Pazopanib-induced posterior reversible encephalopathy syndrome with possible syndrome of inappropriate secretion of antidiuretic hormone: an incidental or pathophysiological association?

Introduction:Pazopanib is an oral protein kinase inhibitor(PKI)that targets vascular endothelial growth factor(VEGF)receptors,fibroblastic growth factor receptors,platelet-derived growth factor receptors,and stem cell factor that inhibits VEGF-induced cellular proliferation.Pazopanib is approved for use in advanced renal cell carcinoma and subtypes of advanced soft-tissue sarcoma(Deguchi et al.,2018).Major adverse drug reactions of pazopanib include hypertension,high-grade hyponatremia and posterior reversible encephalopathy syndrome(PRES)(Berardi et al.,2016;Deguchi et al.,2018).In clinical trials,few investigations have been conducted to determine the aetiology of PKI-associated hyponatremia,the mechanism remains therefore unknown.Only rare cases of PKI-induced syndrome of inappropriate secretion of antidiuretic hormone(SIADH)(Largeau et al.,2019),and none with pazopanib,have been reported.PRES is a clinical and radiological entity where a bilateral white matter oedema,occurring predominantly in the posterior occipital and parietal lobes,is associated with several neurologic symptoms.Interestingly,a recent review suggests that SIADH could be a symptom of PRES(Largeau et al.,2019).To our knowledge,this is the first case published where pazopanib-induced PRES occurs contemporaneously with possible SIADH.

症状性脑内动脉粥样硬化性血栓形成性狭窄的前瞻性研究:GESICA研究

Background: Symptomatic intracranial atherothrombotic stenoses (ICAS) are associated with high rates of cerebrovascular ischemic events. Objective: To conduct a prospective multicenter study to evaluate the natural history of ICAS and, in those patients refractory to medical treatment, the outcomes associated with intracranial angioplasty. Methods: Patients aged 18 to 80 were enrolled with symptoms attributed to a single ICAS of ≥50%. Optimal medical therapy of vascular risk factors and preventive antithrombotic therapy were at the discretion of the local investigator. Patients were eligible for intracranial angioplasty after experiencing recurrent stroke despite medical therapy. Neurologic and ultrasonographic examinations were performed at study inclusion, 3 months after enrollment, and every 6 months of follow-up thereafter, for 36 months. Results:One hundred two patients were included, with a mean age of 63.3 ±10.4 years. Intracranial artery stenoses involved the vertebral artery in 22.5%, the basilar artery in 25.5%, the middle cerebral artery in 26.5%, and the internal carotid artery in 25.5%. In 27.4%of the patients, the stenoses had clinical hemodynamic characteristics. During a mean follow-up of 23.4 months, 38.2%of the patients had a cerebrovascular event: ischemic stroke in 13.7%and TIA in 24.5%. Among patients with a hemodynamically significant stenosis, 60.7%had a recurrent stroke or TIA in the territory of the stenotic artery; this association was significant in univariate analysis.Twenty-eight patients underwent an endovascular procedure with a neurologic periprocedural complication rate of 14.2%.The overall vascular death rate was 8.8%. Conclusions: Despite medical treatment, the 2-year recurrence rate of ischemic events in the territory of the stenotic artery was 38.2%. Cardiovascular events occurred in 18.6%of patients. Clinically significant hemodynamic stenoses were associated with stroke recurrence and may help identify a high risk subset of patients.

躯干前屈与帕金森病的MRI表现

躯干前屈的特点是仅在站立或行走时才有脊柱过度前屈。这种症状的起源不清，但近来的临床报告称躯干前屈与帕金森病（PD）有关，提示脑部受累在躯干前屈的发病机制中起一定作用。本研究的目的是探讨PD病人躯干前屈源于中枢神经系统的假说。17例伴有躯干前屈的PD病人前瞻性纳入研究，与10例没有躯干前屈的PD病人及12名正常人行对照性研究。10例没有躯干前屈的PD病人与17例伴有躯干前屈的PD病人相匹配。在三维MRI上测量脑、纹状体核的标准化体积，以及中脑和桥脑的横截面积。

线粒体细胞病患者的脑部MRI表现

Background: Mitochondrial cytopathies (MCs) are a heterogeneous group of clini cal entities, some of which have classic phenotypes. Magnetic resonance imaging (MRI) has been reported to be helpful in the diagnosis of MC. Objective: To corr elate the most common brain MRI findings reported in patients with MC with the c linical findings in patients in different MC subgroups. Design: Case series. Set ting: Patients with MCs seen at the Instituto National de Ciencias Médicas y Nu tritin Salvador Zubirn, Mexico City, Mexico. Patients: Twenty-one patients with MC with the following phenotypes: chronic progressive external ophthalmople gia (n=7), Kearns-Sayre syndrome (n=7), mitochondrial neurogastrointestinal enc ephalopathy (n=6), and myoclonic epilepsy with ragged red fiber myopathy (n=1). Results: Brain MRI abnormalities were found in 20 (95%) of 21 patients. The mos t frequent abnormalities were widespread white matter hyperintensity in 19 patie nts (90%), supratentorial cortical atrophy in 18 patients (86%), and cerebella r atrophy in 13 patients (62%). Widespread white matter hyperin tensity (P < .001) and supratentorial cortical atrophy (P=.001) were each corr elated significantly with MC. Subsequent subgroup analyses showed that the absen ce of basal ganglia hyperintensity was correlated with Kearns-Sayre syndrome (P < .001) and the presence of supratentorial cortical atrophy was correlated with mitochondrial neurogastrointestinal encephalopathy (P=.005). Conclusions: The p resence of widespread white matter hyperintensity and/or supratentorial cortical atrophy in brain MRI may help to establish the diagnosis of MC. The radiologist has a role to play in the workup of MC by confirming the diagnosis and possibly distinguishing different subgroups of MC.