| 1. |
- Fällmar, David, et al.
(författare)
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The extent of neuroradiological findings in COVID-19 shows correlation with blood biomarkers, Glasgow coma scale score and days in intensive care
- 2022
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Ingår i: Journal of neuroradiology. - : Elsevier. - 0150-9861 .- 1773-0406. ; 49:6, s. 421-427
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Tidskriftsartikel (refereegranskat)abstract
- Background and purposeA wide range of neuroradiological findings has been reported in patients with coronavirus disease 2019 (COVID-19), ranging from subcortical white matter changes to infarcts, haemorrhages and focal contrast media enhancement. These have been descriptively but inconsistently reported and correlations with clinical findings and biomarkers have been difficult to extract from the literature. The purpose of this study was to quantify the extents of neuroradiological findings in a cohort of patients with COVID-19 and neurological symptoms, and to investigate correlations with clinical findings, duration of intensive care and biomarkers in blood.Material and methodsPatients with positive SARS-CoV-2 and at least one new-onset neurological symptom were included from April until July 2020. Nineteen patients were examined regarding clinical symptoms, biomarkers in blood and MRI of the brain. In order to quantify the MRI findings, a semi-quantitative neuroradiological severity scale was constructed a priori, and applied to the MR images by two specialists in neuroradiology.Results and conclusionsThe score from the severity scale correlated significantly with blood biomarkers of CNS injury (glial fibrillary acidic protein, total-tau, ubiquitin carboxyl-terminal hydrolase L1) and inflammation (C-reactive protein), Glasgow Coma Scale score, and the number of days spent in intensive care. The underlying radiological assessments had inter-rater agreements of 90.5%/86% (for assessments with 2/3 alternatives). Total intraclass correlation was 0.80.Previously reported neuroradiological findings in COVID-19 have been diverse and heterogenous. In this study, the extent of findings in MRI examination of the brain, quantified using a structured report, shows correlation with relevant biomarkers.
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| 2. |
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| 3. |
- Virhammar, Johan, et al.
(författare)
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Acute necrotizing encephalopathy with SARS-CoV-2 RNA confirmed in cerebrospinal fluid
- 2020
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Ingår i: Neurology. - 0028-3878 .- 1526-632X. ; 95:10, s. 445-449
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Tidskriftsartikel (refereegranskat)abstract
- Here, we report a case of COVID-19–related acute necrotizing encephalopathy where SARS-CoV-2 RNA was found in CSF 19 days after symptom onset after testing negative twice. Although monocytes and protein levels in CSF were only marginally increased, and our patient never experienced a hyperinflammatory state, her neurologic function deteriorated into coma. MRI of the brain showed pathologic signal symmetrically in central thalami, subinsular regions, medial temporal lobes, and brain stem. Extremely high concentrations of the neuronal injury markers neurofilament light and tau, as well as an astrocytic activation marker, glial fibrillary acidic protein, were measured in CSF. Neuronal rescue proteins and other pathways were elevated in the in-depth proteomics analysis. The patient received IV immunoglobulins and plasma exchange. Her neurologic status improved, and she was extubated 4 weeks after symptom onset. This case report highlights the neurotropism of SARS-CoV-2 in selected patients and emphasizes the importance of repeated lumbar punctures and CSF analyses in patients with suspected COVID-19 and neurologic symptoms.
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| 4. |
- Abdelhak, Ahmed, et al.
(författare)
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Prognostic performance of blood neurofilament light chain protein in hospitalized COVID-19 patients without major central nervous system manifestations: an individual participant data meta-analysis.
- 2023
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Ingår i: Journal of neurology. - : Springer. - 1432-1459 .- 0340-5354. ; 270:7, s. 3315-3328
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Tidskriftsartikel (refereegranskat)abstract
- To investigate the prognostic value of blood neurofilament light chain protein (NfL) levels in the acute phase of coronavirus disease 2019 (COVID-19).We conducted an individual participant data (IPD) meta-analysis after screening on MEDLINE and Scopus to May 23rd2022. We included studies with hospitalized adult COVID-19 patients without major COVID-19-associated central nervous system (CNS) manifestations and with a measurement of blood NfL in the acute phase as well as data regarding at least one clinical outcome including intensive care unit (ICU)admission, need of mechanical ventilation (MV) and death. We derived the age-adjusted measures NfL Z scores and conducted mixed-effects modelling to test associations between NfL Z scores and other variables, encompassing clinical outcomes. Summary receiver operating characteristic curves (SROCs) were used to calculate the area under the curve (AUC) for blood NfL.We identified 382 records, of which 7 studies were included with a total of 669 hospitalized COVID-19 cases (mean age 66.2±15.0years, 68.1% males). Median NfL Z score at admission was elevated compared to the age-corrected reference population (2.37, IQR: 1.13-3.06, referring to 99th percentile in healthy controls). NfL Z scores were significantly associated with disease duration and severity. Higher NfL Z scores were associated with ahigher likelihood of ICU admission, need ofMV, and death. SROCs revealed AUCs of 0.74, 0.80 and 0.71 for mortality, need ofMV and ICU admission, respectively.Blood NfL levels were elevated in the acute phase of COVID-19 patients without major CNS manifestations and associated with clinical severity and poor outcome. The marker might ameliorate the performance of prognostic multivariable algorithms in COVID-19.
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| 5. |
- Acosta, Stefan, et al.
(författare)
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Engaging patients and caregivers in establishing research priorities for aortic dissection
- 2019
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Ingår i: SAGE Open Medicine. - : Sage Publications. - 2050-3121. ; 7, s. 1-7
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Tidskriftsartikel (refereegranskat)abstract
- Objectives: The aim of this study was to establish the top 10 research uncertainties in aortic dissection together with the patient organization Aortic Dissection Association Scandinavia using the James Lind Alliance concept. Methods: A pilot survey aiming to identify uncertainties sent to 12 patients was found to have high content validity (scale content validity index = 0.91). An online version of the survey was thereafter sent to 30 patients in Aortic Dissection Association Scandinavia and 45 caregivers in the field of aortic dissection. Research uncertainties of aortic dissection were gathered, collated and processed. Results: Together with research priorities retrieved from five different current guidelines, 94 uncertainties were expressed. A shortlist of 24 uncertainties remained after processing for the final workshop. After the priority-setting process, using facilitated group format technique, the ranked final top 10 research uncertainties included diagnostic tests for aortic dissection; patient information and care continuity; quality of life; endovascular and medical treatment; surgical complications; rehabilitation; psychological consequences; self-care; and how to improve prognosis. Conclusion: These ranked top 10 important research priorities may be used to justify specific research in aortic dissection and to inform healthcare research funding decisions.
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| 6. |
- Banote, Rakesh Kumar, et al.
(författare)
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Quantitative proteomic analysis to identify differentially expressed proteins in patients with epilepsy
- 2021
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Ingår i: Epilepsy Research. - : Elsevier BV. - 0920-1211 .- 1872-6844. ; 174
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Tidskriftsartikel (refereegranskat)abstract
- There is a great need for biomarkers in epilepsy, particularly markers of epileptogenesis. A first seizure will lead to epilepsy in 20-45 % of cases, but biomarkers that can identify these individuals are missing. The purpose of this study was to identify potential biomarkers of epilepsy/epileptogenesis in a cohort of adults with new-onset seizures, using quantitative proteomic analysis. Plasma was collected from 55 adults with new-onset seizures and sufficient follow-up to identify epilepsy. After a follow up period of two years, 63.6 % of the cohort had a diagnosis of epilepsy, whereas 36.4 % of patients only had a single seizure. Plasma proteins were extracted and labelled with tandem mass tags, then analyzed using mass spectrometry approach. Proteins that were up- or downregulated by >= 20 % and with a pvalue of <0.05 were considered as differentially expressed and were also annotated to their processes and pathways. Several proteins were differentially expressed in the epilepsy group compared to controls. A total of 1075 proteins were detected, out of which 41 proteins were found to be significantly dysregulated in epilepsy patients. Many of these have been identified in experimental studies of epilepogenesis. We report plasma proteome profiling in new-onset epilepsy in a pilot study with 55 individuals. The identified proteins could be involved in pathways associated with epileptogenesis. The results should be seen as hypothesisgenerating and targeted, confirmatory studies are needed.
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| 7. |
- Bergerum, Carolina, 1967-
(författare)
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Patient and public involvement in hospital quality improvement interventions : the mechanisms, monitoring and management
- 2022
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- This dissertation focuses on the mechanisms, monitoring and management of patient and public involvement in hospital quality improvement (QI) interventions. Findings from a literature review generated an initial programme theory (PT) on active patient involvement in healthcare QI interventions (Paper 1). Empirical studies were also undertaken in order to describe what was actually happening in the hospital QI teams and what patients and professionals experience influence their joint involvement (Paper 2), and to compare hospital leaders’ and managers’ experiences of managing QI interventions involving patients and the public (Paper 3). Finally, it was studied how patient-reported measures stimulate patient involvement in QI interventions in practice (Paper 4). The research had a qualitative design. The approach was descriptive and comparative, and the studies were carried out prospectively. Data were collected in two hospital organisations in Sweden and in one hospital organisation in the Netherlands. Data collection methods were a literature search (Paper 1), interviews and field observations (Paper 2 and 3) and data collection meetings (Paper 4). Altogether, 93 team meetings and meetings between the team leaders and management were attended and a total of 20 days of study visits with different forms of meetings were made. Twelve patients, 12 healthcare professionals and 17 and 8 hospital leaders and managers, respectively, participated in the interviews and data collection meetings. Realist synthesis was used to formulate the initial PT (Paper 1). Constructivist grounded theory was used to analyse and describe what was happening in the QI teams and how it was experienced by the team members (Paper 2). To compare hospital leaders’ and managers’ different, contextual meanings in Sweden and the Netherlands, the reflexive thematic analysis informed by critical realism was used (Paper 3). To order, manage and map data from 31 examples of local QI interventions associated to patient-reported measures, the framework method was used (Paper 4). The results formulate a generic PT on the mechanisms, monitoring and management perspectives of co-produced QI interventions in hospital services where patients and the public are involved. The PT provides a hypothesis on the various mechanisms at play and outcomes obtained at the different levels of hospital organisations in the process. It is argued that focus should be on experiences, interaction, relationships and dialogue, integration of context, and the matching of hospital resources to patient and public demands and needs. Subsequently, the outcome will be the resources and reasoning interplay resulting in actions and processes, experiences and knowledge, ‘product’ benefits, emotions, judgements and motivations. Monitoring constitutes an important feedback loop to enable such learnings. The PT aligns the perspectives of the clinical microsystem, improvement science and the service-dominant logic, and has a potential to explain how patient and public involvement in QI interventions might work.
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| 8. |
- Cunningham, Janet, et al.
(författare)
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Antibody Responses to Severe Acute Respiratory Syndrome Coronavirus 2 in the Serum and Cerebrospinal Fluid of Patients With Coronavirus Disease 2019 and Neurological Symptoms
- 2022
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Ingår i: Journal of Infectious Diseases. - : Oxford University Press (OUP). - 0022-1899 .- 1537-6613. ; 225:6, s. 965-970
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Tidskriftsartikel (refereegranskat)abstract
- Antibody responses to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in serum and cerebrospinal fluid (CSF) samples from 16 patients with coronavirus disease 2019 and neurological symptoms were assessed using 2 independent methods. Immunoglobulin G (IgG) specific for the virus spike protein was found in 81% of patients in serum and in 56% in CSF. SARS-CoV-2 IgG in CSF was observed in 2 patients with negative serological findings. Levels of IgG in both serum and CSF were associated with disease severity (P < .05). All patients with elevated markers of central nervous system damage in CSF also had CSF antibodies (P = .002), and CSF antibodies had the highest predictive value for neuronal damage markers of all tested clinical variables.
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| 9. |
- Cunningham, Janet L, et al.
(författare)
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Anti-SARS-CoV2 antibody responses in serum and cerebrospinal fluid of COVID-19 patients with neurological symptoms.
- 2022
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Ingår i: The Journal of infectious diseases. - : Oxford University Press (OUP). - 1537-6613 .- 0022-1899. ; 225:6, s. 965-970
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Tidskriftsartikel (refereegranskat)abstract
- Antibody responses to SARS-CoV-2 in serum and CSF from 16 COVID-19 patients with neurological symptoms were assessed using two independent methods. IgG specific for the virus spike protein was found in 81% of cases in serum and in 56% in CSF. SARS-CoV-2 IgG in CSF was observed in two cases with negative serology. Levels of IgG in both serum and CSF were associated with disease severity (p<0.05). All patients with elevated markers of CNS damage in CSF also had CSF antibodies (p=0.002), and CSF antibodies had the highest predictive value for neuronal damage markers of all tested clinical variables.
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| 10. |
- Dagiasi, Ioanna, et al.
(författare)
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Treatment of epilepsy in multiple sclerosis
- 2018
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Ingår i: Seizure-European Journal of Epilepsy. - : Elsevier BV. - 1059-1311 .- 1532-2688. ; 58, s. 47-51
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Tidskriftsartikel (refereegranskat)abstract
- Purpose: The prevalence of epilepsy is increased in multiple sclerosis (MS), but information on AED treatment and seizure outcome is scarce. We describe epilepsy characteristics including the use of AEDs and proportion of seizure-free patients at two tertiary hospitals in Sweden. Method: We retrospectively studied electronic medical records of all patients with a diagnosis of MS and seizures at Sahlgrenska university hospital and Uppsala university hospital. Clinical data were reviewed until 2017. Results: We identified a total of 62 MS patients with at least one seizure. Median age at the first seizure (before or after MS) was 41 years (range 0-80). The most common MS disease course at the first seizure was secondary progressive MS, the neurological disability was considerable, and most patients had several MRI lesions at their first seizure. The first EEG demonstrated epileptiform discharges in 38% and unspecific pathology in 40%. Current seizure status could be determined for 37 patients. Out of these, 46% had been seizure free for more than one year at last follow-up. The majority of patients (65%) were on monotherapy at last follow-up. Carbamazepine was the most commonly used first AED, with a retention rate of 52%. No individual AED was associated with a particularly high rate of seizure freedom. The most common reason for discontinuation of the first AED was side-effects. Conclusion: Seizure freedom rates were low, perhaps indicating a need for higher ambitions in management. Side effects of AEDs may be a particular concern when treating epilepsy in patients with MS. (C) 2018 British Epilepsy Association. Published by Elsevier Ltd. All rights reserved.
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| 11. |
- Fahlström, Markus, et al.
(författare)
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Evaluation of Arterial Spin Labeling MRI : Comparison with 15O-Water PET on an Integrated PET/MR Scanner
- 2021
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Ingår i: Diagnostics (Basel). - : MDPI. - 2075-4418. ; 11:5
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Tidskriftsartikel (refereegranskat)abstract
- Cerebral blood flow (CBF) measurements are of high clinical value and can be acquired non-invasively with no radiation exposure using pseudo-continuous arterial spin labeling (ASL). The aim of this study was to evaluate accordance in resting state CBF between ASL (CBFASL) and 15O-water positron emission tomography (PET) (CBFPET) acquired simultaneously on an integrated 3T PET/MR system. The data comprised ASL and dynamic 15O-water PET data with arterial blood sampling of eighteen subjects (eight patients with focal epilepsy and ten healthy controls, age 21 to 61 years). 15O-water PET parametric CBF images were generated using a basis function implementation of the single tissue compartment model. Cortical and subcortical regions were automatically segmented using Freesurfer. Average CBFASL and CBFPET in grey matter were 60 ± 20 and 75 ± 22 mL/100 g/min respectively, with a relatively high correlation (r = 0.78, p < 0.001). Bland-Altman analysis revealed poor agreement (bias = −15 mL/100 g/min, lower and upper limits of agreements = −16 and 45 mL/100 g/min, respectively) with a negative relationship. Accounting for the negative relationship, the width of the limits of agreement could be narrowed from 61 mL/100 g/min to 35 mL/100 g/min using regression-based limits of agreements. Although a high correlation between CBFASL and CBFPET was found, the agreement in absolute CBF values was not sufficient for ASL to be used interchangeably with 15O-water PET.
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| 12. |
- Frithiof, Robert, et al.
(författare)
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Critical illness polyneuropathy, myopathy and neuronal biomarkers in COVID-19 patients: A prospective study
- 2021
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Ingår i: Clinical Neurophysiology. - : Elsevier BV. - 1388-2457 .- 1872-8952. ; 132:7, s. 1733-1740
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Tidskriftsartikel (refereegranskat)abstract
- Objective: The aim was to characterize the electrophysiological features and plasma biomarkers of critical illness polyneuropathy (CIN) and myopathy (CIM) in coronavirus disease 2019 (COVID-19) patients with intensive care unit acquired weakness (ICUAW). Methods: An observational ICU cohort study including adult patients admitted to the ICU at Uppsala University Hospital, Uppsala, Sweden, from March 13th to June 8th 2020. We compared the clinical, electrophysiological and plasma biomarker data between COVID-19 patients who developed CIN/CIM and those who did not. Electrophysiological characteristics were also compared between COVID-19 and non-COVID-19 ICU patients. Results: 111 COVID-19 patients were included, 11 of whom developed CIN/CIM. Patients with CIN/CIM had more severe illness; longer ICU stay, more thromboembolic events and were more frequently treated with invasive ventilation for longer than 2 weeks. In particular CIN was more frequent among COVID-19 patients with ICUAW (50%) compared with a non-COVID-19 cohort (0%, p = 0.008). Neurofilament light chain (NfL) and glial fibrillary acidic protein (GFAp) levels were higher in the CIN/CIM group compared with those that did not develop CIN/CIM (both p = 0.001) and correlated with nerve amplitudes. Conclusions: CIN/CIM was more prevalent among COVID-19 ICU patients with severe illness. Significance: COVID-19 patients who later developed CIN/CIM had significantly higher NfL and GFAp in the early phase of ICU care, suggesting their potential as predictive biomarkers for CIN/CIM. (c) 2021 International Federation of Clinical Neurophysiology. Published by Elsevier B.V. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).
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| 13. |
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| 14. |
- Halawa, Imad, et al.
(författare)
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Hypoglycemia and risk of seizures : A retrospective cross-sectional study
- 2015
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Ingår i: Seizure. - : Elsevier BV. - 1059-1311 .- 1532-2688. ; 25, s. 147-149
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Tidskriftsartikel (refereegranskat)abstract
- Purpose: Few studies have been dedicated to assess neurological symptoms in relations to hypoglycemia. In this study we investigated the association between different levels of hypoglycemia and the occurrence of epileptic seizures in patients without a prior diagnosis of epilepsy. Method: A retrospective cross-sectional study. Results: We identified 388 individuals from a laboratory database in Swedish regional hospital who had been found to have a glucose value of <= 3.5 mM between January and December 2009. Medical records were reviewed. Hypoglycemia was defined at three different categories: 0-2 mM (40 patients), 2.1-3 mM (154 patients) and 3.1-3.5 mM (194 patients). 14 patients had disturbance of consciousness including 3 with seizures. The majority of cases had coma, a generalized tonic-clonic seizure was seen only when s-glucose dropped below 2.0 mM. Two cases with focal seizure were noted, one at s-glucose 2.0 mM, and one at s-glucose 3.3 mM. The absolute risks (95% confidence interval) for having major neurological symptoms at glucose levels of <= 2.0 mM were 0.25 (0.13-0.41), 0.02 (0-0.06) at 2.1-3.0 mM and 0.01 (0-0.03) at 3.1-3.5 mM. Conclusion: Coma is the most common neurological symptom related to hypoglycemia. Epileptic seizures are rare and not as common as previously assumed.
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| 15. |
- Hansen, Julia, et al.
(författare)
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Cause of death in patients with poststroke epilepsy: Results from a nationwide cohort study.
- 2017
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Ingår i: PloS one. - : Public Library of Science (PLoS). - 1932-6203. ; 12:4
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Tidskriftsartikel (refereegranskat)abstract
- The risk of death is increased for persons with epilepsy. The literature on causes of death in epilepsy is based mainly on cohorts with epilepsy of mixed aetiologies. For clinical purposes and improved understanding of mortality in different epilepsies, more information is needed on mortality in epilepsies of specific causes. In poststroke epilepsy (PSE), seizures occur in a setting of vascular disease and high mortality rates. The extent to which epilepsy contributes to mortality in this patient group is poorly understood. We therefore aimed to describe causes of death (COD) in PSE on a national scale. A previously identified cohort of 7740 patients with epilepsy or seizures after a stroke in 2005-2010 was investigated. A total of 4167 deaths occurred before the end of 2014. The standardized mortality ratio for the study cohort was 3.56 (95% CI: 3.45-3.67). The main underlying causes of death were disorders of the circulatory system (60%) followed by neoplasms (12%). Diseases of the nervous system were the sixth leading underlying COD (3%), and epilepsy or status epilepticus was considered the underlying COD in approximately a similar proportion of cases as neurodegenerative disorders (0.9% and 1.1%, respectively). Epilepsy was considered a contributing COD in 14% of cases. Our findings highlight the importance of optimal management of vascular morbidity in patients with PSE. The large proportion of patients with epilepsy as a contributing COD indicate the need of high ambitions also regarding the management of seizures in patients with PSE.
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| 16. |
- Juran, Stephanie A, et al.
(författare)
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Unilateral Resection of the Anterior Medial Temporal Lobe Impairs Odor Identification and Valence Perception
- 2015
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Ingår i: Frontiers in Psychology. - : Frontiers Media S.A.. - 1664-1078. ; 6
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Tidskriftsartikel (refereegranskat)abstract
- The anterior medial temporal lobe (TL), including the amygdala, has been implicated in olfactory processing, e.g., coding for intensity and valence, and seems also involved in memory. With this background, the present study evaluated whether anterior medial TL-resections in TL epilepsy affected intensity and valence ratings, as well as free and cued identification of odors. These aspects of odor perception were assessed in 31 patients with unilateral anterior medial TL-resections (17 left, 14 right) and 16 healthy controls. Results suggest that the anterior medial TL is in particular necessary for free, but also cued, odor identification. TL resection was also found to impair odor valence, but not intensity ratings. Left resected patients rated nominally pleasant and unpleasant odors as more neutral suggesting a special role for the left anterior TL in coding for emotional saliency in response to odors.
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| 17. |
- Kumlien, Christine, et al.
(författare)
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Research priorities to prevent and treat diabetic foot ulcers-A digital James Lind Alliance Priority Setting Partnership
- 2022
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Ingår i: Diabetic Medicine. - : John Wiley & Sons. - 0742-3071 .- 1464-5491. ; 39:11
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Tidskriftsartikel (refereegranskat)abstract
- Aim To establish outcomes of a priority setting partnership between participants with diabetes mellitus and clinicians to identify the top 10 research priorities for preventing and treating diabetic foot ulcers (DFUs). Methods Due to the COVID-19 pandemic, the James Lind Alliance Priority Setting Partnership process was adapted into a digital format which involved a pilot survey to identify understandable uncertainties with high relevance for participants tested by calculating the content validity index; a main survey answered by 53 participants living with diabetes and 49 clinicians; and a final digital workshop to process and prioritise the final top 10 research priorities. Results The content validity index was satisfactory for 20 out of 25 uncertainties followed by minor changes and one additional uncertainty. After we processed the 26 uncertainties from the main survey and seven current guidelines, a list of 28 research uncertainties remained for review and discussion in the digital workshop. The final top 10 research priorities included the organisation of diabetes care; screening of diabetes, impaired blood circulation, neuropathy, and skin properties; vascular surgical treatment; importance of self-care; help from significant others; pressure relief; and prevention of infection. Conclusion The top 10 research priorities for preventing and treating DFUs represent consensus areas from persons living with diabetes and clinicians to guide future research. These research priorities can justify and inform strategic allocation of research funding. The digitalisation of James Lind Alliance methodology was feasible.
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| 18. |
- Kumlien, Johan, et al.
(författare)
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Urinary excretion of a glucose-containing tetrasaccharide. A parameter for increased degradation of glycogen
- 1988
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Ingår i: Clinica Chimica Acta. - : Elsevier BV. - 0009-8981. ; 176:1, s. 39-48
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Tidskriftsartikel (refereegranskat)abstract
- The urinary excretion of a glucose-containing oligosaccharide, Glc alpha[1-6Glc alpha[1-4Glc alpha[1-4Glc, (Glc4) has been measured in various physiological and pathological conditions. The Glc4 content of 24 h samples from the same individual was relatively constant, whereas 2 h samples showed up to 4-fold variations in Glc4 concentration. This variation is associated mainly with increased excretion of Glc4 after meals. A carbohydrate-rich diet, starvation or a protein-rich diet, and intense physical activity all affected the urinary excretion of Glc4. Both oral and intravenous administration of glycogen in a Rhesus monkey resulted in increased excretion of Glc4. When Glc4 itself was injected intravenously in small amounts renal clearance was rapid and complete. In contrast, injection of a larger amount resulted in incomplete (approximately 10%) renal clearance, probably due to uptake and metabolism of the oligosaccharide. In patients with glycogen storage diseases, certain malignancies, and pancreatitis, 24 h urinary Glc4 excretion exceeded the normal range. The diagnostic implications of these observations deserve evaluation. The results presented suggest a need for standardization of nutritional status and physical activity when monitoring urinary Glc4 excretion for diagnostic purposes.
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| 19. |
- Larsson, David, 1986, et al.
(författare)
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Retention rate of first antiepileptic drug in poststroke epilepsy: A nationwide study
- 2019
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Ingår i: Seizure. - : Elsevier BV. - 1059-1311 .- 1532-2688. ; 64, s. 29-33
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Tidskriftsartikel (refereegranskat)abstract
- Purpose: To describe the retention rates of first antiepileptic drugs (AEDs) in patients with poststroke epilepsy on a nationwide scale. Methods: The Swedish Stroke Register, which has 94% coverage and high-resolution data on stroke, comorbidities, and disability, was cross-referenced to the National Patient Register, Drug Register, and Cause-of-Death Register. Patients with onset of AED-treated epilepsy after stroke in 2005–2010 were included. An algorithm based on prescription renewal intervals was used to analyze treatment data until the end of 2014. Results: A total of 4991 patients were included. First AEDs analyzed were carbamazepine (n = 2373), valproic acid (n = 943), levetiracetam (n = 555), lamotrigine (n = 519), phenytoin (n = 176), and oxcarbazepine (n = 89). The five-year retention rate was highest for lamotrigine (75%, 95%CI:70.4–79.4), followed by levetiracetam (69%, 95%CI:62.9–74.3), oxcarbazepine (68%, 95%CI:55.2–79.8), valproic acid (62%, 95%CI:57.8–66.4), carbamazepine (60%, 95%CI:57.6–62.4), and phenytoin (55%, 95%CI:45.2–64.0). There were minor differences in baseline characteristics with low levels of disability being slightly more common in patients treated with lamotrigine and levetiracetam. Atrial fibrillation and hypertension were more common in patients treated with levetiracetam, and atrial fibrillation was less common in patients treated with carbamazepine. In a Cox model adjusted for baseline characteristics, the risk of discontinuation was lower for lamotrigine (HR 0.53, 95%CI:0.43-0.67) and levetiracetam (HR 0.75, 95%CI:0.60-0.94) when compared to carbamazepine. Conclusions: Lamotrigine and levetiracetam have higher retention rates than carbamazepine in poststroke epilepsy. This is in agreement with existing small RCTs in this patient group. © 2018 British Epilepsy Association
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| 20. |
- Lindqvist, Isa, et al.
(författare)
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Myoclonus in patients with COVID-19 : Findings of autoantibodies against brain structures in cerebrospinal fluid
- 2023
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Ingår i: European Journal of Neurology. - : John Wiley & Sons. - 1351-5101 .- 1468-1331. ; 30:10, s. 3142-3148
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Tidskriftsartikel (refereegranskat)abstract
- Background and purposeCOVID-19 is associated with multiple neurological manifestations. The clinical presentation, trajectory, and treatment response for three cases of myoclonus during COVID-19 infection, with no previous neurological disease, are decsribed.MetodsAnalysis of cerebrospinal fluid from the cases using indirect immunohistochemistry.ResultsAntibodies against rodent brain tissue, and similarities in staining patterns were observed, indicating the presence of antineuronal immunoglobulin G autoantibodies targeting astrocytes in the hippocampus.ConclusionOur results demontrate cerebrospinal fluid antineuronal antibodies indicating an an autoimmune involvment in the pathogenesis in COVID-19 associated myoclonus.
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| 21. |
- Lindskog, Cecilia, et al.
(författare)
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Protein Expression Profile of ACE2 in the Normal and COVID-19-Affected Human Brain.
- 2022
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Ingår i: Journal of Proteome Research. - : American Chemical Society (ACS). - 1535-3893 .- 1535-3907. ; 21:9, s. 2137-2145
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Tidskriftsartikel (refereegranskat)abstract
- SARS-coronavirus 2 (SARS-CoV-2) that caused the coronavirus disease 2019 (COVID-19) pandemic has posed to be a global challenge. An increasing number of neurological symptoms have been linked to the COVID-19 disease, but the underlying mechanisms of such symptoms and which patients could be at risk are not yet established. The suggested key receptor for host cell entry is angiotensin I converting enzyme 2 (ACE2). Previous studies on limited tissue material have shown no or low protein expression of ACE2 in the normal brain. Here, we used stringently validated antibodies and immunohistochemistry to examine the protein expression of ACE2 in all major regions of the normal brain. The expression pattern was compared with the COVID-19-affected brain of patients with a varying degree of neurological symptoms. In the normal brain, the expression was restricted to the choroid plexus and ependymal cells with no expression in any other brain cell types. Interestingly, in the COVID-19-affected brain, an upregulation of ACE2 was observed in endothelial cells of certain patients, most prominently in the white matter and with the highest expression observed in the patient with the most severe neurological symptoms. The data shows differential expression of ACE2 in the diseased brain and highlights the need to further study the role of endothelial cells in COVID-19 disease in relation to neurological symptoms.
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| 22. |
- Mulder, Jan, et al.
(författare)
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Autoimmune Encephalitis Presenting With Malignant Catatonia in a 40-Year-Old Male Patient With COVID-19
- 2021
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Ingår i: American Journal of Psychiatry. - : American Psychiatric Association Publishing. - 0002-953X .- 1535-7228. ; 178:6, s. 485-489
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- A 40-year-old man who had previously had symptoms of and a positive test for COVID-19, but had no other previous medical or psychiatric conditions or medication, presented to the emergency unit with acute debut of agitation, grimacing, and repetitive speech and movements (verbigeration and stereotypies); his behavior was bizarre, disorganized, hyperkinetic, and uncooperative and met DSM-5 criteria for catatonia. Twenty-two days before admission, the patient had developed COVID-19-related respiratory symptoms and fatigue, which did not require hospital care. He had tested positive for SARS-CoV-2 RNA in a naso-pharyngeal swab using the Abbott RealTime SARSCoV-2 assay on the Abbott m2000 platform (day 14; Figure 1A). Anosmia and ageusia were not present. During the several days before admission, he had suffered from a headache. On admission (day 22), he no longer had respiratory symptoms but he did have a fever (38.4 degrees C). He made no eye contact, his reflexes were normal, and Babinski's sign was absent. Treatment with antibiotics and acyclovir was initiated until the tests excluded bacterial infection and herpes encephalitis. Brain CT, MRI, and blood tests were unremarkable. The patient was lightly sedated with midazolam, followed with dexmedetomidine. Neuroleptics were not used. Lumbar puncture showed a high red blood cell count (19,000 cellsx10(6)/L) secondary to traumatic lumbar puncture. CSF cell count indicated pleocytosis, with 23x10(6)/L mononuclear and 8x10(6)/L polymorphonuclear cells. Signs of blood-brain barrier disruption were present, with elevated albumin levels in CSF, at 838 mg/L (reference, <400 mg/L), and the CSF/serum albumin quotient was 15.6 (reference, <6.8). Interleukin-6 (IL-6) in CSF was elevated at 102.1 pg/mL ( reference, <5 pg/mL), but CSF levels of neurofilament light chain (NfL), glial fibrillary acidic protein (GFAP), and tau protein were normal. PCR tests for SARS- CoV-2 were repeatedly negative in CSF and nasopharyngeal swabs. Antineuronal antibodies against N-methyl-D-aspartate receptor (NMDAR), glutamic acid decarboxylase, contactin-associated protein-like 2, leucine-rich, glioma inactivated 1, and ganglioside antibodies in serum and CSF were negative (Euroimmune, Lubeck, Germany). Hours later, the patient's state deteriorated, and his temperature rose to 39 degrees C. He became mutistic and showed signs of autonomic instability, with recurrent episodes of fluctuating heart rate and arterial blood pressure and periods of oxygen desaturation (Figure 1B). The hypertension was difficult to treat, despite high doses of clonidine and labetalol. Plasma lactate levels varied between 0.6 and 8 mmol/L (reference, 0.8-2.0 mmol/L), but myoglobulin and creatine kinase myocardial band (CKMB) remained normal. The patient's pupil size, reaction to light, and oculocephalic reflex were normal. Slow, horizontal roving eye movements were noted. The patient displayed decorticate posturing and increased tonus; he resisted movement of arms and jaw but had normal tonus in the legs. Hyperreflexia was present, with bilateral foot clonus and Babinski's sign but no neck stiffness. Anesthesia was induced with propofol and clonidine to facilitate endotracheal intubation. D-Dimer was slightly elevated (1.2 mg/L; reference <0.5 mg/L), without signs of thromboembolic events. Respiration and cardiovascular function remained stable. Continuous EEG monitoring showed nonspecific slowing with left hemisphere predominance without epileptiformactivity. An episode of asystole with spontaneous recovery, episodes of bradycardia of 27 bpm and repeated P waves without QRS complexes were interpreted as third-degree atrioventricular block. Signs of autoimmune encephalitis were present, but this case did not meet the proposed criteria (1, 2). Standard radiological findings were normal, and the discrete pleocytosis and elevated protein in CSF was nonspecific. Although the diagnosis remained uncertain, parainfectious autoimmune encephalitis was still suspected. Plasmapheresis was initiated and repeated three times over 4 days. After two courses, the patient was extubated and was autonomically stable. Eye movement was normalized and hyperreflexia was less prominent, but bilateral Babinski's sign persisted. Treatment was initiated with 1 g methylprednisolone per day. On day 28, the patient showed a dramatic improvement. He was awake, oriented, and communicative but had no memories from the past several days. He was distracted by complex visual hallucinations of black and white figures (animals and famous people) appearing on his right side. He described them as being in a mirror (suspected polyopia). These figures were often stationary but could make gestures. He also described an experience of feeling that the world was different-strange and unreal, with brighter colors (suspected hyperchromatopsia and derealization). He had frequent episodes of failing to recognize his right hand and leg as his own and experienced their movement as unexpected (alien hand syndrome). He denied the presence of other perceptual disturbances. His understanding of Swedish, his second language, seemed intact, but his responses were mostly monosyllabic. He could name his children and give his personal identification number but was slow and made mistakes in naming the months. Mild visual object agnosia was present. Simultanagnosia was prominent, he showed deficits in isolating figures in a tangled pictorial array, and he could depict details but excluded the global features of complex pictures. He could recall one of three objects after a short delay and draw a correct clock but required three repetitions of the instructions. He had difficulty mirroring and performing fine movements. Finally, he showed no signs of visual neglect and could read text. The patient's EEG was normal. A second lumbar puncture showed pleocytosis, 10 mononuclear cells and 1 polymorphonuclear cell x10(6)/L, elevated IgG levels and IgG index, and two oligoclonal bands in CSF not represented in serum, indicating intrathecal production of antibodies. The IL-6 level in CSF was normalized. GFAP and tau remained normal, but NfL was increased to 1,030 ng/L (reference, <890 ng/L). A second MRI and a standard neurological examination on day 31 were normal. The hallucinations were less frequent. The patient described increased emotional lability and mental fatigue, with disturbed short-term memory and decision making. He also found it challenging to recognize the voices and faces of acquaintances. Serology on day 33 was strongly positive (index 8.88 S/CO [signal/cutoff]) for IgG against SARS- CoV-2 analyzed with the CE-labeled SARS- CoV-2 IgG kit with nucleoprotein-based antigen with the Abbott Architect i2000SR Analyzer at the Laboratory of Clinical Microbiology, Uppsala University Hospital, as previously described (3). [F-18]fluorodeoxyglucose ([F-18]FDG) PET scan on day 35 (after treatment) showed high bilateral uptake in the striatum (caudate nucleus and putamen) compared with the cortex (Figure 1C). Using immunohistochemistry in the research lab, we detected IgG autoantibodies against mouse brain neuronal proteins in serum and CSF collected at admission (Figure 2). Neuronal labeling intensity was strongest in the CA3 in the hippocampal formation, layer V in the somatosensory cortex, and the paraventricular and reticular nucleus in the thalamus. A subset of ependymal cells located in the ventricle wall and choroid plexus revealed strong immunoreactivity of the (peri)nuclear compartment and cytoplasm. Immunoreactivity of neuropil was most intense in the caudate putamen, revealing neuronal processes and spine-like structures. Posttreatment IgG immunoreactivity in the (peri)nuclear compartment and neuropil was notably reduced, reaching the levels of reference CSF and serum.
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| 23. |
- Remberger, Mats, et al.
(författare)
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Improved survival after allogeneic hematopoietic stem cell transplantation in recent years : A single-center study
- 2011
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Ingår i: Biology of blood and marrow transplantation. - : Elsevier BV. - 1083-8791 .- 1523-6536. ; 17:11, s. 1688-1697
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Tidskriftsartikel (refereegranskat)abstract
- We analyzed the outcome of allogeneic hematopoietic stem cell transplantation (HSCT) over the past 2 decades. Between 1992 and 2009, 953 patients were treated with HSCT, mainly for a hematologic malignancy. They were divided according to 4 different time periods of treatment: 1992 to 1995, 1996 to 2000, 2001 to 2005, and 2006 to 2009. Over the years, many factors have changed considerably regarding patient age, diagnosis, disease stage, type of donor, stem cell source, genomic HLA typing, cell dose, type of conditioning, treatment of infections, use of granulocyte-colony stimulating factor (G-CSF), use of mesenchymal stem cells, use of cytotoxic T cells, and home care. When we compared the last period (2006-2009) with earlier periods, we found slower neutrophil engraftment, a higher incidence of acute graft-versus-host disease (aGVHD) of grades II-IV, and less chronic GVHD (cGHVD). The incidence of relapse was unchanged over the 4 periods (22%-25%). Overall survival (OS) and transplant-related mortality (TRM) improved significantly in the more recent periods, with the best results during the last period (2006-2009) and a 100-day TRM of 5.5%. This improvement was also apparent in a multivariate analysis. When correcting for differences between the 4 groups, the hazard ratio for mortality in the last period was 0.59 (95% confidence interval [CI]: 0.44-0.79; P < .001) and for TRM it was 0.63 (CI: 0.43-0.92; P = .02). This study shows that the combined efforts to improve outcome after HSCT have been very effective. Even though we now treat older patients with more advanced disease and use more alternative HLA nonidentical donors, OS and TRM have improved. The problem of relapse still has to be remedied. Thus, several different developments together have resulted in significantly lower TRM and improved survival after HSCT over the last few years.
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| 24. |
- Taxiarchis, Apostolos, et al.
(författare)
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Extracellular vesicles in plasma and cerebrospinal fluid in patients with COVID-19 and neurological symptoms
- 2024
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Ingår i: International Journal of Laboratory Hematology. - : John Wiley & Sons. - 1751-5521 .- 1751-553X. ; 46:1, s. 42-49
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Tidskriftsartikel (refereegranskat)abstract
- Introduction:Increased levels of extracellular vesicles (EVs) are associated with haemostatic disturbances in various clinical settings. However, their role in COVID-19 patients is still not fully clear. In the present study we investigated EVs in plasma from patients with COVID-19 and neurological symptoms in relation to the activation of coagulation.Methods:Nineteen COVID-19 patients with neurological symptoms and twenty-three aged-matched healthy individuals were included. Global coagulation assays were performed and levels of EVs were determined by flow-cytometry in plasma and cerebrospinal fluid (CSF).Results:A procoagulant state characterized by significantly increased overall coagulation- (OCP) and overall haemostatic potential (OHP), diminished overall fibrinolytic potential (OFP) together with a denser fibrin structure was found in patients with COVID-19. Flow cytometry revealed elevated levels of plasma circulating EVs derived from neutrophils (MPO+) and platelets (CD61+), as well as EVs expressing phosphatidylserine (PS+) and complement component C5b-9 (TCC+) in patients with COVID-19 compared with controls. The concentrations of PS+, CD61+ and TCC+ EVs were positively correlated with OCP and OHP in COVID-19 patients. Moreover, we identified CD61+, MPO+ and endothelial cell-derived EVs, as well as EVs exposing PS and TCC in the CSF of patients suffering from neurological symptoms during COVID-19.Conclusion:The unique finding in this study was the presence of EVs in the CSF of COVID-19 patients with neurologic manifestations as well as higher expression of complement protein on circulating plasma EVs. EVs may indicate blood-brain barrier damage during SARS-COV-2 infection.
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| 25. |
- Vasaitis, Lilian, et al.
(författare)
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Histopathological findings in the landscape of IgG4-related pathology in patients with pituitary dysfunction : Review of six cases
- 2021
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Ingår i: Journal of neuroendocrinology. - : John Wiley & Sons. - 0953-8194 .- 1365-2826. ; 33:3
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Tidskriftsartikel (refereegranskat)abstract
- IgG4-related hypophysitis (IgG4-RH) is increasingly being reported as an isolated entity or, less frequently, as a manifestation of a multiorgan IgG4-related disease (IgG4-RD), in which typical histopathology is a cornerstone for the diagnosis. We aimed to describe the histopathological changes in the surgical specimens from patients with clinical signs of pituitary disease that fulfilled the current diagnostic criteria for IgG4-RH. Histopathological features were correlated with clinical and radiological findings. Of 19 patients with pituitary dysfunction and inflammatory changes in the surgical pituitary specimen operated on during 2011-2019, we identified five patients with typical IgG4-related pathology (lymphoplasmacytic infiltration with more than 10 IgG4-positive plasma cells per one high power microscopic field, representing at least 40% of all plasma cells and at least focal storiform fibrosis). One patient with diabetes insipidus and pachymeningitis with IgG4-related changes in a biopsy from the dura was also included. Additional histopathological changes that typically are not part of the IgG4-RH were observed: Rathke's cleft cyst in four and granulomatous changes in two patients. One patient had an elevated serum IgG4 level and systemic manifestations that could be associated with the systemic IgG4-RD. Our findings indicate that pure IgG4-RH is uncommon. All patients with pituitary dysfunction, beyond typical IgG4-related pathology, had other pathological findings that could trigger the secondary IgG4-response. Both primary pathology and secondary IgG4-related features should be reported in patients with pituitary dysfunction because their co-occurrence may cause atypical clinical and imaging features, and unexpected response to surgical and pharmacological treatment. The current criteria for the diagnosis of IgG4-RH can lead to overdiagnosis of IgG4-RH if additional pathological changes are not taken into consideration. The classification criteria of IgG4-RD proposed by the American College of Rheumatology/European League Against Rheumatism could help classify patients more properly as IgG4-RH if applied to the pituitary gland.
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| 26. |
- Virhammar, Johan, et al.
(författare)
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Biomarkers for central nervous system injury in cerebrospinal fluid are elevated in COVID-19 and associated with neurological symptoms and disease severity
- 2021
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Ingår i: European Journal of Neurology. - : Wiley. - 1351-5101 .- 1468-1331. ; 28:10, s. 3324-3331
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Tidskriftsartikel (refereegranskat)abstract
- Background and purpose: Neurological symptoms have been frequently reported in hospitalized patients with coronavirus disease 2019 (COVID-19), and biomarkers of central nervous system (CNS) injury are reported to be increased in plasma but not extensively studied in cerebrospinal fluid (CSF). This study examined CSF for biomarkers of CNS injury and other pathology in relation to neurological symptoms and disease severity in patients with neurological manifestations of COVID-19. Methods: Nineteen patients with neurological symptoms and mild to critical COVID-19 were prospectively included. Extensive analysis of CSF, including measurement of biomarkers of CNS injury (neurofilament light chain [NfL] protein, glial fibrillary acidic protein [GFAp], and total tau), was performed and compared to neurological features and disease severity. Results: Neurological symptoms included altered mental status (42%), headache (42%), and central (21%) and peripheral weakness (32%). Two patients demonstrated minor pleocytosis, and four patients had increased immunoglobulin G levels in CSF. Neuronal autoantibody testing using commercial tests was negative in all patients. Increased CSF levels of NfL protein, total tau, and GFAp were seen in 63%, 37%, and 16% of patients, respectively. Increased NfL protein correlated with disease severity, time in intensive care, and level of consciousness. NfL protein in CSF was higher in patients with central neurological symptoms. Conclusions: Although limited by the small sample size, our data suggest that levels of NfL protein, GFAp, and total tau in CSF are commonly elevated in patients with COVID-19 with neurological symptoms. This is in contrast to the standard CSF workup where pathological findings are scarce. NfL protein, in particular, is associated with central neurological symptoms and disease severity.
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| 27. |
- Weber, Johan, et al.
(författare)
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Evaluation for epilepsy surgery - Why do patients not proceed to operation?
- 2019
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Ingår i: Seizure-European Journal of Epilepsy. - : Elsevier BV. - 1059-1311 .- 1532-2688. ; 69, s. 241-244
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Tidskriftsartikel (refereegranskat)abstract
- Purpose: To investigate the reasons for not proceeding to surgery in patients undergoing presurgical evaluation for epilepsy. Methods: A retrospective cohort study of 401 consecutive patients who were evaluated for but did not proceed to surgery for epilepsy between 1990 and 2016 at three Swedish epilepsy surgery centers was performed. Reasons for not proceeding to surgery were categorized as inconclusive investigation, seizure onset within eloquent cortex, evidence of multiple seizure foci, infrequent seizures, risk of postoperative severe cognitive decline, patient or caregiver declining surgery or invasive investigation, severe psychiatric or somatic comorbidity, patient death during evaluation and complications during the evaluation. Chi-square tests were performed to compare ordered categorical variables. Results: During the entire time period the main reasons for rejection were inconclusive investigation (34,4%) and multifocal seizure onset (20,0%). The risk for severe cognitive decline postoperatively was more often a cause for rejection in more recent years. Patients declining invasive EEG or surgery accounted for a minor but not insignificant proportion (14,2%) of rejections. Conclusions: Inconclusive results from the presurgical evaluation and multifocal epilepsy were the main causes for not proceeding to surgery. The proportion of patients opting to abstain from surgery was low compared to other recent studies.
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| 28. |
- Zelano, Johan, 1981, et al.
(författare)
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Association between poststroke epilepsy and death : A nationwide cohort study
- 2016
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Ingår i: European Stroke Journal. - : SAGE PUBLICATIONS LTD. - 2396-9873 .- 2396-9881. ; 1:4, s. 272-278
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Tidskriftsartikel (refereegranskat)abstract
- Introduction: Poststroke epilepsy (PSE) is the most common form of acquired epilepsy after middle age. The primary aim of this study was to study the impact of PSE on prognosis. A secondary aim was to validate recent findings from smaller studies on the risk of developing PSE on a nationwide scale.Patients and methods: We performed a nationwide cohort study based on comprehensive national registries and included patients without a prior epilepsy diagnosis surviving more than 2 months after stroke, identified by the Swedish Stroke Register (Riksstroke) and linked to the National Patient Register and Cause of Death Register. Cox proportional time-updated hazard model was used to assess the risk of death, with or without multivariable adjustment for possible confounders, and multiple Cox regression was used to examine associations between PSE and clinical characteristics.Results: In 106,455 patients, PSE (defined as a seizure diagnosis more than 7 days after stroke) was detected in 7.3%, with lower cumulative incidence after ischemic stroke (6.4%) than after intracerebral haemorrhage (12.4%). Stroke severity, intracerebral haemorrhage and young age were associated with a risk of PSE. The risk of death was increased in patients with PSE (hazard ratio: 1.68, 95% confidence interval: 1.25-1.53). Also with adjustments for age, comorbidities and stroke severity, an increased risk of death associated with PSE remained.Discussion: Studies are needed on potential causes of increased mortality in PSE, such as a direct seizure-related mortality, less ambitious secondary stroke prophylaxis or rehabilitation, or impact of antiepileptic drugs on cardiovascular risk.
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| 29. |
- Zelano, Johan, et al.
(författare)
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Clinical course of poststroke epilepsy : a retrospective nested case-control study
- 2015
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Ingår i: Brain and Behavior. - : Wiley. - 2162-3279 .- 2162-3279. ; 5:9
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Tidskriftsartikel (refereegranskat)abstract
- Introduction: Recently, several epidemiological studies have demonstrated that epilepsy develops after approximately 10% of all cerebrovascular lesions. With an aging population, poststroke epilepsy is likely to be of increasing relevance to neurologists and more knowledge on the condition is needed. Patients with poststroke epilepsy are likely to differ from other epilepsy patient populations regarding age, side-effect tolerability, comorbidities, and life expectancy, all of which are important aspects when counselling newly diagnosed patients to make informed treatment decisions. Method: We have here performed a nested case-control study on 36 patients with poststroke epilepsy and 55 controls that suffered stroke but did not develop epilepsy. The average follow-up time was between 3 and 4 years. Results: In our material, two-thirds of patients achieved seizure freedom and 25% experienced a prolonged seizure (status epilepticus) during the follow-up period. Cases consumed more health care following their stroke, but did not suffer more traumatic injuries. Interestingly, the mortality among cases and controls did not differ significantly. This observation needs to be confirmed in larger prospective studies, but indicate that poststroke epilepsy might not infer additional mortality in this patient group with considerable comorbidities. Conclusions: The observations presented can be of value in the counselling of patients, reducing the psychosocial impact of the diagnosis, and planning of future research on poststroke epilepsy.
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| 30. |
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| 31. |
- Zelano, Johan, et al.
(författare)
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Hyponatremia augments kainic-acid induced status epilepticus in the mouse : A model for dysmetabolic status epilepticus
- 2013
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Ingår i: Epilepsy Research. - : Elsevier BV. - 0920-1211 .- 1872-6844. ; 106:1-2, s. 29-34
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Tidskriftsartikel (refereegranskat)abstract
- Status epilepticus (SE) is a dreaded neurological emergency. A reignited interest in SE has resulted in a more adaptive use of treatment protocols. More knowledge on SE of various aetiologies is therefore needed. We are interested in treatment of SE under hyponatremia, and have here evaluated whether SE induced by systemic kainic acid could be a suitable platform for such studies. Acute hyponatremia was induced in C57/BL6 mice by intraperitoneal injection of dDAVP and water loading. Hyponatremic mice displayed an increased frequency of epileptiform spikes on EEG and 5/9 hyponatremic mice displayed electrographic seizures. After kainic acid (20mg/kg) treatment, hyponatremic mice displayed significantly longer time with electrographic seizure activity, which was also seen after treatment with diazepam (20mg/kg). We conclude that hyponatremia augments kainic acid-induced SE, This model might be a valuable platform for studies on treatment of SE in hyponatremia.
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| 32. |
- Zelano, Johan, et al.
(författare)
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Infections in status epilepticus : A retrospective 5-year cohort study
- 2014
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Ingår i: Seizure. - : Elsevier BV. - 1059-1311 .- 1532-2688. ; 23:8, s. 603-606
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Tidskriftsartikel (refereegranskat)abstract
- Purpose: Status epilepticus (SE) has attracted renewed interest lately, and efforts are made to optimize every treatment stage. For refractory SE, optimal supporting care involves mechanical ventilation and intensive care unit (ICU) admission. Infections often complicate SE and recently a single-centre observational study demonstrated an association between infections and poor short-term outcome of SE in a cohort of severely ill patients. We have here attempted to replicate those findings in a different cohort. Method: We performed a retrospective observational study and included all patients with a diagnosis of SE during 2008-2012 at a Swedish tertiary referral centre. Results: The cohort consisted of 103 patients (53% female, 47% male, median age 62 years, range 19-87 years). In house mortality was less than 2 and 70% of the patients' were discharged home. The most common aetiologies of SE were uncontrolled epilepsy (37%) and brain tumours (16%). A total of 39 patients suffered infections during their stay. Presence of infection was associated with mechanical ventilation (OR 3.344, 95% Cl 1.44-7.79) as well as not being discharged home (OR2.705, 95% Cl 1.14-6.44), and duration of SE was significantly longer in patients with infection (median 1 day vs. 2.5 days, p < 0.001). Conclusion: We conclude that the previously described association between infections, a longer SE duration, and an unfavourable outcome of SE seems valid also in SE of less severe aetiology.
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| 33. |
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| 34. |
- Zelano, Johan, et al.
(författare)
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Levetiracetam as alternative stage two antiepileptic drug in status epilepticus : A systematic review
- 2012
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Ingår i: Seizure. - : Elsevier BV. - 1059-1311 .- 1532-2688. ; 21:4, s. 233-236
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Forskningsöversikt (refereegranskat)abstract
- Background: The role of new antiepileptic drugs (AED) in the treatment of status epilepticus (SE) is of interest, especially in benzodiazepine-resistant status epilepticus where phenytoin is deemed inappropriate due to allergy or comorbidity. Levetiracetam (LEV) is a new AED with few side effects. It is easy to administer. Reports exist of its use in SE in adults. Aims: To clarify the evidence for use of LEV as an alternative stage two AED in treatment of SE by a systematic review of the literature. Method: An online MEDLINE search identified 118 articles. The abstracts were screened for studies written in English, in which (1) at least two adults had been treated, and (2) LEV had been administered intravenously as the first AED, on its own or together with benzodiazepines. Ten studies were included. Results: Out of the ten studies, seven were retrospective observational, two prospective observational, and one prospective randomized. The studies described a total of 334 patients. The most common reason for administrating LEV was that standard treatment was deemed inappropriate. The efficacy ranged from 44% to 94%, with higher efficacy reported in the retrospective studies. Conclusions: The evidence for use of LEV as an alternative stage two AED in SE is limited. The higher efficacy reported in retrospective studies indicates possible publication bias, and caution is advised when the results of these retrospective studies are considered in clinical decision-making.
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| 35. |
- Zelano, Johan, 1981, et al.
(författare)
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Neuronal antibodies in adult patients with new-onset seizures: A prospective study
- 2019
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Ingår i: Brain and Behavior. - : Wiley. - 2162-3279. ; 9:11
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Tidskriftsartikel (refereegranskat)abstract
- Objectives Immunotherapy in addition to antiepileptic drugs can improve seizure freedom rates in autoimmune epilepsy, highlighting the importance of early diagnosis. A diagnosis of autoimmune epilepsy can be supported by presence of serum antibodies to neuronal antigens. We asked how often neuronal antibodies are found in the serum of unselected adult patients with new-onset seizures and whether such testing could improve detection of autoimmune epilepsy. Material and Methods We included 44 patients over the age of 25 presenting after at least one unprovoked seizure to the Neurology Clinic at Sahlgrenska University Hospital, Gothenburg, Sweden. The median time between the first-ever seizure in life and the serum sampling was 50 days (range 22-11,000). Antibody testing in serum was performed according to the manufacturer's instructions. The patients were followed for at least 1 year. Results Epilepsy could be diagnosed already at the first visit in 21/44 patients (47.7%). Two patients (4.5%) were positive for neuronal antibodies: one against contactin-associated protein 2 (CASPR-2) and one against glutamate acid decarboxylase (GAD). Three patients (6.7%) displayed very weak immunoreactivity that was deemed clinically insignificant. One of the antibody-positive patients had only a single seizure. The other had a focal cortical dysplasia and was seizure-free on levetiracetam. None of the five patients with antibodies or immunoreactivity displayed any feature of autoimmune epilepsy. Conclusions We conclude that indiscriminate testing in patients presenting to a first seizure clinic with new-onset seizures or epilepsy is unlikely to improve detection of autoimmune epilepsy.
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| 36. |
- Zelano, Johan, 1981, et al.
(författare)
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Pre-stroke seizures: A nationwide register-based investigation
- 2017
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Ingår i: Seizure-European Journal of Epilepsy. - : Elsevier BV. - 1059-1311 .- 1532-2688. ; 49, s. 25-29
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Tidskriftsartikel (refereegranskat)abstract
- Purpose: The relationship between cerebroyascular disease and seizures is clearly illustrated by poststroke epilepsy. Seizures can also be the first manifestation of cerebrovascular disease and case control studies have demonstrated that seizures carry an increased risk of subsequent stroke. Thus, seizures could serve as a marker for vascular risk that merits intervention, but more data is needed before proper trials can be conducted. The occurrence of pre-stroke seizures has not been assessed on a national scale. We asked what proportion of strokes in middle-aged and elderly patients was preceded by seizures. Methods: All patients over 60 years of age with first-ever stroke in 2005-2010 (n = 92,596) were identified in the Swedish stroke register (Riksstroke) and cross-sectional data on a history of a first seizure or epilepsy diagnosis in the ten years preceding stroke were collected from national patient registers with mandatory reporting. Results: 1372 patients (1.48%) had a first seizure or epilepsy diagnosis registered less than ten years prior to the index stroke. The mean latency between seizure and stroke was 1474 days (SD 1029 days). Conclusions: Seizures or epilepsy preceded 1.48% of strokes in patients > 60 years of age. Based on recent national incidence figures, 5-20% of incident cases of seizures or epilepsy after 60 years of age could herald stroke, depending on age group. These proportions are of a magnitude that merit further study on how to reduce the risk of stroke in patients with late-onset seizures or epilepsy. (C) 2017 British Epilepsy Association. Published by Elsevier Ltd. All rights reserved.
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| 37. |
- Åhs, Fredrik, et al.
(författare)
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Medial temporal lobe resection attenuates superior temporal sulcus response to faces
- 2014
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Ingår i: Neuropsychologia. - : Elsevier BV. - 0028-3932 .- 1873-3514. ; 61, s. 291-298
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Tidskriftsartikel (refereegranskat)abstract
- Face perception depends on activation of a core face processing network including the fusiform face area, the occipital face area and the superior temporal sulcus (STS). The medial temporal lobe (MTL) is also involved in decoding facial expression and damage to the anterior MTL, including the amygdala, generally interferes with emotion recognition. The impairment in emotion recognition following anterior MTL injury can be a direct result from injured MTL circuitry, as well as an indirect result from decreased MTL modulation of areas in the core face network. To test whether the MTL modulates activity in the core face network, we used functional magnetic resonance imaging to investigate activation in the core face processing network in patients with right or left anterior temporal lobe resections (ATR) due to intractable epilepsy. We found reductions of face-related activation in the right STS after both right and left ATR together with impaired recognition of facial expressions. Reduced activity in the fusiform and the occipital face areas was also observed in patients after right ATR suggesting widespread effects on activity in the core face network in this group. The reduction in face-related STS activity after both right and left ATR suggests that MTL modulation of the STS may facilitate recognition of facial expression.
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