Hemispheric White Matter Research Articles

Prospective assessment of white matter integrity in adult stem cell transplant recipients.

Hematopoietic stem cell transplantation (HSCT) is often used in the treatment of hematologic disorders. Although it can be curative, the pre-transplant conditioning regimen can be associated with neurotoxicity. In this prospective study, we examined white matter (WM) integrity with diffusion tensor imaging (DTI) and neuropsychological functioning before and one year after HSCT in twenty-two patients with hematologic disorders and ten healthy controls evaluated at similar intervals. Eighteen patients received conditioning treatment with high-dose (HD) chemotherapy, and four had full dose total body irradiation (fTBI) and HD chemotherapy prior to undergoing an allogeneic or autologous HSCT. The results showed a significant decrease in mean diffusivity (MD) and axial diffusivity (AD) in diffuse WM regions one year after HSCT (p-corrected <0.05) in the patient group compared to healthy controls. At baseline, patients treated with allogeneic HSCT had higher MD and AD in the left hemisphere WM than autologous HSCT patients (p-corrected <0.05). One year post-transplant, patients treated with allogeneic HSCT had lower fractional anisotropy (FA) and higher radial diffusivity (RD) in the right hemisphere and left frontal WM compared to patients treated with autologous HSCT (p-corrected <0.05).There were modest but significant correlations between MD values and cognitive test scores, and these were greatest for timed tests and in projection tracts. Patients showed a trend toward a decline in working memory, and had lower cognitive test scores than healthy controls at the one-year assessment. The findings suggest a relatively diffuse pattern of alterations in WM integrity in adult survivors of HSCT.

Dl-3-n-butylphthalide is effective for demyelination: A case-combined study

Demyelinating diseases is common in neurology department, but its treatment is still not clear. A 40-year-old male who was addicted in heroin was hospitalized and presented worsening altered mental status in hospital. Brain magnetic resonance imaging (MRI) revealed a symmetrical diffuse long T1 and long T2 time abnormalities in the white matter of cerebral hemispheres which indicated demyelination. High-dose intravenous methylprednisolone was not effective as expected. However, after treatment with intravenous Dl-3-n-butylphthalide for 7 days, the patient's symptoms and features of electroencephalogram (EEG) and MRI improved. Hence, ethidium bromide was used in a rat model to evaluate the positive effects of Dl-3-n-butylphthalide in demyelinating diseases. The results indicated that Dl-3-n-butylphthalide prevented white matter from demyelinating by regulating apoptosis through multiple approaches.

Effects of prenatal exposure to air pollutants (polycyclic aromatic hydrocarbons) on the development of brain white matter, cognition, and behavior in later childhood.

Polycyclic aromatic hydrocarbons (PAHs) are ubiquitous and neurotoxic environmental contaminants. Prenatal PAH exposure is associated with subsequent cognitive and behavioral disturbances in childhood. To identify the effects of prenatal PAH exposure on brain structure and to assess the cognitive and behavioral correlates of those abnormalities in school-age children. Cross-sectional imaging study in a representative community-based cohort followed up prospectively from the fetal period to ages 7 to 9 years. The setting was urban community residences and an academic imaging center. Participants included a sample of 40 minority urban youth born to Latina (Dominican) or African American women. They were recruited between February 2, 1998, and March 17, 2006. Morphological measures that index local volumes of the surface of the brain and of the white matter surface after cortical gray matter was removed. We detected a dose-response relationship between increased prenatal PAH exposure (measured in the third trimester but thought to index exposure for all of gestation) and reductions of the white matter surface in later childhood that were confined almost exclusively to the left hemisphere of the brain and that involved almost its entire surface. Reduced left hemisphere white matter was associated with slower information processing speed during intelligence testing and with more severe externalizing behavioral problems, including attention-deficit/hyperactivity disorder symptoms and conduct disorder problems. The magnitude of left hemisphere white matter disturbances mediated the significant association of PAH exposure with slower processing speed. In addition, measures of postnatal PAH exposure correlated with white matter surface measures in dorsal prefrontal regions bilaterally when controlling for prenatal PAH. Our findings suggest that prenatal exposure to PAH air pollutants contributes to slower processing speed, attention-deficit/hyperactivity disorder symptoms, and externalizing problems in urban youth by disrupting the development of left hemisphere white matter, whereas postnatal PAH exposure contributes to additional disturbances in the development of white matter in dorsal prefrontal regions.

Perivascular spaces and headache: A population-based imaging study (HUNT-MRI).

In four previous clinic-based MRI studies headache sufferers (in particular migraineurs) had more perivascular spaces (PVS) than individuals who were headache-free. The present study was part of a large longitudinal, epidemiological study (Nord-Trøndelag Health Survey (HUNT)). The 1006 participants, age 50-65 years at inclusion, had participated in all previous HUNT surveys (1-3), and been randomly selected to a population-based imaging study of the head (HUNT-MRI, 2007-2009). The number of visible PVS in the basal ganglia (BG) and hemispheric white matter (HWM) was compared in headache sufferers (migraine with and without aura, non-migrainous headache) and people who were headache-free. The results showed in general small differences between headache sufferers and headache-free participants. In the cross-sectional analysis migraineurs without aura had fewer PVS than headache-free individuals in BG (OR = 0.84, 95% CI = 0.76--0.94, p value = 0.003) and in BG and HWM together (OR = 0.97, 95% CI = 0.95-1.00, p value = 0.046). No difference between long-term headache sufferers and long-term headache-free individuals with regard to number of PVS was found. In contrast to previous studies, the present large, blinded, population-based study showed no increase in number of dilated PVS among headache sufferers. Fewer PVS among those with migraine without aura may be a spurious finding.

Regional age differences in gray matter diffusivity among healthy older adults.

Aging is associated with microstructural changes in brain tissue that can be visualized using diffusion tensor imaging (DTI). While previous studies have established age-related changes in white matter (WM) diffusion using DTI, the impact of age on gray matter (GM) diffusion remains unclear. The present study utilized DTI metrics of mean diffusivity (MD) to identify age differences in GM/WM microstructure in a sample of healthy older adults (N = 60). A secondary aim was to determine the functional significance of whole-brain GM/WM MD on global cognitive function using the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS). Participants were divided into three age brackets (ages 50-59, 60-69, and 70+) to examine differences in MD and cognition by decade. MD was examined bilaterally in the frontal, temporal, parietal, and occipital lobes for the primary analyses and an aggregate measure of whole-brain MD was used to test relationships with cognition. Significantly higher MD was observed in bilateral GM of the temporal and parietal lobes, and in right hemisphere WM of the frontal and temporal lobes of older individuals. The most robust differences in MD were between the 50-59 and 70+ age groups. Higher whole-brain GM MD was associated with poorer RBANS performance in the 60-69 age group. Results suggest that aging has a significant and differential impact on GM/WM diffusion in healthy older adults, which may explain a modest degree of cognitive variability at specific time points during older adulthood.

Clinical characteristics and follow-up of pediatric patients with neuromyelitis optica and neuromyelitis optica spectrum disorders

To analyze the clinical characteristics of pediatric neuromyelitis optica (NMO) and neuromyelitis optica spectrum disorders (NMOSD). A retrospective analysis was performed evaluating clinical and laboratory characteristics of ten NMO and NMOSD children who were seen in our hospital from December 2010 to May 2014. Median age at onset was 8.9 years (range 0.8-13.8 years). Seven cases were female and three were male. Median disease duration was 1.5 months (range 1-18.5 months). Eight patients fulfilled diagnostic criteria for NMO and two patients fulfilled diagnostic criteria for NMOSD. The two NMOSD patients had recurrent longitudinally extensive transverse myelitis. Four cases had a monophasic disease course, and six cases had a recurrent course. In eight NMO patients, neuritis was the initial presentation. The two NMOSD patients had no neuritis in the first attack. Nine cases had clinical manifestations of myelitis, one case had asymptomatic spinal cord MRI anomaly. Among the ten patients, seven cases had brain lesions, wherein, four cases had the midbrain involvement and in four cases extensive hemispheric white matter was involved. Three cases had medullary involvement. And two cases had posterior limb of the internal capsule involvement, two cases had thalamus involvement. In one case there was pons, cerebellum or corpus callosum involvement, respectively. One case had accompanied brain symptoms. Of the five patients who had symptomatic brain lesions, four cases had encephalopathy accompanied by large hemispheric lesions on MRI, having a presentation similar to acute disseminated encephalomyelitis. And one case had multiple sclerosis like brain lesion. Of the ten patients tested, nine were seropositive for anti-aquaporin-4 autoantibody. One-patient was complicated with systemic lupus erythematosus. Oligoclonal bands were negative in all cases. All patients received treatment for acute attacks with high-dose intravenous methylprednisolone and intravenous gammaglobulin. The symptoms of 8 cases mitigated. Two cases whose symptoms showed no sign of improvement received plasmapheresis for acute attacks. Seven of the patients were followed up. The median duration of follow-up was 19 months (ranged from 13 months to 30 months). The median Expanded disability status (EDSS) score was 3 (range 1-7). Pediatric NMO and(or) NMOSD have a diverse clinical presentation which are more than just optic neuritis and transverse myelitis, including brain symptom. So it may be difficult to distinguish NMO and( or) NMOSD from acute disseminating encephalomyelitis and multiple sclerosis in the early stages of the disease. Antibodies to aquapoin-4 (AQP-Ab) testing is very important for differential diagnosis.

Hyperglycaemia, insulin therapy and critical penumbral regions for prognosis in acute stroke: further insights from the INSULINFARCT trial.

BackgroundRecently, the concept of ‘clinically relevant penumbra’ was defined as an area saved by arterial recanalization and correlated with stroke outcome. This clinically relevant penumbra was located in the subcortical structures, especially the periventricular white matter. Our aims were to confirm this hypothesis, to investigate the impact of admission hyperglycemia and of insulin treatment on the severity of ischemic damages in this area and to study the respective contributions of infarct volume and ischemic damage severity of the clinically relevant penumbra on 3-month outcome.MethodsWe included 99 patients from the INSULINFARCT trial. Voxel-Based Analysis was carried on the Apparent Diffusion Coefficient (ADC) maps obtained at day one to localize the regions, which were more damaged in patients i) with poor clinical outcomes at three months and ii) without arterial recanalization. We determined the intersection of the detected areas, which represents the clinically relevant penumbra and investigated whether hyperglycemic status and insulin regimen affected the severity of ischemic damages in this area. We performed logistic regression to examine the contribution of infarct volume or early ADC decrease in this strategic area on 3-month outcome.FindingsLower ADC values were found in the corona radiata in patients with poor prognosis (p< 0.0001) and in those without arterial recanalization (p< 0.0001). The tracking analysis showed that lesions in this area interrupted many important pathways. ADC values in this area were lower in hyperglycemic than in normoglycemic patients (average decrease of 41.6 ± 20.8 x10−6mm2/s) and unaffected by the insulin regimen (p: 0.10). ADC values in the clinically relevant penumbra, but not infarct volumes, were significant predictors of 3-month outcome.ConclusionThese results confirm that the deep hemispheric white matter is part of the clinically relevant penumbra and show that hyperglycaemia exacerbates the apparition of irreversible ischemic damage within 24 hours in this area. However, early intensive insulin therapy fails to protect this area from infarction.Trial RegistrationClinicalTrials.gov NCT00472381

Marchiafava-Bignami disease with asymmetric extracallosal lesions.

Marchiafava-Bignami disease (MBD) is a rare disease in patients with chronic alcoholism and is characterized by symmetric demyelination and necrosis of the corpus callosum. Clinical features include neuropsychiatric disorders, dysarthria, tetraparesis, astasia-abasia, impaired consciousness and symptoms of interhemispheric disconnection. The lesions in MBD are not restricted to the corpus callosum, but also occur in extracallosal regions. However, no case of MBD with extracallosal lesions confined to one side of the brain has been reported. We present a patient with MBD showing asymmetric extracallosal lesions and complete resolution of magnetic resonance imaging (MRI) abnormalities.

Patterns of Orthographic Working Memory Impairments in Acquired Dysgraphia in Adults: A Case Series analysis

Patterns of Orthographic Working Memory Impairments in Acquired Dysgraphia in Adults: A Case Series analysis

Diffusion-Weighted Lesions in Stroke Patients with Transient Symptoms - Where Are They Located?

Background: MR diffusion-weighted imaging (DWI) has revolutionized neuroimaging and contributed to a tissue-based redefinition of transient ischemic attack (TIA). Stroke patients with DWI lesions may have neurological symptoms that resolve completely within 24 h, suggesting successful vessel recanalization. Prior studies of stroke patients with transient symptoms have not found any predilection for DWI lesions in any specific territory. Other studies have, however, reported an association between higher brain dysfunction and presence of DWI lesions in patients with transient ischemic symptoms, suggesting a high rate of cortical affection in these patients. We sought to see whether DWI location in stroke patients with transient symptoms <24 h differed from those with persistent symptoms ≥24 h. We hypothesized an association between transient symptoms <24 h and cortical DWI lesion localization due to a possible higher rate of vessel recanalization in patients with transient symptoms causing distal cortical infarctions. Methods: Ischemic stroke patients examined with DWI and admitted within 24 h after symptom onset between February 2006 and November 2013 were prospectively registered in a database (The Bergen NORSTROKE Registry). Based on neurological examination 24 h after admission, patients were classified as having either transient symptoms <24 h (DWI <24) or persistent symptoms ≥24 h (DWI ≥24). DWI lesions were classified into different groups depending on lesion location: cortical lesions, confined to the supratentorial cortex; large subcortical lesions, located in the hemispheric white matter, basal ganglia, internal capsule, thalamus or corona radiate with a diameter ≥15 mm; lacunar lesions, located in the same territory as large subcortical lesions with a diameter <15 mm; mixed cortical-subcortical lesions, located in both supratentorial cortex and subcortex; cerebellar lesions, confined to the cerebellum; brain stem lesions, confined to the brain stem; multiple locations, located in more than one of the above defined areas. Results: A total of 142 ischemic stroke patients had DWI <24 and 830 DWI ≥24. Cortical DWI location was more frequent in patients with DWI <24 (54.2% vs. 29.5%, p < 0.001), while proportions of mixed cortical-subcortical lesions (13.4% vs. 26.5%, p = 0.001) and lesions with multiple locations (5.6% vs. 11.1%, p = 0.048) were less frequent as compared to DWI ≥24. Cortical DWI location was independently associated with DWI <24 when adjusted for confounders in multiple regression analyses (OR 1.89, 95% CI 1.28-2.81, p = 0.001). Conclusion: Cortical DWI location was independently associated with transient stroke symptoms <24 h. This may be explained by vessel recanalization, resulting in upstream transportation of remaining particles and distal cortical lesions.

Changes of Migraine‐Related White Matter Hyperintensities After 3 Years: A Longitudinal MRI Study

The aim of this longitudinal study was to investigate changes of migraine-related brain white matter hyperintensities 3 years after an initial study. Baseline quantitative magnetic resonance imaging (MRI) studies of migraine patients with hemispheric white matter hyperintensities performed in 2009 demonstrated signs of tissue damage within the hyperintensities. The hyperintensities appeared most frequently in the deep white matter of the frontal lobe with a similar average hyperintensity size in all hemispheric lobes. Since in this patient group the repeated migraine attacks were the only known risk factors for the development of white matter hyperintensities, the remeasurements of migraineurs after a 3-year long follow-up may show changes in the status of these structural abnormalities as the effects of the repeated headaches. The same patient group was reinvestigated in 2012 using the same MRI scanner and acquisition protocol. MR measurements were performed on a 3.0-Tesla clinical MRI scanner. Beyond the routine T1-, T2-weighted, and fluid-attenuated inversion recovery imaging, diffusion and perfusion-weighted imaging, proton magnetic resonance spectroscopy, and T1 and T2 relaxation time measurements were also performed. Findings of the baseline and follow-up studies were compared with each other. The follow-up proton magnetic resonance spectroscopy studies of white matter hyperintensities showed significantly decreased N-acetyl-aspartate (median values 8.133 vs 7.153 mmol/L, P=.009) and creatine/phosphocreatine (median values 4.970 vs 4.641 mmol/L, P=.015) concentrations compared to the baseline, indicating a more severe axonal loss and glial hypocellularity with decreased intracellular energy production. The diffusion values, the T1 and T2 relaxation times, and the cerebral blood flow and volume measurements presented only mild changes between the studies. The number (median values 21 vs 25, P<.001) and volume (median values 0.896 vs 1.140 mL, P<.001) of hyperintensities were significantly higher in the follow-up study. No changes were found in the hemispheric and lobar distribution of hyperintensities. An increase in the hyperintensity size of preexisting lesions was much more common than a decrease (median values 14 vs 5, P=.004). A higher number of newly developed hyperintensities were detected than disappeared ones (130 vs 22), and most of them were small (<.034 mL). Small white matter hyperintensities in patients with a low migraine attack frequency had a higher chance to disappear than large white matter hyperintensities or white matter hyperintensities in patients with a high attack frequency (coefficient: -0.517, P=.034). This longitudinal MRI study found clinically silent brain white matter hyperintensities to be predominantly progressive in nature. The absence of a control group precludes definitive conclusions about the nature of these changes or if their degree is beyond normal aging.

Central nervous system lymphoma: a description and analysis of patients’ clinical and radiological features

Background: Central nervous system (CNS) lymphoma is a rare brain neoplasm. Its incidence has increased these years, so it should be considered in the differential diagnosis for mass lesions in the CNS. The aim of the study was to describe the radiological and clinical features of patients with CNS lymphoma.Methods: The study was a retrospective study. All patients histopathologically confirmed to have CNS lymphoma from November 2008 to December 2013 in Siloam Hospital Lippo Village were included in the study. Medical records and patients’ MRI results were retrieved to be analyzed.Results: 32 patients were histopathologically diagnosed to have CNS lymphoma. The patients, mean age was 54 ± 15.01 years with slight male predominance. No patient was immuno compromised (CD4 &gt; 500 cells/µL and leukocyte 5,000-11,000 cells/µL). The median interval between the onset of the initial symptoms and diagnosis is 7 weeks. The most common presenting symptoms were headache, mental changes, and neurological deficits related to the location of lesion. MR images show that most lesions were enhanced with contrast, iso-hypointense in T1 weighted imaging (T1WI), iso- to hypointense with perifocal edema in T2 weighted imaging (T2WI), hyperintense in diffusion weighted imaging (DWI), with the most common location was white matter of cerebral hemisphere on one or more lobes and periventricular area, and the tumor could be single or multiple (24%) without clear edges.Conclusion: Short course of neurological worsening (within weeks) should lead a suspicion toward lymphoma. The characteristics of MR images are markedly enhanced by contrast, iso- to hypointense on T1WI and T2WI, and hyperintense in DWI, involving white matter of cerebral hemisphere and periventricular area.

EHMTI-0148. Perivascular spaces and headache: a population-based imaging study (MRI HUNT)

Method The study was part of a large longitudinal epidemiological study (Nord-Trondelag Health Survey (HUNT)). The 1006 participants were 50-65 years at inclusion, had participated in all previous HUNT studies (1, 2 and 3), and had been randomly selected to a population-based imaging study of the head (MRI-HUNT, 2007-2009). The number of dilated PVS in the basal ganglia (BG) and hemispheric white matter (HWM) was compared in headache sufferers (migraine with and without aura, non-migrainous headache) and headache-free. Both cross-sectional and longitudinal analyses were performed.

Long-term clinical and radiological improvement of chronic acquired hepatocerebral degeneration after obliteration of portosystemic shunt: Report of a case

Neurological manifestations are common in patients with decompensated cirrhosis. The majority of these patients show hepatic encephalopathy or chronic acquired (non-Wilsonian) hepatocerebral degeneration (CAHD). They characteristically present with dysarthria, ataxia, involuntary movements, and altered mental status. Neuroradiological examination in patients with hepatic encephalopathy often shows abnormal signals in multiple regions of the brain, such as the pallidum, putamen, caudate nucleus, hemispheric white matter, and ventral midbrain. The pathogenesis of hepatic encephalopathy and CAHD is poorly understood and the response to conventional therapies is often poor.We report a male patient with cirrhosis of unknown cause, who developed slowly progressive cerebellar truncal and limb ataxia and slurred speech. Magnetic resonance imaging (MRI) showed focal T2 hyperintensity in bilateral dentate nuclei and middle cerebellar peduncles (MCPs). After treatment by obliteration of the portosystemic shunt, clinical manifestations and MRI abnormalities were dramatically improved. He was followed for six years until he died of uncontrollable bleeding due to hepatocellular carcinoma. At the last examination 9months before death, he showed no apparent aggravation of neurological symptoms, and no abnormal signal intensities in the MCPs and supratentorial compartment. The clinical course and changes of brain MRI findings of this case are extremely rare, suggesting that obliteration of the portosystemic shunt may be effective for CAHD over long term.

Novel diffusion tensor imaging technique reveals developmental streamline volume changes in the corticospinal tract associated with leg motor control.

Diffusion tensor imaging (DTI) has expanded our knowledge of corticospinal tract (CST) anatomy and development. However, previous developmental DTI studies assessed the CST as a whole, overlooking potential differences in development of its components related to control of the upper and lower extremities. The present cross-sectional study investigated age-related changes, side and gender differences in streamline volume of the leg- and hand-related segments of the CST in children. DTI data of 31 children (1-14 years; mean age: 6±4 years; 17 girls) with normal conventional MRI were analyzed. Leg- and hand-related CST streamline volumes were quantified separately, using a recently validated novel tractography approach. CST streamline volumes on both sides were compared between genders and correlated with age. Higher absolute streamline volumes were found in the left leg-related CST compared to the right (p=0.001) without a gender effect (p=0.4), whereas no differences were found in the absolute hand-related CST volumes (p>0.4). CST leg-related streamline volumes, normalized to hemispheric white matter volumes, declined with age in the right hemisphere only (R=-.51; p=0.004). Absolute leg-related CST streamline volumes showed similar, but slightly weaker correlations. Hand-related absolute or normalized CST streamline volumes showed no age-related variations on either side. These results suggest differential development of CST segments controlling hand vs. leg movements. Asymmetric volume changes in the lower limb motor pathway may be secondary to gradually strengthening left hemispheric dominance and is consistent with previous data suggesting that footedness is a better predictor of hemispheric lateralization than handedness.

Biomechanical studies in an ovine model of non-accidental head injury

This paper presents the head kinematics of a novel ovine model of non-accidental head injury (NAHI) that consists only of a naturalistic oscillating insult. Nine, 7-to-10-day-old anesthetized and ventilated lambs were subjected to manual shaking. Two six-axis motion sensors tracked the position of the head and torso, and a triaxial accelerometer measured head acceleration. Animals experienced 10 episodes of shaking over 30min, and then remained under anesthesia for 6h until killed by perfusion fixation of the brain. Each shaking episode lasted for 20s resulting in about 40 cycles per episode. Each cycle typically consisted of three impulsive events that corresponded to specific phases of the head׳s motion; the most substantial of these were interactions typically with the lamb׳s own torso, and these generated accelerations of 30–70g. Impulsive loading was not considered severe. Other kinematic parameters recorded included estimates of head power transfer, head–torso flexion, and rate of flexion. Several styles of shaking were also identified across episodes and subjects. Axonal injury, neuronal reaction and albumin extravasation were widely distributed in the hemispheric white matter, brainstem and at the craniocervical junction and to a much greater magnitude in lower body weight lambs that died. This is the first biomechanical description of a large animal model of NAHI in which repetitive naturalistic insults were applied, and that reproduced a spectrum of injury associated with NAHI.

Idiopathic progressive chorea: misnomer or still reality? A case with neuropathological disconfirmation

Dear Sir,Most of the rarer causes of chorea have been clarified in thelast decades [1], so that the classic term of ‘‘idiopathicchorea’’ has been critically put into question.A 50-year-old Caucasian woman was referred formarked and progressive generalized chorea. The onset wasabout 1 year before and a depressive syndrome was alsopresent. Past medical and family histories were unre-markable. Slight dysarthria and adiadochokinesia werenoted. Ocular movements were normal. Deep tendonreflexes were diffusely enhanced and plantar response wasin extension bilaterally. Routine serology, ceruloplasmin,tumour markers, HIV serology, onconeural- and auto-antibodies were negative. The anti-streptolysin-O titre wasborderline and careful examination of blood smears failedto demonstrate acanthocytes. A magnetic resonance and a99mTc-ECD SPECT brain scans were not significant. Theneuropsychological assessment evidenced only minorimpairment in selective attention and slight dysexecutivenotes. Genetic testing for Huntigton’s disease (HD, 17/25triplets), DRPLA (150/150), SCA17 (36/37), SCA1 (21/30), SCA2 (23/23), SCA3 (20/22), SCA6 (11/12), SCA7(9/11), and FXTAS (23/23) were negative. Progranulin andPRNP mutations or C9orf72 expansions were absent. Anti-basal ganglia antibodies (ABGA) testing (courtesy ofDr. Giovannoni and Martino, UCL, UK) resulted in a weakpositive binding to pyruvate kinase M1 (60 kDa), while nobinding was shown for both gamma-neuron specific eno-lase, and aldolase C.Since neuroleptics were ineffective, a trial with high-dose IV steroids was attempted, with no immediateimprovement (HD Functional Capacities score: 2/13, stageIV; Folstein Chorea Scale score: 37/57). Three monthslater, only minor changes were noted (HDFCS: 3/13, stageIV; FCS: 27/57). The patient further deteriorated present-ing diffuse spasticity and dystonia. Due to worseningdysphagia the patient was referred for PEG positioning, butshe anyhow died of aspiration pneumonia about 4 yearssince the onset of chorea.The neuropathological study was carried out on forma-lin-fixed sections stained with hematoxylin-eosin, cresylviolet for Nissl substance, Heidenhain-Woelcke for myelin,thioflavine S for amyloid, and silver salts for neurofibrillarychanges (Bodian’s method). Immunohistochemistry wasperformed with antibodies to beta-amyloid (4G8), alpha-synuclein (4D6), ubiquitin (polyclonal), phosphorylated tau(AT8), prion protein (3F4), GFAP (polyclonal), CD3/43,leucocytes common antigen CD45, and MBP (polyclonal).Histopathological examination revealed mild neuronal lossin the cerebral cortex and basal ganglia. Reactive astrogl-iosis and microglia activation were marked in the thalamus,caudate, putamen and substantia nigra (SN) and morepronounced in the brainstem and cerebellum. Slight peri-vascular lymphocytic infiltration was present in the hemi-spheric and cerebellar white matter as well as in thestriatum, thalamus and brainstem. Extracellular deposits orintracellular inclusions were absent but esinophilic, ubiq-uitin-positive inclusions suggestive of Marinesco bodieswere found only in the SN. No clear retrospective corre-lation with imaging data was possible.

Handedness- and Hemisphere-Related Differences in Small-World Brain Networks: A Diffusion Tensor Imaging Tractography Study

Previous behavioral and scanning studies have suggested that handedness is associated with differences in brain morphology as well as in anatomical and functional lateralization. However, little is known about the topological organization of the white matter (WM) structural networks related to handedness. We employed diffusion tensor imaging tractography to investigate handedness- and hemisphere-related differences in the topological organization of the human cortical anatomical network. After constructing left hemispheric/right hemispheric weighted structural networks in 32 right-handed and 24 left-handed healthy individuals, we analyzed the networks by graph theoretic analysis. We found that both the right and left hemispheric WM structural networks in the two groups possessed small-world attributes (high local clustering and short paths between nodes), findings which are consistent with recent results from whole-brain structural networks. In addition, the right hemisphere tended to be more efficient than the left hemisphere, suggesting a high efficiency of general information processing in the right hemisphere. Finally, we found that the right-handed subjects had significant asymmetries in small-world properties (normalized clustering coefficient γ, normalized path length λ, and small-worldness σ), while left-handed subjects had fewer asymmetries. Our findings from large-scale brain networks aid in understanding the structural substrates underlying handedness-related and hemisphere-related differences in cognition and behavior.

Age- and Sex-Related Variations in the Brain White Matter Fractal Dimension Throughout Adulthood: An MRI Study

PurposeTo observe age- and sex-related differences in the complexity of the global and hemispheric white matter (WM) throughout adulthood by means of fractal dimension (FD).MethodsA box-counting algorithm was used to extract FD from the WM magnetic resonance images of 209 healthy adults from three structural layers, including general (gFD), skeleton (sFD), and boundaries (bFD). Model selection algorithms and statistical analyses, respectively, were used to examine the patterns and significance of the changes.ResultsgFD and sFD showed inverse U-shape patterns with aging, with a slighter slope of increase from young to mid-age and a steeper decrease to the old. bFD was less affected by age. Sex differences were evident, specifically in gFD and sFD, with men showing higher FDs. Age × sex interaction was significant mainly in the hemispheric analysis, with men undergoing sharper age-related changes. After adjusting for the volume effect, age-related results remained approximately the same, but sex differences changed in most of the features, with women indicating higher values, specifically in the left hemisphere and boundaries. Right hemisphere was still more complex in men.ConclusionsThis study is the first that investigates the WM FD spanning adulthood, treating age both as a continuous and categorical variable. We found positive correlations between FD and volume, and our results show similarities with those investigating small-world properties of the brain networks, as well as those of functional complexity and WM integrity. These suggest that FD could yield a highly compact description of the structural changes and also might inform us about functional and cognitive variations.

Neurologic Injury in Isolated Sulfite Oxidase Deficiency

We review clinical, neuroimaging, and genetic information on six individuals with isolated sulfite oxidase deficiency (ISOD). All patients were examined, and clinical records, biochemistry, neuroimaging, and sulfite oxidase gene (SUOX) sequencing were reviewed. Data was available on six individuals from four nuclear families affected by ISOD. Each individual began to seize within the first week of life. neurologic development was arrested at brainstem reflexes, and severe microcephaly developed rapidly. neuroimaging within days of birth revealed hypoplasia of the cerebellum and corpus callosum and damage to the supratentorial brain looking like severe hypoxic-ischemic injury that evolved into cystic hemispheric white matter changes. Affected individuals all had elevated urinary S-sulfocysteine and normal urinary xanthine and hypoxanthine levels diagnostic of ISOD. Genetic studies confirmed SUOX mutations in four patients. ISOD impairs systemic sulfite metabolism, and yet this genetic disease affects only the brain with damage that is commonly confused with the clinical and radiologic features of severe hypoxic-ischemic encephalopathy.