Eva Kumlien

Childhood epilepsy, familial hemiplegic migraine, cerebellar ataxia, and a new CACNA1A mutation.

The CACNA1A gene encodes the pore-forming subunit of neuronal P/Q type Ca2+ channels. Mutations in this gene cause a spectrum of neurologic diseases, including familial hemiplegic migraine (FHM) with or without ataxia.1 We report a novel de novo CACNA1A mutation in a Swedish family. Three mutation carriers had FHM and early onset ataxia; additional childhood epilepsy occurred in two . The proband, II-3, is a 54-year-old woman with slowly progressive cerebellar ataxia since childhood and cerebellar atrophy on CT. She was hospitalized at ages 7 and 8 because of decreased consciousness and vomiting for 1 day, starting with a lucid interval after a fall. She experienced four hemiplegic migraine attacks between ages 14 and 30 years and weekly at age 47. Seizures were never observed. Her 32-year-old son (III-5) and 30-year-old daughter (III-6), who have different fathers, showed cerebellar ataxia at age 4. Ataxia is now prominent in both, and brain imaging shows cerebellar atrophy. …

Health-Related Quality of Life After Epilepsy Surgery: A Swedish Multicenter Study

Summary: Purpose: To investigate health‐related quality of life (HRQOL) in relation to seizure outcome as part of a multicenter follow‐up of epilepsy surgery in Sweden.

NMDA‐Receptor Activity Visualized with (S)‐[N‐Methyl‐11C]Ketamine and Positron Emission Tomography in Patients with Medial Temporal Lobe Epilepsy

Summary: Purpose: To determine whether neurochemical activation of the N‐methyl‐D‐aspartate (NMDA) receptor‐gated ion channel shows quantitative changes, measured as binding of 11C‐labeled (S)‐[N‐methyl]ketamine, in patients with medial temporal lobe epilepsy (MTLE).

Cerebral glutamine and glutamate levels in relation to compromised energy metabolism : a microdialysis study in subarachnoid hemorrhage patients

Astrocytic glutamate (Glt) uptake keeps brain interstitial Glt levels low. Within the astrocytes Glt is converted to glutamine (Gln), which is released and reconverted to Glt in neurons. The Glt–Gln cycle is energy demanding and impaired energy metabolism has been suggested to cause low interstitial Gln/Glt ratios. Using microdialysis (MD) measurements from visually noninjured cortex in 33 neurointensive care patients with subarachnoid hemorrhage, we have determined how interstitial Glt and Gln, as a reflection of the Glt–Gln cycle turnover, relate to perturbed energy metabolism. A total of 3703 hourly samples were analyzed. The lactate/pyruvate (L/P) ratios correlated to the Gln/Glt ratios (r = −0.66), but this correlation was not stronger than the correlation between L/P and Glt (r = 0.68) or the correlation between lactate and Glt (r = 0.65). A novel observation was a linear relationship between interstitial pyruvate and Gln (r = 0.52). There were 13 periods (404 h) of ‘energy crisis’, defined by L/P ratios above 40. All were associated with high interstitial Glt levels. Periods with L/P ratios above 40 and low pyruvate levels were associated with decreased interstitial Gln levels, suggesting ischemia and failing astrocytic Gln synthesis. Periods with L/P ratios above 40 and normal or high pyruvate levels were associated with increased interstitial Gln levels, which may represent an astrocytic hyperglycolytic response to high interstitial Glt levels. The results imply that moderately elevated L/P ratios cannot always be interpreted as failing energy metabolism and that interstitial pyruvate levels may discriminate whether or not there is sufficient astrocytic capacity for Glt–Gln cycling in the brain.

Preoperative heart rate variability in relation to surgery outcome in refractory epilepsy

Background: Epilepsy patients may have an impaired autonomic cardiac control, which has been associated with an increased incidence of sudden unexpected death among people with epilepsy (SUDEP). The risk of SUDEP is particularly high among epilepsy surgery candidates with refractory epilepsy. This risk seems to be reduced after successful surgery but whether this is an effect of surgery or reflects pre-existing differences between good and poor responders is under debate. Methods: We used spectral analysis to analyze prospectively heart rate variability (HRV) preoperatively in 21 consecutive patients with temporal lobe epilepsy who were planned for epilepsy surgery. The presurgical HRV based on ambulatory 24 hours EKG recordings was analyzed in relation to seizure control at 1 year after surgery. Results: Patients had significantly lower SD of RR-intervals, total power, very low frequency power and low frequency power than matched healthy controls. Patients with good outcome of surgery (Engel class I; n = 11) did not differ from their controls while those with poor outcome (Engel class II-IV; n = 10) had significantly lower power in all domains than those with a favorable outcome. Conclusions: Measurements of heart rate variability preoperatively indicate that patients with a poor outcome of surgery have a more pronounced impairment of sympathetic as well as parasympathetic cardiac control than those with good outcome. Reduced heart rate variability may be associated with an increased risk of sudden unexpected death among people with epilepsy (SUDEP). Good surgery candidates may a priori have a lower risk of SUDEP.

Seizure risk associated with neuroactive drugs: Data from the WHO adverse drug reactions database

PURPOSE To explore the association between the use of neuroactive drugs and reports of epileptic seizures. MATERIAL Using the WHO adverse drug reactions (ADR) database, VigiBase, we surveyed reports of suspected seizures from 1968 until February 2006. Case reports of ADRs, that were classified as convulsions were collected and compared to the total number of ADRs reported. RESULTS The total number of ADRs was 7,375,325. The number of convulsive events was 71,471. The ratio of convulsive ADRs to the total number of ADRs reported for each drug was evaluated and expressed as a percentage. The 10 drugs most frequently associated with convulsive ADRs were maprotilene (14.42%), escitaloprame (9.78%), buproprione (9.49%), clozapine (9.0%), chlorprothiexene (8.89%), amoxapine (8.74%), donepezil (8.40%), rivastigmine (6.41%), quetiapine (5.90%) and trimipramine (5.69%). CONCLUSIONS Based on the reports in VigiBase, ADR reports relating to antidepressants, antipsychotic and cholinomimetic drugs included seizures more often than other neuroactive drugs.

Long-term outcomes of epilepsy surgery in Sweden A national prospective and longitudinal study

Objective: To investigate prospective, population-based long-term outcomes concerning seizures and antiepileptic drug (AED) treatment after resective epilepsy surgery in Sweden. Methods: Ten- and 5-year follow-ups were performed in 2005 to 2007 for 278/327 patients after resective epilepsy surgery from 1995 to 1997 and 2000 to 2002, respectively. All patients had been prospectively followed in the Swedish National Epilepsy Surgery Register. Ninety-three patients, who were presurgically evaluated but not operated, served as controls. Results: In the long term (mean 7.6 years), 62% of operated adults and 50% of operated children were seizure-free, compared to 14% of nonoperated adults (p < 0.001) and 38% of nonoperated children (not significant). Forty-one percent of operated adults and 44% of operated children had sustained seizure freedom since surgery, compared to none of the controls (p < 0.0005). Multivariate analysis identified ≥30 seizures/month at baseline and long epilepsy duration as negative predictors and positive MRI to be a positive predictor of long-term seizure-free outcome. Ten years after surgery, 86% of seizure-free children and 43% of seizure-free adults had stopped AEDs in the surgery groups compared to none of the controls (p < 0.0005). Conclusions: This population-based, prospective study shows good long-term seizure outcomes after resective epilepsy surgery. The majority of the patients who are seizure-free after 5 and 10 years have sustained seizure freedom since surgery. Many patients who gain seizure freedom can successfully discontinue AEDs, more often children than adults. Classification of evidence: This study provides Class III evidence that more patients are seizure-free and have stopped AED treatment in the long term after resective epilepsy surgery than nonoperated epilepsy patients.

Circadian variation in heart-rate variability in localization-related epilepsy

Summary:  Purpose: Case–control studies of sudden unexpected death in epilepsy (SUDEP) have reported that SUDEP is more likely to occur during sleep and thus presumably during night hours. The circadian variation of heart‐rate variability (HRV) might be of relevance to this risk. We examined night versus daytime HRV in patients with newly diagnosed and refractory localization‐related epilepsy, assessing the effects of drug treatment and epilepsy surgery on the night/daytime HRV ratio.

Positron Emission Tomography with [11C]Deuterium-Deprenyl in Temporal Lobe Epilepsy

Summary: We performed positron emission tomography (PET) with [11C]deuterium‐deprenyl in 9 patients with temporal lobe epilepsy (TLE) undergoing evaluation for possible epilepsy surgery. Seven patients had unilateral and 2 had bilateral mesiotemporal epileptic foci based on the preoperative investigation including ictal EEG discharges and PET with 2‐[18F]fluoro‐2‐deoxyglucose (FDG). Deprenyl is an irreversible inhibitor of mono‐amine oxidase type B (MAO‐B) with a very high affinity for the enzyme. In the brain, MAO‐B is preferentially located in astrocytes, and a previous in vitro study showed increased binding of the ligand in sclerotic hippocampi. Dynamically acquired N‐[methyl‐11C]‐a, a‐di‐deutero‐L‐deprenyl distributions in PET images were analyzed graphically, and the focus regions were assessed visually on the PET images. In addition, the accumulation rate and distribution volume of the tracer relative to the cerebellar cortex were measured in standardized homologous temporal regions by semiquantitative methods. Uptake of [11C]deuterium‐deprenyl was significantly increased in the epileptogenic temporal lobes, both apparently and semiquantitatively. By calculating mean inter‐lobar ratios, we identified the temporal lobe containing the epileptic focus in six unilateral cases. One case was ambiguous but was not falsely localized. The two bilateral cases were correctly identified as such. Our results suggest that PET with [11C]deuterium‐deprenyl might be a useful method for identification of epileptogenic temporal lobes.

Treatment outcome in patients with mesial temporal sclerosis.

The long-term prognosis of pharmacological therapy in patients with mesial temporal sclerosis (MTS) is generally considered poor. On the contrary, successful surgical therapy is frequently reported. We performed a retrospective case record survey of patients with MTS in a comprehensive epilepsy center between 1993 and 1999 in order to develop treatment strategies. The time period allowed access to high-resolution qualitative magnetic resonance imaging (MRI) and a minimum of 1-year outcome assessment. Eighty-three patients with intractable partial epilepsy with MRI and electroencephalograph (EEG) abnormalities and seizure semiology consistent with temporal lobe epilepsy were identified. Thirty-six patients were treated pharmacologically and surgically and 47 patients received only pharmacotherapy. The number of patients who became seizure free was in total 37 (45%); in the surgical group 26 and in the non-surgical group 11. The proportions of seizure-free patients in each group were 72% (surgical) and 23% (non-surgical). Clinical factors such as age, gender, lesion side, previous medical history, duration of illness, seizure frequency and IQ did not correlate to prognosis. A good seizure outcome was associated with early age of seizure onset, low number of previously used antiepileptic drugs (AEDs) and surgical treatment. There is a better long-term outcome in patients with MTS receiving surgical therapy in comparison with medical therapy.