Anatomoelectroclinical features of SEEG-confirmed pure insular-onset epilepsy.

PURPOSE: In this study, we aimed to improve our knowledge of insular epilepsy by studying anatomoelectroclinical correlations in pure insular-onset epilepsy and characterizing differences between anterior and posterior insular-onset seizures. METHODS: Patients in whom seizure-onset zone was confined to the insula and peri-insular sulcus were selected from 301 consecutive presurgical stereo-electroencephalography (EEG) recordings performed between years 2010 and 2017 in two epilepsy centers. Ictal-onset zone in stereo-EEG was delineated visually and quantitatively using epileptogenic index method. Seizure characteristics were reanalyzed, and anatomoelectroclinical correlations were assessed. Characteristics of posterior and anterior insular-onset seizures were compared. RESULTS: Eleven insular cases were identified, five of them with an anterior insular seizure onset and six with a posterior one. Nonpainful somatosensory symptoms and autonomic symptoms were the most common symptoms (73% of patients) followed by speech-related symptoms (55%) and ipsilateral eye blinking (45%). Six patients had seizures restricted to somatosensory or viscerosensory symptoms. In all patients, seizures progressed to motor symptoms. Somatosensory symptoms did not differentiate anterior from posterior insular seizures. However, hyperkinetic signs, speech modifications, and viscerosensory symptoms were related to an anterior insular seizure-onset zone. Pain, asymmetric tonic, focal clonic, and tonic symptoms were more frequent in patients with a posterior insular seizure onset. CONCLUSIONS: Seizure semiology is heterogeneous in pure insular-onset epilepsy. Differences between the anterior and posterior insular seizures reflect the functional organization of the insula. Particularly, the different types of motor symptoms may help to distinguish anterior from posterior insular seizure onset.

Etiology and Long-Term Outcomes of Late-Onset Infantile Spasms.

OBJECTIVES: The purpose of the study was to evaluate the etiology and long-term outcomes of late-onset epileptic spasms (LOS). METHODS: This is a retrospective analysis of all consecutive patients seen at our center with onset of clusters of epileptic spasms between 1 and 3 years of age in 1995 through 2005. RESULTS: Overall, 17 children with LOS were identified. Overall, 14 children (82%) had structural etiology. Six patients received resective surgical treatment. Five had focal cortical dysplasia type 1 (FCD1) histology (29% of all the patients). Overall, 16 children were followed for 2 to 18 years. At the latest follow-up, seizure freedom was observed in 67% of the operated and in 50% of the nonoperated patients. Normal cognition or only mild mental deficiency was observed in nine patients (56%), of whom eight were seizure-free. All patients with intractable spasms had a severe mental deficiency. CONCLUSION: The overall cognitive outcome of LOS was more favorable than in the previous reports and was associated with seizure freedom. FCD1 is a frequent etiology for LOS and the cognitive outcome of patients with FCD1 seemed to be favorable.

Adolescent cervical disc degeneration in MRI does not predict adult headache or neck pain: A 5-year follow-up of adolescents with and without headache.

AIM: The impact of early degenerative changes of the cervical spine on pain in adulthood is unknown. The objective was to determine whether degeneration in adolescence predicts headache or neck pain in young adulthood. METHODS: As part of a follow-up of schoolchildren with and without headache, 17-year-old adolescents with headache at least three times a month (N = 47) and adolescents with no headache (N = 22) participated in a magnetic resonance imaging (MRI) study of the cervical spine. The same adolescents were re-examined by phone interview at the age of 22 years (N = 60/69, 87%). RESULTS: Mild disc degeneration at the age of 17 years was common, but was not associated with either frequent or intensive headache or neck pain at the age of 22 years. Conclusion: Mild degenerative changes of the cervical spine in 17-year-old adolescents cannot be regarded as a cause of future headache or neck pain.

Cerebral glucose utilization measured with high resolution positron emission tomography in epileptic Finnish Spitz dogs and healthy dogs.

In human epileptic patients, changes in cerebral glucose utilization can be detected 2-deoxy-2-[(18) F] fluoro-D-glucose positron emission tomography (FDG-PET). The purpose of this prospective study was to determine whether epileptic dogs might show similar findings. Eleven Finnish Spitz dogs with focal idiopathic epilepsy and six healthy dogs were included. Dogs were examined using electroencephalography (EEG) and FDG-PET, with epileptic dogs being evaluated during the interictal period. Visual and semi-quantitative assessment methods of FDG-PET were compared and contrasted with EEG findings. Three independent observers, unaware of dog clinical status, detected FDG-PET uptake abnormalities in 9/11 epileptic (82%), and 4/8 healthy dogs (50%). Occipital cortex findings were significantly associated with epileptic status (P = 0.013). Epileptic dogs had significantly lower standardized uptake values (SUVs) in numerous cortical regions, the cerebellum, and the hippocampus compared to the control dogs. The lowest SUVs were found in the occipital lobe. White matter normalized and left-right asymmetry index values for all pairs of homologous regions did not differ between groups. Visual evaluation of the EEGs was less sensitive (36%) than FDG-PET. Both diagnostic tests were consensual and specific (100%) for occipital findings, but EEG had a lower sensitivity for detecting lateralized foci than FDG-PET. Findings supported the use of FDG-PET as a diagnostic test for dogs with suspected idiopathic epilepsy. Visual and semiquantitative analyses of FDG-PET scans provided complementary information. Findings also supported the theory that epileptogenesis may occur in multiple brain regions in Finnish Spitz dogs with idiopathic epilepsy.

FDG-PET in healthy and epileptic Lagotto Romagnolo dogs and changes in brain glucose uptake with age.

Regional cerebral metabolism and blood flow can be measured noninvasively with positron emission tomography (PET). 2-[(18) F]fluoro-2-deoxy-D-glucose (FDG) widely serves as a PET tracer in human patients with epilepsy to identify the seizure focus. The goal of this prospective study was to determine whether juvenile or adult dogs with focal-onset epilepsy exhibit abnormal cerebral glucose uptake interictally and whether glucose uptake changes with age. We used FDG-PET to examine six Lagotto Romagnolo dogs with juvenile epilepsy, two dogs with adult-onset epilepsy, and five control dogs of the same breed at different ages. Three researchers unaware of dog clinical status visually analyzed co-registered PET and magnetic resonance imaging (MRI) images. Results of the visual PET analyses were compared with electroencephalography (EEG) results. In semiquantitative analysis, relative standard uptake values (SUV) of regions of interest (ROI) drawn to different brain regions were compared between epileptic and control dogs. Visual analysis revealed areas of hypometabolism interictally in five out of six dogs with juvenile epilepsy in the occipital, temporal, and parietal cortex. Changes in EEG occurred in three of these dogs in the same areas where PET showed cortical hypometabolism. Visual analysis showed no abnormalities in cerebral glucose uptake in dogs with adult-onset epilepsy. Semiquantitative analysis detected no differences between epileptic and control dogs. This result emphasizes the importance of visual analysis in FDG-PET studies of epileptic dogs. A change in glucose uptake was also detected with age. Glucose uptake values increased between dog ages of 8 and 28 weeks and then remained constant.

Corticosteroids versus clobazam for treatment of children with epileptic encephalopathy with spike-wave activation in sleep (RESCUE ESES): a multicentre randomised controlled trial.

BACKGROUND: Epileptic encephalopathy with spike-wave activation in sleep (EE-SWAS) is a rare syndrome associated with cognitive and behavioural regression. On the basis of mostly small observational and retrospective studies, corticosteroids and clobazam are often considered the most effective treatments for this syndrome. We aimed to compare cognitive outcomes of children with EE-SWAS 6 months after starting treatment with either corticosteroids or clobazam. METHODS: We did a multicentre, randomised controlled trial at eight tertiary referral centres for rare epilepsies in seven European countries. Children were eligible to participate if they were aged 2-12 years, were diagnosed with EE-SWAS within 6 months before inclusion, and had not been treated with corticosteroids or clobazam previously. Participants were randomly assigned (1:1) to treatment with corticosteroids (either continuous treatment with 1-2 mg/kg per day of prednisolone orally or pulse treatment with 20 mg/kg per day of methylprednisolone intravenously for 3 days every 4 weeks) or clobazam (0·5-1·2 mg/kg per day orally). The primary outcome was cognitive functioning after 6 months of treatment, which was assessed by either the intelligence quotient (IQ) responder rate (defined as improvement of ≥11·25 IQ points) or the cognitive sum score responder rate (defined as improvement of ≥0·75 points). Safety was assessed by number of adverse events and serious adverse events. Data were analysed in the intention-to-treat population, which included all children as randomised who had primary outcome data available at 6 months. The trial is registered with the Dutch Trial Register, Toetsingonline, NL43510.041.13, and the ISRCTN registry, ISRCTN42686094. The trial was terminated prematurely because enrolment of the predefined number of 130 participants was deemed not feasible. FINDINGS: Between July 22, 2014, and Sept 3, 2022, 45 children were randomly assigned to either corticosteroids (n=22) or clobazam (n=23); two children assigned clobazam dropped out before 6 months and were excluded from the intention-to-treat analysis. At the 6-month assessment, an improvement of 11·25 IQ points or greater was reported for five (25%) of 20 children assigned corticosteroids versus zero (0%) of 18 assigned clobazam (risk ratio [RR] 10·0, 95% CI 1·2-1310·4; p=0·025). An improvement of 0·75 points or more in the cognitive sum score was recorded for one (5%) of 22 children assigned corticosteroids versus one (5%) of 21 children assigned clobazam (RR 1·0, 95% CI 0·1-11·7, p=0·97). Adverse events occurred in ten (45%) of 22 children who received corticosteroids, most frequently weight gain, and in 11 (52%) of 21 children who received clobazam, most often fatigue and behavioural disturbances. Occurrence of adverse events did not differ between groups (RR 0·8, 95% CI 0·4-1·4; p=0·65). Serious adverse events occurred in one child in the corticosteroid group (hospitalisation due to laryngitis) and in two children in the clobazam group (hospitalisation due to seizure aggravation, and respiratory tract infection). No deaths were reported. INTERPRETATION: The trial was terminated prematurely, and the target sample size was not met, so our findings must be interpreted with caution. Our data indicated an improvement in IQ outcomes with corticosteroids compared with clobazam treatment, but no difference was seen in cognitive sum score. Our findings strengthen those from previous uncontrolled studies that support the early use of corticosteroids for children with EE-SWAS. FUNDING: EpilepsieNL, WKZ fund, European Clinical Research Infrastructure Network, and Ming fund.

Applicability of nTMS in locating the motor cortical representation areas in patients with epilepsy.

BACKGROUND: Transcranial magnetic stimulation (TMS) is increasingly used for non-invasive functional mapping in preoperative evaluation for brain surgery, and the reliability of navigated TMS (nTMS) motor representation maps has been studied in the healthy population and in brain tumor patients. The lesions behind intractable epilepsy differ from typical brain tumors, ranging from developmental cortical malformations to injuries early in development, and may influence the functional organization of the cortical areas. Moreover, the interictal cortical epileptic activity and antiepileptic medication may affect the nTMS motor threshold. The reliability of the nTMS motor representation localization in epilepsy patients has not been addressed. METHODS: We compared the nTMS motor cortical representation maps of hand and arm muscles with the results of invasive electrical cortical stimulation (ECS) in 13 patients with focal epilepsy. The nTMS maps were projected to the cortical surface segmented from preoperative magnetic resonance images (MRI), and the positions of the subdural electrodes were extracted from the postoperative low-dose computed tomography (CT) images registered with preoperative MRI. RESULTS: The 3D distance between the average nTMS site and average ECS electrode location was 11 ± 4 mm for the hand and 16 ± 7 mm for arm muscle representation areas. In all patients the representation areas defined with nTMS and ECS were located on the same gyrus, also in patients with abundant interictal epileptic activity on the motor gyrus. CONCLUSIONS: nTMS can reliably locate the hand motor cortical representation area with the accuracy needed for pre-surgical evaluation in patients with epilepsy.

[Tuberous sclerosis]. / Tuberoosiskleroosi.

Tuberous sclerosis is a polymorphic, dominantly inherited syndrome caused by an inactivating mutation in a tumor suppressor gene. The disease involves benign tumors in several distinct organs such as the skin, kidneys, heart and central nervous system. The tumors interfere with organ function, but only some exhibit a significant tendency to grow. The clinical picture of tuberous sclerosis varies from nearly symptomless to a severe disease. Treatment of growing tumors associated with tuberous sclerosis is changing significantly, since their growth can be suppressed with rapamycin and its derivatives.

[EEG under the surface]. / EEG pintaa syvemmältä.

Epilepsy work-up is based on history and scalp EEG. Drug resistant epilepsy should be evaluated in a dedicated epilepsy surgery unit. Sometimes non-invasive studies fail to localize the epileptogenic area in focal epilepsy and then the work up can be complemented with intracranial EEG. Intracranial electrodes are implanted either in the subdural space or intraparenchymally. This is followed by one to two weeks of EEG monitoring in a specialized videotelemetry unit. Intracranial EEG helps to define the borders of the epileptogenic area for resection. The ultimate objective is to render the patient seizure free. The outcome of resective epilepsy surgery depends on the etiology of epilepsy, localization of the epileptogenic area and MR image yield.

Towards optimised extracellular vesicle proteomics from cerebrospinal fluid.

The proteomic profile of extracellular vesicles (EVs) from cerebrospinal fluid (CSF) can reveal novel biomarkers for diseases of the brain. Here, we validate an ultrafiltration combined with size-exclusion chromatography (UF-SEC) method for isolation of EVs from canine CSF and probe the effect of starting volume on the EV proteomics profile. First, we performed a literature review of CSF EV articles to define the current state of art, discovering a need for basic characterisation of CSF EVs. Secondly, we isolated EVs from CSF by UF-SEC and characterised the SEC fractions by protein amount, particle count, transmission electron microscopy, and immunoblotting. Data are presented as mean ± standard deviation. Using proteomics, SEC fractions 3-5 were compared and enrichment of EV markers in fraction 3 was detected, whereas fractions 4-5 contained more apolipoproteins. Lastly, we compared starting volumes of pooled CSF (6 ml, 3 ml, 1 ml, and 0.5 ml) to evaluate the effect on the proteomic profile. Even with a 0.5 ml starting volume, 743 ± 77 or 345 ± 88 proteins were identified depending on whether 'matches between runs' was active in MaxQuant. The results confirm that UF-SEC effectively isolates CSF EVs and that EV proteomic analysis can be performed from 0.5 ml of canine CSF.

Interictal magnetoencephalography in parietal lobe epilepsy - Comparison of equivalent current dipole and beamformer (SAMepi) analysis.

OBJECTIVE: To evaluate a novel analysis method (SAMepi) in the localization of interictal epileptiform magnetoencephalographic (MEG) activity in parietal lobe epilepsy (PLE) patients in comparison with equivalent current dipole (ECD) analysis. METHODS: We analyzed the preoperative interictal MEG of 17 operated PLE patients utilizing visual analysis and: (1) ECD with a spherical conductor model; (2) ECD with a boundary element method (BEM) conductor model; and (3) SAMepi - a kurtosis beamformer method. Localization results were compared between the three methods, to the location of the resection and to the clinical outcome. RESULTS: Fourteen patients had an epileptiform finding in the visual analysis; SAMepi detected spikes in 11 of them. A unifocal finding in both the ECD and in the SAMepi analysis was associated with a better chance of seizure-freedom (p = 0.02). There was no significant difference in the distances from the unifocal MEG localizations to the nearest border of the resection between the different analysis methods. CONCLUSIONS: Localizations of unifocal interictal spikes detected by SAMepi did not significantly differ from the conventional ECD localizations. SIGNIFICANCE: SAMepi - a novel semiautomatic analysis method - is useful in localizing interictal epileptiform MEG activity in the presurgical evaluation of parietal lobe epilepsy patients.

Prevalence and incidence of headache in adolescent Finnish twins.

OBJECTIVES: The study aim was to determinate changes in prevalence and incidence rates of headache among adolescent Finnish twins. METHODS: Questionnaire data were collected during 1994-1998 from a nationwide sample of Finnish families of 11-year-old twins who were born between 1983 and 1987 (n = 6262) and again at ages of 14 and 17. RESULTS: During follow-up, the prevalence of regular headache (ie, at least once a month = RHA) increased from 59% at age 11 to 65% at age 14 and decreased to 63% at age 17. Among boys the prevalence of RHA increased significantly from 59% at age 11 to 62% at age 14 decreasing to 52% at age 17. Among girls the prevalence rates increased significantly between ages of 11 and 14 from 60% to 68% up to 74% at age 17. The prevalence of weekly headache increased in girls between ages of 11 and 14 from 16% to 25%. Incidence of RHA (at least once a month) decreased from 47% at age 14 to 44% at age 17 in girls and from 44% at age 14 to 30% at age 17 in boys. CONCLUSIONS: RHA is more common in girls than boys during puberty, while the incidence of RHA declined especially in boys during same age period.

Seizure-precipitating factors in dogs with idiopathic epilepsy.

BACKGROUND: Stress, sleep deprivation, and infectious diseases are important seizure-precipitating factors in human epilepsy patients. However, these factors have not been thoroughly studied in epileptic dogs. OBJECTIVE: Seizure-precipitating factors are common in dogs with idiopathic epilepsy and the occurrence of these factors associate with the dogs' signalment, personality, and epilepsy-related factors. ANIMALS: Fifty dogs with diagnosed idiopathic epilepsy from the hospital populations of University Veterinary Teaching Hospital of University of Helsinki and Referral Animal Hospital Aisti. METHODS: In a retrospective cross-sectional observational study, owners were interviewed about their dogs' possible seizure-precipitating factors according to a predefined questionnaire. The dogs were identified and selected by searching the medical records of the participating animal hospitals. RESULTS: The prevalence of seizure-precipitating factors in the study population was 74% (37/50). The most frequently reported factors included stress-related situations, sleep deprivation, weather, and hormonal factors. In dogs with focal onset seizures, the number of precipitating factors was 1.9 (95% CI 1.1-3.4) times higher compared to dogs with generalized seizures. CONCLUSIONS AND CLINICAL IMPORTANCE: Seizure-precipitating factors are common in dogs with idiopathic epilepsy, and the nature of these factors is consistent with those of human patients. Aside from antiepileptic medication, acknowledging and avoiding seizure-precipitating factors could help veterinarians achieve better treatment outcomes.

Xenon does not affect gamma-aminobutyric acid type A receptor binding in humans.

BACKGROUND: The noble gas xenon acts as an anesthetic with favorable hemodynamic and neuroprotective properties. Based on animal and in vitro data, it is thought to exert its anesthetic effects by inhibiting glutamatergic signaling, but effects on gamma-aminobutyric acid type A (GABA(A)) receptors also have been reported. The mechanism of anesthetic action of xenon in the living human brain still remains to be determined. METHODS: We used the specific GABA(A) receptor benzodiazepine-site ligand 11C-flumazenil and positron emission tomography to study the GABAergic effects of xenon in eight healthy male volunteers. Each subject underwent two dynamic 60-min positron emission tomography studies awake and during approximately one minimum alveolar concentration of xenon (65%). Bispectral index was recorded. Cortical and subcortical gray matter regions were analyzed using both automated regions-of-interest analysis and voxel-based analysis. RESULTS: During anesthesia, the mean +/- sd bispectral index was 23 +/- 7, and there were no significant changes in heart rate or mean arterial blood pressure. Xenon did not significantly affect 11C-flumazenil binding in any brain region. CONCLUSIONS: Xenon did not affect 11C-flumazenil binding in the living human brain, indicating that the anesthetic effect of xenon is not mediated via the GABA(A) receptor system.

Force production and EMG activity of neck muscles in adolescent headache.

PURPOSE: This study compared the maximal force, EMG/force ratio and co-activation characteristics of the neck-shoulder muscles between 30 adolescents with migraine-type headache, 29 with tension-type headache, and 30 headache-free controls. METHOD: Force was measured with surface electromyography (EMG) from the cervical erector spinae (CES), the sternocleidomastoid (SCM) and trapezius muscles during the maximal isometric neck flexion, neck extension and shoulder flexion. RESULTS: Girls with migraine-type headache had higher EMG/force ratios between the EMG of the left agonist SCM muscle and the corresponding maximal neck flexion (p = 0.030) and neck rotation force to the right side (p = 0.024) than the girls with tension-type headache. Migrainous girls had more co-activation of right antagonist CES muscle during maximal neck flexion force than the girls without headache (p = 0.015). Neck force production showed no significant differences between girls. Girls with tension-type headache displayed lower left shoulder flexion force than girls with migraine-type headache (p = 0.005) or with no headache (p = 0.005). In boys, no significant differences were observed. CONCLUSIONS: Girls with tension-type headache and migraine-type headache have differences in neuromuscular function in the neck-shoulder muscles. The data amplify our knowledge of the neck-shoulder muscle dysfunction in adolescent headache, and may encourage the use of specific rehabilitation methods in the management of different types of headache.

Language mapping with navigated transcranial magnetic stimulation in pediatric and adult patients undergoing epilepsy surgery: Comparison with extraoperative direct cortical stimulation.

OBJECTIVE: Navigated transcranial magnetic stimulation (nTMS) is becoming increasingly popular in noninvasive preoperative language mapping, as its results correlate well enough with those obtained by direct cortical stimulation (DCS) during awake surgery in adult patients with tumor. Reports in the context of epilepsy surgery or extraoperative DCS in adults are, however, sparse, and validation of nTMS with DCS in children is lacking. Furthermore, little is known about the risk of inducing epileptic seizures with nTMS in pediatric epilepsy patients. We provide the largest validation study to date in an epilepsy surgery population. METHODS: We compared language mapping with nTMS and extraoperative DCS in 20 epilepsy surgery patients (age range 9-32 years; 14 children and adolescents). RESULTS: In comparison with DCS, sensitivity of nTMS was 68%, specificity 76%, positive predictive value 27%, and negative predictive value 95%. Age, location of ictal-onset zone near or within DCS-mapped language areas or severity of cognitive deficits had no significant effect on these values. None of our patients had seizures during nTMS. SIGNIFICANCE: Our study suggests that nTMS language mapping is clinically useful and safe in epilepsy surgery patients, including school-aged children and patients with extensive cognitive dysfunction. Similar to in tumor surgery, mapping results in the frontal region are most reliable. False negative findings may be slightly more likely in epilepsy than in tumor surgery patients. Mapping results should always be verified by other methods in individual patients.

Common Variant Burden Contributes to the Familial Aggregation of Migraine in 1,589 Families.

Complex traits, including migraine, often aggregate in families, but the underlying genetic architecture behind this is not well understood. The aggregation could be explained by rare, penetrant variants that segregate according to Mendelian inheritance or by the sufficient polygenic accumulation of common variants, each with an individually small effect, or a combination of the two hypotheses. In 8,319 individuals across 1,589 migraine families, we calculated migraine polygenic risk scores (PRS) and found a significantly higher common variant burden in familial cases (n = 5,317, OR = 1.76, 95% CI = 1.71-1.81, p = 1.7 × 10-109) compared to population cases from the FINRISK cohort (n = 1,101, OR = 1.32, 95% CI = 1.25-1.38, p = 7.2 × 10-17). The PRS explained 1.6% of the phenotypic variance in the population cases and 3.5% in the familial cases (including 2.9% for migraine without aura, 5.5% for migraine with typical aura, and 8.2% for hemiplegic migraine). The results demonstrate a significant contribution of common polygenic variation to the familial aggregation of migraine.

Neck flexor muscle fatigue in adolescents with headache: an electromyographic study.

BACKGROUND: Muscular disorders of the neck region may be of importance for the etiology of tension-type headache. However, in adolescents, there are no data on the association between neck muscle fatigue and headache. AIM: To study differences in fatigue characteristics of the neck flexor muscles in adolescents with and without headache. METHODS: A population-based sample of 17-year-old adolescents with migraine-type headache (N=30), tension-type headache (N=29) and healthy controls without headache (N=30) was examined. Surface EMG data were recorded from the sternocleidomastoid (SCM) muscles bilaterally during an isometric neck flexor endurance test. The spectral median frequency (MF) change during the total endurance time (TMF) and the initial time of 30s (IMF) was calculated. The intensity of discomfort in the neck area was assessed with the visual analogue scale (VAS). RESULTS: The rate of decline in TMF of both SCM muscles was significantly increased in the tension-type headache group compared with controls (right SCM, P=0.030, OR 2.0, 95% 1.2-3.7; left SCM, P=0.009, OR 2.5, 95% 1.4-4.9), while no significant differences were found between controls and subjects with migraine. The rate of decline in IMF, the total endurance time (P=0.050), and VAS did not differ significantly among the study groups. CONCLUSIONS: This preliminary finding shows that increased neck flexor muscle fatigue in adolescents seems to be associated with tension-type headache.

Extracephalic tenderness and pressure pain threshold in children with headache.

BACKGROUND: Sensitisation of the pain detection system has been suggested to be involved in the pathogenesis of recurrent headache. In adults, increased sensitivity to pain has been found in patients with chronic tension type headache. Children with migraine or with unspecific headache report non-headache pains and interictal pericranial muscular tenderness more often than headache-free children. OBJECTIVE: To study if children with different types of headache report non-headache pain more often than children with no headache and if extracephalic muscular tenderness is different in children with headache in comparison to headache-free children. To find out if interval to the headache episode has influence on the extracranial muscular tenderness. DESIGN: A population-based sample of 13-year-old children with migraine (n=48), episodic tension type headache (61) or no headache (59) were interviewed for the occurrence and characteristics of headache and fulfilled a questionnaire on non-headache pain. A structured manual palpation test on muscular tenderness and a pain threshold measurement were done on seven cephalic and three extracephalic points. RESULTS: Children with migraine reported other pains, especially stomach pain and limb pain more often than children with episodic tension type or no headache. There were no significant differences in the extracephalic muscular tenderness or in the pressure pain thresholds between the three groups. CONCLUSIONS: Children with migraine experience more non-headache pains than children with episodic tension type headache and with no headache. However, neither children with migraine nor children with episodic tension type headache show increased interictal extracephalic muscular sensitivity for palpation.