Longstanding overt ventriculomegaly diagnosed in adolescents, not adults: a pediatric case report.

BACKGROUND: Longstanding overt ventriculomegaly in adults (LOVA) is a new form of progressive hydrocephalus characterized by onset in early childhood and gradual progression into adulthood. Patients with LOVA are usually asymptomatic in childhood. The diagnosis of LOVA in adolescence has not been reported. CASE REPORT: A patient with macrocephaly and mild ventriculomegaly from infancy developed headache exacerbation and cognitive dysfunction at the age of 11 years. Brain magnetic resonance imaging showed mild tri-ventriculomegaly with no radiological aggravation compared to imaging at the age of 8 years. No papilledema was observed. Drainage of 15 ml of spinal fluid via a lumbar puncture relieved the headache and cognitive dysfunction. Based on repeated improvements in cognitive function and headaches after spinal fluid drainage, we diagnosed the patient with LOVA with symptom onset in early adolescence. A ventriculoperitoneal shunt was placed, and the headaches disappeared completely. The full-scale intellectual quotient, verbal comprehension, and working memory improved significantly. CONCLUSIONS: LOVA may manifest as early as adolescence. The clinical presentation, age, clinical, radiological features, and management vary, and a spinal tap exam is useful for diagnosing LOVA, even in children. The spinal tap exam may be indicated in children with longstanding ventriculomegaly and deteriorating neurological symptoms to diagnose this "treatable intellectual disability."

Central-variant posterior reversible encephalopathy syndrome in an infant with mid-aortic syndrome: A rare case of symmetric basal ganglia lesions.

Central-variant posterior reversible encephalopathy syndrome is an atypical subtype of posterior reversible encephalopathy syndrome that occurs during rapid fluctuations in blood pressure, leading to cerebrovascular autoregulatory failure and endothelial dysfunction. Few reports have described posterior reversible encephalopathy syndrome in infants. A 4-month-old girl, who was diagnosed a month before with hypoxic ischemic encephalopathy due to sudden cardiac arrest, showed persistent renovascular hypertension with a systolic blood pressure of 200 mmHg. Computed tomography of the head revealed a new-onset low-attenuation area in the bilateral basal ganglia, and computed tomography of the trunk revealed severe long-segment narrowing of the abdominal aorta encompassing the bilateral renal arteries. She was treated with antihypertensive drugs and peritoneal dialysis. Follow-up imaging after blood pressure stabilization showed resolution of the low-attenuation area in the bilateral basal ganglia. We diagnosed her basal ganglia lesions as central-variant posterior reversible encephalopathy syndrome. She suffered from neurological sequelae attributable to hypoxic ischemic encephalopathy but showed no evidence of basal ganglia dysfunction. Here, we report a case of infantile central-variant posterior reversible encephalopathy syndrome involving bilateral basal ganglia lesions with mid-aortic syndrome. The differential diagnosis of infantile symmetric bilateral basal ganglia lesions is broad and includes genetic, acquired metabolic or toxic, infectious, inflammatory, vascular, and neoplastic pathologies. Among them, central-variant posterior reversible encephalopathy syndrome is rare but important because neurological prognosis may be favorable, and specific treatment, such as administration of antihypertensive drugs or discontinuation of drugs that induce posterior reversible encephalopathy syndrome, is possible.

Fatal X-linked lymphoproliferative disease type 1-associated limbic encephalitis with positive anti-alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor antibody.

BACKGROUND: X-linked lymphoproliferative disease type 1 (XLP1) is a rare monogenic immune dysregulation disorder caused by a deficiency of a signaling lymphocyte activation molecule-associated protein (SAP). While many patients with XLP1 present with fatal hemophagocytic lymphohistiocytosis upon Epstein Barr virus (EBV) infection, a small fraction present with limbic encephalitis in the absence of EBV infection. It is poorly understood why SAP deficiency may cause limbic encephalitis in XLP1. CASE: A 12-year-old boy presented with seizures, changes in personality, memory loss, and cognitive deficits during treatment for interstitial pneumonia. A diagnosis of limbic encephalitis was made. Despite treatment against CD8+ T cell-mediated autoimmunity with intravenous methylprednisolone, dexamethasone, intravenous immunoglobulin, plasma exchange, cyclosporine, weekly etoposide, mycophenolate mofetil, and adalimumab, encephalitis progressed until the patient died after one month of treatment intitiation. Post-mortem genetic testing revealed a de novo SH2D1A truncating mutation. Tests for EBV infection were negative. Initial spinal fluid revealed markedly elevated protein levels, mild pleocytosis, and elevation of two chemokines (C-X-C motif chemokine ligand [CXCL] 10 and CXCL 13). Moreover, initial spinal fluid was tested positive for anti-alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor (AMPAR) autoantibody. DISCUSSION: In XLP1-associated limbic encephalitis, anti-AMPAR autoantibody production by the dysregulated immune system due to SAP deficiency might be a pathogenic mechanism of central nervous system manifestations. In addition to the standard treatment for XLP1, targeted treatment against B-cell-mediated immunity might be indicated for patients with XLP1-associated limbic encephalitis.

Monogenic causes of pigmentary mosaicism.

Pigmentary mosaicism of the Ito type, also known as hypomelanosis of Ito, is a neurocutaneous syndrome considered to be predominantly caused by somatic chromosomal mosaicism. However, a few monogenic causes of pigmentary mosaicism have been recently reported. Eleven unrelated individuals with pigmentary mosaicism (mostly hypopigmented skin) were recruited for this study. Skin punch biopsies of the probands and trio-based blood samples (from probands and both biological parents) were collected, and genomic DNA was extracted and analyzed by exome sequencing. In all patients, plausible monogenic causes were detected with somatic and germline variants identified in five and six patients, respectively. Among the somatic variants, four patients had MTOR variant (36%) and another had an RHOA variant. De novo germline variants in USP9X, TFE3, and KCNQ5 were detected in two, one, and one patients, respectively. A maternally inherited PHF6 variant was detected in one patient with hyperpigmented skin. Compound heterozygous GTF3C5 variants were highlighted as strong candidates in the remaining patient. Exome sequencing, using patients' blood and skin samples is highly recommended as the first choice for detecting causative genetic variants of pigmentary mosaicism.

Recurrent acute necrotizing encephalopathy in a boy with RANBP2 mutation and thermolabile CPT2 variant: The first case of ANE1 in Japan.

BACKGROUND: Acute necrotizing encephalopathy (ANE) is a severe encephalopathy associated with acute viral infection. While most ANE cases are sporadic, pathogenic variants in the gene RAN binding protein 2 (RANBP2) have been identified as a major cause of familial or recurrent ANE (ANE1). Although sporadic ANE predominantly affects Asian children, ANE1 is very rare in east Asia. CASE REPORT: A 1-year-7-month-old boy, born to unrelated Japanese parents, presented with a seizure and impaired consciousness after 3 days of fever. Brain magnetic resonance imaging (MRI) showed a characteristic involvement of the bilateral thalami, external capsules, insular cortices, and brainstem, suggesting ANE. He received intravenous steroids. Two months later, he had another episode of acute encephalopathy during respiratory syncytial virus infection, from which he recovered relatively well. The recurrent encephalopathic episodes and the characteristic MRI suggested ANE1. Genetic analyses revealed two variants: a rare heterozygous missense variant of RANBP2 [c.1754C>T; p.Thr585Met], and a thermolabile polymorphism in carnitine palmitoyltransferase 2 (CPT2) [c. 1055T>G; p.Phe352Cys]. CONCLUSION: This is the first case of recurrent ANE with an RANBP2 mutation in Japan. The patient also harbored a CPT2 polymorphism that is linked to acute encephalopathy in Japanese patients. Thus, he had a genetic background with two susceptibility variants for acute encephalopathy, RANBP2 (frequent in the Caucasians), and CPT2 (frequent in the Japanese). Further studies are needed to fully discover the genetic predisposition to familial or recurrent ANE in the Asian population.

Transient Probst Bundle Diffusion Restriction: An Acute Encephalopathy Equivalent to Clinically Mild Encephalopathy with a Reversible Splenial Lesion.

Probst bundles are selectively seen in patients with agenesis of the corpus callosum (CC) and are thought to be homologous to the CC. We herein report a 19-year-old woman with partial agenesis of the CC. She developed acute encephalopathy during Bordetella pertussis infection. Brain magnetic resonance imaging (MRI) showed restricted diffusion of bilateral Probst bundles. She was treated with anti-epileptics and azithromycin and recovered with no neurological sequelae. Follow-up MRI showed the resolution of the diffusion abnormality. The characteristics of diffusion-weighted images on brain MRI and clinical course mimicked those in cases of clinically mild encephalopathy/encephalitis with reversible splenial lesion.

Pd/C-catalyzed chemoselective hydrogenation in the presence of diphenylsulfide.

[Structure: see text] A Pd/C-catalyzed chemoselective hydrogenation using diphenylsulfide as a catalyst poison has been developed. This methodology selectively hydrogenates olefin and acetylene functionalities without hydrogenolysis of aromatic carbonyls and halogens, benzyl esters, and N-Cbz protective groups.