White Matter Atrophy Research Articles

Transient increase in CSF GAP-43 concentration after ischemic stroke

BackgroundCerebrospinal fluid (CSF) biomarkers reflect ongoing processes in the brain. Growth-associated protein 43 (GAP-43) is highly upregulated in brain tissue shortly after experimental ischemia suggesting the CSF GAP-43 concentration may be altered in ischemic brain disorders. CSF GAP-43 concentration is elevated in Alzheimer’s disease patients; however, patients suffering from stroke have not been studied previously.MethodsThe concentration of GAP-43 was measured in longitudinal CSF samples from 28 stroke patients prospectively collected on days 0–1, 2–4, 7–9, 3 weeks, and 3–5 months after ischemia and cross-sectionally in 19 controls. The stroke patients were clinically evaluated using a stroke severity score system. The extent of the brain lesion, including injury size and degrees of white matter lesions and atrophy were evaluated by CT and magnetic resonance imaging.ResultsIncreased GAP-43 concentration was detected from day 7–9 to 3 weeks after stroke, compared to day 1–4 and to levels in the control group (P = 0.02 and P = 0.007). At 3–5 months after stroke GAP-43 returned to admission levels. The initial increase in GAP-43 during the nine first days was associated to stroke severity, the degree of white matter lesions and atrophy and correlated positively with infarct size (rs = 0.65, P = 0.001).ConclusionsThe transient increase of CSF GAP-43 is important to take into account when used as a biomarker for other neurodegenerative diseases such as Alzheimer’s disease. Furthermore, GAP-43 may be a marker of neuronal responses after stroke and additional studies confirming the potential of CSF GAP-43 to reflect severity and outcome of stroke in larger cohorts are warranted.

Measurement of spinal cord atrophy using phase sensitive inversion recovery (PSIR) imaging in motor neuron disease.

BackgroundThe spectrum of motor neuron disease (MND) includes numerous phenotypes with various life expectancies. The degree of upper and lower motor neuron involvement can impact prognosis. Phase sensitive inversion recovery (PSIR) imaging has been shown to detect in vivo gray matter (GM) and white matter (WM) atrophy in the spinal cord of other patient populations but has not been explored in MND.MethodsIn this study, total cord, WM and GM areas of ten patients with a diagnosis within the MND spectrum were compared to those of ten healthy controls (HC). Patients’ diagnosis included amyotrophic lateral sclerosis (ALS), primary lateral sclerosis, primary muscular atrophy, facial onset sensory and motor neuronopathy and ALS-Frontotemporal dementia. Axial 2D PSIR images were acquired at four cervical disc levels (C2-C3, C3-C4, C5-C6 and C7-T1) with a short acquisition time (2 minutes) protocol. Total cross-sectional areas (TCA), GM and WM areas were measured using a combination of highly reliable manual and semi-automated methods. Cord areas in MND patients were compared with HC using linear regression analyses adjusted for age and sex. Correlation of WM and GM areas in MND patients was explored to gain insights into underlying atrophy patterns.ResultsMND patients as a group had significantly smaller cervical cord GM area compared to HC at all four levels (C2-C3: p = .009; C3-C4: p = .001; C5-C6: p = .006; C7-T1: p = .002). WM area at C5-C6 level was significantly smaller (p = .001). TCA was significantly smaller at C3-C4 (p = .018) and C5-C6 (p = .002). No significant GM and WM atrophy was detected in the two patients with predominantly bulbar phenotype. Concomitant GM and WM atrophy was detected in solely upper or lower motor neuron level phenotypes. There was a significant correlation between GM and WM areas at all four levels in this diverse population of MND.ConclusionSpinal cord GM and WM atrophy can be detected in vivo in patients within the MND spectrum using a short acquisition time 2D PSIR imaging protocol. PSIR imaging shows promise as a method for quantifying spinal cord involvement and thus may be useful for diagnosis, prognosis and for monitoring disease progression.

The Shrinking Brain: Cerebral Atrophy Following Traumatic Brain Injury

Cerebral atrophy in response to traumatic brain injury is a well-documented phenomenon in both primary investigations and review articles. Recent atrophy studies focus on exploring the region-specific patterns of cerebral atrophy; yet, there is no study that analyzes and synthesizes the emerging atrophy patterns in a single comprehensive review. Here we attempt to fill this gap in our current knowledge by integrating the current literature into a cohesive theory of preferential brain tissue loss and by identifying common risk factors for accelerated atrophy progression. Our review reveals that observations for mild traumatic brain injury remain inconclusive, whereas observations for moderate-to-severe traumatic brain injury converge towards robust patterns: brain tissue loss is on the order of 5% per year, and occurs in the form of generalized atrophy, across the entire brain, or focal atrophy, in specific brain regions. The most common regions of focal atrophy are the thalamus, hippocampus, and cerebellum in gray matter and the corpus callosum, corona radiata, and brainstem in white matter. We illustrate the differences of generalized and focal gray and white matter atrophy on emerging deformation and stress profiles across the whole brain using computational simulation. The characteristic features of our atrophy simulations—a widening of the cortical sulci, a gradual enlargement of the ventricles, and a pronounced cortical thinning—agree well with clinical observations. Understanding region-specific atrophy patterns in response to traumatic brain injury has significant implications in modeling, simulating, and predicting injury outcomes. Computational modeling of brain atrophy could open new strategies for physicians to make informed decisions for whom, how, and when to administer pharmaceutical treatment to manage the chronic loss of brain structure and function.

Local Injection of Endothelin-1 in the Early Neonatal Rat Brain Models Ischemic Damage Associated with Motor Impairment and Diffuse Loss in Brain Volume

Cerebral palsy is an irreversible movement disorder resulting from cerebral damage sustained during prenatal or neonatal brain development. As survival outcomes for preterm injury improve, there is increasing need to model ischemic injury at earlier neonatal time-points to better understand the subsequent pathological consequences. Here we demonstrate a novel neonatal ischemic model using focal administration of the potent vasoconstrictor peptide, endothelin-1 (ET-1), in newborn rats. The functional and histopathological outcomes compare favourably to those reported following the widely used hypoxic ischemia (HI) model. These include a robust motor deficit sustained into adulthood and recapitulation of hallmark features of preterm human brain injury, including atrophy of subcortical white matter and periventricular fiber bundles. Compared to procedures involving carotid artery manipulation and periods of hypoxia, the ET-1 ischemia model represents a rapid and technically simplified model more amenable to larger cohorts and with the potential to direct the locus of ischemic damage to specific brain areas.

Novel Homozygous Mutation of the AIMP1 Gene: A Milder Neuroimaging Phenotype With Preservation of the Deep White Matter

BackgroundMutations in AIMP1, which plays an important role in the development and maintenance of axon-cytoskeleton integrity and regulating neurofilaments, cause neurodegeneration of variable severity and white matter abnormalities. MethodsFrom the patient records we analyzed the clinical evaluation, molecular genetics, neurodiagnostic, and neuroradiological investigations. ResultsWe describe six members of a large consanguineous family with a phenotype of severe neurodegeneration in the form of developmental delays, progressive microcephaly, epilepsy, and failure to thrive. MRI showed callosal atrophy and T2 hyperintensity in the superficial white matter. The periventricular and deep white matter structures were, however, preserved. MR spectroscopy demonstrated N-acetylaspartate preservation without evidence of neuroinflammation. Exome sequencing showed a novel homozygous mutation of the AIMP1 gene in all individuals: c.917A>G (p.(Asp306Gly)). ConclusionsThis novel homozygous mutation of the AIMP1 gene is characterized by preserved development of the periventricular and deep white matter structures as demonstrated by MRI and MR spectroscopy correlation.

Tensor-based morphometry using scalar and directional information of diffusion tensor MRI data (DTBM): Application to hereditary spastic paraplegia.

Tensor-based morphometry (TBM) performed using T1-weighted images (T1WIs) is a well-established method for analyzing local morphological changes occurring in the brain due to normal aging and disease. However, in white matter regions that appear homogeneous on T1WIs, T1W-TBM may be inadequate for detecting changes that affect specific pathways. In these regions, diffusion tensor MRI (DTI) can identify white matter pathways on the basis of their different anisotropy and orientation. In this study, we propose performing TBM using deformation fields constructed using all scalar and directional information provided by the diffusion tensor (DTBM) with the goal of increasing sensitivity in detecting morphological abnormalities of specific white matter pathways. Previously, mostly fractional anisotropy (FA) has been used to drive registration in diffusion MRI-based TBM (FA-TBM). However, FA does not have the directional information that the tensors contain, therefore, the registration based on tensors provides better alignment of brain structures and better localization of volume change. We compare our DTBM method to both T1W-TBM and FA-TBM in investigating differences in brain morphology between patients with complicated hereditary spastic paraplegia of type 11 (SPG11) and a group of healthy controls. Effect size maps of T1W-TBM of SPG11 patients showed diffuse atrophy of white matter. However, DTBM indicated that atrophy was more localized, predominantly affecting several long-range pathways. The results of our study suggest that DTBM could be a powerful tool for detecting morphological changes of specific white matter pathways in normal brain development and aging, as well as in degenerative disorders.

Evaluation of different ulegyria patterns with magnetic resonance imaging

Ulegyria is a parenchymal sequel of hypoxic ischemic encephalopathy causing mushroom-like appearance in gyri. Aim of the present study was to evaluate clinico-radiological findings of patients who applied with different clinical features, predominantly epilepsy, and who were found to have ulegyria formations in MRI examinations. The study included a total of 30 patients (12 female and 18 male) who applied with different types of seizures in February 2011–August 2016 period and had brain MRI examinations using 1.5T MRI scanner. Mushroom-shaped gyri accompanied by gliosis and atrophy in subcortical white matter were considered ulegyria. Locations, MRI features and accompanying pathologies of ulegyria formations were studied. Age of the patients ranged from 4 to 62 (mean 26.0 ± 13.8). Both cerebral lobes were involved in 18 patients. In terms of involved area, symmetrical or asymmetrical involvements were observed in occipital lobes in 26 patients, parietal lobes in 19, frontal lobes in 12 and temporal lobes in 4. The most common involvement type was bilateral occipital and bilateral parieto-occipital lobe involvements with five patients each. Lesions were symmetrical in 11 patients. Six patients had cingulate gyrus atrophy. Nineteen patients had different levels of symmetrical or asymmetrical ventricular dilatation. Cranial asymmetry was observed in six patients with unilateral involvement and in one patient with generalized involvement. Although ulegyria predominantly involves parasagittal watershed areas in MRI examinations of patients applying with epilepsy, clinical manifestations and appearance of lesions could vary depending upon the size of involved area and level of injury.

A comparison of brain magnetic resonance imaging lesions in multiple sclerosis by race with reference to disability progression

BackgroundWe compared the magnetic resonance imaging (MRI) features between Japanese and Caucasian patients with multiple sclerosis (MS), and identified the relationships between MRI features and disability.MethodsFrom the baseline data of phase II fingolimod trials, 95 Japanese and 246 Caucasian relapsing-remitting MS patients were enrolled. The number, volume, and distribution of brain MRI lesions were evaluated using T2-weighted (T2W) images. Cross-sectional total normalized brain volume (NBV), normalized cortical gray matter volume, normalized deep gray matter volume (NDGMV), normalized white matter volume (NWMV), and normalized thalamic volume were measured.ResultsJapanese patients had significantly lower Expanded Disability Status Scale (EDSS) scores than Caucasian patients (mean 2.0 vs. 2.3, p = 0.008), despite a similar disease duration. Japanese patients showed a trend towards fewer T2W-lesions (median 50 vs. 65, p = 0.08) and significantly lower frequencies of cerebellar and parietal lobe lesions (p = 0.02 for both) than Caucasian patients. There were no differences in T2W-lesion volume between races, whereas Japanese patients had a significantly larger T2W-lesion volume per lesion compared with Caucasian patients (median 140 mm3 vs. 85 mm3, p < 0.0001). T2W-lesion volumes were positively correlated with EDSS scores in Japanese patients (p < 0.0001). In both races, NBV, normalized cortical gray matter volume, NDGMV, and thalamic volume were negatively correlated with disease duration and EDSS scores (p < 0.01 for all). NWMV was negatively correlated with disease duration and EDSS scores only in Caucasian patients (p = 0.03 and p = 0.004, respectively). NBV, NDGMV, NWMV, and thalamic volume were consistently smaller in Japanese compared with Caucasian patients throughout the entire examined disease duration (p = 0.046, p = 0.01, p = 0.005, and p = 0.04, respectively). Japanese patients had a significantly faster reduction in NDGMV (p = 0.001), particularly for thalamic volume (p = 0.001), with disease duration compared with Caucasian patients.ConclusionsGray matter atrophy is a common denominator for disability in Japanese and Caucasian patients. Additional contributory factors for disability include T2W-lesion volume in Japanese patients and white matter atrophy in Caucasian patients. Less frequent parietal and cerebellar involvement with fewer T2W-lesions may underlie milder disability in Japanese patients.

Age specificity in fornix-to-hippocampus association.

Both white and grey matter atrophy with age, but it is still unclear how decline in white matter relates to decline in grey matter, and how this relationship varies with age. In a group of healthy adults from 20 to 80years old, divided into three age groups by tertiles, we cross-sectionally examined the white-to-grey matter associations in the fornix and the hippocampus, and tested if and how the fornix-to-hippocampus relationship differs across the age groups. Both structures were also tested as predictors for performance on a memory test, the Selective Reminding Task (SRT). Participants were imaged with T1-weighted magnetic resonance imaging (MRI) and diffusion-weighted imaging (DWI), from which the hippocampal volume, fractional anisotropy (FA), and mean diffusivity (MD) for the bilateral crus and body of the fornix were calculated. Our data showed that even after accounting for age, sex, and motion parameters, fornix integrity predicted hippocampal volume in the two older age groups (middle and old age) for the crus of the fornix, and only in the oldest age group for the body of the fornix. Furthermore, fornix integrity significantly predicted SRT performance, whereas hippocampal volume did not; this relationship was also observed only in the oldest age group, and absent in the two younger age groups. The age specificity of the relationships suggests that the fornix-to-hippocampus relationship only manifests once brain structures begin to atrophy in old age, and that fornix integrity is a more sensitive measure for episodic memory than is hippocampal volume.

Chronic near lifetime toluene exposure in rodents does not replicate solvent abuse leukoencephalopathy in humans

Toluene is an organic solvent used in industry and as a substance of abuse. The latter situation may be associated with a leukoencephalopathy characterized by white matter atrophy, multifocal myelin loss, and macrophages that contain birefringent granular inclusions. To determine if rodents can develop the same white matter damage, we studied archived rodent brain samples from three near-lifetime toluene carcinogenicity experiments. Rats and mice were exposed to toluene via an inhalation chamber at 1200 ppm for 6.5 h daily, 5 days per week, for 103 weeks. Rats were exposed to toluene via oral gavage of 800 mg/kg, 4 days per week, for 104 weeks. In gavage-exposed brains, immunohistochemical staining was used to detect reactive astroglial and microglial changes, neuron populations, and cytochrome P450 upregulation. None of the white matter changes reported in human toluene abuse were identified in the rat or mouse brains. In a blinded analysis, a mild widespread increase in reactive microglia was detected in female rats that received toluene by gavage at 800 mg/kg. However, no significant differences were detected in neurons or astrocytes. Potential reasons for the absence of changes are discussed. We conclude that rodent studies designed to study carcinogenicity of toluene might not adequately model abuse exposure.

Polarization-sensitive optical coherence tomography reveals gray matter and white matter atrophy in SCA1 mouse models

Spinocerebellar ataxia type 1 (SCA1) is a fatal inherited neurodegenerative disease. In this study, we demonstrate the label-free optical imaging methodology that can detect, with a high degree of sensitivity, discrete areas of degeneration in the cerebellum of the SCA1 mouse models. We used ATXN1[82Q] and ATXN1[30Q]-D776 mice in which the transgene is directed only to Purkinje cells. Molecular layer, granular layer, and white matter regions are analyzed using the intrinsic contrasts provided by polarization-sensitive optical coherence tomography. Cerebellar atrophy in SCA1 mice occurred both in gray matter and white matter. While gray matter atrophy is obvious, indications of white matter atrophy including different birefringence characteristics, and shortened and contorted branches are observed. Imaging results clearly show the loss or atrophy of myelinated axons in ATXN1[82Q] mice. The method provides unbiased contrasts that can facilitate the understanding of the pathological progression in neurodegenerative diseases and other neural disorders.

Executive dysfunction and altered cerebrovascular activity in a rodent model of vascular cognitive impairment

Most basic science research has focused on overt stroke caused by blockage of major blood vessels. Less attention has been paid to small vessel disease giving rise to covert stroke that often leads to vascular cognitive impairment (VCI). One reason for this may be the relative lack of relevant animal models. This talk will describe a model of VCI induced in middle-aged Sprague-Dawley rats exposed to a diet high in saturated fats, salt and refined sugar (HFSS). In Experiment 1, rats fed HFSS and subjected to a small mediodorsal (MD) thalamic stroke with or without concomitant cerebral hypoperfusion experienced significant executive dysfunction. In Experiment 2, dietary influences on functional, physiological and anatomical parameters were assessed. We found significant hypertension, blockage of brain microvessels (2-photon microscopy) and white matter atrophy in HFSS diet animals. As in Experiment 1, profound, specific set-shifting executive dysfunction was noted following both small MD infarcts (0.332 mm3) and the HFSS diet. In summary, these data describe a middle-aged animal model of VCI that includes clinically-relevant metabolic disturbances and small vessel disease and as such may be helpful in developing new cognitive therapies.

Severe Traumatic Brain Injury Patients without Focal Lesion but with Behavioral Disorders: Shrinkage of Gray Matter Nuclei and Thalamus Revealed in a Pilot Voxel-Based MRI Study.

After a traumatic brain injury (TBI), behavioral disorders can occur without major focal brain lesion, and in these situations, their pathophysiology remains unclear. The aim of this study is to examine whether TBI patients with behavioral disorders but without any focal damage, as observed from an initial clinical CT scan, present subtle volumetric alterations that could be measured voxel-by-voxel in the whole brain with MRI. Eight male adults with severe TBI who had behavioral sequela but not major focal cerebral lesion and 17 age-matched controls underwent a volumetric T1-weighted 1.5T MRI. A two step analysis was performed. First, gray matter (GM) and white matter (WM) volumes were compared between groups using voxel-based morphometry. Second, we examined brain regions systematically damaged using the sum of the individual binary maps obtained from z-maps thresholded at -1.75 for significant GM and WM atrophy. TBI patients had lower GM volume than controls (p < 0.001, uncorrected) in the right parahippocampal gyrus; left and right superior, middle, and inferior temporal gyri; left superior frontal gyrus; right middle frontal gyrus; thalami; mammillary bodies; caudate nuclei; insulae; cerebellar cortex; and vermis. WM volume was lower (p < 0.001, uncorrected) in the TBI group than in controls in the periventricular area and around the basal nuclei. We found shrinkage in the dorsomedial thalami in each of the TBI patients, and in the posterior part of the right putamen and caudate nuclei in seven TBI patients. Shrinkage in the dorsomedial thalami and in the posterior part of the right putamen and caudate nuclei may be a common effect of the disseminated microscopic lesions, and be associated with behavioral issues in severe TBI patients without major focal lesions.

Patterns of Regional Gray Matter and White Matter Atrophy in Patients Starting Fingolimod or Natalizumab: A 2-Year Tensor-Based Morphometry Study (P1.377)

Patterns of Regional Gray Matter and White Matter Atrophy in Patients Starting Fingolimod or Natalizumab: A 2-Year Tensor-Based Morphometry Study (P1.377)

Cerebral microbleeds associated with white matter and deep gray matter atrophy in community-dwelling populations (S15.005)

Cerebral microbleeds associated with white matter and deep gray matter atrophy in community-dwelling populations (S15.005)

Regional brain volumetry and brain function in severely brain-injured patients.

The relationship between residual brain tissue in patients with disorders of consciousness (DOC) and the clinical condition is unclear. This observational study aimed to quantify gray (GM) and white matter (WM) atrophy in states of (altered) consciousness. Structural T1-weighted magnetic resonance images were processed for 102 severely brain-injured and 52 healthy subjects. Regional brain volume was quantified for 158 (sub)cortical regions using Freesurfer. The relationship between regional brain volume and clinical characteristics of patients with DOC and conscious brain-injured patients was assessed using a linear mixed-effects model. Classification of patients with unresponsive wakefulness syndrome (UWS) and minimally conscious state (MCS) using regional volumetric information was performed and compared to classification using cerebral glucose uptake from fluorodeoxyglucose positron emission tomography. For validation, the T1-based classifier was tested on independent datasets. Patients were characterized by smaller regional brain volumes than healthy subjects. Atrophy occurred faster in UWS compared to MCS (GM) and conscious (GM and WM) patients. Classification was successful (misclassification with leave-one-out cross-validation between 2% and 13%) and generalized to the independent data set with an area under the receiver operator curve of 79% (95% confidence interval [CI; 67-91.5]) for GM and 70% (95% CI [55.6-85.4]) for WM. Brain volumetry at the single-subject level reveals that regions in the default mode network and subcortical gray matter regions, as well as white matter regions involved in long range connectivity, are most important to distinguish levels of consciousness. Our findings suggest that changes of brain structure provide information in addition to the assessment of functional neuroimaging and thus should be evaluated as well. Ann Neurol 2018;83:842-853.

Visual Rating Scales of White Matter Hyperintensities and Atrophy: Comparison of Computed Tomography and Magnetic Resonance Imaging

GoalMagnetic resonance imaging (MRI) is the preferred modality for research on structural age-related brain changes. However, computed tomography (CT) is widely available and has practical and cost advantages over MRI for large-scale brain imaging research studies in acutely unwell patients. However, the relationships between MRI and CT measures of white matter hyperintensities (WMH) and atrophy are unclear. We examined the relationships between visual ratings of WMH, atrophy, and old infarcts in patients who had both CT and MRI scans.Materials and MethodsPatients who had both CT and MRI scans in the International Stroke Trial-3 were studied. In both modalities, 2 raters independently completed standardized visual rating scales for WMH, and for central and superficial atrophy using a 5-point scale. In addition, 1 rater recorded old infarcts according to size and location.FindingsSeventy patients with a mean age of 69 years were studied. There were moderate to substantial intrarater CT–MRI agreements for periventricular components of WMH scales (weighted Κappa = .55-.75). Agreements for basal ganglia ratings were lower (weighted Κappa = .18-.44), partly because of the misclassification of prominent perivascular spaces. Atrophy scales showed moderate to substantial CT–MRI agreements (weighted Κappa = .44-.70). MRI was more sensitive in the detection of smaller infarcts and cavitated lesions.ConclusionsStandardized visual rating scales of white matter lesions and atrophy mostly show substantial agreement between CT and MRI. Clinical CT scans have a strong potential for wider exploitation in research studies, particularly in acutely unwell populations.

White matter lesions and brain atrophy in systemic lupus erythematosus patients: correlation to cognitive dysfunction in a cohort of systemic lupus erythematosus patients using different definition models for neuropsychiatric systemic lupus erythematosus.

Aim The aim of this study was to evaluate the extent of white matter lesions, atrophy of the hippocampus and corpus callosum, and their correlation with cognitive dysfunction (CD), in patients diagnosed with systemic lupus erythematosus (SLE). Methods Seventy SLE patients and 25 healthy individuals (HIs) were included in the study. To evaluate the different SLE and neuropsychiatric SLE (NPSLE) definition schemes, patients were grouped both according to the American College of Rheumatology (ACR) definition, as well as the more stringent ACR-Systemic Lupus International Collaborating Clinics definition. Patients and HIs underwent a 3 Tesla brain MRI and a standardized neuropsychological test. MRI data were evaluated for number and volume of white matter lesions and atrophy of the hippocampus and corpus callosum. Differences between groups and subgroups were evaluated for significance. Number and volume of white matter lesions and atrophy of the hippocampus and corpus callosum were correlated to cognitive dysfunction. Results The total volume of white matter lesions was significantly larger in SLE patients compared to HIs ( p = 0.004). However, no significant differences were seen between the different SLE subgroups. Atrophy of the bilateral hippocampus was significantly more pronounced in patients with NPSLE compared to those with non-NPSLE (right: p = 0.010; left p = 0.023). Significant negative correlations between cognitive test scores on verbal memory and number and volume of white matter lesions were present. Conclusion SLE patients have a significantly larger volume of white matter lesions on MRI compared to HIs and the degree of white matter lesion volume correlates to cognitive dysfunction, specifically to verbal memory. No significant differences in the number or volume of white matter lesions were identified between subgroups of SLE patients regardless of the definition model used.

Risk Factors for Postoperative Delirium After Deep Brain Stimulation Surgery for Parkinson Disease

The aim of this study was to investigate the incidence of and risk factors for postoperative delirium (POD) after deep brain stimulation (DBS) surgery in patients with Parkinson disease. We analyzed the preoperative T1-weighted magnetic resonance imaging data of 71 patients with Parkinson disease who underwent DBS surgery. Multiple regression analysis was performed with age, l-dopa equivalent daily dose, laterality of the surgery, target regions, number of electrode trajectories tried, gray matter volume, and white matter (WM) volume as explanatory variables and the duration (number of days) of POD as the response variable. In addition, regional brain atrophy associated with POD was investigated by means of voxel-based morphometry. Excluding patients with outliers, 61 patients were included in the analyses. POD had occurred in 26 of the 61 patients (42.6%). Age and total WM volume were shown by multiple regression analysis to correlate significantly with the duration of POD (P < 0.05 and < 0.01, respectively). WM was significantly reduced in the temporal stem, and the reduction in volume correlated significantly with the duration of POD (P < 0.001). Gray matter atrophy was not associated with POD. We found that age and WM atrophy in the temporal stem are factors predictive of POD after DBS surgery. In aged patients with temporal stem atrophy, surgical procedures and postoperative management should be carefully explored to reduce the risk of postoperative delirium.

Progressive neurodegeneration following spinal cord injury: Implications for clinical trials.

ObjectiveTo quantify atrophy, demyelination, and iron accumulation over 2 years following acute spinal cord injury and to identify MRI predictors of clinical outcomes and determine their suitability as surrogate markers of therapeutic intervention.MethodsWe assessed 156 quantitative MRI datasets from 15 patients with spinal cord injury and 18 controls at baseline and 2, 6, 12, and 24 months after injury. Clinical recovery (including neuropathic pain) was assessed at each time point. Between-group differences in linear and nonlinear trajectories of volume, myelin, and iron change were estimated. Structural changes by 6 months were used to predict clinical outcomes at 2 years.ResultsThe majority of patients showed clinical improvement with recovery stabilizing at 2 years. Cord atrophy decelerated, while cortical white and gray matter atrophy progressed over 2 years. Myelin content in the spinal cord and cortex decreased progressively over time, while cerebellar loss decreases decelerated. As atrophy progressed in the thalamus, sustained iron accumulation was evident. Smaller cord and cranial corticospinal tract atrophy, and myelin changes within the sensorimotor cortices, by 6 months predicted recovery in lower extremity motor score at 2 years. Whereas greater cord atrophy and microstructural changes in the cerebellum, anterior cingulate cortex, and secondary sensory cortex by 6 months predicted worse sensory impairment and greater neuropathic pain intensity at 2 years.ConclusionThese results draw attention to trauma-induced neuroplastic processes and highlight the intimate relationships among neurodegenerative processes in the cord and brain. These measurable changes are sufficiently large, systematic, and predictive to render them viable outcome measures for clinical trials.