Epidemiological, level III; Therapeutic, level IV.

Patients with multiple sclerosis present with focal lesions throughout the spinal cord. There is a clinical need for non-invasive measurements of spinal cord activity and functional organization in multiple sclerosis, given the cord's critical role in the disease. Recent reports of spontaneous blood oxygenation level-dependent fluctuations in the spinal cord using functional MRI suggest that, like the brain, cord activity at rest is organized into distinct, synchronized functional networks among grey matter regions, likely related to motor and sensory systems. Previous studies looking at stimulus-evoked activity in the spinal cord of patients with multiple sclerosis have demonstrated increased levels of activation as well as a more bilateral distribution of activity compared to controls. Functional connectivity studies of brain networks in multiple sclerosis have revealed widespread alterations, which may take on a dynamic trajectory over the course of the disease, with compensatory increases in connectivity followed by decreases associated with structural damage. We build upon this literature by examining functional connectivity in the spinal cord of patients with multiple sclerosis. Using ultra-high field 7 T imaging along with processing strategies for robust spinal cord functional MRI and lesion identification, the present study assessed functional connectivity within cervical cord grey matter of patients with relapsing-remitting multiple sclerosis (n = 22) compared to a large sample of healthy controls (n = 56). Patient anatomical images were rated for lesions by three independent raters, with consensus ratings revealing 19 of 22 patients presented with lesions somewhere in the imaged volume. Linear mixed models were used to assess effects of lesion location on functional connectivity. Analysis in control subjects demonstrated a robust pattern of connectivity among ventral grey matter regions as well as a distinct network among dorsal regions. A gender effect was also observed in controls whereby females demonstrated higher ventral network connectivity. Wilcoxon rank-sum tests detected no differences in average connectivity or power of low frequency fluctuations in patients compared to controls. The presence of lesions was, however, associated with local alterations in connectivity with differential effects depending on columnar location. The patient results suggest that spinal cord functional networks are generally intact in relapsing-remitting multiple sclerosis but that lesions are associated with focal abnormalities in intrinsic connectivity. These findings are discussed in light of the current literature on spinal cord functional MRI and the potential neurological underpinnings.

BACKGROUND The study aimed to evaluate whether simplified chemotherapy followed by dose-reduced irradiation was effective for treating patients (ages 3-21 years) with localized germinoma. The primary endpoint was 3-year progression free survival (PFS) rate. METHODS Patients with a complete response to chemotherapy with carboplatin and etoposide received 18Gy WVI +12Gy boost to the tumor bed. Patients with partial response proceeded to 24Gy WVI + 12Gy. Longitudinal cognitive functioning was evaluated prospectively on ALTE07C1 and was a primary study aim. RESULTS 151 patients were enrolled; 137 were eligible. Among 90 evaluable patients, 74 were treated with 18Gy and 16 with 24Gy WVI. The study failed to demonstrate non-inferiority of the 18Gy WVI regimen compared to the design threshold of 95% 3-year PFS rate, where, per design, patients who could not be assessed for progression at 3 years were counted as failures. The KM-based 3-year PFS estimates were 94.5 ±2.7% and 93.75 ± 6.1% for the 18Gy and 24Gy WVI cohorts, respectively. Collectively, estimated mean IQ and attention/concentration were within normal range. A lower mean attention score was observed at 9 months for patients treated with 24Gy. Acute effects in processing speed were observed in the 18Gy cohort at 9 months which improved at 30-month assessment. CONCLUSIONS While a failure according to the prospective statistical noninferiority design, this study demonstrated high rates of chemotherapy responses, favorable KM based PFS and OS estimates in the context of reduced irradiation doses and holds promise for lower long-term morbidities for patients with germinoma.

Pancreatic islet transplantation into type 1 diabetic patients is currently being performed by intraportal infusion. This method, albeit reproducible, has some disadvantages including potential development of portal hypertension, hemorrhage, and an inability to retrieve or detect the transplanted tissue. Other transplant sites have been examined in animal models including the omentum, peritoneal cavity, and the spleen. A transplant site that has not been successful in supporting functional islet tissue transplantation in humans is the subcutaneous space due primarily to the lack of a well-defined vascular bed. This site has many favorable characteristics such as ease of access for transplantation and potential for removal of the transplanted tissue with a minimally invasive surgical procedure. This report addresses the evaluation of a subcutaneously placed device for the support of rat syngeneic islet transplantation in a streptozocin-induced diabetic model. The data generated support the use of this device for islet engraftment. In addition, beta cell function in this device compared favorably with the function of islets transplanted to the renal subcapsular space as well as islets within the native pancreas.

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Background and Purpose: The display resolution of the Apple iPad® is 1024 × 768 pixels, which is greater than that required for generating the typical CT or MRI images. The purpose of this study is to determine if specific CT and MR sequences can be interpreted accurately on mobile device/PACS software platforms when compared to a traditional stationary high resolution monitor/PACS radiological workstation. If so, this allows radiologists to provide comparable interpretation as if they were onsite at an imaging center or hospital. Materials and Methods: This study is an investigator initiated, single site, retrospective, nonrandomized, IRB approved study. Five radiologists were included in this study. Each independently interpreted specific CT and MR sequences on traditional high-resolution LCD monitors via eFilm® software as well as an iPad® mobile device using Osirix® software program. Repeat interpretations were performed, with 4 weeks minimum interval between interpretations of each patient. This investigation included: 50 patients with CTA perfusion imaging, 50 patients with MRI of the brain, and 50 patients with MRI of the spine, which were image study orders generated through emergency room requests. Subsequently, interpretive results of each radiologist for each patient were statistically compared to evaluate for intra-observer and inter-observer reliability. Results: The parameters set within the CTA perfusion brain studies demonstrated excellent intra-observer variability. All of the parameters within the MRI brain studies demonstrated excellent intra-observer variability with a Cohen's kappa value > 0.75. The Cohen's kappa values for the board certified neuroradiologist demonstrated excellent variability for all parameters; the resident radiologists had good variability, with a majority of kappa values near 0.75. Conclusions: The data and statistical analysis demonstrated that portable mobile devices such as the Apple iPad® can display adequate resolution of CT and MRI sequences to accurately diagnose acute central nervous system injuries and other non-acute pathology.

Mutations in the torsinA-interacting protein 1 (TOR1AIP1) gene result in a severe muscular dystrophy with minimal literature in the pediatric population. We review a case of TOR1AIP1 gene mutation in a 16-year-old Caucasian female with a long history of muscle weakness. Extensive clinical workup was performed and MRI at time of initial presentation demonstrated no significant muscular atrophy with heterogenous STIR hyperintensity of the lower extremity muscles. MRI findings seven years later included extensive atrophy of the lower extremities, with severe progression, including the gluteal muscles, iliopsoas, rectus femoris, and obturator internus. There was also significant atrophy of the rectus abdominis and internal and external oblique muscles, and iliacus muscles. The MRI findings showed more proximal involvement of lower extremities and no atrophy of the tibialis anterior, making TOR1AIP1 the more likely genetic cause. Muscle biopsy findings supported TOR1AIP1 limb-girdle muscular dystrophy. Though rare, TOR1AIP1 gene mutation occurs in pediatric patients and MRI can aid in diagnosis and help differentiate from other types of muscular dystrophy. Genetic and pathology workup is also crucial to accurate diagnosis and possible treatment of these patients.

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