Baş Ağrısı ve Santral Sinir Sistemi Enfeksiyonları
Özet
Baş ağrısı; menenjit, ensefalit ve beyin apsesi dahil olmak üzere intrakraniyal enfeksiyonların en sık görülen nörolojik belirtilerinden biridir. Ayrıca inflamasyon, dehidrasyon ve metabolik bozuklukların bir sonucu olarak sistemik enfeksiyonlara da sıklıkla eşlik eder. Epidemiyolojik çalışmalar, bireylerin yaklaşık %60'ının yaşamları boyunca en az bir kez enfeksiyon kaynaklı baş ağrısı yaşadığını göstermektedir. Santral sinir sistemi (SSS) enfeksiyonlarında baş ağrısı, izole bir başlangıç belirtisi olarak ya da daha geniş bir klinik sendromun parçası şeklinde ortaya çıkabilir ve özellikleri altta yatan patojene göre değişiklik gösterir. Bununla birlikte, yalnızca baş ağrısının klinik özellikleri; bakteriyel, viral, fungal ve paraziter etiyolojiler arasında ayrım yapmak için yeterli özgüllüğe sahip değildir. Enfeksiyon kaynaklı baş ağrısının patofizyolojisi çok faktörlüdür; meningeal inflamasyon, meningeal traksiyon, artmış intrakraniyal basınç ve trigeminovasküler sistemin aktivasyonunu içerir. Baş ağrısına ateş, bilinç değişikliği, fokal nörolojik defisitler veya meningeal irritasyon bulgularının eşlik etmesi, SSS enfeksiyonu şüphesi uyandırmalı; acil tanısal değerlendirme ve uygun antimikrobiyal tedavinin başlatılmasını gerektirmelidir. Moleküler tanı yöntemleri ve antimikrobiyal tedavideki önemli gelişmelere rağmen, SSS enfeksiyonları dünya genelinde ciddi morbidite ve mortaliteye yol açmaya devam etmektedir. Baş ağrısını yalnızca spesifik olmayan bir belirti olarak değil, yaşamı tehdit eden enfeksiyöz bir sürecin potansiyel bir göstergesi olarak kabul etmek; tanısal doğruluğu artırmak, zamanında tedaviyi sağlamak ve hasta sonuçlarını iyileştirmek açısından büyük önem taşır. Bu bağlamda Tıbbi Mikrobiyoloji laboratuvarı; hızlı, doğru ve etiyolojik tanı sağlayarak kanıta dayalı klinik karar verme süreçlerini desteklemesi ve SSS enfeksiyonu olan hastaların yönetimini iyileştirmesi bakımından kilit bir rol oynamaktadır.
Headache is one of the most common neurological manifestations of intracranial infections, including meningitis, encephalitis, and brain abscesses. It also frequently accompanies systemic infections as a consequence of inflammation, dehydration, and metabolic disturbances. Epidemiological studies suggest that nearly 60% of individuals experience infection-related headache at least once during their lifetime. In central nervous system (CNS) infections, headache may occur as an isolated presenting symptom or as part of a broader clinical syndrome, with its characteristics varying according to the underlying pathogen. Nevertheless, the clinical features of headache alone lack sufficient specificity to distinguish between bacterial, viral, fungal, and parasitic etiologies. The pathophysiology of infection-related headache is multifactorial, involving meningeal inflammation, meningeal traction, increased intracranial pressure, and activation of the trigeminovascular system. The coexistence of headache with fever, altered mental status, focal neurological deficits, or signs of meningeal irritation should immediately raise suspicion for a CNS infection and prompt urgent diagnostic evaluation and initiation of appropriate antimicrobial therapy. Despite substantial advances in molecular diagnostics and antimicrobial treatment, CNS infections continue to impose considerable morbidity and mortality worldwide. Recognizing headache as a potential indicator of a life-threatening infectious process, rather than merely a nonspecific symptom, is essential for improving diagnostic accuracy, facilitating timely therapeutic intervention, and optimizing patient outcomes. In this context, the Medical Microbiology laboratory plays a pivotal role by providing rapid, accurate, and etiological diagnosis, thereby supporting evidence-based clinical decision-making and improving the management of patients with CNS infections.
Referanslar
Marchioni E, Minoli L. Headache attributed to infections: nosography and differential diagnosis. In: Hallett M, editor. Handbook of Clinical Neurology. Amsterdam: Elsevier; 2010. p. 601–626. doi:10.1016/S0072-9752(10)97052-8.
Rasmussen BK, Olesen J. Symptomatic and nonsymptomatic headaches in a general population. Neurology. American Academy of Neurology; 1992;42(6):1225–1231. doi:10.1212/WNL.42.6.1225.
Ramesh R, Ranganathan LN. Headache in infections. Current Opinion in Neurology. Wolters Kluwer; 2025;38(3):281–287. doi:10.1097/WCO.0000000000001348.
Messlinger K, Strassman A, Burstein R. Anatomy and physiology of pain sensitive cranial structures. In: Silberstein SD, Lipton RB, Dodick DW (eds.) Wolff's Headache and Other Head Pain. 8th ed. New York: Oxford University Press; 2008. p. 95–104.
McGill F, Heyderman RS, Panagiotou S, et al. Acute bacterial meningitis in adults. Lancet. Elsevier; 2016;388(10063):3036–3047. doi:10.1016/S0140-6736(16)30654-7.
Tuomanen E, Liu H, Hengstler B, et al. The induction of meningeal inflammation by components of the pneumococcal cell wall. Journal of Infectious Diseases. Oxford University Press; 1985;151(5):859–868.
Kim KS. Investigating bacterial penetration of the blood-brain barrier for the pathogenesis, prevention, and therapy of bacterial meningitis. ACS Infectious Diseases. American Chemical Society; 2020;6(1):34–42. doi:10.1021/acsinfecdis.9b00307.
Hoffmann O, Dirnagl U, Weber JR. The trigeminovascular system in bacterial meningitis. Microscopy Research and Technique. Wiley; 2001;53(3):188–192. doi:10.1002/jemt.1090.
Weber JR, Sakai F. Headache attributed to infection. In: Olesen J (ed.) The Secondary Headaches. New York: Oxford University Press; 2005. p. 981–988.
Gladstone J, Bigal ME. Headaches attributable to infectious diseases. Current Pain and Headache Reports. Springer Nature; 2010;14(4):299–308. doi:10.1007/s11916-010-0125-7.
Headache Classification Committee of the International Headache Society (IHS). The International Classification of Headache Disorders, 3rd edition (beta version). Cephalalgia. SAGE Publications; 2013;33(9):629–808. doi:10.1177/0333102413485658.
Kumar S, Verma R, Garg RK, et al. Prevalence and outcome of headache in tuberculous meningitis. Neurosciences (Riyadh). 2016;21(2):138–144. doi:10.17712/nsj.2016.2.20150771.
Sampaio Rocha-Filho PA. Headache associated with COVID-19: epidemiology, characteristics, pathophysiology, and management. Headache. Wiley; 2022;62(6):650–656. doi:10.1111/head.14319.
Fernandez-de-Las-Peñas C, Gómez-Mayordomo V, Cuadrado ML, et al. The presence of headache at onset in SARS-CoV-2 infection is associated with long-term post-COVID headache and fatigue: a case-control study. Cephalalgia. SAGE Publications; 2021;41(13):1332–1341. doi:10.1177/03331024211020404.
Brouwer MC, van de Beek D. Management of bacterial central nervous system infections. In: Tselis AC, Booss J (eds.) Handbook of Clinical Neurology. Vol. 140. Amsterdam: Elsevier; 2017. p. 349–364. doi:10.1016/B978-0-444-63600-3.00019-2.
He T, Kaplan S, Kamboj M, et al. Laboratory diagnosis of central nervous system infection. Current Infectious Disease Reports. Springer Nature; 2016;18(11):35. doi:10.1007/s11908-016-0545-6.
Rzaska M, Niewiadomski S, Karwacki Z. Molecular mechanisms of bacterial infections of the central nervous system. Anaesthesiology Intensive Therapy. 2017;49(5):387–392. doi:10.5603/AIT.2017.0080.
Barker R, Wharton SB. Infection in brain damage. In: Fawcett JW, Rosser AE, Dunnett SB (eds.) Brain Repair. Oxford: Oxford University Press; 2001. p. 55–78.
Wizemann TM, Heinrichs JH, Adamou JE, et al. Use of a whole-genome approach to identify vaccine molecules affording protection against Streptococcus pneumoniae infection. Infection and Immunity. American Society for Microbiology; 2001;69(3):1593–1598. doi:10.1128/IAI.69.3.1593-1598.2001.
Brouwer MC, Tunkel AR, van de Beek D. Epidemiology, diagnosis, and antimicrobial treatment of acute bacterial meningitis. Clinical Microbiology Reviews. American Society for Microbiology; 2010;23(3):467–492. doi:10.1128/CMR.00070-09.
Ladhani S, Slack MPE, Heys M, et al. Fall in Haemophilus influenzae serotype b (Hib) disease following implementation of a booster campaign. Archives of Disease in Childhood. BMJ Publishing Group; 2008;93(8):665–669. doi:10.1136/adc.2007.134486.
Keskin E, Öz M, Çakır Y, et al. Akut bakteriyel menenjit tanılı hastalarda etken bakteriler ve antimikrobiyal duyarlılıkları: retrospektif değerlendirme. Türk Mikrobiyoloji Cemiyeti Dergisi. 2024;54(2):135–143. doi:10.54453/TMCD.2024.1260800.
van de Beek D, Brouwer MC, Hasbun R, et al. Community-acquired bacterial meningitis. Nature Reviews Disease Primers. Nature Publishing Group; 2016;2:16074. doi:10.1038/nrdp.2016.74.
Buzgan T, Karahocagil MK, Irmak H, et al. İki yüz dört bakteriyel menenjit olgusunun retrospektif olarak incelenmesi. Türkiye Klinikleri Tıp Bilimleri Dergisi. 2010;30(5):1675–1682.
Çelik İ, Özden M, Kılıçoğlu A, et al. Yüz yirmi bir menenjit olgusunun retrospektif olarak değerlendirilmesi. Klimik Dergisi. 2003;16(1):11–14.
Kaya A, Taşyaran MA, Parlak M, et al. Atatürk Üniversitesi Enfeksiyon Hastalıkları Kliniğine son on yılda yatan akut bakteriyel menenjit olguları. Mikrobiyoloji Bülteni. 1995;29(3):250–254.
van de Beek D, Brouwer MC, Koedel U, et al. Community-acquired bacterial meningitis. Lancet. Elsevier; 2021;398(10306):1171–1183. doi:10.1016/S0140-6736(21)00883-7.
Davis LE. Acute bacterial meningitis. Continuum (Minneapolis, Minn.). 2018;24(5):1264–1283. doi:10.1212/CON.0000000000000657.
Pagliano P, Ascione T, Boccia G, et al. Listeria monocytogenes meningitis in the elderly: epidemiological, clinical and therapeutic findings. Le Infezioni in Medicina. 2016;24(2):105–111.
Nudelman Y, Tunkel AR. Bacterial meningitis: epidemiology, pathogenesis and management update. Drugs. Springer Nature; 2009;69(18):2577–2596. doi:10.2165/11530590-000000000-00000.
Voetsch AC, Angulo FJ, Jones TF, et al. Reduction in the incidence of invasive listeriosis in FoodNet sites, 1996–2003. Clinical Infectious Diseases. Oxford University Press; 2007;44(4):513–520. doi:10.1086/511039.
Allen UD, Navas L, King SM. Effectiveness of intrapartum penicillin prophylaxis in preventing early-onset group B streptococcal infection: results of a meta-analysis. Canadian Medical Association Journal. 1993;149(11):1659–1665.
Schrag S, Gorwitz R, Fultz-Butts K, et al. Prevention of perinatal group B streptococcal disease: revised guidelines from CDC. MMWR Recommendations and Reports. Centers for Disease Control and Prevention; 2002;51(RR-11):1–22.
Karadağ FY, Hızel K, Gelişen O. Doğum eylemindeki gebelerde grup B streptokok kolonizasyonu. Journal of the Turkish Society of Obstetrics and Gynecology. 2013;10:16–20.
van de Beek D, de Gans J, Spanjaard L, et al. Group A streptococcal meningitis in adults: report of 41 cases and a review of the literature. Clinical Infectious Diseases. Oxford University Press; 2002;34(9):e32–e36. doi:10.1086/339541.
Perera N, Abulhoul L, Green MR, et al. Group A streptococcal meningitis: case report and review of the literature. Journal of Infection. Elsevier; 2005;51(1):E1–E4. doi:10.1016/j.jinf.2004.09.004.
Federico G, Tumbarello M, Spanu T, et al. Risk factors and prognostic indicators of bacterial meningitis in a cohort of 3580 post-neurosurgical patients. Scandinavian Journal of Infectious Diseases. 2001;33(7):533–537. doi:10.1080/00365540110026648.
Jensen AG, Espersen F, Skinhøj P, et al. Staphylococcus aureus meningitis: a review of 104 nationwide consecutive cases. Archives of Internal Medicine. 1993;153(16):1902–1908.
Brouwer MC, Keizerweerd GD, de Gans J, et al. Community-acquired Staphylococcus aureus meningitis in adults. Scandinavian Journal of Infectious Diseases. 2009;41(5):375–377. doi:10.1080/00365540902849390.
Pintado V, Meseguer MA, Fortún J, et al. Clinical study of 44 cases of Staphylococcus aureus meningitis. European Journal of Clinical Microbiology and Infectious Diseases. Springer; 2002;21(12):864–868. doi:10.1007/s10096-002-0848-4.
Kim BN, Peleg AY, Lodise TP, et al. Management of meningitis due to antibiotic-resistant Acinetobacter species. Lancet Infectious Diseases. Elsevier; 2009;9(4):245–255. doi:10.1016/S1473-3099(09)70055-6.
Reichert MC, Medeiros EA, Ferraz FA. Hospital-acquired meningitis in patients undergoing craniotomy: incidence, evolution, and risk factors. American Journal of Infection Control. Elsevier; 2002;30(3):158–164. doi:10.1067/mic.2002.119925.
Unhanand M, Mustafa MM, McCracken GH Jr, et al. Gram-negative enteric bacillary meningitis: a twenty-one-year experience. Journal of Pediatrics. Elsevier; 1993;122(1):15–21. doi:10.1016/S0022-3476(05)83484-1.
Nkoumou MO, Betha G, Kombila M, et al. Bacterial and mycobacterial meningitis in HIV-positive compared with HIV-negative patients in an internal medicine ward in Libreville, Gabon. Journal of Acquired Immune Deficiency Syndromes. 2003;32(3):345–346.
Molyneux EM, Tembo M, Kayira K, et al. The effect of HIV infection on paediatric bacterial meningitis in Blantyre, Malawi. Archives of Disease in Childhood. BMJ Publishing Group; 2003;88(12):1112–1118. doi:10.1136/adc.88.12.1112.
Franco-Paredes C, Lammoglia L, Hernández I, et al. Epidemiology and outcomes of bacterial meningitis in Mexican children: 10-year experience (1993–2003). International Journal of Infectious Diseases. Elsevier; 2008;12(4):380–386. doi:10.1016/j.ijid.2007.09.009.
Thigpen MC, Whitney CG, Messonnier NE, et al. Bacterial meningitis in the United States, 1998–2007. New England Journal of Medicine. Massachusetts Medical Society; 2011;364(21):2016–2025. doi:10.1056/NEJMoa1005384.
Redington JJ, Tyler KL. Viral infections of the nervous system: update on diagnosis and treatment. Archives of Neurology. American Medical Association; 2002;59(5):712–718. doi:10.1001/archneur.59.5.712.
Chadwick DR. Viral meningitis. British Medical Bulletin. Oxford University Press; 2006;75–76(1):1–14. doi:10.1093/bmb/ldl003.
Henquell C, Chambon M, Bailly JL, et al. Prospective analysis of 61 cases of enteroviral meningitis: interest of systematic genome detection in cerebrospinal fluid irrespective of cytologic examination results. Journal of Clinical Virology. Elsevier; 2001;21(1):29–35. doi:10.1016/S1386-6532(00)00179-7.
Al-Qahtani SM, Shati AA, Alqahtani YA, et al. Etiology, clinical phenotypes, epidemiological correlates, laboratory biomarkers and diagnostic challenges of pediatric viral meningitis: descriptive review. Frontiers in Pediatrics. Frontiers Media; 2022;10:923125. doi:10.3389/fped.2022.923125.
Dagan R, Jenista JA, Menegus MA. Association of clinical presentation, laboratory findings, and virus serotypes with the presence of meningitis in hospitalized infants with enterovirus infection. Journal of Pediatrics. Elsevier; 1988;113(6):975–978. doi:10.1016/S0022-3476(88)80566-0.
Masri A, Dwaikat A, Haroun N, et al. Aseptic meningitis and its viral etiologies, clinical characteristics and management practices in children: a retrospective hospital-based study from Jordan. Cureus. 2022;14(4):e24383. doi:10.7759/cureus.24383.
Huang CC, Liu CC, Chang YC, et al. Neurologic complications in children with enterovirus 71 infection. New England Journal of Medicine. Massachusetts Medical Society; 1999;341(13):936–942. doi:10.1056/NEJM199909233411302.
Tyler KL. Herpes simplex virus infections of the central nervous system: encephalitis and meningitis, including Mollaret’s meningitis. Herpes. 2004;11(Suppl 2):57A–64A.
Alford CA Jr, Dolin R, Hirsch MS, et al. Herpes simplex encephalitis and clinical trial design. Lancet. Elsevier; 1982;1(8279):1013–1014. doi:10.1016/S0140-6736(82)92347-8.
T.C. Sağlık Bakanlığı Halk Sağlığı Genel Müdürlüğü. Zoonotik ve Vektörel Hastalıklar Dairesi Başkanlığı dokümanları. Ankara: T.C. Sağlık Bakanlığı; 2025.
Gundamraj V, Hasbun R. Viral meningitis and encephalitis: an update. Current Opinion in Infectious Diseases. Wolters Kluwer; 2023;36(3):177–185. doi:10.1097/QCO.0000000000000927.
Cantu RM, Das JM. Viral meningitis. In: StatPearls. Treasure Island (FL): StatPearls Publishing; 2026.
Beltran-Reyes P, Ostrosky-Zeichner L, Gonzalez-Lara MF. Update on diagnosis and treatment of fungal meningitis: lessons from recent outbreaks. Current Opinion in Infectious Diseases. Wolters Kluwer; 2024;37(6):437–442. doi:10.1097/QCO.0000000000001094.
Mohamed SH, Nyazika TK, Ssebambulidde K, et al. Fungal CNS infections in Africa: the neuroimmunology of cryptococcal meningitis. Frontiers in Immunology. Frontiers Media; 2022;13:804674. doi:10.3389/fimmu.2022.804674.
Dian S, Ganiem AR, Ekawardhani S. Cerebral toxoplasmosis in HIV-infected patients: a review. Pathogens and Global Health. Taylor & Francis; 2023;117(1):14–23. doi:10.1080/20477724.2022.2156630.
Del Brutto OH. Human neurocysticercosis: an overview. Pathogens. MDPI; 2022;11(10):1212. doi:10.3390/pathogens11101212.
Güémez A, García E. Primary amoebic meningoencephalitis by Naegleria fowleri: pathogenesis and treatments. Biomolecules. MDPI; 2021;11(9):1320. doi:10.3390/biom11091320.
