Search

Abstract Anti-N-methyl- d -aspartate receptor (anti-NMDAR) encephalitis is a type of immune-mediated encephalitis, which is a new category of treatment-responsive paraneoplastic encephalitis. In patients with this disease, electroencephalography (EEG) shows non-specific findings, but recently, a unique EEG pattern, named the extreme delta brush, was detected in 40% of adult patients and was suggested to be specific to this type of encephalitis. Here, we describe a two-year-old boy with anti-NMDAR encephalitis, who presented with speech arrest and disturbances of gait and cognition several weeks after developing febrile convulsions. In the early stages of the disease, EEG showed 14–16 Hz, continuous, fast waves characterized by a high amplitude (200–500 µV), very diffuse spreading, and a sharp morphology, during light sleep only, which was compatible with extreme spindles. As the patient's symptoms worsened, this finding was replaced by rhythmic, diffuse, high-voltage, slow waves. Immediately after immunomodulatory therapies, including intravenous methylprednisolone and immunoglobulin, his clinical manifestations and EEG abnormalities appeared to improve. We propose that although the extreme spindle is a non-specific finding of this type of encephalitis, early EEG monitoring might be necessary to detect not only the extreme delta brush pattern, but also non-specific findings, including extreme spindles, which would aid early diagnosis and treatment. [ABSTRACT FROM AUTHOR]

Background: Rufinamide, a triazole derivative, is a novel antiepileptic drug (AED) chemically unrelated to other current AEDs. Previous studies on pediatric epilepsy treatment with rufinamide have demonstrated a frequency of leukopenia as an adverse event of 0.5%, and there has been no report of the development of agranulocytosis. Here, we report a patient with Lennox–Gastaut syndrome (LGS) who developed agranulocytosis associated with fever and skin rash with rufinamide. To the best of our knowledge, this is the first reported case of agranulocytosis induced by rufinamide. Patient: A 10-year-old boy with a history of herpes encephalitis at the age of 1 year developed LGS, and was administered rufinamide as add-on therapy to valproate, lamotrigine, and clonazepam because of difficulties in controlling tonic seizures. Eighteen days after initiation of rufinamide, agranulocytosis developed associated with high fever and skin rash, all of which resolved after withdrawal of rufinamide. Bone marrow aspiration demonstrated normocellular marrow with selective decrease of mature myeloid series, and suggested that agranulocytosis was not related to malignancy or serious infection. Conclusion: This case suggests that rufinamide may induce the potentially serious adverse effect of agranulocytosis. Patients should be monitored for clinical signs of agranulocytosis and consideration should be given to routine blood count determination for early detection of this. [ABSTRACT FROM AUTHOR]

Alexander disease (AxD) is a rare fatal leukodystrophy caused by a dominant missense mutation in the glial fibrillary acidic protein. In a mouse model of AxD, the pathological astrocyte causes a pronounced immune response. The inflammatory environment in the brain might play an important role in the neuronal dysfunction of AxD. A 3-month-old girl diagnosed with infantile AxD presented with severe intractable seizures and a deteriorated neurological state. Steroid pulse therapy was effective at preventing the epileptic activity and progressive white matter abnormalities on magnetic resonance images, but the effect was temporary. Levels of interleukin (IL)-6, IL-8, and macrophage chemotactic protein 1 (MCP-1) in the cerebrospinal fluid were high at onset and reduced transiently after steroid pulse therapy. These results suggest that inflammatory responses of astrocyte and microglia can contribute to the neuropathology of AxD. Robust immunomodulation that targets activated astrocytes and microglia may be a novel therapeutic strategy to improve neurological prognosis in AxD. [ABSTRACT FROM AUTHOR]

Background In Japan, adrenocorticotropic hormone (ACTH) therapy has been the mainstay of treatment of West syndrome. Conventional ACTH therapy is administered short-term with efficacy, yet the relapse rate is high. Relapse after initial ACTH therapy is a poor prognostic factor for long-term seizure control and outcome of cognitive function. Here, we report successful long-term weekly ACTH therapy for relapsed WS in a tuberous sclerosis complex (TSC) child after conventional ACTH therapy. Patient The patient had a series of epileptic spasms (ES) and hypsarrhythmia at age 3 months. She was diagnosed with WS associated with TSC, and was treated with conventional ACTH therapy at age 4 months, and a second course of ACTH therapy at age 8 months. Both courses of therapy were transiently effective. A third course of ACTH therapy was started at age 1 year and 2 months, and long-term weekly ACTH therapy was continued thereafter. During this therapy, both ES and hypsarrhythmia remained completely resolved. Therapy was continued, and dose reduction was started when the patient was 2 years and 10 months old. No serious adverse events had occurred during this therapy. Conclusion This case demonstrated that long-term weekly ACTH may be safe and effective. Although at present, this therapy may only be considered for relapsed symptomatic WS patients, it may be a good alternative therapy when frequent relapses occur after favorable response to conventional ACTH therapy. [ABSTRACT FROM AUTHOR]

• The effect of ketogenic diet therapy on intractable epilepsy in infantile Alexander disease has not well characterized. • In all the cases, ketogenic diet therapy controlled well the drug-resistant seizures and suppressed the epileptic activities on EEG. • In all the cases, the brain MRI findings deteriorated, even after the epilepsies were controlled. • The concentrations of astroglial chemokines and proinflammatory cytokines in the CSF of the patients decreased but remained still high. • Our results support previous reports arguing neuroinflammation involvement in the pathophysiology of infantile Alexander disease. In infantile Alexander disease (iAxD), one of the serious symptoms is intractable epilepsy, and some reports have suggested that neuroinflammation may be involved in the pathophysiology of the disease. Drug-resistant seizures adversely affect not only the quality of life of the caregivers and patients, but also patients' lifespan. Thus, controlling epilepsy is clinically important. For intractable childhood epilepsy, ketogenic diet therapy (KDT) is well-established, but its effects on iAxD have not been characterized. Here, we describe the use of KDT in three iAxD patients experiencing drug-resistant seizures. In all three cases, the formerly intractable epilepsies were well controlled by KDT. However, the brain magnetic resonance imaging findings deteriorated even after the epilepsy was controlled. In addition, the concentrations of monocyte chemotactic protein-1 and proinflammatory cytokines in the cerebrospinal fluid of the patients remained still high. KDT is effective in controlling epilepsy in iAxD. Our results clinically support previous reports arguing the involvement of neuroinflammation in the pathophysiology of iAxD. Although KDT cannot prevent disease progression, earlier initiation might contribute to a better prognosis. [ABSTRACT FROM AUTHOR]