MFG-E8 (LACTADHERIN): a novel marker associated with cerebral amyloid angiopathy.

Brain accumulation of amyloid-beta (Aß) is a crucial feature in Alzheimer´s disease (AD) and cerebral amyloid angiopathy (CAA), although the pathophysiological relationship between these diseases remains unclear. Numerous proteins are associated with Aß deposited in parenchymal plaques and/or cerebral vessels. We hypothesized that the study of these proteins would increase our understanding of the overlap and biological differences between these two pathologies and may yield new diagnostic tools and specific therapeutic targets. We used a laser capture microdissection approach combined with mass spectrometry in the APP23 transgenic mouse model of cerebral-ß-amyloidosis to specifically identify vascular Aß-associated proteins. We focused on one of the main proteins detected in the Aß-affected cerebrovasculature: MFG-E8 (milk fat globule-EGF factor 8), also known as lactadherin. We first validated the presence of MFG-E8 in mouse and human brains. Immunofluorescence and immunoblotting studies revealed that MFG-E8 brain levels were higher in APP23 mice than in WT mice. Furthermore, MFG-E8 was strongly detected in Aß-positive vessels in human postmortem CAA brains, whereas MFG-E8 was not present in parenchymal Aß deposits. Levels of MFG-E8 were additionally analysed in serum and cerebrospinal fluid (CSF) from patients diagnosed with CAA, patients with AD and control subjects. Whereas no differences were found in MFG-E8 serum levels between groups, MFG-E8 concentration was significantly lower in the CSF of CAA patients compared to controls and AD patients. Finally, in human vascular smooth muscle cells MFG-E8 was protective against the toxic effects of the treatment with the Aß40 peptide containing the Dutch mutation. In summary, our study shows that MFG-E8 is highly associated with CAA pathology and highlights MFG-E8 as a new CSF biomarker that could potentially be used to differentiate cerebrovascular Aß pathology from parenchymal Aß deposition.

Diabetes, Albuminuria and the Kidney-Brain Axis.

Cognitive decline and kidney disease are significant public health problems that share similar characteristics and risk factors. The pathophysiology of the kidney-brain axis is not completely understood, and studies analysing the relationship between the biomarkers of kidney damage and cognitive impairment show different results. This article focuses on the epidemiological and clinical aspects concerning the association of albuminuria, a marker for endothelial dysfunction and microvascular disease, and cognitive impairment in patients with chronic kidney disease, diabetic kidney disease and end-stage kidney disease. Most studies show a positive relationship between albuminuria and cognitive impairment in all groups, but evidence in type 2 diabetes (T2D) patients is limited. We briefly discuss the mechanisms underlying these associations, such as damage to the microvascular circulation, leading to hypoperfusion and blood pressure fluctuations, as well as increased inflammation and oxidative stress, both in the brain and in the kidneys. Further clinical and epidemiological studies developed to understand the interplay between the kidneys and brain diseases will hopefully lead to a reduction in cognitive impairment in these patients.

Circulating AQP4 Levels in Patients with Cerebral Amyloid Angiopathy-Associated Intracerebral Hemorrhage.

Cerebral amyloid angiopathy (CAA) is a major cause of lobar intracerebral hemorrhage (ICH) in elderly patients. Growing evidence suggests a potential role of aquaporin 4 (AQP4) in amyloid-beta-associated diseases, including CAA pathology. Our aim was to investigate the circulating levels of AQP4 in a cohort of patients who had suffered a lobar ICH with a clinical diagnosis of CAA. AQP4 levels were analyzed in the serum of 60 CAA-related ICH patients and 19 non-stroke subjects by enzyme-linked immunosorbent assay (ELISA). The CAA-ICH cohort was divided according to the time point of the functional outcome evaluation: mid-term (12 ± 18.6 months) and long-term (38.5 ± 32.9 months) after the last ICH. Although no differences were found in AQP4 serum levels between cases and controls, lower levels were found in CAA patients presenting specific hemorrhagic features such as ≥2 lobar ICHs and ≥5 lobar microbleeds detected by magnetic resonance imaging (MRI). In addition, CAA-related ICH patients who presented a long-term good functional outcome had higher circulating AQP4 levels than subjects with a poor outcome or controls. Our data suggest that AQP4 could potentially predict a long-term functional outcome and may play a protective role after a lobar ICH.

Comparison of Plasma Lipoprotein Composition and Function in Cerebral Amyloid Angiopathy and Alzheimer's Disease.

Cerebral amyloid angiopathy (CAA) refers to beta-amyloid (Aß) deposition in brain vessels and is clinically the main cause of lobar intracerebral hemorrhage (ICH). Aß can also accumulate in brain parenchyma forming neuritic plaques in Alzheimer's disease (AD). Our study aimed to determine whether the peripheral lipid profile and lipoprotein composition are associated with cerebral beta-amyloidosis pathology and may reflect biological differences in AD and CAA. For this purpose, lipid and apolipoproteins levels were analyzed in plasma from 51 ICH-CAA patients (collected during the chronic phase of the disease), 60 AD patients, and 60 control subjects. Lipoproteins (VLDL, LDL, and HDL) were isolated and their composition and pro/antioxidant ability were determined. We observed that alterations in the lipid profile and lipoprotein composition were remarkable in the ICH-CAA group compared to control subjects, whereas the AD group presented no specific alterations compared with controls. ICH-CAA patients presented an atheroprotective profile, which consisted of lower total and LDL cholesterol levels. Plasma from chronic ICH-CAA patients also showed a redistribution of ApoC-III from HDL to VLDL and a higher ApoE/ApoC-III ratio in HDL. Whether these alterations reflect a protective response or have a causative effect on the pathology requires further investigation.

Ambulatory Blood Pressure Levels in the Prediction of Progression of Cerebral Small Vessel Disease.

OBJECTIVES: We aimed to study the value of ambulatory blood pressure monitoring (ABPM) in predicting the global progression of cerebral small vessel disease (cSVD). DESIGN: Longitudinal cohort study. SETTING: Data from the population-based Investigating Silent Strokes in Hypertensives study. PARTICIPANTS: Individuals with hypertension who were 50 to 70 years of age and stroke free at baseline. In baseline and follow-up visits, patients underwent magnetic resonance imaging and ABPM. MEASUREMENTS: Ambulatory systolic blood pressure (SBP) and diastolic blood pressure (DBP) levels were studied as continuous variables and dichotomized according to good or poor control on the basis of 125/75 (24 hours), 130/80 (day), and 110/65 (night) mm Hg cutoff values. Whole cSVD progression was qualitatively scored with 1 point when an incident lesion (incident lacunar infarcts, deep cerebral microbleeds, white matter hyperintensities, and basal ganglia enlarged perivascular spaces) was detected. The score ranged from 0 to 4. RESULTS: We followed up 233 participants with a median age of 65 years within 4 years. A total of 61 (26.2%) and 23 (9.9%) subjects showed cSVD progression in one and two or more markers, respectively. Baseline ambulatory SBP and DBP and nighttime pulse pressure (PP) values were positively correlated with the number of incident cSVD lesions. Interestingly, patients without incident lesions showed greater differences between office and ambulatory BP, thus suggesting an increased white coat effect. Poor DBP control, nighttime PP, and DBP white coat effect were independently associated with cSVD progression. The inclusion of these metrics in a clinical model resulted in a significant increase in the prediction of incident lesions (integrated discrimination improvement = 9.09%; P value <.001). CONCLUSION: ABPM may help assess cSVD risk of progression, especially by the identification of poor BP control, masked hypertension, and increased nighttime PP. J Am Geriatr Soc 68:2232-2239, 2020.

Kidney function changes and their relation with the progression of cerebral small vessel disease and cognitive decline.

AIMS: We aimed to study whether worsening in markers of kidney function parallels the progression in cerebral small vessel disease (cSVD) and cognitive decline. METHODS: Data from the ISSYS (Investigating Silent Strokes in Hypertensives Study), a longitudinal population-based study in hypertensives aged 50-70 and dementia and stroke-free at baseline. At both visits, patients underwent a brain MRI, a cognitive diagnosis (normal aging or mild cognitive impairment, [MCI]) and urine and blood sampling collection. We assessed the incidence of infarcts and cerebral microbleeds, and the progression of white matter hyperintensities at periventricular (PVH) and deep areas. We determined changes in albumin-creatinine ratio and estimated glomerular filtration rate (eGFR). These changes were dichotomized into microalbuminuria at follow-up -either in subjects with or without baseline microalbuminuria- and significant decline in eGFR -lowest quintile of eGFR change (-10.57 mL/min/1.73m2)-. RESULTS: 360 patients were followed-up for 4 years. 80 (23%) patients presented microalbuminuria at follow-up and 68 (20.1%) experienced a significant eGFR decline. Considering cSVD change, we found a relationship between microalbuminuria at follow-up and progression in PVH (ß = 0.31, P-value = .01). Regarding cognitive decline, presence of microalbuminuria at follow-up related to a steeper decrease in memory function (ß = -0.36, P-value<.01). Moreover, patients with significant decline in eGFR were at higher risk of incident MCI (OR = 3.54, P-value = .02). These associations were independent of progression of cSVD. CONCLUSION: The worsening in markers of kidney function paralleled the decrease in cognition and the progression of cSVD, and this may be explained by common shared underlying risk factors.

Prevalence of hippocampal enlarged perivascular spaces in a sample of patients with hypertension and their relation with vascular risk factors and cognitive function.

OBJECTIVES: The clinical importance of hippocampal enlarged perivascular spaces (H-EPVS) remains uncertain. We aimed to study their association with vascular risk factors, cognitive function and mild cognitive impairment (MCI). METHODS: Data were obtained from the ISSYS (Investigating Silent Strokes in hYpertensives, a magnetic resonance imaging Study) cohort, which is a prospective study of patients with hypertension aged 50-70 with no prior stroke or dementia. Participants were clinically evaluated and underwent a cognitive screening test, Dementia Rating Scale-2, which includes five cognitive subscales (attention, initiation/perseveration, conceptualisation, construction and memory). Besides, they were diagnosed with MCI or normal ageing following standard criteria. H-EPVS were manually counted on brain MRI according to a previous scale and defined as extensive when H-EPVS count was ≥7 (upper quartile). Multivariate models were created to study the relationship between H-EPVS, vascular risk factors and cognitive function. RESULTS: 723 patients were included; the median age was 64 (59-67) and 51% were male. Seventy-two patients (10%) were diagnosed with MCI and 612 (84.6%) had at least 1 H-EPVS. Older age (OR per year=1.04, 95% CI 1.01 to 1.08) and poor blood pressure treatment compliance (OR=1.50, 95% CI 1.07 to 2.11) were independently associated with extensive H-EPVS. Regarding cognitive function, H-EPVS were independently and inversely correlated with verbal reasoning (ß=-0.021, 95% CI -0.038 to -0.003). No association was found between H-EPVS and MCI. CONCLUSIONS: H-EPVS are a frequent finding in patients with hypertension and are associated with ageing and poor hypertension treatment compliance. Besides, H-EPVS are associated with worse verbal reasoning function.

Longitudinal Neuroimaging Analysis in Mild-Moderate Alzheimer's Disease Patients Treated with Plasma Exchange with 5% Human Albumin.

BACKGROUND: Recently, modifications of Aß1-42 levels in CSF and plasma associated with improvement in memory and language functions have been observed in patients with mild-moderate Alzheimer's disease (AD) treated with plasma exchange (PE) with albumin replacement. OBJECTIVE: To detect structural and functional brain changes in PE-treated AD patients as part of a Phase II clinical trial. METHODS: Patients received between 3 and 18 PE with albumin (Albutein® 5%, Grifols) or sham-PE (controls) for 21 weeks (divided in one intensive and two maintenance periods) followed by 6-month follow-up. Brain perfusion assessed by SPECT scans using an automated software (NeuroGam®) and brain structural changes assessed by MRI were performed at weeks 0 (baseline), 21, and 44 (with additional SPECT at weeks 9 and 33). Statistical parametric mapping (voxel-based analysis, SPM) and Z-scores calculations were applied to investigate changes to baseline. RESULTS: 42 patients were recruited (39 evaluable; 37 analyzed: 18 PE-treated; 19 controls). There was a trend toward decreasing hippocampi and total intracranial volume for both patient groups during the study (p < 0.05). After six months, PE-treated patients had less cerebral perfusion loss than controls in frontal, temporal, and parietal areas, and perfusion stabilization in Brodmann area BA38-R during the PE-treatment period (p < 0.05). SPM analysis showed stabilization or absence of progression of perfusion loss in PE-treated patients until week 21, not observed in controls. CONCLUSIONS: Mild-moderate AD patients showed decreased brain volume and impairment of brain perfusion as expected for the progression of the disease. PE-treatment with albumin replacement favored the stabilization of perfusion.

Cognitive Composites Domain Scores Related to Neuroimaging Biomarkers within Probable-Amnestic Mild Cognitive Impairment-Storage Subtype.

The probable-amnestic (Pr-a) mild cognitive impairment (MCI)-storage subtype is a phenotype with 8.5 times more risk of conversion to dementia, mainly Alzheimer's disease (AD), than the possible non-amnestic (Pss-na) MCI. The aim of this study was to find the optimized cognitive composites (CCs) domain scores most related to neuroimaging biomarkers within Pr-aMCI-storage subtype patients. The Fundació ACE (ACE) study with 20 Pr-aMCI-storage subtype subjects (MCI) were analyzed. All subjects underwent a neuropsychological assessment, a structural MRI, FDG-PET, and PIB-PET. The adjusted hippocampal volume (aHV) on MRI, the standard uptake value ratio (SUVR) on FDG-PET and PIB-PET SUVR measures were analyzed. The construction of the CCs domain scores, and the aHV on MRI and FDG-PET SUVR measures, were replicated in the parental AB255 study database (n = 133 MCI). Partial correlations adjusted by age, gender, and education were calculated with the associated p-value among every CC domain score and the neuroimaging biomarkers. The results were replicated in the "MCI due to AD" with memory storage impairments from ADNI. Delayed Recall CC domain score was significantly correlated with PIB-PET SUVR (ß= -0.61, p = 0.003) in the ACE study and also with aHV on MRI (ß= 0.27, p = 0.01) and FDG-PET SUVR (ß= 0.27, p = 0.01) in the AB255 study. After a median survival time of 20.6 months, 85% from the ACE MCI converted to AD. The replication of our results in the ADNI dataset also confirmed our findings. Delayed Recall is the CC domain score best correlated with neuroimaging biomarkers associated with prodromal AD diagnosis.

ApoA1, ApoJ and ApoE Plasma Levels and Genotype Frequencies in Cerebral Amyloid Angiopathy.

The involvement of apolipoproteins, such as the ApoE4 isoform, in Alzheimer's disease (AD) and cerebral amyloid angiopathy (CAA) highlights the fact that certain lipid carriers may participate in soluble ß-amyloid (Aß) transport. Our general aim was to characterize the soluble levels of the apolipoproteins apoE, apoA1 and apoJ/clusterin and their genotype status in patients with CAA. We analyzed the genotypes frequency of APOA1 (rs5069, rs670), CLU (rs11136000, rs1532278, rs7012010, rs9331888) and APOE (rs429358, rs7412) in a cohort of patients with CAA-associated intracerebral hemorrhage (ICH) (n = 59) and compared the results with those from hypertension-associated ICH (n = 42), AD patients (n = 73) and controls (n = 88). In a subgroup of patients, we also determined the plasma concentrations of apoE, apoA1 and apoJ/clusterin. We found increased plasma apoJ/clusterin levels in CAA patients compared to AD patients or controls after adjusting for sex and age (CAA vs. controls, p = 0.033; CAA vs. AD, p = 0.013). ApoA1 levels were not altered between groups, although a strong correlation was observed between plasma Aß(1-40) and apoA1 among CAA patients (r = 0.583, p = 0.007). Regarding plasma apoE concentration, a robust association between circulating levels and genotype status was confirmed (p < 0.001). Whereas the APOE4 frequency was higher in AD (p < 0.001) and CAA (p = 0.013), the APOA1 and CLU genotypes were not different among groups. In the CAA cohort, the risk-linked CLU variant (C) rs11136000 was associated with white matter hyperintensities (p = 0.045) and the presence of lobar microbleeds (p = 0.023) on MRI. In summary, our findings suggest that apoA1 may act as a physiological transporter of Aß(1-40) and that apoJ/clusterin appears to be a chaperone related to distinctive lesions in CAA brains.

Differentiated clinical presentation of early and late-onset Alzheimer's disease: is 65 years of age providing a reliable threshold?

Early-onset and late-onset Alzheimer's disease (EOAD and LOAD) are two forms of the disease with the same characteristic neuropathological hallmarks. However, higher burdens of neuritic plaques and neurofibrillary tangles in frontal and parietal lobes have been found in EOAD than in LOAD patients. Thus, the EOAD subjects may have a differentiated clinical presentation compared to the LOAD ones. Some authors have found less hippocampal memory presentations and more focal cortical abnormalities (such as visuoconstructive or executive dysfunction) in EOAD than LOAD patients. The aim of the present study was to determine which initial clinical profiles differ between EOAD and LOAD; and to analyze whether another age cut-off could discriminate better between EOAD and LOAD clinical presentations than the conventional limit of 65. All patients fulfilling NINCDS-ADRDA criteria for probable Alzheimer's disease who referred to our Hospital between October 2007 and December 2012 were included in the study. The conventional age limit of 65 was established to distinguish between EOAD and LOAD. Baseline neuropsychological scores, adjusted for age and education, were compared between both groups. A total of 181 patients (38 EOAD, 143 LOAD) entered in the analysis. Sex distribution and time of evolution of symptoms did not differ between groups. The EOAD patients performed worse than LOAD in attentional, imitation praxis and verbal learning tests. In addition, the age cut-off of 70 was found to differentiate between early- and late-onset groups better than the standard cut-off of 65 years old. Our results support a differentiated neuropsychological impairment pattern in EOAD compared to LOAD.

Determination of neuronal antibodies in suspected and definite Creutzfeldt-Jakob disease.

IMPORTANCE: Creutzfeldt-Jakob disease (CJD) and autoimmune encephalitis with antibodies against neuronal surface antigens (NSA-abs) may present with similar clinical features. Establishing the correct diagnosis has practical implications in the management of care for these patients. OBJECTIVE: To determine the frequency of NSA-abs in the cerebrospinal fluid of patients with suspected CJD and in patients with pathologically confirmed (ie, definite) CJD. DESIGN, SETTING, AND PARTICIPANTS: A mixed prospective (suspected) and retrospective (definite) CJD cohort study was conducted in a reference center for detection of NSA-abs. The population included 346 patients with suspected CJD and 49 patients with definite CJD. MAIN OUTCOMES AND MEASURES: Analysis of NSA-abs in cerebrospinal fluid with brain immunohistochemistry optimized for cell-surface antigens was performed. Positive cases in the suspected CJD group were further studied for antigen specificity using cell-based assays. All definite CJD cases were comprehensively tested for NSA-abs, with cell-based assays used for leucine-rich glioma-inactivated 1 (LGI1), contactin-associated protein-like 2 (CASPR2), N-methyl-d-aspartate (NMDA), and glycine (GlY) receptors. RESULTS: Neuronal surface antigens were detected in 6 of 346 patients (1.7%) with rapid neurologic deterioration suggestive of CJD. None of these 6 patients fulfilled the diagnostic criteria for probable or possible CJD. The target antigens included CASPR2, LGI1, NMDAR, aquaporin 4, Tr (DNER [δ/notch-like epidermal growth factor-related receptor]), and an unknown protein. Four of the patients developed rapidly progressive dementia, and the other 2 patients had cerebellar ataxia or seizures that were initially considered to be myoclonus without cognitive decline. The patient with Tr-abs had a positive 14-3-3 test result. Small cell lung carcinoma was diagnosed in the patient with antibodies against an unknown antigen. All patients improved or stabilized after appropriate treatment. None of the 49 patients with definite CJD had NSA-abs. CONCLUSIONS AND RELEVANCE: A low, but clinically relevant, number of patients with suspected CJD had potentially treatable disorders associated with NSA-abs. In contrast, none of 49 patients with definite CJD had NSA-abs, including NMDAR-abs, GlyR-abs, LGI1-abs, or CASPR2-abs. These findings suggest that cerebrospinal fluid NSA-abs analysis should be included in the diagnostic workup of patients with rapidly progressive central nervous system syndromes, particularly when they do not fulfill the diagnostic criteria of probable or possible CJD.

Reversible hemichorea associated with extracranial carotid artery stenosis.

Hemichorea associated with carotid artery occlusive disease is extremely rare. It has been recently suggested that carotid artery stenosis should be considered in the differential diagnosis of chorea, even in the absence of a preceding stroke or transient ischemic attack. Although the pathophysiology of this condition is still under discussion, some reports suggest that impaired cerebral blood flow in the basal ganglia is a key contributing factor. We herein report a case of hemichorea related to severe stenosis of the left internal carotid artery with no basal ganglia lesions on brain MRI. After carotid revascularization, hemichorea gradually subsided and reversible left thalamic and putaminal hypoperfusion were demonstrated by functional neuroimaging. This case report supports the hypothesis about the central role of hemodynamic ischemia in the pathophysiology of hemichorea associated with carotid artery stenosis, and highlights the importance of vascular imaging studies for the early identification of carotid disease in patients with chorea, even in the absence of other clinical signs.

Amnesia global transitoria tras la toma de tadalafilo / No disponible

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Lack of evidence for arterial ischemia in transient global amnesia.

BACKGROUND AND PURPOSE: Lesions in diffusion-weighted imaging (DWI-L) have been commonly described in transient global amnesia (TGA). We investigated a possible relationship between brain ischemia and TGA. METHODS: Twenty-eight patients underwent transcranial and carotid Doppler ultrasonography (including microembolus detection) and MRI within 24 hours of TGA onset (including DWI, perfusion-weighted imaging and angio-MRI). MRI was repeated at 48 to 96 hours (21 patients) and 30 days (18 patients). RESULTS: Punctate DWI-L were observed in 16 patients (57%) and were not attributable to perfusion abnormalities, arterial stenoses or underlying cardioembolic disease. MRIs performed between 12 and 72 hours showed the highest frequency of DWI-L (88%; P<0.001). No pathological findings were observed at 30 days. CONCLUSIONS: These results suggest that TGA is not related to cerebral arterial ischemia.

Respuesta. Causas vasculares de amnesia global transitoria / Reply. Vascular causes of transient global amnesia

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[Recurrent Transient Global Amnesia, a manifestation of ischemic cerebrovascular disease]. / La amnesia global transitoria recurrente, una manifestación de la enfermedad isquémica cerebrovascular.

BACKGROUND AND OBJECTIVE: Transient Global Amnesia (TGA) is a self-limited anterograde memory loss related classically to transient ischemic attacks (TIA), migraine and epilepsy. This study intended to describe clinical characteristics, the vascular risk factors and the evolution of TGA and to define clinical factors associated with recurrence. PATIENTS AND METHOD: Of 139 patients with TGA, 124 were followed up for a mean time of 71.9 (39) months; these patients were compared with other 124 patients with TIA. The TGA group was subdivided in 2 subgroups: Unique-TGA (98 cases): 1 episode, and recurrent-TGA (26 cases): 2 or more episodes. Recurrent-TGA were also compared with unique-TGA and the TIA groups. RESULTS: The mean age of patients of the TGA group was 63 (7.96) and 58% were women. 30% had a history of migraine and 30% had anxiety. The risk of annual recurrence was 4.4%. Recurrent-TGA patients had more electroencephalographic registers showing non-epileptogenic abnormalities. The TIA group had more vascular risk factors and displayed more ischemic events during the follow-up. Recurrent-TGA patients had the same vascular risk factors as TIA patients and they also had a significantly more frequent history of stroke and trend to suffer new ischemic events than patients in the unique-TGA group. CONCLUSIONS: There is no vascular pathology substrate in TGA patients, suggesting an ischemic etiology due to arteriosclerosis or cardioembolism. Patients with recurrent TGA constitute a subgroup with more vascular risk factors and an increased risk to suffer new strokes. For that reason we propose that these patients be studied as ischemic patients.

La amnesia global transitoria recurrente, una manifestación de la enfermedad isquémica cerebrovascular / Recurrent transient global amnesia, a manifestation of ischemic cerebrovascular disease

Fundamento y objetivo: La amnesia global transitoria (AGT) es un trastorno autolimitado de memoria anterógrada relacionado clásicamente con ataques isquémicos transitorios (AIT), migraña y epilepsia. Este estudio intenta describir las características clínicas, el perfil de factores de riesgo vascular y la evolución de la AGT comparándola con un grupo de AIT y definir variables asociadas a la recurrencia. Pacientes y método: De un grupo de 139 AGT se realizó un seguimiento medio (desviación estándar) de 71,9 (39) meses a 124 pacientes a quienes comparamos con otros 124 pacientes con AIT. Las AGT se subdividen en 2 grupos: AGT únicas (98 casos) y AGT recurrentes (26 casos). Se compararon las AGT recurrentes con las únicas y con los AIT. Resultados: La edad media de los pacientes con AGT era 63 (7,96) años y un 58% eran mujeres. Un 30% tenía antecedentes de migraña y el 30% de ansiedad. El riesgo de recurrencia anual fue del 4,4%. Las AGT recurrentes tenían más alteraciones electroencefalográficas inespecíficas. El grupo AIT tenía más factores de riesgo vascular y presentaron más episodios isquémicos posteriormente. Las AGT recurrentes y los AIT tenían los mismos factores de riesgo vascular. Las AGT recurrentes tenían más antecedentes de ictus y tendencia a presentar más episodios isquémicos que las AGT únicas. Conclusiones: En la AGT no hay un sustrato de enfermedad vascular que haga pensar en una causa isquémica por arteriosclerosis o cardioembolismo. Las AGT recurrentes son un subgrupo con mayor riesgo vascular y tendencia a tener más ictus, por lo que deberían estudiarse desde el punto de vista vascular

Background and objective: Transient Global Amnesia (TGA) is a self-limited anterograde memory loss related classically to transient ischemic attacks (TIA), migraine and epilepsy. This study intended to describe clinical characteristics, the vascular risk factors and the evolution of TGA and to define clinical factors associated with recurrence. Patients and method: Of 139 patients with TGA, 124 were followed up for a mean time of 71.9 (39) months; these patients were compared with other 124 patients with TIA. The TGA group was subdivided in 2 subgroups: Unique-TGA (98 cases): 1 episode, and recurrent-TGA (26 cases): 2 or more episodes. Recurrent-TGA were also compared with unique-TGA and the TIA groups. Results: The mean age of patients of the TGA group was 63 (7.96) and 58% were women. 30% had a history of migraine and 30% had anxiety. The risk of annual recurrence was 4.4%. Recurrent-TGA patients had more electroencephalographic registers showing non-epileptogenic abnormalities. The TIA group had more vascular risk factors and displayed more ischemic events during the follow-up. Recurrent-TGA patients had the same vascular risk factors as TIA patients and they also had a significantly more frequent history of stroke and trend to suffer new ischemic events than patients in the unique-TGA group. Conclusions: There is no vascular pathology substrate in TGA patients, suggesting an ischemic ethiology due to arteriosclerosis or cardioembolism. Patients with recurrent TGA constitute a subgroup with more vascular risk factors and an increased risk to suffer new strokes. For that reason we propose that these patients be studied as ischemic patients