Asymptomatic cerebral small vessel disease in adults with low cardiovascular risk.

Introduction: Cerebral small vessel disease (CSVD) frequently occurs in individuals with vascular risk factors. This condition might go unrecognised or result in only mild functional deficits. Objective: To evaluate the relationship between cardiovascular (CV) risk calculated with the HEARTS app and CSVD burden in a population without cardio-cerebrovascular diseases, and to estimate the prevalence of CSVD in low risk (LR) individuals. Methods: Asymptomatic subjects with vascular risk factors were included from primary health areas in Havana. The WHO's revised CV disease risk prediction chart (HEARTS app) was applied to all individuals, who were classified into two groups: LR and moderate/high risk (M/HR). Brain MRI was performed in all subjects. Results: 170 patients were included: 43 (25.3%) classified as low CV risk and 127 (74.7%) had M/HR CV risk. Half of the neurologically healthy individuals included displayed cerebral small vessel involvement (51.2%). White matter hyperintensities (WMH) and enlarged perivascular spaces were the most frequent lesions observed in both groups. WMH were more severe and more severe global score for CSVD were more frequent in the M/HR group (57.5%). It was noteworthy that 32.6% of LR-patients also exhibited more severe CSVD. The multivariate regression analysis revealed an independent association of arterial hypertension and age with the severity of CSVD. Conclusions: CV risk stratification through the HEARTS app has limited utility for predicting brain health in individuals with low CV risk. Identifying silent CSVD in individuals with apparently low CV risk is important, especially if they suffer from arterial hypertension.

A Shift in SARS-CoV-2 Omicron Variant's Entry Pathway Might Explain Different Clinical Outcomes.

Globally, SARS CoV-2 omicron variant has led to a notable increase of COVID-19 diagnoses, although with less severe clinical manifestations and decreased hospitalizations. The omicron wave swelled faster than previous waves, completely displacing the delta variant within weeks, and creating worldwide concern about final, successful pandemic control. Some authors contend that symptoms associated to omicron differ from 'traditional' symptoms and more closely resemble those of the common cold. One major COVID-19 symptom frequent with other variants-loss of taste and smell-is rarely present with omicron. This may be of interest, since it has also been suggested that direct SARS-CoV-2 invasion into the brainstem through the olfactory nerves by transsynaptic pathways could provide one explanation for the acute respiratory distress syndrome refractory to treatment. Brainstem infection by SARS-CoV-2 can severely damage the respiratory center, triggering functional deviations that affect involuntary respiration, leading to acute respiratory distress syndrome refractory to treatment, the main cause of death in COVID-19 patients. A shift in the omicron SARS-CoV-2 entry pathway from cell-surface fusion, triggered by TMPRSS2, to cathepsin-dependent fusion within the endosome, may affect transmission, cellular tropism and pathogenesis. Therefore, we can hypothesize that this entrance modification may impact transmission from the olfactory nerve to the brainstem through transsynaptic pathways. A decrement of the virus's direct invasion into the brainstem could diminish respiratory center dysfunction, reducing acute respiratory distress syndrome and the need for mechanical ventilation.

Proposal for the functional assessment of acute inflammatory neuropathy (FAAIN) in Guillain-Barré syndrome.

BACKGROUND: Guillain Barré syndrome (GBS) functional assessment is necessary in clinical practice, research and clinical trials. Existing instruments are not sensitive to change and are not applicable to the current GBS clinical spectrum. OBJECTIVE: To construct a functional assessment for acute inflammatory neuropathies (FAAIN-GBS), inclusive for current GBS spectrum that assesses extension and intensity separately. METHODS: FAAIN-GBS subscales were constructed. Its structure and interpretation were defined. It was validated using data from medical record of 167 GBS patients admitted to the Institute of Neurology and Neurosurgery. Cronbach α was used for items reduction and reliability analysis. Bartlett sphericity test was performed. Exploratory factor analysis (EFA) of the main components, with varimax rotation, was applied to evaluate dimensionality and content validity. Hughes scale was used as gold standard for criterion validity. Sensitivity, specificity and area under the receiver operating characteristic curves (AUROC), were calculated. Construct validity was assessed by confirmatory factor analysis (CFA). RESULTS: FAAIN-GBS is made up of two subscales (extension and intensity). The final score is obtained by averaging both dimensions. Internal consistency was acceptable (Cronbach 0.745). EFA showed three dimensions: intensity, spinal extension and cranial extension. Spearman correlation between FAAIN-GBS and Hughes scale was 0.463. Sensitivity (0.714) and specificity (0.986) values showed the good behavior of the scale; AUROC was 0.93. CONCLUSION: FAAIN-GBS was constructed and a first step of validation was made, showing good internal consistency and validity. New prospective studies with large populations will be necessary to perfect this instrument that could be useful in neurological practice.

Hypoxemia and Cytokine Storm in COVID-19: Clinical Implications.

One of the most dreadful complications that can occur during the course of COVID-19 is the cytokine storm-also known as cytokine release syndrome-a form of systemic inflammatory response syndrome triggered by SARS-CoV-2 infection. The cytokine storm is an activation cascade of auto-amplifying cytokines, which leads to excessive activation of immune cells and generation of pro-inflammatory cytokines. It occurs when large numbers of white blood cells are activated and release inflammatory cytokines, in turn activating even more white blood cells, finally resulting in an exaggerated pro-inflammatory-mediated response and ineffective anti-inflammatory control, leading to tissue damage, multiorgan failure, acute respiratory distress syndrome and death. Although cytokine storm pathogenesis is multifactorial, we hypothesize there is a close association between hypoxemia and cytokine storms in COVID-19, although it is difficult to establish the direction of this relationship. Most probably they coexist and, given enough time, one triggers the other in a chain reaction. Careful analysis of the day-to-day clinical evolution of COVID-19 indicates that there are short and slight periods of hypoxemia (confirmed by pulse oximetry and arterial gasometry), even on the day of the onset of persistent cough and/or shortness of breath. We propose the use of continuous positive airway pressure in early stages of COVID-19, at the onset of respiratory symptoms. This non-invasive ventilation method may be useful in individualized treatments to prevent early hypoxemia in COVID-19 patients and thus avoid triggering a cytokine storm. We believe such an approach is relevant everywhere, and in Cuba in particular, since the country has initiated national production of mechanical ventilation systems, including non-invasive ventilators. Moreover, as Cuba's COVID-19 protocols ensure early patient admission to isolation centers or hospitals, clinicians can prescribe the early use of continuous positive airway pressure as soon as respiratory symptoms begin, averting early hypoxemia and its triggering effect on cytokine storm development, and consequently, avoiding acute respiratory distress syndrome, multi-organ failure, and death.

Infección por COVID-19 y accidente cerebrovascular / COVID-19 Infection and Stroke

La actual pandemia de COVID-19 causada por el virus SARS-CoV-2, se caracteriza por una alta morbilidad y mortalidad. Algunos estudios han reportado que la frecuencia de ictus en pacientes infectados con el virus oscila entre un 5-20 por ciento. A pesar de estas cifras alarmantes, las vías por las cuales el virus llega al sistema nervioso central y los mecanismos fisiopatológicos por los que puede ocurrir un ictus en estos pacientes no han sido totalmente esclarecidos. Numerosos estudios han demostrado que la infección por SARS-CoV-2 está asociada a un estado protrombótico, capaz de causar un tromboembolismo arterial y venoso. Además, se ha reportado una respuesta inflamatoria exacerbada, con reclutamiento de células sanguíneas y una secreción desproporcionada de citoquinas proinflamatorias. También la hipoxia y fenómenos cardioembólicos han sido propuestos como posibles mecanismos. Es esencial definir con exactitud los mecanismos fisiopatológicos que vincula la infección por SARS-CoV-2 con la ocurrencia del ictus, con la finalidad de aplicar tratamientos más específicos y evitar futuras complicaciones(AU)

The actual Coronavirus Disease 2019 (COVID-19) infection is an ongoing pandemic, characterized by high morbidity and mortality produced by SARS-CoV-2 virus. Studies reported a stroke frequency around 5-20 percent in infected patients; however, SNC invasion and pathophysiological mechanisms related to stroke in COVID-19 patients are still unknown. Several studies have demonstrated that SARS-CoV-2 infection is linked to a prothrombotic state causing venous and arterial thromboembolism. Also, an overstated inflammatory response with recruitment of blood cells and disproportioned secretion of proinflammatory cytokines has been reported. Finally, cardioembolism and hypoxia have been proposed as surrogate mechanisms. It is essential to define the pathophysiological mechanisms of stroke during the infection in order to apply more specific treatments to avoid further stroke complications(AU)

CSF oligoclonal band frequency in a Cuban cohort of patients with multiple sclerosis. comparison with Latin American countries and association with latitude.

BACKGROUND: The diagnostic sensitivity of CSF specific oligoclonal bands (OCBs) in multiple sclerosis (MS), using state of the art methods, has been clearly established to be over 95% in patients with a predominantly Caucasian background. This is not the case for other geographical regions, where reports of OCB prevalence can be much lower, and a relationship between OCB frequency and latitude has been suggested. OBJECTIVE: The aim of the present study was to assess the frequency of OCBs in a cohort of MS patients evaluated at the Institute of Neurology and Neurosurgery (Havana, Cuba), and to review the scientific literature in order to investigate the possible relationship between OCB status and latitude in the region of Latin America. METHODS: Fifty-three patients (47 with definite MS and 6 with clinically isolated syndrome - CIS) were included. Isoelectric focusing (IEF) with IgG immunoblotting for OCB analyses, was performed placing paired CSF and serum samples in the same analytical run. PubMed, Scielo and Google Scholar were searched for papers containing information concerning CSF OCB status (employing isoelectric focusing with IgG immunoblotting) in patients with definite MS in Latin America and the Caribbean. RESULTS: In Cuban patients with definite MS, an OCB prevalence of 87% was observed, while the frequency in CIS patients was lower (67%). The prevailing pattern was that of OCBs restricted to the CSF (type 2), which was observed in 71% of definite MS patients and in all CIS patients with intrathecal IgG synthesis. OCB prevalence was slightly lower, but very close to that reported in Caucasian populations. Comparison with other Latin American countries revealed a significant correlation between OCB prevalence and latitude. CONCLUSIONS: A prevalence of CSF restricted OCBs of 87% was observed in definite MS patients, a frequency which was slightly lower, but similar to that reported in Caucasian populations. The analysis of OCB frequency in Latin American countries revealed a possible relationship between OCB prevalence and latitude, but this must be further investigated in more countries and larger samples of patients.

Neuroinflammation and Neuromodulation in Neurological Diseases.

Neuroimmunology is a relatively young science. This discipline has emerged today from the research field as a mature and fully developed innovative research area that integrates not only pure topics of neuroimmunology, but also expands on wider fields such as neuroplasticity, neuronal reserve and neuromodulation in association with clinical events, amongst which behavioral disorders stand out. The Cuban School of Neuroimmunology-a recent meeting that took place in Havana, Cuba-focused on topics based on the molecular mechanisms of neuroinflammation in neurological disorders involving behavioral manifestations, such as multiple sclerosis (MS), autism, cerebellar ataxias, Alzheimer´s disease and stroke among others, as well as on the use of new interventional technologies in neurology. Professor Luis Velazquez, from the Cuban Academy of Sciences, dictated an interesting lecture on Spinocerebellar ataxias, a genetic disorder where recent hypotheses related to the influence of neuroinflammation as a neurobiological factor influencing the progression of this disease have emerged. At the same time, the use of new interventional technologies in neurology was discussed, including those referring to novel disease modifying therapies in the course of MS and the use of transcranial magnetic stimulation in several neurological diseases, the latter reinforcing how interventional strategies in the form of non-invasive bran stimulation can contribute to physical rehabilitation in neurology. This paper summarizes the highlights of the most relevant topics presented during the First Cuban School of Neuroimmunology, organized by the Cuban Network of Neuroimmunology, held in June 2019.

Cuban Epidemic Neuropathy: Insights into the Toxic-Nutritional Hypothesis through International Collaboration.

From 1991 to 1993, an epidemic of optic and peripheral neuropathy-the largest of the century-broke out in Cuba, affecting more than 50,000 people. Initially the main clinical features were decreased visual acuity, central and cecocentral scotomas, impaired color vision and absence of the papillomacular bundle. Later, peripheral and mixed optic-peripheral forms began to appear. Due to the magnitude of the epidemic, the Cuban government requested help from the international community at the 46th World Health Assembly in 1993. PAHO and WHO immediately responded by sending a mission of international experts. Several hypotheses regarding the pathogenesis of Cuban epidemic neuropathy were put forward including: toxic, nutritional, genetic and infectious. The authors refer to extensive studies by researchers sponsored by the Cuban government and PAHO/WHO, joined by scientists from several other countries, including the USA. This paper describes their multidisciplinary work, particularly devoted to investigating the hypothesis of a primary toxic-nutritional cause of the epidemic. Clinical aspects, such as case definition and clinical description, were vital issues from the start. Cuban physicians who first examined patients received a clear impression of its toxic-nutritional origin, later confirmed by international experts. Research then focused on the mechanisms contributing to damage under the toxic-nutritional hypothesis. These included injuries to the mitochondrial oxidative phosphorylation pathway, nutritional deficiencies, excitotoxicity, formate toxicity and dysfunction of the blood-brain barrier. It was expected that the results of such international collaboration into this major health problem would also shed more light on mechanisms underlying other nutritional or tropical myeloneuropathies. KEYWORDS Optic neuritis, optic neuropathy, peripheral neuropathy, neurotoxicity syndromes, disease outbreaks, international cooperation, Cuba Erratum: Page 30, first complete paragraph, line 7, "Two models were developed independently by Cuban researchers" should read "Two models were developed independently by AAS and AGQ."

Cuantificación de la inmunoglobulina G y la albúmina en el líquido cefalorraquídeomediante las modificaciones de las técnicas para otros fluidos biológicos / Immunoglobulin G and albumin quantification in the cerebrospinal fluid by m odifications in techni ques for other biological fluids

Objetivo:Evaluar los resultados de la estimación del estado funcional de la barrera sangre–líquido cefalorraquídeo (LCR)y la síntesis intratecal de inmunoglobulina G (IgG) por el sistema nervioso central mediante las modificaciones de las técnicas comerciales diseñadas para otros fluidos biológicos.Métodos:A muestras de LCR y suero de 61 pacientes se les realizaron electroforesis de disco en geles de poliacrilamida y cuantificación de proteínas totales (PT)en el Instituto de Neurología y Neurocirugía, Habana, Cuba (INN), entre los meses de abril y diciembre de 2014. Se determinaronlas concentraciones de albúmina e IgGempleando paralelamente técnicas comerciales modificadas en ellaboratorio y métodos validados para estos estudios. Se calculó el cociente albúmina (Qalb)y el índice IgG, como indicadores del estado funcional de labarrera sangre–LCR (BS-LCR)y de la síntesis intratecal (SIT), respectivamente.Resultados:Las PT y los patrones de electroforesis se correlacionaron con el Qalby albúmina, realizado por las técnicas modificadas. No se encontraron diferencias significativas entre las cuantificaciones de las técnicas validadas y modificadas para los valoresde albúmina en LCR (Z=0,41; p=0,6791), albúmina en suero (Z=0,08; p=0,9382), el Qalb (Z=0,21; p=0,8361), IgG en LCR (Z=1,65; p=0,0995) e índice IgG (Z=1,10; p=0,2721).Conclusiones:Se demuestra que estas modificaciones en técnicas comerciales diseñadas para otros fluidos bilógicos resultan útiles para estimar la funcionalidad de la BS–LCR y calcular la SIT de inmunoglobulinas. Las modificaciones introducidas a la técnica turbidimétrica y al UMELISA pueden ser estandarizadas para su validación en el diagnóstico de daño de la BS–LCR y de síntesis intratecal de IgG por el sistema nervioso(AU)

Objective:To evaluate the results of estimating the functional status of blood–cerebrospinal fluid barrier (B–CSFB) and intrathecal immunoglobulin synthesis (ITS)of IgG for central nervous systemby modifiedcommercial techniques designed for other biological fluids.Methods:Disc polyacrylamide gel electrophoresis and quantification of CSF total protein in CSF and serum of 61 patients were conductedat the Institute of Neurology and Neurosurgery (INN) between April and September 2014. The concentration of albumin and IgG was determined by commercial standardized techniques and by modifications of commercial techniques. Albumin ratio and IgG index were calculated and employed to evaluate B–CSFB permeability and ITS, respectively.Results:Total protein and protein electrophoresis patterns were correlated with the quantifications performed by modified commercial techniques. There was no significant difference between validated commercial techniques and modified techniques for quantifications of CSF albumin(Z=0,41; p=0,6791),serum albumin (Z=0,08; p=0,9382),Qalb (Z=0,21; p=0,8361), CSF IgG (Z=1,65; p=0,0995) andIgG index (Z=1,10; p=0,2721).Conclusions:The immunological studies in CSF obtained from modifying commercial techniques designed for other biological fluids are(AU)

Serum neuron specific enolase could predict subclinical brain damage and the subsequent occurrence of brain related vascular events during follow up in essential hypertension.

The object of this work was to explore if blood based biomarkers of brain damage could predict subclinical brain lesions and clinical outcome during follow-up in asymptomatic hypertensive patients. This was a cross-sectional study including 101 patients with essential hypertension and no clinical evidence of neurological disease and 53 healthy controls, followed by a longitudinal study of 62 hypertensive patients for an average of 33 months. Serum concentrations of two brain specific proteins (S100B and neuron specific enolase - NSE) were determined at inclusion. Fundoscopic exploration, brain MRI and echocardiographic studies were also performed. Clinical outcome at follow-up was registered: transient ischemic attack (TIA), stroke, vascular headache or migraine, cardiovascular events and death. Higher serum NSE and S100B concentrations were observed in hypertensive patients; and multiple regression analysis revealed independent associations of clinical variables and more severe white matter lesions only with NSE concentration. A panel combining two clinical variables (blood pressure>140/90 and years of hypertension>10) and serum NSE>13 µg/L predicted more severe white matter lesions with 80% sensitivity and 94.4% specificity. Higher NSE levels at inclusion were associated not only with the occurrence of vascular events related with the CNS (stroke, TIA and vascular headache), but also with an earlier presentation of these events during the follow-up period. Serum NSE concentration could be a useful biomarker to predict subclinical brain damage and future vascular events related with the CNS in hypertension. Blood based biomarkers could aid in filtering hypertensive patients with a higher risk of cerebrovascular disease for brain MRI scanning.

Association of status redox with demographic, clinical and imaging parameters in patients with Huntington's disease.

UNLABELLED: Huntington's disease (HD) is an autosomal dominant, progressive neurodegenerative disorder, caused by an expanded trinucleotide CAG sequence of the huntingtin (Htt) gene, which encodes a stretch of glutamines in the Htt protein. The mechanisms of neurodegeneration associated with the accumulation of Htt aggregates still remains unclear. OBJECTIVES: To determine oxidative stress biomarkers in HD patients and their relationship with clinical, demographic and neuroimaging parameters. DESIGN AND METHODS: Fourteen patients and 39 controls paired by age and sex participated in this study. Oxidative damage was assayed in blood by measuring malondialdehyde (MDA) and advanced oxidative protein products (AOPPs). Antioxidant status was determined by activities of superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), glutathione reductase (GR), reduced glutathione (GSH), protein thiols and total antioxidant capacity (FRAP). The Unified Huntington Disease Rating Scale (UHDRS) and neuroimaging studies were also employed. RESULTS: MDA, AOPP and GPx were significantly increased in HD patients with respect to the control group, while GR activity was decreased. FRAP correlated with age of disease onset, AOPP with motor severity (UHDRS score), age of patients and age of disease onset. Caudate atrophy was associated with lower plasma concentrations of GSH. CONCLUSIONS: These findings point to a redox imbalance in HD patients. GR activity could be a potential biomarker for symptom onset in asymptomatic gene carriers, while plasmatic GSH could be useful in monitoring the progression of neurodegeneration - as an expression of caudate atrophy - during the course of the disease.

Optical Coherence Tomographic Comparison of Cuban Epidemic and Leber's Hereditary Optic Neuropathy.

Following the epidemic of optic and peripheral neuropathy, which occurred in Cuba between 1991 and 1993, a number of patients have been re-evaluated, including testing with optical coherence tomography (OCT) and electrophysiology. At the same time, a number of patients with Leber's hereditary optic neuropathy have also been evaluated. The purpose of this study was to detect residual loss of retinal nerve fibre layer (RNFL) in patients who suffered Cuban epidemic optic neuropathy (CEON), and to compare these findings with those in patients with Leber's hereditary optic neuropathy (LHON). Optical coherence tomography as well as clinical examinations were performed on 11 patients diagnosed with CEON 15 years following the epidemic and 14 patients with LHON. OCT in CEON patients showed thinning of the RNFL in the temporal sector and normal thickness in other quadrants. However, patients with chronic LHON had more diffuse RNFL loss throughout the retina. OCT findings corresponded with clinical findings in CEON and LHON. There was drop out of the papillomacular bundle in both diseases. Two patients in the acute stages of LHON and three LHON carriers showed thinning of the temporal RNFL only. This is the first report of OCT in CEON that shows residual damage in the papillomacular bundle compared with chronic LHON where there is more diffuse and progressive loss of the RNFL. The importance of OCT for the diagnosis and evaluation of similar optic neuropathies is emphasised.

Short-term prognostic value of serum neuron specific enolase and S100B in acute stroke patients.

OBJECTIVE: To explore the value of blood markers for brain injury as outcome predictors in acute stroke. DESIGN AND METHODS: The study included 61 patients with acute stroke (44 ischemic and 17 hemorrhagic) and a high risk control group (79 individuals with no known history of neurological disease). Serum neuron specific enolase (NSE) and S100B were determined by immunoassay (CanAg Diagnostics, Sweden). Outcome at 60 days was evaluated with clinical scales. RESULTS: Higher concentrations of NSE and S100B were measured in patients compared to high risk controls, but they were not related to stroke severity on admission. NSE was associated with functional neurological outcome at 60 days and to the degree of recovery, whereas S100B exhibited a strong correlation with depression symptoms at 60 days. CONCLUSIONS: The measurements of serum concentrations of NSE and S100B after acute stroke may be clinically relevant for predicting functional neurological outcome and post-stroke depression, respectively.

Dose effect evaluation and therapeutic window of the neuro-EPO nasal application for the treatment of the focal ischemia model in the Mongolian gerbil.

Cerebrovascular disease is the third leading cause of death and the leading cause of disability in Cuba and in several developed countries. A possible neuroprotective agent is the rHu-EPO, whose effects have been demonstrated in models of brain ischemia. The Neuro-EPO is a derivative of the rHu-EPO that avoids the stimulation of erythropoiesis. The aim of this study was to determine the Neuro-EPO delivery into the central nervous system (CNS) to exert a neuroprotective effect in cerebral ischemia model of the Mongolian gerbil. The Neuro-EPO in a rate of 249.4 UI every 8 hours for 4 days showed 25% higher viability efficacy (P > 0.01), improving neurological score and behavior of the spontaneous exploratory activity, the preservation of CA3 areas of the hippocampus, the cortex, and thalamic nuclei in the focal ischemia model of the Mongolian gerbil. In summary, this study, the average dose-used Neuro-EPO (249.4 UI/10 µL/every 8 hours for 4 days), proved to be valid indicators of viability, neurological status, and spontaneous exploratory activity, being significantly lower than that reported for the systemically use of the rHu-EPO as a neuroprotectant. Indeed, up to 12 h after brain ischemia is very positive Neuro-EPO administration by the nasal route as a candidate for neuroprotection.

Increased serum S-100B and neuron specific enolase - Potential markers of early nervous system involvement in essential hypertension.

OBJECTIVES: To investigate the occurrence of subclinical neurologic involvement in patients with essential hypertension employing serum biochemical markers. DESIGN AND METHODS: Fifty patients with essential hypertension and 42 controls with no clinical evidence of neurological disease were recruited. Serum S100B protein and neuron specific enolase (NSE) were determined by employing immunoassay kits from CanAg Diagnostics AB (Sweden). Brain MRI and fundoscopic exploration were conducted. RESULTS: S-100B and NSE levels were significantly higher in hypertensive patients than in controls. In hypertensive patients, multivariate analysis revealed that NSE was independently associated with two variables expressing severity of hypertension: diastolic blood pressure and grade of retinopathy. Brain MRI studies demonstrated higher NSE levels in patients with more severe white matter lesions. CONCLUSIONS: Raised NSE levels are associated with a higher severity of hypertension and of white matter lesions, providing preliminary evidence that suggests the presence of silent brain damage in a subset of hypertensive patients.

Treatment with nasal neuro-EPO improves the neurological, cognitive, and histological state in a gerbil model of focal ischemia.

Vascular illness of the brain constitutes the third cause of death and the first cause of disability in Cuba and many other countries. Presently, no medication has been registered as a neuroprotector. Neuroprotection with intranasal Neuro-EPO (EPO, erythropoietin) has emerged as a multifunctional therapy that plays a significant role in neural survival and functional recovery in an animal model of stroke. On the other hand, there is limited access to the brain through the blood brain barrier (BBB) for intravenously applied EPO, and the high EPO dosages needed to obtain a protective effect increase the danger of elevated hematocrit levels and practically exclude chronic or subchronic treatment with EPO. A promising approach has been recently developed with a nonerythropoietic variant of EPO, Neuro-EPO, with low sialic acid content, a very short plasma half-life, and without erythropoietic activity, probably similar to endogenous brain EPO. The objective of this work was to determine the neuroprotective effect of intranasal Neuro-EPO in comparison with the human recombinant EPO injected intraperitoneally in the acute phase of cerebral ischemia, employing the common carotid artery occlusion model in gerbils. Neuro-EPO has demonstrated a better neuroprotective effect, evidenced through increased viability, improvements of the neurological state and cognitive functions, as well as protection of the CA3 region of the hippocampus, temporal cortex, and the thalamus. In conclusion, the intranasal application of Neuro-EPO has a better neuroprotective effect than intraperitoneal EPO, evidenced by the significant improvement of neurological, cognitive, and histological status in the animal model of stroke employed.

An epidemiological study of neuromyelitis optica in Cuba.

INTRODUCTION: Two population-based studies of neuromyelitis optica (NMO) in non-white populations provided prevalence rates of 0.32 and 3.1 per 100,000 population. OBJECTIVE: To estimate NMO prevalence in the multiethnic Cuban population by nation-wide case ascertainment. METHODS: The study was conducted from October 1, 2003 to November 30, 2004. Ninety percent of general practitioners and all neurologists responded positively to the request for information on cases suspected of optic neuritis (ON), transverse myelitis (TM), multiple sclerosis, or NMO. Among the population of 11,177,743 there were 798 suspected cases, including 89 with possible NMO, relapsing ON (RON) and TM. Of the 89, 87 were examined by two of us (Cabrera JA, Lara R) who selected the NMO cases according to the 1999 Mayo Clinic criteria as well as those with relapsing TM and RON. RESULTS: 58 cases provided a prevalence rate of 0.52 per 100,000 (95% CI 0.39-0.67). The 7 males and 51 females gave rates of 0.13 (CI 0.05-0.26) and 0.91 (CI 0.68-1.20). The estimated average annual incidence rate was 0.053 per 100,000 (CI 0.040-0.068). Prevalence rates did not differ significantly among the three ethnic groups. Black NMO cases were significantly older, with more relapses and motor deficit, as well as more abnormalities in brainstem evoked potentials and in brain MRI (not meeting MS criteria). The predominant clinical form was relapsing over monophasic. CONCLUSIONS: This Cuban multiethnic population had a prevalence of NMO of 0.52 per 100,000 and an estimated average annual incidence rate of 0.053 per 100,000 with no differences by ethnicity. Black patients were older, with more relapses and motor impairment.

Association between Blood Lipids and Types of Stroke.

Introduction: Many studies to date on the link between blood lipid levels and cerebrovascular disease have been hampered by conceptual and methodological limitations, especially failure to separate different types of stroke. Objective: Determine the relationship between serum lipid levels and the occurrence of different types of stroke. Methods: Two case and control studies were undertaken. The first consisted of three groups: subjects with cerebral infarction (CI), subjects with cerebral hemorrhage (CH) and a control group of healthy individuals with no history of cerebrovascular disease. The second study included three groups: those with atheromatous CI, those with CI of other etiology, and the healthy control group. The influence of variables such as age, sex, and presence of risk factors was also assessed. Results: CI patients were found to have higher total cholesterol levels (p<0.01), low-density lipoprotein (LDL) cholesterol (p<0.01), and triglycerides (p<0.01) than those in the control group. CH patients had lower total cholesterol levels (p<0.05), and higher triglycerides levels (p<0.05) than the control group. The second study revealed a link between blood lipid levels and CI only in cases of atheromatous stroke. This association was prevalent in women, and was independent of other risk factors. Conclusions: The type of stroke (ischemic or hemorrhagic) and the etiopathogenic subtype of CI must be considered when studying association between blood lipids and occurrence of stroke. Elevated levels of total cholesterol, LDL and triglycerides are associated with occurrence of atheromatous CI, while low total cholesterol levels and high triglycerides levels are associated with the CH occurrence.