✓ A sensitive enzyme-linked immunosorbent assay (ELISA) was used in a retrospective study of placental alkaline phosphatase (PLAP) levels in serum, cerebrospinal fluid (CSF), and intratumoral cyst fluid in primary intracranial germinoma. The ELISA showed no cross-reactivity with intestinal alkaline phosphatase except in very high concentrations, after samples had been heat-treated. Three patients with germinoma were studied for serum PLAP levels and in all the levels were elevated (3.78, 0.52, and 2.11 IU/liter). Two of the germinoma patients were studied for PLAP levels in the CSF, and both had elevated levels (0.83 and 9.83 IU/liter). The intratumoral cyst fluid in one case of germinoma was tested for PLAP and the level was found to be very high (603 IU/liter). These PLAP levels decreased concomitantly with the reduction in tumor size during irradiation. Serum PLAP levels were measured in 40 control adult male individuals and in the CSF of 20 nonpregnant patients with subarachnoid hemorrhage. The upper normal limits were 0.20 and 0.11 IU/liter in the serum and the CSF, respectively. All PLAP levels measured in the serum of patients with various brain tumors were 0.18 IU/liter or less. This study strongly suggests that PLAP is a clinically useful tumor marker for primary intracranial germinoma.
Jun Shinoda, Hiromu Yamada, Noboru Sakai, Takashi Ando, Toshifumi Hirata, and Yoshiaki Miwa
Takahiro Makino, Shota Takenaka, Gensuke Okamura, Yusuke Sakai, Hideki Yoshikawa, and Takashi Kaito
Dorsal spinal cord herniation is reportedly a rare condition. Here, the authors report an unusual case of dorsal spinal cord herniation at the thoracolumbar junction presenting with scalloping of ossification of the ligamentum flavum (OLF). A 75-year-old woman with a 2-year history of bilateral leg dysesthesia presented with progressive gait ataxia. Neurological examination showed bilateral patellar tendon hyperreflexia with loss of vibratory sensation and proprioception in her bilateral lower extremities. CT myelography revealed a posterior kink and dorsal herniation of the spinal cord at T11–12, with OLF between T10–11 and T12–L1. In addition, scalloping of the OLF was observed at T11–12 at the site of the herniated spinal cord. This scalloping was first noted 9 years previously and had been gradually progressing. The patient underwent surgical repair of the spinal cord herniation. Subsequently, her spinal cord herniation and vibratory sensation and proprioception in both legs partly improved, but gait ataxia remained unchanged. Dorsal spinal cord herniation reportedly occurs under conditions of vulnerability of the dorsal dura mater. In this case, acquired vulnerability of the dorsal dura mater owing to previous epidural catheter placement into the thoracolumbar space may have resulted in dorsal spinal cord herniation.
Hidemitsu Sakai, Hiroshi Takagi, Hirotoshi Ohtaka, Takamaru Tanabe, Takashi Ohwada, and Kenzoh Yada
✓ The authors report the cases of 37 patients encountered during the past 4 years who exhibited acute extradural hematoma but were initially treated conservatively because no or only small hematomas were observed on admission. The frequency of hematoma enlargement, hematoma size, and changes in the level of consciousness and intracranial pressure (ICP) were examined in these patients. The hematomas enlarged in 24 (64.9%) of the 37 patients, and attained a maximum thickness of 25 mm or greater in 19 patients (51.3%). The level of consciousness could be closely observed during enlargement of the hematomas in 13 patients: the level remained unchanged in eight, deteriorated in two, and improved in three, indicating relative stability in the state of consciousness despite the marked changes in hematoma size. The patients whose hematoma enlarged after the initial examination included three who underwent initial CT examination 5 hours after the injury. In five patients enlargement of extradural hematomas was observed unexpectedly during conservative treatment under ICP monitoring.
The ICP also remained stable in three patients until the follow-up examination, but showed a rapid increase in two after a period of stability. However, there was no difference in the final size of the hematomas between the patients showing an increase in ICP and those who did not. These findings suggest that extradural hematomas enlarge progressively at rates varying with the condition of the source of hemorrhage. Moreover, a period of stability in the level of consciousness, such as the lucid interval seen in patients with extradural hematoma, is considered to be a period during which compensatory mechanisms can maintain the stability of the intracranial condition during progressive enlargement of the hematoma.
Katsunobu Takenaka, Hiromu Yamada, Noboru Sakai, Takashi Ando, Toshihiko Nakashima, and Yasuaki Nishimura
✓ The purpose of this study was to determine the effects of cerebrospinal fluid (CSF) from patients with subarachnoid hemorrhage (SAH) on cytosolic free calcium in cultured rat vascular smooth-muscle cells using the fluorescent intracellular calcium indicator fura-2/AM. Samples of CSF were collected from 12 patients (seven with and five without vasospasm) on Days 2, 6, 11, and 16 after SAH. Control CSF samples were obtained from five patients 6 to 9 months after they had undergone successful aneurysm surgery following an SAH. All CSF samples in both the non-vasospasm and vasospasm groups, regardless of the day of sampling after the SAH, induced significantly higher transient intracellular calcium elevations when compared to levels induced by control CSF. Furthermore, the addition of 2 mM ethyleneglycol-bis (β-aminoethylether)-N,N'-tetra-acetic acid (EGTA) caused a slight reduction in the peak height in the CSF-induced intracellular calcium rise which declined more rapidly to basal levels than those studied without EGTA. In the non-vasospasm group, the intracellular calcium concentration remained stable after SAH throughout the study period. In contrast, in the vasospasm group, this concentration was highest on Day 2 post-SAH, but sharply decreased on Day 6 and rose again on Day 11. This result correlated with the clinical signs of vasospasm in these patients. These findings indicated that the intracellular calcium elevations induced by CSF obtained after SAH were due to the combination of the influx of extracellular calcium and the mobilization of intracellular calcium from storage sites. The changes in intracellular calcium concentrations in vascular smooth-muscle cells induced by CSF obtained from patients on successive days following SAH suggest that the substances that induce this repeat calcium elevation on Day 11 post-SAH may be the key spasmogens for vasospasm after SAH.
Tsubasa Sakai, Takashi Tsuji, Takashi Asazuma, Yoshiyuki Yato, Osamu Matsubara, and Koichi Nemoto
✓The authors report a case of spontaneous resorption of intradural disc material in a patient with recurrent intradural lumbar disc herniation and review magnetic resonance (MR) imaging and histopathological findings. Intradural lumbar disc herniation is rare, and most patients with this condition require surgical intervention due to severe leg pain and vesicorectal disturbance. In the present case, however, the recurrent intradural herniated mass had completely disappeared by 9 months after onset. Histological examination of intradural herniated disc tissue demonstrated infiltrated macrophages and angiogenesis within the herniated tissue, and Gd-enhanced MR images showed rim enhancement not only at the initial presentation, but also at recurrence.
The authors conclude that when rim enhancement is present on Gd-enhanced MR images, there is a possibility of spontaneous resorption even though the herniated mass may be located within the intradural space. Moreover, when radiculopathy is controllable and cauda equina syndrome is absent, conservative therapy can be selected.
Kazutoshi Yokoyama, Yoshitaka Asano, Takatsugu Murakawa, Mitsuaki Takada, Takashi Ando, Noboru Sakai, Hiromu Yamada, and Hitoshi Iwata
✓ Brain arteriovenous malformations are considered to originate from a congenital maldevelopment of the brain vessels. Although there have been occasional reports suggesting a familial incidence of these lesions, data for only 10 families have been accumulated in the literature. The authors report on six such cases in three families. This high rate of occurrence of familial cases suggests an involvement of genetic factors.
Masahiro Funaba, Yasuaki Imajo, Hidenori Suzuki, Norihiro Nishida, Yuji Nagao, Takuya Sakamoto, Kazuhiro Fujimoto, and Takashi Sakai
Neurological and imaging findings play significant roles in the diagnosis of degenerative cervical myelopathy (DCM). Consistency between neurological and imaging findings is important for diagnosing DCM. The reasons why neurological findings exhibit varying sensitivity for DCM and their associations with radiological findings are unclear. This study aimed to identify associations between radiological parameters and neurological findings in DCM and elucidate the utility of concordance between imaging and neurological findings for diagnosing DCM.
One hundred twenty-one patients with DCM were enrolled. The Japanese Orthopaedic Association (JOA) score, radiological parameters, MRI and kinematic CT myelography (CTM) parameters, and the affected spinal level (according to multimodal spinal cord evoked potential examinations) were assessed. Kinematic CTM was conducted with neutral positioning or at maximal extension or flexion of the cervical spine. The cross-sectional area (CSA) of the spinal cord, dynamic change in the CSA, C2–7 range of motion, and C2–7 angle were measured. The associations between radiological parameters and hyperreflexia, the Hoffmann reflex, the Babinski sign, and positional sense were analyzed via multiple logistic regression analysis.
In univariate analyses, the upper- and lower-limb JOA scores were found to be significantly associated with a positive Hoffmann reflex and a positive Babinski sign, respectively. In the multivariate analysis, a positive Hoffmann reflex was associated with a higher MRI grade (p = 0.026, OR 2.23) and a responsible level other than C6–7 (p = 0.0017, OR 0.061). A small CSA during flexion was found to be significantly associated with a positive Babinski sign (p = 0.021, OR 0.90). The presence of ossification of the posterior longitudinal ligament (p = 0.0045, OR 0.31) and a larger C2–7 angle during flexion (p = 0.01, OR 0.89) were significantly associated with abnormal great toe proprioception (GTP).
This study found that the Hoffmann reflex is associated with chronic and severe spinal cord compression but not the dynamic factors. The Babinski sign is associated with severe spinal cord compression during neck flexion. The GTP is associated with large cervical lordosis. These imaging features can help us understand the characteristics of the neurological findings.
Yasuaki Tamaki, Toshinori Sakai, Ryo Miyagi, Takefumi Nakagawa, Tateaki Shimakawa, Koichi Sairyo, and Takashi Chikawa
A 64-year-old man was referred to the authors with low-back pain (LBP) and right leg pain with a history of previously diagnosed lumbar disc herniation (LDH) at L4–5. He had undergone 2 percutaneous endoscopic lumbar discectomies (PELDs) for the herniation at another institution, and according to the surgical record of the second surgery, a dural tear occurred intraoperatively but was not repaired. Postoperative conservative treatments such as an epidural block and blood patch had not relieved his persistent LBP or right leg pain. Upon referral to the authors, MRI and myelography revealed an intradural LDH. The herniated mass was removed by durotomy, and posterior lumbar interbody fusion was performed. His symptoms were partially improved after surgery. Primary suture is technically difficult when a dural tear occurs during PELD. Therefore, close attention should be paid to avoiding such tears, and surgeons should increase their awareness of intradural LDH as a possible postoperative complication of PELD.
Katsunobu Takenaka, Hiromu Yamada, Noboru Sakai, Takashi Ando, Toshihiko Nakashima, Yasuaki Nishimura, Yukio Okano, and Yoshinori Nozawa
✓ To clarify the mechanism of contractive effects in arteries caused by oxyhemoglobin, changes in the concentration of cytosolic calcium ([Ca++]1) before and after exposure to oxyhemoglobin were measured in vitro in cultured vascular smooth-muscle cells obtained from rat aorta. This was accomplished by preloading these cells with a fluorescent intracellular Ca++ probe fura-2/AM.
Oxyhemoglobin induced a significant elevation of [Ca++]1 in vascular smooth-muscle cells which was sustained for 10 minutes. This response was completely abolished by chelating extracellular calcium with ethyleneglycol-bis (β-aminoethylether)-N,N′-tetra-acetic acid (EGTA). Oxyhemoglobin induced no accumulation of mass content of inositol 1,4,5-trisphosphate (IP3(1,4,5)). The oxyhemoglobin-induced elevation of [Ca++]1 was not blocked by verapamil, a calcium antagonist. Serotonin induced a rapid, transient increase of [Ca++]1 followed by a sustained elevation above baseline for 5 minutes. Additions of EGTA or verapamil had a small effect on the peak height of serotonin-induced [Ca++]1 elevation, but the [Ca++]1 level declined more quickly to the basal level in treated compared with control cells.
These results indicate that oxyhemoglobin-induced [Ca++]1 elevation is caused by the influx of extracellular calcium, which is independent of the verapamil-blocked voltage-gated calcium channel. The long-lasting high elevation of [Ca++]1 caused by oxyhemoglobin suggests that oxyhemoglobin may contribute to the production of abnormal contractions and/or irreversible damage in vascular smooth-muscle cells.
Hiromichi Ando, Masanao Saio, Noriyuki Tamakawa, Naoyuki Ohe, Takashi Nakayama, Hai Yu, Yasuhiko Kaku, Toru Iwama, Jun Shinoda, Noboru Sakai, and Tsuyoshi Takami
Object. It is well known that the central nervous system (CNS) is an immunologically privileged site. To characterize CD8+ tumor-infiltrating lymphocytes (TILs) recovered from the CNS, the authors compared these cells with TILs recovered from subcutaneous tissue by using a B7.1 gene—modified tumor implantation model.
Methods. The authors established a B7.1 gene—modified EL4 murine lymphoma cell line (EL4-B7.1) and implanted the cells into the CNS to observe the duration of tumor-free survival. Although EL4-B7.1 cells were completely rejected in a subcutaneous implantation model, 40% of animals died after the CNS implantation (all animals in which the parent tumor was implanted died within 16 days). Therefore, the authors isolated TILs from each implantation site and analyzed the expressions of activation antigens CD25 and CD69 by performing the anti-CD8 magnetic beads separation method and flow cytometric analysis. After implantation of the parent tumor, there was no difference in the number of TILs from each site (CD25 1.7–3.2%, CD69 21.9–34.3%). After implantation of the B7.1-modified tumor, the CD25-expressing TIL population from the subcutaneous site was 4.68 times higher than that from the CNS site (17.8% compared with 3.8%). Based on these findings, the authors used a mitomycin C—treated EL4-B7.1 subcutaneous vaccination with various protocols. Vaccination before tumor challenge was sufficient to prevent the development of the tumor. For animals with established tumor, the vaccination protocol was able to prolong host survival (p = 0.0053).
Conclusions. The data clearly demonstrate that the CNS environment fails to activate CD8+ TILs fully. These are the first data indicating in detail a difference between CD8+ TILs from the CNS and those from other sites based on a B7.1-modified tumor model.