MELAS Diagnostic Criteria for Stroke-Like Episodes
The diagnosis of MELAS syndrome requires three invariant criteria: (1) stroke-like episode before age 40 years, (2) encephalopathy characterized by seizures and/or dementia, and (3) lactic acidosis and/or ragged-red fibers on muscle biopsy. 1 The diagnosis is considered secure when at least two additional features are present: normal early development, recurrent headache, or recurrent vomiting. 1
Cardinal Diagnostic Features
The American Heart Association identifies the following cardinal features that define MELAS syndrome 2:
- Exercise intolerance 2
- Onset before 40 years of age 2
- Seizures 2
- Ragged-red fibers on muscle biopsy 2
- Lactic acidosis 2
- Stroke-like manifestations 2
Many patients also experience migraine-like headaches. 2
Distinguishing Stroke-Like Episodes from Acute Ischemic Stroke
Clinical Features That Favor MELAS Over Acute Ischemic Stroke
A validated clinical scoring system (SLEECS - SLE Early Clinical Score) assigns one point to each of the following features 3:
- Younger age (typically <40 years) 3
- Hearing loss 3
- Lower body mass index 3
- Combination of headache and/or seizures at presentation 3
- Elevated serum lactate 3
- Absence of hemiparesis 3
A SLEECS score ≥4 has 80% sensitivity and 100% specificity for diagnosing stroke-like episodes in MELAS. 3
Imaging Characteristics
The American Heart Association notes that ischemic lesions in MELAS preferentially involve the posterior cerebral hemispheres but do not conform to specific arterial territories 2, which is a critical distinguishing feature from typical ischemic stroke. 4
On MRI, lesions most commonly appear in temporal-occipital-parietal lobes, cortical or subcortical areas, and may also involve frontal lobe, thalamus, and basal ganglia. 4 MR spectroscopy demonstrates elevated lactic acid peaks in lesion sites, normal brain tissues, and cerebrospinal fluid. 4
Genetic Confirmation
The American Heart Association reports that blood leukocyte DNA reveals the A3243G mutation in 80% of MELAS patients. 2 However, not all patients with clinical MELAS have this typical mtDNA point mutation, and some patients with the mutation may have clinical syndromes other than MELAS. 1
Additional Diagnostic Clues
Patients may present with 2:
The American Academy of Otolaryngology-Head and Neck Surgery emphasizes that sudden bilateral hearing loss with confusion, elevated serum lactic acid, and stroke-like episodes should raise immediate suspicion for MELAS. 5
Critical Pitfalls to Avoid
Do not administer thrombolytic therapy for suspected acute ischemic stroke until MELAS is excluded in young patients (<40 years) presenting with stroke-like symptoms, especially when lesions do not conform to vascular territories. 2, 6 The stroke-like syndrome in MELAS results from altered cellular metabolism affecting small cerebral vessels or dysfunction of autoregulatory mechanisms, not from thrombotic occlusion. 2
The rarity and complexity of MELAS make it among the most difficult diagnoses to establish, requiring a high index of suspicion in young patients with atypical stroke presentations. 7 Muscle biopsy revealing COX-negative muscle fibers and SDH-stained ragged-red fibers, combined with genetic testing for mtDNA mutations, remains the gold standard for diagnosis. 4