Nicholas Lawn

Ictal SPECT analysis in epilepsy: subtraction and statistical parametric mapping techniques.

Seizures are associated with an increase in regional cerebral blood flow (rCBF). In partial seizures the increased blood flow closely corresponds with the site of seizure origin. Using tracers that accumulate and remain “fixed” in different areas of the brain proportional to rCBF at the time of injection, ictal SPECT is now an important tool for localization of seizures in a presurgical evaluation. However, the best methods for interpretation of partial seizure-induced changes in rCBF remain unclear. Numerous computer-aided tools have been used to increase objectivity and accuracy of ictal SPECT analysis. This review examines the uses of ictal-interictal subtraction methods and statistical parametric mapping (SPM) to enhance interpretation and utility of ictal SPECT. The review covers the evolution of advanced ictal SPECT imaging analysis techniques and the authors’ clinical experience with the use of subtraction and SPM methods. The authors discuss the impact of ictal SPECT subtraction or difference imaging methods and the initial evidence for proof-of-principle that SPM can be used to provide objective, accurate analysis of ictal SPECT scans in patients with temporal and extratemporal lobe epilepsy. The limitations of both methodologies are discussed, and suggestions for further study of validation, improvement, and routine clinical implementation of advanced analysis methods are provided.

Amphetamine-associated seizures: Clinical features and prognosis

Forty‐four patients presenting with first‐ever seizure within 24 h of illicit use of amphetamine or related analogs (amphetamine‐associated seizures, AAS) were identified over 8 years. Patients with AAS were compared to control groups of other first‐ever seizure patients (provoked n = 126 and unprovoked n = 401). Cumulative probability of recurrence was calculated using Kaplan‐Meier analysis. Seizure recurrence and development of epilepsy were less likely in patients with AAS compared to provoked or unprovoked controls. Forty percent of patients with AAS had clinical risk factors for epilepsy, epileptiform abnormalities on electroencephalography (EEG), or an epileptogenic lesion on neuroimaging. Sleep deprivation was more frequently present in those with AAS. AAS likely relate to an intrinsic proconvulsant effect of these drugs combined with patient susceptibility and environmental factors.

Anti-NMDA receptor encephalitis associated with ictal asystole

Anti-N-methyl-D-aspartate receptor (NMDAR) encephalitis usually presents with psychiatric symptoms, behavioural changes, impaired consciousness, seizures and autonomic instability. Ictal asystole is a rare phenomenon associated with complex partial seizures. It is implicated as a potential cause of sudden unexpected death in epilepsy. We report a 41-year-old woman who presented with anti-NMDAR encephalitis. During continuous video electroencephalogram and cardiac monitoring, an episode of ictal asystole was detected. We discuss the potential link between anti-NMDAR encephalitis and ictal asystole. Treatment options for ictal asystole in the setting of anti-NMDAR encephalitis are also discussed.

When is it safe to return to driving following first-ever seizure?

Objectives The risk of recurrence following a first-ever seizure is 40–50%, warranting driving restriction during the early period of highest risk. This restriction must be balanced against the occupational, educational and social limitations that result from patients being ineligible to drive. The recommended duration of non-driving after a first seizure varies widely between jurisdictions, influenced by various factors including the community perception of an acceptable relative level of risk for an accident (the accident risk ratio; ARR). Driving restrictions may be based on individualised risk assessments or across-the-board guidelines, but these approaches both require accurate data on the risk of seizure recurrence. Methods 1386 patients with first-ever seizure were prospectively analysed. Seizure recurrence was evaluated using survival analysis. The duration of non-driving required for a range of risks of seizure recurrence and ARRs was calculated. Additionally, the actual occurrence of seizures while driving was prospectively determined during follow-up. Results For a risk of seizure recurrence to fall to 2.5% per month, corresponding to a monthly risk of a seizure while driving of 1.04 per thousand and an ARR of 2.6, non-driving periods of 8 months are required for unprovoked first-ever seizure, and 5 months for provoked first-ever seizure. Of patients with a seizure recurrence, 14 (2%) occurred while driving, with the monthly risk falling to less than 1/1000 after 6 months. Conclusions Our data provide a quantitative approach to decisions regarding a return to driving in patients with first-ever provoked or unprovoked seizure.

Are seizures in the setting of sleep deprivation provoked

It is generally accepted that sleep deprivation contributes to seizures. However, it is unclear whether a seizure occurring in the setting of sleep deprivation should be considered as provoked or not and whether this is influenced by seizure type and etiology. This information may have an important impact on epilepsy diagnosis and management. We prospectively analyzed the influence of sleep deprivation on the risk of seizure recurrence in patients with first-ever unprovoked seizures and compared the findings with patients with first-ever provoked seizures. Of 1026 patients with first-ever unprovoked seizures, 204 (20%) were associated with sleep deprivation. While the overall likelihood of seizure recurrence was slightly lower in sleep-deprived patients with first-ever seizures (log-rank p=0.03), sleep deprivation was not an independent predictor of seizure recurrence on multivariate analysis. Seizure recurrence following a first-ever unprovoked seizure associated with sleep deprivation was far more likely than for 174 patients with a provoked first-ever seizure (log-rank p<0.0001). Our findings support the International League Against Epilepsy recommendation that seizures occurring in the setting of sleep deprivation should not be regarded as provoked.

First seizure in the older patient: Clinical features and prognosis

PURPOSE The prognosis of first seizure in the elderly has rarely been studied. Despite this, anti-epileptic drug treatment following first seizure is often recommended in older adults due to the perception that recurrence is inevitable and associated with significant morbidity. This study aims to establish whether older patients presenting with first-ever seizure are more likely to have a second seizure or not, and to examine their clinical features including seizure-related morbidity. METHODS Prospective observational study of adults seen by a hospital-based first seizure service between 2000 and 2011. The prognosis and clinical features of older (aged ≥65 years) and younger (aged 16-64 years) patients were compared. KEY FINDINGS 139 of 1008 patients with first-ever unprovoked seizure were aged ≥65 years (mean age 74 years). The majority of these older patients were healthy (95% ambulant, 81% Rankin score ≤2). The likelihood of a second seizure at one year was 53% (95% CI 45-62) in older patients and 48% (95% CI 44-51) in younger patients. Independent predictors of seizure recurrence were remote symptomatic etiology, first seizure arising from sleep, epileptiform abnormality on EEG and partial seizures but not age. Older patients were less likely to suffer a seizure-related injury with both the presenting seizure and the first recurrence. CONCLUSIONS With first-ever seizure age is not an independent predictor of seizure recurrence and older patients are less likely to sustain a seizure-related injury. Treatment decisions in older patients presenting with first-ever seizure should be based on established risk factors for seizure recurrence rather than age.

Ictal Single-Photon Emission Computed Tomography Imaging in Extra Temporal Lobe Epilepsy Using Statistical Parametric Mapping

Purpose. To examine the application of statistical parametric mapping (SPM) to analyze ictal single‐photon emission computed tomography (SPECT) scans in surgical candidates with extratemporal lobe epilepsy. Methods. The authors selected patients who underwent successful ictal SPECT acquisition in the process of surgical treatment of intractable partial epilepsy. Thirteen patients were identified who met inclusion criteria for confident seizure localization from either intracranial electroencephalogram recordings or epilepsy surgery outcome. In these cases, ictal scans were registered to an in‐house‐developed normal SPECT atlas composed of 14 spatially normalized brains of normal subjects. SPM96 was used to test on a voxel‐by‐voxel basis for statistically significant increases in blood flow associated with each patients ictal scan. The results were then mapped back onto the patients magnetic resonance image (MRI) for final interpretation. Statistical parametric mapping (SPM) analysis of ictal SPECT scans was compared to both conventional visual interpretation and the analysis of subtraction ictal SPECT co‐registered to MRI (SISCOM). Results. Ten of 13 patient scans showed localizing focal ictal increases in regional cerebral blood flow, all of which were concordant with ultimate epilepsy localization. Of the 3 cases not localized with SPM, 1 was localized by conventional visual interpretation and another, not localized by visual interpretation, was correctly localized with SISCOM. Two cases not localized by SISCOM were localized by both visual and SPM analysis. Conclusions. This work provides supportive evidence for proof of principle that SPM can be used to provide objective, accurate analysis of ictal SPECT scans in patients with extratemporal lobe epilepsy.

Is the first seizure epilepsy--and when?

Epilepsy has recently been redefined to include a single unprovoked seizure if the probability of recurrence is ≥60% over the following 10 years. This definition is based on the estimated risk of a third seizure after two unprovoked seizures, using the lower‐limit 95% confidence interval (CI) at 4 years, and does not account for the initially high recurrence rate after first‐ever seizure that rapidly falls with increasing duration of seizure freedom. We analyzed long‐term outcomes after the first‐ever seizure, and the influence of duration of seizure freedom on the likelihood of seizure recurrence, and their relevance to the new definition of epilepsy.

Evidence for an excitatory GABAA response in human motor cortex in idiopathic generalised epilepsy

PURPOSE Impaired GABAergic inhibition has been implicated in the pathophysiology of epilepsy. The possibility of a paradoxical excitatory effect of GABA in epilepsy has been suggested, but has not been investigated in vivo. We investigated pre- and post-synaptic GABAergic mechanisms in patients with idiopathic generalised epilepsy (IGE). METHOD In 10 patients and 12 control subjects we explored short- and long-interval intracortical inhibition (SICI, LICI; post-synaptic GABAA and GABAB-mediated respectively) and long-interval intracortical facilitation (LICF; pre-synaptic disinhibition) using transcranial magnetic stimulation. RESULTS While post-synaptic GABAB-mediated inhibition was unchanged in IGE (p=0.09), LICF was reduced compared to controls (controls: 141±17% of baseline; untreated patients: 107±12%, p=0.2; treated patients: 79±10%, p=0.003). GABAA-mediated inhibition was reduced in untreated patients (response amplitude 56±4% of baseline vs. 26±6% in controls, p=0.004) and normalised with treatment (37±12%, p=0.5 vs. controls). When measured during LICI, GABAA-mediated inhibition became excitatory in untreated IGE (response amplitude 120±10% of baseline, p=0.017), but not in treated patients. CONCLUSION Pre- and post-synaptic GABA-mediated inhibitory mechanisms are altered in IGE. The findings lend in vivo support to evidence from experimental models and in vitro studies of human epileptic brain tissue that GABA may have a paradoxical excitatory role in ictogenesis.

Teaching Neuro Images : New-onset focal epilepsy : The curious case of the camel and the jawbone

A 54-year-old right-handed woman was referred for evaluation of drug-resistant epilepsy. At age 16, while riding in a park in Perth, Western Australia, she had been thrown from her horse, which had been startled by a rogue camel. There was no significant head injury but the patient subsequently noted a “clicky” jaw. At age 37, she developed recurrent episodes involving a sense of disconnection followed by dysphasia.