Thomas Ng

Consensus neuropathological diagnosis of common dementia syndromes: testing and standardising the use of multiple diagnostic criteria

Abstract. The aim of this study was to assess the variation between neuropathologists in the diagnosis of common dementia syndromes when multiple published protocols are applied. Fourteen out of 18 Australian neuropathologists participated in diagnosing 20 cases (16 cases of dementia, 4 age-matched controls) using consensus diagnostic methods. Diagnostic criteria, clinical synopses and slides from multiple brain regions were sent to participants who were asked for case diagnoses. Diagnostic sensitivity, specificity, predictive value, accuracy and variability were determined using percentage agreement and kappa statistics. Using CERAD criteria, there was a high inter-rater agreement for cases with probable and definite Alzheimers disease but low agreement for cases with possible Alzheimers disease. Braak staging and the application of criteria for dementia with Lewy bodies also resulted in high inter-rater agreement. There was poor agreement for the diagnosis of frontotemporal dementia and for identifying small vessel disease. Participants rarely diagnosed more than one disease in any case. To improve efficiency when applying multiple diagnostic criteria, several simplifications were proposed and tested on 5 of the original 20 cases. Inter-rater reliability for the diagnosis of Alzheimers disease and dementia with Lewy bodies significantly improved. Further development of simple and accurate methods to identify small vessel lesions and diagnose frontotemporal dementia is warranted.

Pigmented central neurocytoma: case report and literature review.

A case of pigmented central neurocytoma is reported. The tumor showed histologic, immunophenotypic, and ultrastructural features of central neurocytoma. The pigment consisted of an intimate association of lipofuscin and neuromelanin. Pigmented neuroepithelial tumors are rare, and the pigments may be neuromelanin or melanin. Pigmented central neurocytoma has not been described to date. The low proliferation rate of the tumor suggests a delayed turnover of tumor cells as a possible cause of lipofuscin accumulation. Autocatalytic peroxidation of lipofuscin is a possible mechanism of neuromelanin formation.

First evidence of overlaps between HIV-Associated Dementia (HAD) and non-viral neurodegenerative diseases: proteomic analysis of the frontal cortex from HIV+ patients with and without dementia.

BackgroundThe pathogenesis of HIV-associated dementia (HAD) is poorly understood. To date, detailed proteomic fingerprinting directly from autopsied brain tissues of HAD and HIV non-dementia patients has not been performed.ResultHere, we have analyzed total proteins from the frontal cortex of 9 HAD and 5 HIV non-dementia patients. Using 2-Dimensional differential in-gel electrophoresis (2-DIGE) to analyze the brain tissue proteome, 76 differentially expressed proteins (p < 0.05; fold change>1.25) were identified between HAD and HIV non-dementia patients, of which 36 protein spots (based on 3D appearance of spots on the images) were chosen for the mass spectrometry analysis. The large majority of identified proteins were represented in the energy metabolic (mitochondria) and signal transduction pathways. Furthermore, over 90% of the protein candidates are common to both HAD and other non-viral neurodegenerative disease, such as Alzheimers disease. The data was further validated using specific antibodies to 4 proteins (CA2, GS, CKMT and CRMP2) by western blot (WB) in the same samples used for 2D-DIGE, with additional confirmation by immunohistochemitsry (IHC) using frontal lobe tissue from different HAD and HIV+ non-dementia patients. The validation for all 4 antibodies by WB and IHC was in concordance with the DIGE results, lending further credence to the current findings.ConclusionThese results suggest not only convergent pathogenetic pathways for the two diseases but also the possibility of increased Alzheimers disease (AD) susceptibility in HAD patients whose life expectancy has been significantly increased by highly active antiretroviral therapy.

Evidence for predilection of macrophage infiltration patterns in the deeper midline and mesial temporal structures of the brain uniquely in patients with HIV-associated dementia.

BackgroundHIV-1 penetrates the central nervous system, which is vital for HIV-associated dementia (HAD). But the role of cellular infiltration and activation together with HIV in the development of HAD is poorly understood.MethodsTo study activation and infiltration patterns of macrophages, CD8+ T cells in relation to HIV in diverse CNS areas of patients with and without dementia. 46 brain regions from two rapidly progressing severely demented patients and 53 regions from 4 HIV+ non-dementia patients were analyzed. Macrophage and CD8+ T cell infiltration of the CNS in relation to HIV was assessed using immuno-histochemical analysis with anti-HIV (P24), anti-CD8 and anti-CD68, anti-S-100A8 and granzyme B antibodies (cellular activation). Statistical analysis was performed with SPSS 12.0 with Students t test and ANOVA.ResultsOverall, the patterns of infiltration of macrophages and CD8+ T cells were indiscernible between patients with and without dementia, but the co-localization of macrophages and CD8+ T cells along with HIV P24 antigen in the deeper midline and mesial temporal structures of the brain segregated the two groups. This predilection of infected macrophages and CD8+ T cells to the middle part of the brain was unique to both HAD patients, along with unique nature of provirus gag gene sequences derived from macrophages in the midline and mesial temporal structures.ConclusionStrong predilection of infected macrophages and CD8+ T cells was typical of the deeper midline and mesial temporal structures uniquely in HAD patients, which has some influence on neurocognitive impairment during HIV infection.

Extraventricular neurocytoma with atypical features and ganglionic differentiation

Extraventricular neurocytoma (EVN) is an unusual variant of central neurocytoma located outside the ventricular system. Both tumours share a similar histology characterised by monotonous populations of round-to-oval cells with scanty cytoplasm separated by neuropil and branching capillaries. We report an EVN arising from the right frontal lobe near the olfactory tract in a 34-year-old male with worsening chronic epilepsy. Our patients tumour exhibited many uncommon features including ganglionic differentiation, increased mitotic activity and a high proliferative index. We discuss the important differential diagnoses given the site of the tumour as well as the differentiating features from olfactory neuroblastoma, oligodendroglioma, anaplastic ganglioglioma and supra-tentorial primitive neuroectodermal tumour.

Intraventricular rhabdoid meningioma

Rhabdoid meningioma is a rare variant of meningioma, often found in tumour recurrences. We report a 55-year-old woman with a history of intraventricular fibroblastic meningioma, who developed headache and tinnitus 5 years after complete resection of the initial tumour. Imaging confirmed a recurrent tumour in the intraventricular location. Histological analysis revealed rhabdoid meningioma. We reviewed the literature and were unable to find any previously reported cases of intraventricular rhabdoid meningioma.

Late onset Rasmussen's encephalitis with triple pathology

Rasmussens encephalitis is a devastating illness characterized by intractable focal seizures due to chronic localised encephalitis. We report on a rare variant of delayed onset Rasmussens encephalitis with triple pathology. A 27-year-old male, who was initially diagnosed with seizures when he was 16 years old, presented with focal seizures that became refractory to multiple anticonvulsants. Multiple investigations, including subdural electrode monitoring, revealed foci of onset in the right frontotemporal region. The patient underwent right front-temporal lobectomy. Post-operatively, the seizures became more severe and he developed new epilepsia partialis continua. Treatment with intravenous immunoglobulin was unsuccessful. He subsequently underwent a right hemispherectomy that rendered him seizure free. The three pathologies identified were old ischemic changes, type II cortical dysplasia and stage II Rasmussens encephalitis.

Papillary tumour of the pineal region: cytological features and implications for intraoperative diagnosis

Sir,Papillary tumours of the central nervous system are very uncommon. Even rarer are reports of tumours with papillary features occurring in the pineal region, which include choroid plexus tumours...

Papillary glioneuronal tumor of the frontal lobe

Glioneuronal tumors of the central nervous system (CNS) comprise a group of generally low-grade tumors expressing glial and neuronal cells of varying differentiation. Papillary glioneuronal tumor (PGNT) is a new tumor identified in the World Health Organizations classification of CNS tumors (2007). We report a patient with PGNT and highlight the diagnostic features, including a description of spidery astrocytes.

Rosette-forming glioneuronal tumour of the lateral ventricle in a patient with neurofibromatosis 1

We report a 33-year-old man with neurofibromatosis type 1 (NF-1) with a rosette-forming glioneuronal tumour (RGNT) in the lateral ventricle. The patient had been treated with radiotherapy and chemotherapy for a typical juvenile pilocytic astrocytoma of the hypothalamus seven years prior. MRI revealed a contrast-enhancing mass in the anterior horn of the left lateral ventricle. Histological examination demonstrated two distinct regions characterised by a rosette-forming neurocytic component and an astrocytic predominant component. Immunohistochemical studies showed glial fibrillary acidic protein and S-100 positivity in the astrocytic component and neuron-specific enolase was positive in the neurocytic cells. Although RGNT has been reported at other sites within the central nervous system, this report documents a previously undescribed lateral ventricular location of a rare RGNT in an asymptomatic patient with NF-1.