Meningitis Clinical Presentation

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 to 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 two of the following four 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.

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.

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.

Approximately 25% of patients have concomitant sinusitis or otitis that could predispose to S pneumoniae meningitis. ^[23]  In contrast, patients with subacute bacterial meningitis and most patients with viral meningitis present with neurologic symptoms developing over 1 to 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 to 10 days.

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 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 and Leptospira infection. Laboratory workers dealing with these animals also are at increased risk of contracting LCM. Animal contact leading to meningitis may vary from routine care of certain animals (like horses and S equi meningitis or campylobacter fetus meningitis associated with regular contact with cattle, goat and sheep), from cuts /scratches and bites from animals or indirect exposure (eg, swimming in water contaminated with animal urine as is the case with leptospirosis). Consumption of unpasteurized milk and cheese also predisposes to brucellosis, as well as to L monocytogenes infection.

History regarding the eating of raw or undercooked snails, crab, shrimp, fish, poultry, and snake should point to one of the causes for eosinophilic meningitis. Meningitis due to Baylisascariasis is seen in kids playing in dirt with racoon feces.

Other exposures and organisms associated with meningitis are as listed below. ^[21]

Other Exposures and Organisms Associated with Meningitis (Open Table in a new window)

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 for 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. Patients with a travel history should be evaluated for any meningotropic viruses endemic in the local geographic area.

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.

The classic triad of meningitis consists of fever, nuchal rigidity, and altered mental status, but not all patients have all three, 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, most patients with bacterial meningitis have a stiff neck, but the meningeal signs are insensitive for diagnosis of meningitis. ^[24]  Increased blood pressure with bradycardia may also be present. Vomiting occurs in 35% of patients.

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.

Non blanching petechiae and cutaneous hemorrhages may be present in meningitis caused by N meningitidis. Other causes of a petechial purpuric rash may be enteroviral disease, RMSF, West Nile encephalitis, bacterial endocarditis with meningeal involvement (50%), H influenzae, S pneumoniae, or S aureus. ^[25]  Arthritis is seen with meningococcal infection and with M pneumoniae infection, but is less common with other bacterial species.

Presence of movement disorders (tremor, myoclonus, Parkinsonism) and acute flaccid paralysis is often seen in patients with West Nile meningoencephalitis. ^[20]

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% to 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% to 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. ^[24]  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 patient’s 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.

The Waterhouse-Friderichsen syndrome due to fulminant meningococcemia can result in large petechial/bullous hemorrhages in the skin and mucous membrane, DIC, and septic shock.

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% to 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 for accelerated progression.

Lyme meningitis

Although rare during stage 1 of Lyme disease, central nervous system (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 to 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 disease–associated 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 disseminated coccidioidomycosis; 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. ^[23]

Aseptic meningitis

In contrast to patients with bacterial meningitis, patients with aseptic meningitis syndrome usually appear clinically nontoxic, with no vascular instability(See Aseptic Meningitis.). In many cases, a cause for meningitis is not apparent after the 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.

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
• Septic Thrombosis of dural venous sinuses
• 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 matter–white matter junction.

Subdural effusion

In children with meningitis who are younger than 1 year, 20% to 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.