A novel treatment-responsive encephalitis with frequent opsoclonus and teratoma

Among 249 patients with teratoma-associated encephalitis, 211 had N-methyl-D-aspartate receptor antibodies and 38 were negative for these antibodies. Whereas antibody-positive patients rarely developed prominent brainstem-cerebellar symptoms, 22 (58%) antibody-negative patients developed a brainstem-cerebellar syndrome, which in 45% occurred with opsoclonus. The median age of these patients was 28.5 years (range = 12-41), 91% were women, and 74% had full recovery after therapy and tumor resection. These findings uncover a novel phenotype of paraneoplastic opsoclonus that until recently was likely considered idiopathic or postinfectious. The triad of young age (teenager to young adult), systemic teratoma, and high response to treatment characterize this novel brainstem-cerebellar syndrome753435441United States Department of Health & Human Services National Institutes of Health (NIH) - USA; United States Department of Health & Human Services National Institutes of Health (NIH) - USA NIH National Cancer Institute (NCI); Fundacio la Marato de TV3; Instituto de Salud Carlos III; KWF Kankerbestrijding; McKnight Neuroscience of Brain Disorders award; Instituto de Salud Carlos III; ICRE

A novel treatment-responsive encephalitis with frequent opsoclonus and teratoma

Among 249 patients with teratoma‐associated encephalitis, 211 had N‐methyl‐D‐aspartate receptor antibodies and 38 were negative for these antibodies. Whereas antibody‐positive patients rarely developed prominent brainstem-cerebellar symptoms, 22 (58%) antibody‐negative patients developed a brainstem-cerebellar syndrome, which in 45% occurred with opsoclonus. The median age of these patients was 28.5 years (range = 12-41), 91% were women, and 74% had full recovery after therapy and tumor resection. These findings uncover a novel phenotype of paraneoplastic opsoclonus that until recently was likely considered idiopathic or postinfectious. The triad of young age (teenager to young adult), systemic teratoma, and high response to treatment characterize this novel brainstem-cerebellar syndrome

Rectal artemisinins for malaria: a review of efficacy and safety from individual patient data in clinical studies

<p>Abstract</p> <p>Background</p> <p>Rectal administration of artemisinin derivatives has potential for early treatment for severe malaria in remote settings where injectable antimalarial therapy may not be feasible. Preparations available include artesunate, artemisinin, artemether and dihydroartemisinin. However each may have different pharmacokinetic properties and more information is needed to determine optimal dose and comparative efficacy with each another and with conventional parenteral treatments for severe malaria.</p> <p>Methods</p> <p>Individual patient data from 1167 patients in 15 clinical trials of rectal artemisinin derivative therapy (artesunate, artemisinin and artemether) were pooled in order to compare the rapidity of clearance of <it>Plasmodium falciparum </it>parasitaemia and the incidence of reported adverse events with each treatment. Data from patients who received comparator treatment (parenteral artemisinin derivative or quinine) were also included. Primary endpoints included percentage reductions in parasitaemia at 12 and 24 hours. A parasite reduction of >90% at 24 hours was defined as parasitological success.</p> <p>Results</p> <p>Artemisinin and artesunate treatment cleared parasites more rapidly than parenteral quinine during the first 24 hours of treatment. A single higher dose of rectal artesunate treatment was five times more likely to achieve >90% parasite reductions at 24 hours than were multiple lower doses of rectal artesunate, or a single lower dose administration of rectal artemether.</p> <p>Conclusion</p> <p>Artemisinin and artesunate suppositories rapidly eliminate parasites and appear to be safe. There are less data on artemether and dihydroartemisinin suppositories. The more rapid parasite clearance of single high-dose regimens suggests that achieving immediate high drug concentrations may be the optimal strategy.</p

The distinct pattern of movement disorders in Caspr2 and LGI1 antibody associated autoimmune encephalitis

Objective: The aim of this study was (1) to investigate the prevalence of movement disorders in a large cohort of patients with encephalitis with LGI1 and CASPR2 antibodies and (2) to compare clinical phenomenology between patients with Caspr2 and LGI1 antibodies. Background: Movement disorders are a common clinical feature in NMDAR encephalitis. However, their frequency and phenomenology in other common antibody‐defined autoimmune encephalitis subtypes is less well studied. Autoimmune encephalitis with antibodies targeting the neuronal proteins LGI1 or CASPR2 are other frequently observed neuronal autoantibodies in patients with autoimmune encephalitis. Methods: Retrospective analysis of 280 patients from 5 different referral centers with encephalitis and antibodies against LGI1 or CASPR2 in serum and/or CSF was performed with a focus on the clinical presence of movement disorders. Results: FBDS were observed in 25.5% of patients with LGI1 antibodies while other movement disorders (chorea 1.9%, myoclonus 1.9%, tremor 0.9%) were rare or absent (ataxia, tics, dystonia and parkinsonism). In contrast patients with Caspr2 antibodies presented significantly more frequent with ataxia (23%, p = <0.0001), myoclonus (12.6%, p = 0.001) and tremor (10.3%, p = 0.001) while chorea (1.7%) and parkinsonism (1.7%) were rare. Prominent myoclonus was found in 22 patients with Caspr2 antibodies. In 2 patients myoclonus was the only clinical finding in the context of Caspr2 autoimmunity while in the remaining patients myoclonus presented in combination with well‐known anti–Caspr2 antibody‐related syndromes. However, myoclonus was the presenting symptom in 40.9% (n=9) patients. Topographically, myoclonus was generalized in 36.4% (n=8), multifocal in 40.9% (n=9 [6 lower limbs, 3 upper limbs]) and segmental in 9% (n=2) of patients. In the majority of patients (59.1%, n=13) myoclonus was aggravated or exclusively triggered by orthostatism (76.9%, n=10) and/or walking (38.5%, n=5). In 27.3% (n=6) myoclonus presented as a pure paroxysmal kinesiogenic movement disorder. Immunotherapy lead to complete allevation or major improvement of myoclonus in 81.8% (n=18). Conclusions: Movement disorders are a common feature in patients with autoimmune encephalitis with LGI1 and CASPR2 antibodies. Interestingly, the pattern of movement disorders differed between patient groups, which could help to guide diagnosis

A novel treatment-responsive encephalitis with frequent opsoclonus and teratoma

Among 249 patients with teratoma-associated encephalitis, 211 had N-methyl-D-aspartate receptor antibodies and 38 were negative for these antibodies. Whereas antibody-positive patients rarely developed prominent brainstem-cerebellar symptoms, 22 (58%) antibody-negative patients developed a brainstem-cerebellar syndrome, which in 45% occurred with opsoclonus. The median age of these patients was 28.5 years (range = 12-41), 91% were women, and 74% had full recovery after therapy and tumor resection. These findings uncover a novel phenotype of paraneoplastic opsoclonus that until recently was likely considered idiopathic or postinfectious. The triad of young age (teenager to young adult), systemic teratoma, and high response to treatment characterize this novel brainstem-cerebellar syndrome. ANN NEUROL 2014;75:435-441753435441NIH [RO1NS077851, RO1MH094741]National Cancer Institute [RO1CA89054]Fundacio la Marato de TV3Fondo de Investigaciones Sanitarias, Madrid, Spain [PI11/01780, PI12/00611]Dutch Cancer Society [KWF2009-4451]McKnight Neuroscience of Brain Disorders awardInstituto Carlos III [FI12/00366]NIH [RO1NS077851, RO1MH094741]National Cancer Institute [RO1CA89054]Fondo de Investigaciones Sanitarias, Madrid, Spain [PI11/01780, PI12/00611]Dutch Cancer Society [KWF2009-4451]Instituto Carlos III [FI12/00366

A novel treatment-responsive encephalitis with frequent opsoclonus and teratoma

Among 249 patients with teratoma‐associated encephalitis, 211 had N‐methyl‐D‐aspartate receptor antibodies and 38 were negative for these antibodies. Whereas antibody‐positive patients rarely developed prominent brainstem-cerebellar symptoms, 22 (58%) antibody‐negative patients developed a brainstem-cerebellar syndrome, which in 45% occurred with opsoclonus. The median age of these patients was 28.5 years (range = 12-41), 91% were women, and 74% had full recovery after therapy and tumor resection. These findings uncover a novel phenotype of paraneoplastic opsoclonus that until recently was likely considered idiopathic or postinfectious. The triad of young age (teenager to young adult), systemic teratoma, and high response to treatment characterize this novel brainstem-cerebellar syndrome