Neural network and logistic regression diagnostic prediction models for giant cell arteritis: development and validation.

PURPOSE: To develop and validate neural network (NN) vs logistic regression (LR) diagnostic prediction models in patients with suspected giant cell arteritis (GCA). Design: Multicenter retrospective chart review. METHODS: An audit of consecutive patients undergoing temporal artery biopsy (TABx) for suspected GCA was conducted at 14 international medical centers. The outcome variable was biopsy-proven GCA. The predictor variables were age, gender, headache, clinical temporal artery abnormality, jaw claudication, vision loss, diplopia, erythrocyte sedimentation rate, C-reactive protein, and platelet level. The data were divided into three groups to train, validate, and test the models. The NN model with the lowest false-negative rate was chosen. Internal and external validations were performed. RESULTS: Of 1,833 patients who underwent TABx, there was complete information on 1,201 patients, 300 (25%) of whom had a positive TABx. On multivariable LR age, platelets, jaw claudication, vision loss, log C-reactive protein, log erythrocyte sedimentation rate, headache, and clinical temporal artery abnormality were statistically significant predictors of a positive TABx (P≤0.05). The area under the receiver operating characteristic curve/Hosmer-Lemeshow P for LR was 0.867 (95% CI, 0.794, 0.917)/0.119 vs NN 0.860 (95% CI, 0.786, 0.911)/0.805, with no statistically significant difference of the area under the curves (P=0.316). The misclassification rate/false-negative rate of LR was 20.6%/47.5% vs 18.1%/30.5% for NN. Missing data analysis did not change the results. CONCLUSION: Statistical models can aid in the triage of patients with suspected GCA. Misclassification remains a concern, but cutoff values for 95% and 99% sensitivities are provided (https://goo.gl/THCnuU).

Multiple Cranial Nerve Palsies in Giant Cell Arteritis.

Giant cell arteritis (GCA) is a systemic vasculitis of medium and large arteries often with ophthalmic involvement, including ischemic optic neuropathy, retinal artery occlusion, and ocular motor cranial nerve palsies. This last complication occurs in 2%-15% of patients, but typically involves only 1 cranial nerve. We present 2 patients with biopsy-proven GCA associated with multiple cranial nerve palsies.

Traumatic disruption of the optic chiasm.

A 27-year-old man developed a persistent bitemporal hemianopia after severe head trauma sustained in a high-speed motor vehicle accident. The initial brain MRI revealed hemorrhagic contusion of the optic chiasm. A brain MRI performed 4 weeks later demonstrated complete chiasmal transection, a phenomenon rarely documented with imaging.

Unusually mild tuberous sclerosis phenotype is associated with TSC2 R905Q mutation.

OBJECTIVE: To report the clinical manifestations and functional aspects of Tuberous Sclerosis Complex (TSC), resulting from Codon 905 mutations in TSC2 gene. METHODS: We performed a detailed study of the TSC phenotype and genotype in a large French-Canadian kindred (Family A). Subsequently, clinical and molecular data on 18 additional TSC families with missense mutations at the same codon of TSC2 were collected. Functional studies were performed on the different missense changes and related to the phenotype. RESULTS: A 2714G>A (R905Q) mutation was identified in Family A. The TSC phenotype in this family was unusually mild and characterized by hypomelanotic macules or focal seizures that remitted spontaneously or were easily controlled with medication. Diagnostic criteria were met in only a minority of mutation carriers. Other families with the R905Q mutation were found to have a similar mild phenotype. In contrast, patients with a 2713C>T (R905W) or a 2713C>G (R905G) mutation had more severe phenotypes. Although all three amino acid substitutions were pathogenic, the R905W and R905G substitutions affected tuberin function more severely than R905Q. INTERPRETATION: Codon 905 missense mutations in TSC2 are relatively common. The TSC2 R905Q mutation is associated with unusually mild disease, consistent with functional studies. Combined with previous reports, it is apparent that certain TSC2 missense mutations are associated with a mild form of tuberous sclerosis, which in many patients does not meet standard diagnostic criteria. These findings have implications for the large number of patients with limited clinical features of TSC and for genetic counseling in these families.