Search Results (69)

Pediatric new daily persistent headache (NDPH) is a clinically defined headache subtype that remains controversial due to a lack of unique and objective mechanistic features. For many headache subtypes, different, and sometimes unique, patterns of structural and functional changes can be observed in the brain, supporting a unique role for neuroimaging in identifying the presence and type of headache experienced. To date, there has been little research into pediatric NDPH and how it may have a unique mechanism relative to other headache subtypes. We review published research that addressed structural and functional neuroimaging in persons with NDPH. We found that research to date supports differences in both brain structure and function in persons with NDPH relative to healthy controls. Such differences reflect both cortical and sub-cortical regions of the brain. No studies to date have evaluated brain data between persons with NDPH and other headache subtypes. We discuss application of machine learning and artificial intelligence to validate NDPH as a unique headache diagnosis. We believe that future work pursuing both neuroimaging alongside machine learning can help inform the classification and differential diagnosis of pediatric patients with NDPH from other chronic headache conditions. Full article

Background and Objectives: Chronic headache after craniotomy is common and may include neuropathic subtypes (scar neuroma pain, occipital neuralgia). However, no large series has quantified these phenotypes. We conducted a single-center retrospective review (n = 5624 adult craniotomy patients) to estimate the prevalence of post-craniotomy neuropathic pain and to describe its characteristics. Materials and Methods: Institutional records were screened to identify craniotomy patients referred to a multidisciplinary pain clinic (n = 272). Eligible cases were reviewed in tiers: (1) exclusion of primary headache and noncranial pain; (2) identification of “probable neuropathic cranial pain” based on documented neuropathic features (lancinating/scalp pain, trigger tenderness, dermatomal distribution); and (3) subgroup categorization into occipital neuralgia-like, supraorbital/supratrochlear neuralgia-like, and scar-site neuropathic pain phenotypes. The supraorbital/supratrochlear subgroup was defined by frontal or frontotemporal postoperative pain in the supraorbital region, local tenderness or Tinel-like hypersensitivity over the supraorbital/supratrochlear course, and/or response to supraorbital–supratrochlear nerve block. Data extracted included demographics, timing (surgery to pain referral), pain characteristics, and treatments (blocks, radiofrequency, medications). Results: Of 5624 craniotomy patients, 272 (4.8%) had pain clinic encounters. The initial review identified 124 cases with chronic post-craniotomy headache requiring follow-up; after detailed chart classification, probable neuropathic cranial pain was present in 111 cases (2% of the cohort). Among the 111 probable neuropathic cranial pain cases, the dominant regional phenotype was occipital neuralgia-like pain. In addition, eight patients (7.2%) demonstrated a supraorbital/supratrochlear neuralgia-like phenotype, predominantly after frontal or frontotemporal craniotomies. Scar-site neuropathic pain frequently coexisted with both regional phenotypes, supporting a partially overlapping spectrum rather than mutually exclusive categories. The median time from surgery to pain referral was several months (≈12–18 months). Management commonly included occipital nerve blocks (±steroid); some patients received pulsed radiofrequency ablation of the occipital nerves, and most were trialed on neuropathic analgesics (gabapentinoids, SNRIs, etc., according to neuropathic pain guidelines). Conclusions: A clinically meaningful subset of post-craniotomy patients develops chronic neuropathic cranial pain, most commonly with occipital, supraorbital/supratrochlear, or scar-related features. Because most postoperative headaches are managed through neurosurgical follow-up and improve without pain clinic referral, the present cohort likely underestimates the true burden of neuropathic post-craniotomy pain while enriching for its most refractory neuralgic presentations. This is nevertheless the subgroup that must be recognized, discussed with patients, studied prospectively, and targeted in future prevention strategies. Full article

Background: Immune-mediated hypophysitis comprises a heterogeneous group of inflammatory pituitary disorders, including primary lymphocytic hypophysitis, immune checkpoint inhibitor (ICI)-induced hypophysitis, IgG4-related hypophysitis, and paraneoplastic autoimmune hypophysitis. Although these entities share immune-mediated mechanisms, they differ substantially in clinical presentation, imaging features, and therapeutic implications. Methods: This narrative review synthesizes current evidence on the pathophysiology, clinical manifestations, radiological characteristics, diagnostic approach, and management of immune-mediated hypophysitis, with particular emphasis on etiological heterogeneity. Results: Hypopituitarism—particularly ACTH deficiency—is the most frequent and clinically relevant manifestation, as secondary adrenal insufficiency may be life-threatening if not promptly recognized and treated. It is often accompanied by headache, arginine vasopressin deficiency, or mass effect depending on the subtype. Magnetic resonance imaging typically shows symmetrical pituitary enlargement and stalk thickening in inflammatory forms, although findings vary according to etiology and may be minimal in certain subtypes such as PD-1/PD-L1 inhibitor-associated hypophysitis. Distinct clinical phenotypes are observed across subtypes, particularly in ICI-induced hypophysitis and IgG4-related disease. Diagnosis relies on the integration of endocrine, radiological, and clinical features, supported by clinicoradiological scoring systems in selected cases. Management is primarily based on prompt hormone replacement, with selective use of glucocorticoids or immunosuppressive therapies depending on disease severity and underlying etiology. Conclusions: Immune-mediated hypophysitis represents a clinically relevant and increasingly recognized spectrum of disorders requiring a multidisciplinary and etiology-specific approach. Early recognition is essential to prevent life-threatening endocrine complications. Advances in the understanding of immunopathogenic mechanisms and the identification of reliable biomarkers may enable earlier diagnosis and more personalized therapeutic strategies. Full article

Background: Sleep disturbance is a well-recognized contributor to headache burden, yet the specific sleep domains associated with disability may differ between episodic migraine (EM) and episodic cluster headache (ECH). Methods: In this prospective observational study, 20 EM patients, 21 ECH patients, and 18 age-, sex-, and BMI-matched healthy controls (HCs) were evaluated during interictal periods. None of the patients were receiving prophylactic headache treatment. Sleep was assessed using the Pittsburgh Sleep Quality Index (PSQI), Insomnia Severity Index (ISI), Epworth Sleepiness Scale (ESS), and Sleep Hygiene Index (SHI). Psychological status was measured with the Hospital Anxiety and Depression Scale (HADS). Headache-related disability was assessed using the Headache Impact Test-6 (HIT-6) as a continuous outcome. Separate multivariable linear regression models were constructed for each headache group. Results: Both headache groups showed significantly impaired sleep and higher anxiety and depression scores compared with controls (all p < 0.001). HIT-6 scores did not differ between EM and ECH (p = 0.770 after Bonferroni correction). In multivariable regression, excessive daytime sleepiness (ESS) independently predicted disability in EM (B = 1.633, p = 0.033; R² = 0.571). In ECH, global sleep quality (PSQI; B = 0.701, p = 0.004) and sleep hygiene (SHI; B = 0.557, p = 0.033) were independently associated with HIT-6 (R² = 0.562). No significant multicollinearity was observed (all VIF < 2.5). Conclusions: Sleep disturbance is prevalent in both EM and ECH; however, the sleep domains associated with disability differ between phenotypes. Daytime sleepiness is more relevant in EM, whereas global sleep quality and sleep hygiene are more strongly associated with disability in ECH. These findings support a phenotype-specific approach to sleep assessment in headache management. Full article

Headache is a common symptom during SARS-CoV-2 infection and may persist beyond three months. Both tension-type and migraine-like headaches have been described during SARS-CoV-2 infection and after immunization. The main objective was to characterize headache phenotype during SARS-CoV-2 infection and its relationship with headache recurrence following reinfection and COVID-19 vaccination in a cohort of healthcare professionals. Secondary aims included profiling primary headaches and identifying predictors of post-COVID-19 headache persistence. We included 109 participants (86.2% women, mean age 45.3 ± 2.5 years). During infection, 49.5% met ICHD-3 criteria for tension-type headache and 12.8% for migraine. Headache recurred in 62.5% after reinfection and 59.2% after vaccination. A primary-headache history was present in 77.9% of sampled patients (25.9% migraine, 47.1% tension-type). The COVID-19 headache phenotype typically mirrored patients’ previous headache type during reinfection and post-vaccination. Persistent headache beyond three months from SARS-CoV-2 infection occurred in 22.9% and was associated with fibromyalgia and obesity. These findings suggest that COVID-19-related headache often mirrors the patient’s pre-existing primary headache and tends to recur with the same phenotype following reinfection or vaccination. Full article

Background: Headache is a common symptom during acute viral infections, and its pathophysiology has been linked with the immune response to the virus. Headache is one of the most frequent symptoms of coronavirus disease 2019 (COVID-19), and it has been associated with a more efficient immune response and a better prognosis. The aim of this article is to evaluate whether vaccination could modify the clinical phenotype and the probability of developing persistent headache after acute COVID-19. Methods: A case–control study comparing the duration of the headache and the clinical phenotype between fully vaccinated individuals and non-vaccinated controls was conducted. Each case was matched with two controls that were paired by age, sex, and prior history of headache. Patients were evaluated by a physician that administered a structured questionnaire and were followed up for at least three months. Results: The sample included 103 cases and 206 controls, with a median age of 42 (inter-quartile range (IQR) 33–51); 68% were female; and 26% had a prior history of headache. Headache had a shorter duration for vaccinated patients (4 (IQR 2–8) vs. 8 (IQR 4–16.5) days, p < 0.001). Vaccinated patients had a higher frequency of holocranial topography, pressing quality, phonophobia, and cranial autonomic symptoms. Conclusions: Our results suggest that full vaccination modifies the clinical phenotype of COVID-19 onset-associated headache and might lead to a shorter duration. These findings could represent an additional benefit of COVID-19 vaccines, which could extend to the post-COVID-19 phase and decrease the probability of a persistent disabling symptom such as headache. Full article

Background/Objectives: Headache attributed to rhinosinusitis (HRS) is uncommon in children but often misdiagnosed as migraine or tension-type headache (TTH). Overlapping phenotypes, incidental sinus findings on neuroimaging, and limited communication in younger patients complicate diagnosis and lead to inappropriate treatment. Methods: We retrospectively analyzed 3065 pediatric patients (<19 years) presenting with headache at two tertiary neurology clinics (2014–2023) with ≥1 year follow-up. Headaches were classified by ICHD-3 criteria. HRS diagnosis required radiologic sinus pathology and ≥50% improvement within 72 h of antibiotic or decongestant therapy. Demographic, clinical, neuroimaging, and family history data were collected. Symptom profiling used principal component analysis (PCA) and k-means clustering; multivariate logistic regression identified independent predictors. Results: Of 3065 patients, 32.7% had migraines, 15.5% TTH, and 4.5% HRS. Nearly one-third of HRS cases were initially misclassified. Compared with migraine and TTH, HRS patients were younger (median 9 years), more often male, and enriched in preschool age. Independent predictors included shorter duration (<1 h; OR 0.62), higher intensity (OR 2.165), nasal symptoms (OR 9.836), hearing impairment (OR 22.52), allergic rhinitis (OR 8.468), and family history of HRS (OR 32.602) (all p < 0.001). PCA showed overlap but distinct clustering: HRS was characterized by sinonasal and otologic features, whereas migraine clustered around sensory hypersensitivity. Conclusions: Pediatric HRS shows distinct predictors—young age, acute severe headache, nasal and auditory symptoms, allergic history, and family history—despite overlap with migraine and TTH. Structured use of these predictors with otolaryngologic assessment may improve diagnostic accuracy, reduce misclassification, and avoid unnecessary neuroimaging or inappropriate therapy. Full article

Introduction: Alcohol-induced headaches are one of the most prevalent types of headaches. The International Classification of Headache Disorders defined them as throbbing and bilateral, and their phenotype combines characteristics of migraines and headaches secondary to low cerebrospinal fluid pressure. We aimed to evaluate the factors associated with the presence of a headache as a hangover symptom. Methods: This was a prospective cohort study, including 32 healthy individuals who voluntarily consumed alcohol and completed self-administered questionnaires during three separate alcohol consumption and hangover episodes. Results: A headache was a hangover symptom in 55/96 (57.3%) episodes. The phenotype was predominantly holocranial (94.5%), frontal (98.2%), and pressing (67.2%), with a median intensity of 6 (IQR 4–8). Headaches worsened with physical activity (100%) and had orthostatic changes (89.1%). A prior history of headaches was associated with headache occurrence (odds ratio: 3.480; 95% confidence interval (CI): 1.084 to 11.177), and headache precipitation by standing up was associated with a shorter duration (hazard ratio: 0.257; 95% CI: 0.073 to 0.901). Conclusions: Delayed alcohol-induced headaches had a migraine-like phenotype. An orthostatic pattern suggestive of a low cerebrospinal fluid pressure was associated with a shorter duration of the headache. Full article

Background: This study, designed by the Greek Research Alliance for the Study of Headache and Pain (GRASP), sought to prospectively examine whether the treatment with two consecutive OnabotulinumtoxinA (BoNTA) cycles might improve the frequency and severity of chronic migraine (CM) with comorbid bruxism. We also explored whether the potential BoNTA-related alleviation of bruxism can directly influence the improvements in migraine efficacy outcomes. Methods: A total of 58 CM patients with comorbid bruxism at baseline, attaining two consecutive (quarterly given) BoNTA cycles, were studied. The changes in bruxism-related pain were assessed with the 0–10 numeric scale PI-NRS. Bruxism was clinically diagnosed using the self-report Bruxscreen-Q questionnaire. Any phenotypic changes in bruxism, according to Bruxscreen-Q, from baseline (T0) to the last efficacy evaluation follow-up (T1), were analyzed and then compared. Migraine-related efficacy and disability outcomes, mostly mean headache days (MHD), were also compared between T0 and T1. Results: BoNTA exerted significant improvements in bruxism-related pain, with PI-NRS median scores being significantly reduced from 7 at T0 to 3 at T1 (p < 0.001). The rates of masseter hypertrophy at T1 significantly dropped, compared to T0 (chi-square: 16; p < 0.001). Patients also self-reported significant improvements in the Bruxscreen-Q items at T1, compared to T0. At T1, 41/58 (70.7%) patients responded to BoNTA. The significant decrease in MHD frequency at T1 was positively correlated with improvements in bruxism-related pain severity (Pearson’s correlation: 0.710; p < 0.001). Conclusions: BoNTA exerts dual beneficial effects towards both the reduction of migraine frequency and the alleviation of bruxism-related pain and disability. Both of these effects seem closely interrelated in our study. Full article

Rhinogenic contact point headache (RCPH) represents a diagnostic challenge due to different anatomical presentations and unstandardized imaging markers. This prospective multicenter study involving 120 patients aimed to develop and validate a CT-based imaging framework for RCPH diagnosis. High-resolution CT scans were systematically assessed for seven parameters: contact point (CP) type, contact intensity (CI), septal deviation, concha bullosa (CB) morphology, mucosal edema (ME), turbinate hypertrophy (TH), and associated anatomical variants. Results revealed CP-I (37.5%) and CP-II (22.5%) as predominant patterns, with moderate CI (45.8%) and septal deviation > 15° (71.7%) commonly observed. CB was found in 54.2% of patients, primarily bulbous type (26.7%). Interestingly, focal ME at CP was independently associated with greater pain severity in the multivariate model (p = 0.003). The framework demonstrated substantial to excellent interobserver reliability (κ = 0.76–0.91), with multivariate analysis identifying moderate–severe CI, focal ME, and specific septal deviation patterns as independent predictors of higher pain scores. Our imaging classification system highlights key radiological biomarkers associated with symptom severity and may facilitate future applications in quantitative imaging, automated phenotyping, and personalized treatment approaches. Full article

Chronic pain (CP) represents a multidimensional condition in which cognitive and emotional factors shape the individual experience from perception to action. The purpose of this study was to characterize the functional significance of alterations in neural oscillatory dynamics underlying the transition from resting-state to cognitive load across distinct CP phenotypes. Continuous electroencephalographic data were acquired from patients with headache, migraine, and spine-related pain, as well as healthy controls, during rest and three visual–cognitive–motor (VCM) tasks: reaction time, working memory, and associative learning. First, within CP subgroups, we examined cognitive-load-related changes in oscillatory activity. In migraine patients, alpha/beta power attenuation induced during cognitive processing correlated with higher reported pain intensity. Relative to the spine-related pain group, migraine patients exhibited increased occipital alpha and gamma band activity during working memory and associative learning conditions, as a possible neurophysiological signature of cortical hyperexcitability. By comparing a subset of headache patients to healthy controls, we found elevated resting-state delta and gamma activity in the patient group. Under cognitive load conditions, headache patients showed higher power across delta, theta, beta, and gamma frequency bands. Delta and theta activity elicited during the working memory task correlated negatively with pain intensity. Our results demonstrate that the experience of chronic pain is accompanied by frequency-specific alterations in both resting and cognitive-associated oscillatory dynamics, reflecting impaired visual working-memory processing and top–down modulation of behaviorally relevant stimuli. Full article

Background: Leber’s hereditary optic neuropathy (LHON) is the most common mitochondrial disorder and an inherited optic neuropathy. Recently, two different LHON inheritance types have been discovered: mitochondrially inherited LHON (mtLHON) and autosomal recessive LHON (arLHON). Our case report is the first diagnosed case of arLHON in a patient of Lithuanian descent and confirms the DnaJ Heat Shock Protein Family (Hsp40) Member C30 (DNAJC30) c.152A>G p.(Tyr51Cys) founder variant. Case Presentation: A 34-year-old Lithuanian man complained of headache and sudden, painless loss of central vision in his right eye. On examination, the visual acuity of the right and left eyes was 0.1 and 1.0, respectively. Visual-field examination revealed a central scotoma in the right eye, and visual evoked potentials (VEPs) showed prolonged latency in both eyes. Optical coherence tomography showed thickening of the retinal nerve fiber layer in the upper quadrant of the optic disk in the left eye. Magnetic resonance imaging of the head showed evidence of optic nerve inflammation in the right eye. Blood tests were within normal range and showed no signs of inflammation. Retrobulbar neuritis of the right eye was suspected, and the patient was treated with steroids, which did not improve visual acuity. He later developed visual loss in the left eye as well. A genetic origin of the optic neuropathy was suspected, and a complete mitochondrial DNA analysis was performed, but it did not reveal any pathologic mutations. Over time, the visual acuity of both eyes slowly deteriorated, and the retinal nerve fiber layer (RNFL) thinning of the optic disks progressed. A multidisciplinary team of specialists concluded that vasculitis or infectious disease was unlikely to be the cause of the vision loss, and a genetic cause for the disease was still suspected, although a first-stage genetic test did not yield the diagnosis. Thirty-three months after disease onset, whole-exome sequencing revealed a pathogenic variant in the DNAJC30 gene, leading to the diagnosis of arLHON. Treatment with Idebenone was started 35 months after the onset of the disease, resulting in no significant worsening of the patient’s condition. Conclusion: This case highlights the importance of considering arLHON as a possible diagnosis for patients with optic neuropathy, because the phenotype of arLHON appears to be identical to that of mtLHON and cannot be distinguished by clinicians. Full article

Background: Orofacial pain (OFP) and headache are common and disabling conditions in people with head and neck cancer (HNC), although their clinical characteristics and underlying pain mechanisms remain poorly studied, leading to worse diagnosis and, thus, management. Therefore, this review aims to synthesize the literature regarding clinical features, pain descriptors, mechanisms, and assessment tools of OFP and/or headache in adults with HNC. Methods: A scoping review was conducted following the Arksey and O’Malley framework and reported using PRISMA-ScR guidelines. We searched PubMed, Embase, Scopus, and Web of Science. Quantitative and qualitative original studies were included. Data were charted and summarized using narrative synthesis. Results: Of 3647 records initially retrieved, 32 studies met the inclusion criteria. Most studies were observational and heterogeneous in design, population, and pain assessment methods. OFP was highly prevalent, with neuropathic descriptors (e.g., burning, electric shocks, tingling) reported in 13.1% to 64.5% of patients, although heterogeneity in study design and tools used to assess this potential pain mechanism was high. Pain was frequently localized at the tumor site, although pain in other regions beyond the head and neck was also reported. Pain intensity was generally moderate, although varied across studies. OFP and headache in HNC patients were often neuropathic in nature and contributed significantly to disability and reduced quality of life. Most articles lacked mechanistic classifications of pain, although some suggested that central sensitization may be involved in some patients. Conclusions: Orofacial pain and headache are prevalent, under-characterized symptoms in HNC patients. There is an urgent need for standardized assessments using validated tools to improve phenotyping and inform targeted treatment strategies. Full article

(1) Background: Murine typhus, caused by Rickettsia typhi, is a neglected rickettsial disease and an underdiagnosed cause of acute febrile illness (AFI), particularly in endemic regions such as Indonesia. (2) Case description: We report a case series of four patients presenting with AFI of less than seven days in duration. Three patients were admitted with moderate disease, while one presented with septic shock with the macrophage activation-like syndrome (MALS) phenotype. Common clinical features included myalgia and headache; additional symptoms included cough, sore throat, and abdominal pain. Laboratory findings revealed bicytopenia, elevated transaminases, and raised inflammatory and bacterial infection markers. Common tropical infections—dengue, typhoid fever, and leptospirosis—and other potential sources of infection were excluded early during hospitalization. Diagnosis was confirmed by nucleic acid amplification testing (NAAT), which detected R. typhi in all patients. Doxycycline was initiated following confirmation, leading to defervescence within 36–48 h. (3) Conclusions: Murine typhus remains an underrecognized cause of febrile illness in Indonesia. In the near future, the inclusion of rickettsial testing in the diagnostic protocol of AFI will be crucial, as it enables timely administration of effective, low-cost treatment. Full article

Headache represents one of the most prevalent and disabling conditions in the pediatric population, with significant repercussions on mental and psychological well-being, as well as on academic achievement and social functioning, ultimately leading to a marked reduction in quality of life. Currently, the diagnosis of headache is based on the clinical criteria of the third edition of the International Classification of Headache Disorders (ICHD-3). However, the characteristics of headache may differ between adults and children, as well as the ability of children to provide a complete description of the pain and associated symptoms. The immature narrative skills of children can represent a limitation in defining the clinical phenotype of headache, making the diagnosis more complex. This is even more challenging when extracting information about the characteristics of the headache in children whose verbal expression is poorly developed or completely absent. Given these limitations, clinical psychology has long used drawing as an effective diagnostic instrument to bypass verbal communication barriers. This tool provides unique access to children’s psychological and emotional states, as a direct window into their inner world and as an expressive medium that often generates more detailed, accurate, and clinically actionable information, compared to verbal reports alone. For these reasons, drawing has been recognized as a valuable diagnostic tool for decades, with multiple studies demonstrating specificity and accuracy rates comparable to standard clinical assessments. Particularly for young children, drawings may give access to fundamental information that might otherwise remain inaccessible, thereby allowing both accurate diagnosis and individualized treatment planning. Multiple studies have highlighted and confirmed the graphic differences between representations of various types of headaches and the undeniable utility of an “artistic diagnosis” alongside the clinical one. Furthermore, the literature suggests and encourages the use of drawing in clinical practice, both in the diagnostic process and during subsequent follow-up, as an effective, enjoyable, easy-to-use, and low-cost resource. Accordingly, we propose a narrative review accompanied by a curated collection of drawings that may help identify and categorize specific correlations between graphic representations and clinical phenotypes, such as pain location, quality, intensity, association with nausea and vomiting, photophobia and phonophobia, and types of migraine aura. Our goal is to create a visual reference that can aid clinicians in the accurate interpretation of children’s drawings. Additionally, we aim to promote the integration of this method into routine clinical practice to improve diagnostic precision and support a more child-centered model of care. We also hope to propose new iconographic models to further enrich the diagnostic framework. Full article