Onabotulinumtoxina (craniotomy scar combined with cranial suture line injections) for persistent post craniotomy headache: Case series with long-term follow-up.

BACKGROUND: There is no defined preventive treatment protocol for persistent post-craniotomy headache. In several small case series and individual case reports onabotulinumtoxinA injected into the craniotomy scar has shown possible efficacy. What is lacking is long term follow-up and if focusing on the cranial suture lines along with the craniotomy scar can enhance improvement and provide more sustained benefit. METHODS: Retrospective chart review with case series. RESULTS: Four patients (three women, one man) with ICHD-3 defined persistent post craniotomy headache were treated using a novel onabotulinumtoxinA injection protocol. All the patients presented with continuous head pain of moderate to severe intensity. All had severe allodynia on the side of their craniotomy. All had significant reduction in quality of life. Our application of onabotulinumtoxinA involved injection into both the surgical scar and the transected/irritated cranial suture lines noted on neuroimaging and physical examination. With treatment all patients demonstrated significant benefit including a reduction in daily pain intensity (75%-100%), developing periods of pain freedom (2-7 days per week) and having a dramatic improvement in quality of life (close to 100% in all). The benefit was sustained for at least five years of follow-up. CONCLUSION: From our case series it appears that injection not only along the painful craniotomy scar but into the involved cranial suture lines provides positive efficacy and sustained improvement in patients with persistent post craniotomy headache.

Cigarette smoking history (personal and secondary childhood exposure) in non-cluster headache trigeminal autonomic cephalalgias: A clinic based study.

OBJECTIVE: To look at cigarette smoking history (personal and secondary exposure as a child) in non-cluster headache trigeminal autonomic cephalalgias seen at a headache clinic and to determine smoking exposure prevalence utilizing previously published data. METHODS: Retrospective chart review and PubMed/Google Scholar search. RESULTS: Forty-eight clinic patients met ICHD-3 criteria for non-cluster headache trigeminal autonomic cephalalgias. Four had paroxysmal hemicrania, 75% were smokers and secondary exposure was noted in all. 16 patients had short lasting unilateral neuralgiform headache attacks with conjunctival injection and tearing (SUNCT) or short lasting unilateral neuralgiform headache attacks with autonomic symptoms (SUNA), 12.5% were smokers and secondary exposure was noted in 91%. Twenty-eight patients had hemicrania continua, 21% were smokers and secondary exposure was found in 62.5%.Since 1974 there have been 88 paroxysmal hemicrania, 50 SUNCT or SUNA and 89 hemicrania continua patients with a documented smoking exposure history. From current data and previous studies, a smoking history was noted in 60% paroxysmal hemicrania, 18% SUNCT and SUNA and 21% hemicrania continua patients. CONCLUSION: A cigarette smoking history appears to be connected to paroxysmal hemicrania (personal and secondary exposure) and possibly to SUNCT/SUNA (secondary) and hemicrania continua (secondary).

Update in the understanding of new daily persistent headache.

Background Accumulating evidence suggests various specific triggers may lead to new daily persistent headache (NDPH)-like presentations, suggesting that new daily persistent headache is a heterogenous syndrome, and challenging the concept that new daily persistent headache is a primary headache disorder.Method We searched the PubMed database up to August 2022 for keywords including persistent daily headache with both primary and secondary etiologies. We summarized the literature and provided a narrative review of the clinical presentation, diagnostic work-ups, possible pathophysiology, treatment response, and clinical outcomes.Results and conclusion New daily persistent headache is a controversial but clinically important topic. New daily persistent headache is likely not a single entity but a syndrome with different etiologies. The issue with past studies of new daily persistent headache is that patients with different etiologies/subtypes were pooled together. Different studies may investigate distinct subsets of patients, which renders the inter-study comparison, both positive and negative results, difficult. The identification (and removal) of a specific trigger might provide the opportunity for clinical improvement in certain patients, even when the disease has lasted for months or years. Nonetheless, if there is a specific trigger, it remains unknown or unidentified for a great proportion of the patients. We need to continue to study this unique headache population to better understand underlying pathogenesis and, most importantly, to establish effective treatment strategies that hopefully resolve the continuous cycle of pain.

Reversible cerebral vasoconstriction syndrome developing after an erenumab injection for migraine prevention.

BACKGROUND: Reversible cerebral vasoconstriction syndrome is normally triggered by vasoactive compounds or illicit drugs. A new type of migraine preventive medication blocks calcitonin gene-related peptide utilizing monoclonal antibodies. Calcitonin gene-related peptide is a potent vasodilator for the cerebrovascular system. Could blocking calcitonin gene-related peptide be a trigger for cerebral artery vasospasm in patients susceptible to developing reversible cerebral vasoconstriction syndrome (migraine patients) or in individuals using vasoactive compounds? We present a case of reversible cerebral vasoconstriction syndrome occurring after calcitonin gene-related peptide monoclonal antibody treatment. CASE REPORT: A 43-year -old woman with a history of episodic migraine developed an acute headache with orgasm two days after taking her second injection of erenumab. Ten days after erenumab injection she developed a thunderclap headache while completing a high intensity workout. These new headaches were only left sided. Computed tomography angiography demonstrated mild to moderate areas of narrowing involving the left middle and anterior cerebral arteries, concerning for reversible cerebral vasoconstriction syndrome. She denied exposure to any known reversible cerebral vasoconstriction syndrome precipitant medication or illicit drugs. She did endorse recent exposure to high altitude prior to erenumab therapy. She was started on verapamil 40 mg three times per day and her headache ceased within 24 h of initiating treatment. A repeat CT angiogram completed 4 weeks after the initial study noted resolution of the areas of vessel stenosis. CONCLUSION: A case of reversible cerebral vasoconstriction syndrome developing after treatment with a calcitonin gene-related peptide monoclonal antibody is presented. The timing of the new type of headache occurring 2 days post erenumab injection suggests a possible cause and effect relationship. Reversible cerebral vasoconstriction syndrome as a possible treatment-related complication to the usage of calcitonin gene-related peptide monoclonal antibodies needs to be studied further.

A Case-Control Study of Peripartum Cardiomyopathy Using the Rochester Epidemiology Project.

BACKGROUND: The incidence of peripartum cardiomyopathy (PPCM) is known through referral center databases that may be affected by referral, misclassification, and other biases. We sought to determine the community-based incidence and natural history of PPCM using the Rochester Epidemiology Project. METHODS AND RESULTS: Incident cases of PPCM occurring between January 1, 1970, and December 31, 2014, were identified in Olmsted County, Minnesota. A total of 15 PPCM cases were confirmed yielding an incidence of 20.3 cases per 100,000 live births in Olmsted County, Minnesota. Clinical information, disease characteristics, and outcomes were extracted from medical records in a 27-county region of the Rochester Epidemiology Project including Olmsted County and matched in a 1:2 ratio with pregnant women without PPCM. A total of 48 women were identified with PPCM in the expanded 27-county region. There was 1 death and no transplants over a median of 7.3 years of follow-up. Six of the 23 women with subsequent pregnancies developed recurrent PPCM, all of whom recovered. Migraine and anxiety were identified as novel possible risk factors for PPCM. CONCLUSIONS: The population-based incidence of PPCM was 20.3 cases per 100,000 live births in Olmsted County, Minnesota. Cardiovascular outcomes were generally excellent in this community cohort.

Daily persistent headache after a viral illness during a worldwide pandemic may not be a new occurrence: Lessons from the 1890 Russian/Asiatic flu.

New daily persistent headache was first documented in the medical literature in the 1980s. The leading trigger is a viral illness. As we navigate our way thru the current SARS-CoV-2 pandemic, looking back at past viral epidemics may help guide us for what to expect in the near future in regard to headaches as a persistent manifestation of the SARS-CoV-2 infection. The 1890 viral pandemic known as the "Russian or Asiatic flu", has extensive documentation about the neurologic sequelae that presented months to years after the pandemic ended. One of the complications was daily persistent headache. There are actually many similarities between the viral presentation of the 1890 pandemic and the current SARS-CoV-2 pandemic, which may then suggest that not only will NDPH be part of the neurological sequelae but a possible key consequence of the SARS-CoV-2 infection.

COVID-19 and Headache Medicine: A Narrative Review of Non-Steroidal Anti-Inflammatory Drug (NSAID) and Corticosteroid Use.

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.

New daily persistent headache (NDPH) triggered by a single Valsalva event: A case series.

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.

LASH syndrome: New cases with a broadening clinical phenotype.

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.

A sleep modulated Channelopathy: a novel CACNA1A pathogenic variant identified in episodic Ataxia type 2 and a potential link to sleep alleviated migraine.

BACKGROUND: To describe a patient with sleep alleviated episodic ataxia type 2 with a novel CACNA1A pathogenic variant and provide a possible link to sleep responsive migraine. CASE PRESENTATION: A 26-year-old woman with recurrent attacks of dizziness, nausea, vomiting, ataxia and dysarthria presented for a possible diagnosis of vestibular migraine. Unique to her attacks was if she could fall asleep for as little as 15 min the spells would subside. If however she remained awake the attacks would continue unabated. A presumed diagnosis of episodic ataxia type 2 was made and she became attack free on acetazolamide without recurrence. Genetic testing demonstrated a novel pathogenic variant in CACNA1A on chromosome 19. This pathogenic variant has not been previously reported in the literature and is suggested to truncate the CACNA1A polypeptide by introducing a premature stop codon. CONCLUSION: A case of episodic ataxia type 2 with a novel pathogenic variant in CACNA1A is described. Interestingly, the patient's symptoms would completely alleviate with sleep which suggests a sleep modulated channelopathy. The mechanisms by which sleep could potentially alter this pathogenic variant are hypothesized. A potential link to sleep alleviated migraine is suggested. Further study of this novel pathogenic variant may help us understand not only how sleep can modulate episodic ataxia type 2, but also migraine.

High-Volume Anesthetic Suboccipital Nerve Blocks for Treatment Refractory Chronic Cluster Headache With Long-Term Efficacy Data: An Observational Case Series Study.

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.

An RCVS Spectrum Disorder? New Daily Persistent Headache Starting as a Single Thunderclap Headache (3 New Cases).

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.

Optimism, Pessimism, and Migraine: A Cross-Sectional, Population-Based Study.

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 (ß 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.

Linking Cigarette Smoking/Tobacco Exposure and Cluster Headache: A Pathogenesis Theory.

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.

Cluster Headache Clinical Phenotypes: Tobacco Nonexposed (Never Smoker and No Parental Secondary Smoke Exposure as a Child) versus Tobacco-Exposed: Results from the United States Cluster Headache Survey.

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.

Anticipation in a family with primary familial brain calcification caused by an SLC20A2 variant.

AIM OF THE STUDY: To describe a family with primary familial brain calcification (PFBC) due to SLC20A2 variant showing possible genetic anticipation. MATERIALS AND METHODS: We conducted historical, genealogical, clinical, and radiologic studies of a family with PFBC. Clinical evaluations including neurological examination and head computed tomography (CT) scans of a proband and her father were performed. They provided additional information regarding other family members. To identify a causative gene variant, we performed whole-exome sequencing for the proband followed by segregation analysis in other affected members using direct sequencing. RESULTS: In this family, nine affected members were identified over four generations. The proband suffered from chronic daily headache including thunderclap headache. We identified an SLC20A2 (c.509delT, p.(Leu170*)) variant in three affected members over three generations. Interestingly, the age of onset became younger as the disease passed through successive generations, suggestive of genetic anticipation. CONCLUSIONS AND CLINICAL IMPLICATIONS: For clinical purpose, it is important to consider thunderclap headache and genetic anticipation in PFBC caused by SLC20A2 variants. Further investigation is required to validate our observation.

New daily persistent headache: A lack of an association with white matter abnormalities on neuroimaging.

OBJECTIVE: To provide results from the largest study of new daily persistent headache patients to date and specifically evaluate if patients with primary new daily persistent headache develop white matter abnormalities or infarct-like lesions on neuroimaging. METHODS: Retrospective analysis of patient medical records utilizing an electronic medical record system. All patients were seen at a headache specialty clinic by a single headache neurologist and diagnosed with primary new daily persistent headache during the time period of January 2009 to January 2013. RESULTS: Altogether, 97 patients were diagnosed with primary new daily persistent headache (65 women and 32 men). The mean average age of onset was slightly younger in women than men: 32.4 years vs. 35.8 years. In total, 84 of the 97 new daily persistent headache patients had no white matter abnormalities or infarct-like lesions on magnetic resonance imaging with a gender distribution of 56 women and 28 men. The mean age of onset of this white matter negative subgroup was 31.1 years. Of these individuals, 36% had cardiovascular/cerebrovascular risk factors and 44% had a history of migraine. Only 13 new daily persistent headache patients (nine women, four men) demonstrated white matter abnormalities on magnetic resonance imaging. None had infarct-like lesions. The mean age of onset of this white matter positive subgroup was 54.2 years, significantly older than the white matter negative population (p < .05). All new daily persistent headache patients in the white matter positive subgroup had cardiovascular/cerebrovascular risk factors and dual risk factors were noted in seven of 13 patients. Only 23% had a migraine history. Almost 40% of the patients in the white matter negative group were imaged 3 years after headache onset and at least six patients were imaged at least 9 years or more after onset of new daily persistent headache. Triggering events in both white matter lesion positive and negative populations were typical of the new daily persistent headache population as a whole and not specific to the presence or absence of brain imaging lesions except for a post-surgery trigger, which was significantly more likely to occur in the white matter positive group. Migraine associated symptoms occurred in 77% of the white matter negative subgroup compared with 46% of the white matter positive subgroup, which was a significant difference. CONCLUSION: White matter abnormalities and infarct-like lesions do not appear to occur in primary new daily persistent headache patients. Only new daily persistent headache patients with risk factors (cardiovascular/cerebrovascular or migraine) developed white matter abnormalities on brain magnetic resonance imaging. No patient with new daily persistent headache developed infarct-like lesions. New daily persistent headache triggering events (outside of possibly post-surgery) or the presence of migrainous symptoms did not appear to enhance the development of white matter abnormalities.

Triggering Events and New Daily Persistent Headache: Age and Gender Differences and Insights on Pathogenesis-A Clinic-Based Study.

OBJECTIVE: To define what are the age and gender differences for new daily persistent headache (NDPH) triggering events and how this may relate to the pathogenesis of NDPH. To describe several new triggering events for NDPH. METHODS: All patients were diagnosed with primary NDPH at a headache specialty clinic during the time period of 01/2009 through 01/2013. This was a retrospective analysis of patient medical records utilizing an electronic medical record system. RESULTS: Ninety-seven patients were diagnosed with primary NDPH (65 women and 32 men). The mean average age of onset was younger in women than men 32.4 years vs 35.8 years. Fifty one of ninety seven NDPH patients (53%) did not recognize a triggering event while an infection or flu-like illness triggered NDPH in 22%, a stressful life event in 9%, a procedure (surgical) in 9%, and some "other" recognized trigger in 7%. All of the NDPH patients who developed new onset headache after an invasive surgical procedure were intubated. There was no significant difference in frequency for any of the triggering events between genders. The youngest age of onset was for a post stressful life event trigger while the oldest age of onset was in the post-surgical subgroup. Women developed NDPH at a younger age of onset for all recognized triggers, but there was no significant difference in ages of onset between the genders. There was no significant difference in the number of NDPH patients who had a history of migraine or no history and if they developed NDPH after any triggered event vs no triggering event. However, the majority of patients who developed NDPH after a stressful life event did have a precedent migraine history (67%). Newly noted triggers include: hormonal manipulation with progesterone, medication exposure, chemical/pesticide exposure, massage treatment, and immediately post a syncopal event. CONCLUSION: More than 50% of NDPH sufferers do not recognize a triggering event to their headaches. A key finding from the present study is the recognition that of those patients who developed NDPH after an invasive surgical procedure all required intubation and we speculate a cervicogenic origin to their headaches. The fact that both genders had an almost equal rate of occurrence for most NDPH triggers and almost the same age of onset suggests a common underlying pathogenesis for similar triggering events. A precedent history of migraine did not enhance the frequency of triggered vs nontriggered NDPH except possibly for a stressful life event.

A case of post-traumatic LASH syndrome responsive to indomethacin and melatonin (a man with a unique triad of indomethacin-responsive trigeminal autonomic cephalalgias).

OBJECTIVE: The objective of this article is to present the first post-traumatic/secondary case of LASH syndrome and the first melatonin-responsive case of LASH. METHODS: We present a case report. RESULTS: A 44-year-old man developed three distinct headache syndromes in progression over a 2.5-year time period after a motor vehicle accident. He initially had paroxysmal hemicrania, which he experienced for 15 months, then transitioned to hemicrania continua for 3.5 months, then LASH syndrome, which he endured until he was treated with indomethacin and became pain free. Then after an inability to taper off indomethacin he was placed on melatonin and achieved a pain-free state. CONCLUSION: This is the first post-traumatic/secondary case of LASH syndrome, the first male patient to be documented with LASH, and the first LASH case to show complete alleviation with melatonin. This patient's unique case history provides another example of how multiple trigeminal autonomic cephalalgias can occur in a single individual. This may be one of the first cases of three distinct trigeminal autonomic cephalalgias developing after trauma.

Treatment of hemicrania continua with radiofrequency ablation and long-term follow-up.

OBJECTIVE: The objective of this research is to describe novel procedural treatments for hemicrania continua that allow patients to remain off indomethacin. METHODS: Case reports are presented. RESULTS: We describe four distinct patients with indomethacin-responsive hemicrania continua who were unable to discontinue the use of indomethacin without headache recurrence. No other medications were effective for their syndrome. Secondary causes of headache were ruled out in each case. Each patient underwent diagnostic blockade of either the atlanto-axial joint, C2 dorsal root ganglion or sphenopalantine ganglion depending on their clinical examination and presence of cranial autonomic symptoms. A positive response led to a radiofrequency ablation of the C2 ventral ramus, C2 dorsal root ganglion or sphenopalantine ganglion, which provided headache relief in all case patients as complete as indomethacin. Long-term follow-up of these patients has shown that all have remained essentially headache free without the need for indomethacin. One patient has needed repeat radiofrequency procedures with consistent response. CONCLUSION: Hemicrania continua is defined by its sensitivity to indomethacin but very few patients are able to discontinue the medication without headache recurrence. As the risks of chronic indomethacin use are substantial, alternative treatments are necessary to protect patient health. We are now able to suggest several radiofrequency ablation procedures as effective as indomethacin with long-term follow-up.