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Objective: We examined whether individual neuronal architecture obtained from the brain connectome can be used to estimate the surgical success of anterior temporal lobectomy (ATL) in patients with temporal lobe epilepsy (TLE). Methods: We retrospectively studied 35 consecutive patients with TLE who underwent ATL. The structural brain connectome was reconstructed from all patients using presurgical diffusion MRI. Network links in patients were standardized as Z scores based on connectomes reconstructed from healthy controls. The topography of abnormalities in linkwise elements of the connectome was assessed on subnetworks linking ipsilateral temporal with extratemporal regions. Predictive models were constructed based on the individual prevalence of linkwise Z scores >2 and based on presurgical clinical data. Results: Patients were more likely to achieve postsurgical seizure freedom if they exhibited fewer abnormalities within a subnetwork composed of the ipsilateral hippocampus, amygdala, thalamus, superior frontal region, lateral temporal gyri, insula, orbitofrontal cortex, cingulate, and lateral occipital gyrus. Seizure-free surgical outcome was predicted by neural architecture alone with 90% specificity (83% accuracy), and by neural architecture combined with clinical data with 94% specificity (88% accuracy). Conclusions: Individual variations in connectome topography, combined with presurgical clinical data, may be used as biomarkers to better estimate surgical outcomes in patients with TLE.

The availability of cloud computing services has enabled the widespread adoption of the "software as a service" (SaaS) approach for software distribution, which utilizes network-based access to applications running on centralized servers. In this paper we apply the SaaS approach to neuroimaging-based age prediction. Our system, named "NAPR" (Neuroanatomical Age Prediction using R), provides access to predictive modeling software running on a persistent cloud-based Amazon Web Services (AWS) compute instance. The NAPR framework allows external users to estimate the age of individual subjects using cortical thickness maps derived from their own locally processed T1-weighted whole brain MRI scans. As a demonstration of the NAPR approach, we have developed two age prediction models that were trained using healthy control data from the ABIDE, CoRR, DLBS and NKI Rockland neuroimaging datasets (total N = 2367, age range 6-89 years). The provided age prediction models were trained using (i) relevance vector machines and (ii) Gaussian processes machine learning methods applied to cortical thickness surfaces obtained using Freesurfer v5.3. We believe that this transparent approach to out-of-sample evaluation and comparison of neuroimaging age prediction models will facilitate the development of improved age prediction models and allow for robust evaluation of the clinical utility of these methods.

Neuroimaging has become as important as the use of EEG in the diagnosis and classification of epilepsy. Although functional techniques such as SPECT and PET have played important roles in the workup of patients prior to surgery, MRI remains the principal imaging technique used in epilepsy. Additionally, the multimodal use of imaging is becoming increasingly important in the evaluation of patients with epilepsy. Continuum Lifelong Learning Neurol 2008;14(4):175–187.

Summary: Neuroimaging has important applications in the diagnosis and treatment of patients with seizures and epilepsy. Having replaced computed tomography (CT) in many situations, MRI is the preferred imaging technique for patients with epilepsy. Advances in radionuclide-based techniques such as single-photon emission CT/positron emission tomography and electromagnetic source imaging with magnetoencephalography are providing new insights into the pathophysiology of epilepsy. In addition, techniques such as magnetic resonance spectroscopy are beginning to impact treatment. In this review, I discuss how these techniques are used in clinical practice but more importantly, how imaging findings play an increasing role in neurotherapeutics.

This review discusses the potential utility of broad based use of magnetic resonance (MR) spectroscopic imaging for human epilepsy and seizure localization. The clinical challenges are well known to the epilepsy community, intrinsic in the variability of location, volumetric size and network extent of epileptogenic tissue in individual patients. The technical challenges are also evident, with high performance requirements in multiple steps, including magnet homogeneity, detector performance, sequence design, speed of acquisition in addition to large territory spectral processing. We consider how MR spectroscopy and spectroscopic imaging has been informative for epilepsy thus far, with specific attention to what is measured, the interpretation of such measurements and technical performance challenges. Examples are shown from medial temporal lobe and neocortical epilepsies are considered from 4T, 7T and most recently 3T.

When the diagnosis of Rasmussen's encephalitis is being considered, it is important to rapidly exclude other causes of epilepsia partialis continua and hemiparesis. Although there is no good data from randomized trials of different immune-related therapies, treatment with immunoglobulin G (IgG), steroids, or plasmapheresis is advocated as first-line therapy. It is not unreasonable to institute at least two treatment options (eg, IgG followed by plasmapheresis) if response to the first treatment is poor. Functional hemispherectomy and its variants are associated with a lower long-term complication rate.

Neuroimaging techniques have advanced the diagnosis, management, and understanding of the pathophysiology underlying the epilepsies. High-resolution ultrasound is an important and useful technique in the investigation of prematures and neonates with seizures. Computed tomography (CT) scans have a diminishing role in the investigation of patients with epilepsy, but in the absence of magnetic resonance imaging (MRI), CT may detect gross structural pathology. MRI is the technique of choice for investigation of patients with seizure disorders. MRI provides excellent anatomic information and tissue contrast, resulting in high sensitivity. MRI studies should be customized to answer the appropriate clinical question. Functional imaging techniques including single photon emission computed tomography (SPECT), positron emission tomography (PET), magnetic resonance spectroscopy, and functional MRI are becoming increasingly important in the investigation and management of patients with seizures. These techniques permit noninvasive assessment of the epileptic substrate, functional status, ictal activity, blood flow changes, metabolism, and neuroreceptors. Application of these new techniques promises to advance our understanding and treatment of seizures in children.

The authors evaluated the extent to which the Subdural Pharmacotherapy Device (SPD), chronically implanted over the frontal cortex to perform periodic, localized muscimol-delivery/CSF removal cycles, affects overall behavior, motor performance, electroencephalography (EEG) activity, and blood and CSF neurochemistry in macaque monkeys.Two monkeys were used to adjust methodology and 4 monkeys were subjected to comprehensive testing. Prior to surgery, the animals' behavior in a large test chamber was monitored, and the motor skills required to remove food pellets from food ports located on the walls of the chamber were determined. The monkeys underwent implantation of the subdural and extracranial SPD units. The subdural unit, a silicone strip integrating EEG electrodes and fluid-exchange ports, was positioned over the right frontal cortex. The control unit included a battery-powered, microprocessor-regulated dual minipump and radiofrequency module secured to the cranium. After implantation, the SPD automatically performed periodic saline or muscimol (1.0 mM) deliveries at 12-hour intervals, alternating with local CSF removals at 6-hour intervals. The antiepileptic efficacy of this muscimol concentration was verified by demonstrating its ability to prevent focal acetylcholine-induced seizures. During SPD treatment, the monkeys' behavior and motor performance were again monitored, and the power spectrum of their radiofrequency-transmitted EEG recordings was analyzed. Serum and CSF muscimol levels were measured with high-performance liquid chromatography electrochemical detection, and CSF protein levels were measured with turbidimetry.The SPD was well tolerated in all monkeys for up to 11 months. The behavioral study revealed that during both saline and muscimol SPD treatment, the monkeys could achieve the maximum motor performance of 40 food-pellet removals per session, as before surgery. The EEG study showed that local EEG power spectra were not affected by muscimol treatment with SPD. The neurochemical study demonstrated that the administration of 1.0 mM muscimol into the neocortical subarachnoid space led to no detectable levels of this compound in the blood and cisternal CSF, as measured 1-125 minutes after delivery. Total protein levels were within the normal range in the cisternal CSF, but protein levels in the cortical-site CSF were significantly higher than normal: 361 ± 81.6 mg/dl. Abrupt discontinuation of 3-month, periodic, subdural muscimol treatments induced withdrawal seizures, which could be completely prevented by gradually tapering off the subdural muscimol concentration from 1.0 mM to 0.12-0.03 mM over a period of 2 weeks. The monkeys' general health and weight were maintained. Infection occurred only in one monkey 9 months after surgery.Long-term, periodic, transmeningeal muscimol delivery with the SPD is essentially a safe procedure. If further improved and successfully adapted for use in humans, the SPD can be used for the treatment of intractable focal neocortical epilepsy affecting approximately 150,000 patients in the US.

The interactions between sleep and epilepsy have been recognized for centuries. The electroencephalogram and more recently the polysomnogram have helped us understand these interactions. Certain epilepsy syndromes are more common during sleep, and frequently a sleep disorder is misdiagnosed as epilepsy. Management of epilepsy includes improvements in sleep quality and quantity, and aggressive treatment of epilepsy has a positive impact on sleep disorders.

Lafora disease (LD) is an autosomal recessive disorder characterized by seizures and progressive neurologic deterioration, and is usually fatal within 10 years of onset. LD is a member of the family of progressive myoclonic epilepsies, which are a heterogeneous group of disorders characterized by myoclonic epilepsy, developmental regression, and associated neurologic symptoms. The following is a report and discussion of a 20-year-old man with no relevant past medical history until the age of 16 years when he had his first generalized tonic-clonic seizure. At a recent medical evaluation, he reported having clusters of generalized tonic-clonic seizure activity 2 to 3 times per week, had recently developed status epilepticus, and was having progressive impairment of cognitive function. The unique clinical elements of LD, including later onset of disease, the excellent initial response to anticonvulsants, and the neurophysiologic clues to the diagnosis are discussed and detailed in relation to this man. Additional research is required to discover a third, unknown locus for LD and to further elucidate the features of the laforin and malin complex-associated pathway. No preventative or curative treatment is currently available for LD and treatment focuses on palliation.

Traditional antiepileptic drugs (AEDs) are associated with drug interactions and side effects that limit their safety and tolerability. Side effects of traditional AEDs are especially problematic for children and adolescents, women of childbearing age, and the elderly. Many patients with epilepsy may benefit from switching from a traditional AED to a newer agent because the newer agents are generally better tolerated and are less likely to cause drug interactions. Clinical studies have demonstrated improved therapeutic efficiency with better tolerability in patients switching from a traditional AED to lamotrigine, oxcarbazepine, or topiramate monotherapy or combination therapy.

The role of modern neuroimaging in the management and treatment of patients with seizures and epilepsy continues to expand at a rapid pace. Magnetic resonance imaging (MRI) is now well established as the imaging technique of choice for patients with epilepsy, but new MR-based techniques, such as MR spectroscopy, functional (f)MRI, and fMRI/electroencephalogram, are more frequently being used to increase the yield of MRI in detecting abnormalities associated with epilepsy. In parallel, advances in radioactive-based techniques, such as single photon emission computed tomography, positron emission tomography, and magnetic source imaging, are improving the localization power of these techniques in candidates for epilepsy surgery. Advances in computer power are making possible the co-egistration in space of structural and functional information, thus improving the yield for the detection of lesions associated with epilepsy.

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.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 patient's ictal scan. The results were then mapped back onto the patient's 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).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.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 it a seizure? This question can be difficult for a clinician to answer, and it may be more critical if the possible seizure lasts30 min. Long-duration questionable seizure activity changes the question to, "Is it status epilepticus?" Status epilepticus (SE) can be divided into convulsive and nonconvulsive types. Convulsive SE is the most easily recognized, whereas nonconvulsive SE is more clinically variable and controversial. The term nonconvulsive SE is more often applied to patients who are severely obtunded or comatose with minimal or no motor movements, or in a stupor of altered consciousness reflecting generalized ictal activity. Nonconvulsive SE also can be caused by focal seizure activity, sometimes restricted to deep small volumes of brain in which scalp EEG may not be diagnostic. We present the case of a patient who had dominant limbic hippocampal SE, but in whom the diagnosis could not be confirmed until a modified novel use of the sodium amytal test was performed.

Although once thought to be rare, malformations of cortical development are being increasingly recognized as the underlying cause of developmental delay in children and of epilepsy in children and young adults. Advances in neuroimaging and developmental neurobiology have created the tools by which these important malformations have been investigated. Through a symbiotic type of relationship, these investigations, and the search for a better understanding of these malformations, have led to advances in neuroimaging techniques and better understanding of both normal and abnormal brain development. In this review, the most common malformations or cortical development associated with epilepsy are discussed in regard to their clinical manifestations, classification, imaging appearance and basic neurobiology.

We studied the frequency, clinical and EEG characteristics, and outcome of the epileptic syndrome in 31 patients with a congenital neurologic syndrome characterized by pseudobulbar palsy, cognitive deficits, and bilateral perisylvian polymicrogyria. Seizures were present in 27 of 31 patients (87%) and usually began between the ages of 4 and 12 years; they commonly consisted of atypical absence, atonic/tonic, and generalized tonic-clonic seizures. Partial attacks were present in 26%. EEG demonstrated generalized spike and wave abnormalities and, less frequently, multifocal discharges, predominantly in centro-parietal regions. Seizures were poorly controlled in 65%, with the remaining patients well controlled. Seven patients underwent callosotomy, which resulted in seizure improvement. This study indicates that the epileptic spectrum in this syndrome is broad but follows predictable patterns. Callosotomy is a valuable treatment strategy in those with intractable drop attacks.

Two French-Canadian families with seven cases of hydrocephalus in two generations are presented. The pattern of inheritance is consistent with an X-linked recessive transmission. The clinical and pathologic characteristics of this entity are reviewed. The anomaly of adducted thumbs was present in one patient and its cause is considered. The hypothesis of primary hydrocephalus and secondary compression of the aqueduct as the mechanism for aqueductal stenosis is discussed.