Six Year Old With Chronic Headache: An Unexpected Meningitis Mimic.

The constellation of fevers accompanied by headache and vomiting is a red flag for clinicians that appropriately triggers evaluation for meningitis and other life-threatening diagnoses. When symptoms persist even after these conditions are ruled out, patient care becomes more challenging. We present the case of a 6-year-old male with a history of autism spectrum disorder who presented with 6 months of headaches and associated vomiting and intermittent fevers with negative infectious workup despite cerebrospinal fluid pleocytosis. Serial neuroimaging and laboratory evaluation ultimately led to a diagnosis of myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD) presenting as aseptic meningitis. The clinical and radiographic findings of MOGAD are widely variable and overlap with several other inflammatory conditions, which makes diagnosis challenging. This case highlights the importance of recognizing this rare MOGAD presentation as an infectious meningitis mimic.

A comprehensive analysis of patients with cerebral arteriovenous malformation with headache: assessment of risk factors and treatment effectiveness.

BACKGROUND: Due to the high mortality and disability rate of intracranial hemorrhage, headache is not the main focus of research on cerebral arteriovenous malformation (AVM), so research on headaches in AVM is still scarce, and the clinical understanding is shallow. This study aims to delineate the risk factors associated with headaches in AVM and to compare the effectiveness of various intervention treatments versus conservative treatment in alleviating headache symptoms. METHODS: This study conducted a retrospective analysis of AVMs who were treated in our institution from August 2011 to December 2021. Multivariable logistic regression analysis was employed to assess the risk factors for headaches in AVMs with unruptured, non-epileptic. Additionally, the effectiveness of different intervention treatments compared to conservative management in alleviating headaches was evaluated through propensity score matching (PSM). RESULTS: A total of 946 patients were included in the analysis of risk factors for headaches. Multivariate logistic regression analysis identified that female (OR 1.532, 95% CI 1.173-2.001, p = 0.002), supply artery dilatation (OR 1.423, 95% CI 1.082-1.872, p = 0.012), and occipital lobe (OR 1.785, 95% CI 1.307-2.439, p < 0.001) as independent risk factors for the occurrence of headaches. There were 443 AVMs with headache symptoms. After propensity score matching, the microsurgery group (OR 7.27, 95% CI 2.82-18.7 p < 0.001), stereotactic radiosurgery group(OR 9.46, 95% CI 2.26-39.6, p = 0.002), and multimodality treatment group (OR 8.34 95% CI 2.87-24.3, p < 0.001) demonstrate significant headache relief compared to the conservative group. However, there was no significant difference between the embolization group (OR 2.24 95% CI 0.88-5.69, p = 0.091) and the conservative group. CONCLUSIONS: This study identified potential risk factors for headaches in AVMs and found that microsurgery, stereotactic radiosurgery, and multimodal therapy had significant benefits in headache relief compared to conservative treatment. These findings provide important guidance for clinicians when developing treatment options that can help improve overall treatment outcomes and quality of life for patients.

Post-Covid Conditions and their Effects on the Cardiovascular System.

Background: Rising global concerns about COVID-19 recently gained more research attention due to the ease of person-to-person transmission, various symptoms after healing, and the shortage of effective antiviral therapy. The study aims to analyze post-COVID conditions and clinical manifestations of cardiovascular lesions in patients recovering from COVID-19 infection. Methods: A practical examination of post-COVID conditions manifestation was conducted in a prospective cohort study, involving 250 patients diagnosed with COVID-19 between June 1, 2021, and August 31, 2021. The study specifically focused on analyzing the cardiovascular effects of COVID-19, utilizing data from a subgroup of 200 patients previously discharged from the hospital with elevated troponin levels. The cardiovascular variables assessed included tachycardia, ischemia, heart attack, myocarditis, hypertension, blood clots, and heart failure. Results: It has been observed that among surviving patients, the following symptoms persisted: anosmia/ageusia (59%), severe dyspnea (36.7%), palpitations and complaints related to the cardiovascular sys-tem (15.8%), headaches (13.2%), arthralgia (11.7%), myalgia (9.8%), and hair problems (≥5%). By the 60th day, a reduction in symptoms by 5-10% was noted, and by the 90th day, a decrease in activity by 25-35% was observed. Patients aged 40-60 years exhibited the highest percentage of cardiovascular diseases (75%). Conclusions: Consequently, the SARS-CoV-2 virus underscores the critical importance of cardiological attention in patient care. Cardiac screening results in individuals with COVID-19 reveal a significant prevalence of serious heart problems, affecting over half of the patients. This emphasizes the necessity for heightened vigilance and specialized cardiac care when managing patients with COVID-19.

PACAP38/mast-cell-specific receptor axis mediates repetitive stress-induced headache in mice.

BACKGROUND: Pain, an evolutionarily conserved warning system, lets us recognize threats and motivates us to adapt to those threats. Headache pain from migraine affects approximately 15% of the global population. However, the identity of any putative threat that migraine or headache warns us to avoid is unknown because migraine pathogenesis is poorly understood. Here, we show that a stress-induced increase in pituitary adenylate cyclase-activating polypeptide-38 (PACAP38), known as an initiator of allosteric load inducing unbalanced homeostasis, causes headache-like behaviour in male mice via mas-related G protein-coupled receptor B2 (MrgprB2) in mast cells. METHODS: The repetitive stress model and dural injection of PACAP38 were performed to induce headache behaviours. We assessed headache behaviours using the facial von Frey test and the grimace scale in wild-type and MrgprB2-deficient mice. We further examined the activities of trigeminal ganglion neurons using in vivo Pirt-GCaMP Ca2+ imaging of intact trigeminal ganglion (TG). RESULTS: Repetitive stress and dural injection of PACAP38 induced MrgprB2-dependent headache behaviours. Blood levels of PACAP38 were increased after repetitive stress. PACAP38/MrgprB2-induced mast cell degranulation sensitizes the trigeminovascular system in dura mater. Moreover, using in vivo intact TG Pirt-GCaMP Ca2+ imaging, we show that stress or/and elevation of PACAP38 sensitized the TG neurons via MrgprB2. MrgprB2-deficient mice showed no sensitization of TG neurons or mast cell activation. We found that repetitive stress and dural injection of PACAP38 induced headache behaviour through TNF-a and TRPV1 pathways. CONCLUSIONS: Our findings highlight the PACAP38-MrgprB2 pathway as a new target for the treatment of stress-related migraine headache. Furthermore, our results pertaining to stress interoception via the MrgprB2/PACAP38 axis suggests that migraine headache warns us of stress-induced homeostatic imbalance.

Headache alleviation with nasal irrigation following endoscopic endonasal surgery for pituitary adenomas.

BACKGROUND: Headache is a common occurrence after endoscopic endonasal surgery (EES) for pituitary adenomas and significantly impacts the quality of life of patients. This study aims to investigate the effectiveness of nasal irrigation in relieving postoperative headache after EES. METHODS: A retrospective analysis was conducted on a cohort of 101 patients (Cohort I) who underwent EES for pituitary adenomas to explore the risk factors associated with postoperative headache. Another cohort of 72 patients (Cohort II) who received adjuvant nasal irrigation following surgery was enrolled for further analysis. The Headache Impact Test (HIT-6) was used to score the severity of headache, and patients with a HIT score > 55 were classified as having headache. RESULTS: In Cohort I, 21.78% of patients experienced headache one month after EES, which decreased to 5.94% at the three-month follow-up. Multivariate analysis revealed that postoperative nasal sinusitis (OR = 3.88, 95%CI 1.16-13.03, p = 0.028) and Hardy's grade C-D (OR = 10.53, 95%CI 1.02-109.19, p = 0.049) independently predicted the presence of postoperative headache at one month. At the three-month follow-up, patients with sinusitis had higher HIT-6 scores compared to those without sinusitis (44.43 ± 9.78 vs. 39.72 ± 5.25, p = 0.017). In Cohort II, the incidence of sinusitis at three months was significantly lower than that in Cohort I (p = 0.028). Importantly, both the incidence of headache and HIT-6 scores in Cohort II were significantly lower than those in Cohort I at the one- and three-month follow-ups. CONCLUSIONS: Postoperative sinusitis is an independent risk factor for the development of headache following EES for pituitary adenomas. Prophylactic nasal irrigation helps relieve postoperative headache, possibly by preventing the occurrence of sinusitis.

Headache in Multiple Sclerosis: A Narrative Review.

Background: Multiple sclerosis (MS) is a chronic inflammatory demyelinating disorder of the central nervous system characterized by autoimmune-mediated damage to oligodendrocytes and subsequent myelin destruction. Clinical implications: Clinically, the disease presents with many symptoms, often evolving over time. The insidious onset of MS often manifests with non-specific symptoms (prodromal phase), which may precede a clinical diagnosis by several years. Among them, headache is a prominent early indicator, affecting a significant number of MS patients (50-60%). Results: Headache manifests as migraine or tension-type headache with a clear female predilection (female-male ratio 2-3:1). Additionally, some disease-modifying therapies in MS can also induce headache. For instance, teriflunomide, interferons, ponesimod, alemtuzumab and cladribine are associated with an increased incidence of headache. Conclusions: The present review analyzed the literature data on the relationship between headache and MS to provide clinicians with valuable insights for optimized patient management and the therapeutic decision-making process.

Are the ICHD-3 criteria for headache attributed to idiopathic intracranial hypertension valid? Headache phenotyping and field-testing in newly diagnosed idiopathic intracranial hypertension.

BACKGROUND: Headache burden is substantial in idiopathic intracranial hypertension. The classification of idiopathic intracranial hypertension headache by the International Classification of Headache Disorders (ICHD) is an important tool for research and clinical purposes. METHODS: We phenotyped headaches and tested sensitivity and specificity of the ICHD-3 criteria for idiopathic intracranial hypertension headache in a prospective cohort of patients suspected of idiopathic intracranial hypertension at two tertiary headache centers. RESULTS: Sensitivity was 93% and specificity was 100% of ICHD-3 criteria for idiopathic intracranial hypertension-related headache validated in idiopathic intracranial hypertension (n = 140) and patients in whom idiopathic intracranial hypertension was suspected but disproven (n = 103). The phenotype of new/worsened headaches related to idiopathic intracranial hypertension suspicion was equally migraine-like (p = 0.76) and tension-type-like (p = 0.08). Lumbar puncture opening pressure was higher (p < 0.0001) and pulsatile tinnitus more frequent (p < 0.0001) in idiopathic intracranial hypertension patients, but neither improved the applicability of the headache criteria, nor did papilledema. CONCLUSION: Headache phenotype is not distinct in idiopathic intracranial hypertension. ICHD-3 criteria for idiopathic intracranial hypertension headache are sensitive and specific, but simplicity can be improved without compromising accuracy. We propose that a new or worsened headache temporally related to active idiopathic intracranial hypertension is a sufficient criterion for idiopathic intracranial hypertension headache regardless of headache phenotype or accompanying symptoms, and that elements of idiopathic intracranial hypertension diagnostics (papilledema and opening pressure) be segregated from headache criteria.Trial Registration: ClinicalTrials.gov Identifier: NCT04032379.

Predictive performance of the common red flags in emergency department headache patients: a HEAD and HEAD-Colombia study.

OBJECTIVES: Only a small proportion of patients presenting to an ED with headache have a serious cause. The SNNOOP10 criteria, which incorporates red and orange flags for serious causes, has been proposed but not well studied. This project aims to compare the proportion of patients with 10 commonly accepted red flag criteria (singly and in combination) between patients with and without a diagnosis of serious secondary headache in a large, multinational cohort of ED patients presenting with headache. METHODS: Secondary analysis of data obtained in the HEAD and HEAD-Colombia studies. The outcome of interest was serious secondary headache. The predictive performance of 10 red flag criteria from the SNNOOP10 criteria list was estimated individually and in combination. RESULTS: 5293 patients were included, of whom 6.1% (95% CI 5.5% to 6.8%) had a defined serious cause identified. New neurological deficit, history of neoplasm, older age (>50 years) and recent head trauma (2-7 days prior) were independent predictors of a serious secondary headache diagnosis. After adjusting for other predictors, sudden onset, onset during exertion, pregnancy and immune suppression were not associated with a serious headache diagnosis. The combined sensitivity of the red flag criteria overall was 96.5% (95% CI 93.2% to 98.3%) but specificity was low, 5.1% (95% CI 4.3% to 6.0%). Positive predictive value was 9.3% (95% CI 8.2% to 10.5%) with negative predictive value of 93.5% (95% CI 87.6% to 96.8%). CONCLUSION: The sensitivity and specificity of the red flag criteria in this study were lower than previously reported. Regarding clinical practice, this suggests that red flag criteria may be useful to identify patients at higher risk of a serious secondary headache cause, but their low specificity could result in increased rates of CT scanning. TRIAL REGISTRATION NUMBER: ANZCTR376695.

Shifts in Diagnostic Testing for Headache in the Emergency Department, 2015 to 2021.

Importance: Subarachnoid hemorrhage is typically diagnosed by noncontrast head computed tomography (CT); lumbar puncture is recommended if computed tomography is nondiagnostic, although CT cerebral angiography has been promoted as an alternative to lumbar puncture in this diagnostic pathway. The outcomes of this debate in practice have not been studied. Objective: To determine whether CT cerebral angiography use has increased in lieu of lumbar puncture among emergency department (ED) patients with headache, with an increase in unruptured intracranial aneurysm detection. Design, Setting, and Participants: This retrospective cohort study took place in 21 community EDs of an integrated health care system in Northern California between 2015 and 2021. Participants were adult (aged >17 years) health plan members with a chief concern of headache. Exclusions were prior diagnoses of subarachnoid hemorrhage, unruptured intracranial aneurysm, cerebral arteriovenous malformation, or cerebrospinal fluid shunt. Data were analyzed from October to November 2023. Exposures: CT cerebral angiography and/or lumbar puncture during the ED encounter. Main Outcomes and Measures: Primary and secondary outcomes were 14-day and 90-day unruptured intracranial aneurysm detection, respectively. Safety outcomes were missed diagnoses of subarachnoid hemorrhage or bacterial meningitis. The annual incidence of unruptured intracranial aneurysm detection was normalized to the incidence of subarachnoid hemorrhage (UIA:SAH ratio). Average annualized percentage changes were quantified using joinpoint regression analysis. Results: Among 198 109 included ED encounters, the mean (SD) age was 47.5 (18.4) years; 140 001 patients (70.7%) were female; 29 035 (14.7%) were Black or African American, 59 896 (30.2%) were Hispanic or Latino, and 75 602 (38.2%) were White. Per year, CT cerebral angiography use increased (18.8%; 95% CI, 17.7% to 20.3%) and lumbar punctures decreased (-11.1%; 95% CI, -12.0% to -10.4%), with a corresponding increase in the 14-day UIA:SAH ratio (3.5%; 95% CI, 0.9% to 7.4%). Overall, computed tomography cerebral angiography use increased 6-fold relative to lumbar puncture, with a 33% increase in the detection of UIA. Results were similar at 90 days and robust to sensitivity analyses. Subarachnoid hemorrhage (1004 cases) and bacterial meningitis (118 cases) were misdiagnosed in 5% and 18% of cases, respectively, with no annual trends (P = .34; z1003 = .95 and P = .74; z117 = -.34, respectively). Conclusions and Relevance: In this cohort study of ED patients with headache, increases in CT cerebral angiography use were associated with fewer lumbar punctures and higher detection of unruptured intracranial aneurysms, with no significant change in missed diagnoses of subarachnoid hemorrhage or bacterial meningitis. While this shift in diagnostic strategy appeared safe in the short-term, the long-term consequences remain unclear.

Idiopathic intracranial hypertension associated with SARS-CoV-2 infection in an adult male patient: a case report and review of the literature.

BACKGROUND: Headache is a frequent symptom in coronavirus disease 2019 (COVID-19) patients, and idiopathic intracranial hypertension (pseudotumor cerebri) has been reported among patients who underwent lumbar puncture for persistent headaches. CASE PRESENTATION: A 45-year-old black man presented with dyspnea, cough, fever and headache for 05 days followed by blurring of vision associated with worsening of the headache. Physical examination was significant for tachypnea and oxygen desaturation and there were no abnormal neurologic findings. He tested positive for SARS-CoV-2 with nasopharyngeal swab PCR. His CSF opening pressure appeared high with normal CSF analysis and brain magnetic resonance imaging (MRI) revealed prominent subarachnoid space around the optic nerves and bilateral papilledema. He had significant improvement with medical therapy alone. CONCLUSION: Idiopathic intracranial hypertension (IIH) may occur in association with SARS-CoV-2 infection and should be considered when making a differential diagnosis for headache and blurring of vision. COVID-19 may play a role in the development of intracranial hypertension, even in the absence of known risk factors. Early diagnosis and treatment of IIH has paramount importance to prevent vision loss and other morbidities.

Cranial Neuralgias.

OBJECTIVE: The cranial neuralgias are relatively rare, but recognizing these syndromes and distinguishing among them is critical to reducing unnecessary pain and disability for affected patients. Despite their distinctive features, cranial neuralgias may go undiagnosed or misdiagnosed for several years. A notable proportion of cranial neuralgia presentations are due to secondary causes and require targeted treatment. The purpose of this article is to review the diagnosis and management of cranial neuralgias encountered in clinical practice. LATEST DEVELOPMENTS: In 2020, the International Classification of Orofacial Pain was released for the first time. Modeled after the International Classification of Headache Disorders, it includes updated terminology for cranial neuralgias. The underlying pathophysiology of the cranial neuralgias is currently believed to be rooted in both peripheral and central nociceptive systems. In addition, a growing number of familial cases are being identified. Recent therapeutic advancements include a better understanding of how to utilize older therapies and procedures more effectively as well as the development of newer approaches. ESSENTIAL POINTS: Cranial neuralgia syndromes are rare but important to recognize due to their debilitating nature and greater likelihood of having potentially treatable underlying causes. While management options have remained somewhat limited, scientific inquiry is continually advancing the understanding of these syndromes and how best to address them.

Headaches and Vasculitis.

Vasculitis refers to heterogeneous clinicopathologic disorders that share the histopathology of inflammation of blood vessels. Unrecognized and therefore untreated, vasculitis of the nervous system leads to pervasive injury and disability making this a disorder of paramount importance to all clinicians. Headache may be an important clue to vasculitic involvement of central nervous system (CNS) vessels. CNS vasculitis may be primary, in which only intracranial vessels are involved in the inflammatory process, or secondary to another known disorder with overlapping systemic involvement. Primary neurologic vasculitides can be diagnosed with assurance after intensive evaluation that incudes tissue confirmation whenever possible.

Spontaneous Intracranial Hypotension: Clinical Presentation, Diagnosis, and Treatment Strategies.

Spontaneous intracranial hypotension (SIH) typically presents as an acute orthostatic headache during an upright position, secondary to spinal cerebrospinal fluid leaks. New evidence indicates that a lumbar puncture may not be essential for diagnosing every patient with SIH. Spinal neuroimaging protocols used for diagnosing and localizing spinal cerebrospinal fluid leaks include brain/spinal MRI, computed tomography myelography, digital subtraction myelography, and radionuclide cisternography. Complications of SIH include subdural hematoma, cerebral venous thrombosis, and superficial siderosis. Treatment options encompass conservative management, epidural blood patches, and surgical interventions. The early application of epidural blood patches in all patients with SIH is suggested.

The Postconcussion Syndrome and Posttraumatic Headaches in Civilians, Soldiers, and Athletes.

Posttraumatic headaches are one of the most common and controversial secondary headache types. After a mild traumatic brain, an estimated 11% to 82% of people develop a postconcussion syndrome, which has been controversial for more than 160 years. Headache is estimated as present in 30% to 90% of patients after a mild head injury. Most headaches are tension-type-like or migraine-like. Headaches in civilians, soldiers, athletes, and postcraniotomy are reviewed. The treatments are the same as for the primary headaches. Persistent posttraumatic headaches can continue for many years.

Headache Attributed to a Substance or Its Withdrawal.

Identification of substances that may cause or trigger headache is important to start effective treatment early to prevent unnecessary suffering, deterioration in quality of life, and the development of chronic pain. Treatment in case of medication overuse and other chronic headache should be decisive and effective. Drug withdrawal and introduction of effective prophylactic medication for the underlying headache disorder should be the primary treatment strategy. Typical headache-inducing substances are nitric oxide, phosphodiesterase, cocaine, alcohol, histamine, carbon oxide, and calcitonin gene-related peptide. The withdrawal of caffeine, estrogen, and opioids is most often associated with the development of headache.

The Pseudotumor Cerebri Syndrome.

Pseudotumor cerebri syndrome is a syndrome of increased cerebrospinal fluid pressure without ventriculomegaly, mass lesion, or meningeal abnormality. It is either primary (idiopathic intracranial hypertension, IIH) or secondary. A secondary cause is unlikely when adhering to the diagnostic criteria. Permanent visual loss occurs if undetected or untreated, and the associated headaches may be debilitating. Fulminant disease may result in blindness despite aggressive treatment. This study addresses the diagnosis and management of IIH including new insights into the pathobiology of IIH, updates in therapeutics and causes of overdiagnosis.

Headache due to Vascular Disorders.

Headache and cerebrovascular disease (CVD) are inextricably linked. Although in some cases headache complicating CVD may be little more than a symptomatic afterthought, in other cases, early recognition of headache's role in the CVD process is critical to effective management. In other words, headaches secondary to CVD span a spectrum, and in this article, we will review that spectrum.