The ice pack test in the differential diagnosis of myasthenic diplopia.

PURPOSE: To investigate the diagnostic value and to establish threshold criteria for the ice pack test as an office preliminary test in the differential diagnosis of myasthenic diplopia in comparison with blepharoptosis. DESIGN: Prospective, comparative cohort study. PARTICIPANTS: Eighty-nine patients with a recent onset of diplopia, blepharoptosis, or both were evaluated with orbital cooling in a prospective manner. Forty-eight patients presented with diplopia, 25 patients with both blepharoptosis and ophthalmoplegia and 16 patients with blepharoptosis. TESTING: All patients had the ice pack applied for 5 minutes on both eyelids at the initial orthoptic evaluation. Increasing the duration of cooling to 10 minutes was investigated in 36 diplopic patients. A complete diagnostic work-up was ordered and patients were followed up for a minimum of 6 months before diagnosis of myasthenia gravis was ascertained. MAIN OUTCOME MEASURES: Difference in cover test measurements in primary position or marginal reflex distance before and after the application of the ice pack, specific cause for diplopia and blepharoptosis. RESULTS: Fifteen patients were diagnosed as myasthenic. The optimal cutoff point for a positive response to the ice pack test proved to be a reduction in ocular deviation in primary position by 50% or by 10 prism diopters (PD) or more for presenting deviations larger than 20 PD. By this criterion, sensitivity for the detection of myasthenic diplopia was 76.9% (95% confidence interval [CI], 49.06%-92.50%) for the 5-minute application, compared with 92.3% (95% CI, 63.5%-98.9%) sensitivity demonstrated for blepharoptosis. Increasing the time of application to 10 minutes did not improve the diagnostic value of the test. Specificity was high (98.3%; 95% CI, 90.3%-99.9%) and was demonstrated even in patients with coexisting myasthenic and dysthyroid ophthalmopathy. Patients with oculomotor nerve paresis and Horner syndrome invariably were nonresponsive to the test. CONCLUSIONS: The ice pack test demonstrated high specificity and an acceptable sensitivity in the differential diagnosis of myasthenic diplopia. Data from this series suggest that a partial rather than a complete response to the ice pack test may be expected for myasthenic diplopia. Standardization of the method of application of the ice pack is critical for the interpretation of its effect.

Diagnostic and Management Challenges in Vasoactive Intestinal Peptide Secreting Tumors: A Series of 15 Patients.

OBJECTIVES: Vasoactive intestinal peptide-secreting tumors (VIPomas) are rare functioning neuroendocrine tumors often characterized by a difficult-to-control secretory syndrome and high potential to develop metastases. We hereby present the characteristics of 15 cases of VIPomas and provide a recent literature review. METHODS: This was a retrospective data analysis of 15 patients with VIPoma from 3 different centers and literature research through PubMed database during the last 10 years. RESULTS: Fifteen patients with VIPomas (9 with hepatic metastases at diagnosis) with watery diarrhea and raised VIP levels were studied. Ten patients (67%) had grade 2 tumors, 6 of 15 had localized disease and underwent potentially curative surgery, whereas the remaining 9 received multiple systemic therapies; 3 patients died during follow-up. The median overall survival was 71 months (range, 41-154 months). Patients who were treated with curative surgery (n = 7) had longer median overall survival compared with patients who were treated with other therapeutic modalities (44 vs 33 months). CONCLUSIONS: The management of VIPomas is challenging requiring the application of multiple treatment modalities. Patients who underwent surgical treatment with curative intent appear to have higher survival rate. Central registration and larger prospective studies are required to evaluate the effect of currently employed therapies in these patients.

Increased serum type I interferon activity in organ-specific autoimmune disorders: clinical, imaging, and serological associations.

BACKGROUND: Activation of the type I interferon (IFN) pathway has been implicated in the pathogenesis of systemic autoimmune disorders but its role in the pathogenesis of organ-specific autoimmunity is limited. We tested the hypothesis that endogenous expression of type I IFN functional activity contributes to the pathogenesis of autoimmune thyroid disease (ATD) and type I diabetes (T1DM). METHODS: We studied 39 patients with ATD and 39 age and sex matched controls along with 88 T1DM patients and 46 healthy matched controls respectively. Available clinical and serological parameters were recorded by chart review, and thyroid ultrasound was performed in 17 ATD patients. Type I IFN serum activity was determined in all subjects using a reporter cell assay. The rs1990760 SNP of the interferon-induced helicase 1 gene was genotyped in ATD patients. RESULTS: Serum type I IFN activity was increased in patients with ATD and T1DM compared to controls (p-values: 0.002 and 0.04, respectively). ATD patients with high type I IFN serum activity had increased prevalence of antibodies against thyroglobulin (anti-Tg) and cardiopulmonary manifestations compared to those with low IFN activity. Additionally, the presence of micronodules on thyroid ultrasound was associated with higher type I IFN levels. In patients with T1DM, high IFN levels were associated with increased apolipoprotein-B levels. CONCLUSION: Serum type I IFN activity is increased in ATD and T1DM and is associated with specific clinical, serological, and imaging features. These findings may implicate type I IFN pathway in the pathogenesis of specific features of organ-specific autoimmunity.