Glial cell line-derived neurotrophic factor (GDNF) is a potent neuroprotection and regeneration molecule for dopamine neurons in the substantia nigra. A recent clinical study showed that intraputaminal infusions of GDNF restored the striatal dopaminergic function, resulting in improvement in patients with Parkinson disease. To investigate the efficacy and the safety of this treatment, the histological changes associated with intraputaminal GDNF infusions were investigated in non-human primate models of Parkinson disease. Two types of Parkinson disease model were constructed: unilateral infusion of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridin (MPTP) into the internal carotid artery to induce hemiparkinsonism and intermittent systemic injection to induce Parkinson disease. GDNF (50 μg) was infused into the putamen on the day of the first MPTP treatment and 4 weeks later. The monkey brains were examined by immunohistochemistry 2-4 weeks after the second GDNF infusion. Losses of the nigral dopamine neurons were mild (30-50% loss) on the side of GDNF infusion, and moderate (approximately 70% loss) on the side of vehicle infusion in the Parkinson disease model. The dopamine fibers were thick and dense in the striatum around the GDNF infusion sites. Both GDNF- and vehicle-treated monkeys of the hemiparkinsonian model showed severe decrease of dopamine neurons to 10% of the intact side. Although reactive astrocytes proliferated around the GDNF infusion sites, the densities of striatal neurons involving GABAergic and cholinergic neurons were not affected. Intraputaminal infusions of GDNF have beneficial effects in parkinsonian monkeys, but dose control is required according to the severity of the disease. The specificity for dopamine neurons is quite high and there are no serious histological changes.
The clinical characteristics of perimesencephalic nonaneurysmal subarachnoid hemorrhage (SAH) caused by physical exertion were analyzed to investigate the causes and mechanisms of perimesencephalic nonaneurysmal SAH. Nine of 209 patients with spontaneous SAH were identified as having perimesencephalic nonaneurysmal SAH. Perimesencephalic nonaneurysmal SAH in four males and three females was precipitated by exertion. Age, sex predominance, type of exertion, symptoms, loss of consciousness during bleeding, clinical grade, angiographic spasm, hydrocephalus, delayed ischemic deficit, rebleeding, hypertension, and outcome were evaluated in these seven patients. Outcomes were assessed using the Glasgow Outcome Scale. Patients showed male predominance (57.1%), relatively young age (mean 50 years), low frequency of hypertension (28.6%), good clinical grade (World Federation of Neurological Surgeons grade I or II), and excellent outcomes including no rebleeding, no symptomatic hydrocephalus, and no delayed ischemic deficits. The type of exertion was swimming in two patients, golfing in two patients, heavy lifting in two patients, and bending forward during gymnastics in one patient. Physical exertion including components of the Valsalva maneuver is an important predisposing factor for perimesencephalic nonaneurysmal SAH. Such physical exertion produces increased intrathoracic pressure, which blocks the internal jugular venous return, resulting in elevated intracranial venous pressure or mechanical swelling of the intracranial veins, and leads to venous or capillary breakdown.
Abrupt normalization of cerebral blood flow (CBF) after surgical procedures to improve excessive cerebral hypoperfusion can cause irreversible brain parenchymal damage. Such hyperperfusion, which is caused by inflow at normal blood pressure into maximally dilated fine vessels, is an important complication following carotid endarterectomy (CEA). Strict control of blood pressure in the perioperative period can prevent this complication except in a few patients, who have severe cerebral hypoperfusion and poor cerebrovascular reserve due to extremely severe stenosis of the ipsilateral or the bilateral carotid arteries, for which CEA is indicated. The requirement for improved CBF and the risk of postoperative hyperperfusion conflict in the pathogenesis of these patients. We tried to prevent abrupt improvement in perfusion by attempting gradual restoration of CBF. Superficial temporal artery-middle cerebral artery anastomosis was first performed to improve the poor cerebrovascular reserve by allowing insufficient blood flow. A few weeks later, CEA was performed to completely restore CBF. This surgical approach obtained good results without postoperative problems in four patients. The indications of this surgical management and efficacy of stepwise restoration of CBF to prevent postoperative hyperperfusion depend on careful preoperative evaluation of perfusion studies.
A 30-year-old man presented with an aneurysm of the left posterior inferior cerebellar artery manifesting as subarachnoid hemorrhage and cerebellar infarction. Angiography demonstrated string-of-beads sign typical of fibromuscular dysplasia (FMD) in the extracranial carotid and vertebral arteries. The aneurysm and the parent artery were successfully embolized with Guglielmi detachable coils. Severe vasospasm developed 1 week after admission, and was treated several times by selective injection of vasodilator. A new aneurysm of the left external carotid artery became evident 1 month later, whereas only slight dilation had previously been apparent. This angiographic sequence demonstrated a new arterial dissection. Despite the possibility of damage to the artery during multiple catheterizations, arterial wall changes caused by FMD appear to have been primarily responsible. This case emphasizes the need for particular care in performing vascular interventional procedures in the presence of FMD.
A 50-year-old male patient presented with a rare dural supratentorial hemangioblastoma manifesting as severe headache persisting for 2 months. Neuroimaging revealed a tumoral mass localized in the right parietal lobe near the sagittal sinus. The tumor was totally excised successfully. The postoperative histological diagnosis was hemangioblastoma. Such supratentorial hemangioblastomas can easily be removed because of the arachnoid cleavage plane.
Three female patients aged 50-79 years (mean 61.0 years) presented with extremely rare intradural C-1 root schwannoma manifesting as foramen magnum syndrome. Magnetic resonance imaging revealed the intradural extra-axial tumors extending from the anterior aspect of the medullospinal junction, with a mean major diameter of 2.7 cm. Total resection of the tumors was performed via the lateral suboccipital transcondylar approach after a mean period of 11.7 months from the symptom onset. The final diagnosis of schwannoma of the C-1 ventral root was based on the intraoperative and histological findings. All three patients were successfully rehabilitated, with symptomatic improvement and no evidence of tumor recurrence. All three patients were successfully treated by surgical resection via the lateral suboccipital transcondylar approach. This approach is effective and safe provided individual anatomy, drilling of the occipital condyle, and patient position are considered carefully.
A 65-year-old woman presented with multiple metastases from thyroid follicular carcinoma to the lung, skull, and brain. The skull and brain tumors had been successfully treated by surgery, thyroxine supplementation, and radiosurgery until she died of sudden intracerebral hemorrhage which had no connection with tumor treatment. The lung tumor was treated by conventional irradiation and radioactive ablation. Well-differentiated thyroid carcinoma is a slowly progressive tumor. Follicular carcinoma is thought to have the most optimistic prognosis even with metastases to the lymph nodes and lung. Radioactive ablation using iodine-131 is widely used to treat the primary and/or metastatic lesion. However, the prognosis for patients with brain metastases is poor. Intracranial metastasis of this tumor is rare, but has a mean posttreatment survival of around 12 months. Surgical excision of the metastatic intracranial lesion may be the only effective treatment.
Two patients presented with congenital basilar invagination manifesting as progressive myelopathy. Both patients underwent surgery using a neuronavigation-assisted transoral-transpharyngeal approach. The Brain-LAB Vector Vision navigation system was used for image guidance. The registration accuracies were 0.9 and 1.3 mm. After decompression, posterior stabilization was performed. Both patients had an uneventful postoperative course. The transoral-transpharyngeal approach with the neuronavigation system provides safe exposure and decompression for basilar invagination.
A 40-year-old woman presented with a right petroclival meningioma compressing the brainstem and manifesting as a 6-month history of headache and gait difficulty. The patient underwent subtotal removal of the tumor via an anterior transpetrosal approach. The postoperative course was complicated by cerebrospinal fluid rhinorrhea, bacterial meningitis, and acute hemorrhagic rectal ulcer. The patient was discharged home in good condition after prolonged medical treatment. Four months after the surgery, the patient noted recurrence of gait difficulty. Magnetic resonance (MR) imaging of the brain showed enlargement of the ventricles and no residual brainstem compression. A ventriculoperitoneal shunt was placed, but the symptoms were unchanged. The shunt was removed 2 months later because of infection. The patient’s gait gradually deteriorated, although repeat brain MR imaging showed no significant increase in ventricular size. Ten months after the initial surgery she became paraplegic. MR imaging of the thoracic spine revealed a large arachnoid cyst extending from C-6 to T-6. The patient underwent T2-4 laminectomy, partial removal of the cyst wall, and duraplasty, but no clinical improvement was observed. Preexisting long-tract signs and coincidental hydrocephalus confused the neurological findings and delayed detection of the spinal lesion in this case. Neurosurgeons should be alert to the possibilities of insidious spinal lesion if the patient has progressive neurological disorder which does not match the known cranial lesion.
A 38-year-old man presented with untreated congenital kyphosis associated with progressive spastic gait. To prevent progression of the spastic paralysis, rigid correction of the severe spinal deformity arising from the congenital kyphosis was performed by one-stage posterior closing-wedge osteotomy, without occurrence of neurological complications. Progression of the paralysis has not been identified for 30 months after the operation and a slight improvement in gait was recognized. The current case is categorized as type I deformity of congenital kyphosis in the upper thoracic spine, which is normally treated surgically before the adolescent growth phase begins.