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PURPOSE: This article provides an overview of a diverse group of primary headache disorders that are categorized in the International Classification of Headache Disorders, 3rd Edition (ICHD-3), as "other primary headache disorders." This article provides clinicians with a distilled understanding of the diagnoses and their epidemiology, pathophysiology, and management. RECENT FINDINGS: Cough-induced headache requires neuroimaging to exclude posterior fossa pathology and recently has been reported as a common symptom in patients with CSF-venous fistula. Clinical overlap is observed between patients with primary exercise headache and primary headache associated with sexual activity. Patients with recurrent thunderclap headache associated with sexual activity should be presumed to have reversible cerebral vasoconstriction syndrome until proven otherwise. De novo external-pressure headache is a common sequela among health care workers using personal protective equipment during the COVID-19 pandemic. New daily persistent headache is an important mimicker of chronic migraine or chronic tension-type headache and is distinguished by a daily-from-onset progression of persistent headache; a treatment-refractory course is often observed, and early involvement of a multidisciplinary team, including a psychotherapist, is advised. SUMMARY: Patients with primary headache disorders that are classified as "other primary headache disorders" have presentations with unique diagnostic and management considerations. The disorders are highly recognizable, and an appreciation of the diagnoses will aid clinicians in providing safe and effective care for patients presenting with headache.

Highlights • Trigeminal nerve electrophysiology is commonly abnormal in cases of HFA. • Trigeminal abnormalities are seen in cases with moderate-severe disease. • Both central and peripheral nervous system abnormalities may result in HFA., Objective Hemifacial atrophy (HFA) is a rare disorder characterized by progressive unilateral wasting facial soft tissue, muscle, and/or bone. Trigeminal nerve abnormalities may contribute to or result from disease pathophysiology. We aimed to gain further insights into the role of trigeminal pathophysiology along the HFA severity spectrum. Methods A systematic literature review was performed according to PRISMA standards. Retrospective cases of HFA from the literature and Mayo Clinic EMG database were pooled for descriptive and semi-quantitative analysis. Results Overall, 13 total HFA patients were identified through literature and database reviews. Trigeminal nerve testing was abnormal in 9/13 (69%), exclusively in moderate-severe cases. Abnormalities suggested a peripheral (7/9, 78%) or mixed central/peripheral (2/9, 22%) localization. Trigeminal nerve abnormalities were not identified in any of the 4 cases with mild disease severity. Conclusion Moderate to severe cases of HFA were associated with electrophysiological trigeminal abnormalities. No abnormalities were seen in mild cases of HFA. Significance Trigeminal nerve electrophysiology may serve as a biomarker of moderate-severe disease progression, likely reflecting the consequences of progressive soft tissue atrophy.

Objectives (1) To perform a systematic literature review to evaluate associations between post-dural puncture headache (PDPH) and opening pressure (OP), closing pressure (CP), and volume of cerebrospinal fluid (V) removed. (2) To perform a case-control study to evaluate pressure-volume index (PVI) as a novel risk factor for PDPH. Background According to the International Classification of Headache Diagnoses, 3rd Edition (ICHD-3), the diagnosis of PDPH requires documentation of intracranial hypotension. However, this remains an unproven concept. Methods A systematic literature review was conducted, searching Cochrane Database of Systematic Reviews, Ovid EMBASE, OVID MEDLINE, Scopus, and Web of Science. Study inclusion required a comparison of headache incidence following a LP as a function of OP, CP, and/or V. A retrospective, case-control study with 1:1 matching was conducted utilizing ICHD-3 criteria. Patients with factors that could influence CSF pressure were excluded. Results In our case-control study, we did not identify a paired difference in either median (95% CI) elastance (0.05 [-0.09, 0.11], P = .503) or PVI (4.53 [-7.98, 19.97], P = .678). We identified 22 references, evaluating V (n = 14), OP (n = 11), and/or CP (n = 4). There was no convincing evidence for an association of PDPH with either OP or CP. A minority of studies documenting an association with V included patients with high-volume CSF removal, and/or stratified patients by the timing of the headache onset. Conclusions The overall risk of PDPH does not appear to be influenced by OP, CP, V or PVI. PDPH may be related to V in instances of high-volume removal, and depend on the timing of outcome assessment. Future revision of criteria should consider the existence of immediate and delayed PDPH subtypes, and not presume intracranial hypotension as a mandatory feature.

Objectives To empirically address how thunderclap headache (TCH) is described in a relevant real-world setting. Background TCH refers to a highly recognizable description of a severe headache that reaches maximum severity within 1 minute and endures for at least 5 minutes. The use of a numerical rating scale (NRS) to appraise TCH severity, as well as assessment of TCH progression in patients with pre-existing headache at the time of TCH onset has not been previously evaluated. Methods This was a retrospective case series of adults with a diagnosis of reversible cerebral vasoconstriction syndrome (RCVS), identified through a search of the electronic health record. Individuals meeting International Classification of Headache Disorders, 3rd Edition criteria for acute headache attributed to RCVS were included. Attacks described using a verbal descriptor scale (VDS), NRS, or both were recorded to evaluate acute headache characteristics. Results In all, 56 individuals with available descriptions of 120 acute headaches were included in the study analysis. Patients were female (35, 62.5%) with a median age of 46 (range: 19-67). The majority of patients reported a RCVS trigger (39, 69.6%). Acute headaches were characterized using a VDS (52, 43.3%), NRS (51, 42.5%), or both (17, 14.1%). Acute headaches were always described as severe when a VDS was utilized, and with a median NRS of 10 (range: 4-10). Four patients (7%) did not have a single headache characterized as either severe or with a NRS 8 or greater. In the 10 cases for which there was a pre-TCH baseline headache, it was either rated as mild or with a median NRS of 3 (range: 2-6). Conclusions TCH in RCVS can be recognized using either VDS or NRS, with a broader range of peak intensities than previously recognized. TCH remains recognizable despite pre-existing baseline headache.

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.

INTRODUCTION: Prior studies demonstrating age-related declines in headache prevalence have not accounted for the potentially confounding effects of cognitive impairment. Our primary goal was to assess the relationship between aging and self-reported monthly headache days across the cognitive spectrum. METHODS: A detailed headache questionnaire was included prospectively as part of an annual mailing to participants in the Sanders-Brown Center on Aging longitudinal cohort. RESULTS: The overall survey response rate was 58.6%, yielding a cohort of 332 cognitively normal, 71 mild cognitive impairment (median Mini-Mental Status Examination [MMSE] score = 27, interquartile range [IQR] = 25–28), and 51 demented (median MMSE score = 24, IQR = 19–26) individuals. Current headaches were reported by 22.8%, 25%, and 27.1%, respectively, across normal, mild cognitive impairment, and dementia subgroups. A negative correlation was observed between age and average headache days in cognitively normal (ρ = –0.163, 95% confidence interval [CI] = –0.246 to –0.022, P = 0.004), mild cognitive impairment (ρ = –0.255, 95% CI = –0.274 to 0.229, P = 0.0475), and dementia groups (ρ = –0.295, 95% CI = –0.457 to 0.159, P = 0.068). Ordinary least-squares regression with backward selection identified age alone, but not gender or MMSE, as predicting headache days in the overall cohort. CONCLUSIONS: Aging is associated with a decline in headache days in the absence of any confounding cognitive pathology and is weakly predictive of headache days across the cognitive spectrum. Whether this represents a reporting bias due to dementia or has neurobiological significance warrants further investigation.

ObjectiveTo examine the clinical outcomes of intentional overdoses involving triptans and ergotamines with a retrospective review of the National Poison Data System (NPDS).MethodsThis was a 5-year retrospective cross-sectional study (2014–2018) using the NPDS. Demographics, exposure characteristics, and outcomes were described. Univariate logistic regression was used to estimate the odds ratio (OR) for major effect or death. A multivariable logistic regression model with inclusion criteria of p < 0.1 in univariate analysis was implemented with backwards selection.ResultsIn this population (n = 1,489), multiple exposure was most common (n = 1,145). The mean age was 31.2 years and 1,197 (80.4%) participants were female. Major effects from a single exposure were seen in p = 0.004), multiple product exposure (OR 9.50; 95% CI 2.29–39.48; p = 0.002), and concomitant overdose with benzodiazepines (OR 1.71; 95% CI 1.05–2.78; p = 0.032) or tricyclic antidepressants (OR 3.16; 95% CI 1.88–5.31; p < 0.001).ConclusionThe risk of major effect or death was low and predicted by age, multiple product exposure, and concomitant benzodiazepine or tricyclic antidepressant. The triptan toxidrome consists of hypertension, tachycardia, and drowsiness. The toxic effects of ergotamine are acute gastrointestinal syndrome with vertigo and numbness. No cases of serotonin syndrome were seen.

New daily persistent headache (NDPH) is a rare primary headache disorder, which often has a refractory clinical course. This narrative review seeks to highlight what is known about the development of NDPH, to outline a diagnostic approach to a patient with new daily headache, and to explore management considerations and potential future therapies for patients diagnosed with NDPH. Interval work at the level of case series and cohort studies has identified novel triggering factors (e.g., Valsalva), subgroups with unique temporal profiles (e.g., thunderclap onset), psychophysical profiles (e.g., increased pain catastrophizing), and potential treatment options. The approach to the diagnosis and treatment of NDPH remains individualized, driven by clinical features and challenging in most cases. Earlier identification of patients (e.g., prediction of patients with status migrainosus destined to develop NDPH) may allow for more effective treatment.

Garcia-Azorin et al.1 report on their detailed and cross-sectional appraisal of delayed alcohol-induced headache in approximately 1,100 university students. Their detailed phenotyping substantially deepens and expands our understanding of this common secondary headache syndrome.

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

Objective The objective of this study was to determine associations between cigarette smoking and the existence of headache in a nationally representative sample, with attention to differences in effect estimates between mentholated and non-mentholated cigarettes smoking. Methods We examined cross-sectional associations between cigarette smoking and headache in 8,399 adults who participated in the National Health and Nutrition Examination Survey (NHANES) 1999-2004. The existence of headache was determined by an affirmative response to the question “During the past 3 months, did you have severe headaches or migraines?” Further refinement of headache diagnosis was not possible. We used logistic regression models to examine the association between cigarette smoking and headache. Results The current study included 8,399 participants aged 20 years and over, including 68% (n = 5491) never smokers and 32% (n = 2548) current smokers. Among the current smokers, 24% (n = 739) smoked menthol cigarettes, and 76% (n = 1719) smoked non-menthol cigarettes. Compared with never smokers, after adjustment for potential confounding factors, current smokers were more likely to have headache (OR: 1.38; 95% CI: 1.17-1.62; P

Background: Despite the identification of structures with putative pathophysiological significance in primary headache disorders (e.g., posterior hypothalamus in cluster headache) there appears to be a paucity of human tissue studies examining the neuropathology of these regions. Objective: To synthesize the extent and knowledge pertaining to direct human tissue analysis in primary headache disorders. Methods: Scoping literature review. Results: Of 2718 located articles, 15 were eligible for inclusion. These studies evaluated either migraine (9, 60%) or cluster headache (6, 40%). Approximately 75% were published before or during the era of the first edition of the International Classification of Headache Disorders. The most common study design was case-control (8, 53.3%), and the most commonly examined tissues equally included skin (3, 20%), muscle (3, 20%), and brain (3, 20%). Thematically, these manuscripts generally evaluated peripheral nervous and systemic pathology, as well as more targeted pathophysiological aspects, including mitochondrial and mast cell dysfunction. Conclusions: While interest in this type of study design appears to be waning, histopathological evaluation of human tissue provides unparalleled opportunity to reveal novel pathophysiological insight. Considerations for future study design and reporting of work involving human tissue is suggested based on our review.

We thank Drs. Jackson and Del Bigio for their comments on our case report.1 The authors argue that there were insufficient data to support a diagnosis of rabies encephalitis, but do not offer an alternative, more cohesive explanation for the reported findings. The history of a fulminant and fatal course of new-onset refractory status epilepticus would be consistent, in our viewpoint, with what they believe does not qualify for a “rapid progressive neurologic deterioration.” It is certainly possible that the nonspecific symptoms of personality change and declining academics in the preceding month were unrelated.

This article reports a case of secondary short-lasting unilateral neuralgiform headache with conjunctival injection and tearing following head and neck trauma due to a violent assault. Following the incident, the patient began experiencing 4 to 30 shooting/sharp pain attacks per day in the left anterior temporal and supraorbital areas, with an intensity of 10/10 on a numeric rating scale. Each attack lasted between 10 and 60 seconds. These attacks were accompanied by ipsilateral conjunctival injection, tearing, ptosis of the left eye, blurry vision, and occasional rhinorrhea. Significant improvements in sleep, autonomic symptoms, and pain were observed with a combination of melatonin 10 mg per day, gabapentin 300 mg twice daily, physical therapy, and psychotherapy. This case highlights the relevance of a multidisciplinary approach in the treatment of challenging cases when there is evidence of more than one contributing factor, with the aim of reducing pain and improving the patient's quality of life.

Summary Background In developing countries, mortality in children with very severe pneumonia is high, even with the provision of appropriate antibiotics, standard oxygen therapy, and other supportive care. We assessed whether oxygen therapy delivered by bubble continuous positive airway pressure (CPAP) improved outcomes compared with standard low-flow and high-flow oxygen therapies. Methods This open, randomised, controlled trial took place in Dhaka Hospital of the International Centre for Diarrhoeal Disease Research, Bangladesh. We randomly assigned children younger than 5 years with severe pneumonia and hypoxaemia to receive oxygen therapy by either bubble CPAP (5 L/min starting at a CPAP level of 5 cm H 2 O), standard low-flow nasal cannula (2 L/min), or high-flow nasal cannula (2 L/kg per min up to the maximum of 12 L/min). Randomisation was done with use of the permuted block methods (block size of 15 patients) and Fisher and Yates tables of random permutations. The primary outcome was treatment failure (ie, clinical failure, intubation and mechanical ventilation, death, or termination of hospital stay against medical advice) after more than 1 h of treatment. Primary and safety analyses were by intention to treat. We did two interim analyses and stopped the trial after the second interim analysis on Aug 3, 2013, as directed by the data safety and monitoring board. This trial is registered at ClinicalTrials.gov, number NCT01396759. Findings Between Aug 4, 2011, and July 17, 2013, 225 eligible children were recruited. We randomly allocated 79 (35%) children to receive oxygen therapy by bubble CPAP, 67 (30%) to low-flow oxygen therapy, and 79 (35%) to high-flow oxygen therapy. Treatment failed for 31 (14%) children, of whom five (6%) had received bubble CPAP, 16 (24%) had received low-flow oxygen therapy, and ten (13%) had received high-flow oxygen therapy. Significantly fewer children in the bubble CPAP group had treatment failure than in the low-flow oxygen therapy group (relative risk [RR] 0·27, 99·7% CI 0·07–0·99; p=0·0026). No difference in treatment failure was noted between patients in the bubble CPAP and those in the high-flow oxygen therapy group (RR 0·50, 99·7% 0·11–2·29; p=0·175). 23 (10%) children died. Three (4%) children died in the bubble CPAP group, ten (15%) children died in the low-flow oxygen therapy group, and ten (13%) children died in the high-flow oxygen therapy group. Children who received oxygen by bubble CPAP had significantly lower rates of death than the children who received oxygen by low-flow oxygen therapy (RR 0·25, 95% CI 0·07–0·89; p=0·022). Interpretation Oxygen therapy delivered by bubble CPAP improved outcomes in Bangladeshi children with very severe pneumonia and hypoxaemia compared with standard low-flow oxygen therapy. Use of bubble CPAP oxygen therapy could have a large effect in hospitals in developing countries where the only respiratory support for severe childhood pneumonia and hypoxaemia is low-flow oxygen therapy. The trial was stopped early because of higher mortality in the low-flow oxygen group than in the bubble CPAP group, and we acknowledge that the early cessation of the trial reduces the certainty of the findings. Further research is needed to test the feasibility of scaling up bubble CPAP in district hospitals and to improve bubble CPAP delivery technology. Funding International Centre for Diarrhoeal Disease Research, Bangladesh, and Centre for International Child Health, University of Melbourne.

Elevation in serum carcinoembryonic antigen (CEA) is uncommon in the context of primary CNS neoplasms but can be seen with metastatic brain tumors. CEA elevation can be the presenting feature of a secretory meningioma (SM), a rare subtype of WHO grade I meningioma.

The purpose of this review is to summarize recent updates and distill practical points from the literature which can be applied to the care of patients with suspected and confirmed giant cell arteritis (GCA). Contemporary thinking implicates a fundamental failure of T regulatory cell function in GCA pathophysiology, representing opportunity for novel therapeutic avenues. Tocilizumab has become the first Food and Drug Administration-approved treatment for GCA following demonstration of efficacy and safety in a phase 3 clinical trial. There have been significant parallel advances in both our understanding of GCA pathophysiology and treatment. Tocilizumab, and other agents currently under investigation in phase 2 and 3 clinical trials, presents a new horizon of hope for both disease remission and avoidance of glucocorticoid-related complications.

ObjectiveTo evaluate an observational-behavioral pain tool among individuals with acute poststroke aphasia.MethodsWe performed a randomized, double-blind, controlled study of experimental pain assessment among 36 adult patients with acute poststroke aphasia. Patients were administered 3 levels of mechanical pain, including placebo. The behavioral responses were video recorded and then evaluated by 3 neurology nurses using the Pain Assessment Checklist for Seniors With Limited Ability to Communicate (PACSLAC-II). Pain-specific facial action units were quantified with FaceReader version 6.1.ResultsMedian PACSLAC-II ratings for 0-, 2-, and 4.5-lb weight stimuli were 2 (0, 3), 1 (0, 3), and 2 (1, 5), respectively. Overall, differences were not detected (p = 0.06). Pairwise comparisons with the Wilcoxon method demonstrated significance in differentiating PACSLAC-II ratings of patients experiencing the 4.5-lb stimulus vs either the 2-lb weight (p = 0.03) or placebo (p = 0.05). Overall interrater reliability by the Cronbach α was strong at 0.87, 0.94, and 0.96 for weights of 0, 2, and 4.5 lb, respectively. Pain-specific facial activation and negative valence were observed similarly in placebo and experimental pain groups.ConclusionsAmong our cohort with acute poststroke aphasia, the PACSLAC-II was not able to overall differentiate patients experiencing experimental mechanical pain, although differences in those experiencing the strongest pain stimulus were significant. The detection of pain-specific facial activation and negative valence in the placebo group indicates that pain and distress are unmet needs among stroke patients who are unable to verbally communicate.

A 15-year-old girl, previously healthy with normal developmental history, had an episode of unilateral arm jerking at school followed by transient loss of consciousness. Two weeks later, she presented to the emergency department with recurrent generalized convulsions despite treatment with lorazepam and fosphenytoin. In retrospect, her family reported a 1-month history of personality changes (i.e., listlessness) and decline in academic performance. There was no family history of epilepsy, metabolic disorders, or immunodeficiency. The patient resided in rural northeastern Kentucky. There was no recent travel history.

Objective Chronic migraine is a diagnosis that can be abstracted through the clinical history, although some providers may struggle in properly applying diagnostic criteria. We aimed to learn how well medicine trainees would be able to recognize the diagnostic criteria for chronic migraine and apply that medical knowledge to case vignettes illustrating different symptom interpretation strategies of the identical information. Methods An electronic, anonymous and multiple-choice response questionairre assessing selected trainee characteristics, headache case vignettes, and chronic migraine diagnostic criteria was distributed to all regional medicine program directors and coordinators in Kentucky and surrounding states. Program directors and coordinators could then individually decide whether or not they would forward to their trainees. The primary outcome measure was the frequency of chronic migraine recognition as a function of history style (ie, lumping versus splitting). Secondary outcome measures included recognition of chronic migraine diagnosis as a function of program affiliation (academic versus community), training year, gender, and recognition of ICHD-3 beta chronic migraine diagnostic criteria. Nominal variables were described as counts and percentages, and compared using chi-square tests. Statistical tests were considered to be two-sided and P ≤ .05 was considered to be statistically significant. Statistical analyses were performed using the JMP 11.0.0 (SAS Institute Inc., Cary, NC, USA). Results Fifty-six medicine trainees completed the survey. Episodic migraine and chronic tension-type headache were correctly recognized by 85.7% and 96.4%, respectively. Chronic migraine was recognized by a greater proportion of trainees when the identical information was presented using a lumped versus split symptom interpretation strategy (24.1% vs 3.6%, chi-square = 6.5, df =1, P = .01). Accurate recognition of chronic migraine was more likely among trainees in community versus academic/university program (40% vs 14.7%, chi-square = 4.4, df = 1, P = .03) and among male versus female trainees (33.3% vs 9.5%, chi-square = 3.9, df = 1, P = .04). Interestingly, accurate recognition of chronic migraine diagnosis was neither related to training year nor correct recognition of the ICHD-3 beta diagnostic criteria for chronic migraine. Conclusions Despite accurate individual recognition of episodic migraine and chronic tension-type headache, participants were poor at recognizing that features of these primary headache disorders can co-exist to comprise a uniform diagnosis of chronic migraine. Accurate diagnosis of chronic migraine was improved with use of a lumping strategy to the headache history.

The frequency of not being able to self-report pain after a stroke has not been previously assessed in a population-based sample. We studied the epidemiology of this problem using a cohort of patients hospitalized after a stroke in Olmsted County, Minnesota, from June 1, 2008, to June 1, 2012. Overall, 52 of 388 (13.4%) individuals were unable to provide a meaningful response to either a Faces Pain Scale or Numerical Rating Scale on admission. Inability to self-report pain was associated with measures of stroke severity (P < .0001), aphasia severity (P < .0001), and level of consciousness (P < .0001). Inability to self-report pain on admission was further associated with either subsequent death during the hospitalization (P < .0001) or an inability to provide self-report on dismissal (P < .0001). Our study further defines the epidemiology of the inability to self-report pain after a stroke as being less common than previously thought. Attempts to validate observational pain scales for poststroke patients should focus on those individuals with aphasia and/or depressed levels of consciousness.

Headache attributable to disorders of homeostasis represents a diverse diagnostic category in which external (i.e., high-altitude) or internal (i.e., fasting) demands exceed homeostatic capacity, resulting in symptomatic headaches. Metabolic headaches, especially fasting headache, have been observed to be common in the general population. In many cases, a history of migraine is a risk factor, consistent with the hypothesis of an adaptive, evolutionary role of headache to warn against environmental and physiological threats. Because many exposures may also be interpreted as migraine triggers, some authors have considered certain disorders in this category to more accurately represent primary headache disorders. Nonetheless, these disorders not only represent important clinical entities, recognition of which may prevent medical morbidity, but also interesting exposure-response models to further our understanding regarding headache pathophysiology.

The study of mechanistically defined forms of hypertension may provide insight into the relationship between hypertension and stroke. The author retrospectively studied a cohort of 23 individuals with pseudohyperaldosteronism (PHA), a condition associated with pathologic activation of the distal nephron epithelial sodium channel but low renin and aldosterone levels. During a median follow-up of 11 years (range: 1-30), 4 of 23 (17.4%) patients had a cerebrovascular event recorded. Intracranial hemorrhage was not observed in any patient. Cerebrovascular events tended to occur in older patients, minorities, and patients with a later diagnosis of PHA and additional vascular risk factors. In addition to strict blood pressure control, patients with PHA should have early evaluation and treatment of other vascular risk factors to reduce the risk of stroke.

CONTEXT: McCune-Albright syndrome (MAS) is caused by sporadic mutations of the GNAS. Patients exhibit features of acromegaly. In most patients, GH-secreting pituitary adenomas have been held responsible for this presentation. However, surgical adenomectomy rarely eliminates excess GH production. OBJECTIVE: The aim of this study was to elucidate pituitary pathology in patients with MAS and to explain the basis of failure of adenomectomy to eliminate GH hypersecretion. DESIGN AND SETTING: We conducted a case series at the National Institutes of Health. INTERVENTION(S): Interventions included medical therapy and transsphenoidal surgery. PATIENTS AND MAIN OUTCOME MEASURES: We studied clinical and imaging features and the histology and molecular features of the pituitary of four acromegalic MAS patients. RESULTS: We identified widespread and diffuse pituitary gland disease. The primary pathological changes were characterized by hyperplastic and neoplastic change, associated with overrepresentation of somatotroph cells in structurally intact tissue areas. Genetic analysis of multiple microdissected samples of any type of histological area consistently revealed identical GNAS mutations in individual patients. The only patient with remission after surgery received complete hypophysectomy in addition to removal of multiple GH-secreting tumors. CONCLUSIONS: These findings indicate developmental effects of GNAS mutation on the entire anterior pituitary gland. The pituitary of individual cases contains a spectrum of changes with regions of normal appearing gland, hyperplasia, and areas of fully developed adenoma formation, as well as transitional stages between these entities. The primary change underlying acromegaly in MAS patients is somatotroph hyperplasia involving the entire pituitary gland, with or without development of somatotroph adenoma. Thus, successful clinical management, whether it is medical, surgical, or via irradiation, must target the entire pituitary, not just the adenomas evident on imaging.

Identification of individuals with catatonic disorder secondary to a general medical condition (CD-GMC) may affect both acute and long-term patient management. The authors performed a 20-year retrospective cohort analysis of all patients meeting DSM-IV-TR criteria for catatonic subtypes seen at our institution. Encephalitis was the most common etiologic diagnosis among patients with CD-GMC, and lumbar puncture the test most likely to affect acute management. Univariate logistic-regression analysis utilizing Bonferroni correction for multiple comparisons yielded absence of a psychiatric history and history of clinical seizure as variables increasing the likelihood of a diagnosis of CD-GMC. Prospective evaluation across a larger patient series will be required to better identify patients with catatonia who would benefit from neurologic evaluation.

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

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

Comprehensively assessing the quality of prior preventive treatment attempts often reveals modifiable variables that may account for treatment failure. Similarly, a comprehensive and systematic approach when planning a preventive medication trial is critical for optimizing the chances of treatment success. In this review, we summarize the key elements to be included when assessing the adequacy of a preventive treatment trial. We have developed and included checklists that can be used by providers to improve their assessments of prior preventive treatment trials and to assist with planning a high-quality treatment trial with a new migraine preventive medication.

Episodic status migrainosus is a previously described migraine variant where the exclusive phenotype is that of relapsing status migrainosus. The majority of cases have been reported based on retrospective chart review. A prospectively identified case fulfilling previously published criteria for episodic status migrainosus is reported, with an enduring pattern of attacks meeting criteria for status migrainosus over a 35-year period. A family history in a maternal aunt of a similar phenotype was noted. This prospectively identified case further validates the existence of episodic status migrainosus as a novel nosologic entity. The family history in our case suggests the possibility of genetic susceptibility. Perspective regarding a potential temporal continuum between acute migraine, status migrainosus, and new daily persistent headache is described. Status migrainosus may occur both as a complication of migraine and in the pure form of episodic status migrainosus.

Vertigo and migraine are commonly co-occurring problems. The diagnostic criteria for vestibular migraine have recently been updated in the International Classification of Headache Disorders, 3rd edition (beta version), which allow better detection of this under-recognized condition. In many cases, a diagnosis of vestibular migraine will be established based on a typical history of concurrent migraine headache, photophobia, and/or migraine aura with the vertigo. Certain mimickers, such as Meniere’s disease, likely exist on a pathophysiologic continuum with vestibular migraine. In our review, we provide an update on the salient literature regarding the diagnosis and management of this condition.

Summary Chronic pain is highly prevalent in the ageing population. Individuals with neurological disorders such as dementia are susceptible patient groups in which pain is frequently under-recognised, underestimated, and undertreated. Results from neurophysiological and neuroimaging studies showing that elderly adults are particularly susceptible to the negative effects of pain are of additional concern. The inability to successfully communicate pain in severe dementia is a major barrier to effective treatment. The systematic study of facial expressions through a computerised system has identified core features that are highly specific to the experience of pain, with potential future effects on assessment practices in people with dementia. Various observational–behavioural pain assessment instruments have been reported to be both reliable and valid in individuals with dementia. These techniques need to be interpreted in the context of observer bias, contextual variables, and the overall state of the individual's health and wellbeing.

Background There is a growing body of literature documenting local herpes zoster outbreak following procedures. The mechanism underlying these outbreaks remains elusive. We present a case of zoster following onabotulinumtoxinA (BTX) for migraine and a literature review. Methods Chart and literature review. Case A 72-year-old woman with chronic migraine received BTX injections for 3 years without incident. She had a history of thoracic zoster with subsequent post-herpetic neuralgia. In August 2013, 48 hours after receiving BTX injections, she developed a painful rash in the right V1 distribution consistent with herpes zoster ophthalmicus. One week later the rash had resolved without treatment. Literature review We identified 65 (including 2 from Juel-Jenson) cases of zoster reactivation following minor procedures. These cases tend to be in young patients without specific risk factors. Outbreaks characteristically occur at the level of exposure to local trauma. Discussion Our review suggests that local trauma, regardless of the nature of stimuli, may be sufficient for zoster reactivation. We hypothesize that the stressors in these reported cases exert a local epigenetic influence on viral transcription, allowing for viral reactivation. Conclusion Zoster is a potential complication of BTX administration for chronic migraine in adults. Physician awareness can reduce the significant morbidity associated with this disease.

Giant cell arteritis (GCA) is a medium and large-vessel vasculitis, which is an important cause of secondary headache in older adults. While GCA has a classic presentation occurring after the age of 50, atypical presentations (eg, fever of unknown origin, cough, low or normal erythrocyte sedimentation rate) may lead to a delay in diagnosis. The topography of vascular involvement has implications for disease-related complications, which can result in neurologic disease at multiple levels of the nervous system. The most feared complication, vision loss, fortunately becomes uncommon after initiation of corticosteroids. Corticosteroid treatment should not be withheld while waiting the results of a temporal artery biopsy (TAB), which remains the gold standard for GCA diagnosis. Newer diagnostic modalities, including ultrasound, magnetic resonance imaging, and positron emission tomography can play an important role in directing treatment in cases with negative TAB. After successful control of the disorder, patients should be gradually tapered off corticosteroids, with careful monitoring using both clinical and laboratory parameters to assess for relapse. Corticosteroid-related treatment complications are not uncommon in GCA. There is mixed evidence for use of adjunct corticosteroid-sparing agents (eg, methotrexate), although these should be initiated in the setting of corticosteroid-related morbidity and/or cases with frequent relapse.

The neuralgias are characterized by pain in the distribution of a cranial or cervical nerve. While most often brief, severe, and paroxysmal, continuous neuropathic pain may occur. The most commonly encountered entities include trigeminal, postherpetic, glossopharyngeal, and occipital neuralgia. More unusual cranial neuralgias may occur in periorbital (eg, supraorbital neuralgia) and auricular (eg, nervus intermedius neuralgia) distributions. These disorders may be mimicked by structural and inflammatory/infectious neurologic disease, along with other primary headache disorders (eg, primary stabbing headache). The approach to diagnosis and treatment of this group of headache disorders is reviewed.

Medication overuse headache (MOH) is preventable and treatable. However, MOH is a major contributor to headache-related disability, affecting up to 70% of patients in headache specialty practices (1). The man- agement of MOH is complicated as patients often have difficulty stopping the overused medication and relapse rates following successful detoxification are high, con- sistent with the concept of MOH as a bio-behavioral disorder, with a shared neurobiology to addiction (2). Analgesics appear to carry varying risks for MOH among susceptible patients, with the strongest associ- ations reported for opioid- and butalbital-containing analgesics (3,4). Non-steroidal anti-inflammatory drugs (NSAIDs) carry the lowest risk, and may even be protective in the development of chronic daily head- days 1-7)), allowance for symptomatic treatment using a different medication than that previously overused (starting on day 8), and regular clinic follow-up over a 6-month period. The majority of patients were treated as outpatients (77.7%), but three centers used inpatient detoxification. For these three centers, the patients' dis- tance from the hospital and personal preferences were used to determine inpatient versus outpatient treat- ment. The subjects were mostly female, and afflicted with migraine, although 39 subjects (10.3%) had pure tension-type headache. Subjects were excluded if they had previously failed a prior detoxification protocol, were overusing 'pure' opioids, benzodiazepines or bar- biturates, were currently treated with a preventative medication, and if they had significant psychiatric comorbidity. During the 6-month observation period, a larger proportion of subjects undergoing outpatient detoxification dropped out of the study (33.9%) com- pared with those undergoing inpatient detoxification (12.5%). Based on an intention-to-treat analysis, nearly two-thirds of patients were no longer overusing medications at the end of the study protocol and nearly half had reverted to an episodic headache pattern. Further, less than 10% relapsed during months 2 through 6 (i.e. stopped overusing during month 1, but then restarted overusing between months 2 and 6). Among patients who completed the detoxification treatment, inpatient and outpatient treatment strategies had similar efficacy. The most important conclusion from this study is that MOH is a treatable condition across international borders and healthcare settings, with most patients benefiting from a combination of advice, detoxification

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

Objectives: As residency programs adjust to new duty hour restrictions, the use of cross-coverage systems requiring handoffs will rise. Handoffs are vulnerable to communication failures when unstructured. Accordingly, we implemented a standardized sign-out process on our inpatient neurology services and assessed its effect on completeness and perceived accuracy of handoffs. Methods: Residents spent the first half of their rotations utilizing unstructured sign-out. They transitioned to a structured sign-out system (using the situation-background-assessment-recommendation format) during the second half of their rotations. We analyzed survey responses before and after implementation to evaluate for an effect. Results: Residents utilizing structured sign-out were significantly more likely to share test results with patients/families prior to shift changes ( p = 0.037), update our electronic service list ( p = 0.045), and feel all important data were being transmitted ( p = 0.041). Overall satisfaction (scale 1–10) increased from 6.2 ± 1.6 to 7.4 ± 1.3 ( p = 0.002). Conclusions: Our findings demonstrate that standardized sign-out improves the completeness and perceived accuracy of handoffs. Such improvement has the potential to improve patient safety and quality of care.

While the association between migraine and depression has been well established, there is very little information as to whether effective prophylactic treatment of migraine correlates with improvement in comorbid depression.We analyzed initial visit data from migraine headache patients (n = 961) in the Mayo Headache Registry along with follow-up data (n = 389) from a subset of this cohort. Depressive symptoms were measured utilizing the Beck Depression Inventory II (BDI-II).We found a correlation between BDI-II and migraine frequency for 4 weeks and 3 months prior to the initial visit (Spearman correlation coefficient ρ = 0.335 and 0.349, respectively; p value0.0001 for both). There was a similar albeit weaker correlation between BDI-II vs. migraine intensity over the same periods prior to initial consultation (ρ = 0.147 and 0.170, respectively; p value0.0001 for both). However, there was not a significant difference in BDI-II scores for subjects with aura vs. without aura (p value = 0.12). Among those with follow-up, improvement in BDI-II correlated with a reduction in migraine frequency and intensity (p value = 0.016 and 0.089, respectively). Differences in the degree of improvement of BDI-II score in patients treated with amitriptyline vs. topiramate could not be detected (p = 0.36).BDI-II score was associated with migraine measures but not with the presence of aura at time of clinical presentation. Over follow-up time, an improvement in depression score was correlated with a reduction in migraine frequency, but was not significantly associated with medication type.

Objectives To report the clinical, laboratory, and radiographic features and the response to plasmapheresis in a patient with encephalopathy, opsoclonus, and myoclonus whose cerebrospinal fluid was positive for N-methyl-D-aspartate receptor–IgG. Design Case report. Setting St Marys Hospital, Rochester, Minnesota. Patient A 27-year-old woman with a history of episodic migraine developed subacute progressive myoclonus, opsoclonus, and encephalopathy. Results Magnetic resonance imaging demonstrated nodular leptomeningeal enhancement in the superior cerebellar folia and subsequent T2 hyperintensities in the periventricular regions and amygdala. A positron emission tomographic scan of the head demonstrated predominantly frontotemporoparietal cortical hypometabolism with sparing of the primary sensory and motor cortices. Cerebrospinal fluid examination revealed a lymphocytic pleocytosis, mildly elevated protein level, elevated IgG index, and positive oligoclonal banding. Autoimmune cerebrospinal fluid screening revealed a neural-specific IgG that bound to synapse-rich regions of mouse hippocampus and cerebellar granular layer; the neural-specific IgG was confirmed to be N-methyl-D-aspartate receptor specific. No neoplasm was detected by physical examination or by whole-body computed tomography and positron emission tomography. A 5-day course of high-dose intravenous methylprednisolone sodium succinate yielded limited improvement, and the patient subsequently required intensive care unit admission following a pulseless electrical activity arrest associated with pulmonary embolism. The encephalopathy improved dramatically after plasmapheresis. Conclusions This case highlights opsoclonus and myoclonus as manifestations of autoimmune N-methyl-D-aspartate receptor encephalitis in the setting of a novel appearance on positron emission tomography, and it shows a remarkable clinical response to plasmapheresis.

A 60-year old Muslim man was admitted to the Dhaka Hospital of ICDDR,B with an exacerbation of his chronic obstructive pulmonary disease. Incidental hyperpigmented skin lesions were noticed overlying the dorsum of his ankles, knees, and elbows. Such asymptomatic areas of thickened, lichenified and hyperpigmented skin are called ‘prayer marks’ and are well-imprinted on the knees, ankles, and forehead. These are secondary to prolonged periods of pressure over bony prominences during prayer. The patient's wife stated that the appearance of the elbow marks had coincided with an increase in his breathlessness and subsequent use of his elbows to rise from daily prayers. Prayer marks extending to the elbows could be a sign of worsening chronic disease.

We describe the case of a 59-year-old woman who presented with progressive bilateral vestibidar hypofunction and who was found to have bilateral granulomatous mass lesions of the mesial temporal lobe. Initially, her condition stabilized neurologically with corticosteroids, but a diagnosis of neurosarcoidosis was delayed because of the unusual presentation and persistently normal chest imaging results and serum angiotensin-converting enzyme (ACE) levels. Approximately 1 year after her initial presentation, the patient died of complications of a myocardial infarction and pulmonary embolism. Sarcoidosis should be considered in the differential diagnosis of idiopathic bilateral vestibular hypofunction even if the chest imaging and serum ACE levels are normal, particularly when there is evidence of a multisystem process.

Objective To identify complications of mastocytosis that impact the nervous system across a large cohort. Patients and methods In this retrospective series, we reviewed the electronic medical records of adult patients with a diagnosis of mastocytosis who were referred to a Neurologist at Mayo Clinic in Rochester, MN from January 1, 1999 to December 31, 2008. Results Thirty patients were identified who presented to a Neurologist with symptoms potentially related to the mast cell disease. Twelve of these patients presented with complex spells involving syncope, which frequently preceded a formal diagnosis of mastocytosis. Nine individuals presented with acute back pain which was ultimately deemed symptomatic of vertebral compression fractures. One individual experienced spinal cord compression from a vertebral mast cell infiltrate. Headaches were reported in 78/223 (35%) total patients with mastocytosis. Although details of headaches were insufficiently ascertained to diagnose most, the five individuals in our referral cohort met International Headache Society (IHS) criteria for migraine. Finally, three individuals (1.3%) were identified with multiple sclerosis occurring at variable times after the mast cell diagnosis. Conclusion Symptoms related to mastocytosis may be encountered by neurologists and mimic many common, often idiopathic syndromes including, syncopal spells, back pain, and headache. In our cohort, multiple sclerosis may be over-represented. Mastocytosis should be considered in patients with these presentations, especially when also accompanied by flushing, abdominal cramping or diarrhea.