Mauricio F. Villamar

Focal Modulation of the Primary Motor Cortex in Fibromyalgia Using 4! 1-Ring High-Definition Transcranial Direct Current Stimulation (HD-tDCS): Immediate and Delayed Analgesic Effects of Cathodal and Anodal Stimulation

UNLABELLED Fibromyalgia is a prevalent chronic pain syndrome characterized by altered pain and sensory processing in the central nervous system, which is often refractory to multiple therapeutic approaches. Given previous evidence supporting analgesic properties of noninvasive brain stimulation techniques in this condition, this study examined the effects of a novel, more focal method of transcranial direct current stimulation (tDCS), using the 4×1-ring configuration of high-definition (HD)-tDCS, on overall perceived pain in fibromyalgia patients. In this patient- and assessor-blind, sham-controlled, crossover trial, 18 patients were randomized to undergo single 20-minute sessions of anodal, cathodal, and sham HD-tDCS at 2.0 mA in a counterbalanced fashion. The center electrode was positioned over the left primary motor cortex. Pain scales and sensory testing were assessed before and after each intervention. A finite element method brain model was generated to predict electric field distribution. We found that both active stimulation conditions led to significant reduction in overall perceived pain as compared to sham. This effect occurred immediately after cathodal HD-tDCS and was evident for both anodal and cathodal HD-tDCS 30 minutes after stimulation. Furthermore, active anodal stimulation induced a significant bilateral increase in mechanical detection thresholds. These interventions proved well tolerated in our patient population. PERSPECTIVE 4×1-ring HD-tDCS, a novel noninvasive brain stimulation technique capable of more focal and targeted stimulation, provides significant reduction in overall perceived pain in fibromyalgia patients as compared to sham stimulation, irrespective of current polarity. This technique may have other applications in research and clinical settings, which should be further explored.

Noninvasive Brain Stimulation to Modulate Neuroplasticity in Traumatic Brain Injury

Objective:  To review the use of noninvasive brain stimulation (NBS) as a therapeutic tool to enhance neuroplasticity following traumatic brain injury (TBI).

A feasibility study assessing cortical plasticity in chronic neuropathic pain following burn injury.

The aim of this article is to evaluate the neuroplastic changes associated with chronic neuropathic pain following burn injury and modulation feasibility using transcranial direct current stimulation (tDCS). This is a crossover, double-blinded case series involving three patients with chronic neuropathic pain following burn injury. Participants were randomly assigned to undergo single sessions of both sham and active anodal tDCS over the primary motor cortex, contralateral to the most painful site. Excitability of the motor cortex was assessed before and after each stimulation session with the use of transcranial magnetic stimulation. An overall decrease in cortical excitability was seen after active tDCS only, as characterized by a decrease in intracortical facilitation and amplitude of motor evoked potentials and an increase in intracortical inhibition. Clinical outcomes did not change after a single session of tDCS. Results are consistent with previous studies showing that patients with chronic neuropathic pain have defective intracortical inhibition. This case series shows early evidence that chronic pain following burn injury may share similar central neural mechanisms, which could be modulated using tDCS.

Transcranial direct current stimulation reduces food-craving and measures of hyperphagia behavior in participants with Prader-Willi syndrome.

Prader–Willi syndrome (PWS) is a neurodevelopmental genetic disorder characterized by intellectual disabilities and insatiable appetite with compulsive eating leading to severe obesity with detrimental health consequences. Transcranial direct current stimulation (tDCS) has been shown to modulate decision‐making and cue‐induced food craving in healthy adults. We conducted a pilot double blind, sham‐controlled, multicenter study of tDCS modulation of food drive and craving in 10 adult PWS participants, 11 adult obese (OB) and 11 adult healthy‐weight control (HWC) subjects. PWS and OB subjects received five consecutive daily sessions of active or sham tDCS over the right dorsolateral prefrontal cortex (DLPFC), while HWC received a single sham and active tDCS in a crossover design. Standardized psychometric instruments assessed food craving, drive and hyperphagia by self‐report and caregiver assessment over 30 days. Robust baseline differences were observed in severity scores for the Three‐Factor Eating Questionnaire (TFEQ) and Dykens Hyperphagia Questionnaire (DHQ) for PWS compared to HWC while obese participants were more similar to HWC. Active tDCS stimulation in PWS was associated with a significant change from baseline in TFEQ Disinhibition (Factor II) (Ƶ = 1.9, P < 0.05, 30 days) and Total Scores (Ƶ = 2.3, P < 0.02, 30 days), and participant ratings of the DHQ Severity (Ƶ = 1.8, P < 0.06, 5 days) and Total Scores (Ƶ = 1.9, P < 0.05, 15 days). These findings support sustained neuromodulatory effects and efficacy of tDCS to reduce food drive and behaviors impacting hyperphagia in PWS. Transcranial direct current stimulation may represent a straight‐forward, low risk and low cost method to improve care, management and quality of life in PWS.

Transcranial direct current stimulation (tDCS) and the cardiovascular responses to acute pain in humans.

OBJECTIVE To determine if transcranial direct current stimulation (tDCS) reduces both acute pain perception and the resultant cardiovascular responses. METHODS Data were acquired on 15 healthy subjects at rest and in response to three cold pressor tests: 0, 7, and 14 °C. Subsequently, single sessions of sham and active anodal tDCS (2.0 mA for 40 min) were delivered to the left primary motor cortex (M1). RESULTS Perceived pain was reduced only after active tDCS with the 14 °C cold pressor test. This was accompanied by tendency for lesser increases in heart rate (~2 beats/min, p=0.09) and blood pressure (~3 mmHg, p=0.06). The effect size of tDCS on peak heart rate and blood pressure responses at 14 °C was 0.47 and 0.54, respectively. On the other hand, baseline heart rate, blood pressure, leg blood flow, and leg vascular resistance were unaffected by tDCS. No other responses were affected. CONCLUSIONS Our results demonstrate that M1 anodal tDCS has no effect on basal hemodynamics or cardiovascular autonomic outflow and has only modest effects on the responses to acute pain in healthy humans. SIGNIFICANCE Application of tDCS shifts the pain perception threshold in healthy individuals but does not significantly modulate efferent cardiovascular control at rest or in response to pain.

Rabies encephalitis presenting with new-onset refractory status epilepticus (NORSE)

A 15-year-old girl, previously healthy with normal developmental history, had an episode of unilateral arm jerking at school followed by transient loss of consciousness. Two weeks later, she presented to the emergency department with recurrent generalized convulsions despite treatment with lorazepam and fosphenytoin. In retrospect, her family reported a 1-month history of personality changes (i.e., listlessness) and decline in academic performance. There was no family history of epilepsy, metabolic disorders, or immunodeficiency. The patient resided in rural northeastern Kentucky. There was no recent travel history.

Status epilepticus alert reduces time to administration of second-line antiseizure medications

Background Status epilepticus (SE) is a neurologic emergency with high morbidity and mortality. Delays in SE treatment are common in clinical practice and can be associated with poorer outcomes. Our goal was to determine whether the implementation of an SE alert protocol improves time to administration of a second-line antiseizure medication (ASM) in hospitalized adults. Methods We developed and implemented an inpatient SE alert system. A quasiexperimental cohort study was performed. We analyzed all patients aged 18–85 years who were managed at the University of Kentucky Medical Center using the SE alert protocol between March 2015 and June 2017 (n = 19). Controls were the first 20 consecutive patients treated for SE over the same time period, but who were managed with usual care (i.e., without SE alert protocol). Results Time to administration of a second-line ASM was shorter with the use of the SE alert system (22.21 ± 3.44 minutes) compared to usual care (58.30 ± 6.72 minutes; p < 0.0001). Conclusion Implementation of an SE alert system led to a marked improvement in time to administration of a second-line ASM. Classification of evidence This study provides Class III evidence that for adult inpatients treated for SE, implementation of an SE alert protocol reduces time to administration of second-line ASM.

Pearls & Oy-sters: Persistent elevation of serum carcinoembryonic antigen in secretory meningioma

Elevation in serum carcinoembryonic antigen (CEA) is uncommon in the context of primary CNS neoplasms but can be seen with metastatic brain tumors. CEA elevation can be the presenting feature of a secretory meningioma (SM), a rare subtype of WHO grade I meningioma.

T157. Seizure prediction with autonomic measurements versus intracranial EEG in patients with refractory epilepsy

Introduction There is resurgent interest in the role played by autonomic dysfunction in seizure generation. Advances in wearable sensors make it convenient to track many autonomic variables in patient populations. The purpose of this study is to assess peri-ictal changes in surrogate measures of autonomic activity in epilepsy patients. Methods With IRB approval, 3 patients admitted for invasive presurgical evaluation using intracranial EEG (iEEG) were monitored. Additional sensors for fronto-central EEG, EKG and submental EMG were applied, and variables relevant to autonomic function (AV), specifically electrodermal activity, heart rate, blood volume pulse and skin temperature, were measured by a wrist-worn device. The mean of each AV was computed in 5-s epochs. Several 1-h-long interictal and preictal segments were extracted for analysis: 7 interictal and preictal segments during sleep from patient 1; 6 interictal and preictal segments during sleep, and 8 interictal and 5 preictal segments during wakefulness from patient 2; and 8 interictal and 3 preictal segments during wakefulness from patient 3. Hence, 2 of 3 patients had either only sleep or only wake data. Sleep and wake data were verified using video-EEG and analyzed separately to minimize the potentially confounding effect of vigilance state. Several electrophysiological variables (EV) were estimated in 5-s epochs from the iEEG in the seizure onset zone, and a naive Bayes classifier was trained on these features and tested using 5-fold cross-validation to determine whether preictal and interictal sleep (or wake) epochs could be distinguished from each other using AV or EV features. Results Of 16 EV features, beta power, gamma power (30–45 Hz and 47–75 Hz), line length, and Teager energy were sometimes significantly different for preictal and interictal sleep (or wake) data in each patient (ANOVA: p  Conclusion Appreciable preictal vs interictal sleep (or wake) autonomic changes were documented in patients monitored during Phase II presurgical evaluation. This result suggests that autonomic measurements, which can be conveniently measured using noninvasive devices, have some predictive value for epileptic seizures in certain individuals. Acknowledgements Alpha Omega Alpha Postgraduate Award to MFV; Scholarship support from University of Babylon (Iraq) to AA; a seed grant from EpiC , the University of Kentucky Epilepsy Research Center , to MBO, SS and MFV; and NSF Grant No. 1539068 to SS.

Reversible manifestations of extraparenchymal neurocysticercosis

Movement disorders are uncommon manifestations of neurocysticercosis. When present, most are secondary to parenchymal lesions in the basal ganglia. Rarely, movement disorders can occur in racemose/extraparenchymal neurocysticercosis, an aggressive variant frequently associated with cerebrospinal fluid outflow obstruction and hydrocephalus. Appropriate treatment can reverse neurological manifestations.