Focal cortical dysplasia: long term seizure outcome after surgical treatment.

BACKGROUND: Studies of long term outcome after epilepsy surgery for cortical malformations are rare. In this study, we report our experience with surgical treatment and year to year long term outcome for a subgroup of patients with focal cortical dysplasia (FCD). METHODS: We retrospectively analysed the records of 49 patients (females n = 26; males n = 23; mean age 25 (11) years) with a mean duration of epilepsy of 18 years (range 1-45). Preoperative MRI, histological results based on the Palmini classification and clinical year to year follow-up according to the International League Against Epilepsy (ILAE) classification were available in all patients. RESULTS: 98% of patients had a lesion on preoperative MRI. In addition to lobectomy (n = 9) or lesionectomy (n = 40), 14 patients had multiple subpial transections of the eloquent cortex. The resected tissue was classified as FCD type II b in 41 cases with an extratemporal (88%) and FCD type II a in 8 cases with a temporal localisation (100%). After a mean follow-up of 8.1 (4.5) years, 37 patients (76%) were seizure free, a subgroup of 23 patients (47%) had been completely seizure free since surgery (ILAE class 1a) and 4 patients (8%) had only auras (ILAE class 2). Over a 10 year follow-up, the proportion of satisfactory outcomes decreased, mainly within the first 3 years. During long term follow-up, 48% stopped antiepileptic drug treatment, 34% received a driver's license and 57% found a job or training. CONCLUSION: Surgical treatment of epilepsy with FCD is not only successful in the short term but also has a satisfying long term outcome which remains constant after 3 years of follow-up but is not associated with better employment status or improvement in daily living.

Firing pattern of rat hippocampal neurons: a perforated patch clamp study.

To test whether the slow afterhyperpolarization (sAHP) underlies the filter function of hippocampal granule cells (GCs), we compared the sAHP and spike frequency adaptation between granule cells and CA3 pyramidal cells (PCs) in hippocampal slices employing gramicidin perforated patch clamp recordings to best preserve the physiological cytoplasmic constitution. sAHPs were evoked in GCs and PCs with trains of action potentials in current clamp mode and showed comparable kinetics in both types of cells. The threshold frequency (500 ms firing) triggering a detectable sAHP was approximately 10 Hz and approximately 3 Hz in GCs and PCs, respectively. Half maximal sAHPs were reached at 30 Hz and 8 Hz in GCs and PCs, respectively. Maximal amplitude of sAHPs in GCs amounted to approximately 3.5 mV, was approximately 2-fold smaller than in PCs and could not be further increased with higher firing frequencies. The time course of sAHP activation was investigated with 50 Hz trains of action potentials applied for increasing durations. In both types of cells, the sAHP amplitude increased with a time constant of approximately 400 ms. Nevertheless, sAHP never exceeded 4 mV in GCs but rose to approximately 12 mV in PCs when cells fired for 3 s. The repetitive firing pattern of GCs and PCs was compared by injecting current amplitudes adjusted to provoke an initial firing frequency of 50 Hz. In GCs firing frequency declined slower (tau = 229 ms) and leveled off at a higher tonic firing frequency (28 Hz) when compared to PCs (tau = 126 ms, 18 Hz). We conclude that the intrinsic excitability of GCs cannot be primarily regulated by the sAHP. The sAHP in GCs is minimal most likely due to a small sAHP-channel density as well as to a more rigid control of intracellular Ca(2+) levels.

Calbindin-D28k content and firing pattern of hippocampal granule cells in amygdala-kindled rats: a perforated patch-clamp study.

The dentate gyrus is believed to play an important pathophysiological role during experimentally induced kindling. In this study, we investigated whether an altered content of the calcium binding protein calbindin-D(28k) or an increased intrinsic excitability of hippocampal granule cells contribute to the induction of the kindling phenomenon. We determined the firing pattern of granule cells in hippocampal slices using perforated patch-clamp recordings in current clamp mode. The expression of calbindin-D(28k) and glutamic acid decarboxylase (GAD(67)) by granule cells was analyzed immunohistochemically. Rats developed secondarily generalized limbic seizures within approximately 11 days of twice-daily stimulation of the amygdala. As reported for other kindling paradigms, this protocol induced a clear up-regulation of GAD(67) in granule cells, indicating their involvement in the induced neuronal activity. However, when comparing kindled and control rats, we could not detect any differences in intrinsic excitability: Firing frequency, after-hyperpolarisations, action potentials, input resistance and membrane potentials were nearly identical between both groups. Furthermore, we did not observe any differences in the calbindin-D(28k) immunoreactivity between groups. In every slice, virtually all granule cells were found to be strongly calbindin-D(28k) positive, and there was no apparent reduction in the general level of calbindin-D(28k) expression. We conclude that changes in intrinsic membrane properties or in the calbindin-D(28k) content of granule cells are not necessary for the development of amygdala kindling.