Regional volumes in brain stem and cerebellum are associated with postural impairments in young brain‐injured patients

Many patients with traumatic brain injury (TBI) suffer from postural control impairments that can profoundly affect daily life. The cerebellum and brain stem are crucial for the neural control of posture and have been shown to be vulnerable to primary and secondary structural consequences of TBI. The aim of this study was to investigate whether morphometric differences in the brain stem and cerebellum can account for impairments in static and dynamic postural control in TBI. TBI patients (n = 18) and healthy controls (n = 30) completed three challenging postural control tasks on the EquiTest® system (Neurocom). Infratentorial grey matter (GM) and white matter (WM) volumes were analyzed with cerebellum‐optimized voxel‐based morphometry using the spatially unbiased infratentorial toolbox. Volume loss in TBI patients was revealed in global cerebellar GM, global infratentorial WM, middle cerebellar peduncles, pons and midbrain. In the TBI group and across both groups, lower postural control performance was associated with reduced GM volume in the vermal/paravermal regions of lobules I–IV, V and VI. Moreover, across all participants, worse postural control performance was associated with lower WM volume in the pons, medulla, midbrain, superior and middle cerebellar peduncles and cerebellum. This is the first study in TBI patients to demonstrate an association between postural impairments and reduced volume in specific infratentorial brain areas. Volumetric measures of the brain stem and cerebellum may be valuable prognostic markers of the chronic neural pathology, which complicates rehabilitation of postural control in TBI. Hum Brain Mapp 36:4897–4909, 2015. © 2015 Wiley Periodicals, Inc.     

Measurement and prediction of subjective fatigue following traumatic brain injury.

Numerous outcome studies have found fatigue to be a common problem following traumatic brain injury (TBI). This study examined the magnitude, causes and impact of fatigue following TBI using three subjective fatigue scales, and investigated its relationship with demographic and injury-related factors, and mood. Forty-nine controls and 49 TBI participants (36.2% with GCS score of 13-15, 29.8% with GCS score of 9-12, and 34% with GCS score of 3-8) were seen at a mean of approximately 8 months post injury. All participants completed three subjective fatigue measures, including the Fatigue Severity Scale (FSS), Visual Analogue Scale-Fatigue (VAS-F) and Causes of Fatigue Questionnaire (COF). TBI participants reported a significantly greater impact of fatigue on their lifestyle on the FSS relative to controls, and reported activities requiring physical and mental effort as more frequent causes of fatigue on the COF. There were, however, no significant group differences on subscales of the VAS-F. Greater time since injury and higher education levels were associated with higher fatigue levels, independent of the effects of mood. Injury severity and age were not found to be significant predictors of subjective fatigue severity in TBI participants.     

Correlation between fatigue and brain atrophy and lesion load in multiple sclerosis patients independent of disability

BACKGROUND: Fatigue is a major problem in multiple sclerosis (MS), and its association with MRI features is debated. OBJECTIVE: To study the correlation between fatigue and lesion load, white matter (WM), and grey matter (GM), in MS patients independent of disability. METHODS: We studied 222 relapsing remitting MS patients with low disability (scores or=5; n=197) and low-fatigue groups (FSS相似文献   

Effects of Methylphenidate on Working Memory in Traumatic Brain Injury: A Preliminary fMRI Investigation

As part of a preliminary investigation on the effects of methylphenidate on brain activation during a working memory (WM) task in patients with traumatic brain injury (TBI), patients with TBI received 15 mg of methylphenidate (N = 4) or placebo (N = 5) twice a day for one month in a double-blind, placebo-controlled design. Brain activation was assessed at pre-treatment and on the final treatment day using functional magnetic resonance imaging (fMRI) with an N-back task using faces as stimuli. In a whole brain voxel-wise analysis, methylphenidate, compared to placebo, produced a decrease in brain activation for the 2-load minus 0-load contrast in the anterior cingulate, thalamus, cuneus and cerebellum, regions associated with WM performance. Further, an a priori region of interest analysis with small volume correction found reduced activation in the anterior cingulate. Although based on a small sample size, these preliminary findings suggest methylphenidate may increase processing efficiency associated with cognitive control during WM tasks in patients with TBI.     

Facial affect recognition linked to damage in specific white matter tracts in traumatic brain injury

Emotional processing deficits have recently been identified in individuals with traumatic brain injury (TBI), specifically in the domain of facial affect recognition. However, the neural networks underlying these impairments have yet to be identified. In the current study, 42 individuals with moderate to severe TBI and 23 healthy controls performed a task of facial affect recognition (Facial Emotion Identification Test (FEIT)) in order to assess their ability to identify and discriminate six emotions: happiness, sadness, anger, surprise, shame, and fear. These individuals also underwent structural neuroimaging including diffusion tensor imaging to examine white matter (WM) integrity. Correlational analyses were performed to determine where in the brain WM damage was associated with performance on the facial affect recognition task. Reduced performance on the FEIT was associated with reduced WM integrity (fractional anisotropy, mean diffusivity, axial diffusivity, and radial diffusivity) in the inferior longitudinal fasciculus and inferior-fronto-occipital fasciculus in individuals with TBI. Poor performance on the task was additionally associated with reduced gray matter (GM) volume in lingual gyrus and parahippocampal gyrus. The results implicate a pattern of WM and GM damage in TBI that may play a role in emotional processing impairments.     

Vigilance and fatigue following traumatic brain injury.

Research findings have suggested that individuals with traumatic brain injury (TBI) show greater psychophysiological and subjective costs associated with performing vigilance tasks, but have not examined relationships with fatigue. The present study aimed to investigate vigilance and its relationship with subjective and objective fatigue measures. Forty-six TBI participants and 46 controls completed a 45-minute vigilance task. They also completed a subjective fatigue scale (the VAS-F) and a selective attention task before and after the vigilance task, and had their blood pressure (BP) monitored. TBI participants performed at a lower level on the vigilance task, but performed at a similar level across the duration of the task. Higher subjective fatigue ratings on the VAS-F were associated with more misses on the vigilance task for TBI participants. TBI participants showed greater increases in diastolic BP, and these were associated with greater increases in subjective fatigue ratings on the VAS-F. A subgroup of TBI participants showed a decline in performance on the vigilance task and also showed disproportionate increases in subjective fatigue. Findings provide support for the coping hypothesis, suggesting that TBI individuals expend greater psychophysiological costs in order to maintain stable performance over time, and that these costs are also associated with subjective increases in fatigue.     

Spatiotemporal distribution pattern of white matter lesion volumes and their association with regional grey matter volume reductions in relapsing‐remitting multiple sclerosis

The association of white matter (WM) lesions and grey matter (GM) atrophy is a feature in relapsing‐remitting multiple sclerosis (RRMS). The spatiotemporal distribution pattern of WM lesions, their relations to regional GM changes and the underlying dynamics are unclear. Here we combined parametric and non‐parametric voxel‐based morphometry (VBM) to clarify these issues. MRI data from RRMS patients with progressive (PLV, n = 45) and non‐progressive WM lesion volumes (NPLV, n = 44) followed up for 12 months were analysed. Cross‐sectionally, the spatial WM lesion distribution was compared using lesion probability maps (LPMs). Longitudinally, WM lesions and GM volumes were studied using FSL‐VBM and SPM5‐VBM, respectively. WM lesions clustered around the lateral ventricles and in the centrum semiovale with a more widespread pattern in the PLV than in the NPLV group. The maximum local probabilities were similar in both groups and higher for T2 lesions (PLV: 27%, NPLV: 25%) than for T1 lesions (PLV: 15%, NPLV 14%). Significant WM lesion changes accompanied by cortical GM volume reductions occured in the corpus callosum and optic radiations (P = 0.01 corrected), and more liberally tested (uncorrected P < 0.01) in the inferior fronto‐occipital and longitudinal fasciculi, and corona radiata in the PLV group. Not any WM or GM changes were found in the NPLV group. In the PLV group, WM lesion distribution and development in fibres, was associated with regional GM volume loss. The different spatiotemporal distribution patterns of patients with progressive compared to patients with non‐progressive WM lesions suggest differences in the dynamics of pathogenesis. Hum Brain Mapp, 2010. © 2010 Wiley‐Liss, Inc.     

A fixel‐based analysis of micro‐ and macro‐structural changes to white matter following adult traumatic brain injury

Diffusion tensor imaging is often used to assess white matter (WM) changes following traumatic brain injury (TBI), but is limited in voxels that contain multiple fibre tracts. Fixel‐based analysis (FBA) addresses this limitation by using a novel method of analysing high angular resolution diffusion‐weighted imaging (HARDI) data. FBA examines three aspects of each fibre tract within a voxel: tissue micro‐structure (fibre density [FD]), tissue macro‐structure (fibre‐bundle cross section [FC]) and a combined measure of both (FD and fibre‐bundle cross section [FDC]). This study used FBA to identify the location and extent of micro‐ and macro‐structural changes in WM following TBI. A large TBI sample (N_mild = 133, N_{moderate–severe} = 29) and control group (healthy and orthopaedic; N = 107) underwent magnetic resonance imaging with HARDI and completed reaction time tasks approximately 7 months after their injury (range: 98–338 days). The TBI group showed micro‐structural differences (lower FD) in the corpus callosum and forceps minor, compared to controls. Subgroup analyses revealed that the mild TBI group did not differ from controls on any fixel metric, but the moderate to severe TBI group had significantly lower FD, FC and FDC in multiple WM tracts, including the corpus callosum, cerebral peduncle, internal and external capsule. The moderate to severe TBI group also had significantly slower reaction times than controls, but the mild TBI group did not. Reaction time was not related to fixel findings. Thus, the WM damage caused by moderate to severe TBI manifested as fewer axons and a reduction in the cross‐sectional area of key WM tracts.     

Influence of white matter injury on gray matter reactive gliosis upon stab wound in the adult murine cerebral cortex

Traumatic brain injury frequently affects the cerebral cortex, yet little is known about the differential effects that occur if only the gray matter (GM) is damaged or if the injury also involves the white matter (WM). To tackle this important question and directly compare similarities and differences in reactive gliosis, we performed stab wound injury affecting GM and WM (GM+) and one restricted to the GM (GM?) in the adult murine cerebral cortex. First, we examined glial reactivity in the regions affected (WM and GM) and determined the influence of WM injury on reactive gliosis in the GM comparing the same area in the two injury paradigms. In the GM+ injury microglia proliferation is increased in the WM compared with GM, while proliferating astrocytes are more abundant in the GM than in the WM. Interestingly, WM lesion exerted a strong influence on the proliferation of the GM glial cells that was most pronounced at early stages, 3 days post lesion. While astrocyte proliferation was increased, NG2 glia proliferation was decreased in the GM+ compared with GM‐ lesion condition. Importantly, these differences were not observed when a lesion of the same size affected only the GM. Unbiased proteomic analyses further corroborate our findings in support of a profound difference in GM reactivity when WM is also injured and revealed MIF as a key regulator of NG2 glia proliferation.     

Brain-behavior relationships in young traumatic brain injury patients: Fractional anisotropy measures are highly correlated with dynamic visuomotor tracking performance

Traumatic brain injury (TBI) patients have a high incidence of eye-hand coordination deficits. Diffuse axonal injury is common in TBI and is presumed to contribute to persistent motor problems. Using Diffusion Tensor Imaging (DTI), this study sought to identify changes in (sensori)motor white matter (WM) pathways/regions in a TBI group during the chronic recovery stage. A secondary objective was to examine the relationship between WM integrity and upper-limb visuomotor tracking performance. A young TBI (n = 17) and control (n = 14) group performed a dynamic tracking task, characterized by increasing information processing speed and predictive movement control. DTI scans were administered along with standard anatomical scans. The TBI group was found to perform inferior to the control group on the tracking task. Decreased fractional anisotropy was found in the TBI group in dedicated pathways involved in transmission of afferent and efferent information, i.e., corticospinal tract, posterior thalamic radiation, and optic radiation, due to increased diffusivity parallel and perpendicular to axonal fibre direction. This decrease in WM integrity was associated with inferior visuomotor tracking performance. Moreover, discriminant function analysis demonstrated that the model, based on the combined application of DTI and behavioral measures, was the most effective in distinguishing between TBI patients and controls. This study shows that specific eye-hand coordination deficits in a young TBI group are related to microstructural abnormalities in task-specific cerebral WM structures. Measures of white matter integrity are potentially important biomarkers for TBI that may support prognosis of motor deficits.     

Brain structural damage in spinocerebellar ataxia type 2. A voxel‐based morphometry study

Voxel‐based morphometry (VBM) enables an unbiased in‐vivo whole‐brain quantitative analysis of differences in gray matter (GM), white matter (WM) and cerebro‐spinal fluid (CSF) volumes. We assessed with VBM 20 spinocerebellar ataxia Type 2 (SCA2) patients with mild or moderate cerebellar deficit and 20 age and sex‐matched healthy controls. SCA2 patients showed a significant (P < 0.05 corrected for multiple comparison) symmetric loss of GM in the cerebellar vermis and hemispheres sparing lobules I,II, Crus II,VII, and X, and of the WM in the peridentate region, middle cerebellar peduncles, dorsal pons, and cerebral peduncles. The CSF volume was increased in the posterior cranial fossa. No GM, WM or CSF volume changes were observed in the supratentorial compartment. A mild (P < 0.05, >0.01) correlation was observed between the GM and WM loss and severity of the neurological deficit. In SCA2 patients with mild to moderate cerebellar deficit, GM and WM volume loss and CSF volume increase are confined to the posterior cranial fossa. © 2008 Movement Disorder Society     

Attention following traumatic brain injury: Neuropsychological and driving simulator data,and association with sleep,sleepiness, and fatigue

The objectives of this study were to compare individuals with traumatic brain injury (TBI) and healthy controls on neuropsychological tests of attention and driving simulation performance, and explore their relationships with participants’ characteristics, sleep, sleepiness, and fatigue. Participants were 22 adults with moderate or severe TBI (time since injury ≥ one year) and 22 matched controls. They completed three neuropsychological tests of attention, a driving simulator task, night-time polysomnographic recordings, and subjective ratings of sleepiness and fatigue. Results showed that participants with TBI exhibited poorer performance compared to controls on measures tapping speed of information processing and sustained attention, but not on selective attention measures. On the driving simulator task, a greater variability of the vehicle lateral position was observed in the TBI group. Poorer performance on specific subsets of neuropsychological variables was associated with poorer sleep continuity in the TBI group, and with a greater increase in subjective sleepiness in both groups. No significant relationship was found between cognitive performance and fatigue. These findings add to the existing evidence that speed of information processing is still impaired several years after moderate to severe TBI. Sustained attention could also be compromised. Attention seems to be associated with sleep continuity and daytime sleepiness; this interaction needs to be explored further.     

The effect of hypointense white matter lesions on automated gray matter segmentation in multiple sclerosis

Previous imaging studies assessing the relationship between white matter (WM) damage and matter (GM) atrophy have raised the concern that Multiple Sclerosis (MS) WM lesions may affect measures of GM volume by inducing voxel misclassification during intensity‐based tissue segmentation. Here, we quantified this misclassification error in simulated and real MS brains using a lesion‐filling method. Using this method, we also corrected GM measures in patients before comparing them with controls in order to assess the impact of this lesion‐induced misclassification error in clinical studies. We found that higher WM lesion volumes artificially reduced total GM volumes. In patients, this effect was about 72% of that predicted by simulation. Misclassified voxels were located at the GM/WM border and could be distant from lesions. Volume of individual deep gray matter (DGM) structures generally decreased with higher lesion volumes, consistent with results from total GM. While preserving differences in GM volumes between patients and controls, lesion‐filling correction revealed more lateralised DGM shape changes in patients, which were not evident with the original images. Our results confirm that WM lesions can influence MRI measures of GM volume and shape in MS patients through their effect on intensity‐based GM segmentation. The greater effect of lesions at increasing levels of damage supports the use of lesion‐filling to correct for this problem and improve the interpretability of the results. Volumetric or morphometric imaging studies, where lesion amount and characteristics may vary between groups of patients or change over time, may especially benefit from this correction. Hum Brain Mapp, 2012. © 2011 Wiley Periodicals, Inc.     

Objective electrophysiological fatigability markers and their modulation through tDCS

ObjectiveCognitive fatigability is a frequent symptom after sustained performance. Fatigability is evident in healthy subjects but is also often comorbid in several neuropsychiatric diseases. However, to date, clinical diagnostic almost solely relies on the self-reported subjective experience of fatigue. The goals of this present study were i) to complement the purely subjective fatigue diagnostic with objective electrophysiological fatigability parameters and ii) to prove the potential therapeutic application of transcranial direct current stimulation (tDCS) as a fatigability intervention.MethodsWe performed a pseudo-randomized, sham-controlled, parallel-group trial. Forty healthy participants received either anodal or sham tDCS over the left dorsolateral prefrontal cortex (DLPFC) while they performed an exhaustive cognitive task to induce cognitive fatigability. To assess fatigability changes, we analyzed variations of prepulse inhibition (PPI) and P50 suppression as well as frontomedial theta and occipital alpha power with time-on-task.ResultsThe task reliably induced subjective exhaustion in all participants. Furthermore, we confirmed fatigability-related increases in frontomedial theta and occipital alpha power throughout the task. Additionally, fatigability significantly reduced PPI as well as P50 sensory gating. Anodal tDCS over the left DLPFC successfully counteracted fatigability and reduced the fatigability-related increase in alpha power as well as the decline in both gating parameters.ConclusionOccipital alpha and sensorimotor/sensory gating are suitable parameters to assess the severity of fatigability objectively. Anodal tDCS can counteract fatigability and has therapeutic potential for the treatment of fatigability in neuropsychiatric diseases.SignificanceFatigability can be objectively assessed by electrophysiological measures and attenuated by tDCS.     

Magnetic resonance spectroscopy of fiber tracts in children with traumatic brain injury: A combined MRS – Diffusion MRI study

Traumatic brain injury can cause extensive damage to the white matter (WM) of the brain. These disruptions can be especially damaging in children, whose brains are still maturing. Diffusion magnetic resonance imaging (dMRI) is the most commonly used method to assess WM organization, but it has limited resolution to differentiate causes of WM disruption. Magnetic resonance spectroscopy (MRS) yields spectra showing the levels of neurometabolites that can indicate neuronal/axonal health, inflammation, membrane proliferation/turnover, and other cellular processes that are on‐going post‐injury. Previous analyses on this dataset revealed a significant division within the msTBI patient group, based on interhemispheric transfer time (IHTT); one subgroup of patients (TBI‐normal) showed evidence of recovery over time, while the other showed continuing degeneration (TBI‐slow). We combined dMRI with MRS to better understand WM disruptions in children with moderate‐severe traumatic brain injury (msTBI). Tracts with poorer WM organization, as shown by lower FA and higher MD and RD, also showed lower N‐acetylaspartate (NAA), a marker of neuronal and axonal health and myelination. We did not find lower NAA in tracts with normal WM organization. Choline, a marker of inflammation, membrane turnover, or gliosis, did not show such associations. We further show that multi‐modal imaging can improve outcome prediction over a single modality, as well as over earlier cognitive function measures. Our results suggest that demyelination plays an important role in WM disruption post‐injury in a subgroup of msTBI children and indicate the utility of multi‐modal imaging.     

Increased orbital frontal gray matter volume after cognitive behavioural therapy in paediatric obsessive compulsive disorder

Abstract

Objectives. Identify differences in regional brain volume between medication-free pediatric OCD patients and controls and examine changes after cognitive behavioural therapy. Methods. We assessed 29 medication-free paediatric OCD patients (Age: M =?13.78 years; SD =?2.58; range 8.2–19.0) and 29 controls, matched on age and gender, with T1-weighted MR scans in a repeated measures, pre-post treatment design. Voxel based morphometry (VBM) following diffeomorphic anatomical registration through exponential lie algebra (DARTEL) was used to test voxel-wise for the effects of diagnosis and treatment on regional gray matter (GM) and white matter (WM) volumes. Results. After cognitive behavioural therapy, orbitofrontal GM and capsula externa WM increased in paediatric OCD relative to controls. In patients, changes in symptom severity (delta CY-BOCS) correlated positively with GM volume in the orbitofrontal cortex after treatment. Furthermore, before treatment, paediatric OCD patients, compared to the controls, showed larger GM volume in left frontal pole and left parietal cortex and larger WM volume in cingulum and corpus callosum. Conclusions. Our findings underscore the involvement of the ventral frontal-striatal circuit in paediatric OCD and the plasticity of this circuit in response to the modulatory effects of CBT. The possible relation to brain development is discussed.     

Investigating the interaction between white matter and brain state on tDCS-induced changes in brain network activity

BackgroundTranscranial direct current stimulation (tDCS) is a form of noninvasive brain stimulation whose potential as a cognitive therapy is hindered by our limited understanding of how participant and experimental factors influence its effects. Using functional MRI to study brain networks, we have previously shown in healthy controls that the physiological effects of tDCS are strongly influenced by brain state. We have additionally shown, in both healthy and traumatic brain injury (TBI) populations, that the behavioral effects of tDCS are positively correlated with white matter (WM) structure.ObjectivesIn this study we investigate how these two factors, WM structure and brain state, interact to shape the effect of tDCS on brain network activity.MethodsWe applied anodal, cathodal and sham tDCS to the right inferior frontal gyrus (rIFG) of healthy (n = 22) and TBI participants (n = 34). We used the Choice Reaction Task (CRT) performance to manipulate brain state during tDCS. We acquired simultaneous fMRI to assess activity of cognitive brain networks and used Fractional Anisotropy (FA) as a measure of WM structure.ResultsWe find that the effects of tDCS on brain network activity in TBI participants are highly dependent on brain state, replicating findings from our previous healthy control study in a separate, patient cohort. We then show that WM structure further modulates the brain-state dependent effects of tDCS on brain network activity. These effects are not unidirectional - in the absence of task with anodal and cathodal tDCS, FA is positively correlated with brain activity in several regions of the default mode network. Conversely, with cathodal tDCS during CRT performance, FA is negatively correlated with brain activity in a salience network region.ConclusionsOur results show that experimental and participant factors interact to have unexpected effects on brain network activity, and that these effects are not fully predictable by studying the factors in isolation.     

A longitudinal study of MRI-detected atrophy in secondary progressive multiple sclerosis

MRI measures of tissue atrophy within the central nervous system may reflect the neurodegenerative process which underpins the progressive phase of multiple sclerosis (MS). There has been limited longitudinal investigation of MRI-detected atrophy in secondary progressive MS. This study includes 56 subjects with secondary progressive MS. Subjects were followed up for 2 years and MRI analysis was conducted at 12 month intervals using the following measures: (1) whole brain (WB) volume change; (2) grey and white matter (WM) volumes; (3) central brain volume; (4) upper cervical spinal cord (SC) area; (5) T2 lesion volumes. Clinical measures included the Expanded Disability Status Scale and the MS Functional Composite. All volumetric MRI measures were assessed for sensitivity, responsiveness, reliability and correlation with disability. The mean annual atrophy rate of WB was 0.59% per year and this was the most responsive atrophy measure assessed. Grey matter (GM) atrophy (−1.18% per year) was greater and more responsive than WM atrophy (0.12% per year). The SC demonstrated the highest atrophy rate at 1.63% per year. WB, GM and SC atrophy all correlated with change in the Multiple Sclerosis Functional Composite z score (r = 0.35, 0.42, 0.34), and GM atrophy was the only correlate of change in the 9 Hole Peg Test and Paced Auditory Serial Addition Test performance. None of the MRI measures correlated with Expanded Disability Status Score progression. Measures of WB, GM and SC atrophy all have attributes for use as surrogate markers in secondary progressive MS trials and improvement in the reliability of the GM and SC volume measurements may enhance these further.     

JNCL patients show marked brain volume alterations on longitudinal MRI in adolescence

Abstract   Juvenile neuronal ceroid lipofuscinosis (JNCL, CLN3) is an inherited lysosomal disease. We used longitudinal MRI, for the first time, to evaluate the rate of brain volume alterations in JNCL. Six patients (mean ages of 12.4 years and 17.3 years) and 12 healthy controls were studied twice with 1.5 T MRI. White matter (WM), gray matter (GM) and CSF volumes were measured from the sets of T1-weighted 3-dimensional MR images using a fully automated image-processing procedure. The brain volume alterations were calculated as percentage change per year. The GM and whole brain volumes decreased and the CSF volume increased significantly more in the patients than in controls (p-values for the null hypothesis of equal means were 0.001, 0.004, and 0.005, respectively). We found no difference in the WM volume change between the populations. In patients, the GM volume decreased 2.4 % (SD 0.5 %, p 0.0001 for the null hypothesis of zero mean change between observations), the whole brain volume decreased 1.1 % (SD 0.5 %, p = 0.003), and the CSF volume increased 2.7 % (SD 1.8 %, p = 0.01) per year. In normal controls, only the mean white matter volume was significantly altered (0.8 % increase, SD 0.7 %, and p = 0.001). Conclusion   We demonstrated by longitudinal MRI that the annual rate of the gray matter loss in adolescent JNCL patients is as high as 2.4 %.