Neelan Pillay

Neurovascular decoupling is associated with severity of cerebral amyloid angiopathy

Objectives: We used functional MRI (fMRI), transcranial Doppler ultrasound, and visual evoked potentials (VEPs) to determine the nature of blood flow responses to functional brain activity and carbon dioxide (CO2) inhalation in patients with cerebral amyloid angiopathy (CAA), and their association with markers of CAA severity. Methods: In a cross-sectional prospective cohort study, fMRI, transcranial Doppler ultrasound CO2 reactivity, and VEP data were compared between 18 patients with probable CAA (by Boston criteria) and 18 healthy controls, matched by sex and age. Functional MRI consisted of a visual task (viewing an alternating checkerboard pattern) and a motor task (tapping the fingers of the dominant hand). Results: Patients with CAA had lower amplitude of the fMRI response in visual cortex compared with controls (p = 0.01), but not in motor cortex (p = 0.22). In patients with CAA, lower visual cortex fMRI amplitude correlated with higher white matter lesion volume (r = −0.66, p = 0.003) and more microbleeds (r = −0.78, p < 0.001). VEP P100 amplitudes, however, did not differ between CAA and controls (p = 0.45). There were trends toward reduced CO2 reactivity in the middle cerebral artery (p = 0.10) and posterior cerebral artery (p = 0.08). Conclusions: Impaired blood flow responses in CAA are more evident using a task to activate the occipital lobe than the frontal lobe, consistent with the gradient of increasing vascular amyloid severity from frontal to occipital lobe seen in pathologic studies. Reduced fMRI responses in CAA are caused, at least partly, by impaired vascular reactivity, and are strongly correlated with other neuroimaging markers of CAA severity.

Networks underlying paroxysmal fast activity and slow spike and wave in Lennox-Gastaut syndrome

Objective: To use EEG-fMRI to determine which structures are critically involved in the generation of paroxysmal fast activity (PFA) and slow spike and wave (SSW) (1.5–2.5 Hz), the characteristic interictal discharges of Lennox-Gastaut syndrome (LGS). Methods: We studied 13 well-characterized patients with LGS using structural imaging and EEG-fMRI at 3 tesla. Ten patients had cortical structural abnormalities. PFA and SSW were considered as separate events in the fMRI analysis. Results: Simultaneous with fMRI, PFA was recorded in 6 patients and SSW in 9 (in 2, both were recorded). PFA events showed almost uniform increases in blood oxygen level–dependent (BOLD) signal in “association” cortical areas, as well as brainstem, basal ganglia, and thalamus. SSW showed a different pattern of BOLD signal change with many areas of decreased BOLD signal, mostly in primary cortical areas. Two patients with prior callosotomy had lateralized as well as generalized PFA. The lateralized PFA was associated with a hemispheric version of the PFA pattern we report here. Conclusion: PFA is associated with activity in a diffuse network that includes association cortices as well as an unusual pattern of simultaneous activation of subcortical structures (brainstem, thalamus, and basal ganglia). By comparison, the SSW pattern is quite different, with cortical and subcortical activations and deactivations. Regardless of etiology, it appears that 2 key, but distinct, patterns of diffuse brain network involvement contribute to the defining electrophysiologic features of LGS.

EEG in epilepsy: current perspectives.

The electroencephalogram (EEG) plays an important diagnostic role in epilepsy and provides supporting evidence of a seizure disorder as well as assisting with classification of seizures and epilepsy syndromes. Emerging evidence suggests that the EEG may also provide useful prognostic information regarding seizure recurrence after a single unprovoked attack and following antiepileptic drug withdrawal. Continuous EEG video telemetry monitoring has an established role in the diagnosis of non-epileptic pseudo-seizures and in localizing the seizure focus for epilepsy surgery. Newer tools such as EEG mapping and magneto-encephalogram, although still investigational, appear potentially useful for defining the seizure focus in epilepsy. This review examines the traditional concepts of clinical EEG in the light of newly available data.

Quality of Life after Vagus Nerve Stimulation for Intractable Epilepsy: Is Seizure Control the Only Contributing Factor?

We assessed the impact of vagus nerve stimulation on a cohort of patients with intractable epilepsy. A 1-year prospective trial of vagus nerve stimulation for intractable epilepsy was done in 26 patients. Seizure frequency, anti-epileptic drugs, and quality of life were assessed using QOLIE-89, ELDQOL, and a Likert scale of impact of treatment. Seizures were reduced by more than 50% in 19% of the patients, by less than 50% in 46%, and were unchanged in 35% of them. Antiepileptic drugs were reduced in 43% of the patients. There was a significant improvement in the mean overall QOLIE-89 score and other measures of quality of life, but these did not correlate with changes in seizure frequency. Subjective improvement occurred in 84% of the patients. The quality of life improves in some patients following vagus nerve stimulation for intractable epilepsy. The favorable effects of this treatment may be attributable to additional factors besides seizure control which in this study was modest.

Intraoperative electrocorticography in temporal lobe epilepsy surgery.

Although in clinical use for many years, the validity of intraoperative electrocorticography (ECoG) in guiding resective temporal lobe epilepsy (TLE) surgery is uncertain. Advances in neuroimaging and extraoperative intracranial recordings have contributed greatly to the identification of epileptogenic lesions and cortex, clarifying the limitations of a brief intraoperative interictal recording. Studies of undifferentiated ECoG findings (which classify all interictal cortical spike discharges as equal) tend to not support this method. This article reviews ECoG and presents data from 86 TLE surgeries at the University of British Columbia suggesting that differentiation of ECoG features may enhance the contribution of this time honored method. Specifically, independent foci may be more important for epileptogenesis than synchronous foci, and postexcision activation appears to be a benign phenomenon, while residual spikes unaltered by the resection correlate with a greater proportion of seizure recurrence.

Impact of plasma exchange on indices of demyelination in chronic inflammatory demyelinating polyradiculoneuropathy

We studied the impact of plasma exchange (PE) on indices of primary demyelination in patients of the Canadian multicenter trial of PE in chronic inflammatory demyelinating polyneuropathy (CIDP). Individual motor nerves (median, ulnar, peroneal, tibial) were studied: distal motor latencies (DMLs), proximal and distal compound muscle action potential (M‐wave) amplitudes, negative peak areas and durations, and motor conduction velocities (CVs). Proximal M‐wave amplitudes in individual motor territories, particularly in the ulnar nerve (from below elbow, above elbow, and axillary stimulating sites) demonstrated significant improvement with PE, but not sham exchange. Proximal ulnar M‐wave areas also had significant improvement with PE. Trends toward improvement of individual nerve motor CVs, M‐wave durations, and DMLs did not achieve statistical significance. Proximal M‐wave amplitudes, particularly in the ulnar motor territory, and proximal M‐wave areas (providing a measure of conduction block) were the most sensitive indices of improvement conferred by PE in CIDP. In individual patients, these indices may help judge the efficacy of therapy.

Quality indicators in an epilepsy monitoring unit

Examining and improving the quality of care in epilepsy monitoring units (EMUs) is essential to delivering the best possible care and to mitigating undesirable outcomes. Epilepsy monitoring units are unique in that an admission to an EMU often involves the induction of symptoms (seizures) rather than minimizing and/or treating symptoms, which can lead to an increased risk to patient safety. Very little research has addressed the quality of care and safety in EMUs. The objective of this study was to examine quality indicators in a large population of patients admitted to an EMU in a large health region. Data were collected prospectively on 396 consecutive patients admitted to the EMU for scalp EEG recording from 2008 to 2011 using a standardized data abstraction form. Variables examined included the following: patient demographics, baseline clinical characteristics, EMU admission statistics, and EMU quality indicators. We found that an admission to the EMU was a safe and effective tool in the management of patients with epilepsy and seizure-like events. The number of adverse events during the study period was low at 4.9%. The admission question was answered in 78.8% of cases, and it was partially answered in 6.6%. The need for systematically developed and validated quality indicators in EMUs is emphasized. The research in this area is sparse, and thus these data aid in supporting the utility of EMUs in the management and care of those with seizures and seizure-like events.

Epileptiform activity in neurocritical care patients.

BACKGROUND Non-convulsive seizures have been reported to be common in neurocritical care patients. Many jurisdictions do not have sufficient resources to enable routine continuous electroencephalography (cEEG) and instead use primarily intermittent EEG, for which the diagnostic yield remains uncertain. Determining risk factors for epileptiform activity and seizures could help identify patients who might particularly benefit from EEG monitoring. METHODS We performed a cohort study involving neurocritical care patients with admission Glascow Coma Scale (GCS) scores ≤ 12, who underwent ≥ 1 EEG. EEGs were reviewed for presence of interictal discharges, periodic epileptiform discharges (PEDs), and seizures. Multivariate analysis was used to identify predictors of these findings and to describe their prognostic implications. RESULTS 393 patients met inclusion criteria. 34 underwent cEEG, usually because epileptiform activity was first detected on a routine EEG. The prevalence of PEDs or electrographic seizures was 13%, and was highest with anoxic encephalopathy and central nervous system infections. Other independent predictors for epileptiform activity included a history of convulsive seizure(s), increasing age, deeper coma, and female gender. Although patients with epileptiform activity had higher mortality, this association disappeared after adjustment for confounders. CONCLUSION Approximately 7-8 neurocritical care patients must undergo intermittent EEG monitoring in order to diagnose one with PEDs or seizures. The predictors we identified could potentially help guide use of resources. Repeated intermittent studies, or cEEG, should be considered in patients with multiple risk factors, or when interictal discharges are identified on an initial EEG. It remains unclear whether aggressive prevention and treatment of electrographic seizures improves neurologic outcomes.

Creutzfeldt-Jakob disease: correlation of focal electroencephalographic abnormalities and clinical signs

Three patients are described with pathologically verified Creutzfeldt-Jakob disease (CJD) who presented with localizing clinical signs accompanied by focal electroencephalographic abnormalities including periodic lateralized epileptiform discharges (PLEDS). With further progression of the disease, diffuse background slowing and continuous bisynchronous periodic discharges appeared in all three cases. There was good correlation between the initial focal clinical manifestations and the EEG findings.

Feasibility of using an online tool to assess appropriateness for an epilepsy surgery evaluation

Objectives: To examine the applicability of applying an online tool to determine the appropriateness of referral for an epilepsy surgical evaluation and to determine whether appropriateness scores are concordant with the clinical judgment of epilepsy specialists. Methods: We prospectively applied the tool in 107 consecutive patients with focal epilepsy seen in an epilepsy outpatient clinic. Variables collected included seizure type, epilepsy duration, seizure frequency, seizure severity, number of antiepileptic drugs (AEDs) tried, AED-related side effects, and the results of investigations. Appropriateness ratings were then compared with retrospectively collected information concerning whether a surgical evaluation had been considered. Results: Thirty-nine patients (36.4%) were rated as appropriate for an epilepsy surgical evaluation, all of whom had adequately tried 2 or more appropriate AEDs. The majority of patients (84.6%) rated as appropriate had previously been considered or referred for an epilepsy surgical evaluation. Tool feasibility of use was high, with the exception of assessing whether previous AED trials had been adequate and discrepancies between physician and patient reports of AED side effects. Conclusions: Our evidence-based, online clinical decision tool is easily applied and able to determine whether patients with focal epilepsy are appropriate for a surgical evaluation. Future validation of this tool will require application in clinical practice and assessment of potential improvements in patient outcomes.