Anti–N‐methyl‐D‐aspartate receptor encephalitis: A newly recognized inflammatory brain disease in children

Objective

Anti–N‐methyl‐D ‐aspartate receptor (anti‐NMDAR) encephalitis is a newly recognized antineuronal antibody–mediated inflammatory brain disease that causes severe psychiatric and neurologic deficits in previously healthy children. The present study was undertaken to describe characteristic clinical features and outcomes in children diagnosed as having anti‐NMDAR encephalitis.

Methods

Consecutive children presenting over a 12‐month period with newly acquired psychiatric and/or neurologic deficits consistent with anti‐NMDAR encephalitis and evidence of central nervous system (CNS) inflammation were screened. Children were included in the study if they had confirmatory evidence of anti‐NMDAR antibodies in the serum and/or cerebrospinal fluid. Features at clinical presentation and results of investigations were recorded. Type and duration of treatment and outcomes at last followup were documented.

Results

Seven children were screened, and 3 children with anti‐NMDAR encephalitis were identified. All patients presented with neurologic and/or psychiatric abnormalities, seizures, speech disorder, sleep disturbance, and fluctuating level of consciousness. The 2 older patients had more prominent psychiatric features, while the younger child had significant autonomic instability and prominent involuntary movement disorder. None had an underlying tumor. Immunosuppressive therapy resulted in near or complete recovery; however, 2 of the patients had early relapse necessitating re‐treatment.

Conclusion

Anti‐NMDAR encephalitis is an important cause of neuropsychiatric deficits in children, which must be included in the differential diagnosis of CNS vasculitis and other inflammatory brain diseases. Early diagnosis and treatment are essential for neurologic recovery.

     

Angiography-negative primary central nervous system vasculitis in children: a newly recognized inflammatory central nervous system disease

Inflammatory central nervous system (CNS) diseases in childhood comprise a wide spectrum of heterogeneous conditions. We studied 4 children with primary CNS vasculitis in whom results of magnetic resonance imaging studies were abnormal but results of conventional angiography were normal. We determined that angiography-negative, biopsy-confirmed primary small-vessel CNS vasculitis is a previously unrecognized distinct disease entity in children. The diagnosis must be considered in a child with a progressive, acquired diffuse or focal neurologic deficit, even if the results of conventional angiography are normal. A lesional brain biopsy is required to confirm the diagnosis. Use of immunosuppressive therapy plus aspirin leads to an excellent neurologic outcome.     

Angiography‐negative primary central nervous system vasculitis in children: A newly recognized inflammatory central nervous system disease

Inflammatory central nervous system (CNS) diseases in childhood comprise a wide spectrum of heterogeneous conditions. We studied 4 children with primary CNS vasculitis in whom results of magnetic resonance imaging studies were abnormal but results of conventional angiography were normal. We determined that angiography‐negative, biopsy‐confirmed primary small‐vessel CNS vasculitis is a previously unrecognized distinct disease entity in children. The diagnosis must be considered in a child with a progressive, acquired diffuse or focal neurologic deficit, even if the results of conventional angiography are normal. A lesional brain biopsy is required to confirm the diagnosis. Use of immunosuppressive therapy plus aspirin leads to an excellent neurologic outcome.     

Monocytic fasciitis: a newly recognized clinical feature of tumor necrosis factor receptor dysfunction

Tumor necrosis factor receptor-associated periodic syndrome (TRAPS) is a dominantly inherited autoinflammatory syndrome that results from mutations in TNFRSF1A, the gene that encodes the 55-kd tumor necrosis factor receptor. Clinically, patients present with recurrent episodes of fever in conjunction with localized inflammation at various sites. Myalgia is one of the most characteristic features of this syndrome and is frequently associated with an overlying erythematous, macular rash that, together with the myalgia, displays centrifugal migration. This has previously been believed to occur as a result of myositis. We describe herein the case of a 60-year-old man with TRAPS, in whom magnetic resonance imaging of the left thigh demonstrated edematous changes in the muscle compartments and surrounding soft tissues. A full-thickness wedge biopsy was performed, and hematoxylin and eosin staining and immunohistochemistry analysis of the specimen demonstrated normal myofibrils but a severely destructive monocytic fasciitis. These results suggest that the myalgia experienced by individuals with TRAPS is due to a monocytic fasciitis and not to myositis.     

Scedosporium inflatum: clinical spectrum of a newly recognized pathogen

The clinical course of 11 patients is reported: a newly-described species, Scedosporium inflatum, was isolated from each. Infections were primarily focally invasive and involved musculoskeletal tissues. All but one followed penetrating trauma, often minor, or surgery. Two cases, one fatal, occurred in immunosuppressed patients. In only one case was there presumptive hematogenous spread. In three cases colonization with S. inflatum could not reliably be distinguished from infection. In vitro susceptibility testing of isolates from all patients showed that all were resistant to amphotericin B, miconazole, and ketoconazole and most were resistant to fluconazole and itraconazole. The optimum management of S. inflatum infection is not apparent: Although several patients recovered without antifungal therapy, progressive unremitting infection occurred in an immunocompromised patient and in a previously healthy child despite aggressive antifungal chemotherapy and surgical debridement.     

Whipple's disease: a curable encephalitis

Introduction

Whipple's disease is a rare systemic infectious disorder. It may present with a wide range of clinical manifestations and therefore its diagnosis may be challenging.

Case report

We report a 45-year-old man who presented with acute encephalitis related to Whipple's disease. Despite the negativity of the polymerase chain reaction (PCR) test in cerebrospinal fluid, diagnosis was obtained by histopathology, PCR tests and immunohistochemistry in multiple samples. The outcome with antibiotherapy was considered as “spectacular”.

Conclusion

Whipple's disease is a rare cause of encephalitis. Its diagnosis needs the confrontation of histology and PCR tests in multiple samples. The outcome with an adapted antibiotherapy may be very successful.     

Structural brain lesions in inflammatory bowel disease

Central nervous system (CNS) complications or manifestations of inflammatory bowel disease deserve particular attention because symptomatic conditions can require early diagnosis and treatment, whereas unexplained manifestations might be linked with pathogenic mechanisms. This review focuses on both symptomatic and asymptomatic brain lesions detectable on imaging studies, as well as their frequency and potential mechanisms. A direct causal relationship between inflammatory bowel disease (IBD) and asymptomatic structural brain changes has not been demonstrated, but several possible explanations, including vasculitis, thromboembolism and malnutrition, have been proposed. IBD is associated with a tendency for thromboembolisms; therefore, cerebrovascular thromboembolism represents the most frequent and grave CNS complication. Vasculitis, demyelinating conditions and CNS infections are among the other CNS manifestations of the disease. Biological agents also represent a risk factor, particularly for demyelination. Identification of the nature and potential mechanisms of brain lesions detectable on imaging studies would shed further light on the disease process and could improve patient care through early diagnosis and treatment.     

Characterization of circulating interleukin-1 receptor antagonist expression in children with inflammatory bowel disease

The cytokines IL-1 and IL-6 appear to be important in the pathogenesis of inflammatory bowel disease (IBD). Recently, a naturally occurring interleukin-1 receptor antagonist, designated IL-1ra, which inhibits IL-1 activityin vitro andin vivo has been described. The purpose of the present study was to assess the circulating levels and relative relationships of IL-1ra, IL-1, and IL-6 in children with IBD of varying severity. Serum/plasma samples were obtained from 32 children with ulcerative colitis, 45 with Crohn's disease, and 24 control patients. Cytokine assays were performed by enzymelinked immunoassay. IL-1ra levels were significantly elevated in children with ulcerative colitis or Crohn's disease of moderate/severe activity compared to patients with inactive/mild IBD or control subjects (P<0.001). IL-1 was only detectable in the circulation of two subjects with severe colitis (one ulcerative colitis, one Crohn's disease), and both had extremely elevated IL-1ra levels. IL-1ra levels were significantly related to IL-6 levels for patients with IBD (P<0.00001). Our results suggest that circulating IL-1ra appears in increasing concentrations in children with mounting degrees of disease severity as determined by clinical scoring methods as well as by the level of IL-6. Future work will need to address the clinical and prognostic value of measuring circulating IL-1ra in individuals with inflammatory bowel disease.     

Coronary stent strut fracture after drug-eluting stent implantation: a newly recognized complication

Stent strut fracture (SSF) after drug-eluting stent (DES) implantation may be an important complication after DES implantation particularly in patients undergoing sirolimus eluting stent implantation. Since SSF is a highly relevant adverse event which can result in in-stent restenosis and thrombosis, we believe that DES with flexible stent platform or biodegradable DES may be needed to prevent this potential catastrophic complication.