Signal Intensity In White Matter Research Articles

Characterizing the association between complement-mediated TMA and cognitive dysfunction using MRI and neurocognitive assessment

AbstractComplement-mediated thrombotic microangiopathy (CM-TMA) is a rare, life-threatening thrombotic microangiopathy caused by a defect in the alternative complement pathway. It is associated with renal failure and acute encephalopathy, but long-term neurocognitive effects are uncertain. Using magnetic resonance imaging (MRI) and neurocognitive tests, we can further evaluate the long-term neurocognitive complications in CM-TMA and compare them with controls. In this study, we analyzed microstructural changes in the cerebral white matter and neurocognitive testing results of patients with CM-TMA. Seven adult patients with CM-TMA in remission and 6 healthy controls were included. All patients were treated with C5 complement blockade. They were followed-up for 12 months after study entry. All patients had consecutive MRI scans (standard-of-care and quantitative sequences) to assess for white matter changes and concurrent neurocognitive testing. Patients with CM-TMA had increased white matter signal intensity in most regions of the brain compared with controls. This was accompanied by increased depression and neurocognitive dysfunction (impaired concentration, short-term memory, and verbal memory). These findings were also present up to 12 months after the initial study visit. In summary, patients with previous CM-TMA were found to have significant, albeit nonspecific, cerebral white matter abnormalities, with impaired memory and concentration. Larger studies with longitudinal follow-up to assess neurocognitive complications in CM-TMA are required. This trial was registered at Clinical Trials Ontario (ctontario.ca; project ID: 1318).

Gray–white matter contrast reversal on T1-weighted spin-echo in postmortem brain

PurposeThe image contrast of postmortem magnetic resonance imaging (MRI) may differ from that of antemortem MRI because of circulator arrest, changes in postmortem tissue, and low-body-temperature scanning conditions. In fact, we have found that the signal intensity of white matter (WM) on T1-weighted spin-echo (T1WSE) images of the postmortem brain was lower than that of gray matter (GM), which resulted in image contrast reversal between GM and WM relative to the living brain. However, the reason for this phenomenon is unclear. Therefore, the aim of this study is to clarify the reason why image contrast reversal occurs between GM and WM of the postmortem brain. Materials and methodsTwenty-three corpses were included in the study (mean age, 60.6 years; range: 19–60 years; mean rectal temperature at scan, 6.9℃; range: 4–11℃). On a 1.5 T MRI system, postmortem T1W-SE MRI of the brain was conducted in the 23 corpses prior to medico-legal autopsy. Next, T1 and T2 of the GM and WM at the level of the basal ganglia were determined in the same participants using inversion recovery and multiple SE sequences, respectively. The proton density (PD) was also calculated from the T1 and T2 images (in the same slice). ResultsT1W-SE image contrast between the GM and WM of all postmortem brains was inverted relative to the living brain. T1 (579 ms in GM and 307 ms in WM) and PD (64 in GM and 44 in WM) of the postmortem brain decreased compared with the living brain. While T1 of WM/GM remained below 1 even postmortem, the PD of WM/GM decreased. T2 (110 ms in GM and 98 ms in WM) of the postmortem brain did not differ from the living brain. ConclusionThe decrease in PD of WM/GM in the postmortem brain may be the major driver of contrast reversal between the GM and WM relative to the living brain.

The impact of paramagnetic rim lesions on cortical thickness and gray to white matter contrast in relapsing-remitting multiple sclerosis.

Paramagnetic rim lesions (PRLs) on susceptibility magnetic resonance sequences have been suggested as an imaging marker of disease progression in multiple sclerosis. This retrospective cross-sectional study aimed to investigate the impact of PRLs on cortical thickness and gray matter (GM) to white matter (WM) contrast in relapsing-remitting multiple sclerosis (RRMS). A total of 82 RRMS patients (40 patients with at least 1 PRL and 42 patients without PRL) and 43 healthy controls (HC) were included in this study. The T1-weighted images (T1WI) were processed with the FreeSurfer pipeline. GM to WM signal intensity ratio (GWR) was obtained from T1WI by dividing the GM signal intensity by the WM signal intensity for each vertex. Group differences in cortical thickness and GWR were tested on reconstructed cortical surface. Compared to HC, patients with PRL had thinner mean cortical thickness (P<0.001), higher mean GWR (P=0.001), and lower brain structure volumes (cortex volume, P=0.001; WM volume, P<0.001; deep GM volume, P<0.001). Vertex-based analysis found significant cortical thinning in several regions and increased GWR in a wider range of regions in patients with PRL. The two types of clusters had both overlapping regions and independent regions. However, in patients without PRL, only a few regions showed significant cortical thickness changes. Correlation analysis found that in patients with PRL, only PRL volume showed a significant negative correlation with mean cortical thickness (P=0.048), and PRL volume and count, non-PRL count, and total lesion volume were significantly and positively correlated with mean GWR (P<0.05). There were significant changes in cortical thickness, GWR, and brain structure volume in RRMS patients with PRL that may contribute to further understanding of the pathological mechanisms underlying neurological tissue damage.

Decay in Entorhinal White Matter/Gray Matter contrast in Alzheimer’s Disease Patients is reduced by 40Hz sensory stimulation

AbstractBackgroundPrevious research has shown that white matter (WM) and gray matter (GM) tissues exhibit regionally selective pathological changes in Alzheimer’s disease (AD). The contrast between WM and GM signal intensities (WM/GM contrast) measured by magnetic resonance imaging (MRI) has previously been proposed as a method for quantifying these changes. It has been shown that WM/GM contrast can provide sensitive, independent, and distinct information about pathologies compared with traditional MRI measures. Studies have also shown, including entorhinal WM/GM contrast to traditional MRI measures resulted in better discrimination between AD and controls. We previously demonstrated that 40Hz auditory‐visual stimulation therapy reduced WM atrophy and myelin loss in AD patients. The present study quantified the effects of the therapy on the WM/GM contrast in the entorhinal region.MethodThis study used neuroimaging data from Overture, a phase I/II randomized, placebo‐controlled feasibility study (NCT03556280) in patients on the AD spectrum. Treatment group received 40Hz gamma sensory stimulation daily at home for six months, whereas placebo group received sham stimulation. Structural MRI was obtained at baseline, month 3 and month 6 visits using 1.5 Tesla scanner. FreeSurfer was used to process T1 MRI including entorhinal parcellation and cortical reconstructions for 38 participants (66% Treatment, 34% Placebo). For each vertex, WM signal intensity (WMI) is sampled at 1mm below, and GM signal intensity (GMI) is sampled at 30% of cortical thickness above the WM/GM border. WM/GM contrast was calculated as 100*(WMI–GMI)/(0.5*(WMI+GMI)) %. Bayesian linear mixed effects modeling was used to model changes in WM/GM contrast in the entorhinal region.ResultFollowing 6 months of treatment, we observed that the treatment group demonstrated 0.06±0.99% decrease and the placebo group demonstrated 1.26±1.04% decrease in WM/GM contrast (p&lt;0.022).ConclusionWe found that six months of 40Hz gamma sensory therapy reduced the decline in WM/GM contrast in the entorhinal region. Since WM/GM contrast is associated with AD severity, and the entorhinal region is of particular interest in the early stages of AD, early intervention of the therapy may result in enhanced tissue preservation and reduced neurological damage.

Gray to White Matter Signal Ratio as a novel biomarker of neurodegeneration in Alzheimer’s disease

AbstractBackgroundAlzheimer’s disease (AD) is characterized neuropathologically by ß‐amyloid (Aß) plaques, hyperphosphorylated tau neurofibrillary tangles, and neurodegeneration which leads to a phenotypically heterogeneous cognitive‐behavioral dementia syndrome. Our understanding of how these neuropathological and neurodegeneration biomarkers relate to each other is still evolving. A relatively new approach to measuring structural brain change, gray matter to white matter signal intensity ratio (GWR), quantifies the signal contrast between these tissue compartments, and has emerged as a promising marker of AD‐related neurodegeneration. We sought to validate GWR as a novel MRI biomarker of neurodegeneration.MethodTwenty‐nine amyloid‐, tau‐, and neurodegeneration positive patients with atypical syndromes of AD (16 Posterior Cortical Atrophy, 10 logopenic variant of Primary Progressive Aphasia, and 3 Amnestic Dysexecutive phenotype) and 24 amyloid‐negative control participants underwent structural MRI, 11C‐Pittsburgh Compound B (PiB) PET, and 18F‐flortaucipir (FTP) PET scans. Whole‐cortex vertex‐wise general linear models (GLM) were created to identify areas of the cerebral cortex where AD patients showed abnormal signal in each modality, and Pearson’s correlation coefficients were computed to examine the strength of bivariate associations between each pair of modalities at the group level. We then constructed linear mixed‐effects models to test the relative contribution of each non‐FTP modality to explaining the variance in regional FTP uptake.ResultWe found that GWR was associated with cortical thickness, tau PET, and amyloid PET, with GWR showing a larger magnitude of abnormality than cortical thickness. We also found that combining GWR, cortical thickness, and amyloid PET better explained observed tau PET signal than using these modalities alone, suggesting that the three imaging biomarkers contribute independently and synergistically to explaining the variance in the distribution of tau pathology.ConclusionWe conclude that GWR is a uniquely sensitive in vivo marker of neurodegenerative change that reflects pathological mechanisms which may occur prior to cortical atrophy. By using all of these imaging biomarkers of AD together, we may be better able to capture, and possibly predict, AD neuropathologic changes in vivo, which we hope will ultimately contribute to better endpoints to evaluate the efficacy of therapeutic interventions as we move toward an era of disease‐modifying treatments for this devastating disease.

Cortical gray to white matter signal intensity ratio as a sign of neurodegeneration and cognition independent of β-amyloid in dementia.

Cortical gray to white matter signal intensity ratio (GWR) measured from T1-weighted magnetic resonance (MR) images was associated with neurodegeneration and dementia. We characterized topological patterns of GWR during AD pathogenesis and investigated its association with cognitive decline. The study included a cross-sectional dataset and a longitudinal dataset. The cross-sectional dataset included 60 cognitively healthy controls, 61 mild cognitive impairment (MCI), and 63 patients with dementia. The longitudinal dataset included 26 participants who progressed from cognitively normal to dementia and 26 controls that remained cognitively normal. GWR was compared across the cross-sectional groups, adjusted for amyloid PET. The correlation between GWR and cognition performance was also evaluated. The longitudinal dataset was used to investigate GWR alteration during the AD pathogenesis. Dementia with β-amyloid deposition group exhibited the largest area of increased GWR, followed by MCI with β-amyloid deposition, MCI without β-amyloid deposition, and controls. The spatial pattern of GWR-increased regions was not influenced by β-amyloid deposits. Correlation between regional GWR alteration and cognitive decline was only detected among individuals with β-amyloid deposition. GWR showed positive correlation with tau PET in the left supramarginal, lateral occipital gyrus, and right middle frontal cortex. The longitudinal study showed that GWR increased around the fusiform, inferior/superior temporal lobe, and entorhinal cortex in MCI and progressed to larger cortical regions after progression to AD. The spatial pattern of GWR-increased regions was independent of β-amyloid deposits but overlapped with tauopathy. The GWR can serve as a promising biomarker of neurodegeneration in AD.

Double inversion recovery MRI of subcortical band heterotopia and its variations.

Subcortical band heterotopia (SBH) is a malformation of cortical development diagnosed via MRI. Currently, patients with SBH are classified according to Di Donato's classification. We aimed to show a variation of SBH and the usefulness of double inversion recovery (DIR) images. We retrospectively reviewed the MRI findings of 28 patients with SBH. The patients were classified according to Donato's classification by using conventional MR images, and their DIR findings were reviewed. Of 28 patients, 20 were grade 1 and 8 were grade 2 according to Di Donato's classification. In 15 of 28 patients, the following four types of atypical MRI findings were detected: asymmetry distribution (four cases), coexistence of thin and thick SBH (five cases), and DIR faint abnormal signal intensity in subcortical white matter (five cases) and in deep white matter (five cases). The latter two types were detected on DIR alone and have not been reported. Additionally, these were identified only in the mild group (Di Donato's classification 1-1 or 1-2). DIR is a useful MRI sequence for detecting faint white matter signal abnormalities, and it can aid in the accurate classification of SBH and identification of its variations, which may reflect the pathology of SBH.

Stroke-like presentation of acute toxic leukoencephalopathy due to capecitabine treatment with extensive intramyelinic edema.

Stroke-like presentation of acute toxic leukoencephalopathy due to capecitabine treatment with extensive intramyelinic edema.

Diagnostic value of contrast-enhanced 3D FLAIR sequence in acute optic neuritis.

Contrast-enhanced fluid-attenuated inversion recovery (FLAIR) sequence of the brain has the potential for detecting optic nerve abnormality. This study aimed to compare the diagnostic value of whole-brain contrast-enhanced three-dimensional FLAIR with fat suppression (CE 3D FLAIR FS) sequence in detecting acute optic neuritis to dedicated orbit MRI and clinical diagnosis. Twenty-two patients with acute optic neuritis who underwent whole-brain CE-3D-FLAIR FS and dedicated orbit MRI were retrospectively included. The hypersignal FLAIR of the optic nerve on whole-brain CE-3D-FLAIR FS, enhancement, and hypersignal T2W on orbit images were assessed. The optic nerve to frontal white matter signal intensity ratio on CE-FLAIR FS was calculated as maximum signal intensity ratio (SIR) and mean SIR. Twenty-six hypersignals of optic nerves were found on CE-FLAIR FS from 30 pathologic nerves. The sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and accuracy of CE FLAIR FS brain and dedicated orbital images for diagnosing acute optic neuritis were 77%, 93%, 96%, 65%, and 82% and 83%, 93%, 96%, 72%, and 86%, respectively. Optic nerve to frontal white matter SIR of the affected optic nerves was higher than that of normal optic nerves. Using a cutoff maximum SIR of 1.24 and cutoff mean SIR of 1.16, the sensitivity, specificity, PPV, NPV, and accuracy were 93%, 86%, 93%, 80%, and 89% and 93%, 86%, 93%, 86%, and 91%, respectively. The hypersignal of the optic nerve on whole-brain CE 3D FLAIR FS sequence has qualitative and quantitative diagnostic potential in patients with acute optic neuritis.

Light without TORCH: Periventricular Haemorrhage and Group B Streptococcal Meningitis in a Neonate

Post-infectious hydrocephalus is a common entity needing attention of paediatricians and neurosurgeons. Periventricular Haemorrhage (PVH) affects both preterm and term babies. Risk factors include male gender, short gestation, labour and vaginal delivery. Congenital infections such as Toxoplasma and CMV are associated with hydrocephalus and intracranial calcification. We present an unusual association of Group B Streptococcal infection with periventricular haemorrhage. A Caucasian female was born at 37 weeks gestation by normal vaginal delivery. Birth weight was 2.72kg and OFC was 33cm (50th centile). There were no antenatal problems or maternal infections. On day 2 of life, the patient presented with unusual cry, lethargy and reduced feeding. Group B Streptococcal meningitic septicaemia was confirmed with positive CSF and blood cultures. At 7 weeks, she presented with a two-week history of increasing head circumference. Ventriculo Peritoneal (VP) shunt was inserted for post-infectious hydrocephalus. There was difficulty in waking the patient up post-operatively and subsequent CT Brain showed the presence of multiple high attenuation foci in the periventricular region suggestive of haemorrhage or calcification. MR imaging confirmed numerous foci of abnormal signal intensity in the periventricular white matter, most likely blood products. To our knowledge, this is the first report of an association between Group B Streptococcal meningitis and PVH.

Gray to white matter signal ratio as a novel biomarker of neurodegeneration in Alzheimer’s disease

Alzheimer’s disease (AD) is characterized neuropathologically by β-amyloid (Aβ) plaques, hyperphosphorylated tau neurofibrillary tangles, and neurodegeneration, which lead to a phenotypically heterogeneous cognitive-behavioral dementia syndrome. Our understanding of how these neuropathological and neurodegeneration biomarkers relate to each other is still evolving. A relatively new approach to measuring structural brain change, gray matter to white matter signal intensity ratio (GWR), quantifies the signal contrast between these tissue compartments, and has emerged as a promising marker of AD-related neurodegeneration. We sought to validate GWR as a novel MRI biomarker of neurodegeneration in 29 biomarker positive individuals across the atypical syndromic spectrum of AD. Bivariate correlation analyses revealed that GWR was associated with cortical thickness, tau PET, and amyloid PET, with GWR showing a larger magnitude of abnormality than cortical thickness. We also found that combining GWR, cortical thickness, and amyloid PET better explained observed tau PET signal than using these modalities alone, suggesting that the three imaging biomarkers contribute independently and synergistically to explaining the variance in the distribution of tau pathology. We conclude that GWR is a uniquely sensitive in vivo marker of neurodegenerative change that reflects pathological mechanisms which may occur prior to cortical atrophy. By using all of these imaging biomarkers of AD together, we may be better able to capture, and possibly predict, AD neuropathologic changes in vivo. We hope that such an approach will ultimately contribute to better endpoints to evaluate the efficacy of therapeutic interventions as we move toward an era of disease-modifying treatments for this devastating disease.

A-161 Neuropsychological Findings and Atypical Motoric Features Associated with Hashimoto Encephalopathy in a 52-year-old Male

Abstract Objective: Hashimoto encephalopathy (HE) is a rare neurological condition with pathophysiology associated with elevated autoimmune anti-thyroid antibodies. The condition, associated with Hashimoto’s thyroiditis, is found more commonly in women. Clinical presentations of HE vary significantly, with cognitive deficit and generalized seizures as the most prominent manifestations. While there is robust literature illustrating HE in female populations, literature on HE in male patients, particularly with dominant motoric features, remains limited. Methods: A 52-year-old, right-handed, Caucasian male presented for evaluation reporting difficulties with short-term memory, word-finding, disorientation, and motor deficits. The patient exhibited significant motor symptoms including myotonia, micrographia, fasciculations and paresthesias, phantosmia, and myoclonic jerking, beginning in 2017 with progressive decline. Relevant medical history includes Hashimoto thyroiditis (2021), focal temporal EEG abnormalities (2021), dystonia (2021), and migraines. Prior to presenting concerns, the patient was otherwise generally healthy. Neuroimaging (MRI) revealed increased signal intensity in the subcortical white matter of the right frontal lobe. He was dependent in several instrumental activities of daily living. Results: His premorbid baseline was estimated to be in the average range. His neurocognitive profile was marked by mild impairments in immediate and delayed verbal memory and recognition paradigms, whereas he demonstrated moderate impairments in processing speed and motor functioning. Conculsion: Taken together, his neurocognitive profile, clinical history, and functional independence are consistent with the clinical presentation of HE. His cognitive deficits and epileptiform activity are consistent with prominent manifestations of HE, whereas his pronounced motoric features are seemingly aberrant in HE. Furthermore, post-steroidal treatment revealed increased cognitive proficiency on a single mental status examination.

Universal pulses for homogeneous excitation using single channel coils

PurposeUniversal Pulses (UPs) are excitation pulses that reduce the flip angle inhomogeneity in high field MRI systems without subject-specific optimization, originally developed for parallel transmit (PTX) systems at 7 T. We investigated the potential benefits of UPs for single channel (SC) transmit systems at 3 T, which are widely used for clinical and research imaging, and for which flip angle inhomogeneity can still be problematic. MethodsSC-UPs were designed using a spiral nonselective k-space trajectory for brain imaging at 3 T using transmit field maps (B1+) and off-resonance maps (B0) acquired on two different scanner types: a ‘standard’ single channel transmit system and a system with a PTX body coil.The effect of training group size was investigated using data (200 subjects) from the standard system. The PTX system was used to compare SC-UPs to PTX-UPs (15 subjects). In two additional subjects, prospective imaging using SC-UP was studied. ResultsAverage flip angle homogeneity error fell from 9.5 ± 0.5 % for ‘default’ excitation to 3.0 ± 0.6 % using SC-UPs trained over 50 subjects. Performance of the UPs was found to steadily improve as training group size increased, but stabilized after ~15 subjects.On the PTX-enabled system, SC-UPs again outperformed default excitation in simulations (4.8 ± 0.6 % error versus 10.6 ± 0.8 % respectively) though greater homogenization could be achieved with PTX-UPs (3.9 ± 0.6 %) and personalized pulses (SC-PP 3.6 ± 1.0 %, PTX-PP 2.9 ± 0.6 %).MP-RAGE imaging using SC-UP resulted in greater separation between grey and white matter signal intensities than default excitation. ConclusionsSC-UPs can improve excitation homogeneity in standard 3 T systems without further calibration and could be used instead of a default excitation pulse for nonselective neuroimaging at 3 T.

Magnetic resonance imaging findings of two cases with West syndrome and hypomelanosis of Ito with hemimegalencephaly: a report of two cases

BackgroundHemimegalencephaly is an unusual congenital non-familial malformation of the brain which is characterized by enlargement of the whole or part of one hemisphere due to neural proliferation and dysfunction in the cell migration. The brain stem and cerebellum may also be involved. There are also the common cortical malformation, unusual white matter proliferation, gliosis, and abnormal myelination in hemimegalencephaly. In addition, structural brain abnormalities like atrophy/hypertrophy, demyelination, gliosis, increased thickness of the cortical grey matter, increase signal intensity in the subcortical white matter, abnormal gyral patterns, blurring of the grey-white matter transition, and hamartomatous aspect can be observed on magnetic resonance imaging.Case presentationTwo patients who underwent brain magnetic resonance imaging because of West syndrome and hypomelanosis of Ito were diagnosed as hemimegalencephaly. The first case was a 9-day-old male patient initially diagnosed with West syndrome. On the brain magnetic resonance imaging performed for epilepsy, right total hemimegalencephaly, diffuse polymicrogyria, and heterotopic grey matter foci on the right hemisphere were observed. In addition, right cerebellar dysgenesis, upward angulation in the lateral ventricle's anterior horn, and colpocephalic dilatation in the posterior horn were evident. The second case was a 2-year-old female patient with hypomelanosis of Ito disease. The main reason for her parents' hospital visit was the shortness of the right leg. Initial examination showed the hypopigmented lesions on the right side and hemihypertrophy in the left leg. Brain magnetic resonance imaging revealed mild hemimegalencephaly in the right cerebral hemisphere, T1-weighted isointense, T2-weighted hyperintense white matter lesions extending from the basal ganglia to the ventricular body and the periventricular fronto-parieto-occipital white matter, and dilatation of the lateral ventricle.ConclusionsHemimegalencephaly is a rare condition which may accompany syndromic cases with epilepsy or neurocutaneous disease. Brain magnetic resonance imaging should be performed in patients with a suspicious medical history in order to make the correct diagnosis of hemimegalencephaly and to determine the severity of brain involvement, if any.

Optimization of magnetization transfer contrast for EPI FLAIR brain imaging.

To evaluate the impact of magnetization transfer (MT) on brain tissue contrast in turbo-spin-echo (TSE) and EPI fluid-attenuated inversion recovery (FLAIR) images, and to optimize an MT-prepared EPI FLAIR pulse sequence to match the tissue contrast of a clinical reference TSE FLAIR protocol. Five healthy volunteers underwent 3T brain MRI, including single slice TSE FLAIR, multi-slice TSE FLAIR, EPI FLAIR without MT-preparation, and MT-prepared EPI FLAIR with variations of the MT-preparation parameters, including number of preparation pulses, pulse amplitude, and resonance offset. Automated co-registration and gray matter (GM) versus white matter (WM) segmentation was performed using a T1-MPRAGE acquisition, and the GM versus WM signal intensity ratio (contrast ratio) was calculated for each FLAIR acquisition. Without MT preparation, EPI FLAIR showed poor tissue contrast (contrast ratio = 0.98), as did single slice TSE FLAIR. Multi-slice TSE FLAIR provided high tissue contrast (contrast ratio = 1.14). MT-prepared EPI FLAIR closely approximated the contrast of the multi-slice TSE FLAIR images for two combinations of the MT-preparation parameters (contrast ratio = 1.14). Optimized MT-prepared EPI FLAIR provided a 50% reduction in scan time compared to the reference TSE FLAIR acquisition. Optimized MT-prepared EPI FLAIR provides comparable brain tissue contrast to the multi-slice TSE FLAIR images used in clinical practice.

Cortical Gray to White Matter Signal Intensity Ratio as an Early Sign of Cognitive Decline in Alzheimer's Dementia and Mild Cognitive Impairment

Cortical Gray to White Matter Signal Intensity Ratio as an Early Sign of Cognitive Decline in Alzheimer's Dementia and Mild Cognitive Impairment

The relationship between cortical grey to white matter signal contrast (GWC) and tau pathology in atypical AD

AbstractBackgroundGrey to white matter signal intensity ratio (GWC) has been studied as a novel metric of integrity and as a marker of neurodegeneration in Alzheimer’s disease (AD). Regions with reduced GWC co‐localize with regions of cortical atrophy in AD (Salat et al. 2011; Salat et al. 2009). Cortical atrophy in AD robustly colocalizes with tau pathology measured using tau PET ligands (Putcha et al. 2019). For this study, we hypothesized that GWC co‐localizes with tau pathology and shows greater sensitivity to tau pathology than cortical atrophy across the atypical phenotypic spectrum of AD.MethodWe studied 29 amyloid‐positive atypical AD patients, including 16 patients with posterior cortical atrophy (PCA), 10 with logopenic variant primary progressive aphasia (lvPPA), and 3 with an amnestic dysexecutive presentation. Whole‐cortex maps of GWC and cortical atrophy were generated for each individual using FreeSurfer. Tau PET (18F‐Flortaucipir) signal was projected for each individual to the cortical surface using PETsurfer. Eta squared (η2) was computed to determine the spatial overlap of each measure of neurodegeneration (GWC, cortical atrophy) with tau PET signal for each subject and then averaged across the whole group.ResultBoth GWC and cortical atrophy revealed a pattern of neurodegeneration consistent with AD, including in medial parietal, lateral parietal, and posterior lateral temporal cortices. Lower GWC was also observed in several regions beyond the areas of cortical atrophy in patients including in bilateral dorsolateral and dorsomedial prefrontal cortices. Supporting our hypothesis, there was greater spatial overlap between the GWC and tau PET maps (η2 = 0.30) compared to cortical atrophy and tau PET maps (η2 = 0.24; t=4.49, p=0.0001).ConclusionWhile both measures of neurodegeneration (GWC, cortical atrophy) showed a high degree of spatial overlap with tau PET signal across our sample of atypical AD participants, we conclude that GWC, a novel MRI‐derived biomarker of neurodegeneration in AD, correlates more strongly with AD‐related tau neuropathology than traditional cortical atrophy measures. This suggests that GWC could be a sensitive biomarker of AD‐related tissue changes that may represent neuronal injury or neurodegeneration. Further work is needed to establish how GWC tracks with tau pathology over time.

Novel CSF1R variant in adult-onset leukoencephalopathy masquerading as frontotemporal dementia: a follow-up study

ABSTRACT Adult-onset leukoencephalopathy with axonal spheroids and pigmented glia (ALSP) is a rare white matter degenerative disease manifesting as progressive cognitive decline, pyramidal, and extrapyramidal features resulting from mutations in the colony-stimulating factor-1 receptor (CSF1R) gene. We describe a sporadic case of a young man who developed five months history of progressive cognitive decline with predominant neuropsychiatric symptoms, suggestive of frontotemporal dementia. Brain magnetic resonance imaging (MRI) showed bilateral frontotemporal atrophy, high signal intensities in frontal and high parietal deep white matter with persistent diffusion restriction on follow-up imaging. Genetics showed a novel heterozygous mutation in CSF1R gene confirming the diagnosis of ALSP. Being a rare disease, and given its particular adult-onset presentation especially presenile cognitive impairment, it can pose a unique diagnostic challenge. The study highlights the importance of recognizing the disease early and broadens the clinical, genetic, and imaging spectrum of CSF1R gene mutation.

A Full-term Infant with Seizures.

A Full-term Infant with Seizures.

Pons Calcifications and Striatal Necrosis in ADAR1 Aicardi-Goutières Syndrome.

Aicardi-Goutières is an inherited encephalopathy characterized by acquired microcephaly, basal-ganglia calcification, leukodystrophy, cerebral atrophy, and CSF with chronic lymphocytosis and raised interferon-alpha.1 The neuroimage is usually diagnostic, showing basal ganglia and subcortical calcifications on CT and abnormal white matter signal on MRI. The lesions tend to be stable and no treatment is available. A 19-year-old male presented a neurologic condition with pyramidal and extrapyramidal signs associated with cardiomyopathy, livedo, and chilblains that appeared after acute episodes of encephalopathy (age of 2 and 10) precipitated by meningitis vaccine and salmonellosis, followed by neurologic regression and posterior recovering. CT scan (Fig. 1) identified brainstem calcifications (almost confined to the pons), without evident basal ganglia, internal capsule, white matter or dentate nucleus calcifications (faint calcifications could be seen on right putamen). Brain MRI (Fig. 2) showed T2 and T2 FLAIR bilateral hyperintensity on the putamina with atrophy (striatal necrosis), with no white matter signal intensity alterations. The genetic study—WES based gene panel designed for Aicardi-Goutières (including the analysis of MYORG gene)—identified two heterozygous, likely pathogenic, variants in ADAR1 (NM_001111.4:c.577C > G and c.3116A > G). Compound heterozygosity was confirmed by testing both parents, establishing the diagnosis of ADAR1-related Aicardi-Goutières syndrome (Fig. 3). The absence of white matter involvement is described in ADAR1 mutations and further help us to suggest the diagnosis based on image.1, 2 (1) Research Project: A. Conception, B. Organization, C. Execution; (2) Statistical Analysis: A. Design, B. Execution, C. Review and Critique; (3) Manuscript: A. Writing of the First Draft, B. Review and Critique. C.P.: 1A, 1C, 2A A.F.B.: 3B J.F.: 3B M.M.: 1B, 3B The authors confirm that the approval of an institutional review board was not required for this work. The informed consent was waived. We confirm that we have read the Journal's position on issues involved in ethical publication and affirm that this work is consistent with those guidelines. No funding was used for this work. The authors declare no conflict of interest. No financial disclosures for the previous 12 months to declare.