Superficial siderosis of central nervous system mimicking multiple sclerosis.

INTRODUCTION: Superficial siderosis of the central nervous system is a neurologic disorder mainly characterized by cerebellar involvement, myelopathy, neurosensory hearing loss, and possibly progressive cognitive impairment. Root avulsion due to traumatic plexus injury has been recognized as an extremely rare cause of hemosiderin deposition on leptomeninges and subpial layers of brain and spinal cord parenchyma. CASE REPORT: A 49-year-old man presented with progressively evolving ataxia and spastic paraparesis. CSF oligoclonal bands were indicative of an underlying inflammatory process and raised the possibility of a demyelinating disorder. However, spinal cord and brain MRI revealed hemosiderin deposition along the entire neuraxis. A rigorous electrophysiologic study confirmed a functional impairment in many different levels of the nervous system. CONCLUSION: The demonstration of CSF oligoclonal bands in the reported patient implies that inflammation might be involved in the pathogenesis of superficial siderosis. The diagnosis of this newly recognizable entity needs a high clinical suspicion, but further research is needed to fully elucidate the involved mechanisms.

Campylobacter jejuni O:19 serotype-associated Guillain-Barré syndrome in a child: the first case reported from Greece.

We present a case of Guillain-Barré syndrome (GBS) following Campylobacter jejuni HS serotype O:19 infection in a child. Antibodies against C. jejuni and autoantibodies to the peripheral nerve gangliosides GM1 were positive, a pattern correlating well with the existence of an inflammatory neuropathy like GBS. The patient shared the HLA-B35 and HLA-DR8 antigens, which have been found to be increased in GBS patients with previous C. jejuni infection. As this is the first diagnosed C. jejuni-associated GBS case reported from Greece, further clinical and epidemiologic investigations are warranted.

Highly increased CSF tau protein and decreased beta-amyloid (1-42) in sporadic CJD: a discrimination from Alzheimer's disease?

The aim was to quantify tau protein and beta-amyloid (Abeta42) in the CSF of patients with sporadic Creutzfeldt-Jakob disease (CJD), Alzheimer's disease (AD), and controls. Double sandwich enzyme linked immunosorbent assays (ELISAs) were used for measurements. Tau was increased 58-fold in CJD and 3.5-fold in AD compared with controls, whereas Abeta42 was decreased 0.5-fold in both CJD and AD. A cut off level for tau protein at 2131 pg/ml successfully discriminated CJD from AD (100% specificity and 93% sensitivity). Tau protein concentration in CSF is probably an additional useful marker in differentiating CJD from AD.

Increased cerebrospinal fluid tau protein in multiple sclerosis.

Axonal damage is now being recognized as a common finding in multiple sclerosis (MS) lesions and a cause of irreversible neurological damage. Attempts to identify markers of early axonal damage are of great significance. This prompted us to examine the microtubule-associated protein tau in the cerebrospinal fluid (CSF) of patients with MS vs. controls. Tau was measured by double antibody sandwich ELISA. Increased CSF tau levels were found in MS as compared to controls (medians 249.6 and 135 pg/ml respectively, p<0.001). Half of the MS patients presented with levels above the upper limit of the controls. A significant increase vs. controls was found in both relapsing-remitting and progressive subtypes. These data may indicate axonal impairment in a subpopulation of MS patients and may provide a tool for the estimation of axonal damage during life.

Antibodies to the human 60 kDa heat-shock protein in patients with schizophrenia.

Immune mechanisms are thought to be important in a subpopulation of patients with schizophrenia. We examined the specificity of neural antibodies in patients with schizophrenia to identify a possible antigen. Serum antibodies from patients with schizophrenia and control subjects were tested for binding to protein extracts of human neuroblastoma cells by western blot. Protein antigens were characterised by aminoterminal and internal aminoacid sequence analysis. 14 of 32 (44%) otherwise healthy patients with schizophrenia had antibodies to a neuroblastoma protein of molecular weight 60 kDa. By partial sequence analysis, this protein was identified as the 60 kDa human heat-shock protein (hsp) that is the P1 mitochondrial protein, and which is 50% homologous to the mycobacterial 65 kDa hsp. Antigens that crossreact with hsp65 have been implicated in the pathogenesis of adjuvant-induced arthritis in rats and autoimmune diabetes in mice. Of 100 normal subjects or disease controls, antibodies to hsp60 were found in only 8 patients, all of whom had active infectious or inflammatory disease. Our results support the presence of abnormal immune reactivity involving hsp60 in a subset of patients with schizophrenia. The immune response may be related to the pathogenesis of the disease.

Human monoclonal antineurofilament antibody cross-reacts with a neuronal surface protein.

Increased titres of anti-neurofilament antibodies have been reported in neurodegenerative disorders, and it has been suggested that such antibodies might be pathogenic. We investigated the specificity of an IgA monoclonal antibody (MAb) from a patient with amyotrophic lateral sclerosis which reacted with neurofilaments and bound to the surface of neuroblastoma cells. In Western blots, the immunoaffinity-purified IgA bound to the 220-kD, high-molecular-weight neurofilament protein (NFH) and cross-reacted with several closely migrating protein bands with apparent mobility of 62-68 kD in neuroblastoma cells and extracts of normal human spinal cord. Following crosslinking to the surface of radiolabeled neuroblastoma cells, the IgA MAb immunoprecipitated a 65-kD protein, indicating that the protein was present on the cell surface and available to the antibodies for binding. Several other MAbs to NFH did not immunostain the surface of neuroblastoma cells or bind to the 65-kD protein, indicating that the protein was not a fragment of NFH. Thus, antibody binding to the 65-kD protein, possibly by cross-reacting with NFH, may have contributed to the neuronal degeneration.

The spectrum of neurologic disease associated with anti-GM1 antibodies.

We compared anti-GM1 IgM antibody titers in patients with various neurologic diseases and in normal subjects. We found increased titers in patients with lower motor neuron disease, sensorimotor neuropathy, or motor neuropathy with or without multifocal conduction block. In patients with other diseases, titers are similar to those in normal individuals, suggesting that anti-GM1 antibody levels are not increased nonspecifically after neural injury or inflammatory diseases. Anti-GM1 antibodies in many of the patients occur as monoclonal gammopathies, predominantly of lambda light-chain type, but the antibodies are sometimes polyclonal with normal or increased serum IgM concentrations. Most of the anti-GM1 antibodies appear to react with the Gal(beta 1-3)GalNAc epitope which is shared with asialo-GM1 and GD1b, but in some patients the antibodies are more specific for GM1 and associated with motor neuropathy. Patients with motor or sensorimotor peripheral neuropathy or lower motor neuron disease should be tested for anti-GM1 antibodies or anti-Gal(beta 1-3)GalNAc antibodies, as therapeutic reduction in antibody concentrations was reported to result in clinical improvement in some patients.