A comprehensive assessment of cerebellar damage in multiple sclerosis using diffusion tractography and volumetric analysis.

BACKGROUND: White matter (WM) and grey matter (GM) brain damage in multiple sclerosis (MS) is widespread, but the extent of cerebellar involvement and impact on disability needs to be clarified. OBJECTIVE: This study aimed to assess cerebellar WM and GM atrophy and the degree of fibre coherence in the main cerebellar connections, and their contribution to disability in relapsing-remitting MS (RRMS) and primary progressive MS (PPMS). METHODS: Fourteen patients with RRMS, 12 patients with PPMS and 16 healthy controls were recruited. Cerebellar WM and GM volumes and tractography-derived measures from the middle and superior cerebellar peduncles, including fractional anisotropy (FA), mean diffusivity (MD), and directional diffusivities, were quantified from magnetic resonance imaging (MRI). Patients were assessed on clinical scores, including the MS Functional Composite score subtests. Linear regression models were used to compare imaging measures between 12 RRMS, 11 PPMS and 16 controls, and investigate their association with clinical scores. RESULTS: Patients with PPMS showed reduced FA and increased radial diffusivity in the middle cerebellar peduncle compared with controls and patients with RRMS. In PPMS, lower cerebellar WM volume was associated with worse performance on the upper limb test. In the same patient group, we found significant relationships between superior cerebellar peduncle FA and upper limb function, and between superior cerebellar peduncle FA, MD and radial diffusivity and speed of walking. CONCLUSION: These findings indicate reduced fibre coherence in the main cerebellar connections, and link damage in the whole cerebellar WM, and, in particular, in the superior cerebellar peduncle, to motor deficit in PPMS.

Hippocampal atrophy in relapsing-remitting and primary progressive MS: a comparative study.

BACKGROUND: In multiple sclerosis (MS), demyelination and neuroaxonal damage are seen in the hippocampus, and MRI has revealed hippocampal atrophy. OBJECTIVES: To investigate and compare hippocampal volume loss in patients with relapsing-remitting MS (RRMS) and primary progressive MS (PPMS) using manual volumetry, and explore its association with memory dysfunction. METHODS: Hippocampi were manually delineated on volumetric MRI of 34 patients with RRMS, 23 patients with PPMS and 18 controls. Patients underwent neuropsychological tests of verbal and visuospatial recall memory. Linear regression was used to compare hippocampal volumes between subject groups, and to assess the association with memory function. RESULTS: Hippocampal volumes were smaller in MS patients compared with controls, and were similar in patients with RRMS and PPMS. The mean decrease in hippocampal volume in MS patients was 317 mm(3) (9.4%; 95% CI 86 to 549; p = 0.008) on the right and 284 mm(3) (8.9%; 95% CI 61 to 508; p = 0.013) on the left. A borderline association of hippocampal volume with memory performance was observed only in patients with PPMS. CONCLUSION: Hippocampal atrophy occurs in patients with RRMS and PPMS. Factors additional to hippocampal atrophy may impact on memory performance.

Brain atrophy and lesion load measures over 1 year relate to clinical status after 6 years in patients with clinically isolated syndromes.

BACKGROUND: Conventional MRI lesion measures modestly predict long term disability in some clinically isolated syndrome (CIS) studies. Brain atrophy suggests neuroaxonal loss in multiple sclerosis (MS) with the potential to reflect disease progression to a greater extent than lesion measures. OBJECTIVE: To investigate whether brain atrophy and lesion load, during the first year in patients presenting with CIS, independently predict clinical outcome (development of MS and disability at 6 years). METHODS: 99 patients presenting with CIS were included in the study. T1 gadolinium enhanced and T2 weighted brain MRI was acquired at baseline and approximately 1 year later. Percentage brain atrophy rate between baseline and follow-up scans was analysed using SIENA. RESULTS: Mean annual brain atrophy rates were -0.38% for all patients, -0.50% in patients who had developed MS at 6 years and -0.26% in those who had not. Brain atrophy rate (p = 0.005) and baseline T2 lesion load (p<0.001) were independent predictors of clinically definite MS. While brain atrophy rate was a predictor of Expanded Disability Status Scale (EDSS) score in a univariate analysis, only 1 year T2 lesion load change (p = 0.007) and baseline gadolinium enhancing lesion number (p = 0.03) were independent predictors of EDSS score at the 6 year follow-up. T1 lesion load was the only MRI parameter which predicted Multiple Sclerosis Functional Composite score at the 6 year follow-up. CONCLUSIONS: The findings confirm that brain atrophy occurs during the earliest phases of MS and suggest that 1 year longitudinal measures of MRI change, if considered together with baseline MRI variables, might help to predict clinical status 6 years after the first demyelinating event in CIS patients, better than measurements such as lesion or brain volumes on baseline MRI alone.

MRI measures show significant cerebellar gray matter volume loss in multiple sclerosis and are associated with cerebellar dysfunction.

BACKGROUND: Regional atrophy measures may offer useful information about the causes of specific clinical deficits in multiple sclerosis (MS). OBJECTIVE: To determine the magnitude of cerebellar gray and white matter (GM and WM) atrophy in patients with clinically isolated syndromes (CIS) and MS, and their role in clinical manifestations of cerebellar damage. METHODS: T1-weighted volumetric magnetic resonance imaging (MRI) of 73 patients [29 CIS, 33 relapsing-remitting MS (RRMS), 11 secondary progressive MS (SPMS)] was compared with 25 controls. GM and WM regions were generated using SPM5 and cerebellar regions delineated. Linear regression was used to investigate differences in tissue-specific cerebellar volumes between groups and the association with clinical measures. RESULTS: Mean cerebellar GM volume (CGMV) was 100.1 cm(3) in controls, 96.4 cm(3) in CIS patients, 91.8 cm(3) in RRMS patients, and 88.8 cm(3) in SPMS patients. Mean cerebellar WM volumes (CWMV) were 21.3 cm(3), 20.4 cm(3), 19.9 cm(3), and 18.8 cm(3), respectively. CGMV was reduced by 4.8 cm(3) (P = 0.054) in RRMS patients, and 8.5 cm(3) (P = 0.012) in SPMS patients, relative to controls. Only patients with SPMS showed a borderline significant reduction in CWMV compared with controls (mean 2.1 cm(3), P = 0.053). CGMV was significantly smaller in patients assessed as having cerebellar dysfunction compared with patients who had normal cerebellar function. Significant associations of CGMV and CWMV with performance on the nine-hole peg test were also observed. CONCLUSION: Clinically relevant GM atrophy occurs in the cerebellum of MS patients and is more prominent than WM atrophy. As such, it may provide complementary data to other regional atrophy and intrinsic tissue measures.

A decade of pre-diagnostic assessment in a case of familial Alzheimer's disease: tracking progression from asymptomatic to MCI and dementia.

Detailed study of the very earliest phases of Alzheimer's disease (AD) is seldom possible, especially those changes preceding the development of mild cognitive impairment (MCI), which may occur years before diagnosis. Knowledge of imaging and neuropsychological features of these early stages would add insight into this poorly understood phase of the disease. We present data from a subject who entered a longitudinal study of individuals at risk of familial Alzheimer's disease (FAD), as a healthy volunteer with no memory complaints, undergoing 12 assessments between 1992 and 2003. Longitudinal MRI, neuropsychological and clinical data are presented over the decade preceding this man's diagnosis, through the asymptomatic and prodromal preludes to his presentation with MCI and on to eventual conversion to AD.

The thymus in infancy and childhood. Embryologic, anatomic, and pathologic considerations.

Developmental anatomy and developmental and acquired disorders of the thymus are presented with an emphasis on those disorders that are relevant to infancy and childhood. Presented also is an attempt to correlate functional anatomy and pathologic and clinical findings.

Coarctation of the left pulmonary artery: effects on the pulmonary vasculature of infants.

At autopsy, two infants had unsuspected coarctation of the left pulmonary artery (CoLPA), which was produced by an extension of ductal tissue into the wall of the left pulmonary artery. The first case, a 4-month-old girl, also had a ventricular septal defect and an anomalous branching pattern of the innominate arterial trunk. Pulmonary arterial hypertensive changes were noted in the right lung. In contrast, the left lung showed thin-walled pulmonary arteries. The second case, a term female newborn, had exhibited severe unexplained respiratory distress since birth. Histologic sections of the right lung showed dilated pulmonary arteries with thinned media, whereas the left lung showed a persistent fetal arterial pattern. It is believed that the peripheral pulmonary arterial changes are age-dependent and associated with asymmetric blood flow between the right and left pulmonary arteries. CoLPA is a rare pulmonary artery defect, and early diagnosis of this abnormality is important.

The placental barrier to maternal HIV infection.

Infection with HIV destroys the immune system and causes acquired immunodeficiency syndrome (AIDS). Death results from common bacterial and opportunistic infections that are rare in persons with a healthy immune system. HIV infection frequently is a fatal sexually transmitted disease that can also be transmitted from an infected mother to her offspring.

Pancreatic disorders in pediatric acquired immune deficiency syndrome.

Acute pancreatitis, reported in 17% of pediatric patients with acquired immune deficiency syndrome (AIDS), is said to have a poor prognosis. We describe the pancreatic changes observed at autopsy from 71 children with human immunodeficiency virus (HIV) infection and document their nature, extent, and clinical relevance. The median age at autopsy of the children was 17 months (range, 2 months to 19 years); 38 were boys and 33 were girls. Parental intravenous drug use was the most frequent risk factor for AIDS, followed by blood transfusions. Respiratory failure and sepsis constituted the predominant causes of death. Nonspecific changes, such as edema, inflammation, fibrosis, inspissated material in acini and ducts, and enlarged Langerhans' islet predominated. Acute and chronic pancreatitis were mild except in one instance of a fatal acute probably dideoxyinosine-associated pancreatitis. Pancreatic involvement by opportunistic infections, such as cytomegalovirus (CMV), Mycobacterium avium intracellulare (MAI), and Candida, was focal and rare despite the high prevalence of these infections at autopsy. Focal lymphoplasmacytic infiltration and vascular calcifications were also observed. We conclude that pancreatic changes were frequently noted at autopsy in children with AIDS. They were usually mild, reflected systemic disease states, and were usually not life threatening. The incidence of opportunistic infections of the pancreas was low.

A genetic male infant with female phenotype in camptomelic syndrome: a possible relationship to exposure to oral contraceptives during pregnancy.

PIP: Camptomelic syndrome is a severe malformation disorder affecting infant cartilage and bone formation. This syndrome is also characterized by sex reversal in a significant proportion of phenotypic females. In this case report, the authors describe a typical case of camptomelic syndrome in a black infant who had been exposed in utero to an oral contraceptive (OC). The infant was born after a full-term pregnancy. The mother had taken an OC containing 0.5-1.0 mg norethindrone and 0.035 mg ethinyl estradiol. Exposure had occurred for 6 months after conception. Parents were healthy and unrelated. The infant exhibited significant bone malformation in her legs, arms, feet, spine, and rib cage. Chromosome analysis yielded a normal 46,XY G-banded karyotype. The infant died at the age of 3 years, 6 months. Autopsy findings evidenced a female reproductive system. Microscopic examination of ovarian tissues revealed only immature sex cords; no oocytes were found. The authors briefly comment on camptomelic syndrome cases previously reported and implications of X-Y chromosome-gene effects associated with this syndrome. This may be the second reported case involving exposure to OCs early in pregnancy and sex reversal.^ieng

Pathology of pediatric AIDS.

AIDS in children most often results from the transmission of HIV from an infected mother to her newborn infant. The number of HIV-infected infants and children is increasing. This chapter addresses the natural history of the disease, opportunistic and other infections in afflicted patients, lymphoproliferative syndromes, cardiovascular disease, HIV nephropathy, gastrointestinal pathology, neuropathologic findings, and neoplasms. The authors emphasize that the autopsy is a powerful research tool that allows systematic and thorough review of AIDS cases.

Pericardial effusion and its relationship to cardiac disease in children with acquired immunodeficiency syndrome.

Over 200 children with acquired immunodeficiency syndrome (AIDS) have been followed at our institution. We retrospectively evaluated 45 children from the above group. 26 of the 45 children had a pericardial effusion documented at echocardiography and/or at post-mortem examination. This report describes the association of pericardial effusion, myocarditis, and pericarditis in children with AIDS and the implications for imaging. Half of the children with a pericardial effusion had a normal cardiac silhouette on chest radiography. 18 children with a pericardial effusion, had associated cardiac abnormalities. These abnormalities were ventricular dilatation and/or hypertrophy, myocarditis, or pericarditis. The presence of pericardial effusion also correlated highly with pleural effusion and ascites. The presence of a pleural effusion and a pericardial effusion was almost exclusively seen in the children with cardiac abnormalities. Pericardial effusion and cardiac disease should not only be suspected in any child with radiographic signs of cardiomegaly, but be strongly suspected in any child with pleural effusions or ascites, even with a normal cardiac silhouette, especially if they are not responding to conventional medical therapy and their respiratory condition is not improving.

Histopathology of childhood pneumonia in developing countries.

Acute lower respiratory infection in children is a major cause of morbidity and mortality in developing countries. Viral and bacterial agents incite characteristic host responses at the level of the bronchi, bronchioles, alveolar walls, and air spaces that correlate with the clinical course. A systematic review of histopathologic features will enhance the understanding of the pathogenetic mechanisms and cofactors that influence the disease process, particularly how tissue injury may be influenced by nutritional status and access to antibiotics. Research priorities include immunologic assessment, micronutrient assays, and standardized autopsies in developing countries. DNA probes for organisms and immunocytochemical identification of cell markers in tissue promise a new era in microscopic visualization of pathogen-host interactions. International collaborative research between ministries of public health and medical universities must be encouraged as a means of providing technical assistance and of advancing new knowledge. Systematic standardized autopsy studies from multiple geographic areas may help define pathologic mechanisms, monitor the natural history of disease, and evaluate interventions in diverse populations.

Intestinal cytomegalovirus ganglioneuronitis in children with human immunodeficiency virus infection.

Cytomegalovirus in children with human immunodeficiency virus (HIV) infection can result in widespread involvement of enteric ganglion cells. Intestinal ganglioneuronitis, as noted in the two infants cited, expands the spectrum of neurologic lesions in children with acquired immunodeficiency syndrome (AIDS).