Neurologic complications of bacterial meningitis in adults

INTRODUCTION — Bacterial meningitis continues to result in substantial morbidity and mortality despite the availability of effective antimicrobial therapy. The risk of dying or of developing complications is related to the age and general health of the patient, to the causative pathogen, to the severity and duration of illness at the time of presentation, and occasionally to delays in the initiation of antibiotic therapy. (See "Initial therapy and prognosis of community-acquired bacterial meningitis in adults".)

Complications due to bacterial meningitis can be divided into systemic and neurologic. The neurologic complications of meningitis in adults will be reviewed here. The possible protective role of dexamethasone therapy to prevent neurologic complications in selected patients and more general issues, such as the clinical manifestations, diagnosis, treatment, and prognosis of bacterial meningitis in adults, as well as neurologic complications in neonates and children with bacterial meningitis, are discussed separately. (See "Dexamethasone to prevent neurologic complications of bacterial meningitis in adults" and "Bacterial meningitis in children: Dexamethasone and other measures to prevent neurologic complications" and "Clinical features and diagnosis of acute bacterial meningitis in adults" and "Initial therapy and prognosis of community-acquired bacterial meningitis in adults" and "Treatment of bacterial meningitis caused by specific pathogens in adults" and "Bacterial meningitis in the neonate: Neurologic complications" and "Bacterial meningitis in children: Neurologic complications".)

INCIDENCE — Neurologic complications are not uncommon in adults with bacterial meningitis [1-4]. Neurologic sequelae have been estimated to occur in half of patients surviving bacterial meningitis [5]. In a review of 1412 episodes of community-acquired bacterial meningitis in adults, 21 percent of community-acquired episodes were associated with deficits that resulted in severe or moderate disability [4]. A higher rate of moderate to severe neurologic disability at discharge (34 percent) was noted in a study of 696 adults from the Netherlands [3]. The rate was much higher with pneumococcal compared with meningococcal meningitis (50 versus 12 percent). This finding is consistent with the generally worse outcomes and increased mortality seen with pneumococcal compared with other causes of bacterial meningitis. (See "Initial therapy and prognosis of community-acquired bacterial meningitis in adults", section on 'Mortality'.)

Persistent abnormal neurologic findings may include hearing loss, a major motor deficit, impaired cognition or speech, or cranial nerve palsy. Other neurologic complications are transient. The short duration of neurologic complications was illustrated in a report of 269 adults with community-acquired bacterial meningitis: a neurologic deficit developed in 21 percent during the course of the illness, but only 9 percent had a neurologic deficit at discharge [1].

RISK FACTORS — Baseline features have been used to estimate the individual risk for an adverse neurologic outcome in adults with bacterial meningitis in nine studies involving different populations and settings [6]. Most of these studies were hampered by methodologic problems related to study design, data collection, and/or analysis. As a result, no prognostic scoring system performs well enough to be useful by itself in patient management.

In observational studies, several features were associated with an unfavorable outcome: older age (>65 years), hypotension, seizures, absence of otitis or sinusitis, alcoholism, tachycardia, lower score on the Glasgow Coma Scale, cranial nerve palsy, a cerebrospinal fluid white blood cell count of less than 1000 cells per microL, a positive blood culture, and a high serum C-reactive protein concentration [1,4,7]. Delay in initial antibiotics in the emergency department (median delay of four hours) was also associated with a worse outcome [1]. (See "Initial therapy and prognosis of community-acquired bacterial meningitis in adults", section on 'Avoidance of delay'.)

In addition to the above general risk factors, the rate of complications is greatest in patients with pneumococcal meningitis [1-3]. This may result in part from the persistence of potent biologic activity in the debris of killed bacteria [8]. The debris may stimulate the host inflammatory response, which in turn contributes to tissue damage. This phenomenon may also contribute to the reduction in neurologic complications seen in some patients with pneumococcal meningitis who are treated with dexamethasone. (See "Dexamethasone to prevent neurologic complications of bacterial meningitis in adults".)

NEUROLOGIC COMPLICATIONS — The neurologic complications of bacterial meningitis include:

●Impaired mental status

●Increased intracranial pressure and cerebral edema

●Seizures

●Focal neurologic deficits (eg, cranial nerve palsy, hemiparesis)

●Cerebrovascular abnormalities

●Sensorineural hearing loss

●Intellectual impairment

These complications may be sudden or gradual in onset and can appear at any time after the onset of symptoms, including after the completion of therapy. Impaired mental status is seen most often in patients at the time of presentation; seizures are more often seen during the early acute phase of illness. Although it may also occur early, sensorineural hearing loss is typically not appreciated until the patient has recovered from the acute illness.

Complications that occur after community-acquired meningitis are similar to those that occur after health care-associated meningitis although the pathogens most likely to cause these entities and the predisposing causes are different. For example, health care associated meningitis is more often due to staphylococci and gram-negative bacilli. Health care-associated meningitis is also most often associated with neurosurgical procedures and the placement of ventricular catheters. (See "Clinical features and diagnosis of acute bacterial meningitis in adults", section on 'Presenting manifestations' and "Health care-associated meningitis and ventriculitis in adults: Clinical features and diagnosis" and "Initial therapy and prognosis of community-acquired bacterial meningitis in adults".)

Concern about both the mortality and morbidity of bacterial meningitis has led to the administration of adjunctive dexamethasone in selected patients. The data supporting this approach and the indications for dexamethasone therapy are discussed separately. (See "Dexamethasone to prevent neurologic complications of bacterial meningitis in adults".)

Altered mental status — Altered mental status is a common presenting feature in children and adults with bacterial meningitis. The major cause of severely diminished consciousness and coma is increased intracranial pressure (ICP).

In large studies of bacterial meningitis in adults, the incidence of altered mental status ranged from 71 to 83 percent at presentation [1,2,4]. In other series, coma (defined as Glasgow Coma score <8; (table 1)) was noted in 13 to 16 percent at presentation [2-4].

Increased intracranial pressure — Many patients with bacterial meningitis develop increased ICP, which can produce a number of clinical signs or problems. Mild to moderate increases in ICP typically cause headache, confusion, irritability, nausea, and vomiting. More severe increases can produce one or more of the following:

●Altered mental status that can include coma

●Bradycardia with hypertension (the Cushing reflex)

●Papilledema, sometimes with loss of vision, which has been described in 4 to 9 percent of adults [2,9]

●Cranial nerve palsy, particularly involving the abducens (VI) nerve [9]

●Herniation of the cerebellar tonsils leading to death

(See "Evaluation and management of elevated intracranial pressure in adults", section on 'Clinical manifestations'.)

Raised intracranial pressure in patients with meningitis is primarily due to cerebral edema, which can be caused by vasogenic, cytotoxic, or interstitial mechanisms [10]. The net effect of these processes is the same: an increase in the intercellular fluid volume of the brain, leading to a rise in intracranial pressure.

●Vasogenic cerebral edema usually results from increased permeability of the blood-brain barrier, especially in the choroid plexus endothelium and the endothelium of the cerebral microvasculature.

●Cytotoxic factors released from neutrophils and bacteria can directly produce cerebral edema.

●The inflammation produced by the infection can impede the normal absorption of cerebrospinal fluid (CSF) from the subarachnoid space via the arachnoid villi.

Cerebral perfusion pressure, normally maintained by an autoregulatory mechanism, becomes dependent upon peripheral blood pressure during meningitis because autoregulation is impaired [11,12]. Cerebral edema itself can increase the intracranial pressure and secondarily reduce cerebral blood flow.

The possible presence of cerebral edema should be considered in all critically ill patients with meningitis. Treatment of intracranial hypertension can be initiated if the diagnosis is confirmed by neuroimaging studies or before the diagnosis has been established if it is strongly suspected on clinical grounds (eg, papilledema, fixed dilated pupil). Dexamethasone both decreases intracranial pressure and increases vascular perfusion. (See "Evaluation and management of elevated intracranial pressure in adults" and "Dexamethasone to prevent neurologic complications of bacterial meningitis in adults".)

Seizures — Seizures occur in 14 to 30 percent of adults with acute bacterial meningitis [1-4,13]. The pathogenesis of seizures in meningitis is not well understood. Although fever may be a cofactor in very young children, bacterial toxins or secondary neurochemical changes are presumably the cause of most seizures. In one study, for example, the occurrence of seizures correlated with colony counts of greater than 10⁷ colony-forming units (CFU) in the CSF sample prior to treatment [14].

Seizures can be present at the time of admission or develop during hospitalization. In a prospective study of 696 episodes of community-acquired bacterial meningitis in adults, seizures occurred in 5 percent before admission and 15 percent after admission; the median time between admission and the first seizure was one day [3,13]. Seizures can be generalized or focal.

The incidence of seizures was significantly increased in patients with pneumococcal meningitis (24 versus 5 percent with meningococcal meningitis) [3,13]. Other risk factors for seizures in one of these series were a predisposing condition, tachycardia, low Glasgow Coma Scale score, focal neurologic deficits, a low CSF white blood cell (WBC) count (<1000 cells/mm³), and a higher CSF protein level [13]. In a randomized, placebo-controlled trial of dexamethasone therapy, seizures were less likely in the treated patient group (5 versus 12 percent) [2].

Seizures during an episode of acute meningitis are often a poor prognostic sign in adults [1,13]. In one series of 696 patients with community-acquired bacterial meningitis, seizures were associated with a higher risk of neurologic deficits at hospital discharge (24 versus 6 percent) and death (41 versus 16 percent) [13]. All five patients with status epilepticus in this case series died.

Adults who have seizures during an episode of meningitis have a small but significant risk of seizures after recovery. In a follow-up study of 199 adult survivors of bacterial meningitis, patients with seizures during the acute illness were more likely to develop recurrent seizures within five years than those without seizures in the acute phase (8 versus 2 percent) [15]. A similar frequency of late recurrence (3 percent) was noted in another report [16].

Focal neurologic deficits — Focal neurologic deficits are common complications of meningitis, with an incidence ranging from 20 to 50 percent [2,3]. The deficits include cranial nerve palsy, monoparesis, hemiparesis, gaze preference, visual field defects, aphasia, and ataxia, and most are present on admission [2,3].

As with other neurologic complications, the rate of focal deficits is significantly higher in adults with pneumococcal meningitis compared with other pathogens. In one series, the incidence of focal deficits was 23 percent in pneumococcal meningitis compared with 9 and 3 percent in meningococcal meningitis and patients with negative cultures, respectively [2]. In another series, focal neurologic deficits were present at discharge in 65 percent of those with pneumococcal versus 33 percent with meningococcal meningitis [3].

Most focal deficits resolve with successful treatment of the meningitis, but long-term disability can occur.

Cranial nerve palsy — Cranial nerve palsies have been described in 5 to 11 percent of patients and can occur alone or with other focal abnormalities [2,3,9]. .

Cranial nerve palsies can result from compression due to brain swelling or from perineuritis due to the adjacent meningeal inflammatory reaction [9]. The abducens (VI) nerve is the cranial nerve most commonly affected in meningitis, probably because its long intracranial segment adjacent to the brainstem is highly vulnerable to the elevated intracranial pressure and inflammatory reaction that can occur [9]. Cranial nerves III, IV, and VII also may become impaired in patients with meningitis. Deficits in all of these nerves are usually transient.

Bacterial meningitis can induce arachnoiditis around the optic nerve, which can lead to transient or permanent visual loss. Optic atrophy that results in irreversible total blindness is a rare complication of severe meningitis.

Another rare focal finding in patients with bacterial meningitis is cranial neuropathy due to reactivation of herpes zoster virus (Ramsay Hunt syndrome, also called herpes zoster oticus) [17]. (See "Epidemiology, clinical manifestations, and diagnosis of herpes zoster", section on 'Ramsay Hunt syndrome (herpes zoster oticus)'.)

Hemiparesis — Other focal neurologic signs that may occur in bacterial meningitis include hemiparesis or quadriparesis. The reported incidence of hemiparesis has ranged from 4 to 13 percent [2,3,9]. .

Cerebrovascular complications — Thrombosis, vasculitis, acute cerebral hemorrhage, and mycotic aneurysm formation of large, medium, or small cerebral vessels are potential complications of bacterial meningitis. These diverse processes can manifest similarly as a focal abnormality, such as hemiparesis [9,18].

In a prospective study of 86 adults with bacterial meningitis, cerebral angiography was performed in 27 (31 percent) because one or more of the following findings were present: focal neurologic deficits, abnormalities on computed tomographic (CT) scanning, or persistent coma after three days of antibiotic therapy [18]. Abnormal angiograms were found in 13 of these 27 patients; the abnormal findings included:

●Vessel wall irregularities and focal dilatations

●Arterial occlusions

●Focal arterial bleeding

●Thrombosis of the superior sagittal and cortical veins

In an observational study of 696 patients, cerebral infarction occurred in 174 (25 percent) episodes [19]. Patients with cerebral infarction were older and often presented with predisposing conditions such as otitis and/or sinusitis or an immunocompromised state. Unfavorable outcomes occurred more often in patients with cerebral infarction (62 versus 25 percent of patients without cerebral infarction; odds ratio 3.37, 95% CI 2.19-5.21). Lower CSF white cell counts and high erythrocyte sedimentation rate were found to be independent risk factors for cerebral infarction.

Another report describes a series of six patients who developed cerebral thrombosis affecting the brainstem and/or thalamus as a subacute complication of pneumococcal meningitis 7 to 19 days after initial presentation [20]. All patients had received dexamethasone initially, and five were treated again with high-dose steroids upon deterioration. Two patients survived with moderate to severe disability. Postmortem studies on two patients revealed thrombosis of penetrating arteries without evidence of vasculitis. In another study of 120 patients with community-acquired bacterial meningitis, delayed cerebral injury was seen in five patients, all of whom had received steroids within four hours of antibiotics [21].

Among 68 patients admitted to a neurologic intensive care unit with bacterial meningitis, a reduced level of consciousness at the time of admission and a low white blood cell count in the cerebrospinal fluid were found to be predictive factors for cerebral infarction [22].

A number of other rare cerebrovascular complications have been described in isolated reports. These include hemorrhagic stroke [9,23] and thrombotic infarction and/or subarachnoid hemorrhage into the brainstem [24]. Hemorrhagic strokes presumably occur when the inflammatory reaction in the subarachnoid space produces either vessel erosion or aneurysm formation.

Sensorineural hearing loss — Sensorineural hearing loss may be subtle or inapparent during the early phases of infection. It may be transient or permanent. Transient hearing loss is usually secondary to a conductive disturbance, whereas permanent hearing loss can result from damage to the eighth cranial nerve, cochlea, or labyrinth induced by direct bacterial invasion and/or the inflammatory response elicited by the infection [25-28].

Studies in adults have shown hearing loss in 12 to 14 percent, with a higher rate in pneumococcal meningitis [2,3,29]. The following observations illustrate the range of findings:

●Among 119 survivors in the placebo group in a randomized controlled trial evaluating the efficacy of dexamethasone, hearing loss was present at eight weeks after admission in 12 percent [2]. As with most other neurologic complications, the incidence of hearing loss was greater in patients with Streptococcus pneumoniae infection than in those with Neisseria meningitidis or negative cultures (21 versus 11 and 4 percent, respectively).

●Similar results were noted in the series of 696 adults with bacterial meningitis [3]. Among the 550 survivors to discharge, hearing loss was present in 14 percent, with a higher rate in pneumococcal compared with meningococcal meningitis (22 versus 8 percent).

●In a retrospective study based upon a national registry, among 240 patients with pneumococcal meningitis who underwent audiometry, 129 (54 percent) had a hearing deficit [30]. Fifty of the 129 (39 percent) patients with a hearing deficit were not suspected of having a hearing deficit at hospital discharge. Of the 240 patients, 16 (7 percent) had profound unilateral hearing loss and another 16 (7 percent) had profound bilateral hearing loss. Using multivariate analysis, risk factors for hearing loss were advanced age, female gender, and certain serotypes; serotypes 6B and 14 were associated with a lower risk of hearing loss than serotype 12F.

A mouse model of pneumococcal meningitis suggested a role for the toll-like receptor-associated adapter molecule MyD88 in the development of cochlear inflammation and hearing loss [31].

Intellectual impairment — Neuropsychological impairment is common in survivors of bacterial meningitis. A meta-analysis of three trials including 155 adult survivors of bacterial meningitis found that cognitive impairment occurred in 32 percent of patients [32]. The meta-analysis found no difference in cognitive impairment between survivors of pneumococcal and meningococcal meningitis, although two of the studies included found worse cognitive outcomes in patients with pneumococcal disease [33,34]. Dexamethasone does not appear to alter the incidence of cognitive impairment [32,34]. (See "Dexamethasone to prevent neurologic complications of bacterial meningitis in adults".)

Hydrocephalus — Several studies have reported that hydrocephalus may occur in adults as well as in children with bacterial meningitis. Most patients with this complication have a communicating form of hydrocephalus, although some patients have obstructive (noncommunicating) hydrocephalus. Among adult patients with community-onset bacterial meningitis, the reported incidence of this complication has ranged from 3 to 21 percent [35-37]. No study has been adequately powered to reliably identify predictive factors for this relatively uncommon but important complication.

Unusual complications — A variety of other neurologic complications rarely occur in adults with bacterial meningitis:

●Extra-axial fluid collections that are infected (subdural empyemas) or sterile (subdural effusions or hygromas). Drainage is mandatory if subdural empyema develops. Detecting subdural empyemas and distinguishing them from sterile fluid collections requires correlation between clinical and imaging findings.

●Spinal cord complications such as transverse myelitis or infarction, presumably as a direct result of local vascular changes with secondary cord ischemia [38].

●Brain abscesses and focal cerebritis may be causes of or complications of meningitis. When they are complications of meningitis, they occur with higher frequency in patients infected with certain uncommon causes of meningitis such as Enterobacter or Citrobacter spp [25] and tend to occur in the frontal or temporal lobes at the grey-white matter junction [39].

●Aneurysm formation of focal intracranial vessels, presumably secondary to inflammatory changes in the blood vessel wall [40].

●Ventriculitis, which may manifest as ependymal thickening and enhancement, generalized or segmental ventricular dilatation, and debris in the dependent portions of the ventricles by CT or magnetic resonance imaging [39].

SOCIETY GUIDELINE LINKS — Links to society and government-sponsored guidelines from selected countries and regions around the world are provided separately. (See "Society guideline links: Bacterial meningitis in adults" and "Society guideline links: Hearing loss and hearing disorders in adults".)

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Here are the patient education articles that are relevant to this topic. We encourage you to print or e-mail these topics to your patients. (You can also locate patient education articles on a variety of subjects by searching on "patient info" and the keyword(s) of interest.)

●Basics topic (see "Patient education: Bacterial meningitis (The Basics)")

SUMMARY

●Bacterial meningitis continues to result in substantial morbidity and mortality despite the availability of effective antimicrobial therapy. The risk of dying or of developing complications is related to the age and general health of the patient, the causative pathogen, the severity and duration of illness at the time of presentation, and occasionally to delays in the initiation of antibiotic therapy. (See 'Introduction' above.)

●Neurologic sequelae have been estimated to occur in half of the patients surviving bacterial meningitis. (See 'Incidence' above.)

●Several features are associated with an unfavorable neurologic outcome: older age (>65 years), hypotension, seizures, absence of otitis or sinusitis, alcoholism, tachycardia, lower score on the Glasgow Coma Scale, cranial nerve palsy, a cerebrospinal fluid white blood cell count of less than 1000 cells per microL, a positive blood culture, and a high serum C-reactive protein concentration. The rate of complications is greatest in pneumococcal meningitis. (See 'Risk factors' above.)

●The neurologic complications of bacterial meningitis include (see 'Neurologic complications' above):

•Impaired mental status

•Increased intracranial pressure and cerebral edema

•Seizures

•Focal neurologic deficits (eg, cranial nerve palsy, hemiparesis)

•Cerebrovascular abnormalities

•Sensorineural hearing loss

•Intellectual impairment

Neurologic complications can develop at any time during the course of bacterial meningitis. Impaired mental status is seen in most patients at presentation, and seizures are more often seen during the acute episode. Although also occurring early, sensorineural hearing loss is typically not appreciated until the patient has recovered from the acute illness. (See 'Neurologic complications' above.)

●Concern about both the mortality and morbidity of bacterial meningitis has led to the administration of adjunctive dexamethasone in selected patients. The data supporting this approach and the indications for dexamethasone therapy are discussed separately. (See "Dexamethasone to prevent neurologic complications of bacterial meningitis in adults".)