No abstract

Our objective was to determine the brain magnetic resonance imaging (MRI) abnormalities in a selected group of patients with mucopolysaccharidosis (MPS) types I and II who had only mild clinical manifestations. We retrospectively assessed MRI brain studies in 18 patients with MPS (type I: 6 and type II: 12). We evaluated abnormal signal intensity in the white matter, widening of the cortical sulci, size of the supratentorial ventricles, dilatation of the perivascular spaces (PVS) and enlargement of the subarachnoid spaces. We observed a broad spectrum of findings, and despite severely abnormal MRI studies, no patients had mental retardation. We also observed that dilated PVS, previously believed to be caused by macroscopic deposition of the mucopolysaccharides, had an appearance similar to cerebrospinal fluid (CSF) in all MRI sequences performed, even in FLAIR and trace diffusion weighted images. Based on our results, we believe that with the exception of white matter abnormalities and brain atrophy, all other findings may be related to abnormal resorption of CSF, and there is no relationship between the imaging and clinical manifestations of the disease.

Background: There are limited data on the specific mechanisms of stroke in patients with intracranial atherosclerotic stenosis (ICAS). We undertook this study to describe infarct patterns and likely mechanisms of stroke in a large cohort of patients with ICAS, and to evaluate the relationship of these infarct patterns to angiographic features (collaterals, stenosis location and stenosis severity). Methods: We evaluated infarct patterns in the territory of a stenotic intracranial artery on neuroimaging performed at baseline and during follow-up if a recurrent stroke occurred in patients enrolled in the Warfarin-Aspirin Symptomatic Intracranial Disease (WASID) trial. We defined the likely mechanism of stroke (artery-to-artery embolism, perforator occlusion, hypoperfusion or mixed) according to the site of ICAS and based on the infarct patterns on neuroimaging. Collaterals were assessed using American Society of Interventional and Therapeutic Neuroradiology/Society of Interventional Radiology (ASITN/SIR) grades, and stenosis severity using the WASID trial's measurement technique. We evaluated the association of infarct patterns with angiographic features using χ² tests. Results: The likely mechanisms of stroke based on the infarct patterns at baseline in the 136 patients included in the study were artery-to-artery embolism (n = 69; 50.7%), perforator occlusion (n = 34; 25%), hypoperfusion (n = 12; 8.8%) and mixed (n = 21; 15.5%). Perforator-occlusive infarcts were more frequent in the posterior circulation, and mixed patterns were more prevalent in the anterior circulation (both p < 0.01). Most of the mixed patterns in the anterior circulation combined small pial or scattered multiple cortical infarcts with infarcts in border-zone regions, especially the cortical ones. Isolated border-zone infarcts were not significantly associated with a poor grading for collaterals or the severity of stenosis. Among 47 patients with a recurrent infarct during follow-up, the infarct patterns suggested an artery-to-artery embolic mechanism in 29 (61.7%). Conclusions: Artery-to-artery embolism is probably the most common mechanism of stroke in both the anterior and the posterior circulations in patients with ICAS. An extension of intracranial atherosclerosis at the site of stenosis into adjacent perforators also appears to be a common mechanism of stroke, particularly in the posterior circulation, whereas hypoperfusion as the sole mechanism is relatively uncommon. Further research is important to accurately establish the specific mechanisms of stroke in patients with ICAS, since preliminary data suggest that the underlying mechanism of stroke is an important determinant of prognosis.

Purpose: We studied the impact of mTOR signaling inhibition with rapamycin in head and neck squamous cell carcinoma (HNSCC) in the neoadjuvant setting. The goals were to evaluate the mTOR pathway as a therapeutic target for patients with advanced HNSCC, and the clinical safety, antitumor, and molecular activity of rapamycin administration on HNSCC.Patients and Methods: Patients with untreated stage II-IVA HNSCC received rapamycin for 21 days (day 1, 15 mg; days 2-12, 5 mg) prior to definitive treatment with surgery or chemoradiation. Treatment responses were assessed clinically and radiographically with CT and FDG-PET. Pre-and posttreatment biopsies and blood were obtained for toxicity, immune monitoring, and IHC assessment of mTOR signaling, as well as exome sequencing.Results: Sixteen patients (eight oral cavity, eight oropharyngeal) completed rapamycin and definitive treatment.

No abstract

X-linked monocarboxylate transporter 8 (MCT8) deficiency results from a loss-of-function mutation in the monocarboxylate transporter 8 gene, located on chromosome Xq13.2 (Allan-Herndon-Dudley syndrome). Affected boys present early in life with neurodevelopment delays but have pleasant dispositions and commonly have elevated serum triiodothyronine. They also have marked axial hypotonia and quadriparesis but surprisingly little spasticity early in their disease course. They do, however, have subtle involuntary movements, most often dystonia. The combination of hypotonia and dystonia presents a neurorehabilitation challenge and explains why spasticity-directed therapies have commonly produced suboptimal responses. Our aim was to better define the spectrum of motor disability and to elucidate the neuroanatomic basis of the motor impairments seen in MCT8 deficiency using clinical observation and brain magnetic resonance imaging (MRI) in a cohort of 6 affected pediatric patients. Our findings identified potential imaging biomarkers and suggest that rehabilitation efforts targeting dystonia may be more beneficial than those targeting spasticity in the prepubertal pediatric MCT8 deficiency population.

No abstract

No abstract