Science1 publisher2 min readPublished
Stiff person syndrome lay behind a New York woman's five years of leg stiffness and falls
New York doctors diagnosed stiff person syndrome, estimated at 1 to 2 cases per million a year, about five years after a 50-year-old woman's symptoms began. Her condition improved within days of treatment, though one case cannot show which of her six treatments helped or why the diagnosis took so long.
The Scientist · Science desk
What happened
- Rigidity in her right leg upset her balance and caused frequent falls, and the ibuprofen and physical therapy she was prescribed did not relieve the stiffness or pain.
- Tests at a first hospital showed a normal white cell count and none of the antibodies linked to rheumatoid arthritis, HIV, Lyme disease or Sjogren's disease.
- A month later she arrived at a second hospital unable to bend her legs, walk or sit up, with recurring fever and chills and more than 30 pounds of unexplained weight loss.
- Doctors there found high levels of antibodies that block the enzyme GAD, the clue that pointed them to stiff person syndrome.
- Three months after discharge she could stand without help and walk with a rolling walker.
Compiled by The ScientistSomething wrong?How this is made
Why it matters
- constraint Elevated anti-GAD antibodies appear in up to 80% of people with the syndrome. At least one patient in five lacks the marker, so a negative test cannot rule the disorder out.
- decision The diagnosis drew on earlier tests that found nothing. Once first-line treatment has failed, a clean workup for common causes is a reason to widen the search to rarer ones.
- cost With no cure, her gains depend on continuing treatment: monthly immune globulin, rituximab every six months, and ongoing diazepam and gabapentin while her steroid is tapered.
The antibody result and the bedside exam point the same way. GAD is the enzyme that makes GABA, a chemical messenger that acts like a brake on nerve cell activity, and the antibodies her doctors found stop the enzyme from making it [12]. Without enough GABA, the nerve cells that control muscle movement go into overdrive, and muscles spasm and fail to relax [12]. In stiff person syndrome, those are the cells the immune system attacks [9]. When doctors tried to flex her knee, her quadriceps contracted, and the attempt "was painful for the patient," they wrote in the case report [7].
About five years and one month passed between her first knee and back discomfort and the diagnosis [2]. The last of those months was the steepest. She declined until she could not get out of bed, sit up or turn to either side [6]. Live Science's summary of the case does not say how many clinicians she saw in the earlier years or which conditions they considered. So the record documents the delay but does not explain it. I'd take the case as evidence that the syndrome can sit for years behind knee and back pain that looks ordinary [3][4]. Rarity is part of the context, though the figure is loose. Live Science reports that stiff person syndrome is thought to affect 1 to 2 people per million each year, and that some recent estimates run higher [18].
Her treatment is harder to read. She received intravenous immune globulin and rituximab, two antibody therapies aimed at the immune system, plus prednisone, gabapentin, diazepam and physical therapy [13]. That makes six interventions in all [3]. Within a few days she had improved significantly [14]. According to the report's authors, before discharge she could turn in her bed unassisted, fully flex her left hip and knee, fully flex her right hip, bend her right knee to 110 degrees with assistance, and stand with assistance [15].
The recovery came after the treatment started. The thing this doesn't tell you is which of the six produced it, because the report follows one patient and has no comparison group [1][3].
What to watch
- Publication details of the underlying case report, including how many clinicians saw the patient in the five years before diagnosis and what they suspected.
- Incidence studies that test the recent estimates putting stiff person syndrome above 1 to 2 cases per million people a year.
- Her later follow-up once prednisone is fully withdrawn.