Stiff Person Syndrome

Overview

Stiff person syndrome, sometimes called SPS, is a rare and progressive neurological disorder marked by episodes of muscle stiffness—known as rigidity—and debilitating muscle spasms that can be isolated to an area of the body or involve the entire body. Stimuli like physical touch, noise, or emotional distress can trigger these painful spasms. They can also happen entirely at random.

Over time, people with stiff person syndrome have increased difficulty performing day-to-day activities. They might develop increased curvature of the lumbar spine, often described as walking like a statue, or find it challenging to walk or even move. People with stiff person syndrome are also prone to falling because they don’t have the usual reflexes that allow them to catch themselves. 

Stiff person syndrome typically progresses slowly—symptoms can be mild and intermittent for months or years, but they often become more intense, frequent, and prolonged over time. Treatment can help symptoms stabilize or improve. 

What causes stiff person syndrome?

Stiff person syndrome is an autoimmune disorder, and the majority of patients diagnosed with stiff person syndrome have antibodies to glutamic acid decarboxylase (anti-GAD), an enzyme responsible for making gamma-aminobutyric acid (GABA). GABA is a pivotal neurotransmitter that helps our bodies control muscle movements. It is unclear if anti-GAD directly causes the symptoms of stiff person syndrome or if it represents a marker of an immune response. Close to one third of people with anti-GAD stiff person syndrome have type 1 diabetes mellitus, but other autoimmune co-morbidities (thyroid-related disorders, pernicious anemia, and vitiligo) may also be seen. 

However, doctors sometimes identify antibodies other than anti-GAD in people with stiff person syndrome, and some of these antibodies can be associated with cancer (paraneoplastic stiff person syndrome) and may help predict the treatment response. It is therefore essential to screen for multiple different antibodies in someone with suspected stiff person syndrome.

Whether located in one region of the body or involving the whole body, these muscle spasms can be agonizing. When the legs are affected by a spasm, falling becomes a concern. Spasms that affect the chest and respiratory muscles are frequently severe and may require emergency medical treatment.

Stiff Person Syndrome Diagnosis 

Stiff person syndrome can be challenging to diagnose, and doctors frequently misdiagnose it as Parkinson’s disease, multiple sclerosis, fibromyalgia, psychosomatic illness, or anxiety. Your care team can make a conclusive diagnosis through a combination of symptoms, the presence of co-morbidities, a physical examination, blood and spinal fluid tests measuring anti-GAD and other antibodies, electromyography (EMG), and imaging studies. 

Typically, anti-GAD antibodies are high in those with stiff person syndrome—up to 10 times the normal amount. While doctors also see high anti-GAD levels in people with diabetes, levels indicating stiff person syndrome are at least 10 times above the range for diabetes. Importantly, slightly elevated levels of anti-GAD antibodies can be seen in healthy individuals or as a non-specific marker in people without stiff person syndrome. Misinterpretation of slightly elevated anti-GAD antibody levels represents a widespread reason for misdiagnosis of stiff person syndrome.

Electromyography (EMG) can also be used to record the electrical activity of voluntary muscles at rest and during contraction, while magnetic resonance imaging (MRI) helps rule out the presence of other conditions. Computerized tomography (CT) and lumbar puncture (spinal tap) may also be used. 

• Incomplete Stiff Person Syndrome Variants: Variants of the classic subtype involve specific parts of the body, such as the face (stiff face syndrome), trunk (stiff trunk syndrome), or are isolated to the legs. These presentations are often misdiagnosed, frequently as a functional disorder.

• Progressive Encephalomyelitis with Rigidity and Myoclonus (PERM): PERM is a more severe stiff person syndrome variant that causes reduced consciousness, ataxia, eye movement issues, and other issues that stem from dysfunction of the autonomic nervous system. PERM is a true medical emergency, often requiring full-time management in a hospital setting.

Stiff Person Syndrome Treatments

Stiff person syndrome is a chronic condition that has no cure. That said, symptoms can be managed, depending on their severity.

The medications most often recruited to reduce or alleviate stiff person syndrome symptoms include:

• Symptomatic Therapies
  • Muscle relaxants, such as baclofen, tizanidine, and methocarbamol, are often tried first to reduce the risk of dependence on benzodiazepines, and are effective in reducing muscle spasms and stiffness.
  • GABA receptor modulators, such as benzodiazepines (Valium, Klonopin, Xanax, etc.).
  • Anticonvulsants, such as gabapentin and levetiracetam.
  • Other treatments, including heat therapy, hydrotherapy, massage therapy, and acupuncture, may also offer symptomatic relief.
• Immunomodulatory (disease-modifying) therapies
  • Intravenous immunoglobulins (IVIG)
  • Plasma exchange
  • Corticosteroids
  • Rituximab
  • Stem cell transplantation