New Focus and Strategies for Managing Primary Progressive Multiple Sclerosis

Prognostic indicators for primary progressive multiple sclerosis can include age of onset, inflammation, and even gender, according to Patricia Coyle, MD, who presented a session titled “Primary Progressive MS: Diagnosis, Clinical Course, and Long-Term Management” at the 2014 Annual Meeting of the Consortium of Multiple Sclerosis Centers (CMSC) and the Sixth Cooperative Meeting with Americas Committee for Treatment and Research in Multiple Sclerosis (ACTRIMS).

Coyle, professor and vice chair and director of the MS Comprehensive Care Center, Stony Brook University Medical Center, Stony Brook, NY, said primary progressive multiple sclerosis is characterized by neurodegeneration, neuroaxonal injury, and diffuse inflammation that often has a late onset.

The good news is that, even though the seeds of progression are linked to age, there may be hope for the implementation of wellness/health maintenance regimens for progressive MS, because it helps CNS reserve, she noted.

The key elements of progressive disease are marked by an “insidious onset of symptoms with gradual deterioration, occasional plateaus and minor improvements. Acceptable worsening is independent of relapses (they do not occur),” according to Coyle.

Cognitive decline and myelopathy/spastic paraparesis, progressive cerebellar, and hemiplegia are common in progressive MS.

With primary progressive multiple sclerosis, disease onset is often later in life (mean age 40), and is characterized by macroscopic MRI T2 and T1 lesions. Late onset, defined as after age 50, is also associated with higher rates of primary progressive multiple sclerosis, according to a Boston cohort study of about 4,000 patients.

Coyle noted that the “damage mechanisms” may include microglial activation, oxidative injury, progressive mitochondrial injury, age-dependent iron accumulation, and glutamate excitotxicity.

One study that tested cognitive decline found information processing and word memory were lower in patients with primary progressive multiple sclerosis.

In another study, researchers conducted a retrospective review (from 1990‐2011, N=95 primary progressive multiple sclerosis; 88 had MRI or cerebrospinal fluid results) and found “OCBs were a more sensitive diagnostic criteria than spinal cord MRI lesions.”

Diagnosis of primary progressive multiple sclerosis may include a blood CBD, metabolic panel and MRI (brain and contrast, cervical and thoracic MRI). Other diagnostic tests may include vitamin B1 and 2 anticardiolipin antibodies and HIV.

Coyle said studies of progressive MS are now a major focus of many trials ongoing and planned, many of which are looking at an array of distinct damage mechanisms relating to CNS repair/restoration. Novel agents under review include: fingolimod, ocrelizumab, masitinib (oral protein kinase inhibitor), and epigallocatechin‐gallate (oral green tea flavanoid/catechin). Some others are fluoxetine, ibudilast (oral phosphodiesterase inhibitor) and iIdebenone (oral coenzyme Q10‐like agent).

According to Coyle, the PROMISE and OLYMPUS (Phase III trials of GA and rituximab vs. placebo) did show in a treatment effect in a primary progressive multiple sclerosis subset analysis. Until novel therapies reach the doctor’s office, she said that patients can be referred to health/wellness management and risk factor reduction.

So far, “we have no distinct genes yet associated with primary progressive multiple sclerosis; however, we do know that the disease is characterized by a global inflammatory process and oxidative injury,” Coyle said. She emphasized that, “therapy is not just writing a drug script. Exercise promotes plasticity, improves learning and memory and exercise improves cognitive function.”

“Health maintenance/wellness programs (including walking or aerobic exercise, weight loss, blood pressure control) are critical for symptom management and there should be ongoing assessment and review,” she added.