A Systematic Guideline by the ASPN Workgroup on the Evidence, Education, and Treatment Algorithm for Painful Diabetic Neuropathy: SWEET.

Introduction: Painful diabetic neuropathy (PDN) is a leading cause of pain and disability globally with a lack of consensus on the appropriate treatment of those suffering from this condition. Recent advancements in both pharmacotherapy and interventional approaches have broadened the treatment options for PDN. There exists a need for a comprehensive guideline for the safe and effective treatment of patients suffering from PDN. Objective: The SWEET Guideline was developed to provide clinicians with the most comprehensive guideline for the safe and appropriate treatment of patients suffering from PDN. Methods: The American Society of Pain and Neuroscience (ASPN) identified an educational need for a comprehensive clinical guideline to provide evidence-based recommendations for PDN. A multidisciplinary group of international experts developed the SWEET guideline. The world literature in English was searched using Medline, EMBASE, Cochrane CENTRAL, BioMed Central, Web of Science, Google Scholar, PubMed, Current Contents Connect, Meeting Abstracts, and Scopus to identify and compile the evidence for diabetic neuropathy pain treatments (per section as listed in the manuscript) for the treatment of pain. Manuscripts from 2000-present were included in the search process. Results: After a comprehensive review and analysis of the available evidence, the ASPN SWEET guideline was able to rate the literature and provide therapy grades for most available treatments for PDN utilizing the United States Preventive Services Task Force criteria. Conclusion: The ASPN SWEET Guideline represents the most comprehensive review of the available treatments for PDN and their appropriate and safe utilization.

Outcomes of status epilepticus and their predictors in the elderly-A systematic review.

Status epilepticus (SE) is associated with high mortality and morbidity. Although SE is frequently seen in elderly patients, there is a lack of a cohesive report of outcome measures and associated factors within this population. Our aim was to systematically review studies reporting outcomes of SE among elderly patients and factors influencing these outcomes. A literature search was conducted in PubMed/MEDLINE, EMBASE, CINAHL Complete, and Cochrane Library from database conception to April 22, 2018. A total of 85 studies were included in this systematic review. The included studies show that mortality is higher in elderly patients than in adult patients. Lesional etiologies, higher number of comorbidities, NCSE, RSE, longer hospital and intensive care unit stays, and infection during hospitalization are associated with poor outcome. Future studies should consider measuring functional outcomes, comparative studies between elderly and adults and AED clinical trials specific for elderly with SE.

Diagnosis of pseudoprogression using MRI perfusion in patients with glioblastoma multiforme may predict improved survival.

AIMS: This retrospective study determined the survival of glioblastoma patients with or without pseudoprogression. METHODS: A total of 68 patients were included. Overall survival was compared between patients showing pseudoprogression (in most cases diagnosed using perfusion MRI with ferumoxytol) and in patients without pseudoprogession. MGMT methylation status was also analyzed in the pseudoprogression cases. RESULTS: Median survival in 24 (35.3%) patients with pseudoprogression was 34.7 months (95% CI: 20.3-54.1), and 13.4 months (95% CI: 11.1-19.5) in 44 (64.7%) patients without pseudoprogression (p < 0.0001). The longest survival was a median of 54.1 months in patients with combination of pseudoprogression and (MGMT) promoter methylation. CONCLUSION: Pseudoprogression is associated with better outcome, especially if concurring with MGMT promoter methylation. Patients never diagnosed with pseudoprogression had poor survival. This study emphasizes the importance of differentiating tumor progression and pseudoprogression using perfusion MRI.

Incidence of Pneumocystis jirovecii pneumonia after temozolomide for CNS malignancies without prophylaxis.

AIMS: Prophylaxis against Pneumocystis jiroveci pneumonia (PJP) is currently recommended for patients receiving chemoradiation with temozolomide for newly diagnosed glioblastoma multiforme. At our institution, PJP prophylaxis during temozolomide treatment has not been routinely given because of the paucity of supporting data. We investigated the rate of PJP infections in our patients. PATIENTS & METHODS: We conducted a retrospective chart review of 240 brain tumor patients treated between 1999 and 2012 with temozolomide and no PJP prophylaxis, 127 of which received concurrent chemoradiation. RESULTS: One in 240 patients (0.4%; 95% CI: 0.01-2.00; median total dose: 7375 mg/m(2); interquartile range: 1300) were diagnosed with PJP. CONCLUSION: There was a <1% rate of PJP for brain tumor patients treated with temozolomide until progression without PJP prophylaxis.

Evaluation of pseudoprogression in patients with glioblastoma multiforme using dynamic magnetic resonance imaging with ferumoxytol calls RANO criteria into question.

BACKGROUND: Diagnosis of pseudoprogression in patients with glioblastoma multiforme (GBM) is limited by Response Assessment in Neuro-Oncology (RANO) criteria to 3 months after chemoradiotherapy (CRT). Frequency of pseudoprogression occurring beyond this time limit was determined. Survival comparison was made between pseudoprogression and true progression patients as determined by using perfusion magnetic resonance imaging with ferumoxytol (p-MRI-Fe). METHODS: Fifty-six patients with GBM who demonstrated conventional findings concerning for progression of disease post CRT were enrolled in institutional review board-approved MRI protocols. Dynamic susceptibility-weighted contrast-enhanced p-MRI-Fe was used to distinguish true progression from pseudoprogression using relative cerebral blood volume (rCBV) values. rCBV of 1.75 was assigned as the cutoff value. Participants were followed up using RANO criteria, and survival data were analyzed. RESULTS: Twenty-seven participants (48.2%) experienced pseudoprogression. Pseudoprogression occurred later than 3 months post CRT in 8 (29.6%) of these 27 participants (ie, 8 [14.3%] of the 56 patients meeting the inclusion criteria). Overall survival was significantly longer in participants with pseudoprogression (35.2 months) compared with those who never experienced pseudoprogression (14.3 months; P < .001). CONCLUSIONS: Pseudoprogression presented after 3 months post CRT in a considerable portion of patients with GBM, which raises doubts about the value of the 3-month time limit of the RANO criteria. Accurate rCBV measurement (eg, p-MRI-Fe) is suggested when there are radiographical concerns about progression of disease in GBM patients, regardless of any time limit. Pseudoprogression correlates with significantly better survival outcomes.

Using iron oxide nanoparticles to diagnose CNS inflammatory diseases and PCNSL.

OBJECTIVE: The study goal was to assess the benefits and potential limitations in the use of ultrasmall superparamagnetic iron oxide (USPIO) nanoparticles in the MRI diagnosis of CNS inflammatory diseases and primary CNS lymphoma. METHODS: Twenty patients with presumptive or known CNS lesions underwent MRI study. Eighteen patients received both gadolinium-based contrast agents (GBCAs) and 1 of 2 USPIO contrast agents (ferumoxytol and ferumoxtran-10) 24 hours apart, which allowed direct comparative analysis. The remaining 2 patients had only USPIO-enhanced MRI because of a renal contraindication to GBCA. Conventional T1- and T2-weighted MRI were acquired before and after contrast administration in all patients, and perfusion MRI for relative cerebral blood volume (rCBV) assessment was obtained in all 9 patients receiving ferumoxytol. RESULTS: USPIO-enhanced MRI showed an equal number of enhancing brain lesions in 9 of 18 patients (50%), more enhancing lesions in 2 of 18 patients (11%), and fewer enhancing lesions in 3 of 18 patients (17%) compared with GBCA-enhanced MRI. Four of 18 patients (22%) showed no MRI enhancement. Dynamic susceptibility-weighted contrast-enhanced perfusion MRI using ferumoxytol showed low rCBV (ratio <1.0) in 3 cases of demyelination or inflammation, modestly elevated rCBV in 5 cases of CNS lymphoma or lymphoproliferative disorder (range: 1.3-4.1), and no measurable disease in one case. CONCLUSIONS: This study showed that USPIO-enhanced brain MRI can be useful in the diagnosis of CNS inflammatory disorders and lymphoma, and is also useful for patients with renal compromise at risk of nephrogenic systemic fibrosis who are unable to receive GBCA.

Delayed intracranial hypertension after cranial vault remodeling for nonsyndromic single-suture synostosis.

OBJECT: Delayed intracranial hypertension may occur after cranial vault remodeling for synostosis and may result in visual loss and developmental delay. Delayed intracranial hypertension is relatively common in children with syndromic, multisuture synostosis, but the incidence is poorly defined in children with single-suture nonsyndromic synostosis. This study evaluates the frequency of reoperation for delayed intracranial hypertension after single-suture synostosis repair. METHODS: Patients who had undergone cranial vault remodeling for nonsyndromic single-suture synostosis and were treated at a single tertiary pediatric hospital between July 2000 and December 2010 were analyzed for the occurrence of delayed intracranial hypertension and reoperation for cranial vault remodeling. RESULTS: Eighty-one patients with clinical follow-up of at least 3 years were analyzed from a total of 156 consecutive patients. The average patient age at the initial operation was 9.1 months. Five (6.2%) of 81 patients presented with delayed clinical and ophthalmological signs and symptoms of intracranial hypertension following initial cranial vault reconstruction, confirmed indirectly in each case by CT findings and directly by intracranial pressure monitoring. These 5 patients underwent repeat cranial vault reconstruction. CONCLUSIONS: Calvarial growth restriction and intracranial hypertension occur sporadically following primary cranial vault reconstruction for single-suture nonsyndromic cranial synostosis. In this series, delayed intracranial hypertension occurred only in male patients who underwent primary repair of isolated sagittal synostoses at an age less than or equal to 5 months.

Motor cortex stimulation for trigeminal neuropathic or deafferentation pain: an institutional case series experience.

BACKGROUND: Trigeminal neuropathy is a rare, devastating condition that can be intractable and resistant to treatment. When medical treatment fails, invasive options are limited. Motor cortex stimulation (MCS) is a relatively recent technique introduced to treat central neuropathic pain. The use of MCS to treat trigeminal neuropathic or deafferentation pain is not widespread and clinical data in the medical literature that demonstrate efficacy are limited. METHOD: We retrospectively reviewed patients with trigeminal neuropathic or trigeminal deafferentation pain who were treated at the Oregon Health & Science University between 2001 and 2008 by 1 neurosurgeon using MCS. RESULTS: Eight of 11 patients (3 male, 8 female) underwent successful permanent implantation of an MCS system. All 8 patients reported initial satisfactory pain control. Three failed to experience continued pain control (6 months of follow-up). Five continued to experience long-term pain control (mean follow-up, 33 months). Average programming sessions were 2.2/year (all 8 patients) and 1.55/year (5 patients who sustained long-term pain control). Patients with anesthesia dolorosa or trigeminal deafferentation pain who had previously undergone ablative trigeminal procedures responded poorly to MCS. We encountered no perioperative complications. CONCLUSION: MCS is a safe and potentially effective therapy in certain patients with trigeminal neuropathy.