STIFF PERSON SYNDROME - SYMPTOMS, DIAGNOSIS AND TREATMENT

Pop superstar Celine Dion’s recent announcement on Social Media of being diagnosed with Stiff Person Syndrome (SPS) has drawn attention to this rare neurological disorder that affects about one in a million people.

What is Stiff Person Syndrome?

Stiff Person Syndrome is a rare neurological muscle disorder that affects the nerves, causing stiff muscles and body stiffness. Stiff Person Syndrome is also known as stiff man syndrome or Moersch-Woltman syndrome.

There is no cure for SPS, but there are ways to treat and manage the illness. The ease with which the illness can be managed depends on the age of onset.

Is Stiff Person Syndrome Painful?

According to the Stiff Person Syndrome Research Foundation, SPS causes crippling pain, chronic anxiety, stiffness and muscle spasms. Sometimes, the muscle spasms are powerful enough to dislocate joints and even break bones.

How rare is Stiff Person Syndrome?

The disease is very rare, with estimates of only 1 or 2 cases per million people. This makes it difficult for doctors to diagnose SPS when a patient presents with symptoms such as chronic muscle tightness, muscle rigidity, or stiff legs. Moreover, individually, these symptoms may not necessarily be a sign of SPS, but you should check with your doctor if you are concerned.

What are the Symptoms of Stiff Person Syndrome?

Stiff muscles are the first symptoms of Stiff Person Syndrome felt in the chest and back, spreading thereafter to the rest of the abdomen and the proximal parts of the arms and legs. Eventually, the person may have difficulty moving. The following are the first two signs of Stiff Person Syndrome:

• Rigidity or stiffness of muscles
• Unpleasant muscular cramps

The signs of SPS can develop in other parts of your body or worsen over time. It may take months or even years for symptoms to appear. Some people's symptoms do not change over time. Others have gradually deteriorating symptoms, such as more severe stiffness or spasticity, which can make it difficult for them to carry out daily tasks.

Muscle Rigidity: Your trunk muscles (abdomen, chest, and back) usually become stiff initially. The rigidity is often accompanied by discomfort and pain. The degree of these symptoms can change without any reason or trigger point. Your legs and limbs may be impacted as well. Some patients experience atypical posture as their stiffness worsens, which makes it challenging to walk or move around.

Muscle Spasms: Another sign of SPS is painful muscle spasms. They can affect every part of your body or just a certain area. These spasms can last from a few seconds or minutes to several hours on occasion.

The spasms may be brought on by:

• Loud or unexpected noises
• Physical stimulation or contact
• Temperature variations, especially those in frigid situations.
• Stressful situations

SPS may also include the following:

• Stiffness in the legs: Leg stiffness is not as common as torso muscle stiffness, but muscle tightness in the legs can occur later on as the disease progresses.
• Muscle spasms: Painful spasms of muscles may happen due to tactile, auditory, or emotional triggers.
• Muscle stiffness and spasms in response to certain stimuli: Loud noises and even touch can often trigger muscle rigidity and spasms.
• Muscle pain: Muscle spasms can cause severe muscle pain leading to falls.

SPS can result in complications such as the following:

• Depression and anxiety

• Deformed joints
• Abnormal gait
• Frequent falls
• Lumbar hyperlordosis (curving of the lower back)
• Permanent problems with walking
• Inability to walk
• High blood pressure
• Increased heart rate
• High body temperature

These last three complications are more likely in more severe forms of SPS.

Some SPS sufferers have anxiety and agoraphobia, an acute fear of being outside or going into crowded or open spaces due to the unpredictability of their muscle spasm triggers. This is because avoiding the triggers of muscular spasms is more challenging when out in public.

What causes Stiff Person Syndrome?

To date, the precise cause of Stiff Person Syndrome is unknown. SPS can happen due to multiple reasons, and in some cases, the reason is not even known (Idiopathic SPS). However, it is widely believed to be an autoimmune disorder, in which your immune system kills healthy cells for unidentified reasons.

Is Stiff Person Syndrome genetic?

There is no evidence that SPS is genetic. Rather, it is thought to be an acquired neurological disease.

Types of Stiff Person Syndrome

Autoimmune SPS

Most cases of SPS (up to 80%) are the classic type, thought to be due to an autoimmune reaction. Many SPS patients produce antibodies against anti-glutamic acid decarboxylase(GAD). GAD produces Gamma-aminobutyric acid (GABA), a neurotransmitter that aids the central nervous system (spinal cord and brain) in controlling muscle action. The lack of GABA causes muscle rigidity and autoimmune disease muscle spasms.

The precise part GAD plays in the onset and progression of SPS is still unknown to researchers. It is  crucial to understand that SPS is not a prerequisite for having GAD antibodies. In truth, GAD antibodies are present in a small proportion of the general population without any negative consequences.

Paraneoplastic SPS

In rare cases (about 1% or 2%), Stiff Person Syndrome is due to cancer (paraneoplastic SPS). In people with paraneoplastic SPS, anti-amphiphysin antibodies instead of GABA antibodies are usually present.

Anti-amphiphysin antibodies destroy a protein called amphiphysin; this protein is found in synaptic vesicles.

• Synaptic vesicles are little sacs that contain neurotransmitter chemicals that transmit a nerve impulse from nerve to nerve and nerve to muscle.
• The protein amphiphysin in the synaptic vesicle is important in letting the vesicle properly attach to a nerve or muscle cell.
• In healthy cells, the vesicle attaches to the cell; the impulse is sent, and it continues to move from cell to cell.
• Without the amphiphysin, the vesicle cannot attach properly, and the impulse cannot be sent.
• The antibodies, in this case, disrupt the flow of information by attacking this protein and making it difficult for nerve impulses to travel from cell to cell.

The types of cancer where paraneoplastic SPS can happen include:

• Breast cancer
• Colon cancer
• Kidney cancer
• Lymphoma

Additionally, some SPS patients have no detectable recognized antibodies. It is still being investigated whether there are any unidentified antibodies that are responsible for SPS.

SPS may be confused with certain inflammatory problems of the nervous system and may be comorbid with other autoimmune disorders.

Autoimmune Stiff Person Syndrome often co-occurs with some other conditions, such as vitiligo (a condition where there are uneven amounts of melanin in the skin) and thyroiditis (an inflamed thyroid).

Patients with Stiff Person Syndrome often have more stiffness and pain when under stress or if they have an infection. Symptoms may also vary with different types of SPS. Two other forms of autoimmune SPS are described below:

• A subtype of SPS is Partial Stiff Person Syndrome, such as stiff limb syndrome, where only the arms and legs are affected.
• Progressive Encephalomyelitis with Rigidity and Myoclonus (PERM) is an extremely rare type of SPS. In this form of SPS, the brainstem is also involved, which causes life-threatening problems. Fortunately, PERM is even rarer than classic autoimmune SPS.

Diagnosis of Stiff Person Syndrome

If you experience muscles tightening up for no reason, checking with your doctor is important, even though SPS is a rare illness.

SPS is most often first diagnosed in people between 40 and 60 years of age. Diagnostic tests include the following:

• Stiff Person Syndrome diagnosis is best made by a blood test where antibodies are examined and measured. If SPS presents as an autoimmune neurological disease, then the GAD antibody concentration will be higher than expected.
• Electromyography (EMG) examination is also often done; this is a test of how the muscles are working in response to nerve stimuli.
• An MRI scan helps eliminate other possible diseases of the central nervous system.

Dalakas (2009) came up with six criteria for diagnosis. These are as follows:

1. Presence of autoantibodies against GAD or amphiphysin in a blood sample.
2. EMG results show continuous muscle contractions at the motor unit (nerve cell and the muscle cells it connects to).
3. Stiff muscles on the chest, back, and abdomen, and some limb stiffness.
4. Painful muscle spasms in response to touch and hearing.
5. Positive response to the use of diazepam or other benzodiazepines.
6. No other neurological disease or explanation is found to explain the symptoms.

The association between Stiff Person Syndrome and Multiple Sclerosis

SPS can be confused with multiple sclerosis, another condition involving autoimmunity and inflammation. In some cases, women who were diagnosed with multiple sclerosis (MS) were later found to have SPS.

Muscle stiffness is also sometimes a sign of fibromyalgia, or even an early sign of ALS, two conditions that may also be initially confused with SPS.

Stiff Person Syndrome and Diabetes

Anti-GAD antibodies are found in patients with type 1 diabetes and those with SPS. In at least one case, a woman who had SPS later developed type 1 diabetes.

Researchers found that 10% of type 2 diabetics also had GAD antibodies. SPS that does not involve GAD antibodies is not associated with diabetes. The association of SPS with diabetes is linked to GAD antibodies.

Stiff Person Syndrome and Pernicious Anemia

Pernicious anemia is also an autoimmune disorder that happens when the body is not able to absorb sufficient vitamin B12. Vitamin B12 is needed in red blood cell formation. Some people with SPS also have pernicious anemia.

Stiff Person Syndrome in Pregnancy

A pregnant woman with SPS can have a natural childbirth and deliver a healthy baby that does not have SPS. Furthermore, pregnant women with SPS often experience a decrease in their SPS symptoms. It is thought that pregnancy causes improved immunomodulation (regulation of the immune system).

What is the treatment for Stiff Person Syndrome?

Stiff Person Syndrome is treated by helping patients manage the condition. The following medications focus on alleviating symptoms and helping the immune system function correctly.

• Gabapentin: Helps relax muscles that are in spasm.
• Baclofen: An antispasmodic to help the muscle spasms of SPS.
• Diazepam: Helps relax the muscles and helps with anxiety.
• Tizanidine: A muscle antispasmodic medicine.
• Rituximab: A medication that lowers the antibodies that cause problems for patients with SPS.
• Intravenous immunoglobulin (IVIg): Studies have shown this to be useful in patients with autoimmune SPS.
• Corticosteroids: These are helpful but are not advisable for long-term use.
• Plasmapheresis: This is when blood plasma is removed, treated, and then returned to circulation.

What is the life expectancy for Stiff Person Syndrome?

Life expectancy ranges from about 6 to 28 years, but it depends on when the diagnosis is made and how ill the person is. So, is Stiff Person Syndrome fatal? It depends on the individual’s age.

SPS is fatal when it occurs in babies, who often do not survive longer than a few months. Stiff Person Syndrome life expectancy in middle-aged adults can be several years if treatment begins quickly.

Conclusion

Stiff Person Syndrome is most often an autoimmune neurological disease. Rarely the illness occurs if you have cancer, and in some cases, the cause is unknown. Like other neurological muscle disorders, SPS is debilitating and needs proper treatment to improve symptoms and life expectancies.

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Sources:

• Barker, R. A., Revesz, T., Thom, M., Marsden, C. D., & Brown, P. (1998). Review of 23 patients affected by the stiff man syndrome: clinical subdivision into stiff trunk (man) syndrome, stiff limb syndrome, and progressive encephalomyelitis with rigidity. Journal of Neurology, Neurosurgery & Psychiatry, 65(5), 633-640. https://jnnp.bmj.com/content/65/5/633
• Czempik, P. F., Gawryluk, J., Wiórek, A., Krzystanek, E., & Krzych, Ł. J. (2021). Efficacy and safety of therapeutic plasma exchange in Stiff Person Syndrome. Open Medicine, 16(1), 526-531. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8010154/
• Dalakas, M. C. (2005). The role of IVIg in the treatment of patients with Stiff Person Syndrome and other neurological diseases associated with anti-GAD antibodies. Journal of Neurology, 252(1), i19-i25. https://pubmed.ncbi.nlm.nih.gov/15959668
• Dalakas, M. C. (2009). Stiff Person Syndrome: advances in pathogenesis and therapeutic interventions. Current Treatment Options in Neurology, 11(2), 102-110. https://link.springer.com/article/10.1007/s11940-009-0013-9
• Rubin, M. (2022). Stiff-person syndrome (stiff-man syndrome). https://www.msdmanuals.com/professional/neurologic-disorders/peripheral-nervous-system-and-motor-unit-disorders/stiff-person-syndrome

 

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