Medication Overuse Headaches among Children-The Contribution of Migraine and TTH.

Medication overuse headaches are a frequent phenomenon observed in individuals suffering from chronic headaches. It arises due to the excessive consumption of pain-relief medications, resulting in the escalation and continuous persistence of headache symptoms. Nevertheless, the prevalence and distinctive characteristics of medication overuse headaches in the pediatric population have not been comprehensively explored. The primary objective of this research is to delineate the features of medication overuse headaches in children, particularly emphasizing the investigation of its epidemiology and the diagnostic patterns for headaches. We conducted a retrospective study and analyzed the medical records of children and adolescents who were evaluated at the outpatient pediatric headache clinic at the Bnai Zion Medical Center for headaches during the period spanning 2007 to 2017. Our study encompassed a cohort of 1008 patients experiencing headaches. Among these participants, 268 individuals (26.6%) were diagnosed with migraine, 250 (24.8%) exhibited tension-type headaches (TTH), and 490 (48.6%) were classified as having undifferentiated headaches. Out of the whole group, 65 had chronic headaches: 35 (54%) with migraine, 20 (30%) with tension-type headaches (TTH), and 10 (15%) with the undifferentiated headache of childhood, with the majority (73%) being female. In summary, medication overuse headaches are a prevalent issue among children grappling with chronic headaches. Intriguingly, they appear to be more pronounced within the tension-type headache (TTH) group compared to migraine sufferers and exhibit a higher prevalence among females. This study underscores the significance of early detection and careful management of medication overuse headaches in pediatric cases, shedding light on its distinct characteristics in the realm of childhood headache disorders. Further research is warranted to elucidate the underlying factors contributing to the observed gender disparity and the distinct prevalence rates among different headache subtypes.

Danon Disease: Entire LAMP2 Gene Deletion with Unusual Clinical Presentation-Case Report and Review of the Literature.

Danon disease is a rare x-linked dominant multisystemic disorder with a clinical triad of severe cardiomyopathy, skeletal myopathy, and intellectual disability. It is caused by defects in the lysosome-associated membrane protein-2 (LAMP2) gene. Numerous different mutations in the LAMP2 protein have been described. Danon disease is typically lethal by the mid-twenties in male patients due to cardiomyopathy and heart failure. Female patients usually present with milder and variable symptoms. This report describes a 42-year-old father and his 3-year-old daughter presenting with mild manifestations of the disease. The father has normal intellectual development and normal physical activity. At the age of 13, he was diagnosed with mild ventricular pre-excitation known as Wolf-Parkinson-White syndrome (WPWs), very mild and mostly asymptomatic cardiomyopathy and left ventricular hypertrophy, and at about the age of 25 presented with visual impairment due to cone-rod dystrophy. His daughter showed normal development and very mild asymptomatic electrocardiographic WPWs abnormalities with left mild ventricular hypertrophy. Genetic testing revealed an Xq24 microdeletion encompassing the entire LAMP2 gene. Relevant literature was reviewed as a reference for the etiology, diagnosis, treatment and case management.

High CCL2 Levels Detected in CSF of Patients with Pediatric Pseudotumor Cerebri Syndrome.

Pseudotumor cerebri (PTC) is a disorder characterized by increased intracranial pressure in the absence of a structural lesion or other identifiable cause. Cytokines, which are involved in the regulation of immune responses and inflammation, have been implicated in the pathogenesis of PTC. In a prospective, cross-sectional study at three centers in Israel, we analyzed cerebrospinal fluid (CSF) samples from 60 children aged 0.5-18 years, including 43 children with a definitive diagnosis of PTC and a control group of 17 children. Levels of IL-4, IL-10, IL-17, CCL2, CCL7, CCL8, CCL13, BDNF, and IFN-γ were measured using ELISA kits. Levels of CCL2 were significantly higher in the PTC group compared to the control group (p < 0.05), with no other significant differences in the measured cytokines between the two groups. The groups did not differ significantly in clinical presentation, imaging, treatment, or ophthalmic findings. Our findings provide preliminary evidence that CCL2 may be involved in the pathogenesis of PTC and may serve a potential target for therapy in PTC.

Functional Benefit and Orthotic Effect of Dorsiflexion-FES in Children with Hemiplegic Cerebral Palsy.

Functional electrical stimulation of the ankle dorsiflexor (DF-FES) may have advantages over ankle foot orthoses (AFOs) in managing pediatric cerebral palsy (CP). This study assessed the functional benefit and orthotic effect of DF-FES in children with hemiplegic CP. We conducted an open-label prospective study on children with hemiplegic CP ≥ 6 years who used DF-FES for five months. The functional benefit was assessed by repeated motor function tests and the measurement of ankle biomechanical parameters. Kinematic and spatiotemporal parameters were assessed by gait analysis after one and five months. The orthotic effect was defined by dorsiflexion ≥ 0° with DF-FES at either the mid or terminal swing. Among 26 eligible patients, 15 (median age 8.2 years, range 6-15.6) completed the study. After five months of DF-FES use, the results on the Community Balance and Mobility Scale improved, and the distance in the Six-Minute Walk Test decreased (six-point median difference, 95% CI (1.89, 8.1), -30 m, 95% CI (-83.67, -2.6), respectively, p < 0.05) compared to baseline. No significant changes were seen in biomechanical and kinematic parameters. Twelve patients (80%) who showed an orthotic effect at the final gait analysis experienced more supported walking over time, with a trend toward slower walking. We conclude that the continuous use of DF-FES increases postural control and may cause slower but more controlled gait.

Prospective, Cross-Sectional Study Finds No Common Viruses in Cerebrospinal Fluid of Children with Pseudotumor Cerebri.

Pseudotumor cerebri (PTC) in children is a rare condition whose underlying cause remains largely unknown. No study has yet systematically examined viral infection as a cause of PTC. The current study aimed to characterize PTC in children and investigate the possible role of acute viral infection of the central nervous system in its pathogenesis. A prospective, cross-sectional study was conducted in three centers in Israel. Participants were 50 children aged 0.5-18 years, of whom 27 had a definitive diagnosis of pseudotumor cerebri (the study group) and 23 comprised a control. Data collected included clinical presentation, imaging, treatment, ophthalmic findings, and cerebrospinal fluid (CSF) analysis. Using the ALLPLEXTM meningitis panel, real-time polymerase chain reaction (PCR) was used to test for the presence of 12 common viruses. PTC patients (mean age 12 ± 4.3 years; 14 males, 13 females) had mean opening pressure of 41.9 ±10.2 mmH2O. All PTC patients had papilledema, and 25 (93%) had PTC symptoms. No viruses were found in the PTC group, while in the control group, one patient tested positive for Epstein-Barr virus and another for human herpesvirus type 6. Overall, in our study, PTC was not found to be associated with the presence of viruses in CSF.

Weekend Headaches in School-Age Children.

Children commonly encounter primary headaches, with various factors playing a role in their onset. The daily routine notably contributes to the occurrence of primary headaches in children. This study aims to profile children experiencing headaches on weekends (WH) in comparison to those primarily having headaches midweek (MWH). Out of 109 children visiting a pediatric headache clinic, 60 prospectively filled out questionnaires regarding their headaches. The average age was 11.8 years, and 63% were of female sex. Most of the children suffered from migraine headaches (60%), while the rest suffered from tension-type headaches (TTH, 15%), mixed headaches (17%), or undetermined headaches (8%). None of the children suffered from a headache only on the weekend. In contrast, 14 (23%) children suffered from a headache exclusively in midweek. Children with learning difficulties were similarly distributed between the WH and the MWH groups (48% and 52%, respectively). Children without learning difficulties suffered significantly more from MWH compared to WH (79% vs. 21%, respectively). In conclusion, children did not suffer from WH alone. Self-reported triggers were not significantly different in WH and MWH patients. Proper profiling of headache types and triggers may lead to more accurate management of these patients.

Transcranial Direct Current Stimulation (tDCS) in children with ADHD: A randomized, sham-controlled pilot study.

BACKGROUND: ADHD is a common neurodevelopmental disorder with a pediatric prevalence of 5.2%.While medication treatment for ADHD is effective, it does not address all symptoms and a small but notable subgroup does not respond to medications. Adverse effects limit its use and some parents and participants resist use of medication. Thus, limitations of medication treatment for ADHD motivate searching for other therapeutic options. Transcranial Direct Current Stimulation (tDCS) has been suggested as a treatment for children with ADHD, with mixed results to date. Protocol variables employed, including combined use of cognitive training (CT) and scheduling of sessions, may explain diverse findings to date. The aim of this study was to examine safety, feasibility and efficacy of tDCS combined with CT provided three-times-per week for one-month to treat children with ADHD. METHODS: In a double blind, randomized, sham-controlled pilot study, 25 children with ADHD were randomized to receive 12 sessions of either anodal tDCS or sham-tDCS for 20 min combined with CT three-times-per-week for four weeks. The tDCS anode was over left dorsolateral prefrontal cortex (DLPFC) and cathode over vertex. Assessments were obtained prior to, after 6 sessions, 12 sessions and one-month after intervention. RESULTS: No significant post-intervention differences were found between those receiving tDCS or sham-tDCS. Both groups demonstrated significant improvement on questionnaire measures of ADHD and executive function with mixed results seen on computerized performance measures. Overall, adverse effects were mild with no significant difference between groups. However, three children, all from the tDCS group, experienced headaches with two requiring temporary cessation and one requiring removal from the study. CONCLUSIONS: Anodal tDCS to the DLPFC using the above protocol in children with ADHD did not demonstrate additional treatment benefits beyond that of CT.

Special Issue "Migraine and Headache in Children and Adolescents".

Migraine in developmental age is a common pathology [...].

Migraine abortive treatment in children and adolescents in Israel.

Migraine headaches in children may cause attacks that require abortive treatment. This study evaluated the incidence and efficacy of medications used for relieving migraine headache attacks in the pediatric population in Israel. Children 6-18 years of age who were diagnosed in our pediatric neurology clinic as having migraine headaches were enrolled into the study. Children and their parents recorded the children response to abortive treatment during consecutive migraine attacks. Fifty children, with 116 migraine attacks, were included in the study (30 females; mean age 12; range 6-18). Forty-seven (94%) reported on abortive treatment on the first migraine attack, 43 (86%) on a second migraine attack and 26 (52%) on a third migraine attack. During the first recorded migraine attack, 41 children (87.5%) reported taking only one type of medication for each headache episode, mainly ibuprofen or acetaminophen; less than a quarter used dipyrone (metamizol). Overall the improvement rate after two hours was 65.4% ± 27 for ibuprofen, 59.8 ± 35.3 for acetaminophen and 50.9 ± 27.4 for dipyrone without statistical difference. However, in the first recorded headache episode, males had a significantly better response to acetaminophen, compared to ibuprofen (95% ± 28 vs 75 ± 20). In conclusion, Children with migraine in Israel mainly use a single medication for each headache episode. Ibuprofen is the most commonly used abortive treatment; however, acetaminophen was associated with a better response among some of our patients.

Multidomain Cognitive Impairment in Children With Pseudotumor Cerebri Syndrome.

BACKGROUND: Although prompt and suitable treatment of pseudotumor cerebri syndrome (PTCS) leads to an excellent prognosis and can prevent optic nerve atrophy, adults show long-lasting neurocognitive deficits even with prompt treatment. The purpose of our study was to evaluate cognitive outcomes in pediatric patients with PTCS. METHODS: We performed a prospective study on children diagnosed with PTCS and a healthy control group. Children with pre-existing neurological conditions or psychiatric drug use were excluded. Both groups underwent a neurocognitive evaluation, using the NeuroTrax computerized battery of tests. The PTCS group were tested 3 months after the initial diagnosis. RESULTS: We evaluated 82 children (49 females [60%], 6.5-16 years old, mean age 13.3), including 26 diagnosed with idiopathic PTC and 56 controls. Global cognitive score (P < 0.001), verbal memory (P < 0.001), executive function (P < 0.001), attention (P< 0.003), and information processing speed (P < 0.004) were all significantly lower in the PTCS group. No differences were found between children currently being treated and those whose symptoms had resolved and treatment was stopped. CONCLUSIONS: Children with PTCS experience comprehensive cognitive decline that persists after the resolution of the symptoms and treatment.

Optic Nerve Drusen Is Highly Prevalent Among Children With Pseudotumor Cerebri Syndrome.

Introduction: The clinical presentation of pseudotumor cerebri syndrome (PTCS) usually includes headache, nausea, and vomiting with normal physical examination apart from papilledema and diplopia. However, pseudopapilledema, which can be caused by optic nerve drusen, may lead to misdiagnosis. The prevalence of optic nerve drusen in the general population is 0.5-2%. The purpose of our study was to evaluate the prevalence and risk factors of optic nerve drusen among patients with PTCS. Materials and Methods: Medical records of children evaluated in the pediatric department at Bnai Zion Medical Center due to PTCS between 2008 and 2020 were assessed. Inclusion criteria were children age under 18 years with a PTCS diagnosis and ophthalmic B-mode ultrasonography (US). Exclusion criteria were secondary intracranial hypertension. Results: Thirty-four children were included with a mean age 10.1 years which included 50% boys. A majority of the patients, 24 (72.4%), complained of headaches, while 15 (45.5%) complained of transient visual obscuration, and 9 (26.5%) of vomiting. Visual acuity on presentation was normal (20/20-20/30) in 23 of the children (67%), moderately diminished (20/40-20/80) in 9 (26%), and showing profound loss (20/200) in 2 (7%). Five patients (14.7%) were diagnosed with optic nerve drusen via B-mode ophthalmic ultrasonography (US). However, they still fulfilled the diagnostic criteria for PTCS, and disc swelling improved after treatment. There were no statistically significant differences between the group with optic nerve drusen and the rest of the patients. Conclusions: Optic nerve drusen are common among pediatric patients with PTCS. Diagnosis of optic nerve drusen should not rule out the presence of increased intracranial pressure.

Behavioral Symptoms May Correlate With the Load and Spatial Location of Tubers and With Radial Migration Lines in Tuberous Sclerosis Complex.

Objective: Tuberous sclerosis complex (TSC) is a multisystem neurocutaneous genetic disorder. The clinical manifestations are extensive and include neurological, dermatological, cardiac, ophthalmic, nephrological, and neuropsychiatric manifestations. The prediction and pathophysiology of neuropsychiatric disorders such as emotional symptoms, conduct problems, hyperactivity, and poor social behavior are poorly understood. The aim of the study was to diagnose neuropsychiatric symptoms in individuals with TSC, and to examine their possible correlations with quantity, magnitude, and spatial location of tubers and radial migration (RM) lines. Methods: The cohort comprised 16 individuals with TSC, aged 5-29 years, with normal or low normal intelligence. The participants or their parents were requested to fill Strengths and Difficulties Questionnaire (SDQ) and the TAND (TSC-associated neuropsychiatric disorders) Checklist for assessment of their neuropsychiatric symptoms. Correlations were examined between these symptoms and the magnitude, quantities, and locations of tubers and white matter RM lines, as identified in T2/FLAIR brain MRI scans. Results: The SDQ score for peer relationship problems showed correlation with the tuber load (r = 0.52, p < 0.05). Tuber load and learning difficulties correlated significantly in the temporal and parietal area. Mood swings correlated with tubers in the parietal area (r = 0.529, p < 0.05). RM lines in the temporal area correlated with abnormal total SDQ (r = 0.51, p < 0.05). Anxiety and extreme shyness were correlated with RM lines in the parietal area, r = 0.513, p < 0.05 and r = 0.593, p < 0.05, respectively. Hyperactive/inattention correlated negatively with RM lines in the parietal area (r = -707, p < 0.01). Conclusions: These observations may lead to future studies for precise localization of neuropsychiatric symptoms, thereby facilitating directed therapy.

Reduction in seizure burden in a child with a A350V IQSEC2 mutation using heat therapy with a Jacuzzi.

A child with a A350V IQSEC2 missense mutation resulting in drug-resistant epilepsy stops having seizures when he has a fever. We demonstrate that raising the body temperature of the child using a commercial Jacuzzi dramatically reduces his seizures and appears to improve his social behavioral interactions.

Outcomes of Migraine and Tension-Type Headache in Children and Adolescents.

The aim of our study was to evaluate the long-term outcomes of pediatric migraine and TTH in a clinical setting. We conducted a cohort study. Pediatric patients who visited the pediatric neurology clinic due to diagnoses of migraine or TTH were contacted by phone 8-10 years after their initial diagnosis and interviewed about their outcomes. Of 147 children, we were able to reach 120 (81%) patients. Of these 120 patients, 59 were seen initially due to migraine and 61 due to TTH. For the migraine patients, headaches improved in 48 (81.4%) and worsened in four (6.8%). Regarding diagnosis at follow-up, 59% still had migraine, 17% had TTH, and 23% were headache-free. Aura and photophobia were significantly associated with persistence of a migraine diagnosis. For the TTH patients, headaches improved in 49 (81.7%) and worsened in nine (15.0%). Regarding diagnosis at follow-up, 36.7% still had TTH, 18.3% had migraine, and 45% were headache-free. Of the patients with TTH, 36.7% retained their initial diagnosis compared to 59.3% among the migraine patients. Most pediatric patients presenting with migraine or TTH will experience a favorable outcome over 10 years, with TTH patients having twice the chance of complete resolution.

The yield of CSF molecular testing in febrile neonates.

We retrospectively examined the yield of a cerebrospinal fluid (CSF) multiplex real-time PCR assay of febrile young infants undergoing a full sepsis work-up. Eighty infants were included in the study: Forty-nine (61%) neonates and 31 (39%) 29-90 day-old patients were included in the study. A viral pathogen was detected in 59% (47/80) of the samples, human enterovirus in 53% (42/80) and Human parechovirus in 6% (5/80). The CSF of nearly half of the subjects with CNS infection was without pleocytosis; all CSF cultures were negative. Multiplex PCR CSF testing enhances the diagnosis of pathogen-specific viral CNS infection among febrile young infants.

Migraine and Tension-Type Headache Among Children and Adolescents: Application of International Headache Society Criteria in a Clinical Setting.

INTRODUCTION: The International Headache Society criteria were written in order to help physicians establish a headache diagnosis. However, sometimes children with headache do not seem to fit any diagnosis. The purpose of our study was to assess the application of the criteria in a clinical setting. METHODS: Medical records of children referred for primary headache to the pediatric neurology clinic at Bnai Zion Medical Center from 2008 to 2017 were assessed. RESULTS: A total of 989 patients (range 6-18 years; 53% female) were assessed at our neurology clinic. Twenty-four percent (n = 241) were diagnosed with tension-type headache, 26% (n = 256) with migraine, and 4.5% (45) with mixed headache. In 41.5% (410), we were unable to reach a specific diagnosis. No differences in gender or age were found between the groups. Children in the migraine group used more analgesic treatments to stop the headache attacks compared with the tension-type headache group (50% vs 38%, P = .001). Patients diagnosed with tension-type headache reported having more emotional difficulties (P = .001). No significant differences were found in headache characteristics (ie, location, sidedness, character), frequency, or intensity between the younger children (ages 6-11) and the adolescents (ages 12-18) within either the tension-type headache or migraine groups. CONCLUSIONS: Retrospective application of International Headache Society criteria in a large cohort of children with headaches failed to diagnose a specific type of headache in 41.5% of children. Migraine and tension-type headache were equally prevalent, and both constituted a major burden on our patients' everyday lives. We found no major differences in frequency, intensity, and characteristics of pain between younger children and adolescents.

Sensory processing patterns affect headache severity among adolescents with migraine.

OBJECTIVE: To evaluate the relationship between pain catastrophizing level, sensory processing patterns, and headache severity among adolescents with episodic migraine. BACKGROUND: Catastrophizing about pain is a critical variable in how we understand adjustment to pain and has a unique contribution in predicting pain intensity. Recent reports found that migraine is also related to enhanced sensory sensitivity. However, the relationship between pain severity, pain catastrophizing level and sensory sensitivity requires greater study especially among adolescents. METHODS: Participants were 92 adolescents aged 13-18 years, 40 with episodic migraine and 52 healthy controls. The migraine patients were prospectively recruited from outpatient pediatric neurology clinics. All participants completed the Adolescent/Adult Sensory Profile (AASP), and the Pain Catastrophizing Scale for children (PCS-ch). The migraine groups also completed the PedMIDAS, which measures Headache related disability. RESULTS: Adolescents with migraine had significantly lower tendency to seek sensory input than healthy controls. Elevated rumination and helplessness correlated with higher migraine pain severity. Tendency to avoid sensory input predicted the migraine related disability level. They also significantly higher pain catastrophizing level than healthy controls, as seen in enhanced rumination (p ≤ 0.001) and helplessness (p ≤ 0.05). CONCLUSIONS: Sensory processing difficulties are common among adolescents with episodic migraine. Sensory avoidance may be related to pain experience, and pain catastrophizing and disability level. TRIAL REGISTRATION: ISRCTN ISRCTN73824458. Registered 28 September 2014. retrospectively registered.

Stroke identification using a portable EEG device - A pilot study.

OBJECTIVE: Changes in EEG patterns during stroke are almost immediate; however, a full EEG test takes time and requires highly qualified staff. In this study, we examined whether a short recording using a portable EEG device can differentiate between a stroke and control group. METHODS: EEG samples were collected from patients with an acute ischemic stroke event. The control group comprised healthy volunteers. EEG recordings were recorded using a portable brain wave sensor device. The Revised Brain Symmetry Index (rsBSI) was used to quantify the symmetry of spectral power between the two hemispheres. RESULTS: The investigation group included 33 patients (ages 46-96, mean age 72 years, 66% male) who were diagnosed with ischemic stroke. The control group included 25 healthy individuals. Scores for the rsBSI of non-stroke patients (M=0.1686, SD=0.10) differed significantly from those of ischemic stroke patients (P<0.05, M=0.363, SD=0.25). CONCLUSIONS: A statistically significant difference was observed between a group of stroke patients and a matched group of healthy controls with a short recording using a portable EEG device.

Pseudotumor Cerebri Syndrome: From Childhood to Adulthood Risk Factors and Clinical Presentation.

INTRODUCTION: Although considered uncommon, pseudotumor cerebri syndrome (PTC) is a significant cause of headache among children and adults. However, the presenting symptoms may be different among diverse age groups. In the present study, we compared the risk factors and clinical presentation of PTC across life-from childhood to adulthood. METHODS: A retrospective survey of PTC patients aged 7 years or older between 2011 and 2013 was carried out. Pooled analyses were performed comparing characteristics from our data with those of published data subdivided into 3 age groups: pre-young children, adolescents, and adults. RESULTS: Our cohort consisted of 72 patients: 32 children (10 pre-young children, 22 adolescents) and 40 adults. Within the pre-young children age group: 20% were females versus 82% in the adolescent age group and 85% of the adult age group. Obesity was found in 10% of the young children group, 64% of the adolescents, and 80% of the adults. Headache was reported in 70% young children, 82% adolescents, and 83% adults. Pooled analysis of 1499 patients showed that young children with PTC tend to complain less about headache compared with older ones. Vomiting and visual impairment were most common among adolescents, and dizziness and tinnitus were most common in adults. CONCLUSION: PTC has different risk factors and clinical presentation throughout life. In young children, there is no gender preference and most patients are not obese. Risk factors in adolescents resemble those of adults.