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  1. Article ; Online: Cardiovascular autonomic dysfunction: A cause of acute COVID-19 complications and persistent post-COVID-19 complaints?

    Hilz, Max J

    European journal of neurology

    2023  Volume 30, Issue 5, Page(s) 1170–1171

    MeSH term(s) Humans ; COVID-19/complications ; Autonomic Nervous System Diseases/etiology ; Autonomic Nervous System ; Heart
    Language English
    Publishing date 2023-02-12
    Publishing country England
    Document type Editorial ; Comment
    ZDB-ID 1280785-0
    ISSN 1468-1331 ; 1351-5101 ; 1471-0552
    ISSN (online) 1468-1331
    ISSN 1351-5101 ; 1471-0552
    DOI 10.1111/ene.15719
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  2. Article ; Online: Transcutaneous vagus nerve stimulation - A brief introduction and overview.

    Hilz, Max J

    Autonomic neuroscience : basic & clinical

    2022  Volume 243, Page(s) 103038

    Abstract: Invasive cervical vagus nerve stimulation (VNS) is approved for the treatment of epilepsies, depression, obesity, and for stroke-rehabilitation. The procedure requires surgery, has side-effects, is expensive and not readily available. Consequently, ... ...

    Abstract Invasive cervical vagus nerve stimulation (VNS) is approved for the treatment of epilepsies, depression, obesity, and for stroke-rehabilitation. The procedure requires surgery, has side-effects, is expensive and not readily available. Consequently, transcutaneous VNS (tVNS) has been developed 20 years ago as non-invasive, less expensive, and easily applicable alternative. Since the vagus nerve reaches the skin at the outer acoustic canal and ear, and reflex-responses such as the ear-cough-reflex or the auriculo-cardiac reflex have been observed upon auricular stimulation, the ear seems well suited for tVNS. However, several sensory nerves with variable fiber-density and significant overlap innervate the outer ear: the auricular branch of the vagus nerve (ABVN), the auriculotemporal nerve, greater auricular nerve, and to some extent the lesser occipital nerve. VNS requires activation of Aβ-fibers which are far less present in the ABVN than the cervical vagus nerve. Thus, optimal stimulation sites and parameters, and tVNS-algorithms need to be further explored. Unravelling central pathways and structures that mediate tVNS-effects is another challenge. tVNS impulses reach the nucleus of the solitary tract and activate the locus-coeruleus-norepinephrine system. However, many more brain areas are activated or deactivated upon VNS, including structures of the central autonomic network and the limbic system. Still, the realm of therapeutic tVNS applications grows rapidly and includes medication-refractory epilepsies, depressive mood disorders, headaches including migraine, pain, heart failure, gastrointestinal inflammatory diseases and many more. tVNS might become a standard tool to enhance autonomic balance and function in various autonomic, neurological, psychiatric, rheumatologic, as well as other diseases.
    MeSH term(s) Vagus Nerve Stimulation/methods ; Transcutaneous Electric Nerve Stimulation/methods ; Vagus Nerve/physiology ; Brain/physiology ; Afferent Pathways/physiology
    Language English
    Publishing date 2022-09-27
    Publishing country Netherlands
    Document type Journal Article ; Review
    ZDB-ID 2020105-9
    ISSN 1872-7484 ; 1566-0702
    ISSN (online) 1872-7484
    ISSN 1566-0702
    DOI 10.1016/j.autneu.2022.103038
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  3. Article ; Online: Transcutaneous vagus nerve stimulation and the realm of its therapeutic hopes and physiologic enigmas.

    Hilz, Max J / Bolz, Armin

    Autonomic neuroscience : basic & clinical

    2022  Volume 243, Page(s) 103039

    Abstract: Vagus nerve stimulation (VNS) is an established treatment option for patients with treatment resistant epilepsy and depression. However, the procedure is invasive and has side-effects. Transcutaneous vagus nerve stimulation (tVNS) is a non-invasive ... ...

    Abstract Vagus nerve stimulation (VNS) is an established treatment option for patients with treatment resistant epilepsy and depression. However, the procedure is invasive and has side-effects. Transcutaneous vagus nerve stimulation (tVNS) is a non-invasive alternative. Particularly transcutaneous stimulation at the outer ear is gaining increasing interest. While the scope of therapeutic tVNS applications is expanding, there are still questions regarding the optimal stimulation parameters and site as well as the physiology and pathways of auricular tVNS. This Special Issue of Autonomic Neuroscience: Basic & Clinical provides an introduction and overview on basic aspects as well as special topics of tVNS.
    MeSH term(s) Humans ; Vagus Nerve Stimulation/methods ; Vagus Nerve/physiology ; Transcutaneous Electric Nerve Stimulation/methods
    Language English
    Publishing date 2022-09-28
    Publishing country Netherlands
    Document type Editorial
    ZDB-ID 2020105-9
    ISSN 1872-7484 ; 1566-0702
    ISSN (online) 1872-7484
    ISSN 1566-0702
    DOI 10.1016/j.autneu.2022.103039
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  4. Article ; Online: Cardiovascular autonomic regulation correlates with cognitive performance in patients with a history of traumatic brain injury.

    Wang, Ruihao / Muresanu, Dafin / Hösl, Katharina / Hilz, Max J

    Neurological sciences : official journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology

    2023  Volume 44, Issue 10, Page(s) 3535–3544

    Abstract: Background and objective: Traumatic brain injury (TBI) may afflict brain areas contributing to both cardiovascular autonomic regulation and cognitive performance. To evaluate possible associations between both functions in patients with a history of TBI ...

    Abstract Background and objective: Traumatic brain injury (TBI) may afflict brain areas contributing to both cardiovascular autonomic regulation and cognitive performance. To evaluate possible associations between both functions in patients with a history of TBI (post-TBI-patients), we determined correlations between cardiovascular autonomic regulation and cognitive function in post-TBI-patients.
    Methods: In 86 post-TBI-patients (33.1 ± 10.8 years old, 22 women, 36.8 ± 28.9 months after injury), we monitored RR intervals (RRI), systolic and diastolic blood pressures (BPsys, BPdia), and respiration (RESP) at rest. We calculated parameters of total cardiovascular autonomic modulation (RRI-standard-deviation (RRI-SD), RRI-coefficient-of-variation (RRI-CV), RRI-total-powers), sympathetic (RRI-low-frequency-powers (RRI-LF), normalized (nu) RRI-LF-powers, BPsys-LF-powers) and parasympathetic modulation (root-mean-square-of-successive-RRI-differences (RMSSD), RRI-high-frequency-powers (RRI-HF), RRI-HFnu-powers), sympathetic-parasympathetic balance (RRI-LF/HF-ratios), and baroreflex sensitivity (BRS). We used the Mini-Mental State Examination and Clock Drawing Test (CDT) to screen the general global and visuospatial cognitive function, and applied the standardized Trail Making Test (TMT)-A assessing visuospatial abilities and TMT-B assessing executive function. We calculated correlations between autonomic and cognitive parameters (Spearman's rank correlation test; significance: P < 0.05).
    Results: CDT values positively correlated with age (P = 0.013). TMT-A values inversely correlated with RRI-HF-powers (P = 0.033) and BRS (P = 0.043), TMT-B values positively correlated with RRI-LFnu-powers (P = 0.015), RRI-LF/HF-ratios (P = 0.036), and BPsys-LF-powers (P = 0.030), but negatively with RRI-HFnu-powers (P = 0.015).
    Conclusions: In patients with a history of TBI, there is an association between decreased visuospatial and executive cognitive performance and reduced parasympathetic cardiac modulation and baroreflex sensitivity with relatively increased sympathetic activity. Altered autonomic control bears an increased cardiovascular risk; cognitive impairment compromises quality of life and living conditions. Thus, both functions should be monitored in post-TBI-patients.
    MeSH term(s) Humans ; Female ; Young Adult ; Adult ; Quality of Life ; Autonomic Nervous System ; Cardiovascular System ; Brain Injuries, Traumatic/complications ; Blood Pressure/physiology ; Cognition ; Heart Rate/physiology
    Language English
    Publishing date 2023-05-25
    Publishing country Italy
    Document type Journal Article
    ZDB-ID 2016546-8
    ISSN 1590-3478 ; 1590-1874
    ISSN (online) 1590-3478
    ISSN 1590-1874
    DOI 10.1007/s10072-023-06857-y
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  5. Article ; Online: Cardiac stunning as first manifestation of multiple sclerosis: A case report reminding us not to overlook cardiovascular autonomic dysfunction in multiple sclerosis.

    Hilz, Max J

    Multiple sclerosis (Houndmills, Basingstoke, England)

    2016  Volume 22, Issue 6, Page(s) 847–848

    Abstract: Autonomic dysfunction is common but frequently overlooked in multiple sclerosis (MS) patients. The case of a Tako-Tsubo cardiomyopathy on which this commentary is based shows that centrally triggered autonomic dysfunction may be the first life- ... ...

    Abstract Autonomic dysfunction is common but frequently overlooked in multiple sclerosis (MS) patients. The case of a Tako-Tsubo cardiomyopathy on which this commentary is based shows that centrally triggered autonomic dysfunction may be the first life-threatening manifestation of MS.
    MeSH term(s) Confusion ; Humans ; Multiple Sclerosis ; Takotsubo Cardiomyopathy
    Language English
    Publishing date 2016-03-18
    Publishing country England
    Document type Journal Article ; Comment
    ZDB-ID 1290669-4
    ISSN 1477-0970 ; 1352-4585
    ISSN (online) 1477-0970
    ISSN 1352-4585
    DOI 10.1177/1352458516638559
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  6. Article ; Online: Rapid recovery of poststroke cardiac autonomic dysfunction: Causes to be considered.

    Wang, Ruihao / Moeller, Sebastian / Akhundova, Aynur / Marthol, Harald / Kollmar, Rainer / Köhrmann, Martin / Hilz, Max J

    European journal of neurology

    2023  Volume 30, Issue 8, Page(s) 2488–2497

    Abstract: Background and purpose: Acute stroke frequently causes cardiovascular-autonomic dysfunction (CAD). Studies of CAD recovery are inconclusive, whereas poststroke arrhythmias may wane within 72 h. We evaluated whether poststroke CAD recovers within 72 h ... ...

    Abstract Background and purpose: Acute stroke frequently causes cardiovascular-autonomic dysfunction (CAD). Studies of CAD recovery are inconclusive, whereas poststroke arrhythmias may wane within 72 h. We evaluated whether poststroke CAD recovers within 72 h upon stroke onset in association with neurological improvement or increased use of cardiovascular medication.
    Methods: In 50 ischemic stroke patients (68 ± 13 years old) who-prior to hospital-admission-had no known diseases nor took medication affecting autonomic modulation, we assessed National Institutes of Health Stroke Scale (NIHSS) scores, RR intervals (RRIs), systolic and diastolic blood pressure (BP), respiration rate, parameters reflecting total autonomic modulation (RRI SD, RRI total powers), sympathetic modulation (RRI low-frequency powers, systolic BP low-frequency powers), and parasympathetic modulation (square root of mean squared differences of successive RRIs [RMSSD], RRI high-frequency powers), and baroreflex sensitivity within 24 h (Assessment 1) and 72 h after stroke onset (Assessment 2) and compared data to those of 31 healthy controls (64 ± 10 years). We correlated delta NIHSS values (Assessment 1 - Assessment 2) with delta values of autonomic parameters (Spearman rank correlation tests; significance: p < 0.05).
    Results: At Assessment 1, patients were not yet on vasoactive medication and had higher systolic BP, respiration rate, and heart rate, that is, lower RRIs, but lower RRI SD, RRI coefficient of variance, RRI low-frequency powers, RRI high-frequency powers, RRI total powers, RMSSDs, and baroreflex sensitivity. At Assessment 2, patients were on antihypertensives, had higher RRI SD, RRI coefficient of variance, RRI low-frequency powers, RRI high-frequency powers, RRI total powers, RMSSDs, and baroreflex sensitivity but lower systolic blood pressure and NIHSS values than at Assessment 1; values no longer differed between patients and controls except for lower RRIs and higher respiration rate in patients. Delta NIHSS scores correlated inversely with delta values of RRI SD, RRI coefficient of variance, RMSSDs, RRI low-frequency powers, RRI high-frequency powers, RRI total powers, and baroreflex sensitivity.
    Conclusions: In our patients, CAD recovery was almost complete within 72 h after stroke onset and correlated with neurological improvement. Most likely, early initiation of cardiovascular medication and probably attenuating stress supported rapid CAD recovery.
    MeSH term(s) Humans ; Middle Aged ; Aged ; Aged, 80 and over ; Autonomic Nervous System ; Autonomic Nervous System Diseases/etiology ; Blood Pressure/physiology ; Heart ; Baroreflex/physiology ; Stroke/complications ; Heart Rate/physiology
    Language English
    Publishing date 2023-05-23
    Publishing country England
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 1280785-0
    ISSN 1468-1331 ; 1351-5101 ; 1471-0552
    ISSN (online) 1468-1331
    ISSN 1351-5101 ; 1471-0552
    DOI 10.1111/ene.15853
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  7. Article ; Online: Cardiovascular autonomic dysfunction after stroke.

    Jimenez-Ruiz, Amado / Racosta, Juan M / Kimpinski, Kurt / Hilz, Max J / Sposato, Luciano A

    Neurological sciences : official journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology

    2021  Volume 42, Issue 5, Page(s) 1751–1758

    Abstract: Strokes are the paradigmatic example of the sudden impairment of the cerebral regulation of cardiac autonomic regulation. Although several aspects of dysautonomic cardiovascular regulation post stroke remain unanswered, there has been a wealth of ... ...

    Abstract Strokes are the paradigmatic example of the sudden impairment of the cerebral regulation of cardiac autonomic regulation. Although several aspects of dysautonomic cardiovascular regulation post stroke remain unanswered, there has been a wealth of research in this area in the last decade. In this article, we present a state-of-the-art review on the anatomical and functional organization of cardiovascular autonomic regulation, and the pathophysiology, incidence, time course, diagnosis, clinical aspects, prognosis, and management of post-stroke cardiovascular autonomic dysfunction.
    MeSH term(s) Autonomic Nervous System ; Autonomic Nervous System Diseases/diagnosis ; Autonomic Nervous System Diseases/etiology ; Cardiovascular System ; Heart Rate ; Humans ; Stroke/complications
    Language English
    Publishing date 2021-03-09
    Publishing country Italy
    Document type Journal Article ; Review
    ZDB-ID 2016546-8
    ISSN 1590-3478 ; 1590-1874
    ISSN (online) 1590-3478
    ISSN 1590-1874
    DOI 10.1007/s10072-021-05128-y
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  8. Article ; Online: Posterior circulation ischemic stroke not involving the brainstem is associated with cardiovascular autonomic dysfunction.

    Wang, Ruihao / Köhrmann, Martin / Kollmar, Rainer / Koehn, Julia / Schwab, Stefan / Kallmünzer, Bernd / Hilz, Max J

    European journal of neurology

    2022  Volume 29, Issue 9, Page(s) 2690–2700

    Abstract: Background and purpose: Ischemic stroke may induce cardiovascular autonomic dysfunction, but most previous studies have included patients with anterior circulation ischemic stroke or brainstem stroke. It remains unclear whether posterior circulation ... ...

    Abstract Background and purpose: Ischemic stroke may induce cardiovascular autonomic dysfunction, but most previous studies have included patients with anterior circulation ischemic stroke or brainstem stroke. It remains unclear whether posterior circulation ischemic stroke (PCIS) without brainstem involvement also compromises cardiovascular autonomic modulation (CAM). Therefore, we aimed to assess CAM in PCIS patients with and without brainstem involvement.
    Methods: In four subgroups of 61 PCIS patients (14 occipital lobe, 16 thalamic, 12 cerebellar, and 19 brainstem strokes) and 30 healthy controls, we recorded RR intervals (RRIs), systolic (SBP) and diastolic blood pressure (DBP), and respiration at supine rest during the first week after stroke onset. We calculated parameters reflecting total CAM (RRI-standard deviation [RRI-SD], RRI-total powers), predominantly sympathetic CAM (RRI-low-frequency [LF] powers and SBP-LF powers] and parasympathetic CAM (root mean square of successive RRI differences [RMSSD], RRI-high-frequency [HF] powers), sympathetic-parasympathetic balance (RRI-LF/HF ratios), and baroreflex sensitivity (BRS). Values were compared among the four PCIS groups and controls using one-way ANOVA Kruskal-Wallis tests, with post-hoc analyses. Significance was assumed for p < 0.05.
    Results: In each PCIS subgroup, values for RRI, RRI-SD, RMSSD, RRI-HF powers, and BRS were significantly lower, while SBP-LF powers were higher than in the controls. Only in patients with occipital lobe stroke were RRI-LF/HF ratios significantly higher than in controls. Otherwise, autonomic variables did not differ among the four PCIS subgroups.
    Conclusions: During the first week after stroke onset, our PCIS patients with occipital lobe, thalamic, cerebellar, or brainstem strokes all had reduced cardiovagal modulation, compromised baroreflex, and increased peripheral sympathetic modulation. The RRI-LF/HF ratios suggest that sympathetic predominance is slightly more prominent after occipital lobe stroke. PCIS may trigger cardiovascular autonomic dysfunction even without brainstem involvement.
    MeSH term(s) Autonomic Nervous System ; Autonomic Nervous System Diseases/etiology ; Baroreflex/physiology ; Blood Pressure/physiology ; Brain Stem ; Heart Rate/physiology ; Humans ; Ischemic Stroke ; Stroke/complications
    Language English
    Publishing date 2022-06-13
    Publishing country England
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 1280785-0
    ISSN 1468-1331 ; 1351-5101 ; 1471-0552
    ISSN (online) 1468-1331
    ISSN 1351-5101 ; 1471-0552
    DOI 10.1111/ene.15427
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  9. Article ; Online: Cardiovascular medication seems to promote recovery of autonomic dysfunction after stroke.

    Wang, Ruihao / Köhrmann, Martin / Kollmar, Rainer / Koehn, Julia / Schwab, Stefan / Kallmünzer, Bernd / Hilz, Max J

    Journal of neurology

    2022  Volume 269, Issue 10, Page(s) 5454–5465

    Abstract: Background: Stroke may compromise cardiovascular-autonomic modulation (CAM). The longitudinal post-stroke CAM alterations remain unclear as previous studies excluded patients with cardiovascular medication. This study evaluated whether CAM dysfunction ... ...

    Abstract Background: Stroke may compromise cardiovascular-autonomic modulation (CAM). The longitudinal post-stroke CAM alterations remain unclear as previous studies excluded patients with cardiovascular medication. This study evaluated whether CAM dysfunction improves after several months in patients under typical clinical conditions, i.e., without excluding patients with cardiovascular medication.
    Methods: In 82 ischemic stroke patients [33 women, 64.9 ± 8.9 years, NIHSS-scores 2 (interquartile range 1-5)], we evaluated the applications of cardiovascular medication before stroke, during autonomic tests performed within 1 week, 3 and 6 months after stroke onset. We determined resting RR intervals (RRI), systolic, diastolic blood pressures (BPsys), respiration, parameters reflecting total CAM [RRI-standard deviation (RRI-SD), RRI-total powers], sympathetic [RRI-low-frequency powers (RRI-LF), BPsys-LF powers] and parasympathetic CAM [RMSSD, RRI-high-frequency powers (RRI-HF powers)], and baroreflex sensitivity. ANOVA or Friedman tests with post hoc analyses compared patient data with data of 30 healthy controls, significance was assumed for P < 0.05.
    Results: More patients had antihypertensive medication after than before stroke. First-week CAM testing showed lower RRIs, RMSSD, RRI-SDs, RRI-total powers, RRI-HF powers, and baroreflex sensitivity, but higher BPsys-LF powers in patients than controls. After 3 and 6 months, patients had significantly higher RRIs, RRI-SDs, RRI-total powers, RMSSDs, RRI-HF powers, and baroreflex sensitivity, but lower BPsys-LF powers than in the 1st week; RMSSDs and RRI-HF powers no longer differed between patients and controls. However, 6-month values of RRIs, RRI-SDs, and baroreflex sensitivity were again lower in patients than controls.
    Conclusions: Even mild strokes compromised cardiovagal modulation and baroreflex sensitivity. After 3 months, CAM had almost completely recovered. Recovery might be related to the mild stroke severity. Presumably, CAM recovery was also promoted by the increased application of cardiovascular medication. Yet, slight CAM dysfunction after 6 months suggests continuing autonomic vulnerability.
    MeSH term(s) Autonomic Nervous System ; Baroreflex/physiology ; Blood Pressure/physiology ; Female ; Heart Rate/physiology ; Humans ; Primary Dysautonomias ; Respiration ; Stroke/complications ; Stroke/drug therapy
    Language English
    Publishing date 2022-06-12
    Publishing country Germany
    Document type Journal Article
    ZDB-ID 187050-6
    ISSN 1432-1459 ; 0340-5354 ; 0012-1037 ; 0939-1517 ; 1619-800X
    ISSN (online) 1432-1459
    ISSN 0340-5354 ; 0012-1037 ; 0939-1517 ; 1619-800X
    DOI 10.1007/s00415-022-11204-w
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  10. Article ; Online: Incidence, temporal profile and neuroanatomic correlates of poststroke epilepsy.

    Winder, Klemens / Bobinger, Tobias / Seifert, Frank / Mrochen, Anne / Haupenthal, David / Knott, Michael / Dörfler, Arnd / Hilz, Max J / Schwab, Stefan / Fröhlich, Kilian

    Journal of neuroimaging : official journal of the American Society of Neuroimaging

    2023  Volume 33, Issue 4, Page(s) 575–581

    Abstract: Background and purpose: The relationship between ischemic stroke site and occurrence of poststroke epilepsy (PSE) is incompletely understood. This study intended to evaluate incidence and temporal profiles of seizures and to correlate ischemic lesion ... ...

    Abstract Background and purpose: The relationship between ischemic stroke site and occurrence of poststroke epilepsy (PSE) is incompletely understood. This study intended to evaluate incidence and temporal profiles of seizures and to correlate ischemic lesion sites with PSE using voxel-based lesion symptom mapping (VLSM).
    Methods: Patients with imaging-confirmed first-ever ischemic stroke without prior history of epilepsy were prospectively included. Demographic data, cardiovascular risk factors, and National Institute of Health Stroke Scale (NIHSS) scores were assessed. Data on seizures and modified Rankin scale scores were determined within a 90-day period after stroke onset. Ischemic lesion sites were correlated voxel wise with occurrence of PSE using nonparametric permutation test. Age- and sex-matched patients with first-ever ischemic strokes without PSE after 90 days served as controls for the VLSM analysis.
    Results: The stroke database contained 809 patients (mean age: 68.4 ± 14.2 years) with first-ever imaging-confirmed ischemic strokes without history of epilep. Incidence of PSE after 90-day follow-up was 2.8%. Five additional patients were admitted to the emergency department with a seizure after 90-day follow-up. Fifty percent of the seizures occurred in the acute phase after stroke. PSE patients had higher NIHSS scores and infarct volumes compared to controls without PSE (p < .05). PSE patients had infarcts predominantly involving the cerebral cortex. The hemisphere-specific VLSM analysis shows associations between PSE and damaged voxels in the left-hemispheric temporo-occipital transition zone.
    Conclusions: The data indicate that PSE occurs in a small proportion of patients with rather large ischemic strokes predominantly involving the cerebral cortex. Especially patients with ischemic lesions in the temporo-occipital cortex are vulnerable to develop PSE.
    MeSH term(s) Humans ; Middle Aged ; Aged ; Aged, 80 and over ; Incidence ; Epilepsy/diagnostic imaging ; Epilepsy/epidemiology ; Epilepsy/etiology ; Stroke/complications ; Stroke/diagnostic imaging ; Seizures/etiology ; Ischemic Stroke/complications
    Language English
    Publishing date 2023-05-02
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 1071724-9
    ISSN 1552-6569 ; 1051-2284
    ISSN (online) 1552-6569
    ISSN 1051-2284
    DOI 10.1111/jon.13110
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