Applying Deep Learning to Accelerated Clinical Brain Magnetic Resonance Imaging for Multiple Sclerosis.

Background: Magnetic resonance (MR) scans are routine clinical procedures for monitoring people with multiple sclerosis (PwMS). Patient discomfort, timely scheduling, and financial burden motivate the need to accelerate MR scan time. We examined the clinical application of a deep learning (DL) model in restoring the image quality of accelerated routine clinical brain MR scans for PwMS. Methods: We acquired fast 3D T1w BRAVO and fast 3D T2w FLAIR MRI sequences (half the phase encodes and half the number of slices) in parallel to conventional parameters. Using a subset of the scans, we trained a DL model to generate images from fast scans with quality similar to the conventional scans and then applied the model to the remaining scans. We calculated clinically relevant T1w volumetrics (normalized whole brain, thalamic, gray matter, and white matter volume) for all scans and T2 lesion volume in a sub-analysis. We performed paired t-tests comparing conventional, fast, and fast with DL for these volumetrics, and fit repeated measures mixed-effects models to test for differences in correlations between volumetrics and clinically relevant patient-reported outcomes (PRO). Results: We found statistically significant but small differences between conventional and fast scans with DL for all T1w volumetrics. There was no difference in the extent to which the key T1w volumetrics correlated with clinically relevant PROs of MS symptom burden and neurological disability. Conclusion: A deep learning model that improves the image quality of the accelerated routine clinical brain MR scans has the potential to inform clinically relevant outcomes in MS.

Intracranial Complications From Immune Checkpoint Therapy in a Patient With NSCLC and Multiple Sclerosis: Case Report.

BACKGROUND: Immune checkpoint inhibitors (ICIs) have become an increasingly important tool in cancer treatment, revealing durable responses in several different types of tumors, including NSCLCs. Nevertheless, ICIs carry a risk of immune-mediated toxicities. There is a paucity of data for concurrent use of these agents in patients with autoimmune disorders, such as multiple sclerosis (MS). CASE PRESENTATION: We report a case of a man with a history of MS and metastatic NSCLC with brain metastases who had cancer progression after receiving chemotherapy, whole-brain radiation therapy, and stereotactic radiosurgery to brain lesions and was treated with the programmed death-ligand 1 inhibitor, atezolizumab. He had dramatic clinical and radiographic benefit but developed a severe MS flare and neurologic decline precluding further treatment. Considerable growth of a previously radiated brain lesion prompted resection, with pathologic findings consistent with radiation necrosis and demyelination without viable tumor cells. CONCLUSIONS: Although patients with preexisting autoimmune diseases, including MS, might be at an increased risk of developing immune-related adverse events with ICIs, they may also experience anticancer benefit. Intracranial disease can be challenging to accurately diagnose in a patient with MS who previously underwent radiation, as progressing lesions can be tumor growth, MS flare, or radiation necrosis.

Effect of anesthesia on electrocorticography for localization of epileptic focus: Literature review and future directions.

Intraoperative electrocorticography (ECoG) is a useful technique to guide resections in epilepsy surgery and is mostly performed under general anesthesia. In this systematic literature review, we seek to investigate the effect of anesthetic agents on the quality and reliability of ECoG for localization of the epileptic focus. We conducted a systematic search using PubMed and EMBASE until January 2019, aiming to review the effects of anesthesia on ECoG yield. Fifty-eight studies were included from 1016 reviewed. There are favorable reports for dexmedetomidine and remifentanil during ECoG recording. There is inadequate, or sometimes conflicting, evidence to support using enflurane, isoflurane, sevoflurane, and propofol. There is evidence to avoid halothane, nitrous oxide, etomidate, ketamine, thiopental, methohexital, midazolam, fentanyl, and alfentanil due to undesired effects. Depth of anesthesia, intraoperative awareness, and surgical outcomes were not consistently evaluated. Available studies provide helpful information about the effect of anesthesia on ECoG to localize the epileptic focus. The proper use of anesthetic agents and careful dose titration, and effective communication between the neurophysiologist and anesthesiologist based on ECoG activity are essential in optimizing recordings. Anesthesia is a crucial variate to consider in the design of studies investigating ECoG and related biomarkers.

Brief history of electrical cortical stimulation: A journey in time from Volta to Penfield.

OBJECTIVE: To recount the evolution of Electrical Cortical Stimulation (ECS) in localizing brain functions with an emphasis on epilepsy, and a discussion of related instruments and personnel. DESIGN/METHODS: Literature review through historical archives implementing chain-referral sampling. RESULTS: There were important milestones leading to the incorporation of ECS into practice: 1. Aldini's (1802) first known stimulation of exposed brain to defend Galvani's views on excitability in the frog-leg experiment against Volta's, ironically by employing the Voltaic pile. 2. Animal experiments in the 19th-century to study the brain and to optimize the procedure: Rolando (1809) reported on motor induction, Fritsch and Hitzig (ca. 1870) introduced the concepts of bipolar and threshold stimulation, and Ferrier (1873) generated reproducible homunculi in animals. 3. Parallel to 2, advances were made based on clinical observations by Bravais, Todd, Jackson, and Broca among others. 4. First known stimulation in conscious humans by Bartholow (1874) led to catastrophic outcomes. Horsley (1886) performed first intraoperative stimulation on Jackson's epileptic patient. 5. Advances accelerated in the first-half of the 20th century with Cushing (1909) performing first awake-craniotomy eliciting sensory responses to Penfield's work culminating in standardization of clinical use and generation of detailed maps including the famous sensory-motor homunculi. Parallel advances in instrumentation were made from the Leyden jar (1745) to present customizable current-controlled stimulators. CONCLUSIONS: ECS is commonly used in neurosurgery for localization of brain functions and is the benchmark for research studies. Significant leaps have been made since ECS first used in the 19th century. It evolved to remain the gold standard for localization of human brain functions in the 21st century.

Enhanced astrocyte responses are driven by a genetic risk allele associated with multiple sclerosis.

Epigenetic annotation studies of genetic risk variants for multiple sclerosis (MS) implicate dysfunctional lymphocytes in MS susceptibility; however, the role of central nervous system (CNS) cells remains unclear. We investigated the effect of the risk variant, rs7665090G, located near NFKB1, on astrocytes. We demonstrated that chromatin is accessible at the risk locus, a prerequisite for its impact on astroglial function. The risk variant was associated with increased NF-κB signaling and target gene expression, driving lymphocyte recruitment, in cultured human astrocytes and astrocytes within MS lesions, and with increased lesional lymphocytic infiltrates and lesion sizes. Thus, our study establishes a link between genetic risk for MS (rs7665090G) and dysfunctional astrocyte responses associated with increased CNS access for peripheral immune cells. MS may therefore result from variant-driven dysregulation of the peripheral immune system and of the CNS, where perturbed CNS cell function aids in establishing local autoimmune inflammation.

Cefepime induced neurotoxicity: A case series and review of the literature.

Cefepime is a fourth generation cephalosporin which is bactericidal for broad spectrum of organisms. This is a case-series of three patients who presented to our hospital with confusion secondary to cefepime use to treat urinary tract infection (UTI) and health care associated pneumonia (HCAP), after excluding other common etiologies of altered mental status (AMS). Of these three patients, one had progressive expressive aphasia and the other two demonstrated asynchronous myoclonic activity of the limbs. The symptoms were seen within four to five days of initiating the treatment and resolved within three days of discontinuation of cefepime. Acute structural abnormalities were excluded by computed tomography (CT) and magnetic resonance imaging (MRI) of the brain. Electroencephalogram (EEG) showed diffuse slowing activity with triphasic waves consistent with encephalopathy. In one patient, renal function was within normal limits, whereas it was abnormal in two patients. To our knowledge, this is the first report of cefepime induced asynchronous myoclonus and expressive aphasia in a patient with normal kidney function.

Yield of repeat routine MEG recordings in clinical practice.

From 377 consecutive MEG studies for patients with intractable epilepsy performed at the Cleveland Clinic between 2008 and 2011, 19 patients were referred for a repeat MEG. Source localization was done using a single equivalent current dipole (ECD) model on identified interictal spike activity. Clinical, neuroimaging, and concurrent EEG and MEG findings were reviewed. The most common reasons for repeating MEG were as follows: negative initial study in 6 patients, paucity of recorded interictal discharges in 4, failed surgeries in 3, uncertain findings in the first study in 2, and research-related reasons in 4. Repeat MEG provided new localizing findings in 11/19 patients (58%), of whom 6 had negative or rare interictal findings in the first study. Lobar concordance of dipoles was present in 6 (85%) of the 7 patients with positive findings in both MEG studies. This study demonstrates that a repeat MEG may provide new localization data when a previous recording shows limited or no interictal abnormalities.