Neurologist-reviewed summaries of recent research on MS
Dr. Donald Tamulonis MD,
Bon Secours Mercy Health
“Multiple Sclerosis overview”
“Multiple sclerosis is a chronic immune mediated disease of the central nervous system with associated inflammation, demyelination, and neurodegeneration. Despite decades of research, the etiology of this disorder remains elusive, but likely a combination of genetic, environmental and epigenetic factors. This disease has a heterogeneous clinical presentation and variable course which require a detailed approach to diagnose this disorder> The clinician must integrate clinical, imaging and CSF analysis. The diagnostic criteria for MS has evolved from the original description by Charcot in 1868, which included nystagmus, intention tremor and scanning speech. Today MRIs of the brain and spinal cord are essential in making this diagnosis and ruling out other disorders.
Most patients with MS initially present with “clinically isolated syndrome”, which is simply a isolated episode of specific symptoms and objective findings that reflect a single or multifocal in inflammation of the in the central nervous system. These deficits must last longer than 24 hours, to rule out other disorders, as strokes or even seizures. The most frequent problems include optic neuritis, brainstem or cerebellar syndromes, or myelitis. Optic neuritis is the most common presentation which produces decreased vision with a central blind spot as well as retro-orbital or periorbital pain with movements. On testing, impaired color vision, especially the color red, and a Gunn or afferent pupil, as well as normal or mildly swollen update discs are seen. With brainstem or cerebellar syndromes, the patient presents with double vision, unilateral facial numbness, vertigo, and gait instability. The neurologist will see nystagmus, a 6th cranial nerve palsy, and limb or gait clumsiness. With myelitis, or involvement of the spinal cord, the patient will complain of asymmetrical sensory or motor symptoms and deficits, as well as loss of sphincter control. Such presentations include weakness in one arm or one leg, sensory loss in one or all limbs, as well as marked clumsiness when walking.
Once the clinical examination suggest multiple sclerosis, an MRI of the brain and spinal cord must be performed. The typical MS lesions involve the periventricular regions or juxta- cortical areas of the brain. These MS “plaques” may also be seen in the brain stem as well as in the spinal cord. Finally, the optic nerve may show similar lesions as well. Using gadolinium contrast in the MRI displays bright lesions which are indicative of active disease.
In addition, a lumbar puncture is performed to study the spinal fluid. One usually sees slightly elevated cells in this fluid with an elevated IgG index or oligoclonal bands. These last two abnormalities are indicative of inflammation in the spinal cord come again suggesting MS, although other inflammatory diseases may present a similar picture.
Finally, MS is still a diagnosis of exclusion, ruling out other disorders, as strokes, infections, or inherited disorders.
When the diagnosis has been made, neurologists now have numerous, more effective treatments for this disease. All these treatments reduce the inflammatory responses in the brain; but all these treatments lower the patient's immune response and increase the risk of other infections.
MS remains one of the prominent concerns for neurology. However, this is an exciting time for the diagnosis and effective treatment of this disorder. At this time, we can now offer patients hope in treating and controlling this disease.”
Summary by Dr. Don Tamulonis MD, Neurologist
Dr. Michael Kentris MD,
Bon Secours Mercy Health
“Ocrelizumab is a highly effective monoclonal antibody used in the treatment of multiple sclerosis. It is typically given via intravenous (IV) infusions every 6 months. Some patients may have difficulty with the logistics of attending an infusion center for treatment or have difficulty with having IV access obtained. A study was done to determine the relative efficacy of IV vs subcutaneous (SQ) treatments. It was found that the use of SQ ocrelizumab was not inferior to the use of IV ocrelizumab making it a good option for those with the previously mentioned challenges.”
Reference: Subcutaneous Ocrelizumab in Patients With Multiple Sclerosis, Results of the Phase 3 OCARINA II Study
Summary by Dr. Michael Kentris MD, Neurologist
Dr. Harinoor Mann MD,
Bon Secours Mercy Health
“Multiple sclerosis (MS) is a chronic condition affecting over 2.8 million people worldwide, occurring when the body’s immune system mistakenly attacks myelin, the protective sheath surrounding nerve fibers in the central nervous system.
Over the past two decades, treatment options have expanded significantly, with more than 20 disease-modifying therapies (DMTs) currently available. Standard care historically began with early agents like interferons and glatiramer acetate, progressing over time to convenient oral options like fumarates and cladribine, as well as highly effective monoclonal antibodies such as ocrelizumab, ofatumumab, and natalizumab. These anti-CD20 monoclonal antibodies have largely become first-line treatments due to their high potency in preventing relapses, though their benefit against underlying progressive disease remains limited.
To address progressive forms of MS and central nervous system tissue damage, researchers are developing next-generation treatments that target inflammation inside the brain and actively work to repair nerves. Chief among these are Bruton’s tyrosine kinase (BTK) inhibitors, which are oral medications designed to cross the blood-brain barrier. By targeting both B cells and myeloid cells within the central nervous system, BTK inhibitors address compartmentalized inflammation that drives disease progression. Clinical trials highlight their strong potential: tolebrutinib demonstrated a 31% reduction in six-month confirmed disability progression compared to placebo in patients with non-relapsing secondary progressive MS, while fenebrutinib achieved a 90% reduction in new active brain lesions at week 12 in Phase 2 trials and proved non-inferior to ocrelizumab in delaying confirmed disability progression during Phase 3 testing.
Beyond daily medications, intensive cellular therapies are reshaping how severe cases are managed. Autologous Hematopoietic Stem Cell Transplantation (aHSCT) works by wiping out a malfunctioning immune system with medical therapy and rebuilding a healthy one using the patient's own stored stem cells. The National MS Society recommends aHSCT for individuals under 50 who have an MS duration of less than 10 years and continue to experience substantial disease activity despite being on high-efficacy DMTs.
Another major frontier in MS research centers on remyelination, neuroprotection, and targeting potential root causes. Trials with clemastine—an antihistamine and muscarinic receptor antagonist—showed evidence of repairing nerve pathways in the eye, prompting the development of more selective remyelinating drugs. Meanwhile, candidates like simvastatin, lipoic acid, and ibudilast are being evaluated for their ability to protect nerve cells and slow brain atrophy.
Additionally, given the strong link between Epstein-Barr virus (EBV) infection and MS, researchers are testing adoptive T-cell therapies and EBV vaccines to eliminate infected cells and target a possible causal driver. These advancements accompany a major paradigm shift in clinical practice: moving away from traditional step-up escalation approaches in favor of early, high-efficacy treatment.
Growing evidence shows that using potent therapies early in the disease course provides the best opportunity for achieving long-term clinical stability, resetting immune function, and preserving neurological health.”
Summary by Dr. Harinoor Mann MD, Neurologist