[Show abstract][Hide abstract] ABSTRACT: Medication overuse is not uncommon among children and adolescents with primary headache disorders. Medication overuse in adults is associated with increased headache frequency and reduced effectiveness of acute and preventive medications. These issues probably exist in children. While withdrawal of overused medications is generally recommended, it may not result in improved headache frequency in all patients. This review summarizes what is known about predicting the response to medication withdrawal. Strategies for managing children and adolescents with medication overuse are also offered.
Current Pain and Headache Reports 07/2014; 18(7):428. · 1.67 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Objective
To assess the relationship between the phenotype of the “visual snow” syndrome, comorbid migraine, and typical migraine aura on a clinical basis and using functional brain imaging.Background
Patients with “visual snow” suffer from continuous TV-static-like tiny flickering dots in the entire visual field. Most patients describe a syndrome with additional visual symptoms of the following categories: palinopsia (“afterimages” and “trailing”), entopic phenomena arising from the optic apparatus itself (floaters, blue field entoptic phenomenon, photopsia, self-light of the eye), photophobia, nyctalopia (impaired night vision), as well as the non-visual symptom tinnitus. The high prevalence of migraine and typical migraine aura in this population has led to the assumption that “visual snow” is caused by persistent migraine aura. Due to the lack of objective measures, alternative diagnoses are malingering or a psychogenic disorder.Methods(1) The prevalence of additional visual symptoms, tinnitus, and comorbid migraine as well as typical migraine aura was assessed in a prospective semi-structured telephone interview of patients with “visual snow.” Correlations were calculated using standard statistics with P < .05 being considered statistically significant. (2) Areas with increased brain metabolism in a group of “visual snow” patients in comparison to healthy controls were identified using [18F]-2-fluoro-2-deoxy-D-glucose positron emission tomography and statistical parametric mapping (SPM8 with whole brain analysis; statistical significance was defined by P < .001 uncorrected for multiple comparisons).Results(1) Of 120 patients with “visual snow,” 70 patients also had migraine and 37 had typical migraine aura. Having comorbid migraine was associated with an increased likelihood of having palinopsia (odds ratio [OR] 2.8; P = .04 for “afterimages” and OR 2.6; P = .01 for “trailing”), spontaneous photopsia (OR 2.9; P = .004), photophobia (OR 3.2; P = .005), nyctalopia (OR 2.7; P = .01), and tinnitus (OR 2.9; P = .006). Typical migraine aura was associated with an increased likelihood of spontaneous photopsia (OR 2.4; P = .04). (2) After adjusting for typical migraine aura, comparison of 17 “visual snow” patients with 17 age and gender matched controls showed brain hypermetabolism in the right lingual gyrus (Montreal Neurological Institute coordinates 16-78-5; kE = 101; ZE = 3.41; P < .001) and the left cerebellar anterior lobe adjacent to the left lingual gyrus (Montreal Neurological Institute coordinates -12-62-9; kE = 152; ZE = 3.28; P = .001).Conclusions—Comorbid migraine aggravates the clinical phenotype of the “visual snow” syndrome by worsening some of the additional visual symptoms and tinnitus. This might bias studies on “visual snow” by migraineurs offering study participation more likely than non-migraineurs due to a more severe clinical presentation. The independence of entoptic phenomena from comorbid migraine indicates “visual snow” is the main determinant. The hypermetabolic lingual gyrus confirms a brain dysfunction in patients with “visual snow.” The metabolic pattern differs from interictal migraine with some similarities to migrainous photophobia. The findings support the view that “visual snow,” migraine, and typical migraine aura are distinct syndromes with shared pathophysiological mechanisms that need to be addressed in order to develop rational treatment strategies for this disabling condition.
Headache The Journal of Head and Face Pain 06/2014; · 2.94 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Background
Crowned dens syndrome (CDS) is a clinical-radiological entity characterized by acute attacks of neck pain with fever, rigidity, general signs of inflammation, and calcification of the periodontoid articular structures.Methods
Case report with 42 months follow-up.Case descriptionAn 81-year-old man, who had never suffered from headache before July 2010, developed strictly left-sided headaches. The pain was restricted to the left side of the scalp and felt more intense in the frontal area. The intensity was moderate to high with a throbbing quality. The pain had an orthostatic component and was worsened by neck hyperextension and Valsalva maneuvers. Neurological and general examinations were normal, except for a reduced range of motion of the neck. He was prescribed indomethacin orally 25 mg t.i.d. and had a partial response. After a week, he was given a dosage of 50 mg t.i.d. with complete remission of the pain. Brain magnetic resonance imaging was normal, while an magnetic resonance imaging of the cervical spine showed a non-homogeneous mass behind the odontoid process of C2, narrowing the subarachnoid space in C1, stretching the posterior longitudinal ligament, and touching the left vertebral artery. A computed tomography scan showed calcification of the soft tissue around the odontoid process and a thickening of the left C2 root. After 4 months, the indomethacin dosage was reduced step-by-step. Indomethacin was discontinued in March 2012. Since then, the headache has not recurred.DiscussionWe here present the case of a patient with headache and radiological findings of crowned dens. However, the clinical presentation differed from previous CDS cases in the literature in that the pain was unilateral with frontal localization and throbbing quality, as well as an orthostatic component and lack of either fever or inflammatory signs. The differential diagnosis also includes a remitting form of hemicrania continua, presenting with an atypical presentation, with neuroimaging incidental finding of CDS.Conclusion
This case widens the spectrum of the clinical presentation of crowned dens, a condition that should be kept in mind in cases of unilateral headache in older patients.
Headache The Journal of Head and Face Pain 06/2014; · 2.94 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Infant colic is a common and distressing disorder of early infancy. Its etiology is unknown, making treatment challenging. Several articles have suggested a link to migraine.
Cephalalgia : an international journal of headache. 05/2014;
[Show abstract][Hide abstract] ABSTRACT: Medical students routinely have triggers, notably stress and irregular sleep, which are typically associated with migraine. We hypothesized that they may be at higher risk to manifest migraine. We aimed to determine the prevalence of migraine among medical students in Kuwait University.
The journal of headache and pain. 05/2014; 15(1):26.
[Show abstract][Hide abstract] ABSTRACT: Patients with 'visual snow' report continuous tiny dots in the entire visual field similar to the noise of an analogue television. As they frequently have migraine as a comorbidity with ophthalmological, neurological and radiological studies being normal, they are offered various diagnoses, including persistent migraine aura, post-hallucinogen flashback, or psychogenic disorder. Our aim was to study patients with 'visual snow' to characterize the phenotype. A three-step approach was followed: (i) a chart review of patients referred to us identified 22 patients with 'visual snow'. Fifteen had additional visual symptoms, and 20 patients had comorbid migraine, five with aura; (ii) to identify systematically additional visual symptoms, an internet survey (n = 275) of self-assessed 'visual snow' subjects done by Eye On Vision Foundation was analysed. In two random samples from 235 complete data sets, the same eight additional visual symptoms were present in >33% of patients: palinopsia (trailing and afterimages), entoptic phenomena (floaters, blue field entoptic phenomenon, spontaneous photopsia, self-light of the eye), photophobia, and nyctalopia (impaired night vision); and (iii) a prospective semi-structured telephone interview in a further 142 patients identified 78 (41 female) with confirmed 'visual snow' and normal ophthalmological exams. Of these, 72 had at least three of the additional visual symptoms from step (ii). One-quarter of patients had 'visual snow' as long as they could remember, whereas for the others the mean age of onset was 21 ± 9 years. Thirty-two patients had constant visual symptoms, whereas the remainder experienced either progressive or stepwise worsening. Headache was the most frequent symptom associated with the beginning or a worsening of the visual disturbance (36%), whereas migraine aura (seven patients) and consumption of illicit drugs (five, no hallucinogens) were rare. Migraine (59%), migraine with aura (27%), anxiety and depression were common comorbidities over time. Eight patients had first degree relatives with visual snow. Clinical investigations were not contributory. Only a few treatment trials have been successful in individual patients. Our data suggest that 'visual snow' is a unique visual disturbance clinically distinct from migraine aura that can be disabling for patients. Migraine is a common concomitant although standard migraine treatments are often unhelpful. 'Visual snow' should be considered a distinct disorder and systematic studies of its clinical features, biology and treatment responses need to be commenced to begin to understand what has been an almost completely ignored problem.
[Show abstract][Hide abstract] ABSTRACT: Anticonvulsants represent one of the main substance classes used for the preventive treatment of migraine. Efficacy has been demonstrated in randomized placebo-controlled trials for topiramate and valproic acid including divalproex sodium. In the case of topiramate, efficacy has recently been proven for chronic migraine and even medication overuse headache, questioning the established concept of medication withdrawal. However, preventive treatment with anticonvulsants is frequently hampered by side effects that occasionally require treatment discontinuation. In addition, these data indicate that some anticonvulsant drugs are effective in migraine, while a number are clearly not useful. Effective anticonvulsants, such as topiramate and valproate, target nociceptive trigeminovascular and trigeminothalamic dural pathways or mechanisms involved in cortical spreading depression. Dissecting out how the anticonvulsants that do not work differ mechanistically from those that do will almost certainly provide avenues through which one can develop new treatments to bring to patients with migraine.
[Show abstract][Hide abstract] ABSTRACT: Migraine patients have an increased photic-driving response. This 'H-response' (HR) has potential diagnostic value but it is time consuming.
The aim of the study was to establish a fast and standardized test for the study of migraine biology and treatment.
We studied 11 migraine patients and 11 matched control participants. We used stroboscope flashes with a 'chirp'-like linear frequency-increase from 10 to 40 Hz. EEG was recorded from occipital electrodes. Power spectral density was calculated for the stimulus response and corrected for baseline. An HR-estimator was calculated as the average power between 18 and 26 Hz in the stimulation-frequency window.
There was a significant difference for single ( P < 0.05) and for 10 averaged recordings ( P < 0.01) between migraineurs and controls, and a high inter-test reliability (Cronbach's alpha = 0.94).
Chirp-like stimulation to study the H-response is reliable and efficient and might therefore have a potential for acute interventional studies in migraine research.
[Show abstract][Hide abstract] ABSTRACT: Background
Migraine remains poorly treated, with few effective preventive drugs available. We assessed the safety and efficacy of LY2951742, a fully humanised monoclonal antibody to calcitonin gene-related peptide, for migraine prevention.
We did a randomised, double-blind, placebo-controlled, phase 2 proof-of-concept study at 35 centres in the USA. Patients aged 18–65 years with four to 14 migraine headache days per month were randomly assigned (1:1) to LY2951742 or placebo by a computerised randomisation scheme. LY2951742 (150 mg) or placebo were given as a subcutaneous injection once every 2 weeks for 12 weeks. The primary endpoint was the mean change in number of migraine headache days per 28-day period assessed at 9–12 weeks. Safety was assessed over 24 weeks, including the 12-week treatment period and the subsequent 12 weeks after study drug administration. Patients and treating investigators were masked to treatment allocation. Analyses were by intention to treat. A mixed-effects model of repeated measures was used, including patient baseline value, treatment, visit, and treatment-by-visit interaction as fixed effects, and patients as random effects. Safety measures were analysed according to the treatment received. This study has been completed and is registered with ClinicalTrials.gov, NCT01625988.
Between July 31, 2012, and Sept 18, 2013, 218 patients were randomly assigned to LY2951742 (n=108, but one patient withdrew before treatment) or placebo (n=110). The mean change from baseline to week 12 in the number of migraine headache days was −4·2 (SD 3·1; 62·5% decrease) in the LY2951742 group compared with −3·0 (SD 3·0; 42·3% decrease) in the placebo group (least-squares mean difference −1·2, 90% CI −1·9 to −0·6; p=0·0030). Adverse events that occurred more frequently with LY2951742 than with placebo included injection site pain, erythema, or both (21 [20%] of 107 vs seven [6%] of 110), upper respiratory tract infections (18 [17%] vs ten [9%]), and abdominal pain (six [6%] vs three [3%]). There were two serious adverse events reported in the treatment arm and four in the placebo arm, none of which were deemed to be related to the study drug.
These results provide preliminary evidence that LY2951742 might be beneficial in migraine prevention and provide support for the role of calcitonin gene-related peptide in the pathogenesis of migraine. Further controlled studies are needed to assess the safety and efficacy of monoclonal calcitonin gene-related peptide antibodies for the preventive treatment of migraine.
[Show abstract][Hide abstract] ABSTRACT: This study was designed to evaluate the traditional advice to headache sufferers to avoid all triggers (‘Avoidance’), and a novel approach to trigger management (Learning to Cope with Triggers – ‘LCT’) that included graduated exposure to selected triggers to promote desensitization. Individuals (84F, 43M) with migraine and/or tension-type headache were assigned randomly to one of four groups: Waiting-list (Waitlist); Avoidance; Avoidance combined with cognitive behavior therapy (Avoid + CBT); and LCT. Changes in headaches and medication consumption (in parentheses) from pre- to post-treatment were (a minus sign indicates improvement): Waitlist, +11.0% (+15.4%); Avoidance, -13.2% (-9.0%); Avoid + CBT, -30.0% (-19.4%); and LCT, -35.9% (-27.9%). Avoidance did not differ significantly from Waitlist on headaches or medication use, but LCT differed significantly from Waitlist on both measures. Avoid + CBT significantly differed from Waitlist on headaches but not medication consumption. In summary, the study failed to find support for the standard approach to trigger management of advising avoidance, but LCT emerged as a promising strategy. LCT resulted in greater improvement than the other three conditions on all measures of headaches and medication consumption, and was the only treatment condition that significantly differed from the waiting-list control condition in terms of treatment responder rate (50% or greater reduction in headaches) and medication consumption.
[Show abstract][Hide abstract] ABSTRACT: Familial hemiplegic migraine type 1 (FHM-1) is a monogenic subtype of migraine with aura caused by missense mutations in the CACNA1A gene, which encodes the pore-forming α1 subunit of voltage-gated neuronal CaV2.1 (P/Q-type) calcium channels. Transgenic knock-in mice expressing the CACNA1A R192Q mutation that causes FHM-1 in patients show a greater susceptibility to cortical spreading depression, the likely underlying mechanism of human migraine aura. The aim of this study was to compare neuronal activation within the trigeminal pain pathways in response to nociceptive trigeminovascular stimulation in wild-type and R192Q knock-in mice. After sham surgery or electrical stimulation of the superior sagittal sinus for two hours, or stimulation preceded by treatment with naratriptan, mice underwent intracardiac perfusion, and the brain, including the brainstem, was removed. Fos expression was measured in the trigeminocervical complex (TCC) and the lateral (ventroposteromedial, ventrolateral), medial (parafascicular, centromedian) and posterior thalamic nuclei. In the TCC of wild-type animals, the number of Fos-positive cells increased significantly following dural stimulation compared to the sham control group (P<0.001) and decreased after naratriptan treatment (P<0.05). In R192Q knock-in mice, there was no significant difference between the stimulated and sham (P=0.10) or naratriptan pre-treated groups (P=0.15). The number of Fos-positive cells in the R192Q stimulated group was significantly lower compared to the wild-type stimulated mice (P<0.05). In the thalamus, R192Q mice tended to be more sensitive to stimulation compared to the sham control in the medial and posterior nucleus, and between the two strains of stimulated animals there was a significant difference in the centromedian (P<0.005), and posterior nuclei (P<0.05). The present study suggests that the FHM-1 mutation affects more rostral brain structures in this experimental paradigm, which may offer a novel perspective on possible differential effects of mutations causing migraine in terms of phenotype-genotype correlations.
Neurobiology of Disease 12/2013; · 5.62 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Sinusitis is the most frequent misdiagnosis given to patients with migraine.Therefore we decided to estimate the frequency of misdiagnosis of sinusitis among migraine patients.
The study included migraine patients with a past history of sinusitis. All included cases fulfilled the International Classification of Headache Disorders, 3rd edition (ICHD-III- beta) criteria. We excluded patients with evidence of sinusitis within the past 6 months of evaluation. Demographic data, headache history, medical consultation, and medication intake for headache and effectiveness of therapy before and after diagnosis were collected.
A total of 130 migraine patients were recruited. Of these patients 106 (81.5%) were misdiagnosed as sinusitis. The mean time delay of migraine diagnosis was (7.75 +/- 6.29, range 1 to 38 years). Chronic migraine was significantly higher (p < 0.02) in misdiagnosed patients than in patients with proper diagnosis. Medication overuse headache (MOH) was reported only in patients misdiagnosed as sinusitis. The misdiagnosed patients were treated either medically 87.7%, or surgically12.3% without relieve of their symptoms in 84.9% and 76.9% respectively. However, migraine headache improved in 68.9% after proper diagnosis and treatment.
Many migraine patients were misdiagnosed as sinusitis. Strict adherence to the diagnostic criteria will prevent the delay in migraine diagnosis and help to prevent chronification of the headache and possible MOH.
The Journal of Headache and Pain 12/2013; 14(1):97. · 2.78 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Migraine is a common and highly disabling neurological disorder. Despite the complexity of its pathophysiology, substantial advances have been achieved over the past 20 years in its understanding, as well as the development of pharmacological treatment options. The development of serotonin 5-HT1B/1D receptor agonists ("triptans") substantially improved the acute treatment of migraine attacks. However, many migraineurs do not respond satisfactorily to triptans and cardiovascular co-morbidities limit their use in a significant number of patients. As migraine is increasingly considered to be a disorder of the brain, and preclinical and clinical data indicate that the observed vasodilation is merely an epiphenomenon, research has recently focused on the development of neurally acting compounds that lack vasoconstrictor properties. This review highlights the most important pharmacological targets for which compounds have been developed that are highly likely to enter or have already advanced into clinical trials for the acute and preventive treatment of migraine. In this context, preclinical and clinical data on compounds acting on calcitonin gene-related peptide or its receptor, the 5-HT1F receptor, nitric oxide synthase, and acid-sensing ion channel blockers are discussed.
[Show abstract][Hide abstract] ABSTRACT: Our aim was identify brain areas involved in the premonitory phase of migraine using functional neuroimaging. To this end, we performed positron emission tomography scans with H2(15)O to measure cerebral blood flow as a marker of neuronal activity. We conducted positron emission tomography scans at baseline, in the premonitory phase without pain and during migraine headache in eight patients. We used glyceryl trinitrate (nitroglycerin) to trigger premonitory symptoms and migraine headache in patients with episodic migraine without aura who habitually experienced premonitory symptoms during spontaneous attacks. The main outcome was comparing the first premonitory scans in all patients to baseline scans in all patients. We found activations in the posterolateral hypothalamus, midbrain tegmental area, periaqueductal grey, dorsal pons and various cortical areas including occipital, temporal and prefrontal cortex. Brain activations, in particular of the hypothalamus, seen in the premonitory phase of glyceryl trinitrate-triggered migraine attacks can explain many of the premonitory symptoms and may provide some insight into why migraine is commonly activated by a change in homeostasis.
[Show abstract][Hide abstract] ABSTRACT: Chronic migraine is common in pediatrics and generally disabling. In adults, infiltration of the area around the greater occipital nerve can provide short- to medium-term benefit in some patients. This study reports the efficacy of greater occipital nerve infiltrations in pediatric patients with chronic primary headache disorders.
Retrospective chart review of patients <18 years with a chronic primary headache disorder undergoing a first-time injection. Infiltrations were unilateral and consisted of a mixture of methylprednisolone acetate, adjusted for weight, and lidocaine 2%.
Forty-six patients were treated. Thirty-five (76%) had chronic migraine, 9 (20%) new daily persistent headache (NDPH), and 2 (4%) a chronic trigeminal autonomic cephalalgia. Medication overuse was present in 26%. Ages ranged from 7 to 17 years. Follow-up data were available for 40 (87%). Overall, 53% (21/40) benefitted, and 52% (11/21) benefitted significantly. Benefit onset ranged from 0 to 14 days, mean 4.7 (SD 4.3), with mean benefit duration of 5.4 (SD 4.9) weeks. In chronic migraine, 62% (18/29) benefitted, and 56% (10/18) significantly benefitted. In NDPH, 33% (3/9) benefitted; 33% (n = 1) significantly. Neither child with a chronic trigeminal autonomic cephalalgia benefitted. In logistic regression modeling, medication overuse, age, sex, and sensory change in the distribution of the infiltrated nerve did not predict outcome. There were no serious side effects.
Greater occipital nerve injections benefitted 53% of pediatric patients with chronic primary headache disorders. Efficacy appeared greater in chronic migraine than NDPH. Given the benign side effect profile, a greater occipital nerve infiltration seems appropriate before more aggressive approaches.
[Show abstract][Hide abstract] ABSTRACT: "Attack" is often a word associated with migraine, and for good reason. If you suffer from migraine headaches or know someone who does, you are well aware of its crippling nature. This story focuses on new research that has uncovered an important link between migraine and sleep patterns. A better understanding of the relationships among the body's circadian rhythms, the brain's hypothalamus, and a mutated gene holds enormous promise of improved care for the more than 36 million Americans who experience migraine (three times more common in women) and the number of people suffering from familial advanced sleep phase syndrome (FASP).
Cerebrum: the Dana forum on brain science 11/2013; 2013:15.
[Show abstract][Hide abstract] ABSTRACT: Activation and sensitization of trigeminovascular nociceptive pathways is believed to contribute to the neural substrate of the severe and throbbing nature of pain in migraine. Endocannabinoids, as well as being physiologically analgesic, are known to inhibit dural trigeminovascular nociceptive responses. They are also involved in the descending modulation of cutaneous-evoked C-fiber spinal nociceptive responses from the brainstem. The purpose of this study was to determine whether endocannabinoids are involved in the descending modulation of dural and/or cutaneous facial trigeminovascular nociceptive responses, from the brainstem ventrolateral periaqueductal gray (vlPAG). CB1 receptor activation in the vlPAG attenuated dural-evoked Aδ-fiber neurons (maximally by 19%) and basal spontaneous activity (maximally by 33%) in the rat trigeminocervical complex, but there was no effect on cutaneous facial receptive field responses. This inhibitory vlPAG-mediated modulation was inhibited by specific CB1 receptor antagonism, given via the vlPAG, and with a 5-HT1B/1D receptor antagonist, given either locally in the vlPAG or systemically. These findings demonstrate for the first time that brainstem endocannabinoids provide descending modulation of both basal trigeminovascular neuronal tone and Aδ-fiber dural-nociceptive responses, which differs from the way the brainstem modulates spinal nociceptive transmission. Furthermore, our data demonstrate a novel interaction between serotonergic and endocannabinoid systems in the processing of somatosensory nociceptive information, suggesting that some of the therapeutic action of triptans may be via endocannabinoid containing neurons in the vlPAG.
Journal of Neuroscience 09/2013; 33(37):14869-77. · 6.91 Impact Factor