Mitsuhiro Ogura

Intrastriatal Mesencephalic Grafts Affect Neuronal Activity in Basal Ganglia Nuclei and Their Target Structures in a Rat Model of Parkinson’s Disease

Nigrostriatal dopamine (DA) lesions lead to changes of neuronal activity in basal ganglia nuclei such as the globus pallidus (GP, the rodent homolog of lateral globus pallidus), entopeduncular nucleus (EP, the rodent homolog of medial globus pallidus), substantia nigra pars reticulata (SNR), and subthalamic nucleus (STN). We investigated in rats whether embryonic mesencephalic DA neurons grafted in the striatum may affect the lesion-induced alterations of neuronal activity in these structures. Regional neuronal activity was determined by use of quantitative cytochrome oxidase histochemistry. It was also examined in lesioned rats whether the grafts may regulate the expression of c-Fos after systemic administration of apomorphine in the basal ganglia nuclei as well as their target structures, including the ventromedial thalamic nucleus (VM), superior colliculus (SC), and pedunculopontine nucleus (PPN). Lesioned rats exhibited an increased activity of CO in the GP, EP, SNR, and STN ipsilateral to the lesion. Intrastriatal nigral grafts reversed the increases in the CO activity in the EP and SNR, whereas the grafts failed to affect the enzyme activity in the GP or STN. Apomorphine induced an increased expression of c-Fos in the GP, STN, VM, SC, and PPN on the lesioned side. The enhanced expression of this protein in all the structures except for the STN was attenuated by nigral grafts. The present results indicate that intrastriatal DA neuron grafts can normalize the lesion-induced changes of neuronal activity in the output nuclei of the basal ganglia as well as their target structures.

Cortically evoked responses of human pallidal neurons recorded during stereotactic neurosurgery

Responses of neurons in the globus pallidus (GP) to cortical stimulation were recorded for the first time in humans. We performed microelectrode recordings of GP neurons in 10 Parkinsons disease (PD) patients and 1 cervical dystonia (CD) patient during surgeries to implant bilateral deep brain stimulation electrodes in the GP. To identify the motor territories in the external (GPe) and internal (GPi) segments of the GP, unitary responses evoked by stimulation of the primary motor cortex were observed by constructing peristimulus time histograms. Neurons in the motor territories of the GPe and GPi responded to cortical stimulation. Response patterns observed in the PD patients were combinations of an early excitation, an inhibition, and a late excitation. In addition, in the CD patient, a long‐lasting inhibition was prominent, suggesting increased activity along the cortico‐striato‐GPe/GPi pathways. The firing rates of GPe and GPi neurons in the CD patient were lower than those in the PD patients. Many GPe and GPi neurons of the PD and CD patients showed burst or oscillatory burst activity. Effective cathodal contacts tended to be located close to the responding neurons. Such unitary responses induced by cortical stimulation may be of use to target motor territories of the GP for stereotactic functional neurosurgery. Future findings utilizing this method may give us new insights into understanding the pathophysiology of movement disorders.

Reduced pallidal output causes dystonia

Dystonia is a neurological disorder characterized by sustained or repetitive involuntary muscle contractions and abnormal postures. In the present article, we will introduce our recent electrophysiological studies in hyperkinetic transgenic mice generated as a model of DYT1 dystonia and in a human cervical dystonia patient, and discuss the pathophysiology of dystonia on the basis of these electrophysiological findings. Recording of neuronal activity in the awake state of DYT1 dystonia model mice revealed reduced spontaneous activity with bursts and pauses in both internal (GPi) and external (GPe) segments of the globus pallidus. Electrical stimulation of the primary motor cortex evoked responses composed of excitation and subsequent long-lasting inhibition, the latter of which was never observed in normal mice. In addition, somatotopic arrangements were disorganized in the GPi and GPe of dystonia model mice. In a human cervical dystonia patient, electrical stimulation of the primary motor cortex evoked similar long-lasting inhibition in the GPi and GPe. Thus, reduced GPi output may cause increased thalamic and cortical activity, resulting in the involuntary movements observed in dystonia.

Ictal asomatognosia due to dominant superior parietal cortical dysplasia

We report a 23-year-old man with left dominant parietal cortical dysplasia manifesting as ictal asomatognosia. The man had experienced seizures, during which he underwent ictal asomatognosia as a feeling of loss of his right extremities. Scalp electroencephalography (EEG) showed interictal discharges in the left parietal region of his brain. Magnetic resonance fluid-attenuated inversion recovery (FLAIR) imaging revealed a hyperintense lesion in the left superior parietal lobule. A [(123)I]-iomazenil (IMZ) single-photon-emission CT scan demonstrated an area of low IMZ binding coincident with the lesion observed in the MRI scan. Invasive EEG monitoring showed ictal discharges in the cortex posterior to the postcentral sulcus. High-frequency electrical stimulation of the same area of the cortex also induced asomatognosia of the patients right forearm. We performed a corticectomy of the anterior part of the superior parietal lobule, which resulted in no new neurological deficits. The seizures disappeared after surgery with the maintenance of preoperative medication. Therefore, the anterior part of the superior parietal lobule may be a symptomatogenic zone for ictal asomatognosia.

Management of Non-benign Meningiomas with Gamma Knife Radiosurgery

OBJECTIVE Results of Gamma Knife radiosurgery (GKS) were retrospectively evaluated in 16 patients with histologically confirmed atypical and anaplastic intracranial meningiomas. MATERIALS AND METHODS There were nine men and seven women (mean age 61.0 years). Atypical meningiomas were diagnosed in nine cases and anaplastic meningiomas in seven. In nine patients there was malignant transformation of a tumor that had initially proved to be benign. In total, 21 radiosurgical procedures were performed. The mean tumor volume at the time of GKS was 7.1 cm3. The mean marginal and maximum irradiation doses were 18.8 and 37.0 Gy, respectively. The mean length of follow-up after treatment was 37.1 months. FINDINGS Of 21 radiosurgical procedures, 6 (29 %) led to stabilization of tumor growth during the mean follow-up of 40.5 months. It was significantly associated with small lesion volume (P = 0.02), and greater marginal (P = 0.04) and maximum (P = 0.02) irradiation doses. Seven patients underwent eight surgical resections of a progressing tumor during the mean period of 26.1 months after irradiation. Five patients (31 %) died because of tumor progression within the average time period of 16.8 months after GKS. Overall, at the time of the last follow-up just two patients (13 %) had no evidence of tumor regrowth, and only three patients (19 %) maintained good activities of daily living during 12, 59, and 69 months, respectively, after radiosurgery. CONCLUSION GKS has limited efficacy in cases of non-benign meningioma. Better tumor control rates can be attained for small neoplasms treated with greater marginal and maximum irradiation doses.

Surgical treatment and outcome of skull base meningiomas with extracranial extensions

OBJECTIVE Recurrent cranial base meningiomas occasionally extend into craniofacial structures, and are one of the most difficult tumors to surgically manage. We reviewed our experience of surgical treatment in a series of patients with meningiomas showing extensive extracranial extensions. METHODS We surgically treated a total of 10 patients with recurrent cranial base meningiomas with large extension to multiple craniofacial structures. All patients underwent orbitozygomatic or zygomatic frontotemporal craniotomy for surgical resection of the tumor. An endoscopic endonasal technique was also employed, if necessary, as an adjunct to the transcranial approach. RESULTS Eight patients were treated solely with a frontotemporal approach associated with an extended resection of the floor of the middle fossa. In 2 patients, an endoscopic endonasal approach was additionally required for resection of tumors located in the nasal cavity and ethmoid sinus. A gross total resection was achieved without serious surgical complications in 9 out of the 10 patients. In all patients, the tumors were found to invade the surrounding tissue such as the bone and skeletal muscle to varying degrees. CONCLUSION Our data indicate that recurrent craniofacial meningiomas can usually be managed by using a lateral cranial base approach. Whereas it would be expected that a radical resection may prevent further recurrence with an acceptable quality of life, a long-term follow-up would be required for confirming the benefit of this treatment strategy.

Late-onset tumefactive multiple sclerosis

A patient with tumefactive multiple sclerosis (MS) initially presented at the age of 87 years; the revised diagnostic criteria from the International Panel on MS (2001) were fulfilled. Late-onset MS and tumefactive demyelinating lesions are discussed. This case suggests that MS can occur at any age. MS should be borne in mind for differential diagnosis if a brain tumor-like lesion with little mass effect and edema is found in an elderly patient.

Optogenetic Activation of the Sensorimotor Cortex Reveals “Local Inhibitory and Global Excitatory” Inputs to the Basal Ganglia

Abstract To understand how information from different cortical areas is integrated and processed through the cortico‐basal ganglia pathways, we used optogenetics to systematically stimulate the sensorimotor cortex and examined basal ganglia activity. We utilized Thy1‐ChR2‐YFP transgenic mice, in which channelrhodopsin 2 is robustly expressed in layer V pyramidal neurons. We applied light spots to the sensorimotor cortex in a grid pattern and examined neuronal responses in the globus pallidus (GP) and entopeduncular nucleus (EPN), which are the relay and output nuclei of the basal ganglia, respectively. Light stimulation typically induced a triphasic response composed of early excitation, inhibition, and late excitation in GP/EPN neurons. Other response patterns lacking 1 or 2 of the components were also observed. The distribution of the cortical sites whose stimulation induced a triphasic response was confined, whereas stimulation of the large surrounding areas induced early and late excitation without inhibition. Our results suggest that cortical inputs to the GP/EPN are organized in a “local inhibitory and global excitatory” manner. Such organization seems to be the neuronal basis for information processing through the cortico‐basal ganglia pathways, that is, releasing and terminating necessary information at an appropriate timing, while simultaneously suppressing other unnecessary information.

MRI Based Sulcal Pattern Analysis for Diagnosis and Clinical Application in Neurosurgery

MRI is used not only for anatomical location and characterization but also for 3D views of sulci and gyri. T1WI-MRI captured with 3D-volume acquired 3D-views of sulci and gyri on fifty healthy volunteers and two patients. The software that we developed analyzed and labeled sulcal patterns of cerebral cortex automatically comparing to a standard brain model. We focused the post-central sulcus (PoC) and 2 neighboring sulci with an inter-sulcal analysis (Relations) including an inter-sulci junction (PoC and cingulate sulcus posterior [Cing]). The value of PoC-Cing Relations of focal cortical dysplasia (FCD) is higher than that of normal, while the value of glioma is much less among that of normal. The PoC of FCD and a few normal brains have junction with Cing. This informative value and a presence of inter-sulci junction suggest that cortical folding dynamics might influence the folding patterns of cerebral cortex. This sulcal labeling can analyze normal and abnormal patient’s brains for clinical use.

Stimulation of Globus Pallidus

In recent years, the subthalamic nucleus (STN) and globus pallidus internus (GPi) have been targeted with deep brain stimulation (DBS) for the treatment of Parkinson’s disease (PD). Because there are unique clinical effects associated with DBS treatment in each target, the target should be selected depending on an individual patient’s symptoms. Here, we provide a detailed introduction to our surgical method of GPi-DBS. In order for DBS to be maximally effective, the most important part of the procedure is optimal electrode positioning at the target. To do so, each step of the surgery, including stereotactic head frame placement, target coordinate determination, microelectrode recordings (MERs), and macrostimulation should be accurately performed. To reduce the risk of placement error, it is important to position the stereotactic frame with its axes orthogonal to the standard anatomic planes of the brain. During stereotactic surgical procedures, there are two possible approaches for locating the target: indirect targeting, aiming at a target with coordinates relative to anatomical landmarks, or direct targeting, aiming at a visible target with absolute coordinates using the stereotactic space of the frame as a reference. Image-guided stereotactic procedures alone are not adequate for placing a DBS lead; physiological studies are also important for confirming final placement. We routinely use MERs and macrostimulation for physiological confirmation. The electrode track location is estimated by measuring the length of the area where high-frequency discharges are recorded. Macrostimulation is the most useful tool during GPi targeting because it can confirm if the location is the so-called “sweet spot.”