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The article presents a case study of a 37-year-old female with a history of epilepsy, epidermoid cyst and focal complex seizures consistent with the diagnosis of neuronal intermediate filament inclusion disease (NIFID). The diagnosis was confirmed after magnetic resonance imaging (MRI) of the brain, neuropsychological and histological examination. The link of NIFID with frontotemporal lobal degeneration (FTD), accumulations of neuronal intermediate filaments and FET proteins is discussed.

Aims Parkinson's disease (PD) and dementia with Lewy bodies (DLB) are pathologically characterized by intraneuronal α-synuclein aggregates and thus labelled as Lewy body disorders (LBD). Conjoint cortical α-synuclein, tau and amyloid-β (Aβ), and striatal Aβ aggregates, have been related to dementia in LBD. Interpretation of current and emerging in vivo molecular imaging of these pathologies will need of precise knowledge of their topographic distribution. We aimed to assess these pathologies further down the encephalon across the LBD-spectrum. Methods Semiquantitative rating of α-synuclein, Aβ and hyperphosphorylated tau aggregates in midbrain (and cerebellum in the case of Aβ as it represents the last β-amyloidosis stage) sections from cases representative of the LBD-spectrum (PD non-dementia, PD-dementia, DLB; n = 10 each) compared to controls ( n = 10) and Alzheimer's disease (AD; n = 10). Results α-synuclein midbrain scores rose from controls to AD and then LBD irrespective of dementia. Aβ and tau were more prominent in the tectum/tegmentum, increasing from controls to LBD (mostly in dementia cases in the case of Aβ), and then peaking in AD. By contrast, cerebellar Aβ scores were marginal across the LBD-spectrum, as opposed to AD, only showing a trend towards greater involvement in LBD cases with dementia. Conclusions Frequency and severity of Aβ and tau pathologies in the midbrain across the LBD-spectrum were midway between controls and AD, with Aβ in the tectum/tegmentum being associated with dementia. These findings might have potential implications in the eventual interpretation of regional uptake of in vivo molecular imaging of these pathologies. [ABSTRACT FROM AUTHOR]

The article presents a neuropathological study of a 60-year-old man with frontotemporal lobar degenerations (FTLD) to determine the correlation of TARDBP mutation p.Ile383Val with semantic dementia and complex proteinopathy. The study investigates the temporally accentuated atrophy. The study concludes that the presence of p.Ile383Val mutation in TARDBP indicates a complex clinico-genetic-neuropathological relationships within the continuum FTLD-amyotrophic lateral sclerosis (ALS).

In Parkinson’s disease (PD), cognitive decline and psychiatric symptoms may occur and very often co-exist, eventually leading to PD-dementia. We report three patients with PD who presented striking psychiatric manifestations along with mild cognitive decline not progressing to dementia across the course of disease and in which postmortem neuropathological study revealed, besides alpha-synuclein inmunoreactive Lewy-body pathology, concomitant four-repeat tau positive argyrophilic grain pathology. We consider that argyrophilic grains might have modulated the clinical presentation of PD in these patients, being the main substrate of their prominent psychiatric symptoms in the absence of definite dementia. [ABSTRACT FROM AUTHOR]

E. Martinez-Saez, E. Gelpi, M. J. Rey, I. Ferrer, T. Ribalta, T. Botta-Orfila, C. Nos, J. Yagüe and R. Sanchez-Valle (2012) Neuropathology and Applied Neurobiology 38, 153-161 Hirano body-rich subtypes of Creutzfeldt-Jakob disease Background: In definite Creutzfeldt-Jakob disease (CJD), morphological and immunohistochemical patterns are useful to identify molecular subtypes. Severe cerebellar pathology and hippocampal involvement helps to identify VV subtypes. The rare VV1 variant (<1%), more frequent in young individuals, is additionally characterized by the presence of ballooned neurones in affected areas. In 1985, Cartier et al. described a family cluster of three individuals with an ataxic CJD form, showing, in addition to severe cerebellar and hippocampal involvement, the presence of frequent Hirano bodies (HB) in CA1 pyramidal neurones. HB are frequently found in aged individuals with Alzheimer pathology although they are not a specific finding. Aims and methods: In this study, we evaluated the presence of HB in hippocampi of 54 genetically and molecularly characterized CJD cases, aiming to elucidate whether additional morphological features could be helpful to point to molecular subtypes. Results: We identified nine cases (four VV1, one out of three MV2K, three out of six MV2K+2C and one MV carrying a 96-base pair insertion) with abundant, partly bizarre and clustered HB in CA1 sector, not observed in other subtypes. The presence of HB was independent of hippocampal involvement by the disease itself. Conclusions: Clusters of abundant HB might be found in rare CJD subtypes such as VV1, MV2K/MV2K+2C and some genetic cases. In addition to histopathological and PrP immunohistochemical deposition patterns, their presence might be a useful additional morphologic feature that could point to the molecular subtype, especially when genetic and/or Western blot analyses are not available. [ABSTRACT FROM AUTHOR]

A letter to the editor is presented in response to the article about Creutzfeldt-Jakob disease in the September 20, 2007 issue.

Reports on the Ten Years of EC-Funded Concerted Actions on the Neuropathology of Prion Disease: Report on the Final Scientific Meeting held in Austria from October 31 to November 2003. Discussion on the basic aspects of transmissible spongiform encephalopathy; Progress in prion disease research; Guest speakers.

The article presents a case study of a 59-year old man with a 1-year history of subtle verb conjugation difficulties. His evaluation showed spared object recognition and single-world comprehension but mild difficulty in sentence repetition. He developed severe behavioral symptoms that required treatment with atypical antipsychotics and non-cholinergic antidepressive drugs. The patient's findings suggested nigrostriatal terminal dysfunction.

We report the case of a 28 year old man who had received a cadaverous dura mater graft after a traumatic open skull fracture with tearing of the dura at the age of 5 years. A clinical suspicion of Creutzfeldt-Jakob disease (CJD) was confirmed by a brain biopsy 5 months prior to death and by autopsy, thus warranting the diagnosis of iatrogenic CJD (iCJD) according to WHO criteria. Immunohistochemistry showed widespread cortical depositions of disease associated prion protein (PrP(sc)) in a synaptic pattern, and western blot analysis identified PrP(sc) of type 2A according to Parchi et al. Surprisingly, we found Alzheimer-type senile plaques and cerebral amyloid angiopathy in widespread areas of the brain. Plaque-type and vascular amyloid was immunohistochemically identified as deposits of beta-A4 peptide. CERAD criteria for diagnosis of definite Alzheimer's disease (AD) were met in the absence of neurofibrillar tangles or alpha-synuclein immunoreactive inclusions. There was no family history of AD, CJD, or any other neurological disease, and genetic analysis showed no disease specific mutations of the prion protein, presenilin 1 and 2, or amyloid precursor protein genes. This case represents (a) the iCJD case with the longest incubation time after dural grafting reported so far, (b) the youngest documented patient with concomitant CJD and Alzheimer-type neuropathology to date, (c) the first description of Alzheimer-type changes in iCJD, and (d) the second case of iCJD in Austria. Despite the young patient age, the Alzheimer-type changes may be an incidental finding, possibly related to the childhood trauma. [ABSTRACT FROM AUTHOR]

Aims: The Ki67 tumour cell proliferation index is an independent prognostic factor in ependymoma patients. Essential prerequisites for validation of the Ki67 index as a histopathological biomarker are the reproducibility of this factor and its prognostic influence by different observers (proof of objective clinical and analytical performance). To this end, the aim was to analyse systematically inter- and intraobserver agreement and reproducibility of the prognostic impact of the Ki67 index in intracranial ependymoma. Methods and results: The study cohort contained 78 cases of intracranial ependymoma. In all cases, the Ki67 index was assessed by four experienced observers (EOs) and by four inexperienced observers (IOs) using the manual hot-spot method. There was considerable agreement on Ki67 index assessment. There was higher observer agreement among EOs compared with IOs. For each observer, survival analysis showed significant association of low Ki67 index with favourable patient outcome. Conclusions: Our data show that the Ki67 index in intracranial ependymoma is a reproducible and robust prognostic factor and can be considered a promising histopathological candidate biomarker. Attainment of biomarker status requires further translational studies in the context of prospective therapeutic trials. [ABSTRACT FROM AUTHOR]

We report the case of a 28 year old man who had received a cadaverous dura mater graft after a traumatic open skull fracture with tearing of the dura at the age of 5 years. A clinical suspicion of Creutzfeldt-Jakob disease (CJD) was confirmed by a brain biopsy 5 months prior to death and by autopsy, thus warranting the diagnosis of iatrogenic CJD (iCJD) according to WHO criteria. Immunohistochemistry showed widespread cortical depositions of disease associated prion protein (PrPSC) in a synaptic pattern, and western blot analysis identified PrPSC of type 2A according to Parchi et al. Surprisingly, we found Alzheimer-type senile plaques and cerebral amyloid angiopathy in widespread areas of the brain. Plaque-type and vascular amyloid was immunohistochemically identified as deposits of beta-A4 peptide. CERAD criteria for diagnosis of definite Alzheimer's disease (AD) were met in the absence of neurofibrillar tangles or alpha- synuclein immunoreactive inclusions. There was no family history of AD, CJD, or any other neurological disease, and genetic analysis showed no disease specific mutations of the prion protein, presenilin 1 and 2, or amyloid precursor protein genes. This case represents (a) the iCJD case with the longest incubation time after dural grafting reported so far, (b) the youngest documented patient with concomitant CJD and Alzheimer-type neuropathology to date, (c) the first description of Alzheimer-type changes in iCJD, and (d) the second case of iCJD in Austria. Despite the young patient age, the Alzheimer-type changes may be an incidental finding, possibly related to the childhood trauma. [ABSTRACT FROM AUTHOR]

Background and purpose: Argyrophilic grain disease (AGD) is a limbic‐predominant 4R‐tauopathy. AGD is thought to be an age‐related disorder and is frequently detected as a concomitant pathology with other neurodegenerative conditions. There is a paucity of data on the clinical phenotype of pure AGD. In elderly patients, however, AGD pathology frequently associates with cognitive decline, personality changes, urine incontinence and cachexia. In this study, clinicopathological findings were analysed in individuals younger than 75. Methods: Patients were identified retrospectively based on neuropathological examinations during 2006–2017 and selected when AGD was the primary and dominant pathological finding. Clinical data were obtained retrospectively through medical records. Results: In all, 55 patients (2% of all examinations performed during that period) with AGD were identified. In seven cases (13%) AGD was the primary neuropathological diagnosis without significant concomitant pathologies. Two patients were female, median age at the time of death was 64 years (range 51–74) and the median duration of disease was 3 months (range 0.5–36). The most frequent symptoms were progressive cognitive decline, urinary incontinence, seizures and psychiatric symptoms. Brain magnetic resonance imaging revealed mild temporal atrophy. Conclusions: Argyrophilic grain disease is a rarely recognized limbic tauopathy in younger individuals. Widening the clinicopathological spectrum of tauopathies may allow identification of further patients who could benefit from tau‐based therapeutic strategies. [ABSTRACT FROM AUTHOR]

The article presents three case studies involving amyotrophic lateral sclerosis (ALS) without abnormal cytoplasmic accumulation of fused in sarcoma (FUS) mutation. The three cases described ALS-FUS with TATA-binding protein-associated factor 15 (TAF15) and Trn1 accumulation without FUS mutation. Findings in the study showed an older age of onset and different morphological phenotypes in terms of disease duration in ALS-FUS cases without mutations.

The article discusses progressive supranuclear palsy (PSP) as a low-prevalence atypical parkinsonism with early falls and late hallucinations, psychosis and dementia thus causing challenges in its differential diagnosis from Parkinson's disease (PD) and corticobasal degeneration. Topics include frontotemporal lobar degeneration-fused in sarcoma proteinopathy(FTLD-FUS) of the neuronal intermediate filament inclusion disease type, brain imaging techniques, and gene sequencing analysis.

Objective: To determine the pathologic substrates in patients with rapid eye movement (REM) sleep behavior disorder (RBD) with or without a coexisting neurologic disorder. Methods: The clinical and neuropathologic findings were analyzed on all autopsied cases from one of the collaborating sites in North America and Europe, were evaluated from January 1990 to March 2012, and were diagnosed with polysomnogram (PSG)-proven or probable RBD with or without a coexisting neurologic disorder. The clinical and neuropathologic diagnoses were based on published criteria. Results: 172 cases were identified, of whom 143 (83%) were men. The mean±SD age of onset in years for the core features were as follows – RBD, 62±14 (range, 20–93), cognitive impairment (n =147); 69±10 (range, 22–90), parkinsonism (n =151); 68±9 (range, 20–92), and autonomic dysfunction (n =42); 62±12 (range, 23–81). Death age was 75±9years (range, 24–96). Eighty-two (48%) had RBD confirmed by PSG, 64 (37%) had a classic history of recurrent dream enactment behavior, and 26 (15%) screened positive for RBD by questionnaire. RBD preceded the onset of cognitive impairment, parkinsonism, or autonomic dysfunction in 87 (51%) patients by 10±12 (range, 1–61) years. The primary clinical diagnoses among those with a coexisting neurologic disorder were dementia with Lewy bodies (n =97), Parkinson’s disease with or without mild cognitive impairment or dementia (n =32), multiple system atrophy (MSA) (n =19), Alzheimer’s disease (AD)(n =9) and other various disorders including secondary narcolepsy (n =2) and neurodegeneration with brain iron accumulation-type 1 (NBAI-1) (n =1). The neuropathologic diagnoses were Lewy body disease (LBD)(n =77, including 1 case with a duplication in the gene encoding α-synuclein), combined LBD and AD (n =59), MSA (n =19), AD (n =6), progressive supranulear palsy (PSP) (n =2), other mixed neurodegenerative pathologies (n =6), NBIA-1/LBD/tauopathy (n =1), and hypothalamic structural lesions (n =2). Among the neurodegenerative disorders associated with RBD (n =170), 160 (94%) were synucleinopathies. The RBD-synucleinopathy association was particularly high when RBD preceded the onset of other neurodegenerative syndrome features. Conclusions: In this large series of PSG-confirmed and probable RBD cases that underwent autopsy, the strong association of RBD with the synucleinopathies was further substantiated and a wider spectrum of disorders which can underlie RBD now are more apparent. [ABSTRACT FROM AUTHOR]

G. G. Kovacs, A. J. M. Rozemuller, J. C. van Swieten, E. Gelpi, K. Majtenyi, S. Al-Sarraj, C. Troakes, I. Bódi, A. King, T. Hortobágyi, M. M. Esiri, O. Ansorge, G. Giaccone, I. Ferrer, T. Arzberger, N. Bogdanovic, T. Nilsson, I. Leisser, I. Alafuzoff, J. W. Ironside, H. Kretzschmar and H. Budka (2013) Neuropathology and Applied Neurobiology 39, 166-178 Neuropathology of the hippocampus in FTLD-Tau with Pick bodies: a study of the BrainNet Europe Consortium Aims: Frontotemporal lobar degeneration with Pick bodies (Pick's disease) is characterized by the presence of tau immunoreactive spherical structures in the cytoplasm of neurones. In view of confusion about the molecular pathology of Pick's disease, we aimed to evaluate the spectrum of tau pathology and concomitant neurodegeneration-associated protein depositions in the characteristically affected hippocampus. Methods: We evaluated immunoreactivity (IR) for tau (AT8, 3R, 4R), α-synuclein, TDP43, p62, and ubiquitin in the hippocampus, entorhinal and temporal cortex in 66 archival cases diagnosed neuropathologically as Pick's disease. Results: Mean age at death was 68.2 years (range 49-96). Fifty-two (79%) brains showed 3R immunoreactive spherical inclusions in the granule cells of the dentate gyrus. These typical cases presented mainly with the behavioural variant of frontotemporal dementia, followed by progressive aphasia, mixed syndromes or early memory disturbance. α-Synuclein IR was seen only in occasional spherical tau-positive inclusions, TDP-43 IR was absent, and 4R IR was present only as neurofibrillary tangles in pyramidal neurones. Aβ IR was observed in 16 cases; however, the overall level of Alzheimer's disease-related alterations was mainly low or intermediate ( n = 3). Furthermore, we identified six cases with unclassifiable tauopathy. Conclusions: (i) Pick's disease may occur also in elderly patients and is characterized by a relatively uniform pathology with 3R tau inclusions particularly in the granule cells of dentate gyrus; (ii) even minor deviation from these morphological criteria suggests a different disorder; and (iii) immunohistological revision of archival cases expands the spectrum of tauopathies that require further classification. [ABSTRACT FROM AUTHOR]

The article presents a case study of a 62-year-old woman with right hand resting tremor and good levodopa response. The patient undergo electroencephalography (EEG) and brain magnetic resonance imaging (MRI), in which the EEG reveals slow base rhythm. Moreover, a moderate neuronal loss and gliosis were observed to the patient. It also discusses Pick pathology in Parkinson's disease patients with dementia.

Iatrogenic Creutzfeldt-Jakob disease (iCJD) is mainly associated with dura mater (DM) grafts and administration of human growth hormones (hGH). Data on disease course in DM-CJD are limited. We describe the clinical and diagnostic findings in this patient group with special emphasis on MRI signal alterations. Ten DM-CJD patients were studied for their clinical symptoms and diagnostic findings. The MRIs were evaluated for signal increase of the cortical and subcortical structures. DM-CJD patients had a median incubation time of 18 years and median disease duration of 7 months. The majority of patients were MM homozygous at codon 129 of the prion protein gene ( PRNP) and presented with gait ataxia and psychiatric symptoms. No correlation between the graft site and the initial disease course was found. The MRI showed cortical and basal ganglia signal increase each in eight out of ten patients and thalamic hyperintensity in five out of ten cases. Of interest, patients with thalamic signal increase were homozygous for methionine. The MRI findings in DM-CJD largely resemble those seen in sporadic CJD, as the cortex and basal ganglia are mainly affected. [ABSTRACT FROM AUTHOR]

Background: In the literature on cortical degenerative processes and primary progressive aphasia, language disorders have been discussed as the initial sign of higher cortical dysfunction. Verbal perseveration has also been cited to precede the occurrence of other cortical signs. In this paper we present language data from an autopsy-confirmed case of Creutzfeldt-Jakob disease (CJD) who exhibited profound verbal perseveration as the initial symptom. Aims: This case report aims to provide a description of the extent and pattern of verbal perseveration in a client with the rapidly progressing fatal CJD. Language test data and medical data, i.e., EEG and neuropathology - which confirm the diagnosis of CJD - are presented. Methods & Procedures: Language testing was performed with our patient to determine the nature of the language disorder at a time when the diagnosis of CJD had not yet been made. The tape-recorded sessions were transcribed and the language data analysed. Outcomes & Results: The pervasive perseverative behaviour mirrors the underlying language-processing difficulties and the magnitude of the progression of the disease process. Perseverative errors account for between 87% and 95% of the language-processing errors on the various language tasks. In general, the first items of each task were responded to correctly, indicating that our client was trying to meet the various test demands and at the time of testing was still able to process language, albeit in a very restricted manner. Conclusions: The rapid deterioration of language functions in our case and in other reported cases necessitates acting quickly without delay. Immediate recognition and analysis of the language disturbance and verbal perseverative behaviour may provide relevant information for differentially diagnosing clients presenting with various cortical degenerative diseases at an early stage. [ABSTRACT FROM AUTHOR]

Abstract: Standard postoperative treatment of medulloblastoma consists of craniospinal irradiation and chemotherapy. Currently, only clinical factors are used for therapy stratification. To optimise treatment and patient outcome, biological prognostic markers are needed. In the present study we tested the prognostic influence of four histopathological parameters considered in recent publications as prognostic factors in medulloblastoma. We analysed a series of 82 Austrian medulloblastoma patients who were treated according to the consecutive HIT protocols for medulloblastoma conducted by the German Society of Paediatric Haematology and Oncology. Histological subtype and immunohistochemical expression of erbB-2, TRKC, and survivin were determined on paraffin embedded tumour tissue and correlated with patient outcome. Statistical analysis showed a significant correlation of high expression levels of survivin with decreased survival. None of the other investigated histopathological factors correlated significantly with patient outcome. Our data indicate that high survivin expression is related to unfavourable clinical outcome in medulloblastoma patients. [Copyright &y& Elsevier]

Analyzes aniline derivatives in oil related to the Toxic Oil Syndrome (TOS) using HPLC-mass spectrometry (MS) and HPLC-MS/MS with an atmospheric pressure ionization source. Correlation between fatty acid anilides and propanediol derivatives and fatty acid composition of the oils with regards to relative abundance; Dependence of the quantity of anilides found in TOS-related oils on the nature of the oil.