OBJECTIVE: New daily persistent headache (NDPH) is a primary headache disorder characterized by the sudden onset of continuous pain and its intractability to treatment. It is more prevalent in the pediatric population than the adult population, but remains understudied and underdiagnosed. The purpose of the current article is to provide a current overview of new daily persistent headache in the pediatric and adolescent population, including history, pathophysiology, clinical findings, current and emerging treatment options, and the results of recent studies and meta-analyses.
RESULTS: Despite recent studies and meta-analyses showing significant phenotypic overlap between chronic migraine and NDPH in the pediatric population, multiple recent studies have come to conflicting conclusions about the overlap of medication overuse in headache and pediatric NDPH. Recent studies reveal alterations in neuroimaging, particularly in functional connectivity, in patients with NDPH. Patients frequently remain treatment-refractory even to medications that have historically proven helpful in this population; however, new treatment options, including calcitonin gene-related peptide (CGRP) monoclonal antibodies, may be more effective.
CONCLUSIONS: NPDH remains a perplexing and difficult-to-manage condition for both children and adults. Despite a higher prevalence in the pediatric population, there are relatively few studies to guide the evaluation and treatment of NDPH in pediatric and adolescent patients. Early treatment, both pharmacological and non-pharmacological, should be employed to reduce disability. Overall, further studies are needed to better understand pathogenesis and to identify more effective therapeutic strategies, both pharmacological and non-pharmacological.

To evaluate the safety and efficacy of eptinezumab for the treatment of chronic refractory headache in adolescents.
Chronic refractory headache can lead to school absences and impaired quality of life in adolescents, and currently there are no pharmacologic treatments with level A evidence for headache prevention for this population. While observational data suggest that monoclonal antibodies to calcitonin gene-related peptide or its receptor may be helpful for adolescents who have refractory primary headache disorders, evidence is lacking for the use of eptinezumab.
This was a single-center, retrospective chart review. Demographic and headache phenotypic data were collected. Outcome measures included headache intensity and frequency pre- and post-infusion(s), and improvement in function or in associated symptoms. Adverse events were also collected.
Nine patients with chronic migraine and two with new daily persistent headache received a first dose of 100 mg of eptinezumab. All of them had daily headache and nine had continuous headache at baseline. After the first infusion of 100 mg, two patients were no longer having daily headache, one patient stopped having continuous headache, and four patients noted headache intensity reduction. Additionally, one patient described a reduction in nausea and vomiting, and another patient noted improvement in function. Six patients received a second eptinezumab infusion of 100 mg, three had a third one, and one patient had four infusions of 100 mg. After the second infusion, one patient noted reduction in headache frequency, one experienced lower headache intensity, and two described pain \"improving.\" With the third and fourth infusions, patients continued to report improvement in headache intensity. Subsequent infusions of 300 mg resulted in further reductions in headache frequency and intensity for some patients. Eptinezumab was overall well tolerated.
While this was a small sample, findings suggest that eptinezumab may be a safe and effective treatment for chronic, refractory headache in adolescents.

OBJECTIVE: To describe the clinical features of new daily persistent headache (NDPH) at an outpatient neurology clinic with a subspecialty interest in headache in Houston, Texas.
METHODS: A retrospective chart review was performed by a neurologist subspecialty certified in headache medicine of all patients seen from September 1, 2011 through February 28, 2020 (8.5 years) with a provisional diagnosis of NDPH and abstracted charts meeting criteria for primary NDPH.
RESULTS: A total of 328 patients met the International Classification of Headache Disorders, 3rd edition criteria including 215 (65.5%) female patients. The mean age of onset was 40.3 years (range 12-87 years) with a mean age at first consultation in the study clinic of 42.6 years (range 12-87 years). The median [25th, 75th] duration of NDPH at initial consultation was 0.7 [0.3, 2.0] years, and at last visit, it was 1.9 [0.7, 4.8] years. The headaches were side-locked unilateral in 28/328 (8.5%). 12/328 cases (3.6%) with a thunderclap onset are reported. There was no obvious seasonal or other cyclical variation. The pain was usually moderate to severe and more often severe for the migraine phenotype (MP; 260/328 [79.3%] of cases) than for the tension-type phenotype (TTP). Precipitating factors were the following: stressful life events, 67/328 (20.4%); upper respiratory infection or flu-like illness, 33/328 (10.1%); and extracranial surgery, 5/328 (1.5%). Exacerbating or aggravating factors similar to migraine triggers were more often reported with the MP than with the TTP in this sample. For the MP, vertigo or dizziness was reported by 19/260 (7.3%) and a visual aura by 21/260 (8.1%) with descriptions provided. The prognostic types were the following for all patients: persisting (refractory), 305/328 (93.0%); relapsing-remitting, 9/328 (2.7%); and remitting (self-limited), 14/328 (4.3%).
CONCLUSIONS: NDPH is typically of moderate to severe intensity often with migraine features without obvious seasonal or other cyclical variation. Most cases are refractory. 3.6% have a thunderclap onset often with a good response to treatment.

Introduction: Botulinum neurotoxin type-A (BoNTA) is licensed for the treatment of chronic migraine (CM), but it has been tested off-label as a therapeutic choice in other primary headaches (PHs). We aimed to provide a systematic review and expert opinion on BoNTA use in PHs, beyond CM.Areas covered: After providing an overview on PHs and mechanism of BoNTA action, we report the results of a systematic review, according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) recommendations, of BoNTA therapeutic trials in PHs beyond CM. Studies and results were reviewed and discussed, and levels of evidence were graded. We also collected data on relevant ongoing trials.Expert opinion: Although there are contradictory findings on PHs other than CM, BoNTA may represent a therapeutic option for patients who do not respond to conventional prophylactic treatments. Based on limited available evidence, BoNTA may be considered in refractory tension-type headache, trigeminal autonomic cephalalgias, primary stabbing headache, nummular headache, hypnic headache, and new daily persistent headache, after the primary nature of cephalalgia has been documented and other drugs have failed. Experienced physicians in BoNTA treatment are required to guide the therapeutic protocol for each patient to optimize good and safe outcomes.

BACKGROUND: New daily persistent headache (NDPH) presents with a sudden onset headache which continues without remission within 24 h. Although rare, NDPH is important because it is one of the most treatment refractory primary headache disorders and can be highly disabling to the individuals. In this structured review, we describe the current knowledge of epidemiology, clinical features, trigger factors, pathophysiology, diagnosis and therapeutic options of NDPH to better understand this enigmatic disorder. The prevalence of NDPH estimated to be 0.03% to 0.1% in the general population and is higher in children and adolescents than in adults. Individuals with NDPH can pinpoint the exact date their headache started. The pain is constant and lacks special characteristics but in some has migraine features. The exact pathogenic mechanism of NDPH is unknown, however pro-inflammatory cytokines and cervicogenic problems might play a role in its development. The diagnosis of NDPH is mainly clinical and based on a typical history, but proper laboratory investigation is needed to exclude secondary causes of headache. Regarding treatment strategy, controlled drug trials are absent. It is probably best to treat NDPH based upon the predominant headache phenotype. For patients who do not respond to common prophylactic drugs, ketamine infusion, onabotulinum toxin type A, intravenous (IV) lidocaine, IV methylprednisolone and nerve blockade are possible treatment options, but even aggressive treatment is usually ineffective.
CONCLUSIONS: NDPH remains poorly understood but very burdensome for the individual. Multi-center randomized controlled trials are recommended to gain better understanding of NDPH and to establish evidence based treatments.

New daily persistent headache (NDPH) is an idiopathic headache syndrome characterized by the abrupt onset of an unremitting, daily, continuous headache without an antecedent escalating headache pattern, and not attributable to other primary or secondary headache disorders. We review the history of NDPH in terms of its characterization and classification, and then interview Dr. Walter Vanast, the neurologist who initially described NDPH three decades ago, to gain his perspective now that there is more widespread recognition and interest in this syndrome.