Epidemiology of seropositive myasthenia gravis in Sardinia: A population-based study in the district of Sassari.

INTRODUCTION/AIMS: The global incidence and prevalence of myasthenia gravis (MG) range between 6-31/million and 10-37/100,000, respectively. Sardinia is a high-risk region for different immune-mediated disorders, but the epidemiology of MG remains unclear. We determined the epidemiology of MG with acetylcholine receptor (AChR)-immunoglobulin G (IgG) and muscle-specific tyrosine kinase (MuSK)-IgG in the district of Sassari (North-Western Sardinia; population, 325,288). METHODS: From the laboratory of the University Hospital of Sassari (reference for AChR/MuSK-IgG testing in Sardinia since 1998) and the main neurology units in Sardinia, we retrospectively identified MG patients with (1) AChR-IgG and/or MuSK-IgG positivity by radioimmunoprecipitation assay; and (2) residency in the district of Sassari. Incidence (January 2010-December 2019) and prevalence (December 31, 2019) were calculated. RESULTS: A total of 202 patients were included (incident, 107; prevalent, 180). Antibody specificities were AChR (n = 187 [93%]) and MuSK (n = 15 [7%]). The crude MG incidence (95% confidence interval) was 32.6 (26.8-39.2)/million, while prevalence was 55.3 (47.7-63.9)/100,000. After age-standardization to the world population, incidence decreased to 18.4 (14.3-22.5)/million, while prevalence decreased to 31.6 (26.1-37.0)/100,000. Among incident cases, age strata (years) at MG onset were: <18 (2%), 18-49 (14%), 50-64 (21%), and ≥65 (63%). DISCUSSION: Sardinia is a high-risk region for MG, with a prevalence that exceeds the European threshold for rare disease. Identification of the environmental and genetic determinants of this risk may improve our understanding of disease pathophysiology.

Vocal Fold Paralysis After Spinal and Epidural Anesthesia: A Case Report and Scoping Review.

OBJECTIVES: Cranial nerve paralysis is a rare complication of spinal and epidural anesthesia, and some cases of vocal fold paralysis (VFP) have been reported. The aim of this article is to report a case, identify evidence supporting the possibility of VFP being a complication of spinal and epidural anesthesia and to investigate the frequency, the characteristics, and the possible mechanisms of such a complication. DATA SOURCES: CINAHL Complete, Google Scholar, Cochrane Library, Pubmed, and EMBASE. METHODS: Case report according to CARE guidelines; scoping review according to PRISMA-ScR criteria. All types of studies that reported on patients of any age and sex, all types of spinal/epidural anesthesia regardless of the location and of drugs used were included. A data extraction sheet was completed for each study selected for inclusion based on the full-text screenings. Extracted data included: study characteristics, participant characteristics, intervention characteristics, outcome measures, clinical investigations. The study did not receive external funding. RESULTS: Eight studies met inclusion criteria and a total of 13 events (in 12 patients, including ours) were reported to date. Although there are some hypotheses in regard to the mechanism underlying the phenomena, including mechanical and inflammatory ones, the exact cause is still unclear. CONCLUSIONS: Only few cases of VFP after spinal or epidural anesthesia have been reported to date; however, it seems possible that VFP might be a potential underreported complication of such procedures. We believe that more research on the topic is warranted, especially considering the wide population potentially at risk. LEVEL OF EVIDENCE: NA Laryngoscope, 2024.

Prolonged Secondary Stroke Prevention with Edoxaban: A Long-Term Follow-Up of the SATES Study.

BACKGROUND: Little evidence is available on the long-term efficacy and safety of edoxaban, mainly due to the recent release date. The primary objective of the study was to evaluate the safety of edoxaban, defined by the incidence of major bleedings. We then aimed to evaluate the incidence of thromboembolic events and the persistence of edoxaban therapy in the long-term. METHODS: In this observational cohort study, we included ischemic stroke patients enrolled in a previous study to evaluate the safety and efficacy of long-term edoxaban treatment. Data were collected by a trained investigator through a structured telephone interview. RESULTS: Sixty-three subjects (median age 81.0 (73.5-88.0) years, 38.1% male) were included in the study, with a mean follow-up of 4.4 ± 0.7 years (range: 3.2-5.5 years). Only one patient (1.6%, 0.4%/year) presented a major extracranial bleeding, and none had cerebral hemorrhage. Six thromboembolic events occurred in five patients (7.9%): three recurrent strokes, two transient ischemic attacks, and one myocardial infarction (2.2%/year). Over a follow-up period of more than three years, 13 patients discontinued edoxaban (20.6%). Conclusions: Edoxaban seems to be effective and safe in the long-term. The persistence rate of edoxaban therapy is optimal after more than three years of treatment.

Association of Obstructive Sleep Apnea and Atrial Fibrillation in Acute Ischemic Stroke: A Cross-Sectional Study.

Background: There is a growing body of evidence suggesting a link between obstructive sleep apnea (OSA) and atrial fibrillation (AF). The primary objective of this study is to evaluate the association between OSA and AF in acute ischemic stroke. The secondary objective is to describe the clinical features of patients with acute ischemic stroke and concomitant OSA. Methods: We enrolled consecutive patients with acute ischemic stroke. All patients underwent full-night cardiorespiratory polygraphy. To determine if there is an association between AF and OSA, we compared the observed frequency of this association with the expected frequency from a random co-occurrence of the two conditions. Subsequently, patients with and without OSA were compared. Results: A total of 174 patients were enrolled (mean age 67.3 ± 11.6 years; 95 males). OSA and AF were present in 89 and 55 patients, respectively. The association OSA + AF was observed in 33/174 cases, which was not statistically different compared to the expected co-occurrence of the two conditions. Patients with OSA showed a higher neck circumference and body mass index, a higher prevalence of hypertension and dysphagia, and a higher number of central apneas/hypoapneas. In the multivariate analysis, dysphagia and hypertension were independent predictors of OSA. A positive correlation was observed between OSA severity, BMI, and neck circumference. The number of central apneas/hypoapneas was positively correlated with stroke severity. Conclusions: Our data suggest that OSA and AF are highly prevalent but not associated in acute stroke. Our findings support the hypothesis that OSA acts as an independent risk factor for stroke.

Decompressive hemicraniectomy in patients with malignant middle cerebral artery infarction: A real-world study.

BACKGROUND: Malignant middle cerebral artery infarction (mMCA) is a devastating disease with rates of fatality as high as 80%. Decompressive hemicraniectomy (DHC) reduces mortality, but many survivors inevitably remain severely disabled. This study aimed to analyze patients with mMCA undergoing DHC or best medical treatment (BMT) baseline characteristics and factors linked to therapeutic choice and determinants of prognosis. METHODS: We recorded clinical and radiological features of patients undergoing BMT or DHC. The two groups were compared for epidemiology, clinical presentation, neuroimaging, and prognosis. Regression analysis was performed to identify predictors of surgical treatment and outcome. RESULTS: One hundred twenty-five patients were included (age 67.41 ± 1.39 yo; 65 M). Patients undergoing DHC (N = 57) were younger (DHC 55.71 ± 1.48 yo vs. BMT 77.22 ± 1.38) and had midline shift (DHC 96.5% (55/57) vs. BMT 35.3% (24/68), a larger volume of the affected hemisphere and reduced ventricles volume as compared to BMT. The chance of surgery depended on age (Exp(B) = 0.871, p < 0.001), clinical status at onset (NIHSS Exp(B) = 0.824, p = 0.030) and volume of the ventricle of the affected hemisphere (Exp(B) = 0.736, p = 0.006). Death rate during admission was significantly lower for DHC (DHC 15% (6/41) vs BMT 71.7% (38/53), Fisher's test = 30.234, p < 0.001). CONCLUSION: Although DHC may cause prolonged hospitalization and long-term disabled patients, it is a lifesaving therapy that should be considered for selected patients with mMCA but perioperative complications and cost-utility should be considered. Patients and families should be correctly counseled about this therapeutic choice and its short- and long-term consequences.

Role of Favorable Perfusion Imaging in Predicting the Outcome of Patients with Acute Ischemic Stroke due to Large Vessel Occlusion Undergoing Effective Thrombectomy: A Single-Center Study.

INTRODUCTION: We sought to verify the predicting role of a favorable profile on computed tomography perfusion (CTP) in the outcome of patients with acute ischemic stroke (AIS) due to large vessel occlusion (LVO) undergoing effective mechanical thrombectomy (MT). METHODS: We retrospectively enrolled 25 patients with AIS due to LVO and with a CTP study showing the presence of ischemic penumbra who underwent effective MT, regardless of the time of onset. The controls were 25 AIS patients with overlapping demographics and clinical and computed tomography angiography features at admission who had undergone successful MT within 6 h from onset and without a previous CTP study. The outcome measure was the modified Rankin Scale (mRS) score at 90 days. RESULTS: Sixty-four percent of the study patients had an mRS score of 0-1 at 90 days versus 12% of the control patients (p < 0.001). Patients of the study group had a more favorable distribution of disability scores (median mRS [IQR] score of 0 [0-2] vs. 2 [2-3]). Multivariate analysis showed that the selection of patients based on a favorable CTP study was strongly associated (p < 0.001) with a better neurological outcome. CONCLUSIONS: In our small-sized and retrospective study, the presence of ischemic penumbra was associated with a better clinical outcome in patients with AIS due to LVO after MT. In the future, a larger and controlled study with similar criteria of enrollment is needed to further validate the role of CTP in patient selection for MT, regardless of the time from the onset of symptoms.

Corticomotor Plasticity Predicts Clinical Efficacy of Combined Neuromodulation and Cognitive Training in Alzheimer's Disease.

OBJECTIVE: To investigate the efficacy of repetitive transcranial magnetic stimulation (rTMS) combined with cognitive training for treatment of cognitive symptoms in patients with Alzheimer's disease (AD). A secondary objective was to analyze associations between brain plasticity and cognitive effects of treatment. METHODS: In this randomized, sham-controlled, multicenter clinical trial, 34 patients with AD were assigned to three experimental groups receiving 30 daily sessions of combinatory intervention. Participants in the real/real group (n = 16) received 10 Hz repetitive transcranial magnetic stimulation (rTMS) delivered separately to each of six cortical regions, interleaved with computerized cognitive training. Participants in the sham rTMS group (n = 18) received sham rTMS combined with either real (sham/real group, n = 10) or sham (sham/sham group, n = 8) cognitive training. Effects of treatment on neuropsychological (primary outcome) and neurophysiological function were compared between the 3 treatment groups. These, as well as imaging measures of brain atrophy, were compared at baseline to 14 healthy controls (HC). RESULTS: At baseline, patients with AD had worse cognition, cerebral atrophy, and TMS measures of cortico-motor reactivity, excitability, and plasticity than HC. The real/real group showed significant cognitive improvement compared to the sham/sham, but not the real/sham group. TMS-induced plasticity at baseline was predictive of post-intervention changes in cognition, and was modified across treatment, in association with changes of cognition. INTERPRETATION: Combined rTMS and cognitive training may improve the cognitive status of AD patients, with TMS-induced cortical plasticity at baseline serving as predictor of therapeutic outcome for this intervention, and potential mechanism of action. CLINICAL TRIAL REGISTRATION: www.ClinicalTrials.gov, identifier NCT01504958.

Prospective Observational Study of Safety of Early Treatment with Edoxaban in Patients with Ischemic Stroke and Atrial Fibrillation (SATES Study).

New direct oral anticoagulants are recommended for stroke prevention in patients with non-valvular atrial fibrillation (NVAF). However, no data are available regarding the optimal time to start oral anticoagulation after acute stroke. The aim of our study was to evaluate the occurrence of symptomatic bleedings within 90 days from acute cardioembolic stroke in patients who received early treatment with Edoxaban. The study was conducted according to an observational prospective uncontrolled design. Secondary endpoints were the incidence of major bleeding (MB), hemorrhagic transformation within the first week of Edoxaban treatment, minor bleeding, and recurrent stroke. We included patients with Alberta Stroke Program Early Computed Tomography Score (ASPECTS) ≥ 6, NVAF, no previous treatment with any other anticoagulant, preserved swallowing function. Patients with estimated Glomerular Filtration Rate < 50 mL/min, body weight < 60 kg, receiving cyclosporine, dronedarone, erythromycin, ketoconazole, or previous treatment with any other anticoagulant were excluded. We enrolled 75 elderly patients with moderate disability. We did not observe any symptomatic intracranial bleeding or recurrent stroke after 3 months of treatment with early administration of Edoxaban, while two gastrointestinal MB, and 11 minor bleedings were reported. Asymptomatic bleeding was evaluated with a brain Magnetic Resonance Imaging performed 5 days after starting anticoagulant treatment with Edoxaban. Specifically, we observed small petechiae in 12% of the patients, confluent petechiae in 6.6% of the patients, and small hematoma of the infarcted area in 2.7% of the patients. No intralesional hematoma or hemorrhagic lesion outside the infarcted area were observed. According to our data, the early use of Edoxaban seems to be safe in patients after cardioembolic stroke. However, due to the small size of the study sample, and the short follow-up period, further studies are needed.

Dysphagia and Obstructive Sleep Apnea in Acute, First-Ever, Ischemic Stroke.

BACKGROUND: Obstructive sleep apnea (OSA) and dysphagia are common in acute stroke and are both associated with increased risk of complications and worse prognosis. The aims of the present study were (1) to evaluate the prevalence of OSA and dysphagia in patients with acute, first-ever, ischemic stroke; (2) to investigate their clinical correlates; and (3) to verify if these conditions are associated in acute ischemic stroke. METHODS: We enrolled a cohort of 140 consecutive patients with acute-onset (<48 hours), first-ever ischemic stroke. Computed tomography (CT) and magnetic resonance imaging scans confirmed the diagnosis. Neurological deficit was measured using the National Institutes of Health Stroke Scale (NIHSS) by examiners trained and certified in the use of this scale. Patients underwent a clinical evaluation of dysphagia (Gugging Swallowing Screen) and a cardiorespiratory sleep study to evaluate the presence of OSA. RESULTS: There are 72 patients (51.4%) with obstructive sleep apnea (OSA+), and there are 81 patients (57.8%) with dysphagia (Dys+). OSA+ patients were significantly older (P = .046) and had greater body mass index (BMI) (P = .002), neck circumference (P = .001), presence of diabetes (P = .013), and hypertension (P < .001). Dys+ patients had greater NIHSS (P < .001), lower Alberta Stroke Programme Early CT Score (P < .001), with greater BMI (P = .030). The association of OSA and dysphagia was greater than that expected based on the prevalence of each condition in acute stroke (P < .001). CONCLUSIONS: OSA and dysphagia are associated in first-ever, acute ischemic stroke.

Prognostic Value of EEG Microstates in Acute Stroke.

Given the importance of neuronal plasticity in recovery from a stroke and the huge variability of recovery abilities in patients, we investigated neuronal activity in the acute phase to enhance information about the prognosis of recovery in the stabilized phase. We investigated the microstates in 47 patients who suffered a first-ever mono-lesional ischemic stroke in the middle cerebral artery territory and in 20 healthy control volunteers. Electroencephalographic (EEG) activity at rest with eyes closed was acquired between 2 and 10 days (T0) after ischemic attack. Objective criteria allowed for the selection of an optimal number of microstates. Clinical condition was quantified by the National Institute of Health Stroke Scale (NIHSS) both in acute (T0) and stabilized (T1, 5.4 ± 1.7 months) phases and Effective Recovery (ER) was calculated as (NIHSS(T1)-NIHSS(T0))/NIHSS(T0). The microstates A, B, C and D emerged as the most stable. In patients with a left lesion inducing a language impairment, microstate C topography differed from controls. Microstate D topography was different in patients with a right lesion inducing neglect symptoms. In patients, the C vs D microstate duration differed after both a left and a right lesion with respect to controls (C lower than D in left and D lower than C in right lesion). A preserved microstate B in acute phase correlated with a better effective recovery. A regression model indicated that the microstate B duration explained the 11% of ER variance. This first ever study of EEG microstates in acute stroke opens an interesting path to identify neuronal impairments with prognostic relevance, to develop enriched compensatory treatments to drive a better individual recovery.

Static Magnetic Field Stimulation over Parietal Cortex Enhances Somatosensory Detection in Humans.

The role of neuronal oscillations in human somatosensory perception is currently unclear. To address this, here we use noninvasive brain stimulation to artificially modulate cortical network dynamics in the context of neurophysiological and behavioral recordings. We demonstrate that transcranial static magnetic field stimulation (tSMS) over the somatosensory parietal cortex increases oscillatory power specifically in the alpha range, without significantly affecting bottom-up thalamocortical inputs indexed by the early cortical component of somatosensory evoked potentials. Critically, we next show that parietal tSMS enhances the detection of near-threshold somatosensory stimuli. Interestingly, this behavioral improvement reflects a decrease of habituation to somatosensation. Our data therefore provide causal evidence that somatosensory perception depends on parietal alpha activity.SIGNIFICANCE STATEMENT Artificially increasing alpha power by placing a powerful magnetic field over the somatosensory cortex overcomes the natural decline in detection probability of a repeated near-threshold sensory stimulus.

Thrombus in Transit: A Potentially Life-threatening Complication of Cerebral Sinus Thrombosis.

We report the case of a 41-year-old, 7-weeks-pregnant patient, presenting with headache and generalized seizure due to cerebral venous thrombosis complicated by jugular thrombosis and thrombus dislocation into right cardiac cavities. The patient was treated with intravenous heparin, and underwent embolectomy in extracorporeal circulation. This case illustrates the variability of cerebral venous thrombosis progression and a potentially life-threatening condition even during anticoagulant therapy.

Thalamic Amnesia Mimicking Transient Global Amnesia.

INTRODUCTION: Transient global amnesia is a benign syndrome and one of the most frequent discharges from the emergency department that can hardly be distinguished from other mimicking diseases. No consensus in the evaluation of transient global amnesia has yet been found in the emergency setting. CASE REPORT: We describe a 69-year-old woman who presented to our emergency department with an abrupt onset of anterograde amnesia, preceded by a similar amnesic episode misinterpreted as transient global amnesia. Neuroradiologic, neuropsychological, and neurophysiological evaluations supported the diagnosis of vascular thalamic amnesia. CONCLUSIONS: We report a patient who clinically fulfilled transient global amnesia's criteria and in whom nevertheless was disclosed a thalamic ischemic lesion on neuroimaging.This case report highlights the importance of performing neuroradiologic screening in the emergency department even when clinical history and physical findings are highly suggestive for transient global amnesia.

Neurofibromatosis type 1 associated with vertebrobasilar dolichoectasia and pontine ischemic stroke.

Neurofibromatosis type 1 (NF1) is a heterogeneous, common, neurocutaneous disorder presenting different complications during a life span, including cerebrovascular dysplasia. To our knowledge this is the first reported case of NF1 associated with vertebrobasilar dolichoectasia and pontine ischemic stroke. We describe a 57-year-old man with NF1 who presented an acute onset right-sided facial palsy and hemiplegia, dysarthria, and gait imbalance. Magnetic resonance imaging showed an acute left paramedian pontine infarct and a hypoplastic right vertebral artery. Brain Computed Tomography Angiography revealed the occurrence of vertebrobasilar dolichoectasia. Co-occurrence of VBD and NF1 might not be merely casual and it may significantly heighten the mortality rate in this multisystem disorder. We suggest a possible role of VBD in the genesis of our patient's clinical-radiological features and prompt the early detection of asymptomatic arteriopathy in individuals with NF1 in order to ameliorate patients' quality of life and life expectancy.

Spontaneous sternocleidomastoid muscle hematoma following thrombolysis for acute ischemic stroke.

Spontaneous or traumatic bleeding is a common complication of systemic thrombolysis in patients with acute ischemic stroke. We report the case of an 83 y.o. woman with right facio-brachio-crural hemiparesis, left deviation of the head and aphasia who developed, after thrombolytic therapy, a spontaneous sternocleidomastoid muscle hematoma that regressed few days later. To our knowledge, this is the first case reported in the literature of asymptomatic and spontaneous skeletal muscle hematoma following thrombolysis for the treatment of acute ischemic stroke. The occurrence of lateral cervical tuberculosis lymphadenitis ipsilateral to sternocleidomastoid muscle hematoma may suggest a causal relationship between local chronic inflammation of active mycobacterial infection and thrombolysis-related extravasation. This case should suggest caution in thrombolytic treatment in patients with chronic immune dysregulation and vascular inflammation such as extra-pulmonary tuberculosis.

Risk factor and etiology analysis of ischemic stroke in young adult patients.

BACKGROUND: Approximately 10%-14% of ischemic strokes occur in young adults. AIMS: To investigate risk factors and etiologies of strokes of young adults admitted to the "stroke unit" of Policlinico "Gemelli" of Rome from December 2005 to January 2013. METHODS: In all, 150 consecutive patients younger than 50 years diagnosed with ischemic stroke were enrolled. Clinical evaluation consisted of a complete neurologic examination and the National Institutes of Health Stroke Scale. Diagnostic workup consisted of anamnesis, extensive laboratory, radiologic, and cardiologic examination. Stroke etiologies were classified according to the Trial of Org 10172 in Acute Stroke Treatment. RESULTS: Patients' mean age was 41 ± 8.0 years. The most common risk factors were dyslipidemia (52.7%), smoking (47.3%), hypertension (39.3%), and patent foramen ovale (PFO, 32.8%). Large-artery atherosclerosis was diagnosed as the cause of stroke in 17 patients (11.3%). Cardioembolism was presumed in 36 patients (24%), most of them presented a PFO at transesophageal echocardiography. Small-vessel occlusion was diagnosed in 12 patients (8%); all of them were hypertensive and most of them presented additional risk factors. Forty-one patients (27.3%) presented a stroke of other determined etiology and 44 (29.3%) presented a stroke of undetermined etiology. The 3-year survival was 96.8% and recurrent strokes occurred in only 3 cases. CONCLUSIONS: Traditional vascular risk factors are also very common in young adults with ischemic stroke, but such factors increase the susceptibility to stroke dependent to other causes as atherosclerosis and small-artery occlusion represent less than 20% of cases. Prognosis quoadvitam is good, being characterized by low mortality and recurrence rate.

Spinal hemangioblastoma presenting with low back pain in pregnancy.

BACKGROUND CONTEXT: Low back pain (LBP) is a very common complaint in pregnancy. For this reason, it is often considered directly attributable to the pregnancy rather than a medical problem requiring diagnostic workup. Pregnancy-related LBP should be differentiated from the rare cases of LBP associated with serious spinal diseases. Hemangioblastoma is a vascular tumor of the central nervous system that very rarely can involve the spinal cord. Pregnancy can increase the growth of hemangioblastomas, leading to the appearance of neurologic symptoms. PURPOSE: To describe an unusual cause of LBP in pregnancy. STUDY DESIGN: A case report. METHODS: A 38-year-old woman, with a history of surgical resection of a cerebellar hemangioblastoma at the age of 15 years, presented at 38 weeks of gestation with worsening LBP and numbness of the lower limbs. Diagnostic workup led to a diagnosis of spinal hemangioblastoma. The tumor was removed after cesarean section in the 39th week of gestation. RESULTS: The detection of spinal hemangioblastoma resulted in a good outcome for both mother and infant. CONCLUSIONS: This case emphasizes the main role of clinical evaluation in establishing the diagnostic workup, especially in pregnancy. Although LBP is commonly reported, this patient's medical history and the presence of clinical signs on neurologic examination suggested the need for further investigation.