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Neurol. Int., Volume 17, Issue 3 (March 2025) – 9 articles

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13 pages, 4471 KiB  
Article
The Impact of Biseasonal Time Changes on Migraine
by Carl H. Göbel, Katja Heinze-Kuhn, Axel Heinze, Anna Cirkel and Hartmut Göbel
Neurol. Int. 2025, 17(3), 40; https://doi.org/10.3390/neurolint17030040 - 5 Mar 2025
Viewed by 202
Abstract
Background: Changes in the daily rhythm can trigger migraine attacks. The sensitivity for triggering attacks is closely linked to the regulation of biological rhythms controlled by the hypothalamus. In over 70 countries around the world, the time is changed between daylight savings [...] Read more.
Background: Changes in the daily rhythm can trigger migraine attacks. The sensitivity for triggering attacks is closely linked to the regulation of biological rhythms controlled by the hypothalamus. In over 70 countries around the world, the time is changed between daylight savings time and standard time twice a year due to legal regulations. The aim of this study was to investigate whether the time change has an influence on migraine. Methods: In this retrospective study, the headache frequency of patients with episodic or chronic migraine at a tertiary headache center in the years 2020, 2021, and 2022 was evaluated. The primary outcome measure was the frequency of migraine occurrence on either Sunday or Monday of the time change weekend compared to Sunday or Monday before or Sunday or Monday after the time change. Results: Data from 258 patients were analyzed (86.8% women; average age: 51.5 years; average headache frequency: 7.7 days/month; 83.3% episodic migraine). Our results showed a significant increase of 6.4% in migraine frequency on the Sunday and/or Monday in the week after the time change in spring compared to the week before the change. In autumn, conversely, there was a significant reduction of 5.5% in migraine frequency on the Sunday and/or Monday one week after the time change compared to the week before the change. The factor responsible for the significant changes was the increase in migraines on Monday one week after the time change in spring and the decrease in migraines on Sunday one week after the time change in autumn. Conclusions: When switching from standard time to daylight savings time in the spring, the frequency of migraines increases significantly one week after the time change. In autumn, in comparison, there is an inverse trend with a reduction in migraine frequency. These data suggest that synchronization is disturbed when switching to daylight savings time. Conversely, synchronization normalizes in autumn. In view of the high prevalence of migraines, this can have extensive individual and social consequences. Full article
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<p>Recorded period from the Sunday before (−7 days) the time change (day 0) to the second Monday after the time change (day +8). Headache data were analyzed for Sunday (day 0) and Monday (day +1) of the actual time change weekend and for Sunday (day −7) and Monday (day −6) one week before and after the time change (day +7 and day +8).</p>
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<p>Absolute age distribution of the evaluated patients.</p>
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<p>Number of evaluable time change phases per patient. Maximum of 6 phases recorded, spring and autumn 2020, 2021, and 2022. A complete data set of a time change consists of week −1, W0, and week +1.</p>
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<p>Average migraine frequency on Sunday and/or Monday at the 3 time points day −7 and day −6 (week before the time change), day 0 and day +1 (weekend of the time change), and day +7 and day +8 (week after the time change) in spring. The frequency of migraines on Sunday and/or Monday on day +7 and day +8 after the time change was significantly higher than on day −7 and day −6 before the time change (<span class="html-italic">p</span> = 0.019) and than on the time change weekend (day 0 and day +1) itself (<span class="html-italic">p</span> = 0.040).</p>
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<p>Average migraine frequency on Sunday and/or Monday at the time points day −7 and day −6 (week before the time change), day 0 and day +1 (weekend of the time change), and day +7 and day +8 (week after the time change) in autumn. The frequency of migraines on Sunday and/or Monday on day +7 and day +8 after the time change was significantly lower than on day −7 and day −6 before the time change (<span class="html-italic">p</span> = 0.040). The migraine frequency on the time change weekend day 0 and day +1 was lower than in the previous week on day −7 and day −6, but the difference was not significant (<span class="html-italic">p</span> = 0.14).</p>
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<p>Average migraine frequency on Sunday and/or Monday at the 3 time points day −7 and day −6, day 0 and day +1 as well as time point day +7 and day +8 in spring in the presence of episodic migraine versus chronic migraine. There was a significant difference in episodic migraine between the time points day −7 and day −6 before the time change and day +7 and day +8 after the time change (<span class="html-italic">p</span> = 0.0342).</p>
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<p>Average migraine frequency on Sunday and/or Monday at the 3 time points day −7 and day −6, day 0 and day +1 as well as time point day +7 and day +8 in autumn in the presence of episodic migraine versus chronic migraine. The frequencies for chronic migraine did not differ significantly. In contrast, there was a significant difference between the time points day −7 and day −6 before the time change and day +7 and day +8 after the time change for episodic migraine (<span class="html-italic">p</span> = 0.0255).</p>
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12 pages, 263 KiB  
Article
The Impact of Age on Outcomes in Seizure Hospitalizations—Analysis of a National Sample
by Anudeep Surendranath, Saurabh Singhal, Rahul Khanna, Subhendu Rath and Temenuzhka Mihaylova
Neurol. Int. 2025, 17(3), 39; https://doi.org/10.3390/neurolint17030039 - 4 Mar 2025
Viewed by 141
Abstract
Objective: Seizures are a critical public health issue, with incidence rising significantly after age 50. Using this inflection point, we divided patients into two age groups to examine the impact of age on patient characteristics and hospitalization outcomes for seizures. Methods: Using the [...] Read more.
Objective: Seizures are a critical public health issue, with incidence rising significantly after age 50. Using this inflection point, we divided patients into two age groups to examine the impact of age on patient characteristics and hospitalization outcomes for seizures. Methods: Using the 2021 National Inpatient Sample (NIS), a nationally representative database, we conducted a retrospective cohort analysis of adult patients aged ≥18 years admitted with a principal diagnosis of seizures. Patients were divided into two age groups: 18–49 and ≥50 years. Outcomes included in-hospital mortality, length of stay, and hospital charges. Multivariate logistic and linear regression models adjusted for confounders were employed to assess the association between age and outcomes. Results: The cohort included 211,055 patients, with 59% aged ≥50 years. Older patients were more likely to have Medicare coverage (66% vs. 16%, p < 0.01), to reside in the south (41% vs. 38%, p < 0.01), and to have a higher proportion of White individuals (62% vs. 54%, p < 0.01). Younger patients were more likely to be Hispanic (15% vs. 9%, p < 0.01), admitted to urban hospitals (96% vs. 94%, p < 0.01), and treated at teaching hospitals (84% vs. 79%, p < 0.01). After adjusting for confounders, older adults had over twice the odds of in-hospital mortality compared with younger patients (adjusted OR 2.17; 95% CI, 1.61–2.92; p < 0.01). They also experienced longer hospital stays (mean difference 0.7 days; 95% CI, 0.54–0.92; p < 0.01) and higher hospital charges (mean increase USD 4322; 95% CI, USD 1914–6731; p < 0.01). Significance: Age is an independent predictor of in-hospital mortality, longer hospitalizations, and higher costs in seizure-related admissions. These findings underscore the need for age-specific management strategies to improve outcomes and optimize healthcare resource utilization for older adults with seizures. Full article
16 pages, 1141 KiB  
Article
Using Immunoliposomes as Carriers to Enhance the Therapeutic Effectiveness of Macamide N-3-Methoxybenzyl-Linoleamide
by Karin J. Vera-López, María Aranzamendi-Zenteno, Gonzalo Davila-Del-Carpio and Rita Nieto-Montesinos
Neurol. Int. 2025, 17(3), 38; https://doi.org/10.3390/neurolint17030038 - 3 Mar 2025
Viewed by 204
Abstract
Background/Objectives: Epilepsy is one of the most common chronic neurological disorders, characterized by alterations in neuronal electrical activity that result in recurrent seizures and involuntary body movements. Anticonvulsants are the primary treatment for this condition, helping patients improve their quality of life. However, [...] Read more.
Background/Objectives: Epilepsy is one of the most common chronic neurological disorders, characterized by alterations in neuronal electrical activity that result in recurrent seizures and involuntary body movements. Anticonvulsants are the primary treatment for this condition, helping patients improve their quality of life. However, the development of new drugs with fewer side effects and greater economic accessibility remains a key focus in nanomedicine. Macamides, secondary metabolites derived from Maca (Lepidium meyenii), represent a promising class of novel drugs with diverse therapeutic applications, particularly in the treatment of neurological disorders. Methods: In this study, we optimized the potential of the macamide N-3-methoxybenzyl-linoleamide (3-MBL) as an anticonvulsant agent through its encapsulation in PEGylated liposomes conjugated with OX26 F(ab′)2 fragments. Results: These immunoliposomes exhibited a size of 120.52 ± 9.46 nm and a zeta potential of −8.57 ± 0.80 mV. Furthermore, in vivo tests using a pilocarpine-induced status epilepticus model revealed that the immunoliposomes provided greater efficacy against epileptic seizures compared to the free form of N-3-methoxybenzyl-linoleamide at the same dose. Notably, the observed anticonvulsant effect was comparable to that of carbamazepine, a traditional FDA-approved antiepileptic drug. Conclusions: This pioneering work employs liposomal nanocarriers to deliver macamides to the brain, aiming to set a new standard for the use of modified liposomes in anticonvulsant epilepsy treatment. Full article
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<p>Schematic representation of the use of liposomes as carriers of macamide 3-MBL. (<b>a</b>) Macamide and liposomes used in in vivo tests. The colors on the surface of the calculated electrostatic potential for 3-MBL indicate regions of high electron density (red) and low electron density (blue). Neutral zones are represented in white. (<b>b</b>) Possible mechanisms of action of immunoliposomes in the human brain.</p>
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<p>Seizure inhibition (%) on pilocarpine-induced status epilepticus after the administration of diazepam (DZP), carbamazepine (CBZ), N-3-methoxybenzyl-linoleamide at 1.0 mg/kg (3-MBL-1), N-3-methoxybenzyl-linoleamide at 10.0 mg/kg (3-MBL-10), PEGylated liposomes loaded with N-3-methoxybenzyl-linoleamide at 1.0 mg/kg (PL-1), and PEGylated OX26 F(ab′)2 immunoliposomes loaded with N-3-methoxybenzyl-linoleamide at 1.0 mg/kg (IL-1). The percentage of seizure inhibition is expressed as the mean ± S.D. Bars represent the standard deviation. <span class="html-italic">n</span> = 6. * <span class="html-italic">ANOVA test</span> = Significantly different to the response displayed by the group that received Diazepam at 4.0 mg/kg. # <span class="html-italic">ANOVA test</span> = significantly different to the response displayed by the group that received carbamazepine at 25.0 mg/kg. <span class="html-italic">ns*</span> = not significantly different to the response displayed by the group that received diazepam at 4.0 mg/kg. <span class="html-italic">ns<sup>#</sup></span> = not significantly different to the response displayed by the group that received Carbamazepine at 25.0 mg/kg.</p>
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10 pages, 7275 KiB  
Case Report
Confusing Onset of MOGAD in the Form of Focal Seizures
by Małgorzata Jączak-Goździak and Barbara Steinborn
Neurol. Int. 2025, 17(3), 37; https://doi.org/10.3390/neurolint17030037 - 27 Feb 2025
Viewed by 106
Abstract
MOGAD is a demyelinating syndrome with the presence of antibodies against myelin oligodendrocyte glycoprotein, which is, next to multiple sclerosis and the neuromyelitis optica spectrum, one of the manifestations of the demyelinating process, more common in the pediatric population. MOGAD can take a [...] Read more.
MOGAD is a demyelinating syndrome with the presence of antibodies against myelin oligodendrocyte glycoprotein, which is, next to multiple sclerosis and the neuromyelitis optica spectrum, one of the manifestations of the demyelinating process, more common in the pediatric population. MOGAD can take a variety of clinical forms: acute disseminated encephalomyelitis (ADEM), retrobulbar optic neuritis, often binocular (ON), transverse myelitis (TM), or NMOSD-like course (neuromyelitis optica spectrum disorders), less often encephalopathy. The course may be monophasic (40–50%) or polyphasic (50–60%), especially with persistently positive anti-MOG antibodies. Very rarely, the first manifestation of the disease, preceding the typical symptoms of MOGAD by 8 to 48 months, is focal seizures with secondary generalization, without typical demyelinating changes on MRI of the head. The paper presents a case of a 17-year-old patient whose first symptoms of MOGAD were focal epileptic seizures in the form of turning the head to the right with the elevation of the left upper limb and salivation. Seizures occurred after surgical excision of a tumor of the right adrenal gland (ganglioneuroblastoma). Then, despite a normal MRI of the head and the exclusion of onconeural antibodies in the serum and cerebrospinal fluid after intravenous treatment, a paraneoplastic syndrome was suspected. After intravenous steroid treatment and immunoglobulins, eight plasmapheresis treatments, and the initiation of antiepileptic treatment, the seizures disappeared, and no other neurological symptoms occurred for nine months. Only subsequent relapses of the disease with typical radiological and clinical picture (ADEM, MDEM, recurrent ON) allowed for proper diagnosis and treatment of the patient both during relapses and by initiating supportive treatment. The patient’s case allows us to analyze the multi-phase, clinically diverse course of MOGAD and, above all, indicates the need to expand the diagnosis of epilepsy towards demyelinating diseases: determination of anti-MOG and anti-AQP4 antibodies. Full article
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<p>EEG trace: rapid intraictal rate (December 2020).</p>
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<p>EEG recording: postictal theta waves (December 2020).</p>
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<p>Transverse FLAIR brain magnetic resonance image showing numerous foci of increased signal between the basal nuclei (December 2021).</p>
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<p>Transverse FLAIR brain magnetic resonance image showing area of increased signal in the right middle cerebellar peduncle (December 2021).</p>
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<p>FLAIR image of brain magnetic resonance imaging in the transverse plane showing a demyelinating focus in the right hemisphere of the cerebellum, including its peduncle (March 2022).</p>
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<p>Transverse FLAIR brain magnetic resonance image showing a subcortical demyelinating focus in the right frontal lobe (March 2022).</p>
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<p>Spinal cord MRI showing foci of increased signals of thoracic and cervical spine on T2 sequences (March 2022).</p>
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<p>MRI of optic nerves showing a dilatation and edema of the proximal left optic nerve (March 2022).</p>
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<p>Transverse FLAIR brain magnetic resonance image showing two new subcortical foci of increased signals: one located in the right frontal lobe measuring 13 × 7 mm and another in the left parietal lobe measuring 19 × 14 mm. (May 2022).</p>
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<p>MRI of optic nerves showing the right optic nerve with blurred outlines (May 2022).</p>
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17 pages, 8202 KiB  
Review
Current Management of Aneurysmal Subarachnoid Hemorrhage
by Jay Max Findlay
Neurol. Int. 2025, 17(3), 36; https://doi.org/10.3390/neurolint17030036 - 26 Feb 2025
Viewed by 144
Abstract
The diagnosis of aneurysmal subarachnoid hemorrhage (aSAH) is most difficult in patients who are in good clinical condition with a small hemorrhage, especially when a ruptured aneurysm might not be considered, or if a computed tomographic (CT) scan is not obtained, or if [...] Read more.
The diagnosis of aneurysmal subarachnoid hemorrhage (aSAH) is most difficult in patients who are in good clinical condition with a small hemorrhage, especially when a ruptured aneurysm might not be considered, or if a computed tomographic (CT) scan is not obtained, or if when a CT is obtained, the findings are subtle and missed by an inexperienced reviewer. All acute onset (thunderclap) headaches should be considered ruptured aneurysms until proven otherwise. Treatment begins with immediate control of pain and blood pressure, placement of an external ventricular drain (EVD) in poor-grade patients and those with acute hydrocephalus on CT scanning, administration of antifibrinolytic tranexamic acid, and then repair of the aneurysm with either surgical clipping or endovascular techniques as soon as the appropriate treatment team can be assembled. After securing the aneurysm, aSAH patient treatment is focused on maintaining euvolemia and a favorable systemic metabolic state for brain repair. A significant and aneurysm-specific threat after aSAH is delayed arterial vasospasm and resulting cerebral ischemia, which is detected by vigilant bedside examinations for new-onset focal deficits or neurological decline, assisted with daily transcranial Doppler examinations and the judicious use of vascular imaging and cerebral perfusion studies with CT. The management of diagnosed symptomatic vasospasm is the prompt induction of hypertension with vasopressors, but if this fails to reverse deficits quickly after reaching a target systolic blood pressure of 200 mmHg, endovascular angioplasty is indicated, providing CT scanning rules out an established cerebral infarction. Balloon angioplasty should be considered early for all patients found to have severe angiographic vasospasm, with or without detectable signs of ischemic neurological deterioration due to either sedation or a pre-existing deficit. Full article
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<p>CT scan through the basal subarachnoid cisterns showing thick, hyperdense (white) clots in a 52-year-old woman who was drowsy and confused after an acute onset headache (Hunt and Hess and WFNS grade III). Note the thicker clot in the right Sylvian and insular cisterns (left side of the figure).</p>
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<p>CT angiogram of the same patient shows two right-sided saccular aneurysms (left side of figure), the larger at the right MCA bifurcation and the second arising from the right ICA (up to 20% of aSAH patients have more than one aneurysm). Given that the MCA aneurysm was larger and associated with thicker Sylvian and insular clots, we could be confident it was the source of the bleeding, but both aneurysms were repaired with microsurgical clipping on the day of admission.</p>
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<p>CT scan showed a thin layer of hyperdense subarachnoid blood encircling the upper brainstem, typical of a peri mesencephalic SAH. The 44-year-old patient presented with a GCS of 15 following a sudden-onset headache. CT angiography was normal.</p>
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<p>CT scan showing focal hyperdense subarachnoid clots near the midbrain and tentorial incisura, typical of a peri mesencephalic SAH. The 51-year-old patient presented with a GCS of 15 following a thunderclap headache. CT angiography was normal.</p>
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<p>CT scan through the basal subarachnoid cisterns showing thick, hyperdense clots in a 31-year-old man who was drowsy and confused after a sudden onset headache with vomiting (Hunt and Hess and WFNS grade III). Note the thickest clot is in the left Sylvian fissure surrounding the left MCA (The following figures are all from the same patient).</p>
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<p>CT scan through the lateral ventricles showing intraventricular blood, indicating a Fisher grade 4 aSAH associated with a high risk of delayed cerebral vasospasm. An EVD was inserted.</p>
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<p>Catheter angiography immediately prior to coiling of a small anterior communicating aneurysm, just several millimeters in diameter. Note the normal caliber of the blood vessels to be compared with the next series of figures.</p>
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<p>Seven days later, the patient became more lethargic with a new right-sided weakness. Velocities in the middle cerebral arteries on transcranial Doppler exceed 200 cm/s, indicating significant vasospasm. Hypertension was induced (see text), and after a CT ruled out cerebral infarction, a following catheter angiogram showed severe left MCA narrowing (<b>a</b>), where the thickest subarachnoid clot was located on the initial CT, and moderate vasospasm of the right MCA (<b>b</b>).</p>
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<p>Post-angioplasty showing excellent reversal of the left MCA and proximal ACA vasospasm (<b>a</b>) the right MCA (<b>b</b>). All vasospastic vessels that could be reached with the balloon catheter were treated). The patient’s clinical condition improved and remained stable until full recovery.</p>
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<p>An example of acute hydrocephalus following aSAH secondary to a ruptured ACommA in a clinical aSAH grade 3 28-year-old woman. The red arrows point to subarachnoid blood in the cisterns, sulci, and interhemispheric fissure, and the yellow arrows point to prominent ventricles. This degree of hydrocephalus, while not florid, was clear with visible temporal horns (normally not visible in young adults) (<b>a</b>), and “rounding” of the frontal horns of the lateral ventricles (<b>b</b>). Combined with the flattening of the cerebral sulci (<b>c</b>), this CT scan is indicative of dangerously raised intracranial pressure, especially in a young patient requiring early EVD insertion.</p>
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16 pages, 1717 KiB  
Article
Shifting Outcomes: Superior Functional Recovery in Embolic Stroke of Undetermined Source Compared to Cardioembolic Stroke
by Jessica Seetge, Balázs Cséke, Zsófia Nozomi Karádi, Edit Bosnyák and László Szapáry
Neurol. Int. 2025, 17(3), 35; https://doi.org/10.3390/neurolint17030035 - 25 Feb 2025
Viewed by 128
Abstract
Background/Objectives: An embolic stroke of undetermined source (ESUS) is a subtype of ischemic stroke characterized by a non-lacunar infarct in the absence of a clearly identifiable embolic source, despite comprehensive diagnostic evaluation. While ESUS patients are typically younger, have fewer cardiovascular comorbidities, and [...] Read more.
Background/Objectives: An embolic stroke of undetermined source (ESUS) is a subtype of ischemic stroke characterized by a non-lacunar infarct in the absence of a clearly identifiable embolic source, despite comprehensive diagnostic evaluation. While ESUS patients are typically younger, have fewer cardiovascular comorbidities, and experience milder strokes than those with cardioembolic strokes (CEs), their functional recovery remains underexplored. Methods: We retrospectively analyzed data from 374 ischemic stroke patients (n = 94 ESUS, n = 280 CE) admitted to the Department of Neurology, University of Pécs, between February 2023 and September 2024. Functional recovery was assessed using the modified Rankin Scale (mRS). Propensity score matching (PSM) was performed to balance the baseline characteristics, and the mRS-shift was compared between groups. Independent predictors of mRS-shift were identified using Huber regression and extreme gradient boosting (XGBoost). Results: The ESUS patients were significantly younger (60.7 ± 13.8 years vs. 75.1 ± 11.3 years, p < 0.001), had lower pre-morbid modified Rankin Scale (pre-mRS) scores (0.34 ± 0.91 vs. 0.81 ± 1.23, p < 0.001), were less likely to have hypertension (75.5% vs. 86.1%, p = 0.027) and diabetes (23.4% vs. 36.8%, p = 0.024), and presented with milder strokes (National Institutes of Health Stroke Scale [NIHSS] score at admission: 5.4 ± 4.5 vs. 8.1 ± 6.3, p < 0.001, and 72 h post-stroke: 3.0 ± 4.4 vs. 6.5 ± 6.3, p < 0.001) compared to the CE patients. After adjusting for baseline differences, the ESUS patients demonstrated significantly greater functional recovery than the CE patients (adjusted mRS-shift: 1.84 ± 1.14 vs. 2.53 ± 1.69, p = 0.022). Age, pre-mRS score, and NIHSS score at 72 h post-stroke were the strongest predictors of mRS-shift, with an older age, a higher pre-mRS score, and a greater stroke severity significantly decreasing the odds of recovery. Conclusions: The ESUS patients showed superior functional recovery compared to the CE patients, even after accounting for baseline differences. These findings highlight the need for further research into the pathomechanisms underlying ESUSs and the development of optimal treatment strategies to improve patient outcomes. Full article
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<p>A flowchart of the study. Abbreviations: mRS = modified Rankin Scale, ESUS = embolic stroke of undetermined source, pre-mRS = pre-morbid modified Rankin Scale, HT = hypertension, DM = diabetes mellitus, smoking = current smoking, alcohol = alcohol consumption, NIHSS = National Institutes of Health Stroke Scale at admission, 72hNIHSS = National Institutes of Health Stroke Scale 72 h post-stroke.</p>
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<p>Distribution of 90-day mRS. Abbreviations: mRS = modified Rankin Scale, ESUS = embolic stroke of undetermined source, CE = cardioembolic stroke.</p>
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<p>Density plot of adjusted mRS-shift. Abbreviations: mRS = modified Rankin Scale, ESUS = embolic stroke of undetermined source, CE = cardioembolic stroke.</p>
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<p>A forest plot of the predictors of mRS-shift. Abbreviations: mRS = modified Rankin Scale, pre-mRS = pre-morbid modified Rankin Scale, NIHSS = National Institutes of Health Stroke Scale at admission, 72hNIHSS = National Institutes of Health Stroke Scale 72 h post-stroke, INR = international normalized ratio, SC = standard care, TL = thrombolysis, MT = mechanical thrombectomy, OR = odds ratio. * The odds ratios are displayed on a logarithmic scale to enhance the visualization of both small and large confidence intervals. Note: The predictors with statistically significant effects (<span class="html-italic">p</span> &lt; 0.05) are highlighted in red; MT, while not reaching statistical significance, demonstrates a strong trend in this direction. The size of each marker (‘X’) is proportional to the odds ratio, providing a visual representation of the effect size.</p>
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<p>A beeswarm plot of the mean SHAPs values of the predictors of mRS-shift. Abbreviations: SHAPs = SHapley Additive exPlanations, mRS = modified Rankin Scale, 72hNIHSS = National Institutes of Health Stroke Scale 72 h post-stroke, pre-mRS = pre-morbid modified Rankin Scale, INR = international normalized ratio, NIHSS = National Institutes of Health Stroke Scale at admission, TL = thrombolysis, MT = mechanical thrombectomy, SC = standard care. * The range was adjusted for visual consistency. Note: Each dot represents an observation from the test set, with the color indicating the feature value (darker = higher). The SHAPs values on the x-axis show the contribution of each predictor to the model’s prediction of the mRS-shift. The spread of the dots along the x-axis highlights the variability in feature impact across different patients.</p>
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14 pages, 7603 KiB  
Article
Ultrasound-Guided Percutaneous Nerve Stimulation in Post-Stroke Spasticity: A Case Report
by Francesco Sartori, Albert Puig-Diví and Javier Picañol
Neurol. Int. 2025, 17(3), 34; https://doi.org/10.3390/neurolint17030034 - 24 Feb 2025
Viewed by 188
Abstract
Introduction: Post-stroke spasticity (PSS) significantly impacts the quality of life for stroke survivors. While various treatments exist, options for refractory cases are limited. Ultrasound-guided percutaneous peripheral nerve stimulation (pPNS), commonly used in pain management, has not been studied for its potential use in [...] Read more.
Introduction: Post-stroke spasticity (PSS) significantly impacts the quality of life for stroke survivors. While various treatments exist, options for refractory cases are limited. Ultrasound-guided percutaneous peripheral nerve stimulation (pPNS), commonly used in pain management, has not been studied for its potential use in spasticity management. This case report aims to evaluate the sensorimotor effects of pPNS in a patient with severe PSS. Case description: A 38-year-old male with severe PSS and functional limitations post-ischemic stroke in the middle cerebral artery underwent a six-week pPNS protocol (12 sessions). Low-frequency (2 Hz) stimulation targeted the median, musculocutaneous, and anterior interosseous nerves, while medium-frequency (10 Hz) stimulation targeted the posterior interosseous and radial nerves. Spasticity was assessed using the Modified Ashworth Scale (MAS) and Tardieu Scale (TS). Somatosensory assessments included tactile thresholds, pressure pain thresholds, and conditioned pain modulation (CPM). Outcomes: Spasticity decreased significantly, with reductions of 60.4% and 67.0% in elbow and wrist MAS scores, respectively, and a 49.5% reduction in TS scores. However, spasticity levels returned to baseline between sessions. Somatosensory assessments revealed increased tactile thresholds, decreased pressure pain thresholds, and an 81.3% reduction in CPM. The intervention was well tolerated, with minor transient effects, and the patient preferred pPNS over botulinum toxin injections. Conclusions: pPNS may effectively reduce spasticity and modulate somatosensory thresholds in PSS. These preliminary findings highlight its potential as an alternative treatment for refractory PSS, warranting further research with larger sample sizes and control groups to assess its broader clinical applicability. Full article
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<p>(<b>A</b>) Diagram of the case report, comprising 12 intervention sessions. Spasticity changes were assessed at each session, while comprehensive somatosensory evaluations were conducted at baseline, midpoint, and study completion. (<b>B</b>) Primary regions of the upper limb where somatosensory assessments of pressure pain thresholds and tactile thresholds were conducted. This figure was generated using <a href="http://BioRender.com" target="_blank">BioRender.com</a> (Version 1.0.0.3) under a licensed agreement.</p>
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<p>(<b>A</b>) Graphical representation of the ultrasound-guided intervention on the affected upper limb. (<b>B</b>) Probe positioning for ultrasound guidance of the intervention targeting the musculocutaneous nerve (upper panel) and the median nerve (lower panel). (<b>C</b>) Probe positioning for ultrasound guidance of the intervention targeting the radial nerve (upper panel) and the posterior interosseous nerve (lower panel). (<b>D</b>) Diagram of the interventions performed, illustrating a medium-frequency protocol and a low-frequency protocol. (<b>E</b>) Upper panel: Ultrasound visualization of the musculocutaneous nerve. Lower panel: Ultrasound visualization of the median nerve. (<b>F</b>) Upper panel: Ultrasound visualization of the radial nerve. Lower panel: Ultrasound visualization of the posterior interosseous nerve. In (<b>E</b>,<b>F</b>), pattern nerves are indicated by white arrowheads. Panel A was generated using <a href="http://BioRender.com" target="_blank">BioRender.com</a> under a licensed agreement.</p>
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<p>(<b>A</b>) Manual assessment of spasticity in the upper limb through passive mobilization to obtain Tardieu Spasticity Scale (TSS) scores. (<b>B</b>) Illustration of passive mobilization of the upper limb with ultrasound guidance for precise intervention positioning. (<b>C</b>) Comparative analysis of the spasticity index at the elbow using the Tardieu Spasticity Scale (TSS) before and after percutaneous peripheral nerve stimulation (pPNS). (<b>D</b>) Longitudinal changes in the spasticity index at the elbow across 12 intervention sessions, based on TSS measurements, contrasting pre-pPNS (black circles) and post-pPNS (blue squares) scores. (<b>E</b>) Comparative analysis of the Modified Ashworth Scale (MAS) scores for the elbow and wrist pre- and post-pPNS intervention. (<b>F</b>) Temporal progression of the MAS scores for the elbow across 12 sessions, comparing pre-pPNS (black circles) and post-pPNS (blue squares) results. (<b>G</b>) Temporal progression of the MAS scores for the wrist across 12 sessions, comparing pre-pPNS (black circles) and post-pPNS (red squares) results.</p>
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<p>Tactile and pressure pain threshold comparisons, alongside conditioned pain modulation, for the affected and unaffected upper limbs before and after pPNS intervention. (<b>A</b>) Baseline tactile thresholds (measured in grams) across various regions of the affected and unaffected limbs prior to intervention. Positive values indicate higher tactile thresholds, suggesting reduced sensitivity, while negative values indicate lower thresholds, suggesting heightened sensitivity. (<b>B</b>) Pre- vs. post-pPNS changes in tactile thresholds in the unaffected limb. (<b>C</b>) Pre- vs. post-pPNS changes in tactile thresholds in the affected limb. (<b>D</b>) Baseline pressure pain thresholds (PPT, kg/cm<sup>2</sup>) for the affected and unaffected limbs before intervention. Higher PPT values indicate lower sensitivity to pressure pain, while lower values reflect higher sensitivity. (<b>E</b>) Pre- vs. post-pPNS changes in PPT for the unaffected limb. (<b>F</b>) Pre- vs. post-pPNS changes in PPT for the affected limb. (<b>G</b>) Conditioned pain modulation (CPM) effects, showing normalized data over three sessions (left panel) and a summary comparison pre- and post-intervention (right panel). Abbreviations: VF, Von Frey filaments; PPT, pressure pain threshold; CPM, conditioned pain modulation; pPNS, percutaneous peripheral nerve stimulation.</p>
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19 pages, 2860 KiB  
Article
Tracking Migraine Symptoms: A Longitudinal Comparison of Smartphone-Based Headache Diaries and Clinical Interviews
by Nicolas Vandenbussche, Jonas Van Der Donckt, Mathias De Brouwer, Bram Steenwinckel, Marija Stojchevska, Femke Ongenae, Sofie Van Hoecke and Koen Paemeleire
Neurol. Int. 2025, 17(3), 33; https://doi.org/10.3390/neurolint17030033 - 24 Feb 2025
Viewed by 141
Abstract
Background/Objectives: By leveraging the capabilities of a smartphone-based headache diary, the objective of this study was to determine the amount of agreement between migraine-associated symptomatology during headache events and the symptoms documented during clinician-led intake interviews. Methods: This was a 90-day longitudinal, [...] Read more.
Background/Objectives: By leveraging the capabilities of a smartphone-based headache diary, the objective of this study was to determine the amount of agreement between migraine-associated symptomatology during headache events and the symptoms documented during clinician-led intake interviews. Methods: This was a 90-day longitudinal, smartphone-based headache calendar study for participants diagnosed with migraine. Registered headache events were labeled as “definite migraine”, “probable migraine”, and “not migraine” in accordance with the International Classification of Headache Disorders, Third Edition (ICHD-3) criteria. Symptoms’ agreement with clinician-led intake interviews (agreement percentages and kappa coefficients), symptoms’ similarity between headache events within users (percentage), and amount of newly registered ICHD-3 symptoms per participant were calculated. Results: Twenty-seven participants provided 505 headache events eligible for analysis. The median agreement between recorded headache event symptomatology and clinician-led intake interview phenotyping ranged between 40% (for events fulfilling “not migraine” criteria) and 55.5% (“definite migraine”) (p < 0.001). Higher intraparticipant headache event pair similarity was observed for “definite migraine” pairs (p < 0.01), along with a decreasing trend in similarity as the attack-pair headache distance increases. Over half of the participants registered at least one new ICHD-3 symptom during the study. Conclusions: Electronic diary registrations show substantial longitudinal variability in intrapersonal headache symptomatology, with the similarity of headache events declining over time. The registration of a new ICHD-3 symptom was the rule rather than the exception. Full article
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Figure 1
<p>User interface for the submission of answers during the clinician-led intake interview. Blue tick boxes are checkboxes (multiple answers possible).</p>
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<p>Headache registration interface for participants during the longitudinal phase of the study. (<b>a</b>) The overview of headache events registered in a timeline. (<b>b</b>) The headache registry module with different steps to be completed.</p>
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<p>Overview of available headache event pairs per 5-day bin. The x-axis indicates the distance in days between the headache intervals of an event pair. Only events of the same participant with the same attack scoring can be paired. The vertical black dashed line indicates the upper headache-pair threshold.</p>
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<p>Headache event symptomatology agreement with clinician-led intake interviews and its trend over time. Each data point in the subplots corresponds to a bias-free headache event (<span class="html-italic">n</span> = 505), color-coded by the ICHD-3 headache event label. The subplots are divided into columns on the basis of the symptom subset, showing either agreement with the clinician-led intake interviews (Rows 1–2) or the number of checked symptoms (Row 3). Subplots (<b>A</b>–<b>C</b>) use box plots to depict the distribution of intake agreement for different subgroups, with statistical differences determined by the two-sided Mann–Whitney U test. Subplots (<b>D</b>–<b>F</b>) illustrate the trend of this intake agreement for the study period, with a first-order regression line and a 95% confidence interval for each headache event label group. The third row (subplots (<b>G</b>–<b>I</b>)), formatted similarly to the row above, displays the count of checked symptoms over time, but uses a locally weighted regression to emphasize local trends. Finally, the subplot (<b>J</b>) represents a histogram that counts the available headache events for each label group over time, using 5-day bins. Note: <span class="html-italic">p</span>-values: **** = <span class="html-italic">p</span> &lt; 0.0001, *** = <span class="html-italic">p</span> &lt; 0.001, ** = <span class="html-italic">p</span> &lt; 0.01, * = <span class="html-italic">p</span> &lt; 0.05. Abbreviations: ICHD-3, International Classification of Headache Disorders Third Edition; Q1, first quartile; Q3, third quartile.</p>
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<p>Per-participant mean IoU symptom similarity using paired headache event bins (bin size = 5 days). All subplots display median-aggregated IoU values of headache event pairs, using 5-day bins based on the headache distance of each pair. The headache event pairs were formed by combining headache events from each participant that have the same group label (i.e., “definite migraine”, “probable migraine”, or “not migraine”) and are color-coded accordingly. The columns of the first two subplot rows (subplots (<b>A</b>–<b>F</b>)) indicate the symptom sublists. In the first row (<b>A</b>–<b>C</b>), box plots illustrate the distribution of these per-participant mean-aggregated similarity values across different subgroups, with the two-sided Mann–Whitney U test indicating statistical differences. The second row (<b>D</b>–<b>F</b>) visualizes the similarity trend over time, represented by the distance of headache event pairs, featuring a first-order regression line and a 95% confidence interval for each classification group. The bottom subplot (<b>G</b>) is a histogram that counts the number of participants providing these mean aggregated values for each corresponding headache event label and 5-day bin. Note: <span class="html-italic">p</span>-values: **** = <span class="html-italic">p</span> &lt; 0.0001, *** = <span class="html-italic">p</span> &lt; 0.001, ** = <span class="html-italic">p</span> &lt; 0.01, * = <span class="html-italic">p</span> &lt; 0.05. Abbreviations: ICHD-3, International Classification of Headache Disorders, Third Edition; IoU, intersection over union.</p>
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<p>Number of participants registering new canonical ICHD-3 symptoms (<span class="html-italic">n</span> = 27).</p>
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20 pages, 3290 KiB  
Review
Evidence-Based Approach to Cerebral Vasospasm and Delayed Cerebral Ischemia: Milrinone as a Therapeutic Option—A Narrative Literature Review and Algorithm Treatment Proposition
by Pedro Batarda Sena, Marta Gonçalves, Bruno Maia, Margarida Fernandes and Luís Bento
Neurol. Int. 2025, 17(3), 32; https://doi.org/10.3390/neurolint17030032 - 21 Feb 2025
Viewed by 560
Abstract
Aneurysmal subarachnoid hemorrhage (aSAH) is a severe neurocritical condition often complicated by cerebral vasospasm (CVS), leading to delayed cerebral ischemia (DCI) and significant morbidity and mortality. Despite advancements in management, therapeutic options with robust evidence remain limited. Milrinone, a phosphodiesterase type 3 (PDE3) [...] Read more.
Aneurysmal subarachnoid hemorrhage (aSAH) is a severe neurocritical condition often complicated by cerebral vasospasm (CVS), leading to delayed cerebral ischemia (DCI) and significant morbidity and mortality. Despite advancements in management, therapeutic options with robust evidence remain limited. Milrinone, a phosphodiesterase type 3 (PDE3) inhibitor, has emerged as a potential therapeutic option. Intravenous milrinone demonstrated clinical and angiographic improvement in 67% of patients, reducing the need for mechanical angioplasty and the risk of functional disability at 6 months (mRS ≤ 2). Side effects, including hypotension, tachycardia, and electrolyte disturbances, were observed in 33% of patients, occasionally leading to early drug discontinuation. Based on the evidence, we propose a treatment algorithm for using milrinone to optimize outcomes and standardize its application in neurocritical care settings. Full article
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<p>Milrinone dose and titration flowchart summary [<a href="#B20-neurolint-17-00032" class="html-bibr">20</a>,<a href="#B21-neurolint-17-00032" class="html-bibr">21</a>,<a href="#B23-neurolint-17-00032" class="html-bibr">23</a>,<a href="#B26-neurolint-17-00032" class="html-bibr">26</a>,<a href="#B27-neurolint-17-00032" class="html-bibr">27</a>,<a href="#B28-neurolint-17-00032" class="html-bibr">28</a>,<a href="#B35-neurolint-17-00032" class="html-bibr">35</a>].</p>
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<p>Hemodynamic and neurological monitoring orientations [<a href="#B10-neurolint-17-00032" class="html-bibr">10</a>,<a href="#B20-neurolint-17-00032" class="html-bibr">20</a>,<a href="#B21-neurolint-17-00032" class="html-bibr">21</a>,<a href="#B22-neurolint-17-00032" class="html-bibr">22</a>,<a href="#B23-neurolint-17-00032" class="html-bibr">23</a>,<a href="#B24-neurolint-17-00032" class="html-bibr">24</a>,<a href="#B26-neurolint-17-00032" class="html-bibr">26</a>,<a href="#B27-neurolint-17-00032" class="html-bibr">27</a>,<a href="#B28-neurolint-17-00032" class="html-bibr">28</a>,<a href="#B31-neurolint-17-00032" class="html-bibr">31</a>,<a href="#B35-neurolint-17-00032" class="html-bibr">35</a>].</p>
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<p>Proposed algorithm for the management of CVS in aSAH using Milrinone. The algorithm outlines a step-by-step approach to diagnosing and treating CVS in patients with aSAH. It includes criteria for patient selection, initiation of milrinone therapy, dosage titration, and indications for advanced monitoring and endovascular treatment.</p>
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<p>Protocol for milrinone administration in CVS. This figure continues the protocol with a detailed protocol for milrinone administration, including initial bolus dosing, continuous infusion titration based on the severity of vasospasm, and steps for managing drug-related complications such as hypotension. [<a href="#B1-neurolint-17-00032" class="html-bibr">1</a>,<a href="#B23-neurolint-17-00032" class="html-bibr">23</a>,<a href="#B24-neurolint-17-00032" class="html-bibr">24</a>,<a href="#B26-neurolint-17-00032" class="html-bibr">26</a>,<a href="#B36-neurolint-17-00032" class="html-bibr">36</a>,<a href="#B48-neurolint-17-00032" class="html-bibr">48</a>,<a href="#B51-neurolint-17-00032" class="html-bibr">51</a>].</p>
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