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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 The trigeminal autonomic cephalalgias are a group of primary headache syndromes marked by severe head pain and associated cranial autonomic symptoms which can include a full or partial Horner’s syndrome. Rarely, the eye-related symptoms will become fixed even between headache attacks. There is minimal documentation that the Horner’s syndrome can be reversed if successful treatment of the underlying headache disorder is initiated. Case reports Two cases are presented of trigeminal autonomic cephalalgia subtypes with chronic persistent Horner’s syndromes that alleviated with treatment of the underlying primary headache disorder. Patient 1, an 82-year-old Caucasian woman, presented with hemicrania continua with a partial Horner’s syndrome that was present for 2 years. She was unable to take indomethacin as she was on anticoagulation. After a C2–3 diagnostic facet injection, not only did she become pain free but her ptosis completely resolved. She then underwent a radiofrequency facet neurotomy with complete alleviation of head pain and complete resolution of her ptosis. Patient 2, a 21-year-old Caucasian woman, presented with long-lasting autonomic symptoms with hemicrania syndrome and a fixed miosis and ptosis of 6 months’ duration. After achieving 2 months of pain freedom on indomethacin her Horner’s syndrome completely resolved. Conclusion A chronic fixed partial or full Horner’s syndrome can occur in trigeminal autonomic cephalalgia subtypes, but it can also be reversed in patients with treatment even after months to years of duration. This would suggest that the sympathetic dysfunction leading to the eye-related symptoms is from irritation of the sympathetic chain rather than permanent injury as the result of vasodilatory trauma after trigeminal autonomic reflex activation.

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.

Objective: To define a new type of head pain syndrome termed “cranial suture headache” which is a localized headache originating along the cranial suture lines of the skull. Background: Well localized headaches maybe extracranial in origin. As trigeminal nociceptors are localized within the cranial sutures of the skull, these fibrous joints maybe the source of head pain for some patients. Methods: Case series. To diagnose cranial suture headache, the patient’s pain had to be localized to the skull and elicited/mimicked by mild to moderate palpation over one or more distinct cranial suture lines. Results: Ten cases are presented. Most of the patients were women (9/10). The headache started daily from onset in all cases. Range of age of headache onset was 32–64 years. Headache was one sided, unless confined to the midline and typically lacked any migrainous and/or cranial autonomic symptoms. Most cranial suture headaches localized to either the sagittal, coronal or squamosal suture lines. Headache duration prior to diagnosis was on average 8.5 years. Triggering events: three began immediately after head trauma, two had very remote head trauma, one was post infectious, one was post craniotomy, while three patients had no known triggering event. All patients were treatment refractory failing at least three preventive medications. All improved with localized anesthetic injection to the suture line(s) and/or onabotulinum toxin A injection only to the cranial sutures. Discussion: Without the recognition of cranial suture-based pain, patients may have unremitting headaches that can last years to decades. The observation that “cranial suture” headache improves with localized treatment only to the cranial sutures would seem to suggest the extracranial origin of the pain.

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.

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.

Is it possible that some mitochondrial DNA (mtDNA) mutations enhance the risk of developing a headache disorder while other mutations actually confer a protective effect? Mitochondrial disorders have been linked to migraine but very rarely to cluster headache (CH). The true pathogenesis of CH is unknown but a linkage to cigarette smoking is irrefutable. Leber’s hereditary optic neuropathy is a syndrome of bilateral vision loss that typically manifests in a patient’s 20s and 30s, is male predominant, and its sufferers are heavy smokers and heavy drinkers. Tobacco exposure is so linked to the condition that only smokers appear to develop vision loss while nonsmokers remain unaffected carriers of their mutations. In essence, the Leber’s hereditary optic neuropathy population is the CH population but at present there have been no reported cases of CH in this mitochondrial subgroup. Thus, could the effects of the mtDNA mutations found in Leber’s hereditary optic neuropathy, which involve complex I of the electron transport chain, actually confer a protective effect against the development of CH? This article will delve into this theory.

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.

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.

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.

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.

To describe a new subtype of chronic daily headache in women of a specific age group.Case series.Eight patients were included in the presented case series. The average age of onset of this distinct headache condition is 57 years. All patients were either perimenopausal or in menopause when the headaches started. The syndrome is marked by bilateral head pain that starts daily from onset and is typically at its most severe intensity the first thing in the morning before arising or when in the supine position. Immediate worsening in Trendelenburg appears to be an almost diagnostic test for the syndrome and occurred in all patients. The majority of the patients had a history of episodic migraine, but the migraines were either very well controlled or had ceased by the time the new headache arose. The bulk of the patients (6/8) were either overweight or obese, although two patients were of normal body mass index (BMI). Neuroimaging showed no abnormalities. All patients responded to cerebrospinal fluid (CSF) pressure-/volume-lowering medications (acetazolamide or spironolactone), but only one patient was able to completely taper off treatment without headache recurrence.This newly defined subtype of chronic daily headache appears to be caused by a state of elevated CSF pressure. It is hypothesized that a combination of an elevated BMI and the presence of cerebral venous insufficiency leads to this form of daily headache.

A case is presented of a woman with a history of daily persistent head pressure and dizziness who developed a cytotoxic lesion of the splenium of the corpus callosum after an acute withdrawal of chronic acetazolamide treatment and then, in quick succession, a CSF pressure/volume drop with a lumbar puncture. This is the first documentation that rapid alterations of CSF pressure/volume may trigger cytotoxic lesions in the central nervous system.

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 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.

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 Sao 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

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.

Objective To describe a second case of treatment refractory chronic cluster headache responsive to clomiphene citrate and with long-term follow-up. Methods Case report with 7-year evaluation. Case A 63-year-old man with a 17-year history of chronic cluster headache preceded to have significant adverse events or was nonresponsive to multiple cluster headache preventive medications including verapamil, lithium, valproic acid, topiramate, baclofen as well as greater occipital nerve blocks and inpatient hospitalization. The patient experienced 3-5 headaches per day. On clomiphene citrate 100 mg/day he became 100% pain-free and remained so for 3.5 years with only mild fatigue as a side effect. He then had cluster headache recurrence and did well on gabapentin for another 3 years with repeat headache recurrence. Clomiphene was restarted, and he became pain-free once again. Discussion This is the second reported case of the effective use of clomiphene citrate for the preventive treatment of medicinal refractory chronic cluster headache. This is the first case to report long-term follow-up of this neurohormonal treatment. Clomiphene citrate appears to be safe for extended use in chronic cluster headache even in an elderly sufferer and has a minimal side effect profile. The mechanism of action of how clomiphene prevents cluster headache may involve both its ability to enhance testosterone production and its ability to bind to hypothalamic estrogen receptors. Clomiphene citrate should join the list of alternative cluster headache prophylactic treatments to be considered by headache specialists when conventional cluster headache preventives are ineffective.

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.

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.

Objective To assess the efficacy of melatonin as a preventive therapy for hemicrania continua in a larger population of patients than has previously been studied. Background Hemicrania continua is defined by its sensitivity to indomethacin. Rarely can patients be fully tapered off indomethacin without headache recurrence; thus, the risks associated with chronic indomethacin usage are substantial for these individuals. Melatonin, a pineal hormone with a similar chemical structure to indomethacin, has shown efficacy as a preventive agent for hemicrania continua in isolated case reports. Melatonin would be a preferential alternative prophylactic treatment to indomethacin because of its minimal side effect profile. How truly effective melatonin is as a preventive for hemicrania continua is unknown at present and needs further study. Methods Retrospective analysis of all International Classification of Headache Disorders-3 beta diagnosed hemicrania continua patients treated with both indomethacin and melatonin at the Geisinger Headache Center from July 2011 to January 2014. Results Eleven patients were treated (9 women, 2 men). Two patients became pain free on melatonin, while partial relief was noted in 3 other patients; thus, they were able to lower their dose of indomethacin but could not achieve pain freedom with melatonin alone. Six patients had no response. Melatonin dosing needed for response ranged from 3 to 30 mg. In the partial relief responders, indomethacin dosing decreased by 50% to 75%. Conclusion From this single clinic investigation, only a small percent of subjects with hemicrania continua (less than 20%) will achieve pain freedom on melatonin, thus clearly not matching the effectiveness of indomethacin. However, the addition of melatonin to indomethacin may allow around 45% of patients to have complete or partial relief of their headache with the subsequent ability to reduce or eliminate their indomethacin dosage, which may lead to a decrease in medical morbidity over time secondary to less exposure to indomethacin.

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.

Objective. To show that demand valve oxygen is an effective acute treatment for cluster headache and to compare this oxygen delivery technique with standard cluster headache therapy of continuous flow oxygen. Methods. Single-center, open-label, two-period, two-treatment crossover design, pilot study was used. Subjects treated with one of two sequences: first, headache treated with continuous flow oxygen (100% oxygen at 15 liters per minute), and subsequent with demand valve oxygen, or vice versa. Treatment began when pain was at least moderate. Subjects taught a specific breathing technique for demand valve oxygen that included initial period of hyperventilation. Primary end point was headache response (moderate-to-very-severe pain reduced to mild or none) after 30 minutes of treatment. Results. Three subjects completed the trial, while a fourth completed demand valve oxygen only. All had chronic cluster headache. All subjects treated with demand valve oxygen became pain-free (time in minutes: 15, 19, 6, 8). Three of four had no recurrence within 24 hours. Demand valve oxygen reduced cranial autonomic symptoms in all and resolved them in two subjects. For continuous flow oxygen, two of three subjects became pain-free (20, 10 minutes). Continuous flow oxygen reduced but did not eliminate cranial autonomic symptoms. Continuous flow oxygen had higher recurrence rates. No adverse events noted with either treatment. Conclusion. Demand valve oxygen appears to be an effective acute treatment for cluster headache. All subjects became headache-free. Time to pain freedom was fast (average 12 minutes). The small number of study subjects does not allow a direct comparison of efficacy between demand valve oxygen and continuous high flow oxygen.

Head pain can be generated by a multitude of structures, but the brain parenchyma itself is not one of them. The brain has either no or minimal sensory innervation with pain fibers. However, the coverings of the brain (meninges), meningeal blood vessels, and large cerebral arteries and veins all are highly innervated, and thus when stimulated, could cause head pain (Fig. 1). In addition, neck structures and paranasal sinuses can contribute to head pain. This chapter will look at the potential pain sensitive intracranial and extracranial structures.

Objective To present results from the United States Cluster Headache Survey regarding gender differences in cluster headache demographics, clinical characteristics, diagnostic delay, triggers, treatment response and personal burden. Background Very few studies have looked at the gender differences in cluster headache presentation. The United States Cluster Headache Survey is the largest study of cluster headache sufferers ever completed in the United States and it is also the largest study of female cluster headache patients ever presented. Methods The total survey consisted of 187 multiple choice questions which dealt with various issues related to cluster headache including: demographics, clinical characteristics, concomitant medical conditions, family history, triggers, smoking history, diagnosis, treatment response and personal burden. A group of questions were specifically targeted to female cluster headache patients. The survey was placed on a website from October to December 2008. For all survey responders the diagnosis of cluster headache needed to be made by a neurologist but there was no validation of the headache diagnosis by the authors. Results 1134 individuals completed the survey (816 male, 318 female). Key Points that define the differences between female and male cluster headache include: a. Age of onset: women develop cluster headache at an earlier age than men and are more likely to develop a second peak of cluster headache onset after 50 years of age. b. Family history: woman cluster headache sufferers are more likely to have a family history of both cluster headache and migraine and have an increased familial risk of Parkinson's disease. c. Comorbid conditions: female cluster headaches sufferers are significantly more likely to experience depression and have asthma than males. d. Aura issues: aura with cluster headache is equally common in both sexes, but aura duration is shorter in women. Women are much more likely to experience sensory, language and brainstem auras. e. Pain location: cluster headache pain is typically retro-orbital in location in both sexes but women are significantly more likely to experience cluster headache pain in the jaw, cheek and ear than men. f. Associated symptoms: women with cluster headache develop more “migrainous” associated symptoms than men, especially nausea and they are also more likely to have self-injurious behavior than men. g. Triggers: women with cluster headache are much less likely to have alcohol trigger a headache, but are significantly more likely to have “migrainous” triggers for their cluster headaches than men. h. Smoking issues: women are much less likely to have a smoking history than male cluster headache sufferers, more likely to have never smoked prior to cluster headache onset. i. Cycle issues: spring and fall are the most common time to start a cluster headache cycle in both sexes. Women are statistically significantly less likely to start a cluster headache cycle in the months of October–December than men. Women have more attacks per day and higher pain intensity nighttime attacks than men. j. Treatment: in regard to acute treatment women statistically were less response to sumatriptan injectable and nasal spray than men, but statistically more likely to respond to inhaled lidocaine. There was equal efficacy in the sexes to inhaled oxygen but slower response in women. For preventive treatment no significant gender differences were noted, but overall women were less responsive to almost all preventives than men. k. Diagnostic delay: there remains a significant diagnostic delay for cluster headache patients in both sexes but women were more likely to be diagnosed after 10 years of symptom onset than males and significantly fewer women were diagnosed correctly at an initial physician visit than men. l. Female specific issues: cluster headache does not appear to be influenced by menses or menopause but 50% of the survey responders stated their headaches improved with pregnancy. Cluster headache does not appear to alter fertility rates in female cluster headache sufferers. m. Personal burden: cluster headache causes significantly more personal burden in women than men with more loss of employment and/or need of disability, as well as more homebound days. Conclusion Overall women and men with cluster headache have a similar presentation but there are some distinct differences that have been suggested in smaller studies of female cluster headache that we have now verified, while some of our study conclusions have not been shown previously. One major limitation to the study is a lack of validation of diagnosis. A substantial false positive cluster headache diagnosis rate, especially in females, cannot be excluded by the study methods utilized.

Object Spontaneous intracranial hypotension is an important cause of headaches and an underlying spinal CSF leak can be demonstrated in most patients. Whether CSF leaks at the level of the skull base can cause spontaneous intracranial hypotension remains a matter of controversy. The authors' aim was to examine the frequency of skull base CSF leaks as the cause of spontaneous intracranial hypotension. Methods Demographic, clinical, and radiological data were collected from a consecutive group of patients evaluated for spontaneous intracranial hypotension during a 9-year period. Results Among 273 patients who met the diagnostic criteria for spontaneous intracranial hypotension and 42 who did not, not a single instance of CSF leak at the skull base was encountered. Clear nasal drainage was reported by 41 patients, but a diagnosis of CSF rhinorrhea could not be established. Four patients underwent exploratory surgery for presumed CSF rhinorrhea. In addition, the authors treated 3 patients who had a postoperative CSF leak at the skull base following the resection of a cerebellopontine angle tumor and developed orthostatic headaches; spinal imaging, however, demonstrated the presence of a spinal source of CSF leakage in all 3 patients. Conclusions There is no evidence for an association between spontaneous intracranial hypotension and CSF leaks at the level of the skull base. Moreover, the authors' study suggests that a spinal source for CSF leakage should even be suspected in patients with orthostatic headaches who have a documented skull base CSF leak.

Objective To present results from the United States (US) Cluster Headache Survey including data on cluster headache demographics, clinical characteristics, suicidality, diagnostic delay, triggers, and personal burden. Background There are few large-scale studies looking at cluster headache patients and none from the USA. This manuscript will present data from The US Cluster Headache Survey, the largest survey ever completed of cluster headache patients living in the USA. Methods The total survey was composed of 187 multiple-choice questions that dealt with issues related to cluster headache including demographics, clinical characteristics, comorbid medical conditions, family history, triggers, smoking history, and personal burden. The survey was placed on a Web site from October through December 2008. Results A total of 1134 individuals completed the survey (816 male, 318 female). Some key highlights from the survey include the following: (1) diagnostic delay: there remains a significant diagnostic delay for cluster headache patients on average 5+ years with only 21% receiving a correct diagnosis at time of initial presentation. (2) Suicidality: suicidal ideations are substantial, occurring in 55%. (3) Eye color: the predominant eye color in cluster headache patients is brown and blue, not hazel as suggested in previous descriptions. (4) Laterality: cluster headache has a right-sided predominance. (5) Attack profile: in US cluster headache sufferers, most attacks occur between early evening and early morning hours with peak time of headache onset between midnight and 3 am; the circadian periodicity for cluster headache is present but is not as predominant in the population as previously thought. (6) Triggers: beer is the most common type of alcohol trigger in US cluster headache patients; noted migraine triggers such as weather changes and smells are also very common cluster headache triggers. (7) Medical comorbidities: peptic ulcer disease does not have a high prevalence in US cluster headache patients as suggested by previous literature; cluster headache is associated with a low prevalence of cardiac disease as well as cerebrovascular disease even though the majority of patients are chronic heavy smokers. In US cluster headache sufferers, there appears to be comorbidity with restless leg syndrome, and this has not been demonstrated in non-US cluster headache populations. (8) Personal burden: cluster headache is disabling to the individual as almost 20% of cluster headache patients have lost a job secondary to cluster headache, while another 8% are out of work or on disability secondary to their headaches. Conclusion Some findings from the US Cluster Headache Survey expound on what is currently known about cluster headache, while some of the results contradict what has been previously written, while other information is completely new about this fascinating headache disorder.

Objective.— To describe the syndrome of migraine with binocular blindness. Background.— Rarely do migraine patients complain of losing vision in both eyes during an attack of headache. There are no large clinic-based studies looking at the prevalence of binocular blindness in migraine sufferers and no information about patient demographics, neuroimaging, and laboratory testing. Methods.— Over a 14-month time period, 383 new patients with a diagnosis of migraine were seen at the Geisinger Headache Center. All patients were asked if they ever experienced an episode of complete bilateral blindness along with their headaches. Those with a positive history had coagulopathy testing as well as brain magnetic resonance imaging and magnetic resonance angiography of the intracranial circulation. Results.— A total of 6 patients or only 1.6% of the new migraine patients had episodes of binocular blindness with their headaches. All were female and each had a history of migraine for at least 3 years. Five patients had a diagnosis of migraine without aura, while one had a diagnosis of basilar-type migraine. In all patients the blindness episodes occurred in isolation during a migraine headache. In all but one patient the blindness was instantaneous and not a slow evolution. In 2 patients the blindness episode only occurred 1 time; in 3 patients episodes occurred more than once but were rare, while 1 patient had blindness with 50% of her headaches. In regard to duration, in 2 patients blindness lasted only several seconds, 2 patients between 2 and 10 minutes, 1 patient 30 minutes and 1 patient 60-120 minutes. Neuroimaging was normal in all. Three patients had a history of smoking and 3 never smoked. Coagulopathy testing was abnormal in all patients. Two patients were homozygous for methylenetetrahydrofolate reductase (MTHFR) 677TT polymorphism, but both had normal homocysteine levels; 3 patients were heterozygous for MTHFR 677CT polymorphism and 1 had elevated homocysteine levels and 1 patient had a positive lupus anticoagulant (had the most frequent episodes of blindness). Conclusion.— Binocular blindness with migraine headache is a very rare occurrence at least in a headache specialty clinic population. It is a female-predominant event and occurs mostly in migraine patients who do not have a history of aura. Blindness episodes can be very brief or prolonged and many do not fit the typical duration of a migraine aura. They are typically infrequent events and may occur only 1 time without recurrence. Migraine with binocular blindness may reflect an underlying clotting disorder. A possible etiology outside of a coagulopathy-related event is retinal spreading depression.

New daily persistent headache is a recognized form of primary chronic daily headache. It is unique in its presentation and course. The goal of this article is to discuss the clinical characteristics, triggering factors, possible underlying pathogenesis and treatment options for this unique headache disorder. At present prognosis for new daily persistent headache is considered poor with very few effective treatment options. A new treatment paradigm for new daily persistent headache based on triggering events will be suggested. The current International Classification of Headache Disorders 2 criteria for new daily persistent headache will also be discussed including its apparent inadequacies and revised criteria will be recommended.

Objective.—To present results from the United States Cluster Headache Survey concerning the use of inhaled oxygen as acute treatment for cluster headache (CH). Background.—Several small clinic and community-based investigations have indicated that more than 50% of CH patients have never used oxygen for the treatment of their headaches.This statistic is alarming and the reasons why they have not tried oxygen have not been determined. Methods.—The United States Cluster Headache Survey is the largest study ever completed looking at CH sufferers living in the United States.The total survey consisted of 187 multiple choice questions,84 questions dealt with oxygen use,efficacy and economics. The survey was placed on a website from October to December 2008. Results.—A total of 1134 individuals completed the survey (816 male, 318 female).Among them 868 patients had episodic CH while 266 had chronic CH.Ninety-three percent of survey responders were aware of oxygen as a CH therapy;however, 34% had never tried oxygen. Forty-four percent of patients had to suggest oxygen to their physicians to get prescribed. Twelve percent of physicians refused to prescribe oxygen. Fifty percent using oxygen never received training on proper use. Forty-five percent had to find their own source for oxygen. On prescriptions only 45% specified flow rate, 50% stated CH as diagnosis and 28% indicated mask type. Seventy percent of the surveyed population felt oxygen was effective but only 25% was presently using oxygen. Potential reasons for this finding include: oxygen is slow to onset; prescribed oxygen flow rates are too low for efficacy and most CH patients need to raise flow rates during attacks to achieve response.The efficacy of oxygen does not vary by the age of the patient, gender, the number of CH attacks per day, and smoking history. Episodic CH responds better and faster to inhaled oxygen than chronic CH. Oxygen plus a triptan may be more efficacious and faster at aborting a CH than a triptan alone. Sixteen percent of CH patients state that oxygen is unaffordable while 12% are getting welder grade oxygen because of costs of medical grade oxygen, and this form of oxygen could be potentially dangerous to the individual user. Conclusions.—Oxygen is underutilized by CH patients living in the United States. Current recommended oxygen treatment regime is not meeting the needs of many CH patients. Prescribed oxygen flow rates are too low for efficacy. Oxygen can be expensive and very difficult to obtain. Physicians need to be better educated on the use of inhaled oxygen for CH.

The trigeminal autonomic cephalalgias (TACs) are a group of primary headache syndromes all marked by headache and associated autonomic features. The TACs include cluster headache, paroxysmal hemicrania, hemicrania continua, and short-lasting unilateral neuralgiform headache attacks with conjunctival injection and tearing syndrome. Diagnosis is made after looking at headache frequency, duration, and accompanying symptoms. Each TAC has its own unique treatment modality, which is discussed in depth.

Objective To determine if patients with new daily persistent headache (NDPH) have elevated levels of tumor necrosis factor alpha (TNF alpha) in the CSF. Background NDPH is considered one of the most treatment resistant of all headache syndromes. This reflects a lack of understanding of its pathogenesis. As a certain percentage of NDPH patients have their headaches start after an infection, the possibility of a persistent state of systemic or CNS inflammation comes into question. TNF alpha is a proinflammatory cytokine involved in brain immune and inflammatory activities, as well as in pain initiation. The goal of this study was to look at TNF alpha levels in the CSF of NDPH patients, to determine if CNS inflammation may play some role in the pathogenesis of this condition. Methods CSF TNF alpha levels were studied in 38 patients: 20 with NDPH and a control population of 16 patients with chronic migraine (CM), and 2 with post-traumatic headache (PT). Results CSF TNF alpha levels were elevated in 19 of 20 NDPH patients, 16 of 16 CM patients, and both PT patients. Serum TNF alpha levels were normal in most of the study subjects. Conclusion An elevation of CSF TNF alpha levels was found in almost all NDPH patients and suggest a role for TNF alpha in the pathogenesis of this condition. Surprisingly, all CM and PT patients tested had elevated CSF TNF alpha levels. In most patients with elevated CSF levels, serum TNF alpha levels were normal. All of these syndromes may be manifestations of CNS inflammation. As most of the positive-tested patients showed minimal to no improvement during aggressive inpatient treatment, persistent elevation of CSF TNF alpha levels may be one of the causes of treatment refractory CDH.

Purpose of review This article discusses the treatment of status migrainosus in the emergency department and the treatment of intractable migraine in an inpatient setting. Recent findings Multiple agents of various drug classes have been tried for the treatment of acute migraine in the emergency department, but few have adequate medical evidence to support their use. Opioids, which are less effective than other medications used for the acute treatment of migraine and also carry the risk of adverse CNS side effects, habituation, and addiction, have been prescribed for migraine in the emergency department at an increasing rate over the last decade, which is a worrisome trend. Very few patients with migraine derive sustained relief from pain after emergency department treatment, and most have a high frequency of headache recurrence. Summary Treatment of status migrainosus and intractable migraine should focus on adequate fluid hydration and combination IV therapy with multiple nonopioid medications from multiple drug classes. Dopamine receptor antagonists appear to have some of the highest medical evidence for efficacy.

Acupuncture, traditional Chinese needle therapy, has become widely used for the relief of headache. The history of the practice of acupuncture in the United States and the theoretical framework for acupuncture in Chinese medicine are reviewed. The basic scientific background and clinical application of acupuncture in the headache management are discussed.

Cluster headache is a primary headache syndrome that is under-diagnosed and in many instances under-treated. The pain produced during a cluster headache is more severe than that generated by any other primary headache. Cluster headache is very stereotyped in its presentation and fairly easy to diagnose with an in-depth headache history. Cluster headache is easy to treat in most individuals if the correct medications are used and the correct dosages are given. The following manuscript presents information on the clinical presentation of cluster headache and both medicinal and surgical interventions.

A number of primary headache syndromes are marked by their short duration of pain. Many of these syndromes have their own unique treatment, so they must be recognized by practicing physicians. In this article, a number of the short-lasting headache disorders are reviewed, including chronic paroxysmal hemicrania, SUNCT syndrome, hypnic headache, exploding head syndrome, primary stabbing headache, and cough headache.

Trigeminal neuralgia and glossopharyngeal neuralgia are extremely painful conditions that typically afflict an older population. Distinct clinical characteristics guide the diagnosis of these unique syndromes. Treatment involves medication first and then surgical procedures if a patient is refractory to medicinal therapy. Antiepileptic medications are the most effective agents for these disorders.

Recently, cluster headache has been shown to occur with aura, suggesting that as more cluster patients are seen by headache specialists new forms of this well-defined primary headache syndrome will be identified. This study presents three atypical presentations of cluster headache: persistent or unremitting cluster, periodic cluster, and reflex or event-related cluster. Case reports are presented with an explanation as to why these headaches should be considered cluster headache.

Background.—Olanzapine, a thienobenzodiazepine, is a new “atypical” antipsychotic drug. Olanzapine's pharmacologic properties suggest it would be effective for headaches, and its propensity for inducing acute extrapyramidal reactions or tardive dyskinesia is relatively low. We thus decided to assess the value of olanzapine in the treatment of chronic refractory headache. Methods.—We reviewed the records of 50 patients with refractory headache who were treated with olanzapine for at least 3 months. All previously had failed treatment with at least four preventative medications. The daily dose of olanzapine varied from 2.5 to 35 mg; most patients (n = 19) received 5 mg or 10 mg (n = 17) a day. Results.—Treatment resulted in a statistically significant decrease in headache days relative to baseline, from 27.5 ± 4.9 before treatment to 21.1±10.7 after treatment (P

Cluster headache is one of the primary headache disorders. It is considered the most severe headache syndrome known to humans. In most instances, this disorder is readily treatable when the correct medications are utilized at the correct dosages. Cluster headache treatment involves abortive, transitional and preventive therapy strategies.

Cluster headache is the most severe headache syndrome known to humans. In most instances, this disorder is readily treatable when the correct medications are utilized at the correct dosages. Cluster treatment involves abortive, transitional, and preventive therapy strategies, all of which are discussed in this article.

New daily persistent headache (NDPH) is a subtype of chronic daily headache. The literature on NDPH is scant and its true aetiology is unknown. A retrospective chart review was carried out from a computerized database at the Jefferson Headache Centre from August 1997 to May 2000 to identify patients with NDPH using the Silberstein et al. criteria. Forty women and 16 men were identified. Age of onset ranged from 12 to 78 years. The peak age of onset was the second and third decade in women and the fifth decade in men. Eighty-two per cent of patients were able to pinpoint the exact day their headache started. Onset occurred in relation to an infection or flu-like illness in 30%. A prior headache history was found in 38% of patients. A family history of headache was documented in 29%. The duration of daily headache ranged from 1.5 h to 24 h; 79% were continuous. Nausea occurred in 68% of patients, photophobia in 66%, phonophobia in 61%, and lightheadedness in 55%. Laboratory testing and neuroimaging in all patients was normal except for Epstein-Barr virus antibody titres, which were positive in 71% of seven patients tested, representing past infection. NDPH appears to be a female-predominant disorder, marked by a continuous daily headache with associated migrainous symptoms. Over 80% of patients could state the exact date their headache began. One-third of patients developed NDPH with a flu-like illness.