Expanding the genotypic and phenotypic spectrum of severe serine biosynthesis disorders.

Serine biosynthesis disorders comprise a spectrum of very rare autosomal recessive inborn errors of metabolism with wide phenotypic variability. Neu-Laxova syndrome represents the most severe expression and is characterized by multiple congenital anomalies and pre- or perinatal lethality. Here, we present the mutation spectrum and a detailed phenotypic analysis in 15 unrelated families with severe types of serine biosynthesis disorders. We identified likely disease-causing variants in the PHGDH and PSAT1 genes, several of which have not been reported previously. Phenotype analysis and a comprehensive review of the literature corroborates the evidence that serine biosynthesis disorders represent a continuum with varying degrees of phenotypic expression and suggest that even gradual differences at the severe end of the spectrum may be correlated with particular genotypes. We postulate that the individual residual enzyme activity of mutant proteins is the major determinant of the phenotypic variability, but further functional studies are needed to explore effects at the enzyme protein level.We are indebted to all families for participating in this study. We would like to acknowledge Dr. Natasha Laidlew, who initially suggested the diagnosis in one of the cases and provided important phenotypic information, and Dr. María-Luisa Martínez-Fernández for the critical management of biosamples in ECEMC Program of Spain. Financial assistance was received in support of the study by grants from the German Federal Ministry of Education and Research (BMBF) (GeNeRARe, FKZ: 01GM1519D) to M. Z. and from the Institute of Health Carlos III: Convenio ISCIII-ASEREMAC, and Fundación 1000 sobre Defectos Congénitos, of Spain to E. B.-S. and I. R. G.S

TIPIC Syndrome: Beyond the Myth of Carotidynia, a New Distinct Unclassified Entity

International audienceThe differential diagnosis of acute cervical pain includes nonvascular and vascular causes such as carotid dissection, carotid occlusion, or vasculitis. However, some patients present with unclassified vascular and perivascular changes on imaging previously reported as carotidynia. The aim of our study was to improve the description of this as yet unclassified clinico-radiologic entity. MATERIALS AND METHODS: From January 2009 through April 2016, 47 patients from 10 centers presenting with acute neck pain or tenderness and at least 1 cervical image showing unclassified carotid abnormalities were included. We conducted a systematic, retrospective study of their medical charts and diagnostic and follow-up imaging. Two neuroradiologists independently analyzed the blinded image datasets. RESULTS: The median patient age was 48 years. All patients presented with acute neck pain, and 8 presented with transient neurologic symptoms. Imaging showed an eccentric pericarotidian infiltration in all patients. An intimal soft plaque was noted in 16 patients, and a mild luminal narrowing was noted in 16 patients. Interreader reproducibility was excellent. All patients had complete pain resolution within a median of 13 days. At 3-month follow-up, imaging showed complete disappearance of vascular abnormalities in 8 patients, and a marked decrease in all others. CONCLUSIONS: Our study improved the description of an unclassified, clinico-radiologic entity, which could be described by the proposed acronym: TransIent Perivascular Inflammation of the Carotid artery (TIPIC) syndrome

Factors Associated With Fast Early Infarct Growth in Patients With Acute Ischemic Stroke With a Large Vessel Occlusion.

The optimal methods for predicting early infarct growth rate (EIGR) in acute ischemic stroke with a large vessel occlusion (LVO) have not been established. We aimed to study the factors associated with EIGR, with a focus on the collateral circulation as assessed by the hypoperfusion intensity ratio (HIR) on perfusion imaging, and determine whether the associations found are consistent across imaging modalities. Retrospective multicenter international study including patients with anterior circulation LVO-related acute stroke with witnessed stroke onset and baseline perfusion imaging (MRI or CT) performed within 24 hours from symptom onset. To avoid selection bias, patients were selected from (1) the prospective registries of 4 comprehensive stroke centers with systematic use of perfusion imaging and including both thrombectomy-treated and untreated patients and (2) 1 prospective thrombectomy study where perfusion imaging was acquired per protocol, but treatment decisions were made blinded to the results. EIGR was defined as infarct volume on baseline imaging divided by onset-to-imaging time and fast progressors as EIGR ≥10 mL/h. The HIR, defined as the proportion of time-to-maximum (Tmax) >6 second with Tmax >10 second volume, was measured on perfusion imaging using RAPID software. The factors independently associated with fast progression were studied using multivariable logistic regression models, with separate analyses for CT- and MRI-assessed patients. Overall, 1,127 patients were included (CT, n = 471; MRI, n = 656). Median age was 74 years (interquartile range [IQR] 62-83), 52% were male, median NIH Stroke Scale was 16 (IQR 9-21), median HIR was 0.42 (IQR 0.26-0.58), and 415 (37%) were fast progressors. The HIR was the primary factor associated with fast progression, with very similar results across imaging modalities: The proportion of fast progressors was 4% in the first HIR quartile (i.e., excellent collaterals), ∼15% in the second, ∼50% in the third, and ∼77% in the fourth (p < 0.001 for each imaging modality). Fast progression was independently associated with poor 3-month functional outcome in both the CT and MRI cohorts (p < 0.001 and p = 0.030, respectively). The HIR is the primary factor associated with fast infarct progression, regardless of imaging modality. These results have implication for neuroprotection trial design, as well as informing triage decisions at primary stroke centers

Clinical spectrum and prognostic value of CNS MOG autoimmunity in adults: The MOGADOR study

International audienc