Try a new search

Format these results:

Searched for:





Total Results:


Novelty preference assessed by eye tracking: A sensitive measure of impaired recognition memory in epilepsy

Leeman-Markowski, Beth A; Martin, Samantha P; Hardstone, Richard; Tam, Danny M; Devinsky, Orrin; Meador, Kimford J
OBJECTIVE:Epilepsy patients often report memory deficits despite normal objective testing, suggesting that available measures are insensitive or that non-mnemonic factors are involved. The Visual Paired Comparison Task (VPCT) assesses novelty preference, the tendency to fixate on novel images rather than previously viewed items, requiring recognition memory for the "old" images. As novelty preference is a sensitive measure of hippocampal-dependent memory function, we predicted impaired VPCT performance in epilepsy patients compared to healthy controls. METHODS:We assessed 26 healthy adult controls and 31 epilepsy patients (16 focal-onset, 13 generalized-onset, 2 unknown-onset) with the VPCT using delays of 2 or 30 s between encoding and recognition. Fifteen healthy controls and 17 epilepsy patients (10 focal-onset, 5 generalized-onset, 2 unknown-onset) completed the task at 2-, 5-, and 30-minute delays. Subjects also performed standard memory measures, including the Medical College of Georgia (MCG) Paragraph Test, California Verbal Learning Test-Second Edition (CVLT-II), and Brief Visual Memory Test-Revised (BVMT-R). RESULTS:The epilepsy group was high functioning, with greater estimated IQ (p = 0.041), greater years of education (p = 0.034), and higher BVMT-R scores (p = 0.024) compared to controls. Both the control group and epilepsy cohort, as well as focal- and generalized-onset subgroups, had intact novelty preference at the 2- and 30-second delays (p-values ≤ 0.001) and declined at 30 min (p-values > 0.05). Only the epilepsy patients had early declines at 2- and 5-minute delays (controls with intact novelty preference at p = 0.003 and p ≤ 0.001, respectively; epilepsy groups' p-values > 0.05). CONCLUSIONS:Memory for the "old" items decayed more rapidly in overall, focal-onset, and generalized-onset epilepsy groups. The VPCT detected deficits while standard memory measures were largely intact, suggesting that the VPCT may be a more sensitive measure of temporal lobe memory function than standard neuropsychological batteries.
PMID: 38636142
ISSN: 1525-5069
CID: 5646602

Impact of Multiple Sclerosis Subtypes on Pain Management in Patients With Trigeminal Neuralgia After Stereotactic Radiosurgery: An International Multicenter Analysis

De Nigris Vasconcellos, Fernando; Mashiach, Elad; Alzate, Juan Diego; Bernstein, Kenneth; Rotman, Lauren; Levy, Sarah; Qu, Tanxia; Wegner, Rodney E; Shepard, Matthew J; Patel, Samir; Warnick, Ronald E; Moreno, Nuria Martínez; Martínez Álvarez, Roberto; Picozzi, Piero; Franzini, Andrea; Peker, Selçuk; Samanci, Yavuz; Elguindy, Ahmed N; Palmer, Joshua D; Lunsford, L Dade; Jose, Shalini G; Wei, Zhishuo; Niranjan, Ajay; Blagui, Sarra; Iorio-Morin, Christian; Mathieu, David; Briggs, Robert G; Yu, Cheng; Zada, Gabriel; Dayawansa, Samantha; Sheehan, Jason; Schulder, Michael; Goenka, Anuj; Begley, Sabrina; Khilji, Hamza; Urgošík, Dušan; Liščák, Roman; Kondziolka, Douglas
BACKGROUND AND OBJECTIVES/OBJECTIVE:Trigeminal neuralgia affects approximately 2% of patients with multiple sclerosis (MS) and often shows higher rates of pain recurrence after treatment. Previous studies on the effectiveness of stereotactic radiosurgery (SRS) for trigeminal neuralgia did not consider the different MS subtypes, including remitting relapsing (RRMS), primary progressive (PPMS), and secondary progressive (SPMS). Our objective was to investigate how MS subtypes are related to pain control (PC) rates after SRS. METHODS:We conducted a retrospective multicenter analysis of prospectively collected databases. Pain status was assessed using the Barrow National Institute Pain Intensity Scales. Time to recurrence was estimated through the Kaplan-Meier method and compared groups using log-rank tests. Logistic regression was used to calculate the odds ratio (OR). RESULTS:Two hundred and fifty-eight patients, 135 (52.4%) RRMS, 30 (11.6%) PPMS, and 93 (36%) SPMS, were included from 14 institutions. In total, 84.6% of patients achieved initial pain relief, with a median time of 1 month; 78.7% had some degree of pain recurrence with a median time of 10.2 months for RRMS, 8 months for PPMS, 8.1 months for SPMS (P = .424). Achieving Barrow National Institute-I after SRS was a predictor for longer periods without recurrence (P = .028). Analyzing PC at the last available follow-up and comparing with RRMS, PPMS was less likely to have PC (OR = 0.389; 95% CI 0.153-0.986; P = .047) and SPMS was more likely (OR = 2.0; 95% CI 0.967-4.136; P = .062). A subgroup of 149 patients did not have other procedures apart from SRS. The median times to recurrence in this group were 11.1, 9.8, and 19.6 months for RRMS, PPMS, and SPMS, respectively (log-rank, P = .045). CONCLUSION/CONCLUSIONS:This study is the first to investigate the relationship between MS subtypes and PC after SRS, and our results provide preliminary evidence that subtypes may influence pain outcomes, with PPMS posing the greatest challenge to pain management.
PMID: 38051068
ISSN: 1524-4040
CID: 5595452

Cannabinoid treatments in epilepsy and seizure disorders

Devinsky, Orrin; Jones, Nicholas A; Cunningham, Mark O; Jayasekera, B Ashan P; Devore, Sasha; Whalley, Benjamin J
Cannabis has been used to treat convulsions and other disorders since ancient times. In the last few decades, preclinical animal studies and clinical investigations have established the role of cannabidiol (CBD) in treating epilepsy and seizures and support potential therapeutic benefits for cannabinoids in other neurological and psychiatric disorders. Here, we comprehensively review the role of cannabinoids in epilepsy. We briefly review the diverse physiological processes mediating the central nervous system response to cannabinoids, including Δ9-tetrahydrocannabinol (Δ9-THC), cannabidiol, and terpenes. Next, we characterize the anti- and proconvulsive effects of cannabinoids from animal studies of acute seizures and chronic epileptogenesis. We then review the clinical literature on using cannabinoids to treat epilepsy, including anecdotal evidence and case studies as well as the more recent randomized controlled clinical trials that led to US Food and Drug Administration approval of CBD for some types of epilepsy. Overall, we seek to evaluate our current understanding of cannabinoids in epilepsy and focus future research on unanswered questions.
PMID: 37882730
ISSN: 1522-1210
CID: 5628142

An iPSC line (FINi003-A) from a male with late-onset developmental and epileptic encephalopathy caused by a heterozygous p.E1211K variant in the SCN2A gene encoding the voltage-gated sodium channel Nav1.2

Ovchinnikov, Dmitry A; Jong, Sharon; Cuddy, Claire; Dalby, Kelly; Devinsky, Orrin; Mullen, Saul; Maljevic, Snezana; Petrou, Steve
Many developmental and epileptic encephalopathies (DEEs) result from variants in cation channel genes. Using mRNA transfection, we generated and characterised an induced pluripotent stem cell (iPSC) line from the fibroblasts of a male late-onset DEE patient carrying a heterozygous missense variant (E1211K) in Nav1.2(SCN2A) protein. The iPSC line displays features characteristic of the human iPSCs, colony morphology and expression of pluripotency-associated marker genes, ability to produce derivatives of all three embryonic germ layers, and normal karyotype without SNP array-detectable abnormalities. We anticipate that this iPSC line will aid in the modelling and development of precision therapies for this debilitating condition.
PMID: 38479087
ISSN: 1876-7753
CID: 5644322

Alignment of brain embeddings and artificial contextual embeddings in natural language points to common geometric patterns

Goldstein, Ariel; Grinstein-Dabush, Avigail; Schain, Mariano; Wang, Haocheng; Hong, Zhuoqiao; Aubrey, Bobbi; Schain, Mariano; Nastase, Samuel A; Zada, Zaid; Ham, Eric; Feder, Amir; Gazula, Harshvardhan; Buchnik, Eliav; Doyle, Werner; Devore, Sasha; Dugan, Patricia; Reichart, Roi; Friedman, Daniel; Brenner, Michael; Hassidim, Avinatan; Devinsky, Orrin; Flinker, Adeen; Hasson, Uri
Contextual embeddings, derived from deep language models (DLMs), provide a continuous vectorial representation of language. This embedding space differs fundamentally from the symbolic representations posited by traditional psycholinguistics. We hypothesize that language areas in the human brain, similar to DLMs, rely on a continuous embedding space to represent language. To test this hypothesis, we densely record the neural activity patterns in the inferior frontal gyrus (IFG) of three participants using dense intracranial arrays while they listened to a 30-minute podcast. From these fine-grained spatiotemporal neural recordings, we derive a continuous vectorial representation for each word (i.e., a brain embedding) in each patient. Using stringent zero-shot mapping we demonstrate that brain embeddings in the IFG and the DLM contextual embedding space have common geometric patterns. The common geometric patterns allow us to predict the brain embedding in IFG of a given left-out word based solely on its geometrical relationship to other non-overlapping words in the podcast. Furthermore, we show that contextual embeddings capture the geometry of IFG embeddings better than static word embeddings. The continuous brain embedding space exposes a vector-based neural code for natural language processing in the human brain.
PMID: 38553456
ISSN: 2041-1723
CID: 5645352

Long-term radiographic and endocrinological outcomes of stereotactic radiosurgery for recurrent or residual nonfunctioning pituitary adenomas

Shaaban, Ahmed; Dumot, Chloé; Mantziaris, Georgios; Dayawansa, Sam; Peker, Selcuk; Samanci, Yavuz; Nabeel, Ahmed M; Reda, Wael A; Tawadros, Sameh R; Abdel Karim, Khaled; El-Shehaby, Amr M N; Emad Eldin, Reem M; Ragab Abdelsalam, Ahmed; Liscak, Roman; May, Jaromir; Mashiach, Elad; De Nigris Vasconcellos, Fernando; Bernstein, Kenneth; Kondziolka, Douglas; Speckter, Herwin; Mota, Ruben; Brito, Anderson; Bindal, Shray K; Niranjan, Ajay; Lunsford, L Dade; Benjamin, Carolina Gesteira; Almeida, Timoteo; Mao, Jennifer Z; Mathieu, David; Tourigny, Jean-Nicolas; Tripathi, Manjul; Palmer, Joshua David; Matsui, Jennifer; Crooks, Joseph; Wegner, Rodney E; Shepard, Matthew J; Sheehan, Jason P
OBJECTIVE:Stereotactic radiosurgery (SRS) is used for the treatment of residual/recurrent nonfunctional pituitary adenoma (NFPA). The aim of this study was to evaluate the factors related to long-term tumor control and delayed endocrinopathies following SRS. METHODS:This retrospective, multicenter study included patients with recurrent/residual NFPA treated with single-fraction SRS; they were then divided into two arms. The first arm included patients with at least 5 years of radiographic follow-up and all patients with local tumor progression. The second arm included patients with at least 5 years of endocrinological follow-up and all patients who developed endocrinopathy. Study endpoints were tumor control and new or worsening hypopituitarism after SRS and were analyzed using Cox regression and Kaplan-Meier methodology. RESULTS:There were 360 patients in the tumor control arm (median age 52.7 [IQR 42.9-61] years, 193 [53.6%] males) and 351 patients in the hypopituitarism arm (median age 52.5 [IQR 43-61] years, 186 [53.0%] males). The median follow-up in the tumor control evaluation group was 7.95 (IQR 5.7-10.5) years. Tumor control rates at 5, 8, 10, and 15 years were 93% (95% CI 90%-95%), 87% (95% CI 83%-91%), 86% (95% CI 82%-90%), and 69% (95% CI 59%-81%), respectively. The median follow-up in the endocrinopathy evaluation group was 8 (IQR 5.9-10.7) years. Pituitary function preservation rates at 5, 8, 10, and 15 years were 83% (95% CI 80%-87%), 81% (95% CI 77%-85%), 78% (95% CI 74%-83%), and 71% (95% CI 63%-79%), respectively. A margin dose > 15 Gy (HR 0.8, 95% CI 0.7-0.9; p < 0.001) and a delay from last resection to SRS > 1 year (HR 0.9, 95% CI 0.7-0.9; p = 0.04) were significant factors related to tumor control in multivariable analysis. A maximum dose to the pituitary stalk ≤ 10 Gy (HR 1.1, 95% CI 1.09-1.2; p < 0.001) was associated with pituitary function preservation. New visual deficits after SRS occurred in 7 (1.94%) patients in the tumor control group and 8 (2.3%) patients in the endocrinopathy group. Other new cranial nerve deficits post-SRS occurred in 4 of 160 patients with data in the tumor control group and 3 of 140 patients with data in the endocrinopathy group. CONCLUSIONS:SRS affords favorable and durable tumor control for the vast majority of NFPAs. Post-SRS hypopituitarism occurs in a minority of patients, but this risk increases with time and warrants long-term follow-up.
PMID: 38518285
ISSN: 1933-0693
CID: 5640862

Beyond the Final Heartbeat: Neurological Perspectives on Normothermic Regional Perfusion for Organ Donation after Circulatory Death

Kirschen, Matthew P; Lewis, Ariane; Rubin, Michael A; Varelas, Panayiotis N; Greer, David M
Normothermic regional perfusion (NRP) has recently been used to augment organ donation after circulatory death (DCD) to improve the quantity and quality of transplantable organs. In DCD-NRP, after withdrawal of life-sustaining therapies and cardiopulmonary arrest, patients are cannulated onto extracorporeal membrane oxygenation to reestablish blood flow to targeted organs including the heart. During this process, aortic arch vessels are ligated to restrict cerebral blood flow. We review ethical challenges including whether the brain is sufficiently reperfused through collateral circulation to allow reemergence of consciousness or pain perception, whether resumption of cardiac activity nullifies the patient's prior death determination, and whether specific authorization for DCD-NRP is required. ANN NEUROL 2024.
PMID: 38501716
ISSN: 1531-8249
CID: 5640372

Progression free survival of myeloma patients who become IFE-negative correlates with the detection of residual monoclonal free light chain (FLC) by mass spectrometry

Giles, H V; Drayson, M T; Kishore, B; Pawlyn, C; Kaiser, M; Cook, G; de Tute, R; Owen, R G; Cairns, D; Menzies, T; Davies, F E; Morgan, G J; Pratt, G; Jackson, G H
Deeper responses are associated with improved survival in patients being treated for myeloma. However, the sensitivity of the current blood-based assays is limited. Historical studies suggested that normalisation of the serum free light chain (FLC) ratio in patients who were negative by immunofixation electrophoresis (IFE) was associated with improved outcomes. However, recently this has been called into question. Mass spectrometry (MS)-based FLC assessments may offer a superior methodology for the detection of monoclonal FLC due to greater sensitivity. To test this hypothesis, all available samples from patients who were IFE negative after treatment with carfilzomib and lenalidomide-based induction and autologous stem cell transplantation (ASCT) in the Myeloma XI trial underwent FLC-MS testing. FLC-MS response assessments from post-induction, day+100 post-ASCT and six months post-maintenance randomisation were compared to serum FLC assay results. Almost 40% of patients had discordant results and 28.7% of patients with a normal FLC ratio had residual monoclonal FLC detectable by FLC-MS. FLC-MS positivity was associated with reduced progression-free survival (PFS) but an abnormal FLC ratio was not. This study demonstrates that FLC-MS provides a superior methodology for the detection of residual monoclonal FLC with FLC-MS positivity identifying IFE-negative patients who are at higher risk of early progression.
PMID: 38499538
ISSN: 2044-5385
CID: 5640222

Clinical outcomes among initial survivors of cryptogenic new-onset refractory status epilepsy (NORSE)

Costello, Daniel J; Matthews, Elizabeth; Aurangzeb, Sidra; Doran, Elisabeth; Stack, Jessica; Wesselingh, Robb; Dugan, Patricia; Choi, Hyunmi; Depondt, Chantal; Devinsky, Orrin; Doherty, Colin; Kwan, Patrick; Monif, Mastura; O'Brien, Terence J; Sen, Arjune; Gaspard, Nicolas
OBJECTIVE:New-onset refractory status epilepticus (NORSE) is a rare but severe clinical syndrome. Despite rigorous evaluation, the underlying cause is unknown in 30%-50% of patients and treatment strategies are largely empirical. The aim of this study was to describe clinical outcomes in a cohort of well-phenotyped, thoroughly investigated patients who survived the initial phase of cryptogenic NORSE managed in specialist centers. METHODS:Well-characterized cases of cryptogenic NORSE were identified through the EPIGEN and Critical Care EEG Monitoring Research Consortia (CCEMRC) during the period 2005-2019. Treating epileptologists reported on post-NORSE survival rates and sequelae in patients after discharge from hospital. Among survivors >6 months post-discharge, we report the rates and severity of active epilepsy, global disability, vocational, and global cognitive and mental health outcomes. We attempt to identify determinants of outcome. RESULTS:Among 48 patients who survived the acute phase of NORSE to the point of discharge from hospital, 9 had died at last follow-up, of whom 7 died within 6 months of discharge from the tertiary care center. The remaining 39 patients had high rates of active epilepsy as well as vocational, cognitive, and psychiatric comorbidities. The epilepsy was usually multifocal and typically drug resistant. Only a minority of patients had a good functional outcome. Therapeutic interventions were heterogenous during the acute phase of the illness. There was no clear relationship between the nature of treatment and clinical outcomes. SIGNIFICANCE/CONCLUSIONS:Among survivors of cryptogenic NORSE, longer-term outcomes in most patients were life altering and often catastrophic. Treatment remains empirical and variable. There is a pressing need to understand the etiology of cryptogenic NORSE and to develop tailored treatment strategies.
PMID: 38498313
ISSN: 1528-1167
CID: 5640142

Listeria monocytogenes brain abscesses presenting as contiguous, tubular rim-enhancing lesions on Magnetic Resonance Imaging: Case series and literature review

Kim, Daniel D; Sadic, Mohammad; Yarabe, Boniface; Loftus, James R; Lieberman, Evan; Young, Matthew G; Jain, Rajan; Dogra, Siddhant
Listeriosis has more than a 50% mortality when the central nervous system is involved, necessitating rapid diagnosis and treatment. We present four patients with brain abscesses in the setting of diagnosed neurolisteriosis, all of which demonstrated an odd presentation of multiple small, contiguous tubular lesions with rim enhancement on magnetic resonance imaging. Our review of published cases of neurolisteriosis suggests that this may be a useful pattern to identify neurolisteriosis abscesses, allowing earlier detection and therapy.
PMID: 38494758
ISSN: 2385-1996
CID: 5639982