Perspectives of epilepsy surgery in resource-poor countries: a study in Georgia.

BACKGROUND: To identify patients with concordant seizure semiology, interictal epileptiform discharges on standard EEG and brain MRI changes to define the patients with pharmacoresistant epilepsy (PRE) who would be suitable for epilepsy surgery according to non-invasive protocol. METHODS: The medical records of the patients with epilepsy seen in Epilepsy Center of Institute of Neurology and Neuropsychology (ECINN) (Tbilisi, Georgia) were reviewed retrospectively. The diagnostic work-up included neurological examination, standard EEG, and MRI. The degree of concordance of the seizure semiology, EEG, and neuroimaging was used to determine the potential candidates for surgery. The probability of seizure freedom rate was estimated based on known predictive values of anatomical, electrophysiological, and semiological characteristics. RESULTS: A total of 83 (25 %) patients met the criteria of PRE. Fourteen (17 %) patients had complete concordance of seizure semiology, MRI, and EEG. Out of these patients, 11 had mesial temporal sclerosis on MRI and three had focal cortical dysplasia (FCD). Estimated seizure-free surgical success rate in this group was 75-95 % without the need for further investigations. Out of 25 (30 %) non-lesional MRI cases, the concordance of seizure semiology and EEG was in nine patients with probable success rate up to 60 %. Thirteen patients (16 %) had discordant EEG and MRI data and were not suitable for surgery without further testing. CONCLUSIONS: A significant portion of PRE patients with concordant anatomical, electrophysiological, and semiological characteristics can be treated surgically in resource-limited countries. Nevertheless, most patients will still require further investigation for proper localization of epileptogenic focus.

Accelerated and enhanced effect of CCR5-transduced bone marrow neural stem cells on autoimmune encephalomyelitis.

The suppressive effect of neural stem cells (NSCs) on experimental autoimmune encephalomyelitis (EAE), an animal model of multiple sclerosis (MS), has been reported. However, the migration of NSCs to inflammatory sites was relatively slow as was the onset of rather limited clinical benefit. Lack of, or low expression of particular chemokine receptors on NSCs could be an important factor underlying the slow migration of NSCs. To enhance the therapeutic effect of NSCs, in the present study we transduced bone marrow (BM)-derived NSCs with CCR5, a receptor for CCL3, CCL4, and CCL5, chemokines that are abundantly produced in CNS-inflamed foci of MS/EAE. After i.v. injection, CCR5-NSCs rapidly reached EAE foci in larger numbers, and more effectively suppressed CNS inflammatory infiltration, myelin damage, and clinical EAE than GFP-NSCs used as controls. CCR5-NSC-treated mice also exhibited augmented remyelination and neuron/oligodendrocyte repopulation compared to PBS- or GFP-NSC-treated mice. We inferred that the critical mechanism underlying enhanced effect of CCR5-transduced NSCs on EAE is the early migration of chemokine receptor-transduced NSCs into the inflamed foci. Such migration at an earlier stage of inflammation enables NSCs to exert more effective immunomodulation, to reduce the extent of early myelin/neuron damage by creating a less hostile environment for remyelinating cells, and possibly to participate in the remyelination/neural repopulation process. These features of BM-derived transduced NSCs, combined with their easy availability (the subject's own BM) and autologous properties, may lay the groundwork for an innovative approach to rapid and highly effective MS therapy.

Lacosamide use in refractory idiopathic primary generalized epilepsy.

Treatment of refractory idiopathic primary generalized epilepsy can be very challenging, with limited drug options, especially in young women of childbearing age. Here we describe the cases of two young women with refractory idiopathic primary generalized epilepsy refractory to multiple antiepileptic drugs in monotherapy or combination before achieving a long-term remission with adjunctive lacosamide (LCS) treatment. Larger, randomized prospective studies are necessary to establish the effectiveness of lacosamide in these patients.

Parieto-occipital lobe epilepsy caused by a POLG1 compound heterozygous A467T/W748S genotype.

We describe a 16-year-old woman with a rare POLG1 A467T/W748S genotype, with a wide range of neurological manifestations, including focal parieto-occipital lobe seizures, migraine headaches, cerebellar ataxia, sensory-motor axonal neuropathy, and impairment of visual perception and cognitive function. Treatment of epilepsy in patients with a POLG1 compound heterozygous A467T/W748S genotype is very challenging; the epilepsy may preferentially respond to sodium channel blockers. The POLG1-related syndrome has a variable clinical course, and disease morbidity and mortality may be correlated with the genotype.

Latency to first seizure after temporal lobectomy predicts long-term outcome.

PURPOSE: Temporal lobectomy is a well-established treatment for refractory temporal lobe epilepsy, yet many patients experience at least one seizure postoperatively. Little is known about the prognostic significance of the time from surgery to first seizure relapse in predicting long-term outcome. METHODS: In a retrospective analysis of patients who reported at least one complex partial seizure (CPS) or generalized tonic­clonic seizure (GTCS) after anterior temporal lobectomy (n = 268), we used a nominal response logistic model to predict the odds ratio (OR) of a seizure outcome based on length of the latency period from surgery to first postoperative seizure. A modified Engel outcome class scheme was used. We controlled for factors known to influence postoperative outcome, including history of tonic­clonic seizures, intelligence quotient (IQ), preoperative seizure frequency, magnetic resonance imaging (MRI) findings, and history of febrile convulsions. RESULTS: In the univariate analysis, the latency from surgery to the first postoperative disabling seizure was significantly associated with long-term outcome. Longer latency was associated with higher odds of being seizure-free or improved (modified Engel's classes 1, 2, and 3) relative to the unimproved state (class 4) (p < 0.001, 0.001 and 0.004, respectively). Conversely, a shorter latency increased the likelihood of achieving the worst prognosis (class 4) relative to class 1 (p < 0.001). Multivariate analysis yielded similar results. DISCUSSION: Latency to the first postoperative seizure predicts long-term outcome, with short latencies portending poor prognosis and long latencies portending a good prognosis. This information can be used for patient counseling and may influence decisions regarding reoperation.

Sporadic hemiplegic migraine and epilepsy associated with CACNA1A gene mutation.

Familial hemiplegic migraine (FHM) is a clinically and genetically heterogeneous disease most commonly linked to CACNA1A gene mutation. Epilepsy rarely occurs in FHM and is seen predominantly with specific CACNA1A gene mutations. Here we report a sporadic case of FHM1 linked to S218L CACNA1A gene mutation with the triad of prolonged hemiplegic migraine, cerebellar symptoms, and epileptic seizures. Epilepsy in this syndrome follows the pattern of isolated unprovoked seizures occurring only during childhood and hemiplegic migraine-provoked seizures occurring during adulthood. Clinical and electrographic status epilepticus can occur during prolonged migraine attacks. We suggest that patients with seizures, ataxia, and hemiplegic migraine be genetically tested for FHM. Patients with prolonged hemiplegic migraine attacks and confusion should be tested with continuous EEG recording to ascertain whether electrographic status is occurring, as intensive antiepileptic treatment not only resolves status but immediately stops hemiplegic migraine and improves associated neurological deficits.

Characteristics and clinical significance of subclinical seizures.

PURPOSE: To define characteristics of subclinical seizures (SCS) and their prognostic significance after epilepsy surgery. METHODS: Reports from intracranial video-EEG monitoring were reviewed for patients who had epilepsy surgery between 1989 and 2003. Relationships between SCS and clinical seizures were categorized as either: complete colocalization (Group A), when both SCS and clinical seizures originated from the same single focus, or incomplete and no colocalization (Group B), when some or all SCS and clinical seizures originated from different foci in different lobes or hemispheres. RESULTS: A total of 111 patients were included in this review. Seventy-one (64%) patients had 2,821 SCS and most SCS came from the mesial temporal lobe. The mean duration of SCS was shorter than complex partial seizures and generalized tonic-clonic seizures but similar to simple partial seizures. SCS rarely propagated beyond the site of origin and the majority of SCS had the same area of origin as clinical seizures. Sixty-five patients had both SCS and clinical seizures and underwent resective surgery. Group A patients had a higher seizure-free outcome rate (77.5%) than Group B patients (37.5%). The colocalization rate of SCS and clinical seizures may impact seizure-free outcome. The presence or absence of SCS, SCS duration, and extent of propagation of SCS did not influence surgical outcome. CONCLUSION: SCS commonly originate from the same cortical area as clinical seizures and are related to postsurgical outcome. These findings suggest they should be viewed as having similar significance in the surgical decision process as clinical seizures.

Prognosis after late relapse following epilepsy surgery.

OBJECTIVES: To assess prognosis after late relapse in patients who are seizure free for the first 5 years after epilepsy surgery. METHODS: Patients who were seizure free for the first 5 years after resective epilepsy surgery were included. Date of first seizure recurrence, current seizure status, medication, age, and type of surgery were prospectively registered. Non-parametric statistics were used. RESULTS: One hundred and fifty-nine patients were studied. Thirty-two had at least one recurrent seizure. Time to event analysis showed an annual relapse rate of 4% between years 5 and 10 after surgery. At study termination, 143 of 159 patients (89.9%) were in terminal remission. For 30 patients with late relapse and at least 1-year follow-up thereafter, 53% were in terminal remission and 30% had experienced only rare or nocturnal seizures. Medication use was not associated either with likelihood of relapse or entering remission after relapse. CONCLUSIONS: Patients who are seizure free for the first 5 years after epilepsy surgery remain at risk for seizure recurrence. These relapses are often isolated events, and the long-term prognosis after relapse is often good. Relapse rates were similar in patients on and off AEDs, but the relation between AED taper and relapse is uncertain since patient groups may not be similar.

Antiepileptic drugs and relapse after epilepsy surgery.

PURPOSE: To evaluate whether the postoperative, antiepileptic drug (AED) regimen influences seizure recurrence after anterior temporal lobectomy when considering the putative mechanism of action and possible neuroprotective effects. METHODS: This was a retrospective study. Patients who had an anterior temporal lobectomy for refractory epilepsy, whose preoperative MRI indicated mesial temporal sclerosis, were included. Postoperative AED regimens were compared with regard to seizure-outcome, considering the putative mechanism of action (sodium channel blockers, non-sodium channel blockers, and mixed mechanisms) or possible neuroprotective effect (levetiracetam, topiramate, tiagabine and zonisamide versus others). Time-to-event (first seizure after surgery) analysis was used to produce a Kaplan-Meier estimate of seizure recurrence, and groups were compared using Cox proportional hazard analysis. RESULTS: 226 patients (103 males and 123 females; mean age 42 +/- 11 years) were studied. The rates of postoperative seizure recurrence were not significantly different between the three groups regardless of the use of AEDs with different mechanisms of action (p = 0.23). Fifty patients were receiving possibly neuroprotective AEDs and 176 patients were not. Rates of seizure recurrence were not significantly different between these two groups either (p = 0.11). The differences between one-year seizure-free rates were not significant when we compared levetiracetam versus phenytoin or carbamazepine. DISCUSSION: There appeared to be no advantage or disadvantage to either prescribing drugs with different mechanisms of action or using drugs with possible neuroprotective effect after temporal lobectomy. Prospective studies with larger sample sizes may be of benefit to further explore this issue.

Interictal epileptiform discharges and asystole.

We describe a case of a patient with Lennox-Gastaut syndrome who had asystole and sinus bradycardia during interictal epileptiform abnormalities on EEG. Video-EEG/EKG monitoring prior to corpus callosotomy recorded consistent prolongation of the R-R interval on the EKG during bursts of epileptiform abnormalities (generalized paroxysmal fast activity), which became transiently more pronounced after surgery. These findings reveal that interictal epileptiform abnormalities may cause significant cardiac arrhythmias in some individuals.

Hemispheric lateralization and language skill coherence in temporal lobe epilepsy.

Patients with an early onset of temporal lobe epilepsy (TLE) are at an increased risk for language reorganization. It is unknown whether this reorganization involves a full shift of all language skills to the contralateral hemisphere, or whether it can be partial and involve only a subset of language skills. In this study we report dominance concordance patterns for five separate language skills measured during the Intracarotid Amobarbital Procedure (IAP) for 124 TLE patients. We examined whether the language skills show similar or independent lateralization patterns. We compare these patterns in early versus late seizure onset groups with either a left or right temporal lobe seizure focus. The data showed that the rates of atypical representation ranged from 25.8% for reading to 14.5% of the sample for speech. A majority of patients (60%) showing atypical language representation do so on more than one skill. While multiple atypicalities were common, the proportion of patients showing atypical representation on all five skills was strikingly low (5.6% of the total sample). Our data suggest that language systems are not independent and do not shift and reorganize in isolation, and no pairs of skills seem more likely to reorganize than others. There was also evidence that language is not monolithic with all language skills reorganizing together. The latter suggests that the pressures compelling atypical representation may not work equally on all language skills.

The effectiveness of low-frequency stimulation for mapping cortical function.

OBJECTIVE: To establish the efficacy and safety of low-frequency electrical stimulation for cortical brain mapping. METHODS: Cortical function was mapped using electrical stimulation in epilepsy patients with chronically implanted intracranial subdural electrodes. Contacts overlying motor, sensory, visual, and language cortex were stimulated at frequencies of 5, 10, and 50 Hz, using current levels ranging from 1 to 17.5 mA for 3-5 s. The current intensity and incidence at which functional alterations and afterdischarges (ADs) occurred were recorded. The modified McNemar test for nonindependent measures was used to analyze the data. RESULTS: 122 electrode contact pairs were electrically stimulated at least two different frequencies in 14 patients. Functional alterations were obtained at all stimulation frequencies (5, 10, and 50 Hz) at generally similar rates. The likelihood of producing an AD correlated with stimulation frequency, and lower-frequency stimulation was less likely to provoke an AD. Higher current intensity was required to induce both functional responses and ADs at low-frequency stimulation than high-frequency stimulation. While overall rates of producing functional changes were similar, differences in functional response with regard to frequency were noted at individual cortical sites. CONCLUSION: 5- and 10-Hz stimulation are as effective for mapping cortical function as 50-Hz stimulation and produce fewer ADs. We recommend that mapping of cortical function be started with 5-Hz-frequency stimulation. Higher frequencies should be used in suspect cortex if no symptoms or signs are produced with 5-Hz stimulation.