Association between kinetic semiology of psychogenic nonepileptic spells and seizure type in dual disorder.

PURPOSE: Epilepsy is diagnosed in 20% of patients with psychogenic nonepileptic spells (PNES). The semiology of PNES and epileptic seizures (ES) overlaps in some patients. It is unclear whether the motor phenotype of PNES predicts the type of ES. METHODS: Video segments of EEGs in patients with PNES and ES treated in the Epilepsy Monitoring Unit at the University of Nebraska Medical Center were reviewed. Videos were categorized according to the validated motor-based classification of PNES. Ratings of kinetic PNES events were analyzed to determine if there was an association with focal or generalized ES. If available, the video segments of ES were categorized as hypokinetic or hyperkinetic based on the constellation of focal or generalized movements and other semiological features. RESULTS: Among 43 patients with documented PNES-ES (median age 34, interquartile range (IQR) 26-45), 27.9% were male. The largest proportion of patients (39.5%) had focal temporal epilepsy (TE). Other diagnostic groups included focal frontal (FE, 25.6%), generalized (GE, 25.6%), or other (9.3%) epilepsies. Thirty-three PNES patients (82.5%) were rated as having a hypokinetic phenotype. On average, hypokinetic PNES patients were receiving a median of 3 (IQR 2-4) anticonvulsants, compared to a median of 2 (IQR 2-3) in hyperkinetic PNES patients (p = 0.06). While the group with coexisting FE had a higher prevalence of hyperkinetic semiology (45.4%) than either the TE (11.7%) or GE (18.1%) patients, there was no significant association between the ES type and kinetic status of PNES. Among 20 patients who had video recordings of both PNES and ES, 40% displayed the concordant hypokinetic phenotypes for PNES and seizures while 15% had hyperkinetic presentation of both event types. Among additional 16 patients with scalp EEG-negative suspected nonepileptic events and documented ES, 6 had the recordings of seizures and 3 have presented with concordant hypokinetic PNES and ES. CONCLUSION: In patients with PNES and ES, the hypokinetic semiology of PNES prevails over hyperkinetic semiology in TE and GE syndromes. The motor status of PNES does not predict the phenotype of coexisting ES. The concordant kinetic semiology is present in more than half of the patients with dual diagnosis and available video data.

Utilization of brain imaging in evaluating patients with psychogenic nonepileptic spells.

BACKGROUND: Psychogenic nonepileptic spells (PNES) are paroxysmal movements or sensory events that resemble epileptic seizures but lack corresponding ictal electrographic changes. A confirmed diagnosis of PNES is only accomplished via video electroencephalogram (vEEG) monitoring. Prior to diagnosis, patients are often assessed with neurodiagnostic imaging and their conditions treated with anticonvulsant medications, both of which are of limited clinical value and contribute to the higher cost of care. In this study, we assessed the relationship between the semiological features of PNES, medication regimen, or psychiatric comorbidities and the frequency of referrals for brain imaging tests prior to diagnosis of PNES. METHODS: This is a retrospective chart review of 224 adult patients diagnosed as having PNES at a level 4 epilepsy care center from 2012 to 2017. Patients with coexisting epilepsy were excluded. The 882 segments of vEEG records were reviewed for semiology of spells, and patients were categorized into one of seven distinct phenotypic classes according to the accepted clinical classification. The frequency of neurodiagnostic tests completed for each patient prior to vEEG was correlated with PNES phenotype and other clinical characteristics. RESULTS: There were 68 (30%) males and 156 (70%) females diagnosed as having PNES with a median age of 36 years. Seventy-four percent of patients were receiving one or several anticonvulsant medications, and 67% of patients were treated with psychotropic medications other than benzodiazepines. The most prevalent PNES events were characterized by semirhythmic small amplitude movements in the extremities (class 2; 34%) followed by those resembling tonic-clonic seizures (class 4; 28%). Neurodiagnostic imaging tests including computed tomography (CT) and magnetic resonance imaging (MRI) of the brain were performed at least once in 60% of patients and 4 times or more in 11% prior to vEEG. There was a significant association between the frequency of neurodiagnostic tests and the PNES phenotype (p = 0.02). Specifically, patients with sensory changes (class 6) had more imaging tests than those with primitive gesturing and truncal posturing (classes 1 and 5, respectively). Additionally, patients diagnosed with 3 or more psychiatric disorders underwent significantly more neurodiagnostic tests relative to patients diagnosed with two or fewer psychiatric disorders (p = 0.03). Furthermore, patients whose conditions were treated with anticonvulsant medications tended to undergo more imaging scans prior to vEEG as compared with the patients whose conditions were not being treated with anticonvulsants. CONCLUSIONS: These findings suggest that the frequency of brain imaging obtained prior to the definitive diagnosis of PNES is influenced by semiology of spells and the psychiatric health of patients. Patients who demonstrate minimal paroxysmal movements in the settings of multiple psychiatric comorbidities represent a particularly challenging patient phenotype which is linked to more frequent referrals for brain imaging. These patients should be promptly referred for vEEG to improve diagnostic accuracy and prevent treatment with anticonvulsants as well as referrals for serial neurodiagnostic tests.

1,25-Dihydroxyvitamin D3 suppressed experimental autoimmune encephalomyelitis through both immunomodulation and oligodendrocyte maturation.

1,25-Dihydroxyvitamin D3 (1,25(OH)2D3) has recently been found to have the anti-inflammatory potential to suppress experimental autoimmune encephalomyelitis (EAE), an animal model of multiple sclerosis; however, its direct effect on neural cells is not clear. In the current study we show that 1,25(OH)2D3 treatment effectively suppressed clinical signs of ongoing EAE and reduced inflammation and demyelination scores in the central nervous system (CNS). The treatment significantly decreased production/expression of pro-inflammatory cytokines IFN-γ, GM-CSF and IL-17A, while it increased anti-inflammatory cytokines IL-4 and IL-10. Further, 1,25(OH)2D3 treatment effectively elevated the numbers of neural stem cells, oligodendrocyte precursor cells, as well as oligodendrocytes in disease lesions in the CNS. These results, together with its in vitro effect of inducing oligodendrocyte differentiation as shown in our previous findings, demonstrate that 1,25(OH)2D3 suppressed EAE not only by its immunomodulatory capacity, but also by its effect on oligodendrocyte differentiation and maturation, and thus has potential for remyelination and neural repair.

[The mechanism of the glial cells involved in neuropathic pain].

Neuropathic pain is caused by lesion or disease of somatosensory system. The glial cell includes astrocyte and microglia in central nervous system (CNS), as well as satellite cell and Schwann cell in peripheral nervous system (PNS). Neural lesion activates the glial cell, inducing its morphology changes and certain protein expression. By interacting with neurons, the glial cell plays important roles in both the initiation and maintenance of neuropathic pain. In this review, we present recent progress in the study of glial mechanisms underlying neuropathic pain.

Extracting seizure frequency from epilepsy clinic notes: a machine reading approach to natural language processing.

OBJECTIVE: Seizure frequency and seizure freedom are among the most important outcome measures for patients with epilepsy. In this study, we aimed to automatically extract this clinical information from unstructured text in clinical notes. If successful, this could improve clinical decision-making in epilepsy patients and allow for rapid, large-scale retrospective research. MATERIALS AND METHODS: We developed a finetuning pipeline for pretrained neural models to classify patients as being seizure-free and to extract text containing their seizure frequency and date of last seizure from clinical notes. We annotated 1000 notes for use as training and testing data and determined how well 3 pretrained neural models, BERT, RoBERTa, and Bio_ClinicalBERT, could identify and extract the desired information after finetuning. RESULTS: The finetuned models (BERTFT, Bio_ClinicalBERTFT, and RoBERTaFT) achieved near-human performance when classifying patients as seizure free, with BERTFT and Bio_ClinicalBERTFT achieving accuracy scores over 80%. All 3 models also achieved human performance when extracting seizure frequency and date of last seizure, with overall F1 scores over 0.80. The best combination of models was Bio_ClinicalBERTFT for classification, and RoBERTaFT for text extraction. Most of the gains in performance due to finetuning required roughly 70 annotated notes. DISCUSSION AND CONCLUSION: Our novel machine reading approach to extracting important clinical outcomes performed at or near human performance on several tasks. This approach opens new possibilities to support clinical practice and conduct large-scale retrospective clinical research. Future studies can use our finetuning pipeline with minimal training annotations to answer new clinical questions.

Recognizing encephalopathy in immune checkpoint inhibitor therapy: A single-center experience.

BACKGROUND: In this pilot study, we examined the characteristics of patients with and without central nervous system (CNS) malignancies who developed immune checkpoint inhibitor (ICI)-induced encephalopathy. METHODS: We identified adult patients treated with ICIs between 1 January 2013 and 9 May 2018 at our tertiary care center who developed encephalopathy within 30 days of the last dose of ICI without other explained causes. Demographic and clinical features were compared between patients with primary and metastatic malignant CNS tumors and those without. RESULTS: Of the 480 patients treated with ICIs, 14 (2.9%) developed encephalopathy induced by nivolumab (8), pembrolizumab (4), and combined ipilimumab-nivolumab (2). Median age was 64.5 years. Patients with CNS malignancies tolerated more treatment cycles and developed encephalopathy later than patients without CNS lesions (20 and 32 days, respectively, p = 0.04) following ICI initiation. Four of seven patients with CNS tumors developed new contrast-enhancing lesions on brain imaging despite having no changes on imaging for a median of 61 (30-545) days. Electroencephalogram (EEG) revealed features of generalized dysfunction in patients in both cohorts. Two patients without and three with CNS malignancies were treated with steroids. Two thirds of patients without and 29% of those with CNS malignancies expired during ICI therapy or shortly thereafter. CONCLUSIONS: Lack of the uniform evaluation limits the definitive conclusion of the cause of encephalopathy in some patients but reflects the standard of care at the time of their assessment. ICI-associated neurotoxicity presenting with encephalopathy is an ominous complication of ICI therapy, especially if left untreated. Prompt recognition and involvement of multidisciplinary care, including neurologists, would facilitate timely administration of recommended therapies.