João Pedro Marto

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.

POST-NOAC: Portuguese observational study of intracranial hemorrhage on non-vitamin K antagonist oral anticoagulants.

Background There is a lower reported incidence of intracranial hemorrhage with non-vitamin K antagonist oral anticoagulants compared with vitamin K antagonist. However, the functional outcome and mortality of intracranial hemorrhage patients were not assessed. Aims To compare the outcome of vitamin K antagonists- and non-vitamin K antagonist oral anticoagulants-related intracranial hemorrhage. Methods We included consecutive patients with acute non-traumatic intracranial hemorrhage on oral anticoagulation therapy admitted between January 2013 and June 2015 at four university hospitals. Clinical and demographic data were obtained from individual medical records. Intracranial hemorrhage was classified as intracerebral, extra-axial, or multifocal using brain computed tomography. Three-month functional outcome was assessed using the modified Rankin Scale. Results Among 246 patients included, 24 (9.8%) were anticoagulated with a non-vitamin K antagonist oral anticoagulants and 222 (90.2%) with a vitamin K antagonists. Non-vitamin K antagonist oral anticoagulants patients were older (81.5 vs. 76 years, p = 0.048) and had intracerebral hemorrhage more often (83.3% vs. 63.1%, p = 0.048). We detected a non-significant trend for larger intracerebral hemorrhage volumes in vitamin K antagonists patients (p = 0.368). Survival analysis adjusted for age, CHA2DS2VASc, HAS-BLED, and anticoagulation reversal revealed that non-vitamin K antagonist oral anticoagulants did not influence three-month mortality (hazard ratio (HR) = 0.83, 95% confidence interval (CI) = 0.39–1.80, p = 0.638). Multivariable ordinal regression for three-month functional outcome did not show a significant shift of modified Rankin Scale scores in non-vitamin K antagonist oral anticoagulants patients (odds ratio (OR) 1.26, 95%CI 0.55–2.87, p = 0.585). Conclusions We detected no significant differences in the three-month outcome between non-vitamin K antagonist oral anticoagulants- and vitamin K antagonists-associated intracranial hemorrhage, despite unavailability of non-vitamin K antagonist oral anticoagulants-specific reversal agents.

Impact of stroke education on middle school students and their parents: A cluster randomized trial

Background School students are an attractive target for stroke education due to the potential impact on stroke prevention and recognition. Additionally, these students can drive behavioral changes in their families. Aim To evaluate the impact of stroke education on school students, in terms of students’ and parents’ acquired stroke knowledge. Methods A structured questionnaire on knowledge of stroke was filled out by eighth-grade students and one of their parents in seven public schools. In four of these schools, students attended a stroke lecture; educational flyers and magnetic posters were distributed and parent education was encouraged. Students and parents of the other three schools were included in a control group. Students and parents, of both intervention and control groups, were resubmitted to the initial structured questionnaire within one week of the stroke lecture and three months later. Results We included 764 students and 344 parents, 383 (50.1%) and 210 (61.0%) in the intervention group. Correct test scores for students before, within one week, and three months after the intervention were 54.49% versus 55.03% (p = 0.418), 98.69% versus 60.89% (p < 0.001), and 95.58% versus 75.7% (p < 0.001) in the intervention and control groups, respectively. Correct test scores for parents at the same time points were 68.78% versus 64.47% (p = 0.107), 96.89% versus 71.42% (p < 0.001), and 94.58% versus 76.54% (p < 0.001) in the intervention and control groups, respectively. Conclusions School-based interventions may improve stroke knowledge in middle school students and their parents.

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.

A Young Woman with Ischemic Stroke: Should We Pay More Attention to Varicella Zoster Infection

Ischemic and hemorrhagic stroke are recognized complications of Varicella zoster virus (VZV) infections, although uncommon and poorly documented. The authors report the case of a 31-year-old woman admitted with acute ischemic stroke of the right posterior cerebral artery and a history of a thoracic rash 1 month before. Aspirin and simvastatin were prescribed, but the patient suffered a stepwise deterioration the following days, with new areas of infarction on brain imaging. Despite no evidence of cardiac or large vessel embolic sources, anticoagulation was started empirically 6 days after stroke onset. One week later, symptomatic hemorrhagic transformation occurred. The diagnosis of VZV vasculopathy was then considered, and treatment with acyclovir and prednisolone was started with no further vascular events. Cerebrospinal fluid analysis and digital subtraction angiography findings corroborated the diagnosis. The patient was discharged to the rehabilitation center with a modified Rankin scale (mRS) score of 4. On the 6-month follow-up, she presented only a slight disability (mRS score 2). In conclusion, VZV vasculopathy needs to be considered in young adults with stroke. A high index of suspicion and early treatment seem to be important to minimize morbidity and mortality. Anticoagulation should probably be avoided in stroke associated with VZV vasculopathy.

Cerebral Cavernous Malformation: A Portuguese Family with a Novel CCM1 Mutation

Introduction: Cerebral cavernous malformation (CCM) is a vascular disorder characterized by the presence of central nervous system cavernomas. In familial forms, mutations in three genes (CCM1/KRIT1, CCM2/MGC4607 and CCM3/PDCD10) were identified. We describe a Portuguese family harboring a novel CCM1 mutation. Case Presentation: The proband is a woman who at the age of 55 years started to have complex partial seizures and episodic headache. Although nothing was found during her neurological examination, brain MRI showed bilateral, supra- and infratentorial cavernomas. She had a sister who, at the age 61 years, suffered a tonic-clonic seizure. Neurological examination was normal and imaging investigation demonstrated a right frontal intracerebral hemorrhage and multiple cavernomas. In the following years, she suffered several complex partial seizures and had a new intracerebral hemorrhage located in the right temporal lobe. Genetic analysis was performed and a novel nucleotide substitution, i.e. c.1927C>T (p.Gln643*) within the exon 17 of the CCM1 gene, was detected in both sisters. The substitution encodes a stop codon, with a consequent truncated KRIT1 protein, therefore supporting its pathogenic role. Further affected family members were detected, suggesting an autosomal dominant pattern of inheritance. Conclusion: We report a Portuguese family with a novel CCM1 (KRIT1) mutation – c.1927C>T (p.Gln643*). A better knowledge of the phenotype-genotype correlation is needed to improve the management of CCM patients.

Cholesterol is Inefficiently Converted to Cholesteryl Esters in the Blood of Cardiovascular Disease Patients

Shotgun lipidomic analysis of 203 lipids in 13 lipid classes performed on blood plasma of donors who had just suffered an acute coronary syndrome (ACS, n = 74), or an ischemic stroke (IS, n = 21), or who suffer from stable angina pectoris (SAP, n = 78), and an age-matched control cohort (n = 52), showed some of the highest inter-lipid class correlations between cholesteryl esters (CE) and phosphatidylcholines (PC) sharing a common fatty acid. The concentration of lysophospatidylcholine (LPC) and ratios of concentrations of CE to free cholesterol (Chol) were also lower in the CVD cohorts than in the control cohort, indicating a deficient conversion of Chol to CE in the blood plasma in the CVD subjects. A non-equilibrium reaction quotient, Q′, describing the global homeostasis of cholesterol as manifested in the blood plasma was shown to have a value in the CVD cohorts (Q′ACS = 0.217 ± 0.084; Q′IS = 0.201 ± 0.084; Q′SAP = 0.220 ± 0.071) that was about one third less than in the control cohort (Q′Control = 0.320 ± 0.095, p < 1 × 10−4), suggesting its potential use as a rapid predictive/diagnostic measure of CVD-related irregularities in cholesterol homeostasis.

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.

Teaching Video NeuroImages: Candy sign The clue to the diagnosis of neurosyphilis

A 45-year-old man presented with rapid progressive cognitive decline and behavioral symptoms. Neurologic examination revealed global cognitive impairment and episodic, nonrhythmic, brief contractions of the left orofacial muscles (video at Neurology.org). Serologic tests for syphilis were positive without HIV coinfection. CSF analysis revealed cell count 15/μL (mononuclear), hyperproteinorrachia (100 mg/dL), normal glycorrachia, intrathecal immunoglobulin G synthesis (index-3.09), oligoclonal bands (type 2), and venereal disease research laboratory titer of 1/4. MRI revealed bilateral nonspecific white matter changes. Although rare and seldom documented, this dyskinesia, coined candy sign, is considered pathognomonic of neurosyphilis.1 Improvement with penicillin was observed, but response to treatment seems to be variable.2

PP-033 Nystatin-lidocaine lozenges: innovation in the treatment of oral mucositis

Background Oral mucositis is often challenging to manage as the lesions can be very painful. It can compromise nutrition, oral hygiene and increase the risk of infection. It is important to develop oral formulations that enhance treatment compliance, improve the administration and ensure the effectiveness of the drug. Lozenges are described as an effective alternative to mouthwash, especially for their versatility, ease of administration and extended time in the oral cavity. Purpose To describe the developmental process and stability studies performed of an innovative formulation of nystatin and lidocaine lozenges for the treatment of oral mucositis. Material and methods An optimised lozenge formulation was developed. Different excipients such as gelatine, polyethylene glycol, sucrose, glycerine and gum arabic were tested. The aim was to obtain chemical and physical properties suitable for administration, storage and therapeutic compliance. Full pharmaceutical quality testing was carried out, specifically for this dosage form including disintegration and dissolution testing performed with artificial saliva. Appropriate stability-indicating analytical methodology (HPLC) was developed to quantify nystatin and lidocaine. The microbiological and stability tests are still ongoing. Results A stable formulation of soft lozenges was obtained, presenting suitable palatability for oral administration. It can easily be compounded with standard hospital pharmacy equipment. The compounded product has suitable pharmaceutical characteristics, such as mass and content uniformity, disintegration time (15 min), dissolution rate and a pH value suitable for oral administration. Conclusion Nystatin-lidocaine lozenges can be an effective alternative to mouthwashes for the treatment of oral mucositis due to their versatility, excellent palatability and easier administration. This formula’s major advantage is the fact that patients can control for how long the drugs are retained in the oral cavity and consequently manage their pain treatment. The process of clinical application will validate efficacy and optimum dosing frequency. References Marto J, Salgado A, Almeida AJ. Rev-Port-Farmacoterapia 2011;3(3):154–64 Strickley RG, Iwata Q, Wu S, et al. Pediatric drugs—a review of commercially available oral formulations. J Pharm Sci 2008;97:1731–74 No conflict of interest.