Signs Of Cerebral Atrophy Research Articles

Central nervous system anomalies in 41 Chinese children incontinentia pigmenti

IntroductionIncontinentia pigmenti (IP) is a rare neuroectodermal dysplasia caused by a defect in the IKBKG gene. The pathogenesis of central nervous system injury is believed to be related to microvascular ischemia. Currently, few treatment strategies are available for the inflammatory phase.Materials and methodsThis retrospective descriptive analysis included the clinical data of 41 children with IP collected from 2007 to 2021 in Xi’an, China, comprising clinical characteristics, imaging findings, blood cell analysis, skin histopathology, and genetic data.ResultsFourteen children (34%) aged 4 days to 5 months exhibited clinical signs and symptoms, including convulsions, delayed psychomotor development following neurological damage, and revealed significant MRI abnormalities, including ischemia, hypoxia, cerebral hypoperfusion, hemorrhage, encephalomalacia, and cerebral atrophy. Eight of the 24 patients (33%) presented with retinal vascular tortuosity and telangiectasis, accompanied by neovascularization and hemorrhage. Thirty-eight children (93%) had elevated eosinophils (mean: 3.63 ± 4.46 × 109), and 28 children (68%) had significantly elevated platelets (mean: 420.16 ± 179.43 × 109). Histopathology of skin revealed microvascular extravasation and vasodilation with perivascular and intravascular eosinophilic infiltration.ConclusionBrain injury in IP occurs during infancy until 5 months of age, which is also the acute dermatitis phase accompanied by eosinophilia and an increased platelet count. This study provides evidence of microvascular damage to the skin and fundus during the inflammatory phase. The mechanism of microvascular damage may be similar to that in the brain.

Age-related decline in cerebral oxygen consumption in multiple sclerosis

Cerebral oxygen metabolism is altered in relapsing-remitting multiple sclerosis (RRMS), possibly a result of disease related cerebral atrophy with subsequent decreased oxygen demand. However, MS inflammation can also inhibit brain metabolism. Therefore, we measured cerebral blood flow (CBF) and cerebral metabolic rate of oxygen (CMRO2) using MRI phase contrast mapping and susceptibility-based oximetry in 44 patients with early RRMS and 36 healthy controls. Cerebral atrophy and white matter lesion load were assessed from high-resolution structural MRI. Expanded Disability Status Scale (EDSS) scores were collected from medical records. The CMRO2 was significantly lower in patients (−15%, p = 0.002) and decreased significantly with age in patients relative to the controls (−1.35 µmol/100 g/min/year, p = 0.036). The lower CMRO2 in RRMS was primarily driven by a higher venous oxygen saturation in the sagittal sinus (p = 0.007) and not a reduction in CBF (p = 0.69). There was no difference in cerebral atrophy between the groups, and no correlation between CMRO2 and MS lesion volume or EDSS score. Therefore, the progressive CMRO2 decline observed before the occurrence of significant cerebral atrophy and despite adequate CBF supports emerging evidence of dysfunctional cellular respiration as a potential pathogenic mechanism and therapeutic target in RRMS.

A case of left posterior cortical atrophy presenting with kana-predominant reading impairment

The patient was an 85-year-old man with a one-year history of difficulty reading kana. Neuropsychological evaluation revealed kana (phonogram)-selective reading impairment and kanji (ideogram)-dominant writing impairment. MRI revealed significant cerebral atrophy in the left occipital cortex, leading to the clinical diagnosis of posterior cortical atrophy (PCA). Cerebrospinal fluid amyloid β1-42 levels were reduced, and amyloid PET showed accumulation in the posterior cingulate cortex, precuneus, and frontal lobe. In contrast, tau PET showed no accumulation in the atrophied brain areas. Episodes of REM sleep behavior disorder and decreased uptake on meta-iodobenzylguanidine (MIBG) myocardial scintigraphy suggested the involvement of Lewy body pathology. PCA with distinct laterality has been rarely reported, and ‍this is the first case to present Kana-selective reading impairment and Kanji-dominant writing impairment with neurodegenerative background.

Multimodal magnetic resonance imaging after experimental moderate and severe traumatic brain injury: A longitudinal correlative assessment of structural and cerebral blood flow changes.

Traumatic brain injury (TBI) is a worldwide problem that results in death or disability for millions of people every year. Progressive neurological complications and long-term impairment can significantly disrupt quality of life. We demonstrated the feasibility of multiple magnetic resonance imaging (MRI) modalities to investigate and predict aberrant changes and progressive atrophy of gray and white matter tissue at several acute and chronic time points after moderate and severe parasagittal fluid percussion TBI. T2-weighted imaging, diffusion tensor imaging (DTI), and perfusion weighted imaging (PWI) were performed. Adult Sprague-Dawley rats were imaged sequentially on days 3, 14, and 1, 4, 6, 8, and 12 months following surgery. TBI caused dynamic white and gray matter alterations with significant differences in DTI values and injury-induced alterations in cerebral blood flow (CBF) as measured by PWI. Regional abnormalities after TBI were observed in T2-weighted images that showed hyperintense cortical lesions and significant cerebral atrophy in these hyperintense areas 1 year after TBI. Temporal DTI values indicated significant injury-induced changes in anisotropy in major white matter tracts, the corpus callosum and external capsule, and in gray matter, the hippocampus and cortex, at both early and chronic time points. These alterations were primarily injury-severity dependent with severe TBI exhibiting a greater degree of change relative to uninjured controls. PWI evaluating CBF revealed sustained global reductions in the cortex and in the hippocampus at most time points in an injury-independent manner. We next sought to investigate prognostic correlations across MRI metrics, timepoints, and cerebral pathology, and found that diffusion abnormalities and reductions in CBF significantly correlated with specific vulnerable structures at multiple time points, as well as with the degree of cerebral atrophy observed 1 year after TBI. This study further supports using DTI and PWI as a means of prognostic imaging for progressive structural changes after TBI and emphasizes the progressive nature of TBI damage.

Intracranial Pressure Dysfunction Following Severe Intracerebral Hemorrhage in Middle-Aged Rats

Rising intracranial pressure (ICP) aggravates secondary injury and heightens risk of death following intracerebral hemorrhage (ICH). Long-recognized compensatory mechanisms that lower ICP include reduced cerebrospinal fluid and venous blood volumes. Recently, we identified another compensatory mechanism in severe stroke, a decrease in cerebral parenchymal volume via widespread reductions in cell volume and extracellular space (tissue compliance). Here, we examined how age affects tissue compliance and ICP dynamics after severe ICH in rats (collagenase model). A planned comparison to historical young animal data revealed that aged SHAMs (no stroke) had significant cerebral atrophy (9% reduction, p ≤ 0.05), ventricular enlargement (9% increase, p ≤ 0.05), and smaller CA1 neuron volumes (21%, p ≤ 0.05). After ICH in aged animals, contralateral striatal neuron density and CA1 astrocyte density significantly increased (12% for neurons, 7% for astrocytes, p ≤ 0.05 vs. aged SHAMs). Unlike young animals, other regions in aged animals did not display significantly reduced cell soma volume despite a few trends. Nonetheless, overall contralateral hemisphere volume was 10% smaller in aged ICH animals compared to aged SHAMs (p ≤ 0.05). This age-dependent pattern of tissue compliance is not due to absent ICH-associated mass effect (83.2 mm3 avg. bleed volume) as aged ICH animals had significantly elevated mean and peak ICP (p ≤ 0.01), occurrence of ICP spiking events, as well as bilateral evidence of edema (e.g., 3% in injured brain, p ≤ 0.05 vs. aged SHAMs). Therefore, intracranial compliance reserve changes with age; after ICH, these and other age-related changes may cause greater fluctuation from baseline, increasing the chance of adverse outcomes like mortality.

Analysis of clinical and imaging features of 6 cases of linear scleroderma en coup de sabre with central nervous system involvement in children

Objective: To summarize the clinical and imaging features of linear scleroderma en coup de saber (LSCS) with central nervous system involvement in children. Methods: The clinical data(clinical manifestations and imaging features) of 6 children diagnosed with LSCS with central nervous system involvement who were admitted to Beijing Children's Hospital Affiliated to Capital Medical University from May 2019 to November 2021 were retrospectively analyzed. Results: The 6 patients were all female, aged 6.8 (3.3, 11.0) years at the time of diagnosis, and aged 3.0 (1.7, 4.1) years at the time of discovery of facial skin lesions. Facial skin lesions appeared before neurological symptoms in 5 cases, and neurological symptoms appeared 2 months before skin lesions in 1 case. All the patients had "sword wound" skin lesions on the forehead with alopecia. Neurological manifestations included epileptic seizures in 6 cases, focal neurological defects in 5 cases, and headaches in 2 cases. The intracranial lesions were all ipsilateral to the skin lesions. The magnetic resonance imaging (MRI) of 6 cases showed abnormal signals mainly involving white matter in 1 hemisphere, and 3 cases showed local encephalomalacia. The scattered low signal was observed in 5 cases on susceptibility weighted imaging. Localized brain parenchyma or leptomeninges enhancement was seen on Gadolinium-enhanced sequences in 5 cases. Scattered foci of calcification on the affected side were seen on cranial CT in 4 cases. Skin biopsy was performed in 2 cases. Part of the lesion of the brain was removed in 1 case, and the pathological findings suggested small vasculitis, which was consistent with skin pathological changes. All patients received symptomatic treatment with antiepileptic drugs. Oral prednisone combined with methotrexate was given in 4 cases, and 1 case was given oral prednisone only. One case was presumed to be in the resting stage of the disease due to significant cerebral atrophy in half of the brain, and only antiepileptic drugs were added. The patients were followed up for 6-36 months. The skin lesions of scleroderma and alopecia did not progress in 5 cases, and hemifacial atrophy was developed in 1 case, which was considered to be combined with Parry-Romberg syndrome. The seizures were controlled in 4 cases. One case had reduced seizure frequency but left hemiplegia. One patient still had intractable epilepsy and paroxysmal headache. Conclusions: LSCS with central nervous system involvement is more common in girls, with seizures and neurological defects as the main manifestations. Intracranial lesions are mostly ipsilateral to the skin lesions. Cerebral microbleeds, calcification, and encephalomalacia foci are common, and the pathological changes in skin and intracranial lesions are consistent with small-vessel vasculitis. Prednisone combined with methotrexate treatment has shown some efficacy, but some children remain with refractory epilepsy and neurological deficit symptoms.

Superficial Siderosis and Microbleed Restricted in Cortex Might Be Correlated to Atrophy and Cognitive Decline in Sneddon's Syndrome.

Objective: Sneddon's syndrome is a rare non-inflammatory arteriopathy affecting small and medium-sized arteries, characterized by a generalized livedo reticularis and recurrent transient ischemic attack or ischemic stroke. Hemorrhagic stroke was reported in limited cases, but microbleeds and superficial siderosis were rarely issued. We aimed to investigate the hemorrhagic imaging features of Sneddon's syndrome and explore the possible mechanism and clinical relevance.Methods: Clinical data and cerebral MR imaging including T2* sequence of seven consecutive patients with Sneddon's syndrome were reviewed.Results: The most common neurological manifestations were cognitive impairment and stroke attack (71.4%), followed by seizures and movement disorder (28.6%). Cerebral microbleeds were detected in six patients on T2* sequence, all of them presented with cortical microbleeds, only one of them with microbleeds in basal ganglion. More than five microbleeds were observed in four of these six patients. The majority of the microbleeds were predominantly cortical restricted and especially located in the cortical watersheds. Multiple superficial siderosis were identified mainly involving cortical watersheds in five cases. Significant cerebral atrophy with prominent secondary white matter hyperintensities in bilateral cortical watersheds were also observed. Abnormal tortuous and multiple focal occlusion of bilateral distal MCA were shown in one patient by DSA. No stenosis of proximal segment of cerebral arteries was detected in all the patients.Conclusions: This is the first report illustrating abundant cortical microbleeds and superficial siderosis mainly involved the anterior and posterior cortical watersheds in Sneddon's syndrome. The surprisingly identical topographic distribution of hemorrhagic lesions and the obvious atrophy suggest cerebral atrophy might be secondary to the microangiopathy related hemorrhagic lesions and further contribute to the neurological deficit, especially the early cognitive decline in Sneddon syndrome.

Abstract WP476: Remarkable Hemorrhagic Imaging Manifestations Might Be Responsible for the Prominent Atrophy and Cognitive Decline in Sneddon Syndrome

Objective: Sneddon syndrome is a rare non-inflammatory arteriopathy affecting small and medium-sized arteries, characterized by a generalized livedo reticularis and recurrent ischemic stroke. Hemorrhagic stroke was reported in limited cases, but microbleeds and superficial siderosis were rarely issued, which might be underdiagnosed due to the limitation of technique. We aimed to investigate the hemorrhagic imaging features of Sneddon syndrome and explore the possible mechanism and clinical relevance. Methods: Clinical data and cerebral MR imaging including T2* sequence of 6 consecutive patients with Sneddon syndrome were reviewed. Results: The most common neurological manifestations were cognitive impairment and stroke attack(66.7%), followed by seizures(33.3%) and movement disorder(16.7%). Cerebral microbleeds were detected in all the patients on T2* sequence,four of whom presented more than 5 microbleeds.The majority of the microbleeds were predominantly cortical restricted and especially located in the cortical watersheds. Multiple superficial siderosis were identified and mainly involved cortical watersheds in 5 cases. Significant cerebral atrophy with prominent secondary white matter hyperintensities in bilateral cortical watersheds were also observed. Abnormal tortuous and multiple focal occlusion of bilateral distal MCA were shown in 1 patient by DSA. No stenosis of proximal segment of cerebral arteries was detected in all the patients. Conclusions: This is the first report illustrating abundant cortical microbleeds and superficial siderosis mainly involved the anterior and posterior cortical watersheds in Sneddon syndrome. The surprisingly identical topographic distribution of hemorrhagic lesions and the corresponding obvious atrophy suggest cerebral atrophy might be secondary to the microangiopathy related hemorrhagic lesions and further contribute to the neurological deficit, especially the early cognitive decline in Sneddon syndrome,although further investigation is needed to elucidate the precise underlying pathogenesis. These highlight cortical microbleeds and superficial siderosis located in cortical watershed and the secondary atrophy in youth might be highly indicative of Sneddon syndrome.

Editors' note: Diffuse Lewy body disease manifesting as corticobasal syndrome: A rare form of Lewy body disease

The heterogeneity of pathology in corticobasal syndrome (CBS) is known but incompletely characterized. In this retrospective autopsy series by Kasanuki et al., investigators identified 11 patients with an antemortem diagnosis of CBS with autopsy-proven findings of diffuse Lewy body disease (DLBD). Compared with the autopsy specimens of 22 patients with dementia with Lewy bodies (DLBs), those with CBS clinically, but DLBD pathologically, were younger at symptom onset, had less REM sleep behavior disorder, more axial rigidity, and pyramidal symptoms, and histopathologically exhibited more significant cerebral atrophy and thinning of the corpus callosum. However, these are not the only features that may differentiate DLBs from CBS. Infante and colleagues recall 1 patient seen at their center with atypical CBS and phosphorylated α-synuclein (p-syn) deposits in cutaneous nerves of the skin. These authors suggest that skin biopsy may be helpful in circumstances where diagnostic uncertainty exists in clinically overlapping dementia syndromes. The heterogeneity of pathology in corticobasal syndrome (CBS) is known but incompletely characterized. In this retrospective autopsy series by Kasanuki et al., investigators identified 11 patients with an antemortem diagnosis of CBS with autopsy-proven findings of diffuse Lewy body disease (DLBD). Compared with the autopsy specimens of 22 patients with dementia with Lewy bodies (DLBs), those with CBS clinically, but DLBD pathologically, were younger at symptom onset, had less REM sleep behavior disorder, more axial rigidity, and pyramidal symptoms, and histopathologically exhibited more significant cerebral atrophy and thinning of the corpus callosum. However, these are not the only features that may differentiate DLBs from CBS. Infante and colleagues recall 1 patient seen at their center with atypical CBS and phosphorylated α-synuclein (p-syn) deposits in cutaneous nerves of the skin. These authors suggest that skin biopsy may be helpful in circumstances where diagnostic uncertainty exists in clinically overlapping dementia syndromes.

Frequent globular neuronal cytoplasmic inclusions in the medial temporal region as a possible characteristic feature in multiple system atrophy with dementia.

Multiple system atrophy (MSA) is an adult-onset neurodegenerative disease, which is characterized clinically by parkinsonism, cerebellar ataxia and/or autonomic dysfunction, and pathologically by alpha-synuclein-related multisystem neurodegeneration, so-called alpha-synucleinopathy, which particularly involves the striatonigral and olivopontocerebellar systems, with glial cytoplasmic inclusions and neuronal cytoplasmic/nuclear inclusions (NCIs/NNIs). In the recent consensus criteria for the diagnosis of MSA, dementia is described as one of the features not supporting a diagnosis of MSA. However, MSA with dementia has been reported, although the location of the lesion responsible for the dementia remains unclear. In the present study, we aimed to investigate where this lesion may be found, by analyzing 12 autopsy-proven MSA cases, with a particular focus on the medial temporal region. Three of 12 cases with MSA had dementia (MSA-D). Compared with MSA cases without dementia, MSA-D cases had frequent globular NCIs (G-NCIs) in the medial temporal region, especially in their subiculum. In addition, MSA-D cases could be divided into two types; MSA-D with distinct fronto-temporal lobar degeneration (FTLD type) and without distinct fronto-temporal lobar degeneration (non-FTLD type). There was no association between dementia and Alzheimer pathologies, such as neurofibrillary tangles and senile plaques. We suggest that frequent G-NCIs in the medial temporal region, and particularly the subiculum, is one of the important pathological findings of MSA-D, even when a case with MSA-D reveals no significant cerebral atrophy.

The spectrum of neuroradiological features in Menkes disease: Widening of the cerebral venous sinuses

Menkes disease, an inherited disorder of copper transport, shows a spectrum of different neuroradiological findings. Diffuse brain atrophy, deficient myelination, and subdural hematoma/hygroma were described. Anomalies of the cerebral arteries with elongation and tortuosity are known. We report the neuroradiological follow up of a patient suffering from Menkes disease confirmed by the identification of a deletion of ATP 7A gene. Ultrasound scanning at the age of two months demon- strated normal brain morphology. One month later, magnetic resonance imaging (MRI) showed vermian hypoplasia, brain atro- phy and retarded myelination. Marked widening of cerebral venous sinuses in conventional angiography and in magnetic resonance venography was detected and led to arterial cerebral angiography, which did not disclose an arteriovenous fistula. Despite parenteral copper therapy, on MRI follow up seven months later, extra-axial blood and hygroma were visible and the signs of cerebral atrophy and myelination deficit were more pronounced. In Menkes disease, neuroradiological anomalies can occur early and progress rapidly despite copper therapy. When evaluating magnetic resonance angiography results in neurode- generative diseases, Menkes disease should be suspected not just when cerebral arterial anomalies are demonstrated. Widening of the cerebral venous sinuses might be caused by secondary to brain atrophy or involvement of the vein walls.

Vitamin B12 Deficiency: A Treatable Cause of Developmental Delay In Infancy

Neuronal regression and developmental delay in infants has varied aetiology, and vitamin B12 deficiency is a rare but treatable cause. Vitamin B12 deficiency in infancy is a rare but treatable cause of developmental delay and neuronal regression. Maternal vitamin B12 deficiency is usually secondary to pernicious anaemia or to a strict vegetarian diet and can cause serious neurological abnormalities among exclusively breastfed infants. Clinical picture include apathy, irritability, poor eye contact, lethargy, vomiting and feeding difficulties, developmental regression, hypotonia, tremor, myoclonic jerks, involuntary movements and seizures.1 Neurological manifestations usually appear between 2 and 12 months of age.2 Signs of cerebral atrophy have been detected on neuroimaging studies. Infants born to vitamin-B12-deficient mothers have a very limited hepatic stock of vitamin B12 and can develop symptoms within a few months. Persistent neurological damage can be prevented with early diagnosis and treatment.3, 4 Although supplementation of vitamin B12 appears to result in a rapid clinical improvement, there is a concern over long-term prognosis with cognitive impairment. It is important to emphasise that vitamin B12 supplementation during pregnancy should be provided for strict vegetarians and individuals with pernicious anaemia to avoid irreversible neurological damage.

The gray aspects of white matter disease in multiple sclerosis

The major inflammatory disease of the central nervous system is multiple sclerosis (MS). It is often considered a 2-stage disease with an initial inflammatory attack on myelin involving the 2 hallmarks of adaptive immunity: antigen-specific T cells and antibodies directed to protein and lipid components of the myelin sheath (1). This concerted attack involving the adaptive immune system is followed by a “degenerative” course involving the myelin itself, the oligodendrocytes that produce it, and the underlying axons and their neuronal cell bodies themselves in the gray matter. All of this culminates in significant cerebral atrophy as MS progresses (2). Whether or not there is really such a sequential and bifurcated temporal course between “inflammation” in the white matter, followed by neurodegeneration in the gray matter, is actually an open question. In this issue of PNAS, Derfuss et al. (3) identify, via a multifaceted approach including proteomics, one of the first examples of a target recognized by both T cells and antibodies that is located in gray matter. The target is contactin-2, a homologue of transiently-expressed axonal glycoprotein-1 (TAG-1) expressed on axons and in the juxtaparanodal region of oligodendrocytes producing myelin to insulate these axons (4), and by neurons in gray matter (5, 6).

Cerebrovascular Effects of Hemodialysis in Chronic Kidney Disease

Patients with end-stage renal disease (ESRD) undergoing hemodialysis are known to suffer cognitive deficits and stroke of unknown etiology. It has been suspected that the treatment itself may contribute to the syndrome by unknown mechanisms, which we investigated in this study. End-stage renal disease patients on hemodialysis (n=19) or peritoneal dialysis (PD, n=5) were compared with 14 healthy controls. Subjects participated in magnetic resonance imaging (MRI) measurements of cerebral atrophy, cerebral blood flow (CBF) arterial spin labeled-MRI (ASL-MRI), quantitative Doppler blood flow through the internal carotid artery, and cerebral oxymetry. The Doppler and oxymetry procedures were also performed at the beginning and end of a single hemodialysis session. End-stage renal disease patients on hemodialysis showed significant cerebral atrophy, associated with longer hemodialysis duration and cognitive deficits, including focal bilateral lesions in the caudate nucleus and midbrain. Cerebral oxygenation was extremely low before dialysis (rSO(2) 41+/-13, compared with 70+/-2 in controls, P<0.02) and improved only slightly after dialysis. Carotid blood flow was also very low at the start of dialysis (115+/-28 mL/sec, versus 193+/-56 in controls, P<0.005) but normalized at the end of the session (181 mL/sec). The PD patients showed intermediate values, between the hemodialysis and controls. Notably, duration of hemodialysis treatment predicted global gray-matter volume (r=-0.74), change of blood flow during dialysis (r=-0.65), and baseline rSO(2) (r=-0.65). The findings suggest that ESRD patients on hemodialysis suffer low CBF during the interdialytic cycle. Coupled with low cerebral oxygenation levels and atherosclerosis, this may contribute significantly to the etiology of the observed cerebral atrophy, cognitive deficits, and high stroke prevalence.

Cognitive and neuroimaging findings in physically abused preschoolers

Aims: To characterise the cognitive, motor, and language skills of toddlers and preschoolers who had been physically abused and to obtain concurrent MRIs of the brain. Methods: A between groups...

Dementia associated with the antiphospholipid syndrome: clinical and radiological characteristics of 30 patients.

To analyse the clinical and radiological characteristics of patients with dementia associated with the antiphospholipid syndrome (APS). Twenty-five patients were identified by a computer-assisted (MEDLINE, National Library of Medicine, Bethesda, MD) search of the literature to locate all cases of dementia associated with APS published in English, Spanish and French from 1983 to 2003. Additionally, we included five patients from our clinics. There were 21 (70%) females and 9 (30%) males. The mean age of patients was 49+/-15 yr (range 16-79 yr). Fourteen (47%) of the patients suffered from primary APS, 9 (30%) had systemic lupus erythematosus and 7 (23%) had 'lupus-like' syndrome. Ten (33%) patients had Sneddon's syndrome and 2 (7%) had cerebral lesions described as Binswanger's disease. Other APS-related manifestations included thrombocytopenia in 12 (40%) patients, cerebrovascular accidents in 11 (37%), heart valve lesions in 8 (27%), deep vein thrombosis in 7 (28%), migraine in 7 (23%), seizures in 4 (13%); five of the 21 (24%) female patients had nine spontaneous abortions. Lupus anticoagulant was present in 21/29 (72%) patients and anticardiolipin antibodies were present in 24/29 (83%) patients. Cortical infarcts were found in 19 (63%) patients, subcortical infarcts in 9 (30%), basal ganglia infarcts in 7 (23%) and signs of cerebral atrophy in 11 (37%). Anticoagulation was used in 14/25 (56%) patients, steroids in 12/25 (48%), aspirin in 6/25 (24%) and dypiridamole in 5/25 (20%). Dementia is an unusual manifestation of APS but one which has a high disability impact in a patient's daily life. In order to prevent these consequences, an echocardiographic and cerebral CT or MRI evaluation are recommended in all patients with APS. Furthermore, ruling out APS should be recommended in the clinical approach to dementia, especially in young patients.

112 Sonographic Diagnosis of Cerebral Atrophy at Discharge is Related to Unfavourable Neurodevelopmental Outcome at Three Years of Age

Background: In contrast to IVH and PVL, it is not yet clear, if minor abnormalities on neonatal cranial ultrasound -periventricular flares, ventricularmegaly, widened interhemispherics fissure or extracerebral space as signs of cerebral atrophy–are related to adverse outcome. Aim of the present study was to correlate these ultrasound findings to neurodevelopmental outcome at three years of age.

The application of serial MRI analysis techniques to the study of cerebral atrophy in late-onset dementia

We have used a serial MR image analysis technique previously developed for studies of cerebral atrophy in early-onset dementia and applied it to a study of late-onset dementia patients with images acquired using a different scanner and scan sequence. Validation and optimisation tests showed that with only small changes to key analysis parameters the technique can successfully be applied to previously untested data with dissimilar image characteristics. The overall accuracy in estimation of cerebral atrophy using the technique was determined to be between 2 and 4 ml (1 σ) depending on the conditions during image acquisition. By comparing the results of alternative registration techniques we demonstrate the potential of using of fully automated 9 DOF image registration as an effective and efficient means of correcting for scanner pixel size variations, even in the presence of significant cerebral atrophy. Applied to the late-onset dementia study, patients were found to have significantly increased mean atrophy rates ( p<0.001) compared to controls. In general the analysis technique is shown to be a robust, accurate and transferable tool of potential value for future studies of dementia and related neuro-degenerative disorders.

White matter lesions, quantitative magnetic resonance imaging, and dementia.

The authors performed quantitative and qualitative image analysis on a sample of the elderly population of Cache County, Utah, relating neuroimaging findings to Mini-Mental Status Examination (MMSE) scores and the presence of the apolipoprotein E epsilon4 allele. Neuroimaging measures included white, gray, and hippocampal volumes; a ventricle-to-brain ratio (VBR); and qualitative ratings of white matter lesions (WMLs) in the periventricular (PV) and centrum semiovale (CS) regions. Subjects included 85 persons with possible and probable Alzheimer disease (AD), 21 with vascular dementia (VaD), 30 with cognitive symptoms classified as mild/ambiguous (M/A), a heterogenous group of 39 non-AD or VaD subjects but diagnosed with some form of neuropsychiatric disorder ("Mixed Neuropsychiatric" group), and 20 normal control subjects aged 65 years or older. Controlling for age, sex, and length of disease, the authors found that AD and VaD subjects differed significantly from control subjects on WMLs, but only the VaD subjects significantly differed from M/A subjects. The two dementia groups also displayed, as expected, significant cerebral atrophy. The WMLs generally increased with age and severity of dementia. PV WMLs were significantly but only modestly associated with white matter volume loss and greater impairment on the MMSE. Modest correlations were also present between the quantitative measures of cerebral structure and MMSE performance. However, when degree of cerebral atrophy was controlled by using the VBR measure, WML effects on MMSE performance became nonsignificant, with the only significant relationship remaining being that between hippocampal volume and MMSE performance. There were no significant qualitative or quantitative findings related to presence of the epsilon4 allele and MMSE performance. The role of WMLs in aging and dementia is discussed.

Neuroimaging methods to evaluate the etiology and consequences of epilepsy

Magnetic resonance imaging (MRI) is widely available and is generally the imaging method of first choice for identifying the structural basis of seizure disorders, having both sensitivity and specificity. Positron emission tomography (PET) and single photon emission computed tomography (SPECT) scans may be more sensitive in some patients when MRI is unremarkable, but do not confer specificity of etiological diagnosis. Methods to assess the consequences of epilepsy on the brain need to be quantitative, reliable, reproducible and safe. They must be acceptable to patients and to a healthy control group for repeated use, and the acquisition and analytical methods must be stable over years. Longitudinal studies are necessary to determine whether secondary cerebral damage occurs as a consequence to the epilepsies. Patient groups will be heterogeneous in this regard and analysis will need to be not only of changes in group means, but also of the number of patients who show significant changes in imaging parameters, that exceed the limits of test–retest reliability and of changes in age-matched controls. MRI is an attractive tool to evaluate the presence and development of cerebral damage in patients with epilepsy as it is readily available, non-invasive, and acceptable to patients and controls. MRI volumetry is reliable and reproducible, but the sensitivity of the method to detect subtle abnormalities has not yet been established. Preliminary analysis of longitudinal studies of patients with newly diagnosed and chronic active epilepsy suggests that 10% of newly diagnosed patients and 25% of those with chronic active epilepsy develop significant cerebral, hippocampal or cerebellar atrophy over 3.5 years. MR spectroscopy may be more sensitive for detecting abnormalities, but the test–retest reliability is less good. Other MRI tools such as diffusion tensor imaging (DTI) may be useful methods for evaluating secondary cerebral damage acutely and chronically.