Blood Treatment Safe, Promising for Stiff-Person Syndrome

Pauline Anderson

July 26, 2022

Therapeutic plasma exchange (TPE) is safe, well-tolerated, and improves symptoms in most patients with stiff-person spectrum disorders (SPSD), a group of rare neuroimmunological disorders, a small preliminary study suggests.

Dr Scott D. Newsome

While the intervention might seem "scary," as it requires central venous access and sometimes hospitalization, the new results indicate it should only be considered for the "right" patients, study investigator Scott D. Newsome, DO, associate professor of neurology, Johns Hopkins University, Baltimore, Maryland, told Medscape Medical News.

"We showed that this is a safe treatment intervention and the adverse events are few in number and quite manageable," Newsome said.

The findings were presented at the American Academy of Neurology (AAN) Summer Conference: Autoimmune Neurology and Neurology Year in Review, held 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 in the torso and limbs. Individuals with this phenotype can have gait problems, falls, and myelopathic features on exam.

A less common phenotype is SPS-plus. It includes classic musculoskeletal symptoms as well as cerebellar and/or brain-stem involvement. Patients with this phenotype can experience double vision and problems with speech and swallowing.

As part of the downstream effects of low GABA levels, anxiety and other mood symptoms are "incredibly common," Newsome noted. Patients can suffer a spasm from sudden unexpected movements or sounds, and some experience agoraphobia because they fear they will fall if they go outside.

Most individuals with SPSD are middle-aged white women; but, as with other immune-related conditions, the condition does occur in patients with diverse backgrounds and across age groups.

Treatment of SPSD typically involves symptomatic therapies. Benzodiazepines are the cornerstone of such therapies given their main mechanism of action of enhancing GABAergic pathways and their positive treatment response.

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

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

Non-pharmacological interventions are also useful and can include stretching and balance training, heat or aqua therapy, deep tissue massage, manual manipulation, acupuncture, and acupressure.

"Icing on the Cake"

TPE, also known as plasmapheresis, involves separating and removing plasma from blood and replacing it with an albumin solution. The idea, said Newsome, is to remove antibodies and proteins that contribute to immune dysregulation.

A main goal of TPE, as with other immune therapies, is to halt worsening of the disease, he noted.

"Some people with SPSD will experience acute exacerbations or subacute progression of their disease despite ongoing maintenance treatment. If either of these scenarios occurs, and the individual has not tried TPE, we will strongly consider using TPE in hopes to plateau the worsening they're experiencing," Newsome said.

"And if the person has improvement in their overall function with TPE, that's icing on the cake," he added.

For the current study, researchers included 39 patients with SPSD (81% women; mean age, 48 years), most of whom received TPE at Johns Hopkins Hospital. The majority had either classic SPS or SPS-plus.

Of the total study population, 24 were on concurrent immune therapy (21 on IVIG, 3 on rituximab).

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

Symptom Improvement, Fewer Meds

Results showed that a few months after the procedure, 55% of participants reported improvement in symptoms and almost 60% needed less muscle relaxing medications.

"Decreasing the need for symptomatic medications is a win" as these drugs can be sedating and patients are keen to take fewer pills, said Newsome.

In addition, 33% of patients reported improved gait function, and 14% had improved modified Rankin Scale (mRS) scores. A large portion of patients had no further worsening in their symptoms and function with TPE.

On average, patients who responded were 8 years younger than those who did not (mean age, 43 years vs 50 years, respectively). However, this was not statistically significant because the study was not sufficiently powered to detect predictive factors to treatment, the investigators note.

None of the other predictive factors evaluated, including time to immune therapy, sex, and clinical phenotype (classic SPS, SPS-plus, or other) was associated with treatment response.

That symptoms were either improved or stabilized in a large majority of study participants is notable because all were worsening clinically prior to TPE, Newsome pointed out.

These new results should reassure patients and clinicians about the safety and efficacy of plasmapheresis, he noted.

"It's well tolerated in most people; it has very few side effects, most of which are well tolerated and can be dealt with; and for a portion of people it can help treat not only the subjective symptoms but overall objective functionality," he said.

From a literature review, Newsome and colleagues also identified an additional 42 patients treated with TPE. Of these, 76% reported some degree of symptomatic improvement. However, 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, assistant professor and senior associate consultant, Mayo Clinic, Jacksonville, Florida, said the results of the small retrospective study suggest TPE may be a kind of "rescue therapy" for refractory patients and might help "buy time" for other therapies to start working.

"The data suggest TPE may be worth looking into as a possible add-on therapy, recognizing that benefits are probably going to be in terms of symptoms and use of spasmodic medications," said Day, who was not involved with the research.

That no patient died from complications from TPE is a credit to the study team, he noted. "If we are going to get these same results, it needs to be done at a center with similar levels of experience with plasmapheresis," Day said.

However, the results also show the intervention "is not a perfect solution either," he added. "We still need better therapies."

The study did not receive outside funding. Newsome reported consultant fees for scientific advisory boards from Biogen, Genentech, Bristol Myers Squibb, EMD Serono, Greenwich Biosciences, Novartis, and Horizon Therapeutics; is an adviser for Autobahn; is the study lead PI for a Roche clinical trial; was a clinical adjudication committee member for a medDay Pharmaceuticals clinical trial; and received research funding (paid directly to institution) from Biogen, Roche, Genentech, The Stiff Person Syndrome Research Foundation, National Multiple Sclerosis Society, Department of Defense, and Patient Centered Outcomes Institute. Day has disclosed no relevant financial relationships.

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

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