Bilateral hypogeusia and food aversion due to lacunar infarct in the right dorsomedial pontine tegmentum.

A 70-year-old right-handed housewife suffered an acute loss of taste, an unpleasant change in the taste of foods and liquids, and a strong aversion to all kinds of food due to a small lacune in the right dorsomedial pontine tegmentum. Eating became so unpleasant that she lost 7 kg in three weeks. Olfaction and the sensibility of the tongue were spared. The right medial longitudinal fascicle, the central tegmental tract, or both, were injured by the tegmental lesion. A discrete right-sided lesion in the upper pontine tegmentum may cause a reversible syndrome consisting of bilateral hypogeusia which is more severe ipsilaterally.

Association between APOE-ε4 allele and cognitive function is mediated by Alzheimer's disease pathology: a population-based autopsy study in an admixed sample.

BACKGROUND: Apolipoprotein E ε4 allele (APOE-ε4) is the main genetic risk factor for late-onset Alzheimer's disease (AD) and may impact cognitive function also via other neuropathological lesions. However, there is limited evidence available from diverse populations, as APOE associations with dementia seem to differ by race. Therefore, we aimed to evaluate the pathways linking APOE-ε4 to cognitive abilities through AD and non-AD neuropathology in an autopsy study with an admixed sample. METHODS: Neuropathological lesions were evaluated following international criteria using immunohistochemistry. Participants were classified into APOE-ε4 carriers (at least one ε4 allele) and non-carriers. Cognitive abilities were evaluated by the Clinical Dementia Rating Scale sum of boxes. Mediation analyses were conducted to assess the indirect association of APOE-ε4 with cognition through AD-pathology, lacunar infarcts, hyaline arteriosclerosis, cerebral amyloid angiopathy (CAA), Lewy body disease (LBD), and TAR DNA-binding protein 43 (TDP-43). RESULTS: We included 648 participants (mean age 75 ± 12 years old, mean education 4.4 ± 3.7 years, 52% women, 69% White, and 28% APOE-ε4 carriers). The association between APOE-ε4 and cognitive abilities was mediated by neurofibrillary tangles (ß = 0.88, 95% CI = 0.45; 1.38, p < 0.001) and neuritic plaques (ß = 1.36, 95% CI = 0.86; 1.96, p < 0.001). Lacunar infarcts, hyaline arteriosclerosis, CAA, LBD, and TDP-43 were not mediators in the pathway from APOE-ε4 to cognition. CONCLUSION: The association between APOE-ε4 and cognitive abilities was partially mediated by AD-pathology. On the other hand, cerebrovascular lesions and other neurodegenerative diseases did not mediate the association between APOE-ε4 and cognition.

The etiologies of post-stroke depression: Different between lacunar stroke and non-lacunar stroke.

OBJECTIVES: Depression is common after both lacunar stroke and non-lacunar stroke and might be associated with lesion locations as proven by some studies. This study aimed to identify whether lesion location was critical for depression after both lacunar and non-lacunar strokes. METHODS: A cohort of ischemic stroke patients was assigned to either a lacunar stroke group or a non-lacunar stroke group after a brain MRI scan. Neurological deficits and treatment response was evaluated during hospitalization. The occurrence of depression was evaluated 3 months later. Logistic regressions were used to identify the independent risk factors for depression after lacunar and non-lacunar stroke respectively. RESULTS: 83 of 246 patients with lacunar stroke and 71 of 185 patients with non-lacunar stroke developed depression. Infarctions in the frontal cortex, severe neurological deficits, and a high degree of handicap were identified as the independent risk factors for depression after non-lacunar stroke, while lesion location was not associated with depression after lacunar stroke. CONCLUSION: The main determinants for depression after lacunar and non-lacunar stroke were different. Lesion location was critical only for depression after non-lacunar stroke.

Immune-Inflammatory, Metabolic, Oxidative, and Nitrosative Stress Biomarkers Predict Acute Ischemic Stroke and Short-Term Outcome.

Immune-inflammatory, metabolic, oxidative, and nitrosative stress (IMO&NS) pathways and, consequently, neurotoxicity are involved in acute ischemic stroke (IS). The simultaneous assessment of multiple IMO&NS biomarkers may be useful to predict IS and its prognosis. The aim of this study was to identify the IMO&NS biomarkers, which predict short-term IS outcome. The study included 176 IS patients and 176 healthy controls. Modified Rankin scale (mRS) was applied within 8 h after IS (baseline) and 3 months later (endpoint). Blood samples were obtained within 24 h after hospital admission. IS was associated with increased white blood cell (WBC) counts, high sensitivity C-reactive protein (hsCRP), interleukin (IL-6), lipid hydroperoxides (LOOHs), nitric oxide metabolites (NOx), homocysteine, ferritin, erythrocyte sedimentation rate (ESR), glucose, insulin, and lowered iron, 25-hydroxyvitamin D [25(OH)D], total cholesterol, and high-density lipoprotein (HDL) cholesterol. We found that 89.4% of the IS patients may be correctly classified using the cumulative effects of male sex, systolic blood pressure (SBP), glucose, NOx, LOOH, 25(OH)D, IL-6, and WBC with sensitivity of 86.2% and specificity of 93.0%. Moreover, increased baseline disability (mRS ≥ 3) was associated with increased ferritin, IL-6, hsCRP, WBC, ESR, and glucose. We found that 25.0% of the variance in the 3-month endpoint (mRS) was explained by the regression on glucose, ESR, age (all positively), and HDL-cholesterol, and 25(OH)D (both negatively). These results show that the cumulative effects of IMO&NS biomarkers are associated with IS and predict a poor outcome at 3-month follow-up.

Outcome after intravenous thrombolysis in patients with acute lacunar stroke: An observational study based on SITS international registry and a meta-analysis.

BACKGROUND: Intravenous thrombolysis (IVT) for lacunar stroke (LS) is debated, as the underlying pathophysiological mechanism may not be thrombogenic. AIMS: To investigate outcomes after IVT in LS in the SITS International Stroke Thrombolysis Register and perform a meta-analysis. METHODS: LS was identified by both baseline NIHSS-subscores and discharge ICD-10 codes, and contrasted by IVT to non-IVT treated. IVT patients were predominantly from Europe, non-IVT patients predominantly from South America and Asia. Outcome measurements were functional independence (modified Rankin Scale [mRS] score ≤2), excellent outcome (mRS ≤ 1), and mortality at three months. Matched-control comparisons of symptomatic intracerebral hemorrhage (SICH) between IVT-treated LS and IVT-treated non-LS patients were performed. Additionally, we performed a meta-analysis. RESULTS: Median age for IVT-treated LS patients (n = 4610) was 66 years vs. 64 years and NIHSS score was 6 vs. 3, compared to non-IVT-treated LS (n = 1221). Univariate outcomes did not differ; however, IVT-treated LS patients had higher adjusted odds ratios (aOR) for functional independence (aOR = 1.65, 95% CI = 1.28-2.13) but similar mortality at three months (aOR = 0.57, 0.29-1.13) than non-IVT-LS. Propensity-score matched analysis showed that IVT-treated LS patients had a 7.1% higher chance of functional independency than non-IVT LS patients (p < 0.001). IVT-treated LS patients had lower odds for SICH (aOR = 0.33, 0.19-0.58 per SITS, aOR = 0.40, 0.27-0.57 per ECASS-2) than matched non-LS controls, which was mirrored in the meta-analysis. CONCLUSIONS: Our adjusted results show that IVT treatment in LS patients was associated with better functional outcome than non-IVT-treated LS and less SICH than IVT-treated non-LS patients.

Perfil clínico diferencial entre los infartos lacunares y los infartos cerebrales aterotrombóticos / Differential clinical profile of lacunar infarcts compared to atherothrombotic brain infarcts

Aims and objectives: The present study makes a comparative analysis between the clinical profile of lacunar infarcts (LI) and that of atherothrombotic brain infarcts (ABI). Methods: Hospital-based descriptive study of 1809 consecutive patients admitted over a period of 24 years with a diagnosis of lacunar cerebral infarction (n = 864) or atherothrombotic cerebral infarction (n = 945). A comparative analysis of the demographic data, cerebral vascular risk factors, clinical data and hospital evolution between both subtypes of cerebral infarction was performed using a univariate and multivariate statistical methodology. Results: LI accounted for 26.5% and ABI for 28.9% of all cerebral infarctions in the registry. The variables directly and independently associated with ABI were: ischemic heart disease, previous transient ischemic attack, previous cerebral infarction, peripheral vascular disease, anticoagulant therapy, age > 85 years, vegetative symptoms, decreased level of consciousness, sensory deficit, visual deficit, speech disorders, and neurological, respiratory and urinary complications during hospital admission. In contrast, the absence of neurological symptoms at hospital discharge was directly associated with LI. Conclusions: LI and ABI have a distinct clinical profile. The best functional prognosis of LI during the acute phase of the disease is characteristic. In contrast, ICAs have a higher atherosclerotic burden and a worse prognosis.

Fundamentos y objetivo: El objetivo del estudio es efectuar un análisis comparativo entre el perfil clínico de los infartos lacunares (IL) y el perfil de los infartos cerebrales aterotrombóticos (ICA). Métodos: Estudio hospitalario descriptivo de 1809 pacientes consecutivos ingresados durante un período de 24 años con el diagnóstico de infarto cerebral de tipo lacunar (n = 864) o por infarto cerebral aterotrombótico (ICA) (n = 945). Se realizó un análisis comparativo de los datos demográficos, factores de riesgo vascular cerebral, datos clínicos y de evolución hospitalaria utilizando una metodología estadística univariada y, posteriormente, multivariada. Resultados: Los IL representaron el 26.5% y los ICA el 28.9% del total de infartos cerebrales del registro. Las variables asociadas directamente y de forma independiente con los ICA fueron: cardiopatía isquémica, ataque isquémico transitorio previo, infarto cerebral previo, enfermedad vascular periférica, uso de anticoagulantes, edad > 85 años, síntomas vegetativos, disminución del nivel de conciencia, déficit sensitivo, déficit visual, trastornos del habla y complicaciones neurológicas, respiratorias y urinarias durante el ingreso hospitalario. En cambio, la ausencia de sintomatología neurológica al alta se asoció directamente con los IL. Conclusiones: Los IL y los ICA tienen un perfil clínico diferenciado. Es característico el mejor pronóstico funcional de los IL durante la fase aguda de la enfermedad. En cambio, los ICA presentan mayor carga aterosclerótica y peor pronóstico evolutivo.

Blood pressure gradients in cerebral arteries: a clue to pathogenesis of cerebral small vessel disease.

RATIONALE: The role of hypertension in cerebral small vessel disease is poorly understood. At the base of the brain (the 'vascular centrencephalon'), short straight arteries transmit blood pressure directly to small resistance vessels; the cerebral convexity is supplied by long arteries with many branches, resulting in a drop in blood pressure. Hypertensive small vessel disease (lipohyalinosis) causes the classically described lacunar infarctions at the base of the brain; however, periventricular white matter intensities (WMIs) seen on MRI and WMI in subcortical areas over the convexity, which are often also called 'lacunes', probably have different aetiologies. OBJECTIVES: We studied pressure gradients from proximal to distal regions of the cerebral vasculature by mathematical modelling. METHODS AND RESULTS: Blood flow/pressure equations were solved in an Anatomically Detailed Arterial Network (ADAN) model, considering a normotensive and a hypertensive case. Model parameters were suitably modified to account for structural changes in arterial vessels in the hypertensive scenario. Computations predict a marked drop in blood pressure from large and medium-sized cerebral vessels to cerebral peripheral beds. When blood pressure in the brachial artery is 192/113 mm Hg, the pressure in the small arterioles of the posterior parietal artery bed would be only 117/68 mm Hg. In the normotensive case, with blood pressure in the brachial artery of 117/75 mm Hg, the pressure in small parietal arterioles would be only 59/38 mm Hg. CONCLUSION: These findings have important implications for understanding small vessel disease. The marked pressure gradient across cerebral arteries should be taken into account when evaluating the pathogenesis of small WMIs on MRI. Hypertensive small vessel disease, affecting the arterioles at the base of the brain should be distinguished from small vessel disease in subcortical regions of the convexity and venous disease in the periventricular white matter.

Basilar Artery Dolichoectasia: Prevalence and Correlates With Markers of Cerebral Small Vessel Disease in Community-Dwelling Older Adults.

BACKGROUND: Basilar artery (BA) dolichoectasia has been associated with cerebral small vessel disease (SVD). However, studies have focused on stroke patients, and results cannot be extrapolated to the population at large. In this study, we aimed to assess prevalence of BA dolichoectasia and its association with SVD in community-dwelling older adults living in rural Ecuador. METHODS: Atahualpa residents aged ≥60 years underwent brain magnetic resonance imaging and magnetic resonance angiography of intracranial vessels. Following Smoker's criteria, the mean BA diameter plus 2 standard deviation defined ectasia. In addition, a location lateral to the lateral margin of the clivus of dorsum sellae or a bifurcation at the third ventricle floor or higher defined dolichosis. Associations between BA abnormalities and imaging markers of SVD were assessed by the use of regression models adjusted for demographics and cardiovascular risk factors. RESULTS: Of 346 participants, 11 (3.2%) had ectasia, 40 (11.6%) had dolichosis, and 47 (13.6%) had dolichoectasia (ectasia, dolichosis, or both). BA diameter was only associated with severity of white matter hyperintensities (P = .038). Dolichosis was associated with deep cerebral microbleeds (P = .002) but not with white matter hyperintensities. Dolichoectasia was associated with both white matter hyperintensities (P = .031) and cerebral microbleeds (P = .001). There were no associations with lacunar infarcts or enlarged perivascular spaces in any model. CONCLUSIONS: Prevalence of BA dolichoectasia in this rural setting is similar to that reported in other populations. Associations with imaging markers of SVD differ according to whether the subject has ectasia or dolichosis.

Síndrome de Percheron / Percheron syndrome

El infarto talámicoparamediano bilateral sincrónico,llamado habitualmente infarto de la arteria de Percheron, se considera infrecuente y de difícil diagnóstico clínico. Se presenta a una paciente de 50 años, con infarto talámico bilateral, que presentó un cuadro de desorientación, visión borrosa y doble en horas de la mañana, sin referir pérdida de conciencia. En la tomografía axial computarizada de cráneo simple se evidenció una hipodensidad talámica bilateral, compatible con un infarto agudo a este nivel, por oclusión de la arteria de Percheron. Es importante el reconocimiento de esta variante anatómica para establecer el mecanismo del infarto talámico bilateral.

Multiple Lacunar Infarcts in Paroxysmal Nocturnal Hemoglobinuria.

Paroxysmal nocturnal hemoglobinuria (PNH) is a rare acquired disease characterized by clonal hematopoietic stem cell disorder, with increased mortality and morbidity. Venous thrombosis is the most common cause of mortality in PNH. The relationship between PNH and cerebrovascular disease is unclear; few cases are reported in the literature, most of them related to cerebral venous thrombosis; In PNH the involvement of intracranial and extracranial arterial sites is very rare. We report a case of a 49-year-old woman who has a medical history of diabetes mellitus, hypertension, and PNH and presented multiple lacunar strokes in a routine consultation with a hematologist. A brain computed tomography (CT) scan showed lacunar infarcts, and magnetic resonance image showed acute ischemic stroke, multiple territory lacunar infarctions, and focal area of microbleeds in gradient echo sequence. A CT angiography showed V3 and V4 branches of the left vertebral artery occluded by a thrombus, and the posterior inferior cerebellar artery occluded, whereas the carotid system was normal. We discuss the presentation and physiopathology of stroke in PNH and other cases reported in the literature review.

Distinct non-cerebrovascular risk factors for ischemic lacunar stroke and non-lacunar stroke: preliminary results.

Stroke is a non-communicable disease of increasing socioeconomic importance in aging populations. This study compared the risk factors implicated in two subtypes of ischemic stroke: lacunar stroke (LS) and non-lacunar stroke (NLS). A retrospective case control study was conducted on a total of 368 patients [220 cases (59.8%) of NLS and 148 cases (40.2%) of LS] with first-time onset of ischemic stroke. Multivariate logistic regression was performed to compare multiple non-cerebrovascular risk factors between the two groups. More patients with a history of diabetes were found in the NLS than the LS group (40.5 vs 26.4%), and that both fasting glucose and HbA1C levels before the onset of stroke were higher in NLS than LS patients. Multivariate analysis revealed that patients with a history of diabetes were 1.57 times more likely to have NLS than LS (OR = 1.57, 95%CI = 0.95-3.26). Moreover, male patients were more likely to develop NLS than females (OR = 1.46, 95%CI = 0.79-2.69), and patients with elevated fibrinogen levels were 1.4 times more likely to develop NLS than LS (OR = 1.40, 95%CI = 1.09-1.80). Additionally, patients who were heavy drinkers (OR = 1.39, 95%CI = 0.68-2.84) or smokers (OR = 1.62, 95%CI = 0.91-2.89) were more likely to develop NLS than LS. Other risk factors, such as hypertension, dyslipidemia, age, and average blood pressure, did not differ between the two types of stroke. Thus, distinct non-cerebrovascular risk factors (male gender, long history of diabetes, elevated fibrinogen, heavy smoking, and heavy drinking) are associated with a higher risk of developing non-lacunar stroke than lacunar stroke.

The association of ankle-brachial index with silent cerebral small vessel disease: results of the Atahualpa Project.

BACKGROUND: An abnormal ankle-brachial index has been associated with overt stroke and coronary heart disease, but little is known about its relationship with silent cerebral small vessel disease. AIM: To assess the value of ankle-brachial index as a predictor of silent small vessel disease in an Ecuadorian geriatric population. METHODS: Stroke-free Atahualpa residents aged ≥60 years were identified during a door-to-door survey. Ankle-brachial index determinations and brain magnetic resonance imaging were performed in consented persons. Ankle-brachial index ≤0.9 and ≥1.4 were proxies of peripheral artery disease and noncompressible arteries, respectively. Using logistic regression models adjusted for age, gender, and cardiovascular health status, we evaluated the association between abnormal ankle-brachial index with silent lacunar infarcts, white matter hyperintensities, and cerebral microbleeds. RESULTS: Mean age of the 224 participants was 70 ± 8 years, 60% were women, and 80% had poor cardiovascular health status. Ankle-brachial index was ≤0.90 in 37 persons and ≥1.4 in 17. Magnetic resonance imaging showed lacunar infarcts in 27 cases, moderate-to-severe white matter hyperintensities in 47, and cerebral microbleeds in 26. Adjusted models showed association of lacunar infarcts with ankle-brachial index ≤ 0.90 (OR: 3.72, 95% CI: 1.35-10.27, P = 0.01) and with ankle-brachial index ≥ 1.4 (OR: 3·85, 95% CI: 1.06-14.03, P = 0.04). White matter hyperintensities were associated with ankle-brachial index ≤ 0.90 (P = 0.03) and ankle-brachial index ≥ 1.4 (P = 0.02) in univariate analyses. There was no association between ankle-brachial index groups and cerebral microbleeds. CONCLUSIONS: In this population-based study conducted in rural Ecuador, apparently healthy individuals aged ≥60 years with ankle-brachial index values ≤0.90 and ≥1.4 are almost four times more likely to have a silent lacunar infarct. Ankle-brachial index screening might allow recognition of asymptomatic people who need further investigation and preventive therapy.

Incompleteness of the Circle of Willis correlates poorly with imaging evidence of small vessel disease. A population-based study in rural Ecuador (the Atahualpa project).

BACKGROUND: Studies looking for an association between incompleteness of the Circle of Willis (CoW) and small vessel disease (SVD) markers are scarce and conflicting. We aimed to evaluate this association in an unbiased population-based study conducted in Atahualpa (rural Ecuador). METHODS: Atahualpa residents 60 years of age or more were identified during a door-to-door survey and invited to undergo magnetic resonance imaging for identification of SVD markers, including white matter hyperintensities (WMHs), strokes, and deep microbleeds. Magnetic resonance imaging (MRA) was used for classifying the CoW according to the presence or absence of one A1 segment of the anterior cerebral artery or one or both P1 segments of posterior cerebral arteries. RESULTS: Of 311 eligible persons, 258 were enrolled. Mean age was 70 ± 8 years, 59% were women, and 74% had a poor cardiovascular health (CVH) status. Of these, 172 patients (67%) had WMH, 40 patients (16%) had SVD-related strokes, and 23 patients (9%) had deep microbleeds. MRA revealed a complete CoW in 157 persons (61%). Persons with SVD markers were older than those without markers (P < .0001). A poor CVH status was noted in 79% of persons with at least 1 SVD marker and in 65% of those with no markers (P = .02). Logistic regression models showed no association of incompleteness of the CoW with any marker of SVD-alone or in combination-after adjusting for age, sex, and CVH status. CONCLUSIONS: Lack of association between incompleteness of CoW and SVD markers suggest that genetically determined variants in the intracranial vasculature are not responsible for the high prevalence of SVD among native South American populations.

Heminegligência / Hemineglect

A heminegligência, um fenômeno em que uma disfunção leva a uma desatenção da metade do campo visual e da percepção corporal, geralmente decorre de lesões do hemisfério parietal e está associado a um pior prognóstico quando acompanhada de anosognosia. O objetivo deste estudo é apresentar o caso de um paciente do sexo masculino, 73 anos, que desenvolveu heminegligência espacial associada à anosognosia e hemianopsia à esquerda decorrentes de um acidente vascular encefálico isquêmico (AU)

Hemineglect, a phenomenon in which a dysfunction leads to inattention of half the visual fi eld and body perception, usually results from damage to the parietal hemisphere and is associated with a worse prognosis when accompanied by anosognosia. The objective of this study is to present the case of a male patient, 73, who developed spatial hemineglect and anosognosia associated with left hemianopia resulting from an ischemic stroke (AU)

Irregularly shaped lacunar infarction: risk factors and clinical significance.

OBJECTIVE: Our study focused on acute lacunar infarct shapes to explore the risk factors and clinical significance of irregularly shaped lacunar infarctions. METHODS: Based on the shape of their acute lacunar infarct, patients (n=204) were classified into the "regular" group or "irregular" group. The characteristics of the lacunar infarction were compared between the regular and irregular groups, between patients with and without neurological deterioration, and between patients with different modified Rankin scale (mRS) scores. The risk factors for irregularly shaped lacunar infarctions, neurological deterioration, and high mRS scores were identified. RESULTS: Blood pressure variability (BPV) was an independent risk factor for irregularly shaped lacunar infarction. Infarction size, prevalence of advanced leukoaraiosis, and irregularly shaped lacunar infarcts were independent risk factors for higher mRS scores. CONCLUSIONS: The irregularly shaped lacunar infarcts were correlated with BPV. Irregularly shaped lacunar infarctions and leukoaraiosis may be associated with unfavorable clinical outcomes.

ACV lacunar talámico y piramidal bulbar en adulto joven diabético: reporte de caso / Lacunar stroke in thalamic and bulbar pyramid in a young diabetic adult: case report

Reportamos el caso de un paciente con enfermedad diabética tipo 1 que sufrió un ACV isquémico lacunar talámico derecho y simultáneamente otro en la pirámide bulbar derecha, con manifestaciones sensitivas y motoras. Este cuadro clínico se consideró asociado a microangiopatía vascular por el antecedente personal de diabetes tipo 1 y debido a que los demás estudios realizados durante la atención médica no mostraron otra causa aparente.

We report a patient with Diabetes mellitus who suffers simultaneus ischemic stroke at the rigth talamus and the ipsilateral bulbar pyramid. This vascular phenomenom was attributed to vascular microangiopathy as part of type 1 diabetes mellitus. Remaining work up ruled out other causes for acute ischemic stroke.