Quantifying the administration and monitoring time burden of several disease-modifying therapies for relapsing multiple sclerosis in the United Kingdom: A time and motion study.

BACKGROUND: The treatment landscape for relapsing multiple sclerosis (MS) has changed dramatically in recent decades, including an increasing number of high-efficacy disease-modifying therapies (DMTs) with varied administration and monitoring requirements. Coupled with greater focus on earlier treatment, these factors have resulted in stretching of the capacity of MS specialist services and allied healthcare professionals (HCPs). To assist with the effective planning of MS services in the UK NHS, this study quantified the administration and monitoring time burden associated with high-efficacy DMTs (alemtuzumab, cladribine tablets, fingolimod, natalizumab, and ocrelizumab) for relapsing MS. METHODS: A Time and Motion (T&M) study was conducted across four MS centres in the UK, over 3-4 months per centre (Aug 2019-Feb 2021). Time dedicated by HCPs (including but not limited to neurologists, MS specialist nurses, infusion nurses, and healthcare assistants) to pre-specified drug administration and monitoring activities, elicited during pre-study interviews at each centre, was assessed for each of the selected DMTs. Administration activities included: installing peripheral access; pre-medication administration (if needed); preparing drug for infusion; infusion initiation, monitoring, and disconnection; and patient monitoring post-infusion. Monitoring activities included: booking appointments for blood draws; blood draw; retrieval and review of blood results; maintaining blood records and follow-up with the patient; checking availability of MRI results and follow-up with the patient; booking appointments for neurologist or nurse consultations; and checking patient files prior to clinic visits. A T&M model was built using observational T&M study results, data obtained through pre-study interviews, as well as stipulated monitoring intervals from relevant Summaries of Product Characteristics for the selected DMTs, to estimate active HCP time with each DMT, extrapolated over a period of 4 years per-patient. RESULTS: For oral DMTs, projected total active HCP time (monitoring only) per-patient over 4 years was 14.7 h for cladribine tablets and 19.2 h for fingolimod. For infused DMTs, total time (administration and monitoring) for alemtuzumab was 37.7 h (6.0 and 31.6 h, respectively), 48.1 h for natalizumab (17.4 and 30.8 h, respectively), and 23.5 h for ocrelizumab (6.1 and 17.4 h, respectively). CONCLUSIONS: While active HCP time varied across centres, infused DMTs were projected to require the greatest amount of HCP time associated with administration and monitoring over 4 years versus oral DMTs. These findings may assist MS-specific HCPs in planning and delivering the equitable provision of DMT services for patients with relapsing MS.

Network analysis characterizes key associations between subjective fatigue and specific depressive symptoms in early relapsing-remitting multiple sclerosis.

BACKGROUND: Fatigue is common and disabling in multiple sclerosis (MS), yet its mechanisms are poorly understood. In particular, overlap in measures of fatigue and depression complicates interpretation. We applied a multivariate network approach to quantify relationships between fatigue and other variables in early MS. METHODS: Data were collected from patients with newly diagnosed immunotherapy-naïve relapsing-remitting MS at baseline and month 12 follow-up in FutureMS, a Scottish nationally representative cohort. Subjective fatigue was assessed by Fatigue Severity Scale. Detailed phenotyping included measures assessing each of physical disability, affective disorders, cognitive performance, sleep quality, and structural brain imaging. Network analysis was conducted to estimate partial correlations between variables. Baseline networks were compared between those with persistent and remitted fatigue at one-year follow up. RESULTS: Data from 322 participants at baseline, and 323 at month 12, were included. At baseline, 154 patients (47.8%) reported clinically significant fatigue. In the network analysis, fatigue severity showed strongest connections with depression, followed by Expanded Disability Status Scale. Conversely, fatigue severity was not linked to objective cognitive performance or brain imaging variables. Even after controlling for measurement of "tiredness" in our measure of depression, four specific depressive symptoms remained linked to fatigue. Results were consistent at baseline and month 12. Overall network strength was not significantly different between groups with persistent and remitted fatigue (4.89 vs 2.90, p = 0.11). CONCLUSIONS: Our findings support robust links between subjective fatigue and depression in early relapsing-remitting MS. Shared mechanisms between specific depressive symptoms and fatigue could be key targets of treatment and research in MS-related fatigue.

A systematic review of European regional and national guidelines: a focus on the recommended use of nabiximols in the management of spasticity in multiple sclerosis.

INTRODUCTION: Spasticity is a common, debilitating symptom of multiple sclerosis (MS) with several treatment options including the cannabinoid-based treatment, nabiximols. The purpose of this review was to examine the existing clinical practice guidelines that direct the management of multiple-sclerosis-associated spasticity (MSS), to identify areas of similarity and divergence, and suggest where standardization and improvement may be obtained. AREAS COVERED: Published literature (PubMed), websites of relevant European Medical Associations and Health Technology Assessment bodies were systematically searched to identify guidelines describing the pharmacological management of MSS, focussing on European countries where nabiximols (Sativex® oromucosal spray) is approved. Sixteen publicly available guidelines were identified. Analysis was focused on, but not restricted to, the use of nabiximols in the wider context of the pharmacological treatment of MSS. EXPERT OPINION/COMMENTARY: We believe that currently MSS is insufficiently treated and this would be improved if a clear and detailed set of guidelines were available and implemented in daily practice. We would welcome the update and amalgamation of the existing guidelines by an international panel, using an evidence-based approach, into a single guideline that is more detailed and standardized in its approach to the initiation, monitoring and optimization of anti-spasticity drugs.

People with multiple sclerosis often experience tight or stiff muscles and an inability to control those muscles. This is known as spasticity, which can have a devastating impact on a person's ability to carry out their daily activities. In addition to physiotherapy, doctors can prescribe various medicines to improve spasticity; these are known as anti-spasticity treatments. Often, prescription choices are steered by guideline documents, written by medical experts. These documents contain important information such as when to prescribe, what to prescribe, how much to prescribe and how to measure how well the treatment is working. The purpose of this study was to examine whether the guidelines that guide the prescription of anti-spasticity treatments in people with multiple sclerosis in Europe, are fit for purpose for day-to-day medical practice. In particular, this article examines how the guidelines represent the newer cannabis-based treatment known as nabiximols, sold under the name Sativex oromucosal spray, which has become more widely available in many European countries over the last 10 years.

Clinical trials in amyotrophic lateral sclerosis: a systematic review and perspective.

Amyotrophic lateral sclerosis is a progressive and devastating neurodegenerative disease. Despite decades of clinical trials, effective disease-modifying drugs remain scarce. To understand the challenges of trial design and delivery, we performed a systematic review of Phase II, Phase II/III and Phase III amyotrophic lateral sclerosis clinical drug trials on trial registries and PubMed between 2008 and 2019. We identified 125 trials, investigating 76 drugs and recruiting more than 15 000 people with amyotrophic lateral sclerosis. About 90% of trials used traditional fixed designs. The limitations in understanding of disease biology, outcome measures, resources and barriers to trial participation in a rapidly progressive, disabling and heterogenous disease hindered timely and definitive evaluation of drugs in two-arm trials. Innovative trial designs, especially adaptive platform trials may offer significant efficiency gains to this end. We propose a flexible and scalable multi-arm, multi-stage trial platform where opportunities to participate in a clinical trial can become the default for people with amyotrophic lateral sclerosis.

The epidemiology of multiple sclerosis in the Scottish Highlands: Prevalence, incidence and time to confirmed diagnosis and treatment initiation.

INTRODUCTION: Although multiple sclerosis (MS) is frequent in the northern hemisphere, there have not been recent epidemiological studies in the Scottish Highlands about MS. OBJECTIVES: To get updated data regarding MS prevalence, incidence and mortality in the Highlands. Time between symptom onset and MS diagnosis was also evaluated in incident MS cases and the pattern of use of disease-modifying therapies (DMTs) was analysed. METHODS: Study population was people with MS under the care of the Highland Health and Social Care Partnership. The catchment area included North area (Wick, Thurso, Brora, Invergordon), Center (Inverness, Aviemore, Nairn, Fort William), and West coast (Ullapool, Skye). Data were obtained from the MS database at Raigmore hospital (prevalence, midyear 2017) and the prospective hospital-register based study (diagnosis) that was carried out over a 12-month period, in 2016. The 2010 McDonald criteria for diagnosis of new MS cases were used. Crude prevalence and incidence and 95% confidence interval (CI) were calculated for the MS adult onset population, and data was standardised to the European standard population 2013; cause-specific mortality rate was analysed. Pattern of use of DMTs during the first year of diagnosis was also registered. RESULTS: 745 patients were registered in the MS database. 75.4% (562 cases) were females, and female/male ratio was 3:1. Mean age of population was 54.1 ± 14.1 years (range: 15-95 years). Mean number of years since diagnosis was 8.5 ± 4.6 years. Estimated prevalence for the population aged 15 and older was 376 cases per 100,000 inhabitants (95% CI: 354-399). 36 incident MS cases were registered in 2016 (88.8% females; mean age 40.4 ± 12.1 years). Annual incidence in Highlands was 18.2 per 100,000 inhabitants (95% CI: 14-24). The mean period of time from symptom onset to diagnosis was 38.8 ± 43.2 months. 47.2% (17/36) did not take any DMT during the first year after the diagnosis. CONCLUSION: Prevalence and incidence of MS in the Scottish Highlands is high. Although the gap period between symptom onset and diagnosis is moderate, a significant proportion of recently diagnosed MS patients were not keen to start a DMT the first year after the diagnosis.

Neurological complications of Zika virus infection.

INTRODUCTION: Zika virus (ZIKV) disease is a vector-borne infectious disease transmitted by Aedes mosquitoes. Recently, ZIKV has caused outbreaks in most American countries. Areas covered: Publications about neurological complications of ZIKV infection retrieved from pubmed searchers were reviewed, and reference lists and relevant articles from review articles were also examined. Vertical/intrauterine transmission leads to congenital infection and causes microcephaly and congenital ZIKV syndrome. ZIKV preferentially infects human neural progenitor cells and triggers cell apoptosis. ZIKV RNA has been identified in foetal brain tissue and brains of microcephalic infants who died; amniotic fluid and placentas of pregnant mothers; and umbilical cord, cerebro-spinal fluid and meninges of newborns. The increase in the number of Guillain-Barre syndrome (GBS) cases during the ZIKV outbreak in the Americas provides epidemiological evidence for the link between ZIKV infection and GBS. Less frequently reported ZIKV neurological complications include encephalitis/meningoencephalitis, acute disseminated encephalomyelitis, myelitis, cerebrovascular complications (ischemic infarction; vasculopathy), seizures and encephalopathy, sensory polyneuropathy and sensory neuronopathy. Analysis of GBS incidence could serve as an epidemiological 'marker' or sentinel for ZIKV disease and other neurological complications associated to ZIKV. Expert commentary: An expanding spectrum of neurological complications associated with ZIKV infection is being recognised.

Infectious diseases causing autonomic dysfunction.

OBJECTIVES: To review infectious diseases that may cause autonomic dysfunction. METHODS: Review of published papers indexed in medline/embase. RESULTS: Autonomic dysfunction has been reported in retrovirus (human immunodeficiency virus (HIV), human T-lymphotropic virus), herpes viruses, flavivirus, enterovirus 71 and lyssavirus infections. Autonomic dysfunction is relatively common in HIV-infected patients and heart rate variability is reduced even in early stages of infection. Orthostatic hypotension, urinary dysfunction and hypohidrosis have been described in tropical spastic paraparesis patients. Varicella zoster reactivation from autonomic ganglia may be involved in visceral disease and chronic intestinal pseudo-obstruction. Autonomic and peripheral nervous system dysfunction may happen in acute tick-borne encephalitis virus infections. Hydrophobia, hypersalivation, dyspnea, photophobia, and piloerection are frequently observed in human rabies. Autonomic dysfunction and vagal denervation is common in Chagas disease. Neuronal depopulation occurs mainly in chagasic heart disease and myenteric plexus, and megacolon, megaesophagus and cardiomyopathy are common complications in the chronic stage of Chagas disease. Parasympathetic autonomic dysfunction precedes left ventricle systolic dysfunction in Chagas disease. A high prevalence of subclinical autonomic neuropathy in leprosy patients has been reported, and autonomic nerve dysfunction may be an early manifestation of the disease. Autonomic dysfunction features in leprosy include anhidrosis, impaired sweating function, localised alopecia ,and reduced heart rate variability. Urinary retention and intestinal pseudo-obstruction have been described in Lyme disease. Diphtheritic polyneuropathy, tetanus and botulism are examples of bacterial infections releasing toxins that affect the autonomic nervous system. CONCLUSIONS: Autonomic dysfunction may be responsible for additional morbidity in some infectious diseases.

Clinical management of infectious cerebral vasculitides.

A wide range of infections (virus, bacteria, parasite and fungi) may cause cerebral vasculitides. Headache, seizures, encephalopathy and stroke are common forms of presentation. Infection and inflammation of intracranial vessels may cause pathological vascular remodelling, vascular occlusion and ischemia. Vasculitis in chronic meningitis may cause ischemic infarctions, and is associated with poor outcome. Appropriate neuroimaging (CT-angiography, MR-angiography, conventional 4-vessel angiography) and laboratory testing (specific antibodies in blood and CSF, CSF culture and microscopy) and even brain biopsy are needed to quickly establish the aetiology. Enhancement of contrast, wall thickening and lumen narrowing are radiological signs pointing to an infectious vasculitis origin. Although corticosteroids and prophylactic antiplatelet therapy have been used in infectious cerebral vasculitis, there are no randomized clinical trials that have evaluated their efficacy and safety. Stable mycotic aneurysms can be treated with specific antimicrobial therapy. Endovascular therapy and intracranial surgery are reserved for ruptured aneurysms or enlarging unruptured aneurysms.

Post-Ebolavirus disease syndrome: what do we know?

As the current Zaire ebolavirus disease outbreak in West Africa fades, the health problems of the more than 16,500 survivors have come to light. A wide range of mental and physical symptoms may occur during the convalescence stage. Reported symptoms of "post-Ebolavirus disease syndrome" (PEVDS) include chronic joint and muscle pain, fatigue, anorexia, hearing loss, blurred vision, headache, sleep disturbances, low mood and short-term memory problems. PEVDS has been associated with a decrease in functionality and difficulties to return to work. Further studies are needed to fully categorize the clinical spectrum of PEVDS. Diagnostic criteria and surrogate markers for the early diagnosis of PEVDS, and implementation of specialized health services to treat and follow-up survivors are also needed.

Post-Ebolavirus disease syndrome: What do we know?

As the current Zaire ebolavirus disease outbreak in West Africa fades, the health problems of the more than 16,500 survivors have come to light. A wide range of mental and physical symptoms may occur during the convalescence stage. Reported symptoms of "post-Ebolavirus disease syndrome" (PEVDS) include chronic joint and muscle pain, fatigue, anorexia, hearing loss, blurred vision, headache, sleep disturbances, low mood and short-term memory problems. PEVDS has been associated with a decrease in functionality and difficulties to return to work. Further studies are needed to fully categorize the clinical spectrum of PEVDS. Diagnostic criteria and surrogate markers for the early diagnosis of PEVDS, and implementation of specialized health services to treat and follow-up survivors are also needed.

Meningococcal meningitis: vaccination outbreak response and epidemiological changes in the African meningitis belt.

The main approach to controlling epidemics of meningococcal meningitis in the African meningitis belt has been reactive vaccination campaigns with serogroup A polysaccharide vaccine once the outbreak reached an incidence threshold. Early reactive vaccination is effective in reducing morbidity and mortality. A recent paper in International Health has shown that earlier reactive vaccination campaigns may be even more effective than increasing the coverage area of vaccination. Monovalent serogroup A conjugate vaccine programs have recently been launched to prevent transmission in endemic areas in the African meningitis belt. Conjugate vaccines can induce immunological memory and have impact on pharyngeal carriage. However, reactive vaccination still has a role to play taking into account the dynamic changes in the epidemiology of meningitis in this area.

Psychometric evaluation of the Stroke Impact Scale 3.0.

BACKGROUND: The Stroke Impact Scale 3.0 (SIS 3.0) is widely used to measure quality of life in stroke survivors; however, previous studies have not tested the original 8-factor structure of the scale. In addition, previous studies have shown floor and ceiling effect and weak reliability within the scale. OBJECTIVE: The aim of this study was to evaluate the psychometric characteristics of the SIS 3.0, including its construct validity (factorial structure, concurrent and contrasting group validity), floor and ceiling effect, and reliability. METHOD: A cross-sectional design was used to study 392 stroke survivors enrolled in 16 rehabilitation facilities across Italy. Factorial structure of the SIS 3.0 was tested with confirmatory factor analysis. Concurrent and contrasting group validities were evaluated with other scales measuring functional capacities, neurological functions, cognition, anxiety, depression, and generic quality of life. Floor and ceiling effects were evaluated by determining the percentages of patients with the minimum and the maximum score at SIS 3.0. Reliability was determined by Cronbach's α and test-retest. RESULTS: Participants were 71 years old on average (SD, 11 years); 55% were men. Confirmatory factor analysis revealed a new 4-factor structure that fitted the data better than the original 8-factor structure did. Concurrent and contrasting group validity of the new 4-factor structure was supportive and no floor and ceiling effects were found. Internal consistency and test-retest reliability ranged between 0.79 and 0.98. CONCLUSION: The new factorial structure of the SIS 3.0 with 4 factors showed better psychometric properties than the original 8-factor structure did. This evidence supports further use of the SIS 3.0 in clinical practice and research.

Carga y calidad de vida en cuidadores de pacientes con enfermedad de Parkinson / Burden and quality of life in caregivers of Parkinson’s disease patients

Cuidar crónicamente a un paciente con enfermedad de Parkinson (EP) puede repercutir significativamente en la salud y el bienestar físico, emocional y social del cuidador. La carga en cuidadores se asocia con el grado de afectación motora y la presencia de síntomas no motores (psiquiátricos, cognitivos y conductuales) en los pacientes. La gravedad de la EP, medida por los estadios de Hoehn-Yahr, y la presencia de complicaciones de la terapia dopaminérgica también influyen en la carga en los cuidadores. Los síntomas no motores de la EP son los principales factores predictivos de carga en el cuidador, e incluyen depresión, demencia y alucinaciones. La carga del cuidador se incrementa conforme progresan los síntomas no motores y la dependencia. Asimismo, la presencia de depresión en cuidadores es el principal factor que afecta a su calidad de vida. Los factores de riesgo de sobrecarga deberían ser identificados y tratados de modo precoz. Por ello, es necesario implementar programas de apoyo sociosanitario para reducir la carga en los cuidadores de pacientes con EP (AU)

Caring chronically a Parkinson’s disease (PD) patient has a significant negative effect on the health, well-being and psychosocial functioning of the carers. Caregiver burden has been associated with both motor and non-motor (psychiatric, cognitive and behavioural symptoms) impairment in PD patients. The severity of the disease, as measured by the Hoehn-Yahr stages, and the presence of dopaminergic therapy complications, have been correlated with greater carer burden. Nonmotor symptoms such as depression, dementia and hallucinations are the main predictors of carer burden. The burden of caregivers may increase with the progression of disability and the worsening of non-motor symptoms. Depression in caregivers is the most important factor affecting their quality of life. Risk factors of caregiver burden should be early identified and treated. Social and health programs are needed to reduce burden in PD caregivers (AU)

Tackling chronic migraine: current perspectives.

In the last decade, several diagnostic criteria and definitions have been proposed for chronic migraine (CM). The third edition of the International Classification of Headache Disorders-3 beta, published in 2013, has revised CM diagnostic criteria. CM is defined as "headache occurring on 15 or more days per month for more than 3 months, which has the features of migraine headache on at least 8 days per month." Patients who meet the criteria for CM and for medication-overuse headache should be given both diagnoses. Worldwide, CM prevalence ranges 1%-3%, and its incidence has been estimated to be 2.5% per year. CM is associated with disability and poor quality of life. Modifiable risk factors include (among others): migraine progression (defined as an increase in frequency and severity of migraine attacks); medication and caffeine overuse; obesity; stressful life events; and snoring. CM patients have a significantly higher frequency of some comorbid conditions, including chronic pain, psychiatric disorders, respiratory illness, and some vascular risk factors. Management includes identification and control of comorbidities and risk factors that predispose to CM; treatment and prevention for medication overuse; early treatment for migraine attacks; and an adequate preventive therapy for CM. Several randomized controlled clinical trials have shown the efficacy of topiramate, amitriptyline, onabotulinumtoxinA, and cognitive-behavioral therapy in CM.

Stroke subtypes and comorbidity among ischemic stroke patients in Brasilia and Cuenca: a Brazilian-Spanish cross-cultural study.

BACKGROUND: With the increase in life expectancy worldwide, changes in stroke subtypes and burden of stroke population are expected in both developing and developed countries. Prevalence of stroke subtypes and comorbidity in ischemic stroke patients was assessed in Brasilia, Brazil, and Cuenca, Spain. METHODS: This was an international (Brazilian-Spanish) cross-sectional study. Stroke subtypes were assessed by means of Trial of ORG 10172 in Acute Stroke Treatment (TOAST) classification. Modified Rankin scale was used to measure functional recovery and the Cumulative Illness Rating Scale for Geriatrics (CIRS-G) was used to assess comorbidity. RESULTS: A total of 500 patients (mean age 66.2 ± 16.4 years; 48% female; 48.2% Spanish) were included in the study. Spanish patients were significantly older than Brazilian ones (76.4 ± 11.2 versus 56.7 ± 14.6 years; P < .0001). Prevalence of ischemic cardiopathy (20.3% versus 6.2%) and atrial fibrillation (25.7% versus 6.6%) was significantly higher in Spanish stroke patients, whereas they less frequently used tobacco (28.3% versus 52.9%); P less than .0001. Prevalence of stroke subtypes in Spanish and Brazilian stroke patients was: stroke of undetermined etiology (58.1% versus 32.4%), cardioembolism (24.5% versus 11.6%), lacunar infarct (11.6% versus 25.5%), atherothrombotic (3.7% versus 19.7%), and other causes (2.1% versus 10.8%); P less than .0001. The Spanish sample had a significantly higher frequency of comorbidities. The CIRS-G total score and CIRS-G mean number of affected organs significantly increased with age, and correlated with the level of functional dependence as measured by Rankin scale (rS = 0.50; P = .0005). CONCLUSION: Spanish stroke people had a higher frequency of comorbid conditions, atrial fibrillation, and cardioembolism and these facts were associated with age. Atherothrombotic and lacunar strokes were more common in the younger Brazilian stroke population.

Neurological manifestations of dengue viral infection.

Dengue is the most common mosquito-borne viral infection worldwide. There is increased evidence for dengue virus neurotropism, and neurological manifestations could make part of the clinical picture of dengue virus infection in at least 0.5%-7.4% of symptomatic cases. Neurological complications have been classified into dengue virus encephalopathy, dengue virus encephalitis, immune-mediated syndromes (acute disseminated encephalomyelitis, myelitis, Guillain-Barré syndrome, neuritis brachialis, acute cerebellitis, and others), neuromuscular complications (hypokalemic paralysis, transient benign muscle dysfunction and myositis), and dengue-associated stroke. Common neuro-ophthalmic complications are maculopathy and retinal vasculopathy. Pathogenic mechanisms include systemic complications and metabolic disturbances resulting in encephalopathy, direct effect of the virus provoking encephalitis, and postinfectious immune mechanisms causing immune-mediated syndromes. Dengue viruses should be considered as a cause of neurological disorders in endemic regions. Standardized case definitions for specific neurological complications are still needed.

Neurological complications of dengue virus infection.

Dengue is the second most common mosquito-borne disease affecting human beings. In 2009, WHO endorsed new guidelines that, for the first time, consider neurological manifestations in the clinical case classification for severe dengue. Dengue can manifest with a wide range of neurological features, which have been noted--depending on the clinical setting--in 0·5-21% of patients with dengue admitted to hospital. Furthermore, dengue was identified in 4-47% of admissions with encephalitis-like illness in endemic areas. Neurological complications can be categorised into dengue encephalopathy (eg, caused by hepatic failure or metabolic disorders), encephalitis (caused by direct virus invasion), neuromuscular complications (eg, Guillain-Barré syndrome or transient muscle dysfunctions), and neuro-ophthalmic involvement. However, overlap of these categories is possible. In endemic countries and after travel to these regions, dengue should be considered in patients presenting with fever and acute neurological manifestations.

American trypanosomiasis.

American trypanosomiasis is a parasitic disease caused by the flagellate protozoan Trypanosoma cruzi. Chagas disease is endemic in Latin America, where an estimated 10-14 million people are infected, and an emerging disease in Europe and the USA. Trypanosoma cruzi is transmitted by blood-sucking bugs of the family Reduviidae. Rhodnius prolixus, Panstrongylus megistus, Triatoma infestans, and T. dimidiata are the main vectors in the sylvatic cycle. Non vector-borne transmission includes blood transfusion, congenital and oral transmission, transplantation, and accidental infections. Most cases of acute infection occur in childhood and are usually asymptomatic, although severe myocarditis and meningoencephalitis may occur. Approximately 30% of T. cruzi-infected people will develop the chronic stage of the disease. Chronic chagasic cardiomyopathy is characterized by progressive heart failure, arrhythmias, intraventricular conduction defects, sudden death, and peripheral thromboembolism. Acute exacerbation can occur in individuals with involvement of cellular immunity such as advanced AIDS (acquired immunodeficiency syndrome), and transplant-associated immunosuppression. Neurological involvement may present with encephalitis, meningoencephalitis, or a space-occupying cerebral lesion called chagoma. Chagas disease is a major cause of ischemic stroke in Latin America. Several epidemiological studies have found an association between T. cruzi infection and cardioembolic ischemic stroke. Benznidazole and nifurtimox are the two available trypanocide drugs against T. cruzi.