Familial hemiplegic migraine type 2 due to a novel missense mutation in ATP1A2.

BACKGROUND: The mechanisms of genotype-phenotype interaction in Familiar Hemiplegic migraine type 2 (FHM2) are still far from clear. Different ATP1A2 mutations have been described, with a spectrum of phenotypes ranging from mild to severe. No genotype-phenotype correlations have been attempted. CASE PRESENTATION: We describe an Italian family with FHM and a missense ATP1A2 variant (L425H) not previously described. The clinical picture was mild in all the affected members. CONCLUSIONS: Co-segregation of the variant with the aura phenotype was complete in this family, suggesting a 100% penetrance. In silico protein prediction softwares indicate that this variant may change the 3D structure of ATPA1A2 at the cytoplasmic loop between the two central transmembrane helices. Milder FHM phenotypes are rarely reported in literature, likely because case reports are biased towards the most severe phenotypes, with milder forms possibly misdiagnosed as sporadic migraine with aura forms (MAs), even with complex auras. Further studies taking into account intra-familiar variability and functional consequences on the channel protein may help clarify genotype-phenotype correlations.

Headache and neck.

Cervicogenic headache (CEH) is currently identified with different diagnostic criteria. The latest one is the International classification of headache disorders (ICHD), 3rd edition (2018). At the present time, there are not enough published articles with reliable sensitivity and specificity that may support a classification for clinical and research purposes. Current literature suggests improvement to the classification(s). The ICHD criteria should be modified to reach an optimal sensitive and specific level to identify CEH as a secondary headache. The B, C1, and C2 criteria should be implemented with proposed suggestions. The C3 criterion should be upgraded. Criteria such as mechanical precipitation of pain by digital pressure on neck trigger points and specific movements, strictly unilateral pain without side-shift, diffuse unilateral shoulder and arm pain, pain starting posteriorly and spreading anteriorly should be integral part of the classification.

Cathodal tDCS Guided by Thermography as Adjunctive Therapy in Chronic Migraine Patients: A Sham-Controlled Pilot Study.

Objective: To explore the efficacy of cathodal tDCS applied ipsilateral to the cold patch, as determined by thermographic evaluation, in the treatment of chronic migraine. Background: Transcranial direct current stimulation (tDCS) is a non-invasive and safe technique that modulates the activity of the underlying cerebral cortex. tDCS has been extensively tested as a possible treatment for chronic pain and migraine with controversial results mainly due to the different setting procedure and location of electrodes. Since the presence of a hypothermic patch region detected through thermography has been suggested as a possible support for headache diagnosis, this "cold patch" could considered as possible effective location for tDCS application. Methods: Forty-five patients with chronic migraine were randomized to receive either cathodal (25 patients) or sham tDCS, for 5 consecutive daily sessions plus a recall session after 1 month. Cathodal tDCS was delivered at 1.5 mA for 15 min in each session. Subjects were evaluated before treatment (baseline, T0), and after 10 (T10), 60 (T60), and 120 (T120) days after treatment. The number of attacks, duration of attacks, pain intensity, number of days with headache, and number of analgesics were collected at each time evaluation. Results: Patients in the tDCS group showed a significant improvement compared to the sham group, during the whole study period in the frequency of migraine attacks (tDCS vs. sham: -47.8 ± 50.1% vs. -14.2 ± 16.5%, p = 0.004), number of days with headache (tDCS vs. sham: -42.7 ± 65.4% vs. -11.3 ± 18.0%, p = 0.015), duration of attacks (tDCS vs. sham: -29.1 ± 43.4% vs. -7.5 ± 17.6%, p = 0.016), intensity of the pain during an attack (tDCS vs. sham -31.1 ± 36.9% vs. 8.3 ± 13.5%, p = 0.004), and number of analgesics (tDCS vs. sham -54.3 ± 37.4% vs. -16.0 ± 19.6%, p < 0.0001). Conclusion: Our results suggest that cathodal tDCS is an effective adjuvant technique in migraine provided that an individual correct montage of the electrodes is applied, according to thermographic investigation.

Impact of Medical Care on Symptomatic Drug Consumption and Quality of Life in Headache: A One-Year Population Study.

Background: Chronic headache is one of the most common pain conditions, often leading to symptomatic drug overuse. The aim of this study was to provide data on symptomatic drug consumption in an Italian outpatient population and to describe how the clinical picture of headache may change after headache experts take charge of the care of affected individuals. Methods: A total of 199 adults complaining of chronic headache were recruited through 32 pharmacies in the Pavia health district. Participants underwent four evaluations: a baseline assessment (T0) and three follow-up evaluations performed by a neurologist at 3, 6, and 12 months (T3, T6, and T12, respectively). On each occasion, they underwent a complete neurological assessment and received therapeutic adjustments to achieve better management of their headache. Results: On the basis of a preliminary telephone interview, the prevalence rates of chronic headache and medication overuse headache (MOH) were 16 and 12%, respectively. At 12 months of follow-up, we observed a significant decrease in the frequency of attacks (T0: 9 ± 9/month vs. T12: 2 ± 2/month; p < 0.001), in the number of days/month with headache (T0: 11 ± 9 vs. T12: 4 ± 4; p < 0.001) and in single attack duration (T0: 34 ± 30 h vs. T12: 10 ± 19 h; p < 0.001). Careful headache management resulted in a significant decrease in analgesic consumption (T0: 12 ± 16 vs. T12: 4 ± 6 doses/month; p = 0.014) and a significant increase in quality of life, measured using the Migraine Disability Assessment Scale (MIDAS) and Headache Under-Response to Treatment (HURT) scales (p < 0.001). Conclusions: Headache management by a specialist is more effective than self-treatment, resulting in an overall benefit for headache patients.

The Treatment of Trigeminal Autonomic Cephalalgias: An Overview.

Trigeminal autonomic cephalalgias (TACs) are primary headaches that include cluster headache (CH), paroxysmal hemicrania (PH), and short-lasting unilateral neuralgiform headache attacks (SUNHAs) with conjunctival injection and tearing (SUNCT) or cranial autonomic features (SUNA). Hemicrania continua (HC) is another form that has been ascribed to TACs for clinical and pathophysiologic reasons. Cluster headache is the most common of these syndromes, even if comparatively rare, with a lifetime prevalence of around 1 in 1,000. TACs share many aspects from a pathophysiologic standpoint (a hypothalamic activation may be involved in all forms initiating the attacks), but differences in attack duration and frequency and in extent of treatment response distinguish one from the other. This review focuses on the treatments currently available for these headaches according to the most recent guidelines. Due to the low frequency of most TACs, there are little data from randomized controlled trials; therefore, evidence from simple open studies in small case series or single-case observations are reported. Promising results have been recently obtained with novel modes of drug administration, invasive pericranial interventions, and different strategies such as neurostimulation. There are also some future treatments being studied at present.

Frontal infrared thermography in healthy individuals and chronic migraine patients: Reliability of the method.

BACKGROUND: The use of frontal infrared thermography in the diagnosis of primary headaches provided scattering results due to measurement fluctuations and different types of headaches or research protocols. OBJECTIVE: This study aims to assess the reliability of frontal infrared thermography in healthy individuals and provide a preliminary evaluation in chronic migraine patients using a commercial infrared thermal camera. METHODS: Thermographic images were acquired in 20 controls and 15 patients at three consecutive time-points in two daily sessions. The Side Difference and Asymmetry Index parameters were defined. The reproducibility of the measurements, the correlation of Asymmetry Index and Side Difference with clinical evaluations and patient perceptions, and the ability of the parameters to discriminate between patients and controls were investigated. RESULTS: We reported a good reproducibility of the measurements (Inter-class Correlation Coefficient > 0.75 and Coefficient of Variation < 13.4%), independent from external factors. The Side Difference was significantly different between patients and controls ( p < 0.001). The Asymmetry Index showed good correlation with the side of unilateral pain ( p = 0.0056). CONCLUSIONS: Frontal infrared thermography can be used to quantify the difference between the right and the left side of frontal vascular changes in chronic migraine patients, provided that standardized conditions are satisfied.

Corrigendum: Shortlasting, Unilateral, Neuralgiform, Headache Attacks With Conjunctival Injection, Tearing, Sweating and Rhinorrhea: The Term and New View Points.

[This corrects the article DOI: 10.3389/fneur.2018.00262.].

Shortlasting, Unilateral, Neuralgiform, Headache Attacks With Conjunctival Injection, Tearing, Sweating and Rhinorrhea: The Term and New View Points

A solitary patient with symptoms similar to those of shortlasting unilateral neuralgiform conjunctival injection and tearing (SUNCT) was first mentioned in 1978. The term SUNCT was first used in 1991. SUNCT is an acronym; the "S" signifies "Shortlasting"; the "U" symbolizes "Unilateral"; "N" stands for "Neuralgiform"; the "C" for "Conjunctival injection"; and "T" for "Tearing." The term short-lasting unilateral neuralgiform headache attacks with cranial autonomic symptoms were marketed in 2004. The terminology and new view points are discussed and nosography proposal for SUNCT is presented.

Recent advances in migraine therapy.

Migraine is a common and highly disabling neurological disorder associated with a high socioeconomic burden. Effective migraine management depends on adequate patient education: to avoid unrealistic expectations, the condition must be carefully explained to the patient soon as it is diagnosed. The range of available acute treatments has increased over time. At present, abortive migraine therapy can be classed as specific (ergot derivatives and triptans) or non-specific (analgesics and non-steroidal anti-inflammatory drugs). Even though acute symptomatic therapy can be optimised, migraine continues to be a chronic and potentially progressive condition. In addition to the drugs officially approved for migraine prevention by international governmental regulatory agencies, numerous different agents are commonly used for this indication, showing various levels of evidence of efficacy and tolerability. Guidelines published in recent years, based on evidence-based medicine data on migraine prophylaxis, are a useful source of guidance, especially for primary care physicians and neurologists without specific expertise in headache medicine. Although the field of pharmacological migraine prevention has seen few advances in recent years, potential novel approaches are now being developed. This review looks at emerging pharmacological strategies for acute and preventive migraine treatment that are nearing or have already entered the clinical trial phase. Specifically, it discusses preclinical and clinical data on compounds acting on calcitonin gene-related peptide or its receptor, the serotonin 5-HT1F receptor, nitric oxide synthase, and acid-sensing ion channel blockers.

The Neuropharmacology of Cluster Headache and other Trigeminal Autonomic Cephalalgias.

Trigeminal autonomic cephalalgias (TACs) are a group of primary headaches including cluster headache (CH), paroxysmal hemicrania (PH) and short-lasting unilateral neuralgiform headache with conjunctival injection and tearing (SUNCT). Another form, hemicrania continua (HC), is also included this group due to its clinical and pathophysiological similarities. CH is the most common of these syndromes, the others being infrequent in the general population. The pathophysiology of the TACs has been partly elucidated by a number of recent neuroimaging studies, which implicate brain regions associated with nociception (pain matrix). In addition, the hypothalamic activation observed in the course of TAC attacks and the observed efficacy of hypothalamic neurostimulation in CH patients suggest that the hypothalamus is another key structure. Hypothalamic activation may indeed be involved in attack initiation, but it may also lead to a condition of central facilitation underlying the recurrence of pain episodes. The TACs share many pathophysiological features, but are characterised by differences in attack duration and frequency, and to some extent treatment response. Although alternative strategies for the TACs, especially CH, are now emerging (such as neurostimulation techniques), this review focuses on the available pharmacological treatments complying with the most recent guidelines. We discuss the clinical efficacy and tolerability of the currently used drugs. Due to the low frequency of most TACs, few randomised controlled trials have been conducted. The therapies of choice in CH continue to be the triptans and oxygen for acute treatment, and verapamil and lithium for prevention, but promising results have recently been obtained with novel modes of administration of the triptans and other agents, and several other treatments are currently under study. Indomethacin is extremely effective in PH and HC, while antiepileptic drugs (especially lamotrigine) appear to be increasingly useful in SUNCT. We highlight the need for appropriate studies investigating treatments for these rare, but lifelong and disabling conditions.

Cervicogenic headache: too important to be left un-diagnosed.

A comparison has been made between the cervicogenic headache criteria in the new IHS classification of headaches (3rd edition-beta version) and The Cervicogenic Headache International Study Group's (GHISG) criteria from 1998. In a more recent version, the CHISG criteria consist of 7 different items. While "core cases" of cervicogenic headache (CEH) usually fulfill all 7 criteria, the IHS classification--3rd edition beta version--fulfills only 3 criteria. Although the new three beta version represents an improvement from the previous one, it does not quite seem to live up to the expectations for a diagnostic system for routine, clinical use.

Hemicrania continua: major shortcomings in the new classification.

Hemicrania continua ( HC) was described and coined by Sjaastad and Spierings in 1984. Later cases, carrying this appellation should, grossly, conform to this original description. The proposed classification criteria (ICHD, 3rd edition beta version) for HC has major shortcomings, and ordinary HC cases do not fulfill the proposed criteria. Relatively rare symptoms and signs are e.g. made obligatory (point C 1). And the recommended dosage of indomethacin- both test and long-term dosages-is unallowably high. In this way, bogus HC cases are systematically created. This irrational diagnostic system is in urgent need of a major revision.

Diagnostic and therapeutic errors in cluster headache: a hospital-based study.

BACKGROUND: Cluster headache (CH) is a severe, disabling form of headache. Even though CH has a typical clinical picture it seems that its diagnosis is often missed or delayed in clinical practice. CH patients may thus face: misdiagnosis, unnecessary investigations and delays in accessing adequate treatment. This study was conducted to investigate the occurrence of diagnostic and therapeutic errors with a view to improving the clinical and instrumental work-up in affected patients. METHODS: Our study comprised 144 episodic CH patients: 116 from Italy and 28 from Eastern European countries (Moldova, Ukraine, Bulgaria). One hundred six patients (73.6%) were examined personally and 38 (26.4%) were evaluated through telephone interviews conducted by headache specialists using an ad hoc questionnaire developed by the authors. RESULTS: The sample was predominantly male (M:F ratio 2.79:1) and had a mean age of 42.4 ± 9.8 years; approximately 76% of the patients had already consulted a physician about their CH at the onset of the disease. The mean interval between onset of the disease and first consultation at a headache center was 4.1 ± 5.6 years. The patients had consulted different specialists prior to receiving their CH diagnosis: neurologists (49%), primary care physicians (35%), ENT specialists (10%), dentists (3%), etc. Misdiagnoses at first consultation were recorded in 77% of the cases: trigeminal neuralgia (22%), migraine without aura (19%), sinusitis (15%), etc. The average "diagnostic delay" was 5.3 ± 6.4 years and the condition was diagnosed approximately ("doctor delay": one year). Instrumental and laboratory investigations were carried out in 93% of the patients prior to diagnosis of CH. Some of the patients had never received abortive or preventive medications, either before or after diagnosis. Medical prescription compliance: 88% of the cases. CONCLUSIONS: Our results emphasize the need to improve specialist education in this field in order to improve recognition of the clinical picture of CH and increase knowledge of the proper medical treatments for de novo CH. Continuous medical education on CH should target general neurologists, primary care physicians, ENT specialists and dentists. A study on a larger population of CH patients may further improve error-avoidance strategies.

The evolution of headache from childhood to adulthood: a review of the literature.

Headache is one of the most common disorders in childhood, with an estimated 75% of children reporting significant headache by the age of 15 years. Pediatric migraine is the most frequent recurrent headache disorder, occurring in up to 28% of older teenagers. Headaches rank third among the illness-related causes of school absenteeism and result in substantial psychosocial impairment among pediatric patients. The aim of this study was to clarify the evolution of the clinical features of primary headache in the transition from childhood to adulthood through a review of relevant data available in the PubMed and Google Scholar databases for the period 1988 to July 2013.The search strategy identified 15 published articles which were considered eligible for inclusion in the analysis (i.e., relevant to the investigation of pediatric headache outcome). All were carried out after the publication of the first version of the International Classification of Headache Disorders (ICHD-I). The availability of data on the evolution of primary headaches over a period of time is important from both a clinical and a public health perspective. The identification of prognostic factors of the evolution of headache (remission or evolution into another headache form) over time should be an objective of future headache research for the development of prevention strategies. Given that headache is a major factor contributing to school absenteeism and poorer quality of life not only in childhood but also in adolescence, understanding the natural history and the management of the different headache forms is vital for our future.