Unveiling variability: A systematic review of reproducibility in visual EEG analysis, with focus on seizures.

OBJECTIVE: Reproducibility is key for diagnostic tests involving subjective evaluation by experts. Our aim was to systematically review the reproducibility of visual analysis in clinical electroencephalogram (EEG). In this paper, we give data on the scope of EEG features found, and detailed reproducibility data for the most studied feature. METHODS: We searched four databases for articles reporting reproducibility in clinical EEG, until June 2023. Two raters screened 24 553 citations, and then 2736 full texts. Quality was assessed according to the GRRAS guidelines. RESULTS: We found 275 studies (268 interrater and 20 intrarater), addressing 606 different EEG features. Only 38 EEG features had been studied in >2 studies. Most studies had <50 patients and EEGs. The most often addressed feature was seizure detection (62 papers). Interrater reproducibility of seizure detection was substantial-to-almost-perfect with experienced raters and raw EEG (kappa .62-.88). With experienced raters and transformed EEG, reproducibility was substantial (kappa .63-.70). Inexperienced raters had lower reproducibility. Seizure lateralization reproducibility was moderate to substantial (kappa .58-.77) but lower than for seizure detection. SIGNIFICANCE: Most EEG reproducibility studies are done only once. Intrarater studies are rare. The reproducibility of visual EEG analysis is variable. Interrater reproducibility for seizure detection is substantial-to-perfect with experienced raters and raw EEG, less with inexperienced raters or transformed EEG. The results of visual EEG analysis vary within the same rater, and between raters. There is a need for larger collaborative studies, using improved methodology, as well as more intrarater studies of EEG interpretation.

Spike count and morphology in the classification of epileptiform discharges.

Purpose: The purpose of this study is to investigate the impact of Bergen Epileptiform Morphology Score (BEMS) and interictal epileptiform discharge (IED) candidate count in EEG classification. Methods: We included 400 consecutive patients from a clinical SCORE EEG database during 2013-2017 who had focal sharp discharges in their EEG, but no previous diagnosis of epilepsy. Three blinded EEG readers marked all IED candidates. BEMS and IED candidate counts were combined to classify EEGs as epileptiform or non-epileptiform. Diagnostic performance was assessed and then validated in an external dataset. Results: Interictal epileptiform discharge (IED) candidate count and BEMS were moderately correlated. The optimal criteria to classify an EEG as epileptiform were either one spike at BEMS > = 58, two at > = 47, or seven at > = 36. These criteria had almost perfect inter-rater reliability (Gwet's AC1 0.96), reasonable sensitivity of 56-64%, and high specificity of 98-99%. The sensitivity was 27-37%, and the specificity was 93-97% for a follow-up diagnosis of epilepsy. In the external dataset, the sensitivity for an epileptiform EEG was 60-70%, and the specificity was 90-93%. Conclusion: Quantified EEG spike morphology (BEMS) and IED candidate count can be combined to classify an EEG as epileptiform with high reliability but with lower sensitivity than regular visual EEG review.

No effect of electrical transcranial direct current stimulation adjunct treatment for epilepsia partialis continua in POLG disease.

We report a 15-year-old female with POLG-related mitochondrial disease who developed severe multifocal epilepsia partialis continua, unresponsive to standard anti seizure drug treatment and general anesthesia. Based on an earlier case report, we treated her focal seizures that affected her right upper limb with 20-min sessions of transcranial direct current stimulation (tDCS) at an intensity of 2 mA on each of five consecutive days. The cathode was placed over the left primary motor cortex, the anode over the contralateral orbitofrontal cortex. Surface electromyography (EMG) were recorded 20 min before, 20 min during, and 20 min after four of five tDCS sessions to measure its effect on the muscle jerks. The electroencephalography (EEG) was recorded before and after tDCS to measure the frequency of spikes. Our results showed no statistically or clinically significant reduction of seizures or epileptiform activity using EEG and EMG, with this treatment protocol. To our knowledge, this is only the second time that adjunct tDCS treatment of epileptic seizures has been tried in POLG-related mitochondrial disease. Taken together with the positive findings from the earlier case report, the present study highlights that more data are needed to determine if, and under which parameters, the treatment is effective.

Can serum GAD65 antibody levels predict neurological disease or cancer?

The clinical relevance of antibodies that bind to glutamic acid decarboxylase 65 (GAD65) is controversial regarding diagnostic utility in screening for neurological disease or cancer. We did a retrospective study of 3152 GAD65 antibody-positive patients to examine whether analysis of the antibody levels could predict neurological disease or cancer. Serum GAD65 antibody levels were not associated with any of the following groups: neurological disease, neurological disease and diabetes, diabetes only, no neurological diagnosis and no diabetes mellitus, or cancer. Analysis of serum GAD65 antibody levels had no prognostic value in neurological disease or cancer. GAD65 antibodies should therefore be measured in selective cases of autoimmune neurological diseases.

Visual EEG reviewing times with SCORE EEG.

OBJECTIVE: Visual EEG analysis is the gold standard for clinical EEG interpretation and analysis, but there is no published data on how long it takes to review and report an EEG in clinical routine. Estimates of reporting times may inform workforce planning and automation initiatives for EEG. The SCORE standard has recently been adopted to standardize clinical EEG reporting, but concern has been expressed about the time spent reporting. METHODS: Elapsed times were extracted from 5889 standard and sleep-deprived EEGs reported between 2015 and 2017 reported using the SCORE EEG software. RESULTS: The median review time for standard EEG was 12.5 min, and for sleep deprived EEG 20.9 min. A normal standard EEG had a median review time of 8.3 min. Abnormal EEGs took longer than normal EEGs to review, and had more variable review times. 99% of EEGs were reported within 24 h of end of recording. Review times declined by 25% during the study period. CONCLUSION: Standard and sleep-deprived EEG review and reporting times with SCORE EEG are reasonable, increasing with increasing EEG complexity and decreasing with experience. EEG reports can be provided within 24 h. SIGNIFICANCE: Clinical standard and sleep-deprived EEG reporting with SCORE EEG has acceptable reporting times.

Combined variants in reading epilepsy; coexisting anterior and posterior variants camouflaged as heat cramps where the patient finds his own diagnosis searching the internet.

Reading epilepsy is a form of reflex-induced seizures. Two entities are postulated as part of a clinical spectrum; one anterior variant with jaw jerks and orofacial myoclonia and another posterior variant with visual symptoms and alexia or dyslexia. We present a case with suggestible evidence of both conditions coexisting within the same patient, a finding that, to our knowledge, has not been previously reported. The diagnosis in this specific case was contributed to by the patient searching the internet.

Immunotherapies influence the influenza vaccination response in multiple sclerosis patients: an explorative study.

BACKGROUND: The immunogenicity of influenza vaccines in MS patients undergoing immunomodulatory treatment is not well studied. OBJECTIVES: This explorative study investigated the influence of immunomodulatory treatment on MS patients receiving pandemic H1N1 (swine flu) vaccination in 2009 and seasonal influenza vaccination in 2010. METHODS: We investigated the immune response to pandemic H1N1 vaccination among 113 MS patients and 216 controls during the pandemic of 2009. We also investigated the serological response to seasonal influenza vaccination (2010 - 2011 season) among 49 vaccinated and 62 non-vaccinated MS patients, versus 73 controls. We evaluated these vaccine responses by haemagglutination inhibition assay. RESULTS: MS patients receiving immunomodulatory treatment had reduced protection (27.4%), compared to controls (43.5%) (p = 0.006), after pandemic H1N1 vaccination (2009). The rates of protection were not influenced by interferon beta treatment (44.4% protected), but were reduced among patients receiving glatiramer acetate (21.6%), natalizumab (23.5%), and mitoxantrone (0.0%). A similar pattern emerged after MS patients received a seasonal influenza vaccination in 2010. CONCLUSIONS: These findings suggest that MS patients receiving immunomodulatory therapies other than interferon beta should be considered for a vaccine response analysis and perhaps be offered a second dose of the vaccine, in cases of insufficient protection.

Guillain-Barré syndrome and adjuvanted pandemic influenza A (H1N1) 2009 vaccines: a multinational self-controlled case series in Europe.

BACKGROUND: The risk of Guillain-Barré syndrome (GBS) following the United States' 1976 swine flu vaccination campaign in the USA led to enhanced active surveillance during the pandemic influenza (A(H1N1)pdm09) immunization campaign. This study aimed to estimate the risk of GBS following influenza A(H1N1)pdm09 vaccination. METHODS: A self-controlled case series (SCCS) analysis was performed in Denmark, Finland, France, Netherlands, Norway, Sweden, and the United Kingdom. Information was collected according to a common protocol and standardised procedures. Cases classified at levels 1-4a of the Brighton Collaboration case definition were included. The risk window was 42 days starting the day after vaccination. Conditional Poisson regression and pooled random effects models estimated adjusted relative incidences (RI). Pseudo likelihood and vaccinated-only methods addressed the potential contraindication for vaccination following GBS. RESULTS: Three hundred and three (303) GBS and Miller Fisher syndrome cases were included. Ninety-nine (99) were exposed to A(H1N1)pdm09 vaccination, which was most frequently adjuvanted (Pandemrix and Focetria). The unadjusted pooled RI for A(H1N1)pdm09 vaccination and GBS was 3.5 (95% Confidence Interval (CI): 2.2-5.5), based on all countries. This lowered to 2.0 (95% CI: 1.2-3.1) after adjustment for calendartime and to 1.9 (95% CI: 1.1-3.2) when we accounted for contra-indications. In a subset (Netherlands, Norway, and United Kingdom) we further adjusted for other confounders and there the RI decreased from 1.7 (adjusted for calendar month) to 1.4 (95% CI: 0.7-2.8), which is the main finding. CONCLUSION: This study illustrates the potential of conducting European collaborative vaccine safety studies. The main, fully adjusted analysis, showed that the RI of GBS was not significantly elevated after influenza A(H1N1)pdm09 vaccination (RI = 1.4 (95% CI: 0.7-2.8). Based on the upper limits of the pooled estimate we can rule out with 95% certainty that the number of excess GBS cases after influenza A(H1N1)pdm09 vaccination would be more than 3 per million vaccinated.

Antipsychotic-induced hyperprolactinemia: a cross-sectional survey.

OBJECTIVE: To investigate the prevalence of hyperprolactinemia and common hyperprolactinemia-related symptoms and explore the association between them in patients using a modern antipsychotic drug regimen and, in addition, investigate the prevalence of the inert fraction of prolactin called macroprolactin, which, to our knowledge, has not been investigated systematically in this population before. Macroprolactin may cause misdiagnosis of hyperprolactinemia. METHOD: A cross-sectional design was applied, and 106 patients who were using antipsychotics for symptoms of psychosis were included. RESULTS: Hyperprolactinemia was found in 39% of the patients. Women were overrepresented in the group with the highest prolactin levels. Macroprolactin was not detected in any cases. Several of the second-generation antipsychotics were associated with hyperprolactinemia. Pearson correlation between prolactin level and symptoms revealed no association, and some patients did not report any symptoms despite grossly elevated levels of biologically active prolactin. CONCLUSIONS: The results suggest that hyperprolactinemia is still an important and prevalent side effect. In patients using antipsychotics with prolactin-elevating potential, prolactin levels should be routinely measured to prevent potential long-term complications of "silent" hyperprolactinemia, although we are still in the early stages of knowing what to do with the information.