Clinical Presentation of Meningitis in Adults

Prof. Dr. Serhat Ünal FACP, FEFIM Hacettepe University, Faculty of Medicine Department of© Infectious by author Diseases , ANKARA

Meningitis Update ESCMIDESCMID PostgraduateOnline Lecture Educational Library Course September 2013, İzmir Why Is Clinical Examination Important? "If, in a fever, the neck be turned awry on a sudden, so that the sick can hardly swallow, and yet no tumour appear, it is mortal.- © by author

ESCMID“Aphorism Online XXXV Lecture of Hippocrates Library” Meningitis • Meningitis is a clinical syndrome characterized by inflammation of the meninges • Infectious Meningitis – caused by a variety of infectious agents • bacteria, viruses, fungi, and parasites. • Clinical signs and symptoms at presentation may predict prognosis • Only 25% of adults© by have author a classic presentation and are not a diagnostic dilemma. • ESCMIDMany patients Online have a Lecture less obvious Library presentation

Mace SE, Emerg Med Clin N Am 2008;38:281 Spanos A et al JAMA 1998;262:2700 Clinicians Suspecting Meningitis

• While taking the patient's history • Examine for – General symptoms of infection • such as fever, chills, and myalgias – Symptoms suggesting central nervous system infection © by author • photophobia, headache, nausea and vomiting, focal neurologic symptoms, or changes in mental status ESCMID Online Lecture Library Clinical Presantation of Meningitis (Dept. Of Emergency)

The suspicion of ABM is critically dependent on the early recognition of the meningitis syndrome.

• 156 patients with meningitis -Taiwan – I nitial ED diagnosis was correct in only 58% of the cases. • The 3 most common© by alternative author diagnoses – Nonmeningeal infection ESCMID– Metabolic encephalopathy Online Lecture Library – Nonspecific conditions

Chern CH, Ann Emerg Med. 2001;38. Causes of Fever and Headache

Viral infections without meningitis Meningitis Encephalitis Cerebral abscess Severe sepsis Non-specific symptoms of other infections, e.g. pneumonia, urinary tract infection (UTI), Dengue,© by malaria, author typhoid Local head and neck infections, e.g. sinusitis, tooth abscess, tonsillitisESCMID Online Lecture Library Non-infectious conditions, e.g. sub-arachnoid haemorrhage, cerebral venous thrombosis, pontine haemorrhage © by author ESCMID Online Lecture Library

Mace SE, Emerg Med Clin N Am 2008;38:281 Risk Factors

• During late summer and • Enteroviruses infections early fall in temperate climates.

• During winter and • Mumps, measles, and spring seasons. © by authorvaricella zoster viruses • Arthropod-borne viruses (eg, • During the warmer ESCMID Online LectureSt. Louis encephalitis, Library California months). encephalitis virus group )

Clues Patient’s History • A history of exposure to a • N. menigitidis patient with a similar illness ( eg close contact with an index case of meningococcemia )

• A history of sexual contact and high-risk behavior© by author• HSV, HIV

• The geographic location and • Endemic mycosis ESCMIDa travel history Online Lecture– Histoplasma Library capsulatum and Blastomyces dermatitidis – Borrelia burgdorferi Clues Patient’s History • intake of unpasteurized • L. monocytogenes, milk and cheese Brucellosis

• Animal contacts • Rabies (aseptic meningitis) – Animal bite eg, skunk,

raccoon, dog, fox, bat

• Laboratory workers • LCM

Is the Duration of Symptoms Important ? • Acute or subacute /chronic. – Acute meningitis denotes the evolution of symptoms within hours to several days • Median duration of symptomps before admission – 24 h ( 1h-14 d) – Subacute / chronic meningitis has an onset and duration of weeks to months.© by author • 2-4 wks - subacute ESCMID• > 4 wks chronic Online Lecture Library – The manifestations of subacute and chronic meningitis may be similar to those of acute meningitis, but the illness evolves more slowly. (3) Etiology and Classification

• Acute bacterial meningitis is usually characterized by an acute onset of meningeal symptoms and neutrophilic pleocytosis. – Streptococcus pneumoniae meningitis, meningococcal meningitis, or Haemophilus influenzae meningitis. • Fungal and parasitic causes of meningitis are also termed according© to by their author specific etiologic agent, – such as Cryptococcal meningitis, Histoplasma ESCMIDmeningitis, andOnline Amebic Lecturemeningoencephalitis. Library Etiology and Classification • Aseptic meningitis – Clinical and laboratory evidence for meningeal inflammation BUT negative routine bacterial cultures. – In many cases, a cause is not apparent after initial evaluation – The presentation© isby often author similar to that of ABM – Generally benign course that resolves without ESCMIDspecific therapy. Online Lecture Library

Mace SE, Emerg Med Clin N Am 2008;38:281 Sadoun T et al. Emergency Med 2009; Emergency Medicine Practice 11:9:1 Aseptic Meningitis • Aseptic meningitis is most commonly a result of viral infection –viral meningitis – The most common cause is enterovirus – It can also be due to a fungal, parasitic, or atypical bacterial infection. • Other causes – Medications, reactions© by toauthor vaccines, and specific systematic diseases with meningeal or ESCMIDparameningeal Online involvement. Lecture Library

Mace SE, Emerg Med Clin N Am 2008;38:281 Sadoun T et al. Emergency Med 2009; Emergency Medicine Practice 11:9:1 Meningitis Encephalitis The presence or absence of normal brain function is the important distinguishing feature

• Abnormalities in brain • Brain function remains function are common normal • A ltered mental status, • Uncomfortable, lethargic, or motor or sensory deficits, distracted by headache altered behavior and personality changes, and speech or movement © by authordisorders

SeizuresESCMID, postictal Online states, hemiparesis Lecture, flaccidLibrary paralysis, and paresthesias with clinical features of both Meningitis Encephalitis The presence or absence of normal brain function is the important distinguishing feature

The distiction between the two entities is frequently blurred since some patients may have both a parenchymal and meningeal process with clinical features of both. © by author • Labeled as having meningitis or encephalitis based ESCMIDupon which Online features predominateLecture Library in the illness • These patients can best be described as having meningoencephalitis Intracranial Abscess • A focal infection that begins as a localized area of inflammation • The presenting signs and symptoms of a brain abscess – Often nonspecific – Vary according to the location – Severity of the primary infection – Virulence of the bacterium© by author – Size and location(s) of the cerebral abscess ESCMID– P atient’s ability Online to mount Lecture an adequate Libraryimmune response. Zeidman SM, et al. Neurosurgery. 1995;36(1):189-193. Lee TH, et al. J Neurol Neurosurg Pscychiatry. 2007;78(3):303-309. Seydoux C, et al. Clin Infect Dis. 1992;15(3):394-401. Intracranial Abscess • Headache is the most common presenting symptom – Gradual in onset, constant and progressive in nature, and moderate to severe in intensity • Sudden worsening of the headache with new meningismus – rupture of the abscess into the intraventricular space, a life-threatening complication • Fever – only half of patients© andby low author-grade in a significant number. • Focal neurologic deficits – variably present depending on the size and location of the ESCMIDbrain abscess Online. Lecture Library Zeidman SM, et al. Neurosurgery. 1995;36(1):189-193. Lee TH, et al. J Neurol Neurosurg Pscychiatry. 2007;78(3):303-309. Seydoux C, et al. Clin Infect Dis. 1992;15(3):394-401. Factors Affecting Clinical Presentations • Encephalitis vs meningitis • Meningitis vs brain abcsess • İmmunocompromised ( HIV, cancer ) • Underlying diseases (SLE, DM, Chronic renal failure) • Extreme age© (by very author young or elderly ) ESCMID• Prior antimicrobial Online Lecture treatment Library

Mace SE, Emerg Med Clin N Am 2008;38:281 Sadoun T et al. Emergency Med 2009; Emergency Medicine Practice 11:9:1 Factors Affecting Clinical Presentations • Elderly individuals, especially those with underlying comorbidities (eg, diabetes, renal and liver disease) – present with lethargy and an absence of meningeal symptoms. • Patients with neutropenia – subtle symptoms© of bymeningeal author irritation. • Other immunocompromised hosts, including organ and tissue transplant recipients and ESCMIDpatients with Online HIV and AIDS Lecture Library – an atypical presentation. Mace SE, Emerg Med Clin N Am 2008;38:281 Sadoun T et al. Emergency Med 2009; Emergency Medicine Practice 11:9:1 Physical Examination • More clinically useful than history • Classic triad (fever, neck stiffness, and altered mental status) – comm-aqc M %44 • + headache – 95% of all patients had at least two of four symptoms – 99% for the presence© by of author 1 of these findings – The absence of fever, neck stiffness, and altered ESCMIDmental status Online effectively Lecture eliminates meningitisLibrary

Atta J et al JAMA 1999;282:175 van de Beek D N Engl J Med 2004;351(18):1849–59 Mace SE, Emerg Med Clin N Am 2008;38:281. Physical Examination

• Positive Kernig’s and Brudzinski’s signs are hallmarks of meningitis. • Kernig’s and Brudzinski’s signs were present in only about half of adults with meningitis. © by author

ESCMID Online Lecture Library Atta J et al JAMA 1999;282:175 van de Beek D N Engl J Med 2004;351(18):1849–59 Mace SE, Emerg Med Clin N Am 2008;38:281. © by author ESCMID Online Lecture Library © by author ESCMID Online Lecture Library Physical Examination • Fever – Pooled sensitivity 85% (77%-95% ) – Low specificity 45% • Neck stiffness – Pooled sensitivity 70% (83%-94%) • Kernig’s sign – Sensitivity 57% • Brudzinski nape of© neck by signauthor – Sensitivity 97% • BrudzinskiESCMID contralateral Online Lecture reflex sign Library • Sensitivity 66% Atta J et al JAMA 1999;282:175 van de Beek D N Engl J Med 2004;351(18):1849–59.

In many studies, Kernig’s and Brudzinski were not well studied

• Kerning’s sign – Sensitivity 9% – Specificity 100% • Neck stiffness – Sensitivity 15% – Specificity 100%. • Brudzinksi © by author – Sensitivity 57% • ESCMIDKernig + Brudzinski Online Lecture Library – Sensitivity 97%

Uchihara T, Tsukagoshi H. Headache. 1991;31:167-171. Physical Examination • Jolt accentuation, or amplification of a headache – with rapid horizontal head rotation at a rate of 2 to 3 rotations per second – Sensitivity of© by97% author – Specificity of 60% ESCMID Online Lecture Library Attia J,et al. JAMA. 1999;282(2):175-181. van de Beek D et al. N Engl J Med. 2004;351(18):1849-1859. Uchihara T, Tsukagoshi H. Headache. 1991;31(3):167-171. Neman DH. Ann Emerg Med. 2004;44(1):71-73. Physical Examination • Alterations in mental status – Ranging from confusion to coma, • Pooled sensitivity of 67% (78% -83%) • In low –risk patients, normal mental status may be helpful in ruling out meningitis.

Atta J et al JAMA 1999;282:175 • Alterations in mental© by status author – Aseptic < bacterial meningitis • Moderate to severe mental status abnormalities (3% vs ESCMID44%, respectively). Online Lecture Library

Magnussen CR. N Y State J Med. 1980;80:901-906. Physical Examination • Meningitis should be in the differential diagnosis when the combination of fever plus a seizure occurs. – Seizures occur in 5% to 28% of adults who have meningitis • In geriatric patients, frequently the only presenting sign ©of meningitisby author is confusion or an altered mental status. ESCMID Online LectureDurand ML, et al.. Library N Engl J Med. 1993;328:21 -28 Pfister HW Arch Neurol 1993;50(6):575–81. Hussein AS Medicine (Baltimore) 2000;79(6):360–8. Choi C. Clin Geriatric Med 1992;8(4):889–902 Physical Examination

• Rash 22% - %26 – 92% N.meningitidis

• In patients with meningococcemia – A petechial rash 73%, – Purpura 20%

– A mong patients with© bycommunity author-acquired bacterial meningitis , overall incidence of N meningitidis was low (14%) ESCMID Online Lecture Library • P ooled sensitivity of a rash for the diagnosis of meningitis was poor

Rashes N.meningitidis

• Papilledema and other signs of increased ICP may be present – Coma, increased blood pressure with bradycardia, and cranial nerve III palsy may be present. – The presence of papilledema also suggests a possible alternate© bydiagnosis author (eg, brain abscess).

ESCMID Online Lecture Library van de Beek D et al. N Engl J Med. 2004;351(18):1849-1859. Physical Examination • Patients with severe meningeal irritation spontaneously tripod position – The knees and hips flexed, the back arched at a lordotic angle, the neck extended, and the arms brought back to support the thorax. • Focal neurologic deficits – 1/3 pts – Palsy or dysfunction of cranial nerves III, VI, VII, and VIII • Focal cerebral abnormalities© by author – Hemiparesis, monoparesis, and aphasia ESCMID– Ischemia and Online infarction Lecturesecondary to Librarycerebral infectious thrombophlebitis complicate meningitis

van de Beek D et al. N Engl J Med. 2004;351(18):1849-1859. Physical Examination

• Arthritis 7% – N.meningitidis 12% • Early-onset arthritis and monoarticular arthritis were more common in patients with pneumococcal meningitis than in patients with meningococcal© by meningitis. author

ESCMID Online Lecture Library

van de Beek D et al. N Engl J Med. 2004;351(18):1849-1859. Systemic findings upon physical examination may provide clues to the etiology

• Morbilliform rash with • Viral etiology (eg, Epstein- pharyngitis and Barr virus [EBV], adenopathy cytomegalovirus [CMV], adenovirus, HIV). • Macules and petechiae that rapidly evolve into • Meningococcemia (with purpura © by authoror without meningitis)

• ESCMIDVesicular lesions Online in a Lecture Library dermatomal distribution • VZV Systemic findings upon physical examination may provide clues to the etiology

• Sinusitis or otitis • S pneumoniae, H influenzae

• Rhinorrhea or otorrhea • CSF leak from a basilar skull S pneumoniae fracture,

• Hepatosplenomegaly and • a systemic disease, lymphadenopathy © by authorincluding viral (eg, mononucleosislike syndrome in EBV, CMV, and ESCMID Online LectureHIV) and fungalLibrary (eg, disseminated histoplasmosis) disease. Systemic findings upon physical examination may provide clues to the etiology

• Murmur • Endocarditis

• Parotitis • Mumps

• The presence of a • Bacterial M ventriculoperitoneal© by author shunt or a cochlear ESCMIDimplant Online Lecture Library

Wiberg K et al. Southern Med J 2008;101:10:1012

696 episodes of community-acquired acute bacterial meningitis

In terms of clinical findings

Fever - 79.8% © by author Headache - 88.2% ESCMID Online Lecture Library Stiffness of the neck - 89.8% Does This Adult Patient Have Acute Meningitis? • Medline search for articles from 1966-1997, English and French articles, describing clinical accuracy of examinations. – In a meta-analysis of 845 patients, 139 studies • the sensitivity and specificity of these classic symptoms were poor. • Fever is the most© by common author manifestation (95%), while stiff neck and headache are less common. ESCMID• The negative Online predictive Lecture value of theseLibrary symptoms - % 99-100

Atta J et al JAMA 1999;282:175 Does This Adult Patient Have Acute Meningitis? Studies Assessing Clinical Presentation of Patients

Atta J et al JAMA 1999;282:175 Does This Adult Patient Have Acute Meningitis? Sensitivity of Clinical History in the Diagnosis of Meningitis

Atta J et al JAMA 1999;282:175 History Results • Individual items of the clinical history have low accuracy for the diagnosis of meningitis in adults – Pooled sensitivity • Headache, 50% • Nausea/vomiting, 30% – Neck stiffness + headache + nausea/vomiting • Sensitivity, 28% • From the prospective© by study: author Spec ificities ESCMID– 15% for a nonpulsatile Online Lectureheadache, Library – 50% for a generalized headache – 60% for nausea and vomiting. Atta J et al JAMA 1999;282:175 History Results

• Clinical history alone is not useful in establishing a diagnosis of meningitis –Many patients - impaired mental status of patients with meningitis • pooled sensitivity, 67% –who are relatively© by incapableauthor of providing an accurate clinical history. ESCMID Online Lecture Library

Atta J et al JAMA 1999;282:175 Does This Adult Patient Have Acute Meningitis? Sensitivity of the Physical Examination in the Diagnosis of Meningitis

Atta J et al JAMA 1999;282:175 The clinical features of meningitis are a reflection of the underlying pathophysiologic processes

A. Chaudhuri et al. 2008 EFNS European Journal of Neurology 15, 649–659 Elderly Patients • A subtle clinical presentation of meningitis • L ess likely to have neck stiffness and meningeal signs • More likely to have mental status changes, seizures, neurologic deficits, and even hydrocephalus • More likely a high© byfever author and even be afebrile • M ental status changes ESCMID– From delirium Online to psychosis, Lecture senility, Library a transient ischemia attack, or a stroke.

Kulchycki LK, Edlow JA.Emerg Med Clin North Am 2006;24(3):273–98 Adedipe A, Lowenstein R Emerg Med Clin North Am 2006;24:433–48.. Elderly Patients • Classic signs and symptoms of meningeal irritation are unreliable in the elderly and make the diagnosis of meningitis more difficult • Not uncommon false-positive findings of meningitis • Signs and symptoms of meningeal irritation may be found in healthy elderly people. – the presence of limited neck mobility and cervical spine disease. © by author • Meningitis in the elderly frequently ESCMID– Associated Online with a delay Lecture in diagnosis Library – High mortality rate Kulchycki LK, Edlow JA.Emerg Med Clin North Am 2006;24(3):273–98 Adedipe A, Lowenstein R Emerg Med Clin North Am 2006;24:433–48..

Listeria meningitis

• Increased tendency to have seizures and focal neurologic deficits early in the course of infection • Some pts present with a syndrome of rhombencephalitis – ataxia, cranial nerve palsies, and/or nystagmus • Fever 92% © by author • Altered sensorium 65% • ESCMIDFocal neurologic Online deficits Lecture 37% Library

Mylonakis E et al. Medicine 1998;77:313 Brouwer MC et al. Clin Infect Dis 2006;43:1233 Listeria Meningoencephalitis

• Clinical presentation – From a mild illness with fever and mental status changes to a fulminant course with coma. • Most pts – subacute illness – 42% of pts meningeal irritation – Focal neurologic ©sign by – e ncephaliticauthor component • Cranial nerve abnormalities, ataxia, tremors, hemiplegia, and ESCMIDdeafness Online Lecture Library • Seizures can occur and often begin later in the course

Mylonakis E et al. Medicine 1998;77:313 Brouwer MC et al. Clin Infect Dis 2006;43:1233 Evidence of Systemic Viral Infection • Myalgias, fatigue, anorexia • Enterovirus infection – The presence of exanthemas – Symptoms of pericarditis, myocarditis, or conjunctivitis – Syndromes of pleurodynia, herpangina, and hand- foot-and-mouth© disease by author • A history of recurrent bouts of benign aseptic ESCMIDmeningitis Online Lecture Library – Mollaret syndrome, which is caused by HSV.

HIV-1 Meningitis

• The clinical findings resolve without treatment.

• Pts may be erroneously assumed to have a benign cause of viral meningitis

• A high index of suspicion for primary HIV © by author infection in patients at increased risk for ESCMIDacquisition Online of this virus Lecture Library

Herpes simplex meningitis

• Primary HSV has been increasingly recognized as a cause of viral meningitis in adults. • Viral meningitis in immunocompetent adults is generally caused by HSV-2 – In contrast to HSV encephalitis – HSV-1 • Pts with primary genital herpes – 13%-36% meningeal involvement (headache, photophobia and meningismus ) © by author • Primary HSV-2 meningitidis –ESCMID85% genital lesionsOnline Lecture Library – Generally precede the onset of CNS symptoms by seven days. Kupila T et al. Neurology 2006;66:75 Landry ML et al. Am J Med 2009;122:688

Recurrent (Mollaret's) Meningitis • A form of recurrent benign lymphocytic meningitis (RBLM) – Uncommon illness – Characterized by greater than three episodes of fever and meningismus lasting two to five days, followed by spontaneous resolution – A large patient-to-patient variation in the time course to recurrence© by that author can vary from weeks to years. ESCMID– ½ pts - transient Online neurological Lecture manifestations, Library • Seizures, hallucinations, diplopia, cranial nerve palsies, or altered consciousness. Shalabi M et al. CID 2006;43:1194 Schlensinger Y et al. CID 1995;20:842 Chan TY et al. Diag Cytopathol 2003;28:227 Recurrent (Mollaret's) Meningitis

• The most common etiologic agent in Mollaret's meningitis is HSV-2 – Many patients do not have evidence of genital lesions at the time of presentation • On Papanicolaou's stain of CSF – Large granular plasma cells is considered pathognomonic • Noninfectious etiologies for Mollaret's meningitis – An intracranial epidermoid© by cystauthor or other cystic abnormalities in the brain ESCMID– Meningeal irritation Online due to Lectureintermittent leakage Library of irritating squamous material into the CSF Shalabi M et al. CID 2006;43:1194 Schlensinger Y et al. CID 1995;20:842 Chan TY et al. Diag Cytopathol 2003;28:227 Other Viruses • Lymphocytic choriomeningitis virus – İ nfluenza-like systemic illness + headache and meningismus. – A minority of patients - orchitis, parotitis, myopericarditis, or arthritis. • Mumps – Aseptic meningitis - the most frequent extrasalivary complication of mumps – Common cause of viral© bymeningitis author 10%- 20% of all cases – The most frequent manifestations ESCMID• Headache, low Online-grade fever, andLecture mild nuchal rigidity.Library – The onset of meningitis is variable • before, during, or after an episode of mumps parotitis. İhekwaba U et al. CID 2008;47:783 MMWR Morb Mortal Wkly Rep 2005;54:747

Other Viruses • A number of other viruses can infrequently be associated with viral meningitis • In certain areas of the United States, arthropod-borne viruses can cause aseptic meningitis. – West Nile virus, St. Louis encephalitis virus, and California encephalitis virus associated with encephalitis. • Aseptic meningitis© bycan alsoauthor be associated with – Primary varicella zoster infection ESCMID– Herpes zoster, Online EBV,CMV Lecture, human herpes Library virus-6, and adenoviruses. İhekwaba U et al. CID 2008;47:783 MMWR Morb Mortal Wkly Rep 2005;54:747 Chronic Meningitis

• The symptoms - static, fluctuate, and/or slowly worsen. • The symptoms and clinical course of chronic meningitis vary widely from patient to patient. © by author ESCMID Online Lecture Library Tan TQ et al. Semin Pediatr Infect Dis 2003;14:131 Cohen BA. Curr Neurosci Rep 2005;5:429 Clinically useful or important clues to the cause of chronic meningitis

CLUE DIAGNOSIS

Positive tuberculin skin test Tuberculosis

Residence or travel to the Southwestern Coccidioidomycosis United States, Southern California or Mexico

Hypothalamic, optic or pituitary lesions on Sarcoidosis cranial imaging

Sarcoidosis, Behcet's disease, Vogt-Koyanagi- Uveitis/iritis Harada syndrome Radiculopathy and/or cranial nerve palsies© by Lymeauthor disease Prior residence in Mexico, Central or South America, India, Sub-Saharan Africa or the Cysticercosis CaribbeanESCMID Online Lecture Library

Exposure to unpasturized milk or contact with cows, goats, swine or sheep (including Brucellosis butchering or working in a packing house) Clinically useful or important clues to the cause of chronic meningitis

CLUE DIAGNOSIS

Peripheral 7th nerve paralysis Sarcoidosis Diabetes insipidus Sarcoidosis Poliosis (whitening of the eyebrows and Vogt-Koyanagi-Harada syndrome eyelashes and vitiligo) Recurrent genital or oral ulcerations Behcet's disease A preexisting immunosuppressive condition or Cryptococcosis, tuberculosis, toxoplasmosis, therapy endemic mycoses

Nocardiosis, actinomycosis, aspergillosis, Predominately neutrophilic cerebrospinal© byfluid author systemic lupus erythematosus, chemical or (CSF) pleocytosis drug-induced meningitis ESCMID Online Lecture Library Coccidioidomycosis, lymphoma, Eosinophilic CSF pleocytosis Angiostrongylus, cysticercosis, schistosomiasis

Hypogammaglobulinemia Echovirus Chronic Candida Meningitis • Clinically resembles meningitis caused by tuberculosis or cryptococcosis. • Headache, fever, and nuchal rigidity - the most common findings, • Vomiting, confusion, visual disturbances, and cranial nerve palsies © by author • HIV-infected pts the major clinical features ESCMID– headache +Onlinefever in the Lecture absence of Libraryfocal neurologic symptoms Voice RA et al. Clin Infect Dis 1994:19.60 Casado JL et al. Clin Infect Dis 1997;25:673 TB Meningitis • Early recognition of TB meningitis is of paramount importance . • The clinical outcome depends greatly upon the stage at which therapy is initiated • The usual presentation - a subacute febrile illness • About one-third of patients on presentation have underlying generalized© by author (miliary ) tuberculosis ESCMID– careful fundoscopic Online examination Lecture often Library shows choroidal tubercles Al-Deeb SM et al. Clin Neuro Neurosurg 1992;94:Suppl S30 Kent SJ et al. Clin Infect Dis 1993:17:987 TB Meningitis • Abnormalities on chest radiograph – 50% – Ranging focal lesions to a subtle miliary pattern • Tuberculin skin test – Majority positive – A negative result does not exclude the diagnosis • Atypical features – Acute , rapidly progressive like pyogenic meningitis – Slowly progressive© dementia by author over months or even years characterized by personality change, social withdrawal, loss of libido, and memory deficits ESCMID– An encephalitic Online course manifested Lecture by Librarystupor, coma, and convulsions without overt signs of meningitis. Al-Deeb SM et al. Clin Neuro Neurosurg 1992;94:Suppl S30 Kent SJ et al. Clin Infect Dis 1993:17:987 Cryptococcal Meningoencephalitis • Clinical presentation in HIV seronegative patients is variable – Symptoms for up to several months prior to diagnosis OR – Severe headache for a few days, intermittent headache for months, or with no headache. – Many patients - subacute meningitis or meningoencephalitis© by author • Fever is observed in 50% ESCMID• Headache, lethargy,Online coma, Lecture personality changes,Library and memory loss typically develop over 2 to 4 weeks

Pappas G et al. Clin Infcet Dis 2001;33:690 Cryptococcal Meningoencephalitis

• Solid organ transplant recipients – 2,8% pts – The Median time to disease onset – 21 m – 68% of pts - > 1 years after tx – 25 % of pts – fungemia • Untreated cryptococcal© by author fatal meningitis is also frequentlyESCMID Online Lecture Library Husain S et al Emerg. Infect Dis 2001;7:375 Vilchez RA et al Am J Transplant 2020;2:575 AIDS-associated cryptococcal meningoencephalitis • AIDS-defining illness – 60% of the HIV-infected patients in whom it is diagnosed • It rarely occurs in patients with < CD4 T- lymphocyte 100/microL. • Symptoms typically begin indolently over a period of one to© two by weeks. author • The most common symptoms ESCMID– Fever, malaise, Online and headache Lecture . Library – Stiff neck, photophobia, and vomiting are seen in ¼ -1/3 of patients. Rex JH et al. Clin Infcet Dis 2000;30:47

AIDS-associated cryptococcal meningoencephalitis • The initial physical examination may be underwhelming • On presentation – 24 % of pts - altered mentation – 6 % of pts focal neurological deficits • Other manifestations© by ofauthor disseminated disease may be evident, ESCMID– Cough, tachypnea Online and Lecture skin lesions Libraryresembling molluscum contagiosum Rex JH et al. Clin Infcet Dis 2000;30:47

Other Classification

• Inflammation of the central nervous system can be “community or nosocomial in origin.” © by author ESCMID Online Lecture Library Van de Beek D et al. N Engl J Med 2010;362:146-54. Healthcare Associated Meningitis • Meningitis is the most common CNS infection. – 100 000 discharges • 20 for cancer pts • 5-12 for solid organ tx pts – Second most common CNS infection after craniotomy - 22% – The most common© by form author of CNS infection after venticulat shut placement – 76% ESCMID Online Lecture Library

Moore CC , Farr BM, Scheld WM Central Nervours System Infections Hospital Infcetion Ed: Jarvis WR, 2007, p573 Healthcare Associated Meningitis • A clinical suspicion of nosocomial bacterial meningitis – Prompt a diagnostic workup and antimicrobial therapy. • Fever and a decreased level of consciousness are the most consistent clinical features – Fever not seen ©in postsurgicalby author pts • ESCMIDMeningitis usually Online begins Lecture within 10Library days of neurosurgery.

Van de Beek D. Et al. N Engl J Med 2010;362:146-54.

Healthcare Associated Meningitis

• Difficult to recognize

– Nonspecific findings

– P ts who are sedated,

– Pts who have just undergone neurosurgery, or © by author – Pts who have an underlying disease that may ESCMIDmask the symptoms.Online Lecture Library

Van de Beek D. Et al. N Engl J Med 2010;362:146-54. Healthcare Associated Meningitis • Infections associated with cerebrospinal fluid shunts – nonspecific symptoms • such as low-grade fever or general malaise – signs of meningeal irritation - < 50% of patients. © by author – Symptoms and signs of infection may also be associated ESCMIDwith the distal Online portion of Lecturethe shunt (i.e., Library peritonitis or bacteremia). Van de Beek D. Et al. N Engl J Med 2010;362:146-54. Healthcare Associated Meningitis

• In nonsurgical pts, clinical manifestations are more diagnostically useful indicator. – Geriatric pts and other immunosupressed pts may not show clasical manifestations. • The clinical picture© oftenby author is more dfficult to interpret for nosocomial than for comm-acq ESCMIDmeningitis Online Lecture Library

Van de Beek D. Et al. N Engl J Med 2010;362:146-54. HCA Meningoencephalitis

• After corneal and dural tx taken from cadavers • After NS using contaminanted instruments or electrodes. • Rabies and CJD© by author ESCMID Online Lecture Library