Alzheimer's disease (AD) is the most common cause of dementia, with global case numbers projected to reach 153 million in 20501. AD is highly heritable, with twin-based heritability estimates of 60-80%2. Although 1,200 causal loci are predicted to exist for AD3, approximately 80 loci have been associated with AD in two recent studies4,5. Low single-nucleotide polymorphism (SNP)-based heritability estimates have prompted the suggestion that little further common-variant risk remains to be found6. Here we analysed data from 109,479 cases, 74,141 proxy cases, 2,131,799 controls and 499,708 proxy controls from diverse ancestries, identifying 118 loci in a multi-ancestry analysis and 9 additional loci in ancestry-specific analyses, 48 of which are new. We identified new AD risk genes, prioritized potential drug targets, and found that genes upregulated in microglia and downregulated in neurons in cases compared with controls were enriched for AD-associated genetic risk. Moreover, we improved polygenic prediction and estimated a SNP heritability of 16%, nearly threefold higher than previous estimates. Together, our findings show that the common-variant contribution to AD has been substantially underestimated, and reveal new molecular and cellular mechanisms as well as specific targets for future drug development research.

Recent literature has assessed the potential of Echinacea products to reduce respiratory tract infections (RTIs) and antibiotic use but has not comprehensively evaluated safety within a risk-benefit framework. Our systematic review and meta-analysis reviewed relevant databases for adverse events (AEs) in clinical trials comparing oral Echinacea (all species and preparations) with placebo, active or no-treatment groups. AEs were classified by System Organ Class (SOC) and compared with individual case safety reports (ICRs) from EudraVigilance (EVDAS). Across 48 clinical studies (N = 10,115), 2,396 AEs were reported. AE occurrence was lower in Echinacea groups compared with any control (22.7% vs. 24.8%, p = 0.014) and to placebo control only (29.1% vs. 32.3%; p = 0.005). In therapeutic settings, after excluding pressed juice formulations, Echinacea significantly reduced AEs by up to 21.1% (19.8% vs. 25.1%; p < 0.0001). Preventive studies in healthy participants showed comparable AE rates between Echinacea and control groups (21.3% vs. 22.3%; p = 0.411). Serious AEs (SAEs) accounted for 0.09% and 0.08% of events for Echinacea and any control, respectively; no fatal SAEs were reported. Spontaneous EVDAS reports mostly concerned gastrointestinal (17.7%), general (13.1%), and nervous system disorders (10.3%, e.g. headache), whereas skin and subcutaneous tissue events (16.1%) were less prominent in clinical trials, which predominantly investigated high-quality pharmaceutical extracts.Principally, oral Echinacea products demonstrate a high level of safety, with preparation-dependent qualitative differences. Pharmaceutical-grade ethanolic extracts showed further reductions in AEs versus control, possibly reflecting clinical efficacy and supporting positive risk-benefit evaluation for RTI management and antibiotic stewardship.

Dural arteriovenous fistulas (dAVFs) are rare intracranial vascular abnormalities that may present with varied and sometimes atypical clinical features. While proptosis is commonly associated with anterior cranial or cavernous sinus fistulas, it is unusual in posterior fossa dAVFs. We present the case of a 41-year-old man with progressive redness, swelling, and protrusion of the left eye over six months, without associated pain, diplopia, headache, or cranial nerve deficits. Ocular examination revealed preserved visual acuity and extraocular movements, with normal fundus findings. An initial diagnosis of a cavernous sinus fistula was considered. However, brain MRI with time-of-flight sequences revealed a left temporal dAVF with feeders from the external carotid artery and drainage into the vein of Labbé and transverse sinus, with a possible connection to the superior division of the middle cerebral artery. On clinical re-examination, a bruit was noted in the left occipitotemporal region. Doppler and transcranial Doppler studies confirmed mixed arterial and venous flow. The patient was referred for digital subtraction angiography and embolization. The symptoms of dAVFs vary depending on the shunt characteristics, location, and venous drainage pattern. Ocular signs are uncommon in noncavernous dAVFs. In this case, venous reflux through the vein of Labbé may explain the isolated proptosis. Management is guided by angioarchitecture and associated risk features, with high-risk fistulas requiring timely intervention. This case highlights the need to consider cranial dural AVFs in the differential diagnosis of isolated proptosis, as timely diagnosis and treatment are crucial.

Pituitary apoplexy is a rare endocrine emergency resulting from either acute haemorrhage or infarction within the pituitary gland. Although apoplexy occurs most frequently in a pre-existing pituitary adenoma, apoplexy could be the first presentation of a previously unknown adenoma. Acute headaches, visual disturbances, and neurological symptoms are common presenting symptoms in apoplexy; however, these symptoms may overlap with other neurological emergencies, which necessitate a holistic approach of clinical, radiological, and hormonal evaluation for suspected cases of apoplexy to confirm the diagnosis. Here we present a diagnostically challenging case of a 66-year-old man who presented with a sudden severe headache. His background history included a presumed intraventricular neurocytoma under surveillance. Initial CT head scan suggested possible haemorrhage within a known intraventricular mass (neurocytoma) with no obvious changes within the pituitary gland. However, subsequent MRI head demonstrated radiological features consistent with pituitary apoplexy. Later in his admission, he exhibited bilateral peripheral visual field constriction and early papilledema on fundoscopy. Hormonal testing showed evidence of hypopituitarism. The patient was managed conservatively with intravenous hydrocortisone replacement. During admission, he developed bilateral pulmonary emboli, for which he was treated with anticoagulation. While he was on anticoagulation, he developed intracranial haemorrhage, which led to his death after discharge from the hospital. This case demonstrates the importance of considering pituitary apoplexy in a challenging radiological and clinical presentation. A pre-existing neurological lesion (neurocytoma) makes a holistic approach, including MRI imaging and early hormonal evaluation are essential for timely diagnosis and treatment of pituitary apoplexy. The clinical challenge of having concurrent haemorrhagic and thrombotic events necessitates an individualised approach after balancing the benefits and risks of using anticoagulation treatment.

Headache is a prominent acute and persistent neurological manifestation of COVID-19, representing both as a significant clinical challenge and a valuable model for understanding the neurotropic effects of SARS-CoV-2. This review synthesizes evidence showing that the epidemiology of COVID-19 headache is distinctly shaped by younger age, female sex, and a prior history of headache disorders; its clinical phenotypes are diverse, strongly associating with chemosensory dysfunctions such as anosmia; and its core pathophysiology involves neuroinflammation (e.g., cytokine-mediated pathways), trigeminovascular activation, and sex-specific neuroendocrine-immune interactions. Although acute headache often responds to conventional analgesics, persistent cases-a major component of Post-Acute Sequelae of COVID-19 (PASC)-necessitate a multidisciplinary management approach. This contrasts with the typically self-limiting headache following vaccination. Future research should prioritize longitudinal studies to define chronicity, mechanistic investigations into sex-specific pathways, and the development of phenotype-specific, personalized therapeutic strategies.

Cerebral venous sinus thrombosis (CVST) is an uncommon but potentially life-threatening neurological complication of systemic lupus erythematosus (SLE) that requires prompt recognition and treatment. We report the case of an 18-year-old Bangladeshi woman with established SLE who presented with a 10-day history of severe headache followed by rapidly progressive bilateral proptosis and sudden, painless bilateral visual loss. Neurological examination revealed complete bilateral visual loss, bilateral ptosis, restricted extraocular movements and multiple cranial nerve deficits. She had active SLE with severe thrombocytopaenia and haematological involvement. Brain magnetic resonance imaging and magnetic resonance venography demonstrated extensive thrombosis involving the superior sagittal, bilateral transverse and sigmoid and cavernous sinuses. Antiphospholipid antibody testing, including lupus anticoagulant, anticardiolipin antibodies and Anti-β2-glycoprotein I antibodies, was negative. The patient received therapeutic anticoagulation, high-dose corticosteroids and immunosuppressive therapy with rituximab, followed by haematological and neurological improvement and subsequent recanalisation of the thrombosed dural venous sinuses. However, bilateral visual loss persisted, with optic disc pallor and optic atrophy. Optical coherence tomography, visual evoked potential testing, dedicated orbital imaging and formal neuro-ophthalmological assessment were not performed; therefore, the precise mechanism of visual loss could not be definitively established. Nevertheless, ischaemic optic neuropathy was considered the most likely mechanism given the clinical presentation and extensive CVST. This case highlights that extensive CVST may occur in active SLE despite negative antiphospholipid antibody testing. It underscores the importance of early neuroimaging, timely anticoagulation and appropriate immunosuppressive therapy to minimise the risk of persistent neurological and visual sequelae.