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Objectives: To evaluate the short-term mortality of adult patients presenting to the emergency department (ED) with altered mental status (AMS) as compared to other common chief complaints., Methods: Observational cohort study of adult patients (age ≥ 40) who presented to an academic ED over a 1-year period with five pre-specified complaints at ED triage: AMS, generalized weakness, chest pain, abdominal pain, and headache. Primary outcomes included 7 and 30-day mortality. Hazard ratios (HR) were calculated with 95% confidence intervals (CI) using Cox proportional hazards models adjusted for age, acuity level, and comorbidities., Results: A total of 9850 ED visits were included for analysis from which 101 (1.0%) and 295 (3.0%) died within 7 and 30 days, respectively. Among 683 AMS visits, the 7-day mortality rate was 3.2%. Mortality was lower for all other chief complaints, including generalized weakness (17/1170, 1.5%), abdominal pain (32/3609, 0.9%), chest pain (26/3548, 0.7%), and headache (4/840, 0.5%). After adjusting for key confounders, patients presenting with AMS had a significantly higher risk of death within 7 days of ED arrival than patients presenting with chest pain (HR 3.72, 95% CI 2.05 to 6.76, p < .001). Similarly, we found that patients presenting with AMS had a significantly higher risk of dying within 30 days compared to patients with chest pain (HR 3.65, 95% CI 2.49 to 5.37, p < .001), and headache (HR 2.09, 95% CI 1.09 to 4.01, p = .026). Differences were not statistically significant for comparisons with abdominal pain and generalized weakness, but confidence intervals were wide., Conclusion: Patients presenting with AMS have worse short-term prognosis than patients presenting to the ED with chest pain or headache. AMS may indicate an underlying brain dysfunction (delirium), which is associated with adverse outcomes and increased mortality., Competing Interests: Declaration of Competing Interest The authors of this manuscript have no conflict of interest to disclose., (Copyright © 2021 Elsevier Inc. All rights reserved.)

The COVID-19 pandemic has infected more than 22 million people worldwide. Although much has been learned about COVID-19, we do not know much about its neurological features and their outcome. This observational study was conducted on the patients of Imam Hossein Hospital, and 361 adult patients (214 males) with confirmed diagnosis of COVID-19 from March 5, 2020 to April 3, 2020, were enrolled. Data was gathered on age, sex, comorbidities, initial symptoms, symptoms during the disease course, neurological symptoms, and outcome. The mean age of the patients was 61.90 ± 16.76 years. The most common initial symptoms were cough, fever, and dyspnea. In 21 patients (5.8%), the initial symptom was neurological. History of dementia was associated with severe COVID-19 disease (odds ratio = 1.28). During the course of the disease, 186 patients (51.52%) had at least one neurological symptom, the most common being headache (109 [30.2%]), followed by anosmia/ageusia (69, [19.1%]), and dizziness (54, [15%]). Also, 31 patients had neurological complications (8.58%). Anosmia, ageusia, dizziness, and headache were associated with favorable outcome (P < 0.001), while altered mental status and hemiparesis were associated with poor outcome. The mortality rate of patients who had neurological complications was more than twice than that of patients without neurological complication (P = 0.008). Almost half of the patients experienced at least one neurological symptom, which may be the initial presentation of COVID-19. Dementia appears to be associated with severe COVID-19. Mortality was higher in patients with neurological complications, and these patients needed more intensive care.

Introduction: Headache is one of the most frequent neurologic manifestations in COVID-19. We aimed to analyze which symptoms and laboratory abnormalities were associated with the presence of headache and to evaluate if patients with headache had a higher adjusted in-hospital risk of mortality., Methods: Retrospective cohort study. We included all consecutive patients admitted to the Hospital with confirmed SARS-CoV-2 infection between March 8th and April 11th, 2020. We collected demographic data, clinical variables and laboratory abnormalities. We used multivariate regression analysis., Results: During the study period, 576 patients were included, aged 67.2 (SD: 14.7), and 250/576 (43.3%) being female. Presence of headache was described by 137 (23.7%) patients. The all-cause in-hospital mortality rate was 127/576 (20.0%). In the multivariate analysis, patients with headache had a lower risk of mortality (OR: 0.39, 95% CI: 0.17-0.88, p = 0.007). After adjusting for multiple comparisons in a multivariate analysis, variables that were independently associated with a higher odds of having headache in COVID-19 patients were anosmia, myalgia, female sex and fever; variables that were associated with a lower odds of having headache were younger age, lower score on modified Rankin scale, and, regarding laboratory variables on admission, increased C-reactive protein, abnormal platelet values, lymphopenia and increased D-dimer., Conclusion: Headache is a frequent symptom in COVID-19 patients and its presence is an independent predictor of lower risk of mortality in COVID-19 hospitalized patients.

Background: Migraine carries a high global burden, disproportionately affects women, and has been implicated as a risk factor for cardiovascular disease. Migraine with aura has been consistently associated with increased risk of cardiovascular mortality. However, published evidence on relationships between migraine or non-migraine headache and all-cause mortality is inconclusive. Therefore, we aimed to estimate the effect of non-migraine headache and migraine as well as migraine subtypes on all-cause and cause-specific mortality in women., Methods: In total, 27,844 Women's Health Study participants, aged 45 years or older at baseline, were followed up for a median of 22.7 years. We included participants who provided information on migraine (past history, migraine without aura, or migraine with aura) or headache status and a blood sample at study start. An endpoints committee of physicians evaluated reports of incident deaths and used medical records to confirm deaths due to cardiovascular, cancer, or female-specific cancer causes. We used multivariable Cox proportional hazards models to estimate the effect of migraine or headache status on both all-cause and cause-specific mortality., Results: Compared to individuals without any headache, no differences in all-cause mortality for individuals suffering from non-migraine headache or any migraine were observed after adjustment for confounding (HR = 1.01, 95%CI, 0.93-1.10 and HR = 0.96, 95% CI: 0.89-1.04). No differences were observed for the migraine subtypes and all-cause death. Women having the migraine with aura subtype had  a higher mortality due to cardiovascular disease (adjusted HR = 1.64, 95%CI: 1.06-2.54). As an explanation for the lack of overall association with all-cause mortality, we observed slightly protective signals for any cancer and female-specific cancers in this group., Conclusions: In this large prospective study of women, we found no association between non-migraine headache or migraine and all-cause mortality. Women suffering from migraine with aura had an increased risk of cardiovascular death. Future studies should investigate the reasons for the increased risk of cardiovascular mortality and evaluate whether changes in migraine patterns across the life course have differential effects on mortality.

Acute invasive fungal rhinosinusitis (AIFRS) can spread beyond the sinonasal cavity. It is necessary to analyze the association between the specific site involved in the extrasinonasal area and the survival rate to predict patient prognosis. We investigated 50 patients who had extrasinonasal lesions on preoperative gadolinium (Gd)-enhanced magnetic resonance imaging (MRI) scan and underwent wide surgical resection of AIFRS. The specific sites with loss of contrast enhancement (LoCE) on Gd-enhanced MRI were analyzed for AIFRS-specific survival rate. The most common underlying disease was diabetes mellitus followed by hematological malignancy. The most common symptoms were headache and facial pain. Seven patients (14.0%) expired because of AIFRS progression. Poor prognosis was independently associated with LoCE at the skull base on preoperative MRI (HR = 35.846, P = 0.004). In patients with AIFRS extending to the extrasinonasal area, LoCE at the skull base was an independent poor prognostic factor.

Background: Severe headaches, projectile vomiting, focal neurological deficits and early onset seizure are regarded as early warning symptoms of subarachnoid hemorrhage (SAH). Earlier diagnosis based on such warning symptoms theoretically would improve the clinical prognosis. However, it is still not clear whether the prognosis is correlated with early warning symptoms. Here, we reviewed warning symptoms and other predictive factors in the emergency room (ER) setting and examined their correlations with mortality., Methods: Ninety saccular aneurysmal SAH cases were reviewed in a single medical center between January 2011 and December 2013. We examined differences in mortality rate related to warning symptoms, SAH scales, onset-to-ER time, hydrocephalus, and aneurysm size, location, and complexity. Logistic regression analyses were performed to determine the correlations of warning symptoms and other predictive factors with mortality. Receiver operating characteristic (ROC) curve analysis was used to calculate the area the under curve (AUC) of SAH mortality prediction tools., Results: Warning headache, projectile vomiting, the Hunt and Hess scale, Fisher scale, World Federation of Neurological Surgeons (WFNS) grading scale, and modified WFNS (m-WFNS) scale, body mass index, aneurysm complexity and hydrocephalus were significantly different between the survivors and the decedents. The warning headache and WFNS grade were strongly correlated with mortality. The rate of prognostic prediction improved from 90.4% to 94.6% when warning headache was additionally evaluated., Conclusions: With growing healthcare costs and recognition of the value of palliative care, early identification via warning headache and a detailed clinical history review is necessary for cases of aSAH., (Copyright © 2019 Chang Gung University. Published by Elsevier B.V. All rights reserved.)

From April to September 2017, Bangladesh experienced a huge outbreak of acute Chikungunya virus infection in Dhaka. This series describes the clinical and laboratory features of a large number of cases (690; 399 confirmed and 291 probable) suffered during that period. This observational study was carried out at Dhaka Medical College Hospital, Bangladesh. The median age of the patients at presentation was 38 years (IQR 30-50) with a male (57.3%) predominance. Hypertension and diabetes were the most common comorbidities. The mean (±SD) duration of fever was 3.7 (±1.4) days. Other common manifestations were arthralgia (99.2%), maculopapular rash (50.2%), morning stiffness (49.7%), joint swelling (48.5%), and headache (37.6%). Cases were confirmed by anti-chikungunya IgG (173; 43.3%), IgM (165; 42.3%), and reverse transcription polymerase chain reaction (44; 11.0%). Important laboratory findings include high erythrocyte sedimentation rate (156; 22.6%), raised serum glutamic pyruvic transaminase (73; 10.5%), random blood sugar (54; 7.8%), leukopenia (72; 10.4%), thrombocytopenia (41; 5.9%), and others. The oligo-articular (453; 66.1%) variety of joint involvement was significantly more common compared with the poly-articular (237; 34.5%) variety. Commonly involved joints were the wrist (371; 54.1%), small joints of the hand (321; 46.8%), ankle (251; 36.6%), knee (240; 35.0%), and elbow (228; 33.2%). Eleven cases were found to be complicated with neurological involvement and two of them died. Another patient died due to myocarditis. Public health experts, clinicians, and policymakers could use the results of this study to construct the future strategy tackling chikungunya in Bangladesh and other epidemic countries.

Introduction: This study investigated whether a 9.6% decrease in the use of head computed tomography (HCT) for patients presenting to the emergency department (ED) with a chief complaint of headache was followed by an increase in proportions of death or missed intracranial diagnosis during the 22.5-month period following each index ED visit., Methods: We reviewed the electronic medical records of all patients sampled during a quality improvement effort in which the aforementioned decrease in HCT use had been observed. We reviewed notes from the ED, neurology, neurosurgery, and primary care services, as well as all brain imaging results to determine if death occurred or if an intracranial condition was discovered in the 22.5 months after each index ED visit. An independent, blinded reviewer reviewed each case where an intracranial condition was diagnosed after ED discharge to determine whether the condition was reasonably likely to have been related to the index ED visit's presentation, thereby representing a missed diagnosis., Results: Of the 582 separate index ED visits sampled, we observed a total of nine deaths and 10 missed intracranial diagnoses. There was no difference in the proportion of death (p = 0.337) or missed intracranial diagnosis (p = 0.312) observed after a 9.6% reduction in HCT use. Among patients who subsequently had visits for headache or brain imaging, we found that these patients were significantly more likely to have not had a HCT done during the index ED visit (59.2% vs. 49.6% (p = 0.031) and 37.1% vs. 26% (p = 0.006), respectively)., Conclusion: Our study adds to the compelling evidence that there is opportunity to safely decrease CT imaging for ED patients. To determine the cost effectiveness of such reductions further research is needed to measure what patients and their healthcare providers do after discharge from the ED when unnecessary testing is withheld., Competing Interests: Conflicts of Interest: By the WestJEM article submission agreement, all authors are required to disclose all affiliations, funding sources and financial or management relationships that could be perceived as potential sources of bias. No author has professional or financial relationships with any companies that are relevant to this study. There are no conflicts of interest or sources of funding to declare.

Purpose: The aim of this study is to describe the symptoms and signs of central nervous system (CNS) tumors in a pediatric population and to assess the time interval between the onset of the disease and the time of the diagnosis., Methods: A retrospective observational study was conducted at our Oncology Pediatric Unit between January 2000 and November 2011. We included 75 children between 5 months and 16 years (mean age of 7.8 ± 4.7 years), with male to female ratio of 3:2. The tumor localization was supratentorial in 51% of cases, and the most frequent histological type was low-grade astrocytoma (48%)., Results: Presenting symptoms were headache (31%), vomiting (31%), seizures (21%), and behavioral change (11%). The most common symptoms at diagnosis were headache (51%), vomiting (51%), visual difficulties (37%), seizures (24%), and behavioral change (21%). By the time of diagnosis, neurologic examination was altered in 68% of our patients. Vomiting (44%) and behavioral change (44%) were the most frequent symptoms in children under 4 years of age, headache (61%) and vomiting (54%) in children older than 4 years. The median interval between symptoms' onset and diagnosis was 4 weeks (range 0 to 314 weeks). A longer symptom interval was associated with younger age, infratentorial localization and low-grade tumors. The differences in symptom intervals between the different age, location, and grade groups were not statistically significant. Survival probability was influenced by tumor grade but not by diagnostic delay or age of the child., Conclusions: Headache and vomiting are the earliest and commonest symptoms in children with brain tumors. Visual symptoms and signs and behavioral change are often present. Abnormalities in neurological examination are reported in most of the children. Intracranial hypertension symptoms suggest the need for a neurological clinical examination and an ophthalmological assessment.

Objective: To accurately describe patient characteristics and the clinical presentation of fatal colloid cysts., Methods: A systematic literature search of 3 popular databases was performed. Inclusion criteria were individuals with sudden-onset death and colloid cysts identified on imaging and/or autopsy. The cause of death must have been ascribed to the colloid cyst to be eligible for data extraction. Deaths precipitated by lumbar puncture were excluded. Clinical data were extracted and descriptive statistics were ascertained. Subgroup analyses were performed to compare adults with pediatric patients., Results: A total of 107 patients were included in the quantitative synthesis. The mean age was 28.5 years (standard deviation 13.3, range 6-79 years). Male and female patients were affected equally. Headache was the most frequent symptom (n = 86, 80%). There were 6 patients (5 adults and 1 child) who reported positional headaches. The mean duration of signs and symptoms was shorter in adults versus pediatric patients (2.1 days vs. 6.5 days, P = 0.02), and more adults presented with signs and symptoms for less than 24 hours than did pediatric patients (38% vs. 6%, P = 0.01). Colloid cyst mean diameter was 2.0 cm (standard deviation 1.1, range 0.5-7.9 cm) and 96% measured 1 cm or larger., Conclusions: Our data suggests that the prodrome preceding sudden death in the setting of a colloid cyst may be shorter in adults. Also, most fatal colloid cysts measured 1 cm or larger., (Copyright © 2017. Published by Elsevier Inc.)

Objective: Metastatic brain tumors are the most common brain tumors in adults. Patients with metastatic brain tumors have poor prognoses with median survival of 6-12 months. Seizures are a major presenting symptom and cause of morbidity and mortality. In this article, risk factors for the onset of preoperative seizures and postoperative seizure control are examined., Methods: Adult patients who underwent resection of one or more brain metastases at a single institution between 1998 and 2011 were reviewed retrospectively., Results: Of 565 patients, 114 (20.2%) patients presented with seizures. Factors independently associated with preoperative seizures were preoperative headaches (P = 0.044), cognitive deficits (P = 0.031), more than 2 intracranial metastatic tumors (P = 0.013), temporal lobe location (P = 0.031), occipital lobe location (P = 0.010), and bone involvement by tumor (P = 0.029). Factors independently associated with loss of seizure control after surgical resection were preoperative seizures (P = 0.001), temporal lobe location (P = 0.037), lack of postoperative chemotherapy (P = 0.010), subtotal resection of tumor (P = 0.022), and local recurrence (P = 0.027). At last follow-up, the majority of patients (93.8%) were seizure-free. Thirty patients (5.30%) in total had loss of seizure control, and only 8 patients (1.41%) who did not have preoperative seizures presented with new-onset seizures after surgical resection of their metastases., Conclusions: The brain is a common site for metastases from numerous primary cancers, such as breast and lung. The identification of factors associated with onset of preoperative seizures as well as seizure control postoperatively could aid management strategies for patients with metastatic brain tumors. Patients with preoperative seizures who underwent resection tended to have good seizure control after surgery., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Objective: To evaluate headache severity, and its correlation with clinical, cerebrospinal fluid, and neuroimaging parameters of tuberculous meningitis (TBM) patients, and its impact on outcome., Methods: This prospective observational study was conducted at King George`s Medical University, Lucknow, India between October 2012 and March 2014. Ninety-five newly diagnosed TBM patients underwent detailed clinical, laboratory, and neuroimaging evaluation. A numeric rating scale was used to assess the headache severity, and patients were grouped into mild, moderate, severe, and intolerable groups. Patient outcome was evaluated at 6-months follow up., Results: Holocranial stabbing type headache (p=0.002), modified Barthel index &#8804;12 (p<0.001), diplopia (p=0.055), seizures (p<0.001), visual impairment (p=0.024), cranial nerve palsy (p=0.002), meningeal signs (p=0.016), definite cases of TBM (p=0.001), British Medical Research Council stage III (p<0.001), and CSF protein >2.5 g/l (p<0.001) were significantly associated with severity of headache. Neuroradiological features significantly associated with severity of headache were meningeal enhancement (p=0.015), basal exudates (p<0.001), and hydrocephalus (p=0.003). Eleven out of 15 patients who died had intolerable headache at admission. Significant predictors of poor outcome in severe and intolerable headache groups were CSF protein>2.5g/L, cranial nerve palsies, paraparesis, and infarcts. Patients of the mild and moderate headache group were headache free at 6 months follow up with good outcome., Conclusion: Severity of headache was associated with multiple clinical, CSF protein, and radiological factors. As intolerable and severe headache had an unfavorable impact on outcome, we could prognosticate the TBM patients on the basis of headache severity.

Background: There is conflicting evidence for the association between migraine and increased mortality risk. The aim of this study was to investigate the relationship between migraine and non-migrainous headache, and all-cause mortality and cardiovascular mortality., Methods: In this prospective population-based cohort study from Norway, we used baseline data from the second Nord-Trøndelag Health Survey (HUNT2), performed between 1995 and 1997 in the County of Nord-Trøndelag. These data were linked with a comprehensive mortality database with follow-up through the year 2011. A total of 51,853 (56% of invited) people were categorized based on their answers to the headache questions in HUNT2 (headache free, migraine or non-migrainous headache). Hazard ratios (HRs) of mortality during a mean of 14.1 years of follow-up were estimated using Cox regression., Results: During the follow-up period 9408 died, 4321 of these from cardiovascular causes. There was no difference in all-cause mortality between individuals with migraine and non-migrainous headache compared to those without headache or between headache status and mortality by cardiovascular disease. There was, however, among men with migraine without aura a reduced risk of death by cardiovascular diseases (HR 0.72, 95% confidence interval 0.56-0.93). This relationship was not evident in women., Conclusion: In this large, prospective cohort study there was no evidence for a higher all-cause mortality or cardiovascular mortality among individuals with migraine., (© International Headache Society 2015.)

Thrombotic thrombocytopenia purpura (TTP) and atypical hemolytic uremic syndromes (aHUS) are distinct clinical disorders characterized by hemolytic anemia, thrombocytopenia, microthrombi, and end organ damage. TTP is characterized by a low ADAMTS13 activity level at diagnosis of <10 % ADAMTS13 activity, while aHUS is characterized as having >10 % ADAMTS13 activity. Despite clinical remission, survivors of thrombotic microangiopathy suffer significant comorbidity and decreased quality of life (QOL) than their healthy counterparts. The reason for this is unclear. Is it a lingering effect from their initial acute episode or ongoing subclinical injury/inflammation despite clinical remission? Common clinical complaints validated in practice include increased depression, deficits in memory, concentration, mood, and mental endurance. We suspect headaches may be an important clinical tool toward understanding patient morbidity and decreased QOL. To date, no studies report headache frequency or severity in this population. To answer this question, adult patients >3 months since their last acute episode of TTP or aHUS were approached to take a Headache Impact Test (HIT-6) survey. Between June 1, 2013 and May 30, 2014, 31 patients in remission (21 patients with prior TTP and 10 patients with prior aHUS) completed the HIT-6 survey. The survey scores were then compared to the HIT-6 normative population data established by Qualitymetric incorporated. Overall, TTP patients had a significantly higher average HIT-6 score of 59.9 compared to an average HIT-6 score of 51 seen in sex-matched controls (SD 9.6, p value 0.002). No significant difference was seen in the HIT-6 scores of aHUS patients. Of TTP patients studied, approximately 57 % (12/21) had three or more episodes and were >24 months since the last episode. The average time since last acute episode in TTP patients was 37.5 months. There was no significant correlation between TTP survivor HIT-6 scores and the number of prior episodes (1, 2, or >3) or timing from the last episode (3-6, 7-12, 13-24, or >24 months). About 19/21 (90 %) patients, who are TTP survivors, also had a normal ADAMTS13 activity level (>10 %) on the day of the survey. Our study suggests that headaches have significant impact on TTP survivors and should be followed in the clinical setting to prevent undue patient morbidity. Larger studies are needed to understand how headaches impact long-term survival and risk of relapse.

A 47-year-old man with a severe headache disorder, taking meperidine injections 8 to 12 times a day and approximately 6 butalbital-containing tablets per day, was denied hospitalization for the management of headache and died while awaiting evaluation for detoxification by a psychiatric facility. The criteria for hospitalization and the implications of the denial of care by insurance companies are explored. The biases against the publication of such cases are reviewed.

The aim of this study is to analyse how the mortality risk varies with mild or severe pain in different locations: chest, back and hips, shoulders, the extremities, abdomen, rectum and head. A Swedish nationally representative sample of 1930 persons born 1892-1915 were interviewed in 1968 (ages 53-76). Survivors were also interviewed in 1974 and 1981 if they had not passed the age of 75 years. Proportional hazard regression was used to analyze mortality risk among persons ages 53-98 years for the period 1968-1991. Relationships were found between mortality risk and headache, chest pain, abdominal pain, pain in the extremities and rectal pain. No relationships were found between mortality and pain in back and hips or in shoulders. There was a correlation between chest pain and increased mortality among both men and women, but the association was significantly stronger among men. There was a significant association between severe rectal pain and mortality among men but no similar association among women. Significant associations between mortality and chest pain and abdominal pain were found among persons younger than 80 years, but not among those older than 80 years. Pain is an indicator of the quality of life and a symptom of underlying medical conditions. The finding that there are relationships between mortality risk and pain in the chest, abdomen, rectum, the extremities and head may be of clinical relevance. These results, however, must be further investigated since the relationships between reported pain and mortality do not imply that pain in these locations is necessarily symptomatic of lethal diseases. Abdominal pain, rectal pain and headache may be indicators of diseases but can also be side effects of treatments for other diseases correlated with higher mortality.

In a prospective study of 178 episodes of community-acquired native valve infective endocarditis seen at St Thomas' Hospital between 1969 and 1987, 59 patients (33 per cent) presented with neurological disorders that included meningitis, toxic confusion, major thromboembolic phenomena and headache. A neurological presentation occurred in 54 per cent of all cases of staphylococcal endocarditis, but in only 19 per cent of episodes of 'viridans' streptococcal and enterococcal endocarditis. Overall one-third of patients with staphylococcal endocarditis presented with clinical features of meningitis (40 per cent with no cardiac murmur). The mortality rate for community-acquired native valve endocarditis was higher for those with a neurological presentation than without.