Postinfectious Process Research Articles

Mielitis transversa aguda asociada con infección por SARS-CoV-2

In addition to causing respiratory problems, SARS-CoV-2 can cause a wide spectrum of neurological complications such as headaches, ageusia, anosmia, encephalopathy, cerebrovascular disease, Guillain-Barré syndrome and other polyneuropathies, meningoencephalitis, acute necrotizing hemorrhagic encephalopathy, and central nervous system syndromes associated with inflammation. In this review we present 39 cases of acute transverse myelitis (ATM) associated to SARS-CoV-2 infection. All cases had a positive polymerase chain reaction (PCR) nasopharyngeal swab and/or antigen test. Biochemical analyses confirmed the absence of other pathogens and autoantibody-mediated neuroinflammatory disease, except for two cases, one with autoantibodies against the oligodendrocyte myelin glycoprotein (anti-MOG IgG) and another with anti-MOG IgG and anti-glutamic acid decarboxylase (anti-GAD65). Magnetic Resonance Imaging (MRI) studies confirmed the diagnosis of ATM. Although causality cannot be inferred, it is likely that isolated cases of ATM are the consequence of a para or post-infectious process in SARS-CoV-2. In this work, the probable causes of ATM associated with SARS-CoV-2 are discussed. The understanding of the mechanisms behind these neurological disorders triggered by a viral infection will help to optimize the therapeutic strategies for patient management. Keywords: SARS-CoV-2; COVID-19; transverse myelitis; long COVID; demyelination; nervous system.

Guillain Barre Syndrome as a Presentation of post Covid-19 Infection among Children: A Case Series

During the second wave of Covid-19 pandemic, children presented with myriad of central nervous system manifestations and one of them was Guillain-Barré syndrome (GBS). It is caused by various viruses including recent Covid-19 infection by either direct invasion or post infectious process. Most of these cases were reported in adults and very few in children. Here, we report a case series of five children with GBS along with positive Covid-19 antibodies, probably first from India. All patients responded well to intravenous immunoglobulin without any residual weakness. Hence, we could probably link casual association of Covid-19 infection with GBS.

Клинико-лабораторные аспекты реактивных тромбоцитозов у детей

To determine the cause of thrombocytosis in the peripheral blood, the results of laboratory studies of children aged 8–15 years in two observation groups were analyzed: a) children with clinical manifestations of sinusitis after acute respiratory viral infections (12 people) b) children with reduced hemoglobin levels in peripheral blood (20 people ). Unified and automated hematological and biochemical research methods were carried out. Two main causes of thrombocytosis were established in the observation groups: the presence of a post-infectious inflammatory process, which was laboratory confirmed by an increase in acute-phase C-reactive protein in the blood serum; the presence of iron deficiency hypochromic anemia, which was laboratory confirmed by a decrease in serum iron and a decrease in hemoglobin in peripheral blood

The pathogenesis of neurologic symptoms of the postacute sequelae of severe acute respiratory syndrome coronavirus 2 infection.

The coronavirus disease 2019 (COVID) pandemic has resulted in significant mortality and morbidity globally. Patients who survive infection may develop continuing disease collectively known as the postacute sequelae of severe acute respiratory syndrome coronavirus 2 infection (PASC), which includes neurologic symptoms especially fatigue and cognitive impairment. The pathogenic mechanisms driving PASC are unknown although a postinfectious process, persistent infection, or lasting pathophysiological changes that occur during acute infection are all suspected to contribute. Here we review the current evidence underlying potential pathogenic mechanisms of the neurological complications of PASC with particular emphasis on the evidence for postinfectious immune processes and viral persistence. Immune dysregulation favoring persistent inflammation, including neuroinflammation and enhanced autoimmunity, are present in patients with COVID and likely contribute to the development of PASC. Limited evidence of viral persistence exists but may explain the ongoing inflammatory processes and affinity maturation observed in some patients recovering from COVID infections. No specific studies to date have tied persistent infection to PASC. CNS trauma, in particular hypoxic changes in the CNS, and psychiatric complications occur with greater frequency in patients with COVID and may contribute to the development of PASC. Future research is needed to fully understand the pathophysiological mechanisms driving PASC.

SARS-CoV-2-associated Guillain-Barré syndrome in four patients: what do we know about pathophysiology?

BackgroundA growing number of Guillain–Barré syndrome (GBS) and Miller Fisher Syndrome (MFS) cases following severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection are reported. Nevertheless, this association is still debated, and pathophysiology remains unclear.MethodsBetween April and December 2020, in three hospitals located in Brussels, Belgium, we examined four patients with GBS following SARS-CoV-2 infection.Results Neurological onset occurred 3 weeks after SARS-CoV-2 symptoms in all patients. Three patients presented with acute inflammatory demyelinating polyneuropathy (AIDP) and had negative anti-ganglioside testing: two suffered from a severe SARS-CoV-2 infection and had good clinical outcome after intravenous immunoglobulin (IVIG) treatment; one with mild SARS-CoV-2 infection had spontaneously favorable evolution without treatment. The fourth patient had critical SARS-CoV-2 infection and presented acute motor and sensory axonal neuropathy (AMSAN) with clinical features highly suggestive of brainstem involvement, as well as positive anti-ganglioside antibodies (anti-GD1b IgG) and had partial improvement after IVIG.ConclusionsWe report four cases of SARS-CoV-2-associated GBS. The interval of 3 weeks between SARS-CoV-2 symptoms and neurological onset, the clinical improvement after IVIG administration, and the presence of positive anti-ganglioside antibodies in one patient further support the hypothesis of an immune-mediated post-infectious process. Systematic extensive antibody testing might help for a better understanding of physiopathology.Supplementary InformationThe online version contains supplementary material available at 10.1007/s13760-021-01787-y.

Incidence rate of MIS-C in paediatrics: A good reason to vaccinate children against SARS-CoV-2.

Vaccines are a fundamental weapon against a number of infections that may cause severe disease or sequelae, both in the absence or presence of etiologic therapy, or have a high socio-economic impact in terms of hospital admissions or requests for medical examination. COVID-19, a serious infection due to SARS-CoV-2, exemplifies all these characteristics. In Italy, paediatric SARS-CoV-2 infection presented in most cases with few symptoms or even in asymptomatic form, although nearly 20% of children enrolled in a nationwide registry developed complications, especially in the presence of comorbidities.1 However, in some children and adolescents, SARS-CoV-2 infection was associated with the so-called multisystemic inflammatory disease (MIS-C), which required hospitalisation and therapies. MIS-C is thought to be caused by a postinfectious inflammatory process and manifests clinically with signs and symptom like those of Kawasaki disease (KD) but is also marked by clinical manifestations unusual in KD, particularly gastrointestinal complaints and myocarditis, often leading to myocardial failure and shock.2 Despite the occurrence of this potentially life-threatening condition because of the general notion of a modest clinical severity of COVID-19 in paediatrics, especially when compared with its massive impact in adults, the opinion that SARS-CoV-2 ‘does not harm children’ has become widespread among doctors and, consequently, in the mass media and public opinion. This has led to an increase in perplexity, especially among families, regarding the need to vaccinate children against SARS-CoV-2. To investigate whether this impression of the absence of serious illness was supported by epidemiological data, we evaluated the rate of MIS-C per 100 000 (DR) residents <19 years of Liguria, a region located in northwest Italy. On January 1st 2021, Liguria had a total of 1 509 805 residents, with 214 395 <19 years.3 From March 2020 to June 2021, all cases of MIS-C observed in the region were centralised, and 22 patients were diagnosed according to predefined criteria for MIS-C2 (although seven of them also met the American Heart Association criteria for KD),4 leading to a DR of 10.3. Noteworthy, there were 10 (45%) patients with myocardial disfunction, 6 (60%) of them with an ejection fraction <50%. Moreover, 4 (18%) of patients underwent abdominal surgery for suspect acute appendicitis, which eventually was not confirmed by laparotomy. To compare the frequency of SARS-CoV-2-related MIS-C with other severe infections observed in the same age group, we evaluated the DR of tuberculosis and invasive disease due to Neisseria meningitidis, starting from episodes recorded in a regional registry in the period 2007–2020. The mean number of episodes per year was 5 (range 1–14) for tuberculosis and 3 (range 0–7) for invasive meningococcal disease. Figure 1 reports the DR for the three conditions. The DR for tuberculosis and invasive meningococcal disease are very similar, whereas that for MIS-C is about 5- to 10-fold higher. The major weakness of this analysis is that the DR for tuberculosis and meningococcal infection could be somewhat inaccurate, considering the method used for their estimation. However, we believe that the possible reduced accuracy in the calculation of DR for these two diseases should not significantly change the order of magnitude of the rates and, therefore, the difference with MIS-C. In conclusion, our data show that although children rarely develop severe COVID-19, they have a significant risk of developing a serious and potentially life-threatening condition secondary to a delayed, immune-mediated reaction to SARS-CoV-2, with rates higher than those of other serious paediatric infections. Importantly, the long-term outcome of MIS-C is still unclear, and the risk of residual cardiac damage is not yet established. In our opinion, in addition to the general need to interrupt the chain of contagion, the high DR for MIS-C and its unknown long-term consequences represent important reasons for carrying out anti-COVID vaccination in children and adolescents. Open Access Funding provided by Universita degli Studi di Genova within the CRUI-CARE Agreement. The authors declare no conflict of interest.

COVID-19-associated multisystem inflammatory syndrome in children presenting uniquely with sinus node dysfunction in the setting of shock

SARS-CoV-2, which causes the disease COVID-19, generally has a mild disease course in children. However, a severe post-infectious inflammatory process known as multisystem inflammatory syndrome in children has been observed in association with COVID-19. This inflammatory process is a result of an abnormal immune response with similar clinical features to Kawasaki disease. It is well established that multisystem inflammatory syndrome in children is associated with myocardial dysfunction, coronary artery dilation or aneurysms, and occasionally arrhythmias. The most common electrocardiographic abnormalities seen include premature atrial or ventricular ectopy, variable degrees of atrioventricular block, and QTc prolongation, and rarely, haemodynamically significant arrhythmias necessitating extracorporeal membrane oxygenation support. However, presentation with fever, hypotension, and relative bradycardia with a left axis idioventricular rhythm has not been previously reported. We present a case of a young adolescent with multisystem inflammatory syndrome in children with myocarditis and a profoundly inappropriate sinus node response to shock with complete resolution following intravenous immunoglobulin.

Multisystem inflammatory syndrome in children (MIS-C) and COVID-19: a review of the literature

Multisystem Inflammatory Syndrome in Children (MIS-C) is a novel pediatric hyperinflammatory syndrome that has recently emerged globally as a potential complication of COVID-19 infection and has features similar to Kawasaki Disease (KD). In this article, a review existing literature on MIS-C was conducted to identify trends in patient characteristics, clinical and biological features, treatment, and outcomes. MIS-C affects previously healthy school-age children, with over-representation of those of Black and Afro-Caribbean descent. It presents with fever, gastrointestinal complaints, and KD-type features including rash and conjunctivitis. Laboratory and imaging studies demonstrate evidence of systemic inflammation and myocarditis. Accordingly, children are often critically ill and require intensive care admission and organ support. However, prompt anti-inflammatory treatment with intravenous immunoglobulin, steroids, and aspirin appears to lead to favourable outcomes. Though evidence of current coronavirus infection by RT-PCR is variable, most children have positive serology results indicating prior infection, which supports theories of MIS-C as a dysfunctional post-infectious immune process. Though similar to KD in some ways, MIS-C has important differences in its patient characteristics, clinical features, and cardiac involvement. Large-scale case registries and analysis of resulting data will be crucial to refining our understanding of MIS-C to ensure optimal outcomes for children worldwide.

Encephalitis Associated with COVID-19 Infection in an 11-Year-Old Child

Neurological complications associated with COVID-19 infection are not well understood in children or adults. An adult with acute necrotizing encephalitis associated with COVID-191Yeh E.A. Collins A. Cohen M.E. et al.Detection of coronavirus in the central nervous system of a child with acute disseminated encephalomyelitis.Pediatrics. 2004; 113: e73-e76Crossref PubMed Scopus (219) Google Scholar and a child with acute disseminated encephalomyelitis and non-COVID coronavirus2Poyiadji N. Shahin G. Noujaim D. et al.COVID-19-associated acute necrotizing encephalopathy: CT and MRI features.Radiology. 2020; : 201187Crossref PubMed Scopus (927) Google Scholar have been reported. The infection is typically mild in children, and no neurological complications were reported in the 171 children from Wuhan Children’s Hospital.3Lu X. Zhang L. Du H. et al.SARS-CoV-2 infection in children.N Engl J Med. 2020; 382: 1663-1665Crossref PubMed Scopus (1578) Google Scholar In preliminary data from US cases, headache was the only neurological symptom.4CDC COVID-19 Response TeamCoronavirus disease 2019 in children – United States, February 12-April 2, 2020.MMWR Morb Mortal Wkly Rep. 2020; 69: 422-426Crossref PubMed Scopus (0) Google Scholar We describe an 11-year-old previously well child who presented with status epilepticus requiring four anticonvulsant medications and cerebrospinal fluid evidence for encephalitis (921 red cells, 16 white cells, 8% neutrophils [normal 0% to 6%] with protein of 97 [normal: 40 to 170 mg/dL], and glucose of 92 [normal: 20 to 100 mg/dL]). He had a two-day history of generalized weakness without respiratory symptoms or fever at home; emergency room temperature was 102.7°F. Head computed tomography was negative. Electroencephalography revealed frontal intermittent delta activity. Nasopharyngeal swab was positive for COVID-19 as well as rhinovirus/enterovirus but the latter was absent in cerebrospinal fluid polymerase chain reaction. Recovery without treatment was complete in six days. We believe this is the first child reported with COVID-19 viral encephalitis, and the condition was reversible. How coronavirus affects the brain is not known. This child’s findings suggest that direct brain infection may be possible. An autoimmune process may also be possible. The acuteness of our patient’s neurological manifestations coupled with the occurrence of fever and generalized systemic weakness mitigates against a postinfectious process. Because the virus binds the surface spike protein to the human angiotensin-converting enzyme 2 receptor (ACE-2) and ACE-2 is present in the brain vascular endothelium, a vascular process with clotting and infarction may also be possible, although this was not the mechanism in our patient.5Clerkin K.J. Fried J.A. Raikhelkar J. et al.Coronavirus disease 19 (Covid-19) and cardiovascular disease.Circulation. 2020; 141: 1648-1655Crossref PubMed Scopus (964) Google Scholar, 6Zhang Y. Xiao M. Zhang S. et al.Coagulopathy and antiphospholipid antibodies in patients with Covid-19.N Engl J Med. 2020; 382: e38Crossref PubMed Scopus (1408) Google Scholar, 7Jiang T. Gao L. Lu J. et al.ACE2-Ang-(1-7)-Mas axis in brain: a potential target for prevention and treatment of ischemic stroke.Curr Neuropharm. 2013; 11: 209-217Crossref PubMed Scopus (91) Google Scholar Although preliminary, we recommend screening children presenting with encephalitis for COVID-19 as infected patients require special precautions to prevent further spread.

(287) Interscalene Brachial Plexus Block with Dexamethasone for Treatment of Parsonage-Turner Syndrome

CD is an 83y M with a history of COPD, non-Hodgkin lymphoma, and lung CA who presented with acute onset non-dermatomal left arm pain. The patient had developed a viral infection 2 weeks prior, and soon after developed left shoulder and arm pain. Imaging and labs did not show rheumatologic, infectious, or cervical nerve cause, however EMG was consistent with brachial plexopathy. A presumptive diagnosis of Parsonage-Turner syndrome was made, and conservative measures were initiated. Unfortunately, the patient did not note improvement with medications, PT, or TENS unit. He was then scheduled for an ultrasound-guided interscalene brachial plexus nerve block with Bupivacaine and Dexamethasone. After the injection, the patient noted > 50% improvement in pain and was able to better participate in physical therapy and significantly increased functionality of his upper extremity. Parsonage-Turner syndrome is a rare autoimmune neuropathy of the brachial plexus, most commonly affecting the upper trunk. It is idiopathic in nature, however may be linked to a post-infectious or post-immunization process. It often presents as acute onset neck, shoulder and arm pain which can progress to weakness, and may often be confused with cervical radiculopathy or thoracic outlet syndrome. Common physical exam features include a slight winging of the scapula, as well as the potential for motor weakness and loss of sensation that does not follow a dermatomal pattern. Imaging, including CT/MRI or plain film, is not always helpful in diagnosis. However, electrodiagnostic testing such as EMG can usually localize the defect to the root level. Conservative therapies are the gold standard for treatment, however some evidence points to improvement with systemic steroids. We believe targeted steroid injections can be an effective therapy for Parsonage Turner Syndrome.

353. HSV-Induced Anti-NMDAR Encephalitis

Background N-Methyl-d-aspartate receptor (NMDAR) is a glutamate receptor on nerve cells that controls synaptic plasticity and memory function. Anti-NMDAR encephalitis is a rare autoimmune disease causes by antibodies (Ab) against GluN1 subunit of the NMDAR. Preceding Herpes simplex virus-1 encephalitis (HSVE) is a well-recognized infectious trigger. First reported in female patients with ovarian teratoma, and more recently with germ cell tumors in males.MethodsA 61-year-old male presented with agitation, behavioral changes, and confusion. Eight months prior, he was diagnosed with HSVE and treated with 21 days of intravenous acyclovir. Following therapy, he suffered from residual cognitive and personality changes with slow recovery until 3 months prior to admission encephalopathy again worsened. An extensive investigation was unrevealing except for a CSF lymphocytic pleocytosis, positive anti-NMDAR Ab titer 1:64 and imaging changes consistent with post-viral encephalitis. At that point, HSV-induced anti-NMDAR encephalitis was diagnosed. A PET scan did not show any occult malignancies. Two cycles of plasmapheresis were attempted over 4 months period with limited success in improving his worsening neurologic deficits.ResultsHSVE induced autoimmune encephalitis is a rare complication, primarily affecting children and young adults. Auto Ab develop 1–4 weeks after HSVE, manifesting as choreoathetosis and/or orofacial dyskinesia in children and psychiatric symptoms in young adults. CSF Ab titer is highly sensitive and specific. Proposed mechanisms include either viral reactivation or a post-infectious autoimmune process. Immunotherapy with tumor resection (if present) has been promising with less frequent need for second-line therapy in primary condition, compare with HSVE-induced condition where tumors have not been reported and resistance to first-line therapy has been observed. Progressive decline in neurologic function post HSVE prompted an evaluation for paraneoplastic conditions in our patient that ultimately revealed the diagnosis. The unique feature of this case is the age of the patient and preceding HSVE which triggered this autoimmune process.ConclusionPhysicians should consider anti-NMDAR encephalitis in the differentials for relapsing patients post HSVE.Disclosures All authors: No reported disclosures.

Emergence and treatment of chikungunya arthritis.

To review the emergence, clinical features, pathogenesis, and treatment of acute chikungunya (CHIK) fever and chronic CHIK arthritis. Since 2004, CHIK, an arboviral infection, has spread throughout the world, infecting millions of people. The illness occurs in two phases: an acute viremic infection followed by chronic arthritis. In less developed countries, there are limited resources and effective treatment. For acutely ill CHIK fever patients, management is symptomatic. The treatment of chronic CHIK arthritis should be determined by an understanding of pathogenesis. Is chronic CHIK arthritis a persistent viral infection or a postinfectious inflammatory process? Multiple proinflammatory cytokines, chemokines, and growth factors have been identified in chronic CHIK arthritis. Attempts to isolate CHIK virus from synovial fluid have been unsuccessful. Given pathogenetic similarities (as well as differences) compared with rheumatoid arthritis and the painful, disabling nature of the arthritis, it is not surprising that disease-modifying antirheumatic drugs such as methotrexate have begun to be used. CHIK infection has emerged with major arthritic epidemics for which evidence-based therapy is limited. But there is an opportunity to improve the treatment of chronic CHIK arthritis and, from this disease, to gain understanding of the pathogenesis and treatment of inflammatory arthritis more generally.

Gastroparesis: A Review of Current Diagnosis and Treatment Options.

Gastroparesis (GP) is a chronic neuromuscular disorder of the upper gastrointestinal tract. The incidence of GP is not well described; however, the number of individuals affected by symptoms of GP in the United States is estimated to be over 4 million. The etiology of GP is diverse. Approximately 25% of cases are associated with diabetes, whereas nearly 50% are classified as idiopathic; many of these latter cases likely represent a postinfectious process. Connective tissue disorders, autoimmune disorders, prior gastric surgery, ischemia, and medications make up the vast majority of the remaining cases. The pathophysiology of GP is also diverse. Abnormalities in fundic tone, antroduodenal dyscoordination, a weak antral pump, gastric dysrhythmias, and abnormal duodenal feedback all contribute to delays in gastric emptying and symptom expression. Characteristic symptoms of GP include nausea, vomiting, epigastric pain, early satiety, and weight loss. The diagnosis of GP is made using a combination of characteristic symptoms in conjunction with objective evidence of delayed gastric emptying in the absence of mechanical obstruction. Once the diagnosis is made, treatment options include dietary modification, medications to accelerate gastric emptying, antiemetic agents, gastric electrical stimulation, and surgery. In the following sections we will provide an overview of the health care impact of GP, describe the underlying pathophysiology, and review treatment options using an evidence-based approach.

Severe necrotizing myelopathy from toxacariasis

We present a 25 year old female veterinarian technician presenting with rapidly progressive quadriplegia in less then 12 hours. Her symptoms occurred at work with initially bilateral hand weakness followed by arm and leg weakness. Before the end of the day she was on a ventilator in the ICU. MRI showed a hyperintense longitudinal T2 signal extending from the cervical medullary junction to T1. Extensive cervical spinal cord edema with cord expansion was noted. CSF showed normal protein and cell count with no oligoclonal banding. A post-infectious inflammatory process causing transverse myelitis was presumed and she was given IVIG, steroids, and plasmapheresis with no improvement. A serum ELISA test for IgG to Toxocara was reactive at titre of 1:800 at 3 weeks after her initial presentation. Her serum IgE levels was elevated at 169 x 10x3 U/L (Normal &lt;87 x 10x3 U/L). At 4 weeks, she was commenced on albendazole at 800 mg per day for two months. A repeat serum ELISA test at 6 weeks and 2 weeks into her treatment with albendazole showed a declining titre of 1:200 consistent with recent Toxocara infection. At 10 weeks, her ELISA test was non-reactive. Unfortunately she did not respond to albendazole treatment and she shows minimal improvement now 1.5 years later.

Corticosteroids may favor proliferation of thoracic inflammatory myofibroblastic tumors

Inflammatory myofibroblastic tumor (IMT) was thought to represent a benign post-infectious or post-inflammatory process cured by surgical resection. However, reports of cases with an aggressive clinical course suggest the need for caution about the prognosis. The treatment of choice is a complete surgical resection, while medical treatment options are limited. Corticosteroid therapy has been used with some success in unresectable lesion. However, rapid progression of lung IMT after prednisone treatment has been reported, raising the hypothesis that corticosteroids may favor a tumultuous proliferation of this lesion, possibly through immunosuppression. We here report a similar observation and suggest that other mechanisms may be involved. A 5-year and 6-month-old boy presented with a 72 hr history of breathlessness, initially responsive to albuterol and prednisone. He represented 15 days later with increasing symptoms despite further prednisone treatment. CT chest scan showed a mass lesion in the tracheal lumen, which on biopsy was found to be an IMT. The possibility that prednisone may have an enhancing effect on IMT cell proliferation is demonstrated through IMT cell culture and discussed.

HMGB1 blockade attenuates experimental autoimmune myocarditis and suppresses Th17‐cell expansion

High-mobility group box 1 (HMGB1), a non-histone nuclear protein, has been implicated in cardiovascular diseases. Dilated cardiomyopathy (DCM), one of the leading causes of heart failure, is often caused by coxsackievirus B3-triggered myocarditis and promoted by the post-infectious autoimmune process. Th17 cells, a novel CD4(+) T subset, may be important in the pathogenesis of autoimmune myocarditis. In the present study, we attempted to block HMGB1 function with a monoclonal antibody specific for HMGB1 B box and investigated the effects of the blockade on Th17 cells and experimental autoimmune myocarditis (EAM). After induction of EAM, HMGB1 protein levels were significantly elevated both in the heart and blood. Administration of an anti-HMGB1 B box mAb attenuated cardiac pathological changes and reduced the number of infiltrating inflammatory cells in the heart during EAM. These protective effects of HMGB1 blockade correlated with a reduced number of Th17 cells in local tissues and lower levels of IL-17 in the serum. Furthermore, in vitro, studies demonstrated that HMGB1 promoted Th17-cell expansion. Therefore, we speculate that HMGB1 blockade ameliorates cardiac pathological changes in EAM by suppressing Th17 cells.

O-(2-18F-Fluoroethyl)-L-Tyrosine PET Predicts Failure of Antiangiogenic Treatment in Patients with Recurrent High-Grade Glioma

The objective of this study was to compare MRI response assessment with metabolic O-(2-(18)F-fluoroethyl)-L-tyrosine ((18)F-FET) PET response evaluation during antiangiogenic treatment in patients with recurrent high-grade glioma (rHGG). Eleven patients with rHGG were treated biweekly with bevacizumab-irinotecan. MR images and (18)F-FET PET scans were obtained at baseline and at follow-up 8-12 wk after treatment onset. MRI treatment response was evaluated by T1/T2 volumetry according to response assessment in neurooncology (RANO) criteria. For (18)F-FET PET evaluation, an uptake reduction of more than 45% calculated with a standardized uptake value of more than 1.6 was defined as a metabolic response (receiver-operating-characteristic curve analysis). MRI and (18)F-FET PET volumetry results and response assessment were compared with each other and in relation to progression-free survival (PFS) and overall survival (OS). At follow-up, MR images showed partial response in 7 of 11 patients (64%), stable disease in 2 of 11 patients (18%), and tumor progression in 2 of 11 patients (18%). In contrast, (18)F-FET PET revealed 5 of 11 metabolic responders (46%) and 6 of 11 nonresponders (54%). MRI and (18)F-FET PET showed that responders survived significantly longer than did nonresponders (10.24 vs. 4.1 mo, P = 0.025, and 7.9 vs. 2.3 mo, P = 0.015, respectively). In 4 patients (36.4%), diagnosis according to RANO criteria and (18)F-FET PET was discordant. In these cases, PET was able to detect tumor progression earlier than was MRI. In rHGG patients undergoing antiangiogenic treatment, (18)F-FET PET seems to be predictive for treatment failure in that it contributes important information to response assessment based solely on MRI and RANO criteria.

Influenza-Associated Encephalopathy With Elevated Antibody Titers to Pandemic (H1N1) 2009 Influenza

Pandemic H1N1 influenza (pH1N1) has been associated with encephalopathy, but the role of adaptive immunity in disease pathogenesis remains unclear. A child presented with seizures 5 days after onset of respiratory symptoms with pH1N1, with no detectable virus in cerebrospinal fluid. The authors compared her serum cytokines and pH1N1 antibody titers to those of 22 children with pH1N1, seasonal influenza, or other respiratory viral infections. They also compared her cerebrospinal fluid biomarkers to those of 20 children with confirmed or probable central nervous system infection or viral infection without central nervous system involvement. Her serum antibody titers were several-fold higher, and levels of proinflammatory cytokines in cerebrospinal fluid and serum were lower than those of controls. Antibody titers in cerebrospinal fluid were undetectable. The delayed onset of neurologic manifestations, normal cytokine levels in serum and cerebrospinal fluid, markedly elevated hemagglutinating and neutralizing antibody titers, and absence of virus and antibodies in cerebrospinal fluid raise the possibility of a post-infectious autoimmune-mediated process.

Post-infectious new daily persistent headache may respond to intravenous methylprednisolone

New daily persistent headache (NDPH) is a subtype of chronic daily headache (CDH) that starts acutely and continues as a daily headache from the onset. It is considered as one of the most treatment refractory of all headache syndromes. The pathophysiology is largely unknown. Viral infections, extracranial surgery, and stressful life events are considered as triggers for the onset of NDPH. A few patients may have the onset of their symptoms during an infection. Here we report nine patients with NDPH like headache. All of them had a history suggestive of extracranial infections a few weeks prior to the onset of headache. All patients received intravenous methyl prednisolone (IV MPS) for 5 days. Intravenous MPS was followed by Oral steroids for 2–3 weeks in six patients. The relief of headache started between the second and fifth days of infusion in all patients. The steady improvement in headache continued and seven patients experienced almost complete improvement within 2 weeks. Two other patients showed complete improvement between 6 and 8 weeks after initiation of IV MPS therapy. We conclude that NDPH-like headache may occur as a post infectious process following a recent infection. We also speculate on the possible mechanisms of headache in our patients.

Neurologic dengue manifestations associated with intrathecal specific immune response

Dengue infection is caused by a flavivirus, with 4 virus serotypes (types 1 to 4). The serotypes 2 and 3 represent the principal agents related to nervous system involvement. Neurologic involvement occurs in 4%-5% of dengue infection cases. The major mechanisms of the disease may be related to direct viral infection or postinfectious autoimmune process. The detection of intrathecal synthesis of specific antibodies has been used to support neurologic diagnosis as a proof of local reaction. It may be quantitatively calculated by the specific antibody index. To determine if patients with neurologic manifestations associated with dengue produce specific antibodies in the CNS and to determine the antibodies' clinical and pathophysiologic relevance. CSF and serum were evaluated for dengue immunoglobulin M (IgM) and immunoglobulin G (IgG) antibodies by ELISA and for intrathecal synthesis of IgG antibodies to the dengue virus. Subjects included 10 patients IgM seropositive for dengue virus diagnosed with myelitis, encephalitis, optic neuromyelitis, or Guillain-Barré syndrome. All patients had IgG and IgM antibodies to dengue virus in their sera; 7 were IgM positive and 9 were IgG positive for dengue virus in CSF. Only the 3 patients with myelitis had intrathecal synthesis of specific IgG antibodies. Intrathecal synthesis of antibodies to dengue virus occurs in the CNS. It may be used as a marker of myelitis associated with dengue, and it seems to be related to the pathogenesis of spinal cord disease due to direct viral invasion.