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Modern multiple sclerosis care is not only about confirming the diagnosis. It is important to determine disease activity, estimate the risk of future progression and choose a treatment strategy that controls the disease as early as possible and reduces the risk of irreversible neurological disability.
Dr. Lidiia Prakhova is a neurologist and Doctor of Medical Sciences specializing in neuroimmunology and demyelinating diseases of the central nervous system. During a consultation in Israel, the diagnosis, MRI scans and additional investigations can be reassessed, the effectiveness of current treatment reviewed, and options for starting or changing therapy discussed.
No single symptom is specific to multiple sclerosis. What matters is the nature of the neurological episode, its duration, objective neurological findings and the results of appropriate investigations.
Optic neuritis may cause reduced vision, impaired color perception and pain with eye movement.
Numbness, tingling, altered sensation in a limb, or a sensory level affecting the trunk may occur.
New weakness of an arm or leg, difficulty walking or reduced hand dexterity may represent a demyelinating event.
Diplopia, vertigo, imbalance or incoordination may result from involvement of the brainstem or cerebellum.
Weakness, sensory changes and bladder dysfunction may occur when inflammatory lesions affect the spinal cord.
Fatigue, pain, spasticity, bladder problems and cognitive symptoms are common during the course of MS.
The 2024 revisions of the McDonald criteria can allow MS to be diagnosed earlier in appropriate patients, while still requiring careful assessment that the clinical and MRI presentation is typical for multiple sclerosis.
Even when MRI lesions are present, another diagnosis may better explain the patient's symptoms. Reassessment is particularly important when the clinical presentation or MRI pattern is atypical for MS, or when the disease behaves unexpectedly during treatment.
AQP4-IgG-positive neuromyelitis optica spectrum disorder requires a fundamentally different long-term treatment strategy.
MOG-IgG-associated disease can cause optic neuritis, myelitis and inflammatory brain syndromes that may initially resemble multiple sclerosis.
Nonspecific white matter abnormalities are much more common than MS and require particularly careful interpretation with increasing age or vascular risk factors.
Depending on the presentation, Susac syndrome, systemic autoimmune disease, infection, metabolic disease or inherited white matter disorders may need to be considered.
Distinct inflammatory attacks occur, followed by complete or partial recovery.
Gradual disability accumulation may nevertheless occur even without obvious relapses — a process known as PIRA.
Neurological function gradually worsens from the beginning of the disease, although additional inflammatory activity may also occur.
After a period of relapsing disease, persistent gradual worsening of neurological function becomes increasingly prominent.
New inflammatory attacks may leave persistent neurological deficits.
New inflammatory activity may appear on MRI even when the patient notices no new symptoms.
The long-term aim is to preserve walking, vision, hand function and cognitive abilities.
Gradual deterioration can occur independently of obvious clinical relapses.
NEDA — no evidence of disease activity — commonly refers to the absence of relapses, new MRI lesions and confirmed disability worsening. It remains a useful clinical concept, but stable conventional MRI and the absence of relapses do not always exclude slow progression.
Modern treatment selection is increasingly moving away from a rigid “first-line, then second-line” sequence. The decision depends on disease activity, prognostic factors, age, pregnancy plans, the risks of each treatment and patient preferences.
Treatment starts with a therapy of moderate efficacy, followed by escalation if disease activity is not adequately controlled.
This approach may remain reasonable in selected patients with lower disease activity and a more favorable prognostic profile.
A highly effective therapy is used early, particularly when features associated with a less favorable prognosis are present.
Contemporary real-world evidence increasingly supports this approach in appropriately selected patients, while long-term efficacy and safety must always be considered together.
| Treatment group | Examples | Role in treatment strategy |
|---|---|---|
| Moderate-efficacy therapies | interferon beta, glatiramer acetate, teriflunomide, dimethyl fumarate | May be suitable for selected patients with lower disease activity, or when long-term safety experience is a particularly important consideration. |
| Oral higher-efficacy strategies | S1P receptor modulators, cladribine and other therapies | Selection depends on MS activity, infection and cardiovascular risks, laboratory findings and reproductive plans. |
| High-efficacy monoclonal antibodies | natalizumab, ocrelizumab, ofatumumab and other anti-CD20 therapies | Can rapidly and strongly suppress inflammatory disease activity, but require individualized assessment of infection and other treatment-related risks. |
| Immune reconstitution strategies | cladribine, alemtuzumab; in selected cases, autologous hematopoietic stem cell transplantation | Used in carefully selected situations and requires individualized assessment of expected benefit and risk. |
This is not an exhaustive list. Regulatory approval and availability of individual therapies vary between countries.
A treatment should not automatically be continued simply because it is well tolerated. Disease control needs to be reassessed regularly.
A confirmed inflammatory attack after the therapy has had sufficient time to become effective may indicate inadequate disease control.
New or enlarging T2 lesions or gadolinium-enhancing lesions may appear without a clinical relapse.
Gradual deterioration in walking, hand function or other abilities requires assessment for possible PIRA.
Infections, laboratory abnormalities or changes in an individual's risk profile may require a different strategy.
Reproductive plans can substantially affect treatment selection and dosing schedules.
The balance between treatment benefit and immunotherapy risk changes with age, and lower-intensity treatment may sometimes be considered.
Modern MS monitoring increasingly combines relapses, neurological examination and MRI with additional biomarkers that may provide information about nervous system injury.
MRI remains central for monitoring inflammatory disease activity and the development of new lesions. The appropriate interval depends on disease stage and treatment.
Elevated serum NfL reflects neuroaxonal injury and may be associated with inflammatory activity and a less favorable disease course.
GFAP is being studied as an additional biomarker that may be particularly relevant to chronic injury and progression-dominant MS biology.
PIRA — progression independent of relapse activity — describes confirmed disability accumulation that is not directly associated with a clinical relapse.
Progressive disability was previously associated mainly with later stages of MS. It is now recognized that PIRA can occur during relapsing disease and represents an important mechanism of long-term disability accumulation.
There may be no clear new relapses, and conventional MRI may appear relatively stable, while walking distance gradually decreases, weakness increases, hand function worsens, or balance and other abilities slowly decline.
The absence of relapses does not always mean complete disease control. Objective neurological function therefore needs to be followed over time, rather than focusing only on attacks and MRI lesions.
Treatment of primary and secondary progressive MS depends on age, inflammatory activity, rate of worsening, disability level and the individual disease phenotype.
Management should not be reduced to the question of whether a disease-modifying drug is available. Spasticity, impaired walking, pain, bladder dysfunction, fatigue and other potentially treatable contributors to disability also need to be addressed.
Treatment differs from classic relapsing MS and depends partly on age and evidence of inflammatory disease activity.
In 2026, treatment options for SPMS expanded, including a new therapeutic option for selected patients with progression in the absence of recent relapses.
Rehabilitation should target the actual mechanism of disability: weakness, foot drop, spasticity, impaired balance, fatigue, heat sensitivity or a combination of several problems.
Traditional ankle-foot orthoses, lightweight dynamic supports and functional electrical stimulation can be considered for foot drop.
FES activates muscles during the appropriate phase of gait and may improve walking function in selected patients.
New wearable systems combine motion sensors with multichannel electrical stimulation of several muscle groups in the leg.
Early small studies in MS have shown improvements in selected gait parameters, but these technologies do not yet replace conventional rehabilitation.
Robotic rehabilitation and exoskeletons can allow large numbers of repeated gait movements, including in patients with significant motor impairment.
Studies suggest possible short-term benefits for walking, balance and endurance, although optimal patient selection remains uncertain.
In Uhthoff's phenomenon, increased body temperature temporarily worsens neurological symptoms.
Cooling garments, cooling vests and pre-cooling strategies may improve exercise tolerance and functional mobility in some patients.
Epidural spinal cord stimulation and brain–spine interfaces have enabled controlled walking in selected patients with severe traumatic spinal cord injury.
These technologies are not currently established treatments for paraparesis caused by multiple sclerosis. Spinal neuromodulation is beginning to be investigated in progressive MS, but the evidence remains preliminary.
Fatigue requires assessment of sleep, mood, medications, activity, heat sensitivity and neurological factors.
Treatment may combine rehabilitation, oral medication, focal botulinum toxin therapy and other approaches depending on the pattern of spasticity.
Weakness, spasticity, sensory loss, balance impairment and fatigue often contribute simultaneously.
Cerebellar tremor can significantly affect hand function and daily activities and may require a combination of strategies.
Pain in MS may be neuropathic, musculoskeletal, related to spasticity or caused by specific syndromes such as trigeminal neuralgia.
Reduced libido and disturbances of sensation, arousal, erection and orgasm are common in MS and should be actively assessed rather than ignored.
Regular individually adapted exercise can help preserve endurance, strength, balance and functional independence.
Smoking is associated with a less favorable MS course and is an important modifiable risk factor.
No diet replaces disease-modifying therapy, but nutrition, body weight and correction of clinically relevant deficiencies are part of comprehensive MS care.
Most women with multiple sclerosis can plan a pregnancy. The goal is not simply to stop all treatment, but to create a strategy that protects both maternal disease control and fetal safety.
Particular care is required when stopping therapies associated with return or rebound of inflammatory activity. Other treatment strategies may allow disease control to continue after therapy has been given before conception.
The 2024 McDonald criteria incorporate the optic nerve, cerebrospinal fluid kappa free light chains, the central vein sign and paramagnetic rim lesions into modern diagnostic pathways. These tools can support earlier diagnosis in appropriate patients while emphasizing diagnostic specificity.
The concept of PIRA has shown that disability can accumulate independently of clinical attacks. This changes the way treatment response is monitored: asking only whether new relapses have occurred is no longer sufficient.
In the HERCULES trial, the BTK inhibitor tolebrutinib reduced the risk of confirmed disability progression in patients with non-relapsing secondary progressive MS.
In June 2026, tolebrutinib received European Union marketing authorization under the brand name Cenrifki for adults with SPMS who had not experienced relapses during the previous two years. Liver function monitoring is required during treatment.
Regulatory status and availability differ between countries, including Israel.
On September 1, 2026, positive topline results were announced from the Phase III REMODEL-1 and REMODEL-2 trials of remibrutinib in relapsing multiple sclerosis.
Remibrutinib reduced annualized relapse rates versus teriflunomide and met key MRI endpoints. Full data still need scientific presentation and evaluation, and remibrutinib is not currently an approved MS treatment.
Serum NfL can provide additional information about neuroaxonal injury, while GFAP is increasingly studied in relation to progression-dominant disease biology. Their role is to complement clinical evaluation and MRI, not replace them.
Compare symptoms, neurological findings, MRI, cerebrospinal fluid and additional investigations with current diagnostic criteria.
Evaluate the actual images, lesion pattern and evolution, and whether they are characteristic of multiple sclerosis.
Assess disease risk and compare escalation with an early high-efficacy treatment strategy.
Review relapses, MRI activity, progression, laboratory monitoring and relevant biomarkers.
Determine whether new clinical or MRI activity represents an inadequate response to the current therapy.
Integrate age, comorbidities, reproductive plans, progression, symptom management and rehabilitation.
A consultation may be particularly useful after a new MS diagnosis, when there is uncertainty about the diagnosis, new disease activity despite treatment, gradual worsening without relapses, a need to choose or change therapy, or a complex progressive course of multiple sclerosis.
European Medicines Agency. Cenrifki (tolebrutinib): European marketing authorization issued 19 June 2026 for adults with SPMS without relapses in the previous two years.