A translocation causing increased alpha-klotho level results in hypophosphatemic rickets and hyperparathyroidism.

Phosphate homeostasis is central to diverse physiologic processes including energy homeostasis, formation of lipid bilayers, and bone formation. Reduced phosphate levels due to excessive renal loss cause hypophosphatemic rickets, a disease characterized by prominent bone defects; conversely, hyperphosphatemia, a major complication of renal failure, is accompanied by parathyroid hyperplasia, hyperparathyroidism, and osteodystrophy. Here, we define a syndrome featuring both hypophosphatemic rickets and hyperparathyroidism due to parathyroid hyperplasia as well as other skeletal abnormalities. We show that this disease is due to a de novo translocation with a breakpoint adjacent to alpha-Klotho, which encodes a beta-glucuronidase, and is implicated in aging and regulation of FGF signaling. Plasma alpha-Klotho levels and beta-glucuronidase activity are markedly increased in the affected patient; unexpectedly, the circulating FGF23 level is also markedly elevated. These findings suggest that the elevated alpha-Klotho level mimics aspects of the normal response to hyperphosphatemia and implicate alpha-Klotho in the selective regulation of phosphate levels and in the regulation of parathyroid mass and function; they also have implications for the pathogenesis and treatment of renal osteodystrophy in patients with kidney failure.

Superficial endometrial spread of squamous cell cervical carcinoma: a diagnostic challenge at magnetic resonance imaging.

The magnetic resonance imaging findings in a case of superficial endometrial spread of squamous cervical carcinoma are presented. Early enhancement of a relatively small cervical mass was associated with a fluid-distended endometrial cavity. An irregular layer of early-enhancing tumor was seen lining the endometrial cavity. Histopathologic examination confirmed the presence of an invasive squamous cell carcinoma of the cervix that superficially spread into the lower uterine segment and endometrial cavity, replacing most of the endometrial lining as a layer of tumor. The tumor also deeply invaded the myometrium in a permeative fashion throughout the bulk of the uterine body. Failure to appreciate the cervical abnormality might have resulted in an imaging diagnosis of endometrial carcinoma. We report this challenging case to broaden the described spectrum of magnetic resonance imaging findings in cervical carcinoma, because recognition of this unusual pattern of tumor spread may facilitate correct radiological interpretation.

Systematic comparison of perfusion-CT and CT-angiography in acute stroke patients.

OBJECTIVE: To systematically evaluate the accuracy of noncontrast computed tomography (NCT), perfusion computed tomography (PCT), and computed tomographic angiography (CTA) in determining site of occlusion, infarct core, salvageable brain tissue, and collateral flow in a large series of patients suspected of acute stroke. METHODS: We retrospectively identified all consecutive patients with signs and symptoms suggesting hemispheric stroke of < 48 hours in duration who were evaluated on admission by NCT, PCT, and CTA, and underwent a follow-up CT/CTA or magnetic resonance imaging (MRI) and magnetic resonance angiography (MRA) within 6 months of initial imaging. Two neuroradiologists evaluated NCT for hypodensity, PCT for infarct core and salvageable brain tissue, and CTA source images and maximal intensity projections for site of occlusion, infarct core, and collateral flow. Follow-up CTA and MRA were assessed for persistent arterial occlusion or recanalization. Follow-up CT and MRI were reviewed for final infarct location and volume, and used as a gold standard to calculate sensitivity (SE) and specificity (SP) of initial imaging. RESULTS: A total of 113 patients were considered for analysis, including 55 patients with a final diagnosis of stroke. CTA source images were the most accurate technique in the detection of the site of occlusion (SE = 95%; SP = 100%). Decreased cerebral blood volume on PCT was the most accurate predictor of final infarct volume (SE = 80%; SP = 97%), Increased mean transit time on PCT was predictive of the tissue at risk for infarction in patients with persistent arterial occlusion. CTA maximal intensity projections was the best technique to quantify the degree of collateral circulation. INTERPRETATION: The most accurate assessment of the site of occlusion, infarct core, salvageable brain tissue, and collateral circulation in patients suspected of acute stroke is afforded by a combination of PCT and CTA.

Selection of acute ischemic stroke patients for intra-arterial thrombolysis with pro-urokinase by using ASPECTS.

BACKGROUND: Previous studies have suggested that baseline computed tomographic (CT) scans might be a useful tool for selecting particular ischemic stroke patients who would benefit from thrombolysis. The aim of the present study was to assess whether the baseline CT scan, assessed with the Alberta Stroke Program Early CT Score (ASPECTS), could identify ischemic stroke patients who might particularly benefit from intra-arterial thrombolysis of middle cerebral artery occlusion. METHODS: Baseline and 24-hour follow-up CT scans of patients randomized within 6 hours of symptoms to intra-arterial thrombolysis with recombinant pro-urokinase or control in the PROACT-II study were retrospectively scored by using ASPECTS. Patients were stratified into those with ASPECTS >7 or < or =7. Independent functional outcome at 90 days was compared between the 2 strata according to treatment assignment. RESULTS: The analysis included 154 patients with angiographically confirmed middle cerebral artery occlusion. The unadjusted risk ratio of an independent functional outcome, in favor of treatment, in the ASPECTS >7 group was 5.0 (95% confidence interval [CI], 1.3 to 19.2) compared with 1.0 (95% CI, 0.6 to 1.9) in the ASPECTS < or =7 group. After adjustment for baseline characteristics, the risk ratio in the ASPECTS score >7 was 3.2 (95% CI, 1.2 to 9.1). Similar favorable treatment effects were observed when secondary outcomes were used, but these did not reach statistical significance. CONCLUSIONS: Ischemic stroke patients with a baseline ASPECTS >7 were 3 times more likely to have an independent functional outcome with thrombolytic treatment compared with control. Patients with a baseline ASPECTS < or =7 were less likely to benefit from treatment. This observation suggests that ASPECTS can be both a useful clinical tool and an important method of baseline risk stratification in future clinical trials of acute stroke therapy.