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Advanced Neurology Multiple sclerosis: Immunopathogenesis

5. Smouldering MS acute inflammation do not further halt the development
of progressive volume loss of the brain and spinal cord, it
Progression independent of relapse activity or smouldering has been proposed that smouldering MS plays a role in the
MS is characterized by impairment progression while process of CNS volume loss [70-73] .
the patient is in remission with no obvious MRI lesion
[69]
findings . It is suggested that the “real MS” originates Table 1 shows the clinical characteristics of different
from a primary smouldering process that coexists with subtypes of multiple sclerosis.
inflammation . Whether MS is an autoimmune disease The typical manifestation of RRMS is ON, which is
[70]
or a CNS-intrinsic disease remains contentious in the present in 25% of patients. The analysis of clinical, imaging,
scientific literature. The autoimmune hypothesis of and genetic data suggested that PPMS and SPMS share a
MS, also called outside-in, is supported by the fact that high level of similarities . The risk of conversion from ON
[6]
immunosuppressive therapies, such as alemtuzumab, to MS is explained by laboratory, clinical, and radiological
hematopoietic stem cell transplantation, or natulizumab, findings. Lesions suggestive of demyelination on MRI
are effective in the treatment process. However, in RRMS, examinations are the most compelling factors indicating
effective suppression of the immune system does not the conversion to MS [74,75] . A study on the Turkish patients
always prevent disability in the long-term .
[69]
who had undergone the first seizure ON found that
It is suggested that MS is an inside-out disease in unilateral ON was present in 67.3% of patients (104 total),
which focal inflammatory activity is a concomitant positive CSF in 62.5%, and Vitamin D deficiency in 65.2%.
feature of primary CNS neurodegeneration. Some The ON in 83 patients (79.9%) converted to MS, and it took
possible pathogenetic components of smouldering MS an average of 2.74 years for the second relapse to occur .
[74]
include acute axonal and synaptic loss, demyelination, In the Iranian population, the ON in only 42.2% of patients
CNS microglia/macrophage activation, chronic oxidative converted to MS. The study also found that women were
stress, iron accumulation, mitochondrial damage and more likely to become converters (OR = 3.4, CI = 1.83 –
dysfunction, and infection . 6.32, P ≤ 0.001). Brain lesions were also found in 63.2%
[70]
There is a strong contrast between clinical, MRI, and of patients with original ON, and white matter lesions
pathologic studies. Clinical and MRI data have classified were the most significant factor determining the higher
MS as a biphasic disease, dominated by inflammation risk of conversion to MS (OR = 5.15 CI = 2.64 – 10.07,
at baseline and preceded by non-inflammatory P < 0.001) . In the MSBase cohort study of demographics,
[75]
neurodegeneration. In contrast, pathologic findings show conversion to MS was observed in 741 (66.2%) of
continuous inflammation and demyelination even in the 1119 patients with CIS. Time taken for conversion to MS
later or terminal stages of MS [25,71] . Since therapies for was longer in treated compared with non-treated subjects:

Table 1. Clinical characteristics of multiple sclerosis subtypes
Relapsing-remitting Secondary progressive Primary progressive
Mean age 20–40 years 10–15 years after initial disease ≥40 years
onset
Female to male ratio 3:1 3:1 1:1
Manifestations Optic neuritis, acute partial transverse Progressive myelopathy, brainstem Progressive myelopathy,
myelitis, brainstem syndromes or cerebellar syndrome brainstem or cerebellar syndrome
Frequency of manifestations at 85% Not applicable 10 – 15%
the beginning
Course Episodes of acute worsening of neurologic Gradual neurologic deterioration Steady functional decline from
functioning with total or partial recovery following a relapsing course with disease onset without relapses or
or without relapses remission
Conventional brain MRI Lesion load burden is higher compared Rare active lesions: subpial Lesion load burden is lower
with primary progressive MS: Active demyelination and cortical atrophy compared with relapsing MS:
lesions are common, cortical lesions are less are more common Rare active lesions, subpial
common demyelination and cortical
atrophy are more common
Conventional spinal cord MRI Lower lesion load Higher lesion load Higher lesion load
Adapted from Amezcua .
[6]
Abbreviation: MRI: Magnetic resonance imaging

Volume 2 Issue 3 (2023) 7 https://doi.org/10.36922/an.1319