Hallmarks of primary headache: part 4 – rare headache syndromes

Background and aim: “Other primary headaches” is a group of heterogeneous headache disorders described in Chapter 4 of the third edition of the International Classification of Headache Disorders (ICHD-III). Due to the limited number of cases, most of these disorders are considered rare and represent a diagnostic and therapeutic challenge for clinicians and headache specialists. To increase knowledge, improve their recognition, and foster research on these rare headache disorders, this review provides a comprehensive up-to-date description of their hallmarks, including epidemiologic data, key clinical characteristics, proposed pathophysiological mechanisms, and suggested treatments. Principal findings: Diagnosing rare headache disorders is challenging. A few key clinical features can help improve their recognition and distinction. These include identifying a specific trigger or stimulus for headache development such as cough, exercise, or sexual activity, a particular pattern of onset or recurrence, like for hypnic headache, primary thunderclap headache, or new daily persistent headache, or a unique scalp location for the pain such as for nummular headache or epicrania fugax. These clinical details are crucial for narrowing the differential diagnosis and making the correct diagnosis. However, regardless of the specificity of the clinical presentation, secondary causes must be ruled out when facing patients with these rare clinical presentations. Limited evidence on the pathophysiology and treatment of these disorders is available, and high-quality studies are lacking. Conclusions: Accurate diagnosis and additional research on these rare headache disorders are needed. Multicenter and international collaborations within the framework of international headache societies and among tertiary headache centers are key to developing efficient and high-quality registries and databases. Additionally, clinical trials are needed to develop evidence supporting the treatments current in use and to address the unmet needs of these rare diseases. Only through these efforts it will be possible to design specific studies to increase our understanding of these rare disorders and improve the quality of life of individuals living with these conditions.