| Domain | Established finding | Evidence strength/type | Suggested ontology terms |
|---|---|---|---|
| Definition / phenotype | Hemicrania continua is a primary headache disorder characterized by persistent strictly unilateral head pain with superimposed exacerbations and cranial autonomic features; it is classically defined by complete response to indomethacin. The broader headache review notes HC is “more complex” but retains the “rapid and absolute response to indomethacin in almost all cases” property within indomethacin-responsive headaches (pqac-00000003, pqac-00000004). | Established clinical classification; review-level synthesis; disease-defining therapeutic response | headache; unilateral headache; lacrimation; conjunctival injection; ptosis; miosis; photophobia; phonophobia; nausea |
| Anatomy | Primary structures implicated are the trigeminal system and trigeminocervical complex, with involvement of brainstem and sometimes hypothalamic regions in functional imaging models of TAC-like disorders; disease localizes to the nervous system and is typically unilateral (pqac-00000004, pqac-00000005). | Established systems-neuroscience model; indirect for HC-specific localization | trigeminal nerve; trigeminocervical complex; brainstem; hypothalamus; nervous system |
| Mechanism / pathophysiology | Best-supported model is network dysfunction involving trigeminal nociceptive afferents and cranial parasympathetic outflow. The review states nociceptive inputs from cranial and upper cervical structures converge in the TCC, which is “fundamental to transmission” of head/neck nociceptive information (pqac-00000004, pqac-00000005). | Moderate evidence; human neuroanatomical/pathophysiologic inference rather than molecular proof | trigeminal autonomic reflex; trigeminocervical complex; parasympathetic nervous system; brainstem |
| Genetics / molecular / omics gaps | No validated causal gene, inheritance pattern, pathogenic variant, disease-specific biomarker, or established transcriptomic/proteomic/metabolomic signature was identified from the available evidence. | Evidence gap / negative finding | no established causal gene; no established biomarker |
| Diagnostics | Diagnosis is clinical, anchored to ICHD-3 phenotype plus confirmation of complete indomethacin responsiveness; neuroimaging is important to exclude secondary mimics because structural lesions can present as HC-like syndromes. | Strong clinical consensus; supportive review-level evidence | headache disorder diagnosis; magnetic resonance imaging; differential diagnosis; indomethacin test |
| First-line treatment | Indomethacin is the defining and first-line therapy; complete response is central to diagnosis. The recent review explicitly highlights “rapid and absolute response to indomethacin in almost all cases” (pqac-00000003). | Strongest treatment evidence; long-standing clinical standard | indomethacin; nonsteroidal anti-inflammatory drug |
| Alternatives / refractory disease | When indomethacin is not tolerated, evidence for alternatives is limited and lower quality; reported options include melatonin, topiramate, gabapentin, COX-2 inhibitors, nerve blocks, botulinum toxin, vagus nerve stimulation, and occipital nerve stimulation. | Low-quality evidence; case series/refractory-care practice | melatonin; topiramate; gabapentin; occipital nerve stimulation; vagus nerve stimulation; botulinum toxin |
| Epidemiology | HC is uncommon/rare in practice; current estimates are mainly from clinic-based studies rather than population-based surveillance, so prevalence is uncertain and likely under-recognized. | Limited epidemiology; clinic-based meta-analytic literature exists but population certainty is low | rare disease; headache disorder epidemiology |
| Prognosis | Disorder is usually chronic but treatment-responsive when true HC is present; major morbidity is pain burden, disability, and medication toxicity from long-term indomethacin rather than mortality. | Moderate clinical experience; limited longitudinal natural-history data | chronic pain; disability; adverse drug effect |
| Clinical trials | Registered interventional trial NCT04303845 evaluated erenumab 140 mg for HC, Phase 2, but was terminated after enrolling 2 participants; eligibility required ≥12 months of unremitting HC by ICHD-3 and prior/current complete indomethacin response (pqac-00000000). | Direct registry evidence | NCT04303845; erenumab; monoclonal antibody therapy |
| Real-world implementation / registry | NCT01842763 is an active-not-recruiting French observational database of occipital nerve stimulation in refractory chronic headache disorders including HC; planned data include efficacy, safety, and potential predictors of response, with total enrollment 246 across headache subtypes (pqac-00000001, pqac-00000002). | Direct registry evidence; mixed-disorder observational dataset | NCT01842763; occipital nerve stimulation; patient registry |
| Animal / model systems | No validated naturally occurring animal disease, species-specific model, or HC-specific genetic/cellular model was identified in the available evidence. | Evidence gap / negative finding | no established animal model; no established cellular model |


*Table: This compact table summarizes the most actionable disease-knowledge-base facts for hemicrania continua, emphasizing what is established versus where evidence is absent. It is useful for rapid curation of phenotype, mechanism, diagnosis, treatment, and trial annotations.*