Increase In Radial Diffusivity Research Articles

Severe central nervous system demyelination in Sanfilippo disease.

Chronic progressive neuroinflammation is a hallmark of neurological lysosomal storage diseases, including mucopolysaccharidosis III (MPS III or Sanfilippo disease). Since neuroinflammation is linked to white matter tract pathology, we analyzed axonal myelination and white matter density in the mouse model of MPS IIIC HgsnatP304L and post-mortem brain samples of MPS III patients. Brain and spinal cord tissues of human MPS III patients, 6-month-old HgsnatP304L mice and age- and sex-matching wild type mice were analyzed by immunofluorescence to assess levels of myelin-associated proteins, primary and secondary storage materials, and levels of microgliosis. Corpus callosum (CC) region was studied by transmission electron microscopy to analyze axon myelination and morphology of oligodendrocytes and microglia. Mouse brains were analyzed ex vivo by high-filed MRI using Diffusion Basis Spectrum Imaging in Python-Diffusion tensor imaging algorithms. Analyses of CC and spinal cord tissues by immunohistochemistry revealed substantially reduced levels of myelin-associated proteins including Myelin Basic Protein, Myelin Associated Glycoprotein, and Myelin Oligodendrocyte Glycoprotein. Furthermore, ultrastructural analyses revealed disruption of myelin sheath organization and reduced myelin thickness in the brains of MPS IIIC mice and human MPS IIIC patients compared to healthy controls. Oligodendrocytes (OLs) in the CC of MPS IIIC mice were scarce, while examination of the remaining cells revealed numerous enlarged lysosomes containing heparan sulfate, GM3 ganglioside or "zebra bodies" consistent with accumulation of lipids and myelin fragments. In addition, OLs contained swollen mitochondria with largely dissolved cristae, resembling those previously identified in the dysfunctional neurons of MPS IIIC mice. Ex vivo Diffusion Basis Spectrum Imaging revealed compelling signs of demyelination (26% increase in radial diffusivity) and tissue loss (76% increase in hindered diffusivity) in CC of MPS IIIC mice. Our findings demonstrate an important role for white matter injury in the pathophysiology of MPS III. This study also defines specific parameters and brain regions for MRI analysis and suggests that it may become a crucial non-invasive method to evaluate disease progression and therapeutic response.

49 Longitudinal White Matter Changes in First Time Mild Traumatic Brain Injury in Relationship with Cognitive Performance: A Diffusion Tensor Imaging Study

Objective:The objective of the study was to examine longitudinal changes in the white matter tracts with diffusion tensor imaging (DTI), neuropsychological performance, and the associate between the two in adults with a mild traumatic brain injury (mTBI).Participants and Methods:Sixteen adult patients (age = 38.5(12.8); 75% female) seeking medical care at an emergency department for their first mTBI and 15 healthy adults (age = 30.5(11.3); 33% female) from the community were recruited. DTI and the neuropsychological evaluation were performed at 7 days and 4-months post-injury. The neuropsychological evaluation consisted of the CNS Vital Signs computerized neurocognitive test battery and 2 trials of the Paced Auditory Serial-Addition Test.Results:Results showed a significant decrease in fractional anisotropy (FA) and an increase in radial diffusivity (RD) of the right uncinate fasciculus as well as a significant decrease in FA and axial diffusivity (AD) of the right inferior fronto-occipital fasciculus over the 4-month follow-up period in the mTBI group compared to the Control group.The FA of multiple white matter tracts at baseline were positively associated with working memory, sustained attention, and complex attention at baseline in the mTBI group but not the Control group. The global mean cerebral diffusivity for FA at baseline was positively associated with working memory and sustained attention at 4-months post-injury.Conclusions:The current findings of abnormal white matter suggest an oxidative stress reaction as a result of mTBI altering the diffusivity of some white matter tracts. Furthermore, the disruption of the white matter tracts at baseline may serve as a biomarker for identifying mTBI and those who may have prolonged cognitive difficulties in working memory and attention as a result of the mTBI.

MRI with generalized diffusion encoding reveals damaged white matter in patients previously hospitalized for COVID-19 and with persisting symptoms at follow-up.

There is mounting evidence of the long-term effects of COVID-19 on the central nervous system, with patients experiencing diverse symptoms, often suggesting brain involvement. Conventional brain MRI of these patients shows unspecific patterns, with no clear connection of the symptomatology to brain tissue abnormalities, whereas diffusion tensor studies and volumetric analyses detect measurable changes in the brain after COVID-19. Diffusion MRI exploits the random motion of water molecules to achieve unique sensitivity to structures at the microscopic level, and new sequences employing generalized diffusion encoding provide structural information which are sensitive to intravoxel features. In this observational study, a total of 32 persons were investigated: 16 patients previously hospitalized for COVID-19 with persisting symptoms of post-COVID condition (mean age 60 years: range 41-79, all male) at 7-month follow-up and 16 matched controls, not previously hospitalized for COVID-19, with no post-COVID symptoms (mean age 58 years, range 46-69, 11 males). Standard MRI and generalized diffusion encoding MRI were employed to examine the brain white matter of the subjects. To detect possible group differences, several tissue microstructure descriptors obtainable with the employed diffusion sequence, the fractional anisotropy, mean diffusivity, axial diffusivity, radial diffusivity, microscopic anisotropy, orientational coherence (Cc) and variance in compartment's size (CMD) were analysed using the tract-based spatial statistics framework. The tract-based spatial statistics analysis showed widespread statistically significant differences (P < 0.05, corrected for multiple comparisons using the familywise error rate) in all the considered metrics in the white matter of the patients compared to the controls. Fractional anisotropy, microscopic anisotropy and Cc were lower in the patient group, while axial diffusivity, radial diffusivity, mean diffusivity and CMD were higher. Significant changes in fractional anisotropy, microscopic anisotropy and CMD affected approximately half of the analysed white matter voxels located across all brain lobes, while changes in Cc were mainly found in the occipital parts of the brain. Given the predominant alteration in microscopic anisotropy compared to Cc, the observed changes in diffusion anisotropy are mostly due to loss of local anisotropy, possibly connected to axonal damage, rather than white matter fibre coherence disruption. The increase in radial diffusivity is indicative of demyelination, while the changes in mean diffusivity and CMD are compatible with vasogenic oedema. In summary, these widespread alterations of white matter microstructure are indicative of vasogenic oedema, demyelination and axonal damage. These changes might be a contributing factor to the diversity of central nervous system symptoms that many patients experience after COVID-19.

Multiparametric magnetic resonance imagingfor detection of pathological changes in the central nervous system of a mouse model of multiple sclerosis in vivo.

Multiple sclerosis (MS) is an autoimmune disease involving demyelination and axonal damage in the central nervous system (CNS). In this study, we investigated pathological changes in the lumbar spinal cord of C57BL/6 mice induced with progressive experimental autoimmune encephalomyelitis (EAE) disease using 9.4-T magnetic resonance imaging (MRI). Multiparametric MRI measurements including MR spectroscopy, diffusion tensor imaging (DTI) and volumetric analyses were applied to detect metabolic changes in the CNS of EAE mice. Compared with healthy mice, EAE mice showed a significant reduction in N-acetyl aspartate and increases in choline, glycine, taurine and lactate. DTI revealed a significant reduction in fractional anisotropy and axial diffusivity and an increase in radial diffusivity in the lumbar spinal cord white matter (WM), while in the grey matter (GM), fractional anisotropy increased. High-resolution structural imaging also revealed lumbar spinal cord WM hypertrophy and GM atrophy. Importantly, these MRI changes were strongly correlated with EAE disease scoring and pathological changes in the lumbar (L2-L6), particularly WM demyelination lesions and aggregation of immune cells (microglia/macrophages and astrocytes) in this region. This study identified changes in MRI biomarker signatures that can be useful for evaluating the efficacy of novel drugs using EAE models in vivo.

Machine learning-based prediction of motor status in glioma patients using diffusion MRI metrics along the corticospinal tract

Along tract statistics enables white matter characterization using various diffusion MRI metrics. These diffusion models reveal detailed insights into white matter microstructural changes with development, pathology and function. Here, we aim at assessing the clinical utility of diffusion MRI metrics along the corticospinal tract, investigating whether motor glioma patients can be classified with respect to their motor status. We retrospectively included 116 brain tumour patients suffering from either left or right supratentorial, unilateral World Health Organization Grades II, III and IV gliomas with a mean age of 53.51 ± 16.32 years. Around 37% of patients presented with preoperative motor function deficits according to the Medical Research Council scale. At group level comparison, the highest non-overlapping diffusion MRI differences were detected in the superior portion of the tracts’ profiles. Fractional anisotropy and fibre density decrease, apparent diffusion coefficient axial diffusivity and radial diffusivity increase. To predict motor deficits, we developed a method based on a support vector machine using histogram-based features of diffusion MRI tract profiles (e.g. mean, standard deviation, kurtosis and skewness), following a recursive feature elimination method. Our model achieved high performance (74% sensitivity, 75% specificity, 74% overall accuracy and 77% area under the curve). We found that apparent diffusion coefficient, fractional anisotropy and radial diffusivity contributed more than other features to the model. Incorporating the patient demographics and clinical features such as age, tumour World Health Organization grade, tumour location, gender and resting motor threshold did not affect the model’s performance, revealing that these features were not as effective as microstructural measures. These results shed light on the potential patterns of tumour-related microstructural white matter changes in the prediction of functional deficits.

Alterations in white matter integrity in cognitively stable Down syndrome correlate with plasma neurofilament light chain: Evidence of early myelin breakdown

AbstractBackgroundAlterations in white matter (WM) integrity occur in adults with DS during the early stage of dementia. These changes may be documented by diffusion tensor imaging wherein increases in radial diffusivity (RD), a marker of dysmyelination or myelin breakdown, occur in commissural and limbic pathways in DS. Neurofilament light chain (NfL) is a support protein within large, myelinated axons specifically within the cerebral white matter and is released into blood following axonal damage and is increased in DS. In this study, we evaluated the association between plasma NfL concentrations and RD.MethodThirty cognitively stable adults with DS from the Alzheimer Disease in Down Syndrome (part of the ABC‐DS) study, (18 M, 12 F: mean age 47.1 years SD 5.2 years), underwent DTI and plasma NfL concentration measurements. Plasma NfL was assayed using the Simoa platform. Diffusion MRI connectometry was conducted using q‐space diffeomorphic reconstruction and a multiple regression model to assess the associations between plasma NfL and white matter radial diffusivity (RD). The Spearman correlation coefficient, and its 95% confidence interval (CI), was used to quantify the monotonic association between plasma NfL and RD.ResultConsistent with our hypothesis, we found positive associations between plasma NfL and RD increases, in several WM higher order association tracts, including the corpus callosum (0.46, 95% CI 0.11‐0.70, p=0.012), the cingulum bundle (L: 0.62, 0.34‐0.80, p&lt;0.001; R: 0.54 0.23‐0.76, p=0.002) and the uncinate fasciculus (L: 0.17, ‐0.20‐0.50, p=0.367; R: 0.51, 0.18‐0.73, p=0.004).ConclusionOur findings support an important link between alterations in WM myelin integrity, particularly of higher order association areas, and axonal degeneration in cognitively stable adults with Down syndrome. These findings support an important role of WM alterations in adults with DS who are at risk for and who develop AD earlier than in sporadic AD cases. WM might provide an important and novel target for intervention. Additional research is needed to understand the underlying neuropathological processes, including the potential contribution of neuronal dysfunction and/or loss to our findings. Acknowledgements: NIH grant U01AG051412. We are grateful to our participants, families, the agencies serving individuals with ID, and our dedicated staff.

Impairment and Plasticity of Language-Related White Matter in Patients With Brain Arteriovenous Malformations

Language dysfunction is rarely seen in patients with unruptured brain arteriovenous malformation (AVM) albeit the AVM nidus involving language areas, which provides a unique disease model to study language reorganization. The objective of this study was to investigate the impairment and reorganization patterns and characteristics of language-related white matter in AVMs located at different brain areas. Thirty-three patients with AVMs involving language areas were prospectively enrolled. Patients were categorized into 3 groups according to the lesion locations: the frontal (14 patients), temporal (15 patients), and parietal groups (4 patients). Thirty age- and sex-matched healthy controls were enrolled as comparison. All participants underwent diffusion tensor imaging scans, and automated fiber quantification method was applied to quantitatively study the difference of segmented language-related white matter connectivity between 3 AVM groups and control group. Language functions were normal in all subjects according to Western Aphasia Battery test. In the frontal group, fractional anisotropy (FA) value decreased in the left arcuate fascicle and increased in left superior longitudinal fasciculus and uncinate fascicle; in the temporal group, FA values decreased in left inferior fronto-occipital fascicle and inferior longitudinal fascicle and increased in right anterior thalamic radiation and uncinate fascicle; in the parietal group, FA values decreased in left arcuate fascicle and inferior longitudinal fascicle and increased in bilateral anterior thalamic radiations and uncinate fascicles and right inferior fronto-occipital fascicle. In fascicles with decreased FA values, the increase of radial diffusivity was common, and fascicles with increased FA values usually presented along with increased axial diffusivity values. Remodeling of language-related white matter occurs when traditional language areas are involved by AVM nidus, and its reorganization patterns vary with locations of AVM nidus. Fascicle impairment is mainly caused by the myelin deficits, and its plasticity may be dominated by the axon remodeling procedure.

Expansion of chronic MS lesions is associated with an increase of radial diffusivity in periplaque white matter

Background: Expansion of chronic multiple sclerosis (MS) lesion is associated with slow-burning inflammation at lesion rim. However, the underlying mechanisms leading to expansion are not fully understood. Objective: To investigate the relationship between diffusivity markers of demyelination and axonal loss in perilesional white matter and lesion expansion in relapsing-remitting MS (RRMS). Methods: T1, FLAIR and diffusion tensor images were acquired from 30 patients. Novel single-streamline technique was used to estimate diffusivity in lesions, perilesional white matter and normal-appearing white matter (NAWM). Results: Significant association was found between baseline periplaque radial diffusivity (RD) and subsequent lesion expansion. Conversely, periplaque axial diffusivity (AD) did not correlate with lesion growth. Baseline RD (but not AD) in periplaque white matter of expanding lesions was significantly higher compared with non-expanding lesions. Correlation between increase of both RD and AD in the periplaque area during follow-up period and lesion expansion was noticeably stronger for RD. Increase of RD in periplaque area was also much higher compared to AD. There was significant increase of AD and RD in the periplaque area of expanding, but not in non-expanding, lesions. Conclusion: Periplaque demyelination is likely to be an initial step in a process of lesion expansion and, as such, potentially represents a suitable target for remyelinating therapies.

Empty Sella Syndrome as a Window Into the Neuroprotective Effects of Prolactin.

Background: The goal of this study was to relate diffusion MR measures of white matter integrity of the retinofugal visual pathway with prolactin levels in a patient with downward herniation of the optic chiasm secondary to medical treatment of a prolactinoma.Methods: A 36-year-old woman with a prolactinoma presented with progressive bilateral visual field defects 9 years after initial diagnosis and medical treatment. She was diagnosed with empty-sella syndrome and instructed to stop cabergoline. Hormone testing was conducted in tandem with routine clinical evaluations over 1 year and the patient was followed with diffusion magnetic resonance imaging (dMRI), optical coherence tomography (OCT), and automated perimetry at three time points. Five healthy controls underwent a complementary battery of clinical and neuroimaging tests at a single time point.Results: Shortly after discontinuing cabergoline, diffusion metrics in the optic tracts were within the range of values observed in healthy controls. However, following a brief period where the patient resumed cabergoline (of her own volition), there was a decrease in serum prolactin with a corresponding decrease in visual ability and increase in radial diffusivity (p < 0.001). Those measures again returned to their baseline ranges after discontinuing cabergoline a second time.Conclusions: These results demonstrate the sensitivity of dMRI to detect rapid and functionally significant microstructural changes in white matter tracts secondary to alterations in serum prolactin levels. The inverse relations between prolactin and measures of white matter integrity and visual function are consistent with the hypothesis that prolactin can play a neuroprotective role in the injured nervous system.

Subclinical post-traumatic stress symptomology and brain structure in youth with chronic headaches

Background/aimsPost-traumatic stress symptoms (PTSS) and chronic pain often co-occur at high rates in youth. PTSS may alter brain structure thereby contributing to headache chronicity. This study examined whether PTSS and altered limbic circuitry were associated with headache frequency in youth. MethodsThirty youth aged 10–18 years with chronic headaches and 30 age- and sex-matched controls underwent a 3T MRI scan. Volumes of the hippocampus and amygdala were obtained from T1-weighted images. Mean fractional anisotropy (FA, an index of white matter structure) axial and radial diffusivity values of the cingulum and uncinate fasciculus were extracted from diffusion-weighted images. Youth reported on their headaches daily, for one-month, and self-reported pubertal status, emotion regulation, adverse childhood experiences (ACEs) and PTSS using validated measures. Volumes of the hippocampus and amygdala and diffusivity values of the cingulum and uncinate were compared between patients and controls. Hierarchical linear regressions were used to examine the association between PTSS, subcortical volumes and/or diffusivity values and headache frequency. ResultsMean FA values of the cingulum were higher in patients compared to controls (P = 0.02, Cohen’s d = 0.69). Greater PTSS (P = 0.04), smaller amygdala volumes (P = 0.01) and lower FA of the cingulum (P = 0.04) were associated with greater headache frequency, after accounting for age, puberty, pain duration, emotion regulation, and ACEs (Adjusted R2 ≥ 0.15). Headache frequency was associated with increases in radial diffusivity (P = 0.002, Adjusted R2 = 0.59), as opposed to axial diffusivity (n.s.). ConclusionsPTSS, smaller amygdalar volume, and poorer cingulum structural connectivity were associated with headache frequency in youth, and may underlie headache chronicity.

Altered microstructural pattern of white matter in Cushing’s disease identified by automated fiber quantification

A growing body of evidence suggests that altered brain structure plays a crucial role in the pathogenesis of neuropsychological abnormalities induced by hypercortisolism in patients with Cushing’s disease. While most studies mainly focus on gray matter, white matter structure has been largely overlooked. In the current study, we conducted a cross-sectional diffusion tensor imaging study on 58 patients with Cushing’s disease and 54 matched healthy individuals to profile the microstructural pattern using automated fiber quantification and investigate its association with neuroendocrine and neuropsychological deficits. The study revealed that microstructural pattern showed a widespread mean diffusivity, radial diffusivity increase, fractional anisotropy decrease and partial axial diffusivity increase among tracts notably in corpus callosum forceps, inferior fronto-occipital fasciculus, inferior longitudinal fasciculus, superior longitudinal fasciculus, uncinate fasciculus and arcuate fasciculus, while within the same tract abnormalities localized to specific positions. Moreover, compromised microstructural pattern of white matter in specific tracts and locations along the trajectory were associated with ACTH and cortisol concentration and cognitive decline in patients with Cushing’s disease. Collectively, our study elucidates the form of white matter pathology induced by hypercortisolism and its association with cognitive decline which may provide further targets for early identification and intervention of Cushing’s disease.

Simvastatin maintains white matter integrity in healthy middle‐aged adults with increased risk for Alzheimer’s disease: A secondary analysis of a randomized controlled trial

AbstractBackgroundThe brain is the most cholesterol‐rich organ and myelin contains 70% of total brain cholesterol. Statins are potent cholesterol‐lowing medications used by millions of adults for prevention of cerebrovascular disease, yet the effect of statins on cholesterol‐rich brain white matter (WM) is largely unknown. In this study, diffusion tensor imaging (DTI) data collected during an 18‐month randomized controlled trial in healthy middle‐aged adults with a parental family history of Alzheimer’s disease (ClinicalTrial.gov NCT00939822) was used to determine the effect of simvastatin (40mg/daily) on WM integrity.Method73 participants were randomly assigned to drug or placebo (placebo group: N=38, baseline age 55.7±8.0yrs, 76.3% female; simvastatin group: N=35, baseline age 56.7±6.3yrs, 68.6% female) and underwent MRI (T1‐weighted, T2FLAIR, and DTI at baseline, 6m, 12m, and 18m). DTI parameter maps were used for longitudinal WM microstructure and tract‐based spatial statistics analyses. Total gray matter (GM), WM, and WM hyperintensity (WMH) volumes were calculated from T1‐weighted and T2FLAIR imaging. ANCOVA models (covariates: age, sex, APOE4‐genotype) tested the effect of treatment group on percent change in neuroimaging measures at each study visit. Model‐based path analysis tested whether the effects of simvastatin on WM microstructure were mediated by change in serum total cholesterol (TC) levels.ResultThere were no differences in baseline neuroimaging measures between treatment groups. At 18 months, the simvastatin group showed significantly attenuated decline in fractional anisotropy (FA) and attenuated increase in radial diffusivity (RD) in total WM relative to the placebo group (Fig1). At 12 and 18 months, the simvastatin group showed preserved WM volume relative the placebo group, but no differences in GM or WMH volume (Fig2). Approximately 30% of the effect of simvastatin on change in WM microstructure was mediated by change in serum TC (Fig3).Conclusion18 months of simvastatin use in statin‐naïve middle‐aged adults resulted in preserved WM microstructure and volume compared to placebo, suggestive of a potential protective effect of simvastatin on WM. Changes in FA and RD (but not axial diffusivity) suggest simvastatin‐induced alterations in myelin content, and partial mediation by change in serum TC suggests pleotropic effects of simvastatin on WM.

White matter pathology in patients with borderline personality disorder: A review of controlled DTI studies.

Neuroimaging, especially diffusion tensor imaging (DTI), has emerged as a helpful tool in assessing and characterizing white matter (WM) integrity. The resultant early treatment from early diagnosis is crucial because treatment is often more efficacious. Borderline personality disorder (BPD) is a challenging disorder to diagnose and treat, and has been reported to have various neurobiologic abnormalities. We conducted a search of the literature to review WM pathology findings in BPD. A search was conducted to identify systematic reviews and meta-analyses published from January 2000 to September 2019 that assessed WM integrity in BPD. Four studies were included. One study demonstrated no difference in WM between BPD and healthy controls. Another study found decreased fractional anisotropy (FA) within the corpus callosum (CC) and orbitofrontal regions. A subsequent randomized controlled trial reported a decrease in FA within the fornix, CC, and right superior/anterior corona radiata with associated increase in radial diffusivity in the left anterior thalamic radiation. The fourth study found a decrease in the axial diffusivity within the cingulum, inferior longitudinal fasciculus, and inferior frontoccipital fasciculus. Our review concludes that BPD is associated with measurable WM pathology. Methods such as DTI might emerge as useful tools in the management of BPD. More controlled studies are needed to validate our conclusions.

Diffusion tensor imaging in borderline personality disorder showing prefrontal white matter alterations

Borderline personality disorder (BPD) has repeatedly been linked to alterations in fronto-limbic dysfunction. In this study, we tested the hypothesis of disturbed structural connectivity in underlying fibre tracts and their relation to symptom profiles. We analysed diffusion tensor imaging (DTI) data from 18 female BPD patients and 38 female healthy controls. Group comparisons showed significant (p < .05, FDR adjusted) increase of radial diffusivity (RD) in the right frontal lobe, including the uncinate fasciculus, anterior thalamic radiation, and inferior fronto-occipital fasciculus, as well as overall apparent diffusion coefficient (ADC) increases in the anterior and posterior internal capsule. Symptom correlations, based on the BSL-95 questionnaires, within the BPD sample showed significant negative correlations of dysphoria with ADC the left and right anterior thalamic radiation, and positive correlations of fractional anisotropy with self-perception scores in the right superior corona radiata. While our findings add to the fronto-limbic dysfunction model of BPD, they provide additional evidence of links to its affective core pathology, particularly frontotemporal and fronto-thalamic systems.

A preliminary examination of the relationship between biomechanical measures and structural changes in the brain

Introduction Currently, biomechanics has not been able to effectively predict when a mild traumatic brain injury may occur as a result of head impact. To improve prediction of brain trauma and the development of protective innovations, it is important to create an understanding of the relationship between the biomechanics of the head impact event and the structural damage incurred by the brain as a result of that event. The purpose of this research was to examine the relationship between diffusion tensor imaging measures and biomechanical characteristics of a head impact. Methods Diffusion tensor imaging was conducted on concussed subjects to identify regions of white matter structural differences. The injury event was reconstructed using physical and finite element methods to identify the biomechanical parameters of the impact as well as strain to the regions of the brain. Results A significant relationship was found between shear strain, rotational acceleration, and impact velocity on increases in radial diffusivity and mean diffusivity in the fornix. Linear acceleration was also found to have a weaker but significant relationship with a decrease in radial diffusivity in the cingulum hippocampus. Conclusion These results demonstrate that impacts resulting in high shear strains may affect radial diffusivity and mean diffusivity measures, and that impact mechanics likely have an important role in what regions may present differences in diffusion tensor imaging measures.

Altered integrity of corpus callosum in generalized epilepsy in relation to seizure lateralization after corpus callosotomy.

Generalized-onset seizures are usually conceptualized as engaging bilaterally distributed networks with no clear focus. However, the authors previously reported a case series demonstrating that in some patients with generalized-onset seizures, focal seizure onset could be discovered after corpus callosotomy. The corpus callosum is considered to be a major pathway for seizure generalization in this group of patients. The authors hypothesized that, in patients with generalized-onset seizures, the structure of the corpus callosum could be different between patients who have lateralized seizures and those who have nonlateralized seizures after corpus callosotomy. The authors aimed to evaluate the structural difference through statistical analysis of diffusion tensor imaging (DTI) scalars between these two groups of patients. Thirty-two patients diagnosed with generalized-onset motor seizures and without an MRI lesion were included in this study. Among them, 16 patients developed lateralized epileptic activities after corpus callosotomy, and the remaining 16 patients continued to have nonlateralized seizures after corpus callosotomy. Presurgical DTI studies were acquired to quantify the structural integrity of the corpus callosum. The DTI analysis showed significant reduction of fractional anisotropy (FA) and increase in radial diffusivity (RD) in the body of the corpus callosum in the lateralized group compared with the nonlateralized group. The authors' findings indicate the existence of different configurations of bilateral epileptic networks in generalized epilepsy. Generalized seizures with focal onset relying on rapid spread through the corpus callosum might cause more structural damage related to demyelination in the corpus callosum, showing reduced FA and increased RD. This study suggests that presurgical DTI analysis of the corpus callosum might predict the seizure lateralization after corpus callosotomy.

Re-emergent tremor in patients with Parkinson’s disease: an imaging study

BACKGROUND AND PURPOSE: Re-emergent tremor (ReT) is the tremor that reappears after a variable period of latency while maintaining posture. Little is known about the mechanisms that contribute to the origin of this silent period (SP). Our aim was to compare the imaging characteristics of patients with and without ReT and find the structural correlate of SP if any. MATERIALS AND METHODS: Fifteen patients with ReT (Group 1) and eighteen patients without ReT (patients with rest tremor and postural tremor, but no latency) were evaluated clinically, electrophysiologically, with diffusion tensor imaging (DTI) and voxel-based morphometry (VBM). DTI parameters of different regions of interest were analyzed and compared with that of 37 healthy age- and gender-matched controls. RESULTS: No statistically significant difference was observed between the two groups in terms of age, duration of disease, levodopa equivalent dose, or severity of the disease. However, in the left supplementary motor area (SMA), there was a significant reduction of fractional anisotropy and an increase of radial diffusivity and mean diffusivity in patients with ReT (Group 1) as compared to patients without ReT (Group 2) and healthy controls. The results of the VBM analysis were not significant. CONCLUSION: The presence of abnormality of SMA suggests that patients with ReT have a different pathophysiological mechanism as compared to patients without ReT. This is a novel finding implicating a possible contribution of the frontal lobe to the genesis of SP in ReT. ReT could be a distinct clinical entity within the tremor dominant subtype.

Daily profile of arterial pressure and brain microstructural changes in patients with hypertension-related cerebral small vessel disease

Introduction. Application of modern antihypertensive medications has improved the course of arterial hypertension (AH), but has not led to the expected decrease in small vessel disease (SVD) incidence and its complications. This fact encourages further investigation of hypertension-related mechanisms of brain damage. Objective: to study the relation between daily profile of blood pressure and brain microstructure changes in patients with both SVD and AH. Material and methods. The study included 64 patients (38 – 59.4%) female, mean age 59.4±5.4 years) with both SVD and AH. Ambulatory blood pressure monitoring and diffusion-tensor MRI were obtained for all participants. The relation between studied parameters was estimated using the multivariate statistical analysis method – linear regression analysis. Results. Сhanges in daily profile of blood pressure according to ambulatory blood pressure monitoring data was associated with microstructure abnormalities of the juxtacortical white matter hyperintensities (jWMH) of anterior frontal lobes, temporal-parietal regions and left posterior cingulate cortex. An increase and variability of diastolic blood pressure were of primary importance in brain microstructural damage in mentioned areas leading to mean diffusivity and radial diffusivity increase. Conclusion. The revealed relation between daily profile of blood pressure and brain microstructural changes indicating increase of free water diffusivity and myelin damage in jWMH and posterior cingulate cortex corresponds to the experimental data on the breakdown of the autoregulation reaction in cortex arteries and further increase of brain-blood barrier permeability with descending vasogenic edema in brain damage in hypertensive patients. An increase and variability of diastolic blood pressure have primary importance to microstructural damage of white matter in patients with SVD receiving antihypertensive treatment.

Demyelination precedes axonal loss in the transneuronal spread of human neurodegenerative disease.

The spread of neurodegeneration through the human brain network is reported as underlying the progression of neurodegenerative disorders. However, the exact mechanisms remain unknown. The human visual pathway is characterized by its unique hierarchical architecture and, therefore, represents an ideal model to study trans-synaptic degeneration, in contrast to the complexity in neural connectivity of the whole brain. Here we show in two specifically selected patient cohorts, including (i) glaucoma patients with symmetrical bilateral hemifield defects respecting the horizontal meridian (n = 25, 14 females, 64.8 ± 10.1 years; versus 13 normal controls with similar age/sex distributions); and (ii) multiple sclerosis patients without optic radiation lesions (to avoid potential effects of lesions on diffusivity measures) (n = 30, 25 females, 37.9 ± 10.8 years; versus 20 controls), that there are measurable topographic changes in the posterior visual pathways corresponding to the primary optic nerve defects. A significant anisotropic increase of water diffusion was detected in both patient cohorts in the optic radiations, characterized by changes in perpendicular (radial) diffusivity (a measure of myelin integrity) that extended more posteriorly than those observed in parallel (axial) diffusivity (reflecting axonal integrity). In glaucoma, which is not considered a demyelinating disease, the observed increase in radial diffusivity within the optic radiations was validated by topographically linked delay of visual evoked potential latency, a functional measure of demyelination. Radial diffusivity change in the optic radiations was also associated with an asymmetrical reduction in the thickness of the calcarine cortex in glaucoma. In addition, 3 years longitudinal observation of the multiple sclerosis patient cohort revealed an anterograde increase of radial diffusivity in the anterior part of optic radiations which again was retinotopically associated with the primary damage caused by optic neuritis. Finally, in an animal model of optic nerve injury, we observed early glial activation and demyelination in the posterior visual projections, evidenced by the presence of myelin-laden macrophages. This occurred prior to the appearance of amyloid precursor protein accumulation, an indicator of disrupted fast axonal transport. This study demonstrated strong topographical spread of neurodegeneration along recognized neural projections and showed that myelin and glial pathology precedes axonal loss in the process, suggesting that the mechanism of trans-synaptic damage may be at least partially mediated by glial components at the cellular level. The findings may have broad biological and therapeutic implications for other neurodegenerative disorders.

Pathological Insights From Quantitative Susceptibility Mapping and Diffusion Tensor Imaging in Ice Hockey Players Pre and Post-concussion.

Myelin sensitive MRI techniques, such as diffusion tensor imaging and myelin water imaging, have previously been used to reveal changes in myelin after sports-related concussions. What is not clear from these studies, however, is how myelin is affected: whether it becomes degraded and possibly removed, or whether the myelin sheath loosens and becomes “decompacted”. Previously, our team revealed myelin specific changes in ice hockey players 2 weeks post-concussion using myelin water imaging. In that study, 45 subjects underwent a pre-season baseline scan, 11 of which sustained a concussion during play and received follow-up scans: eight were scanned within 3 days, 10 were scanned at 14 days, and nine were scanned at 60 days. In the current retrospective analysis, we used quantitative susceptibility mapping, along with the diffusion tensor imaging measures axial diffusivity and radial diffusivity, to investigate this myelin disruption. If sports-related concussive hits lead to myelin fragmentation in regions of lowered MWF, this should result in a measurable increase in magnetic susceptibility, due to the anisotropic myelin fragmenting into isotropic myelin debris, and the diamagnetic myelin tissue being removed, while no such changes should be expected if the myelin sheath simply loosens and becomes decompacted. An increase in radial diffusivity would likewise reveal myelin fragmentation, as myelin sheaths block water diffusion out of the axon, with little to no changes expected for myelin sheath loosening. Statistical analysis of the same voxels-of-interest that were found to have reduced myelin water fraction 2 weeks post-concussion, revealed no statistically significant changes in magnetic susceptibility, axial diffusivity, or radial diffusivity at any time-point post-concussion. This suggests that myelin water fraction changes are likely due to a loosening of the myelin sheath structure, as opposed to fragmentation and removal of myelin debris.