What is Stiff Person Syndrome?
Stiff person syndrome (SPS) is a rare condition affecting the central nervous system that leads to stiffness and muscle spasms that can be triggered by stimuli, such as a sudden noise or touch. These spasms typically affect the muscles in the middle of the body, upper arms, and thighs. The syndrome was first reported in 1956 by Frederick Moersch and Henry Woltman, who studied 14 patients showing steady tightening sensations in the spine, abdomen, and thigh muscles. This condition, also known as Moersch-Woltman Syndrome, was formerly named stiff-man syndrome.
There are mainly three types of SPS – Classic SPS, Partial SPS variants, and Progressive encephalomyelitis with rigidity and myoclonus (PERM). Classic SPS is the most common type, found in 70 to 80% of SPS patients, and is linked to the presence of anti-glutamic acid decarboxylase (anti-GAD) antibodies, which are proteins produced by the immune system that mistakenly target and react with a person’s own tissues or organs. This condition develops slowly and tends to worsen over time, often leading to permanent disability and in some cases can be fatal. SPS often occurs alongside other autoimmune disorders, diseases where your body’s immune system attacks its own cells, including Type 1 Diabetes, autoimmune thyroid disease, pernicious anemia, celiac disease, and vitiligo, a condition where skin loses its color in patches.
The different clinical variants of SPS include stiff limb syndrome, jerky SPS, cerebellar variant, SPS with epilepsy, and dystonia, a movement disorder in which a person’s muscles contract uncontrollably. There is also a variant associated with various types of cancer, including cancers of the breast, colon, thyroid, and lung, and lymphomas, generally shows symptoms before the cancer itself is detected. The form known as PERM, also first characterized in 1956 and called SPS-plus syndrome includes muscle stiffness, widespread involuntary jerking of muscles (myoclonus), and significant autonomic instability, a condition where your autonomic nervous system, which controls your body’s automatic functions like heart rate, blood pressure, and digestion, doesn’t work as it should.
Increasingly, this disorder is being linked to the immune system. Discovering associated antibodies, its coexistence with other autoimmune diseases and cancers has greatly improved our understanding of how the disease works and how best to treat it.
What Causes Stiff Person Syndrome?
Stiff person syndrome (SPS) is a disorder where your body’s immune system attacks its own cells and tissues, specifically those within areas of your nervous system. These attacks interfere with certain inhibitory synapses, which are the areas where nerve cells communicate with each other. This results in faulty communication due to low levels of a neurotransmitter, essentially the brain’s chemical messenger, called gamma-aminobutyric acid (GABA).
SPS can sometimes be associated with the development of certain types of cancer. This form, known as paraneoplastic SPS, only accounts for 5% to 10% of all cases. It’s usually characterized by the presence of antibodies against amphiphysin and, less frequently, against gephyrin. The most common cancers associated with this form of SPS include breast cancer, colon cancer, small cell lung cancer, thymus and thyroid gland cancers, and Hodgkin’s lymphoma.
Genes also seem to play a role in SPS. People with specific genes, known as DQB1 and DRB1 MHC-II alleles, are found to be more likely to develop both the idiopathic (of unknown cause) and paraneoplastic variants of SPS.
Risk Factors and Frequency for Stiff Person Syndrome
Classic SPS, or Stiff Person Syndrome, is pretty rare in the general population, typically affecting only 1 to 2 out of every million people. It’s more common in females, who tend to get it twice as often as males. This is true regardless of race. Most people start showing symptoms when they’re between 20 and 60 years old, usually in their thirties or forties.
There’s another form of this called PERM, which commonly affects older adults in their fifties and sixties. It’s also pretty rare for children to have SPS, as only about 5% of cases occur in kids.
Signs and Symptoms of Stiff Person Syndrome
Classic Stiff-Person Syndrome, or SPS, is a health condition that starts off slow but gradually worsens over several months. Initially, patients may experience a stiffness or rigid feeling in the muscles located in the middle and lower portions of the back. This is due to both the abdominal and back muscles contracting continuously. This can lead to difficulties in bending and turning, with many patients describing their walking style as similar to that of a “tin-man”. The stiffness can then spread to the upper and lower body.
Eventually, this can lead to multiple long-term skeletal abnormalities such as an increased inward curvature of the lower back, joint deformities, and abnormal posturing. This results in a “statue-like” appearance. This could be accompanied with difficulties in walking and numerous falls. Additionally, individuals may develop painful muscle spasms throughout the body and overly reactive startle responses triggered by unexpected touch, sights, or sounds as well as intense emotions. Many patients also struggle with depression, specific fears or phobias, fear of open spaces, anxiety especially related to the fear of triggering spasms, and pathological startling.
Often, due to the accompanying psychiatric conditions, SPS gets diagnosed incorrectly as a neurological disorder or a primary psychiatric condition. The symptoms of SPS are often more pronounced during the day and can be worse with physical and emotional stress, cold weather, and infection. Muscles in the hands, feet, and face are usually unaffected until the later stages of the disease. The frequency and duration of painful spasms fluctuate. In severe cases, these spasms can last for hours, requiring emergency medical attention and treatment with intravenous muscle relaxants. In rare occurrences, the muscles used for breathing can also be affected.
Partial SPS Variants include Stiff limb syndrome, where spasms occur in an isolated limb, usually leaving the trunk muscles unaffected. The stiff limb may even take an abnormal posture resembling dystonia. While over time stiffness may involve other muscles, it typically remains most severe in one limb. Then, there’s also Stiff trunk syndrome where spasms affect only the mid-body region, leaving limbs unaffected. There are rare cases with irregularities affecting eye movement. SPS-Cer Variant presents itself with a lack of coordination, an unstable walk, and irregular, jerky eye movements, all occurring along with stiffness.
At times, SPS can appear as a byproduct of cancer (Paraneoplastic SPS) and more often has greater stiffness in the neck and upper body. Patients usually show a quicker response to therapy and a significant improvement once the cancer is removed.
Progressive Encephalomyelitis with Rigidity and Myoclonus (PERM) is a more severe form of SPS. It usually manifests as a series of flare-ups and receding periods with far-reaching involvement of different parts of the brain and spinal cord, including the brainstem. This could lead to decreased or altered consciousness, abnormal functioning of the eye muscles, in-coordination, and failure of the body’s automatic nervous system.
Testing for Stiff Person Syndrome
A diagnosis of Stiff Person Syndrome (SPS), a rare neurological disorder characterized mostly by stiffness and muscle spasms, is usually made after a thorough physical examination by a doctor, supported by specific tests and laboratory results.
The most commonly used criteria to diagnose SPS were revised by Dalakas in 2009 and include:
- Stiffness in the muscles of the limbs, abdomen, and lower back region
- Spasms that can be triggered by sudden touches or sounds
- Evidence of non-stop muscle activity even when the person is trying to relax, as demonstrated by a test called electromyography (EMG)
- No other neurological issues that could explain the symptoms
- The presence of specific antibodies in the blood (anti-GAD65 or anti-amphiphysin)
- Improvement in symptoms after taking a group of medicines called benzodiazepines
High amounts of anti-GAD antibodies (more than 10,000 IU/mL) in the blood can support the diagnosis of SPS. A cerebrospinal fluid (CSF) test, where a sample of the fluid surrounding your brain and spinal cord is analyzed, is usually normal in SPS. In a variant of SPS called progressive encephalomyelitis with rigidity and myoclonus (PERM), the CSF test may show a slight increase in cells, elevated protein levels, and the presence of specific antibodies.
Tests like nerve conduction studies and needle EMG are also useful. They help rule out other diseases that affect the nerves and muscles, and confirm the diagnosis of SPS. These tests typically show continuous muscle activity even when the person is trying to relax.
Scans of the brain and spinal cord, such as MRI, are often carried out to rule out other causes of muscle stiffness and rigidity. These scans are usually normal in SPS. However, a special type of MRI test called magnetic resonance spectroscopy can sometimes show changes in the levels of a brain chemical called GABA.
If a symptom involves cancer (known as a paraneoplastic variant), it’s important to check for specific antibodies and carry out tests to look for cancer. Since about 35% of people diagnosed with SPS also have type 1 diabetes, and about 5% have a thyroid autoimmune disease, doctors often test for these conditions as well.
Treatment Options for Stiff Person Syndrome
Treatment options for Stiff Person Syndrome (SPS), a rare neurological disorder, can be grouped into two main types: treatments to help with symptoms and treatments meant to change the progression of the disease, which is often referred to as immunotherapy.
Firstly, symptomatic management is typically used when patients are first diagnosed with the disease. This approach is aimed at reducing stiffness, rigidity, and painful muscle spasms, which are common symptoms in SPS. It’s often achieved by using medications that enhance the effects of GABA, a neurotransmitter (brain chemical) responsible for reducing the activity of nerve cells in the brain. Commonly used medications include benzodiazepines (a type of sedative), baclofen (a muscle relaxer), gabapentin (a nerve pain medication), and vigabatrin (an antiepileptic drug). Diazepam, a type of benzodiazepine, is usually given to patients with SPS, but caution is needed as tolerance and addiction to this medication can develop over time. Baclofen is also a popular choice. Other muscle relaxers like dantrolene and tizanidine are used as well. Treatments for any accompanying conditions, like seizures (abnormal electrical activity in the brain) or mental health problems, are also part of the symptom management plan.
Secondly, disease-modifying therapy is used to target the immune system to try and reduce or eliminate autoantibodies (antibodies that mistakenly attack the body’s own cells). For this, Intravenous Immunoglobulin (IVIG) therapy is utilized and is known to help improve patients’ conditions for up to a year after treatment. However, plasma exchange therapy (a procedure where the plasma in your blood is replaced with new plasma or a plasma substitute) isn’t as well understood, and some patients have only had temporary or no improvement after this intervention.
Certain drugs such as corticosteroids are debatable in their effectiveness for SPS. Rituximab, a type of drug that targets specific cells in the immune system, has shown long-lasting benefits for some patients, although it’s only been tested in non-randomized trials. Other drugs that work on the immune system, including mycophenolate mofetil, azathioprine, cyclophosphamide, cyclosporine, tacrolimus, and sirolimus, have been used with different outcomes.
What else can Stiff Person Syndrome be?
When a doctor is diagnosing Stiff Person Syndrome (SPS), they have to consider a wide range of other conditions that could be causing similar symptoms. These include:
- Myelopathy: This is a condition where the spinal cord gets compressed or inflamed, and it could be caused by several factors, such as infections or inadequate blood supply,
- Myopathies and muscular dystrophies: These are a group of diseases that cause muscle weakness or loss of muscle tissue,
- Parkinson’s disease and related conditions,
- Autoimmune encephalitis: This is a rare condition where the body’s immune system mistakenly attacks the brain,
- Primary lateral sclerosis: This is a rare type of motor neuron disease that leads to muscle weakness and disability,
- Progressive multiple sclerosis: This is a type of multiple sclerosis where symptoms steadily worsen over time without periods of recovery,
- Generalized or focal dystonia: This is a type of movement disorder that causes muscle contractions,
- Neuromyotonia: This is a condition where the muscles spontaneously contract,
- Isaac syndrome: This is a rare neurological disorder associated with continuous muscle stiffness, cramps, and twitching,
- Ankylosing spondylitis: This is an inflammatory arthritis affecting the spine and large joints,
- Hereditary spastic paraplegia: This is a group of inherited disorders that cause stiffness and weakness in the leg muscles,
- Hereditary hyperekplexia: This is a condition where the person has an exaggerated startle reaction,
- Leukodystrophies: These are rare, progressive, metabolic, genetic diseases that affect the brain, spinal cord and often the peripheral nerves,
- Neuroleptic malignant syndrome, serotonin syndrome, or malignant hypothermia: These are potentially life-threatening conditions triggered by certain medications,
- Tetanus: This is a serious bacterial infection that causes muscle stiffness and spasms, particularly in the jaw and neck,
- Functional neurological disorder: This is a condition where there’s a problem with the functioning of the nervous system.
It’s important for doctors to carefully rule out these and other similar conditions when diagnosing SPS.
What to expect with Stiff Person Syndrome
The future health and wellbeing of patients with Stiff Person Syndrome (SPS) can be influenced by various factors. These include the severity of their symptoms, the length of time the symptoms have been present, whether the patient also has cancer, and how well they respond to treatment. It’s incredibly important to begin treatment as soon as possible, as this can help to slow down the condition’s progression and prevent serious long-term issues.
Most patients who undergo treatment for SPS see improvement in their condition, but they may still experience periods of worsening symptoms due to physical factors or emotional stress. Despite the various treatments available, some patients will unfortunately experience their disease getting worse over time. This can result in permanent damage to their bones and muscles, the inability to walk, and disability.
From one ongoing study, it was found that only 19% of people with SPS were able to work after 4 years. The physical and social restrictions brought on by the condition have a significant impact on patients’ quality of life.
Possible Complications When Diagnosed with Stiff Person Syndrome
People with Stiff Person Syndrome (SPS) are more likely to have issues related to the bones and muscles. These can include an overly curved lower back, abnormal joint shapes, and muscle shrinkage. These problems can cause unusual body positions and walking patterns, which increase the chances of falling. As SPS gets worse, sudden touch or sounds could cause a disease of the involuntary nervous system. This could lead to symptoms like rapid heartbeat, high blood pressure, and a high body temperature.
Common Issues Associated with Stiff Person Syndrome:
- Overly curved lower back
- Abnormal joint shapes
- Muscle shrinkage
- Unusual body positions and walking patterns
- Increase in chances of falling
- Rapid heartbeat
- High blood pressure
- High body temperature
