(Marco’s first two Neuroinflammatory blogs lead us into sensory gating and glutatmate excitoxoicity and now he dives into a rare neurological disorder called Stiff Person Syndrome (SPS) (sometimes misdiagnosed as Fibromyalgia) with factors (high glutamate levels, increased sensitivity to stimulation, autoimmune manifestations, possibly infectious onset) that makes it an intriguing, if unusual, possible cousin of ME/CFS/FM
Let’s see what we can learn from another disorder with a funny name and a decided unfunny outcome. For myself overexertion is a call for increased sensitivity to stimulation, a high ‘startle reflex’, stiff, painful muscles and a decided downturn in coordination; a stiff person indeed. Cort )
Glutamate/GABA Imbalance and Stiff Person Syndrome
In Parts I and II, I proposed that the same neuroinflammatory vicious cycle underlies a range of neurological, psychiatric and neurodegenerative conditions that may result in a variety of symptoms and hence different diagnostic labels. I have suggested that ME/CFS may be one of these neuroinflammatory conditions.
Intuitively, it is relatively easy to accept that neuroinflammation can result in a wide range of sensory processing problems, ‘mood’ disorders and cognitive symptoms however for many, if not most of us, ME/CFS is a profoundly ‘physical’ condition characterised by muscular pain, exercise intolerance and post-exertional malaise.
It may not be quite so easy to accept that an imbalance in the neurotransmitters glutamate and GABA could cause many of the symptoms found in ME/CFS but the disorder below demonstrates that they’re clearly capable of causing those symptoms and more.
Stiff Person Syndrome
An extreme example of the potential impact a glutamate/GABA imbalance can have is the unfortunately named stiff person syndrome (SPS). This relatively benign name belies the true nature of a debilitating and at times fatal progressive illness (Duddy, Baker, 2009). Stiff person syndrome (SPS) is rare, affecting only one in one million of the population (Wikipedia) and as a consequence is often misdiagnosed but it shares some interesting characteristics with ME/CFS/FM type disorders.
This disorder is characterised by the sudden onset of muscle rigidity severe enough to cause muscle and joint damage and even spontaneous bone fractures. In the course of an attack the muscles of SPS sufferers can become so contracted and rigid that they’ll fall over suddenly and are unable to protect themselves from injury. Consequently they frequently end up at hospital for treatment of cuts, bruises and fractures. These seizure-like episodes are impossible to predict and often leave SPS sufferers confined to their homes.
The National Institutes of Health, National Institute of Neurological Disorders and Stroke (NINDS) provide a concise summary of the disease (paragraph breaks and bolding added):
“What is Stiff-Person Syndrome?
Stiff-person syndrome (SPS) is a rare neurological disorder with features of an autoimmune disease. SPS is characterized by fluctuating muscle rigidity in the trunk and limbs and a heightened sensitivity to stimuli such as noise, touch, and emotional distress, which can set off muscle spasms. Abnormal postures, often hunched over and stiffened, are characteristic of the disorder.
People with SPS can be too disabled to walk or move, or they are afraid to leave the house because street noises, such as the sound of a horn, can trigger spasms and falls. SPS affects twice as many women as men.
It is frequently associated with other autoimmune diseases such as diabetes, thyroiditis, vitiligo, and pernicious anemia. Scientists don’t yet understand what causes SPS, but research indicates that it is the result of an autoimmune response gone awry in the brain and spinal cord.
The disorder is often misdiagnosed as Parkinson’s disease, multiple sclerosis, fibromyalgia, psychosomatic illness, or anxiety and phobia. A definitive diagnosis can be made with a blood test that measures the level of glutamic acid decarboxylase (GAD) antibodies in the blood.
People with SPS have elevated levels of GAD, an antibody that works against an enzyme involved in the synthesis of an important neurotransmitter in the brain (GABA).
Is there any treatment?
People with SPS respond to high doses of diazepam and several anti-convulsants, gabapentin and tiagabine. A recent study funded by the NINDS demonstrated the effectiveness of intravenous immunoglobulin (IVIg) treatment in reducing stiffness and lowering sensitivity to noise, touch, and stress in people with SPS.
What is the prognosis?
Treatment with IVIG, anti-anxiety drugs, muscle relaxants, anti-convulsants, and pain relievers will improve the symptoms of SPS, but will not cure the disorder. Most individuals with SPS have frequent falls and because they lack the normal defensive reflexes; injuries can be severe. With appropriate treatment, the symptoms are usually well controlled.
What research is being done?
The National Institute of Neurological Disorders and Stroke (NINDS) conducts research related to SPS in its laboratories at the National Institutes of Health (NIH), and also supports additional research through grants to major medical institutions across the country. A study using the drug Rituximab proved ineffective in treating individuals with the disorder. Current research is focused on understanding the cause of the disease and the role of the anti-GAD antibodies.”
In the context of the previous discussion, it is worth re-emphasizing some similarities between Stiff Person Syndrome/ME/CFS, Fibromyalgia and other ‘neuro-inflammatory’ conditions :
- SPS misdiagnoses include Parkinson’s, fibromyalgia and a range of anxiety disorders including phobia and psychogenic movement disorders;
- SPS is considered to be an autoimmune disease involving raised levels of glutamic acid decarboxylase (GAD) antibodies – which effectively lowers levels of GABA, taking the brakes off the excitatory neurotransmitter glutamate
- like many autoimmune diseases SPS affects twice as many women as men;
- Like ME/CFS, SPS patients are reported to respond to Rituximab: (in a series of case studies inc Bates et al, 2005, Fekete and Jankovic, 2012) although these results have yet to be replicated in clinical trials;
- Current treatments contain several drugs used in ME/CFS such as anticonvulsants, gabapentin, tiageine, IVIG and some that might work such as Baclofen (Whelan, 1980 etc) and diazepam;
- Given reports of metabolic syndrome and one doctor’s report of increased rates of diabetes in his practice, it’s intriguing that SPS effects diabetics at a much higher rate than the general population;
- most intriguingly, SPS attacks (exacerbation of symptoms) can be triggered by sensory input including loud noises, emotions or stress or exercise (Rodgers-Neame); ie, it appears to have a sensory gating component. There appears to be no literature investigating a sensory gating deficit (as described in Part I) in SPS. SPS patients, however, have been shown to have an exaggerated acoustic startle response. (Matsumoto et al, 1994)
An imbalance in the excitatory and inhibitory neurotransmitters glutamate and GABA is implicated in a wide range of neuropsychiatric (ASD, schizophrenia, bipolar disorder, major depressive disorder, OCD etc) and in pain (fibromyalgia, interstitial cystitis, IBS) and movement disorders (Parkinson’s, Huntington’s) and perhaps chronic fatigue syndrome (ME/CFS).
Current research provides hints that a similar etiology may underlie a range of ‘neuroinflammatory’ conditions including ME/CFS.
- Get the References here
- Part II of Stiff Person Syndrome examining at anxiety, autoimmunity and infection in SPS will be up soon.
The Neuroinflammation Series from Marco
- Part I: Not Fatigue After All? New Model Suggests Other Symptoms Better Explain Chronic Fatigue Syndrome (ME/CFS)
- Part II: Glutamate – One More Piece in the Chronic Fatigue Syndrome (ME/CFS) Puzzle? The Neuroinflammatory Series