What is the definition of a Multiple Sclerosis (MS) flare?

Definition of a Multiple Sclerosis Flare

An MS flare (also called a relapse or attack) is defined as a new or worsening neurological symptom lasting at least 24 hours, caused by acute inflammatory demyelination in the central nervous system, occurring in the absence of fever or infection, and separated from any previous attack by at least 30 days. 1, 2

Core Diagnostic Criteria

Duration and timing requirements:

• The neurological disturbance must persist for a minimum of 24 hours to qualify as a true attack 1, 2
• Separate attacks must be at least 30 days apart from the onset of the first event to the onset of the second event 2
• Single paroxysmal episodes (such as one isolated tonic spasm) do not constitute a relapse, but multiple episodes occurring over 24 hours do qualify 2

Nature of symptoms:

• The symptoms must represent true neurological dysfunction with objective clinical evidence, not pseudoattacks triggered by fever, infection, or elevated body temperature 1, 2
• The attack reflects acute focal inflammation of the central nervous system 3

Distinguishing True Flares from Pseudoflares

A pseudoflare is critical to recognize:

• It represents temporary worsening of pre-existing MS symptoms without new inflammatory activity 1
• Common triggers include increased core body temperature, infection, heat exposure, or metabolic stress 1
• Unlike true flares, pseudoflares do not show new or enhancing lesions on MRI 1

The distinction matters clinically:

• Misinterpreting a true flare as a pseudoflare delays appropriate corticosteroid treatment 1
• Conversely, misdiagnosing a pseudoflare as a true relapse leads to unnecessary steroid exposure with potential side effects 1

Objective Evidence Supporting Flare Diagnosis

MRI findings:

• True flares often demonstrate new T2-hyperintense lesions or gadolinium-enhancing lesions on brain or spinal cord MRI 1
• The presence of gadolinium enhancement indicates active inflammation and blood-brain barrier breakdown 4
• However, some patients with genuine clinical flares may not show new MRI activity, so imaging must be interpreted in clinical context 1

Neurological examination:

• A thorough neurological assessment is necessary to determine whether symptoms represent new deficits or exacerbation of existing ones 1
• The examination should assess for potential triggers of pseudoflares such as infection or hyperthermia 1

Common Clinical Presentations of MS Flares

Typical manifestations include:

• Long tract signs: myelopathy, asymmetric spastic paraplegia, urinary dysfunction, or Lhermitte's sign 3
• Optic neuritis presenting with vision loss, eye pain, or color desaturation 3
• Brainstem syndromes such as bilateral internuclear ophthalmoplegia 3
• Cortical syndromes or multifocal presentations are less common 3

Critical Pitfalls to Avoid

Diagnostic errors:

• Failing to exclude infection or fever as the cause of symptom worsening before diagnosing a true flare 1, 2
• Not waiting the full 24-hour period before classifying symptoms as a relapse 1, 2
• Diagnosing a new flare when symptoms occur less than 30 days from a previous attack 2
• Relying solely on MRI findings without clinical correlation, as imaging and clinical activity do not always align 1

Broader context:

• Although a universally accepted definition of flares has been debated, most experts agree that a flare represents a measurable increase in disease activity that usually leads to treatment modification 4
• Flares are common throughout the disease course and contribute significantly to organ damage accumulation and worse long-term outcomes 4