We reviewed treatments with drugs for Parkinson disease (PD). Since the induction of Levodopa, the prognosis has significantly improved. The most recent guideline from the Japanese Neurological Association recommends that neurologists treat patients with dopamine agonists rather than that with Levodopa in the early stages of PD. However, recent reports such as the ELLDOPA study have indicated that Levodopa is not toxic and may have the potential to prevent the progression of the disease. In contrast, a SPECT study using β-CIT in ELLDOPA could not confirm Levodopa's neuroprotection properties nor its ability to halt progression of the disease. However, this study indicated that Levodopa may have neuroprotection activities that work against the progression of the disease. When considering motor complications, dopamine agonists may be the first choice for early stage treating PD. Levodopa also may offer neuroprotection for PD. Thus, the potential of Levodopa and dopamine agonists for neuroprotection should be reevaluated. Although the prognosis of PD can be significantly improved, merely improving daily activity and quality of life is not enough for patients with PD. Thus, neuroscientists should discover novel drugs that can prevent the progression of PD.

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We report our methods, effects and indication of deep brain stimulation of the globus pallidus internus (GPi-DBS) for patients with Parkinson disease (PD). During microrecordings, the primary motor cortex (M1) was stimulated by subdural strip electrode. Then we record single unit activities from pallidal neurons and analyze the response of the neuronal activity evoked by the M1 stimulation. Using this method, more precise localization of the stimulating electrode is expected. The effect of GPi-DBS is seen in all of the parkinsonian symptoms, but the more prominent effect is recognized in tremor, rigidity and drug-induced-dyskinesia. For these symptoms, the effects of the stimulation persist for more than three years. Less possibility of inducing neuropsychological adverse effect is another feature of GPi-DBS. Despite the lack of definitive comparative evidence, STN-DBS is favored over GPi-DBS for treatment of PD. However, we should be cautious about ruling out GPi-DBS as a treatment option. GPi-DBS may be a more valuable option than STN-DBS for patients with dose-limiting dyskinesia, and with a lower threshold of neuropsychological adverse complications.

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Over the last several years, STN-DBS has gained acceptance and become the neurosurgical treatment of choice for PD. To ensure a successful outcome, however, it is important to select appropriate candidates. The ideal candidate has idiopathic PD, suffers from complications of chronic levodopa therapy despite optimal medical management, and has no cognitive impairment or active psychiatric issues. In addition, a good preoperative response to levodopa predicts a good outcome after STN-DBS. Two advantages of STN-DBS were identified. Firstly, the stimulation can supplement a reduced action of levodopa during the off-period. It thus improves the patient's daily activities performance through the attenuation of motor fluctuations. Secondly, the stimulation can replace part of the action of levodopa during the on-period. It thus attenuates dopa-induced dyskinesia through a reduced dose of medication. More importantly, the stimulation improves the daily activities performance in dopa-intolerant patients who are only administered a small dose of levodopa because of unbearable side effects. On the other hand, there is accumulating evidence that STN-DBS may result in adverse non-motor outcomes. Therefore the effect of STN-DBS on the mood state in PD, and antidepressant, depressant, and mania-induced effects were also reported. However, from our experience, the average depression scale score of patients was improved by STN-DBS. Although there was a limitation in our study attributable to varied results, it was suggested that, in general, STN-DBS hadan antidepressant effect in PD.

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Adeno-associated viruses (AAV) are small, non-enveloped, single-stranded DNA viruses of the Parvoviridae family. More than one hundred genotypes of AAVs have been isolated from primates, in which they seem to be non-pathogenic. AAV-2 has been the most extensively studied, particularly as a vector for gene therapy. Pure and high titer recombinant AAV (rAAV) vectors can be generated using a helper plasmid containing the minimum adenovirus genome sequences necessary for helper functions. These rAAV vectors offer safe, efficient, and long-term expression of transgenes in mammalian brain neurons without triggering a substantial immune response. rAAV vectors have led to significant functional recovery in animal models, making their use in gene therapy for Parkinson disease (PD) promising. Three different rAAV vector-based protocols for treating for PD are currently in phase 1 clinical trials. One is the gene transfer of aromatic L-amino acid decarboxylase (AADC) in combination with oral administration of L-dopa. Although patients would still need to take L-dopa to control their PD symptoms with this approach, the dose could be lowered and the duration of the ON period prolonged. If two other enzymes, tyrosine hydroxylase and guanosine triphosphate cyclohydrolase I, could also be provided, L-dopa could be produced in the striatum, making the patient drug-free. The gene expression has to be regulated since excess synthesis of dopamine may cause adverse effects. The second clinical trial is transduction of the subthalamic nucleus with rAAV vectors expressing glutamic acid decarboxylase (GAD) to produce γ-aminobutyric acid (GABA), an inhibitory transmitter. The aim of the strategy is to modulate the activity of subthalamic neurons, an effect similar to deep brain stimulation. The third clinical trial is delivery of an rAAV vector expressing neurturin, a neurotrophic factor for dopaminergic neurons, into the putamen to block or slow down the ongoing degeneration. Neuro-imaging techniques and genetic analyses of familial patients could help identify individuals at risk for PD before they develop symptoms. They would be able to receive early the gene therapy given to symptomatic PD patients. Gene therapy using rAAV vectors seems to be a promising way of treating PD.

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To evaluate risk factors pertaining to the likelihood of rupture in unruptured cerebral aneurysms, the authors examined and compared a consecutive series of some 272 unruptured and 230 ruptured saccular cerebral aneurysms. Results from the analysis highlighted a number of significant findings, including a higher incidence of ruptured cerebral aneurysms in females in their 60s. It was also noted that the middle cerebral and paraclinoid to intracavernous internal carotid arteries tended to be common locations for unruptured cerebral aneurysms, while anterior communicating and posterior communicating arteries more commonly exhibited ruptures. Similarly, bleb formations were observed with a significantly higher frequency in ruptured cerebral aneurysms than in unruptured aneurysms. This evaluation strongly implies that not only the size of aneurysms but other factors such as age, sex, location of aneurysms and existence of bleb formations need to be considered when deciding treatment options in patients with unruptured cerebral aneurysms.

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Extracranial carotid artery aneurysm is rare and there are few reports of vascular reconstructions for giant aneurysms larger than 5cm. We recently encountered such a case complicated by chronic renal failure. A 60-year-old man presented with a pulsatile mass on the left side of his neck and left lower cranial nerve palsy. Neuroradio-logical imaging demonstrated a 60×40×60mm saccular aneurysm of left CCA bifurcation. Three days before surgery, he presented with right hemiparesis and CT demonstrated a small left frontal lobar hemorrhage. We therefore postponed surgery but the aneurysm continued to increase (64×42×65mm). We performed aneurysmec-tomy and CCA and ICA interposition with synthetic vascular graft. Extracranial carotid artery aneurysm rarely resolves spontanously and cerebral ischemic events often occur in such cases. Concerning this aneurysm, aggressive treatment is recommended.

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We report a case of malignant tumor of nasal cavity that was invading the orbit and anterior cranial base treated by craniofacial resection. The cranial procedure was performed by reflection of dismasking facial skin flap and a facial approach for the maxillectomy performed by a sublabial superior gingival incision were combined. En block excision with a safety margin was successfully achieved due to the wide exposure of the tumor made possible with this procedure. The en block specimen included bilateral cribliform plates, the ipsilateral orbit and its contents, the upper side of the sphenoid body and maxilla, and the nasal septum. After the resection, the anterior cranial base was reconstructed using a titanium mesh plate, and the orbito-facial reconstruction was accomplished using a free abdominal fatty graft. The patient's cosmetic results were acceptable due to the orbital reconstruction and the preservation of facial nerve function.

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We report a case of secretory meningioma in a 64-year-old woman who presented with depression and abnormal behavior. MRI demonstrated a well-enhanced tumor in the left middle fossa. The tumor was 3cm in diameter and accompanied by remarkable brain edema in the left temporal lobe. Carotid angiograms showed multiple aneurysms of the bilateral internal carotid arteries. Through a left frontotemporal craniotomy, total removal of the tumor and neck clipping of the aneurysm of the left internal carotid artery were performed. After surgery, the patient's symtoms improved and the edema disappeared. The tumor cells had many eosinophilic pseudopsammoma bodies. On immunohistochemistry, the tumor was positive for CEA and EMA and diagnosed as secretory meningioma. Tumor cells were also positive for VEGF, which was possibly related to the severe brain edema in this case. Clinical and histopathological features of secretory meningioma are discussed.

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A 59-year old man who developed brain metastasis of hepatocellular carcinoma (HCC) after treatment with living-donor liver transplantation was presented. It was difficult to detect the brain metastasis with only a systemic positron-emission computed tomographic study before transplantation. In the treatment of HCC by living-donor liver transplantation, enhanced studies with computed tomographic scans or magnetic resonance imaging might be recommended to exclude brain metastasis before transplantation.

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