Leptomeningeal carcinomatosis mimicking Creutzfeldt-Jakob disease: clinical features, laboratory tests, MRI images, EEG findings in an autopsy-proven case.

Leptomeningeal carcinomatosis (LC) refers to diffuse seeding of the leptomeninges by tumor metastases. The clinical presentation may differ and the diagnosis may be difficult especially when cancer has not yet been diagnosed. We report a case of LC, where the clinical picture and a specific change in cerebrospinal fluid suggested the diagnosis of a prion disease.

Atypical Alzheimer's disease: a case report.

This paper deals with an unusual case of Alzheimer's disease with early onset, no family history, myoclonus, tonic generalized seizures and pseudo-periodic spikes on EEG. The demise occurred after 8 years of progressive cognitive deterioration; the pathological examination showed "Pick-like" atrophy, neurofibrillary tangles, senile plaques, congophilic angiopathy and cerebellar amyloid plaques. The genetical research could not support the hypothesis of a mutation of Presenilin 1 and 2 genes.

Epilepsy in glioblastoma multiforme: correlation with glutamine synthetase levels.

Purpose: The hypothesis addressed by this study is that a glutamine synthetase (GS) deficiency in neoplastic astrocytes is a possible molecular basis associated with seizure generation in glioblastoma multiforme (GBM).

Methods: Quantitative Western blot analysis of GS was performed in 20 individuals operated for malignant glioma.

Results: The levels of GS in patients with GBM and epilepsy were significantly lower (range 0.

Ataxia and migraine-like headache in a girl with a cerebellar developmental venous anomaly.

Cerebral developmental venous anomalies (DVAs) are generally considered as anatomical variants of the venous system without clinical importance. We report the case of a 15-year-old girl with recurrent episodes of migraine-like headache who presented with subacute vertigo and ataxia associated with intense occipital pain. Magnetic resonance imaging (MRI) showed a DVA with signal modifications of the surrounding brain parenchyma in the left cerebellar hemisphere.

Correlation between clinical/neurophysiological findings and quality of life in Charcot-Marie-Tooth type 1A.

Quality of life (QoL), as defined by the Short Form 36, has previously been shown to be abnormal in patients with Charcot-Marie-Tooth disease (CMT), both for Physical Composite Scores (PCS) and Mental Composite Scores (MCS). We have now extended these observations in a multicenter evaluation of 89 patients with Charcot-Marie-Tooth disease type 1A, the most common form of CMT. Both the PCS and MCS were abnormal also in this cohort, compared with the Italian population at large.

Novel mitochondrial tRNA Leu(CUN) transition and D4Z4 partial deletion in a patient with a facioscapulohumeral phenotype.

Point mutations in mtDNA-encoded tRNA genes frequently cause isolated myopathies but rarely cause the facioscapulohumeral phenotype. We report on a patient affected with chronic progressive weakness of facioscapulohumeral/peroneal muscles whose muscle biopsy showed a mitochondrial myopathy. mtDNA direct sequencing and RFLP analysis revealed a heteroplasmic transition T12313C which disrupts a conserved site in the T Psi C stem of the tRNA(Leu(CUN)) gene and fulfills the accepted criteria of pathogenicity.

A novel mutation of aprataxin associated with ataxia ocular apraxia type 1: phenotypical and genotypical characterization.

Ataxia oculomotor apraxia type 1 (AOA1) is the most common form of autosomal recessive ataxia in Japan, and the second in Portugal after Friedreich ataxia. AOA1 is typically characterized by early-onset cerebellar ataxia, oculomotor apraxia, hypoalbuminemia, hypercholesterolemia and late axonal sensori-motor neuropathy. AOA1 is associated with the aprataxin gene (APTX) encoding a protein involved in DNA repair.

Neuropathology of mitochondrial diseases.

The term "mitochondrial diseases" (MD) refers to a group of disorders related to respiratory chain dysfunction. Clinical features are usually extremely heterogeneous because MD may involve several tissues with different degrees of severity. Muscle and brain are mostly affected, probably because of their high dependence on oxidative metabolism.

Limb ataxia and proximal intracranial territory brain infarcts: clinical and topographical correlations.

Background: Limb ataxia is classically attributed to cerebellar hemispheric lesions, although isolated lesions of the inferior cerebellar peduncle (ICP) in the medulla may also cause this sign. It is still unclear why only some patients with acute cerebellar infarcts in the posterior inferior cerebellar artery (PICA) territory present with limb ataxia. The proximal intracranial posterior circulation (P-PC) territory includes structures fed by the intracranial vertebral arteries (ICVAs): the medulla, supplied by small ICVAs branches, and posterior inferior portion of the cerebellum, fed by PICA.

Charcot-Marie-Tooth disease type 2E, a disorder of the cytoskeleton.

The neurofilament light chain (NF-L) is a major constituent of intermediate filaments and plays a pivotal function in the assembly and maintenance of axonal cytoskeleton. Mutations in the NF-L gene (NEFL) cause autosomal dominant neuropathies that are classified either as axonal Charcot-Marie-Tooth (CMT) type 2E (CMT2E) or demyelinating CMT type 1F (CMT1F). The pathophysiological bases of the disorder(s) are elusive.

Endothelial adhesion molecule expression is unaltered in the peripheral nerve from patients with AIDS and distal sensory polyneuropathy.

Some evidence suggests that endothelial dysfunction, including altered expression of cell adhesion molecules contributes to pathophysiology of nervous system disorders in the course of HIV infection. In this immunohistochemical study we investigated and compared the expression of E-selectin, intercellular adhesion molecule-1 (ICAM-1), platelet endothelial cell adhesion molecule-1 (PECAM-1) in peripheral nerve blood vessels from patients with distal sensory polyneuropathy (DSP) and control patients with other axonal neuropathies. Similar quantitative pattern of immunoreactivity was found in patients with DSP and controls.

Gene dosage sensitivity of a novel mutation in the intracellular domain of P0 associated with Charcot-Marie-Tooth disease type 1B.

Autosomal dominant Charcot-Marie-Tooth disease type 1B (CMT1B) is caused by heterozygous mutations in the extracellular domain of P0. Here, we investigated clinically, electrophysiologically and pathologically a pedigree with a novel mutation in the intracellular domain of P0 (P0ic). The mutational analysis included denaturing high performance liquid chromatography (DHPLC) and nucleotide sequencing.

Human immunodeficiency virus-associated peripheral neuropathies.

Peripheral neuropathy has emerged as the most common neurologic complication of human immunodeficiency virus (HIV) infection. It will continue to play an Important role in HIV Infection given the fact that HIV-infected Individuals are living longer, are at risk of long-term metabolic complications, and face an Increasing exposure to potentially neurotoxic antiretroviral drugs. We review the various types of peripheral neuropathy that have been associated with HIV infection, including distal symmetrical polyneuropathy, toxic neuropathy from antiretroviral drugs, diffuse infiltrative lymphocytosis syndrome, inflammatory demyelinating polyneuropathies, multifocal mononeuropathies, and progressive polyradiculopathy.

Overexpression of ErbB2 and ErbB3 receptors in Schwann cells of patients with Charcot-Marie-tooth disease type 1A.

Axon-derived neuregulins (NRGs) are a family of growth factors whose binding to ErbB tyrosine kinase receptors promotes the maturation, proliferation and survival of Schwann cells (SCs). Correct NRG/ErbB signaling is essential for the homeostasis of axonal-glial complexes and seems to play a role in peripheral nerve repair. The potential involvement of ErbB receptors in human peripheral neuropathies has not been clarified.

An unusual transthyretin gene missense mutation (TTR Phe33Val) linked to familial amyloidotic polyneuropathy.

Familial amyloidotic polyneuropathy is a rare autosomal dominant disease, with clinical symptoms beginning in most kindreds within the third to seventh decades of life. The primary defect results from one of a number of mutations in the transthyretin (TTR) gene. Over 80 mutations in the TTR gene have been described.

Identification of distinct N-terminal truncated forms of prion protein in different Creutzfeldt-Jakob disease subtypes.

In prion diseases, the cellular prion protein (PrP(C)) is converted to an insoluble and protease-resistant abnormal isoform termed PrP(Sc). In different prion strains, PrP(Sc) shows distinct sites of endogenous or exogenous proteolysis generating a core fragment named PrP27-30. Sporadic Creutzfeldt-Jakob disease (sCJD), the most frequent human prion disease, clinically presents with a variety of neurological signs.

Hepato-cerebral syndrome: genetic and pathological studies in an infant with a dGK mutation.

Focal spongy degeneration of the white matter and Purkinje cell loss were the neuropathological hallmarks in an infant with hepato-cerebral syndrome and a 4-bp GATT duplication (nucleotides 763-766) in exon 6 of the dGK gene. Liver disease became manifest in the first months of life and was followed by progressive cirrhosis and death at 31 months. Neurological symptoms appeared later and were mild, in agreement with the limited brain pathology.

Mutations in a gene encoding a novel SH3/TPR domain protein cause autosomal recessive Charcot-Marie-Tooth type 4C neuropathy.

Charcot-Marie-Tooth disease type 4C (CMT4C) is a childhood-onset demyelinating form of hereditary motor and sensory neuropathy associated with an early-onset scoliosis and a distinct Schwann cell pathology. CMT4C is inherited as an autosomal recessive trait and has been mapped to a 13-cM linkage interval on chromosome 5q23-q33. By homozygosity mapping and allele-sharing analysis, we refined the CMT4C locus to a suggestive critical region of 1.

Central-peripheral sensory axonopathy in a juvenile case of Alpers-Huttenlocher disease.

Peripheral ataxia is reported in a juvenile case of Alpers-Huttenlocher disease (AHD). Neurophysiological and neuropathological investigations revealed a central-peripheral axonopathy, affecting the deep sensation carried by the peripheral nerve fibres and the posterior tracts of the cord, due to neuronal loss of the sensory ganglia. Involvement of the sensory pathways is regarded as a major feature of juvenile AHD.