Two children with lymphocytic hypophysitis presenting with positive anti-rabphilin-3A antibody.

Lymphocytic hypophysitis (LYH) is a rare chronic inflammatory disease characterized by lymphocytic infiltration of the anterior or posterior pituitary gland and hypothalamus. LYH is subdivided into lymphocytic adenohypophysitis (LAH), lymphocytic infundibulo-neurohypophysitis (LINH), and lymphocytic panhypophysitis (LPH) depending on the primary site. Most cases occur in adults, with few cases reported in children, and it is especially important to distinguish LYH from suprasellar malignancies, such as germ cell tumors and other neoplastic diseases. Although a biopsy is necessary for definitive diagnosis, it is desirable to be able to diagnose the disease without biopsy if possible, especially in children, because of the surgical invasiveness of the procedure. Recently, serum anti-rabphilin-3A antibodies have attracted attention as diagnostic markers for LYH, especially in LINH, but there are only a few reports on pediatric patients. In the present study, we experienced two children with LPH and LAH, respectively, who tested positive for anti-rabphilin-3A antibodies. This is the first report of children with LYH other than LINH positive for anti-rabphilin-3A antibodies, and anti-rabphilin-3A antibodies may be a useful non-invasive diagnostic marker not only for LINH but also for LYH in general. We also discuss the sensitivity and specificity of anti-rabphilin-3A antibody testing in cases where histological diagnosis has been made.

Prediction of intracerebral hemorrhage in patients with out-of-hospital cardiac arrest using post-resuscitation electrocardiogram: An observational cohort study.

Aim: We evaluated the characteristics of patients with intracerebral hemorrhage in nontraumatic out-of-hospital cardiac arrests (OHCA) after return of spontaneous circulation (ROSC) to identify patients who required brain computed tomography as the next diagnostic workup. Methods: We conducted a retrospective cohort study on 1303 consecutive patients with nontraumatic OHCA who were admitted to Miyazaki Prefectural Nobeoka Hospital between 2008 and 2020. Among these, 454 patients achieved sustained ROSC. We excluded 126 patients with obvious extracardiac causes. Clinical and demographic characteristics of patients and post-resuscitation 12-lead electrocardiogram were compared. Patients were categorized into the intracerebral hemorrhage (n = 32, 10%) and no intracerebral hemorrhage group (n = 296). All causes of intracerebral hemorrhage were diagnosed based on brain computed tomography images by board-certified radiologists. Results: We included 328 patients (mean age, 74 years; women, 36%) who achieved ROSC. Logistic regression analyses showed that female sex, younger age (<75 years), no shockable rhythm changes, tachycardia (≥100 bpm), lateral ST-segment elevation, and inferior ST-segment depression on post-resuscitation electrocardiogram were independently associated with intracerebral hemorrhage. We developed a new predictive model for intracerebral hemorrhage by considering 1 point for each of the six factors. The odds ratio for intracerebral hemorrhage increased 2.36 for each 1-point increase (P < 0.001). A score ≥ 4 had 43.7% sensitivity, 90.8% specificity, 34.1% positive predictive value, and 93.7% negative predictive value. Conclusion: Our new predictive model might be useful for risk stratification of intracerebral hemorrhage in patients with OHCA who achieved ROSC.

Meningioma in Down Syndrome.

BACKGROUND: Down syndrome comprises multiple malformations and is due to trisomy of chromosome 21. There is epidemiologic evidence that individuals with Down syndrome are at decreased risk for solid tumors including brain tumors. It has been suggested that some genes expressed on the extra copy of chromosome 21 act as tumor suppressor genes and contribute to protection against tumorigenesis. CASE DESCRIPTION: We report the first case to our knowledge of a patient with Down syndrome, an 8-year-old boy, with an intracranial meningioma, in which the status of chromosome 21 was examined. The diagnosis was based on histologic examination of the surgically resected tumor. Postoperatively, the patient's neurologic status improved, and there was no tumor regrowth in the next 2 years. Fluorescence in situ hybridization for chromosome 22 confirmed high allele loss involving the neurofibromin 2 gene locus, a finding typical in meningiomas. Fluorescence in situ hybridization also revealed chromosome 21 heterogeneity in tumor cells; not only cells with trisomy 21 but also cells with disomy and monosomy 21 were present. All blood cells from the patient manifested trisomy 21. CONCLUSIONS: Deletion of the chromosome 21 allele may be associated with tumorigenesis of meningioma in Down syndrome. This supports the hypothesis that some genes whose expression is increased on the extra copy of chromosome 21 function as tumor suppressor genes and that they contribute to the reduced tumor incidence in individuals with Down syndrome.

Lack of Reelin causes malpositioning of nigral dopaminergic neurons: evidence from comparison of normal and Reln(rl) mutant mice.

The reeler gene (Reln(rl), formerly rl) product Reelin controls neuronal migration and positioning and thereby plays a key role in brain development. Mutation of Reln leads to widespread disruption of laminar cortical regions and ectopia in some brainstem nuclei. In the embryonic striatum of normal mice, a substantial expression of reelin mRNA has been documented; however, the anomalous positioning of neurons in the basal ganglia of reeler mice remains to be studied. We provide first evidence for a potential role of Reelin in the developmental formation of the substantia nigra. In reeler mutant mice lacking Reelin, dopaminergic neurons destined for the substantia nigra fail to migrate laterally and become anomalously clustered just lateral to the ventral tegmental area. Their axons appear to project to striatal patches forming "dopamine islands." Results from the normal mice show that, at the midembryonic stage, Reelin identified with CR-50 is highly concentrated in the ventral mesencephalon, where nigral dopaminergic neurons are in progress to migrate laterally to their eventual position of the adult brain. A combination of CR-50 labeling and anterograde axonal tracing provided evidence that embryonic striatal neurons may supply the ventral portion of the mesencephalon with Reelin through their axonal projections. We hypothesize that Reelin plays a role in the positioning of nigral dopaminergic neurons and that it can act as an environmental cue at a remote site far from its birthplace via a transaxonal delivery system.

Neuronal cell migration for the developmental formation of the mammalian striatum.

The mammalian striatum is the largest receptive component of the basal ganglia circuit. It is involved in the control of various aspects of motor, cognitive, and emotional functions. In the telencephalon, the striatum has a unique histological property totally different from the cortical area and its ontogenesis remains largely unknown. In this review, we introduce recent advances in the understanding of neuronal cell migration, one of the most critical processes in the early phase of histogenesis that occurs in the embryonic striatum. It appears that there are three major modes of neuronal cell migration in the developmental formation of the striatum. They are (radial) outward, tangential, and inward migration, supplying the striatum with projection neurons, interneurons, and early-generated transient neurons that originate in the preplate, respectively. We challenge the classical concept that the striatum is solely derived from the restricted germinal area located in the basal telencephalon by providing evidence that striatal development requires the intermixture of different types of neurons originating from distinct regions of the telencephalon.

Involvement of reelin and Cajal-Retzius cells in the developmental formation of vertical columnar structures in the cerebral cortex: evidence from the study of mouse presubicular cortex.

The mammalian cerebral cortex is organized into horizontal and vertical arrays of neurons and their fiber connections that form anatomically and physiologically distinct laminar and columnar compartments. However, the developmental mechanism(s) underlying this dichotomous pattern remains a mystery. We provide anatomical evidence suggesting that reelin, a diffusible protein produced and secreted by Cajal-Retzius cells, is involved in the developmental formation of the vertical cell structures in the mouse presubicular cortex, the unique site where the vertical columnar arrays of cortical plate neurons and their dendritic branches are clearly identified during the early postnatal period. Our results also suggest that reelin plays a role in the formation of these vertical structures by acting as an inhibitory or stop signal for cortical plate neurons and their dendritic extensions. In addition to having perturbed horizontal laminae, reeler mutant mice, lacking reelin, display disruption of these vertical structures. Based on the present findings, we hypothesize that reelin and Cajal-Retzius cells regulate the developmental formation of not only horizontal laminations, but also vertical columnar structures in the cerebral cortex.

Impact of posterior GPI pallidotomy on leg tremor in Parkinson's disease.

Although stereotactic thalamotomy is the mainstay in the surgical treatment of tremor in patients with Parkinson's disease (PD), this surgery is not favored and is even a matter of potential concern in the treatment of leg tremor since it carries a significant risk of injury to the internal capsule. In this study we have carried out a quantitative assessment of leg tremor alleviation in 12 patients with PD after MRI-/microelectrode-guided stereotactic ablation of the posterior part of the globus pallidus internus (GPi). The results showed that posterior GPi pallidotomy combined with drug therapy is a satisfactorily effective therapeutic strategy to treat parkinsonian leg tremor.