Role of the temporal pole in temporal lobe epilepsy seizure networks: an intracranial electrode investigation.

OBJECTIVE A convergence of clinical research suggests that the temporal pole (TP) plays an important and potentially underappreciated role in the genesis and propagation of seizures in temporal lobe epilepsy (TLE). Understanding its role is becoming increasingly important because selective resections for medically intractable TLE spare temporopolar cortex (TPC). The purpose of this study was to characterize the role of the TPC in TLE after using dense electrocorticography (ECoG) recordings in patients undergoing invasive monitoring for medically intractable TLE. METHODS Chronic ECoG recordings were obtained in 10 consecutive patients by using an array customized to provide dense coverage of the TP as part of invasive monitoring to localize the epileptogenic zone. All patients would eventually undergo cortico-amygdalohippocampectomy. A retrospective review of the patient clinical records including ECoG recordings, neuroimaging studies, neuropathology reports, and clinical outcomes was performed. RESULTS In 7 patients (70%), the TP was involved at seizure onset; in 7 patients (70%), there were interictal discharges from the TP; and in 1 case, there was early spread to the TP. Seizure onset in the TP did not necessarily correlate with preoperative neuroimaging abnormalities of the TP. CONCLUSIONS These data demonstrate that TPC commonly plays a crucial role in temporal lobe seizure networks. Seizure onset from the TP would not have been predicted based on available neuroimaging data or interictal discharges. These findings illustrate the importance of thoroughly considering the role of the TP prior to resective surgery for TLE, particularly when selective mesial resection is being considered.

A randomized, double-blind, placebo-controlled crossover study of the effects of levetiracetam on cognition, mood, and balance in healthy older adults.

OBJECTIVE: The cognitive and mood effects of levetiracetam (LEV) in older adults are not known. This study compared the cognitive and mood effects of LEV to placebo in healthy older adults. METHODS: Cognitive, mood, and balance variables were compared between LEV and placebo using a randomized, double-blind, placebo-controlled crossover study with two 5-week treatment periods. Healthy volunteers (n = 20) aged 65-80 (mean age 72.4) received either LEV or placebo in which the LEV target dose was 1,000 mg/day. Volunteers, aged 65-80, were without epilepsy to limit potentially confounding the impact of seizures and/or underlying neuropathology on outcomes. LEV was initiated at 250 mg twice a day for 2 weeks, then increased to 500 mg twice a day for 2 weeks, and then tapered to 250 mg twice a day for 1 week. This was randomized with placebo for the two treatment arms. Measures included standardized neuropsychological, mood, and balance tests yielding 32 variables. Balance was assessed using subjective report (e.g., A-B neurotoxicity scale) and objective data (e.g., Berg Balance Scale). RESULTS: Average LEV serum concentration was 16.9 (standard deviation [SD} 7.7). Repeated-measures analysis of variance (ANOVA) found no differences between LEV and placebo phases for 29 (90.6%) of 32 variables including no change in balance. Performance on LEV was better than placebo on a visual memory (MCG Complex Figure Recall; p = 0.007) and two attention tests (Trail Making Test, Part A, p = 0.009; Stroop Interference, p = 0.004). There was a trend for greater irritability and fatigue (POMS Anger and Fatigue) during the LEV phase (p = 0.029, p = 0.035). Effect-size changes were generally small (Cohen d < 0.5). SIGNIFICANCE: LEV was well tolerated in this elderly population in terms of cognition, mood, and balance. When anticonvulsant medication is indicated for older adults, LEV has pharmacokinetic advantages, and these data indicate no adverse impact on cognition or balance.

Triple pathology in epilepsy: coexistence of cavernous angiomas and cortical dysplasias with other lesions.

Coexistence of cortical dysplasias (CD) with cavernomas has rarely been reported. We reviewed our surgical specimens from patients who underwent surgery for pharmacoresistant epilepsy between 2003 and 2008, and identified seven cases with cavernoma, of whom two had overlying CD. In addition, each of these patients had a third form of a potentially epileptogenic lesion: hippocampal sclerosis in one, and venous angioma in the other. We conclude that CD is heterogeneous, with milder forms appearing to co-exist with other pathologies, including vascular abnormalities and hippocampal sclerosis.

Pharmacotherapeutics of epilepsy: use of lamotrigine and expectations for lamotrigine extended release.

The goal in managing patients with epilepsy is complete seizure freedom. Pharmacotherapeutic management of epilepsy is complicated by multiple syndromes, inter-individual differences in drug sensitivities, inter-individual differences in drug disposition, and drug interactions. Most anti-epileptic drugs (AEDs) have a therapeutic window with only a 2- to 3-fold concentration range. Extended release formulations offer advantages over their immediate release counter parts with less fluctuation in the serum concentration vs time curve and improved compliance. However, missed doses are more likely to result in prolonged "sub-therapeutic serum concentrations". Best clinical outcome may sometimes require twice daily dosing of extended release formulations even though approved for once daily dosing, as this optimally balances pharmacokinetics against compliance. Lamotrigine (LTG) is a broad spectrum AED with efficacy in partial and generalized epilepsy syndromes and good tolerability. Its metabolism is affected by co-medications which may be inducing, neutral or inhibiting of hepatic glucuronidation. Furthermore, though the average half-life in monotherapy is about 24 hours, there is a large inter-individual variation that may, including the extremes, approach a range of 10-fold. LTG-XR is expected to decrease fluctuation of serum concentration in the presence of hepatic inducing or neutral drugs. However, optimal clinical benefit in some patients may require twice daily dosing when metabolism is rapid.

Subjective preference for lamotrigine or topiramate in healthy volunteers: relationship to cognitive and behavioral functioning.

OBJECTIVE: Outcomes research emphasizes patient self-assessment and preferences in optimizing treatment. We previously showed that lamotrigine produces significantly less cognitive and behavioral impairment compared with topiramate. In the current study we extend these observations to subject self-report of preference for lamotrigine or topiramate independent of potentially confounding effects of seizures or seizure control. Additionally, drug preference was related to effects of lamotrigine and topiramate on objective neuropsychological tests as well as self-perception on behavioral instruments. METHODS: Thirty-seven healthy volunteers completed a double-blind, randomized crossover design incorporating two 12-week treatment periods of lamotrigine and topiramate each titrated to a dose of 300 mg/day. Evaluation of 23 objective neuropsychological and 15 subjective behavioral measures occurred at four times: pretreatment baseline, first treatment, second treatment, and posttreatment baseline. Preference for lamotrigine or topiramate was assessed, while blinding was maintained, at the final study visit when each subject was asked which drug he or she would prefer to take. RESULTS: A large majority (70%) preferred lamotrigine, 16% stated preference for topiramate, and 14% had no preference (drugs equivalent). Consistent with preference, those preferring lamotrigine performed better on 19 of 23 objective and 13 of 15 subjective behavioral measurements while on lamotrigine. Inconsistent with preference, subjects preferring topiramate performed better on 19 of 23 objective and 9 of 15 subjective behavioral measures while on lamotrigine. Topiramate preference also did not correlate with IQ, serum concentration, body mass index, age, or gender. Topiramate preference did relate to responses on the Profile of Mood States. CONCLUSION: Lamotrigine was preferred by the majority of subjects, congruent with objective neuropsychological and subjective behavioral measures. In contrast, for those stating a preference for topiramate the results on objective neuropsychological measures were impaired while fewer complaints were noted on the Profile of Mood States. This suggests that preference for topiramate may be determined by an effect on mood.

Neurosarcoidosis presenting with simple partial seizures and solitary enhancing mass: case reports and review of the literature.

A 37-year old woman, who had presented 5 years earlier with suspected simple partial seizures, returned with seizures increasing in frequency and intensity, confirmed by video/electroencephalography (VEEG) monitoring with left frontotemporal onset. A low-grade tumor was suspected, given a magnetic resonance imaging (MRI) study demonstrating enlargement of the left amygdala, anterior hippocampus, and adjacent mesial temporal neocortex, with modest gadolinium enhancement, and a positron emission tomography (PET) scan showing increased metabolism within that region. Surgical resection of the left mesial temporal lobe was performed and pathology revealed pathogen-free granulomas. She was given a diagnosis of sarcoidosis (following chest computed tomography that showed hilar adenopathy). She was treated with oral steroids for neurosarcoidosis with no further epileptic seizures in 19 months of follow-up. The second case was a young man, with known pulmonary sarcoidosis, who developed simple partial seizures and, later, complex partial seizures, with MRI revealing a left insular mass. Stereotactic biopsy again demonstrated pathogen-free granulomas. He has also done well in 4 years of follow-up. Review of the literature suggests that seizures associated with sarcoidosis do not invariably imply a poor prognosis. Certain features-multifocal parenchymal involvement, hydrocephalus, and chronic meningitis-were associated with poor outcome. In contrast, cases with isolated mass lesions often fared well.

Idiopathic generalized tonic-clonic seizures limited to exercise in a young adult.

Loss of consciousness limited to exercise should suggest a cardiovascular etiology even when clonic activity is reported. Infrequently, epilepsy patients report a preponderance of their seizures related to exertion. In these patients, seizures also occur independent of exercise. This is a report of a normal young adult woman with episodes of loss of consciousness limited to exercise. During cardiac stress testing with simultaneous electroencephalography, she developed generalized paroxysms of epileptiform discharges preceding a generalized tonic-clonic seizure. This case demonstrates the utility of simultaneous cardiac stress testing with electroencephalography in confirming exercise-related seizures and distinguishing epilepsy from syncope.

Transverse myelitis associated with Acinetobacter baumanii intrathecal pump catheter-related infection.

OBJECTIVE: To describe a late neurologic complication of intrathecal pump implantation and show the methods used for the diagnosis and successful treatment of transverse myelitis in this setting. CASE REPORT: A 32-year-old man with a chronic abdominal pain syndrome presented with right lower-extremity numbness 2 months after the placement of an intrathecal morphine pump. This progressed to bilateral lower extremity and ascending sensory loss to T12-L1 dermatome, significant lower-extremity weakness, constipation with overflow incontinence, and detrusor instability causing urinary incontinence in discrete episodes over the following 2 months consistent with a myelopathy. Magnetic resonance imaging (MRI) of the thoracic spine and cerebrospinal fluid (CSF) analysis were consistent with transverse myelitis. The intrathecal pump was removed and an Acinetobacter baumanii catheter-tip infection was diagnosed. Clinical course improved with the co-administration of intravenous corticosteroids and antibiotics, with significant clinical improvement within 30 days. CONCLUSIONS: Clinicians should recognize transverse myelitis as a possible late complication of intrathecal pump placement. Early medical intervention and removal of the intrathecal pump may be necessary to prevent irreversible spinal cord damage and may support good recovery.

Ketamine for refractory status epilepticus: a case of possible ketamine-induced neurotoxicity.

A 44-year-old man with treated neurosyphilis presented with subclinical status epilepticus (SE) refractory to intravenous high-dose lorazepam, phenytoin, and valproic acid over 4 days. Ketamine infusion was instituted after low-dose propofol sedation with gradual control of electrographic seizures over 72h. Reevaluation 3 months later revealed diffuse cerebellar and worsened cerebral atrophy, consistent with animal models of N-methyl-D-aspartate antagonist-mediated neurotoxicity. Animal studies of prolonged ketamine therapy are required before widespread human use in SE.