Academic literature on the topic 'Migraine with aura'

Data from the Prolonged Migraine Prevention (PROMPT) with Topiramate trial were evaluated post hoc to determine whether topiramate could prevent migraine auras, and whether its efficacy in preventing migraine headaches was similar in patients with (MA; n = 269) and without (MoA; n = 542) aura. Migraines and auras were recorded during prospective baseline, 6-month open-label (OL) topiramate and 6-month double-blind (DB), placebo-controlled phases. In the last 28 OL days, migraines without aura and migraine auras decreased by 43.1% and 54.1%, respectively, in MA patients. MoA patients experienced a 44.3% reduction in migraines. In the DB phase, increases in migraines with placebo vs. topiramate were similar to the full study, but were generally not statistically significant, probably due to lack of power in the subgroup analysis. Similarly, there were no statistically significant changes in number of auras between groups. Thus, topiramate appears to reduce migraine auras in parallel with headache reductions, which are similar in patients with and without aura.

Background: Migraines are a broad spectrum of disorders classified by the type of aura with some requiring attentive treatment. Vasoconstrictors, including triptans, should be avoided in the acute phase of migraines with brainstem aura, in hemiplegic migraine, and in retinal migraine. This study investigated the characteristics and burden of these migraines. Methods: Medical charts of 278 Japanese pediatric patients with migraines were retrospectively reviewed. Migraine burden of migraines with brainstem aura, hemiplegic migraines, and retinal migraine was assessed using the Headache Impact Test-6™ (HIT-6) and the Pediatric Migraine Disability Assessment scale (PedMIDAS). Results: Of 278 patients screened, 12 (4.3%) patients with migraines with brainstem aura (n = 5), hemiplegic migraines (n = 2), and retinal migraine (n = 5) were enrolled in the study. All patients had migraine with/without typical aura, whereas some patients had coexisting migraine with another type of headache (chronic tension-type headache in 3 patients, and 1 each with frequent episodic tension-type headache, headache owing to medication overuse, and chronic migraine). Migraines with brainstem aura, hemiplegic migraines, and retinal migraine patients with coexisting headaches had higher HIT-6 or PedMIDAS scores, whereas migraines with brainstem aura, hemiplegic migraines, and retinal migraine patients without coexisting headache did not show high HIT-6 or PedMIDAS scores. Conclusion: All migraines with brainstem aura, hemiplegic migraines, and retinal migraine patients experienced migraine with or without typical aura, and some patients having other coexisting headaches also had high PedMIDAS and HIT-6 scores. PedMIDAS and HIT-6 should not be considered diagnostic indicators of migraines with brainstem aura, hemiplegic migraines, or retinal migraine. In clinical practice for headaches in children, careful history taking and proactive assessment of the aura are needed for accurate diagnosis of migraines with brainstem aura, hemiplegic migraines, and retinal migraine.

The most common type of migraine aura is multifaceted visual aura, such as scintillating scotoma or geometrical patterns, visual hallucinations in which a physical body is extremely rare. We report a paediatric case of migraine in which visual hallucinations appeared as auras in the form of a human body. The patient was an 11-year-old girl suffering from migraine with curious visual aura. The auras were atypical visual hallucinations that were sometimes accompanied by auditory hallucinations. Approximately 5–20 min before the headache, the patient would see a middle-aged man wearing sunglasses in her field of vision. Acetaminophen (10 mg/kg) and Japanese herbal medicine administered when necessary effectively treated the headaches. Finally, the patient was no longer complaining of her hallucination auras. Although the pathophysiology of migraines accompanied by auras is unclear, it appears that cerebral blood flow and cortical spreading depression are involved in auras.

We present a diagnostic aura diary for prospective recordings of migraine with aura. Three questionnaires are supplemented with sheets for drawings and plottings of visual and sensory auras. Twenty patients recorded 54 attacks of migraine with aura and 2 attacks of migraine aura without headache. The visual and sensory aura were usually gradually progressive, reaching maximum development in 15 and 25 min (median) respectively and had a total duration of 20 and 55 min (median) respectively. Approximately 13% of the attacks had acute onset of visual aura associated with other features more typical of migraine. The visual and sensory auras always preceded typical migraine headache, and headache occurring before aura symptoms was always of the tension type, The migraine headache was milder than in attacks of migraine without aura and often did not have migraine characteristics. In attacks with unilateral head pain, headache and aura symptoms were contralateral in 90% and ipsilateral in 10%.

Purpose: Different types of migraine may be studied separately to understand their epidemiology and pathophysiology better. No studies have investigated patients with associated factors of anxiety severity in migraine without auras. Therefore, in this study, anxiety and its associated factors were investigated in a sample of Saudi Arabian patients with migraine without aura. Methods: A cross-sectional study of 122 conveniently sampled migraine patients at Madinah hospitals, Saudi Arabia, completed the Generalized anxiety disorder-7 scale (GAD-7), and a tool for social, demographics, and clinical information. Results: The majority of patients who did not have an aura with their migraine were female (67.2%); many did not report participating in sports activities (58.2%), or have a family history of migraine-headaches (74.6%). Anxiety severity was higher in migraine-without-aura patients, and those undergoing treatment for co-morbid conditions (β = .547, p = .042), those without family history of migraine/chronic headache (β = .016, p = .016), and patients with high frequency of migraine medication use (β = .009, p = .009). Discussion: The correlation of the anxiety severity level in patients who have migraines without aura may have important clinical, and epidemiological implications. females with their change in hormonal stat have a higher prevalence of migraine without aura, those with no habitual sport activity, and family history of migraine may indicate the need for targeted screening for migraine in these groups. Keywords: migraine; headache; sports; family history; trauma; GAD

Background For future experimental studies or the development of targeted pharmaceutical agents, a deeper insight into the pathophysiology of migraine is of utmost interest. Reliable methods to trigger migraine attacks including aura are desirable to study this complex disease in vivo. Methods To investigate hypoxia as a trigger for migraine and aura, we exposed volunteers diagnosed with migraine, with (n = 16) and without aura (n = 14), to hypoxia utilizing a hypoxic chamber adjusted to a FiO2 of 12.6%. The occurrence of headache, migraine, aura, and accompanying symptoms were registered and vital signs were collected for 6 hours under hypoxia and 2 hours of follow-up. A binary logistic regression analysis examined the probability of triggering headaches, migraines, aura, photo- and phonophobia. Findings Of 30 participants, 24 (80.0%) developed headaches and 19 (63.3%) migraine, five (16.7%) reported aura. Two patients that developed aura never experienced aura symptoms before in their life. The increase of mean heart frequency was higher in patients developing headaches or migraine. Mean SpO2 during hypoxia was 83.39%. Conclusion Hypoxia was able to trigger migraine attacks and aura independently of any pharmacological agent.

Background Hemiplegic migraine is a rare form of migraine with aura characterized by motor aura. Although auras in hemiplegic migraine are typically complex with two or more aura symptoms, neglect has been rarely described. Case report We report the case of a 20-year-old woman with sporadic hemiplegic migraine that was investigated for the presence of unilateral spatial neglect (USN) during aura in one of her migraine attacks. Transient hemispatial neglect was observed during a right-sided migraine attack with left sensory-motor hemisyndrome; after migraine resolution there was a total recovery. Conclusions Our case demonstrates that USN may be a symptom of aura. To our knowledge, this is the first report of USN during aura in an adult with sporadic hemiplegic migraine.

Nella tesi è descritto un modello matematico per l'aura emicranica e, più precisamente, per lo scotoma scintillante (schema di fortificazione) e per la Cortical Spreading Depression, il fenomeno neuropatofisiologico alla base dell'aura. In particolare è spiegato un modello cinematico per l'evoluzione della CSD nella corteccia visiva primaria, considerata un mezzo debolmente eccitabile, la mappa retino-corticale e il modello, tramite fibrato, dei Pinwheels di V1.

Cortical spreading depression (CSD), the underlying mechanism behind migraine aura, occurs when neurons become depolarized and lose function, while releasing signaling molecules that propagate this condition. Spreading depression occurs when abnormal flow of ions across the cell membranes of a neural cell depolarizes the cell and activates detrimental signaling pathways that cause the same disruptive ion flow to occur in nearby neural or glial cells. After depolarization, cells affected by CSD are not able to return to their normal state and remain nonfunctional for some time. This lack of function causes symptoms of migraine aura. Calcium and glutamate signaling may be primary drivers of the CSD; inhibition of either tends to prevent CSD, whereas their activation promotes it. Cerebral blood flow and oxygen consumption are considered measures of cell function during CSD and further demonstrate the significance of CSD on a larger scale. This is a review of current research about these elements of migraine aura.

Migraine is a painful neurological disease that affects at least 12% of the Australian population. It is generally characterized by recurrent head pain usually accompanied by nausea, vomiting, neurological disturbance, photo-and phonophobia. Migraine has been classified by the international headache society (IHS) into two most common types, migraine with aura (MA) and migraine without aura (MO). The underlying pathophysiology of this debilitating disease is still partially understood and there are no known diagnostic markers for these common types of migraine. Current diagnosis of migraine is based on patient reported symptoms. Studies have shown several health conditions such as epilepsy, depression and stroke to be co-morbid with migraine. Current migraine treatments work with varying efficacy and often have adverse side effects. A greater understanding of this debilitating and painful disease is thus pertinent for developing new and improved migraine treatment. Both familial clustering and twin studies have shown evidence for significant genetic mechanisms to underlie migraine pathogenesis. Migraine is thus currently defined as a complex multifactorial disorder which involves an interaction between genetic and environmental factors. We have not yet identified all migraine genes but a number of genes, causative mutations and susceptibility variants have been identified and are already of significant clinical relevance. Currently the detection of 3 rare subtypes of migraine (Familial Hemiplegic Migraine 1, 2 and 3) and several related conditions with symptom overlap (Episodic Ataxia 2, Spinocerebellar Ataxia Type 6 and Cerebral Autosomal Dominant Arteriopathy with Sub cortical Infarcts and leucoencephalopathy (CADASIL) is undertaken by sequencing, with susceptibility variants for common types of migraine detected by sequencing or genotyping.
Thesis (PhD Doctorate)
Doctor of Philosophy (PhD)
School of Medical Science
Griffith Health
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Migraine is a serious neurological disorder that affects the central nervous system causing painful attacks of headache. Attacks of head pain vary widely in intensity, frequency and duration lasting from anywhere between 4-72 hours and are often accompanied by further symptoms of nausea, vomiting, photo- and phonophobia. In 1988, a group of world leaders in the diagnosis of migraine formed the International Headache Society (IHS) and compiled and published a consensus set of diagnostic criteria known as International Classification of Headache Disorders, ICHD-I 1988. This was the first classification system and was subsequently updated in 2004, ICHD-II 2004 and more recently a 3rd Edition beta version has been released (ICHD-3rd Ed Beta Version) and is the gold standard for diagnosing headache disorders. Migraine displays two main subtypes termed migraine with or without aura (MA and MO respectively). The two forms are distinguished from each other based on the development of aura, a period of variable and diverse neurological symptoms that precede the headache phase.
Thesis (PhD Doctorate)
Doctor of Philosophy (PhD)
School of Medical Science
Science, Environment, Engineering and Technology
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This research was conducted to expand the understanding of the role of the X chromosome in common and familial typical migraine. The primary objective of this study was to identify new X chromosomal genetic targets that cause migraine. Overall this research has identified nine genetic targets of interest. Various obstacles were encountered throughout this study, but the knowledge gained for overcoming these obstacles are invaluable for implementation and improvement of future genetic studies investigating the X chromosome.

Migraine is a painful temporarily incapacitating disorder that affects an estimated 12% of the general population including 18% of adult women and 6% of adult men. The disorder involves two main subtypes termed migraine with or without aura (MA and MO respectively). Migraine can present with a variety of symptoms that vary between individuals and between episodes experienced by a single individual. This disorder causes significant social and economic burden and alarmingly is often poorly treated. A direct cause of this is a lack of understanding of the underlying pathology of migraine. Migraine is believed to be a neurogenic disorder that involves temporary disruption of pathways that receive and respond to sensory signals. While numerous environmental triggers may have been identified the exact mechanisms that cause the disruption are still largely unknown. However, familial aggregation of migraine suggests significant genetic contributors.
Thesis (PhD Doctorate)
Doctor of Philosophy (PhD)
School of Medical Science
Griffith Health
Full Text

Migraine is a common, debilitating neurovascular disease charactensed by severe recurrent headache, nausea and vomiting, photophobia and phonophobia. It is clinically diagnosed based on criteria specified by the International Headache Society (IHS), defining two major classes of migraine: migraine with aura (MA) and migraine without aura (MO) MA sufferers experience neurovascular disturbances that precede the headache phase of an attack. Although migraine is partly influenced by environmental determinants, there is a significant genetic component, with disease heritability estimated to be up to 60% and mode of transmission multifactorial. The disorder is common with a large Dutch study reporting lifetime prevalence estimates of 33% in women and 13.3% in men, with an earlier study estimating 24% of women and 12% of men in the overall population. Mutations in various ion channel genes are responsible for neuromuscular and other neurological disorders. Inherited ion channel mutations or 'channelopathies' are increasingly found to be the cause of various neurological disorders in humans. In familial hemiplegic migraine (FHM), a rare subtype of migraine with aura, mutations in the CACNA1A gene (localised at C19p13) have been fbund (FHM1). This gene codes for the alphalA subunit of the neuronal voltage-dependent P/Q-type calcium channel. Recently a second gene, ATP1A2 (FHM2) (localised at C1q23), was implicated in some EHM families. The ATP1A2 ion channel gene, codes for the alpha2 subunit of the Na+, K+ ion ATPase pump. These findings of mutations in these genes have focused attention on central nervous system ionic channels and helped to better understand EHM pathophysiology, where the best genetic evidence providing molecular insight into migraine still comes flom the mutations detected in the rare form of migraine with aura; FHM. Migraine family studies, at the Genomic Research Centre (GRC), have utilised linkage analysis methods in providing results that have indicated suggestive linkage to the FHM1-CACNA1A region on l9p13, in a large multigenerational family (Migraine Family 1; MEl) affected with typical migraine. Also linkage studies conducted within the GRC have implicated an additional susceptibility region on chromosome 1q31, but still not ruling out a second susceptibility region on C1q23, with the possibility of there being two distinct loci, on the chromosome lq region. The focus of research in this thesis is on two main chromosomal regions, which were tested for migraine susceptibility on chromosome 1 and chromosome 19. The research involved a cross-disciplinary approach utilising association, linkage and mutation screening approaches. Allelic candidate gene studies can provide a suitable method for locating genes of small effect that contribute to complex genetic disorders, such as migraine. Family linkage studies are useful for detection of chromosomal susceptibility regions and association studies are powerful when a plausible candidate gene and a sequence variant with potential functional relevance is examined. Mutation screening studies can indicate a direct cause of disorders such as migraine, where possible sequence variants may alter the translation of proteins in genes, causing the disease. The first gene exanted on chromosome 19 was that of the Low Density Lipoprotein Receptor (LDLR) gene. The LDLR gene is a cell surface receptor that plays an important role in cholesterol homeostasis. We investigated the (TA)n polymorphism in exon 18 of the LDLR gene on chromosome l9pl3.2 performing an association analysis in 244 typical migraine affected patients, 151 suffering from migraine with aura, 96 with migraine without aura and 244 unaffected controls. The populations consisted of Caucasians only and controls were age and sex matched. The results showed no significant difference between groups for allele frequency distributions of the (TA)n polymorphism even after separation of the migraine affected individuals into subgroups of MA and MO affected patients. This is in contradiction to Mochi et al, 2003 who found a positive association of this variant with MO. Our study discusses possible differences between the two studies and extends this research by investigating circulating cholesterol levels in a migraine affected genetically-isolated population. Another gene examined on chromosome l9pl3 was the insulin receptor gene (1NSR). The aim of this study was to investigate through direct sequencing the INSR gene in DNA samples from a migraine affected family previously showing linkage to chromosome l9pl3 in an attempt to detect disease associated mutations. The insulin receptor gene (INSR) on chromosome 19pl3.3-13.2 is a gene of interest since a number of SNPs located within the gene have been implicated in migraine with (MA) and without aura (MO). Six DNA samples obtained from non-founding migraine affected members of migraine family one (MF 1) were used in this study. Genomic DNA was sequenced for the 1NSR gene in exons 1-22 and the promoter region. In the six migraine family member samples, previously reported single nucleotide polymorphisms (SNP5) were detected within two exonic DNA coding regions of the INSR gene. These SNPs, in exon 13 and 17, do not alter the normal INSR polypeptide sequence. In addition, intron 7 also revealed a DNA base sequence variation. For the 5' untranslated promoter region of the gene, no mutations were detected. In conclusion, this study detected no INSR mutations in affected members of a chromosome 19 linked migraine pedigree. Hence, migraine linkage to this chromosomal region may involve other candidate genes. The NOTCH3 gene on C19p13.2-p13.l has previously been shown to be a gene involved in cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) and may also be implicated in migraine as there are some symptom similarities between the two disorders. The TNFSF7 gene localised on Cl9pl3 is homologous to the ligands of the TNF receptor family, including TNF-alpha and TNF-beta, genes that have both been previously associated with migraine. This study investigated the migraine susceptibility locus at Cl9p13 studying two genes that may be involved in the disorder. The NOTCH3 gene was analysed by sequencing all exons with known CADASIL mutations in a family (MF1) that has previously been shown to be linked to Cl9pl3. The sequencing results for affected members of this pedigree proved to be negative for all known sequence variants giving rise to mutation causing amino acid changes for CADASIL. The direct sequencing results displayed that of a normal coding sequence for the NOTCH3 gene F or the TNFSF7 gene, this was investigated through SNP association analysis using a matched case-control migraine diagnosed population. Chi-square results showed non-significant P values across all populations tested against controls except for the MO subgroup which displayed a weak association with the TNFSF7 SNP (genotype, allele analysis P = 0.036, P = 0 017 respectively). Our results suggest that common migraine is not caused by any known CADASIL mutations in the NOTCH3 gene of interest however, the TNFSF7 gene displayed signs of involvement in a MO affected population, but, further studies are needed to confirm these results and to further explore a TNF receptor - migraine potential interaction. A final examination on chromosome 19 involved a case report of an extremely rare and severe form of migraine. As stated earlier Familial Hemiplegic Migraine (FHM) is a severe rare sub-type of migraine and gene mutations on chromosome 19 have been identified in the calcium channel gene CACNA1A (Cl9pl3) fOr FHM. Recently a gene mutation (S218L) for a dramatic syndrome originating from FHM, commonly named 'migraine coma', has implicated exon 5 of the CACNA1A gene. The occurrence of trivial head trauma, in FHM patients, may also be complicated by severe, sometimes even fatal, cerebral edema and coma occurring after a lucid interval. Hemiplegic migraine has also been found to be sporadic in which both forms share a similar spectrum of clinical presentations and genetic heterogeneity. The case report presented in this study enhances the involvement of the S218L CACNA1A mutation in the extremely rare disorder of minor head trauma induced migraine coma. It not only proves to be a powerful diagnostic tool in detecting cases of FHM head trauma induced coma but also for sporadic hemiplegic migraine (SHM) coma subjects. We conclude from this case study that the S218L mutation, in the CACNA1A calcium channel subunit gene, is involved in sporadic hemiplegic migraine (SHM), delayed cerebral edema and coma after minor head trauma. This thesis also involved analysis of chromosome 1 for migraine susceptibility, where FHM studies provided a foundation fOr common migraine research on chromosome 1. Studies have suggested that mutations in the CACNA1A gene on chromosome l9p cause FHM in only approximately 50% of affected pedigrees. The CACNAIA gene has previously been tested, within the Genomics Research Centre, in the common forms of migraine; however no new mutations or the FHM mutations were detected in these MA/MO affected samples. A second FHM susceptibility locus maps to chromosome 1q23 and mutations in the ATP1A2 gene have recently been implicated in two Cl-linked FHM pedigrees. As FHM is considered a rare and severe form of MA, it is possible that the chromosome 1q23 locus, and the ATP1A2 gene, may be involved in the common forms of migraine with (MA) and possibly without aura (MO). Also, we have previously reported evidence of linkage to microsatellite markers on chromosome 1q31 in a large pedigree affected predominately with MA, which suggests the possibility that there are two distinct loci for migraine susceptibility on chromosome 1. The objectives of this study were to extend our linkage analysis of chromosome lq microsatellite markers in predominantly migraine with aura pedigrees. Also, our aim was to test the novel FHM-2 ATP1A2 gene for involvement in these migraine affected pedigrees and a previous pedigree (Migraine Family 14; MF 14) showing evidence of linkage of markers to Clq31. This was performed by a chromosome 1 scan (31 markers) in 21 multiplex pedigrees affected mainly with MA. Also, the known FHM-2 ATP1A2 gene mutations were tested, by sequencing, fOr involvement in MA and MO in these pedigrees. Mutation screening by direct sequencing was also performed throughout the coding areas of the ATP1A2 gene in 3 MA individuals fiom MF14. The results of this study detected evidence for linkage in our migraine pedigrees at chromosome 1q23, to microsatellite markers spanning the ATP1A2 (FHM-2) gene. However testing of the known ATP1A2 gene mutations (for FHM) in migraine probands of pedigrees showing excess allele sharing was negative, with no mutations detected in these migraineurs. Sequencing of the entire coding areas of the gene through 3 MA affecteds from MF14, a pedigree showing significant linkage to this region, was also negative for mutations. In conclusion, this study reported that microsatellite markers on chromosome 1q23 show evidence of excess allele sharing in MA and some MO pedigrees, suggesting linkage to the common forms of migraine and the presence of a susceptibility gene in this region. The new FHM-2 (ATPIA2 gene) mutations reported by Fusco et al, 2003 do not cause migraine in probands of affected pedigrees showing excess allele sharing to markers in this genomic region. Also no mutations were detected in all exons of the ATP1A2 gene in 3 MA affected individuals from a large pedigree (MF14) showing linkage to this region. Investigation in this thesis continued on chromosome 1, with other genes being examined on C1q23, as well as the C1q31 region for a migraine susceptibility locus or gene. Previously in our laboratory, evidence for linkage was shown to migraine at C1q31 in one family predominantly affected with MA, with microsatellite markers in this region. The initial Cl study (above; ATP1A2 gene) has also provided evidence for linkage to the chromosome 1 locus 1q23, with evidence for excess allele sharing of markers in predominantly MA affected pedigrees. To further investigate both chromosome I loci, an investigation with six candidate genes that lie within the C1q23 and 1q31 regions through association analysis was undertaken. The results from this study reported non-significant chi-square results, showing P values greater than 0.05 across all SNPs (and a CA rpt) tested. An exception was the rs704326 SNP from exon 43 of the CACNA1E gene on C1q31. P values significantly less than 0.001 were obtained in the total migraine population and the MA subgroup, with similar frequency comparisons ascertained in both genotype and allele analysis. Examination through contingency table analysis of the CACNA1E flequency data indicated that the risk allele (A) was over-represented in the migraine group compared to the control group. Further comparison of the genotype data indicated a difference in frequency distributions (P less than 0 0001). Stratified analyses of migraine subtypes indicated that this association was specifically attributed to the MA subtype group. Odds ratios produced an OR of 4.14 with a 95% CI of 2.36 - 7.26 (P less than 0.0001). The positive association results obtained within the CACNA1E gene are interesting in the fact that FHM is considered to be a rare and severe form of migraine with aura (MA) and FHM-1 is caused by mutations contained within the calcium channel gene CACNA1A (localized at Cl9p13). The idea that FHM and specifically an FHM gene in the C1q31 genomic region may also contribute to susceptibility to the more common forms of migraine i e. migraine with aura, strongly supports and reinforces the idea that a common defective gene may be influencing both FHM and typical migraine. In conclusion, this thesis undertook a cross-disciplinary approach to genetic research of a complex disorder. The research involved linkage, association and mutation analysis strategies of migraine. This research implicated a specific variant on chromosome 1 and further supported the heterogeneic nature of migraine. Future directions into migraine research should involve further investigation of this specific variant and this genomic region. Such studies may aid in the development of more precise diagnosis and treatment methods for this complex disorder.

Migraine is a common, debilitating neurovascular disease charactensed by severe recurrent headache, nausea and vomiting, photophobia and phonophobia. It is clinically diagnosed based on criteria specified by the International Headache Society (IHS), defining two major classes of migraine: migraine with aura (MA) and migraine without aura (MO) MA sufferers experience neurovascular disturbances that precede the headache phase of an attack. Although migraine is partly influenced by environmental determinants, there is a significant genetic component, with disease heritability estimated to be up to 60% and mode of transmission multifactorial. The disorder is common with a large Dutch study reporting lifetime prevalence estimates of 33% in women and 13.3% in men, with an earlier study estimating 24% of women and 12% of men in the overall population. Mutations in various ion channel genes are responsible for neuromuscular and other neurological disorders. Inherited ion channel mutations or 'channelopathies' are increasingly found to be the cause of various neurological disorders in humans. In familial hemiplegic migraine (FHM), a rare subtype of migraine with aura, mutations in the CACNA1A gene (localised at C19p13) have been fbund (FHM1). This gene codes for the alphalA subunit of the neuronal voltage-dependent P/Q-type calcium channel. Recently a second gene, ATP1A2 (FHM2) (localised at C1q23), was implicated in some EHM families. The ATP1A2 ion channel gene, codes for the alpha2 subunit of the Na+, K+ ion ATPase pump. These findings of mutations in these genes have focused attention on central nervous system ionic channels and helped to better understand EHM pathophysiology, where the best genetic evidence providing molecular insight into migraine still comes flom the mutations detected in the rare form of migraine with aura; FHM. Migraine family studies, at the Genomic Research Centre (GRC), have utilised linkage analysis methods in providing results that have indicated suggestive linkage to the FHM1-CACNA1A region on l9p13, in a large multigenerational family (Migraine Family 1; MEl) affected with typical migraine. Also linkage studies conducted within the GRC have implicated an additional susceptibility region on chromosome 1q31, but still not ruling out a second susceptibility region on C1q23, with the possibility of there being two distinct loci, on the chromosome lq region. The focus of research in this thesis is on two main chromosomal regions, which were tested for migraine susceptibility on chromosome 1 and chromosome 19. The research involved a cross-disciplinary approach utilising association, linkage and mutation screening approaches. This research implicated a specific variant on chromosome 1 and further supported the heterogeneic nature of migraine. Future directions into migraine research should involve further investigation of this specific variant and this genomic region. Such studies may aid in the development of more precise diagnosis and treatment methods for this complex disorder.
Thesis (PhD Doctorate)
Doctor of Philosophy (PhD)
School of Medical Science
Full Text

Aims: Test the putative contribution of 17-beta-estradiol in the development of spreading depression (SD) events and head pain in awake, non-restrained rats. Main Methods: Female, Sprague-Dawley rats were intact or underwent ovariectomy followed one week later by surgery to place electrodes onto the dura to detect epidural electroencephalographic activity (dEEG). dEEG activity was recorded two days later for 12 hours after systemic administration of 17-beta-estradiol (180 mu g/kg, i.p.). A separate set of rats were observed for changes in exploratory, ambulatory, fine, and rearing behaviors; periorbital allodynia was also assessed. Key Findings: A bolus of 17-beta-estradiol significantly elevated serum estrogen levels, increased SD episodes over a 12-hour recording period and decreased rearing behaviors in ovariectomized rats. Pre-administration of ICI 182,780, an estrogen receptor antagonist, blocked 17-beta-estradiol-evoked SD events and pain behaviors; similar results were observed when the antimigraine therapeutic sumatriptan was used. Significance: These data indicate that an estrogen receptor-mediated mechanism contributes to SD events in ovariectomized rats and pain behaviors in both ovariectomized -and intact-rats. This suggests that estrogen plays a different role in each phenomenon of migraine where intense fluctuations in concentration may influence SD susceptibility. This is the first study to relate estrogen peaks to SD development and pain behaviors in awake, freely moving female rats, establishing a framework for future preclinical migraine studies.

This case is illustrative of migraine during pregnancy. In pregnancy, due to changes in the level of estrogen, migraines are often more frequent in the first trimester. The natural history for migraine, especially migraine without aura, is that 70% get better by the second trimester. A general strategy for management of migraines during pregnancy is illustrated. In general, prophylactic medications are not used during pregnancy, and migraines are treated symptomatically. Tables of the usual migraine medications to treat both the acute headache and to prevent migraine are included, along with their pregnancy classification and breast feeding safety. The chapter is meant to be a practical guide to migraine management during pregnancy and postpartum.

Migraine and its association with stroke is a topic that has received much attention due to the high prevalence of migraine and the often devastating outcomes of stroke. There is a nearly two-fold increased risk of stroke in patients with migraine. In addition, this risk is higher in younger adults, particularly women under 45 years old, and in those with increased frequency of migraine with aura attacks. This chapter seeks to explore migraine-induced stroke, migrainous infarction, as well as the risk associated with ischemic stroke in patients with migraines. Furthermore, proposed mechanisms for stroke related to migraine, such as cortical spreading depression, arterial dissection, and patent foramen ovale, will be discussed.

Background: Migraine is characterized as a strong migraine attack with aura, presenting signs and symptoms such as nausea and vomiting, and when intensified and out of control it is called complicated migraine (CM). In addition, CM causes biopsychosocial problems to the patient, causing difficulties or inability to perform functions, such as work, among others. Objectives: To analyze the number of hospitalizations for CM in northeastern Brazil from 2010 to 2020. Design and setting: Cross-sectional, descriptive and observational epidemiological study conducted in the city of São Luís (MA), Brazil. Methods: The source of the data was the Authorizations for Hospital Admission by CM, in northeastern Brazil, between January 2010 and December 2020, by the DATASUS system, using the keywords “treatment of complicated migraine”. Results: The northeast region showed a total of 12,602 hospitalizations for CM treatment, with the state of Maranhão accounting for most hospitalizations (3323). In the northeast, the year 2019 showed the highest prevalence (2260), while the year 2010 showed the lowest prevalence (517). Moreover, in the northeast region there was a total expenditure of 525,428.01 dollars on hospital services. The state of Pernambuco spent the most on hospital services for the treatment of CM (168,934.85 dollars). Conclusion: In this study, the northeastern region presented a significant increase in the cases of CM in the period studied. In addition, the state of Maranhão was the most affected by CM and the state of Pernambuco generated most of the expenses for the treatment of this pathology.

Introduction: The increased use of devices during the SARS-CoV-2 pandemic is noteworthy. The democratization of technological products caused a significant increase an its use by the population across the globe. This has caused a consistent increase in the appearance of some diseases among users of those devices. Thus, a concern arises about the student context and its high workload online during the pandemic. Objective: Analyze the association between the use of digital devices and the incidence of headache among students during the pandemic. Design and setting: A literature review was conducted on the topic. Methods: We included 15 original articles in English and Portuguese from MEDLINE, Pubmed, and Google Academic databases, selected from 2011 to 2021. Results: In cross-sectional studies, reports of headache were higher in individuals who use digital devices frequently compared to those who do not use them, and migraine attacks with aura and use of analgesics were more recurrent in the first group. Several causal mechanisms between headache and the use of digital devices have already been proposed, such as exposure to electromagnetic fields, neck posture, stress and sleep alterations without, however, having any evidence. Conclusion: We conclude that the excessive use of electronic devices can increase the incidence and duration of headache. However, the literature on the subject is still limited. Therefore, there is an urgent need for research that controls exposure to digital devices in order to analyze the causal relationship between electronic devices and headache.

A migranea hemiplegica e uma forma rara de migranea com aura que inclui fraqueza motora plenamente reversivel. Objetivo: descrever um caso de paciente portador de migranea hemiplegica ressaltando sua importancia como diagnostico diferencial no departamento de emergencia. Relato de caso: Paciente feminina, 55 anos, admitida no pronto socorro com cefaleia holocraniana associada a afasia, sem deficit motor. Historico de episodios recorrentes de cefaleia na infancia e adolescencia. Sinais vitais estaveis, exame clinico foi normal. Solicitada TC de cranio, sem alteracoes. Internada para investigacao com retorno espontaneo da fala e melhora da cefaleia no quinto dia. Retornou uma semana apos com quadro semelhante agora associado a hemiplegia a esquerda, sem alteracoes na nova TC de cranio e demais exames complementares, com melhora espontanea ao terceiro dia. Repetiu mesmo quadro 2 meses do ultimo episodio quando foi aventada hipotese diagnostica de migranea hemiplegica. Recebeu alta com topiramato e amitriptilina e encaminhada ao ambulatorio de neurologia. Discussao: a cefaleia e um dos sintomas mais frequentes nos atendimentos de pronto socorro, representando 1-4 % em unidades de emergencia. Ter em mente diagnosticos diferenciais pode ser um fator crucial para o prognostico do paciente.,