Aggressive Course in Encephalitis With Opsoclonus, Ataxia, Chorea, and Seizures. The First Pediatric Case of γ-Aminobutyric Acid Type B Receptor Autoimmunity

IMPORTANCE: Autoantibodies to the γ-aminobutyric acid type B (GABAB) receptor have recently been identified as a cause of autoimmune encephalitis. Most patients with GABAB encephalitis have presented with limbic encephalitis. About half of the cases reported have been paraneoplastic in origin, with the majority of tumors representing small cell lung cancer. OBSERVATIONS: We describe a 3-year-old boy who presented with a mixed movement disorder (opsoclonus, ataxia, and chorea) as well as seizures refractory to treatment. His seizures required continuous pentobarbital sodium infusion to be controlled. Despite treatment with intravenous corticosteroids and immunoglobulins, the patient ultimately died of overwhelming sepsis. CONCLUSIONS AND RELEVANCE: To our knowledge, this report represents the first pediatric case of GABAB-associated encephalitis. Our patient presented with encephalopathy, refractory seizures, and a mixed movement disorder rather than limbic encephalitis. γ-Aminobutyric acid type B receptor autoimmunity deserves consideration in pediatric patients presenting with encephalitis. Immune-mediated encephalitis with autoantibodies directed against synaptic proteins has become an important component of the differential diagnosis of patients with encephalitis. Current estimates suggest that a substantial proportion of patients once suspected to have viral encephalitis in fact have an autoimmune etiology for their symptoms.1 Additional autoantigen targets continue to be identified, and the phenotypic spectrum associated with autoimmune encephalitis continues to expand. We describe a 3-year-old patient who presented with acute-onset confusion, opsoclonus, chorea, and intractable seizures. Neuroimaging disclosed involvement of the brainstem, basal ganglia, and hippocampi. γ-Aminobutyric acid type B (GABAB) receptor autoantibodies were identified in the serum and cerebrospinal fluid (CSF). Despite immunomodulating therapy, the patient died of overwhelming sepsis. To our knowledge, this is the first description of a pediatric patient with GABAB receptor autoantibodies. The presence of opsoclonus, ataxia, and chorea expands the clinical phenotype and indicates that GABAB receptor autoimmunity should be considered in cases of pediatric encephaliti

Response to treatment in a prospective national infantile spasms cohort

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/134499/1/ana24594.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/134499/2/ana24594_am.pd

Response to second treatment after initial failed treatment in a multicenter prospective infantile spasms cohort

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/135085/1/epi13557_am.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/135085/2/epi13557.pd

Aggressive Course in Encephalitis With Opsoclonus, Ataxia, Chorea, and Seizures. The First Pediatric Case of γ-Aminobutyric Acid Type B Receptor Autoimmunity

IMPORTANCE: Autoantibodies to the γ-aminobutyric acid type B (GABAB) receptor have recently been identified as a cause of autoimmune encephalitis. Most patients with GABAB encephalitis have presented with limbic encephalitis. About half of the cases reported have been paraneoplastic in origin, with the majority of tumors representing small cell lung cancer. OBSERVATIONS: We describe a 3-year-old boy who presented with a mixed movement disorder (opsoclonus, ataxia, and chorea) as well as seizures refractory to treatment. His seizures required continuous pentobarbital sodium infusion to be controlled. Despite treatment with intravenous corticosteroids and immunoglobulins, the patient ultimately died of overwhelming sepsis. CONCLUSIONS AND RELEVANCE: To our knowledge, this report represents the first pediatric case of GABAB-associated encephalitis. Our patient presented with encephalopathy, refractory seizures, and a mixed movement disorder rather than limbic encephalitis. γ-Aminobutyric acid type B receptor autoimmunity deserves consideration in pediatric patients presenting with encephalitis. Immune-mediated encephalitis with autoantibodies directed against synaptic proteins has become an important component of the differential diagnosis of patients with encephalitis. Current estimates suggest that a substantial proportion of patients once suspected to have viral encephalitis in fact have an autoimmune etiology for their symptoms.1 Additional autoantigen targets continue to be identified, and the phenotypic spectrum associated with autoimmune encephalitis continues to expand. We describe a 3-year-old patient who presented with acute-onset confusion, opsoclonus, chorea, and intractable seizures. Neuroimaging disclosed involvement of the brainstem, basal ganglia, and hippocampi. γ-Aminobutyric acid type B (GABAB) receptor autoantibodies were identified in the serum and cerebrospinal fluid (CSF). Despite immunomodulating therapy, the patient died of overwhelming sepsis. To our knowledge, this is the first description of a pediatric patient with GABAB receptor autoantibodies. The presence of opsoclonus, ataxia, and chorea expands the clinical phenotype and indicates that GABAB receptor autoimmunity should be considered in cases of pediatric encephaliti

Acid-sensing ion channel-1a in the amygdala, a novel therapeutic target in depression-related behavior

No animal models replicate the complexity of human depression. However, a number of behavioral tests in rodents are sensitive to antidepressants and may thus tap important underlying biological factors. Such models may also offer the best opportunity to discover novel treatments. Here, we used several of these models to test the hypothesis that the acid-sensing ion channel-1a (ASIC1a) might be targeted to reduce depression. Genetically disrupting ASIC1a in mice produced antidepressant-like effects in the forced swim test, the tail suspension test, and following unpredictable mild stress. Pharmacologically inhibiting ASIC1a also had antidepressant-like effects in the forced swim test. The effects of ASIC1a disruption in the forced swim test were independent of and additive to those of several commonly used antidepressants. Furthermore, ASIC1a disruption interfered with an important biochemical marker of depression, the ability of stress to reduce BDNF in the hippocampus. Restoring ASIC1a to the amygdala of ASIC1a-/- mice with a viral vector reversed the forced swim test effects, suggesting that the amygdala is a key site of ASIC1a action in depression-related behavior. These data are consistent with clinical studies emphasizing the importance of the amygdala in mood regulation, and suggest that ASIC1a antagonists may effectively combat depression. Copyright © 2009 Society for Neuroscience

Comparison of Cosyntropin, Vigabatrin, and Combination Therapy in New-Onset Infantile Spasms in a Prospective Randomized Trial

In a randomized trial, we aimed to evaluate the efficacy of cosyntropin injectable suspension, 1 mg/mL, compared to vigabatrin for infantile spasms syndrome. An additional arm was included to assess the efficacy of combination therapy (cosyntropin and vigabatrin) compared with cosyntropin monotherapy. Children (2 months to 2 years) with new-onset infantile spasms syndrome and hypsarhythmia were randomized into 3 arms: cosyntropin, vigabatrin, and cosyntropin and vigabatrin combined. Daily seizures and adverse events were recorded, and EEG was repeated at day 14 to assess for resolution of hypsarhythmia. The primary outcome measure was the composite of resolution of hypsarhythmia and absence of clinical spasms at day 14. Fisher exact test was used to compare outcomes. 37 children were enrolled and 34 were included in the final efficacy analysis (1 withdrew prior to treatment and 2 did not return seizure diaries). Resolution of both hypsarhythmia and clinical spasms was achieved in in 9 of 12 participants (75%) treated with cosyntropin, 1/9 (11%) vigabatrin, and 5/13 (38%) cosyntropin and vigabatrin combined. The primary comparison of cosyntropin versus vigabatrin was significant (64% [95% confidence interval 21, 82],  \u3c .01). Adverse events were reported in all 3 treatment arms: 31 (86%) had an adverse event, 7 (19%) had a serious adverse event, and 15 (42%) had an adverse event of special interest with no difference between treatment arms. This randomized trial was underpowered because of incomplete enrollment, yet it demonstrated that cosyntropin was more effective for short-term outcomes than vigabatrin as initial treatment for infantile spasms