Molecularly determined total tumour load in lymph nodes of stage I-II colon cancer patients correlates with high-risk factors. A multicentre prospective study.

Stage I-II (pN0) colorectal cancer patients are surgically treated although up to 25 % will eventually die from disease recurrence. Lymph node (LN) status is an independent prognostic factor in colorectal cancer (CRC), and molecular tumour detection in LN of early-stage CRC patients is associated with an increased risk of disease recurrence and poor survival. This prospective multicentre study aimed to determine the relationship between LN molecular tumour burden and conventional high-risk factors in stage I-II colon cancer patients.

Coexistence of protease sensitive and resistant prion protein in 129VV homozygous sporadic Creutzfeldt-Jakob disease: a case report.

Introduction: The coexistence of different molecular types of classical protease-resistant prion protein in the same individual have been described, however, the simultaneous finding of these with the recently described protease-sensitive variant or variably protease-sensitive prionopathy has, to the best of our knowledge, not yet been reported.

Case Presentation: A 74-year-old Caucasian woman showed a sporadic Creutzfeldt-Jakob disease clinical phenotype with reactive depression, followed by cognitive impairment, akinetic-rigid Parkinsonism with pseudobulbar syndrome and gait impairment with motor apraxia, visuospatial disorientation, and evident frontal dysfunction features such as grasping, palmomental reflex and brisk perioral reflexes. She died at age 77.

A novel form of human disease with a protease-sensitive prion protein and heterozygosity methionine/valine at codon 129: Case report.

Background: Sporadic Creutzfeldt-Jakob disease (sCJD) is a rare neurodegenerative disorder in humans included in the group of Transmissible Spongiform Encephalopathies or prion diseases. The vast majority of sCJD cases are molecularly classified according to the abnormal prion protein (PrPSc) conformations along with polymorphism of codon 129 of the PRNP gene. Recently, a novel human disease, termed "protease-sensitive prionopathy", has been described.

Somatic mosaicism in a case of apparently sporadic Creutzfeldt-Jakob disease carrying a de novo D178N mutation in the PRNP gene.

Transmissible spongiform encephalopathies (TSEs) are a group of rare fatal neurodegenerative disorders. Creutzfeldt-Jakob disease (CJD) represents the most common form of TSE and can be classified into sporadic, genetic, iatrogenic and variant forms. Genetic cases are related to prion protein gene mutations but they only account for 10-20% of cases.

A novel PRNP Y218N mutation in Gerstmann-Sträussler-Scheinker disease with neurofibrillary degeneration.

Gerstmann-Sträussler-Scheinker (GSS) disease is a prion disease associated with prion protein gene (PRNP) mutations. We report a novel PRNP mutation (Y218N) associated with GSS disease in a pathologically confirmed case and in two other affected family members. The clinical features of these cases met criteria for possible Alzheimer disease and possible frontotemporal dementia.

Phenotypic variability in familial prion diseases due to the D178N mutation.

Background: Between January 1993 and December 2003, 19 patients with familial prion diseases due to the D178N mutation were referred to the regional epidemiological registry for spongiform encephalopathies in the Basque Country in Spain, a small community of some 2,100,000 inhabitants.

Methods: Ten further patients belonging to the same pedigrees were retrospectively ascertained through neurological or neuropathological records. In four of the patients, the diagnosis was confirmed by analysing DNA obtained from paraffin blocks.

Tau-predominant-associated pathology in a sporadic late-onset Hallervorden-Spatz syndrome.

Hallervorden-Spatz syndrome (HSS) is a heterogeneous clinicopathological disorder currently included within the broader title of neurodegeneration with brain iron accumulation (NBIA). The classic histological hallmarks of HSS are axonal spheroids and excessive iron-containing granules accompanied by neuronal loss and gliosis in the globus pallidus and substantia nigra reticulata. In the modern literature, attention has been drawn to the co-occurrence of two other histological markers: Lewy bodies mainly composed of abnormal alpha-synuclein, and neurofibrillary tangles due to hyperphosphorilated tau aggregation.

A novel mutation (K317M) in the MAPT gene causes FTDP and motor neuron disease.

Background: Frontotemporal dementia with parkinsonism is often linked to chromosome 17 and is related to mutations in the MAPT gene. In some families the genetic basis is still unknown. The authors report two pedigrees with FTDP-17 harboring a novel mutation (K317M) in exon 11 in the MAPT gene.

Familial prion diseases in the Basque Country (Spain).

In 1995, a surveillance system for prion diseases was set up in the Basque Country, an autonomous region in northern Spain (2.1 million inhabitants). In the period from January 1993 to December 2003, we diagnosed 21 patients with familial prion diseases prospectively and another 4 patients retrospectively.

Parkinson's disease-like presentation of multiple system atrophy with poor response to STN stimulation: a clinicopathological case report.

We report on a clinicopathological case of multiple system atrophy with good response to levodopa and subsequent development of motor complications. Because the subject complied with all the inclusion criteria (Core Assessment Program for Surgical Interventional Therapies in Parkinson's Disease), bilateral subthalamic nucleus deep brain stimulation electrodes were implanted.

The new mutation, E46K, of alpha-synuclein causes Parkinson and Lewy body dementia.

Familial parkinsonism and dementia with cortical and subcortical Lewy bodies is uncommon, and no genetic defect has been reported in the previously described sibships. We present a Spanish family with autosomal dominant parkinsonism, dementia, and visual hallucinations of variable severity. The postmortem examination showed atrophy of the substantia nigra, lack of Alzheimer pathology, and numerous Lewy bodies which were immunoreactive to alpha-synuclein and ubiquitin in cortical and subcortical areas.

Dementia, amyotrophy, and periodic complexes on the electroencephalogram: a diagnostic challenge.

Background: The clinical diagnosis of neurodegenerative diseases is a challenge to the neurologist. In many cases the diagnosis becomes neuropathological only after the autopsy. Several consensus criteria have been defined for the clinical diagnosis of different neurodegenerative diseases, among them the various types of dementia as well as prion-induced diseases.

Value of limited necropsy in HIV-positive patients.

We performed limited autopsy with histological examination of tissue cores obtained percutaneously using the Tru-Cut needle and the Jamshidi trocar in 150 adult HIV-positive patients. Data were compared retrospectively with the antemortem clinical diagnosis. Eighty-one percent of the patients were male, and 78% were intravenous drug users.