Monozygotic Twins with Legg-Calvé-Perthes Disease and with Non-Identical Lumbosacral Malformation: a Case Report and Literature Review.

The authors present the cases of monozygotic male twins with right-sided Legg-Calvé-Perthes disease (LCPD) with different formation of the lumbosacral junction. This is likely the fi rst description of a lumbosacral junction formation disorder associated with identical twins who were both treated for LCPD as children. The disease began at 6 and 9 years of age and during treatment as well as in adulthood signifi cantly different bone formation of the lumbosacral transitional vertebra, was observed in both brothers. Twin A has a unilateral right-sided fusion of the enlarged L5 transverse process with the ipsilateral sacral ala, twin B has a complete sacralization of the fi fth lumbar vertebra. The LCPD treatment outcomes in the twins were consistent with the results from large studies, i.e., age at the time of LCPD onset is the main factor infl uencing the prognosis, however the morphological difference in the transitional vertebrae in these monozygotic twins was signifi cantly. Key words: lumbosacral transitional vertebra, lumbosacral junction formation, sacralization of lumbar vertebra, megatransverse of vertebra L5.

[Avascular Necrosis of Femoral Head and Coxarthrosis Progression after Acetabular Fractures]. / Avaskulární nekróza hlavice femuru a progrese koxartrózy po zlomeninách acetabula.

PURPOSE OF THE STUDY Non-operative and operative treatment of acetabular fractures is associated with a risk of development of posttraumatic avascular necrosis of femoral head or with the development of posttraumatic coxarthrosis. The purpose of the study was to identify the occurrence of these two complications in patients in our group and to determine the risk factors for the development of these complications. MATERIAL AND METHODS The retrospective study was conducted in two Level I trauma centres in the period from 2009 to 2014. The group included patients with an acetabular fracture. The inclusion criteria were the following: outpatient follow-up for the period of 3 years after the injury, full radiology and CT documentation. The exclusion criteria were the following: pathological fractures, missing documentation after the union, insufficient follow-up period or dissent of the patient. The inclusion criteria were met by 192 patients, 48 women and 144 men, with the mean age of 48.9 years. The following basic epidemiological data were monitored: age, sex, cause of injury, type of fracture according to the Letournel classification, occurrence of associated injuries and type of therapy. The patients undergoing non-operative treatment as well as patients undergoing operative treatment underwent clinical and radiological examinations at 3 and 6 weeks after the injury, then at 3, 6 and 12 months after the injury, subsequent follow-up checks were done at a year-interval up to 3 years after the injury. RESULTS The posttraumatic avascular necrosis of femoral head developed in 22 patients (11.7%, 17 men, 5 women, p = 0.1159), with the mean age of 55.3 years (STDEVP 15.5, range from 22 to 82). The average time to the development of femoral head necrosis was 13.1 months (STDEVP 17.0, range from 1 to 80), median 6 months, 95% percentile 34 months. In a total of 16 patients necrosis developed within 18 months after injury, while in 6 patients after a longer period of time. Progression of coxarthrosis was observed in 63 patients (33.5%, 44 men and 19 women, p = 0.0447). Within 24 months progression was seen in 55 patients, beyond 2 years in 8 patients. Confirmed as risk factors for the development of posttraumatic avascular necrosis of femoral head and progression of posttraumatic coxarthrosis were the age 60 years and above (p = 0.0023), posttraumatic medialisation of the femoral head greater than 2 mm (p < 0.0001), displacement in the weight bearing area within the acetabulum greater than 2 mm (p < 0.0001), operative treatment (p = 0.0014), combined surgical approach (p = 0.0044), and higher caput-collum-diaphyseal (CCD) angle of proximal femur (p = 0.0142). At risk for the development of avascular necrosis were the A5 type fractures (p = 0.0214) and B2 type fractures (p = 0.0218), at risk for the development of coxarthrosis were the C1 type fractures (p = 0.0122). The isolated fractures of the anterior column were by contrast associated with a significantly lower risk for development of both the AVN (p = 0.0052) and posttraumatic coxarthrosis (p = 0.0006), the isolated fractures of the posterior wall were associated only with a higher risk for AVN and coxarthrosis summation (p = 0.0399), and the same applies to the T fractures (B3, p = 0.0200). DISCUSSION Majority of current studies regarding acetabular fractures focuses on operative treatment, short-term complications and comparison of outcomes of operative and non-operative treatment. Only a few studies are dedicated to epidemiological data, or risk factors for the development of medium-term and long-term complications. In the presented study attention was paid to two main complications arising from these fractures and requiring subsequent operative treatment: posttraumatic avascular necrosis of femoral head and posttraumatic coxarthrosis. The limitations of the study are its retrospective nature, summation of groups from two trauma centres (potential bias in patient enrolment or in assessing radiographs), lower frequency of clinical surveillance in non-operatively treated patients after healing, a fairly low number of non-operatively treated patients - especially those with osteoporosis-related insufficiency fractures. Ranking among the relative limitations is also the Letournel classification which, though most commonly used at present, shows a low level of correlation in comparisons by more evaluators. CONCLUSIONS Confirmed as significant risk factors for the development of posttraumatic avascular necrosis of the femoral head and posttraumatic coxarthrosis progression were the age of 60 and above, posttraumatic medialisation of the femoral head greater than 2 mm, displacement involving the weight bearing area of the acetabulum greater than 2 mm, operative treatment, combined operative approach. At risk are also the transverse fractures (A5 according to the Letournel classification), transverse posterior wall fractures (B2 according to the Letournel classification) and at risk for the development of coxarthrosis are both-column fractures with the high fracture line of the anterior column (C1 according to the Letournel classification). Femoral neck valgosity was a risk factor for the development of femoral head necrosis. Conversely, sex and instability of osteosynthesis detected on the radiograph within 3 months postoperatively were not confirmed as the risk factors for the development of aforementioned complications. To verify the results of this retrospective study other multicentric and prospective studies should be conducted. Key words: complications of treatment of acetabular fractures, risk factors for avascular necrosis of femoral head, risk factors for coxarthrosis.

The involvement of selected membrane transport mechanisms in the cellular uptake of (177)Lu-labeled bombesin, somatostatin and gastrin analogues.

INTRODUCTION: Radiolabeled receptor-targeting peptides are a useful tool for the diagnostic imaging and radiotherapy of some malignancies. However, the retention of radioactivity in the kidney may result in renal radiotoxic injury. This study seeks to evaluate the role of endocytic receptor megalin, renal SLC influx transporters and fluid phase endocytosis (FPE) in the cellular accumulation of radiolabeled peptides. METHODS: In vitro transport cellular studies using megalin ligands (RAP, albumin), fluid phase endocytosis (FPE) inhibitor rottlerin and low temperature were employed to evaluate the transport mechanisms of the peptides. Cells transfected with hOAT1 or hOCT2 were used to analyze the role of these SLC transporters. Somatostatin ((177)Lu-DOTA-[Tyr(3)]octreotate, (177)Lu-DOTA-[1-Nal(3)]octreotide), gastrin ((177)Lu-DOTA-sargastrin) and bombesin ((177)Lu-DOTA-[Pro(1),Tyr(4)]bombesin, (177)Lu-DOTA-[Lys(3)]bombesin, (177)Lu-PCTA-[Lys(3)]bombesin) analogues were involved in the study. RESULTS: RAP, albumin and low temperature decreased the accumulation of all the studied peptides significantly. With one exception, rottlerin caused the concentration dependent inhibition of the cellular accumulation of the radiopeptides. No significant differences in the uptake of the peptides between the control cells and those transfected with hOAT1 or hOCT2 were observed. CONCLUSION: The study showed that active transport mechanisms are decisive for the cellular accumulation in all tested (177)Lu-labeled somatostatin, gastrin and bombesin analogues. Besides receptor-mediated endocytosis by megalin, FPE participates significantly in the uptake. The tested types of renal SLC transporters are not involved in this process.

Curcumin inhibits COPD-like airway inflammation and lung cancer progression in mice.

Recent studies have demonstrated that K-ras mutations in lung epithelial cells elicit inflammation that promotes carcinogenesis in mice (intrinsic inflammation). The finding that patients with chronic obstructive pulmonary disease (COPD), an inflammatory disease of the lung, have an increased risk of lung cancer after controlling for smoking suggests a further link between lung cancer and extrinsic inflammation. Besides exposure to cigarette smoke, it is thought that airway inflammation in COPD is caused by bacterial colonization, particularly with non-typeable Hemophilus influenzae (NTHi). Previously, we have shown that NTHi-induced COPD-like airway inflammation promotes lung cancer in an airway conditional K-ras-induced mouse model. To further test the role of inflammation in cancer promotion, we administered the natural anti-inflammatory agent, curcumin, 1% in diet before and during weekly NTHi exposure. This significantly reduced the number of visible lung tumors in the absence of NTHi exposure by 85% and in the presence of NTHi exposures by 53%. Mechanistically, curcumin markedly suppressed NTHi-induced increased levels of the neutrophil chemoattractant keratinocyte-derived chemokine by 80% and neutrophils by 87% in bronchoalveolar lavage fluid. In vitro studies of murine K-ras-induced lung adenocarcinoma cell lines (LKR-10 and LKR-13) indicated direct anti-tumoral effects of curcumin by reducing cell viability, colony formation and inducing apoptosis. We conclude that curcumin suppresses the progression of K-ras-induced lung cancer in mice by inhibiting intrinsic and extrinsic inflammation and by direct anti-tumoral effects. These findings suggest that curcumin could be used to protract the premalignant phase and inhibit lung cancer progression in high-risk COPD patients.

Dynamic programming generation of boundaries of local coordinatized submanifolds in the neocortex: application to the planum temporale.

Dynamic programming is used to define boundaries of cortical submanifolds with focus on the planum temporale (PT) of the superior temporal gyrus (STG), which has been implicated in a variety of neuropsychiatric disorders. To this end, automated methods are used to generate the PT manifold from 10 high-resolution MRI subvolumes ROI masks encompassing the STG. A procedure to define the subvolume ROI masks from original MRI brain scans is developed. Bayesian segmentation is then used to segment the subvolumes into cerebrospinal fluid, gray matter (GM), and white matter (WM). 3D isocontouring using the intensity value at which there is equal probability of GM and WM is used to reconstruct the triangulated graph representing the STG cortical surface, enabling principal curvature at each point on the graph to be computed. Dynamic programming is used to delineate the PT manifold by tracking principal curves from the retro-insular end of the Heschl's gyrus (HG) to the STG, along the posterior STG up to the start of the ramus and back to the retro-insular end of the HG. A coordinate system is then defined on the PT manifold. The origin is defined by the retro-insular end of the HG and the y-axis passes through the point on the posterior STG where the ramus begins. Automated labeling of GM in the STG is robust with L(1) distances between Bayesian and manual segmentation in the range 0.001-0.12 (n = 20). PT reconstruction is also robust with 90% of the vertices of the reconstructed PT within about 1 voxel (n = 20) from semiautomated contours. Finally, the reliability index (based on interrater intraclass correlation) for the surface area derived from repeated reconstructions is 0.96 for the left PT and 0.94 for the right PT, thus demonstrating the robustness of dynamic programming in defining a coordinate system on the PT. It provides a method with potential significance in the study of neuropsychiatric disorders.

Rate of caudate atrophy in presymptomatic and symptomatic stages of Huntington's disease.

Previous research by our group demonstrated a longitudinal change in caudate volume for symptomatic subjects with Huntington's disease (HD), and suggested that volume of the caudate may be a useful outcome measure for therapeutic studies in symptomatic patients. The current study was designed to determine whether longitudinal change in caudate atrophy could be documented in presymptomatic carriers of the HD gene mutation, and to compare rate of change in these subjects with rate of change in mildly and moderately affected symptomatic patients. We measured caudate volumes on serial magnetic resonance image scans from 30 patients at three stages of HD: 10 presymptomatic; 10 with mild symptoms, as indicated by scores on the Quantified Neurological Exam (QNE) < or =35; and 10 with moderate symptoms (QNE >45). The mean interscan interval was 36 months. When analyzed separately, both symptomatic groups and the presymptomatic group demonstrated a significant change in caudate volume over time. Amount of change over time did not differ significantly among the three groups. We conclude that change in caudate volume may be a useful outcome measure for assessing treatment effectiveness in both presymptomatic and symptomatic subjects.

Elucidating the contributions of processing speed, executive ability, and frontal lobe volume to normal age-related differences in fluid intelligence.

One theory of normal cognitive aging asserts that decreases in simple processing speed mediate the age-related decline of fluid intelligence. Another possibility is that age-related atrophic changes in frontal brain structures undermine the functioning of executive abilities, thereby producing the same decline. In this study, we used principal components analysis to derive a measure of fluid-spatial intelligence in 197 normal adults between 20 and 92 years of age. Measures of perceptual comparison speed, working memory, and executive ability, as well as regional brain volumes based on high resolution magnetic resonance imaging were obtained from a subsample of 112 participants. We then conducted a series of hierarchical multiple regression analyses to test whether (1) the processing speed theory, (2) frontal-executive theory, or (3) some combination of these best accounted for age-related variation in fluid intelligence. The results showed that perceptual comparison speed, executive ability, and frontal lobe volume each made significant contributions to a regression equation that explained 57% of the variance in fluid intelligence. These findings suggest that both the processing speed and frontal-executive theory of cognitive aging are partially correct and complement one another.

Measurement of the planum temporale (PT) on magnetic resonance imaging scans: temporal PT alone and with parietal extension.

The planum temporale (PT) has been of interest because of (1) its consistent left greater than right asymmetry among right-handed and most left-handed normal individuals; and (2) its relation to language, another variable shown to be highly left-lateralized in normal subjects. Individuals with neurodevelopmental disorders have been reported to show abnormal PT asymmetry (either reversed or absent asymmetry). Several studies have been conducted measuring the PT on MRI scans, although the results do not always concur. We review some of these studies and discuss methodological differences between them. Additionally, we propose a method that has proved to be highly reliable for the measurement of both temporal PT and its parietal extension (PT+).

Sex differences in inferior parietal lobule volume in schizophrenia.

OBJECTIVE: The inferior parietal lobule is a heteromodal association cortical region that has been implicated in the pathophysiology of schizophrenia. Inferior parietal lobule gray matter volumes have been shown to differ between healthy male and female subjects, with male subjects having larger left volumes. The authors sought to determine whether these volumetric sex differences also exist in patients with schizophrenia. METHOD: The authors used magnetic resonance imaging to measure inferior parietal lobule volumes of 15 pairs of male and female schizophrenic subjects who were individually matched to each other and to 15 pairs of healthy male and female subjects. RESULTS: Male schizophrenic patients exhibited a reversal of the normal left-greater-than-right male asymmetry in this region and had left inferior parietal lobule gray matter volumes that were significantly smaller than those of healthy male subjects. Female schizophrenic patients did not differ significantly from healthy female subjects in left or right inferior parietal lobule volume or in asymmetry. CONCLUSIONS: This study provides further evidence of brain morphology sex differences in schizophrenia that possibly contribute to the differential clinical disease expression in men and women.

White matter hyperintensity volume in late-onset and early-onset schizophrenia.

BACKGROUND: Late life onset schizophrenia (sometimes termed "late paraphrenia") has been theorized to be due to neuro-degenerative processes affecting individuals with latent vulnerability to schizophrenia. However, neuro-imaging studies using computed tomography (CT) and magnetic resonance imaging (MRI) investigating possible degenerative anatomic correlates (atrophy, white matter disease, and strokes) to late onset psychoses have yielded conflicting findings. The variation in these findings may be due to differences in study design, case ascertainment, and measurement methods. OBJECTIVE: The present study compares a continuous measure of total volume of white matter hyperintensities (WMHs) in age, race, and gender-ratio matched groups of late-onset schizophrenic, elderly, early-onset schizophrenic and control subjects. METHOD: Our method of WMH measurement yielded an explicit volume and is an alternative to frequently used ordinal measures. RESULTS: We found no significant differences in the WMH volumes between these three groups. This finding is consistent with a prior study (Symonds et al., 1997. J Neuropsychiat Clin Neurosci 9: 251 - 258), that used ordinal measures.

MRI volumes of amygdala and hippocampus in non-mentally retarded autistic adolescents and adults.

OBJECTIVE: To determine whether volumes of hippocampus and amygdala are abnormal in people with autism. BACKGROUND: Neuropathologic studies of the limbic system in autism have found decreased neuronal size, increased neuronal packing density, and decreased complexity of dendritic arbors in hippocampus, amygdala, and other limbic structures. These findings are suggestive of a developmental curtailment in the maturation of the neurons and neuropil. METHODS: Measurement of hippocampus, amygdala, and total brain volumes from 1.5-mm coronal, spoiled gradient-recalled echo MRI scans in 14 non-mentally retarded autistic male adolescents and young adults and 14 individually matched, healthy community volunteers. RESULTS: Amygdala volume was significantly smaller in the autistic subjects, both with (p = 0.006) and without (p = 0.01) correcting for total brain volume. Total brain volume and absolute hippocampal volume did not differ significantly between groups, but hippocampal volume, when corrected for total brain volume, was significantly reduced (p = 0.04) in the autistic subjects. CONCLUSIONS: There is a reduction in the volume of amygdala and hippocampus in people with autism, particularly in relation to total brain volume. The histopathology of autism suggests that these volume reductions are related to a reduction in dendritic tree and neuropil development, and likely reflect the underdevelopment of the neural connections of limbic structures with other parts of the brain, particularly cerebral cortex.

Sex differences in the inferior parietal lobule.

The inferior parietal lobule (IPL) - a neocortical region and part of the heteromodal association cortex (HASC) - has been hypothesized to exhibit sexual dimorphism, as do other HASC regions, particularly with regard to asymmetry. Using a reliable method for measuring IPL gray matter volume based upon individual sulcal-gyral landmarks, we measured this region on magnetic resonance imaging scans from a sample of 15 individually matched pairs of normal male and female subjects. Male subjects showed significantly larger left, but not right, IPL volumes when compared to females. Males also showed a leftward (left > right) asymmetry for the IPL, with a less marked opposite asymmetry in females. Such sexual dimorphisms may possibly underlie the subtle cognitive differences observed between the sexes.

Lack of normal pattern of cerebral asymmetry in familial schizophrenic patients and their relatives--The Maudsley Family Study.

Lack of the normal cerebral asymmetry has been reported in schizophrenia. We wished to test the hypothesis that this lack of the normal pattern of asymmetry is familial and that it can be found in both schizophrenic and non-schizophrenic family members. In particular, we wanted to know whether those relatives who appear to be transmitting liability to the illness also demonstrate the loss of normal asymmetry. We studied families with several members affected with schizophrenia. We carried out volumetric measurements of prefrontal, premotor, sensorimotor and occipitoparietal regions in each hemisphere using 3D reconstructed MRI images in 29 schizophrenic patients, 55 of their first degree relatives, and 39 unrelated control subjects on contiguous thin slices of the brain. Nine of the unaffected relatives appeared to be transmitting the liability for schizophrenia (e.g. the mother of a schizophrenic patient who, although not psychotic herself, had a schizophrenic parent or sibling). We termed them presumed obligate carriers and the remaining 46 relatives presumed non-obligate carriers. The healthy control subjects showed larger right than left prefrontal regions and larger left than right sensorimotor and occipitoparietal regions. The schizophrenic patients showed lack of this normal brain asymmetry in the prefrontal, sensorimotor and occipitoparietal cortical regions. The presumed obligate carriers were similar to the schizophrenic patients in exhibiting lack of asymmetries in these cortical regions, while the presumed non-obligate relatives showed lack of asymmetry only in the occipitoparietal region. There was no overall reduction in total or regional brain volumes among the groups. Our findings indicate that lack of the normal pattern of frontal and occipital asymmetry is a marker for genetic liability to schizophrenia in families multiply affected with schizophrenia.

MRI volumes of the hippocampus and amygdala in adults with Down's syndrome with and without dementia.

OBJECTIVE: This study sought to determine whether volumes of the hippocampus and amygdala are disproportionately smaller in subjects with Down's syndrome than in normal comparison subjects and whether volume reduction is greater in Down's syndrome subjects with dementia. METHOD: The subjects were 25 adults with Down's syndrome (eight with dementia) and 25 cognitively normal adults who were individually matched on age, sex, and race. Magnetic resonance imaging measures included volumes of the hippocampus, amygdala, and total brain. Nineteen of the Down's syndrome subjects had follow-up scans (interscan interval = 9-41 months). RESULTS: Nondemented Down's syndrome subjects had significantly smaller volumes of the hippocampus, but not the amygdala, than their comparison subjects, even when total brain volume was controlled for. Volumes of both the hippocampus and the amygdala were smaller in the demented Down's syndrome subjects than in their comparison subjects, even when total brain volume was controlled for. Age was not correlated with volume of the hippocampus or amygdala among the nondemented Down's syndrome subjects and the comparison subjects; age was correlated with volume of the amygdala, but not the hippocampus, among the Down's syndrome subjects with dementia. Changes in volume over time were not statistically significant for either the demented or the nondemented subjects. CONCLUSIONS: Hippocampal volume, while disproportionately small for brain size in individuals with Down's syndrome, remains fairly constant through the fifth decade of life in those without dementia. All subjects over age 50 who had Down's syndrome demonstrated volume reduction in the hippocampus as well as clinical signs of dementia. Dementia was also associated with volume reductions in the amygdala that exceeded reductions in total brain volume.

Brain changes in schizophrenia. Volumetric MRI study of families multiply affected with schizophrenia--the Maudsley Family Study 5.

BACKGROUND: Structural brain abnormalities have been reported in schizophrenia. We tested the hypothesis that these abnormalities represented a marker for the genetic liability to schizophrenia in a sample of people with schizophrenia and their relatives from families multiply affected with the disorder. METHOD: We compared 31 people with schizophrenia, 57 relatives and 39 unrelated control subjects. Volumetric measurement of brain structures was carried out using stereological principles from three-dimensional reconstructed magnetic resonance images. RESULTS: Subjects with schizophrenia had larger lateral ventricles than their relatives and the normal control subjects. Relatives who were 'presumed obligate carriers' had larger left lateral ventricles than other relatives and the control subjects. Subjects with schizophrenia showed smaller whole brain and cerebellar volumes and larger lateral ventricles than their age- and gender-matched unaffected siblings. CONCLUSIONS: In families multiply affected with schizophrenia lateral ventricular enlargement distinguishes people with schizophrenia and presumed obligate carriers from other relatives and unrelated control subjects. These changes may be a marker for a genetic liability to schizophrenia.

Mesial temporal lobe measurements on magnetic resonance imaging scans.

Changes in the mesial temporal lobe, particularly in the hippocampus, amygdala, and entorhinal cortex, are reported to occur in several neuropsychiatric conditions. Neuroimaging provides a non-invasive means of studying these changes. We present a method for reliably measuring the hippocampus, amygdala, and entorhinal cortex on MRI. The advantages of our method include high reliability, the use of orthogonal views in delineating boundaries and circumscription of measurement such that no tissue of any one anatomic structure is included in the measurement of another structure.

Structural evaluation of the prefrontal cortex in schizophrenia.

OBJECTIVE: Altered prefrontal cortical function has been repeatedly implicated in the pathophysiology of schizophrenia. Attempts to determine whether this altered function is associated with structural changes in the prefrontal cortex have been hampered by the failure to examine more anatomically and functionally homogeneous regions. The authors have developed a reliable set of anatomical landmarks for subdividing the prefrontal cortex into superior, middle, inferior, and orbital regions, in order to determine whether patients with schizophrenia exhibit selective morphological abnormalities of the prefrontal cortex. METHOD: Magnetic resonance imaging (MRI) studies were obtained in 24 normal control subjects (14 men and 10 women) and 18 patients with schizophrenia (12 men and six women) by using a high-resolution thin spoiled-gradient recall acquisition in the steady-state protocol. The MRI images were used to determine prefrontal gray matter volumes for the four prefrontal regions and prefrontal total gray and white volumes. RESULTS: Patients with schizophrenia exhibited selective gray matter volume reductions in the right and left inferior prefrontal cortex. There were no significant group differences in the other prefrontal regions. Patients with schizophrenia also exhibited decreased prefrontal total white matter and total volumes; there was no significant difference in prefrontal total gray matter volume. CONCLUSIONS: Patients with schizophrenia are characterized by relatively selective reductions in inferior prefrontal cortex gray matter volumes.

MRI brain changes in subjects with Down syndrome with and without dementia.

Individuals with Down syndrome (DS), a disorder of known genetic etiology (trisomy of chromosome 21), exhibit several types of structural brain abnormalities that are detectable pathologically and by MRI. In addition, in middle age, individuals with DS develop histological and, in some cases, clinical features of Alzheimer's disease (AD). Abnormalities in MRI scans of 50 adults with DS, 11 of whom had clinical dementia, are described and compared with those of 23 cognitively normal, healthy subjects who were matched for age, sex, and race. Qualitative visual analogue scale (VAS) ratings on MRI hard copies for all subjects and computer-aided volume measures for a subsample of subjects were carried out. On VAS, subjects with DS had larger lateral ventricles, a higher frequency of posterior fossa arachnoid cysts/megacisterna magna and fewer scans rated as normal compared with controls. Quantitatively, total brain and gray-matter volumes were reduced in DS, as were the volumes of the left hippocampus and amygdala; ventricle volumes were larger. Post hoc comparisons of subjects with DS with and without dementia revealed that on VAS the former had more generalized atrophy for age, mesial temporal shrinkage, and third ventricular enlargement. Similarly, total brain, left hippocampus, and left amygdala volumes were reduced quantitatively in subjects with DS with dementia, while ventricular volumes were increased.