GA binding protein augments autophagy via transcriptional activation of BECN1-PIK3C3 complex genes
2014; 10 (9): 1622-1636
Histologic Artifacts of Autolytic Müller Cell Foot Process Swelling in Postmortem Examination of Infant Eyes: Potential Pitfall in the Evaluation of Traumatic Retinal Hemorrhages.
Mutant LRRK2 enhances glutamatergic synapse activity and evokes excitotoxic dendrite degeneration.
Biochimica et biophysica acta
2014; 1842 (9): 1596-1603
Retinal hemorrhages are an important sequela of fatal head trauma. The accurate pathologic diagnosis of retinal hemorrhages has critical implications for determination of the manner of death.We describe an autolytic postmortem histologic artifact of eosinophilic Müller cell foot process swelling that mimics a nerve fiber layer hemorrhage. From April 24, 2012, through November 11, 2014, we conducted postmortem examination of the eyes of 23 infants and children who were referred to our institution for possible nonaccidental head trauma. A focal artifact of Müller cell foot process swelling was identified in most patients (16 of 23) up to 4 years of age. Three infants, all of whom were younger than 3 months, demonstrated diffusely swollen Müller cell foot processes with intensely eosinophilic cytoplasm that mimicked erythrocytes of nerve fiber layer hemorrhages. The difference in the mean age between patients with diffuse eosinophilic artifacts (1.7 months) and patients with only a multifocal, focal, or absent artifact (13.3 months) was 11.6 months (95% CI, 6.5-16.7 months). Glycophorin C immunohistochemical analysis was useful to differentiate this artifact from nerve fiber layer hemorrhage.Our case review demonstrates an artifact of eosinophilic Müller cell foot processes swelling in postmortem examination of young infant eyes, a potential pitfall in the diagnosis of retinal hemorrhages. Our findings have important implications for the diagnosis of retinal hemorrhages in potential cases of nonaccidental head injury.
View details for DOI 10.1001/jamaophthalmol.2015.0493
View details for PubMedID 25837496
Tectal pineal cyst in a 1-year-old girl
2014; 45 (3): 653-656
Mutations in leucine-rich repeat kinase 2 (LRRK2), which are associated with autosomal dominant Parkinson's disease, elicit progressive dendrite degeneration in neurons. We hypothesized that synaptic dysregulation contributes to mutant LRRK2-induced dendritic injury. We performed in vitro whole-cell voltage clamp studies of glutamatergic receptor agonist responses and glutamatergic synaptic activity in cultured rat cortical neurons expressing full-length wild-type and mutant forms of LRRK2. Expression of the pathogenic G2019S or R1441C LRRK2 mutants resulted in larger whole-cell current responses to direct application of AMPA and NMDA receptor agonists. In addition, mutant LRRK2-expressing neurons exhibited an increased frequency of spontaneous miniature excitatory postsynaptic currents (mEPSCs) in conjunction with increased excitatory synapse density as assessed by immunofluorescence for PSD95 and VGLUT1. Mutant LRRK2-expressing neurons showed enhanced vulnerability to acute synaptic glutamate stress. Furthermore, treatment with the NMDA receptor antagonist memantine significantly protected against subsequent losses in dendrite length and branching complexity. These data demonstrate an early association between mutant LRRK2 and increased excitatory synapse activity, implicating an excitotoxic contribution to mutant LRRK2 induced dendrite degeneration.
View details for DOI 10.1016/j.bbadis.2014.05.016
View details for PubMedID 24874075
Co-occurrence of a cerebral cavernous malformation and an orbital cavernous hemangioma in a patient with seizures and visual symptoms: Rare crossroads for vascular malformations.
Surgical neurology international
2014; 5: S148-54
Glial cysts of the pineal gland can frequently be found in adults and children, but only rarely do they enlarge to become clinically relevant. We report a unique presentation of a pineal cyst in the midbrain tectum of a 16-month-old girl who initially presented with ptosis and strabismus. Preoperative imaging studies and intraoperative findings revealed no continuity between the tectal cyst and the pineal gland proper. We surmise that this tectal pineal cyst may have arisen from duplicated pineal gland tissue.
View details for DOI 10.1016/j.humpath.2013.10.002
View details for Web of Science ID 000331854400028
Occult pigmented ganglioglioma in an adult male with chronic posttraumatic epilepsy.
2013; 32 (3): 192-195
Cerebral cavernous malformations (CCMs) are angiographically occult vascular malformations of the central nervous system. As a result of hemorrhage and mass effect, patients may present with focal neurologic deficits, seizures, and other symptoms necessitating treatment. Once symptomatic, most often from hemorrhage, CCMs are treated with microsurgical resection. Orbital cavernous hemangiomas (OCHs) are similar but distinct vascular malformations that present within the orbital cavity. Even though CCMs and OCHs are both marked by dilated endothelial-lined vascular channels, they are infrequently seen in the same patient.We provide a brief overview of the two related pathologies in the context of a patient presenting to our care with concomitant lesions, which were both resected in full without complication.This is the first known report that describes a case of concomitant CCM and OCH and explores the origins of two pathologies that are rarely encountered together in neurosurgical practice. Recognition of disparate symptomatologies is important for properly managing these patients.
View details for DOI 10.4103/2152-7806.134810
View details for PubMedID 25071938