The Role of Neurohospitalism in a Specialized Cardiovascular Hospital.

INTRODUCTION: Cardiology and cardiothoracic surgery are among the specialties that most commonly require neurology inpatient consultations. We aimed to study the neurology referrals by the cardiovascular-specialized hospital included in our tertiary hospital center. METHODS: Retrospective study of consecutive patients referred for neurology inpatient consultation between January 1, 2020, and December 31, 2022. We analyzed referrals, patients' characteristics, and the approach taken. A detailed subanalysis was performed for patients diagnosed with acute ischemic stroke (AIS). RESULTS: 143 patients were observed (mean age 67.3 years, 46 [32.2%] females). Most frequent referral reasons were suspected AIS deficits (39.2%), altered mental status (19.6%), suspected seizures (13.3%), and neuroprognostication (11.9%). Mean referral-to-consult time was 2.7 days, and 117 (81.8%) consults were in-person. Additional investigation, treatment changes, and outpatient clinic referral were proposed, respectively, in 79.7%, 60.1%, and 19.6% of patients. Most common diagnoses were AIS (45.5%), hypoxic-ischemic encephalopathy (18.9%), and delirium (7.0%). Regarding patients with AIS (n = 62), most common stroke causes were post-cardiac procedure (44.6%), infective endocarditis (18.5%), aortic dissection (10.8%), acute myocardial infarction (10.8%), and anticoagulant withdrawal in patients with atrial fibrillation (6.2%). Thirty-four AIS patients were diagnosed less than 24 h since last seen well, of which four (6.2%) were treated (three with thrombolysis and one with mechanical thrombectomy). CONCLUSION: AIS is the most common reason for referral in our cardiovascular hospital. Our results highlight the importance of the availability of a neurologist/neurohospitalist with stroke expertise for consultation of inpatients admitted in a specialized cardiovascular hospital.

Impact of white-matter mask selection on DTI histogram-based metrics as potential biomarkers in cerebral small vessel disease.

OBJECTIVE: Histogram-based metrics extracted from diffusion-tensor imaging (DTI) have been suggested as potential biomarkers for cerebral small vessel disease (SVD), but methods and results have varied across studies. This work aims to assess the impact of mask selection for extracting histogram-based metrics of fractional anisotropy (FA) and mean diffusivity (MD) on their sensitivity as SVD biomarkers. METHODS: DTI data were collected from 17 SVD patients and 12 healthy controls. FA and MD maps were estimated; from these, histograms were computed on two whole-brain white-matter masks: normal-appearing white-matter (NAWM) and mean FA tract skeleton (TBSS). Histogram-based metrics (median, peak height, peak width, peak value) were extracted from the FA and MD maps. These were compared between groups and correlated with the patients' cognitive scores (executive function and processing speed). RESULTS: White-matter mask selection significantly impacted FA and MD histogram metrics. In particular, significant interactions were found between Mask and Group for FA peak height (p = 0.027), MD Median (p = 0.035) and MD peak width (p = 0.047); indicating that the mask used affected their ability to discriminate between groups. In fact, MD peak width showed a significant 8.8% increase in patients when using TBSS (p = 0.037), but not when using NAWM (p = 0.69). Moreover, the mask may have an effect on the correlations with cognitive measures. Nevertheless, MD peak width (TBSS: r = - 0.75, NAWM: r = - 0.71) and MD peak height (TBSS: r = 0.65, NAWM: r = 0.62) remained significantly correlated with executive function, regardless of the mask. CONCLUSION: The impact of the processing methodology, in particular the choice of white-matter mask, highlights the need for standardized MRI data-processing pipelines.

Intravenous Thrombolysis for Acute Ischemic Stroke After Recent Myocardial Infarction: Case Series and Systematic Review.

Background and Purpose- The safety of IV r-tPA (intravenous tissue-type plasminogen activator) for acute ischemic stroke (AIS) treatment after recent myocardial infarction (MI) is still a matter of debate. We studied the safety of delivering IV r-tPA to AIS patients with a MI within the preceding 3 months. Methods- Retrospective review of consecutive AIS admitted to 2 tertiary university hospitals' and systematic literature review for AIS patients with history of MI in the previous 3 months. Patients were divided into 2 groups: treated or not treated with standard IV r-tPA dose for AIS. Cardiac complications (cardiac rupture/tamponade, intracardiac thrombus embolization, or life-threatening arrhythmias) were compared between groups and assessed by type of MI (non-ST-segment-elevation myocardial infarction [STEMI], or STEMI) and time elapsed between vascular events. Results- One hundred and two patients were included; 46 (45.1%) were derived from literature review. Median age (interquartile range) was 64 (53-75) years old, and 69 (67.6%) were men. Forty-seven (46.1%) received IV r-tPA. In the treated group, 25 (53.2%) and 23 (48.9%) patients had, respectively, concurrent AIS and MI and STEMI, in comparison with 12 (21.8%; P=0.002) and 36 (65.5%; P=0.110) patients in the nontreated. Four (8.5%) IV r-tPA-treated patients died from confirmed or presumed cardiac rupture/ tamponade, all with a STEMI in the week preceding stroke. This complication occurred in 1 (1.8%) patients in the nontreated group (P=0.178). There were no differences in thrombus embolization (1 [2.1%) versus 2 [3.6]; P=1.000) and life-threatening arrhythmias (3 [6.4%) versus 7 [12.7]; P=0.335). No non-STEMI patients receiving IV r-tPA had cardiac complications. Conclusions- In patients with AIS and recent or concurrent MI, MI type and the time elapsed between the 2 events should be taken into consideration when deciding to deliver IV r-tPA. Although recent non-STEMI or concurrent events seem safe, STEMI in the week preceding stroke should prompt caution. The low number of events and publication bias may have influenced our conclusions.

Bismuth encephalopathy- a rare complication of long-standing use of bismuth subsalicylate.

BACKGROUND: Drugs containing bismuth, although usually safe, may rarely cause neurotoxicity. CASE PRESENTATION: We describe the case of a 44-year-old woman treated with bismuth subsalicylate for about 20 years, who developed abnormal behaviour and postural instability in two weeks. On examination, she had greyish discoloration of teeth, was confused and presented generalized myoclonic jerks. In the next days, her clinical condition deteriorated, with a reduction in alertness and more exuberant myoclonus. Brain MRI was unremarkable. CSF revealed mild elevation of protein content (47 mg/dL; reference range: 15-45 mg/dL) and elevation of white blood cell count (10/µL). Bismuth levels in urine (375 µg/L), serum (260 µg/L) and CSF (21.4 µg/L) samples were highly above the threshold for toxicity. Following supportive treatment and bismuth discontinuation, she made a full recovery within weeks. CONCLUSIONS: Although rare, bismuth encephalopathy should be considered in patients presenting with subacute encephalopathy and myoclonus. This encephalopathy can be subacute even after a chronic exposure. Cessation of bismuth can lead to a complete resolution in weeks.

Autonomic nervous system response to remote ischemic conditioning: heart rate variability assessment.

BACKGROUND: Remote ischemic conditioning (RIC) is a procedure applied in a limb for triggering endogenous protective pathways in distant organs, namely brain or heart. The underlying mechanisms of RIC are still not fully understood, and it is hypothesized they are mediated either by humoral factors, immune cells and/or the autonomic nervous system. Herein, heart rate variability (HRV) was used to evaluate the electrophysiological processes occurring in the heart during RIC and, in turn to assess the role of autonomic nervous system. METHODS: Healthy subjects were submitted to RIC protocol and electrocardiography (ECG) was used to evaluate HRV, by assessing the variability of time intervals between two consecutive heart beats. This is a pilot study based on the analysis of 18 ECG from healthy subjects submitted to RIC. HRV was characterized in three domains (time, frequency and non-linear features) that can be correlated with the autonomic nervous system function. RESULTS: RIC procedure increased significantly the non-linear parameter SD2, which is associated with long term HRV. This effect was observed in all subjects and in the senior (> 60 years-old) subset analysis. SD2 increase suggests an activation of both parasympathetic and sympathetic nervous system, namely via fast vagal response (parasympathetic) and the slow sympathetic response to the baroreceptors stimulation. CONCLUSIONS: RIC procedure modulates both parasympathetic and sympathetic autonomic nervous system. Furthermore, this modulation is more pronounced in the senior subset of subjects. Therefore, the autonomic nervous system regulation could be one of the mechanisms for RIC therapeutic effectiveness.

Effect of patients' expectations on clinical response to fampridine treatment.

INTRODUCTION: Patient expectation of treatment outcome is one of the primary mechanisms underlying the placebo effect. In multiple sclerosis trials with symptomatic treatments, a robust placebo effect is observed, which might be related to patient expectations. The aim of this study was to evaluate whether patient expectations regarding fampridine treatment influence the clinical response after 4 weeks and 6 months of treatment. MATERIALS AND METHODS: We designed and carried out a prospective study from June 2015 to August 2017. Before treatment, patients completed a questionnaire including a scale evaluating their expectations regarding the treatment. The effect of baseline positive expectancy on the response status after 4 weeks and 6 months of treatment was analyzed through univariable and, when applicable, multivariable analysis. RESULTS: A total of 47 consecutive patients were included in the study. At week 4, 37 (78.7%) patients were classified as responders; a one-point increase in the positive expectancy questionnaire was significantly associated with a fourfold increase in the likelihood of being a responder [OR = 4.020 (95% CI 1.082-14.933); p = 0.038]. At 6 months, 43 patients completed follow-up. The number of responders decreased to 28; at this point, positive expectancy at baseline was no longer associated with response status. CONCLUSION: Baseline positive expectancy regarding fampridine was determinant of the clinical response after 4 weeks of treatment. However, in the long term, fampridine efficacy was not dependent on expectations prior to treatment.

Vascular White Matter Lesions in Young Adults: A Neurology Outpatient Clinic Registry.

INTRODUCTION: Although frequently assumed to be age-related changes, vascular white matter lesions (WML) are sometimes found in young adults. Etiology is usually attributed to sporadic small vessel disease; nevertheless, genetic disorders may also be implicated. We aimed to characterize the population of young adults with vascular WML in Neurology outpatient clinics. METHODS: Neurologists from 12 Portuguese hospitals were invited to include patients aged 18-55 years evaluated in consultation, with vascular WML on MRI, scoring II or III in the Fazekas scale. Central imaging validation was performed by 2 independent, blinded, Neuroradiologists. Demographic and clinical data were collected as well as results of investigations performed. RESULTS: During 2 years, 77 patients were included (mean age 47.7 years). Vascular risk factors were present in 88.3% patients (hypertension in 53.2%) and previous history of stroke in 36.4%. Patients without history of stroke were younger (46.6 ± 7.2 vs. 49.6 ± 3.9 years, p = 0.045) and had fewer vascular risk factors (p < 0.001). They were more frequently females (87.8 vs. 46.4%, p < 0.001), and headache (30.6 vs. 3.6%, p = 0.007), contrary to focal symptoms (16.3 vs. 53.6%, p = 0.001), was the most frequent reason of referral. Etiological investigations performed differed between Neurologists. A genetic disorder was identified in 6 out of 58 patients (CADASIL n = 5; COL4A1 n = 1). CONCLUSION: Young adults with vascular WML evaluated in Neurology outpatient clinics concentrate in the oldest age groups. Vascular risk factors should be screened carefully in this population. Among patients without history of stroke, females largely outweigh males. Diagnostic investigations performed do not follow a standardized protocol.

Women Who Have Ischemic Strokes Have a Higher Burden of Left Atrial Fibrosis Than Men.

Background and Purpose- Women with atrial fibrillation (AF) have a higher risk of stroke than men who have AF. Atrial fibrosis is a marker of atrial disease that precedes the appearance of AF increasing the risk of ischemic stroke. We aimed to determine whether female sex is independently associated with left atrial fibrosis in stroke patients. Methods- We prospectively included a consecutive sample of ischemic stroke patients aged over 50 years of age. Late gadolinium enhancement cardiac magnetic resonance imaging was performed to quantify the severity of left atrial fibrosis and the wall pattern of its distribution. A multivariable linear regression analysis was performed to determine whether female sex was independently associated with left atrial fibrosis after adjusting for potential confounders namely AF and age. Results- One hundred twenty-four patients were deemed eligible; 117 patients were included (7 were excluded because of cardiomyopathy identified by cardiac magnetic resonance imaging). All had usable cardiac magnetic resonance imaging data. Fifty-three patients (45.3%) were women. Women were older and were less frequently treated with angiotensin-converting-enzyme inhibitors. Ninety-one patients had any degree of atrial fibrosis. Women had a higher percentage of atrial fibrosis than men-median (interquartile range)-18% (17) versus 10% (20). In a multivariable linear regression model adjusted for demographics, medications, AF, comorbidities, and cardiac parameters, female sex was found to be independently associated with left atrial fibrosis. Women were found to have more 4.70% of left atrial fibrosis than men (95% CI, 0.70-8.71%; P=0.02) after controlling for confounders. Conclusions- Female sex was found to be independently associated with left atrial fibrosis after controlling for confounders such as AF and age. Further studies are needed to understand if this contributes to the increased stroke risk related to AF in women compared with men.

Patients With Undetermined Stroke Have Increased Atrial Fibrosis: A Cardiac Magnetic Resonance Imaging Study.

BACKGROUND AND PURPOSE: Some patients with ischemic strokes that are currently classified as having an undetermined cause may have structural or functional changes of the left atrium (LA) and left atrial appendage, which increase their risk of thromboembolism. We compared the LA and left atrial appendage of patients with different ischemic stroke causes using cardiac magnetic resonance imaging. METHODS: We prospectively included a consecutive sample of ischemic stroke patients. Patients with structural changes on echocardiography currently considered as causal for stroke in the Trial of ORG 10172 in Acute Stroke Treatment (TOAST) classification were excluded. A 3-T cardiac magnetic resonance imaging was performed. RESULTS: One hundred and eleven patients were evaluated. Patients with an undetermined cause had a higher percentage of LA fibrosis (P=0.03) than patients with other stroke causes and lower, although not statistically significant, values of LA ejection fraction. Patients with atrial fibrillation and undetermined stroke cause showed a similar value of atrial fibrosis. CONCLUSIONS: The LA phenotype that was found in patients with undetermined cause supports the hypothesis that an atrial disease may be associated with stroke.

European expert consensus statement on therapeutic goals in Fabry disease.

BACKGROUND: Fabry disease, an inherited lysosomal storage disorder, causes multi-organ pathology resulting in substantial morbidity and a reduced life expectancy. Although Fabry disease is an X-linked disorder, both genders may be affected, but generally to a lesser extent in females. The disease spectrum ranges from classic early-onset disease to non-classic later-onset phenotypes, with complications occurring in multiple organs or being confined to a single organ system depending on the stage of the disease. The impact of therapy depends upon patient- and disease-specific factors and timing of initiation. METHODS: A European panel of experts collaborated to develop a set of organ-specific therapeutic goals for Fabry disease, based on evidence identified in a recent systematic literature review and consensus opinion. RESULTS: A series of organ-specific treatment goals were developed. For each organ system, optimal treatment strategies accounted for inter-patient differences in disease severity, natural history, and treatment responses as well as the negative burden of therapy and the importance of multidisciplinary care. The consensus therapeutic goals and proposed patient management algorithm take into account the need for early disease-specific therapy to delay or slow the progression of disease as well as non-specific adjunctive therapies that prevent or treat the effects of organ damage on quality of life and long-term prognosis. CONCLUSIONS: These consensus recommendations help advance Fabry disease management by considering the balance between anticipated clinical benefits and potential therapy-related challenges in order to facilitate individualized treatment, optimize patient care and improve quality of life.

Evidence of amyloid-ß cerebral amyloid angiopathy transmission through neurosurgery.

Amyloid-ß (Aß) is a peptide deposited in the brain parenchyma in Alzheimer's disease and in cerebral blood vessels, causing cerebral amyloid angiopathy (CAA). Aß pathology is transmissible experimentally in animals and through medical procedures in humans, such as contaminated growth hormone or dura mater transplantation in the context of iatrogenic prion disease. Here, we present four patients who underwent neurosurgical procedures during childhood or teenage years and presented with intracerebral haemorrhage approximately three decades later, caused by severe CAA. None of these patients carried pathogenic mutations associated with early Aß pathology development. In addition, we identified in the literature four patients with a history of neurosurgical intervention and subsequent development of CAA. These findings raise the possibility that Aß pathology may be transmissible, as prion disease is, through neurosurgical procedures.

Portuguese Observational Study of Ischaemic Stroke in Patients Medicated with Non-Vitamin K Antagonist Oral Anticoagulants.

INTRODUCTION: Clinical trials and subsequent meta-analyses showed advantages of non-vitamin K antagonists oral anticoagulants (NOACs) over vitamin K antagonists (VKAs) in patients with non-valvular atrial fibrillation. The impact of preadmission anticoagulation in acute ischaemic stroke (AIS) has not been established. OBJECTIVE: To compare functional outcome of patients with AIS with preadmission NOACs vs. VKAs. METHODS: A retrospective analysis was conducted on consecutive AIS patients under oral anticoagulation (VKAs or NOACs) admitted in 4 Portuguese hospitals within a period of 30 months. Two primary outcomes were defined and compared between VKA and NOAC groups: symptomatic intracerebral hemorrhage transformation (sICH) and modified Rankin Scale (mRS) at 3 months. RESULTS: Four hundred sixty-nine patients were included, of whom 332 (70.8%) were treated with VKA and 137 (29.2%) with NOAC. Patients' median age was 78.0 and 234 (49.9%) were male. NOAC-treated patients had a higher median CHA2DS2-VASc score than those under VKA (5.0 vs. 4.0, p = 0.023). The two primary outcomes showed no statistical differences between the VKAs' group and the NOACs' group (sICH: 5.4 vs. 5.4% [p = 0.911]; mRS at 3 months: 3.0 vs. 3.0 [p = 0.646], respectively). CONCLUSION: Preadmission anticoagulation with NOACs in AIS has a functional impact similar to that of VKAs.

Prediabetes Is Associated with Unfavorable Outcome in Young Adult Patients with Ischemic Stroke.

BACKGROUND: Prediabetes has been associated with unfavorable short-term outcome in patients with ischemic stroke (IS). However, its effect in the subset of young adult patients has not been fully assessed. Our aim was to study the association between prediabetes and 3-month outcome in young adult patients with IS. METHODS: This is a retrospective analysis of consecutive patients aged 18-55 years with a clinical diagnosis of acute IS between January 2010 and December 2016. According to their glucose profile, patients were divided in 3 groups: normal glucose metabolism, prediabetes, and diabetes. The outcome at 3 months was assessed by the modified Rankin Scale (mRS) and dichotomized as good (mRS score ≤2) and poor (mRS score >2) outcomes. RESULTS: A total of 247 patients were included, the median age was 49 years (interquartile range 42-53), and 144 (58.3%) were men. Prediabetes was diagnosed in 79 patients (32.0%) and diabetes was diagnosed in 45 patients (18.2%). Prediabetic (adjusted odds ratio [OR] 2.4, 95% confidence interval [CI] 1.1-5.1, P = .031) and diabetic (adjusted OR 2.8, 95% CI 1.3-6.1, P = .020) patients had a worse prognosis at 3 months. A statistical significant shift in the distribution of the mRS score at 3 months was found in prediabetic (adjusted OR 2.5, 95% CI .3-1.5, P = .002) and diabetic (adjusted OR 3.74, 95% CI .5-2.2, P = .002) patients. CONCLUSION: In young adults with IS, prediabetes and diabetes increase the risk of unfavorable outcome at 3 months.

Steroid-responsive painful ophthalmoplegia: Tolosa-Hunt syndrome, Eales disease, or both?

Introduction Tolosa-Hunt syndrome (THS) is one of the most common 'benign' causes of painful ophthalmoplegia. Diagnosis is based on clinical and imaging findings and the exclusion of other causes because there is no specific biomarker for the syndrome. Eales disease, an idiopathic inflammatory venous disease that primarily affects the eye, can also affect the central (as stroke or myelitis) and peripheral nervous system. Case report We report the case of a 32-year-old woman with a subacute left ophthalmoplegia and evidence of a gadolinium-enhanced lesion suggesting an inflammatory granuloma that resolved within 48 hours after treatment with steroids. A diagnosis of THS was considered at this time. On a follow-up ophthalmological examination, a diagnosis of Eales disease with involvement of the left eye was made. The patient was treated successfully. Conclusion Eales disease could be a cause of painful ophthalmoplegia and may mimic THS. Long-term follow-up of patients diagnosed with THS may be necessary to exclude other diagnoses.

Herbal Supplements Association with Reversible Cerebral Vasoconstriction Syndrome: A Case Report.

BACKGROUND: Reversible cerebral vasoconstriction syndrome (RCVS) is a clinico-radiologic syndrome characterized by thunderclap headache and reversible multifocal arterial constrictions that resolves within 3 months. RCVS can be either spontaneous or related to a trigger; vasoactive drugs including over-the-counter medicine are common culprits. Nevertheless, there are sparse data on the association of herbal supplements in the genesis of unexplained RCVS. METHODS: We describe a case of RCVS with a temporal association with the consumption of a diet pill composed of green tea, L-carnitine, and conjugated linoleic acid. We reviewed the literature describing RCVS cases associated with consumption of herbal supplements or plants. RESULTS: A 50-year-old black woman presented at the emergency room with a thunderclap headache less than 1 week after beginning a new herbal supplement with weight loss purpose. Angiographic study revealed multiple arterial constriction of virtually all intracranial territories that were reversed 28 days later. The patient was discharged with minimal symptoms. From our review, we identified 5 previous reports of herbal product-related triggers. CONCLUSIONS: Different factors can trigger RCVS. Besides our case, at least 5 other nutraceutical products were described to be associated with the disorders, 3 of them in patients without any other clear cause. Clinicians should be aware of the possible role of herbal supplements in RCVS, and their use should be systematically assessed in large RCVS cohorts to clarify this association.

Association of depressive symptoms with allodynia in patients with migraine: A cross-sectional study.

Aims Migraine and depression have a strong association. We aimed to determine whether this relationship was particularly evident in migraineurs with allodynia. Methods A cross-sectional study was carried out of 98 consecutive patients with episodic migraine presenting for their first evaluation in an outpatient clinic. The participants completed a demographic questionnaire, the Allodynia Symptom Checklist and the Hospital Anxiety and Depression Scale (HADS). Results Among the migraineurs, 75 (77%) reported allodynia. Allodynia was associated with higher median HADS-Anxiety (9 vs. 6, p = 0.038) and HADS-Depression (6 vs. 4, p = 0.014) scores. In a multiple regression model, the HADS-Depression scores were independently associated with allodynia (odds ratio 1.236, 95% confidence interval 1.046-1.461). An increased severity of allodynia correlated with higher depression scores ( r = 0.224; p = 0.027). Conclusion Anxious and depressive symptoms are more common in migraineurs with allodynia than in those without allodynia. Further studies are necessary to clarify the relationship between depressive symptoms and allodynia, as well as its therapeutic implications in migraine.

The Stroke Chronometer-A New Strategy to Reduce Door-to-Needle Time.

BACKGROUND AND OBJECTIVE: In acute stroke patients' treatment, time is of utmost importance. Significant efforts must be made to reduce door-to-needle time (DNT), taking into account its effect on treatment efficacy and patients' prognosis. The objective of this study is to assess the effect of implementing a countdown timer in the acute stroke emergency room, on door-to-computed tomography time (DCTT) and DNT. METHODS: Implementation of protocol that postulates the activation of a countdown timer every time an acute stroke patient is admitted. DCTT and DNT in patients submitted to thrombolysis were compared before and after the implementation of the chronometer. Multivariate analysis of DNT and DCTT was conducted adjusted to age, sex, National Institutes of Health Stroke Scale at admission, time from stroke onset to admission, and anterior circulation. RESULTS: Of the 76 patients treated with thrombolysis in 2015 in our hospital, 71 had stroke code activation by the emergency medical services or at hospital admission. Protocol was initiated on July 1, with 41 patients (58%) included in the second semester. The Stroke Chronometer implementation resulted in a reduction of the mean DCTT from 27.1 to 18.4 minutes (P = .004; 95% CI 2.56-12.45) and of the mean DNT from 52.7 to 39.2 minutes (P = .016; 95% CI 2.49-23.18), respectively, first and second semesters. CONCLUSION: The Stroke Chronometer strategy has revealed to be an effective method to reduce DCTT and DNT.