Late relapse of anti-N-methyl-d-aspartate receptor encephalitis with amusia and transiently reduced uptake in 123I-iomazenil single-photon emission computed tomography.

INTRODUCTION: Anti-N-methyl-d-aspartate receptor (NMDAR) encephalitis has a high relapse rate at approximately 10-20%. Most relapses occur within 2 years from onset, and 5 years after onset is rare. We report a case of anti-NMDAR encephalitis relapse with amusia 10 years after the initial encephalitis and discuss the usefulness of 123I-iomazenil single-photon emission computerized tomography (IMZ-SPECT) for its diagnosis. CASE: A 13-year-old left-handed girl presented with a depressed level of consciousness and focal to bilateral tonic-clonic seizures. Cerebrospinal fluid (CSF) analysis showed a mildly increased white blood cell count, elevated neopterin levels, and positive oligoclonal bands. Brain MRI was normal. IMZ-SPECT revealed reduced uptake in the right frontoparietal region. She received intravenous pulse methylprednisolone (IVMP) and high-dose intravenous immunoglobulin for autoimmune encephalitis; her symptoms resolved without neurological deficits. At 23 years old, she had mild right-sided numbness, dysarthria, amusia, and tonic-clonic seizures. Although the CSF analysis and brain MRI were normal, IMZ-SPECT revealed reduced uptake, indicating a relapse of encephalitis. IVMP administration resolved the symptoms. After discharge, the initial and relapse CSF analysis revealed anti-NMDAR antibodies. CONCLUSION: An anti-NMDAR encephalitis relapse 10 years after onset has never been reported. IMZ-SPECT may help in the diagnosis of anti-NMDAR encephalitis.

Metabolic Signature of MELAS/Leigh Overlap Syndrome in Patient-specific Induced Pluripotent Stem Cells Model.

Background: Mitochondrial myopathy, Encephalopathy, Lactic Acidosis, Stroke-like episodes/Leigh overlap syndrome (MELAS) is caused by defects in the mitochondrial respiratory chain. It is still largely unknown how these mitochondrial respiratory chain defects affect cellular metabolisms and lead to variable clinical phenotypes. Here, we analyzed metabolic signatures in a cellular model of MELAS/ Leigh overlap syndrome using untargeted gas chromatography coupled to mass spectrometry (GC-MS). . Methods: We obtained fibroblasts from a MELAS/Leigh overlap syndrome patient carrying the heteroplasmic m.10191T>C mutation, and generated induced pluripotent stem cells (iPSCs) from these fibroblast. Isogenic iPSC clones carrying two different loads of the heteroplasmic mutation (ND3hig-iPSC, ND3"*w- iPSC-) were subjected to metabolome analysis. Metabolite profiles, which were identified by GC-MS, were analyzed by principal component analysis (PCA). Results: We were able to identify about 40 metabolites in control fibroblasts and iPSCs. Upon comparative metabolome analysis between fibroblasts and iPSCs, lactic acid and proline were distinct between the two groups. When we compared patient fibroblasts and control fibroblasts, no significant distinct metabolites were found. On the other hand, patient specific iPSC with high mutational load (ND3high_ iPSC) showed a distinct metabolite profile compared with ND3""-iPSC and control-iPSCs. Metabolites that contributed to this distinction were pyruvate, malic acid, palmitic acid, stearic acid, and lactic acid. This metabolomic signature was only seen in the undifferentiated state of iPSCs and was lost upon differentiation Conclusions: These findings suggest that patient specific iPSC technology is useful to elucidate unique pathogenic metabolic pathways ,6mitochondrial chain diseases.

Glucocorticoids promote neural progenitor cell proliferation derived from human induced pluripotent stem cells.

Glucocorticoids (GCs) are frequently used for treating and preventing chronic lung disease and circulatory dysfunction in premature infants. However, there is growing concern about the detrimental effects of systemic GC administration on neurodevelopment. The first choice of GCs to minimize the adverse effects on the developing brain is still under debate. We investigated the effect of commonly used GCs such as dexamethasone (DEX), betamethasone (BET) and hydrocortisone (HDC) on the proliferation of human-induced pluripotent stem cell (iPSC)-derived neuronal progenitor cells (NPCs). In this study, NPCs were treated with various concentrations of GCs and subjected to cell proliferation assays. Furthermore, we quantified the number of microtubule-associated protein 2 (MAP2) positive neurons in NPCs by immunostaining. All GCs promoted NPC proliferation in a dose-dependent manner. We also confirmed that MAP2-positive neurons in NPCs increased upon GC treatment. However, differential effects of GCs on MAP2 positive neurons were observed when we treated NPCs with H2O2. The total numbers of NPCs increased upon any GC treatment even under oxidative conditions but the numbers of MAP2 positive neurons increased only by HDC treatment. GCs promoted human iPSCsâ€"derived NPC proliferation and the differential effects of GCs became apparent under oxidative stress. Our results may support HDC as the preferred choice over DEX and BET to prevent adverse effects on the developing human brain.

Twelve-year-old girl with intracranial epidural abscess and sphenoiditis.

We report the case of a 12-year-old girl with an intracranial epidural abscess and sphenoiditis. Although she had no history of sinusitis, she developed acute severe headache, fever, and vomiting. Emergent CT and MRI showed a spherical space-occupying lesion of diameter 3 cm in the right cranial fossa with rim enhancement. The lesion was thought to be an epidural abscess adjacent to the right sphenoiditis. On the basis of the MRI findings, we performed emergent surgery to drain the abscess and sinusitis because of severe and rapidly worsening headaches. The patient showed great improvement the day after the operation. Intravenous antibiotics were administered for 8 days. She has completely recovered, with neither sequelae nor recurrence at 7 months after the operation. We believe that this report will be a useful reference for cases of acute onset headache and may be helpful in diagnosis and treatment decisions for severe sinusitis-related intracranial abscess in childhood.

[Review of images in children with septo-optic dysplasia based on MRI and SPECT].

We reviewed MRI and SPECT images in 10 patients with septo-optic dysplasia (SOD). MRI was performed in all of them. Six of them had bilateral optic nerve atrophy and abnormality of midline brain structures (e. g., septum pellucidum, corpus callosum). Four cases had one-sided optic nerve atrophy. They have ipsilateral or bilateral cortical dysplasia. It may suggest that one of the pathogenesis of SOD is a disruption of the anterior cerebral artery at embryonic site. SPECT was performed in 3 patients with cortical dysplasia. At cortical dysplasia area, CBF-SPECT and IMZ-SPECT showed the same RI count as the normal cortex. This finding is compatible with the fact that few patients with SOD have epileptic seizures.

Thrombotic microangiopathy due to malignant hypertension following corticosteroid therapy for microscopic polyangitis.

A 78-year-old woman was treated with 40 mg of prednisolone for microscopic polyangitis, and favorable effects were observed. However, her blood pressure increased and she developed severe thrombocytopenia. Thrombotic microangiopathy (TMA) due to malignant hypertension was suspected and she was treated with an angiotensin-converting enzyme inhibitor; her platelet count then rose. She showed a close temporal relationship between initiation of corticosteroid therapy and the onset of TMA. Corticosteroid therapy should be used with caution in patients with underlying vascular endothelial damage.