Cognitive fMRI and soluble telencephalin assessment in patients with localization- related epilepsy Introduction Cognitive impairment is a frequent comorbid disorder in patients with epilepsy (1). Patients experiencing cognitive problems often display short-term memory impairment and bradyphrenia, which is probably a consequence of prefrontal and frontotemporal dysfunction. Cognitive impairment has a negative impact on the quality of life of many patients with epilepsy. Therefore, it would be useful to identify early markers for prefrontal and frontotemporal dysfunction prior to the clin- ical manifestation of this dysfunction. We have investigated whether telencephalin is a marker for altered prefrontal and frontotemporal function. Soluble telencephalin [intercellular adhesion molecule 5 (ICAM-5)] is a neuronal glycoprotein. Increased concentrations of soluble telencephalin in serum and cerebrospinal fluid were reported in temporal lobe epilepsy and acute herpes-simplex encephalitis (2). Telencephalin was suggested as a marker for neuronal damage (3), which could be associated with prefrontal and frontotemporal dysfunction. Generally, prefrontal and frontotemporal dys- function can be assessed by using neuropsycholog- Acta Neurol Scand 2008: 118: 232–239 DOI: 10.1111/j.1600-0404.2008.01005.x Copyright Ó 2008 The Authors Journal compilation Ó 2008 Blackwell Munksgaard ACTA NEUROLOGICA SCANDINAVICA Jansen JFA, Vlooswijk MCG, de Baets MH, de Krom MCTFM, Rieckmann P, Backes WH, Aldenkamp AP for the SEGAED study group. Cognitive fMRI and soluble telencephalin assessment in patients with localization-related epilepsy. Acta Neurol Scand 2008: 118: 232–239. Ó 2008 The Authors Journal compilation Ó 2008 Blackwell Munksgaard. Objectives – The use of telencephalin as a possible marker for altered cortical function as demonstrated by functional MRI was investigated in a pilot study with 16 patients with localization-related epilepsy and secondarily generalized seizures. Materials and methods – Functional MRI of verbal working memory performance (Sternberg paradigm) and self-regulatory control processes (Stroop paradigm) was used to examine cortical activation in 16 patients with localization-related epilepsy and secondarily generalized seizures. Additionally, blood serum concentrations of soluble telencephalin (marker for neuronal damage) were determined. Results – In three patients (one temporal and two frontal focus), telencephalin was detected. All three patients had lower functional MRI activation in the frontotemporal region (P = 0.04), but not in other regions (P > 0.35) compared with patients without detectable telencephalin. Additionally, an association of levetiracetam and frontotemporal activation was observed. Conclusions – These preliminary data in a heterogeneous group suggest an association between decreased frontotemporal activation on fMRI and both detectable telencephalin serum levels and levetiracetam use. Future longitudinal studies with larger patient groups are required to confirm these observations. It is hypothesized that altered local function of the frontotemporal cortex in localization-related epilepsy might be better predicted by the biochemical marker telencephalin than epilepsy characteristics such as seizure focus. J. F. A. Jansen 1,2 **, M. C. G. Vlooswijk 3 **, M. H. de Baets 3 , M. C. T. F. M. de Krom 3 , P. Rieckmann 4 , W. H. Backes 1 , A. P. Aldenkamp 3 , for the SEGAED study group 1,3 * 1 Department of Radiology, Maastricht University Hospital, the Netherlands; 2 Biomedical NMR, Department of Biomedical Engineering, Eindhoven University of Technology, the Netherlands; 3 Department of Neurology, Maastricht University Hospital, the Netherlands; 4 Department of Neurology, Julius- Maximilians University Hospital, Würzburg, Germany Key words: cognition; epilepsy; functional magnetic resonance imaging; neuropsychology; telencephalin; levetiracetam Jacobus F.A. Jansen, Department of Radiology, Maastricht University Hospital, PO Box 5800, 6202 AZ Maastricht, the Netherlands Tel.: +31 43 387 5893 Fax: +31 43 387 6909 e-mail: jansenjfa@gmail.com *For a list of other investigators, see the Appendix. **Authors contributed equally. Accepted for publication January 28, 2008 232