The clinical value of amplitude-integrated electroencephalography in a historical cohort with neonatal encephalopathy: A comparison of short-term versus prolonged-period monitoring.

BACKGROUND: To compare the amplitude-integrated electroencephalography (aEEG) monitoring (short-term versus prolonged-period) for neonatal seizure detection and outcome. METHODS: The aEEG monitoring in a historical cohort (n = 88, preterm:42, and term:46) with neonatal encephalopathy between 2010-2022 was re-evaluated for neonatal seizures (electrographic, electro-clinical, and clinical seizures) and EEG background scoring. The cohort was dichotomized: group I (short-period with 6-12 h, n = 36) and group II (prolonged-period with 24-48 h, n = 52). Both monitoring types were evaluated for the diagnostic accuracy of the "patients with seizures" and for outcome characteristics (early death as well as adverse outcomes at 12 months of age). RESULTS: A total of 67 (76 %) neonates of the cohort were diagnosed as "patients with seizures": electrographic-only seizures in 10 (15 %), electro-clinical seizures in 22 (33 %), and clinical-only seizures in 35 (52 %). The aEEG provides the "patients with seizures" in neonates with a 36.5 % rate with both types of monitoring: 17/36 (47.2 %) with short-term and 15/52 (28.8 %) with prolonged-period monitoring. The prolonged period aEEG had higher diagnostic values for seizure detection (sensitivity = 0.73 and negative predictivity value = 0.81). However, the aEEG background scores were similar for both types of aEEG monitoring, respectively (the mean ± SD: 4.73 ± 2.9 versus 4.4 ± 4. p = 0.837). The aEEG scoring was correlated with the magnitude of brain injury documented with MRI, the early death, and the adverse outcome at 12 months of age. CONCLUSIONS: Both aEEG types are valuable for monitoring the "patients with seizures" and outcome characteristics.

Revolutionizing migraine management: advances and challenges in CGRP-targeted therapies and their clinical implications.

Migraine, a prevalent neurological disorder, affects approximately 14.1% of the global population and disproportionately impacts females. This debilitating condition significantly compromises quality of life, productivity, and incurs high healthcare costs, presenting a challenge not only to individuals but to societal structures as a whole. Despite advances in our understanding of migraine pathophysiology, treatment options remain limited, necessitating ongoing research into effective therapies. This review delves into the complexity of migraine management, examining the roles of genetic predisposition, environmental influences, personalized treatment approaches, comorbidities, efficacy and safety of existing acute and preventive treatments. It further explores the continuum between migraine and tension-type headaches and discusses the intricacies of treating various migraine subtypes, including those with and without aura. We emphasize the recent paradigm shift toward trigeminovascular activation and the release of vasoactive substances, such as calcitonin gene-related peptide (CGRP), which offer novel therapeutic targets. We assess groundbreaking clinical trials, pharmacokinetic and pharmacodynamic perspectives, safety, tolerability, and the real-world application of CGRP monoclonal antibodies and gepants. In the face of persisting treatment barriers such as misdiagnosis, medication overuse headaches, and limited access to specialist care, we discuss innovative CGRP-targeted strategies, the high cost and scarcity of long-term efficacy data, and suggest comprehensive solutions tailored to Turkiye and developing countries. The review offers strategic recommendations including the formulation of primary care guidelines, establishment of specialized outpatient clinics, updating physicians on novel treatments, enhancing global accessibility to advanced therapies, and fostering patient education. Emphasizing the importance of lifestyle modifications and holistic approaches, the review underscores the potential of mass media and patient groups in disseminating critical health information and shaping the future of migraine management.

Other primary headache disorders: Data from the HEAD-MENA-A study in Africa, Asia, and the Middle East.

OBJECTIVE: Other primary headache disorders (OPHD) are under-investigated compared to frequent primary headache types like migraine, tension-type headache, and trigeminal autonomic cephalalgias. Knowledge of the distribution and characteristics of OPHD subtypes is crucial for their recognition. We aimed to determine the prevalence at the hospital and headache clinics and clinical characteristics of OPHDs in patients from 13 countries. METHODS: We analyzed a large dataset from the cross-sectional study Head-MENA-A (Middle East, North Africa, Asia). Consecutive patients over 10 years of age presenting with headaches were included from outpatient, inpatient, and emergency settings. A structured questionnaire addressing demographics, headache characteristics, accompanying symptoms, and triggers was administered. Headache subtypes were diagnosed according to the ICHD-3 criteria. RESULTS: Among patients complaining of headaches (n = 3722), 106 (2.9%) were diagnosed with OPHD. Fifty-two patients (1.4% of all headache patients) had only OPHD, while 54 (1.5%) had both OPHD and a co-existing primary headache (mostly migraine). All OPHDs were more common in females. The most frequent subtypes were new daily persistent headache and primary stabbing headache (0.2% each among all admitted patients). Photophobia and phonophobia were the most frequent accompanying symptoms, while physical activity (28.8%), stress (15.4%), and the Valsalva maneuver (15.4%) were the most common triggering factors. The majority of triggering factors were more pronounced in patients with both migraine and OPHD. CONCLUSIONS: Other primary headaches are rare and heterogeneous. Their high co-existence with migraine suggests shared predisposing factors, hinting at a "headache continuum" concept for primary headaches.

Global uncertainty in the diagnosis of neurological complications of SARS-CoV-2 infection by both neurologists and non-neurologists: An international inter-observer variability study.

INTRODUCTION: Uniform case definitions are required to ensure harmonised reporting of neurological syndromes associated with SARS-CoV-2. Moreover, it is unclear how clinicians perceive the relative importance of SARS-CoV-2 in neurological syndromes, which risks under- or over-reporting. METHODS: We invited clinicians through global networks, including the World Federation of Neurology, to assess ten anonymised vignettes of SARS-CoV-2 neurological syndromes. Using standardised case definitions, clinicians assigned a diagnosis and ranked association with SARS-CoV-2. We compared diagnostic accuracy and assigned association ranks between different settings and specialties and calculated inter-rater agreement for case definitions as "poor" (κ ≤ 0.4), "moderate" or "good" (κ > 0.6). RESULTS: 1265 diagnoses were assigned by 146 participants from 45 countries on six continents. The highest correct proportion were cerebral venous sinus thrombosis (CVST, 95.8%), Guillain-Barré syndrome (GBS, 92.4%) and headache (91.6%) and the lowest encephalitis (72.8%), psychosis (53.8%) and encephalopathy (43.2%). Diagnostic accuracy was similar between neurologists and non-neurologists (median score 8 vs. 7/10, p = 0.1). Good inter-rater agreement was observed for five diagnoses: cranial neuropathy, headache, myelitis, CVST, and GBS and poor agreement for encephalopathy. In 13% of vignettes, clinicians incorrectly assigned lowest association ranks, regardless of setting and specialty. CONCLUSION: The case definitions can help with reporting of neurological complications of SARS-CoV-2, also in settings with few neurologists. However, encephalopathy, encephalitis, and psychosis were often misdiagnosed, and clinicians underestimated the association with SARS-CoV-2. Future work should refine the case definitions and provide training if global reporting of neurological syndromes associated with SARS-CoV-2 is to be robust.

Cross-sectional, hospital-based analysis of headache types using ICHD-3 criteria in the Middle East, Asia, and Africa: the Head-MENAA study.

BACKGROUND: Headaches are frequent neurological disorders that are yet to be unveiled and treated comprehensively worldwide. Bearing in mind that the distribution of headache subtypes in neurology clinics (NC) is essential for planning appropriate diagnostic and therapeutic approaches, the primary goals of this multi-centric study are to carry out inter-regional comparisons by using current diagnostic criteria with evaluations of neurologists to delineate headache burden. METHODS: A cross-sectional study between April 1 and May 16, 2022 was conducted with the participation of 13 countries from the Middle East, Asia, and Africa. Patients were included in the study on a specific day each week during five consecutive weeks. All volunteers over the age of 18 and whose primary cause for admission was headache were examined. The patients admitted to NC or referred from emergency services/other services were evaluated by neurologists by means of the International Classification of Headache Disorders (ICHD-3) criteria. RESULTS: Among the 13,794 patients encountered in NC, headache was the primary complaint in 30.04%. The headache patients' mean age was 42.85 ± 14.89 (18-95 years), and 74.3% were female. According to the ICHD-3 criteria, 86.7% of the main group had primary headache disorders, 33.5% had secondary headaches, 4% had painful cranial neuropathies along with other facial and headaches, and 5.2% had headaches included in the appendix part showing some overlapping conditions. While the most common primary headache was migraine without aura (36.8%), the most common secondary headache was medication-overuse headache (MOH) (9.8%). Headaches attributed to COVID-19, its secondary complications, or vaccines continue to occur at rates of 1.2%-3.5% in current neurology practice. Pain severity was significantly lower in Ivory Coast and Sudan than in Türkiye, Turkish Republic of Northern Cyprus, Iran, Egypt, Senegal, Tatarstan, and Azerbaijan (p < 0.001). CONCLUSIONS: The study showed that migraine is still the most common motive for admissions to NC in different regions. Furthermore, MOH, an avoidable disorder, is the most common secondary headache type and appears to be a significant problem in all regions. Remarkably, pain perception differs between regions, and pain intensity is lower in Africa than in other regions.

The net impact of clinical seizures on outcome characteristics in infants with neonatal encephalopathies at 12 months of age.

PURPOSE: To assess the impact of clinical neonatal seizures on outcome characteristics of preterm and term newborns with neonatal encephalopathy (NE). METHODS: We designed a prospective comparative study with 53 babies (preterm neonates: 26 and term neonates: 27) with NE: group 1 (preterm neonates with seizures, n = 13), group 2 (preterm neonates without seizures, n = 13), group 3 (term neonates with seizures, n = 13) and group 4 (term neonates without seizures, n = 14). The functional outcome characteristics of the survivors were assessed by the Ankara Developmental Screening Inventory (ADSI) and the Guide for Monitoring Child Development (GMCD) at 12 months of age. RESULTS: Clinically defined acute symptomatic seizures were diagnosed with prompt conventional EEG / amplitude-integrated EEG in preterm (92.3%) and term neonates (81.4%) with etiology-specific diagnoses of NE. There were no differences between the study groups regarding seizure semiology and EEG characteristics. A primary adverse outcome was defined in 22 (41.5%) of the cohort. However, only 15.3% of infants had an unfavorable functional outcome with ADSI at 12 months. Among the survivors, there was no significant difference between the study groups regarding ADSI scores. The GMDC test revealed normal development in 50% of survivors with seizures in the preterm group and 83% in the term group. CONCLUSION: There was no significant difference between the characteristics of functional outcomes at 12 months in preterm and term neonates with NE for clinical seizures.

Imaging Features to Predict Response to Olfactory Training in Post-Traumatic Olfactory Dysfunction.

OBJECTIVES/HYPOTHESIS: Prognosis of post-traumatic olfactory dysfunction is poor, with medical treatment options showing limited success rates. Olfactory training (OT) has been introduced as a potential therapeutic option in olfactory dysfunction. We aimed to identify the imaging features that would predict a better response to OT and create an imaging-based prognostic scale. METHODS: We retrospectively reviewed 52 patients that underwent OT at our center for post-traumatic olfactory dysfunction. Olfactory functions at the time of initial presentation and at completion of OT were evaluated using Sniffin' Sticks test and threshold discrimination identification (TDI) scores were calculated. Patients were divided into responders (ROT group: 16 cases) and non-responders (n-ROT group: 36 cases) to OT based on TDI score change (cut-off 5.5 point). Morphological measurements of olfactory fossa, olfactory bulb volume and signal abnormalities, olfactory nerve filia integrity, siderosis, encephalomalacic changes in olfactory cortex, and other cortical regions were reviewed. RESULTS: There was no significant difference between the two groups in terms of age, gender distribution, olfactory dysfunction duration, head-trauma severity, and initial TDI scores. A model incorporating five variables: cribriform plate fracture, olfactory fossa depth (cut-off: 4.9 mm), olfactory bulb encephalomalacia, olfactory bulb volume (cut-off: 27.1 mm3 ), and siderosis was developed. This model had an area under the curve (AUC) of 0.950, and a cut-off value of 1 had 76.5% sensitivity and 97.1% specificity in prediction of response to OT. CONCLUSIONS: We developed an imaging-based scoring system with good specificity that can be used as an adjunctive tool for patient counseling, and optimal selection of management options. LEVEL OF EVIDENCE: 4 Laryngoscope, 131:E2243-E2250, 2021.

Effect of Asbestos Exposure on the Frequency of EGFR Mutations and ALK/ROS1 Rearrangements in Patients With Lung Adenocarcinoma: A Multicentric Study.

OBJECTIVE: The aim of this study is to investigate the effect of asbestos exposure on cancer-driver mutations. METHODS: Between January 2014 and September 2018, epidermal growth factor receptor (EGFR), anaplastic lymphoma receptor tyrosine kinase (ALK), and c-ros oncogene 1 receptor tyrosine kinase gene (ROS1) alterations, demographic characteristics, asbestos exposure, and asbestos-related radiological findings of 1904 patients with lung adenocarcinoma were recorded. RESULTS: The frequencies of EGFR mutations, ALK, and ROS1 rearrangements were 14.5%, 3.7%, and 0.9%, respectively. The rates of EGFR mutations and ALK rearrangements were more frequent in asbestos exposed non-smokers (48.7% and 9%, respectively). EGFR mutation rate was correlated to female gender and not-smoking, ALK rearrangement rate was correlated to younger age, not-smoking, and a history of asbestos exposure. CONCLUSIONS: The higher rate of ALK rearrangements in asbestos-exposed lung adenocarcinoma cases shows that asbestos exposure may most likely cause genetic alterations that drive pulmonary adenocarcinogenesis.

Two Cases with Ring Chromosome 13 at either End of the Phenotypic Spectrum.

Ring chromosome 13 is a rare genetic condition with an incidence of 1/58,000 in live births. Major clinical features of patients with ring chromosome 13 include growth and developmental retardation, microcephaly, facial dysmorphism, ambiguous genitalia, anal atresia, eye malformations, retinoblastoma, and hand, foot, and toe abnormalities. The severity of the phenotype depends on the amount of genetic material lost during ring chromosome formation. Here, we report 2 cases with ring chromosome 13 at either end of the phenotypic spectrum.

Greater occipital nerve block in the treatment of triptan-overuse headache: A randomized comparative study.

OBJECTIVES: This study aims to investigate the efficiency of a single and repeated greater occipital nerve (GON) block using lidocaine in the treatment of triptan-overuse headache (TOH), whose importance has increased lately. MATERIALS AND METHODS: In the study, 105 consecutive subjects diagnosed with TOH were evaluated. The subjects were randomized into three groups. In Group 1 (n=35), only triptan was abruptly withdrawn. In Group 2 (n=35), triptan was abruptly withdrawn and single GON block was performed. In Group 3 (n=35), triptan was abruptly withdrawn and three-stage GON block was performed. All patients were injected bilaterally with a total amount of 5 cc 1% lidocaine in each stage. During follow-up, the number of headache days per month, the severity of pain (VAS), the number of triptans used, and hsCRP and IL-6 levels were recorded three times; in the pretreatment period, in the second month post-treatment, and in the fourth month post-treatment. They were then compared. RESULTS: There was a statistically significant difference in the post-treatment fourth month in comparison with the pretreatment period in Group 3 (P<.05). Compared to Group 1, the number of headache days, VAS, and decrease in triptan need in Group 3 was statistically significant compared to Group 2 (P<.05). Compared to pretreatment, in the fourth month post-treatment, both hsCRP and IL-6 levels were lower only in Group 3 (P<.05). CONCLUSIONS: We are of the opinion that repeated GON block in addition to the discontinuation of medication has significant efficacy for TOH cases.

Anti-inflammatory effect of caffeine is associated with improved lung function after lipopolysaccharide-induced amnionitis.

BACKGROUND: Although caffeine enhances respiratory control and decreases the need for mechanical ventilation and resultant bronchopulmonary dysplasia, it may also have anti-inflammatory properties in protecting lung function. OBJECTIVE: We hypothesized that caffeine improves respiratory function via an anti-inflammatory effect in lungs of a lipopolysaccharide (LPS)-induced pro-inflammatory amnionitis rat pup model. METHODS: Caffeine was given orally (10 mg/kg/day) from postnatal day (p)1 to p14 to pups exposed to intra-amniotic LPS or normal saline. Expression of IL-1ß was assessed in lung homogenates at p8 and p14, and respiratory system resistance (Rrs) and compliance (Crs) as well as CD68 cell counts and radial alveolar counts were assessed at p8. RESULTS: In LPS-exposed rats, IL-1ß and CD68 cell counts both increased at p8 compared to normal saline controls. These increases in pro-inflammatory markers were no longer present in caffeine-treated LPS-exposed pups. Rrs was higher in LPS-exposed pups (4.7 ± 0.9 cm H2O/ml·s) at p8 versus controls (1.6 ± 0.3 cm H2O/ml·s, p < 0.01). LPS-exposed pups no longer exhibited a significant increase in Rrs (2.8 ± 0.5 cm H2O/ml·s) after caffeine. Crs did not differ significantly between groups, although radial alveolar counts were lower in both groups of LPS-exposed pups. CONCLUSIONS: Caffeine promotes anti-inflammatory effects in the immature lung of prenatal LPS-exposed rat pups associated with improvement of Rrs, suggesting a protective effect of caffeine on respiratory function via an anti-inflammatory mechanism.

The prevalence of chronic and episodic migraine in children and adolescents.

BACKGROUND AND PURPOSE: Migraine is the most important cause of headache leading to a decrease in the quality of life in children and adolescents. The prevalence of episodic (EM) and chronic migraine (CM) increases with increasing age, which especially focused in recent years. METHODS: To evaluate the prevalence and determinants of migraine in children and adolescents, we performed this school-based epidemiological study. First part of the study was performed in 2001 that included 5562 children. Second part of the study was performed in 2007 in adolescents including 1155 young. After the main reports published, we made a new analysis in the database that focused on migraine. RESULTS: Totally, 10.4% of the children, predominantly the girls, received the diagnosis of migraine when they grew older (1.7% CM, 8.6% EM). CM frequency increased with increasing ages (doubled at 12 years, P = 0.035). The significant risk factors for having CM were found to be age, gender, and father and sibling headache histories. Most of the clinical characteristics of migraine are far from classical knowledge in children with CM. In adolescents, 18.6% were diagnosed as migraine (1.5%CM, 17.1%EM) with a predominance of girls without age difference. When they reached puberty after 6 years, double the number of cases with CM was headache free. Most of the young changed their headache characteristics during the follow-up period independent from management strategies. CONCLUSIONS: Our results showed that CM is an important cause of headache in both children and adolescents with some defining headache characteristics and risk factors concentrated in different age-groups.

Abnormal MRI in a patient with 'headache with neurological deficits and CSF lymphocytosis (HaNDL)'.

A 27-year-old woman was admitted to the Emergency Department with right upper-extremity numbness and mild weakness followed by a bifrontal throbbing headache for 30 min, which was similar to a headache lasting for 12 h that had occurred 3 days ago. Laboratory tests were unremarkable except for cerebrospinal fluid (CSF) lymphocytic pleocytosis. On the following day, a headache episode with left hemiparesis and hemihypoaesthesia, left hemifield visio-spatial inattention, anosagnosia and confusion recurred. The headache was diagnosed as headache and neurological deficits with cerebrospinal fluid lymphocytosis (HaNDL) syndrome according to the criteria of the second edition of the International Classification of Headache Disorders. Simultaneously performed magnetic resonance imaging (MRI) revealed swelling of the grey matter, CSF enhancement in the sulci of the right temporal and occipital regions and hypoperfusion of the same brain regions. During the following 10 days two more similar episodes recurred and during the ensuing 12 months the patient remained headache free. Neuroimaging findings of the HaNDL syndrome are always thought as virtually normal. MRI abnormalities in our patient have not been reported in HaNDL syndrome previously, although they have been reported in hemiplegic migraine patients before. The findings in our case suggest that hemiplegic migraine and HaNDL syndrome may share a common pathophysiological pathway resulting in similar imaging findings and neurological symptoms.

The sensitivity of clinical diagnostic methods in the diagnosis of diabetic neuropathy.

This study assessed the sensitivity of various methods for the clinical diagnosis of diabetic peripheral neuropathy. A total of 147 randomly selected patients with diabetes mellitus and 65 age- and sex-matched healthy controls were evaluated by various clinical (the neuropathy symptom score [NSS], the neuropathy disability score [NDS], vibration perception thresholds [VPTs], Tinel's sign and Phalen's sign), laboratory (fasting plasma glucose and glycosylated haemoglobin levels) and electro-physiological (nerve conduction studies, H-reflex and F-wave measurements) methods. In the patient group, 8.2% had an abnormal NSS, 28.5% had a positive Phalen's sign, 32.6% had a positive Tinel's sign, 42.8% had an abnormal VPT and 57.1% had an abnormal NDS. Significant correlations were found between electro-physiologically confirmed neuropathy and the two provocation tests and abnormal VPTs. In conclusion, assessment with a complete neurological examination and standard electrophysiological tests is very important for the diagnosis of diabetic peripheral neuropathy and the prevention of morbidity in patients with or without symptoms.

Seizure development after stroke.

Although there have been many studies on seizures following stroke, there is still much we do not know about them. In this study, we evaluated the characteristics of seizures in stroke patients. There were 2267 patients with a first-ever stroke, and after excluding 387 patients, 1880 were available for analysis. Of these 1880 patients, we evaluated 200 patients with seizures and 400 patients without seizures. We investigated the seizures according to age, gender, stroke type, the aetiology of ischaemic stroke and the localisation of the lesion. The seizures were classified as early onset and late onset and the seizure type as partial, generalised or secondarily generalised. Seizures occurred in 200 (10.6%) of 1880 strokes. The number of patients with seizures were 138 (10.6%) in ischaemic stroke group and 62 (10.7%) in haemorrhagic stroke group. Patients with ischaemic strokes had 41 embolic (29.7%) and 97 thrombotic (70.3%) origin, and these were not statistically significant in comparison with controls. Cortical involvement for the development of seizures was the most important risk factor (odds ratios = 4.25, p < 0.01). It was concluded that embolic strokes, being younger than 65 years old, and cortical localisation of stroke were important risks for developing seizures.

The relationship between migraine and atopic disorders-the contribution of pulmonary function tests and immunological screening.

This cross-sectional clinical study was conducted in order to explore the relationship between atopic disorders and migraine. We evaluated 186 consecutive patients with migraine. Patients with a history of atopic disorders were compared with the others during headache-free intervals, for their headache characteristics, pulmonary test (PFT) performances and immunological screenings, through appropriate statistical methods. Of the patients with migraine, 77 (41.4%) reported at least one atopic disorder. PFT screening showed a general decreased pulmonary capacity and an important correlation between a positive history of atopic disorders and both increased eosinophil and IgE levels in headache-free periods. It should be discussed whether screening with PFT or immunological tests helps in early detection of progressive lung disease which might develop in these patients.

Sepsis induces early phrenic nerve neuropathy in rats.

The aim of the present study was to investigate the electrophysiology of the phrenic nerve and the diaphragm muscle during sepsis. In total, 26 rats underwent either sham laparotomy or caecal ligation and puncture (CLP). Electrophysiology was evaluated via a phrenic nerve conduction study and needle electromyography of the diaphragm, prior to CLP, 6 and 24 h post-CLP and on day 7. The histopathology of the diaphragm muscle and phrenic nerve was also examined on day 7. In the sepsis group, the phrenic nerve conduction study showed decreased amplitude of compound action potential (CMAP), and prolongation in the duration and the latency of CMAP. The diaphragmatic needle electromyography showed decreased amplitude and frequency of the motor unit action potential (MUP), and prolongation in the duration of MUP, at all time points, compared with the pre-CLP values. The electrophysiological abnormalities were consistent with axonal and demyelinating phrenic nerve neuropathy. Electrophysiological abnormalities were present at 6 h with worsening at 24 h and on day 7. Histopathological examination showed normal muscular fibres and focally slight myelin degenerations of the phrenic nerve fibres. In conclusion, sepsis induced phrenic nerve neuropathy as early as the 6th h in rats.

The sensitivity and specificity of the case definition criteria in diagnosis of headache: a school-based epidemiological study of 5562 children in Mersin.

The objectives of the present study were to estimate the prevalence of recurrent headaches in schoolchildren (ranging from 2nd to 5th degrees) in Mersin city of Turkey and to determine the sensitivity, specificity, positive predictive value and positive likelihood ratio of the diagnostic headache characteristics in children with migraine and Tension Type Headache (TTH) using neurologist's diagnosis as the gold standard. The stratified sample of study was composed of 5562 children. The prevalence of recurrent headache was 49.2% (2739 of 5562) and the prevalence of current headache was 31.3% (859 of 2739). TTH was more common than migraine (24.7% vs. 10.4%). The most sensitive headache characteristic for migraine was 'severity of pain' and the most sensitive definitive symptom is 'duration of headache' in children with TTH. IHS-based symptom definition criteria are highly beneficial in diagnosis of childhood headache, if used together with detailed clinical assessment.