Neurodegeneration and its potential markers in the diagnosing of secondary progressive multiple sclerosis. A review

Abstract

Approximately 70% of relapsing-remitting multiple sclerosis (RRMS) patients will develop secondary progressive multiple sclerosis (SPMS) within 10–15 years. This progression is characterized by a gradual decline in neurological functionality and increasing limitations of daily activities. Growing evidence suggests that both inflammation and neurodegeneration are associated with various pathological processes throughout the development of MS; therefore, to delay disease progression, it is critical to initiate disease-modifying therapy as soon as it is diagnosed. Currently, a diagnosis of SPMS requires a retrospective assessment of physical disability exacerbation, usually over the previous 6–12 months, which results in a delay of up to 3 years. Hence, there is a need to identify reliable and objective biomarkers for predicting and defining SPMS conversion. This review presents current knowledge of such biomarkers in the context of neurodegeneration associated with MS, and SPMS conversion.

Impact of Cognitive Impairment on Quality of Life in Multiple Sclerosis Patients—A Comprehensive Review

“…In the majority of cases, the disease starts as RRMS. In this phase, inflammation in the CNS, caused by both adaptive and innate immune system components, results in myelin destruction and gradual neurological decline, usually progressing in successive flares that manifest as a brief episode of acute neurological dysfunction, followed by complete or partial remission and the subsequent resolution of symptoms [ 18 ]. Activated immune cells cause CNS lesions leading to symptoms such as visual disturbances, tingling and numbness, fatigue, uro-genital disorders, spasticity, and memory disorders [ 5 ].…”

“…Thus, these patients experience SPMS 10–15 years after the onset of RRMS, in which inability advances independently of relapses. In this situation, acute exacerbations become less common, but the patient experiences a gradual decline in neurological dysfunction, with or without intervals of remission, suffering increasing disability, which may (but not always) be accompanied by new brain lesions [ 18 ]. Many patients often have increased weakness, urinary system disorders, fatigue, stiffness, mental disorders, and psychological impairment [ 5 ].…”

“…The T25FW assesses the time required for the patient to walk the 25-Foot Walk (7.62 m) distance in a habitual manner safely, quickly, and without pausing. The 9HPT assesses manual dexterity by rating the patient’s ability to insert and remove nine pins from holes in a box [ 18 , 26 ]. The EDSS-Plus score is twice as sensitive as the EDSS alone in assessing disability progression in patients with SPMS (59.5% vs. 24.7%) [ 29 ].…”

“…An additional diagnostic instrument for evaluating of cognitive functions in MS patients, which also assesses concentration capacity, attention maintenance, and oculomotor speed, is the Symbol Digit Modalities Test (SDMT) [ 18 ]. The SDMT is a simple substitution task in which the patient matches numbers with symbols, where the answers can be given orally or in writing.…”

“…Consequently, arguably, the best diagnostic tool for monitoring disease progression in patients with SPMS would be one that includes the use of several tests that assess deterioration of clinical status at various levels. In any case, the EDSS currently remains the most common scale in routine clinical practice and is frequently the only one used [ 18 ].…”