Medicine and Health Sciences Commons^™

X-Linked Hypomyelination With Spondylometaphyseal Dysplasia (H-Smd) Associated With Mutations In Aifm1., Noriko Miyake, Nicole I Wolf, Ferdy K Cayami, Joanna Crawford, Annette Bley, Dorothy Bulas, Ryan J Taft, Adeline Vanderver, +Several Additional Authors

Neurology Faculty Publications

An X-linked condition characterized by the combination of hypomyelinating leukodystrophy and spondylometaphyseal dysplasia (H-SMD) has been observed in only four families, with linkage to Xq25-27, and recent genetic characterization in two families with a common AIFM1 mutation. In our study, 12 patients (6 families) with H-SMD were identified and underwent comprehensive assessment accompanied by whole-exome sequencing (WES). Pedigree analysis in all families was consistent with X-linked recessive inheritance. Presentation typically occurred between 12 and 36 months. In addition to the two disease-defining features of spondylometaphyseal dysplasia and hypomyelination on MRI, common clinical signs and symptoms included motor deterioration, spasticity, tremor, …

Ufm1 Founder Mutation In The Roma Population Causes Recessive Variant Of H-Abc., Eline M C Hamilton, Enrico Bertini, Luba Kalaydjieva, Bharti Morar, Dana Dojčáková, Adeline Vanderver, Recessive H-Abc Research Group.

Neurology Faculty Publications

OBJECTIVE: To identify the gene defect in patients with hypomyelination with atrophy of the basal ganglia and cerebellum (H-ABC) who are negative for TUBB4A mutations.

METHODS: We performed homozygosity mapping and whole exome sequencing (WES) to detect the disease-causing variant. We used a Taqman assay for population screening. We developed a luciferase reporter construct to investigate the effect of the promoter mutation on expression.

RESULTS: Sixteen patients from 14 families from different countries fulfilling the MRI criteria for H-ABC exhibited a similar, severe clinical phenotype, including lack of development and a severe epileptic encephalopathy. The majority of patients had a …

Application Of Rns In Refractory Epilepsy: Targeting Insula., Hai Chen, Patricia Dugan, Derek J Chong, Anli Liu, Werner Doyle, Daniel Friedman

Neurology Faculty Publications

Although responsive neurostimulation (RNS) is approved for treatment of resistant focal epilepsy in adults, little is known about response to treatment of specific cortical targets. We describe the experience of RNS targeting the insular lobe. We identified patients who had RNS implantation with at least one electrode within the insula between April 2014 and October 2015. We performed a retrospective review of preoperative clinical features, imaging, electrocardiogram (EEG), intraoperative electrocorticography (ECoG), and postoperative seizure outcome. Eight patients with at least 6 months of postimplant follow-up were identified. Ictal localization was inconclusive with MRI or scalp EEG findings. Intracranial EEG monitoring …

Functionally Pathogenic Ears2 Variants In Vitro May Not Manifest A Phenotype In Vivo, Nathan Mcneill, Alessia Nasca, Aurelio Reyes, Benjamin Lemoine, Brandi Cantarel, Adeline Vanderver, Raphael Schiffmann, Daniele Ghezzi

Neurology Faculty Publications

Objective: To investigate the genetic etiology of a patient diagnosed with leukoencephalopathy, brain calcifications, and cysts (LCC).

Methods: Whole-exome sequencing was performed on a patient with LCC and his unaffected family members. The variants were subject to in silico and in vitro functional testing to determine pathogenicity.

Results: Whole-exome sequencing uncovered compound heterozygous mutations in EARS2, c.328G>A (p.G110S), and c.1045G>A (p.E349K). This gene has previously been implicated in the autosomal recessive leukoencephalopathy with thalamus and brainstem involvement and high lactate (LTBL). The p.G110S mutation has been found in multiple patients with LTBL. In silico analysis supported pathogenicity …

A Defect In Myoblast Fusion Underlies Carey-Fineman-Ziter Syndrome, S Digioia, S Connors, N. Matsunami, J Cannavino, M Rose, N Gillette, Andrea Gropman, +Several Additional Authors

Neurology Faculty Publications

Multinucleate cellular syncytial formation is a hallmark of skeletal muscle differentiation. Myomaker, encoded by Mymk (Tmem8c), is a well-conserved plasma membrane protein required for myoblast fusion to form multinucleated myotubes in mouse, chick, and zebrafish. Here, we report that autosomal recessive mutations in MYMK (OMIM 615345) cause Carey-Fineman-Ziter syndrome in humans (CFZS; OMIM 254940) by reducing but not eliminating MYMK function. We characterize MYMK-CFZS as a congenital myopathy with marked facial weakness and additional clinical and pathologic features that distinguish it from other congenital neuromuscular syndromes. We show that a heterologous cell fusion assay in vitro and allelic …

The Specific Vulnerabilities Of Cancer Cells To The Cold Atmospheric Plasma-Stimulated Solutions., Dayun Yan, Haitao Cui, Wei Zhu, Niki Nourmohammadi, Julian Milberg, Lijie G Zhang, Jonathan H Sherman, Michael Keidar

Neurological Surgery Faculty Publications

Cold atmospheric plasma (CAP), a novel promising anti-cancer modality, has shown its selective anti-cancer capacity on dozens of cancer cell lines in vitro and on subcutaneous xenograft tumors in mice. Over the past five years, the CAP-stimulated solutions (PSS) have also shown their selective anti-cancer effect over different cancers in vitro and in vivo. The solutions used to make PSS include several bio-adaptable solutions, mainly cell culture medium and simple buffered solutions. Both the CAP-stimulated medium (PSM) and the CAP-stimulated buffered solution (PSB) are able to significantly kill cancer cells in vitro. In this study, we systematically compared the anti-cancer …

Universal Connection Through Art: Role Of Mirror Neurons In Art Production And Reception., Bartlomiej Piechowski-Jozwiak, François Boller, Julien Bogousslavsky

Neurology Faculty Publications

Art is defined as expression or application of human creative skill and imagination producing works to be appreciated primarily for their aesthetic value or emotional power. This definition encompasses two very important elements—the creation and reception of art—and by doing so it establishes a link, a dialogue between the artist and spectator. From the evolutionary biological perspective, activities need to have an immediate or remote effect on the population through improving survival, gene selection, and environmental adjustment, and this includes art. It may serve as a universal means of communication bypassing time, cultural, ethnic, and social differences. The neurological mechanisms …

Pediatric Intrafalcine Empyema From A Sinogenic Origin: A Case Report., Kyle Mueller, John Myseros

Neurological Surgery Faculty Publications

Sinusitis and otitis are common within the pediatric population. If left untreated, these can extend intracranially and lead to the development of infections in the various intracranial compartments resulting in a high rate of morbidity and mortality. We report the first case of an intrafalcine empyema, absent subdural purulence, in a patient with the likely spread from a sinogenic origin. This case illustrates the novelty of this as a pathological entity as well as the surgical considerations for intrafalcine purulence in the absence of expected subdural collections.

Presurgical Language Fmri: Mapping Of Six Critical Regions, Christopher Benjamin, Patricia Walshaw, Kayleigh Hale, William D. Gaillard, +Several Additional Authors

Neurology Faculty Publications

Language mapping is a key goal in neurosurgical planning. fMRI mapping typically proceeds with a focus on Broca's and Wernicke's areas, although multiple other language-critical areas are now well-known. We evaluated whether clinicians could use a novel approach, including clinician-driven individualized thresholding, to reliably identify six language regions, including Broca's Area, Wernicke's Area (inferior, superior), Exner's Area, Supplementary Speech Area, Angular Gyrus, and Basal Temporal Language Area. We studied 22 epilepsy and tumor patients who received Wada and fMRI (age 36.4[12.5]; Wada language left/right/mixed in 18/3/1). fMRI tasks (two × three tasks) were analyzed by two clinical neuropsychologists who flexibly …

Choriocarcinoma With Brain, Lung And Vaginal Metastases Successfully Treated Without Brain Radiation Or Intrathecal Chemotherapy: A Case Report, Anja Frost, Jonathan Sherman, M. Katayoon Rezaei, Alivia Aron, Micael Lopez-Acevedo

Neurological Surgery Faculty Publications

Highlights:

• • There is no consensus on optimal treatment for GTN and brain metastases.
• • Brain metastasis treated with craniotomy and intravenous, EMA-CO chemotherapy
• • Intravenous high-dose methotrexate may be adequate to treat brain metastases.

A Normative Spatiotemporal Mri Atlas Of The Fetal Brain For Automatic Segmentation And Analysis Of Early Brain Growth., Ali Gholipour, Caitlin K Rollins, Clemente Velasco-Annis, Abdelhakim Ouaalam, Alireza Akhondi-Asl, Onur Afacan, Cynthia M Ortinau, Sean Clancy, Catherine Limperopoulos, Edward Yang, Judy A Estroff, Simon K Warfield

Pediatrics Faculty Publications

Longitudinal characterization of early brain growth in-utero has been limited by a number of challenges in fetal imaging, the rapid change in size, shape and volume of the developing brain, and the consequent lack of suitable algorithms for fetal brain image analysis. There is a need for an improved digital brain atlas of the spatiotemporal maturation of the fetal brain extending over the key developmental periods. We have developed an algorithm for construction of an unbiased four-dimensional atlas of the developing fetal brain by integrating symmetric diffeomorphic deformable registration in space with kernel regression in age. We applied this new …

A Murine Model To Study Epilepsy And Sudep Induced By Malaria Infection., Paddy Ssentongo, Anna E Robuccio, Godfrey Thuku, Derek G Sim, Ali Nabi, Fatemeh Bahari, Balaji Shanmugasundaram, Myles W Billard, Andrew Geronimo, Kurt W Short, Patrick J Drew, Jennifer Baccon, Steven L Weinstein, Frank G Gilliam, José A Stoute, Vernon M Chinchilli, Andrew F Read, Bruce J Gluckman, Steven J Schiff

Neurology Faculty Publications

One of the largest single sources of epilepsy in the world is produced as a neurological sequela in survivors of cerebral malaria. Nevertheless, the pathophysiological mechanisms of such epileptogenesis remain unknown and no adjunctive therapy during cerebral malaria has been shown to reduce the rate of subsequent epilepsy. There is no existing animal model of postmalarial epilepsy. In this technical report we demonstrate the first such animal models. These models were created from multiple mouse and parasite strain combinations, so that the epilepsy observed retained universality with respect to genetic background. We also discovered spontaneous sudden unexpected death in epilepsy …

Embryonic Transcription Factor Expression In Mice Predicts Medial Amygdala Neuronal Identity And Sex-Specific Responses To Innate Behavioral Cues., Julieta E Lischinsky, Katie Sokolowski, Li Peijun, Shigeyuki Esumi, Yasmin Kamal, Meredith Goodrich, Livio Oboti, Timothy R Hammond, Meera Krishnamoorthy, Daniel Feldman, Molly Huntsman, Judy Liu, Joshua G Corbin

Pediatrics Faculty Publications

The medial subnucleus of the amygdala (MeA) plays a central role in processing sensory cues required for innate behaviors. However, whether there is a link between developmental programs and the emergence of inborn behaviors remains unknown. Our previous studies revealed that the telencephalic preoptic area (POA) embryonic niche is a novel source of MeA destined progenitors. Here, we show that the POA is comprised of distinct progenitor pools complementarily marked by the transcription factors Dbx1 and Foxp2. As determined by molecular and electrophysiological criteria this embryonic parcellation predicts postnatal MeA inhibitory neuronal subtype identity. We further find that Dbx1-derived and …

Pediatric High-Grade Glioma: Biologically And Clinically In Need Of New Thinking., Chris Jones, Matthias A Karajannis, David T W Jones, Mark W Kieran, Michelle Monje, Suzanne J Baker, Roger J Packer, +Several Additional Authors

Neurology Faculty Publications

High-grade gliomas in children are different from those that arise in adults. Recent collaborative molecular analyses of these rare cancers have revealed previously unappreciated connections among chromatin regulation, developmental signaling, and tumorigenesis. As we begin to unravel the unique developmental origins and distinct biological drivers of this heterogeneous group of tumors, clinical trials need to keep pace. It is important to avoid therapeutic strategies developed purely using data obtained from studies on adult glioblastoma. This approach has resulted in repetitive trials and ineffective treatments being applied to these children, with limited improvement in clinical outcome. The authors of this perspective, …

Unmasking Of Myoclonus By Lacosamide In Generalized Epilepsy, Daniel Birnbaum, Mohamad Z. Koubeissi

Neurology Faculty Publications

Lacosamide is a new-generation antiseizure medication that is approved for use as an adjunctive treatment and monotherapy in focal epilepsy. Its use in generalized epilepsy, however, has not been adequately evaluated in controlled trials. We report a 67-year-old woman who experienced new-onset myoclonic seizures after initiation of lacosamide. We presume that she had an undiagnosed generalized epilepsy syndrome, likely juvenile myoclonic epilepsy. Myoclonic seizures were not reported before introducing lacosamide and completely resolved after lacosamide was discontinued. This suggests that lacosamide may have the potential to worsen myoclonus, similar to what has been reported with another sodium channel agent, lamotrigine, …

The Role Of Osteopontin And Its Gene On Glucocorticoid Response In Myasthenia Gravis., Yanchen Xie, Hai-Feng Li, Liang Sun, Linda L Kusner, Shuhui Wang, Yunxiao Meng, Xu Zhang, Yu Hong, Xiang Gao, Yao Li, Henry J Kaminski

Neurology Faculty Publications

Biomarkers that assess treatment response for patients with the autoimmune disorder, myasthenia gravis (MG), have not been evaluated to a significant extent. We hypothesized the pro-inflammatory cytokine, osteopontin (OPN), may be associated with variability of response to glucocorticoids (GCs) in patients with MG. A cohort of 250 MG patients treated with standardized protocol of GCs was recruited, and plasma OPN and polymorphisms of its gene, secreted phosphoprotein 1 (SPP1), were evaluated. Mean OPN levels were higher in patients compared to healthy controls. Carriers of rs11728697*T allele (allele definition: one of two or more alternative forms of a gene) were more …

Hemiataxia: A Novel Presentation Of Anti-Nmda Receptor Antibody Mediated Encephalitis In An Adolescent., Greg D Phillips, Gillian N Jones, Maureen Callaghan, Marc P Difazio

Neurology Faculty Publications

Anti-NMDA receptor antibody associated encephalitis as a cause of new-onset neuropsychiatric manifestations in children and adults can represent a significant diagnostic challenge for clinicians. Clinical signs often include encephalopathy, new-onset psychosis, and movement phenomenon. Although orofacial dyskinesias were initially identified as a characteristic movement phenomenon in this type of encephalitis, an expanded range of abnormalities has recently been reported, including isolated ataxia. We report a case of isolated hemiataxia in a young adult with mild initial psychiatric manifestations. A personal and family history of preceding neuropsychiatric symptoms produced diagnostic confusion and resulted in a significant diagnostic and therapeutic delay. Our …

Neurobehavioral Function In Adults Recovering Consciousness After Severe Traumatic Brain Injury: A Scoping Review, Jennifer Weaver, Ann Guernon, Trudy Mallinson, Theresa Louise-Bender Pape, Thomas Harrod

Clinical Research and Leadership Faculty Posters and Presentations

This scoping review aims to report the findings of current literature examining the assessment of neurobehavioral function and recovery along the continuum of disorders of consciousness (DOC) from coma to full consciousness.

•This study is designed to capture the range of constructs researchers have used to measure NBF during recovery of consciousness.

•The research question for this review was: “What constructs are most frequently used to assess neurobehavioral function in adults recovering consciousness after severe TBI?”

Abnormal Glycosylation In Joubert Syndrome Type 10., Megan S Kane, Mariska Davids, Michelle R Bond, Christopher J Adams, Megan E Grout, Ian G Phelps, Gilbert Vezina, +Several Additional Authors

Neurology Faculty Publications

BACKGROUND: The discovery of disease pathogenesis requires systematic agnostic screening of multiple homeostatic processes that may become deregulated. We illustrate this principle in the evaluation and diagnosis of a 5-year-old boy with Joubert syndrome type 10 (JBTS10). He carried the OFD1 mutation p.Gln886Lysfs*2 (NM_003611.2: c.2656del) and manifested features of Joubert syndrome.

METHODS: We integrated exome sequencing, MALDI-TOF mass spectrometry analyses of plasma and cultured dermal fibroblasts glycomes, and full clinical evaluation of the proband. Analyses of cilia formation and lectin staining were performed by immunofluorescence. Measurement of cellular nucleotide sugar levels was performed with high-performance anion-exchange chromatography with pulsed amperometric …

Neurosurgery Concepts: Key Perspectives On Endoscopic Versus Microscopic Resection For Pituitary Adenomas, Surgical Decision-Making In Tuberculum Sellae Meningiomas, Optic Nerve Mobilization During Resection Of Craniopharyngiomas, And Evaluation Of Headache And Quality Of Life After Endoscopic Transphenoidal Surgery For Pituitary Adenomas, Anand Germanwala, Ryan Hofler, Carlito Lagman, Lawrence Chang, Alexander Khaleesi, Jonathan H. Sherman, +Several Additional Authors

Neurological Surgery Faculty Publications

No abstract provided.

Distinct Neural Bases Of Disruptive Behavior And Autism Symptom Severity In Boys With Autism Spectrum Disorder., Y.J. Daniel Yang, Denis G Sukhodolsky, Jiedi Lei, Eran Dayan, Kevin A. Pelphrey, Pamela Ventola

Pediatrics Faculty Publications

BACKGROUND: Disruptive behavior in autism spectrum disorder (ASD) is an important clinical problem, but its neural basis remains poorly understood. The current research aims to better understand the neural underpinnings of disruptive behavior in ASD, while addressing whether the neural basis is shared with or separable from that of core ASD symptoms.

METHODS: Participants consisted of 48 male children and adolescents: 31 ASD (7 had high disruptive behavior) and 17 typically developing (TD) controls, well-matched on sex, age, and IQ. For ASD participants, autism symptom severity, disruptive behavior, anxiety symptoms, and ADHD symptoms were measured. All participants were scanned while …

Malignant Peripheral Nerve Sheath Tumors State Of The Science: Leveraging Clinical And Biological Insights Into Effective Therapies., Aerang Kim, Douglas R Stewart, Karlyne M Reilly, David Viskochil, Markku M Miettinen, Brigitte C Widemann

Pediatrics Faculty Publications

Malignant peripheral nerve sheath tumor (MPNST) is the leading cause of mortality in patients with neurofibromatosis type 1. In 2002, an MPNST consensus statement reviewed the current knowledge and provided guidance for the diagnosis and management of MPNST. Although the improvement in clinical outcome has not changed, substantial progress has been made in understanding the natural history and biology of MPNST through imaging and genomic advances since 2002. Genetically engineered mouse models that develop MPNST spontaneously have greatly facilitated preclinical evaluation of novel drugs for translation into clinical trials led by consortia efforts. Continued work in identifying alterations that contribute …

Neurosurgery Concepts: Key Perspectives On Imaging Characteristics Of Spinal Metastases, Surgery For Low Back Pain, Anesthesia For Disc Surgery, And Laminectomy Versus Laminectomy And Fusion For Lumbar Spondylolisthesis., Carlito Lagman, Lawrance K Chung, Luke Macyszyn, Winward Choy, Zachary A Smith, Nader S Dahdaleh, Angela M Bohnen, Jin M Cho, Chaim B Colen, Edward Duckworth, Anand V Germanwala, Peter Kan, Alexander A Khalessi, Chae-Yong Kim, Sandi Lam, Gordon Li, Michael Lim, Jonathan H Sherman, Vincent Y Wang, Gabriel Zada, Isaac Yang

Neurological Surgery Faculty Publications

No abstract provided.