Meningitis Clinical Presentation

Clues in the patient's clinical history may suggest the specific etiologic agent that caused meningitis to develop. Detailed epidemiologic and predisposing risks should be assessed.

For example, in patients whose symptoms have lasted longer than 1 month and who have CSF pleocytosis, 40% of these individuals have tuberculous meningitis, 7% have cryptococcal meningitis, 8% have neoplasms, and 34% remain undiagnosed. (In these patients, defer ED treatment until the organism is identified.)

Exposures

History of exposure to a patient with a similar illness is an important epidemiologic clue when determining etiology (eg, individuals who were in close contact with an index case of meningococcemia). Record evidence of systemic viral infection (ie, myalgias, fatigue, anorexia). Enteroviral infection is suggested by the presence of exanthemas; symptoms of pericarditis, myocarditis, or conjunctivitis; or syndromes of pleurodynia, herpangina, and hand-foot-and-mouth disease.

Elicit a history of sexual contact and high-risk behavior from the patient. 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, skunk, raccoon, dog, fox, bat). Exposure to rodents suggests infection with LCM virus and Leptospira infection. Laboratory workers dealing with these animals also are at increased risk of contracting LCM.

The intake of unpasteurized milk and cheese predisposes to brucellosis and L monocytogenes infection.

Previous medical treatment and existing conditions

As many as 40% of patients with acute or subacute bacterial meningitis have previously been treated with oral antibiotics (presumably due to misdiagnosis at the time of initial presentation).

The presence of a ventriculoperitoneal shunt and 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 do patients with acute bacterial meningitis, with headache, nausea, minimal fever, and malaise.

The presence of cochlear implants with a positioner has been associated with a higher risk of bacterial meningitis.

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. H capsulatum and B dermatitidis are 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; and B burgdorferi is considered in regions of the northeastern and northern central United States.

Season and temperature

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

Distinguishing acute, subacute, and chronic meningitis helps to identify the causative pathogen for these diseases.

Bacterial and viral meningitis

Otherwise healthy patients within age extremes present with clinically obvious acute bacterial meningitis. In contrast, most patients with subacute bacterial meningitis present a diagnostic challenge. Systemic examination occasionally reveals a pulmonary or otitis media co-infection.

Signs of meningeal irritation include the following:

• Nuchal rigidity or discomfort on neck flexion
• Kernig sign
• Brudzinski sign

Papilledema is present in only one third of meningitis patients with increased ICP; it takes at least several hours to develop.

Focal neurologic signs include the following:

• Isolated cranial nerve abnormalities (principally III, IV, VI, VII) in 10-20% of patients
• Dramatic increase in complications from lumbar puncture, portending a worse outcome

Systemic findings can also be present. Extracranial infection (eg, sinusitis, otitis media, mastoiditis, pneumonia, urinary tract infection) may be noted. Arthritis is seen with N meningitidis but is found less commonly with other bacterial species.

Nonblanching petechiae and cutaneous hemorrhages are seen classically with N meningitidis; however, these also can occur with other bacterial and viral infections. Endotoxic shock with vascular collapse is characteristic of severe N meningitidis infection. Altered mental status, from irritability to somnolence, delirium, and coma, can develop.

Infants may have the following:

• Bulging fontanelle (if euvolemic)
• Paradoxic irritability (ie, quiet when stationary, cries when held)
• High-pitched cry
• Hypotonia
• Examine skin over entire spine for dimples, sinuses, nevi, or tufts of hair, which may indicate a congenital anomaly communicating with the subarachnoid space.

Approximately 25% of patients with bacterial meningitis present acutely, well within 24 hours of onset of symptoms. 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.

About 85% of adults and children with bacterial meningitis exhibit the classic triad of symptoms (ie, fever, headache, and neck stiffness).^[5] These symptoms can develop over several hours or over 1-2 days. Fever is the most common manifestation (95%), while the other 2 symptoms are less common.

However, in a meta-analysis of 845 patients, the sensitivity and specificity of these classic symptoms were poor. Even so, the negative predictive value of these symptoms is high (ie, the absence of fever, neck stiffness, or altered mental status eliminates the diagnosis of meningitis in 99-100% of cases).

Other symptoms can include the following:

• Nausea
• Vomiting
• Photalgia - Discomfort when the patient looks into bright lights (also called photophobia)
• Sleepiness
• Confusion
• Irritability
• Delirium
• Coma

Increased blood pressure with bradycardia can also be present. Vomiting occurs in 35% of patients. Occasionally, if a patient has been taking antibiotics for another infection, meningitis symptoms can take longer to develop or may be less intense.

On physical examination, a skin rash caused by meningococcal meningitis (50%), H influenzae, pneumococcal meningitis, echovirus type 9, or Staphylococcus aureus may be present.^[9] Other neurologic signs include the following:

• Cranial nerve palsies - Resulting from ICP or the presence of exudates encasing the nerve roots
• Focal cerebral signs (10-20%) - May develop as a result of ischemia from vascular inflammation and thrombosis
• Papilledema (< 1%) - Another sign of increased ICP; presence of papilledema suggests not only meningitis but a possible alternate diagnosis (eg, brain abscess)

One quarter of affected patients have a fulminant onset within 24 hours of infection, and there may be a history of a respiratory illness within the preceding 7 days (50%).

Patients with meningitis caused by the mumps virus usually present with the triad of fever, vomiting, and headache. It 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). As many as 40% of patients with acute or subacute bacterial meningitis have previously been treated with oral antibiotics (presumably due to misdiagnosis at time of initial presentation); in patients with partially treated meningitis, seizures may be the sole presenting symptom. Fever and changes in level of alertness or mental status occur less commonly 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 presentation―headache, nausea, minimal fever, and malaise―may 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 he or she may be irritable, vomiting, or feeding poorly. Other symptoms in this age group include temperature instability, high-pitched crying, respiratory distress, and/or bulging fontanelles (late sign in one third of neonates).

Approximately half of affected adults show signs of meningeal irritation, such as nuchal and/or spinal rigidity and a positive Kernig and/or Brudzinski sign.^[9] The Kernig sign is determined in a supine patient by flexing the hip to 90° while the knee is flexed at 90°; an attempt to further extend the knee produces pain in the hamstrings and resistance to further extension. The Brudzinski sign is determined by passively flexing the neck while the patient is in a supine position with extremities extended; this maneuver produces flexion of the hips in patients with meningeal irritation.

Resistance to passive flexion of the neck is also a sign. Exacerbation of existing headache by repeated horizontal movement of the head, at a rate of 2-3 times per second, may also suggest meningeal irritation.

Systemic findings on physical examination may provide clues to the etiology of a patient’s meningitis. Morbilliform rash with pharyngitis and adenopathy may suggest a viral etiology (eg, EBV, CMV, adenovirus, HIV). Macules and petechiae that rapidly evolve into purpura suggest meningococcemia (with or without meningitis). Vesicular lesions in a dermatomal distribution suggest varicella-zoster virus. Genital vesicles suggest HSV-2 meningitis.

Sinusitis or otitis suggests direct extension into the meninges, usually with S pneumoniae and H influenzae. Rhinorrhea or otorrhea suggests a 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, mononucleosis-like syndrome in EBV, CMV, and HIV) and fungal (eg, disseminated histoplasmosis).

The presence of a murmur suggests infective endocarditis with secondary bacterial seeding of the meninges.

General physical findings in viral meningitis are common to all causative agents, but some viruses produce unique clinical manifestations that help in focusing the diagnostic approach. The classically taught triad of meningitis consists of fever, nuchal rigidity, and altered mental status, but not all patients have all 3 symptoms, and almost all patients have headache. The examination reveals no focal neurologic deficits in the majority of cases.

Chronic meningitis

Perform careful general, systemic, and neurologic examinations, looking especially for a BCG vaccination scar, lymphadenopathy, papilledema and tuberculomas during funduscopy, and meningismus.

The presentation of chronic tuberculous meningitis may be acute, but the classic presentation is subacute and spans weeks. Patients generally have a prodrome of fever of varying degrees, malaise, and intermittent headaches. Patients often develop central nerve palsies (III, IV, V, VI, and VII), 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

The median incubation period before the appearance of symptoms in chronic syphilitic meningitis is 21 days (range 3-90 d), during which time spirochetemia develops. Three stages of disease are described, and involvement of the CNS can occur during any of these stages.

Syphilitic meningitis usually occurs during the primary or secondary stage, complicating 0.3-2.4% of primary infections during the first 2 years. Its presentation is similar to other types of aseptic meningitis, with 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 HIV have an increased risk of accelerated progression.

Although rare during stage I of Lyme disease, CNS involvement (with meningitis) may occur in Lyme disease-associated 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 following 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 disease–associated chronic meningitis, with photophobia, nausea, and neck stiffness occurring less frequently. Symptoms of 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.

Infection with C neoformans is characterized by the gradual onset of symptoms, the most common of which is headache.

Coccidioidal meningitis is the most serious form of dissemination, and 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 in the CSF.

Patients infected with B dermatitidis may present with an abscess or fulminant meningitis, while patients infected with H capsulatum may present with headache, cranial nerve deficits, or changes in mental status months prior to diagnosis.

Helminthic eosinophilic meningitis

Following ingestion of A cantonensis, 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.

Aseptic meningitis

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

Go to Aseptic Meningitis for complete information on this topic.

Risk factors for hearing loss after pneumococcal meningitis are female gender, older age, severe meningitis, and infection with certain pneumococcal serotypes (eg, 12F serotype).^[10] In 50% of patients, several complications may develop in the days to weeks following infection.

Immediate complications include the following:

• Septic shock, including DIC
• Coma with loss of protective airway reflexes
• Seizures - 30-40% of children, 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

Seizures

Seizures are a common and important complication that occur in approximately one fifth of patients. The incidence is higher in patients younger than 1 year, reaching 40%. Approximately one half of patients with this complication have repeated seizures. Patients die as a result of diffuse CNS ischemic injury or from systemic complications.

Even with effective antimicrobial therapy, significant neurologic complications have been reported to occur in as many as 30% of survivors following an episode of bacterial meningitis. Closely monitor for the development of these complications.

Cerebral edema

Some degree of cerebral edema is common with bacterial meningitis. This complication is an important cause of death.

Cranial nerve palsy and cerebral infarction

Cranial nerve palsies and the effects of impaired cerebral blood flow, such as cerebral infarction, are caused by increased ICP. In certain cases, repeated lumbar puncture 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 matter–white 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 cases are transient and small to moderate in size. Of these effusions, 2% are infected secondarily and become subdural empyemas. In the empyema, infection and necrosis of the arachnoid membrane permits formation of a subdural collection.

Risk factors include young age, rapid onset of illness, low peripheral WBC count, and high CSF protein. Seizures occur more commonly during the acute course of the disease, although 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 in 30% of patients. This complication 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 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.