Preserved proper naming following left anterior temporal lobectomy is associated with early age of seizure onset

The prevalence of epilepsy worldwide has been estimated to be approximately 0.5–1.0%, and among this population, approximately 30–40% has medically intractable epilepsy, i.e., seizures that are not well controlled with antiepileptic medications, or what is called “pharmacoresistant epilepsy” (Kwan and Brodie, 2000; Jeha et al., 2006). Lack of efficacy of at least two medications, defined as persistent seizures despite maximum drug doses, is required for both the “strict” and “loose” definitions of medical intractability (Berg et al., 2006), but in most cases, patients are tried on many different drugs in an effort to control their seizures. Once intractability is declared for those patients with complex partial epilepsy that is not resulting from a cortical malformation, tumor, or arteriovenous malformation, additional investigations, such as video-EEG monitoring, magnetic resonance imaging, positron emission tomography, neuropsychological testing, and sodium amobarbital testing, are typically pursued in an attempt to identify a focus amenable for surgical removal. Most frequently, a standard anterior temporal lobectomy (ATL) is performed; this typically entails resection of the temporal tip, anterior parts of the parahippocampal and inferior temporal gyri, and portions of mesial structures (amygdala/hippocampus). ATL has been proven to be more efficacious in controlling seizures when compared to medication alone or an alternative surgical procedure, such as a focal cortical resection (Wiebe et al., 2001). In patients who have an ATL, 81% may achieve an Engel Class I outcome 6 months after surgery, i.e., freedom from recurrent seizures, occurrence of only nondisabling seizures such as auras or simple partial seizures, or occurrence of generalized/disabling seizures only after attempted withdrawal of antiepileptic medications (Cohen-Gadol et al., 2006). The probability for maintaining an Engel Class I outcome has been reported to be 78% at one year, 76% at two years, 74% at five years, and 72% one decade after surgery (Cohen-Gadol et al., 2006). Other studies have reported similar results with a probability of 80% or slightly higher for achieving an Engel Class I outcome within 6 months after surgery (Clusmann et al., 2004; Lowe et al., 2004; also see Foldvary et al., 2000; Yoon et al., 2003). Furthermore, quality-of-life assessments have shown significantly improved social functioning in patients for up to one year after epilepsy surgery (Engel et al., 2003). There is, however, another side to this picture. Together with improved control of disabling seizures and improved level of social functioning, ATL can produce cognitive “side effects.” For example, many patients develop postsurgical difficulties with language and memory following left ATL (Stafiniak et al., 1990; Saykin et al., 1995), and such deficits have been shown to persist (Langfitt and Rausch, 1996; Bartha et al., 2004; Alpherts et al., 2006; Hermann et al., 2007). There is considerable variability in outcome, though, and patient profiles literally run the gamut from severe defects to no discernable change following surgery. A number of variables have been studied in an attempt to identify which factors are associated with relatively better and relatively worse outcomes following surgery. Variables that have been shown to predict relatively negative (poorer) cognitive outcomes include older age at seizure onset, male gender, older age at the time of surgery, normal appearing hippocampal material at resection, and a strong preoperative neuropsychological performance (Gleissner et al., 2002; Hermann et al., 2007; Griffin and Tranel, 2007). Just as a focal resection has not correlated with improved efficacy of controlling seizures, the amount of tissue resected has not been consistently proven to be an effective predictor of cognitive performance after left ATL (Griffin and Tranel, 2007). Likewise, a specific approach or technique for surgical resection has not been shown to be correlated with an improved ability in visual confrontational naming. Specifically, naming can be impaired after tailored resections in the left temporal lobe, after standard resections sparing the superior temporal gyrus, and after standard resections including excision of the superior temporal gyrus (Hermann et al., 1999). Age of onset of recurrent seizures has been demonstrated to be a significant predictor of cognitive outcome following ATL, with an earlier age of seizure onset being associated with better cognitive outcome (e.g., Powell et al., 1985; Saykin et al., 1989; Stafiniak et al., 1990; Hermann et al., 1995, 2007; Griffin and Tranel, 2007). Also, when risk factors for epilepsy (e.g., head injury, complicated febrile seizures) have been present at age 5 or earlier, postsurgical declines in naming are more limited, and this may be due to cerebral reorganization of language functions prompted by or associated with brain injury before age 5 (Stafiniak et al., 1990; Pataraia et al., 2004, 2005). Other studies have shown that it is early age of onset of recurrent seizures, rather than the age at which identifiable risk factors or overt brain injury occurred, that is the key factor predicting better outcome (Hermann et al., 2002). Against this background, we have been intrigued by some of the dramatically different patterns of outcomes in our patients with left ATL. We have focused especially on a specific aspect of word retrieval, viz., proper naming. The reason for this is that proper name retrieval—i.e., naming specific persons and places—has been strongly linked to the left anterior temporal region in both lesion (Barr et al., 1990; Graff-Radford et al., 1990; Ellis et al., 1991; Damasio et al., 2004, 1996; Fukatsu et al., 1999; Tsukiura et al., 2002; Seidenberg et al., 2002; Glosser et al., 2003; Snowden et al., 2004; Lah et al., 2004; Tranel, 2006) and functional imaging (Grabowski et al., 2001; Tsukiura et al., 2002, 2003) studies. In patients with left ATL, a notable impairment of proper name retrieval is a frequent postsurgical finding: the majority of left ATL patients complain of this problem, and the defect is obvious on careful examination with appropriate neuropsychological testing. There are, however, striking exceptions: some patients are entirely unscathed by the surgical resection and have normal proper naming following left ATL. The goal of the current study was to identify what factors might account for such exceptions. Based on the literature reviewed earlier, we hypothesized that “protected” proper naming would be associated with a significantly earlier age of onset of epilepsy. We also studied a range of other factors (e.g., age at surgery, education, IQ, seizure outcome) to determine whether age of onset of epilepsy was predictive of proper naming outcome over and above what could be explained by such other factors.