Objective
To evaluate the efficacy and tolerability of single pulse transcranial magnetic stimulation (sTMS) for the preventive treatment of migraine.
Background
sTMS was originally developed for the ...acute treatment of migraine with aura. Open label experience has suggested a preventive benefit. The objective of this trial was to evaluate the efficacy and tolerability of sTMS for migraine prevention.
Methods
The
e
Neura
S
pringTMS
P
ost-Market
O
bservational
U
.S.
S
tudy of Migrain
e
(ESPOUSE) Study was a multicenter, prospective, open label, observational study. From December 2014 to March 2016, patients with migraine (n = 263) were consented to complete a 1-month baseline headache diary followed by 3 months of treatment. The treatment protocol consisted of preventive (four pulses twice daily) and acute (three pulses repeated up to three times for each attack) treatment. Patients reported daily headache status, medication use, and device use with a monthly headache diary. The primary endpoint, mean reduction of headache days compared to baseline, was measured over the 28-day period during weeks 9 to 12. The primary endpoint was compared to a statistically-derived placebo estimate (performance goal). Secondary endpoints included: 50% responder rate, acute headache medication consumption, HIT-6, and mean reduction in total headache days from baseline of any intensity.
Results
Of a total of 263 consented subjects, 229 completed a baseline diary, and 220 were found to be eligible based on the number of headache days. The device was assigned to 217 subjects (Safety Data Set) and 132 were included in the intention to treat Full Analysis Set. For the primary endpoint, there was a −2.75 ± 0.40 mean reduction of headache days from baseline (9.06 days) compared to the performance goal (−0.63 days) (p < 0.0001). The 50% responder rate of 46% (95% CI 37%, 56%) was also significantly higher (p < 0.0001) than the performance goal (20%). There was a reduction of −2.93 (5.24) days of acute medication use, headache impact measured by HIT-6, −3.1 (6.4) (p < 0.0001), and total headache days of any intensity −3.16 days (5.21) compared to the performance goal (−0.63 days) (p < 0.0001). The most common adverse events were lightheadedness (3.7%), tingling (3.2%), and tinnitus (3.2%). There were no serious adverse events.
Conclusions
This open label study suggests that sTMS may be an effective, well-tolerated treatment option for migraine prevention.
Trial registration number
NCT02357381
The new risk estimates led to dose-reduction efforts in pediatric imaging that initially focused on CT. Because of the increased use of CT and the relatively high effective radiation dose per study, ...CT had emerged as a major source of medical radiation received by children in the United States.
Neuroblastoma is a common malignancy observed in infants and young children. It has a varied prognosis, ranging from spontaneous regression to aggressive metastatic tumors with fatal outcomes despite ...multimodality therapy. Patients are divided into risk groups on the basis of age, stage, and biologic tumor factors. Multiple clinical and imaging tests are needed for accurate patient assessment. Iodine 123 ((123)I) metaiodobenzylguanidine (MIBG) is the first-line functional imaging agent used in neuroblastoma imaging. MIBG uptake is seen in 90% of neuroblastomas, identifying both the primary tumor and sites of metastatic disease. The addition of single photon emission computed tomography (SPECT) and SPECT/computed tomography to (123)I-MIBG planar images can improve identification and characterization of sites of uptake. During scan interpretation, use of MIBG semiquantitative scoring systems improves description of disease extent and distribution and may be helpful in defining prognosis. Therapeutic use of MIBG labeled with iodine 131 ((131)I) is being investigated as part of research trials, both as a single agent and in conjunction with other therapies. (131)I-MIBG therapy has been studied in patients with newly diagnosed neuroblastoma and those with relapsed disease. Development and implementation of an institutional (131)I-MIBG therapy research program requires extensive preparation with a focus on radiation protection.
OBJECTIVE:To describe clinical and imaging responses in neurosarcoidosis to infliximab, a monoclonal antibody against tumor necrosis factor–α.
METHODS:Investigators at 6 US centers retrospectively ...identified patients with CNS sarcoidosis treated with infliximab, including only patients with definite or probable neurosarcoidosis following rigorous exclusion of other causes.
RESULTS:Of 66 patients with CNS sarcoidosis (27 definite, 39 probable) treated with infliximab for a median of 1.5 years, the mean age was 47.5 years at infliximab initiation (SD 11.7, range 24–71 years); 56.1% were female; 62.1% were white, 37.0% African American, and 3% Hispanic. Sarcoidosis was isolated to the CNS in 19.7%. Using infliximab doses ranging from 3 to 7 mg/kg every 4–8 weeks, MRI evidence of a favorable treatment response was observed in 82.1% of patients with imaging follow-up (n = 56), with complete remission of active disease in 51.8% and partial MRI improvement in 30.1%; MRI worsened in 1 patient (1.8%). There was clinical improvement in 77.3% of patients, with complete neurologic recovery in 28.8%, partial improvement in 48.5%, clinical stability in 18.2%, worsening in 3%, and 1 lost to follow-up. In 16 patients in remission when infliximab was discontinued, the disease recurred in 9 (56%), typically in the same neuroanatomic location.
CONCLUSIONS:Most patients with CNS sarcoidosis treated with infliximab exhibit favorable imaging and clinical treatment responses, including some previously refractory to other immunosuppressive treatments.
CLASSIFICATION OF EVIDENCE:This study provides Class IV evidence that for patients with CNS sarcoidosis infliximab is associated with favorable imaging and clinical responses.
Although often regarded as a protean illness with myriad clinical and imaging manifestations, neurosarcoidosis typically presents as recognizable syndromes that can be approached in a rational, ...systematic fashion. Understanding of neurosarcoidosis has progressed significantly in recent years, including updated diagnostic criteria and advances in treatment. The diagnosis of neurosarcoidosis is established by the clinical syndrome, imaging and histopathological findings, and exclusion of other causes. Mounting evidence supports the use of tumor necrosis factor inhibitors as an important addition to the therapeutic armamentarium, along with glucocorticoids and steroid-sparing cytotoxic immunosuppressants. In this narrative review, we summarize recent advances in the diagnosis and treatment of neurosarcoidosis.
MDA5 is a cytosolic sensor of double-stranded RNA (ds)RNA including viral byproducts and intermediates. We studied a child with life-threatening, recurrent respiratory tract infections, caused by ...viruses including human rhinovirus (HRV), influenza virus, and respiratory syncytial virus (RSV). We identified in her a homozygous missense mutation in
that encodes MDA5. Mutant MDA5 was expressed but did not recognize the synthetic MDA5 agonist/(ds)RNA mimic polyinosinic-polycytidylic acid. When overexpressed, mutant MDA5 failed to drive luciferase activity from the
promoter or promoters containing ISRE or NF-κB sequence motifs. In respiratory epithelial cells or fibroblasts, wild-type but not knockdown of MDA5 restricted HRV infection while increasing IFN-stimulated gene expression and IFN-β/λ. However, wild-type MDA5 did not restrict influenza virus or RSV replication. Moreover, nasal epithelial cells from the patient, or fibroblasts gene-edited to express mutant MDA5, showed increased replication of HRV but not influenza or RSV. Thus, human MDA5 deficiency is a novel inborn error of innate and/or intrinsic immunity that causes impaired (ds)RNA sensing, reduced IFN induction, and susceptibility to the common cold virus.
A semiquantitative
I-metaiodobenzylguanidine (
I-MIBG) scoring method (the Curie score, or CS) was previously examined in the Children's Oncology Group (COG) high-risk neuroblastoma trial, COG A3973, ...with a postinduction CS of more than 2 being associated with poor event-free survival (EFS). The validation of the CS in an independent dataset, International Society of Paediatric Oncology European Neuroblastoma/High-Risk Neuroblastoma 1 (SIOPEN/HR-NBL1), is now reported.
A retrospective analysis of
I-MIBG scans obtained from patients who had been prospectively enrolled in SIOPEN/HR-NBL1 was performed. All patients exhibited
I-MIBG-avid, International Neuroblastoma Staging System stage 4 neuroblastoma.
I-MIBG scans were evaluated at 2 time points, diagnosis (
= 345) and postinduction (
= 330), before consolidation myeloablative therapy. Scans of 10 anatomic regions were evaluated, with each region being scored 0-3 on the basis of disease extent and a cumulative CS generated. Cut points for outcome analysis were identified by Youden methodology. CSs from patients enrolled in COG A3973 were used for comparison.
The optimal cut point for CS at diagnosis was 12 in SIOPEN/HR-NBL1, with a significant outcome difference by CS noted (5-y EFS, 43.0% ± 5.7% CS ≤ 12 vs. 21.4% ± 3.6% CS > 12,
< 0.0001). The optimal CS cut point after induction was 2 in SIOPEN/HR-NBL1, with a postinduction CS of more than 2 being associated with an inferior outcome (5-y EFS, 39.2% ± 4.7% CS ≤ 2 vs. 16.4% ± 4.2% CS > 2,
< 0.0001). The postinduction CS maintained independent statistical significance in Cox models when adjusted for the covariates of age and
gene copy number.
The prognostic significance of postinduction CSs has now been validated in an independent cohort of patients (SIOPEN/HR-NBL1), with a postinduction CS of more than 2 being associated with an inferior outcome in 2 independent large, cooperative group trials.
Optimization of Pediatric PET/CT Parisi, Marguerite T., MD, MS; Bermo, Mohammed S., MD; Alessio, Adam M., PhD ...
Seminars in nuclear medicine,
05/2017, Volume:
47, Issue:
3
Journal Article
Peer reviewed
PET/CT, the most common form of hybrid imaging, has transformed oncologic imaging and is increasingly being used for nononcologic applications as well. Performing PET/CT in children poses unique ...challenges. Not only are children more sensitive to the effects of radiation than adults but, following radiation exposure, children have a longer postexposure life expectancy in which to exhibit adverse radiation effects. Both the PET and CT components of the study contribute to the total patient radiation dose, which is one of the most important risks of the study in this population. Another risk in children, not typically encountered in adults, is potential neurotoxicity related to the frequent need for general anesthesia in this patient population. Optimizing pediatric PET/CT requires making improvements to both the PET and the CT components of the procedure while decreasing the potential for risk. This can be accomplished through judicious performance of imaging, the use of recommended pediatric18 fluorine-2-fluoro-2-deoxy- d -glucose (18 F-FDG) administered activities, thoughtful selection of pediatric-specific CT imaging parameters, careful patient preparation, and use of appropriate patient immobilization. In this article, we will review a variety of strategies for radiation dose optimization in pediatric18 F-FDG-PET/CT focusing on these processes. Awareness of and careful selection of pediatric-specific CT imaging parameters designed for appropriate diagnostic, localization, or attenuation correction only CT, in conjunction with the use of recommended radiotracer administered activities, will help to ensure image quality while limiting patient radiation exposure. Patient preparation, an important determinant of image quality, is another focus of this review. Appropriate preparative measures are even more crucial in children in whom there is a higher incidence of brown fat, which can interfere with study interpretation. Finally, we will discuss measures to improve the patient experience, the resource use, the departmental workflow, and the diagnostic performance of the study through the use of appropriate technology, all in the context of minimizing procedure-related risks.
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