What is stiff person syndrome?

Stiff person syndrome is a rare autoimmune neurological disorder that most commonly causes muscle stiffness and painful spasms that come and go and can worsen over time. However, some people experience other symptoms such as an unsteady gait, double vision or slurred speech. SPS symptoms are thought to be related to which type of SPS a person has.

Although there is no treatment that cures stiff person syndrome, working with a specialist and maintaining symptom control can make it easier to live with the condition.

SPS most commonly develops in people ages 40 to 50, but in rare cases, it occurs in children and older adults. SPS is thought to affect one to two people in a million. However, SPS experts now consider the syndrome to be a spectrum of disorders, which means it is likely more common than originally thought, although still rare.

Stiff Person Syndrome Symptoms

Stiff person syndrome most often causes painful muscle contractions and spasms that often begin in the legs and back. Spasms can also affect the abdomen, and less often the upper trunk, arms, neck and face.

The spasms can occur in episodes, especially when a person with SPS is surprised or startled, or moves suddenly. Cold temperatures and emotional stress can also set off a muscle spasm. In some people, the spasms are brought on by certain exercises or touch.

The areas where muscle contractions occur can be stiff and board-like. Depending on which part of the body is affected, the contractions can cause:

• Difficulty walking, and the person might space the feet wide to feel more steady
• A stiff or rigid posture due to ongoing spasms in the back or trunk
• Unsteadiness and falling because of sudden spasms, which can lead to injuries
• Shortness of breath if SPS affects muscles in the chest
• Chronic pain
• Exaggerated curve (hyperlordosis) in the lower back that develops over time due to muscle tightness, and changes in the spine alignment can lead to spinal cord compression (myelopathy)
• Anxiety and agoraphobia due to falls caused by spasms

Other less typical symptoms include eye movement problems that cause double vision, speech issues and lack of coordination.

SPS symptoms do not appear in a specific order. For some people, the condition starts with cramps or stiffness in the legs that become gradually worse over weeks, months and years. Others may experience different symptoms before muscle spasms.

Types of Stiff Person Syndrome

Classic Stiff Person Syndrome

Most people with SPS have the classic form. Symptoms include stiffness and spasms in the muscles of the lower back, legs (more than arms) and sometimes abdomen. People with classic SPS may have frequent muscle spasms and walk with a stiff gait, and they can be in pain most of the day.

Partial Stiff Person Syndrome

Less commonly, people with SPS can have partial SPS, sometimes called stiff limb syndrome, stiff leg syndrome or stiff trunk syndrome. With partial SPS, tight muscles and spasms are limited to a specific area, usually one leg. For most people with partial SPS, spasms and contractions do not affect the trunk but, in some cases, they affect part of the chest or abdomen.

Stiff Person Syndrome Plus

Another less common type of the syndrome is SPS plus, which is best described as a combination of classic features (spasms and stiffness) and symptoms that suggest brainstem and/or cerebellar dysfunction. People with SPS plus can have muscle spasms and rigidity along with lack of coordination, double vision, slurred speech and other symptoms.

Other Less Common SPS Types

Other less common SPS conditions that some experts identify as part of the SPS spectrum of disorders include progressive encephalomyelitis with rigidity and myoclonus (PERM), predominant/pure cerebellar ataxia and overlapping syndromes. These types most often have symptoms and exam findings that suggest dysfunction in the brainstem, cerebellum, spinal cord and/or cerebrum.

What causes stiff person syndrome?

Much needs to be learned about how stiff person syndrome develops. It is believed to be an autoimmune disorder — in autoimmune conditions, the body’s immune system attacks healthy tissues. Similar to other autoimmune conditions, SPS affects more women than men.

Most people with stiff person syndrome have unique antibodies in their blood that are made by the body. These antibodies, which block the glutamic acid decarboxylase (GAD) enzyme, are called anti-GAD65 antibodies. GAD helps make the gamma-aminobutyric acid (GABA) neurotransmitter.

When GABA is produced in the body in the right amount, it reduces or blocks certain nerve signals. If GABA doesn’t function as expected, nerve cells can act in incorrect ways. For people with stiff person syndrome, the nervous system becomes hyperexcitable without the proper amount of GABA. This results in physical symptoms such as muscle spasms as well as psychological symptoms, including anxiety. The common triggers (e.g., being startled) of SPS symptoms are also thought to be related to GABA pathway disruption.

SPS is often associated with other autoimmune disorders, including type 1 diabetes, thyroid disorders, pernicious anemia and, less often, vitiligo.

Cancer is rarely associated with SPS (in less than 5% of cases). When cancer is found in people with SPS, it is most commonly breast or lung cancer, and it is typically identified within a few years after SPS symptoms start. Cancer associated with SPS is called paraneoplastic SPS.

Stiff Person Syndrome Diagnosis

Stiff person syndrome is very rare and complex, and its many symptoms can be caused by other, more common conditions. It may take time and several tests to diagnose SPS. If your doctor suspects that your symptoms are due to stiff person syndrome, he or she will review your detailed medical history and perform a physical exam followed by a diagnostic workup. A doctor may make a diagnosis of SPS when there is no better explanation for the symptoms and exam findings.

The following tests can help confirm an SPS diagnosis:

• Blood tests are performed to look at several factors, including the anti-GAD65 antibody. This antibody is present in up to 80% of patients who have classic SPS, and very high levels of the antibody are strong indicators of the condition. Other antibody tests associated with SPS include those to detect the glycine receptor antibody and the amphiphysin antibody. Blood work can also check for non-SPS related antibodies, hemoglobin A1c and vitamin deficiencies.
• Electromyography (EMG) evaluates the body’s nerve and muscle function. If you are taking medications to manage symptoms, such as muscle relaxers, it is important to hold off taking them before this test. This will make your symptoms worse for a short amount of time, but signs of SPS may be easier to see on the EMG.
• A lumbar puncture can help the doctor rule out other causes of your symptoms, as well as help look for SPS markers such as anti-GAD65 antibodies.
• Imaging studies can help your doctor visualize your brain, spinal cord, nerves and other body structures. Usually, imaging studies are performed to rule out other conditions that can seem like SPS. These tests may include MRI of the brain and spine and whole-body fluorodeoxyglucose-positron emission tomography (FDG-PET) with a computerized tomography (CT) scan. FDG-PET with a CT scan and mammogram are also done when there is concern about an underlying cancer.

After the diagnostic workup, your doctor will review the test results with you. If the SPS diagnosis is confirmed, the next priority is creating a custom treatment plan to address your symptoms and prevent them from worsening. Most people with SPS do not need hospitalization as part of treatment. Once the doctor has tailored a plan, you should have regular follow-up visits.

Stiff Person Syndrome Treatment

Stiff person syndrome is a complex condition that affects people in different ways. Also, different types of SPS may require different treatment approaches. A personalized SPS treatment plan typically addresses the syndrome’s autoimmune, neurologic, visual, mobility and pain aspects.

Although currently, no therapy makes stiff person syndrome go away, treatment can help minimize the severity of symptoms and improve quality of life.

Medications to Manage Symptoms

Some medications help reduce spasms, stiffness and pain for people with stiff person syndrome:

• Oral muscle relaxers, such as diazepam, clonazepam, baclofen or tizanidine
• Oral medications that are not muscle relaxers but that have some effect on the GABA neurotransmitter, including gabapentin, pregabalin and tiagabine
• Botulinum toxin, which is sometimes used when there are distinct areas of muscle spasm/tightness

Other medications, such as serotonin reuptake inhibitors (SSRIs), can be added to address physical symptoms triggered by anxiety.

Medications to Target the Immune System

Immune therapies aim to modify or suppress the immune system. Immune-based therapies for stiff person syndrome include:

• Intravenous (injected into a vein) or subcutaneous (given as an infusion under the skin) immunoglobulin
• Plasma exchange
• Intravenous immunosuppressant therapy (e.g., rituximab)
• Oral immunosuppressant therapy (e.g., mycophenolate mofetil, azathioprine)

Other Treatments

Together with medications, nonmedication therapies can make stiff person syndrome symptoms more manageable. Examples include:

• Physical therapy that focuses on stretching, deep tissue myofascial techniques, balance/gait, ultrasound therapy and heat therapy
• Aquatic therapy (very warm temperature)
• Heating pads
• Transcutaneous electrical nerve stimulation
• Stretching
• Osteopathic manipulation
• Qi gong
• Chiropractic treatments
• Massage
• Yoga
• Acupuncture
• Acupressure
• Pilates training
• Cognitive behavioral therapy

These treatments may have different effects for each person with SPS and are worth trying. A combination of medication and nonmedication treatments seems to be the most effective in minimizing the severity and intensity of symptoms over time, but it takes a while to figure out the combination that works best.

Medication to Avoid If You Have SPS

Follow your doctor’s instructions regarding medication. In general, people with stiff person syndrome should avoid:

• Serotonin-norepinephrine reuptake inhibitors such as duloxetine and venlafaxine
• Tricyclic antidepressants such as amitriptyline and nortriptyline
• Narcotics such as oxycodone, hydrocodone, morphine and morphine derivatives, and drugs that contain these substances
• Alcohol can be dangerous, especially for people who are on medications such as diazepam and clonazepam