Stephen VanHaerents

Multiple sclerosis: BAFF and CXCL13 in cerebrospinal fluid.

Background: There is increasing evidence of B-cell involvement in the pathogenesis of multiple sclerosis (MS). B-cell activating factor (BAFF) has an essential role in B-cell homeostasis. The chemokine CXCL13 has an important role in the formation and maintenance of B-cell follicles. Objective: To measure BAFF and CXCL13 levels in the cerebrospinal fluid (CSF) of patients with MS compared to patients with other neurological diseases. Methods: Cytokine/chemokine levels were measured by an enzyme-linked immunosorbent assay (ELISA). Results: In MS patients, BAFF levels were highest in patients with secondary progressive disease, and were higher during relapse in patients with relapsing–remitting and secondary progressive disease. CXCL13 levels were also higher during relapse. There was a positive correlation between CXCL13 and the IgG index, and an inverse correlation between BAFF and the IgG index. The implications of this finding are discussed. Conclusion: During relapse, we found various positive correlations between BAFF, CXCL13 and the cytokines IL-6 and IL-10. These findings show that molecules that are essential for B-cell recruitment, survival, maturation and function may be working in concert to affect B-cell homeostasis in MS and contribute to the pathophysiology of the disease.

Early and persistent ‘extreme delta brush’ in a patient with anti-NMDA receptor encephalitis

Since its original description in 2007, anti-N-methyl-d-aspartate receptor (anti-NMDAR) encephalitis associated with an ovarian teratoma is an increasingly recognized etiology of previously unexplained encephalopathy and encephalitis. Extreme delta brush (EDB) is a novel electroencephalogram (EEG) finding seen in many patients with anti-NMDAR encephalitis. The presence of this pattern is associated with a more prolonged illness, although the specificity of this pattern is unclear. Additionally, the frequency and sensitivity of EDB in anti-NMDAR encephalitis and its implications for outcome have yet to be determined. We report a patient with early evidence of extreme delta brush and persistence of this pattern 17.5 weeks later with little clinical improvement.

Repetitive transcranial magnetic stimulation; A cost-effective and beneficial treatment option for refractory focal seizures

We report a 24 year old man with a progressive epilepsy characterized by myoclonic, generalized tonic–clonic and increasing focal seizures, progressing into medication-refractory focal status epilepticus (recurrent seizures without full recovery of consciousness), ultimately controlled with repetitive transcranial magnetic stimulation (rTMS). He was an academically accomplished young man with normal cognitive and physical development. On day 1 of his course, at age 22, he had several myoclonic jerks followed by his first generalized convulsive seizure. At that time, he reported myoclonic jerks for five years prior. His next seizure occurred 8 months later, and was followed by several additional seizures over subsequent days, leading to intensive care unit (ICU) admission and treatment with multiple antiepileptic medications. On continuous EEG monitoring, seizures were seen arising independently from either the left or right occipital pole, before secondarily generalizing. As antiepileptic medications were added, the right occipital focus was controlled, but seizures continued to occur from the left occipital focus. Based on these findings, an atypical progressive myoclonic epilepsy (PME) was suspected. A comprehensive workup was performed (including CSF profile and cultures, paraneoplastic panel, rheumatologic markers, multiple MRIs, muscle biopsy, apocrine gland biopsy, skin exam, retinal exam, small bowel biopsy, celiac antibodies, and 70-gene compre

Antiglutamic acid decarboxylase 65 (GAD65) antibody-associated epilepsy

Glutamic acid decarboxylase (GAD) antibody-associated encephalitis causes both acute seizures and chronic epilepsy with predominantly temporal lobe onset. This condition is challenging in diagnosis and management, and the incidence of GAD antibody (Ab)-related epilepsy could be much higher than commonly believed. Imaging and CSF evidence of inflammation along with typical clinical presentations, such as adult onset temporal lobe epilepsy (TLE) with unexplained etiology, should prompt testing for the diagnostic antibodies. High serum GAD Ab titer (≥2000U/mL or ≥20nmol/L) and evidence of intrathecal anti-GAD Ab synthesis support the diagnosis. Unlike other immune-mediated epilepsies, antiglutamic acid decarboxylase 65 (GAD65) antibody-mediated epilepsy is often poorly responsive to antiepileptic drugs (AEDs) and only moderately responsive to immune therapy with steroids, intravenous immunoglobulin (IVIG), or plasma exchange (PLEX). Long-term treatment with more aggressive immunosuppressants such as rituximab (RTX) and/or cyclophosphamide is often necessary and may be more effective than current immunosuppressive approaches. The aim of this review is to review the physiology, pathology, clinical presentation, related ancillary tests, and management of GAD Ab-associated autoimmune epilepsy by searching the keywords and to promote the recognition and the initiation of proper therapy for this condition.

Clinical classification of post anoxic myoclonic status

INTRODUCTION Despite decades of research into the prognostic significance of post anoxic myoclonic status (MS), no consistent definition has been used to describe its clinical appearance. We set out to characterize the clinical features of MS and hypothesized that there are distinct clinical subtypes that may have prognostic implications. METHODS Video EEG reports from 2008 to 2016 were searched to identify adult patients with post anoxic MS defined as persistent myoclonus for >30min beginning within 3days of cardiac arrest in a comatose patient. Forty-three patients met inclusion and exclusion criteria. To generate definitions of the clinical features of MS, we reviewed videos of 23 cases and characterized 3 distinct clinical semiologies. An additional 20 cases were independently reviewed and categorized by 3 raters to evaluate inter-rater agreement (IRA). All 43 patients were assigned to a group based on consensus review for the first 23 patients and majority agreement for IRA patients. We also examined the relationship between semiology and outcome. RESULTS Three distinct clinical semiologies of MS were identified: Type 1: distal, asynchronous, variable; type 2: axial or axial and distal, asynchronous, variable; and type 3: axial, synchronous, stereotyped. For IRA, Gwets kappa was 0.64 indicating substantial agreement. Two of 3 type 1 patients (66.6%) and 7.4% of type 2 followed commands whereas none of type 3 followed commands (p=0.03). CONCLUSION We defined and validated a classification system of post anoxic MS based on clinical semiology. This classification may be a useful bedside prognostication tool.

Prefrontal θ-Burst Stimulation Disrupts the Organizing Influence of Active Short-Term Retrieval on Episodic Memory

Abstract Dorsolateral prefrontal cortex (DLPFC) is thought to organize items in working memory and this organizational role may also influence long-term memory. To causally test this hypothesized role of DLPFC in long-term memory formation, we used θ-burst noninvasive stimulation (TBS) to modulate DLPFC involvement in a memory task that assessed the influence of active short-term retrieval on later memory. Human subjects viewed three objects on a grid and then either actively retrieved or passively restudied one object’s location after a brief delay. Long-term memory for the other objects was assessed after a delay to evaluate the beneficial role of active short-term retrieval on subsequent memory for the entire set of object locations. We found that DLPFC TBS had no significant effects on short-term memory. In contrast, DLPFC TBS impaired long-term memory selectively in the active-retrieval condition but not in the passive-restudy condition. These findings are consistent with the hypothesized contribution of DLPFC to the organizational processes operative during active short-term retrieval that influence long-term memory, although other regions that were not stimulated could provide similar contributions. Notably, active-retrieval and passive-restudy conditions were intermixed, and therefore nonspecific influences of stimulation were well controlled. These results suggest that DLPFC is causally involved in organizing event information during active retrieval to support coherent long-term memory formation.

Selective and coherent activity increases due to stimulation indicate functional distinctions between episodic memory networks

Targeted noninvasive stimulation selectively increases activity of the human hippocampal network during memory formation. Posterior-medial and anterior-temporal cortical networks interact with the hippocampus and are thought to distinctly support episodic memory. We causally tested this putative distinction by determining whether targeted noninvasive stimulation could selectively affect neural signals of memory formation within the posterior-medial network. Stimulation enhanced the posterior-medial network’s evoked response to stimuli during memory formation, and this activity increase was coherent throughout the network. In contrast, there was no increase in anterior-temporal network activity due to stimulation. In addition, control stimulation of an out-of-network prefrontal cortex location in a separate group of subjects did not influence memory-related activity in either network. The posterior-medial network is therefore a functional unit for memory processing that is distinct from the anterior-temporal network. These findings suggest that targeted stimulation can lead to network-specific increases in excitability during memory formation and hold promise for efforts to fine-tune network involvement in episodic memory via brain stimulation.

Distinguishing the precision of spatial recollection from its success: Evidence from healthy aging and unilateral mesial temporal lobe resection

ABSTRACT Successful episodic recollection can vary in the precision of the information recalled. The hypothesis that recollection precision requires functional neuroanatomical contributions distinct from those required for recollection success remains controversial. Some findings in individuals with hippocampal lesions have indicated that precision is dependent on the hippocampus. However, other neuroimaging and lesion studies have implicated regions outside of the mesial temporal lobe (MTL) in precision, such as parietal cortex. To further elucidate distinctions of recollection precision versus success, we examined whether they were differentially sensitive to aging and to unilateral MTL lesions. Precision and success were measured using a novel task that required memory for item‐location associations across different spatial contexts. We found impairments in recollection precision, but not success, in older adults (59–80 years) relative to younger adults (18–33 years). Recollection precision was also selectively impaired in individuals with unilateral MTL resections made to treat refractory epilepsy. Moreover, recollection precision was significantly worse when resections included the hippocampus compared to when only non‐hippocampal MTL tissue was resected. These findings suggest that the MTL is critically involved in the high‐resolution binding required to support spatial recollection precision, and thus provide evidence for functional neuroanatomical differences between recollection success and precision. HighlightsRecollection precision but not recollection success was impaired in older adults.Precision was also selectively impaired by unilateral mesial temporal resections.Precision was more impaired when resections included the hippocampus.Findings suggest functional neuroanatomical distinction of success and precision.

S121. The role of intraoperative dermatomal somatosensory evoked potentials in the absence of changes in standard somatosensory evoked potentials during spine surgeries: A case series

Introduction Intraoperative electrophysiological monitoring is used to potentially avoid permanent injury as a result of surgical manipulation. During spine surgeries, standard monitoring of median or posterior tibial nerve somatosensory evoked potentials (SEPs) can be insensitive and fail to identify useful intraoperative changes in neural function. Dermatomal somatosensory evoked potentials (DSEPs) have previously been shown to be valuable in identifying specific nerve root dysfunction during surgeries involving spinal decompression, fusion, or tumor resections. Methods Between 2012 and 2017, 2785 spine surgeries were performed with intraoperative monitoring at our institution. Of these, 1884 cases utilized DSEP monitoring in addition to standard SEPs of the median and posterior tibial nerves. Results We highlight 7 cases during which intraoperative DSEPs were able to independently identify changes that were not observed through standard mixed nerve SEPs. During these cases, we observed improvements that correlated with adequate neural decompression, real-time changes in individual nerve root function, as well as provided intraoperative monitoring feedback to surgeons when reliable SEP signals were not obtained. Conclusion DSEP monitoring can serve as a useful and sensitive adjunct method for intraoperative monitoring that may provide additional information to surgeons and patients undergoing spine surgeries. The limitation of DSEP monitoring is that it requires coordination between anesthesiologists, surgeons, and skilled monitoring technicians.

F77. Etiological spectrum of epilepsia partialis continua

Introduction Epilepsia Partialis Continua (EPC) is typically associated with structural lesions but has been described as a presenting feature of autoimmune and viral encephalitis. The relative proportion of patients with each etiology has not been well characterized. Methods A retrospective, single center analysis was performed based on a query of the EEG database from 1/2012 through 12/2017 (n = 50). The clinical presentation, etiology, presence of a culprit MRI lesion, and EEG findings was recorded. Results 50 patients were identified, 25 were female. Mean age: A structural lesion was seen in 46: neoplastic etiology was present in 13, hemorrhagic stroke in 12, ischemic stroke in 12, posttraumatic epilepsy in 2, autoimmune encephalitis in 2, metabolic in 1, demyelinating in 1, CNS vasculitis in 1. Only 5 patients had no corresponding MRI lesion; two of these had autoimmune encephalitis, 1 had giant cell arteritis, 1 had bacterial meningitis, and 1 was cryptogenic. In three of the five, an ictal pattern was seen on EEG. The two patients without EEG correlate, were noted to have hand clonic and face myoclonic movements respectively. Conclusion EPC in this dataset is mostly associated with neoplastic and vascular etiologies. Autoimmune encephalitis can present without imaging correlate and likely represents one of the most common diagnosis in cryptogenic EPC.