Ictal and interictal MEG in pediatric patients with tuberous sclerosis and drug resistant epilepsy.

PURPOSE: Drug resistant epilepsy (DRE) is common in patients with tuberous sclerosis (TS). Interictal MEG has been shown as a valuable instrument in the presurgical workup. The goal of our study was to evaluate the role of ictal MEG in epileptogenic tuber selection, especially in patients with multiple irritative zones. METHODS: The clinical and MEG data of 23 patients with TS and DRE from two medical/research centers were reviewed. Seven pediatric patients, who had seizures during MEG recording and underwent resection or disconnection surgery, were included into the study. Cortical sources of ictal and interictal epileptiform MEG discharges were compared with epileptogenic zone location in six patients with favorable surgery outcome. RESULTS: In patients who improved substantially after surgery all resected and several other tubers demonstrated epileptiform activity on interictal MEG. Ictal MEG provided crucial information about lobar location of the seizure onset zone (SOZ) in two cases, and in the other four it confirmed the SOZ location derived from the interictal data. In one case, ictal MEG findings were unreliable. In one patient, who did not benefit from surgical treatment, the resected tubers did not overlap with interictal and ictal MEG sources. CONCLUSION: The combination of interictal and ictal MEG is a valuable tool for identification of the epileptogenic tuber/tubers in presurgical work-up in patients with TS.

Behavioral Abnormalities in Lagotto Romagnolo Dogs with a History of Benign Familial Juvenile Epilepsy: A Long-Term Follow-Up Study.

BACKGROUND: Lagotto Romagnolo (LR) dogs with benign juvenile epilepsy syndrome often experience spontaneous remission of seizures. The long-term outcome in these dogs currently is unknown. In humans, behavioral and psychiatric comorbidities have been reported in pediatric and adult-onset epilepsies. HYPOTHESIS/OBJECTIVES: The objectives of this study were to investigate possible neurobehavioral comorbidities in LR with a history of benign familial juvenile epilepsy (BFJE) and to assess the occurrence of seizures after the remission of seizures in puppyhood. ANIMALS: A total of 25 LR with a history of BFJE and 91 control dogs of the same breed. METHODS: Owners of the LR dogs in the BFJE and control groups completed an online questionnaire about each dog's activity, impulsivity, and inattention. Principal component analysis (PCA) served to extract behavioral factors from the data. We then compared the scores of these factors between the 2 groups in a retrospective case-control study. We also interviewed all dog owners in the BFJE group by telephone to inquire specifically about possible seizures or other neurological problems after remission of seizures as a puppy. RESULTS: Lagotto Romagnolo dogs with BFJE showed significantly higher scores on the factors Inattention and Excitability/Impulsivity than did the control group (P = .003; P = .021, respectively). Only 1 of the 25 BFJE LR exhibited seizures after remission of epilepsy in puppyhood. CONCLUSIONS AND CLINICAL IMPORTANCE: Although the long-term seizure outcome in BFJE LR seems to be good, the dogs exhibit behavioral abnormalities resembling attention deficit hyperactivity disorder (ADHD) in humans, thus suggesting neurobehavioral comorbidities with epilepsy.

Combined use of non-invasive techniques for improved functional localization for a selected group of epilepsy surgery candidates.

Invasive cortical mapping is conventionally required for preoperative identification of epileptogenic and eloquent cortical regions before epilepsy surgery. The decision on the extent and exact location of the resection is always demanding and multimodal approach is desired for added certainty. The present study describes two non-invasive preoperative protocols, used in addition to the normal preoperative work-up for localization of the epileptogenic and sensorimotor cortical regions, in two young patients with epilepsy. Magnetoencephalography (MEG) was used to determine the primary somatosensory cortex (S1) and the ictal onset zones. Navigated transcranial magnetic stimulation (nTMS) was used to determine the location and the extent of the primary motor representation areas. The localization results from these non-invasive methods were used for guiding the subdural grid deployment and later compared with the results from electrical cortical stimulation (ECS) via subdural grids, and validated by surgery outcome. The results from MEG and nTMS localizations were consistent with the ECS results and provided improved spatial precision. Consistent results of our study suggest that these non-invasive methods can be added to the standard preoperative work-up and may even hold a potential to replace the ECS in a subgroup of patients with epilepsy who have the suspected epileptogenic zone near the sensorimotor cortex and seizures frequent enough for ictal MEG.

Are signs of temporomandibular disorders stable and predictable in adolescents with headache?

The aim of the present study was to study changes in signs and symptoms of temporomandibular disorders (TMD) and factors predicting TMD signs in adolescents with and without headache. A population-based sample (n = 212) of 13-year-olds with and without headache was re-examined at the age of 16. The study included a questionnaire, face-to-face interview and somatic examination. In addition, a neurological examination, a muscle evaluation and a stomatognathic examination were performed. Significant changes were seen in TMD signs during the follow-up, but TMD signs at the end of the follow-up could not be predicted by baseline headache, sleeping difficulties, depression or muscle pain. TMD signs at the age of 16 were associated with female gender and muscle pain. We conclude that considerable changes in TMD signs occur in the follow-up of adolescents with and without headache. Headache-related TMD are not predictable in adolescents with and without headache.

Characteristics of neck pain associated with adolescent headache.

The objective of the study was to find out what kind of neck pain (NP) is associated with headache (HA) and with various headache variables: frequency, type, intensity, disturbance, and relief with analgesics. A population-based sample of 12-year-olds with and without HA (n = 304) was followed for 4 years. At the age of 16 years, NP was evaluated on the basis of self-reported symptoms and a thorough physical examination of the neck region. Both self-reported and measured NP were associated with HA variables. Co-occurrent NP was found in adolescents with migraine as often as in those with tension-type HA. Especially, muscle pain and intensive, frequent NP were associated with disturbing HA unresponsive to analgesics. The study indicates that concomitant NP should be considered in adolescent HA sufferers, and a thorough cervical and muscle evaluation is recommended when planning the treatment of HA.

Benign familial juvenile epilepsy in Lagotto Romagnolo dogs.

BACKGROUND: Idiopathic childhood epilepsies with benign outcomes are well recognized in human medicine, but are not reported in veterinary literature. We recognized such a neurologic syndrome in Lagotto Romagnolo dogs. ANIMALS: Twenty-five Lagotto Romagnolo puppies from 9 different litters examined because of simple or complex focal seizures and 3 adult Lagotto Romagnolo dogs exhibiting similar clinical signs were used. METHODS: Clinical and diagnostic evaluations of affected dogs were conducted, including electromyography, electroencephalography, and other testing. RESULTS: Seizures in puppies began at 5 to 9 weeks of age and usually resolved spontaneously by 8 to 13 weeks. Those with the most severe seizures also had signs of neurologic disease between these seizures, including generalized ataxia and hypermetria. There were no abnormalities in routine laboratory screenings of blood, urine, and cerebrospinal fluid. Electromyography, brainstem auditory-evoked potentials, and magnetic resonance imaging revealed no specific and consistent abnormalities. Fourteen of 16 (87.5%) affected puppies and 2 of 3 (67%) adult dogs revealed epileptiform activity in the electroencephalogram. Histopathologic examination in 1 puppy and 1 adult dog revealed lesions of Purkinje cell inclusions and vacuolation of their axons restricted to the cerebellum. Pedigree analysis suggests an autosomal recessive mode of inheritance. CONCLUSIONS AND CLINICAL IMPORTANCE: This disorder, with simple or complex focal seizures and cerebellar lesions, represents a newly recognized epileptic syndrome in dogs.

Does neck pain determine the outcome of adolescent headache?

The aim of the study was to examine the influence of concomitant neck pain (NP) on the outcome of headache (HA) frequency and HA type in adolescence. A population-based sample of 13-year-olds with or without HA (n = 228) was followed for 3 years. NP was evaluated at the beginning of the follow-up on the basis of recorded muscle tenderness and self-reported symptoms. During the 3 years of follow-up, changes in both HA type and frequency were common. NP interfering with daily activities at the age of 13 years predicted change from non-frequent (0-1/month) to monthly HA (>1/month), especially in boys (P = 0.03 boys, P = 0.06 girls). The use of physiotherapy predicted persistence of monthly HA in boys (P = 0.004). The changes in HA type were not predictable by NP. In conclusion, the risk of worsening HA in adolescence is more probable if the HA is associated with NP interfering with daily activities.

Changing headache from preschool age to puberty. A controlled study.

The characteristics of disturbing primary headache and the occurrence of headache types were studied by sending a questionnaire to 1132 Finnish families of 6-year-old children. Children with headache in the preceding 6 months and their controls were clinically examined at the ages of 6 and 13. During the follow-up, half of the headaches, classified as migraine at age 6 years, were unchanged and 32% turned into tension-type headache. In children with tension-type headache, the situation was unchanged in 35%, and in 38% of children the headache type had changed to migraine. At preschool age the most common location of headache was bilateral and supraorbital, and at puberty bilateral and temporal. During the follow-up, symptoms concurrent with headache, such as odour phobia, dizziness and balance disturbances became more typical, whereas restlessness, flushing and abdominal symptoms became less marked. The early manifestation of both migraine and tension-type headache predict equally often migraine in puberty with marked changes in concurrent symptoms and pain localization.

Adolescent disc degeneration--no headache association.

The objective of the study was to determine whether adolescents with headache have more disc degeneration in the cervical spine than headache-free controls. This study is part of a population-based follow-up study of adolescents with and without headache. At the age of 17 years, 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. Of the 47 headache sufferers, 17 also had weekly neck pain and 30 had neck pain less than once a month. MRI scans were interpreted independently by three neuroradiologists. Disc degeneration was found in 67% of participants, with no difference between adolescents with and without headache. Most of the degenerative changes were located in the lower cervical spine. In adolescence, mild degenerative changes of the cervical spine are surprisingly common but do not contribute to headache.

Outcome of headache frequency in adolescence.

Only a few studies have been published of the outcome of adolescent headache (HA). The aim of this study was to examine the predictors of the outcome of headache frequency. A population-based sample of 13-year-olds with or without HA (N=228) was followed to the age of 16 years. HA was classified on the basis of a face-to-face interview and clinical examination. The outcomes of monthly HA (>1/month) and non-frequent HA (0-1/month) were studied. Frequent use of analgesics, female gender and multiple non-headache pain predicted the persistence of monthly HA (>1/month). Significant predictors for worsening non-frequent HA (from 0 to 1/month to >1/month) were female gender, consistent migraine and high basic educational level of one parent. Adolescents frequently using analgesics constitute a risk group for a poor outcome of HA. Especially girls meeting this criterion should be considered a target group in the planning and implementing of preventive measures.

Headache children with temporomandibular disorders have several types of pain and other symptoms.

The aim was to investigate the association between temporomandibular disorders (TMD) and overall muscle tenderness, depressive symptoms, sleep difficulties, headache frequency and related symptoms in children with primary headache in comparison with controls. Based on an unselected population sample of 1135 Finnish schoolchildren classified according to the type of headache at age 12, altogether 297 children aged 13-14 from different headache groups and healthy controls were randomly selected for an interview and clinical examinations. Children with migraine had more TMD signs than children with nonmigrainous headaches or healthy controls. High TMD total scores were associated with palpation tenderness in other parts of the body and with frequent headache attacks. We conclude that children with overall headache, migraine in particular, and high total TMD scores showed an increased overall tenderness to muscle palpation and multiply manifested hypersensitivity pain.

Leisure activities in adolescents with headache.

AIM: To investigate the association between different types of headache and leisure activities in 13-y-old schoolchildren. METHODS: A population-based, cross-sectional study was performed through face-to-face interviews with age-matched cohorts with headache and asymptomatic controls. The present study comprised 59 children with migraine, 65 with episodic tension-type headache (TTHA) and 59 headache-free controls. In the interview, besides questions concerning headache, the children were asked open and structured questions about the type and amount of their leisure activities. RESULTS: Children with migraine spent more time in sports activities than children with episodic tension-type headache or children without headache (test for trend, p<0.01; migraine: OR 1.4, 95% CI 1.1-1.9; tension-type headache: OR 0.9, 95% CI 0.7-1.1). The type of leisure activity was not significantly associated with headache type (p>0.05). Children with both migraine and episodic tension-type headache used computers more often than children without headache (test for trend, p<0.05; migraine: OR 1.2, 95% CI 1.1-1.5; tension-type headache: OR 1.3, 95% CI 1.1-1.5). CONCLUSION: This study provides additional data on the activity status and headache complaints in adolescents. The results indicate that frequent computer use is associated with both tension-type headache and migraine, and intensive overall sports activities are characteristic of adolescents with migraine.

Striatal dopaminergic system in dopa-responsive dystonia: a multi-tracer PET study shows increased D2 receptors.

We investigated the integrity of striatal dopaminergic system in seven patients with dopa-responsive dystonia (DRD). Dopamine transporter function ([(11)C]CFT) and D1 ([(11)C]NNC 756) and D2 receptors ([(11)C]raclopride) were studied in same patients using positron emission tomography. Compared to age-adjusted control values the dopamine D2 receptor availability was increased in DRD. The mean age-adjusted [(11)C]raclopride uptake was 116% of the control mean in the putamen (p = 0.004) and 114% in the caudate nucleus (p = 0.007). The mean [(11)C]NNC 756 uptake was not different between DRD patients and controls, the age-adjusted uptake in DRD being 93% of mean control value in the putamen (p = 0.20) and 95% in the caudate nucleus (p = 0.40). The dopamine transporter binding was not altered. The [(11)C]CFT uptake in DRD was 96% of the control value in the putamen (p = 0.64), and 95% in the caudate nucleus (p = 0.44). In conclusion, striatal dopamine D2 receptors availability is increased in DRD whereas dopamine D1 receptors and dopamine transporter ligand binding is unchanged. The pattern of changes in striatal dopaminergic system in DRD is different from that reported in juvenile Parkinson's disease. The increased D2 receptor availability may be due to reduced competition by endogenous dopamine or a compensatory response to dopamine deficiency, or both.

Muscle tenderness in pericranial and neck-shoulder region in children with headache. A controlled study.

Increased pericranial muscle tenderness is connected with tension-type headache in adults. In children, the importance of muscle tenderness in the pericranial or neck-shoulder region in the pathogenesis of different types of headache is unknown. The present study evaluated muscle tenderness in the pericranial and neck-shoulder region in children with migraine, those with tension-type headache and those without headache. An unselected population-based questionnaire study concerning headache was carried out in 1135 Finnish schoolchildren aged 12 years. Of them, 183 children were randomly selected for a face-to-face interview and a clinical examination. Muscle tenderness was recorded by manual palpation and dolorimeter. Children with migraine had increased overall tenderness, recorded by manual palpation, compared with those without headache. They also self-reported tenderness in the neck-shoulder region during daily activities more often than the children of the other groups. Muscle tenderness was not associated with paediatric tension-type headache. The mean pressure pain thresholds did not differ among the three groups. However, a negative correlation between the total tenderness score and the dolorimeter score was found in each group. In conclusion, children with migraine had increased muscle tenderness at palpation of the pericranial and neck-shoulder muscles and they also reported pain symptoms in the neck-shoulder region most frequently. Instead, increased pericranial and neck-shoulder muscle tenderness was not associated with tension-type headache in children.

Determinants of tension-type headache in children.

The objective of this study was to study the prevalence, characteristics and predisposing factors of tension-type headache in children. An unselected population-based questionnaire study was carried out in 1409 Finnish schoolchildren aged 12 years. Of them, 1135 (81%) returned an acceptably completed questionnaire. The prevalence of episodic tension-type headache in children was 12% (138 of 1135). Children with episodic tension-type headache also often reported characteristics of pain typical for migraine. Children with frequent and persistent episodic tension-type headache reported stabbing and severe occipital pain, phonophobia and abdominal pain significantly more often than children with infrequent episodic tension-type headache. Neck-shoulder symptoms, symptoms of depression and oromandibular dysfunction were each independently associated with episodic tension-type headache. The father's occupation of a lower-level white-collar worker put the child at a four-fold risk for episodic tension-type headache. We conclude that episodic tension-type headache is as common as migraine in children. It can be associated with depression, oromandibular dysfunction and muscular stress. Especially children with frequent and persistent episodic tension-type headache report characteristics of pain typical for migraine.

Focal and global cortical hypometabolism in patients with newly diagnosed infantile spasms.

OBJECTIVE: To evaluate the occurrence and prognostic importance of focal defects in cerebral cortical glucose metabolism in infants with newly diagnosed symptomatic and cryptogenic infantile spasms. PATIENTS AND METHODS: Ten children with symptomatic and seven with cryptogenic infantile spasms underwent MRI, video-EEG, and PET using fluorodeoxyglucose as a tracer within 2 weeks of diagnosis. PET was repeated at 1 year of age in 12 patients. RESULTS: Cortical hypometabolic foci were found in 13 children (77%) with newly diagnosed spasms (six cryptogenic and seven symptomatic). The hypometabolic foci disappeared in seven of nine reexamined at age 1. The occipital foci disappeared in all (n = 6). Focal findings on PET correlated well with focal findings on video-EEG. There was no difference in quantitative cortical or subcortical glucose metabolic rate at the onset of infantile spasms between children with cryptogenic and symptomatic etiology of spasms. The glucose metabolic rate at the onset of spasms or focal lesions in glucose metabolism did not have prognostic value for seizure outcome. CONCLUSIONS: Infantile spasms are often associated with transient cortical, especially occipital, hypometabolic foci that are not necessarily associated with structural lesions and do not indicate a poor prognosis.

Changes in headache prevalence between pre-school and pre-pubertal ages.

The prevalence rates of headache in first-born children were determined at the ages of 6 and 12 years in over 1000 families. A headache questionnaire was mailed to 1132 families when the children were 6 years old, and to 1126 families when the children were 12 years old. Seven hundred and ninety-eight families responded to both questionnaires. The prevalence of headache before the 6 months preceding the questionnaire ('previous headache') was 19% when the children were 6 years of age and 31% when the children were 12 years of age. The corresponding prevalences of headache during the 6 months immediately proceeding the questionnaire ('present headache') were 16% and 19%. Variation in occurrence of headache was high during follow-up years. Maternal frequent headache (> or = 1/month) was significantly associated with the increase in prevalence of present headache in boys between the ages of 6 and 12 years. Frequent headache in mothers, fathers and siblings, and the occurrence of chronic illness, were also significantly associated with headache in the 12-year-old children.

Neuroanatomical substrata of amusement and sadness: a PET activation study using film stimuli.

The aim of the present study was to explore the neuroanatomical substrata of film-induced amusement and sadness, aiming at maximal reliability by using strict statistics. Film-induced changes in regional cerebral blood flow (rCBF) were measured using positron emission tomography and [15O]water. It appeared that many brain regions were involved similarly and symmetrically in both emotions. Activation of the occipitotemporal and anterior temporal cortex and cerebellum during both emotions agreed well with the earlier findings. Contrary to some earlier studies, the posterior cingulate gyrus and some frontal areas were deactivated in both emotions. The strict explorative analysis did not reveal activations in the limbic or subcorticai structures seen in some earlier studies. However, an additional analysis restricted to the subcortical and limbic system structures revealed bilateral activation of the amygdala in both target emotions. The outcomes of imaginal studies of emotions seem to be largely dependent on the conservativeness of the statistical analysis and very likely also on the method of emotion induction.

Comorbidity of other pains in schoolchildren with migraine or nonmigrainous headache.

OBJECTIVE: To compare the occurrence of pain other than headache in prepubertal children with migraine and those with nonmigrainous headache. STUDY DESIGN: An unselected population-based prospective follow-up study on the occurrence of headache in school-aged children was carried out in 1290 children aged 8 to 9 years. The children (n = 725) who reported headache during the preceding 6 months were sent a more detailed questionnaire concerning the occurrence of pain other than headaches; 622 children (86%) returned an acceptably completed second questionnaire. Of them, 53 (8.5%) had migraine. Nonmigrainous headache was found in 460 children (74%). RESULTS: Children with migraine reported neck-shoulder pain, abdominal pain, back pain, and otalgia significantly more often than those with nonmigrainous headache. The median of the sum of other pains in children with migraine was significantly higher than that in children with nonmigrainous headache. The sum of other pains correlated positively with the frequency of nonmigrainous headache episodes (r =.40; 95% CI.31-.47), but there was no correlation between the sum of other pains and frequency of migraine attacks (r = -0.09; 95% CI -0.36-0.20). CONCLUSION: Children with migraine are more likely to report types of pain other than headaches, regardless of the frequency of attacks. Children with frequent nonmigrainous headaches also report higher frequencies of other types of pain.

Signs and symptoms of temporomandibular disorders in children with different types of headache.

Headache is a common symptom among children and teenagers. Both bruxism and muscle and joint tenderness have been found in children with headache. Children with migraine headache report more temporomandibular disorder (TMD) symptoms than do those with tension-type headache. The aim of the present study was to investigate the association of different types of headache with TMD and sex in children. Altogether 297 randomly selected schoolchildren aged 13-14 years participated in a blind study setting. There were no statistically significant differences between the headache groups with regard to TMD signs, although the migraine and migraine-type headache groups had the highest percentage of subjects with more severe TMD signs. Nor were there any statistical differences between sexes or between the headache groups with regard to subjective symptoms of TMD. The present results with children differed from earlier results with adults. First, no association was found between tension headache and TMD, and, second, no sex difference in TMD children was observed at this age.