Rozen, Todd D.

Objective To summarize the current literature on non‐steroidal anti‐inflammatory drug and corticosteroid use during the coronavirus disease 2019 (COVID‐19) pandemic, recognizing that these are commonly used treatments in the field of headache medicine. Background The use of non‐steroidal anti‐inflammatory drugs and corticosteroids in patients during the COVID‐19 pandemic has been a controversial topic within the medical community and international and national health organizations. Lay press and social media outlets have circulated opinions on this topic despite the fact that the evidence for or against the use of these medications is sparse. In the field of headache medicine, these medications are used commonly and both patients and clinicians may have questions or hesitations pertaining to their use during the COVID‐19 pandemic. Methods A detailed search of the scientific and popular literature was performed. Results There is limited literature pertaining to the safety of non‐steroidal anti‐inflammatory drugs and corticosteroids during the COVID‐19 pandemic. To date, there are no clear scientific data that preclude the use of non‐steroidal anti‐inflammatory drugs in the general population who may acquire COVID‐19 or in those acutely infected with the virus. Several health organizations have concluded that treatment with corticosteroids during active infection should be avoided due to concerns of prolonged viral shedding in the respiratory tract and the lack of survival benefit based on the data from past coronaviruses and influenza virus; specific exceptions exist including treatment for underlying asthma or chronic obstructive pulmonary disease, septic shock, and acute respiratory distress syndrome. Conclusion Scientific information regarding the COVID‐19 pandemic is constantly evolving, and limited or contradictory information can lead to confusion for both patients and clinicians. It is recommended that prior to prescribing non‐steroidal anti‐inflammatory drugs and steroids for the treatment of headache, clinicians have open discussions with their patients about the potential risks and benefits of using these medications during the COVID‐19 pandemic. This manuscript summarizes the currently available evidence and understanding about these risks and benefits to help clinicians navigate such discussions.

Objectives: Cerebral autosomal-dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is inherited microangiopathy characterized by recurrent subcortical infarcts. A majority of those with CADASIL report coexistent migraine with aura. The authors aim to quantitatively describe migraine-related disability within a CADASIL cohort. Methods: A cross-sectional analysis was performed in a cohort of CADASIL. The Migraine Disability Assessment (MIDAS) quantified migraine-related disability. Further metrics obtained include first and last migraine, aura semiology, and therapeutic measures. Results: Twenty-four individuals were included [63% (15/24) female individuals; mean age, 56 y; range, 34 to 81 y]. Fifty-four percent (13/24) reported migraine, whereas 46% (11/24) reporting varying degrees of migraine-related disability. MIDAS Questionnaire scores appeared bimodal: 58% (14/24) scored 0 to 5, 7% (1/24) scored 6 to 10, 7% (1/24) scored 11 to 20 and 33% (8/24) scored over 20. Severe disability was associated with the multiplicity of aura semiologies and poor response to pharmacologic prophylaxis. Conclusions: A bimodal distribution of migraine-related disability was observed. A third of individuals had a severe disability and appeared medically refractory to medical migraine prophylactic measures. This study may serve as a reference point for future trials quantitatively gauging response of novel migraine treatment strategies within this unique population.

Objective To describe three new cases of the headache syndrome of long-lasting autonomic symptoms with hemicrania (LASH), and to establish a clinical phenotype utilizing all LASH cases noted in the medical literature. Methods A case series of patients was evaluated in an academic headache clinic over a two-year time period. LASH syndrome was defined by episodic headache attacks with associated cranial autonomic symptoms that start before headache onset, last the entire duration of the headache and continue on for a period of time after the headache ceases. Results Three patients were noted to have LASH syndrome in a two-year time period (2017–2018). One patient was diagnosed with primary LASH, while two others had probable secondary LASH from a secretory pituitary tumor. The primary LASH patient was female. She had on average one headache per week lasting 1–3 days in duration. She experienced migrainous associated symptoms along with their cranial autonomic symptoms. She also developed a fixed Horner's syndrome along with a typical headache attack, which was present for 6 months at the time of consultation. She had complete headache relief with indomethacin and her miosis and ptosis also resolved with treatment. Secondary LASH was diagnosed in two patients (one male, one female) both with prolactin secreting pituitary microadenomas. One of the patients had his headaches abolish with dopamine agonist therapy while the other patient did not respond to hormonal modulation but became pain free on indomethacin. Secondary LASH patients had less frequent headache episodes and lacked any migrainous associated features, but exhibited agitation with headache. Conclusion LASH syndrome may be rare, but more reported cases are entering the headache literature. The temporal profile of onset and offset of cranial autonomic symptoms is key to making the diagnosis. Primary and secondary LASH may present differently based on gender predominance, the presence of migrainous associated features, and attack frequency. Secondary LASH appears to be indomethacin responsive, suggesting that medication effectiveness should not obviate the need to do testing for secondary etiologies.

Objective To describe 3 new cases of new daily persistent headache (NDPH) starting as a single thunderclap headache. Background NDPH is a form of chronic daily headache that is unique in its temporal profile of onset. Distinct subtypes of NDPH are being described with specific efficacious treatments. A single case of NDPH starting as a single thunderclap headache has been previously reported but no further cases have been documented in the literature. New cases need to be published to better define the syndrome. Methods To report a case series of patients diagnosed with this unique NDPH subtype at an academic headache center from 2016 to 2018. Results Three new cases of NDPH starting as a single thunderclap headache at onset were diagnosed. All patients were female with an average age of onset of 46 years. All presented with neurologic symptoms/stroke‐like spells at headache onset. No defined triggering events were noted in any of the patients. There is a possible seasonal predilection to develop the syndrome around the fall clock change to the winter solstice. Neuroimaging was normal in the case patients. All patients rapidly responded to nimodipine. The duration of headache prior to nimodipine therapy ranged from 3 months to 4 years. Conclusion This NDPH subtype appears to be rare. The key to diagnosis is asking about the temporal profile of the onset of the first ever NDPH headache. None of the case patients had been asked about the initial headache and its pattern of onset. Nimodipine seems to be very effective in treating this NDPH subtype. This syndrome is most likely precipitated by persistent or intermittent cerebral artery vasospasm. It is possibly a subform of the reversible cerebral vasoconstriction syndrome.

Background Optimism and pessimism are related to several mental health and brain disorders, are significant predictors of physical and psychological health outcomes, and implicated as psychosocial determinants of the pain experience. Despite this promising evidence, limited information is available on optimism and pessimism in headache disorders. Objective To evaluate the influence of optimism and pessimism in meeting criteria for migraine and related disability in a population‐based sample. Methods This is an observational, cross‐sectional study. The sample population was selected through a stratified, multi‐stage area probability sample of households, as used by the last Brazilian Census. A validated questionnaire eliciting data on demographics, headache features, migraine‐related disability, depression (PHQ‐9), anxiety (GAD‐7), optimism, and pessimism (life orientation test – revised) was administered to people with migraine and headache‐free control participants from the general population in São Paulo, Brazil via trained interviewers. Six hundred individuals were contacted. The odds for having migraine/no headache diagnosis were calculated by binary logistic regression, and ordinal regression was performed to check associations between migraine‐related disability and optimism. Results A total of 302 individuals (mean ± SD age: 39.7 ± 12.7; BMI: 26.5 ± 5.9) met inclusion criteria and were included, 140 controls (with no history of headache disorders) and 162 people meeting criteria for migraine (29 with chronic migraine, that is, 15 or more headache days/month). People with migraine were less optimistic and more pessimistic than controls, and endorsed higher levels of anxious and depressive symptoms. Pessimism (OR 95% CI = 1.16 [1.05–1.28], P = .005) and anxiety (OR 95% CI = 1.19 [1.10–1.29], P < .001) were predictors of meeting criteria for migraine, while optimism (β 95% CI = −0.915 [−1.643, −0.188], P = .01) was inversely associated with migraine‐related disability. Conclusions Optimism and pessimism are associated with migraine and migraine‐related disability. These concepts should be further explored in people with migraine with regard to their potential influences on clinical research outcomes and treatments.

Objective To describe a new subtype of new daily persistent headache that is triggered by a single Valsalva event. Methods A case series of patients was evaluated in an academic headache clinic over a 3-year time period. Results A total of seven patients (four female and three male) were diagnosed with this new subtype of new daily persistent headache. The headaches all began after a single Valsalva event. Average age at time of headache onset was 41 years (males: 39 years; females: 43 years) with an age range of 20–62 years. All patients developed their syndrome during the months of September to February with November and February being the most cited months (5/7 patients). Immediate worsening in the Trendelenburg position occurred in all patients and appeared to be an almost diagnostic test for the syndrome. No patient had papilledema on funduscopic exam. Five out of seven patients had no prior headache history including cough, exercise or migraine. Four of seven patients were of normal weight, while one was overweight and two were obese. A crowded posterior fossa was identified in five of seven patients on brain MRI. On cerebrospinal fluid pressure/volume lowering medication (acetazolamide, indomethacin and/or spironolactone), five out of seven patients achieved 90% plus improvement in headache frequency while three patients became pain free. Three patients were able to taper off medication without headache recurrence. Conclusion New daily persistent headache after a single Valsalva event appears to be a unique subtype of new daily persistent headache that is responsive to cerebrospinal fluid pressure/volume lowering medications. An abnormal reset of cerebrospinal fluid pressure/intracranial pressure to an elevated state is the presumed pathogenesis and may relate to the patient's baseline neuroanatomy of a crowded posterior fossa. There appears to be a circadian periodicity to the onset of the syndrome. Worsening in the Trendelenburg position is a probable diagnostic test. Defining new daily persistent headache subtypes by triggering event appears to be making a positive inroad in the understanding of this condition and helps present new effective therapies.

Objective To determine the efficacy of high‐volume anesthetic suboccipital nerve blocks (HVSON) for chronic cluster headache (CCH) and to define consistency of response over long‐term use. Background There are studies showing efficacy of greater occipital and suboccipital nerve block injections for CCH and also their possible use as a preventive treatment modality. There are scant data about the long‐term efficacy of repetitive greater occipital and suboccipital nerve injections in CCH. HVSON has not been studied for CH. Methods This was an open label, observational, case series study. Patients with CCH seen at a dedicated headache clinic over a 7‐year time period and injected on at least 2 separate occasions were used for analysis. All were deemed medicinal treatment refractory. HVSON consisted of 9 mL 1% lidocaine and 1 mL triamcinolone 40 mg/mL injected on the side of CH. Results Ten CCH patients were retrospectively studied. Range of mean average response to HVSON (all patients had complete pain freedom) was 1.5–31 weeks (longest: 44 weeks in 2 patients). Only one patient did not respond; 2 patients had 1.5–2 weeks of response; the remainder had at least 4 weeks of response. The mean average duration of effect was 10.3 weeks in the responders. Five patients were injected serially for 2–4 years (30x, 17x, 15x, 10x and 3x, respectively) with a consistent response of 6 weeks, 4 weeks, 12 weeks, 4 weeks, and 31 weeks, respectively, after each injection. Response duration was very reliable per individual patient. All 5 patients felt HVSON was effective as a preventive treatment. Smoking history did not appear to alter treatment response (8/10 were chronic current smokers and 7/8 responded to HVSON). The one patient who received the most injections developed avascular necrosis of the hip; the remainder of the subjects had no adverse events. Conclusion HVSON from this open label study appears to be effective in the preventive treatment of medicinal refractory CCH and shows consistent response over long‐term use with high rates of pain freedom.

Introduction To propose a hypothesis theory to establish a linkage between cigarette smoking and cluster headache pathogenesis. Background Cluster headache is a primary headache syndrome grouped under the trigeminal autonomic cephalalgias. What distinguishes cluster headache from all other primary headache conditions is its inherent connection to cigarette smoking. It is undeniable that tobacco exposure is in some manner related to cluster headache. The connection to tobacco exposure for cluster headache is so strong that even if an individual sufferer never smoked, then that individual typically had significant secondary smoke exposure as a child from parental smoking behavior and in many instances both scenarios exist. The manner by which cigarette smoking is connected to cluster headache pathogenesis is unknown at present. If this could be determined this may contribute to advancing our understanding of cluster headache pathophysiology. Methods/results Hypothesis statement. Conclusion The hypothesis theory will include several principles: (1) the need of double lifetime tobacco exposure, (2) that cadmium is possibly the primary agent in cigarette smoke that leads to hypothalamic‐pituitary‐gonadal axis toxicity promoting cluster headache, (3) that the estrogenization of the brain and its specific sexually dimorphic nuclei is necessary to develop cluster headache with tobacco exposure, and (4) that the chronic effects of smoking and its toxic metabolites including cadmium and nicotine on the cortex are contributing to the morphometric and orexin alterations that have been previously attributed to the primary headache disorder itself.

Objective To present results from the United States Cluster Headache Survey comparing the clinical presentation of tobacco nonexposed and tobacco‐exposed cluster headache patients. Background Cluster headache is uniquely tied to a personal history of tobacco usage/cigarette smoking and, if the individual cluster headache sufferer did not smoke, it has been shown that their parent(s) typically did and that individual had significant secondary smoke exposure as a child. The true nontobacco exposed (no personal or secondary exposure) cluster headache sufferer has never been fully studied. Methods The United States Cluster Headache Survey consisted of 187 multiple choice questions related to cluster headache including: patient demographics, clinical headache characteristics, family history, triggers, smoking history (personal and secondary), and headache‐related disability. The survey was placed on a website from October through December 2008. Results One thousand one hundred thirty‐four individuals completed the survey. One hundred thirty‐three subjects or 12% of the surveyed population had no personal smoking/tobacco use history and no secondary smoke exposure as an infant/child, thus a nontobacco exposed population. In the nonexposed population, there were 87 males and 46 females with a gender ratio of 1.9:1. Episodic cluster headache occurred in 80% of nonexposed subjects. One thousand and one survey responders or 88% were tobacco‐exposed (729 males and 272 females) with a gender ratio of 2.7:1. Eighty‐three percent had a personal smoking history, while only 17% just had parents who smoked with secondary smoke exposure. Eighty‐five percent of smokers had double exposure with a personal smoking history and secondary exposure as a child. Significant highlights from the survey Nonexposed cluster headache subjects are significantly more likely to develop cluster headache at ages 40 years and younger, while the exposed sufferers are significantly more likely to develop cluster headache at 40 years of age and older. Nonexposed patients have a statistically significant higher frequency of a migraine family history. The exposed population is statistically significantly more likely to have a history of head trauma 19% vs the nonexposed population 10% ( P = .02). Tobacco exposed are significantly more likely to transition from episodic to chronic cluster headache (23% vs 14%, P = .02). Cranial autonomic symptoms as well as agitation are more common in tobacco exposed. Nonexposed are less likely to have specific cluster headache triggers. Exposed are significantly more likely to be triggered by alcohol. Tobacco exposed are significantly heavier caffeine users than nonexposed. Nonexposed are significantly more likely to have cluster headache cycles that vary throughout the year than exposed (52% vs 40%, P = .02). Exposed are much more likely to develop cluster headache from 12 am to 6 am than non exposed. Exposed experience significantly more frequent attacks per day and longer duration cycles than nonexposed. A significantly larger percent of the exposed population (57%) has suicidal ideations with their syndrome than nonexposed (43%) ( P = .003). In regard to disability, both subtypes are disabled by their headaches, but exposed have more work related disability and lost home‐days from headache. Both subgroups have a poor overall response to preventive and abortive medication outside of inhaled oxygen and injectable sumatriptan. Conclusion Cluster headache sufferers who were never exposed to tobacco (personal or secondary as a child) appear to present uniquely compared to the tobacco exposed subgroup. The tobacco exposed clinical phenotype appears to have a more severe syndrome based on attack frequency, cycle duration, and headache related disability. Tobacco exposure is associated with cluster headache chronification. The nonexposed subtype appears to have an earlier age of onset, higher rate of familial migraine, and less circadian periodicity and daytime entrainment, suggesting a possible different underlying pathology than in the tobacco exposed sub‐form.