reported in fibromyalgia research. Dr Rus- tributed throughout the tissues of the body. One sell explained that tryptophan can enter into one of type called Kv 1.1 is believed to be involved in neu- two different biochemical pathways, one leading to ropathic pain. Kv 1.1 has been shown to play an the production of serotonin and the other to a important role in pain pathways and the dampening chemical called kynurenine. Kynurenine levels have down of pain signals and when this channel is dys- been found to be higher than normal in fibromyalgia functional symptoms of hyperalgesia and a lowered indicating that tryptophan is channelled into the pain threshold are observed, both classic symptoms kynurenine pathway rather than the serotonin path-of fibromyalgia. Also, the common drugs used to way leading to the low levels of serotonin observed. treat fibromyalgia like Tricyclics, SSRI's and pain- The combined forces of the abnormal levels of these killers like Tramadol are all believed to work by al- chemicals in fibromyalgia can lead to widespread tering the activity of K+ channels. It is possible that allodynia (a lowered pain threshold), with the result
these drugs are successful in combating some of the of touch being perceived as pain.
symptoms of fibromyalgia due to K+ channels been (Dr Russell's talk will be expanded on in an upcom-
at the root cause of the problem. If this proves to be ing article in FaMily magazine.)
the case then new drugs targeted to the specific K+
channels involved could prove to be highly effective
in treating all aspects of fibromyalgia. Dr Jacob Teitelbaum.n Fatigued to Fantas-
Dr Teitelbaum runs a specialised clinic for fi- Dr Jon Russell.n The Neurochemical Basis bromyalgia and chronic fatigue syndrome patients
in Annapolis, Maryland USA. He has devised his Dr Russell is an Associate Professor of medicine at own treatment protocol, which he has used to suc-the University of Texas Health Science Centre in cessfully treat over 2000 patients. This protocol has San Antonio, USA. He is the author of over 85 been tested in a placebo-controlled study and shown original publications into the research of fibromyal- to be effective. gia and holds the position of Editor-in-Chief for the Dr Teitelbaum believes that fibromyalgia is caused Journal of Musculoskeletal pain. Dr Russell spoke by mitochondrial dysfunction that can lead to the about the objective abnormalities that have been dysfunction of the hypothalamus, the main hor-found in the pain pathways of fibromyalgia patients mone-producing gland in the brain. He spoke pas-explaining that fibromyalgia is "no longer consid- sionately about his treatment protocol explaining the ered merely a psychological disorder, a diagnosis to importance of tackling all the major issues of fi-be made by exclusion, or a condition devoid of ob- bromyalgia at the same time in order to achieve sig- jective laboratories findings." nificant results. These important areas are disor- He brought attention to three studies carried out to dered sleep, hormonal deficiencies, nutritional defi-measure the levels of substance P in the cerebral ciencies and opportunistic infections. Disordered spinal fluid (CSF) of fibromyalgia patients. Two of sleep can be tackled using a variety of drugs, for ex-these studies found three times as much substance P ample, Ambien, klonopin, melatonin, amitriptyline and a range of herbal remedies like valerian, pas- duced exercise capacity. Growth hormone is re- sionflower and lemon balm. He pointed out that it leased in a pulsatile fashion during deep sleep and is better to take low levels of several sleep medica- stimulates the body to undergo biochemical and me- tions rather than a high level of just one to insure chanical repair, for example, repairing all the micro-that the medications are cleared from the blood- traumas in the muscles that have built up during the stream by morning to prevent a sleep hangover. He day. Due to deep sleep being disrupted in fi-stressed that it is of vital importance for people with bromyalgia the pulsatile release of growth hormone fibromyalgia to achieve eight-and-a-half hours of is greatly reduced and the body's repair systems be-solid sleep. There are numerous scientific studies come less effective leading to increased muscular reporting abnormal levels of hormones in fi- pain. Growth hormone release is also dependent on bromyalgia, for example, low levels of thyroid hor- the levels of another hormone called somatostatin. mone, growth hormone and cortisol. In his protocol Somatostatin is an inhibitory hormone released by Dr Teitelbaum treats all these hormonal abnormali- the hypothalamus to depress growth hormone secre- ties and is adamant that blood tests cannot be relied tion. The levels of somatostatin are believed to be upon to determine if hormone levels are low. Blood elevated in fibromyalgia due to the overactivity of tests can apparently be very inaccurate and he ad- the stress hormone CRH. vises doctors to go by the clinical symptoms pre- Dr Bennett has carried out studies to investigate the sented by the patient. Nutritional deficiencies in effects of increasing growth hormone in fibromyal-fibromyalgia are also numerous and Dr Teitelbaum gia patients. In one double-blind, placebo-controlled has created his own Formula to include all the nutri- study 25 fibromyalgia patients received growth hor- ents required at the correct dosage levels. This mone injections while another 25 patients were in-Foundation Formula can be purchased over the jected with a placebo. The 25 patients injecting Internet and it is worth pointing out that all of Dr growth hormone showed a prompt increase in IGF-1 Teitelbaum's profits go either to charity or are chan- levels within the first month and these levels were nelled back into fibromyalgia research. Opportunis- sustained throughout the nine month trial. No in- tic infections can include yeast like Candida, bacte- crease in IGF-1 levels was observed in the placebo ria or parasites that reside in the gut interfering with group. (IGF-1 levels in the blood reflect the amount the absorption of nutrients and zapping energy. Can- of growth hormone secreted.) Those receiving dida can be treated by a sugar-free diet combined growth hormone showed significant improvement in with anti-fungal drugs and good bacteria like aci- their symptoms compared to the placebo group. Un- dophilus. Clearing these infections from the gut and fortunately growth hormone is very expensive to the blood stream can apparently have dramatic ef- administer and those patients who were unable to fects. Dr Teitelbaum continually stressed that treat- afford to continue the treatment after the study had ing one of these areas could produce some good re- ended suffered a relapse in their symptoms. In an- sults, however, it is essential to treat all these areas other study Dr Bennett investigated an alternative at the same time to achieve highly significant ef- way of increasing growth hormone by administering a drug called pyridostigmine that works to inhibit A full account of Dr Teitelbaum's protocol can be somatostatin and these results were also very prom-found in his book "Fatigued to Fantastic", which is ising. Dr Bennett's work provides new ways for-available from the Fibromyalgia Association UK. It ward to produce other successful drugs for treating is certainly worth a read. (The significance of the relationship between Fi- (Dr Bennett's talk will be expanded on in an upcom- bromyalgia and low thyroid hormone will be exam- ing article in FaMily magazine.) ined in an upcoming article in FaMily magazine) Dr Robert Bennett.n Growth Hormone Defi-
ciency and Fibromyalgia
In his second talk Dr Bennett explained the impor- Copyright K.E Longley 2002 tant link between growth hormone deficiency and the fibromyalgia and reviewed various studies he has conducted in this area. Adults deficient in growth hormone have symptoms similar to fi-bromyalgia, for example, low energy, muscle weak-ness, impaired cognition, cold intolerance and a re-
I am sorry to hear you have been troubled by symptoms of imbalance and dizziness. Your query appears to contain two elements: 1) dizziness and imbalance related to the time of year, and 2) complementary therapies or supplements for dizziness and imbalance. I will cover these in two sections below. I admit I do not routinely provide much advice in these areas, and don't think other clinicians allied to a more 'medical' model commonly would either. I think this is because there is not enough evidence to back up any recommendations, although I would hope anyone would be open minded to the possibility of stronger evidence becoming available. I have looked at the scientific literature for you, in case I have been missing something. Both of these areas appear to be poorly understood and controversial. The scientific research proves confusing and contradictory, but I will attempt to summarise what I have discovered. Some of the difficulty in carrying out research in these areas relates to different definitions of dizziness, imbalance and vertigo. Often people use the term dizziness to cover feeling light-headed, woozy, giddy, floaty, or unsteady. Vertigo is a term more often used by clinicians and scientists with a stricter definition of an illusion of movement of one's self or the environment, often spinning or rotational sensations. Individuals often mean very different things when they say they are dizzy, and research studies have often defined and categorised dizziness differently when you compare them. Patients get allocated into treatment groups in the studies in quite varying ways. Dizziness and vertigo can be related to many different underlying conditions and it is likely that these conditions need to be considered separately in research studies, but this is often not the case. Finding effective treatments for specific conditions can be compromised when patients are grouped in research studies into a general ‘dizzy patient' category. Vertigo is often the subject of research studies rather than dizziness as vertigo is often considered a defining feature of vestibular disorders (conditions related specifically to the vestibular or balance system, including the vestibular or balance organs in the inner ear), which it is sometimes possible to more clearly define. Any understanding of vertigo might not relate to symptoms of dizziness or imbalance though. I have put my overall summary of these areas first so that you might obtain some quick guidance. More specific and detailed information is then provided if you wish to read further, but these sections are denser to read. In summary There are relatively small numbers of studies into both the seasonality of dizziness and balance disorders, and complementary medicine and therapy in dizziness and imbalance. The studies tend to present conflicting results. Those that have been carried out often use unsatisfactory research methods, use small numbers of subjects, and are liable to publications bias (for example, studies published by the manufacturers of supplements). There is a distinct lack of the ‘gold standard' randomised, double-blind, controlled studies. If you are experiencing seasonal symptoms it is difficult to advise how to manage this as it is difficult to assert any control over the seasons, the weather, or barometric changes. If you are able to determine any triggers that are controllable or avoidable then that would be recommended. Hain (2015) advises to treat any allergy or migraine triggers appropriately, and to try any appropriate treatment prior to the anticipated onset of symptoms. If someone has migraine then we would expect there might be triggers that cause symptoms. Being able to identify triggers might help someone determine that they suffer from migraine. It is important to note that an individual can have migraine or vestibular migraine without any headache, which can mean this diagnosis can be missed. VEDA (2015) advice to patients is to avoid anxiety, as we know this can potentially make any symptoms of dizziness worse, and to educate themselves. I have attached a leaflet from the Meniere's Society that outlines some possible causes of dizziness and imbalance which might help you to decide whether any of the conditions fit with your symptoms. I have also attached a leaflet on
Québec Becomes First Province to Add Victoza® to the Drug Benefit Formulary* for the Treatment of Type 2 Diabetes Mississauga, ON – June 4, 2014 – Novo Nordisk today announces that the Québec government has approved the inclusion of Victoza® (liraglutide), the first once-daily human glucagon-like peptide-1 (GLP-1) analogue, to the Lists of Medications, effective June 2, 2014. The reimbursement of Victoza® by the Québec Health Insurance Board (RAMQ) will allow people living with type 2 diabetes to have access to a treatment to help better manage diabetes. Québec is the first province to provide public access to Victoza®. Effective June 2, 2014, Victoza® is covered for eligible people in Québec, in association with metformin, for the treatment of type 2 diabetes for those whose glycemic control is inadequate and whose body mass index (BMI) is greater than 30 kg/m2 when a dipeptidyl peptidase 4 (DPP-4) inhibitor is contraindicated, not tolerated or ineffective. Authorization for an initial request for treatment with Victoza® is granted for a maximum of 12 months. When submitting the first request for continuation of treatment, the physician must provide proof of a beneficial effect defined by a reduction in the glycated hemoglobin (HbA1c) of at least 0.5 per cent or by the attainment of a target value of seven per cent or less. According to the 2013 Clinical Practice Guidelines from the Canadian Diabetes Association, proper management of type 2 diabetes includes reaching target HbA1c levels within three to six months of initial treatment, reduction in rates of hypoglycemia and weight loss. If these goals are not achieved in the first three to six months, the guidelines suggest incorporating timely adjustments, such as including an anti-hyperglycemic agent.1 Victoza® is an anti-hyperglycemic agent which improves glycemic control by lowering blood glucose and HbA1C levels, with a low risk of hypoglycemia and the added benefit of weight loss.2,3 Perspectives from Key Authorities on Diabetes in Québec: "An important point for type 2 diabetes management is to ensure that most patients are reaching their HbA1c goals," said Dr. Rémi Rabasa-Lhoret, MD, PhD, associate professor, Université de Montréal. "If this is not achieved through diet and exercise and the recommended first-line therapy, metformin, an anti-hyperglycemic treatment like Victoza® should be initiated. The Québec government‟s reimbursement of Victoza® should provide some patients with access to a treatment to better manage their diabetes."