Search

Burning mouth syndrome is a common disorder that frequently affects women in the 5th-7th decade. It is characterized by persisting painful symptoms mainly involving the anterior two-thirds of the tongue. For several years it has been attributed to psychological causes. We investigated the innervation of the epithelium of the tongue to assess whether damage of peripheral nerve fibers underlies the pathogenesis of the disease. We examined 12 patients with clinically definite burning mouth syndrome for at least 6 months. We obtained superficial biopsies of the lateral aspect of the anterior two-thirds of the tongue from all patients and nine healthy controls. Immunohistochemical and confocal microscope co-localization studies were performed with cytoplasmatic, cytoskeletric, Schwann cell, and myelin markers for pathological changes. The density of epithelial nerve fibers was quantified. Patients showed a significantly lower density of epithelial nerve fibers than controls, with a trend toward correlation with the duration of symptoms. Epithelial and sub-papillary nerve fibers showed diffuse morphological changes reflecting axonal degeneration. Our study demonstrates that burning mouth syndrome is caused by a trigeminal small-fiber sensory neuropathy and that superficial biopsy of the tongue can be helpful in assessing the diagnosis. These findings shed light into the pathogenesis of this common disorder and could contribute to evaluate targeted therapies in patients.

The cytoplasmic protein gene product 9.5 (PGP 9.5) is considered a reliable marker for intraepidermal nerve fibers (IENFs). However, PGP 9.5 expression has never been compared with antibodies against the main components of the cytoskeleton. We compared the density of PGP 9.5-positive IENF at the leg with that obtained using a panel of antibodies specific for certain cytoskeletal components, namely, anti-unique beta-tubulin (TuJ1), anti-nonphosphorylated microtubule-associated protein-1B (MAP1B), anti-70 and 200 KDa neurofilament (NF), and antiphosphorylated neurofilament (SMI 312), in 15 healthy subjects and in 10 patients with painful neuropathy. We also performed colocalization studies and investigated the relationship between IENFs and Schwann cells. In both controls and neuropathies, the density of IENF labeled by PGP 9.5, TuJ1, and MAP1B did not differ, whereas that of NF and SMI 312 was significantly lower. Double-staining studies confirmed that antibodies against cytoskeletal markers can be used to reliably stain skin nerve fibers, suggesting that they might provide insight into specific axonal impairment in peripheral neuropathies., (Copyright 2004 Wiley Periodicals, Inc.)

Objective: To investigate some aspects of T-cell-dependent immune function in patients with dementia of the Alzheimer type (DAT)., Design: Assay of interleukin 6 binding on T lymphocytes from patients with DAT, compared with that in healthy controls., Setting: The study included ambulatory patients in a tertiary care center who were diagnosed as having DAT according to the criteria of the National Institute of Neurologic and Communicative Disorders and Stroke., Subjects: Thirty-five patients with DAT without depression (15 women and 20 men; mean +/- SD age, 68.6 +/- 15.8 years) were selected consecutively. They had not taken any medication for at least 3 weeks and did not smoke. Illness severity was evaluated according to the Clinical Dementia Rating Scale. Thirty-five age- and sex-matched healthy nonsmoking subjects with no family history of neuropsychiatric disorders formed the control group., Results: A significant (P < .001) increase in T-lymphocyte interleukin 6 binding was found in patients with DAT compared with healthy controls (mean +/- SE receptors per cell, 305 +/- 7 vs 276 +/- 6, respectively), whereas the ligand-receptor affinity values were similar in the 2 groups (mean +/- SE, 25.9 +/- 0.9 and 25.3 +/- 0.6 nmol/L)., Conclusion: These data indicate a derangement of the immune response in patients with DAT since cell-surface interleukin 6 receptors seem to be related to T-lymphocyte immune function.

Dementia of Alzheimer type (DAT) is a neurodegenerative disease of the central nervous system (CNS), in which an unbalanced cytokine network may lead to an altered immunoregulation. Tumour necrosis factor (TNF)-alpha is a cytokine with manifold effects on the neuroimmune system. Specific TNF-alpha receptors have been found on human peripheral blood lymphocytes. The aim of the present study has been to assay TNF-alpha binding on T cells from DAT patients and healthy sex- and age-matched controls. We found that T lymphocytes from demented patients bear significantly more p60 and p80 TNF-alpha receptors than those from controls (Bmax: 705, 29 vs 131, 6 (mean, SEM) receptors/cell). Such TNF-alpha binding sites, of the same type in DAT patients and healthy subjects (Kd: 67.6, 5.0 vs 70.7, 5.6 (mean, SEM) pM), are functional, since they are able to mediate in vitro NF-kappa B activation. These results are discussed in terms of DAT pathogenesis. Since it has been reported that activated T cells have more TNF-alpha receptors than resting cells, an increased number of lymphocyte TNF-alpha receptors might indicate a systemic immune activation in DAT patients as compared with healthy controls.