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Background and objectivesIdentification of an epileptogenic lesion on structural neuroimaging in individuals with focal epilepsy is important for management and treatment planning. The objective of this study was to determine the frequency of MRI-identified potentially epileptogenic structural abnormalities in a large multicenter study of adolescent and adult patients with newly diagnosed focal epilepsy.MethodsPatients with a new diagnosis of focal epilepsy enrolled in the Human Epilepsy Project observational cohort study underwent 3-Tesla (3T) brain MRI using a standardized protocol. Imaging findings were classified as normal, abnormal, or incidental. Abnormal findings were classified as focal or diffuse, and as likely epilepsy-related or of unknown relationship to epilepsy. Fisher exact tests were performed to determine whether abnormal imaging or abnormality type was associated with clinical characteristics.Results418 participants were enrolled. 218 participants (59.3%) had no abnormalities detected, 149 (35.6%) had abnormal imaging, and 21 (5.0%) had incidental findings. 78 participants (18.7%) had abnormalities that were considered epilepsy-related and 71 (17.0%) had abnormalities of unknown relationship to epilepsy. Older participants were more likely to have imaging abnormalities, while participants with focal and epilepsy-related imaging abnormalities were younger than those without these abnormalities. 131 participants (31.3%) had a family history of epilepsy. Epilepsy-related abnormalities were not associated with participant sex, family history of epilepsy, or seizure type.DiscussionWe found that one in five patients with newly diagnosed focal epilepsy has an MRI finding that is likely causative and may alter treatment options. An additional one in five patients has abnormalities of unknown significance. This information is important for patient counseling, prognostication, and management.

Supplemental Material for Functional brain effects of acute concussion in Australian rules football players by Graeme D Jackson, Michael Makdissi, Mangor Pedersen, Donna M Parker, Evan K Curwood, Shawna Farquharson, Alan Connelly, David F Abbott and Paul McCrory in Journal of Concussion

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The ILAE 2010 report does not classify focal seizures and instead uses “descriptors” to distinguish focal seizures with versus without impaired consciousness. Below, we recall a recent informal conversation that took place while traveling a back road in Australia (true story), discussing problems with the old terms as well as new biological and practical evidence separating events formerly known as complex partial versus simple partial seizures. Impaired level of consciousness is a core distinguishing feature of focal seizures, which arises from established physiological mechanisms and can be readily determined based on behavior in most cases. After some debate, we arrive at succinct terms compatible with the old as well as the new ILAE classification report: Focal Impaired Consciousness Seizures (FICS), and Focal Aware Conscious Seizures (FACS). We hope that this discussion will bring impaired consciousness off the back roads of epilepsy classification, and provide useful names for these two very common seizure types.

Malformations of cerebral cortical development include a wide range of developmental disorders that are common causes of neurodevelopmental delay and epilepsy. In addition, study of these disorders contributes greatly to the understanding of normal brain development and its perturbations. The rapid recent evolution of molecular biology, genetics and imaging has resulted in an explosive increase in our knowledge of cerebral cortex development and in the number and types of malformations of cortical development that have been reported. These advances continue to modify our perception of these malformations. This review addresses recent changes in our perception of these disorders and proposes a modified classification based upon updates in our knowledge of cerebral cortical development.

BACKGROUND: Simultaneous measurement of renal blood flow, renal ATP, renal pH and mean arterial pressure (MAP) might help investigators understand the mechanisms responsible for acute renal failure (ARF) in sepsis. OBJECTIVES: (1) To develop a technique to simultaneously measure MAP, renal blood flow, renal ATP and renal pH in a large mammal during severe sepsis and after circulatory arrest; and (2) To describe preliminary observations during such measurements. METHODS: We implanted a custom-made phosphorus coil around the left kidney and a magnetic resonance-compatible blood flow probe around the renal artery of an adult Merino ewe. We induced severe sepsis by intravenous administration of Escherichia coli and obtained 31P magnetic resonance spectroscopic data at 3tesla, and continuous blood flow and MAP data before and during severe sepsis over several hours. We induced circulatory arrest with potassium chloride and measured the same 31P signal immediately and again 30 minutes later. RESULTS: We successfully and simultaneously measured MAP, renal blood flow, renal ATP and renal pH in a large mammal during severe sepsis and induced circulatory arrest. With these techniques, we observed that, despite marked hypotension, there were limited changes in renal ATP and renal pH, and that renal blood flow increased. A rapid and dramatic decrease in ATP and pH occurred with circulatory arrest. CONCLUSIONS: We have developed a technique to simultaneously monitor MAP, renal blood flow, ATP and pH in a large mammal during severe sepsis. Our initial observations indicate preservation of renal ATP in septic shock.

Background: Indicated intervention prior to the onset of psychosis may help to delay, attenuate or even prevent the illness. To date, successful intervention trials using atypical antipsychotics and/or cognitive behavioural therapy have been reported, but it is not clear that these treatments are targeting the underlying brain pathology. Given our previous findings of progressive grey matter loss over the transition to psychosis, agents that can prevent this, such as lithium, might be useful for preventing or delaying the onset of psychosis. Methods: In this open-label trial, 11 ultra-high-risk patients who received low- dose lithium treatment for four months were compared with 10 similar patients who received only needs-based intervention. Magnetic resonance imaging, including T2 relaxometry and proton spectroscopy was performed prior to initiation of treatment and after four months. Results: Hippocampal T2 declined significantly in the treatment group (p=0.018). No significant group x time effects were seen for brain metabolites, although N-acetyl aspartate (NAA), myo-inositol, creatine and choline all tended to increase with lithium administration and decrease or remain unchanged in the comparison group. Conclusions: Decreased T2 relaxation time and increased concentrations of NAA are indicators of increased neuronal function/viability. Low-dose lithium may help regulate synaptic pruning and reduce neuronal dysfunction associated with the onset of psychosis.

Key points • The clinical aims of MR spectroscopy (MRS) in seizure disorders are to help identify, localize and characterize epileptogeic foci. • Lateralizing MRS abnormalities in temporal lobe epilepsy (TLE) may be used clinically in combi- nation with structural and T2measurements. • Characteristic metabolite abnormalities are decreased N-acetylaspartate (NAA) with increased choline (Cho) and myoinositol (mI) (short-echo time). • Contralateral metabolite abnormalities are frequently seen in TLE, but are of uncertain significance. • In extra-temporal epilepsy, metabolite abnor- malities may be seen where MR imaging (MRI) is normal; but may not be sufficiently local- ized to be useful clinically. • MRS may help to characterize epileptogenic lesions visible on MRI (aggressive vs. indolent neoplastic, dysplasia). • Spectral editing techniques are required to evaluate specific epilepsy-relevant metabolites (e.g. -aminobutyric acid (GABA)) which may be useful in drug development and evaluation. • MRS with phosphorus (31P) and other nucleii probe metabolism of epilepsy, but are less useful clinically.

Purpose: This study used magnetic resonance spectroscopy (MRS) to examine metabolite abnormalities in the temporal and frontal lobe of patients with temporal lobe epilepsy (TLE) of differing severity. Methods: We investigated myoinositol in TLE by using short-echo MRS in 34 TLE patients [26 late onset (LO-TLE), eight hippocampal sclerosis (HS-TLE)], and 16 controls. Single-voxel short-echo (35 ms) MR spectra of temporal and frontal lobes were acquired at 1.5 T and analyzed by using LCModel. Results: The temporal lobe ipsilateral to seizure origin in HS-TLE, but not LO-TLE, had reduced N-acetylaspartate (NA) and elevated myoinositol (MI; HS-TLE NA, 7.8 ± 1.9 mM, control NA, 9.2 ± 1.3 mM; p < 0.05; HS-TLE MI, 6.1 ± 1.6 mM, control mI 4.9 ± 0.8 mM, p< 0.05). Frontal lobe MI was low in both patient groups (LO-TLE, 4.3 ± 0.8 mM; p < 0.05; HS-TLE, 3.6 ±.05 mM; p < 0.001; controls, 4.8 ± 0.5 mM). Ipsilateral frontal lobes had lower MI (3.8 ± 0.7 mM; p < 0.01) than contralateral frontal lobes (4.3 ± 0.8 mM; p < 0.05). Conclusions: MI changes may distinguish between the seizure focus, where MI is increased, and areas of seizure spread where MI is decreased.

Knobloch syndrome [OMIM: (KNO1) #267750] is a rare and clinically heterogeneous autosomal recessive disorder caused by mutations in COL18A1. Knobloch syndrome is characterised by abnormalities of the eye and occipital skull defects however the full phenotypic spectrum is yet to be defined. This report describes a family of four affected sisters with polymicrogyria, refractory seizures, and intellectual impairment of varying severity with a Lennox-Gastaut phenotype, and complex eye abnormalities where a syndromic diagnosis was not initially made. Whole exome sequencing of two affected sisters followed by filtering for rare and potentially disease causing variants in all genes identified compound heterozygous variants in NM_030582.3 (COL18A1): c.3690G > A: p.(Trp1230*) and NM_030582.3 (COL18A1): c.4063_4064delCT: p.(Leu1355Valfs*72). The two variants co-segregated with the affected individuals in the family. Identification of COL18A1 mutations in individuals with a Lennox-Gastaut phenotype and anterior polymicrogyria but lacking the classical occipital encephalocele expands the COL18A1 clinical spectrum. Refereed/Peer-reviewed

We characterized an autosomal-recessive syndrome of focal epilepsy, dysarthria, and mild to moderate intellectual disability in a consanguineous Arab-Israeli family associated with subtle cortical thickening. We used multipoint linkage analysis to map the causative mutation to a 3.2 Mb interval within 16p13.3 with a LOD score of 3.86. The linked interval contained 160 genes, many of which were considered to be plausible candidates to harbor the disease-causing mutation. To interrogate the interval in an efficient and unbiased manner, we used targeted sequence enrichment and massively parallel sequencing. By prioritizing unique variants that affected protein translation, a pathogenic mutation was identified in TBC1D24 (p.F251L), a gene of unknown function. It is a member of a large gene family encoding TBC domain proteins with predicted function as Rab GTPase activators. We show that TBC1D24 is expressed early in mouse brain and that TBC1D24 protein is a potent modulator of primary axonal arborization and specification in neuronal cells, consistent with the phenotypic abnormality described. Refereed/Peer-reviewed