Research AppraisalSystematic Review

Man vs. Machine: can ML algorithms diagnose headaches as accurately as clinicians? A systematic review.

Journal of neurologyManickam, Appukutty, Valliappan, Abirami26 May 2026DOI

Clinical Snapshot

65CEBM
Evidence: ModerateSystematic Review

PICO Framework

P — PopulationAdults with headache disorders
I — InterventionArtificial intelligence and machine learning diagnostic models
C — ComparatorClinician diagnoses using International Classification of Headache Disorders (ICHD) criteria
O — OutcomesDiagnostic accuracy (sensitivity, specificity, AUC-ROC), methodological quality, clinical applicability

Bottom Line

This systematic review of 74 studies involving 154,856 participants found that while AI and machine learning models show promise for diagnosing headache disorders, significant methodological flaws currently prevent clinical implementation. The wide variability in diagnostic accuracy (sensitivity 47.5-100%, specificity 50.4-100%) reflects substantial heterogeneity and methodological issues including spectrum bias, data leakage, and lack of external validation. Only 4 studies performed independent external validation. Models using structured questionnaires showed more realistic accuracies (74-86%), while neuroimaging models frequently produced near-perfect but likely overfit results. The authors conclude that 65 of 74 studies exhibited high risk of bias, primarily due to artificial case-control designs and absent external validation. Future research requires prospective, real-world validation studies before these tools can be safely integrated into clinical practice for headache diagnosis.

Evidence: Moderate

Key Findings

  • P Value: Not reported for pooled analysis

  • Effect Size: Sensitivity 47.5-100%, Specificity 50.4-100%

  • Primary Outcome: Diagnostic accuracy of AI/ML models for headache classification

  • Nnt Or Sensitivity: Realistic models: 74-86% accuracy; Neuroimaging models: near-perfect but likely overfit

  • Confidence Interval: AUC-ROC 0.658-1.000 (wide variability across studies)

Clinical Application

Low feasibility for immediate implementation; requires prospective real-world validation Relevant to Australian neurology and general practice; aligns with TGA requirements for medical device validation before clinical use Currently not applicable to clinical practice due to methodological limitations

Abstract

BACKGROUND: Headache disorders are frequently misdiagnosed. We aimed to systematically evaluate the diagnostic accuracy, methodological quality, and clinical applicability of artificial intelligence (AI) and machine learning (ML) models for classifying adult headache disorders against clinician diagnoses using the International Classification of Headache Disorders (ICHD) criteria. METHODS: In this systematic review, we searched PubMed, Embase, and the Cochrane Library (January 2015-December 2025) for AI/ML diagnostic headache studies. Two reviewers extracted data and assessed risk of bias using the QUADAS-2 tool with the QUADAS-AI extension. Main outcomes were sensitivity, specificity, area under the receiver operating characteristic curve (AUC-ROC), and risk of bias. RESULTS: We included 74 studies encompassing 154,856 participants. Models utilized traditional ML (n = 47), deep learning (n = 18), and hybrid or rule-based approaches (n = 9). Data inputs included neuroimaging (n = 27), multimodal datasets (n = 20), neurophysiological signals (n = 17), and clinical questionnaires (n = 10). Only 4 studies performed independent external validation. Overall sensitivity ranged from 47.5% to 100.0%, specificity from 50.4% to 100.0%, and AUC-ROC from 0.658 to 1.000. Models using structured questionnaires reported realistic accuracies (74-86%), whereas neuroimaging models frequently produced near-perfect, likely overfit estimates. Most studies (65 of 74) exhibited a high risk of bias driven by artificial case-control designs, data leakage, and absent external validation. CONCLUSIONS: AI-based headache diagnostic systems demonstrate promising but highly variable accuracy. Pervasive methodological flaws-specifically severe spectrum bias, data leakage, and a lack of independent external validation-currently preclude clinical implementation. Future studies require prospective, real-world validation to safely integrate these tools into practice.

References

  1. 1.Manickam, Appukutty, Valliappan, Abirami. (2026). Man vs. Machine: can ML algorithms diagnose headaches as accurately as clinicians? A systematic review. Journal of Neurology. https://doi.org/10.1089/neu.2018.5916
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