Patient undergoing MS progression testing
#Imaging #Lesions #Physical Disability
  • Relapse is an acute episode of symptoms that significantly impacts a patient for a short period of time and is followed by recovery1,2
  • Relapse and progression are sometimes said to overlap and otherwise may be considered as completely separate mechanisms2-4
  • Relapse has long been connected with the identification of lesions in the White Matter, but some findings suggest that relapse may also occur due to cortical damage2,4-6

What Is the Impact and Importance of Relapse?

Relapse—an acute episode of symptoms that significantly impacts a patient for a short period of time and is followed by some degree of recovery—is a definitive characteristic of multiple sclerosis (MS).1,2

Once confirmed through magnetic resonance imaging (MRI) findings, relapse defines the disease beyond clinically isolated syndrome—being the first of 2 mechanisms that lead to physical and cognitive disability in MS.1,2,7,8

The second mechanism is progression—a gradual worsening of symptoms that is permanent, with no remission or recovery.7

The transition from isolated relapse events to continuous worsening of symptoms has traditionally marked the shift from relapse-remitting multiple sclerosis to the secondary progressive form of the disease.2

And because both the frequency and recovery rate of relapses are considered to determine the onset of the progressive stage, relapse is a major focus for overall management of the disease.9,10

However, recent research indicates that relapse and progression overlap at times, but also may be completely independent causes of disability accrual, even from the earliest stages of disease.2-4

Relapse recovery without evidence of permanent disability

Relapse leads to stepwise progression of disability

Progression independent of any relapse event

How Do We Detect Neurological Damage From Relapse?

The standard consideration for visualizing relapse damage through brain imagery has been to focus on inflammatory damage to White Matter (WM). Once a relapse occurs, MRI is used to identify newly formed lesions associated with demyelination, axonal transections, and gliotic scarring.2,4

White Matter damage has been a useful marker for confirming neurological damage. Over the years, it has become a more prominent tool in MS management due to the difficulty in visualizing damage to other parts of the central nervous system, such as Grey Matter (GM).5

Is There a Connection Between Relapse and Cortical Damage?

“The possibility that MS-related inflammation may produce, at least in some patients, cortical relapses further confirmed that MS is a more complex CNS disorder than being a simple white matter disease.” —Puthenparampil 20166

The publication by Puthenparampil et al aimed to evaluate the occurrence of relapse due to cortical damage absent of findings in WM.6

Five patients attending the MS center at the University Hospital of Padova, Italy, were included in the assessment. These cases of relapse were found to be associated with newly formed cortical lesions, while no additional damage was detected in the WM.6

Actual Patients From Study

Case 1: Male, 36 years

Icon of 36-year-old man with relapse of acute Wernick's aphasia mimicking an ischemic stroke

Symptoms

Relapse of acute Wernicke’s aphasia (difficulty with language), mimicking an ischemic stroke

Cortical Damage

A previously unidentified snake-like cortical lesion selectively involving the superior and middle temporal gyri of the left hemisphere

WM Damage

No new lesions

Case 2: Female, 32 years

Icon of 32-year-old woman with relapse of acute agraphia with acalculia

Symptoms

Relapse of acute agraphia (difficulty writing) with acalculia (difficulty with basic math)

Cortical Damage

A large cortical lesion in the right frontal lobe, involving the premotor cortex and several small, dot-like lesions in the cortex

WM Damage

No new lesions

Case 3: Male, 45 years

Icon of a 45-year-old man with relapse characterized by acute, moderate hyposthenia

Symptoms

Relapse characterized by acute, moderate hyposthenia (loss of strength) of the left arm and muscle twitching of the hand, spreading to the arm and face

Cortical Damage

A previously unidentified large intracortical lesion, involving the lateral precentral gyrus

WM Damage

No new lesions

Case 4: Female, 43 years

Icon of a 43-year-old woman with relapse characterized by acute onset of left lower limb paroxysmal painful hypertomia

Symptoms

Relapse characterized by acute onset of left lower limb paroxysmal painful hypertonia (increased tightness of muscle)

Cortical Damage

A leukocortical (mixed) lesion in the right hemisphere, involving the motor cortical area

WM Damage

No new lesions

Case 5: Male, 21 years

Icon of a 21-year-old man with relapse characterized by a subcontinuous state of mental confusion with behavioral changes

Symptoms

Relapse characterized by a subcontinuous state of mental confusion with behavioral changes

Cortical Damage

Several cortical lesions in the frontal lobes and a huge cortical lesion in the uncus of the right temporal lobe

WM Damage

Unknown

Summary

Relapse is a definitive characteristic of multiple sclerosis that has most often been confirmed through damage to the White Matter. The cases identified in the study by Puthenparampil et al suggest that GM lesions may play a more important role than previously realized.

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