27. EEG-fMRI of nodule-cortex interaction during interictal spiking in periventricular nodular heterotopia

Abstracts / Journal of Clinical Neuroscience 16 (2009) 1514–1546

We investigated the role of the duration of AED therapy and its impact on bone by assessing the difference in bone health parameters in two AED-treated populations, comparing newly-diagnosed epileptic patients taking AEDs for 66 months and longer-term AED-taking patients (>6 months therapy) using a cross-sectional study design. Mean differences between groups in dual energy xray absorptiometry (DXA) measures including areal bone mineral density (aBMD), bone mineral content (BMC) and area were assessed at the total body (TB) lumbar spine (LS), total hip (TH) and femoral neck (FN) skeletal sites. Mean differences between groups in peripheral quantitative computed tomography (pQCT) parameters taken at the 4% and 38% nondominant radial and tibial bone sites were assessed. These included trabecular and cortical volumetric bone mineral density (TrD, CoD g/cm3), polar and axial stress strain indexes (SSI pol, SSIx, SSIy mm3) and cortical thickness (Cort Thk g/cm3) where the impact of several putative risk factors (age at AED commencement, gender, AED-type, polytherapy and dosage) on these parameters was observed. The study sample consisted of 91 participants. Population 1 comprised 34 newly-diagnosed, short-term AED-taking patients (56% male, 44% female) with a mean age (±SD) of 42.08 ± 14.0 y. Population 2 consisted of 58 longer-term, AED-taking patients (59% male, 41% female) with a mean age of 44.29 ± 17.32 y. Of the 91 participants, pQCT scans were available for 62 individuals. Data were normally distributed and adjusted for age, height and weight. Parametric independent t-tests were then utilised to assess population mean differences. Total hip aBMD presented a highly-significant difference, with those on longer-term AEDs exhibiting lower values (0.97 ± 0.014 g/ cm[2],mean ± SEM) than short-term users (1.05 ± 0.018), p = 0.002 (two tailed). Total body aBMD was marginally different between short-term (1.14 ± 0.018 g/cm2) and long-term users (1.10 ± 0.013), p = 0.051 (two tailed). The 4% tibial trabecular density was the only parameter to display a highly-significant difference between groups, with long-term users (244.36 ± 5.55 mg/cm3) exhibiting lower values than their short-term counterparts (583.71 ± 11.53), p < 0.01 (two tailed). Preliminary examination of clinically-relevant sub-groups revealed several significant mean differences; however, a larger sample is required to confirm these findings. Observations to date provide evidence of poorer bone health with increased AED therapy duration. Therefore, prospective monitoring and assessment of this at-risk population is required to combat the rising incidence of AEDinduced bone disease. * This study is supported by UCB Australia and National Health and Medical Research Council NHMRC. doi:10.1016/j.jocn.2009.07.050

26. In vivo study of the impact of amygdala kindling on the firing pattern of single neurons in the thalamus in a genetic absence epilepsy rat model Çarçak Nihan 1, Onat Filiz 2, Pinault Didier 3, French Chris 4, Gulhan Rezzan 2, O’Brien Terence J 4 1

Istanbul University, Faculty of Pharmacy, Istanbul, Turkey Marmara University School of Medicine, Istanbul, Turkey 3 INSERM U666, Louis Pasteur University, Faculty of Medicine, Strasbourg, France 4 University of Melbourne, Department of Medicine, Melbourne, Australia 2

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Purpose: Genetic Absence Epilepsy Rats from Strasbourg (GAERS) are paradoxically resistant to the progression of amygdaloid kindling. Rhythmic reciprocal oscillatory firing between the cortex and the thalamus plays a critical role in absence seizures. We hypothesized that alteration in neuronal firing in the thalamus may play a role in the resistance to kindling seen in GAERS. Method: Extracellular single neuron recordings were performed in-vivo under neurolept anesthesia in GAERS and NEC rats chronically implanted with a stimulating bipolar electrode in the left amygdala along with the cortical EEG. The recordings were performed in two region of the thalamus critical to the oscillatory thalamocortical rhythms that underlie absence seizures, the thalamic reticular nucleus (TRN) and the ventrobasal thalamus (VB). Kindling stimulations were delivered at afterdischarge thresholds to reach class 5 seizure (maximum stimulations = 30). Results: The in non-kindled rats the interictal firing pattern recorded in TRN cells was similar between GAERS (n = 25 cells, 13 rats) and NEC rats (n = 15 cells, 6 rats) in all parameters examined (mean firing frequency, % burst firing, mean number of action potentials (APs) per burst, maximum number of AP/burst and intraburst firing frequency). Kindled NEC rats (n = 9 cells, 3 rats) showed a decrease in the mean number of APs/burst compared to non-kindled NEC rats (p < 0.05). Kindled GAERS (n = 8 cells, 5 rats) showed significant differences from kindled NEC rats (n = 11 cells, 5 rats) in burst firing of VB neurons; a decreased percentage of burst firing (p < 0.01), decreased maximum number of action potentials (APs) per burst (p < 0.05), and decreased mean intraburst AP firing frequency (p < 0.01). Conclusion: The results of our recordings to date demonstrate changes in the firing patterns of neurons in the thalamus in kindled animals, with differences between GAERS and NEC rats. GAERS rats show less burst firing in the VB thalamus which may reflect an increasing in inhibitory input from the TRN. These findings may have relevance for the understanding of the role played by neuronal firing in the TRN in inhibiting the secondary generalization of limbic seizures. doi:10.1016/j.jocn.2009.07.051

27. EEG-fMRI of nodule-cortex interaction during interictal spiking in periventricular nodular heterotopia Archer JS 1,2, Abbott DF 1, Masterton R 2, Palmer S 2, Jackson GD 1,2 1

The University of Melbourne, Melbourne, Australia Brain Research Institute/Florey Neurosciences Institutes, Melbourne, Australia 2

Introduction: Periventricular nodular heterotopia (PVNH) is a malformation of cortical development where there is persistence of neuronal cells in the ventricular zone during cortical development. 80% of patients with PVNH have epilepsy. However, the association between the periventricular nodular tissue and seizure onset remains unclear. Depth EEG recordings have variously described seizures arising in nodular tissue, simultaneously in cortex and nodular tissue or in cortex alone. The simultaneous acquisition of EEG and functional MRI (EEGfMRI) allows identification of brain regions showing increased activity during epileptiform activity. Compared to EEG, the technique has improved spatial resolution, and captures activity changes over the whole brain, including deep structures. Methods: A 38 year-old female, with multiple bilateral periventricular nodules of heterotopic grey matter, presented for assessment of intractable epilepsy. Video-EEG monitoring confirmed

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Abstracts / Journal of Clinical Neuroscience 16 (2009) 1514–1546

frequent complex partial seizures with an apparent left temporal onset (maximal T5). Using in-house equipment we recorded EEG during 30 minutes of continuous fMRI (3T GE Signa, whole-brain T2 (EPI) images; TR = 3.2 s; 64  64 matrix, 40 slices; resolution = 3.4  3.4  3.2 (+0.2 gap) mm. The EEG record established the timings of epileptiform events (n = 45), which were used in an event related fMRI analysis. Pre-processing and statistical analysis of the fMRI images used SPM2 (http:// www.fil.ion.ucl.ac.uk/spm/). The analysis window was then stepped backwards and forwards in 1.6 sec (half a TR) segments to cover a time window of 19.2 to +19.2 seconds. Each SPM (activation and deactivation) map was thresholded to p < 0.001 uncorrected, and the SPM showing the maximum t-statistic ( 1.6 sec analysis, maximum Z = 5.67) was then used to identify key regions for more detailed time course analysis. Results: EEG-fMRI confirmed BOLD activity changes related to epileptiform activity in several regions of periventricular tissue and overlying cortex, especially in a large chunk of periventricular tissue in the left trigone, and overlying left posterior temporal cortex. Peri-stimulus time histograms of BOLD signal change from key cortical and nodular regions showed signal rising at about the same time in nodular and cortical regions, suggesting a rapid interplay between the two regions. Discussion: We have demonstrated fMRI activity changes in periventricular nodular tissue and overlying cortex during epileptiform activity in PVNH. The peak BOLD response to epileptiform activity occurred about 1.6 seconds earlier than expected, suggesting there may be changes in neuronal activity prior to spikes. During ‘left temporal’ interictal discharges, left posterior temporal cortex and underlying nodular tissue activated, leaving multiple other nodules unaffected. Thus, not all nodular regions appear equally involved in the generation epileptic activity in PVNH. EEG-fMRI can help identify which of multiple potentially epileptogenic regions are the most important in generating spikes and seizures. doi:10.1016/j.jocn.2009.07.052

28. Should the Glasgow Coma Scale start at Zero? Faragher Mark Alfred Hospital Peter MacCallum Cancer Centre Monash University University of Notre Dame Many rating scales are used in neurological practice for clinical and research purposes. The Glasgow Coma Scale (GCS), published in 1974 by Teasdale and Jennett, is the most widely used scoring system used in quantifying the level of consciousness in the comatose patient. The GCS is a practical scale and is often used following traumatic brain injury. The scale is composed of 3 subsections: Eye, Verbal, and Motor. ‘‘Ability to open eyes” is scored 1 to 4, ‘‘best motor response” is scored 1 to 5 and ‘‘best verbal response” to stimulation is scored 1 to 5. Thus a composite score is derived which may range from 3 to 14. In the modified or revised version the ‘‘best motor response” is scored from 1 to 6, thus the composite score may range from 3 – 15. Thus the modified GCS is a thirteen (13) point scale. If the scores are as follows: ‘‘ability to open eyes”: none: score 1; ‘‘best motor response”: no movement: score 1; ‘‘best verbal response to stimulation”: none: score 1; the total will be three (1 + 1 + 1). Thus the worst possible score in the GCS is in fact three not zero. The Italian mathematician Fibonacci c.1170-1250 is credited with introducing the Hindu-Arabic base 10/decimal system comprising numbers 1 - 9 and 0 to Europe. The word ‘‘zero”

derives (via French, Italian and Arabic) from the Sanskrit word sunya meaning void or empty. Thus the biological equivalent of zero could be considered to be death. The use of three as the lowest possible score could be termed a ‘‘suspended zero” as a patient who scores three is deeply comatose but not dead. Thus it is appropriate that the lowest possible score in the GCS is three rather than zero as the patient is deeply comatose rather than dead. doi:10.1016/j.jocn.2009.07.053

29. The Varied Presentations of Hypertrophic Pachymeningitis Liang Christina, Storey Catherine Dept. of Neurology, Royal North Shore Hospital, Sydney, Australia Introduction: Hypertrophic pachymeningitis is an uncommon condition characterised by thickening of the dura mater. Although a predisposing cause is identified in some cases, many are idiopathic. The manner in which patients present is highly variable. Response to treatment is also variable, and there is yet no consensus on its management, whilst relapses are common. Treatment usually starts with corticosteroids, whilst alternative immunosuppressants, surgical decompression, and radiotherapy have also been trialled. Methods: This is a retrospective review of 3 patients, in whom hypertrophic pachymeningitis was confirmed both radiologically and by histopathology. We reviewed their clinical presentation, associated conditions, laboratory evaluation, MRI, progression of disease, treatment trials and clinical outcome. The duration of followup ranged from 5 to 15 years. Their presentations are compared with approximately 60 published cases in the literature. Results: Patient 1 presented with several-years history of intermittent unsteady gait, facial numbness, and diplopia; on a background of pan-hypopituitarism. Although his disease process was a diffuse pachymeningitis, a distinct meningioma developed in the course of his disease. His relapses responded to intermittent increased doses of corticosteroids. Patient 2 presented with seizures, on a background of recently diagnosed rheumatoid arthritis. Her pachymeningitis resolved on treatment with corticosteroid and methotrexate. Patient 3 presented with symptoms of brainstem compression, with no significant associated past history. Her disease progressed with extensive involvement of the spinal dura despite treatment with corticosteroid and methotrexate. She required surgical decompression, and remains significantly impaired. Discussion: Our cases illustrate the inconsistent and often nonspecific presentation, the variable response to treatment and course of hypertrophic pachymeningitis. As with reported cases, the diagnosis is suggested by dural enhancement on gadolinium enhanced MRI, but may not be obvious at disease onset, while a definitive biopsy is required to confirm the diagnosis and exclude primary causes for this MRI finding such as atypical infections, malignancy or carcinomatosis, sarcoidosis, and granulomatous meningitis. doi:10.1016/j.jocn.2009.07.054

30. Acute severe autonomic neuropathy, without significant somatic sensory neuropathy, complicating initial doses of chemotherapy Parratt John, Spies Judith Institute of Clinical Neurosciences, Royal Prince Alfred Hospital and the University of Sydney, Sydney, Australia