Headache is the most common symptom of idiopathic intracranial hypertension (IIH) and may persist despite therapy, with a significant impact on quality of life. Since calcitonin gene-related peptide (CGRP) plays a crucial role in the pathophysiology and management of primary headaches such as migraine, this raises the question whether CGRP also contributes to headache in IIH. Therefore, we compared tear fluid CGRP levels between IIH patients with headache and healthy controls, and in IIH patients before and after CSF pressure normalization by therapeutic lumbar puncture. IIH patients with headache attributed to IIH and healthy controls were included. To avoid confounding with chronic migraine, IIH patients with a chronic migraine phenotype were excluded. Tear fluid was collected from IIH patients and controls. In IIH patients, an additional measurement was performed approximately 3 h after therapeutic lumbar puncture. CGRP levels were analyzed using a commercially available ELISA. Twenty-three IIH patients (all female; age: 34.0 ± 8.8 years) and 20 healthy controls (all female, age: 25.7 ± 5.5 years) were included. IIH patients had 16.4 ± 12.3 headache days per month and headache was mostly bilateral and pressing. Baseline tear fluid CGRP levels were significantly lower in IIH patients compared to healthy controls (2.4 ± 1.2 ng/ml vs. 4.9 ± 4.2 ng/ml, p < 0.001). There was no significant change in CGRP levels in IIH patients before vs. after therapeutic lumbar puncture (2.4 ± 1.2 vs. 2.4 ± 1.7 ng/ml, p = 0.236). Similarly, in the subgroup with immediate headache improvement, CGRP levels remained unchanged (before: 2.2 ± 0.9 ng/ml, after: 2.8 ± 2.4 ng/ml; p = 0.674). Tear fluid CGRP levels were lower in IIH patients with headache but without a chronic migraine phenotype compared to healthy controls. In addition, CSF pressure normalization was not associated with changes in CGRP levels after 3 h. These results do not support a major role of CGRP in IIH-associated headache without a chronic migraine phenotype. The study was previously registered at the German Clinical Trial Register (DRKS www.drks.de) (DRKS00025278), Trial registration date 25.06.2021.
Peripheral nerve blocks (PNBs) represent an accessible, minimally invasive therapeutic approach for headache disorders; however, real-world data on procedural patterns and outcomes in different headache subtypes remain limited. This multicenter study evaluated 2,219 patients (receiving 2250 PNBs) with migraine, tension-type headache (TTH), trigeminal autonomic cephalalgias (TACs), and cranial neuralgias. Demographic features, preventive and acute medicine, target nerves, anaesthetic agents, injection volumes, application intervals, number of sessions, clinical outcomes, and adverse events were analysed. Longitudinal outcomes were assessed with three-level mixed-effects models accounting for repeated visits within patients and patients within centers, using linear mixed models for VAS and cumulative-link mixed models for ordinal headache frequency and analgesic use. Migraine was the predominant diagnosis (77.5%), comprising chronic (55.6%) and episodic (44.4%) forms. Greater occipital nerve block was the dominant procedure in migraine, TTH, and TACs, but was less frequent in neuralgias, both in occipital and trigeminal. Injection volume, application interval, and local anesthetic choice varied by headache type and target nerve. GON volumes were most often 1-2 mL across headache groups, except in neuralgias, where 2-3 mL was most common. PNBs were associated with statistically significant improvements in headache frequency, severity, and duration as well as decrease in analgesic use in all analysed groups and subgroups. Adverse events were uncommon and mainly mild. Intercept-only models indicated modest center-level clustering, with ICCs of 0.093 for VAS scores, 0.134 for headache frequency, and 0.130 for analgesic use. Overall, these findings support PNBs as useful and well-tolerated options while highlighting substantial real-world variation in practice.
New-onset daily persistent headache (NDPH) is a primary headache syndrome characterized by a sudden onset of daily headaches persisting for more than three months in patients with no prior headache history. We report the case of a 49-year-old Indian lady who presented to the neurology outpatient clinic with new daily persistent headache. The headache had an insidious onset, described as continuous, holocranial, and dull aching. Visual analog scale (VAS) of pain severity was estimated to be 8/10. Her medical history was significant for carcinoma of the left breast cT3N1(Stage IIIA), for which she had received treatment two and a half years prior and was subsequently declared disease-free. Although symptomatic treatment for her headache was initiated, she remained refractory to standard therapy. A gadolinium-enhanced magnetic resonance imaging of the brain revealed large, heterogeneous, enhancing areas within the diploic space of the frontal bone. The patient subsequently received palliative external beam radiotherapy. At the 3-month follow-up post radiotherapy, her pain had significantly subsided, with a recorded VAS score of 2/10. In conclusion, patients presenting with acute headaches, particularly in the context of cancer, warrant neuro-radiological imaging. Timely diagnosis of calvarial metastasis is critical in preventing further disease progression and enhancing the patient's quality of life.
There is limited research examining the association between wildfire smoke, an increasingly frequent exposure, and headache-related emergency department (ED) visits, despite headaches being a leading cause of years lived with disability globally. To examine the association between wildfire-sourced fine particulate matter with an aerodynamic diameter of 2.5 μm or less (PM2.5) and ED visit for migraine and other primary headache syndromes (MOPHS) compared with nonwildfire-sourced PM2.5, and to assess the variation across sociodemographic factors. This case-crossover study used conditional logistic regression to examine ED visits during wildfire seasons (May 1 to October 31) from 2010 to 2023 in Alberta and Ontario provinces in Canada. Case days were matched to referent days by day of week, month, year, and forward sortation area (first 3 postal code characters). Seven-day cumulative lags were evaluated. All ED visits recorded in the National Ambulatory Care Reporting System with a primary diagnosis of MOPHS were included. Statistical analyses were conducted from April to December 2025. Total PM2.5 concentrations and wildfire day (WFD). Daily mean wildfire-sourced PM2.5 was estimated using the Canadian Optimized Statistical Smoke Exposure Model. WFDs were defined by smoke plume presence and total PM2.5 concentration exceeding a predefined threshold based on the mean plus 1.5 SD of PM2.5 on days without a smoke plume. Wildfire-sourced PM2.5 was defined as the difference between total PM2.5 concentration on a WFD and expected background PM2.5 concentration on non-WFDs. ED visits for migraine (International Statistical Classification of Diseases and Related Health Problems, Tenth Revision, Canada code G43) and other primary headache syndromes (code G44). Among the 997 701 ED visits for 622 753 patients (mean [SD] age, 24.6 [16.8] years; 760 795 females [76.3%]) for MOPHS identified during the study period, 86.2% of visits were for migraines and 13.8% were for other primary headache syndromes. Wildfire-sourced PM2.5 was associated with a 6.07% (95% CI, 5.75%-6.39%) increase in ED visits. Associations appeared attenuated in the least materially and socially deprived quantile (for both provinces combined, the percentage increase in MOPHS was smallest for the Material and Social Deprivation Index quintile 1: 3.61% [95% CI, 1.93%-5.63%] and largest for quintile 5: 10.42% [95% CI, 7.41%-13.49%]). In contrast, total PM2.5 concentration on non-WFDs was not significantly associated with ED visits (0.21%; 95% CI, -0.20% to 0.62%). In this case-crossover study of ED visits in Alberta and Ontario, acute exposure to wildfire-sourced PM2.5 was associated with increased ED visit for MOPHS; associations were greater in magnitude for wildfire-sourced PM2.5 than nonwildfire-sourced PM2.5. These findings support the need for further research into wildfire smoke and severe headache-related outcomes.
Tension-type headache (TTH) is the most common primary headache, yet accompanying sleep disturbances have not been quantitatively synthesized. PubMed, Embase, Web of Science, and the Cochrane Library were searched from inception to January 3, 2026, for observational studies reporting sleep outcomes in adults with TTH. The primary outcome was the prevalence of poor sleep quality assessed with the Pittsburgh sleep quality index (PSQI). Pooled estimates were calculated using random-effects models. Study quality was assessed with Joanna Briggs Institute checklists. Twenty-seven studies were included. Pooled prevalence of poor sleep quality in TTH was 67% (95% CI 53-79%; I2 = 97%), stable across sensitivity and trim-and-fill analyses. Heterogeneity appeared partly related to recruitment settings. In five studies with non-headache controls, the odds of poor sleep quality were elevated but not significant (OR = 2.39; 95% CI 0.83-6.86; p = 0.08). The pooled mean PSQI score was 9.48 and significantly higher than controls (MD = 3.77; 95% CI 2.32-5.22; p < 0.01). Mean sleep duration was 6.61 h and did not differ significantly from controls. Insomnia was reported in 37%, excessive daytime sleepiness in 13%, and high OSA risk or PSG-defined OSA in 26%, with imprecise estimates. PSQI scores correlated robustly with depression (r = 0.51; FDR q = 0.005), whereas correlations with headache frequency and intensity were nominal and exploratory. Poor subjective sleep quality is common in TTH, particularly among patients presenting to clinical settings, and is associated with depressive symptoms, with exploratory associations with headache burden, supporting consideration of sleep assessment in the clinical evaluation of TTH.
Cervicogenic headache (CGH) is a secondary disorder caused by cervical musculoskeletal dysfunction in the cervical vertebrae, with involvement of the upper three cervical segments. The pain initiates in the neck and is often intensified by head or neck movements. This condition imposes a considerable socioeconomic burden, affecting both community well-being and public health systems. To explore how high-power laser therapy influences pain intensity, suboccipital muscle activity, functional disability, and quality of life (QoL) in patients with CGH. A randomized controlled trial was conducted on 40 participants (both males and females) diagnosed with CGH for a duration of at least 6 months, experiencing unilateral neck pain radiating to the suboccipital region. Participants were randomly allocated into two equal groups. The study group (A) received high-power Laser therapy in addition to a conventional physical therapy program, while the control group (B) received a placebo laser alongside the same conventional physical therapy program. Both groups received 3 times per week for 6 weeks, with each session lasting approximately 45-60 min. Outcome measures included the visual analog scale for pain intensity measurement, electromyography (EMG) to assess suboccipital muscle myoelectric activity, the Headache Impact Test-6 questionnaire to assess participants' functional health and well-being, the Neck Disability Index to assess functional impairment, and the 36-Item Short Form Health Survey to evaluate QoL. Assessments were performed before and after the intervention (6 weeks). Group A showed statistically significant improvements in pain intensity, EMG parameters, functional disability, headache impact, and QoL compared with Group B. High-power laser therapy, when used alongside conventional physiotherapy, may be an effective approach for reducing symptoms and improving functional outcomes in patients with CGH.
Cluster headache is an extremely painful and severely disabling primary headache disorder that, despite its profound impact on quality of life, remains underdiagnosed and undertreated. Effective management requires a structured approach across the cluster cycle, but practical, timeline-based guidance integrating established and emerging therapies is lacking. The authors present a treatment framework organized by clinical timeline: inter-cycle period, cycle onset, active cycle, and resolution, addressing acute abortive, bridge, and prophylactic therapies with evidence quality, dosing, and monitoring. Both established synthetic agents and recently recognized biologic therapies are examined, with particular focus on anti-calcitonin gene-related peptide (CGRP) monoclonal antibodies and forward-looking targets such as PACAP and 5-HT2A. References were identified through searches of PubMed and clinical trial registries from inception to June 2026. Anti-CGRP monoclonal antibodies are a meaningful advance, best positioned as an adjunct to established prophylaxis rather than a replacement. PACAP-targeted therapy is a promising direction whose role in cluster headache remains to be defined. The serotonergic agent psilocybin warrants closer attention, as its early therapeutic signal merits rigorous investigation despite the legal and historical barriers constraining its study.
To explore and describe master's chiropractic students' self-perceived preparedness in diagnosing and managing headache disorders. A qualitative, exploratory, descriptive design was used. Thirteen master's chiropractic students participated in semistructured interviews guided by an interview protocol. Interviews were thematically analyzed using Tesch's 8-step approach. Participants reported and expressed limited preparedness and low initial confidence in diagnosing and managing headache disorders. Educational and environmental challenges were identified as key roles in this result whilst clinical exposure positively influenced students' perceptions of their preparedness. The exploration of students' self-perceived preparedness in diagnosing and managing headache disorders identified multiple contributing factors. Educational and environmental challenges were associated with feelings of limited preparedness. However, increased clinical exposure enhanced both confidence and perceived competence.
Patients who speak languages other than English (LOE) may be at risk of adverse health outcomes. The objective of this study was to evaluate the association of language with diagnostic testing rates and analgesia choice among children with headaches in the emergency department (ED). We hypothesized that spoken language would be associated with rates of neuroimaging and analgesia choice. We conducted a cross-sectional study of children 5-17 years old discharged from an emergency department in Iowa, Maryland, or New Jersey in 2019-2020 with a primary diagnosis of headache. Language was defined as English, Spanish, or other. The outcomes were neuroimaging (computed tomography [CT] or magnetic resonance imaging [MRI]) and intravenous analgesia administration, identified using procedure codes. We used logistic regression to evaluate the associations of language and each outcome, adjusting for age, sex, payor, neighborhood income, state, migraine versus non-migraine diagnosis, and complex chronic condition. Neuroimaging was performed in 22.7% of English-, 17.3% of Spanish-, and 22.4% of other language-speakers. Compared with English, there was only an association between neuroimaging and Spanish (adjusted odds ratio [aOR] 0.83, 95% CI: 0.72-0.95). Intravenous medications were administered in 41.6% English-, 28.0% Spanish-, and 33.7% other language-speakers. Compared with primary English speakers, there was no association between Spanish language (aOR: 0.91, 95% CI: 0.80-1.04) or other language (aOR: 1.18, 95% CI: 0.95-1.45) and intravenous analgesia. There was an association between LOE and neuroimaging. This evaluation should be repeated across different conditions to understand under what conditions language is associated with clinical decision-making and care.
Thunderclap is a rare but important manifestation of type A aortic dissection and may occur as the sole presenting feature in patients who do not experience chest pain.
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BackgroundPatients with migraine are frequently referred to physical therapy, particularly when neck pain is present or symptoms remain inadequately controlled with medical management. Cervical strengthening and stabilization exercises are commonly prescribed; however, the quality and consistency of supporting evidence remain unclear. This review evaluated the effectiveness and safety of cervical-focused exercise interventions for migraine.MethodsA systematic search of nine medical and rehabilitation databases identified studies evaluating cervical or upper-body strengthening and stabilization interventions in individuals aged ≥14 years with migraine diagnosed according to International Classification of Headache Disorders criteria. Eligible studies reported headache or disability outcomes. Methodological quality and risk of bias were assessed using the Downs and Black Checklist, CARE guidelines, and Cochrane Risk of Bias 2 tool. Random-effects meta-analyses were performed for headache frequency, headache intensity, and migraine-related disability.ResultsTwelve studies met inclusion criteria, including five randomized controlled trials, three observational studies, one case report, and three conference abstracts. Interventions varied in duration, supervision, and comparators. Meta-analysis demonstrated a moderate, statistically significant improvement in migraine-related disability (SMD=0.69; 95% CI, 0.19-1.18; I2=70.7%). Effects for headache frequency (SMD=0.61; 95% CI, -0.25-1.47; I2=73.7%) and headache intensity (SMD=0.41; 95% CI, -0.35-1.18; I2=74.1%) were not statistically significant. Observational studies reported within-group improvements.ConclusionsCervical strengthening and stabilization exercises may have potential for improving migraine-related disability; however, current evidence remains insufficient to establish clear benefit for migraine prevention outcomes. Findings are based on very low to low certainty evidence, limited by risk of bias and substantial heterogeneity. Future research should prioritize adequately powered, multicenter randomized controlled trials with rigorous methodology and standardized reporting to determine whether these interventions provide clinically meaningful benefit for individuals with migraine.Registration: Prospero IDCRD420251051356.
Monoclonal antibodies targeting the calcitonin gene-related peptide (CGRP) pathway represent an effective preventive treatment for chronic migraine, including in patients with multiple prior therapeutic failures. However, a substantial proportion of patients exhibit a suboptimal or delayed response. The role of personality traits in modulating treatment response remains poorly understood. In this prospective observational study, adults with chronic migraine received anti-CGRP monoclonal antibodies and were followed for 12 months. Monthly headache days (MHDs), monthly acute medication use (MAM), and disability scores (MIDAS and HIT-6) were recorded at baseline and at 3, 6, and 12 months. Responders were defined as patients achieving a ≥50% reduction in monthly headache days (MHDs) compared with baseline. Changes in disability measures were evaluated as secondary clinical outcomes. Personality traits were assessed using the Millon Clinical Multiaxial Inventory-III. Thirty-eight patients were included, of whom 71% had medication overuse headaches. Responder rates increased over time (31.6% at 3 months and 39.5% at 12 months). Histrionic traits (37.5% vs. 6.7%, p = 0.048) and dysthymic features (21.4% vs. 0%, p = 0.046) were significantly more prevalent among non-responders. Histrionic and dysthymic personality features were associated with a lower likelihood of response to anti-CGRP therapy in patients with chronic migraine. Given the exploratory design, limited sample size, and absence of correction for multiple comparisons, these findings should be considered preliminary and hypothesis-generating. Further studies in larger cohorts are needed to confirm these observations.
Polytherapy in epilepsy is associated with a higher risk of adverse events, poorer adherence, and impaired quality of life. Thus, reducing concomitant antiseizure medications (ASMs) and/or using a newly added ASM such as cenobamate with only 1 other ASM (i.e., bitherapy) may improve tolerability. This post hoc analysis evaluated the impact of the number and type of concomitant ASMs on treatment-emergent adverse events (TEAEs) that occurred in the cenobamate C021 open-label clinical trial. Adjunctive cenobamate was initiated in adults (aged 18-70 years) with uncontrolled focal seizures who were taking 1 to 3 ASMs. The number and type of concomitant ASMs and the frequency, severity, and time to resolution of TEAEs were assessed. The most frequently reported (≥ 10%) TEAEs in the overall population (n = 1340) were somnolence, dizziness, fatigue, and headache. The percentage of patients with dizziness, somnolence, and fatigue increased with increasing numbers of concomitant ASMs, especially when combined with benzodiazepines, chiefly clobazam, and in patients taking ≥ 2 sodium channel blockers. Median time to resolution of frequently reported TEAEs was shorter in patients taking fewer concomitant ASMs, with the exception of fatigue. The proportion of patients experiencing more severe TEAEs (except for headache) also increased with increasing numbers of concomitant ASMs. Patients taking fewer concomitant ASMs reported better tolerability as evidenced by fewer and less severe AEs and faster time to resolution. These findings emphasize the importance of optimizing concomitant ASM regimens through dose adjustments, ASM substitution, and treatment simplification to improve tolerability.
Cerebral venous sinus thrombosis (CVST) is a rare but important complication of bacterial meningitis and is most commonly associated with Streptococcus pneumoniae. We report the case of a 60-year-old man who developed extensive CVST following the completion of a 14-day course of intravenous ceftriaxone for pneumococcal meningitis. Despite biochemical resolution of infection and absence of focal neurological deficits, persistent headache and meningism prompted further neuroimaging, which confirmed the diagnosis. He was treated with anticoagulation, resulting in subsequent radiological resolution of thrombosis, although headaches persisted following recanalisation.
The Leeds Dependence Questionnaire (LDQ) is a validated tool for assessing psychological dependence across various substances and has been adapted for use in headache patients. No study has yet explored the effects of preventive anti-CGRP treatments like atogepant on psychological dependence related to acute migraine medications. We conducted a prospective, real-world, single-center study on patients with migraine who were treated with atogepant 60 mg daily for 12 weeks. LDQ scores were assessed at baseline and after 12 weeks. Monthly headache days (MHDs), acute medication use, and presence of psychiatric comorbidities were collected. A linear mixed-effects model evaluated the effect of treatment over time, adjusting for medication overuse (MO) status and psychiatric comorbidities. We included 43 patients (69.8% with chronic migraine, 67.4% with MO). The LDQ total score significantly decreased from 7.95 ± 5.79 to 6.42 ± 5.08 after treatment (mean difference: -1.53, p = 0.032). Significant improvements were seen in three specific LDQ items reflecting loss of control, compulsive use, and psychological distress. No significant correlation was found between the reduction in LDQ score and the change in acute medication use. Mixed-effects modeling confirmed a significant effect of treatment (p = 0.022), but independent of MO or MOH status or psychiatric comorbidities. Preventive treatment with atogepant is associated with a significant reduction in psychological dependence on acute migraine medications, as measured by the LDQ. These findings support the need to assess dependence-like behavior in clinical migraine care and highlight the potential behavioral benefits of effective preventive treatments.
Myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD) can resemble central nervous system infection in children because fever, headache, vomiting, cerebrospinal fluid pleocytosis, and multifocal brain lesions may coexist. We report a previously healthy 13-year-old boy who developed headache, fever, vomiting, and binocular horizontal diplopia. Examination showed transient exotropia with apparent adduction limitation but no encephalopathy, seizures, limb weakness, pupillary abnormality, optic neuritis, or spinal cord lesion. Cerebrospinal fluid showed mononuclear-predominant pleocytosis with mildly elevated protein. Brain magnetic resonance imaging showed evolving patchy fluid-attenuated inversion recovery hyperintensities in the right temporal lobe, basal ganglia, periventricular region adjacent to the fourth ventricle, and later the right frontal lobe. Extensive microbiological testing was unrevealing. Serum myelin oligodendrocyte glycoprotein immunoglobulin G (MOG-IgG) was repeatedly positive by live cell-based assay, whereas aquaporin-4 immunoglobulin G (AQP4-IgG) and autoimmune encephalitis antibodies were negative. Clinical improvement occurred during overlapping treatment with intravenous immunoglobulin and corticosteroids. On illness day 97, during prednisone tapering following an individualized off-label decision to use rituximab, the patient remained clinically stable. This case highlights that pediatric MOGAD should be considered when an infection-like central nervous system presentation is accompanied by evolving multifocal magnetic resonance imaging abnormalities and negative pathogen studies. Diplopia can be an important focal clue; however, because the ocular motor examination was incomplete, internuclear ophthalmoplegia could not be confirmed.
Carotid-cavernous fistulas (CCFs) are abnormal shunts between the internal carotid artery and the cavernous sinus that may be high-flow direct or low-flow indirect lesions. They present with ocular symptoms and headache and are diagnosed primarily by cerebral angiography. This study evaluated the safety, technical success, and long-term outcomes of endovascular embolization for CCFs. This retrospective single-center study evaluated procedural and clinical outcomes of patients with CCFs treated with endovascular embolization. The evaluated outcomes included immediate procedural success on DSA, symptom resolution, procedure-related complications, and the rate of complete fistula occlusion on follow-up DSA. Twenty-three patients (mean age 57 years; 74% female) underwent endovascular treatment for carotid-cavernous fistulas, including 11 direct and 12 indirect lesions. The most common presenting symptoms were proptosis and orbital pain. Coil embolization was used in all cases, with adjunctive materials in 44% (10/23). Immediate complete occlusion was achieved in 48% (11/23) and complications occurred in 9% (2/23). Final follow-up DSA showed complete fistula closure in 91.3% of patients (21/23). Clinical improvement was achieved in 91.3% (21/23) of the cohort, with complete clinical resolution in 14 patients (61%). The results of our study suggest that long-term radiological and clinical outcomes in patients with CCFs treated with endovascular embolization were very satisfactory across all fistula types. Therefore, modern endovascular methods should be considered during the multidisciplinary evaluation of these patients.
Mucormycosis is an aggressive invasive fungal infection that predominantly affects immunocompromised individuals and may be rapidly fatal if diagnosis and treatment are delayed. We report a man in his sixties with no known immunosuppressive conditions who presented with progressive headache, cranial nerve dysfunction, and sinusitis symptoms. Neuroimaging demonstrated an infiltrative skull base lesion with orbital and intracranial extension, initially suggestive of a neoplastic process. Surgical exploration and histopathological examination revealed invasive rhino-orbital-cerebral mucormycosis with extensive angioinvasion and tissue necrosis. The patient underwent surgical debridement followed by systemic antifungal therapy with amphotericin B, resulting in clinical stabilization and partial neurological recovery. This case highlights the importance of considering invasive fungal infection in the differential diagnosis of skull base masses, even in immunocompetent patients, and underscores the critical role of early biopsy and combined surgical and medical management.
Coccidioidomycosis is a systemic fungal infection caused by Coccidioides immitis and Coccidioides posadasii. Although well recognized in parts of the southwestern United States, it remains underdiagnosed in Mexico and Central America. While most cases present as self-limited pulmonary infection, approximately 1% of immunocompetent individuals develop disseminated disease, with coccidioidal meningitis (CM) being the most severe manifestation. We describe a 46-year-old immunocompetent male from Oaxaca, Mexico, who presented with progressive headache, neurocognitive decline, and altered mental status. Initial cerebrospinal fluid (CSF) analysis suggested cryptococcal meningitis, yet cryptococcal antigen testing and fungal cultures were negative. Empirical antifungal therapy produced only partial improvement. Given his occupational exposure in Texas and evolving clinical course, coccidioidomycosis was suspected. Serologic testing (enzyme immunoassay, EIA) and a coccidioidin skin test were positive, and prolonged CSF culture ultimately yielded Coccidioides spp., confirming CM. High-dose fluconazole led to progressive neurologic recovery, and the patient remains asymptomatic on maintenance therapy. This case highlights the diagnostic challenges of CM in regions where coccidioidomycosis is not traditionally considered endemic. Non-specific presentations and initial negative studies may delay diagnosis, underscoring the importance of epidemiologic suspicion, repeated testing, and prolonged fungal culture. Early recognition and timely initiation of azole therapy are essential to prevent the high morbidity and mortality associated with this condition.