Pretreatment with Clodronate Improved Neurological Function by Preventing Reduction of Posthemorrhagic Cerebral Blood Flow in Experimental Subarachnoid Hemorrhage.

BACKGROUND: Brain perivascular macrophages (PVMs) are potential treatment targets for subarachnoid hemorrhage (SAH), and previous studies revealed that their depletion by clodronate (CLD) improved outcomes after experimental SAH. However, the underlying mechanisms are not well understood. Therefore, we investigated whether reducing PVMs by CLD pretreatment improves SAH prognosis by inhibiting posthemorrhagic impairment of cerebral blood flow (CBF). METHODS: In total, 80 male Sprague-Dawley rats received an intracerebroventricular injection of the vehicle (liposomes) or CLD. Subsequently, the rats were categorized into the prechiasmatic saline injection (sham) and blood injection (SAH) groups after 72 h. We assessed its effects on weak and severe SAH, which were induced by 200- and 300-µL arterial blood injections, respectively. In addition, neurological function at 72 h and CBF changes from before the intervention to 5 min after were assessed in rats after sham/SAH induction as the primary and secondary end points, respectively. RESULTS: CLD significantly reduced PVMs before SAH induction. Although pretreatment with CLD in the weak SAH group provided no additive effects on the primary end point, rats in the severe SAH group showed significant improvement in the rotarod test. In the severe SAH group, CLD inhibited acute reduction of CBF and tended to decrease hypoxia-inducible factor 1α expression. Furthermore, CLD reduced the number of PVMs in rats subjected to sham and SAH surgery, although no effects were observed in oxidative stress and inflammation. CONCLUSIONS: Our study proposes that pretreatment with CLD-targeting PVMs can improve the prognosis of severe SAH through a candidate mechanism of inhibition of posthemorrhagic CBF reduction.

Pituitary Gangliocytoma Producing TSH and TRH: A Review of "Gangliocytomas of the Sellar Region".

PURPOSE: Pituitary gangliocytomas (GCs) are rare neuronal tumors that present with endocrinological disorders, such as acromegaly, amenorrhea-galactorrhea syndrome, and Cushing's disease. Most pituitary GCs coexist with pituitary adenomas pathologically and are diagnosed as mixed gangliocytoma-adenomas. Herein, we report a case of 45-year-old man who presented with the syndrome of inappropriate secretion of thyroid-stimulating hormone (SITSH) and discuss the pathogenesis of pituitary GCs. METHODS: Pituitary magnetic resonance imaging showed an 8-mm homogeneous and poorly enhanced mass inside the pituitary gland. Endoscopic transsphenoidal surgery was performed under a preoperative diagnosis of thyrotroph adenoma. However, the tumor was finally diagnosed as gangliocytoma without an adenomatous component. The tumor was further analyzed via immunohistochemistry and electron microscopy. Additionally, we searched MEDLINE and PubMed for previously published cases of isolated pituitary GCs and analyzed the reported clinicopathological findings. RESULTS: The patient showed complete clinical and endocrinological recovery after an operation. The tumor was positive for thyrotropin (TSH), TSH-releasing hormone (TRH), Pit-1, GATA-2, and most neuronal markers. Electron microscopy demonstrated the presence of intracytoplasmic secretory granules and neuronal processes. Co-secreting hypothalamic and pituitary hormone inside the tumor indicated autocrine/paracrine endocrinological stimulation. CONCLUSION: Herein, we report a case of SITSH caused by an isolated pituitary gangliocytoma, expressing both TSH and TRH, which, to our best knowledge, is the first reported case of such a condition. The multidirectional differentiation and multihormonal endocrine characteristics of these tumors indicate that they are a member of neuroendocrine neoplasms, further supporting that they are derived from neural crest cells.

Leptomeningeal Carcinomatosis After Neoplastic Cerebral Aneurysm Rupture.

BACKGROUND: Several possible mechanisms exist for the spread of a primary tumor to the leptomeninges in leptomeningeal carcinomatosis. This report describes a case caused by direct bleeding in the subarachnoid space from a neoplastic cerebral aneurysm rupture. CASE DESCRIPTION: A 48-year-old Japanese woman, who was diagnosed with breast carcinoma (pT3 pN2 M0) at the age of 45 years and underwent mastectomy and chemotherapy, was admitted in a coma following a sudden-onset severe headache. Computed tomography revealed diffuse hemorrhage in the subarachnoid space, and angiography revealed an aneurysm at the distal middle cerebral artery. Superficial temporal artery-middle cerebral artery bypass, aneurysmal trapping, and aneurysm resection were performed within 24 hours of admission. Staining for AE1/AE3 revealed accumulation of atypical cells with a high nuclear-cytoplasmic ratio in the aneurysmal wall. After showing initial improvement, she developed disturbed consciousness due to complicated ventricular enlargement on day 45. Although the cerebrospinal fluid in the acute phase had no atypical cells, subsequent testing revealed atypical cells, which supported a diagnosis of leptomeningeal carcinomatosis due to breast cancer dissemination. The patient died on day 78 after receiving standard endocrine therapy and radiation therapy. CONCLUSIONS: Tumor cells reach the leptomeninges via hematogenous spread or direct extension from preexisting lesions and can undergo neuraxis dissemination via the cerebrospinal fluid. Subarachnoid hemorrhage and leptomeningeal carcinomatosis are both devastating conditions with extremely poor prognoses. This patient experienced delayed disturbed consciousness leptomeningeal carcinomatosis with decreased performance status, which made it difficult to justify aggressive treatment on the basis of her poor prognosis.

Novel Indirect Revascularization Technique with Preservation of Temporal Muscle Function for Moyamoya Disease Encephalo-Duro-Fascio-Arterio-Pericranial-Synangiosis: A Case Series and Technical Note.

BACKGROUND: Direct and/or indirect bypass surgery is the established approach for preventing stroke in patients with moyamoya disease. However, conventional indirect revascularization, including encephalo-myo-synangiosis, has some disadvantages associated with the mass effect of the temporal muscle under the bone flap and postsurgical depression in the temporal region. We devised a novel indirect revascularization method, using only the temporal fascia, to address the aforementioned disadvantages. METHODS: A skin incision was performed along the superficial temporal artery. The temporal fascia was cut such that the base of the fascia flap was on the posterior side. The fascia and temporal muscles were dissected separately. After turning over the fascia, the muscle was cut such that the base of the muscle flap was on the anterior side. Craniotomy, direct bypass, and encephalo-duro-synangiosis were performed conventionally. Only the temporal fascia was used for indirect revascularization and duraplasty. The muscle was replaced in the anatomically correct position after replacing the bone flap. RESULTS: We performed the aforementioned surgery on 18 (13 women and 5 men) consecutive patients (21 cerebral hemispheres) enrolled between 2012 and 2016. The average age was 28.7 years. The mean follow-up period was 31.6 months. In 17 patients (94%), the symptoms and cerebral blood flow improved. Digital subtraction angiography showed satisfactory angiogenesis from the temporal fascia. Depression in the temporal region and atrophy of the temporal muscle were negligible. CONCLUSIONS: This surgical technique provides good clinical and cosmetic outcomes. It may also be one of the good surgical treatments available for symptomatic moyamoya disease.