Epidemiology and risk factors

In the first few days of illness, seizures occur in about 25% of children with bacterial meningitis and in more than 30% of adults with pneumococcal meningitis. Generalized convulsive seizures may occur as part of the presentation of bacterial meningitis, along with the classic triad of fever, headache, and stiff neck. Of bacterial pathogens, seizures are most often associated with Haemophilus influenzae.13

Early in the course of infection, generalized seizures and a depressed level of consciousness can result from inflammation and bacterial toxin accumulation in the subpial space. As the meningeal infectious process progresses, meningeal veins can become thrombosed, producing focal neurologic deficits including focal seizures.13

In a large meningitis case review performed at Massachusetts General Hospital,11 seizures occurred in 23% of patients with community-acquired meningitis. Seizure occurrence within 24 hours of presentation was a risk factor for death among those patients with single episodes of community-acquired meningitis.

Patients with bacterial meningitis who have been taking oral antibiotics can present with seizure as the sole initial sign or symptom; hence, all patients taking antibiotics who develop a seizure require a lumbar puncture to exclude meningitis. Rosenberg and colleagues reviewed the records of 187 patients with bacterial meningitis.14 Seizures were a presenting manifestation in 13%, and 28% of these patients had been taking antibiotics before diagnosis. Of the pretreated patients, 25% had no signs or symptoms other than seizure, whereas all patients without pretreatment had additional findings (p <.01). Patients with seizures had a poorer outcome than those without seizures.

Listeria represents an important cause of meningitis and meningoencephalitis, frequently complicated by seizures. In a large (n = 820) retrospective case review of CNS listeriosis (excluding pregnancy), patients with Listeria had a significantly lower incidence of meningeal signs than patients with acute meningitis secondary to other bacteria.15 Further, the CSF profile was significantly less likely to have a high white blood cell (WBC) count or elevated protein concentration, and Gram’s stains were negative in two-thirds. One-quarter of the patients with CNS listeriosis developed seizures. Mortality was 26% overall and was higher among the patients with seizures.

Of Rickettsial diseases, only Rocky Mountain spotted fever has significant epileptic comorbidity, with almost 10% of cases manifesting seizure as an acute illness component. Rickettsia rickettsii is transmitted via a number of different tick species. Treatment of infection is by tetracycline or doxycycline. After successful management of acute illness, CNS abnormalities, including EEG abnormalities, can persist in up to 50% of patients.16

Cerebral ischemia is a common complication of bacterial meningitis. Increased cerebral blood flow velocity (CBFV) in intracranial arteries, probably secondary to vasospasm, is a known finding in cerebral ischemia. In a prospective study of intracranial CBFVs via transcranial Doppler sonography in patients with bacterial meningitis, seizures were more frequent (43% vs. 7%) in patients with CBFV greater than 210 cm per second. Because transcranial Doppler sonography is an easily applicable, noninvasive technique for revealing vascular changes, even in severely ill patients, and because data suggest a greater seizure complication risk with increased CBFV, transcranial Doppler sonography could potentially be used to identify high-risk patients who may benefit from seizure prophylaxis.17

Neurologic sequelae in children

Neonatal bacterial meningitis is associated with significant neurologic sequelae. In a retrospective study of infants with culture-proven neonatal meningitis, a review of EEGs obtained during the acute phase of infection demonstrated that the degree of background abnormality was an accurate predictor of outcome.18 Infants who had normal or mildly abnormal backgrounds had normal outcomes, whereas those with markedly abnormal EEGs died or manifested severe neurologic sequelae at follow-up. When the EEG was considered in the context of presence or absence of clinical seizures and level of consciousness, an accurate prediction of neurologic outcome was obtained in 93% of cases.

The EEG patterns in these infants were generally nonspecific, but some abnormalities suggested more specific pathology:

  • positive rolandic sharp waves: deep white-matter necrosis
  • persistent hemispheric voltage attenuation: large-vessel infarction
  • persistent focal voltage attenuation: abscess

Thus, the EEG was valuable both for recognition of subtle and subclinical seizures and for predicting long-term prognosis of infants with neonatal bacterial meningitis.18

Inoue and colleagues compared seizures occurring in the acute phase of aseptic and bacterial meningitis in children. Of the study sample with aseptic meningitis, approximately 5% had seizures. Of this group, 80% developed seizures within 24 hours of onset of the initial symptom (which was fever in 60%), and 60% had repeated seizures on the first day. Of the study sample with bacterial meningitis, approximately 17% had a seizure, which in all cases occurred on the second day of illness.

All the children with bacterial meningitis who had seizures had abnormal head CT. The authors inferred that seizures occurring in the acute phase of aseptic meningitis tend to reflect transient cortical dysfunction secondary to nonstructural mechanisms such as fever or syndrome of inappropriate secretion of antidiuretic hormone (SIADH), whereas seizures complicating bacterial meningitis tend to be associated with structural factors.19

To study risk factors for adverse outcomes from pediatric bacterial meningitis, Grimwood and colleagues prospectively studied 166 cases for 5 to 9 years, employing neurologic, neuropsychologic, audiologic, and behavioral assessments. Statistical analysis revealed that seizures complicating the acute episode were associated with an adverse outcome.20

Baraff and coworkers performed a meta-analysis of reports of pediatric bacterial meningitis to determine the frequency of neurologic sequelae in children 2 months to 19 years of age. Of approximately 1,600 children with acute bacterial meningitis who were evaluated for at least one sequela after hospital discharge, 4.2% had epilepsy as a likely consequence of having had childhood bacterial meningitis.21

In what turned out to be a study of a long-term complication of childhood bacterial meningitis and febrile seizure, Cascino and colleagues performed a prospective investigation of temporal lobe pathology in 13 patients with facial asymmetry and intractable partial epilepsy of temporal lobe origin.22 All patients had a history of childhood bacterial meningitis or febrile seizure. Facial weakness occurred primarily during emotional expression (i.e., spontaneous smiling). Ictal EEG recordings showed that seizure origin was always in the temporal lobe contralateral to the side of facial weakness. Hippocampal atrophy was present in all epileptic temporal lobes, as measured by MRI volume studies. Thus, facial asymmetry and partial epilepsy associated with mesial temporal sclerosis can occur as long-term sequelae of childhood bacterial meningitis.

Adapted from: Goldstein MA and Harden CL. Infectious states. In: Ettinger AB and Devinsky O, eds. Managing epilepsy and co-existing disorders. Boston: Butterworth-Heinemann; 2002;83-133. 
With permission from Elsevier (www.elsevier.com). 

Reviewed By: 
Steven C. Schachter, MD
Sunday, February 29, 2004