[Bone drilling in microvascular decompression for trigeminal neuralgia: high morphological variety of the petrous bone].

Microvascular decompression is now a standard surgical technique for the treatment of trigeminal neuralgia. However, it is occasionally difficult to expose the trigeminal nerves because of the high anatomical variety of vascular or bony structures in the posterior fossa. We reported the case of a 59-year-old woman with trigeminal neuralgia whose site of neurovascular compression could not be observed in microvascular decompression. On approaching the trigeminal nerve, the suprameatal tubercle was so prominent that it prevented adequate visualization of the nerve tract. After drilling out the tubercle concealing the trigeminal nerve behind it, we exposed the nerve entirely and subsequently decompressed it from the superior cerebellar artery. Retrospectively, the suprameatal tubercle was found 3mm high above the posterior surface of the petrous bone. Then, we analyzed the height of suprameatal tubercles in 106 patients who underwent three-dimensional CT of the skull. Mean values of the suprameatal tubercles were 1.4-1.7mm in height, and 5.2% of them were higher than 3mm. The result suggested the high morphological variety of the petrous bone. We emphasize the importance of presurgical evaluation of the petrous bone in trigeminal neuralgia, because the neurovascular compression site may not be exposed sufficiently by the suprameatal tubercle in approximately 5% of the patients.

[Retrospective statistical analysis of clinical factors of recurrence in chronic subdural hematoma: correlation between univariate and multivariate analysis].

OBJECT: Chronic subdural hematoma is common in elderly individuals and surgical procedures are simple. The recurrence rate of chronic subdural hematoma, however, varies from 9.2 to 26.5% after surgery. The authors studied factors of the recurrence using univariate and multivariate analyses in patients with chronic subdural hematoma METHODS: We retrospectively reviewed 239 consecutive cases of chronic subdural hematoma who received burr-hole surgery with irrigation and closed-system drainage. We analyzed the relationships between recurrence of chronic subdural hematoma and factors such as sex, age, laterality, bleeding tendency, other complicated diseases, density on CT, volume of the hematoma, residual air in the hematoma cavity, use of artificial cerebrospinal fluid. RESULTS: Twenty-one patients (8.8%) experienced a recurrence of chronic subdural hematoma. Multiple logistic regression found that the recurrence rate was higher in patients with a large volume of the residual air, and was lower in patients using artificial cerebrospinal fluid. No statistical differences were found in bleeding tendency. CONCLUSION: Techniques to reduce the air in the hematoma cavity are important for good outcome in surgery of chronic subdural hematoma. Also, the use of artificial cerebrospinal fluid reduces recurrence of chronic subdural hematoma. The surgical procedures can be the same for patients with bleeding tendencies.

Histological effects of intraputaminal infusion of glial cell line-derived neurotrophic factor in Parkinson disease model macaque monkeys.

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 microg) 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.

De novo vertebral artery dissecting aneurysm after contralateral vertebral artery occlusion--two case reports.

Two patients developed de novo vertebral artery dissecting aneurysm after contralateral vertebral artery occlusion. A 36-year-old man presented with brainstem ischemia and was treated non-surgically. Subsequent angiography showed spontaneous vertebral artery occlusion at the site of dissection. A 45-year-old man developed subarachnoid hemorrhage due to vertebral artery dissecting aneurysm. He underwent endovascular occlusion of the vertebral artery proximal to the dissecting aneurysm. These patients developed de novo dissecting aneurysm on the contralateral vertebral artery at 13 months and 11 days after unilateral vertebral artery occlusion, respectively. These cases strongly suggest that changes in hemodynamic stress due to unilateral vertebral artery occlusion are related to de novo dissecting aneurysm on the contralateral side. The risk of de novo dissecting aneurysm may be increased by proximal occlusion or trapping of dissecting aneurysm of the contralateral vertebral artery.

Overlesioned hemiparkinsonian non human primate model: correlation between clinical, neurochemical and histochemical changes.

Monkeys treated with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) have been widely used as animal models of Parkinson's disease (PD). Depending on the method of administration different PD models can be developed. Systemic (iv, sc.) MPTP administration can induce an advanced parkinsonian syndrome. However, systemic administration may require intensive animal care after neurotoxin administration, as well as repeated high doses of MPTP to avoid spontaneous recovery. Unilateral intracarotid artery (ICA) MPTP administration induces a stable hemiparkinsonian syndrome, with the advantage of allowing the animal to groom and feed itself and having a control side in the same animal. However, this unilateral syndrome lacks the bilateral characteristics of advanced PD. Bilateral ICA administration can induce a reliable bilateral syndrome but inherent is the risk of severely impairing the animals and leaving them unable to maintain themselves. This report analyzed the PD model induced by administration of unilateral ICA and subsequent intravenous injections of MPTP in rhesus monkeys. The combined method of MPTP administration induces an advanced stable parkinsonian syndrome, in which the ICA injection of MPTP initiates the parkinsonian syndrome primarily in one hemisphere and the subsequent iv. doses (administered as needed) further deplete the dopamine (DA) system to induce a bilateral lesion in a shorter period of time, with fewer side effects. We studied the relationships between the behavioral, biochemical and histochemical changes related to the combined MPTP treatments to further characterize this model. The monkeys were categorized as presenting mild (stage 2) or moderate (stage 3) parkinsonism based on a parkinsonian rating scale. Postmortem biochemical analysis showed massive DA reduction equally in the caudate nucleus and putamen ipsilateral to ICA MPTP infusion, with varying degrees of DA preservation in the contralateral striatum. Differences between stage 2 and stage 3 were attributed to DA concentrations in the caudate nucleus and putamen of the contralateral hemisphere. Tyrosine hydroxylase immunohistochemistry revealed that the midbrain DA neurons of the group A8, A9, and A10 showed differential vulnerability for MPTP. This finding was similar to that observed in idiopathic PD with significant relationships between the clinical stages and cell losses in the group A9 (substantia nigra pars compacta). Positron emission tomography (PET) using [18F] 6-fluoro-L-m- tyrosine (FMT) showed that uptake (Ki) values correlated well with the biochemical data and are good predictors of DA levels in the contralateral striatal regions. Consistent with the immunohistochemical analysis, PET data also showed significant correlations with all groups of the DA cells. Here we describe an animal model that can play an important role in understanding the symptoms and therapeutic basis of PD since different severities of parkinsonian symptoms can be mimicked.

Dopaminergic neuroprotection and regeneration by neurturin assessed by using behavioral, biochemical and histochemical measurements in a model of progressive Parkinson's disease.

Trophic effects of neurturin, a member of the glial cell line-derived neurotrophic factor-family, have been demonstrated on mesencephalic dopaminergic neurons, suggesting its therapeutic potential for Parkinson's disease. This study was designed to test the neuroprotective and regenerative effects of an intrastriatal injection of neurturin based on behavioral, neurochemical and histochemical changes in a rat model of progressive Parkinson's disease. An extensive and progressive dopaminergic lesion was unilaterally made by intrastriatal convection-enhanced delivery of 6-hydroxydopamine (6-OHDA), in which 20 microg of 6-OHDA dissolved in 20 microl of vehicle was infused at a rate of 0.2 microl/min. For neuroprotection study, recombinant human neurturin (5 microg in 5 microl of vehicle) was stereotaxically injected into the unilateral striatum. The 6-OHDA lesion was made on the ipsilateral side 3 days after the neurturin treatment. Tyrosine hydroxylase (TH)-immunoreactive neurons of the substantia nigra were protected from progressive degeneration in the neurturin-treated animals compared with the vehicle-treated animals 2 and 8 weeks after the 6-OHDA lesion. Eight weeks after the 6-OHDA lesion, dopamine concentration significantly increased in the striatum of neurturin-treated animals with improvement of methamphetamine-induced rotation behavior. For neuroregeneration study, 5 microg of neurturin was injected into the striatum 12 weeks after the 6-OHDA lesion. Four weeks after neurturin or vehicle injection, there were no significant differences in the survival of nigral TH-immunoreactive neurons between the groups. However, TH-immunoreactive fibers were thicker and more abundant in the striatum of the neurturin-treated rats compared to those of the control group, suggesting neurturin-induced growth of the dopaminergic axons. Striatal dopamine levels also significantly increased in the neurturin-treated rats compared with those in the control group of rats, accompanied by the recovery of methamphetamine-induced rotation in the neurturin-treated rats. In conclusion, an intrastriatal injection of neurturin is a useful method to protect nigral dopaminergic neurons from extensive cell death in a model of progressive Parkinson's disease, as well as to promote the axonal regeneration and dopaminergic function.

Progressive and extensive dopaminergic degeneration induced by convection-enhanced delivery of 6-hydroxydopamine into the rat striatum: a novel rodent model of Parkinson disease.

OBJECT: A striatal dopamine lesion induces progressive nigral degeneration in rodents; however, intrastriatal injection of 6-hydroxydopamine (6-OHDA) causes only limited lesions due to spontaneous regeneration of the neurons that survive. To make an extensive lesion, the authors used a convection-enhanced delivery (CED) method for intrastriatal infusion of 6-OHDA and evaluated the animals for a model of Parkinson disease (PD). METHODS: Different doses of 6-OHDA were infused into the unilateral striatum in rats by using the CED method. The dopaminergic neuronal degeneration was evaluated based on morphological, biochemical, and behavioral measurements until 8 weeks postlesion. Due to the wide distribution of the drug, CED of 20 microg of 6-OHDA into the striatum was sufficient to obtain a progressive and extensive nigrostriatal lesion as defined by morphological (> 80% cell loss in the substantia nigra [SN]) and biochemical (> 95% decrease in striatal dopamine) criteria. The extent of the lesion manifested as a stable turning behavior with amphetamine (> 6 turns/minute) and apomorphine (> 4 turns/minute). It also appeared that at I week postlesion the apoptotic markers were maximal in neurons of the SN. CONCLUSIONS: A rat model of PD with a progressive and extensive dopamine lesion was successfully made by intrastriatal CED of 6-OHDA. In this model, the therapeutic value can be assessed using behavioral, biochemical, and histochemical measurements. The delay of nigral neuronal death with respect to the time of 6-OHDA administration may provide a therapeutic window for testing neuroprotective strategies.

Idiopathic hypertrophic cranial pachymeningitis associated with total occlusion of the dural sinuses--case report.

A 44-year-old man presented with a rare case of idiopathic hypertrophic cranial pachymeningitis manifesting as generalized seizure. Neuroimaging and pathological examinations showed the typical features of hypertrophic cranial pachymeningitis. Tuberculosis was a possible cause based on the positive purified protein-derived skin test, but the origin of the disease was not confirmed by further examinations. Cerebral angiography showed total occlusion of the dural sinuses with development of the emissary veins. Histological examination of the dura showed thickening of the fibrous tissue with rare inflammatory cells, suggestive of the extremely long duration of the disease. The diagnosis was idiopathic hypertrophic cranial pachymeningitis, but was treated only with anticonvulsants. The disease did not progress during follow up of 3 years. Idiopathic hypertrophic cranial pachymeningitis may have various causes related to unusual forms of infectious or autoimmune disorders.

Microvascular decompression of cranial nerves using sheets of a dural substitute--technical note.

Several types of prosthesis are used for microvascular decompression (MVD) surgery for neurovascular compression syndrome. However, most prostheses adhere to the surrounding neuronal structures and occasionally cause granulomas. The present study evaluated a dural substitute made of expanded polytetrafluoroethylene, the Gore-Tex EPTFE patch, as a prosthesis for MVD. Twelve patients with trigeminal neuralgia, 19 patients with hemifacial spasm (HFS), and two patients with glossopharyngeal neuralgia underwent MVD using the dural substitute. In most cases, one or two sheets of the dural substitute were inserted between the offending artery and the compression site covering the cranial nerve and the brainstem. Thirty of the 33 patients experienced complete relief of the symptoms that lasted for at least 10-75 months after the surgery. HFS recurred one month post-surgery in a patient who underwent MVD using two small sheets. Varied grades of hearing disturbance were observed in three patients with HFS. MVD using dural substitute is an easy and efficient method because it is not necessary to move the offending arteries away from the compression site. Large sheets should be positioned over the compression site for sufficient decompression. However, this technique needs to be improved so that the prosthesis does not affect cranial nerve VIII, as three of 19 patients with HFS showed hearing disturbances despite intraoperative monitoring of the auditory brainstem response.

Presigmoid approach for cavernous angioma in the pons--technical note.

Surgical treatment of brainstem lesions has been encouraged after the development of magnetic resonance imaging. However, direct approaches to intra-axial lesions in the brainstem still carry a high risk of morbidity because the neuronal structures can be injured along the entry routes. We present two patients whose pontine cavernous angiomas were removed via incision of the lateral aspect of the pons with presigmoid approach. The first case, a 41-year-old woman, presented with paresis of the cranial nerves VI, VII, and VIII, and left hemiparesis progressing over 2 weeks caused by a cavernous angioma ventrally located in the lower pons. The second case, a 50-year-old woman, developed dizziness over 2 months due to a large cavernous angioma in the center of the pons. These lesions were totally removed through the presigmoid approach and no additional neurological deficits were observed. An image-guided navigation system was used for the craniotomy and removal of the lesion in the second patient. The presigmoid approach provides a safe route to intra-axial lesions in the pons. A technique for presigmoid craniotomy with one-piece bone flap under the image-guided navigation is also described.

Preclinical models of Parkinson's disease.

Parkinson's disease (PD) is a neurodegenerative disorder in which pigmented midbrain neurons progressively die producing a dopamine (DA) deficit in the striatum, which manifests as an akinetic movement disorder. Experimentally induced striatal DA depletion in animals is a valid model of parkinsonism. The capacity of certain substances to damage catecholaminergic neurons has been used extensively to produce DA deficiency in animals. This unit describes methods for inducing parkinsonism in nonhuman primates and rodents using the neurotoxins 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) and 6-hydroxydopamine (6-OHDA). Additionally, procedures for evaluating the animals are presented.