Language Mapping in Multilingual Patients: Electrocorticography and Cortical Stimulation During Naming

Multilingual patients pose a unique challenge when planning epilepsy surgery near language cortex because the cortical representations of each language may be distinct. These distinctions may not be evident with routine electrocortical stimulation mapping (ESM). Electrocorticography (ECoG) has recently been used to detect task-related spectral perturbations associated with functional brain activation. We hypothesized that using broadband high gamma augmentation (HGA, 60–150 Hz) as an index of cortical activation, ECoG would complement ESM in discriminating the cortical representations of first (L1) and second (L2) languages. We studied four adult patients for whom English was a second language, in whom subdural electrodes (a total of 358) were implanted to guide epilepsy surgery. Patients underwent ECoG recordings and ESM while performing the same visual object naming task in L1 and L2. In three of four patients, ECoG found sites activated during naming in one language but not the other. These language-specific sites were not identified using ESM. In addition, ECoG HGA was observed at more sites during L2 versus L1 naming in two patients, suggesting that L2 processing required additional cortical resources compared to L1 processing in these individuals. Post-operative language deficits were identified in three patients (one in L2 only). These deficits were predicted by ECoG spectral mapping but not by ESM. These results suggest that pre-surgical mapping should include evaluation of all utilized languages to avoid post-operative functional deficits. Finally, this study suggests that ECoG spectral mapping may potentially complement the results of ESM of language

Applications of Ketogenic Diets in Patients with Headache: Clinical Recommendations

Headaches are among the most prevalent and disabling neurologic disorders and there are several unmet needs as current pharmacological options are inadequate in treating patients with chronic headache, and a growing interest focuses on nutritional approaches as non-pharmacological treatments. Among these, the largest body of evidence supports the use of the ketogenic diet (KD). Exactly 100 years ago, KD was first used to treat drug-resistant epilepsy, but subsequent applications of this diet also involved other neurological disorders. Evidence of KD effectiveness in migraine emerged in 1928, but in the last several year's different groups of researchers and clinicians began utilizing this therapeutic option to treat patients with drug-resistant migraine, cluster headache, and/or headache comorbid with metabolic syndrome. Here we describe the existing evidence supporting the potential benefits of KDs in the management of headaches, explore the potential mechanisms of action involved in the efficacy in-depth, and synthesize results of working meetings of an Italian panel of experts on this topic. The aim of the working group was to create a clinical recommendation on indications and optimal clinical practice to treat patients with headaches using KDs. The results we present here are designed to advance the knowledge and application of KDs in the treatment of headaches

DNM1 encephalopathy: A new disease of vesicle fission.

ObjectiveTo evaluate the phenotypic spectrum caused by mutations in dynamin 1 (DNM1), encoding the presynaptic protein DNM1, and to investigate possible genotype-phenotype correlations and predicted functional consequences based on structural modeling.MethodsWe reviewed phenotypic data of 21 patients (7 previously published) with DNM1 mutations. We compared mutation data to known functional data and undertook biomolecular modeling to assess the effect of the mutations on protein function.ResultsWe identified 19 patients with de novo mutations in DNM1 and a sibling pair who had an inherited mutation from a mosaic parent. Seven patients (33.3%) carried the recurrent p.Arg237Trp mutation. A common phenotype emerged that included severe to profound intellectual disability and muscular hypotonia in all patients and an epilepsy characterized by infantile spasms in 16 of 21 patients, frequently evolving into Lennox-Gastaut syndrome. Two patients had profound global developmental delay without seizures. In addition, we describe a single patient with normal development before the onset of a catastrophic epilepsy, consistent with febrile infection-related epilepsy syndrome at 4 years. All mutations cluster within the GTPase or middle domains, and structural modeling and existing functional data suggest a dominant-negative effect on DMN1 function.ConclusionsThe phenotypic spectrum of DNM1-related encephalopathy is relatively homogeneous, in contrast to many other genetic epilepsies. Up to one-third of patients carry the recurrent p.Arg237Trp variant, which is now one of the most common recurrent variants in epileptic encephalopathies identified to date. Given the predicted dominant-negative mechanism of this mutation, this variant presents a prime target for therapeutic intervention

The role for ketogenic diets in epilepsy and status epilepticus in adults

Ketogenic diet (KD) therapies are high fat, low carbohydrate diets designed to mimic a fasting state. Although studies demonstrate KD’s success in reducing seizures stretching back nearly a century, the last 25 years have seen a resurgence in diet therapy for the management of drug-resistant epilepsy in children as well as adults. With ≥50% seizure reduction efficacy rates in adults of 22–55% for the classic KD and 12–67% for the modified Atkins diet, diet therapy may be in many instances comparable to a trial of an additional anti-epileptic medication and potentially with fewer side effects and other health benefits. Moreover, ketogenic diets offer promising new adjunctive strategies for the treatment of acute status epilepticus in the intensive care setting. Here, we review the efficacy and utility of ketogenic diets for the management of chronic epilepsy and refractory status epilepticus in adults and offer practical guidelines for diet implementation and maintenance. Keywords: Ketogenic diet, Modified Atkins diet, Epilepsy, Drug-resistant epilepsy, Refractory status epilepticu

EEG Differences in Two Clinically Similar Rapid Dementias: Voltage-Gated Potassium Channel Complex-Associated Autoimmune Encephalitis and Creutzfeldt-Jakob Disease

Distinguishing treatable causes for rapidly progressive dementia from those that are incurable is vital. Creutzfeldt-Jakob disease (CJD) and voltage-gated potassium channel complex-associated autoimmune encephalitis (VGKC AE) are 2 such conditions with disparate outcomes and response to treatment. To determine the differences in electroencephalography between CJD and VGKC AE, we performed a retrospective review of medical records and examined clinical data, neuroimaging, and electroencephalographs performed in patients admitted for evaluation for rapidly progressive dementia diagnosed with CJD and VGKC AE at the Johns Hopkins Hospital and Bayview Medical Center between January 1, 2007 and December 31, 2015. More patients in the VGKC AE group had seizures (12/17) than those with CJD (3/14; P = .008). Serum sodium levels were lower in those with VGKC AE ( P = .001). Cerebrospinal fluid (CSF) white blood cell count was higher in VGKC AE ( P = .008). CSF protein 14-3-3 ( P = .018) was more commonly detected in CJD, and tau levels were higher in those with CJD ( P < .006). On neuroimaging, diffusion restriction in the cortex ( P = .001), caudate ( P < .001), and putamen ( P = .001) was more frequent in CJD. Periodic sharp wave complexes ( P = .001) and generalized suppressed activity ( P = .008) were more common on initial EEG in CJD. On serial EEGs, generalized periodic discharges ( P = .004), generalized suppressed activity (P=0.008), and periodic sharp wave complexes ( P < .001) were detected more in CJD. This study shows that there are a number of differentiating features between CJD and VGKC AE, and electroencephalography can aid in their diagnoses. Performing serial EEGs better delineates these conditions

Is there a role for diet monotherapy in adult epilepsy?

Ten adults were treated with ketogenic diet monotherapy for epilepsy. Four patients were naïve to antiseizure drugs (ASDs), and six previously tried and stopped ASDs. Of four treatment-naïve participants, two (50%) were free from disabling seizures on Modified Atkins Diet (MAD) monotherapy for >1 year. Two (50%) stopped. Four of six patients (67%) who had previously tried ASDs became seizure-free on diet monotherapy, and two experienced >50% seizure reduction. Side effects included amenorrhea, weight loss, osteoporosis, and hyperlipidemia. Diet monotherapy may be feasible, well-tolerated, and effective for adults with epilepsy who refuse pharmacotherapy and those for whom lifelong diet therapy is recommended

Electroencephalography for diagnosis and prognosis of acute encephalitis

To confirm the previously identified EEG characteristics for HSV encephalitis and to determine the diagnostic and predictive value of electroencephalography (EEG) features for etiology and outcome of acute encephalitis in adults. In addition, we sought to investigate their independence from possible clinical confounders.; This study was performed in the Intensive Care Units of two academic tertiary care centers. From 1997 to 2011, all consecutive patients with acute encephalitis who received one or more EEGs were included. Examination of the diagnostic and predictive value of EEG patterns regarding etiology, clinical conditions, and survival was performed. The main outcome measure was in-hospital death.; Of 103 patients with encephalitis, EEGs were performed in 76 within a median of 1day (inter quartile range 0.5-3) after admission. Mortality was 19.7%. Higher proportions of periodic discharges (PDs) (p=0.029) and focal slowing (p=0.017) were detected in Herpes Simplex virus (HSV) encephalitis as compared to non-HSV encephalitis, while clinical characteristics did not differ. Normal EEG remained the strongest association with a low relative risk for death in multivariable analyses (RR<0.001, p<0.001) adjusting for confounders as coma, global cerebral edema and mechanical ventilation. None of the patients with a normal EEG had a GCS of 15.; Normal EEG predicted survival independently from possible confounders, highlighting the prognostic value of EEG in evaluating patients with encephalitis. EEG revealed higher proportions of PDs along with focal slowing in HSV encephalitis as compared to other etiologies.; EEG significantly adds to clinical, diagnostic and prognostic information in patients with acute encephalitis

Pearls and Pitfalls of Introducing Ketogenic Diet in Adult Status Epilepticus: A Practical Guide for the Intensivist

Background: Status epilepticus (SE) carries an exceedingly high mortality and morbidity, often warranting an aggressive therapeutic approach. Recently, the implementation of a ketogenic diet (KD) in adults with refractory and super-refractory SE has been shown to be feasible and effective. Methods: We describe our experience, including the challenges of achieving and maintaining ketosis, in an adult with new onset refractory status epilepticus (NORSE). Case Vignette: A previously healthy 29-year-old woman was admitted with cryptogenic NORSE following a febrile illness; course was complicated by prolonged super-refractory SE. A comprehensive work-up was notable only for mild cerebral spinal fluid (CSF) pleocytosis, elevated nonspecific serum inflammatory markers, and edematous hippocampi with associated diffusion restriction on magnetic resonance imaging (MRI). Repeat CSF testing was normal and serial MRIs demonstrated resolution of edema and diffusion restriction with progressive hippocampal and diffuse atrophy. She required prolonged therapeutic coma with high anesthetic infusion rates, 16 antiseizure drug (ASD) trials, empiric immunosuppression and partial bilateral oophorectomy. Enteral ketogenic formula was started on hospital day 28. However, sustained beta-hydroxybutyrate levels >2 mmol/L were only achieved 37 days later following a comprehensive adjustment of the care plan. KD was challenging to maintain in the intensive care unit (ICU) and was discontinued due to poor nutritional state and pressure ulcers. KD was restarted again in a non-ICU unit facilitating ASD tapering without re-emergence of SE. Discussion: There are inconspicuous carbohydrates in commonly administered medications for SE including antibiotics, electrolyte repletion formulations, different preparations of the same drug (i.e., parenteral, tablet, or suspension) and even solutions used for oral care―all challenging the use of KD in the hospitalized patient. Tailoring comprehensive care and awareness of possible complications of KD are important for the successful implementation and maintenance of ketosis