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Background: The “1-3-6-12-day rule” for starting direct oral anticoagulants (DOACs) in patients with nonvalvular atrial fibrillation after acute ischemic stroke or transient ischemic attack recommends timings that may be later than used in clinical practice. We investigated more practical optimal timing of DOAC initiation according to stroke severity. Methods: The combined data of prospective registries in Japan, Stroke Acute Management with Urgent Risk-factor Assessment and Improvement-nonvalvular atrial fibrillation (September 2011 to March 2014) and RELAXED (February 2014 to April 2016) were used. Patients were divided into transient ischemic attack and 3 stroke subgroups by the National Institutes of Health Stroke Scale score: mild (0–7), moderate (8–15), and severe (≥16). The early treatment group was defined as patients starting DOACs earlier than the median initiation day in each subgroup. Outcomes included a composite of recurrent stroke or systemic embolism, ischemic stroke, and severe bleeding within 90 days. Six European prospective registries were used for validation. Results: In the 1797 derivation cohort patients, DOACs were started at median 2 days after transient ischemic attack and 3, 4, and 5 days after mild, moderate, and severe strokes, respectively. Stroke or systemic embolism was less common in Early Group (n=785)—initiating DOACS within 1, 2, 3, and 4 days, respectively—than Late Group (n=1012) (1.9% versus 3.9%; adjusted hazard ratio, 0.50 [95% CI, 0.27–0.89]), as was ischemic stroke (1.7% versus 3.2%, 0.54 [0.27–0.999]). Major bleeding was similarly common in the 2 groups (0.8% versus 1.0%). On validation, both ischemic stroke (2.4% versus 2.2%) and intracranial hemorrhage (0.2% versus 0.6%) were similarly common in Early (n=547) and Late (n=1483) Groups defined using derivation data. Conclusions: In Japanese and European populations, early DOAC initiation within 1, 2, 3, or 4 days according to stroke severity seemed to be feasible to decrease the risk of recurrent stroke or systemic embolism and no increase in major bleeding. These findings support ongoing randomized trials to better establish the optimal timing of DOAC initiation.

Background: The present study aimed to clarify the association between left atrial (LA) size and ischemic events after ischemic stroke or transient ischemic attack (TIA) in patients with nonvalvular atrial fibrillation (NVAF). Methods: Acute ischemic stroke or TIA patients with NVAF were enrolled. LA size was classified into normal LA size, mild LA enlargement (LAE), moderate LAE, and severe LAE. The ischemic event was defined as ischemic stroke, TIA, carotid endarterectomy, carotid artery stenting, acute coronary syndrome or percutaneous coronary intervention, systemic embolism, aortic aneurysm rupture or dissection, peripheral artery disease requiring hospitalization, or venous thromboembolism. Results: A total of 1,043 patients (mean age, 78 years; 450 women) including 1,002 ischemic stroke and 41 TIA were analyzed. Of these, 351 patients (34%) had normal LA size, 298 (29%) had mild LAE, 198 (19%) had moderate LAE, and the remaining 196 (19%) had severe LAE. The median follow-up duration was 2.0 years (interquartile range, 0.9–2.1). During follow-up, 117 patients (11%) developed at least one ischemic event. The incidence rate of total ischemic events increased with increasing LA size. Severe LAE was independently associated with increased risk of ischemic events compared with normal LA size (multivariable-adjusted hazard ratio, 1.75; 95% confidence interval, 1.02–3.00). Conclusion: Severe LAE was associated with increased risk of ischemic events after ischemic stroke or TIA in patients with NVAF.

OBJECTIVE We compared outcomes after treatment with direct oral anticoagulants (DOACs) and vitamin K antagonists (VKAs) in patients with atrial fibrillation (AF) and a recent cerebral ischemia. METHODS We conducted an individual patient data analysis of seven prospective cohort studies. We included patients with AF and a recent cerebral ischemia (

A 67-year-old woman was transported to our hospital with abnormal sensation in the left temporal region and unstable gait. She had a history of increased urinary frequency without medication. Head CT showed intracerebral hemorrhage in the left dorsal medulla oblongata. On the day of admission, she became aware of difficulty in urination and the volume of residual urine was 100 ml. Cystometry revealed normal voiding sensation and relatively lower intravesical pressure during voiding effort. The maximum cystometric capacity was also mildly decreased. The lower urinary tract dysfunction in this patient was diagnosed as detrusor underactivity. An α1-adrenoreceptor antagonist, urapidil, was started and her residual urine was decreased. Urapidil was terminated on the 14th day of onset, but her lower urinary tract symptoms did not recur thereafter. The brain MR imaging with magnetization-prepared 2 rapid acquisition gradient-echoes (MP2RAGE) clearly demonstrated a small hematoma in the dorsolateral medulla with surrounding edema. The perihematomal edema initially spread to involve the left lateral tegmentum of the medulla, but it almost disappeared in the follow-up MP2RAGE imaging on the 21st day. At the medulla level, the descending tract from the pontine micturition center is assumed to lie lateral tegmentum. The lower urinary tract dysfunction in this case was presumed to be caused by damage to the descending tract from the pontine micturition center, and the disappearance of perihematomal edema and the compensation by the contralateral tract would have contributed to the early improvement of symptoms.

Aims The bleeding risk of current antithrombotic strategies in clinical settings, including recently developed agents, needs to be clarified. Methods and Design In an investigator-initiated, prospective, multicentre, observational study, patients with cerebrovascular or cardiovascular diseases who were taking oral antiplatelet or anticoagulant agents were enrolled. Compulsory multimodal magnetic resonance images were acquired at baseline to assess cerebral small vessel disease. Six-month follow-up will be performed for two years. The primary outcome is major bleeding as defined by the International Society on Thrombosis and Hemostasis. Results Between October 2016 and March 2019, 5306 patients (71.7 ± 11.2 years old, 1762 women) were enrolled. Previous intracranial haemorrhage was documented in 181 patients (3.4%), cerebrovascular disease (including asymptomatic) requiring antithrombotic therapy in 5006 patients (94.3%), and atrial fibrillation in 1061 patients (20.0%). At entry, 3726 patients (70.2%) were taking antiplatelet agents alone, including 551 (10.4%) using dual antiplatelet agents, 1317 (24.8%) taking anticoagulants alone, and the remaining 263 (5.0%) taking both. The leading antiplatelet agent was clopidogrel (2014 patients), and the leading combination of dual antiplatelet medication was clopidogrel plus aspirin (362). Use of direct oral anticoagulants (1029 patients, 19.4%) exceeded warfarin use (554, 10.4%). The number of pivotal bleeding events exceeded 200 in April 2020. Conclusions This study is expected to provide the incidence of bleeding complications of recent oral antithrombotics in clinical practice and identify their associations with underlying small vessel disease and other biomarkers. Novel risk stratification models for bleeding risk will be able to be created based on the study results.

Background and Purpose— We aimed to compare outcomes of ischemic stroke patients with nonvalvular atrial fibrillation between earlier and later initiation of direct oral anticoagulants (DOACs) after stroke onset. Methods— From data for 1192 nonvalvular atrial fibrillation patients with acute ischemic stroke or transient ischemic attack in a prospective, multicenter, observational study, patients who started DOACs during acute hospitalization were included and divided into 2 groups according to a median day of DOAC initiation after onset. Outcomes included stroke or systemic embolism, major bleeding, and death at 3 months, as well as those at 2 years. Results— DOACs were initiated during acute hospitalization in 499 patients in median 4 (interquartile range, 2–7) days after onset. Thus, 223 patients (median age, 74 [interquartile range, 68–81] years; 78 women) were assigned to the early group (≤3 days) and 276 patients (median age, 75 [interquartile range, 69–82] years; 101 women) to the late (≥4 days) group. The early group had lower baseline National Institutes of Health Stroke Scale score and smaller infarcts than the late group. The rate at which DOAC administration persisted at 2 years was 85.2% overall, excluding patients who died or were lost to follow-up. Multivariable Cox shared frailty models showed comparable hazards between the groups at 2 years for stroke or systemic embolism (hazard ratio, 0.86 [95% CI, 0.47–1.57]), major bleeding (hazard ratio, 1.39 [95% CI, 0.42–4.60]), and death (hazard ratio, 0.61 [95% CI, 0.28–1.33]). Outcome risks at 3 months also did not significantly differ between the groups. Conclusions— Risks for events including stroke or systemic embolism, major bleeding, and death were comparable whether DOACs were started within 3 days or from 4 days or more after the onset of nonvalvular atrial fibrillation–associated ischemic stroke or transient ischemic attack. Registration— URL: https://www.clinicaltrials.gov . Unique identifier: NCT01581502.

Introduction It is unknown whether the type of treatment (direct oral anticoagulant versus vitamin K antagonist) and the time of treatment introduction (early versus late) may affect the functional outcome in stroke patients with atrial fibrillation. We aimed to develop and validate a nomogram model including direct oral anticoagulant/vitamin K antagonist and early/late oral anticoagulant introduction for predicting the probability of unfavourable outcome after stroke in atrial fibrillation-patients. Patients and Methods We conducted an individual patient data analysis of four prospective studies. Unfavourable functional outcome was defined as three-month modified Rankin Scale score 3 -6. To generate the nomogram, five independent predictors including age (25), acute revascularisation treatments (yes, reference, or no), direct oral anticoagulant (reference) or vitamin K antagonist, and early (7 days, reference) or late (8--30) anticoagulant introduction entered into a final logistic regression model. The discriminative performance of the model was assessed by using the area under the receiver operating characteristic curve. Results A total of 2102 patients with complete data for generating the nomogram was randomly dichotomised into training ( n = 1553) and test ( n = 549) sets. The area under the receiver operating characteristic curve was 0.822 (95% confidence interval, CI: 0.800--0.844) in the training set and 0.803 (95% CI: 0.764--0.842) in the test set. The model was adequately calibrated (9.852; p = 0.276 for the Hosmer--Lemeshow test). Discussion and Conclusion Our nomogram is the first model including type of oral anticoagulant and time of treatment introduction to predict the probability of three-month unfavourable outcome in a large multicentre cohort of stroke patients with atrial fibrillation.

Objective To determine the predictors of unfavorable outcomes in acute minor ischemic stroke patients with large vessel occlusion. Methods The derivation cohort included ischemic stroke patients admitted to a comprehensive stroke center within 7 days after onset with large vessel occlusion and an initial National Institutes of Health Stroke Scale score of 5 or less. An unfavorable outcome was defined as dependency (modified Rankin Scale score of 3 to 6) at 3 months from the onset. The predictive values of factors related to an unfavorable outcome were evaluated. External validation was performed from a stroke registry of a tertiary medical center. Results In the derivation cohort, 3839 consecutive patients were screened; a total of 130 patients were included. Twenty-four (18%) patients had unfavorable outcomes. In multivariate analysis, D-dimer ≥1900 μg/l (odds ratio (OR) 3.31, 95% confidence interval (CI) 1.14–9.61, p = .028) and age (OR 2.01, 95% CI 1.05–3.86, p = .035) were independently associated with an unfavorable outcome. No significant differences were observed regarding occluded vessel sites. In the validation cohort, 850 consecutive patients were screened; a total of 74 patients were included. D-dimer ≥1900 μg/l (OR 8.78, 95% CI 1.41–54.61, p = .020) was the only factor independently associated with an unfavorable outcome, as in the derivation cohort. Conclusions A high D-dimer level on admission could help predict unfavorable outcomes in patients with a minor ischemic stroke with large vessel occlusion.

Objective:\ud It is not known whether patients with atrial fibrillation (AF) with ischemic stroke despite oral anticoagulant therapy are at increased risk for further recurrent strokes or how ongoing secondary prevention should be managed.\ud \ud Methods:\ud We conducted an individual patient data pooled analysis of 7 prospective cohort studies that recruited patients with AF and recent cerebral ischemia. We compared patients taking oral anticoagulants (vitamin K antagonists [VKA] or direct oral anticoagulants [DOAC]) prior to index event (OACprior ) with those without prior oral anticoagulation (OACnaive ). We further compared those who changed the type (ie, from VKA or DOAC, vice versa, or DOAC to DOAC) of anticoagulation (OACchanged ) with those who continued the same anticoagulation as secondary prevention (OACunchanged ). Time to recurrent acute ischemic stroke (AIS) was analyzed using multivariate competing risk Fine-Gray models to calculate hazard ratios (HRs) and 95% confidence intervals (CIs).\ud \ud Results:\ud We included 5,413 patients (median age = 78 years [interquartile range (IQR) = 71-84 years]; 5,136 [96.7%] had ischemic stroke as the index event, median National Institutes of Health Stroke Scale on admission = 6 [IQR = 2-12]). The median CHA2 DS2 -Vasc score (congestive heart failure, hypertension, age≥ 75 years, diabetes mellitus, stroke/transient ischemic attack, vascular disease, age 65-74 years, sex category) was 5 (IQR = 4-6) and was similar for OACprior (n = 1,195) and OACnaive (n = 4,119, p = 0.103). During 6,128 patient-years of follow-up, 289 patients had AIS (4.7% per year, 95% CI = 4.2-5.3%). OACprior was associated with an increased risk of AIS (HR = 1.6, 95% CI = 1.2-2.3, p = 0.005). OACchanged (n = 307) was not associated with decreased risk of AIS (HR = 1.2, 95% CI = 0.7-2.1, p = 0.415) compared with OACunchanged (n = 585).\ud \ud Interpretation:\ud Patients with AF who have an ischemic stroke despite previous oral anticoagulation are at a higher risk for recurrent ischemic stroke despite a CHA2 DS2 -Vasc score similar to those without prior oral anticoagulation. Better prevention strategies are needed for this high-risk patient group.

Background and Purpose: Direct oral anticoagulants (DOACs) are widely used for the prevention of ischemic events with non-valvular atrial fibrillation (NVAF). However, it is unknown when DOACs should be started after acute ischemic stroke (AIS) or transient ischemic attack (TIA). The aim of this study was to compare the short- and long-term stroke outcomes between earlier initiation and later initiation of DOACs after onset of AIS. Methods: Patients with NVAF who developed AIS/TIA were enrolled from the database of the prospective, multicenter, observational SAMURAI-NVAF study, and they were divided into two groups according to the date of starting DOACs after stroke onset: within 3 days (E-group) and 4 or more days (L-group). The frequency of ischemic event, bleeding, and death up to 2 years was compared. Result: DOACs were started as the first oral anticoagulants after AIS/TIA in 499 (42%) of 1192 NVAF patients. Of these, 223 patients were assigned to E-group (74±6 years of age, 78 women) and 276 patients to L-group (75±6 years of age, 101 women). E-group had lower scores of National Institutes of Health Stroke Scale (median 3, interquartile range [IQR] 1-8 vs 5, 2-14; P=0.001) and CHAD 2 S-VASc (median 5, IQR, 4-6 vs 5, 4-6; P=0.04) than L-group. No significant difference was observed in the rate of ischemic events (at 3 months: E 4.0% vs L 2.5%, harzard ratio [HR] 1.59, 95% confidence interval [CI] 0.58-4.48; at 2 years: E 9.4% vs L 10.9%, 0.89, 0.50-1.56), bleeding (at 3 months: E 1.4% vs L 2.2%, HR 0.48, 95% CI 0.10-1.88; at 2 years: E 3.6% vs. L 4.0%, 0.97, 0.36-2.51), and death (at 3 months: E 0.5% vs L 0.4%, HR 1.22, 95% CI 0.05-31.52; at 2 years: E 4.5% vs L 8.7%, 0.57, 0.26-1.17) after multivariable adjustment. Conclusion: Early starting of DOACs within 3 days after the onset of AIS/TIA had comparable outcome to later starting of them regarding ischemic events, bleeding, and death.

Background The aim of this study was to elucidate changes in cerebral white matter after shunt surgery in idiopathic normal pressure hydrocephalus (INPH) using diffusion tensor imaging (DTI). Methods Twenty-eight consecutive INPH patients whose symptoms were followed for 1 year after shunt placement and 10 healthy control (HC) subjects were enrolled. Twenty of the initial 28 INPH patients were shunt-responsive (SR) and the other 8 patients were non-responsive (SNR). The cerebral white matter integrity was detected by assessing fractional anisotropy (FA) and mean diffusivity (MD). The mean hemispheric DTI indices and the ventricular sizes were calculated, and a map of these DTI indices was created for each subject. The DTI maps were analysed to compare preshunt INPH with HC and preshunt INPH with 1 year after shunt placement in each INPH group, using tract-based spatial statistics. We restricted analyses to the left hemisphere because of shunt valve artefacts. Results The ventricles became significantly smaller after shunt placement both in the SR and SNR groups. In addition, there was a significant interaction between clinical improvement after shunt and decrease in ventricular size. Although the hemispheric DTI indices were not significantly changed after shunt placement, there was a significant interaction between clinical improvement and increase in hemispheric MD. Compared with the HC group, FA in the corpus callosum and in the subcortical white matter of the convexity and the occipital cortex was significantly lower in SR at baseline, whereas MD in the periventricular and peri-Sylvian white matter was significantly higher in the SR group. Compared with the pre-operative images, the post-operative FA was only decreased in the corona radiata and only in the SR group. There were no significant regions in which DTI indices were altered after shunt placement in the SNR group. Conclusions Brain white matter regions in which FA was decreased after shunt placement were in the corona radiata between the lateral ventricles and the Sylvian fissures. This finding was observed only in shunt-responsive INPH patients and might reflect the plasticity of the brain for mechanical pressure changes from the cerebrospinal fluid system. Electronic supplementary material The online version of this article (doi:10.1186/s12987-016-0048-8) contains supplementary material, which is available to authorized users.

Background/Aims: Frontal lobe dysfunction is believed to be a primary cognitive symptom in idiopathic normal pressure hydrocephalus (iNPH); however, the neuropsychology of this disorder remains to be fully investigated. The objective of this study was to delineate a comprehensive profile of cognitive dysfunction in iNPH and evaluate the effects of cerebrospinal fluid (CSF) shunt surgery on cognitive dysfunction. Methods: A total of 32 iNPH patients underwent neuropsychological testing of memory, attention, language, executive function, and visuoperceptual and visuospatial abilities. Of these 32 patients, 26 were reevaluated approximately 1 year following CSF shunt surgery. The same battery of tests was performed on 32 patients with Alzheimer’s disease (AD) and 30 healthy elderly controls. Results: The iNPH patients displayed baseline deficits in attention, executive function, memory, and visuoperceptual and visuospatial functions. Impairments of attention, executive function, and visuoperceptual and visuospatial abilities in iNPH patients were more severe than in those with AD, whereas the degree of memory impairment was comparable to that in AD patients. A significant improvement in executive function was observed following shunt surgery. Conclusion: Patients with iNPH are impaired in various aspects of cognition involving both ‘frontal’ executive functions and ‘posterior cortical’ functions. Shunt treatment can ameliorate executive dysfunction.

Recent evidence suggests that patients with Alzheimer's disease (AD), as compared with normal individuals, exhibit increased false recognition by stimulus repetition in the Deese-Roediger-McDermott (DRM) task or associative recognition memory tasks, probably due to impaired recollection-based monitoring. However, because of possible alternative explanations for the findings of these previous studies, the evidence for impaired recollection-based monitoring in AD patients remains inconclusive. In this study, we employed stimulus repetition in old/new recognition judgments of single-item picture memory without a factor of association between the stimuli and examined whether AD patients showed increased false item recognition as compared with healthy controls. AD patients and healthy controls studied single-item pictures presented either once or three times. They were later asked to make an old/new recognition judgment in response to (a) Same pictures, pictures identical to those seen at encoding, (b) Similar lures, novel pictures similar to but not identical to those seen at encoding, and (c) Dissimilar lures, novel pictures not similar to those seen at encoding. For Same pictures, repeated presentation of stimuli increased the proportion of "old" responses in both groups. For Similar lures, repeated presentation of stimuli increased the rate of "old" responses in AD patients but not in control subjects. The results of the present study clearly demonstrated elevated false recognition by stimulus repetition in single-item recognition in AD patients. The present findings strongly support the view that AD patients are impaired in their ability to use item-specific recollection in order to avoid false recognition.

A patient with distal myopathy with rimmed vacuoles (DMRV) exhibited Parkinsonism with a severe writing tremor that responded poorly to levodopa. Molecular genetic analysis revealed that the patient had the D176V/V572L compound heterozygous mutation in the UDP-N-acetylglucosamine 2-epimerase/N-acetylmannosamine kinase (GNE) gene. Histopathological examination of a biopsied muscle specimen yielded findings compatible with those of DMRV, which is characterized by the presence of rimmed vacuoles without inflammatory cell infiltration in muscle fibers. The finding of normal cardiac meta-iodobenzylguanide uptake makes the possibility of incidental Parkinson's disease in this patient unlikely. These observations raise the possibility that atypical Parkinsonism is a rare complication of DMRV associated with GNE mutation.

Gait disturbance is the most common symptom in idiopathic normal-pressure hydrocephalus (iNPH). However, its pathophysiology in iNPH has not been clarified. Some researchers have hypothesized that the mesencephalic locomotor region, which is a functionally defined area in the brainstem playing an important role in locomotion, is involved in the development of gait disturbance in iNPH. The purpose of the study was to investigate whether the midbrain is involved in the manifestation of gait disturbance in iNPH. Twenty-one iNPH patients who showed clinical improvements after shunt surgery were studied. Brain magnetic resonance imaging (MRI) was performed and clinical symptoms were assessed before and 1 year after surgery. Gait disturbance was assessed by the Timed Up and Go test and gait subcategory of the iNPH Grading Scale, a validated assessment tool for iNPH symptoms. Anteroposterior, left-to-right diameter and cross-sectional areas of the midbrain were measured at the inferior collicular level of axial images in MRI. The diameters and cross-sectional area of the midbrain at baseline did not show significant correlation with gait assessments at baseline (Spearman’s correlation). The midbrain measurement did not show significant difference between the baseline and postoperative values (paired t test), and its change rates did not show significant correlation with the change (rates) of the gait assessments. In this study there were no findings to suggest involvement of the midbrain in the manifestation of gait disturbance in iNPH. The hypothesis that the mesencephalic locomotor region is involved in the manifestation of gait disturbance in iNPH needs to be reconsidered.

To investigate volumetric changes of the brain and cerebrospinal fluid (CSF) spaces after shunt surgery in shunt-responsive idiopathic normal-pressure hydrocephalus (iNPH), and correlations between the changes and postoperative clinical improvements.Twenty-one patients with shunt-responsive iNPH were studied. Magnetic resonance imaging (MRI) of the brain was performed before and 1year after surgery, and clinical symptoms were assessed by the iNPH Grading Scale, a validated assessment tool of the triad of iNPH, the Modified Rankin Scale, the Timed Up and Go Test, and neuropsychological tests including the Mini-Mental State Examination. The volumes of the left cerebral hemisphere, infratentorial brain, ventricles, and suprasylvian and infrasylvian subarachnoid CSF spaces were measured using an MRI-based volumetric technique.The volumes of the cerebral hemisphere and infratentorial brain did not change significantly after shunt surgery (p=0.231, 0.109, respectively). The volumes of the ventricles and infrasylvian subarachnoid CSF spaces were significantly decreased (p0.0001,0.05, respectively), with a mean change rate of -26.1% and -4.5%, respectively. The volumes of the suprasylvian subarachnoid CSF spaces increased significantly (p0.0001), with a mean change rate of 43.5%. The decrease in ventricular volumes was significantly correlated with clinical improvement.

A patient with distal myopathy with rimmed vacuoles (DMRV) exhibited Parkinsonism with a severe writing tremor that responded poorly to levodopa. Molecular genetic analysis revealed that the patient had the D176V/V572L compound heterozygous mutation in the UDP-N-acetylglucosamine 2-epimerase/N-acetylmannosamine kinase (GNE) gene. Histopathological examination of a biopsied muscle specimen yielded findings compatible with those of DMRV, which is characterized by the presence of rimmed vacuoles without inflammatory cell infiltration in muscle fibers. The finding of normal cardiac meta-iodobenzylguanide uptake makes the possibility of incidental Parkinson's disease in this patient unlikely. These observations raise the possibility that atypical Parkinsonism is a rare complication of DMRV associated with GNE mutation.

Background Glutamic acid decarboxylase (GAD) is the rate-limiting enzyme for producing γ-aminobutyric acid, and it has been suggested that antibodies against GAD play a role in neurological conditions and type 1 diabetes. However, it is not known whether dementia appears as the sole neurological manifestation associated with anti-GAD antibodies in the central nervous system. Case presentation We describe the clinical, neuropsychological, and neuroradiological findings of a 73-year-old female with cognitive dysfunction and type 1A diabetes. Observation and neuropsychological studies revealed linguistic problems, short-term memory disturbance, and frontal dysfunction. MRI showed no significant lesion except for confluent small T2-hyperintensity areas localized in the left basal ganglia. 18F-fluorodeoxy glucose-positron emission tomography (FDG-PET) and 123I-N-isopropyl-p-iodoamphetamine-single photon emission computed tomography (IMP-SPECT) studies showed bifrontal hypometabolism and hypoperfusion. Immunomodulating therapy with intravenous high-dose immunoglobulin resulted in no remission of the cognitive symptoms. Conclusions Cognitive dysfunction may develop as an isolated neurological manifestation in association with type 1A diabetes and anti-GAD autoimmunity. A systematic study with extensive neuropsychological assessment is indicated in patients with type 1 diabetes and anti-GAD autoimmunity.