We describe an autosomal recessive condition characterized with cerebral vasculopathy and early onset of stroke in 14 individuals in Old Order Amish. The phenotype of the condition was highly heterogeneous, ranging from severe developmental disability to normal schooling. Cerebral vasculopathy was a major hallmark of the condition with a common theme of multifocal stenoses and aneurysms in large arteries, accompanied by chronic ischemic changes, moyamoya morphology, and evidence of prior acute infarction and hemorrhage. Early signs of the disease included mild intrauterine growth restriction, infantile hypotonia, and irritability, followed by failure to thrive and short stature. Acrocyanosis, Raynaud’s phenomenon, chilblain lesions, low-pitch hoarse voice, glaucoma, migraine headache, and arthritis were frequently observed. The early onset or recurrence of strokes secondary to cerebral vasculopathy seems to always be associated with poor outcomes. The elevated erythrocyte sedimentation rate (ESR), IgG, neopterin, and TNF-α found in these patients suggested an immune disorder. Through genomewide homozygosity mapping, we localized the disease gene to chromosome (Chr) 20q11.22-q12. Candidate gene sequencing identified a homozygous mutation, c.1411–2A > G, in the SAMHD1 gene, being associated with this condition. The mutation appeared at the splice-acceptor site of intron 12, resulted in the skipping of exon 13, and gave rise to an aberrant protein with in-frame deletion of 31 amino acids. Immunoblotting analysis showed lack of mutant SAMHD1 protein expression in affected cell lines. The function of SAMHD1 remains unclear, but the inflammatory vasculopathies of the brain found in the patients with SAMHD1 mutation indicate its important roles in immunoregulation and cerebral vascular hemeostasis.

Single-photon emission computed tomography (SPECT) has been a mainstay of nuclear medicine practice for several decades. More recently, combining the functional imaging available with SPECT and the anatomic imaging of computed tomography (CT) has gained more acceptance and proved useful in many clinical situations. Most vendors now offer integrated SPECT/CT systems that can perform both functions on one gantry and provide fused functional and anatomic data in a single imaging session. In addition to allowing anatomic localization of nuclear imaging findings, SPECT/CT also enables accurate and rapid attenuation correction of SPECT studies. These attributes have proved useful in many cardiac, general nuclear medicine, oncologic, and neurologic applications in which the SPECT results alone were inconclusive. Optimal clinical use of this rapidly emerging imaging modality requires an understanding of the fundamental principles of SPECT/CT, including quality control issues as well as potential pitfalls and limitations. The long-term clinical and economic effects of this technology have yet to be established.

SUMMARYPurpose: Subtraction ictal single photon emission computed tomography (SPECT) co-registered to magnetic resonance imaging (MRI) (SISCOM) is a useful modality to identify epileptogenic focus. Using this technique, several studies have generally considered the area of highest ictal hyperperfusion, as outlined by thresholding the difference images with a standard z score of 2, to be highly concordant to the epileptogenic focus. In clinical practice, several factors influence ictal hyperperfusion and using different SISCOM thresholds can be helpful. We aimed to systematically evaluate the localizing value of various z scores (1, 1.5, 2, and 2.5) in a seizure-free cohort following resective epilepsy surgery, and to examine the localizing information of perfusion patterns observed at each z score. Methods: Twenty-six patients were identified as having ictal-interictal SPECT images, preoperative and postoperative MRI studies, and having remained seizure free for at least 6 months after temporal or extratemporal surgical resection. SISCOM analysis was performed using preoperative MRI studies, and then blindly reviewed for localization of hyperperfused regions. With the added information from postoperative, coregistered MRI, perfusion patterns were determined.

Most patients who report multiple aura types have localized epilepsy in the nondominant hemisphere, and are good surgical candidates. A common mechanism for multiple auras may be a spreading but restricted EEG seizure activating sequential symptomatogenic zones, but without the ictal activation of deeper structures or contralateral spread to cause loss of awareness and amnesia for the auras.

FUS1 is a novel tumor suppressor gene located in the human chromosome 3p21.3 region. We previously showed that restoration of FUS1 function in 3p21.3-deficient human non-small-cell lung cancer (NSCLC) cells significantly inhibited tumor cell growth in vitro and in vivo. In this study, we evaluated the combined effects of the tumor suppressor FUS1 and the chemotherapeutic drug cisplatin on tumor cell growth and apoptosis induction in NSCLC cells, and explored the molecular mechanism of their mutual action. Exogenous expression of FUS1 by nanoparticle-mediated gene transfer sensitized the response of NSCLC cells to cisplatin, resulting in a 4-to 6-fold increase in tumor-suppressing activity. A systemic treatment with a combination of FUS1-nanoparticles and cisplatin in a human H322 lung cancer orthotopic xenograft mouse model dramatically enhanced the therapeutic efficacy of cisplatin. We also found that the FUS1-enhanced chemosensitivity is associated with the downregulation of MDM2, accumulation of p53 and activation of the Apaf-1-dependent apoptosis pathway. Our results demonstrated an important role of FUS1 in modulating chemosensitivity of lung cancer cells, and suggested that a proper combination of molecular therapeutics such as the proapoptotic tumor suppressor FUS1 and the conventional chemotherapeutic drugs such as cisplatin may be an efficient treatment strategy for human lung cancer.

Subtraction ictal and interictal single photon emission computed tomography can demonstrate complex ictal perfusion patterns. Regions with ictal hyperperfusion are suggested to reflect seizure onset and propagation pathways. The significance of ictal hypoperfusion is not well understood. The aim of this study was to verify whether ictal perfusion changes, both hyper- and hypoperfusion, correspond to electrically connected brain networks. A total of 36 subtraction ictal and interictal perfusion studies were analysed in 31 consecutive medically refractory focal epilepsy patients, evaluated by stereo-electroencephalography that demonstrated a single focal onset. Cortico-cortical evoked potential studies were performed after repetitive electrical stimulation of the ictal onset zone. Evoked responses at electrode contacts outside the stimulation site were used as a measure of connectivity. The evoked responses at these electrodes were compared to ictal perfusion values noted at these locations. In 67% of studies, evoked responses were significantly larger in hyperperfused compared to baseline-perfused areas. The majority of hyperperfused contacts also had significantly increased evoked responses relative to pre-stimulus electroencephalogram. In contrast, baseline-perfused and hypoperfused contacts mainly demonstrated non-significant evoked responses. Finally, positive significant correlations (P < 0.05) were found between perfusion scores and evoked responses in 61% of studies. When the stimulated ictal onset area was hyperperfused, 82% of studies demonstrated positive significant correlations. Following stimulation of hyperperfused areas outside seizure onset, positive significant correlations between perfusion changes and evoked responses could be seen, suggesting bidirectional connectivity. We conclude that strong connectivity was demonstrated between the ictal onset zone and hyperperfused regions, while connectivity was weaker in the direction of baseline-perfused or hypoperfused areas. In trying to understand a patient's epilepsy, one should consider the contribution of all hyperperfused regions, as these are likely not random, but represent an electrically connected epileptic network.

BACKGROUND AND PURPOSE: New-onset refractory status epilepticus is a clinical condition characterized by acute and prolonged pharmacoresistant seizures without a pre-existing relevant neurologic disorder, prior epilepsy, or clear structural, toxic, or metabolic cause. New-onset refractory status epilepticus is often associated with antineuronal antibodies and may respond to early immunosuppressive therapy, reflecting an inflammatory element of the condition. FDG-PET is a useful diagnostic tool in inflammatory and noninflammatory encephalitis. We report here FDG-PET findings in new-onset refractory status epilepticus and their correlation to disease activity, other imaging findings, and outcomes. MATERIALS AND METHODS:Twelve patients who met the criteria for new-onset refractory status epilepticus and who had FDG-PET and MR imaging scans and electroencephalography at a single academic medical center between 2008 and 2017 were retrospectively identified. Images were independently reviewed by 2 radiologists specialized in nuclear imaging. Clinical characteristics and outcome measures were collected through chart review. RESULTS:Twelve patients underwent 21 FDG-PET scans and 50 MR imaging scans. Nine (75%) patients were positive for autoantibodies. All patients had identifiable abnormalities on the initial FDG-PET in the form of hypermetabolism (83%) and/or hypometabolism (42%). Eight (67%) had medial temporal involvement. All patients (n ϭ 3) with N-methyl-D-aspartic acid receptor antibodies had profound bilateral occipital hypometabolism. Initial MR imaging findings were normal in 6 (50%) patients. Most patients had some degree of persistent hyper-(73%) or hypometabolism (45%) after immunosuppressive therapy. FDG-PET hypometabolism was predictive of poor outcome (mRS 4 -6) at hospital discharge (P ϭ .028). CONCLUSIONS:Both FDG-PET hypometabolism and hypermetabolism are seen in the setting of new-onset refractory status epilepticus and may represent markers of disease activity. ABBREVIATIONS: ALE ϭ autoimmune limbic encephalitis; EEG ϭ electroencephalography; GABA-B ϭ ␥-aminobutyric acid B; LGI1 ϭ leucine-rich glioma inactivated 1; NMDA ϭ N-methyl-D-aspartate; NMDA-R ϭ N-methyl-D-aspartate receptor; NORSE ϭ new-onset refractory status epilepticus; VGKC ϭ voltage-gated potassium channel

BackgroundAccumulative evidence in the literature suggests alcohol consumption is a protective factor of the metabolic syndrome (MS). However, few studies investigated the relationship between alcohol consumption and components of MS. We examined association of several types of alcoholic beverage with components of MS among people in rural China.MethodsIn the Nantong Metabolic Syndrome Study (NMSS), a cross-sectional study, a total of 20,502 participants, including 13,505 women and 6,997 men aged 18–74 years, were recruited between 2007 and 2008 in Nantong, China. Socio-economic status, dietary intake, physical exercise, alcoholic beverage consumption, and smoking status information were obtained, and triglycerides (TG), high-density lipoprtein cholesterol (HDL-c), blood pressure (BP) and blood glucose level were examined for all participants. Logistic regression model and the restricted cubic spline approach were used to analyze the associations between alcoholic beverage consumption and MS components.ResultsThe MS prevalence was 21.1% in the whole population, which was significantly low among drinkers (20.6%), compared with non-drinkers (23.6%) in women, and was comparable in men (16.4% versus 17.1%). High HDL-c level was observed among drinkers, compared with non-drinkers in both men and women. Low TG level and Systolic BP (SBP) were found only among rice wine drinkers in women, and high waist circumference, high TG and BP were found among beer and liquor drinkers in men. Furthermore, we found that the highest quartile of rice wine drink in women may decrease 24% risk of high TG, 30% risk of low HDL-c and 43% risk of high glucose among MS components cases respectively, compared with non-drinkers (p for trend <0.01 for those three components). While compared non-drinkers among men, the highest quartile of liquor drink may increase 32% risk of high SBP, 55% risk of high Diastolic BP (DBP) and 34% risk of abdominal obesity among MS components cases respectively, but decrease 45% risk of low HDL-c (p for trend <0.05 for those four components).ConclusionOur data suggested that all alcoholic beverages increased HDL-c level. Rice wine decreased both TG level and blood glucose in women only and it could be one of healthy alcoholic beverages in MS prevention in Chinese women. While excessive liquor consumption increased BP and waist circumference level and it may lead to hypertension and central obesity in Chinese men.