Anne M. McIntosh

Preoperative MRI predicts outcome of temporal lobectomy: An actuarial analysis

we used actuarial methods to study outcome after temporal lobectomy in 135 consecutive patients classified into subgroups according to preoperative MRI findings. Sixty months after surgery, 69% of patients with foreign tissue lesions, 50% with hippocampal sclerosis, and 21% with normal MRIs had no postoperative seizures. An eventual seizure-free state of 2 years or more, whether the patient was seizure-free since surgery or not, was achieved by 80% of patients with foreign tissue lesions, 62% of those with hippocampal sclerosis, and 36% of those with normal MRIs. Outcome was worse in those with normal MRIs than in the other two groups. Early postoperative seizures with later remission (the “mming down” phenomenon) occurred in all groups. Late seizure recurrence was present only in the hippocampal sclerosis group. These data show that preoperative MRI is a useful predictor of outcome and that actuarial analysis provides insight into different longitudinal patterns of outcome in MRI subgroups. This information can now be used in preoperative counseling.

Seizure Outcome after Temporal Lobectomy: Current Research Practice and Findings

Summary:  Purpose: The literature regarding seizure outcome and prognostic factors for outcome after temporal lobectomy is often contradictory. This is problematic, as these data are the basis on which surgical decisions and counseling are founded. We sought to clarify inconsistencies in the literature by critically examining the methods and findings of recent research.

Hippocampal sclerosis studied in identical twins

Objective: To test both the genetic and acquired hypotheses for the etiology of hippocampal sclerosis (HS) by studying with optimized and quantitative MRI three monozygous (MZ) twin pairs in which the index twin had temporal lobe epilepsy and HS. Background: There is conflicting evidence in the literature regarding whether HS is genetic or acquired prenatally, perinatally, or as a consequence of prolonged childhood seizures. Methods: We compared three MZ pairs with 30 age-matched control subjects who had no history of a neurologic disorder; we also used the twins as matched samples to assess subtle differences between the affected and unaffected twins. Results: All of the affected twins had prolonged seizures with fever in early childhood, which stood out as the unique factor common to all affected twins and was absent in all the unaffected twins. HS was present in all affected twins but was absent in the unaffected twin on visual, volumetric, and T2 relaxometry criteria. Comparison of the affected twin with the co-twin revealed that intracranial volume ipsilateral to the HS was relatively small in two of three affected twins. Conclusions: The absence of HS in the unaffected twin is strong evidence against a genetic hypothesis for HS. Neither perinatal problems nor birth order were factors in determining the presence of HS. This twin study supports the notion of HS as an acquired lesion secondary to prolonged seizures in early childhood and suggests that regional abnormalities of intracranial volume are associated with HS.

Effects of vaccination on onset and outcome of Dravet syndrome: a retrospective study

BACKGROUND Pertussis vaccination has been alleged to cause an encephalopathy that involves seizures and subsequent intellectual disability. In a previous retrospective study, 11 of 14 patients with so-called vaccine encephalopathy had Dravet syndrome that was associated with de-novo mutations of the sodium channel gene SCN1A. In this study, we aimed to establish whether the apparent association of Dravet syndrome with vaccination was caused by recall bias and, if not, whether vaccination affected the onset or outcome of the disorder. METHODS We retrospectively studied patients with Dravet syndrome who had mutations in SCN1A, whose first seizure was a convulsion, and for whom validated source data were available. We analysed medical and vaccination records to investigate whether there was an association between vaccination and onset of seizures in these patients. Patients were separated into two groups according to whether seizure onset occurred shortly after vaccination (vaccination-proximate group) or not (vaccination-distant group). We compared clinical features, intellectual outcome, and type of SCN1A mutation between the groups. FINDINGS Dates of vaccination and seizure onset were available from source records for 40 patients. We identified a peak in the number of patients who had seizure onset within 2 days after vaccination. Thus, patients who had seizure onset on the day of or the day after vaccination (n=12) were included in the vaccination-proximate group and those who had seizure onset 2 days or more after vaccination (n=25) or before vaccination (n=3) were included in the vaccination-distant group. Mean age at seizure onset was 18.4 weeks (SD 5.9) in the vaccination-proximate group and 26.2 weeks (8.1) in the vaccination-distant group (difference 7.8 weeks, 95% CI 2.6-13.1; p=0.004). There were no differences in intellectual outcome, subsequent seizure type, or mutation type between the two groups (all p values >0.3). Furthermore, in a post-hoc analysis, intellectual outcome did not differ between patients who received vaccinations after seizure onset and those who did not. INTERPRETATION Vaccination might trigger earlier onset of Dravet syndrome in children who, because of an SCN1A mutation, are destined to develop the disease. However, vaccination should not be withheld from children with SCN1A mutations because we found no evidence that vaccinations before or after disease onset affect outcome.

LGI1 mutations in temporal lobe epilepsies

Background and Objectives: A number of familial temporal lobe epilepsies (TLE) have been recently recognized. Mutations in LGI1 (leucine-rich, glioma-inactivated 1 gene) have been found in a few families with the syndrome of autosomal dominant partial epilepsy with auditory features (ADPEAF). The authors aimed to determine the spectrum of TLE phenotypes with LGI1 mutations, to study the frequency of mutations in ADPEAF, and to examine the role of LGI1 paralogs in ADPEAF without LGI1 mutations. Methods: The authors performed a clinical and molecular analysis on 75 pedigrees comprising 54 with a variety of familial epilepsies associated with TLE and 21 sporadic TLE cases. All were studied for mutations in LGI1. ADPEAF families negative for LGI1 mutations were screened for mutations in LGI2, LGI3, and LGI4. Results: Four families had ADPEAF, 22 had mesial TLE, 11 had TLE with febrile seizures, two had TLE with developmental abnormalities, and 15 had various other TLE syndromes. LGI1 mutations were found in two of four ADPEAF families, but in none of the other 50 families nor in the 21 individuals with sporadic TLE. The mutations were novel missense mutations in exons 1 (c.124T→G; C42G) and 8 (c.1418C→T; S473L). No mutations in LGI2, LGI3, or LGI4 were found in the other two ADPEAF families. Conclusion: In TLE, mutations in LGI1 are specific for ADPEAF but do not occur in all families. ADPEAF is genetically heterogeneous, but mutations in LGI2, LGI3, or LGI4 did not account for families without LGI1 mutations.

Long‐term seizure outcome and risk factors for recurrence after extratemporal epilepsy surgery

Purpose:  We aimed to assess long‐term seizure outcome and risk factors for seizure recurrence in a cohort of patients who have undergone extratemporal resection for management of refractory seizures.

Early seizures after temporal lobectomy predict subsequent seizure recurrence

Patients are understandably anxious if seizures occur immediately after temporal lobectomy. Such “neighborhood” seizures are commonly regarded as irrelevant to seizure outcome and discounted in outcome measurement. We conducted an in‐depth examination of early postoperative seizures (<28 days) and outcome. The risk of recurrence at one postoperative year was calculated using Poisson regression, and statistical adjustments were made for preoperative pathology. Of 321 patients, 69 (22%) experienced early postoperative seizures. These early seizures were associated with subsequent seizure recurrence (rate ratio [RR] 5.9; 95% confidence interval [CI], 4.1–8.4). Among patients with early seizures, the only significant factor was the presence of seizure precipitants, which was associated with a lower recurrence risk. However, when compared with patients with no early seizures, those with precipitants to early seizures had a higher risk of recurrence (RR, 3.0; 95% CI, 1.8–5.2). The risk was higher again for patients without precipitants to early seizures (RR, 7.6; 95% CI, 5.0–11.5). Early seizures and other seizure recurrences in the first postoperative year did not differ in their effect on subsequent outcome (X2 [3] = 3.4, p = 0.33). We conclude that early postoperative seizures are associated with subsequent seizure recurrence. These findings have implications for patient counseling and the measurement of outcome. Ann Neurol 2005;57:283–288

Subtle Microscopic Abnormalities in Hippocampal Sclerosis Do Not Predict Clinical Features of Temporal Lobe Epilepsy

Summary:  Purpose: Subtle microdysplastic features are found in some patients with hippocampal sclerosis (HS) and refractory temporal lobe epilepsy. The significance of these findings is unknown. We investigated their frequency, relation to the pattern of HS, and clinical associations.

Mortality in Dravet syndrome

We measured the mortality rate and the rate of Sudden Unexpected Death in Epilepsy (SUDEP) in Dravet Syndrome (DS). We studied a cohort of 100 consecutively recruited, unrelated patients with DS; 87 had SCN1A mutations. Living cases had a median follow-up of 17 years. Seventeen patients died, at a median age of seven years (inter-quartile range 3-11 years) with causes of death: 10 SUDEP, four status epilepticus, two drowning and one asphyxia. The SUDEP classification included three Definite, one Definite Plus and six Probable. The Dravet-specific mortality rate/1000-person-years was 15.84 (98% CI 9.01-27.85). The Dravet-specific SUDEP rate was 9.32/1000-person-years (98% CI 4.46-19.45). The Dravet-specific SUDEP rate is the only documented syndrome-specific SUDEP rate. SUDEP in DS occurs mainly in childhood. It is also the highest SUDEP rate, considerably higher than the recent 5.1 SUDEP rate/1000-person-years for adults with refractory epilepsy.

Profiles of psychosocial outcome after epilepsy surgery: The role of personality

Purpose:  We have previously found that the developmental time frame of epilepsy onset influences adult personality traits and subsequent adjustment to intractable seizures. In the same cohort of patients we now investigate the influence of these factors on psychosocial outcome after surgical treatment.