Subcortical White Matter Changes Research Articles

Magnetic resonance imaging and positron emission tomography in anti-NMDA receptor encephalitis: A systematic review

Due to a variety of clinical manifestations anti-N-methyl-d-aspartate (NMDA) receptor encephalitis may be difficult to diagnose. Magnetic resonance imaging (MRI) may be used as a component of the workup for encephalopathy. However, the use of MRI in anti-NMDA encephalitis is complicated by wide-ranging reports regarding the frequency of normal MRI findings in this disease. Positron emission tomography (PET) is a modality of imaging that may assess functional rather than structural disturbances. Therefore, this review was conducted to summarise published studies regarding the use of MRI and PET in the diagnosis of anti-NMDA receptor encephalitis. The terms (MR OR magnetic resonance OR PET OR positron emission tomography) AND (NMDA encephalitis OR N-methyl-d-aspartate encephalitis) were used to search the databases PubMed, EMBASE and Scopus on 10/5/2017. These searches returned 1534 results. Sixty studies met the inclusion criteria. The results indicated that fewer than half of MRIs in anti-NMDA receptor encephalitis show abnormal findings. When abnormal findings are present they most commonly include T2/FLAIR medial temporal and frontal hyperintensity, and leptomeningeal contrast enhancement. Cortical grey matter changes were reported in the same number of patients as subcortical white matter changes. The only MRI finding with prognostic significance at this stage is progressive cerebellar atrophy. FDG-PET has been assessed in a few small studies and can demonstrate abnormalities in cases where MRI does not. Further research should aim for larger sample sizes and to report (and attempt to control for) the time between symptom onset and the scan being conducted, and pre-imaging treatments.

P 28 Voxel-based Morphometry (VBM) subcortical white matter changes correlate with disease progression in amyotrophic lateral sclerosis

Introduction Amyotrophic lateral sclerosis (ALS) is a progressive, multisystemic disorder.Signs of lower motor neurone involvement are readily detectable but the involvement of the upper motor neurone is elusive.Hence, we must identify the extent and development of ALS related changes in the brain in different subtypes of ALS to facilitate an early diagnosis and stratification for clinical trials.Previous studies applying Voxel-based morphometry (VBM) provided inconsistent results. Objective The aim of this study is to describe the heterogeneity of ALS with regard to the site of onset (bulbar vs.limb), disease duration (long vs.short), degree of disability (high vs.low) and disease progression rate (rapid vs.slow) in a large cohort of well characterized ALS patients.ALS related MRI changes should correlate with clinical parameters, such as ALSFRS-R score and D50 (50% disease progression in a model of sigmoidal decay of the ALSFRS-R). The long-term aim of this study is to evaluate VBM as a predictive marker for ALS in a representative number of subjects ( n > 100 ). Methods High resolution T1-weighted FLASH 3D scans (fl3d) in 92 ALS patients and 62 healthy controls were analyzed using VBM8 in SPM8 on matlab 2009b.Clinical parameters were collected regularly: disease duration, date and location of the first symptom, rate of disease progression and degree of disability (ALSFRS-R). Based on these clinical parameters, patients were classified into the subgroups and analyzed to determine changes in the gray and white matter. Results The mean age of 62 controls was 53.97y and of the 92 patients 60.24y.The patient group included 24 bulbar and 68 limb onsets.Average disease duration was 25 mo, wherein 26 patients had a long ( ⩾ 24mo) and 35 had a short ( ⩽ 12mo) disease duration.Mean ALSFRS-R was 37.8.46 patients had a “low” degree of disability (ALSFRS-R ⩾ 40), whereas 17 patients were “highly” impaired ( ⩽ 30).Mean progression rate was 0.66.A subgroup with a rapid form of ALS included 16 patients, with a slow form 46.Using VBM, more rapid progression, longer disease duration and more severely affected patients had a more pronounced reduction in GMV in the central, and frontal brain regions, whereas subcortical WM was more severely altered. Conclusion Using VBM in high resolution T1 in a large cohort of ALS patients, we were able to identify the key regions of ALS pathology which correlated well with three clinical progression parameters.It is likely that previous studies were underpowered and ALS related heterogeneity obscured the relevant pathology in computerized voxel-based analyses. Acknowledgement This research is supported by BMBF (Bundesministerium fur Bildung and Forschung) in the framework of the E-RARE programme (PYRAMID) and JPND (OnWebDUALS and SOPHIA) of the European Union in collaboration with the Neuroimaging Society in ALS (NiSALS) MRI repository Jena.

Neurological appearance of celiac disease

Objective: Celiac disease may present as one or more neurological signs and/or symptoms. It may be associated with or complicated by neurological manifestations. We aimed to define the incidence of accompanying neurologic manifestations in children diagnosed celiac disease and interpret our outcomes compare with results of other studies in literature. Methods: The prospective study included 121 children diagnosed with celiac disease. The medical records of all patients were also reviewed. Results: In neurological evaluation, 38 (31.4% ) of the 121 celiac patients had a neurological finding including headache, migraine, vertigo, epilepsy, sensorimotor polyneuropathy, Down syndrome, Turner syndrome and a patient with subcortical white matter changes in MRI. Vitamin deficiency (vitamin B12 and/or vitamin D and/or folic acid) was statistically more common among patients with neurological manifestations. Conclusion: It is important to consider on clinical course of celiac disease different neurological manifestations may be presented.

Cortical gray and subcortical white matter associations in Parkinson's disease

Cortical atrophy has been documented in both Parkinson's disease (PD) and healthy aging, but its relationship to changes in subcortical white matter is unknown. This was investigated by obtaining T1- and diffusion-weighted images from 76 PD and 70 controls at baseline and 18 and 36 months, from which cortical volumes and underlying subcortical white matter axial diffusivity (AD), radial diffusivity (RD), and fractional anisotropy (FA) were determined. Twelve of 69 cortical subregions had significant group differences, and for these, underlying subcortical white matter was explored. At baseline, higher cortical volumes were significantly correlated with lower underlying subcortical white matter AD, RD, and higher FA (ps ≤ 0.017) in PD. Longitudinally, higher rates of cortical atrophy in PD were associated with increased rates of change in AD RD, and FA values (ps ≤ 0.0013) in 2 subregions explored. The significant gray-white matter associations were not found in controls. Thus, unlike healthy aging, cortical atrophy and subcortical white matter changes may not be independent events in PD.

RMND1-Related Leukoencephalopathy With Temporal Lobe Cysts and Hearing Loss—Another Mendelian Mimicker of Congenital Cytomegalovirus Infection

BackgroundLeukoencephalopathy with temporal lobe cysts may be associated with monogenetic conditions such as Aicardi–Goutières syndrome or RNASET2 mutations and with congenital infections such as cytomegalovirus. In view of the fact that congenital cytomegalovirus is difficult to confirm outside the neonatal period, excluding a Mendelian disorder is extremely relevant, changing family planning and medical management in affected families. We performed diagnostic testing in individuals with leukoencephalopathy with temporal lobe cysts without a definitive diagnosis of congenital cytomegalovirus infection. MethodsWe reviewed a large-scale biorepository of patients with unsolved leukodystrophies and identified two individuals with required for meiotic nuclear division 1 (RMND1) mutations and similar magnetic resonance imaging (MRI) features, including temporal lobe cysts. Ten additional subjects with confirmed RMND1 mutations were identified as part of a separate disease specific cohort. Brain MRIs from all 12 individuals were reviewed for common neuroradiological features. ResultsMRI features in RMND1 mutations included temporal lobe swelling, with rarefaction and cystic evolution, enlarged tips of the temporal lobes, and multifocal subcortical white matter changes with confluent periatrial T2 signal hyperintensity. A combination of these features was present in ten of the 12 individuals reviewed. ConclusionsDespite the small number of reported individuals with RMND1 mutations, a clinically recognizable phenotype of leukoencephalopathy with temporal lobe swelling, rarefaction, and cystic changes has emerged in a subset of individuals. Careful clinical phenotyping, including for lactic acidosis, deafness, and severe muscle involvement seen in RMND1 mutation positive individuals, and MRI pattern recognition will be important in differentiating these patients from children with congenital infections like cytomegalovirus.

Subcortical White Matter Changes with Normal Aging Detected by Multi-Shot High Resolution Diffusion Tensor Imaging.

Subcortical white matter builds neural connections between cortical and subcortical regions and constitutes the basis of neural networks. It plays a very important role in normal brain function. Various studies have shown that white matter deteriorates with aging. However, due to the limited spatial resolution provided by traditional diffusion imaging techniques, microstructural information from subcortical white matter with normal aging has not been comprehensively assessed. This study aims to investigate the deterioration effect with aging in the subcortical white matter and provide a baseline standard for pathological disorder diagnosis. We apply our newly developed multi-shot high resolution diffusion tensor imaging, using self-feeding multiplexed sensitivity-encoding, to measure subcortical white matter changes in regions of interest of healthy persons with a wide age range. Results show significant fractional anisotropy decline and radial diffusivity increasing with age, especially in the anterior part of the brain. We also find that subcortical white matter has more prominent changes than white matter close to the central brain. The observed changes in the subcortical white matter may be indicative of a mild demyelination and a loss of myelinated axons, which may contribute to normal age-related functional decline.

MRI features in 17 patients with l2 hydroxyglutaric aciduria

l-2-Hydroxyglutaric (l-2-HG) aciduria is a rare inherited metabolic disease usually observed in children. Patients present a very slowly progressive deterioration with cerebellar ataxia, mild or severe mental retardation, and various other clinical signs including extrapyramidal and pyramidal symptoms, and seizures Goffette et al. [1]. This leukencephalopathy was first described in 1980 Duran et al. [2]. Brain magnetic resonance imaging (MRI) demonstrates nonspecific subcortical white matter (WM) loss, cerebellar atrophy and changes in dentate nuclei and putamen Steenweg et al. [3]. The diagnosis is highlighted by increased levels of l-2-HG in body fluids such as urine and cerebrospinal fluid.The purpose of this study is to retrospectively describe the brain MRI features in l-2-HG aciduria.

Reduced functional reserve in patients with age-related white matter changes: a preliminary FMRI study of working memory.

Subcortical age-related white matter changes (ARWMC) are a frequent finding in healthy elderly people suggested to cause secondary tissue changes and possibly affecting cognitive processes. We aimed to determine the influence of the extent of ARWMC load on attention and working memory processes in healthy elderly individuals. Fourteen healthy elderly subjects (MMSE >26; age 55–80 years) performed three fMRI tasks with increasing difficulty assessing alertness, attention (0-back), and working memory (2-back). We compared activation patterns in those with only minimal ARWMC (Fazekas 0–1) to those with moderate to severe ARWMC (Fazekas 2–3). During the fMRI experiments, the study population showed activation in brain areas typically involved in attention and working memory with a recruitment of cortical areas with increasing task difficulty. Subjects with higher lesion load showed a higher activation at all task levels with only sparse increase of signal with increasing complexity. In the lower lesion load group, rising task difficulty lead to a significant and widely distributed increase of activation. Although the number of patients included in the study is small, these findings suggest that even clinically silent ARWMC may affect cognitive processing and lead to compensatory activation during cognitive tasks. This can be interpreted as a reduction of functional reserve and may pose a risk for cognitive decline in these patients.

Depressive symptoms, atherosclerotic burden and cerebral blood flow disturbances in a cohort of octogenarian men from a general population

BackgroundThe aim of this study was to examine in elderly men a relationship between depressive symptoms, peripheral vascular disease and cerebral blood flow (CBF).MethodsPopulation-based cohort study started with an examination of 809 men at age 55, followed by the first (age 68ys) and second follow up (age 82ys). 128 survivors were examined at age 82 with 99mTc-HMPAO-SPECT to estimate CBF, Zung-Self-Rating-Depression Scale (ZSDS), and Ankle-Brachial Index (ABI). Analysis was performed on men free from stroke and dementia which defined the final study population to 120 subjects.ResultsZSDS in the whole cohort ranged from 0.26 to 0.71 (reference 0.25-1.0). As the frequency of depressive symptoms was low, the case group (n = 31) was defined by ZSDS index above 75th percentile (≥0.48), comprising 9 subjects with mild depression (ZSDS 0.55-0.71) and 22 subjects at 88th percentile and above of the normal range (ZSDS index 0.48-0.54). Cases were more often current smokers at age 68 (44% vs. 24%; p = .02) and had lower systolic blood presure (SBP), lower social and physical activity, and suffered from fatigue, nausea, freezing and leg edema at age 82. Within the case group, ZSDS-index correlated negatively with CBF in subcortical area (r = -.42*), left and right thalamus (r = -.40*, r = -.46**), and right basal nuclei (r = -.35*). ZSDS-index correlated also with ABI at age 82 (right leg r = -.40*; left leg r = -.37*), and with Δ between ABI at age 82 and 68 (right r = -.36*; left r = -.46**). Despite decreasing SBP from age 68 to 82, adjusted multiple regression analysis showed in the case group that higher SBP determined CBF changes in the frontal and parietal areas, independently of ZSDS index, Δ ABI, and smoking.ConclusionIn this population-based cohort of octogenarian men free from stroke or dementia, a proportion of subjects with depressive symptoms was low. Still, men with borderline or mild depression scores had lower social and physical activity, persistent smoking habit, worse peripheral circulation in legs, and cerebral perfusion changes in basal nuclei, thalamus and subcortical white matter. Regional CBF decline could be partly mediated by higher SBP.

Cortical Grey Matter and Subcortical White Matter Brain Microstructural Changes in Schizophrenia Are Localised and Age Independent: A Case-Control Diffusion Tensor Imaging Study

It is still unknown whether the structural brain impairments that characterize schizophrenia (SZ) worsen during the lifetime. Here, we aimed to describe age-related microstructural brain changes in cortical grey matter and subcortical white matter of patients affected by SZ. In this diffusion tensor imaging study, we included 69 patients diagnosed with SZ and 69 healthy control (HC) subjects, age and gender matched. We carried out analyses of covariance, with diagnosis as fixed factor and brain diffusion-related parameters as dependent variables, and controlled for the effect of education. White matter fractional anisotropy decreased in the entire age range spanned (18–65 years) in both SZ and HC and was significantly lower in younger patients with SZ, with no interaction (age by diagnosis) effect in fiber tracts including corpus callosum, corona radiata, thalamic radiations and external capsule. Also, grey matter mean diffusivity increased in the entire age range in both SZ and HC and was significantly higher in younger patients, with no age by diagnosis interaction in the left frontal operculum cortex, left insula and left planum polare and in the right temporal pole and right intracalcarine cortex. In individuals with SZ we found that localized brain cortical and white matter subcortical microstructural impairments appear early in life but do not worsen in the 18–65 year age range.

Changes in subcortical white matter and corpus callosum volumes in patients with type 2 diabetes mellitus

To evaluate the changes in subcortical white matter and corpus callosum volumes in patients with type 2 diabetes mellitus (T2DM). High resolution three-dimensional T1-weighted fast spoiled gradient recalled echo magnetic resonance images were obtained from 16 T2DM patients and 16 normal controls, and 11 T2DM patients also received the same magnetic resonance imaging scans after insulin therapy for 1 year. Volumetric analysis was performed and analysis of covariance and paired t test were applied. A lower volume was demonstrated in T2DM patients than that in the normal controls in bilateral caudal middle frontal lobe, bilateral pars opercularis, right inferior parietal lobe, right inferior temporal lobe, right middle temporal lobe, and left transverse temporal lobe (all P<0.05). After insulin therapy for 1 year, the increased subcortical white matter of brain regions were demonstrated in left medial orbitofrontal lobe, right caudal middle frontal lobe, right inferior parietal lobe, right lingual lobe, right inferior temporal lobe, right middle temporal lobe, left transverse temporal lobe, left entorhinal lobe and left insular lobe at the follow-up level in T2DM patients compared with baseline level (P<0.05). The decreased volumes of subcortical white matter were observed in the bilateral paracentral lobe, right superior forntal lobe and right precuneus lobe in T2DM patients on insulin therapy for 1 year (P<0.05). A decreased trend of subcortical white matter was involved in corpus callosum (P>0.05) and a significant decreased volume was demonstrated in the middle posterior part of corpus callosum after insulin therapy for 1 year(P<0.05). T2DM patients have decreased subcortical white matter of multiple brain regions, and the atrophy of subcortical white matter can be improved by the insulin therapy. The volume analysis of subcortical white matter is a simple and effective tool for the evaluation of white matter damage in T2DM patients.

Subacute Sclerosing Panencephalitis (SSPE) Associated with Basal Ganglia Involvement - Two Case Reports

Magneting resonance imaging in subacute sclerosing panencephalitis (SSPE) usually demonstrates changes in periventicular and subcortical white matter. Basal ganglia, Cerebellum, Spinal cord are less commonly involved. In this article, we report two cases of SSPE associated with basal ganglia involvement. The 1st case a 11 years old boy had the severe symptoms of SSPE with bilateral basal ganglia involvement. The 2nd case a 8 years old girl had right sided hemiplegia. DOI: http://dx.doi.org/10.3329/bjch.v36i3.14289 BANGLADESH J CHILD HEALTH 2012; VOL 36 (3) : 153-155

Brain imaging in normal kids: a community‐based MRI study in Malawian children

To collect normative MRI data for effective clinical and research applications. Such data may also offer insights into common neurological insults. We identified a representative, community-based sample of children aged 9-14years. Children were screened for neurodevelopmental problems. Demographic data, medical history and environmental exposures were ascertained. Eligible children underwent the Neurologic Examination for Subtle Signs (NESS) and a brain MRI. Descriptive findings and analyses to identify risk factors for MRI abnormalities are detailed. One hundred and two of 170 households screened had age-appropriate children. Two of 102 children had neurological problems - one each with cerebral palsy and epilepsy. Ninety-six of 100 eligible children were enrolled. Mean age was 11.9years (SD 1.5), and 43 (45%) were boys. No acute MRI abnormalities were seen. NESS abnormalities were identified in 6 of 96 children (6%). Radiographic evidence of sinusitis in 29 children (30%) was the most common MRI finding. Brain abnormalities were found in 16 (23%): mild diffuse atrophy in 4 (4%), periventricular white matter changes/gliosis in 6 (6%), multifocal punctuate subcortical white matter changes in 2 (2%), vermian atrophy in 1 (1%), empty sella in 3 (3%) and multifocal granulomas with surrounding gliosis in 1 (1%). Having an abnormal MRI was not associated with age, sex, antenatal problems, early malnutrition, febrile seizures, an abnormal neurological examination or housing quality (all P values >0.05). No predictors of radiographic sinusitis were identified. Incidental brain MRI abnormalities are common in normal Malawian children. The incidental atrophy and white matter abnormalities seen in this African population have not been reported among incidental findings from US populations, suggesting Malawi-specific exposures may be the cause.

Brain structure in asymptomatic FMR1 premutation carriers at risk for fragile X-associated tremor/ataxia syndrome

Fragile X-associated tremor/ataxia syndrome (FXTAS), a late-onset movement disorder affecting FMR1 premutation carriers, is associated with cerebral and cerebellar lesions. The aim of this study was to test whether computational anatomy can detect similar patterns in asymptomatic FMR1 premutation carriers (mean age 46.7 years) with qualitatively normal -appearing grey and white matter on brain MRI. We used a multimodal imaging protocol to characterize brain anatomy by automated assessment of gray matter volume and white matter properties. Structural changes in the hippocampus and in the cerebellar motor network with decreased gray matter volume in lobule VI and white matter alterations of the corresponding afferent projections through the middle cerebellar peduncles are demonstrated. Diffuse subcortical white matter changes in both hemispheres, without corresponding gray matter alterations, are only identified through age × group interactions. We interpret the hippocampal fimbria and cerebellar changes as early alterations with a possible neurodevelopmental origin. In contrast, progression of the diffuse cerebral hemispheric white matter changes suggests a neurodegenerative process, leading to late-onset lesions, which may mark the imminent onset of FXTAS.

Early abnormalities in 123I-ioflupane (DaTSCAN) imaging in the fragile X-associated tremor ataxia syndrome (FXTAS): a case report

The fragile X-associated tremor/ataxia (FXTAS) is a late onset neurodegenerative disorder, occurring in male carriers of a premutation expansion (50–200 repeats CGG) in the fragile X mental retardation 1 (FMR1) gene [1], and clinically characterized by phenotypic predominance of either cerebellar ataxia or intention tremor, and variably associated with other features, such as parkinsonism, peripheral neuropathy, autonomic dysfunction and dementia [1]. MRI studies have shown T2-weighted periventricular, subcortical white matter changes, with a specific involvement of middle cerebellar peduncles [1]. The underlying mechanism of FXTAS-associated parkinsonism remains unclear. 123I-ioflupane (DaTSCAN) imaging studies have shown contrasting patterns. In some cases with clear tremor and parkinsonism, DAT scans have been normal [2, 3] although rarely they can be abnormal [4, 5]. In these cases, there has been suggestion of the involvement of the basal ganglia, specifically the dopaminergic system projecting to the putamen. Here, we describe a patient carrying a premutation of FMR1 (82 CGG repeat) and presenting only subtle clinical signs of tremor and typical MRI features and clearly abnormal DaTSCAN examination. A 65-year-old Italian man was admitted to our hospital for the recent appearance of a mild bilateral tremor at upper extremities, which did not impair daily function, and with a genetic confirmation of FMR1 (Xq27.3) premutation (82 CGG repeat expansions). The patient was tested for FMR1 mutations since his daughter was diagnosed with fragile X syndrome with mental retardation at onset. His medical history was not notable for hypertension, hyperlipidemia and thyroid dysfunction. Childhood and adolescent development were normal and his school performance was good. No family history of tremor or movement disorder was reported. General physical examination findings were notable for normal blood pressure without abnormal orthostatic changes. Neurological examination revealed mild action tremor of the upper extremities, with a prevalence of the right arm (7–11 Hz). A moderate rigidity was detected at upper extremities (right [ left). No bradykinesia was detected. Synergy, trajectory, and placement of upperand lower-extremity movements were normal. Cranial nerve findings, deep tendon reflexes, plantar responses, gait and stance were normal. MRI scans showed mild cerebral and cerebellar cortical atrophy. Patchy areas of subependymal and deep white matter of the cerebral hemispheres with increased T2 signal intensity were observed, in the absence of any obvious vascular risk factor. Of note, a slightly increased T2 signal intensity was observed in the middle cerebellar peduncles (Fig. 1). SPECT examination was obtained by injection i.v. with 111 MBq of [123I]FP-CIT for evaluation of striatal dopamine transporter (DAT) density. The uptake of [123I]FP-CIT was significantly reduced in both putamen G. Madeo F. Alemseged A. Pisani (&) Dipartimento di Medicina dei Sistemi, Clinica Neurologica, Universita degli Studi di Roma Tor Vergata, Roma, Italia e-mail: pisani@uniroma2.it

Cortical lesion load associates with progression of disability in multiple sclerosis

Cortical inflammatory lesions have been correlated with disability and cortical atrophy in multiple sclerosis. The extent to which cortical lesion load is associated with longer-term physical and cognitive disability in different multiple sclerosis phenotypes has not yet been investigated. Thus, a 5-year prospective longitudinal study was carried on in a large group of patients with multiple sclerosis. Three hundred and twelve consecutive patients suffering from multiple sclerosis (157 relapsing remitting, 35 paediatric, 45 benign, 44 primary progressive and 31 secondary progressive) were enrolled in a 5-year prospective clinical and neuroimaging study. Several magnetic resonance parameters (including cortical lesion number and volume, contrast-enhancing cortical lesions and grey matter atrophy) were analysed to find associations with clinical and cognitive outcomes. Patients with high cortical lesion load had higher Expanded Disability Status Scale increase (median = 1.5; range = 0-3) during the study than both patients with low cortical lesion load (median = 1.0; range = 1-3, P < 0.001) and without cortical lesions (median = 0.5; range = -1 to 2, P < 0.001). Compared with clinically stable patients, 101 (32.4%) patients showing clinical progression at 5 years had the highest rate of cortical lesion accumulation (P < 0.001). Stepwise regression analysis revealed significant and independent contributions from age (β = 0.55), cortical lesion volume (β = 0.58), T(2) white matter lesion volume (β = 0.34) and grey matter fraction (β = 0.42) as predictors (final model with r(2 )= 0.657, P < 0.001) of Expanded Disability Status Scale change. Disease duration (β = 0.52, P < 0.001), cortical lesion volume (β = 0.67, P < 0.001), grey matter fraction (β = 0.56, P < 0.001) and T(2) white matter lesion volume (β = 0.31, P = 0.040) at baseline were found to be independent predictors of cognitive status at the end of the study. While confirming the relevance of cortical pathology in all multiple sclerosis phenotypes, but benign, our study suggests that grey matter and white matter changes in multiple sclerosis occur, at least, partly independently, and that grey matter, more than white matter, damage is associated with physical and cognitive disability progression. Thus, the combination of grey and white matter parameters gives a more comprehensive view of multiple sclerosis pathology and allows a better understanding of the progressive phase of the disease, which, however, seems more related to cortical damage than to subcortical white matter changes.

Dysexecutive syndrome and cerebrovascular disease in non-amnestic mild cognitive impairment: A systematic review of the literature.

ObjectiveNon-amnestic dysexecutive Vascular Mild Cognitive Impairment (VaMCI) may represent preclinical Vascular Dementia (VaD). The aim of this study was to summarize the clinical, neuropsychological and neuroimaging aspects of VaMCI; and to assess its patterns of progression to dementia.MethodsSearches were made in the ISI Web of Knowledge, PubMed and Lilacs databases, using the terms "mild cognitive impairment" and "executive function". Altogether, 944 articles were retrieved.ResultsVaMCI cases had poorer performances on fronto-executive tasks, a higher prevalence of stroke, presence of periventricular and profound white matter hyperintensities on MRI images, as well as more extrapyramidal signs and behavioral symptoms. Executive dysfunction might be associated with disconnection of fronto-parietal-subcortical circuits. Progression to dementia was associated with baseline deficits in executive function, in simple sustained attention and language, and large periventricular WMH.DiscussionVaMCI develops with impairment in non-memory domains and subcortical white matter changes on MRI images, which are consistent with clinical and neuroimaging findings in VaD.

Serial MR Imaging of Adult-Onset Rasmussen's Encephalitis

A 52-year-old woman was referred for a progressive neurological condition which started a year before with continuous irregular twitching of the right facial and arm muscles as well as the tongue and palate, followed by progressive dysphagia, right hemiparesis, ataxia, dysphasia and dysarthria. Though magnetic resonance imaging (MRI) at clinical presentation and a year after were both normal (Figure A1), Rasmussen's encephalitis (RE) was strongly suspected and treatment with corticosteroids and immunoglobulins were begun. A third MRI, two years after onset, revealed mild T2 hyperintense subcortical white matter changes over the left perisylvian region (Figure A) which confirmed our initial suspicion of RE as she now met clinical, electrophysiological and morphological criterias for RE. While waiting for a cerebral biopsy after unsatisfactory response from antiepileptic drugs, corticosteroids and immunoglobulins, her condition markedly worsened less than three years after onset with the sudden occurrence of status epilepticus requiring intubation and continuous infusions of midazolam and propofol.

Reversible Posterior Leukoencephalopathy Syndrome Preceding End Stage Renal Failure as the Initial Presentation of Connective Tissue Disease

Introduction: Reversible posterior leukoencephalopathy syndrome (RPLS) is a rare clinico-radiological entity that has been infrequently reported in patients with connective tissue diseases, particularly in those with established renal involvement. Case report: A 51 year old female presented with headache, confusion, transient loss of vision and seizures. She was found to have elevated blood pressure. Her level of consciousness deteriorated rapidly necessitating mechanical ventilation. Hematological and biochemical investigations were essentially normal. Brain CT scan revealed widespread subcortical white matter changes which were more prominent in the posterior parietal lobes, raising the possibility of RPLS. Vasculitic screen revealed elevated ANA, anti-Ro and anti-La antibody titers. Her blood pressure was controlled with medications and this was followed by improvement in her neurological condition. Two weeks later, she had a brain MRI scan which was essentially normal, confirming the diagnosis of RPLS. Her renal function, however, deteriorated rapidly during her hospital stay and a renal biopsy showed features consistent with the microangiopathic hemolytic uremic syndrome. She progressed to end stage renal failure and was maintained on regular dialysis. Eight months later she successfully received a kidney transplant. Conclusion: RPLS can be the initial presentation in patients with connective tissue diseases, and this possibility should not be overlooked by the physician. Keywords: connective tissue disease, renal failure, reversible posterior leukoencephalopathy, RPLES

Ultrastructural Cutaneous Microvascular Pathology of Young Adults Aged up to 50 Years with Chronic Kidney Disease and Vascular Cognitive Impairment

Background: Studies suggest a link between chronic kidney disease and cognitive impairment. Skin biopsy is hire in the study of leucoaraiosis since permit establish the responsible vascular pathology of subcortical white matter changes because the pathological hallmark is systemic. The aim was to study the ultrastructural changes of cutaneous small vessel of patients aged up to 50 years with chronic kidney disease (CKD) and vascular cognitive impairment (VCI). Methods: Clinical, laboratorial, cerebral imaging, neuropsycological evaluation for executive functions (Clox test), and skin biopsy to 4 patients aged up to 50 years with CKD and VCI were done. Skin biopsy was prepared for conventional transmission electron microscopy study. Results: Clinical diagnosis included hypertension, diabetes, and CKD in all cases. All cases developed VCI in a relatively short period. Small vessels study revealed small vessel disease type-degenerative microangiopathy. The principal findings were increase of wall–lumen ratio, thickened basal membrane, and collagen fibers proliferation. Conclusions: Cutaneous degenerative microangiopathy is matched with cerebral microvascular pathology and could be important for the development of cognitive impairment in young adults with CKD. The characterization of microvascular pathology in skin biopsies, in this type of patients, could contribute to the knowledge of some pathophysiological and therapeutical topics and possibly be useful in clinical setting. Added patients are needed to establish a complete characterization of microangiopathy.