Blood Treatment Safe, Promising for Stiff-Person Syndrome


A small preliminary study suggests that therapeutic plasmapheresis (TPO) is safe, well tolerated, and improves symptoms in the majority of patients with Stiffness Spectrum Disorders (SPSD), a group of rare neuroimmunological diseases.

Dr. Scott D. Newsom

While the intervention may seem “scary” because it requires central venous access and sometimes hospitalization, the new findings suggest it should only be considered for the “right” patients, researcher Scott D. Newsom, DO, Associate Professor of Neurology, Johns. Hopkins University in Baltimore, Maryland told Medscape Medical News.


“We have shown that this is a safe treatment intervention and the side effects are few and manageable,” Newsom said.

The results were presented at the American Academy of Neurology (AAN) Summer Conference: Review of the Year in Autoimmune Neurology and Neurology, held on July 15 and 16 in San Francisco, California.

GABAergic pathway

Patients with SPSD have antibodies that target parts of the nervous system involved in the GABAergic pathway. Gamma-aminobutyric acid (GABA) is the main inhibitory neurotransmitter in the central nervous system.

The classic phenotype predominantly affects the musculoskeletal system with symptoms including painful spasms and rigidity of the trunk and limbs. Individuals with this phenotype may have gait problems, falls, and myelopathic signs on examination.

A less common phenotype is SPS plus. It includes classic musculoskeletal symptoms as well as involvement of the cerebellum and/or brainstem. Patients with this phenotype may experience double vision and problems with speech and swallowing.


As part of the side effects of low GABA levels, anxiety and other mood symptoms are “incredibly common,” Newsom notes. Patients may suffer from sudden, unexpected movements or sounds, and some experience agoraphobia because they are afraid of falling if they go outside.

Most people with SPSD are middle-aged white women; but, as with other immune-related conditions, this condition does occur in patients from different backgrounds and in different age groups.

Treatment for SPSD usually includes symptomatic therapy. Benzodiazepines are the cornerstone of such therapy given their primary mechanism of action to enhance GABAergic pathways and their positive response to treatment.


Patients usually also require immune therapy such as intravenous immunoglobulin (IVIG) and subcutaneous immunoglobulin, or immunosuppressants such as rituximab.

Opioids and drugs with norepinephrine reuptake inhibition are not recommended for patients with SPSD.

Non-drug interventions are also helpful and may include stretching and balancing exercises, heat or water therapy, deep tissue massage, manual manipulation, acupuncture, and acupressure.

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“Icing on the Cake”

TPO, also known as plasmapheresis, involves separating and removing plasma from the blood and replacing it with an albumin solution. The idea, according to Newsom, is to remove antibodies and proteins that contribute to immune system dysregulation.

He noted that the main goal of TPO, like other methods of immunotherapy, is to stop the progression of the disease.

“Some people with SPSD will experience an acute exacerbation or subacute progression of their disease despite continued supportive care. If any of these scenarios occur and the person has not tried TPE, we would strongly consider using TPE in the hope of stopping the deterioration they have. experience,” Newsom said.

“And if a person improves overall function with TPE, that’s the icing on the cake,” he added.

In the current study, the investigators included 39 SPSD patients (81% women, mean age 48 years), most of whom received TPO at Johns Hopkins. Most had either classic SPS or SPS plus.

Of the total study participants, 24 received concurrent immune therapy (21 IVIG, 3 rituximab).

Four patients had an adverse event. One developed asymptomatic hypotension, one developed linear thrombosis and infection, and two developed non-life-threatening bleeding. There were no deaths or cases of anaphylaxis.

Improvement in symptoms, less medication

The results showed that a few months after the procedure, 55% of the participants reported an improvement in their symptoms, and almost 60% needed less muscle-relaxing medication.

“Reducing the need for symptomatic drugs is a win,” as these drugs can be sedating and patients tend to take fewer pills, Newsom said.

In addition, 33% of patients reported improved gait function and 14% reported improved Modified Rankin Scale (mRS) scores. A significant proportion of patients did not experience further worsening of symptoms and function with TPE.

On average, responders were 8 years younger than those who did not respond (mean age 43 vs. 50 years, respectively). However, this was not statistically significant because the study was underpowered to identify predictive factors for treatment, the researchers note.

None of the other predictive factors evaluated, including time to immunotherapy, gender, and clinical phenotype (classic SPS, SPS-plus, or other), were associated with treatment response.

Newsom noted that the symptoms either improved or stabilized in the vast majority of study participants because all had a clinical worsening to SPE.

He noted that these new results should reassure patients and clinicians about the safety and efficacy of plasmapheresis.

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“It is well tolerated by most people, it has very few side effects, most of which are well tolerated and manageable, and in some people it can help treat not only subjective symptoms but general objective functionality,” he said. .

From a review of the literature, Newsom and colleagues also identified 42 additional patients treated with TPO. Of these, 76% reported some degree of symptomatic improvement. However, the improvement was temporary in all cases, and the degree and duration of improvement varied significantly between patients.

“Not a perfect solution”

Commenting for Medscape Medical News, Gregory S. Day, MD, Associate Professor and Senior Associate Consultant, Mayo Clinic, Jacksonville, Florida, said findings from a small retrospective study suggest TPE could be a sort of “rescue therapy” for refractory patients. and can help “buy time” for other treatments to work.

“The evidence suggests that TPE may be worth considering as a possible add-on therapy, recognizing that benefits are likely to be related to symptoms and the use of antispasmodic drugs,” said Day, who was not involved in the study.

He noted that no patient died from complications after TPO. “If we’re going to get the same results, it needs to be done at a center with a similar level of expertise in plasmapheresis,” Day said.

However, the results also show that intervention “is also not an ideal solution,” he added. “We still need better treatments.”

The study did not receive external funding. Newsom reported on advisory fees for scientific advisory boards from Biogen, Genentech, Bristol Myers Squibb, EMD Serono, Greenwich Biosciences, Novartis and Horizon Therapeutics; autobahn advisor; is the head of a clinical trial at Roche; was a member of the clinical expert committee for the medDay Pharmaceuticals clinical trial; and has received research funding (paid directly to the institution) from Biogen, Roche, Genentech, the Stiff Man Syndrome Research Foundation, the National Multiple Sclerosis Society, the Department of Defense, and the Patient Centered Outcomes Institute. Day did not disclose any relevant financial relationships.

American Academy of Neurology (AAN) Summer Conference: Autoimmune Neuroscience and Neurology: Review of the Year: Poster P1.58. Submitted July 15-16, 2022

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