Successful epilepsy surgery in catastrophic postencephalitic epilepsy

Methods.

All patients with intractable postencephalitic epilepsy surgically treated between 1982 and 1998 at the Montreal Neurologic Institute were evaluated retrospectively. Diagnosis of viral encephalitis was based on history and medical records consistent with CNS infection and involvement of brain parenchyma. Patients with meningitis, brain abscess, febrile convulsions without signs of CNS parenchymal involvement, chronic encephalitis, postinfectious or postvaccination encephalitis, or progressive neurologic diseases were excluded.

We analyzed age at encephalitis, age at first unprovoked seizure, seizure characteristics, MRI and CT scans, neuropsychological studies, and video/EEG, including in seven patients prolonged intracranial EEG monitoring and pathologic results. Patients were classified according to seizure outcome.6 Patients with good outcome were seizure-free or had greater than 75% reduction in the frequency of disabling seizures. Those with poor outcome had no significant change in the frequency of disabling seizures.

Each available patient was interviewed by F.D. or E.T. Handicap and quality of life were assessed by questioning patients about frequency of residual seizures, antiepileptic medications, and performance at work and in activities of daily living. Information about patients not available for interview was obtained from relatives, hospital records, or physicians. Degree of handicap was graded with the Glasgow Outcome Scale (GOS): 1 = death within the first month; 2 = vegetative state; 3 = severe disability (conscious, but partly dependent; patients who were independent in most activities of daily living, but required constant supervision because they were unable to organize their daily activities or leave their home without supervision); 4 = moderate disability (neurologic impairment, but independent; previous occupational and social abilities were no longer present); 5 = good recovery (leading an independent life, with or without minimal neurologic impairment).7

Two-tailed t-test was used for group comparisons on continuous variables, but no statistical analysis was performed on the categorical variables due to small sample sizes.

Results.

Mean age at encephalitis was 13.9 years (SD 10 years, range 7 months to 34 years). Postsurgical outcome was favorable in 9 (40%) patients and poor in the remaining 13 (table 1). Mean follow-up after surgery was 5.6 years (SD 4.4 years; range 6 months to 15 years). Mean age at infection in patients with good outcome after surgery was lower compared to those with poor outcome (9.6 years, SD 8.1, versus 16.9 years, SD 10.2; p = 0.086) (tables 1 and 2⇓). The latent period from the initial insult to the onset of recurrent seizures was shorter in patients with poor outcome (0.08 years, SD 0.28, versus 1.6 years, SD 1.9; p < 0.05).

Seizure onset was localized to one temporal lobe in 6/9 patients with good compared to only 1/13 patients with poor surgical outcome. The majority of patients (7/13) with poor outcome had extratemporal or multifocal seizure onsets. All patients had severe encephalitis including 15 who had status epilepticus (SE) or recurrent attacks during the acute infectious illness. The proportion of SE was lower in the group with favorable outcome (3/9) compared to the group with poor outcome (7/13).

Three patients had mild diffuse atrophy or normal MRI scans. Temporal abnormalities including atrophy, gliosis, and cystic changes were found in 15/19 patients where MRI was available (table 2, figure). These changes were unilateral in five and bilateral in three. Combined temporal and extratemporal abnormalities, including regional or severe diffuse atrophy, with widespread T2 signal changes were found in eight patients (see the figure).

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Figure. (A) Patient 4. Coronal T2-weighted MRI shows prominent left hippocampal and neocortical temporal atrophy with diffuse left hemispheric atrophy. He is seizure-free with no antiepileptic medication 3 years after an anterior temporal resection including the amygdala and 3.5 cm of hippocampus. Age at encephalitis was 8 years. (B) Patient 1. Coronal T2-weighted MRI shows atrophy and gliosis in the right temporal lobe, insular cortex, and orbitofrontal region. This patient is nearly seizure-free 7 years after anterior temporal resection including the amygdala and 2 cm of hippocampus. Age at herpes simplex encephalitis was 30 years.

Mean full-scale IQ was 87 (SD 14). There was no difference between patients with good (85, SD 12) or poor outcome (88, SD 16; p > 0.10).

Patients underwent temporal resection (n = 20), additional extratemporal neocortical resections (n = 2), or frontal resections (n = 2), combined with anterior callosotomy (n = 1). Pathology showed MTS in 13, focal gliosis in 3, and minimal or no changes in 2.

Follow-up interview was obtained in all patients. Mean GOS after encephalitis was 3.8 (SD 0.9). Mean interval between encephalitis and follow-up was 10.9 years (SD 8.9; range 1 to 34). Mean GOS was higher in patients with good surgical outcome (4.4, SD 0.9, versus 3.3, SD 0.6; p < 0.01).

Discussion.

Most patients in this study had catastrophic acute viral encephalitis and therefore represent a highly selected group, which may account for the divergent results between our study compared to previous ones on patients with intractable epilepsy following CNS infections.5,8,9

Age at CNS infection was previously found to be important in predicting the development of MTS, which is associated with good surgical outcome.6,8 In the current study, mean age at encephalitis was younger in patients with good outcome compared to those with poor outcome (9.6 versus 16.9 years), but this difference did not reach statistical significance.

The proportion of those who had had SE was higher in the group with poor outcome compared to those with good outcome (see table 2). The high incidence of SE reflects the severity of the initial disease, which may lead to damage in both hippocampi and extratemporal structures, and therefore obscure the pattern of clear unilateral MTS.

The Cleveland group reported favorable outcome after surgery.8 Their patients had a longer latent period (mean 4.5 years) from the initial CNS insult to the first unprovoked seizure. The latent period was shorter in both groups of our series, particularly in patients with poor surgical outcome (0.08 versus 1.6 years). The severity of the encephalitis and the more widespread nature of the insult may explain the earlier onset of the epilepsy in the current series.

Prognosis after surgical treatment in our patients depended on seizure localization: six of the nine with favorable outcome had unilateral temporal seizure onset, whereas one of the 13 with poor outcome had unilateral temporal ictal onset. The main prognostic factor for our series was not the age at initial brain insult, but the severity of the encephalitis reflected by the GOS.

The longer latency period and the lower incidence of SE in the group with favorable outcome suggest a mechanism different from the other patients with postencephalitic epilepsy. Even if there is clear MTS demonstrated by MRI, neuropsychological testing may reveal diffuse brain dysfunction, and the EEG often detects multiple epileptogenic foci, which are negative prognostic factors for seizure remission.10 Conversely, a normal or only mildly diffusely abnormal MRI is not necessarily a favorable prognostic sign, as some of the patients (38%) with poor outcome had normal MRI or mild structural abnormalities, whereas 66% of the patients with good outcome had bitemporal or extratemporal and diffuse abnormalities.

Previous reports5,7,8 also suggested the presence of a “privileged” subgroup of patients with postencephalitic epilepsy. It is unlikely that this subgroup of individuals can be identified without detailed investigation. Zemskaya et al.4 refer to temporal focalization with many temporal clinical and EEG features in patients with postencephalitic epilepsy. The fact that most patients were treated by temporal resection confirms the apparent localization of maximal abnormality, but this is obviously not sufficient in most patients to lead to a good result. The presence of extratemporal clinical features, coupled with knowledge of the severity of the encephalitis as reflected by the GOS, should lead to caution in the surgical decision and to recognition of the limited improvement that resection may be expected to bring about in many of these patients.

Although our series demonstrates an unfavorable postsurgical prognosis in the majority of patients with postencephalitic epilepsy, a small subgroup of patients develop unilateral temporal epilepsy amenable to surgical treatment with a success rate comparable to that of mesial temporal lobe epilepsy of other cause. In severely affected patients who have evidence of bilateral or diffuse disease, the outcome after surgery is usually disappointing, even after extensive localization studies using invasive intracranial techniques.