History

Only about 44% of adults with bacterial meningitis exhibit the classic triad of fever, headache, and neck
stiffness.[12] These symptoms can develop over several hours or over 1-2 days. In a large prospective study of
696 cases of adults with bacterial meningitis, van de Beek et al reported that 95% of the patients had 2 out of
the following 4 symptoms: fever, headache, stiff neck, and altered mental status. [12]
Other symptoms can include the following:

Nausea
Vomiting
Photalgia (photophobia) - Discomfort when the patient looks into bright lights
Sleepiness
Confusion
Irritability
Delirium
Coma
Approximately 25% of patients with bacterial meningitis present acutely, well within 24 hours of the onset of
symptoms. Occasionally, if a patient has been taking antibiotics for another infection, meningitis symptoms may
take longer to develop or may be less intense.
Approximately 25% of patients have concomitant sinusitis or otitis that could predispose to S
pneumoniae meningitis.[12] In contrast, patients with subacute bacterial meningitis and most patients with viral
meningitis present with neurologic symptoms developing over 1-7 days. Chronic symptoms lasting longer than
1 week suggest the presence of meningitis caused by certain viruses or by tuberculosis, syphilis, fungi
(especially cryptococci), or carcinomatosis.
Patients with viral meningitis may have a history of preceding systemic symptoms (eg, myalgias, fatigue, or
anorexia). Patients with meningitis caused by the mumps virus usually present with the triad of fever, vomiting,
and headache. This follows the onset of parotitis (salivary gland enlargement occurs in 50% of patients), which
clinically resolves in 7-10 days.
As bacterial meningitis progresses, patients of any age may have seizures (30% of adults and children; 40% of
newborns and infants). In patients who have previously been treated with oral antibiotics, seizures may be the
sole presenting symptom; fever and changes in level of alertness or mental status are less common in partially
treated meningitis than in untreated meningitis.
Atypical presentation may be observed in certain groups. Elderly individuals, especially those with underlying
comorbidities (eg, diabetes, renal and liver disease), may present with lethargy and an absence of meningeal
symptoms. Patients with neutropenia may present with subtle symptoms of meningeal irritation.
Other immunocompromised hosts, including organ and tissue transplant recipients and patients with HIV and
AIDS, may also have an atypical presentation. Immunosuppressed patients may not show dramatic signs of
fever or meningeal inflammation.
A less dramatic presentationheadache, nausea, minimal fever, and malaisemay be found in patients with
low-grade ventriculitis associated with a ventriculoperitoneal shunt. Newborns and small infants also may not
present with the classic symptoms, or the symptoms may be difficult to detect. An infant may appear only to be
slow or inactive, or be irritable, vomiting, or feeding poorly. Other symptoms in this age group include
temperature instability, high-pitched crying, respiratory distress, and bulging fontanelles (a late sign in one third
of neonates).
Epidemiologic factors and predisposing risks should be assessed in detail. These may suggest the specific
etiologic agent.

Exposures
A history of exposure to a patient with a similar illness is an important diagnostic clue. It may point to the
presence of epidemic disease, such as viral or meningococcal meningitis.

Elicit any history of sexual contact or high-risk behavior from the patient. Herpes simplex virus (HSV) meningitis
is associated with primary genital HSV infection and HIV infection. A history of recurrent bouts of benign aseptic
meningitis suggests Mollaret syndrome, which is caused by HSV.
Animal contacts should be elicited. Patients with rabies could present atypically with aseptic meningitis; rabies
should be suspected in a patient with a history of animal bite (eg, from a skunk, raccoon, dog, fox, or bat).
Exposure to rodents suggests infection with lymphocytic choriomeningitis virus (LCM) virus
andLeptospira infection. Laboratory workers dealing with these animals also are at increased risk of contracting
LCM.
Brucellosis may be transmitted through contact with infected farm animals (eg, cows or pigs). The intake of
unpasteurized milk and cheese also predisposes to brucellosis, as well as to L monocytogenes infection.

Previous medical treatment and existing conditions

A history of recent antibiotic use should be elicited. As many as 40% of patients who present with acute or
subacute bacterial meningitis have previously been treated with oral antibiotics (presumably because of
misdiagnosis at the time of initial presentation).
The presence of a ventriculoperitoneal shunt or a history of recent cranial surgery should be elicited. Patients
with low-grade ventriculitis associated with a ventriculoperitoneal shunt may have a less dramatic presentation
than those with acute bacterial meningitis, experiencing headache, nausea, minimal fever, and malaise. The
presence of cochlear implants with a positioner has been associated with a higher risk of bacterial meningitis.
Alcoholism and cirrhosis are risk factors for meningitis. Unfortunately, the multiple etiologies of fever and
seizures in patients with alcoholism or cirrhosis make meningitis challenging to diagnose.

Location and travel

Geographic location and travel history are important in the evaluation of patients. Infection with H
capsulatum or B dermatitidis is considered in patients with exposure to endemic areas of the Mississippi and
Ohio River valleys; C immitis is considered in regions of the southwestern United States, Mexico, and Central
America. B burgdorferi is considered in regions of the northeastern and northern central United States, if tick
exposure is a possibility.

Season and temperature

The time of year is an important variable because many infections are seasonal. With enteroviruses (which are
found worldwide), infections occur during late summer and early fall in temperate climates and year-round in
tropical regions. In contrast, mumps, measles, and varicella-zoster virus (VZV) are more common during winter
and spring. Arthropod-borne viruses (eg, West Nile virus, St Louis encephalitis, and California encephalitis
virus) are more common during the warmer months.

Physical Examination
The classic triad of meningitis consists of fever, nuchal rigidity, and altered mental status, but not all patients
have all 3, and almost all patients have headache. Altered mental status can range from irritability to
somnolence, delirium, and coma. The examination reveals no focal neurologic deficits in the majority of cases.
Furthermore, the majority of patients with bacterial meningitis have a stiff neck, but the meningeal signs are
insensitive for diagnosis of meningitis.[13]
Acute bacterial meningitis in otherwise healthy patients who are not at the extremes of age presents in a
clinically obvious fashion. In contrast, most patients with subacute bacterial meningitis pose a diagnostic
challenge. Systemic examination occasionally reveals a pulmonary or otitis media coinfection.
Systemic findings can also be present. Extracranial infection (eg, sinusitis, otitis media, mastoiditis, pneumonia,
or urinary tract infection [UTI]) may be noted. Endotoxic shock with vascular collapse is characteristic of
severe N meningitidis(meningococcal) infection.
General physical findings in viral meningitis are common to all causative agents, but some viruses produce
unique clinical manifestations that help focus the diagnostic approach. Enteroviral infection is suggested by the
presence of the following:

Exanthemas
Symptoms of pericarditis, myocarditis, or conjunctivitis
Syndromes of pleurodynia, herpangina, and hand-foot-and-mouth disease
Increased blood pressure with bradycardia can also be present. Vomiting occurs in 35% of patients.
Nonblanching petechiae and cutaneous hemorrhages may be present in meningitis caused by N
meningitidis (50%), H influenzae, S pneumoniae, or S aureus.[14] Arthritis is seen with meningococcal infection
and with M pneumoniaeinfection but is less common with other bacterial species.

Infants
Infants may have the following:

Bulging fontanelle (if euvolemic)

Paradoxic irritability (ie, remaining quiet when stationary and crying when held)
High-pitched cry
Hypotonia
In infants, the clinicians should examine the skin over the entire spine for dimples, sinuses, nevi, or tufts of hair.
These may indicate a congenital anomaly communicating with the subarachnoid space.

Focal neurologic signs

Focal neurologic signs include isolated cranial nerve abnormalities (principally of cranial nerves III, IV, VI, and
VII), which are present in 10-20% of patients. These result from increased intracranial pressure (ICP) or the
presence of exudates encasing the nerve roots. Focal cerebral signs are present in 10-20% of patients and
may develop as a result of ischemia from vascular inflammation and thrombosis.
Papilledema is a rare finding (< 1% of patients) that also indicates increased ICP, but it is neither sensitive nor
specific: it occurs in only one third of meningitis patients with increased ICP and is present not only in
meningitis but also in brain abscess and other disorders.

Signs of meningeal irritation

For more than 100 years, clinicians have relied on meningeal signs (nuchal rigidity, Kernig sign, and Brudzinski
sign) to evaluate patients with suspected meningitis and help determine who should undergo a lumbar puncture
(LP). However, a prospective study of 297 adults with suspected meningitis documented very low sensitivities
for these signs: 5% for the Kernig sign, 5% for the Brudzinski sign, and 30% for nuchal rigidity. [13] Thus, the
absence of the meningeal signs should not defer the performance of the LP.

Systemic and extracranial findings

Systemic findings on physical examination may provide clues to the etiology of a patients meningitis.
Morbilliform rash with pharyngitis and adenopathy may suggest a viral etiology (eg, Epstein-Barr virus [EBV],
cytomegalovirus [CMV], adenovirus, or HIV). Macules and petechiae that rapidly evolve into purpura suggest
meningococcemia (with or without meningitis). Vesicular lesions in a dermatomal distribution suggest VZV.
Genital vesicles suggest HSV-2 meningitis.
Sinusitis or otitis suggests direct extension into the meninges, usually with S pneumoniae or, less often, H
influenzae. Rhinorrhea or otorrhea suggests a cerebrospinal fluid (CSF) leak from a basilar skull fracture, with
meningitis most commonly caused by S pneumoniae.
Hepatosplenomegaly and lymphadenopathy suggest a systemic disease, including viral (eg, mononucleosislike
syndrome in EBV, CMV, and HIV) and fungal (eg, disseminated histoplasmosis). The presence of a heart
murmur suggests infective endocarditis with secondary bacterial seeding of the meninges.

Chronic meningitis
It is essential to perform careful general, systemic, and neurologic examinations, looking especially for the
following:

Lymphadenopathy

Papilledema and tuberculomas during funduscopy

Meningismus
Cranial nerve palsies
Tuberculous meningitis
The presentation of chronic tuberculous meningitis may be acute, but the classic presentation is subacute and
spans weeks. Patients generally have a prodrome consisting of fever of varying degrees, malaise, and
intermittent headaches. Cranial nerve palsies (III, IV, V, VI, and VII) often develop, suggesting basilar
meningeal involvement.
Clinical staging of tuberculous meningitis is based on neurologic status, as follows:

Stage 1 - No change in mental function, with no deficits and no hydrocephalus

Stage 2 - Confusion and evidence of neurologic deficit
Stage 3 - Stupor and lethargy
Syphilitic meningitis
The median incubation period before the appearance of symptoms in chronic syphilitic meningitis is 21 days
(range, 3-90 days), during which time spirochetemia develops. Syphilitic meningitis usually occurs during the
primary or secondary stage of syphilis, complicating 0.3-2.4% of primary infections during the first 2 years. Its
presentation is similar to those of other types of aseptic meningitis, including headache, nausea, vomiting, and
meningismus.
Meningovascular syphilis occurs later in the course of untreated syphilis, and the symptoms are dominated by
focal syphilitic arteritis (ie, focal neurologic symptoms associated with signs of meningeal irritation) that spans
weeks to months and results in stroke and irreversible damage if left untreated. Patients with concomitant HIV
infection have an increased risk of accelerated progression.
Lyme meningitis
Although rare during stage 1 of Lyme disease, central nervous system (CNS) involvement with meningitis may
occur in Lyme diseaseassociated chronic meningitis and is characterized by the concurrent appearance of
erythema migrans at the site of the tick bite. More commonly, aseptic meningitis syndrome occurs 2-10 weeks
after the erythema migrans rash. This represents stage 2 of Lyme disease, or the borrelial hematogenous
dissemination stage.
Headache is the most common symptom of Lyme diseaseassociated chronic meningitis, with photophobia,
nausea, and neck stiffness occurring less frequently. Somnolence, emotional lability, and impaired memory and
concentration may occur. Facial nerve palsy is the most common cranial nerve deficit. These symptoms of
meningitis usually fluctuate and may last for months if left untreated.
Fungal meningitis
Meningitis from C neoformans usually develops in patients with defective cell-mediated immunity (see CNS
Cryptococcosis in HIV). It is characterized by the gradual onset of symptoms, the most common of which is
headache.
Coccidioidal meningitis is the most serious form of disseminatedcoccidioidomycosis; it usually is fatal if left
untreated. These patients may present with headache, vomiting, and altered mental function associated with
pleocytosis, elevated protein levels, and decreased glucose levels. Eosinophils may be a prominent finding on
CSF analysis.
Patients infected with B dermatitidis may present with an abscess or fulminant meningitis. Patients infected
with H capsulatum may present with headache, cranial nerve deficits, or changes in mental status months
before diagnosis.

Helminthic eosinophilic meningitis

After ingestion of A cantonensis larvae, which are found in raw or undercooked mollusks, most patients with
symptomatic disease present with nonspecific and self-limited abdominal pain caused by larval migration into
the bowel wall. On rare occasions, the larvae can migrate into the CNS and cause eosinophilic meningitis.

Although A cantonensis is prevalent in Southeast Asia and tropical Pacific islands, infestations from this
parasitic nematode have been reported in the United States and the Caribbean. [15]

Aseptic meningitis
In contrast to patients with bacterial meningitis, patients with aseptic meningitis syndrome usually appear
clinically nontoxic, with no vascular instability. (SeeAseptic Meningitis.) In many cases, a cause for meningitis is
not apparent after initial evaluation, and the condition is therefore classified as aseptic meningitis. These
patients characteristically have an acute onset of meningeal symptoms, fever, and CSF pleocytosis that is
usually prominently lymphocytic.

Complications
Immediate complications of meningitis include the following:

Septic shock, including disseminated intravascular coagulation (DIC)

Coma with loss of protective airway reflexes
Seizures, which occur in 30-40% of children and 20-30% of adults
Cerebral edema
Septic arthritis
Pericardial effusion
Hemolytic anemia ( H influenzae)
Delayed complications include the following:
Decreased hearing or deafness
Other cranial nerve dysfunctions
Multiple seizures
Focal paralysis
Subdural effusions
Hydrocephalus
Intellectual deficits
Ataxia
Blindness
Waterhouse-Friderichsen syndrome
Peripheral gangrene

Cerebral edema, cranial nerve palsy, and cerebral infarction

Some degree of cerebral edema is common with bacterial meningitis. This complication is an important cause
of death.
Cranial nerve palsies and the effects of impaired cerebral blood flow, such as cerebral infarction, are caused by
increased ICP. In certain cases, repeated LP or the insertion of a ventricular drain may be necessary to relieve
the effects of this increase.
In cerebral infarction, endothelial cells swell, proliferate, and crowd into the lumen of the blood vessel, and
inflammatory cells infiltrate the blood vessel wall. Foci of necrosis develop in the arterial and venous walls and
induce arterial and venous thrombosis. Venous thrombosis is more frequent than arterial thrombosis, but
arterial and venous cerebral infarctions can be seen in 30% of patients.

Brain parenchymal damage

Brain parenchymal damage is the most important and feared complication of bacterial meningitis. It can lead to
the following disorders:

Sensory and motor deficits

Cerebral palsy
Learning disabilities
Mental retardation

Cortical blindness
Seizures

Cerebritis
Inflammation often extends along the perivascular (Virchow-Robin) spaces into the underlying brain
parenchyma. Commonly, cerebritis results from direct spread of infection, either from otorhinologic infection or
meningitis (including retrograde septic thrombophlebitis) or from hematogenous spread from an extracranial
focus of infection. Parenchymal involvement, with edema and mass effect, may be localized or diffuse.
Cerebritis can evolve to frank abscess formation in the gray matterwhite matter junction.

Subdural effusion
In children with meningitis who are younger than 1 year, 20-50% of cases are complicated by sterile subdural
effusions. Most of these effusions are transient and small to moderate in size. About 2% of them are infected
secondarily and become subdural empyemas. In the empyema, infection and necrosis of the arachnoid
membrane permit formation of a subdural collection.
In addition to young age, risk factors include rapid onset of illness, low peripheral white blood cell (WBC) count,
and high CSF protein level. Seizures occur more commonly during the acute course of the disease, though
long-term sequelae of promptly treated subdural effusions are similar to those of uncomplicated meningitis.

Ventriculitis
Ventriculitis may occur through the involvement of the ependymal lining of the ventricles. This complication
occurs in 30% of patients overall but is especially common in neonates, with an incidence as high as 92%. The
organisms enter the ventricles via the choroid plexuses. As a result of reduced CSF flow, and possibly of
reduced secretion of CSF by the choroid plexus, the infective organisms remain in the ventricles and multiply.

Ventriculomegaly
Ventriculomegaly can occur early or late in the course of meningitis and is usually transient and mild to
moderate in severity. As a result of the subarachnoid inflammatory exudate, CSF pathways may become
obstructed, leading to hydrocephalus. Exudates in the foramina of Luschka and Magendie can cause
noncommunicating hydrocephalus, whereas exudates that accumulate in the basilar cisterns or over the
cerebral convexity can develop into communicating hydrocephalus.