How and why I fell into neuropathology.

I'm going to explain how and why I fell into the Department of Neuropathology at the Pitié-Salpêtrière Hospital of Paris. I'd also like to sketch the history of French neuropathology in the years 1960-2010, as seen by a naive young student, and then by a practicing neuropathologist (often still very naive). As a matter of fact, although the history of neurosciences [1-2] and the Pitié-Salpêtrière Hospital in Paris [3-4] have been the subject of numerous publications, the history of neuropathology in this hospital has been rarely documented [5-6].

[Measles subacute sclerosing panencephalitis (SSPE): A still present and still mysterious fatal disease. History, Diagnosis and Assumptions].

Subacute sclerosing panencephalitis, a late complication of measles, is still present during epidemics of this disease due to insufficient vaccination. After a historical review, the importance of the diagnostic criteria and the pathophysiology of SSEP are discussed. Numerous studies on the parameters of innate immunity and interferon responses tend to show a decrease in the activity of cellular immunity.

Charcot identifies and illustrates amyotrophic lateral sclerosis.

Jean-Martin Charcot described what he called amyotrophic lateral sclerosis in his 12 and 13 lessons published in 1873 by Bourneville. He distinguished the symptoms that were related to the lesion of the anterior horn of the spinal cord and those that were due to the degeneration (that he named "sclerosis") of its lateral column. He thought that "inflammation" progressed from the lateral column to the anterior horn (but the term inflammation is not to be taken in the current meaning): the lesion of the anterior horn was thus "deuteropathic".

Amyloid Angiopathy in Brain Hemorrhage: A Postmortem Neuropathological-Magnetic Resonance Imaging Study.

Background: Risk factors for intracerebral hemorrhage (ICH) include hypertension and cerebral amyloid angiopathy (CAA). The objective of this study was to determine the autopsy prevalence of CAA and the potential overlap with other risk factors among patients who died from ICH and also the correlation of CAA with cerebral microbleeds.

Methods: We analyzed 81 consecutive autopsy brains from patients with ICH.

Accuracy of diagnosis criteria in patients with suspected diagnosis of sporadic Creutzfeldt-Jakob disease and detection of 14-3-3 protein, France, 1992 to 2009.

Diagnostic criteria of Creutzfeldt-Jakob disease (CJD), a rare and fatal transmissible nervous system disease with public health implications, are determined by clinical data, electroencephalogram (EEG), detection of 14-3-3 protein in cerebrospinal fluid (CSF), brain magnetic resonance imaging and prion protein gene examination. The specificity of protein 14-3-3 has been questioned. We reviewed data from 1,572 autopsied patients collected over an 18-year period (1992-2009) and assessed whether and how 14-3-3 detection impacted the diagnosis of sporadic CJD in France, and whether this led to the misdiagnosis of treatable disorders.

ADAM30 Downregulates APP-Linked Defects Through Cathepsin D Activation in Alzheimer's Disease.

Although several ADAMs (A disintegrin-like and metalloproteases) have been shown to contribute to the amyloid precursor protein (APP) metabolism, the full spectrum of metalloproteases involved in this metabolism remains to be established. Transcriptomic analyses centred on metalloprotease genes unraveled a 50% decrease in ADAM30 expression that inversely correlates with amyloid load in Alzheimer's disease brains. Accordingly, in vitro down- or up-regulation of ADAM30 expression triggered an increase/decrease in Aβ peptides levels whereas expression of a biologically inactive ADAM30 (ADAM30(mut)) did not affect Aβ secretion.

Coronary and Basilar Artery Ectasia Are Associated: Results From an Autopsy Case-Control Study.

Background And Purpose: Intracranial artery dolichoectasia (IADE) and coronary artery ectasia have been associated with stroke and myocardial infarction, respectively. Only rarely have cases of coexisting IADE and coronary artery ectasia been reported. We investigated this association in a large consecutive autopsy series.

History of Prions and transmission of protein misfolding.

Since J. Cuillé and P. L.

[New insights into intracellular inclusions and intracellular proteolysis].

Intracellular inclusions seen by the pathologist may have variable significance. Although they are excellent markers of proteolytic disorders, they can also be due to several other mechanisms. This article examines recent data on the morphology, significance and consequences of aging lipofuscins in the brain and retina, neurofibrillary tangles and Lewy bodies, and Birbeck granules associated with Langerhans histiocytosis.

Cycline efficacy on the propagation of human prions in primary cultured neurons is strain-specific.

In prion diseases, a major issue in therapeutic research is the variability of the effect between strains. Stimulated by the report of an antiprion effect in a scrapie model and by ongoing international clinical trials using doxycycline, we studied the efficacy of cyclines against the propagation of human prions. First, we successfully propagated various Creutzfeldt-Jakob disease (CJD) isolates (sporadic, variant, and iatrogenic CJD) in neuronal cultures expressing the human prion protein.

Axonal expression of sodium channels and neuropathology of the plaques in multiple sclerosis.

Aims: Although demyelination is an important cause of neurological deficits in multiple sclerosis (MS), recently axonal pathology and concomitant involvement of sodium channels (Nav) became a focus of major interest. Studies in experimental autoimmune encephalomyelitis (EAE) and MS have shown diffuse expression of Nav1.6 and Nav1.

Substitutions at residue 211 in the prion protein drive a switch between CJD and GSS syndrome, a new mechanism governing inherited neurodegenerative disorders.

Human prion diseases are a heterogeneous group of fatal neurodegenerative disorders, characterized by the deposition of the partially protease-resistant prion protein (PrP(res)), astrocytosis, neuronal loss and spongiform change in the brain. Among inherited forms that represent 15% of patients, different phenotypes have been described depending on the variations detected at different positions within the prion protein gene. Here, we report a new mechanism governing the phenotypic variability of inherited prion diseases.

Consensus classification of human prion disease histotypes allows reliable identification of molecular subtypes: an inter-rater study among surveillance centres in Europe and USA.

The current classification of human sporadic prion diseases recognizes six major phenotypic subtypes with distinctive clinicopathological features, which largely correlate at the molecular level with the genotype at the polymorphic codon 129 (methionine, M, or valine, V) in the prion protein gene and with the size of the protease-resistant core of the abnormal prion protein, PrP(Sc) (i.e. type 1 migrating at 21 kDa and type 2 at 19 kDa).

Association between a Primitive Brain Tumor and Cerebral Aspergillosis.

Cerebral aspergillosis is a rare pathology of poor prognosis in spite of the use of adapted antifungal treatments. This infection of the central nervous system is generally the complication of an invasive aspergillosis with hematogenic scattering from pulmonary focal spots. It can arise in immunocompetent patients treated with prolonged corticotherapy or chemoradiotherapy for cancer.

Fronto-temporal lobar degeneration: neuropathology in 60 cases.

Sixty cases of frontotemporal lobar degeneration (FTLD) were collected over 22 years. Brain weight was negatively correlated with disease duration. The neuronal and/or glial inclusions were labeled by anti-TDP, anti-FUS or anti-TAU antibodies, respectively, in 40, 3 and 12 cases.

Neuropathology of sleep disorders: a review.

Sleep disorders are important manifestations of neurodegenerativediseases and sometimes are clinically evident well before the onset of other neurological manifestations. This review addresses theneuroanatomical basis and the mechanisms of sleep regulation in humans in relation to the neuropathology of entities associated with sleep disturbances in selected diseases, including Alzheimer disease, progressive supranuclear palsy, Lewy body disorders, multiple-system atrophy, and fatal familial insomnia. This includes abnormalities of circadian rhythm, insomnia, narcolepsy, rapid eye movements sleep behavior disorders, and excessive daytime sleepiness.

Nodes of ranvier and paranodes in chronic acquired neuropathies.

Chronic acquired neuropathies of unknown origin are classified as chronic inflammatory demyelinating polyneuropathies (CIDP) and chronic idiopathic axonal polyneuropathies (CIAP). The diagnosis can be very difficult, although it has important therapeutic implications since CIDP can be improved by immunomodulating treatment. The aim of this study was to examine the possible abnormalities of nodal and paranodal regions in these two types of neuropathies.

[Treatment of Alzheimer's disease and future approaches].

The progressive neuronal loss in Alzheimer's disease leads to neurochemical abnormalities which provide the basis for symptomatic treatments. Four cholinesterase inhibitors were released in this indication. Meta-analyses have confirmed a beneficial effect on cognitive functioning and activities of daily living.

Ultrastructural characteristics (or evaluation) of Creutzfeldt-Jakob disease and other human transmissible spongiform encephalopathies or prion diseases.

The authors report on a large series of human prion diseases to establish ultrastructural characteristics that may be useful for their diagnosis. For Creutzfeldt-Jakob disease (CJD and its variant, vCJD) and fatal familial insomnia (FFI) only vacuolation (spongiform change) and the presence of tubulovesicular structures are consistent findings. Other changes, such as the presence of myelinated vacuoles, branching cisternae, neuroaxonal dystrophy, and autophagic vacuoles, were present in different proportions in either CJD or FFI, but they are nonspecific ultrastructural findings that can also occur in other neurodegenerative conditions.

Creutzfeldt-Jakob disease in a patient treated by etanercept for rheumatoid arthritis (RA): just a coincidence?

We describe a patient in whom sporadic Creutzfeldt-Jakob disease (sCJD) occurred one year after the onset of etanercept therapy for rheumatoid arthritis (RA). This association could be a chance occurrence. However, TNF-alpha has been implicated in the pathogenesis of neurodegeneration in sCJD and etanercept might worsen the disease.

Effects of antemortem and postmortem variables on human brain mRNA quality: a BrainNet Europe study.

Well-characterized and preserved human brain tissue that is prepared and stored in brain banks is an essential resource for research in neurological diseases. This study examined the quality of human brain postmortem tissue from multiple laboratories within the BrainNet Europe brain bank network to identify all possible confounding variables and determine how they may affect RNA quality. Antemortem and postmortem information was retrospectively collected for a large cohort of samples.

Is moderate atherosclerotic stenosis in the middle cerebral artery a cause of or a coincidental finding in ischemic stroke?

Background: Few pathological data have focused on the causal link between intracranial atherosclerotic disease and parent artery stroke. The objective of this study was to investigate the cause of middle cerebral artery (MCA) atherosclerotic disease in patients with fatal stroke.

Methods And Results: In 123 patients with unilateral MCA territory infarction we performed a case-control autopsy study evaluating the frequency of atherosclerotic plaque and moderate (<70%) or severe (>or=70%) stenosis in the ipsilateral and contralateral MCA.