Stiff-person syndrome and spectrum disorders

Diagnosis starts with a neurological exam and a detailed history. Doctors look for stiffness in the trunk and legs, an arched lower back (hyperlordosis), unexplained falls, and spasms set off by noise, touch or a sudden startle. A blood test measures antibodies to GAD65. In SPS the level is usually far higher than in type 1 diabetes. Finding GAD antibodies in the spinal fluid also supports the diagnosis. Doctors may test for glycine receptor and amphiphysin antibodies too.

An electromyography (EMG) test records electrical activity in muscles. In SPS it can show stiff muscles firing without a break, with opposing muscles tightening at the same time. Muscle relaxers such as diazepam can hide this finding. MRI of the brain and spine helps rule out other causes of stiffness. To look for a linked cancer, doctors typically use body CT scans and breast imaging, and sometimes a PET-CT scan.

Getting the right diagnosis is often slow. SPS is rare and can look like other conditions, and other conditions can look like SPS. At Mayo Clinic, 173 people were referred from 2016 to 2021 because SPS was suspected. Only 48 of them (28%) turned out to have it. There are no agreed diagnostic criteria yet, though expert groups have proposed some.

Medicines that relax muscles or calm spasms, such as diazepam, baclofen and gabapentin, can ease symptoms. Physical and speech therapy can help people adapt and keep function. When SPS is linked to a cancer, treating the cancer comes first.

IVIG, a treatment made from antibodies donated by thousands of healthy people, reduced stiffness and sensitivity to noise and touch in an NIH-funded study. Other immune treatments, such as plasma exchange and rituximab, are sometimes used. A 2025 review found that much of the evidence for SPS treatments comes from small studies.

An autologous stem cell transplant uses strong chemotherapy and other drugs to reset the immune system, then gives back the person’s own stored blood-forming cells. In a US trial of 23 people, no one died from the treatment. About three in four responded, meaning they could cut their spasm medicines at least in half or stop them. But the benefit was uneven and came mainly in people with on-and-off spasms and normal reflexes. The trial was stopped early because the researchers could not predict who would respond, relapse or go into remission, and an expert commentary called its benefits limited.

A UK center treated four people with severe SPS between 2015 and 2019, and all four improved. These groups are very small, and the high-dose chemotherapy carries serious risks such as infection.

SPS tends to get worse over time, but how fast and how severe it gets differs widely. In a Mayo Clinic study, people who needed help on both sides to walk at their worst point, and older people, tended to do worse. When SPS is linked to a cancer, the stage of the cancer at diagnosis often shapes recovery.

Treatment helps many people. A Mayo Clinic group of 54 people was followed for a median of 9 years. Of those who had immune therapy, 82% reported improvement. At their last visit, about 7 in 10 could look after themselves without help, though about 4 in 10 still needed help on both sides to walk. Falls remain a real risk, because they can cause serious injuries.

Research on survival is limited. A national study from Denmark followed 30 people diagnosed from 2001 to 2022 and found higher death rates than in the general population. The group was very small, so the numbers are uncertain.