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OBJECTIVE: Despite the high frequency of depression in the first year following stroke, few studies have predicted risk of depression after the acute and subacute stroke periods. The aim of this study was to identify, in the acute and subacute periods, measures that would predict major depression during the first year after stroke. METHODS: Study subjects were inpatients with ischemic stroke aged 20-85 years within 6 weeks of onset. Patients were evaluated at baseline and at 3, 6, 9, and 12 months. Patients were diagnosed with major depression using the Structured Clinical Interview for DSM-IV. The severity of depressive symptoms was measured with the Patient Health Questionnaire-9 (PHQ-9) and the Montgomery-Åsberg Depression Rating Scale (MADRS). RESULTS: Of the 152 potential patients who met inclusion criteria, 49 had follow-up evaluations; one patient with major depression in the acute and subacute periods was excluded from the analysis. Among the remaining 48 patients, the number of those with major depression during the first year of stroke onset was five (10.4%). Patients who developed major depression had significantly more depressive symptoms in the acute and subacute stroke phase as assessed by both the PHQ-9 and MADRS. Patients with PHQ-9 scores ≥9 in the acute and subacute stroke phases were significantly more likely to develop major depression in a chronic phase of stroke. CONCLUSIONS: The self-administered PHQ-9 can identify patients in the acute and subacute stroke periods who are at increased risk for developing major depression during the first year after stroke.
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Trastorno Depresivo Mayor/diagnóstico , Valor Predictivo de las Pruebas , Índice de Severidad de la Enfermedad , Accidente Cerebrovascular/complicaciones , Anciano , Femenino , Humanos , Entrevistas como Asunto , Masculino , Escalas de Valoración PsiquiátricaRESUMEN
BACKGROUND: Nonvitamin K antagonist oral anticoagulants (NOACs) are considered superior, or at least noninferior, to warfarin in preventing stroke or systemic embolism in patients with nonvalvular atrial fibrillation. Here, we recruited acute ischemic stroke patients with nonvalvular atrial fibrillation and at least one cerebral microbleed (CMB), and evaluated the proportion of patients who had an increased number of CMBs (%) after receiving anticoagulant therapy with NOACs or with warfarin for 12 months. METHODS: This was a multicenter, prospective, observational cohort study at 20 centers, conducted between 2015 and 2017, in which we recruited 85 patients with at least one CMB detected by 1.5T magnetic resonance imaging (T2*WI) at baseline, who received NOACs or warfarin for at least 12 months. We compared the proportions of patients with increased numbers of CMBs in the NOACs and warfarin treatment groups. RESULTS: The proportions of patients with increased numbers of CMBs at month 12 of treatment were 28.6% and 66.7% in the NOACs and warfarin groups, respectively. The new CMBs showed no specific regional localization in either group. In the NOACs and warfarin groups, physicians prescribed lower-than-standard dosing in 13.3% and 50% of the cases, respectively. The administration of reduced doses at physicians' discretion did not appear to alter the incidence of new CMBs. DISCUSSION: This is the first evidence to suggest efficacy of NOACs for preventing further CMBs in patients with at least one CMB, although no statistical evaluation was carried out.
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Anticoagulantes/administración & dosificación , Fibrilación Atrial/tratamiento farmacológico , Isquemia Encefálica/tratamiento farmacológico , Hemorragias Intracraneales/prevención & control , Accidente Cerebrovascular/tratamiento farmacológico , Vitamina K/antagonistas & inhibidores , Warfarina/administración & dosificación , Administración Oral , Anciano , Anciano de 80 o más Años , Anticoagulantes/efectos adversos , Fibrilación Atrial/diagnóstico , Fibrilación Atrial/epidemiología , Isquemia Encefálica/diagnóstico por imagen , Isquemia Encefálica/epidemiología , Femenino , Humanos , Incidencia , Hemorragias Intracraneales/diagnóstico por imagen , Hemorragias Intracraneales/epidemiología , Japón/epidemiología , Imagen por Resonancia Magnética , Masculino , Persona de Mediana Edad , Proyectos Piloto , Estudios Prospectivos , Recurrencia , Factores de Riesgo , Accidente Cerebrovascular/diagnóstico por imagen , Accidente Cerebrovascular/epidemiología , Factores de Tiempo , Resultado del Tratamiento , Warfarina/efectos adversosRESUMEN
Stroke-associated pneumonia (SAP) is a frequent complication in acute ischemic stroke (IS) patients, especially those receiving tube feeding (TF). In this retrospective study, we investigated whether or not cilostazol, a pluripotent phosphodiesterase III-specific inhibitor with anti-platelet and vasculogenic effects, can prevent SAP in these patients and reduce their duration of stay in intensive care unit/hospitalization. We recruited 158 IS patients receiving TF. Patients' characteristics (including age, gender, past history), National Institute of Health Stroke Scale and serum albumin level on admission, concomitant medications associated with SAP prevention (including cilostazol), and stroke characteristics (bilateral subcortical white matter lesion, brainstem involvement, large infarction, and asymptomatic hemorrhagic infarction) were compared between the SAP(-) and SAP(+) groups. Cilostazol was more frequently used in the SAP(-) group (20.8% vs. 6.1%, p < 0.05). Duration of intensive care unit was longer in patients with SAP (9 ± 8 vs. 6 ± 6 days, p < 0.05). However, the length of stay in an intensive care unit and duration of hospitalization were not reduced due to the prevention of SAP by cilostazol treatment. Cilostazol administration was associated with reduced SAP incidence in acute IS patients receiving TF.
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Cilostazol/administración & dosificación , Nutrición Enteral , Inhibidores de Agregación Plaquetaria/administración & dosificación , Neumonía/prevención & control , Accidente Cerebrovascular/complicaciones , Anciano , Anciano de 80 o más Años , Cilostazol/uso terapéutico , Nutrición Enteral/efectos adversos , Femenino , Humanos , Masculino , Inhibidores de Agregación Plaquetaria/uso terapéutico , Neumonía/etiología , Estudios RetrospectivosRESUMEN
We report an 82-year-old man with recurrence of Mikulicz's disease accompanied with mononeuritis multiplex. On admission, both upper eyelids, the salivary gland, the dorsum of the left hand and both legs were swollen. Neurological examination showed motor weakness of distal limbs (manual muscle testing 3/5) and decreased touch, pain and vibration sensation of the dorsum of the left hand and both legs. Deep tendon reflex in both legs was also decreased. We diagnosed Mikulicz's disease based on high serum immunoglobulin (Ig)G4 (630 mg/dl, 26.1% of total IgG) and lacrimal gland biopsy findings. Clinical symptoms and motor conduction study findings improved after steroid therapy. However, tapering of the steroid dose resulted in recurrence two years later. Steroid therapy is usually effective for IgG4-related neuropathy, and we found that an increase of steroid dose was effective to treat the recurrence. But, in general, a suitable maintenance dose of steroid in combination with an immunosuppressant may be necessary to prevent relapse.
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A 73-year-old man was admitted with sudden right upper-limb weakness. He had a temporal headache on the left side and had a 4-month history of fever. Meandering of the left temporal artery (TA) with induration and high inflammatory responses (white blood cell count 22,500 per microliter, C-reactive protein 35.0 mg/dL, and elevated sedimentation rate [ESR] 80 mm/h) were observed. Glycometabolism and lipid metabolism were normal, and autoimmune antibodies were negative. Cultivation tests revealed no bacteria in either blood culture or cerebrospinal fluid. Brain magnetic resonance imaging (MRI) showed ischemic lesion in the left frontal lobe, while magnetic resonance angiography (MRA) and carotid ultrasonography showed unstable plaque lesions in the left extracranial internal carotid artery (ICA). According to reported criteria (age > 50 years, new onset of headache, abnormality of the TA, and raised ESR), we diagnosed giant cell arteritis (GCA) with acute ischemic stroke (IS) and gave the patient antithrombotic therapy (aspirin 100 mg, cilostazol 200 mg). After admission, hemiparesis progressed but fluctuated. Subsequent MRI showed new lesions in the left watershed area. MRA also showed vasospasm in the middle cerebral artery and C5 portion of the ICA. Considering the correlation with GCA pathophysiology, oral prednisolone therapy was administered. Steroid therapy has prevented stroke recurrence and improved the symptoms and vasospasm. We wish to emphasize that GCA can induce IS via vasospasm, and steroid therapy is recommended.
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Isquemia Encefálica/complicaciones , Isquemia Encefálica/etiología , Arteritis de Células Gigantes/complicaciones , Accidente Cerebrovascular/etiología , Vasoespasmo Intracraneal/complicaciones , Vasoespasmo Intracraneal/etiología , Anciano , Isquemia Encefálica/diagnóstico por imagen , Proteína C-Reactiva/metabolismo , Humanos , Angiografía por Resonancia Magnética , Imagen por Resonancia Magnética , Masculino , Accidente Cerebrovascular/diagnóstico por imagenRESUMEN
A 51-year-old man was admitted to our hospital complaining of preceding throbbing headache and tonic convulsions. Headache and convulsive seizure disappeared and his consciousness recovered to alert within 2 hours after onset. Neurological examination showed no abnormal findings. Laboratory examinations revealed high low-density lipoprotein cholesterol (179 mg/dL), renin (42 ng/mL/hour), aldosterone (265 pg/mL), noradrenaline (1031 pg/mL), and dopamine (79 pg/mL). In brain magnetic resonance imaging (MRI), fluid-attenuated inversion recovery, but not the diffusion-weighted image, showed high signal intensities in white matter in bilateral occipital, parietal, and frontal lobes, with no stenotic changes on magnetic resonance angiography. In addition, the diffusion coefficient of focal lesions was elevated. Decreasing blood flow velocity and separated lumens in the right renal artery trunk were shown by renal artery ultrasonography. Enhanced computed tomography and renal angiography showed right renal partial infarction and isolated stenosis in the right renal artery, accompanied by thrombosed false lumen. No stenotic changes were seen in other peripheral arteries. These findings seemed incompatible with renal dissection and fibromuscular dysplasia, Takayasu's arteritis, and polyarteritis nodosa. Our diagnosis was posterior reversible encephalopathy syndrome (PRES) induced by renal hypertension due to renal artery dissection. To improve the renal artery stenosis and secondary hypertension, we performed plain balloon angioplasty, in addition to administering antihypertensive and lipid-lowering medications. After angioplasty, hypertension and high signal intensity at brain MRI were clearly improved. We would like to emphasize that renal artery angioplasty should be considered as an option for patients with PRES and malignant hypertension.
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Angioplastia , Hipertensión Renovascular/complicaciones , Síndrome de Leucoencefalopatía Posterior/terapia , Aldosterona/sangre , Humanos , Hipertensión Renovascular/sangre , Lipoproteínas LDL/sangre , Masculino , Persona de Mediana Edad , Síndrome de Leucoencefalopatía Posterior/sangre , Síndrome de Leucoencefalopatía Posterior/etiología , Renina/sangre , Resultado del TratamientoRESUMEN
BACKGROUND: Granulocyte colony-stimulating factor (G-CSF) has shown neuroprotective and neurogenerative activities in experimental studies, and our previous phase I clinical study suggested the safety and potential efficacy of low-dose G-CSF in acute ischemic stroke patients. The present phase II trial is aimed to evaluate the effect of G-CSF administration on neurological function and infarct volume, compared with a placebo group. METHODS: Forty-nine acute ischemic stroke patients (29 males, 20 females; 71 ± 10 years) within 24 hours after onset were recruited. Eligible patients were randomized 2:2:1 to receive G-CSF 150 µg/body/day, G-CSF 300 µg/body/day, and placebo, respectively. We evaluated clinical outcome in terms of the National Institutes of Health Stroke Scale, the modified Rankin Scale, and the Barthel Index at 90 days after onset, together with changes in infarct volume on magnetic resonance imaging. RESULTS: We found no serious adverse event, including change in leukocyte levels, which remained below 31,000/µL, at 150 and 300 µg G-CSF/body/day. Clinical outcome scores did not show any significant difference among the 3 groups. Chronological changes in infarct volume also showed no significant difference. CONCLUSIONS: G-CSF was well-tolerated at 150 and 300 µg/body/day in patients with acute ischemic stroke. However, administration of G-CSF at both 150 and 300 µg/body/day neither contributed to functional recovery nor reduced infarct volume at 3 months after onset, compared with the control group. The apparent lack of effectiveness may have been due to the small sample size. A trial of combination therapy with recombinant tissue plasminogen activator and G-CSF is planned.
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Isquemia Encefálica/tratamiento farmacológico , Encéfalo/efectos de los fármacos , Factor Estimulante de Colonias de Granulocitos/administración & dosificación , Accidente Cerebrovascular/tratamiento farmacológico , Anciano , Anciano de 80 o más Años , Encéfalo/diagnóstico por imagen , Encéfalo/fisiopatología , Isquemia Encefálica/diagnóstico por imagen , Isquemia Encefálica/fisiopatología , Evaluación de la Discapacidad , Femenino , Factor Estimulante de Colonias de Granulocitos/efectos adversos , Humanos , Infusiones Intravenosas , Japón , Imagen por Resonancia Magnética , Masculino , Persona de Mediana Edad , Recuperación de la Función , Accidente Cerebrovascular/diagnóstico por imagen , Accidente Cerebrovascular/fisiopatología , Factores de Tiempo , Resultado del TratamientoRESUMEN
In acute phase of ischemic stroke, as neuroprotective and neurogenerative role of granulocyte-colony stimulating factor(G-CSF), anti-apoptotic action, anti-inflammatory and anti-immune effect, and brain protective action against excitatory neurotoxicity have been reported. Several clinical trials in ischemic stroke patients using G-CSF have been carried out and reported the safety, improvement of clinical symptom, and reduction of infarct volume. But the efficacy of G-CSF administration in acute ischemic stroke has not been well proved. Further clinical studies with more patients, more uniform infarct size, and similar distributions of stroke subtype, are needed to clarify its effectiveness. Combined therapy with G-CSF and thrombolysis will be also expected as the next step of clinical trials.
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Factor Estimulante de Colonias de Granulocitos/administración & dosificación , Accidente Cerebrovascular/tratamiento farmacológico , Animales , Antiinflamatorios , Apoptosis/efectos de los fármacos , Ensayos Clínicos como Asunto , Factor Estimulante de Colonias de Granulocitos/farmacología , Humanos , Regeneración Nerviosa/efectos de los fármacos , Fármacos Neuroprotectores , Proteínas Recombinantes/administración & dosificación , Resultado del TratamientoRESUMEN
RATIONALE: Anticoagulants are widely used to prevent recurrence of ischemic stroke in patients with nonvalvular atrial fibrillation, but in some patients, they also cause bleeding, particularly intracranial hemorrhage. One of the independent predictors of intracerebral hemorrhage is the presence of cerebral microbleeds (CMBs); a high incidence of intracerebral hemorrhage is reported in warfarin-treated patients with multiple CMBs. Longitudinal study suggested that the presence of CMBs at baseline is a predictor of new CMBs in warfarin-treated patients. However, there has been no study on the progression of CMBs in patients receiving the non-vitamin K antagonist oral anticoagulants (NOACs). AIMS: This study tests the hypothesis that the incidence of hemorrhagic stroke is lower in patients receiving NOACs (dabigatran, rivaroxaban, apixaban, and edoxaban) than in those receiving warfarin, and this difference reflects the difference in the effects of warfarin and NOACs on the progression of CMBs. DESIGN: We will enroll 200 patients with at least 1 CMB detected by 1.5 T magnetic resonance imaging (T2(∗)-weighted imaging) at baseline and who have received NOACs or warfarin for at least 12 months. Primary end point is the proportion of subjects with an increased number of CMBs at month 12 of treatment with NOACs or warfarin. If the results of this study support the efficacy of NOACs for preventing increase of CMBs, this would be of great interest to domestic and overseas clinicians, in view of the potential therapeutic impact, including that on primary prevention of ischemic stroke.
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Anticoagulantes/administración & dosificación , Anticoagulantes/efectos adversos , Fibrilación Atrial/tratamiento farmacológico , Hemorragia Cerebral/etiología , Accidente Cerebrovascular/tratamiento farmacológico , Warfarina/efectos adversos , Administración Oral , Anciano , Anciano de 80 o más Años , Fibrilación Atrial/complicaciones , Femenino , Humanos , Estudios Longitudinales , Imagen por Resonancia Magnética , Masculino , Proyectos Piloto , Accidente Cerebrovascular/complicaciones , Resultado del TratamientoRESUMEN
OBJECTIVE: Aortic plaque is considered a risk factor of ischaemic stroke, and both ulceration and plaque thickness are considered important. However, the relative importance of aortic plaque and carotid plaque remains unclear. The purpose of this study is to clarify the relation between aortic and carotid plaque lesions and atherosclerotic risk factors in patients with acute ischaemic stroke. METHODS: We enrolled 76 patients with first-ever ischaemic stroke, undergoing transoesophageal echocardiography, whose aetiology of ischaemic stroke was unknown. We divided the patients into two groups according to aortic plaque thickness, based on previous reports, i.e., a high-risk group (over 4mm) and a low-risk group (less than 4mm). We also examined several atherosclerotic risk factors. RESULTS: Mean age, gender and hypertension was not significantly different between the low-risk and high-risk group. HDL-cholesterol (P<0.01), LDL/HDL ratio (P<0.05), non-HDL-cholesterol (P<0.05), HbA1c (P<0.05) and eGFR (P<0.01) were significantly different between the two groups. Max plaque thickness in the carotid artery was correlated with aortic plaque lesions. CONCLUSION: Multiple atherosclerotic risk factors are associated with greater aortic plaque lesions. Aortic plaque is important not only as an embolic source, but also as one of the atherosclerotic markers.
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Aorta/diagnóstico por imagen , Aterosclerosis/diagnóstico por imagen , Isquemia Encefálica/etiología , Arterias Carótidas/diagnóstico por imagen , Accidente Cerebrovascular/etiología , Anciano , Aterosclerosis/sangre , HDL-Colesterol/sangre , LDL-Colesterol/sangre , Ecocardiografía Transesofágica , Femenino , Tasa de Filtración Glomerular , Hemoglobina Glucada/metabolismo , Humanos , Masculino , Persona de Mediana Edad , Factores de RiesgoRESUMEN
To assess the predictive value of cerebral microbleeds (CMBs) on gradient-echo T2*-weighted magnetic resonance imaging for hemorrhagic transformation (HT) after antithrombotic therapy for an acute ischemic stroke, we prospectively examined the relationship between CMBs on T2*-weighted images before the start of therapy and the appearance of HT in a series of patients treated with antithrombotic therapies. The subjects were consecutive acute ischemic stroke patients admitted to Tokai University Hospital (187 subjects, mean age±SD: 74±11 years). The prevalence of CMBs was not significantly different between the subjects with and without HT on computed tomography (CT) (19% versus 36%, P=.081). In both the subgroup of patients treated with anticoagulants and the subgroup treated with antiplatelets, the prevalence of HT was not significantly different between the subjects with and without CMBs (anticoagulants, 9% versus 21%, P=.161; antiplatelets, 0% versus 9%, P=.542). The odds ratios (ORs) of increasing the National Institutes of Health Stroke Scale score (1.14, 95% confidence interval [CI]: 1.04-1.26, P=.005) and decreasing the Alberta Stroke Program Early CT Score on diffusion-weighted images (ASPECTS-DWI) (1.32, 95% CI: 1.10-1.59, P=.003) were significantly increased for the appearance of HT, but the OR of CMBs (.35, 95% CI: .09-1.41, P=.140) was not significantly increased for the appearance of HT. In conclusion, the severity of neurological deficits and the ASPECTS-DWI are closely correlated to the development of HT related to anticoagulants/antiplatelets but not to CMBs on T2*-weighted images.
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Anticoagulantes/efectos adversos , Isquemia Encefálica/tratamiento farmacológico , Hemorragia Cerebral/inducido químicamente , Imagen de Difusión por Resonancia Magnética , Fibrinolíticos/efectos adversos , Inhibidores de Agregación Plaquetaria/efectos adversos , Accidente Cerebrovascular/tratamiento farmacológico , Anciano , Anciano de 80 o más Años , Isquemia Encefálica/diagnóstico , Isquemia Encefálica/epidemiología , Angiografía Cerebral/métodos , Hemorragia Cerebral/diagnóstico , Hemorragia Cerebral/epidemiología , Distribución de Chi-Cuadrado , Evaluación de la Discapacidad , Hospitales Universitarios , Humanos , Japón/epidemiología , Modelos Logísticos , Persona de Mediana Edad , Oportunidad Relativa , Valor Predictivo de las Pruebas , Prevalencia , Estudios Prospectivos , Medición de Riesgo , Factores de Riesgo , Accidente Cerebrovascular/diagnóstico , Accidente Cerebrovascular/epidemiología , Tomografía Computarizada por Rayos X , Resultado del TratamientoRESUMEN
BACKGROUND: Granulocyte colony-stimulating factor (G-CSF; filgrastim) may be useful for the treatment of acute ischemic stroke because of its neuroprotective and neurogenesis-promoting properties, but an excessive increase of neutrophils may lead to brain injury. We examined the safety and tolerability of low-dose G-CSF and investigated the effectiveness of G-CSF given intravenously in the acute phase (at 24 hours) or subacute phase (at 7 days) of ischemic stroke. METHODS: Three intravenous dose regimens (150, 300, or 450 µg/body/day, divided into 2 doses for 5 days) of G-CSF were examined in 18 patients with magnetic resonance imaging (MRI)-confirmed infarct in the territory of the middle cerebral artery. Nine patients received the first dose at 24 hours poststroke (acute group) and 9 patients received the first dose on day 7 poststroke (subacute group; n = 3 at each dose in each group). A scheduled administration of G-CSF was skipped if the patient's leukocyte count exceeded 40,000/µL. Patients received neurologic and MRI examinations. RESULTS: We found neither serious adverse event, drug-related platelet reduction nor splenomegaly. Leukocyte levels remained below 40,000/µL at 150 and 300 µg G-CSF/body/day, but rose above 40,000/µL at 450 µg G-CSF/body/day. Neurologic function improvement between baseline and day 90 was more marked after treatment in the acute phase versus the subacute phase (Barthel index 49.4 ± 28.1 v 15.0 ± 22.0; P < .01). CONCLUSIONS: Low-dose G-CSF (150 and 300 µg/body/day) was safe and well tolerated in ischemic stroke patients, and leukocyte levels remained below 40,000/µL.
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Isquemia Encefálica/tratamiento farmacológico , Factor Estimulante de Colonias de Granulocitos/uso terapéutico , Accidente Cerebrovascular/tratamiento farmacológico , Anciano , Relación Dosis-Respuesta a Droga , Femenino , Factor Estimulante de Colonias de Granulocitos/administración & dosificación , Factor Estimulante de Colonias de Granulocitos/efectos adversos , Humanos , Masculino , Persona de Mediana Edad , Resultado del TratamientoRESUMEN
Background: Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disorder associated with progressive impairment of spinal motor neurons. Continuous research endeavor is underway to fully understand the molecular mechanisms associating with this disorder. Although several studies have implied the involvement of inositol pyrophosphate IP7 in ALS, there is no direct experimental evidence proving this notion. In this study, we analyzed inositol pyrophosphate IP7 and its precursor IP6 in the mouse and human ALS biological samples to directly assess whether IP7 level and/or its metabolism are altered in ALS disease state. Methods: We used a liquid chromatography-mass spectrometry (LC-MS) protocol originally-designed for mammalian IP6 and IP7 analysis. We measured the abundance of these molecules in the central nervous system (CNS) of ALS mouse model SOD1(G93A) transgenic (TG) mice as well as postmortem spinal cord of ALS patients. Cerebrospinal fluid (CSF) and peripheral blood mononuclear cells (PBMCs) from ALS patients were also analyzed to assess if IP7 status in these biofluids is associated with ALS disease state. Results: SOD1(G93A) TG mice showed significant increase of IP7 level in the spinal cord compared with control mice at the late stage of disease progression, while its level in cerebrum and cerebellum remains constant. We also observed significantly elevated IP7 level and its product-to-precursor ratio (IP7/IP6) in the postmortem spinal cord of ALS patients, suggesting enhanced enzymatic activity of IP7-synthesizing kinases in the human ALS spinal cord. In contrast, human CSF did not contain detectable level of IP6 and IP7, and neither the IP7 level nor the IP7/IP6 ratio in human PBMCs differentiated ALS patients from age-matched healthy individuals. Conclusion: By directly analyzing IP7 in the CNS of ALS mice and humans, the findings of this study provide direct evidence that IP7 level and/or the enzymatic activity of IP7-generating kinases IP6Ks are elevated in ALS spinal cord. On the other hand, this study also showed that IP7 is not suitable for biofluid-based ALS diagnosis. Further investigation is required to elucidate a role of IP7 in ALS pathology and utilize IP7 metabolism on the diagnostic application of ALS.
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Treatments for acute stroke have improved over the past years, but have largely been limited to revascularization strategies. The topic of neuroprotection, or strategies to limit brain tissue damage or even reverse it, has remained elusive. Thus, the clinical mainstays for stroke management have focused on prevention. The lack of clinical translation of neuroprotective therapies which have shown promise in the laboratory may, in part, be due to a historic inattention to comorbidities suffered by a majority of stroke patients. With the advent of more stroke models that include one or more relevant comorbidities, it may be possible to identify effective treatments that may translate into new treatments at the clinical level. In the meantime, we review comorbidities in stroke patients, modification of stroke risk factors and available acute stroke treatments in the clinic.
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Accidente Cerebrovascular Isquémico , HumanosRESUMEN
Human T-lymphotropic virus type I (HTLV-I) is a retrovirus associated with adult T-cell lymphoma (ATL) and HTLV-I-associated myelopathy/tropical spastic paraparesis (HAM/TSP). In addition to HAM/TSP and ATL, HTLV-I-associated encephalopathy and cerebellar involvement have been reported. We report a case of an 87-year-old Japanese woman presenting with progressive dysarthria and gait disturbance. Neurological examination showed word-finding difficulty, scanning speech, saccadic eye movements, ocular dysmetria, gaze-evoked nystagmus and bilateral dysmetria. There was no motor weakness or spasticity. HTLV-I antibody was detected in both her serum and cerebrospinal fluid. Cerebrospinal fluid neopterin (57 pg/mL) and IgG index (3.27) were significantly elevated. MRI showed cerebellar swelling. She was finally diagnosed with HTLV-I associated cerebellitis. Two courses of high-dose intravenous methylpredonine therapy attenuated cerebellar ataxia and cerebellar swelling. It suggests that cerebellitis can result from HTLV-I infection, regardless of the existence of ATL or HAM/TSP.
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Ataxia Cerebelosa , Infecciones por HTLV-I , Virus Linfotrópico T Tipo 1 Humano , Leucemia-Linfoma de Células T del Adulto , Nistagmo Patológico , Paraparesia Espástica Tropical , Adulto , Anciano de 80 o más Años , Ataxia Cerebelosa/diagnóstico , Ataxia Cerebelosa/etiología , Femenino , Infecciones por HTLV-I/complicaciones , Infecciones por HTLV-I/diagnóstico , Infecciones por HTLV-I/tratamiento farmacológico , Humanos , Paraparesia Espástica Tropical/complicaciones , Paraparesia Espástica Tropical/diagnóstico , Paraparesia Espástica Tropical/tratamiento farmacológicoRESUMEN
OBJECTIVE: Stroke-associated pneumonia (SAP) is a comorbidity of ischemic stroke related to clinical outcomes. Early enteral nutrition (EEN; within 48 hours) reduces the incidence of infection and length of intensive care unit (ICU)/hospital stay. The relationship between EEN and critical care outcomes, including SAP, in patients with ischemic stroke has been insufficiently studied. METHODS: We recruited 499 patients in this retrospective observational study. We evaluated SAP incidence within 14 days from admission. Patients were divided into an EEN group and a late EN group (LEN; start later than EEN). We compared groups regarding background and length of ICU/hospital stay. RESULTS: EN was started within 48 hours in 236 patients. SAP was diagnosed in 94 patients (18.8%), with most in the LEN group (28.1% vs. 8.5%). Median [interquartile range] lengths of hospitalization (22 [12-30] days vs. 35 [20-45] days) and ICU stay (4 [2-5] days vs. 6 [3-8] days) were longer in the LEN group. EEN reduced the incidence of SAP. By contrast, consciousness disturbance and worsening consciousness level increased the SAP incidence. Increased age and National Institutes of Health Stroke Scale score were associated with start of prolonged EN. CONCLUSIONS: We found that EEN may reduce SAP risk.
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Isquemia Encefálica , Accidente Cerebrovascular Isquémico , Accidente Cerebrovascular , Isquemia Encefálica/terapia , Resultados de Cuidados Críticos , Nutrición Enteral , Humanos , Unidades de Cuidados Intensivos , Tiempo de Internación , Accidente Cerebrovascular/terapiaRESUMEN
Store-operated Ca2+ entry (SOCE) mediated by calcium release-activated calcium (CRAC) channels contributes to calcium signaling. The resulting intracellular calcium increases activate calcineurin, which in turn activates immune transcription factor nuclear factor of activated T cells (NFAT). Microglia contain CRAC channels, but little is known whether these channels play a role in acute brain insults. We studied a novel CRAC channel inhibitor to explore the therapeutic potential of this compound in microglia-mediated injury. Cultured microglial BV2 cells were activated by Toll-like receptor agonists or IFNγ. Some cultures were treated with a novel CRAC channel inhibitor (CM-EX-137). Western blots revealed the presence of CRAC channel proteins STIM1 and Orai1 in BV2 cells. CM-EX-137 decreased nitric oxide (NO) release and inducible nitric oxide synthase (iNOS) expression in activated microglia and reduced agonist-induced intracellular calcium accumulation in microglia, while suppressing inflammatory transcription factors nuclear factor kappa B (NF-κB) and nuclear factor of activated T cells (NFAT). Male C57/BL6 mice exposed to experimental brain trauma and treated with CM-EX-137 had decreased lesion size, brain hemorrhage, and improved neurological deficits with decreased microglial activation, iNOS and Orai1 and STIM1 levels. We suggest a novel anti-inflammatory approach for managing acute brain injury. Our observations also shed light on new calcium signaling pathways not described previously in brain injury models.
Asunto(s)
Lesiones Traumáticas del Encéfalo/metabolismo , Encéfalo/efectos de los fármacos , Bloqueadores de los Canales de Calcio/farmacología , Canales de Calcio Activados por la Liberación de Calcio/metabolismo , Calcio/metabolismo , Microglía/efectos de los fármacos , Animales , Encéfalo/metabolismo , Señalización del Calcio/fisiología , Línea Celular , Inflamación/metabolismo , Interferón gamma/farmacología , Masculino , Ratones , Microglía/metabolismo , FN-kappa B/metabolismo , Óxido Nítrico/metabolismo , Proteína ORAI1/metabolismo , Molécula de Interacción Estromal 1/metabolismoRESUMEN
We report a case of eosinophilic granulomatosis with polyangiitis (EGPA; formerly known as Churg-Strauss syndrome) complicated by perforation of the small intestine and necrotizing cholecystitis. A 69-year-old man with a history of bronchial asthma was admitted with mononeuritis multiplex. The laboratory findings included remarkable eosinophilia. He was treated with corticosteroids and his laboratory indices showed improvement; however, his functional deficits remained. His neuropathy gradually improved after the addition of intravenous immunoglobulin (IVIG). He was subsequently treated with oral prednisolone (40 mg/day) as maintenance therapy. Within a month after finishing IVIG, he developed perforation of the small intestine and necrotizing cholecystitis. Intestinal perforation has often been reported as a gastrointestinal complication of EGPA. In contrast, cholecystitis is a rare complication. We report this case because the manifestation of more than one complication is extremely rare. Gastrointestinal symptoms may be a complication of EGPA itself and/or immunosuppressive treatment.
Asunto(s)
Colecistitis/etiología , Granulomatosis con Poliangitis/complicaciones , Perforación Intestinal/etiología , Intestino Delgado , Corticoesteroides/uso terapéutico , Anciano , Asma/complicaciones , Colecistitis/patología , Humanos , Hipoestesia/tratamiento farmacológico , Hipoestesia/etiología , Inmunoglobulinas Intravenosas/uso terapéutico , Inmunosupresores/uso terapéutico , Masculino , Mononeuropatías/tratamiento farmacológico , Mononeuropatías/etiología , Debilidad Muscular/tratamiento farmacológico , Debilidad Muscular/etiología , Necrosis , Prednisolona/uso terapéuticoRESUMEN
While the mainstay of acute stroke treatment includes revascularization via recombinant tissue plasminogen activator or mechanical thrombectomy, only a minority of stroke patients are eligible for treatment, as delayed treatment can lead to worsened outcome. This worsened outcome at the experimental level has been attributed to an entity known as reperfusion injury (R/I). R/I is occurred when revascularization is delayed after critical brain and vascular injury has occurred, so that when oxygenated blood is restored, ischemic damage is increased, rather than decreased. R/I can increase lesion size and also worsen blood barrier breakdown and lead to brain edema and hemorrhage. A major mechanism underlying R/I is that of poststroke inflammation. The poststroke immune response consists of the aberrant activation of glial cell, infiltration of peripheral leukocytes, and the release of damage-associated molecular pattern (DAMP) molecules elaborated by ischemic cells of the brain. Inflammatory mediators involved in this response include cytokines, chemokines, adhesion molecules, and several immune molecule effectors such as matrix metalloproteinases-9, inducible nitric oxide synthase, nitric oxide, and reactive oxygen species. Several experimental studies over the years have characterized these molecules and have shown that their inhibition improves neurological outcome. Yet, numerous clinical studies failed to demonstrate any positive outcomes in stroke patients. However, many of these clinical trials were carried out before the routine use of revascularization therapies. In this review, we cover mechanisms of inflammation involved in R/I, therapeutic targets, and relevant experimental and clinical studies, which might stimulate renewed interest in designing clinical trials to specifically target R/I. We propose that by targeting anti-inflammatory targets in R/I as a combined therapy, it may be possible to further improve outcomes from pharmacological thrombolysis or mechanical thrombectomy.