Diagnostic dilemma: Woman's 5-year struggle with balance and walking was caused by a 'one-in-a-million' disorder

The patient: A 50-year-old woman in New York

The symptoms: The woman went to the hospital because she could not bend her legs, walk or sit up. She also had chronic lower-back pain, recurring episodes of fever and chills, and unexplained weight loss of more than 30 pounds (14 kilograms).

What happened next: The patient told doctors that, one month earlier, she had visited another hospital due to persistent back pain, stiffness in her knees, fever and significant weight loss. However, she noted that she'd actually begun feeling discomfort in her knees and back about five years before that.

Over time, increased rigidity in her right leg began affecting her balance and caused frequent falls. Doctors prescribed her ibuprofen and physical therapy, but the stiffness and pain continued.

During the patient's first hospital visit, blood tests had revealed that her white blood cell count was normal, suggesting that she was not fighting an infection. She was not producing antibodies that might have suggested she had rheumatoid arthritis, an autoimmune disease that causes joint stiffness. Nor did she have antibodies associated with other several conditions that can cause pain, numbness or stiffness in the extremities, such as HIV, Lyme disease or the autoimmune condition Sjögren's disease.

Nevertheless, over the next month, her symptoms steadily worsened until she couldn't get out of bed; she was also unable to sit up or turn to either side.

At her second hospital visit, the patient's arm had normal movement during an exam, but her leg stiffness prevented doctors from testing the range of motion in her lower extremities. When the doctors tried to flex the woman's knee, it caused contraction in her quadriceps — the large muscle in the front of the thigh — and "was painful for the patient," the doctors wrote in a report of the case.

The diagnosis: Based on her earlier test results and her past and current symptoms, the doctors suspected that the woman had developed an extremely rare autoimmune neurological disorder: stiff person syndrome (SPS).

Autoimmune disorders are characterized by the immune system attacking healthy tissues in the body. In the case of SPS, this rogue immune response targets nerve cells that control muscle contraction. Destruction of these cells disrupts signals to the muscles, causing painful muscle spasms and contractions that affect a person's balance and restrict their movement.

A clue from the woman's blood tests hinted at this condition. Doctors found high levels of antibodies that block the enzyme glutamic acid decarboxylase (GAD). Elevated levels of these antibodies are seen in up to 80% of people with SPS. The anti-GAD antibodies prevent the enzyme from producing a chemical messenger called GABA, which acts like a brake on nerve cell activity. Without enough GABA, the nerve cells that control how muscles move can go into overdrive, which can cause spasms and prevent muscles from relaxing as they normally would.

The treatment: There is no cure for SPS, but medication can help slow the disease's progression and manage symptoms. This patient received intravenous immune globulin, an antibody treatment that regulates the immune system and is often used to treat autoimmune disorders. She also received rituximab, another type of antibody that targets specific immune cells to pare down their activity.

In addition, her doctors prescribed the steroid prednisone, the anticonvulsant gabapentin and the sedative diazepam, along with a regimen of physical therapy to help relax the woman's spasming muscles.

Within a few days, the woman's condition had significantly improved. "Prior to discharge, the patient could turn in her bed unassisted, could flex her left hip and knee fully, could flex [her] right hip fully and right knee with assistance to 110 degrees, and could stand with assistance," the report authors noted.

At a three-month checkup after being discharged, the patient could stand unassisted and walk using a rolling walker. The doctors started reducing her steroid dose, but she continued taking diazepam and gabapentin as prescribed, along with a monthly dose of immune globulin and a maintenance dose of rituximab every six months.

What makes the case unique: Just 1 to 2 in 1 million people are thought to be affected by SPS each year, although by some recent estimates, that number is higher. Its rarity and the slow development of symptoms make the condition challenging for health professionals to recognize and treat. What's more, the mechanisms and progression of the disease are "incompletely understood," the case report authors noted.

Often, SPS is misidentified as other conditions, including psychiatric disorders, Parkinson's disease, multiple sclerosis, or a neurological disorder called dystonia, which causes muscle spasms.

On average, the diagnosis of SPS takes about seven years from the start of symptoms, according to the Stiff Person Syndrome Research Foundation. It is most commonly diagnosed in people ages 40 to 50, but SPS can also appear in older adults and in children. It affects about twice as many women as it does men, according to the National Institute of Neurological Disorders and Stroke.

One well-known person with SPS is singer Celine Dion. She publicly shared her diagnosis in 2022, after her illness led her to cancel multiple shows in 2021. Dion told People magazine that she was experiencing "severe and persistent muscle spasms" and that the pain caused by her condition eventually became so intense that she was sometimes unable to walk.

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