Transorbital penetrating head injury by a wooden chopstick in the cavernous sinus: a case report and literature review.

Penetrating head injury is a relatively rare condition associated with high morbidity and mortality. Although the immediate treatment of penetrating head injury is needed, surgical strategies are varied based on the trajectory of the penetrating objects in the cranium. We present a case of 24-year-old man who sustained a transorbital penetrating injury caused by a wooden chopstick. Neuroimages revealed a linear lesion extending from the left intraorbital segment to the cavernous sinus passing through the superior orbital fissure. The foreign body was successfully removed via the transcranial approach without complications. A careful management based on the perioperative images and correct diagnosis is necessary to avoid unfavorable complications. Four cases of transorbital penetrating injuries have been previously reported, in which the foreign body penetrated through the superior orbital fissure and lodged in the cavernous sinus. The frontotemporal craniotomy with extradural approach can be a useful option to remove foreign bodies around the cavernous sinus regions.

A nationwide epidemiologic, clinical, genetic study of Usher syndrome in Japan.

BACKGROUND: Usher syndrome (USH) typically leads to deaf-blindness, requiring the provision of extensive education and rehabilitation services. Therefore, investigating the prevalence is crucial to requests for proper government support for USH patients. OBJECTIVE: The aim was to perform a nationwide epidemiologic survey of USH in Japan to estimate the prevalence of USH and reveal the relative frequency and characteristics of the three USH subtypes. METHODS: To estimate the number of USH patients visiting hospitals over a 1-year period, 1,628 hospitals were randomly selected from all Departments of Otorhinolaryngology and Ophthalmology in Japan. Subsequently, we collected data regarding the clinical characteristics of each patient treated and the results of genetic testing, if performed. RESULTS: We found that the prevalence of USH was at least 0.4 per 100,000 population. The frequency of clinical subtypes and causal genes for USH were consistent with previous reports. Also, we demonstrated the feasibility of genetic counseling for USH patients based on the results of genetic testing. CONCLUSION: USH is a rare disease, but requires social support due to the severity of symptoms. To minimize these issues, understanding the clinical characteristics and performing comprehensive genetic testing could allow early and accurate diagnosis as well as medical intervention.

[Optic neuropathy from connected intra- and extraorbital lesions in IgG4-related disease].

We present the case of a 74-year-old woman complaining of blurred vision in the left eye who was found to have a unilateral, continuous lesion of the optic nerve and nerve sheath accompanied by an intracranial mass next to the cavernous sinus and meninges. Surgical decompression of the left optic nerve in the optic canal and partial resection of the mass followed by prednisolone administration were successful. Immunohistochemical analysis disclosed abundant infiltration of IgG4-positive plasma cells at >10 cells/high power field. These findings indicated a new pattern of compressive optic neuropathy with confirmed IgG4 histopathological findings. Such an extensive lesion may produce visual disturbance.

Immunoglobulin G4-related dacyroadenitis presenting as bilateral chorioretinal folds from severely enlarged lacrimal glands.

PURPOSE: To describe a case of immunoglobulin G4 (IgG4)-related dacyroadenitis presenting as bilateral chorioretinal folds from eyeball compression by massively enlarged lacrimal glands. OBSERVATIONS: A 51-year-old woman with severely enlarged bilateral lacrimal glands was diagnosed as having IgG4-related dacryoadenitis. The glands strongly compressed the globes, forming chorioretinal folds resembling those found in orbital malignancy. Eventual treatment with oral prednisolone dramatically reduced the volume of the lacrimal glands and released globe compression on magnetic resonance imaging. However, the chorioretinal folds remained in the right fundus and symptoms of blurred vision improved but persisted. CONCLUSIONS AND IMPORTANCE: This is the first account of chorioretinal fold formation by severely enlarged lacrimal glands appearing in IgG4-related dacryoadenitis. Chorioretinal fold formation by an enlarged lacrimal gland occurring bilaterally may represent a basis for suspecting IgG4-related dacryoadenitis. Prompt treatment is recommended for patients presenting with very large lacrimal glands to avoid visual impairment.

The magnetic resonance imaging spectrum of Pelizaeus-Merzbacher disease: A multicenter study of 19 patients.

PURPOSE: We retrospectively evaluated the imaging spectrum of Pelizaeus-Merzbacher disease (PMD) in correlation with the clinical course and genetic abnormality. METHODS: We collected the magnetic resonance imaging (MRI) findings of 19 genetically proven PMD patients (all males, aged 0-29years old) using our integrated web-based MRI data collection system from 14 hospitals. The patterns of hypomyelination were determined mainly by the signals of the cerebrum, corticospinal tract, and brainstem on T2-weighted images (T2WI). We assessed the degree of myelination age on T1-weighted images (T1WI) and T2WI independently, and we evaluated cerebellar and callosal atrophy. The clinical severity and genetic abnormalities (causal mutations of the proteolipid protein gene PLP1) were analyzed together with the imaging findings. RESULTS: The clinical stage tended to be more severe when the whole brainstem, or corticospinal tract in the internal capsule showed abnormally high intensity on T2WI. Diffuse T2-high signal of brainstem was observed only in the patients with PLP1 point mutation. Myelination age "before birth" on T1WI is a second manifestation correlated with the clinically severe phenotypes. On the other hand, eight patients whose myelination ages were > 4months on T1WI were associated with mild clinical phenotypes. Four of them showed almost complete myelination on T1WI with a discrepancy in myelination age between T1WI and T2WI. A random and patchy pattern of myelination on T2WI was noted in one patient with PLP1 point mutation. Advanced myelination was observed in three of the seven followed-up patients. Four patients had atrophy of the cerebellum, and 17 patients had atrophy of the corpus callosum. CONCLUSION: Our multicenter study has demonstrated a wide variety of imaging findings of PMD. Signal intensity of brainstem and corticospinal tract of internal capsule would be the points to presume clinical severity in PMD patients. The spectrum of MRI findings should be kept in mind to diagnose PMD and to differentiate from other demyelinating leukodystrophies.

Primary intraosseous meningioma in the calvaria: morphological feature changes on magnetic resonance images over several years.

Primary intraosseous meningiomas (PIMs) are rare, and their pathogenesis remains unclear. We report the case of a sizable PIM in the calvaria that progressively enlarged over several years and presented temporal changes in the morphological features on magnetic resonance images. Along with discussing the case, we further emphasize the potential pitfalls of diagnosing a PIM in the calvaria.

Urgent Vitrectomy/Phacovitrectomy for Bullous Macula-Off Retinal Detachment: Implications for Optimal Timing of Surgery.

PURPOSE: Recently, an increasing number of ophthalmologists are using vitrectomy as the first line of treatment for retinal detachment (RD). The purpose of the present study was to determine the cutoff time of duration of macular detachment (DMD) after which postoperative best corrected visual acuity (BCVA) decreases sharply in eyes treated with primary vitrectomy. DESIGN: This was a retrospective, noncomparative, interventional case series. METHODS: Fifty-six eyes with macula-on RD and 126 eyes with bullous macula-off RD. RESULTS: Mean postoperative BCVA showed a statistically significant decrease when DMD exceeded 10 days (P = 0.009) with vitrectomy/phacovitrectomy as the primary mode of treatment, which was comparable to previous studies using scleral buckling. Approximately 90% (88%-93%) of eyes achieved a postoperative 20/40 BCVA when DMD was 2 days or less, after which the ratio decreased (P = 0.008) but plateaued around 40% until DMD reached 10 days. On the other hand, only 5.6% of (7/126) eyes with DMD of 3 days or less achieved a postoperative 20/20 BCVA. CONCLUSIONS: As with scleral buckling, the mean postoperative BCVA in eyes with bullous macula-off RD treated with primary vitrectomy/phacovitrectomy dropped significantly when DMD exceeded 10 days. To achieve a good postoperative visual acuity (20/40), urgent surgery with a DMD of 2 days or less is desired. Operative repair within this period, rather than outright emergency surgery, may be appropriate for most cases.

A case of Bardet-Biedl syndrome complicated with intracranial hypertension in a Japanese child.

Bardet-Biedl syndrome (BBS) is a rare heterogeneous autosomal recessive disorder characterized by rod-cone dystrophy, postaxial polydactyly, truncal obesity, hypogonadism, learning disability, and renal anomaly that are caused by ciliary dysfunction. 16 genes have been associated with the BBS phenotype. Although recent pathophysiological studies using animal models have shown that ciliary dysfunction may induce hydrocephalus, there have been no reports of BBS with intracranial hypertension. We here describe a 9-year-old Japanese girl who was diagnosed as having BBS and later received renal transplantation due to chronic renal failure. She also exhibited intracranial hypertension, including papilledema and increased intrathecal pressure (260-300 mmH2O), but her brain magnetic resonance imaging was normal. No genetic abnormalities were detected by DNA chip analysis or exome sequencing. Her papilledema improved following administration of acetazolamide. This is the first report of a case of BBS complicated with intracranial hypertension and its treatment.

pSLA2-M of Streptomyces rochei is a composite linear plasmid characterized by self-defense genes and homology with pSLA2-L.

The 113,463-bp nucleotide sequence of the linear plasmid pSLA2-M of Streptomyces rochei 7434AN4 was determined. pSLA2-M had a 69.7% overall GC content, 352-bp terminal inverted repeats with 91% (321/352) identity at both ends, and 121 open reading frames. The rightmost 14.6-kb sequence was almost (14,550/14,555) identical to that of the coexisting 211-kb linear plasmid pSLA2-L. Adjacent to this homologous region an 11.8-kb CRISPR cluster was identified, which is known to function against phage infection in prokaryotes. This cluster region as well as another one containing two large membrane protein genes (orf78 and orf79) were flanked by direct repeats of 194 and 566 bp respectively. Hence the insertion of circular DNAs containing each cluster by homologous recombination was suggested. In addition, the orf71 encoded a Ku70/Ku80-like protein, known to function in the repair of double-strand DNA breaks in eukaryotes, but disruption of it did not affect the radiation sensitivity of the mutant. A pair of replication initiation genes (orf1-orf2) were identified at the extreme left end. Thus, pSLA2-M proved to be a composite linear plasmid characterized by self-defense genes and homology with pSLA2-L that might have been generated by multiple recombination events.

Surgical treatment for a ruptured true posterior communicating artery aneurysm arising on the fetal-type posterior communicating artery--two case reports and review of the literature.

Only a small number of aneurysms arising on the posterior communicating artery itself (true Pcom aneurysm) have been reported. We report two cases of ruptured true Pcom aneurysms with some characteristic features of true Pcom aneurysm. A 43 year old man suffering from subarachnoid hemorrhage (SAH) had an aneurysm arising on the fetal-type Pcom artery itself, and underwent surgery for clipping. Most of the aneurysm was buried in the temporal lobe, so retraction of the temporal lobe was mandatory. During the retraction, premature rupture was encountered. After tentative dome clipping and the control of bleeding, complete clipping was achieved. Another patient, a 71 year old woman presenting with consciousness disturbance due to SAH, had an aneurysm on the fetal-type Pcom artery itself, and underwent surgery for clipping. It has been generally considered that hemodynamic factor plays an important role in the formation, the growth, and the rupture of the cerebral aneurysm. This factor is especially significant in true Pcom aneurysm formation and rupture. According to the literature, a combination of fetal type Pcom and formation of the true Pcom aneurysm has been reported in most cases (81.8%). Most of the aneurysm can be buried in the temporal lobe, and the retraction of the temporal lobe during the dissection of the neck would be necessary, which causes premature rupture of the true Pcom aneurysm. In the surgery for a true Pcom aneurysm, we should be aware of possible premature rupture when temporal lobe retraction is necessary.

Clinical features of epilepsy with pervasive developmental disorder.

PURPOSE: To clarify the clinical features of patients with epilepsy and pervasive developmental disorder (PDD). METHODS: We examined 12 outpatients with epilepsy as well as PDD at Seiai Rehabilitation Hospital. RESULTS: The patients comprised 7 males and 5 females. The initial neurological symptoms appeared between 5 months and 4 years of age. The interval between the initial neurological symptoms/developmental delay and seizure onset ranged from several months to twenty years. The seizures started at 10-19 years of age in 8 out of the 12 cases. The types of seizures were astatic-drop in 2 cases, tonic-to-astatic in one, atypical absence (decreased consciousness) and generalized tonic clonic seizures (GTCS) in 3 cases, GTCS in 4 cases, or myoclonic and psychomotor in 2 cases. The mental development distributed from normal to extremely severe retardation. Paroxysmal abnormalities on eegs were focal at the frontal area in 7 cases (58%) and other findings in 5 cases. Presumptive risk factors were prenatal in 6 cases (family history for PDD in 1 case, for epilepsy in 1, twin pregnancy in 2 cases, and other in 2 cases), perinatal in 2 patients, postnatal in 1, and unknown in 3 cases. CONCLUSIONS: The seizures occurred most frequently after the onset of neurological symptoms or developmental delay. The frontal lobe dysfunction was associated with seizure onset in 58% of the cases based on the EEG findings. The risk factors were prenatal in 50% of the cases.

Neuroprotection by the NR3A subunit of the NMDA receptor.

Hyperactivation of NMDA-type glutamate receptors (NMDARs) results in excitotoxicity, contributing to damage in stroke and neurodegenerative disorders. NMDARs are generally comprised of NR1/NR2 subunits but may contain modulatory NR3 subunits. Inclusion of NR3 subunits reduces the amplitude and dramatically decreases the Ca2+ permeability of NMDAR-associated channels in heterologous expression systems and in transgenic mice. Since excessive Ca2+ influx into neurons is a crucial step for excitotoxicity, we asked whether NR3A subunits are neuroprotective. To address this question, we subjected neurons genetically lacking NR3A to various forms of excitotoxic insult. We found that cultured neurons prepared from NR3A knock-out (KO) mice displayed greater sensitivity to damage by NMDA application than wild-type (WT) neurons. In vivo, neonatal, but not adult, WT mice contain NR3A in the cortex, and neonatal NR3A KO mice manifested more damage than WT after hypoxia-ischemia. In adult retina, one location where high levels of NR3A normally persist into adulthood, injection of NMDA into the eye killed more retinal ganglion cells in adult NR3A KO than WT mice. These data suggest that endogenous NR3A is neuroprotective. We next asked whether we could decrease excitotoxicity by overexpressing NR3A. We found that cultured neurons expressing transgenic (TG) NR3A displayed greater resistance to NMDA-mediated neurotoxicity than WT neurons. Similarly in vivo, adult NR3A TG mice subjected to focal cerebral ischemia manifested less damage than WT mice. These data suggest that endogenous NR3A protects neurons, and exogenously added NR3A increases neuroprotection and could be potentially exploited as a therapeutic.

Regulation of macrophage procoagulant responses by the tissue factor cytoplasmic domain in endotoxemia.

Tissue factor (TF) is the primary initiator of coagulation, and the TF pathway mediates signaling through protease-activated receptors (PARs). In sepsis, TF is up-regulated as part of the proinflammatory response in lipopolysaccharide (LPS)-stimulated monocytes leading to systemic coagulation activation. Here we demonstrate that TF cytoplasmic domain-deleted (TF(Delta CT)) mice show enhanced and prolonged systemic coagulation activation relative to wild-type upon LPS challenge. However, TF(Delta CT) mice resolve inflammation earlier and are protected from lethality independent of changes in coagulation. Macrophages from LPS-challenged TF(Delta CT) mice or LPS-stimulated, in vitro-differentiated bone marrow-derived macrophages show increased TF mRNA and functional activity relative to wild-type, identifying up-regulation of macrophage TF expression as a possible cause for the increase in coagulation of TF(Delta CT) mice. Increased TF expression of TF(Delta CT) macrophages does not require PAR2 and is specific for toll-like receptor, but not interferon gamma receptor, signaling. The presence of the TF cytoplasmic domain suppresses ERK1/2 phosphorylation that is reversed by p38 inhibition leading to enhanced TF expression specifically in wild-type but not TF(Delta CT) mice. The present study demonstrates a new role of the TF cytoplasmic domain in an autoregulatory pathway that controls LPS-induced TF expression in macrophages and procoagulant responses in endotoxemia.

Role of protease activated receptor 1 and 2 signaling in hypoxia-induced angiogenesis.

OBJECTIVE: Tissue factor (TF) initiates coagulation and indirectly triggers thrombin-dependent protease activated receptor (PAR) signaling. The TF-VIIa complex also directly cleaves PAR2 and promotes angiogenesis in vitro in TF cytoplasmic domain-deleted (TF(deltaCT)) mice. Here we address the effect of PAR1 and PAR2 deficiency on angiogenesis in vivo. METHODS AND RESULTS: In hypoxia-driven angiogenesis of oxygen induced retinopathy (OIR), wild-type, PAR1-/-, PAR2-/-, and TF(deltaCT) mice showed a comparable regression of the superficial vascular plexus during the initial exposure of mice to hyperoxia. However, TF(deltaCT) mice revascularized areas of central vaso-obliteration significantly faster than wild-type animals. Pharmacological inhibition of the TF-VIIa complex, but not of Xa, and blockade of tyrosine kinase receptor pathways with Gleevec reversed accelerated angiogenesis of TF(deltaCT) mice to revascularization rates observed in wild-type mice. Genetic deletion of PAR2, but not of PAR1, abolished enhanced revascularization of TF(deltaCT) mice. PAR1 knock-out animals were indistinguishable from wild-type mice in the model of retinal neoangiogenesis and angiogenesis-dependent subcutaneous tumor growth was unaltered in PAR1- and PAR2-deficient animals. CONCLUSION: Loss of the TF cytoplasmic domain results in accelerated hypoxia-induced angiogenesis mediated by TF-VIIa signaling. PAR2 signaling is sufficient for this proangiogenic effect without apparent contributions of mouse host cell PAR1.

Heme oxygenase-1 induced in muller cells plays a protective role in retinal ischemia-reperfusion injury in rats.

PURPOSE: To investigate the protective roles played by heme oxygenase (HO)-1 and -2 in the rat retina after ischemia-reperfusion injury. METHODS: Retinal ischemia was induced in rats by increasing the intraocular pressure to 110 mmHg for 60 minutes. The expression of HO-1 and -2 in the retina was determined by Western blot, real-time polymerase chain reaction (PCR), and immunohistochemistry. To inhibit the upregulation of HO-1, short interfering (si)RNA of HO-1 was injected intravitreally before ischemia and that of green fluorescent protein (GFP) was used as the control. Muller cell damage was assessed by counting the number of S-100-positive cells. The number of macrophages invading the retina was determined by counting the number of ED-1-positive cells. RESULTS: The expression of HO-1 mRNA and protein was upregulated at 6 hours after reperfusion and peaked at 12 to 24 hours, whereas that of HO-2 was not altered. HO-1 immunoreactivities were detected in Muller cells at 24 hours after reperfusion, and HO-2 immunoreactivities were detected in retinal cells. The HO-1 expression in the retina treated with siRNA of HO-1 was reduced at 12 and 24 hours after reperfusion compared with that injected with siRNA of GFP. The number of S-100-positive cells at 24 hours after reperfusion decreased significantly in retinas treated with HO-1 siRNA (P <0.01). The number of macrophages that had infiltrated the retina was increased in retinas pretreated with the siRNA of HO-1 compared with those treated with siRNA of GFP. On day 14 after reperfusion, HO-1 siRNA-treated retinas showed severe retinal injury and destruction of the retinal architecture. CONCLUSIONS: HO-1 promotes the survival of Muller cells after ischemia-reperfusion injury. Because inhibition of the upregulation of HO-1 resulted in an infiltration of inflammatory cells and destruction of the retina, the authors conclude that HO-1 induced in Muller cells plays a protective role in retinal ischemia-reperfusion.

Ocular manifestations in Blau syndrome associated with a CARD15/Nod2 mutation.

PURPOSE: To report cases of Blau syndrome with a CARD15/Nod2 mutation. DESIGN: Observational and interventional case report. PARTICIPANTS: A 10-year-old Japanese boy (proband) was seen with secondary angle-closure glaucoma (iris bombe), uveitis, skin rashes, and camptodactyly. His sister had posterior synechia and camptodactyly. She had iritis in both eyes during the follow-up period. Both eyes of the father were phthisical because of granulomatous uveitis and secondary glaucoma. The father also had camptodactyly. METHODS: Surgery was performed to release the iris bombe. Ocular inflammation was treated by topical and systemic steroids. Biopsy specimens from the skin rash and from the iris (from iridectomy) were obtained from the proband. Genetic analyses were performed on the proband, his sister, and their mother for a CARD15/Nod2 mutation. MAIN OUTCOME MEASURES: Clinical features, pathologic findings of the skin and iris specimens, and genetic analysis of the CARD15/Nod2 gene. RESULTS: Phacoemulsification, intraocular lens implantation, and peripheral iridectomy released the iris bombe. The biopsy specimen from the skin rash showed noncaseating, granulomatous infiltration with epithelioid cells and lymphocytes. The iridectomy specimen showed nonspecific inflammation. Systemic and topical steroid therapy partly reduced the ocular inflammation. Genetic analyses showed that the proband and his sister had an R334W mutation in the CARD15/Nod2 gene, but their mother was of the wild type. CONCLUSIONS: Blau syndrome should be considered in the differential diagnosis of childhood uveitis. Genetic analysis of the CARD15/Nod2 gene is helpful in the diagnosis.

Gene microarray analysis of experimental glaucomatous retina from cynomologous monkey.

PURPOSE: To systematically explore changes in gene expression in the retina of monkeys with laser-induced glaucoma and to validate the microarray data on eyes with experimental glaucoma. METHODS: Glaucoma was induced in the right eye of four monkeys by repeated argon laser photocoagulation of the trabecular meshwork. The left eye served as the control. Retinas were isolated from glaucomatous and control eyes 30 days after photocoagulation. Gene expression changes were analyzed by human microarray chips which displayed a total of 9182 elements including Expression Sequence Tag (EST) clones. Changes in the expression of some genes were further confirmed by real-time PCR analysis. Immunohistochemical studies to examine protein expression of some gene products were also done for several genes that showed up- or downregulation by the microarray analysis. RESULTS: Two eyes with mild glaucoma and two with severe glaucoma were produced. In the mild and severe glaucomatous retina, the number of upregulated genes was 45 and 18, and the number of downregulated genes was 17 and 21, respectively. The number of genes that were up- or downregulated was 0.7% of all the genes examined. The real-time PCR analysis confirmed expression changes of some genes found in the microarray analysis. Ceruloplasmin was one of the upregulated genes, and it was found by immunohistochemical analyses to be expressed in Müller cells. CONCLUSIONS: Gene expression profiles in laser-induced glaucomatous monkey retinas were determined, and only a very small population of genes was up- or downregulated in glaucomatous eyes. Upregulation of ceruloplasmin protein was found in the Müller cells.