Clinical characteristics and outcome in patients with psychogenic nonepileptic seizures.

OBJECTIVES: To examine baseline clinical features of psychogenic nonepileptic seizures (PNES) in a large cohort and to investigate outcome over a period of up to 10 years. Studies investigating PNES have been limited by differences in diagnostic criteria, short follow-up periods, and the use of limited outcome measures. METHOD: Patients with PNES were identified, using strict diagnostic criteria. Baseline neurological, neuropsychiatric, and neuroimaging data were obtained from medical records. Long-term outcome was assessed with ratings of seizures, psychopathology, and quality of life in a subset of the patients. RESULTS: Patients with PNES (n = 221) experienced long delays in diagnosis (mu, 5.6 years; standard deviation, 7.7 years) and high rates (>60%) of prolonged treatment with antiepileptic drugs. Compared with previous studies, a relatively low proportion (8.1% to 17.9%, depending on diagnostic criteria) had comorbid epilepsy. An unexpected finding was that 22.6% of PNES patients had magnetic resonance imaging abnormalities. Patients assessed at follow-up (n = 61) exhibited poor long-term outcomes with ongoing PNES, high rates of psychopathology, low rates of specialist follow-up, poor quality of life, and poor overall levels of functioning. CONCLUSIONS: These results demonstrate the need for earlier diagnosis of PNES and comorbidities and highlight the need for diagnostic and therapeutic approaches that combine neurological and psychiatric perspectives.

Neuropsychiatric morbidity in focal epilepsy.

BACKGROUND: Previous work has identified elevated prevalence rates for psychiatric disorders in individuals with medically refractory focal epilepsy, particularly temporal lobe epilepsy. Many studies were undertaken before the advent of video electroencephalogram monitoring (VEM) and magnetic resonance imaging (MRI). AIMS: To investigate which characteristics of the focal epilepsy syndromes are associated with the presence of depression or psychosis. METHOD: Three hundred and nineteen individuals with focal epilepsy admitted for VEM were seen over an 11-year period. The lifetime history of depression and psychosis, epileptic site, laterality and type of lesion were determined by clinical assessment, VEM and MRI scan. RESULTS: There was a significant association between the prevalence of depressive symptoms and non-lesional focal epilepsy. There were no significant differences in prevalence of neuropsychiatric disorders between the groups with temporal lobe epilepsy and those with extratemporal lobe epilepsy. CONCLUSIONS: These findings contrast with previous findings in smaller cohorts. The association between non-lesional focal epilepsy and depression may be due to the effects of a more diffuse epileptogenic area.

'MRI-negative PET-positive' temporal lobe epilepsy (TLE) and mesial TLE differ with quantitative MRI and PET: a case control study.

BACKGROUND: 'MRI negative PET positive temporal lobe epilepsy' represents a substantial minority of temporal lobe epilepsy (TLE). Clinicopathological and qualitative imaging differences from mesial temporal lobe epilepsy are reported. We aimed to compare TLE with hippocampal sclerosis (HS+ve) and non lesional TLE without HS (HS-ve) on MRI, with respect to quantitative FDG-PET and MRI measures. METHODS: 30 consecutive HS-ve patients with well-lateralised EEG were compared with 30 age- and sex-matched HS+ve patients with well-lateralised EEG. Cerebral, cortical lobar and hippocampal volumetric and co-registered FDG-PET metabolic analyses were performed. RESULTS: There was no difference in whole brain, cerebral or cerebral cortical volumes. Both groups showed marginally smaller cerebral volumes ipsilateral to epileptogenic side (HS-ve 0.99, p = 0.02, HS+ve 0.98, p < 0.001). In HS+ve, the ratio of epileptogenic cerebrum to whole brain volume was less (p = 0.02); the ratio of epileptogenic cerebral cortex to whole brain in the HS+ve group approached significance (p = 0.06). Relative volume deficits were seen in HS+ve in insular and temporal lobes. Both groups showed marked ipsilateral hypometabolism (p < 0.001), most marked in temporal cortex. Mean hypointensity was more marked in epileptogenic-to-contralateral hippocampus in HS+ve (ratio: 0.86 vs 0.95, p < 0.001). The mean FDG-PET ratio of ipsilateral to contralateral cerebral cortex however was low in both groups (ratio: HS-ve 0.97, p < 0.0001; HS+ve 0.98, p = 0.003), and more marked in HS-ve across all lobes except insula. CONCLUSION: Overall, HS+ve patients showed more hippocampal, but also marginally more ipsilateral cerebral and cerebrocortical atrophy, greater ipsilateral hippocampal hypometabolism but similar ipsilateral cerebral cortical hypometabolism, confirming structural and functional differences between these groups.

The Liverpool Adverse Events Profile: relation to AED use and mood.

PURPOSE: The Liverpool Adverse Events Profile (LAEP) is used as a systematic measure of adverse effects from antiepileptic drugs (AEDs). This study evaluated LAEP in newly diagnosed seizure patients, and examined the relation between LAEP, anxiety, and depression. METHODS: Seizure patients seen in the two First Seizure Clinics were categorized into group A (AEDs commenced after assessment), group B (AEDs commenced before assessment), and group C (no AEDs). LAEP and the Hospital Anxiety and Depression Scale (HADS) were completed at baseline (n=164) and 3 months (n=103). Each LAEP symptom was assessed for baseline frequency, 3-month frequency, and frequency change over a 3-month period. Global scores for LAEP and HADS were analysed at baseline and 3 months. RESULTS: Symptom-reporting patterns were similar between groups. However, increased frequency over a 3-month period occurred for 12 symptoms in group A, 10 in group B, and one in group C. Global LAEP and HADS showed no significant group differences at baseline or changes over a 3-month period. Multiple regression revealed that HADS scores predicted LAEP global scores better than did AED status. Multivariate analyses of variance demonstrated that increased reporting of 16 of 19 LAEP symptoms was significantly related to higher anxiety and depression rates. CONCLUSIONS: In a First Seizure Clinic, LAEP detects changes in specific symptom frequencies when used as a repeated, symptom-by-symptom measure. Increased symptom frequency is associated with diagnostic category/AED treatment, anxiety, and depression. Global LAEP scores do not illustrate differences in symptom reporting between patients.

The extent of resection of FDG-PET hypometabolism relates to outcome of temporal lobectomy.

A significant minority of patients undergoing surgery for medically refractory non-lesional temporal lobe epilepsy (TLE) continue to have seizures, but the reasons for this are uncertain. Fluorodeoxyglucose (FDG) PET shows hypometabolism in a majority of patients with non-lesional TLE, even in the absence of hippocampal atrophy. We examined whether the extent of resection of the area of FDG-PET hypometabolism influenced outcome following surgery for non-lesional TLE. Twenty-six patients who underwent temporal lobectomy for medically refractory TLE with at least 12 months follow-up were studied. The preoperative FDG-PET was compared with 20 non-epileptic controls using SPM99 to identify regions of significant hypometabolism (P < 0.0005, cluster > 200). This image was then co-registered to the postoperative MRI scan. The volume of the FDG-PET hypometabolism that lay within the area of the resected temporal lobe was calculated. The volume of temporal lobe resected was also calculated. Patients with a good outcome had a greater proportion of the total FDG-PET hypometabolism volume resected than those with a poor outcome (24.1% versus 11.8%, P = 0.02). There was no significant difference between the groups in the volume of temporal lobe resected (P = 0.86). Multivariate regression demonstrated that the extent of resection of the hypometabolism significantly correlated with outcome (P = 0.03), independent of the presence of hippocampal sclerosis (P = 0.03) and total brain volume of hypometabolism (P = 0.45). The extent of resection of the region of hypometabolism on the preoperative FDG-PET is predictive of outcome following surgery for non-lesional TLE. Strategies that tailor resection extent to regional hypometabolism may warrant further evaluation.

Tiagabine-induced generalised non convulsive status epilepticus in patients with lesional focal epilepsy.

PURPOSE: To report 3 cases with focal lesional epilepsy that had non-convulsive status epilepticus (NCSE) induced by treatment with tiagabine (TGB) and review the previously published cases. Drugs that enhance GABAnergic transmission are recognised to promote absence seizures in patients with generalised epilepsy syndromes and may on occasions even induce NCSE. However, that TGB can also induce NCSE in focal lesional epilepsy is not widely recognised in clinical practice. METHOD: The clinical history, EEG and MRI findings were reviewed in 3 patients with lesional focal epilepsy who presented to our epilepsy programs over a 12 month period with TGB-induced NCSE. All previously reported cases in the English medical literature were reviewed. RESULTS: The three patients had longstanding complex partial and secondarily generalised seizures refractory to multiple different anti-epileptic drugs. In two cases, MRI demonstrated a focal malformation of cortical development in the left parieto-occipital region and in the third left mesial temporal sclerosis. Following commencement of TGB in one patient and dose escalation in two, prolonged episodes of confusion and poor responsiveness were noted. Prolonged EEG monitoring demonstrated continuous high amplitude, generalised, 2-4 Hz delta activity with intermingled spikes during the episodes of unresponsiveness, consistent with NCSE. The clinical and EEG activity normalised following the administration of IV clonazepam followed by dose reduction or withdrawal of the TGB. Eleven previously reported cases of patients with partial epilepsy and a focal underlying lesion on MRI were identified, all of whom had similar features to that seen in our cases. CONCLUSIONS: These cases illustrate that TGB may induce generalised NCSE in patients with focal lesional epilepsy, in addition to those with generalised syndromes. We hypothesise that patients may have developed an acquired alteration in the sensitivity of their thalamocortical circuitry that renders them more sensitive to the effects of drugs that enhance GABAnergic activity.

EEG dipole source localisation of interictal spikes acquired during routine clinical video-EEG monitoring.

OBJECTIVE: We investigated the feasibility of electroencephalography (EEG) dipole source localisation of interictal epileptiform discharges from data acquired during routine clinical inpatient video-EEG monitoring (VEM) and compared a 19-channel 'routine montage' with a 29-channel 'surgical montage' that includes an additional row of 10 inferior temporal electrodes. METHODS: Twenty consecutive patients who had VEM for the presurgical evaluation of medically refractory partial epilepsy were screened. Thirteen of the patients had focal interictal spikes recorded, and in 11 (85%) these were technically satisfactory for source localisation. Fourteen spike foci were analysed as 3 patients had bilateral independent spikes. EEG data was acquired with 29 electrodes including an inferior temporal row (surgical montage). For comparison, the 10 additional electrodes were excluded from analysis (routine montage). Using NEUROSCAN Source 2.0 software, a computed dipole source localisation of averaged spikes was performed utilising a magnetic resonance imaging-based finite element model. Dipole localisation was compared with that of the Comprehensive Epilepsy Program (CEP) evaluation. RESULTS: Using the surgical montage dipole source localisation was consistent with the CEP spike localisation for 13/14 spikes (93%, P<0.005), compared with only 5/14 spikes (36%) using the routine montage. CONCLUSIONS: Data derived from routine clinical inpatient VEM using a routine montage can yield accurate EEG dipole source localisation, but significantly more accurate localisation is obtained using the surgical montage.

"Convulsive" nonepileptic seizures have a characteristic pattern of rhythmic artifact distinguishing them from convulsive epileptic seizures.

PURPOSE: Approximately 30% of patients admitted for video-EEG monitoring have psychogenic nonepileptic seizures (PNES). Differentiation of "convulsive" PNES from convulsive seizures can be difficult. The EEG often displays rhythmic movement artifact that may resemble seizure activity and confound the interpretation. We sought to determine whether time-frequency mapping of the rhythmic EEG artifact during "convulsive" PNES reveals a pattern that differs from that of epileptic seizures. METHODS: EEGs from 15 consecutive patients with "convulsive" PNESs were studied with time-frequency mapping by using NEUROSCAN and compared with 15 patients with convulsive epileptic seizures. Fast Fourier transforms (FFTs) were performed to determine the dominant frequency for 1- to 2-s windows every 2 s through the seizures. RESULTS: The dominant frequency remained stable within a narrow range for the duration of the PNES, whereas in the epileptic seizures, it evolved through a wide range. The coefficient of variation of the frequency during the seizures was considerably less for patients without epilepsy (median, 15.0%; range, 7.2-23.7% vs. median, 58.0%; range, 34.8-92.1%; p < 0.001). The median frequency did not differ significantly between groups (4.2 vs. 4.6 Hz; p = 0.290). CONCLUSIONS: "Convulsive" PNES display a characteristic pattern on time-frequency mapping of the EEG artifact, with a stable, nonevolving frequency that is different from the evolving pattern seen during an epileptic seizure.

Epilepsy surgery for pathologically proven hippocampal sclerosis provides long-term seizure control and improved quality of life.

PURPOSE: To examine long-term seizure and quality-of-life outcome in a homogeneous group of patients after temporal lobectomy with pathologically proven hippocampal sclerosis (HS). Previous research has had limited follow-up (generally <2 years) and has grouped patients across multiple pathologies. METHODS: Fifty consecutive patients were identified as having had a temporal lobectomy for the treatment of temporal lobe epilepsy at Royal Melbourne Hospital with pathologically proven HS and >or=2 years' follow-up. All patients were sent a postal survey concerning seizure activity, quality of life (QOLIE-89), and antiepileptic drug (AED) use. The mean follow-up was 5.8 years (range, 2-9.2). RESULTS: The rate of complete postoperative seizure freedom was 82% at 12 months, 76% at 24 months, and 64% at 63 months (no further seizure recurrences observed after this time). A class I seizure outcome was achieved by 83.3% of patients. Patients with better seizure outcome had significantly better quality of life (Kendall's tau =-234, p < 0.01). Seizure recurrence was associated with a reduction in AED intake or absorption in five (29%) of 17 cases, including three of the five patients with a first seizure recurrence after 24 months after surgery. CONCLUSIONS: Temporal lobectomy provides continued long-term seizure control in the majority of patients with HS. However, patients remain at risk of seizure recurrence >or=2 years after surgery. Long-term quality of life is dependent on seizure outcome.

Preoperative evaluation for temporal lobe surgery.

Temporal lobe epilepsy (TLE), the most common form of partial epilepsy in adults is often refractory to medical treatment and in these patients epilepsy surgery is considered. Successful surgery is dependent on accurate localisation and lateralisation of the epileptogenic zone. The preoperative evaluation involves a series of assessments and investigations including detailed clinical history, interictal EEG, video-EEG monitoring, MRI, PET, SPECT, and neuropsychology and neuropsychiatric assessment. The role of each of these investigations and assessments in the preoperative evaluation is discussed. Advanced MR techniques including magnetic resonance spectroscopy, MR diffusion and MR perfusion have recently been assessed and are likely to enhance the pre-surgical evaluation of patients with TLE.The surgical outcome and preoperative investigations performed of 80 consecutive patients who underwent temporal lobe surgery between 1993 and 2002 at Royal Melbourne Hospital were reviewed. All patients had MRI, video-EEG monitoring and neuropsychology assessment and 56% a PET scan. During a mean follow-up of 5.9 years 75% had Class 1 outcome, 22% non-Class 1 outcome and 3% were lost to follow-up. The results of preoperative investigations were correlated with outcome. For interictal EEG, seizure semiology, ictal EEG, PET and neuropsychology assessment the surgical outcome of patients in whom results were concordant to side of surgery was compared with those discordant or non-lateralising. There was no significant difference. In 78 of 80 patients MRI revealed mesial temporal sclerosis or a foreign tissue lesion. The outcome was no different between these two groups. Results suggest that in patients with unilateral temporal lobe lesion on MRI and where ictal EEG is either concordant or non-lateralising, other investigations including PET, provide little additional prognostic information.

The morbidity related to atrial fibrillation at a tertiary centre in one year: 9.0% of all strokes are potentially preventable.

Atrial fibrillation is a major risk factor for stroke. Anticoagulant therapy reduces this risk but increases the risk of haemorrhage. We aimed to compare the morbidity related to the treatment of atrial fibrillation with warfarin seen in one year at our hospital, with the morbidity in those patients in whom embolism was potentially preventable. There were 111 patients admitted to our hospital in a 12 month period with nonvalvular atrial fibrillation (NVAF) who had stroke, TIA or peripheral embolism. Atrial fibrillation was identified prior to admission in 87 of these 111 (78%) patients with thromboembolism, yet only 14 of these (16%) were receiving warfarin for stroke prophylaxis. Through chart review, a further 56 (64%) patients with embolism could have been receiving anticoagulant therapy if published clinical guidelines(1) were applied. Therefore, 40 episodes of thromboembolism were potentially preventable. Over the same period, there were 18 patients admitted with haemorrhage related to warfarin therapy for stroke prophylaxis in NVAF, including 10 gastrointestinal, five intracerebral, and three peripheral haemorrhages. Most haemorrhages were associated with a high International Normalized Ratio (INR) and the patients were left less disabled than those with embolism. Only one patient with haemorrhage had an absolute contraindication to warfarin therapy (6%). We conclude that the number of preventable strokes far outweighed the morbidity due to warfarin use in the management of NVAF.