Brainstem Volume Research Articles

Does the proportion of the brainstem change in the Parkinsonism?

Parkinson’s disease (PD) is a slowly progressive neurological disorder that affects movement, muscle control, and balance. It develops as cells are destroyed in certain parts of the brain stem. The aim of this study is to measure the volume and volume fraction of the brainstem parts to examine the differences between affected regions in the PD. For the evaluation of brainstem volume, the sample comprised 18 Parkinson’s patients (8 females and 10 males) in the 2 nd and 3 rd stages the disease, and 20 controls (9 females, 11 males). Magnetic resonance images in DICOM format were analyzed using the Image software. A protocol was developed to segment the parts of the brainstem and their volumes and volume fractions were estimated using the planimetry technique. The mean volume and volume fraction of the midbrain, pons, medulla oblongata and the total brainstem in control were (8.2 cm 3 ±1.14, 27.61%), (16.25 cm 3 ±2.75, 54.37%), (5.32 cm 3 ±0.73, 18.02%), and 29.78 cm 3 ±4.11, respectively. And for patient groups were (7.91 cm 3 ±1.5, 26.64%), (16.25 cm 3 ±2.49, 55.38%), (5.32 cm 3 ±0.89, 17.98%), and 29.78 cm 3 ±4.0, respectively. There were no statistically significant differences between patients and controls for the volume and volume fraction of the brainstem parts (p≥0.05). Our data indicates that patients with PD do not show brainstem volume reduction in comparison with controls. Volumetric brain imaging studies in PD are conflicting with regards to brainstem atrophy. A number of factors may contribute to this variability, including differences in analysis methods, variability in the disorder itself and also due to variations in sampling selection. Our findings are still preliminary; we are trying to find changes associated with substantia nigra and red nucleus to evaluate the relation between the clinical scores of PD patients and imaging results.

P13.16 * COMPLICATIONS AFTER GAMMA KNIFE RADIOSURGERY FOR BRAIN TUMORS LOCATING ADJACENT THE BRAINSTEM

OBJECTIVE: Gamma Knife Radiosurgery (GKRS) is still challenging for the tumors locating adjacent brainstem because of dose limitation to brainstem, and the 12-Gy volume of brainstem has been reported as an important factor for development of radiation-induced complications. We aimed to investigate the incidence and relevant factors of complications after GKRS, while we try to minimize the 12-Gy volume of brainstem. METHODS: We retrospectively reviewed clinical, radiological and dosimetry data of 76 patients who underwent GKRS for brain tumors locating adjacent the brainstem. The most common diagnosis was vestibular schwannoma (n = 41), followed by meningioma (n = 21), metastatic brain tumor (n = 13), and ependymoma (n =1). The mean target volume was 3.7 cc (range, 0.211-12.2) at the time of GKRS, and the mean prescription dose was 12.7 Gy (range 8-20). The mean 12-Gy volume was 0.029 cc (range, 0.002-0.2). The location of tumors was intra-axial in 10 (13.2%) and extra-axial in 66 (86.8%). The 12-Gy volume of brainstem was calculated by intersecting the volume within brainstem from the prescription dose. The signal change of brainstem was defined as signal alteration on T2 or T1-weighted MRI after GKRS. RESULTS: The median clinical follow-up duration was 31.5 ± 14.3 months (range, 0.9-63.6). Among 76 lesions, the signal change of brainstem was observed in 7 (9.2%) with a median interval of 5.5 ± 4.08 months (range, 0.5-12) to development. Three tumors showing the signal change of brainstem were symptomatic, however successfully managed with oral steroid administration. Among various factors, only radiation-induced intratumoral necrosis (RIN) was a significant factor for the development of signal change of brainstem (p = 0.027). RIN was observed in 39 (51.3%) tumors with the median onset time of 5.4 ± 0.9 months after GKRS. The actuarial local tumor control rates at 1, 2 and 3 years after GKRS were 93.7%, 77.7% and 52.8%, respectively. CONCLUSIONS: In our series, the radiation-induced signal change of brainstem was observed in 9.2% after GKRS with an effort to minimize the 12-Gy volume of brainstem and only RIN was a significant relevant factor. Therefore, we suggest that close observation should be required to monitor radiation-induced brainstem injury when RIN is developed in the follow-up imaging after GKRS.

SU-E-T-225: It Is Necessary to Contouring the Brainstem On MRI Images in Radiotherapy of Head and Neck Cancer

Purpose: To analyze the error in contouring the brainstem for patients with head and neck cancer who underwent radiotherapy based on computed tomography (CT) and magnetic resonance (MR) images. Methods: 20 brain tumor and 17 nasopharyngeal cancer patients were randomly selected. Each patient underwent MR and CT scanning. For each patient, one observer contoured the brainstem on CT and MR images for 10 times, and 10 observers from five centers delineated the brainstem on CT and MR images only one time. The inter- and intra-observers volume and outline variations were compared. Results: The volumes of brainstem contoured by inter- and intra-observers on CT and MR images were similar (p>0.05). The reproducibility of contouring brainstem on MR images was better than that on CT images (p<0.05) for both inter- and intra-observer variability. The inter- and intra-observer for contouring on CT images reached mean values of 0.81±0.05 (p>0.05) and of 0.85±0.05 (p>0.05), respectively, while on MR images these respective values were 0.90±0.05 (p>0.05) and 0.92±0.04 (p>0.05). Conclusion: Contouring the brainstem on MR images was more accurate and reproducible than that on CT images. Precise information might be more helpful for protecting the brainstem radiation injury the patients whose lesion were closed to brainstem.

Brain morphology in children with epilepsy and ADHD.

BackgroundAttention deficit hyperactivity disorder (ADHD) is a common comorbidity of childhood epilepsy, but the neuroanatomical correlates of ADHD in epilepsy have yet to be comprehensively characterized.MethodsChildren with new and recent-onset epilepsy with (n = 18) and without (n = 36) ADHD, and healthy controls (n = 46) underwent high resolution MRI. Measures of cortical morphology (thickness, area, volume, curvature) and subcortical and cerebellar volumes were compared between the groups using the program FreeSurfer 5.1.ResultsCompared to the control group, children with epilepsy and ADHD exhibited diffuse bilateral thinning in the frontal, parietal and temporal lobes, with volume reductions in the brainstem and subcortical structures (bilateral caudate, left thalamus, right hippocampus). There were very few group differences across measures of cortical volume, area or curvature.ConclusionsChildren with epilepsy and comorbid ADHD exhibited a pattern of bilateral and widespread decreased cortical thickness as well as decreased volume of subcortical structures and brainstem. These anatomic abnormalities were evident early in the course of epilepsy suggesting the presence of antecedent neurodevelopmental changes, the course of which remains to be determined.

Prospective longitudinal MRI study of brain volumes and diffusion changes during the first year after moderate to severe traumatic brain injury.

The objectives of this prospective study in 62 moderate–severe TBI patients were to investigate volume change in cortical gray matter (GM), hippocampus, lenticular nucleus, lobar white matter (WM), brainstem and ventricles using a within subject design and repeated MRI in the early phase (1–26 days) and 3 and 12 months postinjury and to assess changes in GM apparent diffusion coefficient (ADC) in normal appearing tissue in the cortex, hippocampus and brainstem. The impact of Glasgow Coma Scale (GCS) score at admission, duration of post-traumatic amnesia (PTA), and diffusion axonal injury (DAI) grade on brain volumes and ADC values over time was assessed. Lastly, we determined if MRI-derived brain volumes from the 3-month scans provided additional, significant predictive value to 12-month outcome classified with the Glasgow Outcome Scale—Extended after adjusting for GCS, PTA and age.Cortical GM loss was rapid, largely finished by 3 months, but the volume reduction was unrelated to GCS score, PTA, or presence of DAI. However, cortical GM volume at 3 months was a significant independent predictor of 12-month outcome. Volume loss in the hippocampus and lenticular nucleus was protracted and statistically significant first at 12 months. Slopes of volume reduction over time for the cortical and subcortical GGM were significantly different. Hippocampal volume loss was most pronounced and rapid in individuals with PTA > 2 weeks. The 3-month volumes of the hippocampus and lentiform nucleus were the best independent predictors of 12-month outcome after adjusting for GCS, PTA and age. In the brainstem, volume loss was significant at both 3 and 12 months. Brainstem volume reduction was associated with lower GCS score and the presence of DAI. Lobar WM volume was significantly decreased first after 12 months. Surprisingly DAI grade had no impact on lobar WM volume. Ventricular dilation developed predominantly during the first 3 months, and was strongly associated with volume changes in the brainstem and cortical GM, but not lobar WM volume.Higher ADC values were detected in the cortex in individuals with severe TBI, DAI and PTA > 2 weeks, from 3 months. There were no associations between ADC values and brain volumes, and ADC values did not predict outcome.

Divergent structural brain abnormalities between different genetic subtypes of children with Prader–Willi syndrome

BackgroundPrader–Willi syndrome (PWS) is a complex neurogenetic disorder with symptoms that indicate not only hypothalamic, but also a global, central nervous system (CNS) dysfunction. However, little is known about developmental differences in brain structure in children with PWS. Thus, our aim was to investigate global brain morphology in children with PWS, including the comparison between different genetic subtypes of PWS. In addition, we performed exploratory cortical and subcortical focal analyses.MethodsHigh resolution structural magnetic resonance images were acquired in 20 children with genetically confirmed PWS (11 children carrying a deletion (DEL), 9 children with maternal uniparental disomy (mUPD)), and compared with 11 age- and gender-matched typically developing siblings as controls. Brain morphology measures were obtained using the FreeSurfer software suite.ResultsBoth children with DEL and mUPD showed smaller brainstem volume, and a trend towards smaller cortical surface area and white matter volume. Children with mUPD had enlarged lateral ventricles and larger cortical cerebrospinal fluid (CSF) volume. Further, a trend towards increased cortical thickness was found in children with mUPD. Children with DEL had a smaller cerebellum, and smaller cortical and subcortical grey matter volumes. Focal analyses revealed smaller white matter volumes in left superior and bilateral inferior frontal gyri, right cingulate cortex, and bilateral precuneus areas associated with the default mode network (DMN) in children with mUPD.ConclusionsChildren with PWS show signs of impaired brain growth. Those with mUPD show signs of early brain atrophy. In contrast, children with DEL show signs of fundamentally arrested, although not deviant brain development and presented few signs of cortical atrophy. Our results of global brain measurements suggest divergent neurodevelopmental patterns in children with DEL and mUPD.

Correlations Between Cerebellar and Brain Volumes, Cognitive Impairments, ApoE Levels, and APOE Genotypes in Patients with AD and MCI

Due to the increasing incidence of Alzheimer's disease (AD), many studies have aimed to improve its diagnosis. Particular attention has been focused on measuring volumes of brain structures. Only few studies have investigated whether the cerebellar volume changes with the stage of dementia. It is controversial whether the serum apolipoprotein E (ApoE) level is an appropriate AD marker. This study was designed to clarify the significance of both cerebellar volume measurements and ApoE level measurements as markers of neurodegenerative changes. This study included 55 subjects with AD, 30 subjects with mild cognitive impairments (MCI), and a control group with 30 subjects. We measured the brain, cerebellum, and brain stem volumes with magnetic resonance imaging (MRI). We determined serum ApoE levels, APOE genotypes, and neuropsychological test scores. In the control group, we found that ApoE levels were significantly higher for subjects with the APOE 2/3 genotype than those with the 4/4 genotype. This finding may indicate that ApoE plays a protective role against AD development in subjects with the APOE 2/3 genotype. ApoE levels were not significantly different in patients with AD and MCI. No correlations were found between serum ApoE levels and Mini-Mental State Examination (MMSE) scores or the volumes of brain structures. This study could not confirm the appropriateness of the cerebellum volume as an early AD marker. Correlations were found between cerebellar volume, brain volume, and the MMSE scores.

The Procyonid Social Club: Comparison of Brain Volumes in the Coatimundi (Nasua nasua, N. narica), Kinkajou (Potos flavus), and Raccoon (Procyon lotor)

The present study investigated whether increased relative brain size, including regional brain volumes, is related to differing behavioral specializations exhibited by three member species of the family Procyonidae. Procyonid species exhibit continuums of behaviors related to social and physical environmental complexities: the mostly solitary, semiarboreal and highly dexterous raccoons (Procyon lotor); the exclusively arboreal kinkajous (Potos flavus), which live either alone or in small polyandrous family groups, and the social, terrestrial coatimundi (Nasua nasua, N. narica). Computed tomographic (CT) scans of 45 adult skulls including 17 coatimundis (9 male, 8 female), 14 raccoons (7 male, 7 female), and 14 kinkajous (7 male, 7 female) were used to create three-dimensional virtual endocasts. Endocranial volume was positively correlated with two separate measures of body size: skull basal length (r = 0.78, p < 0.01) and basicranial axis length (r = 0.45, p = 0.002). However, relative brain size (total endocranial volume as a function of body size) varied by species depending on which body size measurement (skull basal length or basicranial axis length) was used. Comparisons of relative regional brain volumes revealed that the anterior cerebrum volume consisting mainly of frontal cortex and surface area was significantly larger in the social coatimundi compared to kinkajous and raccoons. The dexterous raccoon had the largest relative posterior cerebrum volume, which includes the somatosensory cortex, in comparison to the other procyonid species studied. The exclusively arboreal kinkajou had the largest relative cerebellum and brain stem volume in comparison to the semi arboreal raccoon and the terrestrial coatimundi. Finally, intraspecific comparisons failed to reveal any sex differences, except in the social coatimundi. Female coatimundis possessed a larger relative frontal cortical volume than males. Social life histories differ in male and female coatimundis but not in either kinkajous or raccoons. This difference may reflect the differing social life histories experienced by females who reside in their natal bands, and forage and engage in antipredator behavior as a group, while males disperse upon reaching adulthood and are usually solitary thereafter. This analysis in the three procyonid species supports the comparative neurology principle that behavioral specializations correspond to an expansion of neural tissue involved in that function.

Frontal cortical thinning and subcortical volume reductions in early adulthood obesity

Obesity depends on homeostatic and hedonic food intake behavior, mediated by brain plasticity changes in cortical and subcortical structures. The aim of this study was to investigate cortical thickness and subcortical volumes of regions related to food intake behavior in a healthy young adult sample with obesity. Thirty-seven volunteers, 19 with obesity (age=33.7±5.7 (20–39) years body-mass index (BMI)=36.08±5.92 (30.10–49.69)kg/m2) and 18 controls (age=32.3±5.9 (21–40) years; BMI=22.54±1.94 (19.53–24.97)kg/m2) participated in the study. Patients with neuropsychiatric or biomedical disorders were excluded. We used FreeSurfer software to analyze structural magnetic resonance images (MRI) and obtain global brain measures, cortical thickness and subcortical volume estimations. Finally, correlation analyses were performed for brain structure data and obesity measures. There were no between-group differences in age, gender, intelligence or education. Results showed cortical thickness reductions in obesity in the left superior frontal and right medial orbitofrontal cortex. In addition, the obesity group had lower ventral diencephalon and brainstem volumes than controls, while there were no differences in any other subcortical structure. There were no statistically significant correlations between brain structure and obesity measures. Overall, our work provides evidence of the structural brain characteristics associated with metabolically normal obesity. We found reductions in cortical thickness, ventral diencephalon and brainstem volumes in areas that have been implicated in food intake behavior.

Neurological Soft Signs and Brainstem Morphology in First-Episode Schizophrenia

Background: Minor motor and sensory deficits or neurological soft signs (NSS) have frequently been reported in patients with schizophrenia at any stage of their illness. NSS have been demonstrated to correlate with neuroanatomical abnormalities in various brain regions. Despite its important role in the integration and coordination of automatic motor actions, the brainstem has so far rather been ignored in previous neuroimaging studies on NSS in schizophrenia. Method: We investigated 21 right-handed first-episode schizophrenia patients using high-resolution magnetic resonance imaging at 3 T. The severity of NSS was measured with the Heidelberg Scale. Associations between NSS and both brainstem volume and shape changes were examined. Results: Higher NSS scores were significantly associated with structural alterations in the brainstem. According to volume measurements higher NSS scores correlated with global changes of the brainstem. Using shape analyses these associations referred to regionally specific morphometric alterations predominantly in the midbrain and pons. Conclusion: The findings suggest that brainstem morphometric alterations are associated with the severity of NSS in patients with first-episode schizophrenia. They further indicate the involvement of the brainstem in the pathogenesis of schizophrenia.

SU‐E‐T‐274: Dosimetric Indicators of Radiation‐Induced Toxicity in Meningioma Patients

Purpose: In this study, we retrospectively reviewed treatment plans and normal tissue toxicities for patients who were treated for meningiomas to investigate the correlation between DVH parameters and late Grade 3 radiation‐induced brainstem toxicity and hearing or vision changes. Methods: We analyzed data from 26 patients treated for brain meningiomas with either proton radiation or photon IMRT (11 were treated to 54Gy and 15 to 59.4Gy or higher) between 2009 and 2012 at the University of Pennsylvania. Five patients developed late Grade 3 toxicity with the remaining patients having late Grade 2 toxicity or less. Eight patients experienced hearing changes and seventeen experienced vision changes. We evaluated the maximum brainstem dose and volume of brainstem receiving more than 50∼54Gy for late Grade 3 toxicities. We also evaluated maximum and mean doses to the optic structures and cochlea. Statistical significance of the correlation between late Grade 3 toxicity or hearing and vision changes and the above mentioned DVH constraints was evaluated using Fisher exact test (two‐tailed). Results: The proportion of patients with Dmax &gt; 45Gy or Dmean &gt; 30 Gy for the cochlea was significantly greater in patients with hearing changes (p &lt; 0.05 and p &lt; 0.1 respectively). While for the brainstem a difference in the proportion of patients with and without late Grade 3 toxicity and with V54Gy &gt; 5% was observed, this difference did not reach statistical significance. Conclusion: Differences were observed in the DVHs of meningioma patients who experienced radiation injury after radiation therapy. The mean dose to the cochlea is related to the likelihood of developing hearing changes. Based on the results of this study, dose volume parameters (that is, V54Gy) for the brainstem may be expected to be associated with Grade 3 toxicity in a larger cohort of patients.

SU‐E‐T‐679: Implications of Radiobiological Bath and Shower Effects On Brainstem Dose Tolerance

Purpose: To gain insight into radiosurgical brainstem dose tolerance by considering the radiobiological implications of the bath and shower experiments. Methods: Clinical brainstem dose tolerance for radiosurgery is compared to the two extreme cases of hypofractionated whole brain irradiation and trigeminal neuralgia radiosurgery. In 2003 and 2009, experimental results were published wherein a low dose to a large volume (bath) was combined with a high dose to a small volume (shower), for the cases of rat cervical spinal cord and rat parotid gland. Clinically the uniqueness of each patients' tumor requires a customized mixture of bath and shower doses to the adjacent critical structures, whereas in the animal experiments it was possible to systematically vary the bath dose and the shower dose and to statistically analyze the outcomes to study the interactions in detail, although human response may differ. Results: Hypofractionated whole brain irradiation results in essentially uniform bath dose to the brainstem at a single fraction dose equivalent of about 10Gy, according to the LQ model. For radiosurgery, Timmerman's 2008 limit allows 1cc of brainstem to exceed 10Gy in a single fraction. Therefore since the volume of brainstem receiving the bath dose is reduced, it allows a higher shower dose to be received by a small volume, and the corresponding TG101 limit allows a max dose of 15Gy. In the case of trigeminal neuralgia, the bath dose to brainstem is much lower, and some institutions have allowed an extremely high shower dose of 45Gy in a single fraction to the maximum point dose in brainstem, with surprisingly infrequent side effects under conditions of meticulous targeting and dosimetric accuracy. Conclusion: Clinically the tradeoff between doses to large and small volumes is already implicitly taken into account, but comparison to the radiobiological research can help provide insight. Dr. Grimm developed and holds intellectual property rights to the DVH Evaluator software tool which is an FDA‐cleared product in commercial use

Biological and clinical characteristics of individuals at risk for spinocerebellar ataxia types 1, 2, 3, and 6 in the longitudinal RISCA study: analysis of baseline data

Spinocerebellar ataxias (SCAs) are autosomal, dominantly inherited, fully penetrant neurodegenerative diseases. Our aim was to study the preclinical stage of the most common SCAs: SCA1, SCA2, SCA3, and SCA6. Between Sept 13, 2008, and Dec 1, 2011, offspring or siblings of patients with SCA1, SCA2, SCA3, or SCA6 were enrolled into a prospective, longitudinal observational study at 14 European centres. To be eligible for inclusion in our study, individuals had to have no ataxia and be aged 18-50 years if directly related to individuals with SCA1, SCA2, or SCA3, or 35-70 years if directly related to individuals with SCA6. We did anonymous genetic testing to identify mutation carriers. We assessed participants with clinical scales, questionnaires, and performance-based coordination tests. In eight of the 14 centres, participants underwent MRI. We analysed relations between outcome variables and time from onset (defined as the difference between present age and estimated age at ataxia onset). This study is registered with ClinicalTrials.gov, number NCT01037777. 276 participants met inclusion criteria and agreed to participate, of whom 12 (4%) were excluded from final analysis because DNA samples were missing or genotyping failed. Estimated time from onset was -9 years (IQR -13 to -6) in 50 carriers of the SCA1 mutation, -12 years (-15 to -9) in 31 SCA2 mutation carriers, -8 years (-11 to -6) in 26 SCA3 mutation carriers, and -18 years (-22 to -16) in 16 SCA6 mutation carriers. Compared with non-carriers of each mutation, SCA1 mutation carriers had higher median scores on the scale for the assessment and rating of ataxia (SARA; 0·5 [IQR 0-1·0] vs 0 [0-0]; p=0·0052), as did SCA2 mutation carriers (0·5 [0-2·0] vs 0 [0-0·5]; p=0·0037). SCA2 mutation carriers had lower SCA functional index scores than did non-carriers (-0·43 [-0·91 to -0·07] vs 0·09 [-0·30 to 0·56]; p=0·0007). SCA2 mutation carriers had worse composite cerebellar functional scores than did their non-carrier counterparts (0·915 [0·861-0·959] vs 0·849 [0·764-0·886]; p=0·0039). All other differences between carriers and non-carriers were non-significant. In SCA1 and SCA2 mutation carriers, SARA scores were increased in participants who were closer to the estimated age at onset (SCA1: r=0·36, p=0·0112; SCA2: r=0·50, p=0·0038). 83 individuals (30%) underwent MRI. Voxel-based morphometry showed grey-matter loss in the brainstem and cerebellum in SCA1 and SCA2 mutation carriers, and normalised brainstem volume was lower in SCA2 mutation carriers (median 0·015, range 0·012-0·016) than in non-carriers (0·019, 0·017-0·021; p=0·0107). Preclinical SCA1 and SCA2 mutation carriers seem to have mild coordination deficits and abnormalities in the brain that are more common in carriers who are closer to the estimated onset of ataxia. Individuals in this early disease stage could be targeted in future preventive trials. ERA-Net E-Rare and Polish Ministry of Science and Higher Education.

A two-year longitudinal pilot MRI study of the brainstem in autism

Research has demonstrated the potential role of the brainstem in the pathobiology of autism. Previous studies have suggested reductions in brainstem volume and a relationship between this structure and sensory abnormalities. However, little is known regarding the developmental aspects of the brainstem across childhood and adolescence. The goal of this pilot study was to examine brainstem development via MRI volumetry using a longitudinal research design. Participants included 23 boys with autism and 23 matched controls (age range=8–17 years), all without intellectual disability. Participants underwent structural MRI scans once at baseline and again at two-year follow-up. Brainstem volumetric measurements were performed using the BRAINS2 software package. There were no significant group differences in age, gender, handedness, and total brain volume; however, full-scale IQ was higher in controls. Autism and control groups showed different patterns of growth in brainstem volume. While whole brainstem volume remained stable in controls over the two-year period, the autism group showed increases with age reaching volumes comparable to controls by age 15 years. This increase of whole brainstem volume was primarily driven by bilateral increases in gray matter volume. Findings from this preliminary study are suggestive of developmental brainstem abnormalities in autism primarily involving gray matter structures. These findings are consistent with autism being conceptualized as a neurodevelopmental disorder with alterations in brain-growth trajectories. More longitudinal MRI studies are needed integrating longitudinal cognitive/behavioral data to confirm and elucidate the clinical significance of these atypical growth patterns.

Genotype-specific patterns of atrophy progression are more sensitive than clinical decline in SCA1, SCA3 and SCA6

Spinocerebellar ataxias are dominantly inherited disorders that are associated with progressive brain degeneration, mainly affecting the cerebellum and brainstem. As part of the multicentre European integrated project on spinocerebellar ataxias study, 37 patients with spinocerebellar ataxia-1, 19 with spinocerebellar ataxia-3 and seven with spinocerebellar ataxia-6 were clinically examined and underwent magnetic resonance imaging at baseline and after a 2-year follow-up. All patients were compared with age-matched and gender-matched healthy control subjects. Magnetic resonance imaging analysis included three-dimensional volumetry and observer-independent longitudinal voxel-based morphometry. Volumetry revealed loss of brainstem, cerebellar and basal ganglia volume in all genotypes. Most sensitive to change was the pontine volume in spinocerebellar ataxia-1, striatal volume in spinocerebellar ataxia-3 and caudate volume in spinocerebellar ataxia-6. Sensitivity to change, as measured by standard response mean, of the respective MRI measures was greater than that of the most sensitive clinical measure, the Scale for the Assessment and Rating of Ataxia. Longitudinal voxel-based morphometry revealed greatest grey matter loss in the cerebellum and brainstem in spinocerebellar ataxia-1, in the putamen and pallidum in spinocerebellar ataxia-3 and in the cerebellum, thalamus, putamen and pallidum in spinocerebellar ataxia-6. There was a mild correlation between CAG repeat length and volume loss of the bilateral cerebellum and the pons in spinocerebellar ataxia-1. Quantitative volumetry and voxel-based morphometry imaging demonstrated genotype-specific patterns of atrophy progression in spinocerebellar ataxias-1, 3 and 6, and they showed a high sensitivity to detect change that was superior to clinical scales. These structural magnetic resonance imaging findings have the potential to serve as surrogate markers, which might help to delineate quantifiable endpoints and non-invasive methods for rapid and reliable data acquisition, encouraging their use in clinical trials.

Ipsilateral and Contralateral Auditory Brainstem Response Reorganization in Hemispherectomized Patients

Background. Cortical hemispherectomy leads to degeneration of ipsilateral subcortical structures, which can be observed long term after the operation. Therefore, reorganization of the brainstem auditory pathway might occur. The aim of this study was to assess reorganization of brainstem auditory pathways by measuring the auditory brainstem response (ABR) in long-term hemispherectomized patients. Methods. We performed bilateral monaural stimulation and measured bilateral ABR in 8 patients ~20 years after hemispherectomy and 10 control subjects. Magnetic resonance imaging (MRI) was performed in patients to assess structural degeneration. Results. All patients showed degenerated ipsilateral brainstem structures by MRI but no significant differences in bilateral recording ABR wave latencies. However, nonsurgical-side stimulation elicited significantly longer wave V latencies compared to surgical-side stimulation. Differences in bilateral ABR were observed between hemispherectomized patients and control subjects. Waves III and V latencies elicited by nonsurgical-side stimulation were significantly longer than those in control subjects; surgical-side stimulation showed no significant differences. Conclusions. (1) Differences in ABR latency elicited by unilateral stimulation are predominantly due to bilateral brainstem auditory pathway activity rather than to changes in brainstem volume; (2) ABR Waves III and V originate predominantly in the contralateral brainstem; and (3) subcortical auditory pathways appear to reorganize after long term hemispherectomy.

Structural alterations in brainstem of fibromyalgia syndrome patients correlate with sensitivity to mechanical pressure

Fibromyalgia syndrome is a chronic pain disorder characterised by widespread pain and tenderness in muscles and deep tissues. Current theories regarding the pathophysiological origins of fibromyalgia syndrome point towards central sensitisation and a decreased capacity of descending nociceptive controls. Morphological alterations to subcortical brain regions may contribute to such pathophysiological mechanisms, and to pain and other symptoms seen in fibromyalgia. Therefore, we evaluated geometric differences in subcortical structures in fibromyalgia patients relative to healthy people using a novel method of shape analysis. Sixteen female fibromyalgia patients and 15 age and sex matched, healthy control subjects underwent high-resolution T1-weighted magnetic resonance image scanning. Data was analysed using shape analysis of 15 subcortical regions and standard voxel-based morphometry analysis.Fibromyalgia syndrome patients, relative to healthy control participants, exhibited alterations to the shape of the left lateral aspect of the lower brainstem (medulla). The mean total volume of the brainstem was also found to be significantly reduced in the patient group compared to healthy control subjects, and this brainstem volume reduction in patient group significantly correlated with clinical manual tender point scale scores. Voxel-based morphometry analysis revealed that patients also demonstrated decreased local grey matter volumes in the brainstem (pons) and left precuneus, and increased grey matter volumes in bilateral primary somatosensory cortices.Results suggest that the volume reduction and associated geometric shape alterations seen in the brainstem of the patient group may contribute to sensitivity to pressure pain in fibromyalgia syndrome. This finding may be due to structure-related deficiencies in regions subserving descending nociceptive control.

Sodium Benzoate, a D-Amino Acid Oxidase Inhibitor, Increased Volumes of Thalamus, Amygdala, and Brainstem in a Drug-Naïve Patient With Major Depression

Sodium Benzoate, a D-Amino Acid Oxidase Inhibitor, Increased Volumes of Thalamus, Amygdala, and Brainstem in a Drug-Naïve Patient With Major Depression

Dose-volume effects on brainstem dose tolerance in radiosurgery

Dose-volume data concerning the brainstem in stereotactic radiosurgery (SRS) for trigeminal neuralgia (TN) were analyzed in relation to associated complications. The authors present their set of data and compare it with currently cited information on brainstem dose tolerance associated with conventional fractionated radiation therapy and hypofractionated radiation treatment of other diseases. Stereotactic radiosurgery for TN delivers a much higher radiation dose to the brainstem in a single fraction than doses delivered by any other procedures. A literature survey of articles on radiosurgery for TN revealed no incidences of severe toxicity, unlike other high-dose procedures involving the brainstem. Published data on brainstem dose tolerance were investigated and compared with dose-volume data in TN radiosurgery. The authors also performed a biological modeling study of dose-volume data involving the brainstem in cases of TN treated with the Gamma Knife, CyberKnife, and linear accelerator-based systems. The brainstem may receive a maximum dose as high as 45 Gy during radiosurgery for TN. The major complication after TN radiosurgery is mild to moderate facial numbness, and few other severe toxic responses to radiation are observed. The biologically effective dose of 45 Gy in a single fraction is much higher than any brainstem dose tolerance currently cited in conventional fractionation or in single or hypofractionated radiation treatments. However, in TN radiosurgery, the dose falloff is so steep and the delivery so accurate that brainstem volumes of 0.1-0.5 cm(3) or larger receive lower planned and delivered doses than those in other radiation-related procedures. Current models are suggestive, but an extensive analysis of detailed dose-volume clinical data is needed. Patients whose TN is treated with radiosurgery are a valuable population in which to demonstrate the dose-volume effects of an extreme hypofractionated radiation treatment on the brainstem. The result of TN radiosurgery suggests that a very small volume of the brainstem can tolerate a drastically high dose without suffering a severe clinical injury. The authors believe that the steep dose gradient in TN radiosurgery plays a key role in the low toxicity experienced by the brainstem.

Effects of Glutamine on Brain Development in Very Preterm Children at School Age

The amino acid glutamine has been shown to reduce the number of serious neonatal infections in very preterm children, which may benefit long-term brain development. The aims of the current follow-up study were to (1) determine the long-term effects of glutamine-enriched feeding in the first month after birth in very preterm children on measures of brain development at school age, and (2) elucidate a potential mediating role of serious neonatal infections. Fifty-two very preterm children who originally took part in a randomized controlled trial on enteral glutamine supplementation between day 3 and 30 after birth participated at a mean (SD) age of 8.6 (0.3) years. Measures of brain development included volumetric outcomes of major brain structures, as well as fractional anisotropy (FA) values of major white matter tracts. Glutamine supplementation in the first month was associated with medium-sized increases in white matter (d = 0.54, P = .03), hippocampus (d = 0.47, P = .02), and brain stem (d = 0.54, P = .04) volumes at school age. Exploratory analyses using an uncorrected P value indicated higher FA values of the bilateral cingulum hippocampal tract in the glutamine group. All differences were either strongly associated (hippocampus volume, brain stem volume, and FA values of cingulum hippocampal tract) or completely mediated (white matter volume) by the lower number of serious neonatal infections in the glutamine group. Short-term glutamine supplementation after birth increases white matter, hippocampus, and brain stem volumes in very preterm children at school age, mediated by a decrease in serious neonatal infections.