Anthony Martino

An entropy-based model for basal ganglia dysfunctions in movement disorders.

During this last decade, nonlinear analyses have been used to characterize the irregularity that exists in the neuronal data stream of the basal ganglia. In comparison to linear parameters for disparity (i.e., rate, standard deviation, and oscillatory activities), nonlinear analyses focus on complex patterns that are composed of groups of interspike intervals with matching lengths but not necessarily contiguous in the data stream. In light of recent animal and clinical studies, we present a review and commentary on the basal ganglia neuronal entropy in the context of movement disorders.

Non-linear dynamics in parkinsonism

Over the last 30 years, the functions (and dysfunctions) of the sensory-motor circuitry have been mostly conceptualized using linear modelizations which have resulted in two main models: the “rate hypothesis” and the “oscillatory hypothesis.” In these two models, the basal ganglia data stream is envisaged as a random temporal combination of independent simple patterns issued from its probability distribution of interval interspikes or its spectrum of frequencies respectively. More recently, non-linear analyses have been introduced in the modelization of motor circuitry activities, and they have provided evidences that complex temporal organizations exist in basal ganglia neuronal activities. Regarding movement disorders, these complex temporal organizations in the basal ganglia data stream differ between conditions (i.e., parkinsonism, dyskinesia, healthy control) and are responsive to treatments (i.e., l-DOPA, deep brain stimulation). A body of evidence has reported that basal ganglia neuronal entropy (a marker for complexity/irregularity in time series) is higher in hypokinetic state. In line with these findings, an entropy-based model has been recently formulated to introduce basal ganglia entropy as a marker for the alteration of motor processing and a factor of motor inhibition. Importantly, non-linear features have also been identified as a marker of condition and/or treatment effects in brain global signals (EEG), muscular activities (EMG), or kinetic of motor symptoms (tremor, gait) of patients with movement disorders. It is therefore warranted that the non-linear dynamics of motor circuitry will contribute to a better understanding of the neuronal dysfunctions underlying the spectrum of parkinsonian motor symptoms including tremor, rigidity, and hypokinesia.

Rasmussen encephalitis tissue transfer program

To the Editors: Rasmussen encephalitis (RE) was first described in 1958 by Theodore Rasmussen and colleagues at the Montreal Neurological Institute. RE is a very rare neuroinflammatory disease characterized by intractable seizures and progressive unilateral neurologic deficits. For most diagnosed cases, resection or disconnection of the affected cerebral hemisphere is the only effective treatment. The extreme rarity of the disease has hampered efforts to understand the cause of RE and to develop alternative nonsurgical treatments. Usually only one or two RE cases may been seen annually at a pediatric epilepsy surgery center, thus it may take many years to accrue enough surgical specimens for research studies, especially those involving modern molecular techniques. In 2011, The RE Children’s Project (www.REChildrens.org), a nonprofit organization founded to increase awareness of the disease and support research focused on finding a cure, brought together investigators from around the world to launch the RE Children’s Research Consortium and discuss ways to accelerate the pace of RE research. With the support of the RE Children’s Project, researchers at Johns Hopkins School of Medicine and David Geffen School of Medicine at UCLA launched an international Tissue Transfer Program and data bank to speed up the pace of RE research. The goal of the Tissue Transfer Program is to collect RE surgical specimens from epilepsy centers around the world and to make biologic samples and clinical data available for RE research. Between 2011 and 2012, the program was initiated with coordination managed at Johns Hopkins and in 2013 the role was transferred to UCLA. A central repository for the collected samples was established within the Rare Epilepsies and Brain Disease Tissue Bank in the Department of Neurosurgery at UCLA (http://neurosurgery.ucla.edu/rareepilepsies-tissue-bank). Excess material from a planned epilepsy surgery that would otherwise be discarded, per institutional guidelines, would be collected for this purpose. All logistics would be handled by the Rare Epilepsies and Brain Disease Tissue Bank Coordinator at UCLA, who would liaise with donor institutions to facilitate the transfer of surgical specimens at no cost to the participating institution. Institutional review board (IRB) approval was obtained to collect surgical specimens from outside institutions, and to distribute material to other centers with institutionally approved research studies. Since the inception of the Tissue Transfer Program, RE specimens have been collected from 33 surgeries at 19 epilepsy centers in six countries (Fig. 1). Stored specimens include both fixed and frozen brain tissue, cerebrospinal fluid, whole blood, plasma, purified peripheral blood mononuclear cells, and brain-infiltrating lymphocytes. With increased awareness of this program, we hope that the pace of RE research will be accelerated. Epilepsy surgery centers around the world are invited to contribute samples and participate in this international effort to cure RE. Applications to access the RE repository should be directed to the Rare Epilepsies and Brain Disease Tissue Bank Coordinator at UCLA (http://neurosurgery.ucla. edu/rare-epilepsies-tissue-bank-contact-us). The Scientific Advisory Board of the RE Children’s Project will review applications for research studies to ensure a fair and rigorous assessment of the proposed work. In addition to RE, the Rare Epilepsies and Brain Disease Tissue bank is actively collecting specimens from other rare or uncommon pediatric epilepsy surgery cases including hemimegalencephaly (HME), focal cortical dysplasia (FCD), and tuberous sclerosis (TSC). For more information visit http://neurosurgery.ucla.edu/rare-epilepsies-tissue-bank.

An Unusual Cause for Gait Disturbance in a Child

MRI of the brain, which revealed that the cerebellar tonsils were displaced inferiorly through the foramen magnum into the upper cervical canal (Figure 2). Six days after his MRI was performed, he subsequently underwent suboccipital craniectomy, C1-C2 laminectomy, and dural grafting. His postoperative hospital course was significant for aseptic meningitis and adenoviral upper respiratory infection. He was evaluated at the neurosurgery clinic 3 months after his surgery, and he was ambulating without any problems. In addition, 1 year after surgery, the child was evaluated at the pediatric clinic; he was in good health with no complaints; his neurological examination revealed no abnormalities.

Computed tomographic method to quantify electrode lead deformation and subdural gap after lead implantation for deep brain stimulation

BACKGROUND Deep brain stimulation is an effective treatment for movement disorders and psychiatric conditions. Intra-operative and post-operative events can result in brain tissue deformation (i.e. subdural gaps) which may cause lead deformation and its displacement from optimal target. We developed a method to quantify postoperative lead deformation and we present two DBS cases to illustrate the phenomena of lead deformation resulting from the development of subdural gaps. NEW METHOD We present a semi-automatic computational algorithm using Computed Tomography scanning with reconstruction to determine lead curvature relative to a theoretical straight lead between the skull entry site and lead tip. Subdural gap was quantified from the CT scan. RESULTS In 2 patients who had leads implanted, analysis of CT scans was completed within 5 min each. The maximum deviation of the observed lead from the theoretical linear path was 1.1 and 2.6 mm, and the subdural gap was 5.5 and 9.6 mL, respectively. COMPARISON WITH EXISTING METHOD(S) This is the first method allowing a comprehensive characterization of the lead deformation in situ. CONCLUSIONS The computational algorithms provide a simple, semiautomatic method to characterize in situ lead curvature related to brain tissue deformation after lead placement.

Anterior Lumbar Corpectomy with Expandable Titanium Cage Reconstruction: A Case Series of 42 Patients

BACKGROUND Burst fractures involve the anterior and middle columns with an intact posterior column. Deforming forces are magnified at areas of transition, making the thoracolumbar junction highly susceptible to injury. METHODS This is a retrospective review of 42 consecutive patients who underwent single-level anterior lumbar corpectomy using an obelisc expandable titanium cage and lateral fixation for traumatic lumbar burst fractures. RESULTS Myelopathy and sensory dysfunction were the most frequent neurologic deficits initially, occurring in 16 (38%) and 15 (36%) patients, respectively, which both decreased to 5 (13%). At follow-up, 26 patients (68%) were able to ambulate independently. No patient had significant cage displacement or needed cage replacement. Subsidence was minimal in 32 of 39 patients (82%). There were no hardware infections or surgical site infections. Options for stabilization include posterior instrumentation and fusion, anterior corpectomy with interbody fusion, and combination procedures. We believe anterior stabilization is superior because the aim is structural restoration of anterior and middle columns. The aim of posterior fixation is to replace the posterior tension band, which is not affected. There are 3 major surgical components to consider. First is anterior versus posterior decompression of the spinal canal. Second is the choice of autograft or titanium graft. Third is whether to stabilize posteriorly or anterolateral. CONCLUSIONS Anterior corpectomy with an expandable titanium cage and lateral rod fixation is safe and effective with minimal complications. It is a viable alternative to posterior decompression and instrumentation.

Parkinsonian Balance Deficits Quantified Using a Game Industry Board and a Specific Battery of Four Paradigms.

This study describes a cost-effective screening protocol for parkinsonism based on combined objective and subjective monitoring of balance function. Objective evaluation of balance function was performed using a game industry balance board and an automated analyses of the dynamic of the center of pressure in time, frequency, and non-linear domains collected during short series of stand up tests with different modalities and severity of sensorial deprivation. The subjective measurement of balance function was performed using the Dizziness Handicap Inventory questionnaire. Principal component analyses on both objective and subjective measurements of balance function allowed to obtained a specificity and selectivity for parkinsonian patients (vs. healthy subjects) of 0.67 and 0.71 respectively. The findings are discussed regarding the relevance of cost-effective balance-based screening system as strategy to meet the needs of broader and earlier screening for parkinsonism in communities with limited access to healthcare.