Intramedullary spinal AVMs fed by the anterior spinal artery cannot be embolized without risking unacceptable motor deficits, since the feeding arteries may supply the corticospinal tract (CST). An 8-year-old boy underwent successful embolization of such an AVM under general anesthesia using intermittent infusion of embolic material with monitoring of the CST integrity with the corticospinal motor evoked potential (MEP). This case illustrates the value of corticospinal MEP monitoring during therapeutic procedures under general anesthesia which risk interrupting the blood supply to the CST.
Patients with glioblastoma frequently suffer epileptic seizures and often require anticonvulsant therapy during the treatment course. The present study investigated four common antiepileptic drugs, perampanel, carbamazepine (CBZ), sodium valproate (VPA) and levetiracetam (LEV), which are expected to have antitumor effects, and determined the most beneficial drug for the treatment of malignant glioma by comparing antitumor effects such as inhibition of cell proliferation and suppression of migration and invasion (using Transwell assays). The inhibition of cell growth was investigated using six malignant glioma cell lines (A‑172, AM‑38, T98G, U‑138MG, U‑251MG and YH‑13). Significant inhibition of cell proliferation was observed in all six cell lines treated with perampanel, three cell lines treated with CBZ, four cell lines treated with VPA and two cell lines treated with LEV at the therapeutic blood concentration levels for the drugs to be used as antiepileptics. Further antitumor effects in combination with temozolomide were investigated using T98G and U‑251MG cell lines, and were confirmed in both cell lines with perampanel and in T98G cells with LEV, but not observed with CBZ and VPA. Cell migration was significantly suppressed in both T98G and U‑251MG cell lines with perampanel, but not with CBZ, VPA or LEV. To investigate the mechanisms by which perampanel suppresses the migration of malignant glioma cells, the expression of mRNA related to epithelial‑mesenchymal transition following perampanel treatment was analyzed using reverse transcription‑quantitative PCR in the T98G and U‑251MG cell lines. The expression of Rac1 and RhoA, which constitute the cytoskeleton that enhances cell motility, were reduced in both cell lines. Furthermore, the expression of the mesenchymal marker N‑cadherin, which promotes cell migration and infiltration, was decreased, but the expression of the epithelial marker E‑cadherin, which strengthens cell‑cell adhesion and reduces cell motility, was increased. Furthermore, the expression of matrix metalloproteinase‑2, a proteolytic enzyme, was reduced. These effects may reduce cell motility and increase adhesion between cells, suggesting that perampanel treatment suppressed cell migration. In conclusion, the present study suggests that perampanel may be more beneficial in terms of antitumor efficacy than other antiepileptic drugs for the treatment of malignant glioma.
In order to determine adequate therapeutic approaches for cavernous malformations of the third ventricle, the authors reviewed a series of five such malformations managed at their institution and nine others reported in the literature. Four subgroups were identified in terms of the site of origin and could be characterized by different clinical manifestations: visual field defects and endocrine function deficits in patients with malformations in the suprachiasmatic region (six cases); symptoms caused by hydrocephalus in those with malformations in the foramen of Monro region (five cases); and deficits of short-term memory in those with malformations in the lateral wall (two cases) or of the floor of the third ventricle (one case). Unlike cavernous malformations at other locations, malformations of the third ventricle frequently demonstrated rapid growth (43%) and mass effects (71%). The surgical or autopsy findings suggested that the growth was attributable to repeated intralesional hemorrhages. Extralesional hemorrhage was also not uncommon, occurring in 29% of patients. Such tendencies require the adoption of a more aggressive approach to this particular group of cavernous malformations as compared to those in other locations. The risks of regrowth and extralesional hemorrhage appear to be reduced only by complete excision. The surgical approaches adopted should be aimed at providing the best access to the site where the malformation has arisen. The translamina terminalis approach for cavernous malformations in the suprachiasmatic region, the transventricular or transcallosal interfornicial approaches for those in the foramen of Monro region and the transvelum interpositum approach for those in the lateral wall or the floor of the third ventricle appear to be appropriate. In order to select the adequate surgical approach, precise diagnosis of the site of origin is crucial. In addition to neuroimaging techniques, the patient's initial symptoms provide valuable information.
It has been reported that stimulation of the midbrain periaqueductal gray (PAG) is effective for relief of intractable pain. However, this procedure appears to have some disadvantages; i.e., technical difficulty of inserting electrodes exactly, side effects such as abnormal occular movement, and limitation of candidates because of the poor effect on pain in those with morphine-tolerance. Previously the authors reported that stimulation of the thalamic relay nucleus as well as of PAG produced long lasting, profound excitation of raphe-spinal neurons which then inhibit nociceptive dorsal horn neurons. Furthermore, naloxone (which is a specific antagonist of morphine-like substances) was shown to avoid the excitation induced by PAG stimulation, but not that by induced thalamic relay nucleus stimulation. Based on these findings, attempts were made to treat intractable pain with morphine-tolerance by stimulation of thalamic relay nucleus. Prevention of stimulation-tolerance was attempted by administration of monoamine precusors, i.e., l-DOPA and l-tryptophan, on the basis of the experimental observation reported previously. Chronic implantation of a stimulating electrode in the thalamic relay nucleus was performed in five cases which suffered from cancer pain (2 cases), thalamic pain (1 case), and paraplegic pain (2 cases). All of these cases enjoyed excellent relief of pain at least during the initial period. Only one case, which suffered from paraplegic pain developed stimulation-tolerance. Experiences in the other four cases suggested that administration of l-DOPA prevent the stimulation-tolerance. On the other hand, there was no evidence that administration of l-tryptophan interfered with progress of stimulation-tolerance. There were no operative complications and no side effects with this stimulating treatment. In summary, stimulation of the thalamic relay nucleus, which is more safe and acurate when electrode insertion using electrophysiological monitoring is done during operation, is effective in relief of intractable pain, even with morphine-tolerance. Administration of l-DOPA seems to prevent stimulation-tolerance.
The pathophysiological response and morphological damage from concussion caused by rotational angular acceleration impact were studied. In all monkeys tested, concussion syndromes were induced by impact in the range of 26.5 ?? 136.4×103 rad/sec2 with a duration of 1.03 ?? 9.09 msec. The morphological findings revealed two types of brain damage. One was a sharply demarcated vital dye-stained lesion which represented an ischemic lesion with occlusion of small vessels at the base of the lesion in the frontal lobe on the side opposite the impact site. The other consisted of scattered cellular damage in the lower medulla and medullospinal junction without staining by vital dye, which was observed on the monkey suffered from concussion by linear acceleration impact.20) In the vital dye-stained lesions, the local cerebral blood flow was reduced and the partial oxygen pressure decreased until 2 hours after impact. Lactic acid increased, ATP content decreased and there was no increase in free radicals. In the border zone of the lesions, local cerebral blood flow decreased in the first 1 hour, but increased 1.5 hrs after impact. Also, free radicals increased in the border zone despite the lack of change in lactic acid and ATP contents compared with the vital dye-stained lesions themselves. There was no variation in amplitude or latency of the brain stem response to auditory stimulation, but the somatosensory response at the sensory cortex changed to a low amplitude of elongation of the latency in the concussion caused by the rotational acceleration impact. These findings clearly suggest that there are two types of brain damage in concussions caused by rotational acceleration impact.
