Karlo J. Lizarraga

(18)F-FDOPA PET for differentiating recurrent or progressive brain metastatic tumors from late or delayed radiation injury after radiation treatment.

Brain metastases are frequently treated with radiation. It is critical to distinguish recurrent or progressive brain metastases (RPBM) from late or delayed radiation injury (LDRI). The purpose of this study was to examine the diagnostic accuracy as well as the prognostic power of 6-18F-fluoro-l-dopa (18F-FDOPA) PET for differentiating RPBM from LDRI. Methods: Thirty-two patients who had 83 previously irradiated brain metastases and who underwent 18F-FDOPA PET because of an MR imaging–based suggestion of RPBM were studied retrospectively. PET studies were analyzed semiquantitatively (lesion-to-striatum and lesion-to-normal brain tissue ratios based on both maximum and mean standardized uptake values) and visually (4-point scale). The diagnostic accuracy of PET was verified by histopathologic analysis (n = 9) or clinical follow-up (n = 74) on a lesion-by-lesion basis. Receiver operating characteristic curve analysis was used to identify the best diagnostic indices. The power of 18F-FDOPA PET to predict disease progression was evaluated with the Kaplan–Meier and Cox regression methods. Results: The best overall accuracy was achieved by visual scoring, with which a score of 2 or more (lesion uptake greater than or equal to striatum uptake) resulted in a sensitivity of 81.3% and a specificity of 84.3%. Semiquantitative 18F-FDOPA PET uptake indices based on lesion-to-normal brain tissue ratios were significantly higher for RPBM than for LDRI. Among the various predictors tested, 18F-FDOPA PET was the strongest predictor of tumor progression (hazard ratio, 6.26; P < 0.001), and the lesion-to-normal brain tissue ratio or visual score was the best discriminator. The mean time to progression was 4.6 times longer for lesions with negative 18F-FDOPA PET results than for lesions with positive 18F-FDOPA PET results (76.5 vs. 16.7 mo; P < 0.001). 18F-FDOPA PET findings tended to predict overall survival. Conclusion: Metabolic imaging with 18F-FDOPA PET was useful for differentiating RPBM from LDRI. Semiquantitative indices, particularly lesion-to-normal uptake ratios, could be used. A visual score comparing tumor 18F-FDOPA uptake and striatum 18F-FDOPA uptake provided the highest sensitivity and specificity and was predictive of disease progression.

Dengue-associated kidney disease

CONTEXT A mosquito-borne viral illness highly prevalent in the tropics and subtropics, dengue is considered a major global health threat by the World Health Organization. EVIDENCE ACQUISITIONS Directory of Open Access Journals (DOAJ), Google Scholar, PubMed (NLM), LISTA (EBSCO) and Web of Science have been searched. RESULTS An RNA virus from the genus Flavivirus, dengue virus is transmitted by Aedes aegypti,the yellow fever mosquito. Dengue is asymptomatic in as many as one half of infected individuals. Dengue fever is an acute febrile illness accompanied by constitutional symptoms. Dengue hemorrhagic fever and dengue shock syndrome are the severe forms of dengue infection.Dengue infection has been associated with a variety of renal disorders. Acute renal failure is a potential complication of severe dengue infection and is typically associated with hypotension, rhabdomyolysis, or hemolysis. Acute renal failure complicates severe dengue infection in 2-5% of the cases and carries a high mortality rate. Proteinuria has been detected in as high as 74% of patients with severe dengue infection. Hematuria has been reported in up to 12.5% of patients. Various types of glomerulonephritis have been reported during or shortly after dengue infection in humans and mouse models of dengue infection. Mesangial proliferation and immune complex deposition are the dominant histologic features of dengue-associated glomerulonephritis. On a rare occasion, dengue infection is associated with systemic autoimmune disorders involving the kidneys. CONCLUSIONS In the vast majority of cases, dengue infection and associated renal disorders are self-limited.

A systematic review on the role of adjunctive corticosteroids in herpes simplex virus encephalitis: is timing critical for safety and efficacy?

BACKGROUND Most herpes simplex virus encephalitis (HSVE) patients become disabled despite antiviral therapy. Adjunctive corticosteroid therapy may improve outcomes. METHODS This was a systematic review of the literature addressing the use of corticosteroids in HSVE. RESULTS Data suggesting that steroids decrease the immunological response and enhance viral replication originated from non-neural microenvironments. Early steroid administration might be harmful because initial damage in HSVE is mediated by viral replication. Steroid treatment improves outcomes in animal models by inhibiting the subsequent inflammatory response. Clinical observations support a similar benefit in symptomatic HSVE patients. Cerebrospinal fluid inflammatory markers might guide appropriate timing in future clinical practice. CONCLUSIONS Experimental and clinical observations suggest a benefit from adjunctive steroid therapy in HSVE. Nevertheless, current evidence is not yet sufficient to endorse this approach as a standard of practice.

Are Steroids a Beneficial Adjunctive Therapy in the Immunosuppressed Patient with Herpes Simplex Virus Encephalitis

Few reports describe the reactivation of latent herpes simplex virus causing encephalitis (HSVE) in patients undergoing brain radiation therapy and a concomitant steroid regimen. The role for steroid use in the treatment of patients with HSVE has not been fully elucidated. We report the case of a female patient immunosuppressed by steroids and brain radiation who developed HSVE and responded to acyclovir and dexamethasone.

Anti-GBM disease and ANCA during dengue infection.

Anti-glomerular basement membrane (GBM) disease is a severe inflammatory renal disorder due to pathogenic autoantibodies directed mainly against the α3 chain of type IV collagen. In ~1/4 of patients with anti-GBM disease, antineutrophil cytoplasmic antibodies (ANCA) predominantly with myeloperoxidase (MPO) specificity can be detected. Although the inciting stimuli leading to the development of an immune response against the type IV collagen and neutrophils are unknown, evidence indicates that both genetic and environmental factors play a role. Of note, molecular mimicry between self-antigens and nonself-antigens such as antigenic determinants of microorganisms has been implicated in the pathogenesis of anti-GBM disease and ANCA-associated vasculitis. A mosquito-borne viral illness highly prevalent in the tropics and subtropics, dengue can be complicated by acute renal failure, proteinuria, hematuria and glomerulonephritis. We present a 66-year-old woman who was diagnosed with dengue infection and rapidly progressive glomerulonephritis during an outbreak of dengue in Honduras in the summer of 2013. Renal biopsy revealed severe crescentic glomerulonephritis. Immunofluorescence examination demonstrated strong linear IgG deposition along glomerular capillary walls. Serologic tests demonstrated antibodies against GBM, MPO and platelet glycoproteins. The patient was diagnosed with anti-GBM disease associated with p-ANCA with MPO specificity. Despite heavy immunosuppression and plasmapheresis, IgG titers against dengue virus continued to rise confirming the diagnosis of acute dengue infection. We present the first reported case of anti-GBM disease associated with p-ANCA with MPO specificity during dengue infection. This report calls for a heightened awareness of autoimmunity leading to crescentic glomerulonephritis in patients with dengue infection.

18F-fluorodopa positron-emission tomography: an emerging imaging modality for patients with brain metastases

MRI is the preferred method for the diagnosis and monitoring of brain metastases. However, MRI does not provide enough information in some important instances. We explore the potential applications of 18F-fluorodopa (18F-FDOPA) PET for patients with brain metastases. Accurate differentiation between tumor recurrence and radiation injury might be possible with the use of 18F-FDOPA PET. Semi-quantitative and qualitative parameters achieved similar results. Kinetic analysis and time-activity curve patterns could further improve accuracy. 18F-FDOPA PET also had prognostic value in this setting. Combining the high resolution of MRI with the metabolic information provided by 18F-FDOPA PET could improve recurrent tumor contouring precision for biopsy, resection or radiation. The promising applications of 18F-FDOPA PET imaging in the treatment monitoring and planning of brain metastatic tumors require further corroboration but could soon become important instruments to improve diagnostic accuracy, prognosis prediction and treatment planning of the growing population of patients with brain metastatic disease.

Severe mononeuritis multiplex after rituximab in IgM-κ monoclonal gammopathy

Gammopathies are disorders associated with B-cell proliferation. Monoclonal gammopathy of uncertain significance (MGUS), in which this proliferation is nonneoplastic, is observed in up to 7.5% of the elderly population. Immunoglobulin M (IgM)-MGUS may evolve into the B-cell malignancy Waldenstr€ om macroglobulinemia (WM), potentially requiring more aggressive treatment. The prevalence of neuropathy in gammopathies is about 10%, which can increase to 30% in patients with j light chain of immunoglobulin M (IgM-j)-MGUS. Distal acquired demyelinating symmetric neuropathy is associated with IgM-j-MGUS and myelin-associated glycoprotein (MAG) antibodies in > 50% of cases. Although MAG antibodies are considered a causative factor, the pathogenic significance of anti–MAG-negative IgM is less clear in patients with neuropathy. Rituximab is a chimeric murine-human monoclonal antibody against CD20 that results in sustained B-cell depletion. Plasma cells, which retain the ability to produce antibodies, are not targeted by rituximab. Although rituximab was found safe and possibly effective for anti–MAG-positive IgM-associated demyelinating neuropathy in 2 clinical trials, worsening neuropathy of unclear mechanism has been reported. The safety and efficacy of rituximab in anti–MAG-negative IgM neuropathy is even less clear. We report a case of mild axonal sensory neuropathy associated with anti–MAG-negative IgM-j-MGUS that progressed to severe mononeuritis multiplex in the setting of accelerated immune complex deposition after rituximab.