Episodic status migrainosus: A novel migraine subtype.

Objective To report a case series of a novel migraine subtype, which we term as episodic status migrainosus (ESM), characterized by attacks of migraine exclusively lasting more than 72 hours. We hypothesized that this would represent a novel nosologic entity, possibly an unstable migraine phenotype with a high conversion rate to chronic migraine (CM). Methods We conducted a retrospective review of patients diagnosed with status migrainosus at the Mayo Clinic, Rochester, between January 2005 and December 2015. All the records were then manually reviewed for patients with migraine headaches exclusively lasting more than 72 hours. Results We identified 18 patients with ESM, with a female predominance (15(83.3%)) and a median age of onset of 16.5 (IQR 13-19) years. The median monthly attack frequency was two (IQR 1-3), with each attack lasting a median duration of seven (IQR 4-12.5) days. Stress was the most commonly reported precipitant (11 (61.1%)). Migraine with aura was common (10 (55.6%)), as was comorbid depression (10 (55.6%)). Fifteen (83.3%) patients developed CM at a median of 7.8 (IQR 2.6-21.9) years from their first attack. There was no significant association between the time to the development of chronic migraine with either attack frequency or duration. Conclusions and relevance We report the existence of a novel migraine subtype, episodic status migrainosus. This migraine subtype appears to have similar clinical characteristics to episodic migraine with or without aura, except for a notably high tendency to progress to chronic migraine.

Fibromyalgia in migraine: a retrospective cohort study.

BACKGROUND: Migraine is a common and disabling disorder. Fibromyalgia has been shown to be commonly comorbid in patients with migraine and can intensify disability. The aim of this study was to determine if patients with co-morbid fibromyalgia and migraine report more depressive symptoms, have more headache related disability, or report higher intensity of headache as compared to patients with migraine only. Cases of comorbid fibromyalgia and migraine were identified using a prospectively maintained headache database at Mayo Clinic Rochester. One-hundred and fifty seven cases and 471 controls were identified using this database and the Mayo Clinic electronic medical record. FINDINGS: Depressive symptoms as assessed by PHQ-9, intensity of headache, and migraine related disability as assessed by MIDAS were primary measures used to compare migraine patients with comorbid fibromyalgia versus those without. Patients with comorbid fibromyalgia reported significantly higher PHQ-9 scores (OR 1.08, p < .0001) and headache intensity scores (OR 1.149, p = .007). There was no significant difference in migraine related disability (OR 1.002, p = .075). Patients with fibromyalgia were more likely to score in a higher category of depression severity (OR 1.467, p < .0001) and more likely to score in a higher category of migraine related disability (OR 1.23, p = .004). CONCLUSION: Patients with comorbid fibromyalgia and migraine report more depressive symptoms, higher headache intensity, and are more likely to have severe headache related disability as compared to controls without fibromyalgia. Clinicians who care for patients with migraine may consider screening for comorbid fibromyalgia particularly in patients with moderate to severe depressive symptoms, high headache intensity and/or high headache related disability. This is the first matched study to look at these characterisitcs, and it replicates previous findings from unmatched studies.

Injecting under pressure: the pain of low CSF pressure headache responsive to botulinum toxin injections.

Low intracranial pressure headaches can, at times, be refractory to treatment including multiple blood patches and preventative medications. Imaging studies are often unable to demonstrate a cerebrospinal fluid leak that is causing headache and other associated symptoms. Onabotulinum toxin A (BTX) injection is a treatment that has proven efficacy for the treatment of chronic migraine and potentially other headache disorders. We report a patient with a long standing history of refractory low pressure headaches with brain imaging that demonstrated brain sag, and no CSF leak could be identified. She received no sustained benefit from numerous blood patches, and was unresponsive or intolerant to multiple preventative medications. With BTX treatment, the patient continued to have daily headaches, but her pain intensity improved from an average 7/10 to 3/10. This benefit has been sustained over 7 years. This case suggests that BTX may be an effective treatment for headaches due to low intracranial pressure. It also suggests that the beneficial effects of BTX in the treatment of headaches occur through a direct modulation of the nociceptive system rather than merely induction of pericranial muscle relaxation.

Our evolving understanding of migraine with aura.

Migraine aura consists of fully reversible focal neurologic symptoms that may precede or coexist with headache in a significant minority of migraine patients. Typical aura symptoms include visual, sensory, and language disturbances. The most recent International Classification of Headache Disorders, 3rd edition (beta version) has added other aura types such as brainstem localizing symptoms, lateralizing weakness, and monocular visual loss. Currently available data from animal models and functional neuroimaging in humans implicate cortical spreading depression (CSD) as the phenomenon underlying migraine aura. Ongoing study suggests that susceptibility to migraine aura and CSD may be genetically mediated. CSD appears to be a potential target for future development of migraine-specific preventive therapies.

Triggerless neuralgic otalgia: a case series and systematic literature review.

BACKGROUND: Isolated neuralgic pain in the deep ear may arise from either nervus intermedius (NIN) or glossopharyngeal (GPN) neuralgias. Current International Headache Society (IHS) International Classification of Headache Disorders, second edition (ICHD-2) criteria for these cranial neuralgias require the presence of a characteristic trigger. AIM: The aim of this article is to report cases of triggerless neuralgic otalgia to better understand a subset of patients for whom there may be diagnostic uncertainty. METHODS: Methods included an observational cohort series and systematic literature review. RESULTS: We identified five female patients with a median age at symptom onset of 58 (range: 47 to 73). Our patients generally experienced an excellent clinical response to carbamazepine. Patients were contacted by telephone at a median follow-up duration of seven years (range: four to 32) from symptom onset, at which time carbamazepine-free remissions were reported by five of five (100%) of the patients. A systematic review of the literature on neuralgic otalgia led us to conclude that NIN was most common among young women (age < 50), and GPN across a wider range of ages of either gender. Among surgically validated cases reported in the literature, triggers were frequently absent in NIN, and variably noted in GPN. CONCLUSIONS: We conclude that the presence of a trigger is not fundamental, and may be impractical, to the diagnosis of neuralgic otalgia, but remains important for specificity between NIN and GPN.

Human studies in the pathophysiology of migraine: genetics and functional neuroimaging.

The expansion of technologies available for the study of migraine pathophysiology has evolved greatly over the last 15 years. Two areas of rapid progress are investigations focusing on the genetics of migraine and others utilizing novel functional neuroimaging techniques. Genetic studies are increasingly focusing on sporadic migraine and the utilization of unbiased searches of the human genome to identify novel variants associated with disease susceptibility. At the same time, neuroimaging studies have provided novel insights into the altered neuronal and network dynamics of the migrainous brain. These 2 parallel approaches provide complementary insights into the complexity and heterogeneity of migraine.

Longitudinal associations of migraine and depressive symptoms: a cohort analysis.

BACKGROUND: While the association between migraine and depression has been well established, there is very little information as to whether effective prophylactic treatment of migraine correlates with improvement in comorbid depression. METHODS: We analyzed initial visit data from migraine headache patients (n = 961) in the Mayo Headache Registry along with follow-up data (n = 389) from a subset of this cohort. Depressive symptoms were measured utilizing the Beck Depression Inventory II (BDI-II). RESULTS: We found a correlation between BDI-II and migraine frequency for 4 weeks and 3 months prior to the initial visit (Spearman correlation coefficient ρ = 0.335 and 0.349, respectively; p value < 0.0001 for both). There was a similar albeit weaker correlation between BDI-II vs. migraine intensity over the same periods prior to initial consultation (ρ = 0.147 and 0.170, respectively; p value < 0.0001 for both). However, there was not a significant difference in BDI-II scores for subjects with aura vs. without aura (p value = 0.12). Among those with follow-up, improvement in BDI-II correlated with a reduction in migraine frequency and intensity (p value = 0.016 and 0.089, respectively). Differences in the degree of improvement of BDI-II score in patients treated with amitriptyline vs. topiramate could not be detected (p = 0.36). CONCLUSIONS: BDI-II score was associated with migraine measures but not with the presence of aura at time of clinical presentation. Over follow-up time, an improvement in depression score was correlated with a reduction in migraine frequency, but was not significantly associated with medication type.

15th International Headache Congress: basic science highlights.

The 15th Congress of the International Headache Society was held in Berlin from June 23rd to 26th of 2011. Interesting new data from several areas of the basic sciences of headache were presented. This is a review of some of the most exciting platform and poster presentations of the meeting. Research addressing 3 general areas of interest is presented in this review: pathophysiology, pharmacology, and genetics.

Numbness matters: a clinical review of trigeminal neuropathy.

AIM: Trigeminal neuropathies are a group of clinical disorders that involve injury to primary first-order neurons within the trigeminal nerve. We review the spectrum of etiologies underlying both painful and non-painful trigeminal neuropathies, with attention to particularly dangerous processes that may elude the clinician in the absence of a meticulous evaluation. Complications and management issues specific to patients with trigeminal neuropathy are discussed. METHODS: Retrospective literature review. RESULTS: Facial or intraoral numbness, the hallmark of trigeminal neuropathy, may represent the earliest symptomology of malignancy or autoimmune connective tissue disease as sensory neurons are destroyed. Such numbness, especially if progressive, necessitates periodic evaluation and vigilance even years after presentation if no diagnosis can be made. CONCLUSIONS: In the routine evaluation of patients with facial pain, the clinician will inevitably be confronted with secondary pathology of the trigeminal nerves and nuclei. The appearance of numbness, even when pain continues to be the most pressing complaint, necessitates clinical assessment of the integrity of all aspects of the trigeminal pathways, which may also include neurophysiologic, radiographic, and laboratory evaluation.

Primary headache syndromes in systemic mastocytosis.

AIM: To investigate the relationship between clinical mast cell activity and primary headache syndromes. METHODS: We surveyed individuals with systemic mastocytosis, an uncommon disorder associated with increased mast cell activity. Diagnoses of primary headache syndromes in addition to the relationship of headache and symptoms of mastocytosis were ascertained. RESULTS: A response rate of 64/148 (43.2%) was achieved. Headache diagnoses in our respondents (n = 64) were largely migraine (37.5%) and tension-type headaches (17.2%). Typical aura with and without migraine headache was highly represented in our patient population (n = 25, 39%). Three individuals met criteria for primary cough headache (4.7%). Symptoms reflective of mast cell activity were significantly greater in individuals reporting headaches. Patients experiencing headache concurrently with mastocytosis flairs were more likely to be male (p = 0.002), have histaminergic symptoms, such as itching (p = 0.02) and runny nose (p = 0.03), and have unilateral cranial autonomic features (p = 0.04). However, using standardized International Headache Society criteria, we did not identify individuals with cluster headache or other trigeminal autonomic cephalalgias in this population. CONCLUSIONS: Our observational survey-based data supports a clinical relationship between mast cell activity and primary headache syndromes. Generalizability of our results is limited by the low response rate and possible tertiary referral bias.

Pathophysiology of migraine.

Our understanding of migraine pathophysiology is a work in progress. As more is learned about migraine, it seems that the probability of identifying a single unifying explanation for this common disorder becomes less and less. Although the neuroanatomy and elements of pain physiology underlying migraine attacks are probably shared pathophysiologic elements, the emerging complexity of migraine genetics suggests that the acute attack may be the final common expression of more than one type of initiating abnormality. After a brief summary of the neuroanatomic structures involved in the generation of migraine attacks and the traditional theories of migraine, the author focuses on the current understanding of migraine genetics and reviews recent data from the neuroimaging and the neurophysiology of migraine.

Migraine update. Diagnosis and treatment.

Migraine is a common intermittently debilitating neurovascular disorder that affects younger adults, especially women. The diagnosis is generally made based on clinical criteria, with neuroimaging used in some cases to exclude secondary causes of headache. This article reviews current understanding of the mechanisms underlying migraine and approaches to treating it.

How well do headache patients remember? A comparison of self-report measures of headache frequency and severity in patients with migraine.

OBJECTIVE: To compare patient recall of migraine headache frequency and severity over 4 weeks prior to a return visit as reported in an interval questionnaire vs a daily diary. BACKGROUND: Many therapeutic decisions in the management of migraine patients are based on patient recall of response to treatment. As consistent completion of a daily headache diary is problematic, we have assessed the reliability of patient recall in a 1-time questionnaire. METHODS: Headache frequency and average severity (0 to 3-point scale) were reported in an interval questionnaire by 209 patients who had also maintained a daily diary over the same 4-week period. RESULTS: Headache frequency over the previous 4 weeks as reported in interval questionnaires (14.7) was not different from that documented in diaries (15.1), P = .056. However, reported average headache severity on a 0 to 3 scale as reported in the questionnaire (1.84) was worse than that documented in the diaries (1.63), P < .001. CONCLUSIONS: In the management of individual patients, the daily diary is still preferable when available. Aggregate assessment of headache frequency in groups of patients based on recall of the prior 4 weeks is equally as reliable as a diary. Headache severity reported in questionnaires tends to be greater than that documented in daily diaries and may be less reliable.

Transient Neurologic Dysfunction in Migraine.

Transient disturbances in neurologic function are disturbing features of migraine attacks. Aura types include binocular visual, hemi-sensory, language and unilateral motor symptoms. Because of the gradual spreading quality of visual and sensory symptoms, they were thought to arise from the cerebral cortex. Motor symptoms previously included as a type of migraine aura were reclassified as a component of hemiplegic migraine. ICHD-3 criteria of the International Headache Society, added brainstem aura and retinal aura as separate subtypes. The susceptibility to all types of aura is likely to be included by complex and perhaps epigenetic factors.

Functional imaging in primary headache disorders.

Over the past two decades, the development of new functional neuroimaging techniques has improved our understanding of the brain events underlying several primary headache disorders. In migraine and cluster headache, the advent of these techniques has shifted the emphasis in pathophysiological research away from the vessel and back to the brain.

The neurogenic basis of migraine.

There is accumulating evidence of a neurogenic basis of migraine. This evidence arises from both the clinical and experimental domains. Many of the well known clinical features of migraine attacks including the prodrome are not explained by changes in vascular caliber. Despite the fact that ergotamines and triptans are vasoactive does not provide substantive proof that vasoconstriction is their most important mechanism of action. Several effective treatments for migraine, both old and new, do not affect vascular caliber. Experimental evidence from investigation of both the aura and headache phases of migraine clearly supports a neural basis of migraine. All genes thus far conclusively associated with hemiplegic migraine code for neural proteins.