Cognitive effects of lamotrigine compared with topiramate in patients with epilepsy.

OBJECTIVE: To compare the cognitive effects of lamotrigine vs topiramate as adjunctive therapy in adults with epilepsy. METHODS: A multicenter, double-blind, randomized, prospective study was conducted in adults with partial seizures. Lamotrigine or topiramate was introduced as an adjunctive therapy to carbamazepine or phenytoin and titrated over 8 weeks to target doses. These drugs were maintained another 8 weeks (maintenance phase) without dosage changes. The primary endpoint was change from screening to the end of the maintenance phase in a combined analysis of standardized measures of cognition (Controlled Oral Word Association Task [COWA]; Stroop Color-Word Interference; Digit Cancellation; Lafayette Grooved Pegboard, dominant hand; Rey Auditory Verbal Learning Test, delayed recall; and Symbol-Digit Modalities test). RESULTS: For the primary endpoint, cognitive performance at the end of the maintenance phase was better with lamotrigine than with topiramate (415.3 vs 315.1; p < 0.001). On the individual cognitive tests, performance was better with lamotrigine than with topiramate in mean changes from screening on the COWA (p < 0.001), Stroop Color-Word Interference (p = 0.038), and Symbol-Digit Modalities tests (p < 0.001). The treatment effect exceeded the minimum clinically important difference for the COWA and the Symbol-Digit Modalities test. Mean changes from screening in the Performance-On-Line test simulating driving skills reflected better performance with lamotrigine than with topiramate (p = 0.021). The median percentage change from baseline in seizure frequency was lower with lamotrigine than with topiramate during the escalation phase (-80% vs -100%; p = 0.028) but not during the maintenance phase (-75% vs -100%; p = 0.062). The frequencies of cognitive adverse events and of premature withdrawals related to cognitive decline were higher with topiramate than with lamotrigine (6% vs 0%; p = 0.013). CONCLUSION: Lamotrigine had significantly less impact than topiramate on measures of cognition when used as adjunctive therapy for partial seizures.

Video-EEG in the diagnosis of paroxysmal events in children with mental retardation and in children with normal intelligence.

Video-EEG monitoring was performed to evaluate 193 children (91 females, 102 males; mean age 9.6 years, SD 5.7) who presented with paroxysmal events of uncertain etiology. Diagnosis of the type of event, i.e. epileptic or non-epileptic, was successfully established in 130 of 193 patients (67.3%). Seventy children (36%) had mental retardation* (MR). Children with MR were more likely (p<0.05) than children without MR to have events during the studies. Children with and without MR had strikingly similar frequencies of epileptic and non-epileptic events. In participants who had events recorded and characterized, epileptic seizures were identified in 67 children (51.5%), non-epileptic events in 54 children (41.5%), and both epileptic and non-epileptic events in nine children (7%). Improved diagnosis prompted appropriate management. This should encourage more frequent use of video-EEG in children, especially in those with MR, to differentiate epilepsy from behavioral disturbances so that specific treatment can be provided.

Orbito-frontal epilepsy masquerading as temporal lobe epilepsy-a case report.

Temporal lobectomy fails to control seizures in a considerable percentage of patients who do not have hippocampal sclerosis. One theoretical reason for failure of surgery is that some of these patients may in fact have extratemporal epilepsy. We present a 28-year-old woman with clinical and scalp electroencephalogram (EEG) evidence of right temporal lobe epilepsy (TLE) supported by functional imaging with interictal positron emission tomography (PET) and ictal single-photon emission computerized tomography (SPECT). An invasive EEG monitoring was prompted by the discovery of a small right orbito-frontal lesion on MRI. Monitoring documented seizure onset at the lesion, with rapid right temporal involvement. The patient was almost seizure-free after a lesionectomy. The index of suspicion of orbito-frontal epilepsy should be high in patients with apparent TLE when the scalp EEG and neuroimaging data are not congruent, or if temporal lobe pathology cannot be identified on structural imaging.

Safety of long-term treatment with tiagabine.

The aim of this study was to evaluate the safety of long-term treatment with tiagabine. We reviewed the case report forms of patients with refractory partial epilepsy who took tiagabine for longer than 6 months in two long-term studies. We classified all adverse events based on severity and persistence, and recorded the dose at onset of each adverse event. We then divided patients into those treated for 6-12 months, 12-24 months and > 24 months. We compared the adverse event profile and change in seizure frequency among the three groups. Forty-two patients took tiagabine for longer than 6 months. The mean duration of treatment was 22.6 months. The mean monthly seizure frequency was 12.7 at baseline and 8.1 at study termination (36% decrease). The most common adverse events were: tiredness (56%), headache (46%), dizziness (44%), visual symptoms (blurring, difficulty focusing, diplopia) (39%), altered mentation (32%), and tremor (31%). The adverse event profile was comparable among the three groups. Seizure frequency was significantly more improved in the > 24 months group. Long-term treatment with tiagabine is well tolerated. The most important predictor of long-term therapy with tiagabine was the degree of seizure improvement.

Absence seizures with evolution into generalized tonic-clonic activity: clinical and EEG features.

PURPOSE: To report the clinical and electrographic features of absence seizures evolving into generalized tonic-clonic (GTC) activity in six patients with idiopathic generalized epilepsy. METHODS: All patients were referred for evaluation of refractory seizures and underwent video-EEG monitoring after discontinuation of their antiepileptic drugs (AEDs). We analyzed the video-EEG recordings for seizure semiology as well as ictal and interictal activity. We also reviewed the initial clinical data in all patients. RESULTS: All patients were women, with a mean age of 27 years (range, 14-43 years). The mean age at seizure onset was 12 years (range, 5-15 years). Family history was positive for epilepsy in four patients. All patients had recorded seizures with an onset that was characteristic of generalized absence clinically and electrographically, with evolution into GTC activity. The EEG onset was with generalized 2.5-to 5-Hz spike-and-wave discharges, with evolution into faster rhythmic activity. Interictal EEG recordings showed generalized 2-to 5-Hz spike-and-wave discharges. All had normal background activity. All patients were treated with divalproex monotherapy. Five patients have been seizure free, and one had a single breakthrough GTC seizure during a follow-up period of 12-36 months. CONCLUSIONS: GTC activity may evolve from typical absence seizures. This seizure type should be included in the International Classification of Seizures. Its recognition and distinction from complex partial seizures with secondary generalization are important for appropriate therapy.

Limbic encephalitis and hyperactive foci on PET scan.

Two cases of patients with paraneoplastic limbic encephalitis, difficult to control seizures, and unilateral hippocampal hypermetabolism on positron emission tomography (PET) are described. Two women aged 33 and 61 presented with uncontrolled complex partial seizures, profound memory loss and cognitive decline. One was later diagnosed with breast cancer and the other with lung cancer. Video-EEG on the first patient recorded multifocal sharp waves and bilateral independent seizure onsets. The second patient had no epileptiform discharges and bitemporal ictal onset, even though the clinical seizures suggested a right temporal onset. Magnetic resonance imaging (MRI) was normal in both patients. PET scans obtained in the interictal state showed right hippocampal hypermetabolism in both patients. In the second patient, the lung cancer was irradiated with resolution of seizures and improvement of memory function. A PET scan six months later was normal. Subsequent seizure recurrence and worsening of memory led to the discovery of widespread metastases. Limbic encephalitis should be considered in the differential diagnosis of intractable partial epilepsy, particularly if accompanied by severe memory loss and cognitive decline. Treatment of the underlying cancer may be lead to improved seizure control. Hippocampal hypermetabolism may be a common feature on PET, and may indicate subclinical seizure activity.

Brief antiepileptic drug withdrawal prolongs interval to next seizure.

OBJECTIVE: To evaluate the course of seizure control after reinstitution of antiepileptic drugs (AEDs) in patients whose AEDs were discontinued during inpatient EEG-video monitoring. METHODS: The authors studied prospectively patients with intractable epilepsy admitted for EEG-video monitoring with AED withdrawal. They examined seizure diaries in the 2 months preceding admission and recorded the number of seizures during hospitalization and for 2 months after discharge. They also recorded the interval between the last two seizures preceding admission (S-S pre), from the last seizure to admission (S-A), from discharge to the first seizure after discharge (D-S), and between the first and the second seizures following discharge (S-S post). RESULTS: Sixty patients qualified for the study. There was a significant decrease in seizure frequency in the 2 months after discharge compared with baseline (p = 0.02). For patients who had at least two seizures during follow-up, the mean D-S interval was significantly longer than mean S-S pre and S-S post (p < 0.005), whereas the latter two intervals were comparable. Prolongation of D-S was related to duration off AEDs and to the AED restarted, but not to the number or severity of seizures during monitoring. CONCLUSION: Seizure improvement after reinstitution of antiepileptic drugs (AEDs) is due primarily to prolongation of the interval from reinstitution of AEDs to the next seizure. This may reflect increased patient responsiveness to AED therapy after a drug "holiday" and has implications for experimental AED testing in the setting of presurgical evaluation.

The generalized tonic-clonic seizure in partial versus generalized epilepsy: semiologic differences.

PURPOSE: To study differences in the clinical manifestations of generalized tonic-clonic seizures (GTCS) of partial versus generalized onset. METHODS: We studied 10 GTCSs in nine patients with idiopathic generalized epilepsy (IGE) and 10 GTCSs in 10 patients with temporal lobe epilepsy (TLE). Videotaped seizures were reviewed for all clinical features, focusing on asymmetries during different phases of each seizure. RESULTS: In the IGE group, focal features were seen before generalized motor activity in seven seizures. The most common was adversive head turn (six seizures). One patient had opposite direction of head turning in two recorded seizures. The tonic phase was always symmetric. In the last generalized clonic phase, asymmetry or asynchrony of motor activity was seen transiently in three seizures. The TLE group showed focal features before generalization in all seizures. Adversive head turning occurred in nine patients and was always contralateral to the focus. Focal clonic activity occurred before generalization in three and was always contralateral to the focus. The generalized tonic phase was usually asymmetric, and in the last clonic phase, motor activity was asymmetric or asynchronous in eight seizures (p<0.05, IGE vs. TLE). CONCLUSIONS: Brief focal features or asymmetry at onset are common in the GTCSs of IGE. However, asymmetry or asynchrony during the last clonic phase are uncommon in IGE, in contrast to TLE.

The value of combined ambulatory cassette-EEG and video monitoring in the differential diagnosis of intractable seizures.

OBJECTIVE: To evaluate the ability of combined ambulatory cassette-EEG and video monitoring (ACV) to establish a diagnosis in patients with attacks of unknown nature and its impact on their treatment. METHODS: We evaluated ACV in 125 consecutive patients with attacks of unknown nature. Most had intractable attacks suspected of being non-epileptic. Antiepileptic drugs (AEDs) were discontinued or reduced at the start of the procedure. The median duration of monitoring was 3 days (range 1-10). The ACV results and patient records were reviewed, and patients were called for additional follow-up when feasible. RESULTS: Attacks were recorded in 101 patients. They were epileptic in 20 patients, psychogenic in 60, both in 3, and of unknown nature in 18 (usually subjective episodes). The study resulted in AED discontinuation at discharge in 46 patients with recorded psychogenic seizures and 6 with recorded attacks of unknown nature. Three-quarters of patients followed up were free of attacks or improved. CONCLUSIONS: ACV was effective in providing a diagnosis in two-thirds of patients. If psychogenic seizures are suspected in patients on AEDs, ACV may provide the diagnosis and may help exclude epilepsy, without the need for standard EEG-CCTV, which can then be reserved for patients undergoing presurgical evaluation.

Visual field defects after temporal lobe resection: a prospective quantitative analysis.

OBJECTIVE: To evaluate and quantify prospectively visual field changes in patients undergoing temporal lobe resections for intractable epilepsy. BACKGROUND: Visual field abnormalities occur after temporal lobe resections for epilepsy; however, we have not encountered published reports using automated static visual field analysis. METHODS: Humphrey visual fields (program 30-2) were obtained before and after partial temporal lobe resection in 32 consecutive patients with intractable epilepsy. A quantitative point-by-point analysis was made in the affected superior quadrant, and the defects were averaged for the whole patient group. RESULTS: Thirty-one patients developed a visual field defect, but none was aware of the defect. The points nearest fixation were relatively spared. The defects were greatest in the sector closest to the vertical meridian in the eye ipsilateral to the resection. The ipsilateral and contralateral mean field defects also differed in both topography and depth. A significant correlation was found between the extent of lateral temporal lobe resection and the degree of the defect in the contralateral eye. CONCLUSIONS: There are differences in the shape and depth of the ipsilateral and the contralateral field defects not previously reported. These findings demonstrate that certain fibers from the ipsilateral eye travel more anteriorly and laterally in Meyer's loop, and support the hypothesis that visual field defects due to anterior retrogeniculate lesions are relatively incongruous because of anatomic differences in the afferent pathways. Automated perimetry is a sensitive method of evaluating and quantifying visual field defects.

Generalized absence seizures with 10-15 Hz fast discharges.

OBJECTIVE: To report clinical and EEG features in 5 adults with unusual, fast rhythmic discharges accompanying absence seizures. DESIGN AND METHODS: The 5 patients presented with uncontrolled seizures. All had EEG-video monitoring with recorded seizures. Video seizures were reviewed and ictal as well as interictal epileptiform activity was analyzed. The patients were followed up after appropriate therapy for a minimum of 6 months. RESULTS: There were 3 women and two men, with a mean age of 37 years (range: 23-59). Two patients had onset of absence seizures in childhood, one in adolescence and two after age 20. All patients also had generalized tonic-clonic seizures. Ictal EEG recordings showed generalized spike and wave (SW) discharges of variable dominant frequencies (2.5-6 Hz) and intermingled 10-15 Hz generalized rhythmic discharges which also occurred in isolation or as the dominant activity. Interictal recordings showed similar but shorter 2.5-6 Hz generalized SW discharges. The background activity was normal in 3 patients and mildly slow in two who had very frequent absence seizures during the recording period. Four patients became seizure free and one had 75% improvement on appropriate antiabsence therapy. CONCLUSIONS: The fast 10-15 Hz rhythmic discharges that we report appear to occur mostly in adult patients with absence, as well as, generalized tonic-clonic seizures. They can occur in isolation or be embedded in more typical SW discharges accompanying typical absence seizures. Their presence does not imply a poor prognosis for seizure control.

Pediatric manifestations of Hashimoto's encephalopathy.

Hashimoto's encephalopathy is a steroid-responsive encephalopathy associated with elevated blood concentrations of antithyroid antibodies. The patients are usually euthyroid or mildly hypothyroid. The authors report two pediatric patients with Hashimoto's encephalopathy and review the literature. The clinical picture in adolescents, as with adults, is pleomorphic but frequently associated with seizures, confusion, and hallucinations. Alternatively, progressive cognitive decline manifested by a drop in school performance can be observed. The diagnosis of Hashimoto's thyroiditis is often overlooked at presentation and a high degree of suspicion is necessary for proper diagnosis.

Conversion to high dose gabapentin monotherapy in patients with medically refractory partial epilepsy.

PURPOSE: To evaluate the safety and efficacy of high dose gabapentin (GBP) monotherapy (3,000-4,800 mg/day) in patients with medically refractory partial epilepsy. METHODS: GBP monotherapy at daily doses up to 4,800 mg was attempted in patients participating in the open-label phase of a double-blind, dose-controlled, GBP monotherapy trial. For those who achieved monotherapy, the types and severity of adverse events were assessed and the average seizure frequency per 28 days while maintained on the highest daily GBP dose was compared to the seizure frequency during the baseline phase of the double blind trial. Correlation analysis between GBP serum level, total daily dose, and percentage of seizure change from baseline was performed. RESULTS: A total of 45 patients participated in the open-label phase of the trial and 23 (51%) were converted successfully to GBP monotherapy. In those patients, the average daily gabapentin dose was 3,900 mg and the mean length of follow-up was 252 days. Compared to baseline, there was a mean reduction of 54%, 43%, and 14% for simple partial, complex partial and secondarily generalized seizures respectively, while maintained on high-dose GBP monotherapy. A significant linear correlation between daily GBP dosage (2,400-4,800 mg) and resultant mean serum levels was found (r = 0.51; p < 0.01). There was no significant correlation between seizure frequency and total daily GBP dose or with serum levels. High-dose GBP monotherapy was well tolerated; only one patient exited the trial because of adverse events. The most common adverse event was tiredness/sleepiness and was not dose-related. CONCLUSIONS: GBP monotherapy is well tolerated in daily doses of up to 4,800 mg and is effective in a subgroup of patients with medically refractory partial epilepsy.

EEG changes in intrathecal baclofen overdose: a case report and review of the literature.

OBJECTIVE: To review the clinical and EEG manifestations of intrathecal baclofen overdose. METHODS: We identified one patient who had received an overdose of intrathecal baclofen. Information about the clinical course was obtained by reviewing the patient's medical record. EEGs were recorded with the use of the standard 10-20 electrode placement system. RESULTS: The patient received 30 mg baclofen intrathecally. Shortly after the injection he developed respiratory insufficiency and quadriparesis and later became comatose. The first EEG obtained 20 h after the injection showed very frequent quasiperiodic generalized epileptiform discharges. The patient gradually improved clinically and a second EEG obtained 24 h later showed only intermittent bursts of generalized slow wave activity. A repeat EEG study 1 week later was normal. CONCLUSIONS: The EEG in intrathecal baclofen overdose can show quasiperiodic generalized epileptiform discharges. This does not necessarily indicate the presence of underlying potential epileptogenicity, and treatment with an antiepileptic medication is not necessary.

Significance of head turn sequences in temporal lobe onset seizures.

We studied head turning in 239 complex partial seizures with or without generalization, in 32 patients with unilateral temporal lobe epilepsy. Head turns occurred in 73% of seizures that did not evolve to focal jerking or secondary generalization, and in all 41 seizures that secondarily generalized. In seizures without focal jerking or secondary generalization the most common pattern was that of single head turns (70%) which were ipsilateral to the focus in 94%. The next most common pattern was that of two or more head turns, with the first two turns in the same direction (19%), always ipsilateral to the focus. In seizures with secondary generalization, the most common sequence was that of two head turns contralateral to each other (59% of seizures). The first was always ipsilateral to the focus, associated with dystonic posturing in 96%, and was not tonic in character. The second was always contralateral, was tonic in character, and was still present within five seconds of secondary generalization or focal jerking. Our results suggest different patterns and sequences of head turning temporal lobe complex partial seizures without, and those with focal jerking or secondary generalization. Some sequences have powerful lateralizing value that can complement other lateralizing features.

The start-stop-start phenomenon in scalp-sphenoidal ictal recordings.

The start-stop-start (SSS) phenomenon is an apparent abortive ictal onset separated from the main seizure discharge. It was previously described in seizures recorded with subdural electrodes. We have observed this phenomenon in scalp-sphenoidal ictal recordings as well. We retrospectively reviewed 435 seizures recorded with scalp-sphenoidal electrodes from 61 patients with temporal lobe epilepsy. We found SSS onset in 15 seizures of 8 patients, representing 26% of these patients' seizures. The first "start" usually had a narrow field, typically in the sphenoidal electrode. The mean duration of the first "start" was 11 sec and that of the stop 8 sec. The restart had a different morphology and frequency in 87% and had a wider field in 67% of seizures. The clinical onset followed the first start and preceded the restart in most of the seizures. In 1 patient, 1 seizure with SSS was correctly localized and lateralized, whereas 5 of 7 without SSS were falsely lateralized. The recognition of the SSS phenomenon may improve the accuracy of seizure localization in scalp-sphenoidal recordings.

Association of ipsilateral head turning and dystonia in temporal lobe seizures.

We evaluated head turning in 239 complex partial seizures (CPS) with or without generalization in 32 patients with unilateral temporal lobe epilepsy (TLE). Head turns occurred in 187 seizures of 31 patients, more than once in 71 seizures. The first head turn was ipsilateral to the focus in 162 seizures (87%), with a mean latency of 22 s, as compared with 83 s for contralateral first head turns. Concomitant dystonic posturing of the arm occurred with 71% of all ipsilateral head turns and with 16% of all contralateral head turns. The mean difference in absolute latency between the first head turn and concomitant dystonic posturing was 6 s. Examination of all instances of concomitant head turning and dystonic posturing (160) showed them to be contralateral to each other in 154 (96%). Furthermore, the dystonia was contralateral and head turning was ipsilateral to the focus in 149 (93%). Forty-one seizures secondarily generalized, with transitional tonic head deviation contralateral to the focus in 35. Early head turning suggests an ipsilateral temporal seizures focus, particularly when associated with contralateral dystonic posturing. Similar mechanisms may account for both. Tonic head deviation preceding secondary generalization probably has a different mechanism.

Aphasia secondary to partial status epilepticus of the basal temporal language area.

We present a patient with aphasia of several days' duration that was secondary to spontaneous partial status epilepticus arising from the left basal temporal region. Evidence from MRI, EEG, and PET confirmed the origin of the seizures in the basal temporal area. Both the seizure discharges and the aphasia resolved after antiepileptic therapy. This case, to our knowledge, is the first documented example of epileptic aphasia secondary to spontaneous partial status epilepticus originating from the basal temporal area.

Self-injury and incontinence in psychogenic seizures.

Two patients who incurred significant injuries during psychogenic seizures prompted us to do a telephone survey of self-injury and incontinence in 102 consecutive patients diagnosed with psychogenic seizures by EEG-closed-circuit TV (EEG-CCTV) monitoring. Seventy-three patients (or a close family member or friend) were reached by telephone and responded to our survey. During typical attacks of psychogenic seizures, 40% reported injuries, 44% reporting tongue biting, and 44% reported urinary incontinence. Suicide attempts were reported by 32% and were more common in those with self-injury and urinary incontinence. We compared the results of patients with psychogenic seizures with those of 30 patients with refractory epilepsy documented by ictal recordings, using a similar telephone survey. Injuries of all types were more commonly reported by epilepsy patients. Burn injuries were reported only by patients with epilepsy. Suicide attempts were more commonly reported by the psychogenic seizure group. Self-injury and incontinence are commonly reported by psychogenic seizure patients. In view of their significant association with suicide attempts, they may indicate an underlying depression.

Inhibitory motor seizures: correlation with centroparietal structural and functional abnormalities.

Six adults and 2 children with focal inhibitory motor seizures (ictal paralysis) were evaluated during a 4-year period. Paresthesias at seizure onset occurred during some seizures in all patients, and focal clonic activity followed paralysis in 4. EEG-CCTV recordings of the seizures in 2 patients showed that ictal paralysis coincided with an ictal discharge starting in one centroparietal area. MRI showed centroparietal structural lesions in six patients. One patient with a normal MRI scan had right centroparietal hypometabolism on PET. Inhibitory motor seizures must be differentiated from transient ischemic attacks and migraine. In our patients a centroparietal epileptogenic focus was suggested by neuroimaging studies, and in 2 instances by ictal EEG.