Leg Stiffness in a 60-Year-Old Woman: The Curious Cause May Be More Common Than You Think

By Robert Wilson, DO

Presentation: Stiff right leg with pain when bending the knee and ankle

A 60-year-old woman came to Cleveland Clinic in July 2014 with a stiff right leg. Bending her knee and ankle was very painful, and she had to use a walker. She was from western Pennsylvania and had seen a local neurologist who diagnosed a brainstem stroke despite there being no evidence of this on her MRI. She had also seen podiatrists and orthopaedists, who recommended surgery, and she underwent physical therapy, which didn’t relieve her symptoms. Her primary care physician referred her to Cleveland Clinic.

Evaluation

The neurological examination found her right leg to be dystonic and frozen, but her face, arms and nerves had normal function. Her presentation suggested stiff-person syndrome (SPS), a neurological disorder characterized by muscular rigidity — typically in the trunk and limbs and sometimes in the face, arms and abdomen — and muscle spasms. The syndrome is twice as prevalent in women as in men.

People with SPS usually have antibodies to glutamic acid decarboxylase (GAD), a protein involved in the synthesis of gamma-aminobutyric acid (GABA) that helps control muscle movement. Some research indicates that SPS is the result of an autoimmune response. GAD antibodies are also present in patients with other autoimmune disorders, such as diabetes. The patient had high levels of GAD antibodies — 250 U/mL, vs. a normal level of 5 U/mL — which confirmed the diagnosis of SPS.

SPS was first reported as a paraneoplastic syndrome, an autoimmune response to the presence of precancer or cancer in the body that causes an attack on the nervous system. While SPS patients usually do not have cancer, we still do a comprehensive cancer evaluation on all patients with an SPS presentation. The patient did not have cancer.

Treatment

We started treating the patient with immune-modulating intravenous immunoglobulin (IVIg), which we commonly use for SPS patients, and also prescribed the muscle relaxant baclofen. IVIg is administered monthly for three consecutive days. After three months of treatment, the patient was walking normally and today has fully regained function in her right leg.

It usually takes four to six months to see full benefit from IVIg treatment, and most patients continue to receive monthly treatments. The patient was spared unnecessary surgeries that would not have been effective.

Discussion: SPS may be more common than realized

SPS is often characterized as a rare disease, but at Cleveland Clinic we are diagnosing this condition in an increasing number of patients. It may be underreported, as patients often are not diagnosed or, as in this case, are misdiagnosed. Patients whose presentations suggest SPS should be referred to a neurologist familiar with this disorder.

Because it was initially reported in cancer patients, SPS is still strongly associated with cancer, but physicians should be aware that SPS patients usually do not have cancer. It is also important to look beyond the classic presentation of SPS — i.e., severe spine rigidity. Patients can have a variety of presentations, which may include limb stiffness, confusion and primary immune deficiency syndrome. We are diagnosing SPS at an earlier stage, before patients experience more severe symptoms.

The prognosis for SPS has greatly improved as new treatment options have been developed. Many of our patients respond well to IVIg treatment, which does not have long-term complications. Diazepam is also effective in reducing muscle stiffness. Some patients benefit from botulinum toxin injections or plasmapheresis. These are better treatment options than corticosteroids, which are not a good choice for long-term use in younger patients, and chemotherapeutic agents.

In the coming years, we hope to learn more about SPS. Research on neural autoantibodies is a growing area that has potential to increase understanding of GAD antibodies in SPS and other diseases.

Dr. Wilson is an associate staff neurologist in Cleveland Clinic’s Center for Regional Neurosciences.