Medical Specialties Commons^™

A Case Matched Study Examining The Reliability Of Using Impact To Assess Effects Of Multiple Concussions., Trevor Barker, Stephen A. Russo, Gaytri Barker, Mark A Rice, Mary G Jeffrey, Gordon Broderick, Travis J A Craddock

Department of Neurology Faculty Papers

BACKGROUND: Approximately 3.8 million sport and recreational concussions occur per year, creating a need for accurate diagnosis and management of concussions. Researchers and clinicians are exploring the potential dose-response cumulative effects of concussive injuries using computerized neuropsychological exams, however, results have been mixed and/or contradictory. This study starts with a large adolescent population and applies strict inclusion criteria to examine how previous mild traumatic brain injuries affect symptom reports and neurocognitive performance on the Immediate Post-concussion Assessment and Cognitive Testing (ImPACT) computerized tool.

METHODS: After applying exclusion criteria and case matching, 204 male and 99 female participants remained. These participants …

Secondary Hematoma Expansion And Perihemorrhagic Edema After Intracerebral Hemorrhage: From Bench Work To Practical Aspects., Krista Lim-Hing, Fred Rincon

Department of Neurology Faculty Papers

Intracerebral hemorrhages (ICH) represent about 10-15% of all strokes per year in the United States alone. Key variables influencing the long-term outcome after ICH are hematoma size and growth. Although death may occur at the time of the hemorrhage, delayed neurologic deterioration frequently occurs with hematoma growth and neuronal injury of the surrounding tissue. Perihematoma edema has also been implicated as a contributing factor for delayed neurologic deterioration after ICH. Cerebral edema results from both blood-brain barrier disruption and local generation of osmotically active substances. Inflammatory cellular mediators, activation of the complement, by-products of coagulation and hemolysis such as thrombin …

Ar2, A Novel Automatic Muscle Artifact Reduction Software Method For Ictal Eeg Interpretation: Validation And Comparison Of Performance With Commercially Available Software., Shennan Aibel Weiss, Ali Akbar Asadi-Pooya, Sitaram Vangala, Stephanie Moy, Dale H. Wyeth, Iren Orosz, Michael Gibbs, Lara Schrader, Jason Lerner, Christopher K Cheng, Edward Chang, Rajsekar Rajaraman, Inna Keselman, Perdro Churchman, Christine Bower-Baca, Adam L Numis, Michael G Ho, Lekha Rao, Annapoorna Bhat, Joanna Suski, Marjan Asadollahi, Timothy Ambrose, Andres Fernandez, Maromi Nei, Christopher T. Skidmore, Scott Mintzer, Dawn S. Eliashiv, Gary W Mathern, Marc R Nuwer, Michael R. Sperling, Jerome Engel, John M Stern

Department of Neurology Faculty Papers

Objective: To develop a novel software method (AR2) for reducing muscle contamination of ictal scalp electroencephalogram (EEG), and validate this method on the basis of its performance in comparison to a commercially available software method (AR1) to accurately depict seizure-onset location. Methods: A blinded investigation used 23 EEG recordings of seizures from 8 patients. Each recording was uninterpretable with digital filtering because of muscle artifact and processed using AR1 and AR2 and reviewed by 26 EEG specialists. EEG readers assessed seizure-onset time, lateralization, and region, and specified confidence for each determination. The two methods were validated on the basis of …

The Role Of Adenosine Signaling In Headache: A Review., Nathan T. Fried, Melanie B. Elliott, Michael L. Oshinsky

Department of Neurology Faculty Papers

Migraine is the third most prevalent disease on the planet, yet our understanding of its mechanisms and pathophysiology is surprisingly incomplete. Recent studies have built upon decades of evidence that adenosine, a purine nucleoside that can act as a neuromodulator, is involved in pain transmission and sensitization. Clinical evidence and rodent studies have suggested that adenosine signaling also plays a critical role in migraine headache. This is further supported by the widespread use of caffeine, an adenosine receptor antagonist, in several headache treatments. In this review, we highlight evidence that supports the involvement of adenosine signaling in different forms of …

Efficacy And Tolerability Of Adjunctive Brivaracetam In Patients With Prior Antiepileptic Drug Exposure: A Post-Hoc Study., Ali A. Asadi-Pooya, Michael R. Sperling, Steve Chung, Pavel Klein, Anyzeila Diaz, Sami Elmoufti, Jimmy Schiemann, John Whitesides

Department of Neurology Faculty Papers

Brivaracetam (BRV), a selective, high-affinity ligand for synaptic vesicle protein 2A, is a new antiepileptic drug (AED) for adjunctive treatment of focal (partial-onset) seizures in adults with epilepsy. This post-hoc analysis was conducted to explore the efficacy of adjunctive BRV in patients with prior levetiracetam (LEV) exposure and whether changes in efficacy were related to the similar mechanism of action of these two drugs. Data were pooled from three Phase III studies (NCT00490035; NCT00464269; NCT01261325) of adults with focal seizures taking 1-2 AEDs who received placebo or BRV 50-200mg/day without titration over a 12-week treatment period. Patients taking concomitant LEV …

Fsd-C10, A Fasudil Derivative, Promotes Neuroregeneration Through Indirect And Direct Mechanisms., Yan-Hua Li, Chong Xie, Yuan Zhang, Xing Li, Hai-Fei Zhang, Qing Wang, Zhi Chai, Bao-Guo Xiao, Rodolfo Thome, Guang-Xian Zhang, Cun-Gen Ma

Department of Neurology Faculty Papers

FSD-C10, a Fasudil derivative, was shown to reduce severity of experimental autoimmune encephalomyelitis (EAE), an animal model of multiple sclerosis (MS), through the modulation of the immune response and induction of neuroprotective molecules in the central nervous system (CNS). However, whether FSD-C10 can promote neuroregeneration remains unknown. In this study, we further analyzed the effect of FSD-C10 on neuroprotection and remyelination. FSD-C10-treated mice showed a longer, thicker and more intense MAP2 and synaptophysin positive signal in the CNS, with significantly fewer CD4(+) T cells, macrophages and microglia. Importantly, the CNS of FSD-C10-treated mice showed a shift of activated macrophages/microglia from …

Zika Virus-Associated Seizures, Ali Akbar Asadi-Pooya

Department of Neurology Faculty Papers

No abstract provided.

Blood-Brain Barrier Transport Machineries And Targeted Therapy Of Brain Diseases, Jaleh Barar, Mohammad Rafi, Mohamad Mostafa Pourseif, Yadollah Omidi

Department of Neurology Faculty Papers

Introduction: Desired clinical outcome of pharmacotherapy of brain diseases largely depends upon the safe drug delivery into the brain parenchyma. However, due to the robust blockade function of the blood-brain barrier (BBB), drug transport into the brain is selectively controlled by the BBB formed by brain capillary endothelial cells and supported by astrocytes and pericytes. Methods: In the current study, we have reviewed the most recent literature on the subject to provide an insight upon the role and impacts of BBB on brain drug delivery and targeting. Results: All drugs, either small molecules or macromolecules, designated to treat brain diseases …

Intravenous Ketamine For Subacute Treatment Of Refractory Chronic Migraine: A Case Series., Clinton Lauritsen, Santiago Mazuera, Richard B. Lipton, Sait Ashina

Department of Neurology Faculty Papers

BACKGROUND: Refractory migraine is a challenging condition with great impact on health related quality of life. Intravenous (IV) ketamine has been previously used to treat various refractory pain conditions. We present a series of patients with refractory migraine treated with intravenous ketamine in the hospital setting.

METHODS: Based on retrospective chart review, we identified six patients with refractory migraine admitted from 2010 through 2014 for treatment with intravenous ketamine. Ketamine was administered using a standard protocol starting with a dose of 0.1 mg/kg/hr and increased by 0.1 mg/kg/hr every 3 to 4 h as tolerated until the target pain score …

Semiological Classification Of Psychogenic Nonepileptic Seizures., Ali Akbar Asadi-Pooya, Jennifer Tinker, Elizabeth W. Fletman

Department of Neurology Faculty Papers

PURPOSE: We classified patients with psychogenic nonepileptic seizures (PNESs) according to a newly proposed classification system. Then, we investigated the demographic and clinical differences between various classes of the patients.

METHODS: We retrospectively investigated all patients with PNESs admitted to the Jefferson Comprehensive Epilepsy Center from 2012 through 2016. We classified the patients into four distinct classes: patients with generalized motor seizures, patients with akinetic seizures, patients with focal motor seizures, and patients with seizures with subjective symptoms. All patients were interviewed by a neuropsychologist and were administered psychological assessment measures, including questions about PNES risk factors. For the statistical …

Ictal Verbal Help-Seeking: Occurrence And The Underlying Etiology., Ali Akbar Asadi-Pooya, Marjan Asadollahi, Krzysztof Bujarski, Amin H. Rabiei, Narsis Aminian, Dale Wyeth, Michael R. Sperling

Department of Neurology Faculty Papers

PURPOSE: Ictal verbal help-seeking has never been systematically studied before. In this study, we evaluated a series of patients with ictal verbal help-seeking to characterize its frequency and underlying etiology.

METHODS: We retrospectively reviewed all the long-term video-EEG reports from Jefferson Comprehensive Epilepsy Center over a 12-year period (2004-2015) for the occurrence of the term "help" in the text body. All the extracted reports were reviewed and patients with at least one episode of documented ictal verbal help-seeking in epilepsy monitoring unit (EMU) were studied. For each patient, the data were reviewed from the electronic medical records, EMU report, and …

Ictal Kissing: Occurrence And Etiology., Ali Akbar Asadi-Pooya, Elizabeth W. Fletman

Department of Neurology Faculty Papers

Ictal kissing is a rare semiological manifestation in patients with epilepsy. We tried to estimate its occurrence and characterize the underlying etiology. We retrospectively reviewed all video-EEG reports from Jefferson Comprehensive Epilepsy Center over a 12-year period (2004-2015) for the occurrence of the term "kiss". We then searched the electronic database PubMed on September 21, 2016 using the following search terms in the English language: "ictal" OR "seizure" OR "epilepsy" AND "kiss" OR "kissing". Relevant original studies were included. During the study period, 5133 patients were investigated in our epilepsy monitoring unit. One patient (0.02%) had one episode of documented …

Remote Preoperative Tonic-Clonic Seizures Do Not Influence Outcome After Surgery For Temporal Lobe Epilepsy., Ali Akbar Asadi-Pooya, Amin H. Rabiei, Edward J. Gracely, Michael R. Sperling

Department of Neurology Faculty Papers

OBJECTIVES: Tonic-clonic seizures are associated with greater chance of seizure relapse after anterior temporal lobectomy. We investigated whether the interval between the last preoperative tonic-clonic seizure and surgery relates to seizure outcome in patients with drug-resistant mesial temporal lobe epilepsy (MTLE).

METHODS: In this retrospective study, patients were prospectively registered in a database from 1986 through 2014. Postsurgical outcome was categorized as seizure freedom or relapse. The relationship between surgical outcome and the interval between the last preoperative tonic-clonic seizure and surgery was investigated.

RESULTS: One-hundred seventy-one patients were studied. Seventy nine (46.2%) patients experienced tonic-clonic seizures before surgery. Receiver …

Neuromodulation, Stephen Silberstein

Department of Neurology Faculty Papers

Neuromodulation is a new promising treatment for headache disorders. It consists of peripheral nerve neurostimulation and central neurostimulation. © 2016, Touch Briefings. All rights reserved.

Seizure Clusters In Drug-Resistant Focal Epilepsy., Ali Akbar Asadi-Pooya, Maromi Nei, Ashwini Sharan, Michael R. Sperling

Department of Neurology Faculty Papers

We investigated clinical factors associated with seizure clustering in patients with drug-resistant focal epilepsy and any association between seizure clustering and outcome after surgery. We performed a retrospective study including patients with a diagnosis of drug-resistant focal epilepsy who underwent epilepsy surgery. Patients were prospectively registered in a database from 1986 until 2015. Seizure cluster was defined as two or more seizures occurring within 2 days. Potential risk factors for seizure clustering were assessed. To investigate any potential association between seizure clusters and seizure outcome after surgery, time to event analysis was used to produce a Kaplan-Meier estimate of seizure …

Seizure Outcome After Switching Antiepileptic Drugs: A Matched, Prospective Study., Jon Marc Finamore, Michael R. Sperling, Tingting Zhan, Maromi Nei, Christopher T. Skidmore, Scott Mintzer

Department of Neurology Faculty Papers

OBJECTIVE: Outcomes after changing antiepileptic drugs (AEDs) have largely been studied in single cohort series. We recently reported the first study to examine this question in a controlled manner. Here we expand on these results by using a matched, prospective methodology applied to both uncontrolled and well-controlled patients taking any AED.

METHODS: We reviewed all outpatient notes over a 9-month period and identified patients with focal epilepsy who were on monotherapy. We classified those who switched AEDs as case patients, with those remaining on the same drug serving as controls. We matched cases with controls for seizure status (seizure-free in …

Ictal Pain: Occurrence, Clinical Features, And Underlying Etiologies., Ali Akbar Asadi-Pooya, Marjan Asadollahi, Michael R. Sperling

Department of Neurology Faculty Papers

PURPOSE: We analyzed a series of patients with ictal pain to estimate its occurrence and characterize the underlying etiologies.

METHODS: We retrospectively reviewed all the long-term video-EEG reports from Jefferson Comprehensive Epilepsy Center over a 12-year period (2004-2015) for the occurrence of the term "pain" in the text body. All the extracted reports were reviewed, and patients with at least one documented episode of ictal pain in the epilepsy monitoring unit (EMU) were included in the study.

RESULTS: During the study period, 5133 patients were investigated in our EMU. Forty-six patients (0.9%) had at least one documented episode of ictal …

Patient Historical Risk Factors Associated With Seizure Outcome After Surgery For Drug-Resistant Nonlesional Temporal Lobe Epilepsy., Ali Akbar Asadi-Pooya, Maromi Nei, Ashwini Sharan, Michael R. Sperling

Department of Neurology Faculty Papers

OBJECTIVE: To investigate the possible influence of risk factors on seizure outcome after surgery for drug-resistant nonlesional temporal lobe epilepsy (TLE).

METHODS: This retrospective study recruited patients with drug-resistant nonlesional TLE who underwent epilepsy surgery at Jefferson Comprehensive Epilepsy Center and were followed for a minimum of one year. Patients had been prospectively registered in a database from 1991 through 2014. Postsurgical outcome was classified into two groups; seizure free or relapsed. The possible risk factors influencing long-term seizure outcome after surgery were investigated.

RESULTS: Ninety-five patients (42 males and 53 females) were studied. Fifty-four (56.8%) patients were seizure free. …

Ictal Crying, Ali Akbar Asadi-Pooya, Dale Wyeth, Michael R. Sperling

Department of Neurology Faculty Papers

PURPOSE: The purpose of this study was to describe a series of patients with ictal crying to estimate its occurrence and characterize the clinical features and the underlying etiology.

METHODS: We retrospectively reviewed all the long-term video-EEG reports from Jefferson Comprehensive Epilepsy Center over a 12-year period (2004-2015) for the occurrence of the terms "cry" or "sob" or "weep" in the text body. All the extracted reports were reviewed, and patients with at least one episode of documented ictal crying at the epilepsy monitoring unit (EMU) were included in the study.

RESULTS: During the study period, 5133 patients were investigated …

Spike Voltage Topography In Temporal Lobe Epilepsy, Ali Akbar Asadi-Pooya, Marjan Asadollahi, Shoichi Shimamoto, Matthew Lorenzo, Michael R. Sperling

Department of Neurology Faculty Papers

We investigated the voltage topography of interictal spikes in patients with temporal lobe epilepsy (TLE) to see whether topography was related to etiology for TLE. Adults with TLE, who had epilepsy surgery for drug-resistant seizures from 2011 until 2014 at Jefferson Comprehensive Epilepsy Center were selected. Two groups of patients were studied: patients with mesial temporal sclerosis (MTS) on MRI and those with other MRI findings. The voltage topography maps of the interictal spikes at the peak were created using BESA software. We classified the interictal spikes as polar, basal, lateral, or others. Thirty-four patients were studied, from which the …

Auras In Patients With Temporal Lobe Epilepsy And Mesial Temporal Sclerosis., Ali Akbar Asadi-Pooya, Maromi Nei, Ashwini Sharan, Michael R. Sperling

Department of Neurology Faculty Papers

We investigated auras in patients with drug-resistant temporal lobe epilepsy (TLE) and mesial temporal sclerosis (MTS). We also investigated the clinical differences between patients with MTS and abdominal auras and those with MTS and non-mesial temporal auras. All patients with drug-resistant TLE and unilateral MTS who underwent epilepsy surgery at Jefferson Comprehensive Epilepsy Center from 1986 through 2014 were evaluated. Patients with good postoperative seizure outcome were investigated. One hundred forty-nine patients (71 males and 78 females) were studied. Thirty-one patients (20.8%) reported no auras, while 29 patients (19.5%) reported abdominal aura, and 30 patients (20.1%) reported non-mesial temporal auras; …

Long-Term Effect Of Antiepileptic Drug Switch On Serum Lipids And C-Reactive Protein., Scott Mintzer, Rachael Miller, Krunal Shah, Inna Chervoneva, Maromi Nei, Christopher T. Skidmore, Michael R. Sperling

Department of Neurology Faculty Papers

BACKGROUND: Prior studies have shown that switching patients from inducing antiepileptic drugs (AEDs) to lamotrigine, levetiracetam, or topiramate reduces serum lipids and C-reactive protein (CRP). These studies were all of short duration, and some drugs, such as zonisamide, have not been investigated.

METHODS: We recruited 41 patients taking phenytoin or carbamazepine who were being switched to zonisamide, lamotrigine, or levetiracetam. We measured serum lipids and CRP before the switch, >6weeks after, and >6months after. An untreated control group (n=14) underwent similar measurement. We combined these data with those of our previous investigation (n=34 patients and 16 controls) of a very …

Gray Matter Abnormalities In Temporal Lobe Epilepsy: Relationships With Resting-State Functional Connectivity And Episodic Memory Performance., Gaelle Eve Doucet, Xiaosong He, Michael R Sperling, Ashwini Sharan Md, Joseph I Tracy

Department of Neurology Faculty Papers

Temporal lobe epilepsy (TLE) affects multiple brain regions through evidence from both structural (gray matter; GM) and functional connectivity (FC) studies. We tested whether these structural abnormalities were associated with FC abnormalities, and assessed the ability of these measures to explain episodic memory impairments in this population. A resting-state and T1 sequences were acquired on 94 (45 with mesial temporal pathology) TLE patients and 50 controls, using magnetic resonance imaging (MRI) technique. A voxel-based morphometry analysis was computed to determine the GM volume differences between groups (right, left TLE, controls). Resting-state FC between the abnormal GM volume regions was computed, …

Induced Stem Cells As A Novel Multiple Sclerosis Therapy., Chong Xie, Yan-Qun Liu, Yang-Tai Guan, Guang-Xian Zhang

Department of Neurology Faculty Papers

Stem cell replacement is providing hope for many degenerative diseases that lack effective therapeutic methods including multiple sclerosis (MS), an inflammatory demyelinating disease of the central nervous system. Transplantation of neural stem cells or mesenchymal stem cells is a potential therapy for MS thanks to their capacity for cell repopulation as well as for their immunomodulatory and neurotrophic properties. Induced pluripotent stem cell (iPSC), an emerging cell source in regenerative medicine, is also being tested for the treatment of MS. Remarkable improvement in mobility and robust remyelination have been observed after transplantation of iPSC-derived neural cells into demyelinated models. Direct …

Molecular Treatment Effects Of Alemtuzumab In Skeletal Muscles Of Patients With Ibm., Karsten Schmidt, Konstanze Kleinschnitz, Goran Rakocevic, Marinos Dalakas, Jens Schmidt

Department of Neurology Faculty Papers

BACKGROUND: Mechanisms of inflammation and protein accumulation are crucial in inclusion body myositis (IBM). Recent evidence demonstrated that intravenous immunoglobulin failed to suppress cell-stress mediators in IBM. Here we studied the molecular changes in skeletal muscle biopsies from patients with IBM before and after treatment with alemtuzumab.

METHODS: Relevant inflammatory and degeneration-associated markers were assessed by quantitative-PCR and immunohistochemistry in repeated muscle biopsy specimens from patients with IBM, which had been treated in a previously published uncontrolled proof-of-concept trial with alemtuzumab.

RESULTS: There were no significant changes of the mRNA expression levels of the pro-inflammatory chemokines CXCL-9, CCL-4, and the …

Mesial Temporal Lobe Epilepsy With Childhood Febrile Seizure., Ali Akbar Asadi-Pooya, Maromi Nei, Cyrus Rostami, Michael R. Sperling

Department of Neurology Faculty Papers

OBJECTIVES: To evaluate the demographic and clinical manifestations of patients with mesial temporal sclerosis and temporal lobe epilepsy (MTS-TLE) with childhood febrile seizure (FS) and establishing the potential differences as compared to those without FS. We also investigated the surgery outcome in these two groups of patients.

MATERIALS AND METHODS: In this retrospective study, all patients with a clinical diagnosis of drug-resistant TLE due to mesial temporal sclerosis, who underwent epilepsy surgery at Jefferson Comprehensive Epilepsy Center, were recruited. Patients were prospectively registered in a database from 1986 through 2014. Postsurgical outcome was classified into two groups; seizure-free or relapsed. …

Neural Substrate Expansion For The Restoration Of Brain Function., H Isaac Chen, Dennis Jgamadze, Mijail Serruya, D Kacy Cullen, John A Wolf, Douglas H Smith

Department of Neurology Faculty Papers

Restoring neurological and cognitive function in individuals who have suffered brain damage is one of the principal objectives of modern translational neuroscience. Electrical stimulation approaches, such as deep-brain stimulation, have achieved the most clinical success, but they ultimately may be limited by the computational capacity of the residual cerebral circuitry. An alternative strategy is brain substrate expansion, in which the computational capacity of the brain is augmented through the addition of new processing units and the reconstitution of network connectivity. This latter approach has been explored to some degree using both biological and electronic means but thus far has not …

Determinants Of Activity Levels In African Americans With Mild Cognitive Impairment., Barry W. Rovner, Md, Robin J. Casten, Phd, Benjamin E. Leiby, Phd

Department of Neurology Faculty Papers

Engaging in cognitive, social, and physical activities may prevent cognitive decline. In a sample of older African Americans with mild cognitive impairment (MCI; N=221), we investigated the cross-sectional relationships between activity levels and participants' demographic, clinical, and neuropsychological characteristics. The average age of participants was 75.4 years (SD, 7.0); 177 (80.1%) were women. Participation in cognitive/social activities was positively associated with education, depression, literacy, mobility, instrumental activities of daily living (IADL), verbal learning, and subcomponents of executive function. A linear regression identified IADLs, education, depression, and verbal learning as independent predictors. Participation in physical activities was positively associated with sex, …

Factors Associated With Tonic-Clonic Seizures In Patients With Drug-Resistant Mesial Temporal Epilepsy., Ali Akbar Asadi-Pooya, Cyrus Rostami, Amin H. Rabiei, Michael R. Sperling

Department of Neurology Faculty Papers

PURPOSE: Among different seizure types, tonic-clonic seizures are more significant because they are more often associated with morbidity. No prior study has been done to investigate risk factors associated with tonic-clonic seizures in patients with mesial temporal epilepsy.

METHODS: In this retrospective study, all drug-resistant mesial temporal epilepsy patients in the database of patients who underwent epilepsy surgery at Jefferson comprehensive epilepsy center were recruited. These patients were prospectively registered in a database from 1986 till 2014. Patients' age, gender, epilepsy risk factors, age at seizure onset, and preoperative seizure type(s) were registered routinely. Potential risk factors associated with experiencing …

Emerging Immunopharmacological Targets In Multiple Sclerosis., Mojtaba Farjam, Guang-Xian Zhang, Bogoljub Ciric, Abdolmohamad Rostami

Department of Neurology Faculty Papers

Inflammatory demyelination of the central nervous system (CNS) is the hallmark of multiple sclerosis (MS), a chronic debilitating disease that affects more than 2.5 million individuals worldwide. It has been widely accepted, although not proven, that the major pathogenic mechanism of MS involves myelin-reactive T cell activation in the periphery and migration into the CNS, which subsequently triggers an inflammatory cascade that leads to demyelination and axonal damage. Virtually all MS medications now in use target the immune system and prevent tissue damage by modulating neuroinflammatory processes. Although current therapies such as commonly prescribed disease-modifying medications decrease the relapse rate …