Posterior Periventricular Regions Research Articles

132 A Novel Mechanism of Periventricular Strain Observed in Post-Mortem Human Brains for Mild Traumatic Brain Injury

INTRODUCTION: Mild traumatic brain injury (mTBI) can result in a myriad of long-term functional deficits reflecting diffuse axonal disruption. While microstructural anomalies in the periventricular regions of the brain have been identified through immunohistochemical analyses, diffusion tensor imaging and animal models, and contribute to a range of symptoms observed in mTBI, the mechanism of injury is not fully described. METHODS: Post-mortem human brains without space-occupying lesions and significant atrophy were included in this study. Using MRI and anatomical surface landmark localisation, cortical and subcortical markers were implanted along a sagittal plane in anterior, posterior and inferior periventricular regions as well as in the frontal, parietal, occipital and cerebellar lobes. A high-speed, high-resolution, two-dimensional imaging system was employed to measure brain displacement from direct low-velocity frontal impacts. Impact kinematics of the skull were measured using a DTS 6DX SLICE sensor array. Marker displacement in the anterior, inferior and posterior periventricular regions were calculated and individual frame position time-histories for markers' centre of gravity were recorded. RESULTS: Upon impact, the frontal horns of the lateral ventricles were observed to immediately collapse, followed by posterior fluid motion and occipital horn dilation not previously described in the literature. Substantial deformation was recorded in the periventricular areas, resulting in a significantly higher magnitude of strain relative to more superficial subcortical and cortical structures. In comparison, the posterior periventricular region of the brain recorded the highest magnitude of strain. CONCLUSIONS: This study describes the generation of unique high magnitude strain in the periventricular regions from ventricular fluid flow upon low-velocity frontal head impacts. While the clinical significance of the ventricular deformation remains to be elucidated, this represents an important association between the mechanism of injury and diffuse symptomatology observed in mTBI.

The use of vessel wall imaging to detect a de novo microaneurysm on the periventricular anastomoses in moyamoya disease: illustrative case.

Moyamoya disease (MMD) is linked to the formation of intracranial aneurysms. The authors recently observed an effective use of magnetic resonance vessel wall imaging (MR-VWI) to detect de novo unruptured MMD-associated microaneurysms. The authors describe a 57-year-old female who was diagnosed with MMD 6 years ago after suffering a left putaminal hemorrhage. MR-VWI revealed point-like enhancement in the right posterior paraventricular region during the annual follow-up. On the T2-weighted image, this lesion was surrounded by high intensity. Angiography revealed a microaneurysm in the periventricular anastomosis. Right combined revascularization surgery was performed to prevent future hemorrhagic events. Another de novo circumferential enhanced lesion on MR-VWI appeared in the left posterior periventricular region 3 months after surgery. Angiography revealed that the enhanced lesion was a de novo microaneurysm on the periventricular anastomosis. The left combined revascularization surgery went well. The bilateral microaneurysms vanished on follow-up angiography. Unruptured MMD-associated microaneurysms on the periventricular anastomosis can be detected using MR-VWI. Revascularization surgery can eliminate microaneurysms by reducing hemodynamic stress on the periventricular anastomosis.

Abstract- Poster

Introduction:Personality change in post Traumatic Brain Injury occurs in 59.1% of patients.(1)It can present with symptoms of depression, emotional instability, irritability and impulsive behaviour. (2)`Personality changes might not be obvious during the initial period of injury as the sensory and motor deficits will be predominant (3).CASE HISTORY:A 26 year old male with a history of Road traffic accident in 2014 with ensuing severe traumatic brain injury with Right Temporoparietal Subdural hemorrhage and midline shift, conservatively managed.Intial year following the TBI, he had retrograde and antegrade amnesia and needed support for his activities of daily living. Gradually his behavioural changes emerged.The patient had significant social and functional impairment at the time of admission (1-08-2021)and the family sought treatment.EXAMINATION:Higher mental functions-Impairment in delayed recall, abstract and social judgement.Lobar Function tests revealed impairment in abstract, lexical fluency suggestive of frontal damage and impaired recall and verbal memory with emotional and behavioural changes and placidity suggestive of temporal damage.DIAGNOSIS:A diagnosis of F 07.0 ORGANIC PERSONALITY DISORDER according to ICD-10 was made. MRI BRAIN revealed Gliosis in frontal and temporal lobes, Chronic lacunae in posterior Periventricular region, Mild Periventricular deep white matter hyperintensities. He was managed with Haloperidol, sodium valproate and benzodiazepines.CONCLUSION:Post traumatic brain injury organic personality change is a neurobehavioural sequelae of severe TBI.It has considerable overlap with several psychiatric and neurological disorders. Serial follow-up is necessary to evaluate the evolution of deficits and prognosis.

Neuroimaging of Children With Takayasu Arteritis.

Takayasu arteritis is a rare granulomatous chronic vasculitis that affects the aorta and its main branches. Neurologic manifestations can accompany the disease; however, there is no study on neuroimaging in children with Takayasu arteritis. Therefore, we aimed to evaluate cranial magnetic resonance imaging (MRI) in pediatric Takayasu arteritis patients. Demographic, clinical, and laboratory data were obtained retrospectively. The study included 15 pediatric Takayasu arteritis patients. All patients presented with constitutional symptoms. Additionally, 6 patients suffered from headache, 2 had syncope, 1 had loss of consciousness, and 1 had convulsion. All patients underwent cranial and diffusion MRI a median 12 months after diagnosis. Cranial MRI findings were normal in 12 patients, whereas 3 patients had abnormal findings, as follows: stenosis in the M1 and M2 segments of the left middle cerebral artery (n = 1); diffuse thinning of the right internal carotid, middle cerebral, and right vertebral and basilar artery (n = 1); as a sequela, areas of focal gliosis in both the lateral ventricular and posterior periventricular regions (n = 1). Among these 3 patients, 1 had no neurologic complaints. Abnormal MRI findings can be observed in pediatric Takayasu arteritis patients, even those that are asymptomatic; therefore, clinicians should carefully evaluate neurologic involvement in all pediatric Takayasu arteritis patients.

Diastolic Blood Pressure Is Associated With Regional White Matter Lesion Load: The Northern Manhattan Study.

Background and Purpose- Few studies have examined the separate contributions of systolic blood pressure and diastolic blood pressures (DBP) on subclinical cerebrovascular disease, especially using the 2017 American College of Cardiology/American Heart Association Blood Pressure Guidelines. Furthermore, associations with region-specific white matter hyperintensity volume (WMHV) are underexplored. Methods- Using data from the NOMAS (Northern Manhattan Study), a prospective cohort study of stroke risk and cognitive aging, we examined associations between systolic blood pressure and DBP, defined by the 2017 American College of Cardiology/American Heart Association guidelines, with regional WMHV. We used a linear mixed model approach to account for the correlated nature of regional brain measures. Results- The analytic sample (N=1205; mean age 64±8 years) consisted of 61% women and 66% Hispanics/Latinos. DBP levels were significantly related to WMHV differentially across regions (P for interaction<0.05). Relative to those with DBP 90+ mm Hg, participants with DBP <80 mm Hg had 13% lower WMHV in the frontal lobe (95% CI, -21% to -3%), 11% lower WMHV in the parietal lobe (95% CI, -19% to -1%), 22% lower WMHV in the anterior periventricular region (95% CI, -30% to -14%), and 16% lower WMHV in the posterior periventricular region (95% CI, -24% to -6%). Participants with DBP 80 to 89 mm Hg also exhibited about 12% (95% CI, -20% to -3%) lower WMHV in the anterior periventricular region and 9% (95% CI, -18% to -0.4%) lower WMHV in the posterior periventricular region, relative to participants with DBP 90≥ mm Hg. Post hoc pairwise t tests showed that estimates for periventricular WMHV were significantly different from estimates for temporal WMHV (Holms stepdown-adjusted P<0.05). Systolic blood pressure was not strongly related to regional WMHV. Conclusions- Lower DBP levels, defined by the 2017 American College of Cardiology/American Heart Association guidelines, were related to lower white matter lesion load, especially in the periventricular regions relative to the temporal region.

The magnetic resonance imaging (MRI) of brain and cervical spine findings, at time of diagnosis of neuromyelitis optica spectrum disorder patients in Isfahan city

Neuromyelitis optica spectrum disease is a demyelinating disease which mainly involves optic nerve and spinal cord. Most of patients have abnormal brain MRI.The point is involvement of regions with high expression of aquaporin 4 channels. Long extending transverse myelitis (LETM) in cervical region is one of the main signs for NMOSD diagnosis. This is a retrograde study on 105 patients with neuromyelitis optica spectrum disease diagnosis, referred to Isfahan Kashani Hospital MS clinic. Patient's age, age of onset, presenting symptom ,primary brain and cervical MRI findings and Expanded Disability Status Scale(EDSS) recorded. Anti-AQP4 antibody was checked with cell based culturing method in a unique laboratory. 105 cases of NMOSD including 80(76.19%) females and 25(23.81%) males with mean age of onset of 28±12 were recorded. 32(30.47 %) patients were.LETM and segmental spinal lesions were found in 48(45.71%) and 28(26.66%) of all. Diagnostic brain lesions(Including Area postreoma ,brain stem ,thalamus ,hypothalamus, periepandymal area of 3rd and 4th ventricle)and posterior periventricular lesions were seen in 34(32.38%) and 44(41.90%) of them.Also posterior periventricular lesions were present in 16 seropositive and segmental spine lesion were found in 9 (28.12%) of them.49.52% of all patients presented with optic neuritis at the first time and 39.04% referred with myelitis. We found lesions in posterior periventricular region and segmental type myelitis.These lesions did not mentioned in the NMOSD diagnosis criteriayet. Another point is occurrence of vertigo and ataxia in 11 patients as first presentations of the disease which show lesions in regions with high expression of aquaporin 4 channels.

An investigation of cerebrovascular lesions in dementia with Lewy bodies compared to Alzheimer's disease

IntroductionCerebrovascular lesions on MRI are common in Alzheimer's disease (AD) dementia, but less is known about their frequency and impact on dementia with Lewy bodies (DLB). MethodsWhite-matter hyperintensities (WMHs) and infarcts on MRI were assessed in consecutive DLB (n = 81) and AD dementia (n = 240) patients and compared to age-matched and sex-matched cognitively normal subjects (CN) from a population-based cohort. ResultsDLB had higher WMH volume compared to CN, and WMH volume was higher in the occipital and posterior periventricular regions in DLB compared to AD. Higher WMH volume was associated with history of cardiovascular disease and diabetes but not with clinical disease severity in DLB. Frequency of infarcts in DLB was not different from CN and AD dementia. DiscussionIn DLB, WMH volume is higher than AD and CN and appears to be primarily associated with history of vascular disease.

Mild cognitive impairment, poor episodic memory, and late-life depression are associated with cerebral cortical thinning and increased white matter hyperintensities.

In various independent studies to date, cerebral cortical thickness and white matter hyperintensity (WMH) volume have been associated with episodic memory, depression, and mild cognitive impairment (MCI). The aim of this study was to uncover variations in cortical thickness and WMH volume in association with episodic memory, depressive state, and the presence of MCI simultaneously in a single study population. The participants were 186 individuals with MCI (clinical dementia rating [CDR] of 0.5) and 136 healthy elderly controls (HCs; CDR of 0) drawn from two community-based cohort studies in northern Japan. We computed cerebral cortical thickness and WMH volume by using MR scans and statistically analyzed differences in these indices between HCs and MCI participants. We also assessed the associations of these indices with memory performance and depressive state in participants with MCI. Compared with HCs, MCI participants exhibited thinner cortices in the temporal and inferior parietal lobes and greater WMH volumes in the corona radiata and semioval center. In MCI participants, poor episodic memory was associated with thinner cortices in the left entorhinal region and increased WMH volume in the posterior periventricular regions. Compared with non-depressed MCI participants, depressed MCI participants showed reduced cortical thickness in the anterior medial temporal lobe and gyrus adjacent to the amygdala bilaterally, as well as greater WMH volume as a percentage of the total intracranial volume (WMHr). A higher WMHr was associated with cortical thinning in the frontal, temporal, and parietal regions in MCI participants. These results demonstrate that episodic memory and depression are associated with both cortical thickness and WMH volume in MCI participants. Additional longitudinal studies are needed to clarify the dynamic associations and interactions among these indices.

Multifocal and Multicentric Glioblastoma with Leptomeningeal Gliomatosis: A Case Report and Review of the Literature

Glioblastoma (GBM) rarely presents as an infratentorial tumor in adults. The authors present a case of concomitant supratentorial and infratentorial GBM in an adult. A 72-year-old man presented with headache, nausea, vomiting, and lightheadedness. Initial MR images revealed enhancing masses in the right cerebellum and right posterior periventricular region. The patient underwent a suboccipital craniotomy and resection of the cerebellar lesion. Final histopathology was consistent with glioblastoma. The patient went on to receive standard radiation treatment for GBM with concurrent and adjuvant temozolomide. However, the patient experienced clinical deterioration within a few days after starting radiotherapy. He and his family decided to forego treatment and pursue palliative care. The patient expired three months after the initial diagnosis. Autopsy findings supported the diagnosis of GBM with leptomeningeal gliomatosis and involvement of the cerebrum, cerebellum, and spinal cord. The authors review the literature and propose that the pathogenesis of multiple and multicentric GBM may involve neural stem cells within the subventricular zone or could result from tumor dissemination along established CNS routes, such as white matter tracts and CSF pathways.

Abnormalities of magnetic resonance spectroscopy and diffusion tensor imaging are correlated with executive dysfunction in patients with ischemic leukoaraiosis

Abnormal diffusion tensor imaging (DTI) results have been observed in the periventricular white matter in patients with ischemic leukoaraiosis (ILA). However, the underlying pathological changes and their relationship to cognitive impairments are obscure. In addition, damage in the thalamus, an important structure in the executive function network, has been suggested in ILA, but is poorly understood. Twenty patients with ILA and 20 healthy volunteers with similar ages and educational histories underwent DTI, magnetic resonance spectroscopy (MRS) and a neuropsychological assessment. In patients with ILA, we observed an increased mean diffusivity (MD) and decreased levels of N-acetylaspartate (NAA)/creatine (Cr) in the anterior and posterior periventricular region and the thalamus, as well as decreased fractional anisotropy (FA) in the anterior and posterior periventricular regions. MD and NAA/Cr levels in the anterior and posterior periventricular white matter and NAA/Cr levels in the thalamus were correlated with executive function. DTI and MRS abnormalities were consistent with axonal and/or neuronal loss and dysfunction in the anterior and posterior periventricular white matter and the thalamus. This study demonstrates that DTI and MRS techniques can be used to investigate pathological changes in the anterior and posterior periventricular white matter and the thalamus; these changes may be correlated with executive functional changes in patients with ILA.

High Signal Intensity on T2-Weighted MR Imaging at Term-Equivalent Age in Preterm Infants Does Not Predict 2-Year Neurodevelopmental Outcomes

DEHSI on T2-weighted MR imaging in preterm infants at term-equivalent age has been regarded as an unfavorable marker for neurodevelopmental outcome. The aim of this study was to examine the relationship between the presence and extent of DEHSI and neurodevelopmental outcomes. We evaluated the MR images of 160 preterm infants at term-equivalent age. The presence of DEHSI was evaluated in separate regions and classified into 5 grades based on the extent of DEHSI. We also examined within those infants with DEHSI, whether typical signal-intensity characteristics of the posterior periventricular crossroads region were visible. Finally, ADC and FA values within the white matter were analyzed. Neurodevelopmental outcomes were assessed at 2-year corrected age with a standardized neurologic examination and the BSID-II. The grade of DEHSI had significant linear trends with increasing ADC and a trend toward lower FA values. However, there was no relationship between the degree of DEHSI and 2-year neurodevelopmental outcomes. In contrast, 13 infants with DEHSI who did not have visible posterior crossroads had poorer neurodevelopmental outcomes compared with infants with visible posterior crossroads. Although DEHSI may represent disturbances in white matter structure, as illustrated by its relationship to altered ADC and FA values, there is no relationship to short-term neurodevelopment outcome unless there are invisible posterior crossroads, representing a severe form of global high T2 signal intensity.

Mirrored-self misidentification in a patient without dementia: evidence for right hemispheric and bifrontal damage

Mirrored-self misidentification, often referred as the ‘mirror sign’, is a delusion characterized by the inability to recognize one's own reflected image, often associated with the intact capacity to recognize others in the mirror. It has been described mainly in moderate or severe dementia, especially Alzheimer's disease. In the few reported cases without global cognitive impairment, right hemispheric and frontal dysfunctions have been described. We report a 90-year-old man with abrupt onset of the mirror sign after a minor right hemispheric ischemic stroke. Neuropsychological testing revealed preserved cognitive capacities, except for mild to moderate impairment of visuospatial skills, suggesting right hemisphere dysfunction. Neuroimaging showed a small right dorsolateral frontal infarct, and bifrontal encephalomalacia, consistent with a past history of head trauma. Scattered ischemic white matter lesions in posterior periventricular regions were also seen. It seems that the mirror sign is a multifactorial phenomenon that usually requires right hemispheric dysfunction (perceptual abnormalities, loss of familiarity) and frontal damage (loss of judgement and inability to correct wrong beliefs). The right frontal dorsolateral prefrontal cortex seems to have a crucial role in self-recognition.

Brain macro- and microscopic damage in patients with paediatric MS

ObjectiveTo characterise, using conventional and diffusion tensor (DT) MRI, the nature and distribution of lesions and the extent of damage in the brain normal-appearing white matter (NAWM) and grey matter...

Application of autologous bone marrow stem cells in giant axonal neuropathy

Giant axonal neuropathy is a rare disorder of autosomal recessive inheritance, morphologically characterized by accumulation of neurofilaments in enlargements of preterminal regions of central and peripheral axons. We present a 7-year-old girl with thick and tightly curled lackluster hair suffering from giant axonal neuropathy. The diagnosis was confirmed on the brain MRI which showed white matter abnormalities in the anterior and posterior periventricular regions as well as the cerebellar white matter. In view of the same, the patient was given intrathecal autologous bone marrow-derived stem cell therapy as part of the neuroregenerative rehabilitation therapy protocol. The patient showed functional improvements in her disability after receiving the therapy. A detailed case report is presented here with.

Migration, early axonogenesis, and Reelin-dependent layer-forming behavior of early/posterior-born Purkinje cells in the developing mouse lateral cerebellum

BackgroundCerebellar corticogenesis begins with the assembly of Purkinje cells into the Purkinje plate (PP) by embryonic day 14.5 (E14.5) in mice. Although the dependence of PP formation on the secreted protein Reelin is well known and a prevailing model suggests that Purkinje cells migrate along the 'radial glial' fibers connecting the ventricular and pial surfaces, it is not clear how Purkinje cells behave in response to Reelin to initiate the PP. Furthermore, it is not known what nascent Purkinje cells look like in vivo. When and how Purkinje cells start axonogenesis must also be elucidated.ResultsWe show that Purkinje cells generated on E10.5 in the posterior periventricular region of the lateral cerebellum migrate tangentially, after only transiently migrating radially, towards the anterior, exhibiting an elongated morphology consistent with axonogenesis at E12.5. After their somata reach the outer/dorsal region by E13.5, they change 'posture' by E14.5 through remodeling of non-axon (dendrite-like) processes and a switchback-like mode of somal movement towards a superficial Reelin-rich zone, while their axon-like fibers remain relatively deep, which demarcates the somata-packed portion as a plate. In reeler cerebella, the early born posterior lateral Purkinje cells are initially normal during migration with anteriorly extended axon-like fibers until E13.5, but then fail to form the PP due to lack of the posture-change step.ConclusionsPreviously unknown behaviors are revealed for a subset of Purkinje cells born early in the posteior lateral cerebellum: tangential migration; early axonogenesis; and Reelin-dependent reorientation initiating PP formation. This study provides a solid basis for further elucidation of Reelin's function and the mechanisms underlying the cerebellar corticogenesis, and will contribute to the understanding of how polarization of individual cells drives overall brain morphogenesis.

Isolation of Human Multipotent Neural Progenitors from Adult Filum Terminale

Stem cells have been isolated from several CNS regions, including the spinal cord. However, the terminal end of the spinal cord, filum terminale, has been referred to as a fibrovascular tag without neurogenic potential and of no clinical significance. Recently, we were fortunate to acquire some samples of this tissue. We show for the first time that progenitor cells exhibiting the hallmarks of stem cells can be isolated from adult human filum terminale (FTNPs). More specifically, FTNPs self-renew and proliferate to form neurospheres, and exhibit tripotent differentiation into neurons, astrocytes, and oligodendrocytes. Equally important, FTNPs develop the electrophysiological profile of neurons and glia. Whole-cell patch-clamp recordings show beta-III-tubulin(+) neurons exhibiting overshooting action potentials, displaying both the fast inactivating TTX-sensitive sodium current as well as 4-AP and TEA sensitive potassium currents. To assess potency in vivo, FTNPs were transplanted into the posterior periventricular region of control or ischemic rat brains. Despite a vigorous immune response against the xenograft, FTNPs survived and were found not only in the graft area but had also migrated to the lesioned CA1 region. Notwithstanding the immune response, FTNPs differentiated into astrocytes, but no neuronal differentiation was observed in the transplant milieu tested. However, neuronal differentiation in vivo cannot be ruled out and assessment of the conditions necessary to promote neurogenesis in vivo requires more research. Significantly, no tumor formation or aberrant cell morphology was seen in or adjacent to the graft area. Thus, filum terminale provides a novel source of adult human neural progenitor cells that develop into functional neurons with possible clinical applications.

Familial idiopathic basal ganglia calcification: a challenging clinical–pathological correlation

Sir, Familial idiopathic basal ganglia calcification (FIBGC) is characterized by brain calcium deposition and variable combinations of movement disorders, gait impairment, and neuropsychiatric symptoms [1-3, 5-7]. A locus was mapped on chromosome 14 [2], but it fails to account for disease in some families [7]. Penetrance estimates are hampered by inconsistent clinical-radiological correlation, and few detailed pathological reports are available [4, 7]. Herein, we provide clinical, radiological and pathological studies of a patient with FIBGC. We previously reported this family, including one autopsy study [4, 7]. The patient signed informed consent. A right-handed male (patient III-3 in [7]) came to our attention at age 76 with a 50-year history of trunk, upper extremities and oral abnormal movements. Motor symptoms began with writing difficulties, followed by right-predominant abnormal movements of both shoulders. At age 50, he developed progressive speech difficulties with mild memory and gait impairment. Six first-degree and three second-degree relatives had similar symptoms including generalized, oromandibular, axial, limb and cervical dystonia, chorea, postural tremor and ataxia (reported in [7]). The patient had mild recall impairment, speech-induced jaw-opening dystonia, trunk and right-predominant upper extremities chorea, right shoulder postural dystonia, and writer's cramp. Genetic testing was negative for Huntington's disease. Brain CT-scan showed calcification of the basal ganglia, subcortical white matter, thalamus, and cerebellum (Figure 1). Figure 1 Brain axial CT-scan shows third and lateral ventricles enlargement and severe calcification of the cerebellar hemispheres and vermis (a,b), striatum, globus pallidus and thalamus (b,c), and subcortical white matter and occipital cortex (a-d). Basal ganglia ... Over the next five years, the patient became severely dysarthric and unstable with falls. Upper extremities and trunk chorea and dystonia remained unchanged, whereas jaw-opening dystonia worsened. He scored 21/26 on the Mini Mental Status Examination (unable to write or draw), missing points on attention span and recall. The patient subsequently developed severe cognitive impairment and behavioral troubles with agitation and aggressiveness. He became unable to stand, chew or speak, lost 30kg over two years, and died at age 85. The fixed left hemibrain weighed 520g. There was mild frontal-predominant atrophy with enlarged lateral ventricles, and cerebellar atrophy. Brain arteries showed severe atherosclerosis. There was gray discoloration and gritty consistency of the posterior periventricular region, globus pallidus, putamen and anterior thalamus, and mild atrophy of the caudate nucleus (Figure 2a). The cerebellum had yellow-red discoloration and gritty consistency of deep white matter and dentate nucleus region. Figure 2 Macroscopic view (a) shows brown discoloration of globus pallidus (arrow), which had a gritty consistency at autopsy. On histology, von Kossa calcium staining (b) and hematoxylin-eosin staining (c-l) show widespread calcification of cerebellum deep regions ... There was striking vascular and parenchymal mineralization (Figure 2b-l) that stained positive for calcium (Figure 2b). In the cortex, small vessel calcific vasculopathy was prominent in lower cortical layers and at the grey-white junction in the depths of the sulci. Parenchymal calcification was patchy and multifocal in deep subcortical and posterior periventricular regions, putamen, globus pallidus, anterior thalamus, and in the visual cortex. There was massive cerebellar calcification in the hemispheres (cortex and white matter) and in the dentate nucleus. Even in severely affected areas, there was no significant neuronal loss. Mild Alzheimer pathology and amyloid angiopathy were present. There were ischemic changes in subcortical areas and numerous microinfarcts in the cortex and basal ganglia. Overall, the pathology was similar to that of our previous autopsied patient from the same family [4, 7]. Our observation highlights the difficulties in correlating the clinical, radiological and pathological features in FIBGC. Reasons for this include that: a) many family members have widespread calcification without symptoms [7], b) radiologic asymmetry does not always match that of symptoms, c) ataxia is rare despite common severe cerebellar involvement, and d) there is no significant neuronal loss even in severely affected areas. Although basal ganglia and subcortical/periventricular white matter involvement may explain movement disorders and cognitive impairment, the mechanism of neuronal dysfunction remains elusive. Extensive blood vessel and perivascular calcification may suggest a chronic ischemic mechanism leading to neuronal dysfunction only in susceptible brain regions/individuals. Chronic low-grade inflammation has been suggested to favor calcification, a hypothesis that gained support from the report of reactive astrocytes and microglia overexpressing inflammatory molecules around calcified areas [4]. However, using HLA-DR and GFAP immunostaining in our patient, we were unable to demonstrate activated microglia and reactive astrocytes. Alternatively, calcium deposition may alter glial cells metabolism and secondarily impair neuronal function, or only represent a by-standing phenomenon of a yet undefined patho-mechanism involving genetically-determined age-related neuronal dysfunction.

Patterns of cerebral white matter damage and cognitive impairment in adolescents born very preterm

There is increasing evidence about the presence of white matter damage in subjects with a history of premature birth, even in those classified as good outcome because of an apparently normal development. Although intellectual performance is within normal limits in premature children it is significantly decreased compared to paired controls. The purpose of this study was to investigate the relationship between a lower performance intelligence quotient and white matter damage in preterm adolescents. The sample comprised 44 adolescents (mean age±S.D.: 14.4±1.6 years) born before 32 weeks of gestational age and 43 term-born adolescents (14.5±2.1 years). Individual voxel-based morphometry analyses demonstrated that 35/44 (80%) preterm subjects had white matter abnormalities. The centrum semiovale and the posterior periventricular regions were the most frequently affected areas. Correlation analysis showed that in preterms the performance intelligence quotient correlated with the whole-brain white matter volume (r=0.32; P=0.036) but not with grey matter volume. Complementary analysis showed that low scores in the Digit Symbol subtest, a measure of processing speed, in the preterm group correlated with reductions in white matter concentration. These results suggest that white matter damage is highly common and that it persists until adolescence. Hence, diffuse white matter loss may be responsible for performance intelligence quotient and processing speed decrements in subjects with very preterm birth.

Gender differences and age-related white matter changes of the human brain: A diffusion tensor imaging study

Cerebral white matter undergoes various changes with normal aging. This study investigated the association between age, gender, and the global and regional fractional anisotropy (FA) and mean diffusivity (MD) in 145 adults (30 to 80 years old) using diffusion tensor magnetic resonance imaging. We studied sixteen regions of interest in both hemispheres to search for regions that display age- and gender-related white matter changes and also performed a complementary voxel-based analysis without any hypothesis a priori. On a global scale, our results indicate that the full brain FA was negatively correlated with age. The regional analysis showed that the anterior corpus callosum, the bilateral anterior and posterior internal capsule, and the posterior periventricular regions had the most significant age-related FA decrease. On the other hand, the FA in the temporal and occipital regions was not correlated with age. However, in contrast to males, females overall had a significantly lower FA in the right deep temporal regions. More gender differences in precentral, cingulate, and anterior temporal white matter areas were also found, suggesting that microstructural white matter organization in these regions may have a sexual dimorphism. Such differences were mainly due to the increase in diffusion perpendicular to fiber tracts.

TRANSPLANTATION OF STEM CELLS FROM THE ADULT HUMAN BRAIN TO THE ADULT RAT BRAIN

To investigate the migration, proliferation, and differentiation of stem cells and neural progenitor cells (NPCs) from the adult human brain after transplantation into adult rodent brains. Adult human NPCs were obtained from temporal lobe specimens removed because of medical intractable epilepsy. The cells were transplanted into the posterior periventricular region above the hippocampus in the brains of either healthy adult rats (control) or rats with selective injury of the hippocampal CA1 region (global ischemia). In the control animals, grafted cells were mainly distributed from the site of transplantation toward the midline along white matter tracts. The density of transplanted cells elsewhere, including the hippocampus, was low and apparently random. In animals with CA1 damage, NPCs showed targeted migration into the injured area. Cell survival at 10 weeks was 4.7 +/- 0.3% (control, n = 3) and 3.7 +/- 1.1% (ischemia, n = 3); at 16 weeks, cell survival was 3.4 +/- 0.6% (control, n = 2) and 7.2 +/- 1.5% (ischemia, n = 2), i.e., comparable to what has been observed earlier when transplanting embryonic tissue into the human brain or progenitor cells between inbred rats. The number of dividing cells decreased with time. Sixteen weeks after transplantation, 4 +/- 1% (n = 4) of the cells showed proliferative activity. We did not observe signs of tumor formation or aberrant cell morphology. Neuronal differentiation was much slower than what has been observed earlier in vitro or after transplantation to the developing nervous system, and 16 weeks after transplantation many surviving cells were still in maturation. The present study shows that adult human NPCs survive, show targeted migration, proliferate, and differentiate after grafting into the adult rat brain.