Polyneuropathy associated with IgA monoclonal gammopathy of undetermined significance

Although polyneuropathies associated with IgM and IgG monoclonal gammopathies have been well described, polyneuropathy with IgA monoclonal gammopathy of undetermined significance (MGUS) is less commonly seen and has not been well studies. We reviewed the clinical and electrodiagnostic features of 5 such patients, and the sural nerve biopsy findings in 4 of them. One patient was diabetic, while 4 were free of other diagnoses commonly associated with neuropathy. Clinical presentations were varied. Electrodiagnostic and histological studies ranged from primary demyelination to primary axon loss to a mixed axonal/demyelinating picture. Three patients who were treated appeared to respond to prednisone or intravenous gamma globulin, despite clear clinical, electrodiagnostic, and histological differences. We conclude that the polyneuropathy associated with IgA MGUS is heterogeneous, similar to that in IgM and IgG MGUS. A trial of immunomodulating therapy appears to be warranted in such patients if the neuropathy is sufficiently servere. © 1993 John Wiley & Sons, Inc.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/50156/1/880160113_ftp.pd

Brief Communication

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/67313/2/10.1177_088307389801300308.pd

8‐Year‐Old Boy with Progressive Headache

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/99694/1/bpa12074.pd

Low diagnostic yield of sural nerve biopsy in patients with peripheral neuropathy and primary amyloidosis

Patients with primary amyloidosis may develop peripheral neuropathy as an early feature. Sural nerve biopsy is reported to be a sensitive method for diagnosing amyloidosis in such patients. We identified nine patients, ultimately diagnosed as having amyloidosis, who were referred for peripheral neuropathy of undetermined etiology. In six, a sural nerve biopsy demonstrated no amyloid. Subsequent examination of other tissue or of the contralateral sural nerve eventually resulted in the correct diagnosis. We conclude that sural nerve biopsy may be less sensitive than previously believed for the diagnosis of amyloidosis in patients with peripheral neuropathy secondary to amyloid. When the clinical suspicion of amyloidosis is high, a nondiagnostic sural nerve biopsy should not discourage the performance of further investigative studies.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/30401/1/0000021.pd

Magnetic Resonance Imaging of Ethyl-nitrosourea-induced Rat Gliomas: A Model for Experimental Therapeutics of Low-grade Gliomas

Human low-grade gliomas represent a population of brain tumors that remain a therapeutic challenge. Preclinical evaluation of agents, to test their preventive or therapeutic efficacy in these tumors, requires the use of animal nobreak models. Spontaneous gliomas develop in models of chemically induced carcinogenesis, such as in the transplacental N-ethyl-N-nitrosourea (ENU) rat model. However, without the ability to detect initial tumor formation, multiplicity or to measure growth rates, it is difficult to test compounds for their interventional or preventional capabilities. In this study Fisher-334 rats, treated transplacentally with ENU, underwent magnetic resonance imaging (MRI) examination in order to evaluate this approach for detection of tumor formation and growth. ENU-induced intracranial cerebral tumors were first observable in T2-weighted images beginning at 4 months of age and grew with a mean doubling time of 0.487 ± 0.112 months. These tumors were found histologically to be predominately mixed gliomas. Two therapeutic interventions were evaluated using MRI, vitamin A (all-trans retinol palmitate, RP), as a chemopreventative agent and the anti-angiogenic drug SU-5416. RP was found to significantly delay the time to first tumor observation by one month ( P = 0.05). No differences in rates of tumor formation or growth rates were observed between control and RP-treated groups. MRI studies of rats treated with SU-5416 resulted in reduction in tumor growth rates compared to matched controls. These results show that MRI can be used to provide novel information relating to the therapeutic efficacy of agents against the ENU-induced tumor model.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/45391/1/11060_2004_Article_352248.pd

Effect of dietary vitamin A or N-acetylcysteine on ethylnitrosourea-induced rat gliomas

It is our hypothesis that low grade gliomas are the glial counterparts of other precancerous lesions such as colon polyps and, therefore, suitable targets for chemoprevention. Steps in the molecular progression of gliomas have been described, indicating that an accumulation of abnormalities is required for progression to a high grade and interruption of this progression might be possible. An animal model of chemical glial carcinogenesis was used to test this hypothesis. Pregnant rats were injected intravenously with ENU (ethylnitrosourea) on the 18th day of gestation to induce gliomas in the offspring, which were randomized to receive control diet, diet supplemented with vitamin A palmitate, or diet supplemented with N-acetylcysteine. Animals exposed to ENU and receiving a control diet developed brain tumors and had a shortened life expectancy compared with rats unexposed to ENU. The animals treated with NAC showed no statistically significant delay in the time to tumor and no change in the histologic grade of the tumors when compared with animals receiving control diet, but the time to death from any cause of NAC treated animals differed significantly from untreated animals. Animals receiving high dose VA had statistically significantly prolonged time to tumor, survived significantly longer than untreated animals, but had no reduction in the total number of tumors or change in the histologic grade of their tumors. The theoretical basis of these results is likely due to the putative mechanism of action of these agents. These data indicate that glioma chemoprevention is possible and deserves further exploration.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/45387/1/11060_2004_Article_185580.pd

Electrodiagnostic evolution of carcinomatous sensory neuronopathy

Sensory neuronopathy is a well-recognized remote effect of carcinoma. We report the clinical and electrodiagnostic evolution of a sensory neuronopathy in a patient with carcinoma of the lung. Serial electrophysiologic studies suggest transformation from normal peripheral nerve function through early posterior root involvement to absent sensory nerve function. Diffuse motor conduction abnormalities occurred late in the disease, perhaps reflecting motor axon changes associated with disuse.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/50144/1/880120612_ftp.pd

Molecular Lysis of Synovial Lining Cells by In Vivo Herpes Simplex Virus-Thymidine Kinase Gene Transfer

Overview summary Previous studies have shown that synovial lining cells are susceptible to in vivo transfection using purified expression plasmid DNA. Roessler et al. now report on the use of a plasmid that mediates transient overexpression of herpes simplex virus thymidine kinase to transfect synovial lining cells in an animal model of proliferative inflammatory arthritis. After in vivo intraarticular transfection using the pNGVL-TK expression plasmid, the animals were treated with intravenous ganciclovir for a period of 3 days. They report that examination of the synovial tissues 21 days after completion of the gene therapy showed evidence of cytolysis that was confined to the synovial lining cells within inflamed synovium. No evidence of cytolysis or necrosis was observed in articular cartilage present within the treated joints. Similar methods to achieve a molecular lysis of the synovial lining layer may have applicability to the treatment of human inflammatory arthritis.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/63330/1/hum.1998.9.18-2735.pd

The gene for the axonal cell adhesion molecule TAX-1 is amplified and aberrantly expressed in malignant gliomas

The human TAX-1 gene encodes a M r 135,000 glycoprotein that is transiently expressed on the surface of a subset of neurons during development and is involved in neurite outgrowth. The TAX-1 gene has been mapped to a region on chromosome 1 that has been implicated in microcephaly and the Van der Woude syndrome. Using restriction landmark genome scanning to search for amplified genes in gliomas, we found TAX-1 to be amplified in 2 high-grade gliomas among a group of 26 gliomas investigated. Real-time reverse transcription-quantitative PCR analysis detected high levels of TAX-1 mRNA in glial tumors, even in the absence of TAX-1 gene amplification. Immunohistochemical analysis revealed abundant levels of TAX-1 in neoplastic glial cells of glioblastoma multiforme tumors. Because glial tumors are highly invasive and in view of the role of TAX-1 in neurite outgrowth, we investigated the potential role of TAX-1 in glioma cell migration. Using an in vitro assay, we found that the migration of glioma tumor cells is profoundly reduced in the presence of either an anti-TAX-1 antibody or a TAX-1 antisense oligonucleotide. Our findings suggest that TAX-1 plays a role in glial tumorigenesis and may provide a potential target for therapeutic intervention