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S Al-Sarraj

Publications and source records attributed to S Al-Sarraj.

At least 19 recordsLinked to original sources
PubMed2006

How a neuropsychiatric brain bank should be run: a consensus paper of Brainnet Europe II.

The development of new molecular and neurobiological methods, computer-assisted quantification techniques and neurobiological investigation methods which can be applied to the human brain, all have evoked an increased demand for post-mortem tissue in research. Psychiatric disorders are considered to be of neurobiological origin. Thus far, however, the etiology and pathophysiology of schizophrenia, depression and dementias are not well understood at the cellular and molecular level. The following will outline the consensus of the working group for neuropsychiatric brain banking organized in the Brainnet Europe II, on ethical guidelines for brain banking, clinical diagnostic criteria, the minimal clinical data set of retrospectively analyzed cases as well as neuropathological standard investigations to perform stageing for neurodegenerative disorders in brain tissue. We will list regions of interest for assessments in psychiatric disorder, propose a dissection scheme and describe preservation and storage conditions of tissue. These guidelines may be of value for future implementations of additional neuropsychiatric brain banks world-wide.

Brain↗
PubMed2004

Cortical selective vulnerability in motor neuron disease: a morphometric study.

Neuroimaging and neuropsychological studies have revealed that the primary motor cortex (PMC) and the extramotor cortical areas are functionally abnormal in motor neuron disease (MND, amyotrophic lateral sclerosis), but the nature of the cortical lesions that underlie these changes is poorly understood. In particular, there have been few attempts to quantify neuronal loss in the PMC and in other cortical areas in MND. We used SMI-32, an antibody against an epitope on non-phosphorylated neurofilament heavy chain, to analyse the size and density of SMI-32-positive cortical pyramidal neurons in layer V of the PMC, the dorsolateral prefrontal cortex (DLPFC) and the supragenual anterior cingulate cortex (ACC) in 13 MND and eight control subjects. There was a statistically significant reduction in the density of SMI-32-immunoreactive (IR) pyramidal neurons within cortical layer V in the PMC, the DLPFC and the ACC in MND subjects compared with controls [t (19) = 2.91, P = 0.009; estimated reduction 25%; 95% CI = 8%, 40%]. In addition, we studied the density and size of interneurons immunoreactive for the calcium-binding proteins calbindin-D(28K) (CB), parvalbumin (PV) and calretinin (CR) in the same areas (PMC, DLPFC and ACC). Statistically significant differences in the densities of CB-IR neurons were observed within cortical layers V (P = 0.003) and VI (P = 0.001) in MND cases compared with controls. The densities of CR- and PV-IR neurons were not significantly different between MND and control cases, although there were trends towards reductions of CR-IR neuronal density within the same layers and of PV-IR neuronal density within cortical layer VI. Loss of pyramidal neurons and of GABAergic interneurons is more widespread than has been appreciated and is present in areas associated with neuroimaging and cognitive abnormalities in MND. These findings support the notion that MND should be considered a multisystem disorder.

Aged↗
PubMed2004

Pilocytic astrocytoma of the adult--clinical features, radiological features and management.

Pilocytic astrocytoma is a histological subtype of astrocytoma classically located in the cerebellum of children and young adults. Cases occurring over the age of 30 years are rare and have not been classified in terms of their clinical features and management. Suitable cases were identified using diagnostic coding and by reviewing a neuropathology database. Casenotes and neuroradiology were reviewed retrospectively. Ten cases were identified over a 6 year period with an incidence of 0.49 cases per million population per year. Tumours were equally distributed between the supra- and infra-tentorial spaces. The most common symptom was headache occurring in 90%. No patient suffered seizures. Total macroscopic treatment remains the treatment of choice. Pilocytic astrocytoma of the adult is a rare tumour with a favourable prognosis.

Adult↗
PubMed2004

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 alpha-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.

Aged↗
PubMed2004

Intracranial laterally based supratentorial neurenteric cyst.

Neurenteric cysts are rare developmental cysts lined by endodermal derived epithelium. We present the case of a 68-year-old patient presenting with seizures who was found to have an extra-axial low density lesion with associated wall calcification on CT. Aspiration and biopsy of the cyst revealed a neurenteric cyst. Such lesions of the lateral supratentorial convexity are extremely rare and calcification has not been previously reported in these intracranial cysts.

Aged↗
PubMed2003

Early cognitive decline in Creutzfeldt-Jakob disease associated with human growth hormone treatment.

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.

Adult↗
PubMed2002

Ubiquitin-only intraneuronal inclusion in the substantia nigra is a characteristic feature of motor neurone disease with dementia.

Two types of ubiquitinated inclusions have been described in motor neurone disease (MND). (1) Skein or globular ubiquitinated inclusions in the motor neurones (more frequently in the lower motor neurones). This is a characteristic feature of all motor neurone disease categories. (2) Dot-shape or crescentric ubiquitinated inclusions in the upper layers of cortex and dentate gyrus described in cases of motor neurone disease with dementia (DMND). We investigated the substantia nigra (SN) in MND cases; two cases of motor neurone disease inclusion body (MND-IB) dementia, six cases of DMND, 14 cases of MND (including one case from Guam and two cases of familial SOD1 mutation), four cases of Parkinson's disease (PD), and 10 cases of age-matched normal controls. SN and spinal cord sections were stained with ubiquitin (alpha-synuclein, tau, PGM1, SMI-31 and SOD1 antibodies). The neuronal density in SN was quantified by using a computer-based image analysis system. Four out of six DMND cases showed rounded ubiquitin positive inclusions with irregular frayed edges, associated with neuronal loss, reactive astrocytosis and a large number of activated microglia cells. These inclusions are negative with antibodies to (alpha-synuclein, tau, SMI-31 and SOD1). The SN in cases from MND-IB dementia and MND showed occasional neuronal loss and no inclusions. The ubiquitin-only inclusions in SN of DMND cases are similar (but not identical) to the ubiquitinated inclusions described previously in the spinal cord of MND cases and are distinct from Lewy bodies (LBs). The degeneration of SN is most likely a primary neurodegenerative process of motor neurone disease type frequently involving the DMND cases. MND disease is a spectrum and multisystem disorder with DMND located at the extreme end of a spectrum affecting the CNS more widely than just the motor system.

Aged↗
PubMed2002

The glial precursor proteoglycan, NG2, is expressed on tumour neovasculature by vascular pericytes in human malignant brain tumours.

Glial precursor cells express NG2 and GD3 in the developing brain. These antigens are both over-expressed during neoplasia, which suggests they may have specific functions in the malignant progression of human brain tumours. This study describes the expression of NG2 and GD3 in 28 paediatric and adult brain tumours. Glioblastoma biopsy spheroids were also implanted into nude rats to assess the regional distribution of the molecules within the tumour. These xenografts showed extensive infiltration and growth that mimicked the growth patterns of human gliomas in situ. NG2 was identified in 20 out of 28 brain tumours, where the expression was confined to the main mass of the tumour, and was reduced towards the tumour periphery. NG2 was mainly associated with blood vessels on both the pericyte and basement membrane components of the tumour vasculature. Ki67 (MIB-1) labelling indicated that NG2 expression was associated with areas of high cellular proliferation. Conversely, all the tumours expressed GD3, which was present both in the tumour main mass and throughout the periphery. Thus, the expression of NG2 may be indicative of tumour progression and might be an amenable target for future therapeutic interventions.

Adult↗
PubMed2001

Ultrastructural examination is essential for diagnosis of papillary meningioma.

AIMS: Papillary meningioma is a rare meningeal tumour. To date only a few cases have been reported and their immunohistochemical features have not been fully documented. METHODS AND RESULTS: A 49-year-old woman presented with a 2-month history of headaches and memory disturbance. CT and MRI imaging showed an enhancing pineal mass with extension into the occipital lobes and invasion of the splenium. At surgery, the tumour was found to be tough and vascular with a well-defined capsule. No recurrence was noted 19 months after the operation. In another case a 44-year-old woman was admitted with 1-month history of headaches, poor memory, imbalance and diplopia. CT scan showed a large hyperdense, uniformly, enhancing mass within the middle cranial fossa at the petrous ridge. The tumour recurred 19 and 25 months after first resection. The histology of both tumours was similar. The neoplasms contained polygonal cells with a moderate amount of cytoplasm, rounded regular nuclei and distinct cell borders. The cells were arranged radially around the blood vessels (perivascular pattern) and a papillary pattern was seen only focally. Mitotic figures were moderately frequent. Immunohistochemistry showed that both tumours were immunoreactive to vimentin and NSE, whereas GFAP, CAM5.2, EMA, S100 protein and synaptophysin were negative. Electron microscopy revealed interdigitating cell processes, desmosomes and intermediate filaments. CONCLUSIONS: The histological and immunohistochemical features of these two tumours are complex and difficult to interpret. Although papillary meningiomas were considered in our initial differential diagnosis, the final conclusion was possible only when the ultrastructural features were revealed.

Biopsy↗
PubMed2001

A clinical and pathological study of motor neurone disease on Guam.

Despite over 40 years of intensive study, the cause of the high incidence of motor neurone disease (MND) on Guam, and the relationship between this disease and MND seen in the rest of the world are still uncertain. We present a series of 45 cases of Guamanian MND, which reaffirm the clinical similarity between this disease and MND seen in other countries. However, the occurrence of MND among the indigenous Chamorros of Guam is distinguished by four factors: (i) high prevalence; (ii) frequent familial occurrence; (iii) co-occurrence with the parkinsonism-dementia complex (PDC); and (iv) association with an unusual and distinctive linear retinopathy termed Guam retinal pigment epitheliopathy (GRPE). These distinguishing factors were not present in four non-Chamorros who resided on Guam when their MND symptoms occurred. Pathologically, the classical features of MND were seen in Guamanian Chamorro cases including ubiquitin inclusions. Neurofibrillary tangles were frequently seen. The neurofibrillary tangles appeared in the same distribution as described in the PDC but, unlike classical PDC, they were not usually associated with cell loss and occurred less frequently. While neurofibrillary tangle formation and the clinicopathological syndrome of MND may occur in parallel, observations from this series suggest that pathologically classical MND on Guam may occur independently of neurofibrillary degeneration and the clinical features of PDC.

Adult↗
PubMed2001

Spinal meningioma after treatment for Hodgkin disease. Case report.

Long-term survivors of Hodgkin disease may develop second primary tumors caused by the mutagenic effects of radio- and chemotherapy. The authors describe the case of a 35-year-old woman who presented with an unusual meningioma of the cervical spine 9 years after undergoing combined-modality treatment for Hodgkin disease. To the authors' knowledge, this is the first report of spinal meningioma as a complication of such therapy. Whereas radiation-induced intracranial meningiomas are well described in the literature, treatment-induced meningiomas of the spine have not been widely recognized.

Adult↗
PubMed2000

Thalamic degeneration with negative prion protein immunostaining.

A 34-year-old woman presented with an insidious 5-year history of cognitive decline and apathy, associated with hypersomnia, ataxia, and dysarthria. Magnetic resonance imaging of the brain showed cortical and subcortical atrophy. At autopsy we found abnormalities in the subcortical grey matter and brainstem, with a relatively preserved cerebral cortex. The thalami showed symmetrical neuronal loss and astrocytosis, particularly severe in the dorsal medial nucleus, followed by the lateral nuclei group. Prion protein immunostaining was negative, and there was no spongiform change. No mutations were detected in the prion protein gene.

Adult↗
PubMed1999

Investigation of variant Creutzfeldt-Jakob disease and other human prion diseases with tonsil biopsy samples.

BACKGROUND: Prion diseases are associated with the accumulation of an abnormal isoform of cellular prion protein (PrPSc), which is the principal constituent of prions. Prions replicate in lymphoreticular tissues before neuroinvasion, suggesting that lymphoreticular biopsy samples may allow early diagnosis by detection of PrPSc. Variant Creutzfeldt-Jakob disease (variant CJD) is difficult to distinguish from common psychiatric disorders in its early stages and definitive diagnosis has relied on neuropathology. We studied lymphoreticular tissues from a necropsy series and assessed tonsillar biopsy samples as a diagnostic investigation for human prion disease. METHODS: Lymphoreticular tissues (68 tonsils, 64 spleens, and 40 lymph nodes) were obtained at necropsy from patients affected by prion disease and from neurological and normal controls. Tonsil biopsy sampling was done on 20 patients with suspected prion disease. Tissues were analysed by western blot to detect and type PrPSc, by PrP immunohistochemistry, or both. FINDINGS: All lymphoreticular tissues obtained at necropsy from patients with neuropathologically confirmed variant CJD, but not from patients with other prion diseases or controls, were positive for PrPSc. In addition, PrPSc typing revealed a consistent pattern (designated type 4t) different from that seen in variant CJD brain (type 4) or in brain from other CJD subtypes (types 1-3). Tonsil biopsy tissue was positive in all eight patients with an adequate biopsy sample and whose subsequent course has confirmed, or is highly consistent with, a diagnosis of variant CJD and negative in all patients subsequently confirmed to have other diagnoses. INTERPRETATION: We found that if, in the appropriate clinical context, a tonsil biopsy sample was positive for PrPSc, variant CJD could be diagnosed, which obviates the need for a brain biopsy sample to be taken. Our results also show that variant CJD has a different pathogenesis to sporadic CJD.

Adolescent↗
PubMed1999

The assessment of postmortem brain volume; a comparison of stereological and planimetric methodologies.

We compared two methods of estimating the volume of 10 formalin-fixed brains using MRI. MRI was performed and total brain volume was then assessed using two distinct techniques: a stereological point-counting technique based on the Cavalieri principle, and an edge-tracing technique. The total brain volumes obtained using these two techniques were similar and correlated closely with each other (r = 0.97). Both methods could be optimised to a similar degree while maintaining the coefficient of error at an acceptably low level. However, the stereological assessment of brain volume required between 20 min and 30 min per brain, depending on the number of points per sampling grid, compared with 1 h per brain using the planimetric method. Thus, while planimetric and stereological approaches yield very similar results, the stereological method has the advantage of greater speed and, therefore, efficiency.

Aged↗
PubMed1999

Glial cell changes in the white matter in temporal lobe epilepsy.

Temporal lobe gliosis and neuronal loss are pathological hallmarks of complex partial seizures. However, the specificity of glial cell changes is not clear. To assess this we studied surgically resected temporal lobes containing either medial temporal sclerosis (MTS) or temporal lobe epilepsy with tumour (TLET) and compared them with idiopathic epilepsy cases and normal controls. We quantitatively assessed glial cell density and mean nuclear volume in the white matter of various temporal gyri and the deep white matter. There was an increase in mean glial cell nuclear volume in MTS and TLET cases in the white matter of superior temporal gyrus, parahippocampal gyrus and deep white matter but not in the white matter of the middle temporal gyrus. In contrast, the densities of glial cells immunopositive for glial fibrillary acidic protein in the MTS and TLET groups were reduced in all white matter regions when compared with the controls. These changes may indicate that glial cells in the white matter have an active role to play in epilepsy pathogenesis.

Adolescent↗
PubMed1988

N-nitrosoephedrine and N-nitrosopseudoephedrine: their dissolution, absorption, blood clearance and elimination studies.

Dissolution and absorption rates (in vitro); clearance from blood and elimination rates of N-nitrosoephedrine (NEP) and N-nitrosopseudophedrine (NPEP) in mice were determined. The two isomers obeyed first-order kinetics and from the slope of the regression line, the rate constant for each study was obtained. These constants were 0.023, 0.038 min-1 (dissolution); 0.192, 0.225 h-1 (stomach absorption); 2.898, 1.980 h-1 (intestinal absorption); 0.33, 0.55 h-1 (blood clearance) and 0.373, 0.393 h-1 (elimination from whole animal) of NEP and NPEP, respectively, and were tested by Student's t-test. Significant differences in the dissolution, absorption and blood clearance rates of NPEP from those of NEP have been observed (P less than 0.05-0.01). These differences are expected to exert their influence on the metabolic rates and the carcinogenic and/or spectral properties of NEP and NPEP, in a related pattern.

Animals↗