Superficial siderosis complicated by hydrocephalus: bleeding from the dura mater in the cerebrospinal fluid cavity after brain tumor surgery.

BACKGROUND: In most patients with superficial siderosis of the central nervous system, the exact source of bleeding remains unknown and a treatment has not yet been established. METHODS: We herein presented a case of superficial siderosis complicated by hydrocephalus 19 years after supratentorial brain tumor resection. RESULTS: The bleeding source was identified as the dura mater in the intracranial cerebrospinal fluid cavity, and not a recurrent tumor. CONCLUSION: Chronic intracranial bleeding from the dura mater was successfully arrested by replacement of the dura mater with the autologous fascia of the thigh, and hydrocephalus was treated with endoscopic surgery.

Multiple Spinal Syphilitic Gummas Diagnosed by Postoperative Histopathology and Antibiotic Responsiveness: A Case Report.

Neurosyphilis is an infection of the central nervous system by Treponema pallidum. Gummatous neurosyphilis, especially spinal syphilitic gumma, is an exceedingly rare manifestation and may be misdiagnosed as other tumors due to its rarity. A 42-year-old man with a medical history of treatment for syphilis presented with rapidly progressive leg paralysis, leg sensory disturbance, and bladder and rectal disturbance. Spinal MRI demonstrated an intradural extramedullary lesion strongly compressing the spinal cord at the T6/7 level, which was accompanied with dural tail sign and perilesional meningeal thickening at the T6-T8 levels. Small intradural extramedullary lesions were also detected at the T1 and T8 levels. Serological and cerebrospinal fluid examinations for syphilis were both positive. In the treatment of spinal syphilitic gumma, the decompression of the spinal cord by lesionectomy followed by postoperative antibiotic treatment is considered to be an optimal procedure in patients with rapid progression of neurological deterioration. In the present case, the symptomatic main lesion that was compressing the thoracic cord was excised by surgery and analyzed by histopathological examination, and another small asymptomatic lesion was resolved by postoperative antibiotic treatment. Spinal syphilitic gumma was diagnosed using both histopathological findings of the surgically resected lesion and another residual lesion that was resolved by postoperative antibiotic treatment.

A Case Report of Possible Thoracic Interdural Ganglion Cyst.

There are some intraspinal cystic lesions presenting with myelopathy. We report a case of myelopathy caused by a possible thoracic interdural ganglion cyst. A 70-year-old man with subacute bilateral lower extremity numbness, muscle weakness, and gait disturbance presented to our hospital. Magnetic resonance (MR) images showed a cystic lesion which compresses the left dorsolateral intraspinal space of T2-3. During surgery, a ganglion cyst was found without adhering to the periphery of the epidural space. The capsule and contents were removed. He showed postoperative improvement in activities of daily living. A postoperative pathological diagnosis of ganglion cyst was made. The development mechanism of thoracic interdural ganglion cysts is unknown. To our knowledge, this is the first report of this disease. Surgery improved symptoms of a patient with myelopathy caused by thoracic interdural ganglion cysts. This must be considered as one of the cystic lesions presenting with myelopathy.

Critical role of the N-terminal cyclic AMP-binding domain of Epac2 in its subcellular localization and function.

cAMP is a well-known regulator of exocytosis, and cAMP-GEFII (Epac2) is involved in the potentiation of cAMP-dependent, PKA-independent regulated exocytosis in secretory cells. However, the mechanisms of its action are not fully understood. In the course of our study of Epac2 knockout mice, we identified a novel splicing variant of Epac2, which we designate Epac2B, while renaming the previously identified Epac2 Epac2A. Epac2B, which lacks the first cAMP-binding domain A in the N-terminus but has the second cAMP-binding domain B of Epac2A, possesses GEF activity towards Rap1, as was found for Epac2A. Immunocytochemical analysis revealed that exogenously introduced Epac2A into insulin-secreting MIN6 cells was localized near the plasma membrane, while Epac2B was found primarily in the cytoplasm. Interestingly, cAMP-binding domain A alone introduced into MIN6 cells was also localized near the plasma membrane. In MIN6 cells, Epac2A was involved in triggering hormone secretion by stimulation with 5.6 mM glucose plus 1 mM 8-Bromo-cAMP, but Epac2B was not. The addition of a membrane-targeting signal to the N-terminus of Epac2B was able to mimic the effect of Epac2A on hormone secretion. Thus, the present study indicates that the N-terminal cAMP-binding domain A of Epac2A plays a critical role in determining its subcellular localization and potentiating insulin secretion by cAMP. J. Cell. Physiol. 219: 652-658, 2009. (c) 2009 Wiley-Liss, Inc.

Disturbed Consciousness and Coma: Diagnosis and Management of Intracranial Hypotension Caused by a Spinal Cerebrospinal Fluid Leak.

OBJECTIVE: The diagnosis and treatment of intracranial hypotension associated with a spinal cerebrospinal fluid (CSF) leak, especially in comatose patients, have yet to be established. METHODS: Clinical manifestations, neuroimaging findings, and treatment outcomes in 11 patients (Glasgow Coma Scale score 10 ± 4) were described and compared with 36 patients with normal consciousness. RESULTS: Patients with disturbed consciousness were diagnosed at a significantly older age (55 ± 11 years; P < 0.001) than those without (42 ± 8.8 years). Neuroimaging findings in patients with disturbed consciousness were characterized by a smaller midbrain-pons angle (7.8 ± 10°; P < 0.001), brainstem swelling (122%; P = 0.002), and thicker subdural hematomas (16 ± 7.0 mm°; P < 0.001). Epidural blood patch (EBP) alone did not achieve sustained improvements in patients with disturbed consciousness but did in most patients without (94%; P = 0.001). Over the treatment course, 5 patients progressed to coma, which correlated with a high signal intensity on T2-weighted magnetic resonance imaging in the brainstem. Hematoma drainage before EBP caused neurologic deterioration in 2 patients. Simultaneous EBP after hematoma drainage achieved sustained improvements in 5 of 6 patients. Simultaneous microsurgical dural repair after hematoma drainage achieved more rapid improvements in 3 of 3 patients. CONCLUSIONS: Among patients with intracranial hypotension caused by a spinal CSF leak, disturbed consciousness may occur in elderly patients because of severe diencephalic-mesencephalic deformities. Simultaneous EBP after safe hematoma drainage is indicated for these patients. Alternatively, dural repair is indicated for patients for whom the spinal level of dural disease has been identified. Hematoma drainage before EBP is not recommended because it caused deterioration.

Comparative study of perioperative complication rates of cervical laminoplasty performed by residents and teaching neurosurgeons.

Early surgical education is required for neurosurgical residents to learn many surgical procedures. However, the participation of less experienced residents may increase perioperative complication rates. Perioperative complication studies in the field of neurosurgery are being increasingly published; however, studies have not yet focused on cervical laminoplasty. The study population included 193 consecutive patients who underwent cervical laminoplasty in Tokyo Metropolitan Neurological Hospital between 2008 and 2014. Patient and surgeon background factors, as well as perioperative complication rates were retrospectively compared between resident and board-certified spine neurosurgeon groups. Deteriorated or newly developed neurological deficits and surgical site complications within 30days of cervical laminoplasty were defined as perioperative complications. Out of 193 patients, 123 (64%) were operated on by residents as the first operator and 70 (36%) by board-certified spine neurosurgeons. No significant differences were observed in patient and surgeon factors between the two groups, except for hyperlipidemia (13 vs 17, p=0.02). Furthermore, no significant differences were noted in perioperative complication rates between the two groups (7 [5.7%] vs 4 [5.7%], p=1). Cervical laminoplasty performed in a standardized manner by residents who received their surgical training in our hospital did not increase perioperative complication rates, and ensured the safety of patients.

Superficial siderosis of the central nervous system associated with intraspinal hemorrhage from ventral thoracic epidural veins and a ventral spinal CSF leak: case report.

In most patients with superficial siderosis of the CNS, the exact source of bleeding remains unknown because of a lack of objective surgical data. The authors herein describe the case of a 58-year-old man with superficial siderosis of the CNS. The patient also had spinal CSF leakage due to a spinal dural defect. Repair surgery for the dural defect was performed using posterior laminoplasty with a transdural approach without spinal fixation. During repair surgery, the bleeding source was found to be the epidural vein around the defect. The intraoperative and histological results of the present case suggest that epidural veins exposed to CSF represent a chronic bleeding source in patients with superficial siderosis of the CNS complicated by CSF leakage. Dural repair surgery may result in discontinuation of the CSF leaks, resolution of the epidural CSF collection, and cessation of chronic epidural bleeding.

Postoperative epidural haematomas associated with hydrocephalus caused by intraoperative overdrainage of cerebrospinal fluid: two case reports with a literature review of 19 cases.

We report two cases with postoperative epidural haematomas (EDHs) associated with hydrocephalus and discuss the cause of haematoma development on the basis of a literature review. A 13-year-old boy presented with obstructive hydrocephalus caused by a sellar mass lesion. Multifocal EDHs occurred after partial resection of the lesion via a transcallosal approach following ventricular drainage. In the second case, a 26-year-old man who had a history of ventriculoperitoneal shunting for congenital hydrocephalus presented with hydrocephalus caused by ventricular catheter obstruction. An EDH occurred after replacement of the ventricular catheter with a new burr hole opening. On the basis of a review of 19 cases including our two cases, the authors concluded that postoperative EDH development associated with hydrocephalus was mostly caused by intraoperative overdrainage of cerebrospinal fluid, resulting in rapid shrinkage of the brain with dilation of the epidural space, a situation that may have caused dural venous bleeding.

Posterior callosotomy using a parietooccipital interhemispheric approach in the semi-prone park-bench position.

A 2-stage corpus callosotomy is accepted as a palliative procedure for patients older than 16 years with, in particular, medically intractable generalized epilepsy and drop attack seizures and is preferable for a lower risk of disconnection syndrome. Although the methods by which a previously performed craniotomy can be reopened for posterior callosotomy have already been reported, posterior corpus callosotomy using a parietooccipital interhemispheric approach with the patient in a semi-prone park-bench position has not been described in the literature. Here, the authors present a surgical technique for posterior callosotomy using a parietooccipital interhemispheric approach with a semi-prone park-bench position as a second surgery. Although this procedure requires an additional skin incision in the parietooccipital region, it makes the 2-stage callosotomy safer and easier to perform because of reduced intracranial adhesion, less bleeding, and an easier approach to the splenium of the corpus callosum.

Aph-1 contributes to the stabilization and trafficking of the gamma-secretase complex through mechanisms involving intermolecular and intramolecular interactions.

Gamma-secretase cleaves type I transmembrane proteins, including beta-amyloid precursor protein and Notch, and requires the formation of a protein complex comprised of presenilin, nicastrin, Aph-1, and Pen-2 for its activity. Aph-1 is implicated in the stabilization of this complex, although its precise mechanistic role remains unknown. Substitution of the first glycine within the transmembrane GXXXG motif of Aph-1 causes a loss-of-function phenotype in Caenorhabditis elegans. Here, using an untranslated region-targeted RNA interference/rescue strategy in Drosophila Schneider 2 cells, we show that Aph-1 contributes to the assembly of the gamma-secretase complex by multiple mechanisms involving intermolecular and intramolecular interactions depending on or independent of the conserved glycines. Aph-1 binds to nicastrin forming an early subcomplex independent of the conserved glycines within the endoplasmic reticulum. Certain mutations in the conserved GXXXG motif affect the interaction of the Aph-1.nicastrin subcomplex with presenilin that mediates trafficking of the presenilin.Aph-1.nicastrin tripartite complex to the Golgi. The same mutations decrease the stability of Aph-1 polypeptides themselves, possibly by affecting intramolecular associations through the transmembrane domains. Our data suggest that the proper assembly of the Aph-1.nicastrin subcomplex with presenilin is the prerequisite for the trafficking as well as the enzymatic activity of the gamma-secretase complex and that Aph-1 functions as a stabilizing scaffold in the assembly of this complex.

The role of presenilin cofactors in the gamma-secretase complex.

Mutations in presenilin genes account for the majority of the cases of the familial form of Alzheimer's disease (FAD). Presenilin is essential for gamma-secretase activity, a proteolytic activity involved in intramembrane cleavage of Notch and beta-amyloid precursor protein (betaAPP). Cleavage of betaAPP by FAD mutant presenilin results in the overproduction of highly amyloidogenic amyloid beta42 peptides. gamma-Secretase activity requires the formation of a stable, high-molecular-mass protein complex that, in addition to the endoproteolysed fragmented form of presenilin, contains essential cofactors including nicastrin, APH-1 (refs 15-18) and PEN-2 (refs 16, 19). However, the role of each protein in complex formation and the generation of enzymatic activity is unclear. Here we show that Drosophila APH-1 (Aph-1) increases the stability of Drosophila presenilin (Psn) holoprotein in the complex. Depletion of PEN-2 by RNA interference prevents endoproteolysis of presenilin and promotes stabilization of the holoprotein in both Drosophila and mammalian cells, including primary neurons. Co-expression of Drosophila Pen-2 with Aph-1 and nicastrin increases the formation of Psn fragments as well as gamma-secretase activity. Thus, APH-1 stabilizes the presenilin holoprotein in the complex, whereas PEN-2 is required for endoproteolytic processing of presenilin and conferring gamma-secretase activity to the complex.