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Young onset dementia is a challenging clinical problem with potentially devastating medical and social consequences. The differential diagnosis is wide, and includes a number of rare sporadic and hereditary diseases. However, accurate diagnosis is often possible, and all patients should be thoroughly investigated to identify treatable processes. This review presents an approach to the diagnosis, investigation, and management of patients with young onset dementia, with particular reference to common and treatable causes. [ABSTRACT FROM AUTHOR]

Background: Most cases of Creutzfeldt-Jakob disease (CJD) in recipients of human cadaveric growth hormone present with a cerebellar syndrome. Dementia is thought to occur late and as a minor feature of the illness. However, neuropsychology data published on these cases are largely qualitative and anecdotal. The first published case does include a neuropsychological assessment seven months after the onset of a cerebellar syndrome, showing evidence of intellectual decline. Subsequent reports hint that cognitive problems may be present in the initial stages of the illness.Objective: To assess early cognition in Creutzfeldt-Jakob disease in recipients of pituitary derived human growth hormone.Methods: Detailed neuropsychology assessment is reported at referral (mean 4.5 months from the onset of symptoms; range 4 to 6 months) in five patients with histologically proven human growth hormone derived CJD.Results: All cases presented with a cerebellar syndrome and only one had noticed mild memory problems. On formal testing, however, four had demonstrable mild intellectual decline, as measured on the WAIS-R. One case showed selective visual memory impairment and frontal executive dysfunction.Conclusions: These findings suggest that, although not the presenting feature, mild cognitive decline may be evident in the early stages of CJD associated with human cadaveric growth hormone treatment. [ABSTRACT FROM AUTHOR]

Background and objectives The last version of the EFNS dementia guidelines is from 2007. In 2010, the revised guidelines for Alzheimer's disease ( AD) were published. The current guidelines involve the revision of the dementia syndromes outside of AD, notably vascular cognitive impairment, frontotemporal lobar degeneration, dementia with Lewy bodies, corticobasal syndrome, progressive supranuclear palsy, Parkinson's disease dementia, Huntington's disease, prion diseases, normal-pressure hydrocephalus, limbic encephalitis and other toxic and metabolic disorders. The aim is to present a peer-reviewed evidence-based statement for the guidance of practice for clinical neurologists, geriatricians, psychiatrists and other specialist physicians responsible for the care of patients with dementing disorders. It represents a statement of minimum desirable standards for practice guidance. Methods The task force working group reviewed evidence from original research articles, meta-analyses and systematic reviews, published by June 2011. The evidence was classified ( I, II, III, IV) and consensus recommendations graded (A, B, or C) according to the EFNS guidance. Where there was a lack of evidence, but clear consensus, good practice points were provided. Results and conclusions New recommendations and good practice points are made for clinical diagnosis, blood tests, neuropsychology, neuroimaging, electroencephalography, cerebrospinal fluid ( CSF) analysis, genetic testing, disclosure of diagnosis, treatment of behavioural and psychological symptoms in dementia, legal issues, counselling and support for caregivers. All recommendations were revised as compared with the previous EFNS guidelines. The specialist neurologist together with primary care physicians play an important role in the assessment, interpretation and treatment of symptoms, disability and needs of dementia patients. [ABSTRACT FROM AUTHOR]

Aim: To determine rates of cerebral atrophy in individuals with symptoms of memory loss but no objective cognitive impairment (SNCI) and their association with future cognitive decline. Methods: Thirty-two SNCI subjects, 16 with mild cognitive impairment (MCI) and 27 control subjects had clinical assessment and magnetic resonance imaging at baseline and 1 year later. Rates of whole brain atrophy (WBA), hippocampal atrophy (HA) and ventricular enlargement (VE) were measured. Our outcome was clinical diagnosis at 2 years after entry into the study. Results: The MCI group had greater rates of WBA, HA and VE than both controls and SNCI subjects. As a group SNCI subjects did not have significantly greater rates of atrophy than the controls. However, SNCI subjects who progressed to MCI or dementia had increased rates of atrophy compared with those who remained stable. Discussion: Individuals with memory complaints but no objective memory deficits, who progress to MCI or dementia, have increased rates of cerebral atrophy. [ABSTRACT FROM AUTHOR]

We describe two patients with isolated brainstem lesions who exhibited behavioural and cognitive changes that are commonly associated with frontal lobe pathology, as leading clinical features. These cases illustrate the role of distributed neural networks in cognitive and behavioural processes. The brainstem, frontal-subcortical and limbic systems are extensively and reciprocally linked via neurotransmitter projection pathways. We argue that cognitive and behavioural features in patients with brainstem lesions reflect remote effects of brainstem structures on frontal lobe and limbic regions, as a consequence of disruption to ascending neurotransmitter pathways. [ABSTRACT FROM AUTHOR]

The aim of this study was to describe the present involvement of neurologists in dementia management in European countries. Data were obtained from a questionnaire that members of The European Federation of Neurological Societies Scientific Panel on Dementia responded to. Information was obtained from 25 countries in Europe. A progressive decrease in the teaching activity from medical school to board-certified neurologists was reported. Teaching of medical students in dementia is obligatory in most countries, whereas there is no formal obligatory education in dementia after graduation from medical school. Further, in only half of the countries that responded to the questionnaire, obligatory courses in dementia are part of the training in neurology. Except for one country, the post-graduate training programs of board-certified neurologists do not include dementia as an obligatory topic. In only 10 of 25 countries, guidelines for neurologists on dementia evaluation have been published in local language. It is recommended to include obligatory teaching and training in dementia in the catalogue of minimum requirements for specialist training in neurology and this teaching should also be part of the ongoing update of certified neurologists. [ABSTRACT FROM AUTHOR]

Background Symptoms of memory loss are a common complaint within the general population and a frequent reason for seeking medical advice. However, the clinical relevance of these symptoms to future development of neurodegenerative disease is uncertain. The aim of this study is to characterise a cohort of individuals with symptoms of memory loss and varying memory impairment, who will be followed longitudinally with serial neuropsychology and neuroimaging to evaluate the clinical relevance of symptoms of memory loss. Method Fifty-eight subjects with symptoms of memory loss were recruited from the National Hospital for Neurology and Neurosurgery. All subjects underwent clinical assessment, APOE4 genotyping, neuroimaging and neuropsychological tests. Results Those with mild cognitive impairment (MCI) had an increased prevalence of the APOE4 allele, impaired performance on tests of memory, measures of IQ and naming compared to controls. Baseline brain volumes were decreased and ventricular size increased. Those with symptoms of memory loss but no cognitive impairment (SNCI) performed significantly worse on tests of memory than the control group. Conclusions The MCI represent a group with multiple risk factors for progression to AD. The SNCI group may represent a heterogeneous group with some individuals in the early stages of AD whilst others' memory complaints are more likely linked to anxiety or personality traits. Copyright © 2006 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

Cerebral atrophy calculated from serial MRI is a marker of Alzheimer’s disease (AD) progression, and a potential outcome measure for therapeutic trials. Reducing within-subject variability in cerebral atrophy rates by acquiring more than two serial scans could allow for shorter clinical trials requiring smaller patient numbers. Forty-six patients with AD and 23 controls each had up to 10 serial MR brain scans over two years. Whole brain atrophy was calculated for each subject from every scan-pair. 708 volumetric MRI scans were acquired: 2199 measures of atrophy were made for patients, and 1182 for controls. A linear mixed model was used to characterise between and within-individual variability. These results were used to investigate the power of combining multiple serial scans in treatment trials of varying lengths. In AD, the mean whole brain atrophy rate was 2.23%/year (95% CI: 1.90–2.56%/year). The linear mixed model was shown to fit the data well and led to a formula (0.992+(0.82/t)2) for the variance of atrophy rates calculated from two scans “t” years apart. Utilising five optimally timed scans with repeat scans at each visit reduced the component of atrophy rate variance attributable to within-subject variability by ~ 56%, equating to a ~ 40% sample size reduction (228 vs 387 patients per arm to detect 20% reduction in atrophy rate) in a six-month placebo-controlled trial. This benefit in terms of sample size is relatively reduced in longer trials, although adding extra scanning visits may have benefits when patient drop-outs are accounted for. We conclude that sample sizes required in short interval therapeutic trials using cerebral atrophy as an outcome measure may be reduced if multiple serial MRI is performed [ABSTRACT FROM AUTHOR]

Variant Creutzfeldt-Jakob disease (vCJD) is a fatal neurodegenerative disorder. Clinical diagnosis is difficult in the early stages as the disease often presents with non-specific psychiatric and neurological symptoms. To investigate the diagnostic potential of quantitative short TE in vivo MRS, and the nature and anatomical distribution of biochemical abnormalities in vCJD, localised single-voxel spectra (TE/TR 30 ms/2,000 ms) were acquired from three brain regions: thalami, caudate nuclei and frontal white matter. Metabolite concentrations and ratios from three patients with definite or probable vCJD were compared with eight normal age-matched controls. Abnormal signal on T2-weighted MRI was apparent in the pulvinar region in all vCJD patients; this region also showed greatly increased myo-inositol [MI] (mean 2.5-fold, P=0.01) and decreased N-acetyl-aspartate (NAA; mean 2-fold, P=0.01). Two patients also showed increased [MI] (z=17, 11; one with decreased NAA, z=-12) in normal-appearing caudate nuclei. The magnitude of metabolite abnormalities in the thalami in moderately advanced vCJD suggests a potential role in earlier diagnosis. Short TE protocols allow the measurement of MI, which adds discriminant power to the MRS examination. [ABSTRACT FROM AUTHOR]

Introduction: Inherited prion diseases are caused by mutations in the gene which codes for prion protein (PrP), leading to proliferation of abnormal PrP isomers in the brain and neurodegeneration; they include Gerstmann-Stráussler-Scheinker disease (GSS), fatal familial insomnia (FFI) and familial Creutzfeldt-Jakob disease (fCJD). Methods: We studied two patients with symptomatic inherited prion disease (P102L) and two pre-symptomatic P102L gene carriers using quantitative magnetic resonance spectroscopy (MRS). Short echo time spectra were acquired from the thalamus, caudate region and frontal white matter, metabolite levels and ratios were measured and z-scores calculated for individual patients relative to age-matched normal controls. MRS data were compared with structural magnetic resonance imaging. Results: One fCJD case had generalised atrophy and showed increased levels of myo-inositol (MI) in the thalamus (z=3.7). The other had decreased levels of N-acetylaspartate (z=4) and diffuse signal abnormality in the frontal white matter. Both asymptomatic gene carriers had normal imaging, but increased frontal white matter MI (z=4.3, 4.1), and one also had increased MI in the caudate (z=5.3). Conclusion: Isolated MI abnormalities in asymptomatic gene carriers are a novel finding and may reflect early glial proliferation, prior to significant neuronal damage. MRS provides potential non-invasive surrogate markers of early disease and progression in inherited prion disease. [ABSTRACT FROM AUTHOR]

Objective: To assess cognitive function in variant Creutzfeldt-Jakob disease (vCJD). We describe the neuropsychological profiles of 10 cases and compare these data with cross sectional data obtained from patients with histologically confirmed sporadic CJD and cases with inherited prion disease with confirmed mutations in the prion protein gene.Methods: Patients referred to the Specialist Cognitive Disorders Clinic at the National Hospital for Neurology and Neurosurgery and the National Prion Clinic at St Mary's Hospital, London for further investigation of suspected CJD were recruited into the study. The neuropsychological test battery evaluated general intelligence, visual and verbal memory, nominal skills, literacy skills, visual perception and visuospatial functions, and visuospatial and executive function.Results: The results indicate that moderate to severe cognitive decline is a characteristic feature of vCJD. Specifically, verbal and visual memory impairments and executive dysfunction were pervasive in all disease groups. Nominal skills were impaired in variant and sporadic CJD, significantly so when compared with the inherited prion disease group. Perceptual impairment was less frequent in the vCJD group than in the sporadic and inherited groups.Conclusion: This study confirms the occurrence of generalised cognitive decline in patients with vCJD. Although decline in cognitive function ultimately affects all domains, there is a suggestion that some components of visual perception may be spared in vCJD. The results also suggest that nominal function may be preserved in some cases with inherited prion disease. [ABSTRACT FROM AUTHOR]

Objective: To assess cognitive function in variant Creutzfeldt-Jakob disease (vCJD). We describe the neuropsychological profiles of 10 cases and compare these data with cross sectional data obtained from patients with histologically confirmed sporadic CJD and cases with inherited prion disease with confirmed mutations in the prion protein gene. Methods: Patients referred to the Specialist Cognitive Disorders Clinic at the National Hospital for Neurology and Neurosurgery and the National Prion Clinic at St Mary's Hospital, London for further investigation of suspected CJD were recruited into the study. The neuropsychological test battery evaluated general intelligence, visual and verbal memory, nominal skills, literacy skills, visual perception and visuospatial functions, and visuospatial and executive function. Results: The results indicate that moderate to severe cognitive decline is a characteristic feature of vCJD. Specifically, verbal and visual memory impairments and executive dysfunction were pervasive in all disease groups. Nominal skills were impaired in variant and sporadic CJD, significantly so when compared with the inherited prion disease group. Perceptual impairment was less frequent in the vCJD group than in the sporadic and inherited groups. Conclusion: This study confirms the occurrence of generalised cognitive decline in patients with vCJD. Although decline in cognitive function ultimately affects all domains, there is a suggestion that some components of visual perception may be spared in vCJD. The results also suggest that nominal function may be preserved in some cases with inherited prion disease. [ABSTRACT FROM AUTHOR]

Background: Frontotemporal lobar degeneration (FTLD) may be inherited as an autosomal dominant disease. Studying patients "at risk" for developing FTLD can provide insights into the earliest onset and evolution of the disease.Method: We carried out approximately annual clinical, MRI, and neuropsychological assessments on an asymptomatic 51 year old "at risk" family member from a family with FTLD associated with ubiquitin-positive and tau-negative inclusion bodies. We used non-linear (fluid) registration of serial MRI to determine areas undergoing significant regional atrophy at different stages of the disease.Results: Over the first 26 months of the study, the patient remained asymptomatic, but subsequently developed progressive speech production difficulties, and latterly severe orofacial dyspraxia, dyscalculia, frontal executive impairment, and limb dyspraxia. Regional atrophy was present prior to the onset of symptoms, and was initially centred on the left dorsolateral prefrontal cortex and the left middle frontal gyrus. Latterly, there was increasing asymmetric left frontal and parietal atrophy. Imaging revealed excess and increasing global atrophy throughout the study. Neuropsychological evaluation revealed mild intellectual impairment prior to the onset of these clinical symptoms; frontal executive and left parietal impairment subsequently emerged, culminating in widespread cognitive impairment. Fluid registered MRI allowed the emerging atrophy patterns to be delineated.Conclusion: We have demonstrated the onset and progressive pattern of in vivo atrophy in familial FTLD using fluid registered MRI and correlated this with the clinical features. Fluid registered MRI may be a useful technique in assessing patterns of focal atrophy in vivo and demonstrating the progression of degenerative diseases. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Background: Most magnetic resonance imaging (MRI) studies of progressive supranuclear palsy (PSP) are cross-sectional and lack post mortem confirmation of the diagnosis. MRI features described previously in PSP correspond to regions of pathological involvement demonstrated in separate studies, but serial MRI with pathological follow up has not been undertaken. Objective: To investigate whether regions of increased atrophy rates demonstrated in PSP during life using fluid registered serial MRI correspond with pathological findings in confirmed PSP. Methods: A 59 year old male presented with a six month history of balance problems and dysarthria. He had a symmetrical, levodopa unresponsive akinetic-rigid syndrome with a vertical supranuclear gaze palsy. A clinical diagnosis of probable PSP was made. His disease progressed relentlessly and he died five years after onset. Two serial MRI scans undertaken during life were reviewed and fluid (non-linear) registration of the images carried out. Post mortem histopathological analysis of the brain was under-taken to definitively confirm the diagnosis and compare regional pathology with the serial imaging. Results: Fluid registration demonstrated greatest rates of atrophy in the brainstem and frontal cortex, in keeping with the distribution of pathology seen at autopsy. Conclusion: Fluid registration of serial MRI allows the topography and rates of regional atrophy in PSP to be delineated in life. Atrophy patterns correlated well with regional pathological load. These observations suggest that serial MRI with registration may help differentiate PSP from clinically similar conditions and supports its use as a surrogate marker of disease progression. [ABSTRACT FROM AUTHOR]

K. A. Josephs, J. L. Holton, M. N. Rossor, A. K. Godbolt, T. Ozawa, K. Strand, N. Khan, S. Al-Sarraj and T. Revesz (2004) Neuropathology and Applied Neurobiology, doi: 10.1111/j.1365-2990.2004.00545.x Frontotemporal lobar degeneration and ubiquitin immunohistochemistry We set out to determine the frequency of the different pathologies underlying frontotemporal degeneration (FTD) in our brain bank series, by reviewing all cases of pathologically diagnosed FTD over the last 12 years. We identified and reviewed 29 cases of FTD and classified them using the most recent consensus criteria with further histological analysis of 6 initially unclassifiable cases. Detailed histological analysis of these 6 cases revealed variable numbers of ubiquitin-positive (tau and α-synuclein-negative) inclusions in 5 cases, consistent with the diagnosis of frontotemporal lobar degeneration with ubiquitin-only-immunoreactive neuronal changes (FTLD-U). As a consequence of the current re-evaluation, 18 (62%) of the 29 cases with FTD have underlying pathology consistent with FTLD-U. Therefore in our brain bank series of frontotemporal degeneration, most cases were non-tauopathies with FTLD-U accounting for 62% of all the diagnoses. [ABSTRACT FROM AUTHOR]

The use of prion protein (PrP) immunohistochemistry in neuropathology has allowed identification of prion diseases with otherwise atypical histological features. The brains from family members with familial prion diseases can show marked histological variation. A histological and immunohistochemical study was performed on 10 brains of patients with a familial prion disease caused by a 144-base pair (bp) insertion in the prion protein gene. The histology from the cases showed variability in the severity of spongiform change and astrocytosis in both the cerebellum and the cerebrum. There was also variability in the density of microglial cells. The PrP immunohistochemistry revealed that in nine cases there was a similar patch-like deposition of PrP within the molecular layer of the cerebellum. Although in the cerebellum there did seem to be some correlation between the severity of spongiform change, astrocytosis and the density of microglial cells, there was no such correlation between any of these three parameters and the density of PrP staining. There was deposition of β-amyloid precursor protein (β-APP) in the cerebellum, suggesting that disrupted axonal transport had a possible role in the evolution of the disease. The cases illustrate the histological variability that can occur in familial prion diseases despite similarity in PrP staining. They also reveal that the relationship between PrP deposition and cerebral or cerebellar damage might be complex. [ABSTRACT FROM AUTHOR]

Objectives: To determine whether patients presenting with a first transient ischaemic attack (TIA) subsequently show increased rates of brain atrophy compared with age matched controls; and to assess potential risk factors for brain atrophy in this group.Methods: 60 patients with a first, isolated TIA and 26 age and sex matched controls were recruited. None had evidence of cognitive impairment. Vascular risk factors were treated appropriately. All subjects had volumetric imaging at the start of the study and one year later, when they were clinically reassessed. TIA patients also had serial dual echo brain imaging. Rates of whole brain atrophy were calculated from the registered volumetric scans, as was the incidence of new ischaemic lesions. In the TIA group, the degree of white matter disease was assessed. Atrophy rates and blood pressure were compared between patients and controls.Results: 22 patients (37%) developed new "clinically silent" infarcts during follow up. The mean (SD) annualised percentage atrophy rate in the TIA group was significantly higher than in the controls, at 0.82 (0.39)% v 0.33 (0.3)% (p < 0.0001). In the TIA group, diastolic blood pressure (p = 0.004) and white matter disease severity (p < 0.001) were correlated with cerebral atrophy rate. Increased white matter disease was found in patients in whom new ischaemic lesions developed (p < 0.001).Conclusions: Patients presenting with a first TIA have excess global brain atrophy compared with age matched controls over the subsequent year. Increased atrophy rates following a TIA may be directly or indirectly related to increasing white matter disease and diastolic hypertension. Future studies should assess whether this atrophy inevitably leads to cognitive decline, and whether aggressive treatment of risk factors for cerebrovascular disease (particularly hypertension) after a TIA can influence outcome. [ABSTRACT FROM AUTHOR]

Background Frontotemporal lobar degeneration (FTLD) is commonly associated with behavioural disturbances such as disinhibition and aggression; these often result in the use of neuroleptic medication. Methods All available case notes of patients attending a specialist cognitive disorders clinic with a diagnosis of FTLD were selected. This gave 100 subjects (62 male, 38 female). Results In 61 patients significant behavioural disturbances were present. Of these patients, 24 had been prescribed neuroleptics. Significant extrapyramidal side effects were reported in eight patients (33%); in five patients these were severe enough to cause severe mobility problems and in one patient resulted in impaired consciousness. In some instances the extrapyramidal side effects took weeks to wear off. Conclusion These results suggest that patients with FTLD may, as in Lewy body dementia, be particularly sensitive to the extrapyramidal side effects of neuroleptics. We suggest that neuroleptics should be used cautiously in FTLD and treatment should be started at low doses avoiding depot preparations until further prospective studies have been performed. Copyright © 2002 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

The article provides information on hereditary dementias including Alzheimer's disease, familial Creutzfeldt-Jakob disease and Gerstmann-Straussler-Scheinker syndrome. Other genetic diseases where dementia is a prominent if not sole criterion including Huntington's disease, familial British and Danish dementias, and familial encephalopathy with neuroserpin inclusion bodies are discussed. It is suggested that genetic testing should be accompanied by a detailed family history. INSETS: Abbreviations;UK associations and societies providing information for patients;Useful websites for health care professionals.

Focuses on the guidelines for molecular diagnosis of inherited neurologic diseases established by EFNS task force. Coverage of the guidelines; Diagnosis of skeletal muscle channelopathies; Discussion on molecular diagnosis of inherited neuropathies.

The pattern of deposition of amyloid β protein (Aβ) was investigated, using the monoclonal antibodies BA27 and BC05 detecting the C-terminal species Aβ40 and Aβ42(43), in six cases of Alzheimer's disease (AD) due to deletions in exon 9 of PS-1 gene. These cases are characterized histologically by the presence of very large rounded plaques within the frontal cortex, known as ‘cotton wool’ plaques, composed of both Aβ40 and Aβ42(43) that are relatively free from neuritic changes and glial cell components, and usually devoid of a compact amyloid core. In the cerebellum the plaques are almost entirely of a compact type, again composed of Aβ40 and Aβ42(43), with only few diffuse Aβ42(43) containing plaques. The area fraction of Aβ40, and the ratio between Aβ40 and Aβ42(43), in frontal cortex was significantly higher than that seen in other cases of AD due to different PS-1 mutations, or in cases of sporadic AD, all of similar APO E genotype. The area fractions of Aβ42(43), however, did not significantly differ between these three groups. The unusual nature of the Aβ deposition in these cases may reflect the uniqueness of the mutation, which results in a failure to constitutively cleave the PS-1 holoprotein into its active form, and the effect this might have on APP trafficking and catabolism. [ABSTRACT FROM AUTHOR]

Objectives: The clinical neuropsychological, neuroradiological, and neuropathological description of two patients presenting with a frontal gait disturbance.Methods: Clinical case note review, neuropsychological assessment, functional imaging with (15)O(2) and (18)F-fluorodopa PET, and neuropathology.Results: Both patients presented with frontal gait impairment and only later developed more widespread cognitive impairment. In both cases (15)O(2) PET disclosed focal hypometabolism in the medial frontal lobes and in one patient (18)F-fluorodopa uptake into the caudate and putamen was normal. The neuropathological examination in one patient showed Alzheimer's histopathology together with large swollen eosinophilic neurons characteristic of corticobasal degeneration, which were particularly prominent in the medial frontal lobes.Conclusion: Focal degeneration of the medial frontal lobes may present as an isolated gait disturbance and should be considered in the differential diagnosis of patients who present without an obvious structural abnormality on neuroimaging. [ABSTRACT FROM AUTHOR]