Intracranial peripheral primitive neuroectodermal tumor manifesting as abducens nerve palsy.

INTRODUCTION: Peripheral primitive neuroectodermal tumor (PNET) occurring as an extra-axial lesion within the intracranial space and extending to the subarachnoid space is extremely rare. CASE REPORT: An 18-month-old girl presented with an intracranial peripheral PNET manifesting as abducens nerve palsy. Magnetic resonance imaging on admission revealed a lesion affecting the trigeminal and abducens nerves. The tumor was partially removed via the subtemporal approach. Histological examination showed a high-grade, undifferentiated neoplasm of small cell type with positive immunostaining for MIC2. The histological diagnosis was peripheral PNET. OUTCOME: Craniospinal radiotherapy reduced the tumor size, but adjuvant chemotherapy designed for Ewing's sarcomas and PNETs was not effective. She died 1 month after the last chemotherapy, despite whole craniospinal irradiation (total dose 53.2 Gy) and chemotherapy.

Surgical experience of 120 patients with lumbosacral lipomas.

The surgical experience of 120 patients with lumbosacral lipomas is described. 47 of 120 patients were preoperatively found to be neurologically intact, the remaining 73 patients presented with various neurological signs including reflex changes, sensory disturbances, muscle weakness and sphincter problems. Neuro-imagings allowed a classification of lumbosacral lipomas into five types: (1) dorsal type; (2) caudal type; (3) combined type; (4) filar type; and (5) lipomyelomeningocele. Although all 120 patients underwent untethering of the spinal cord, the nerve roots passing through the lipoma itself and the neural tissues protruding externally to the spinal canal, respectively, tended to prevent satisfactory surgical removal of the lipoma in combined type lipomas and lipomyelomeningoceles. During 8.96 years of a mean postoperative follow-up period, there was no significant deterioration in most of the patients and some patients even improved in function. However, two patients with combined type lipomas developed neurological deterioration just after surgery, and five (two dorsal, two caudal and one combined type lipomas) did in the fashion of a late-onset. There are two different patient groups of lumbosacral lipomas; one group (caudal and filar type lipomas, and most of dorsal type lipomas) in whom the surgical anatomy is simple and satisfactory untethering surgery could be done without risk, and another (combined type lipomas and lipomyelomeningocele) in whom surgery would be accompanied with some risk and sometimes complete untethering could not be achieved because of the complicated anatomy of the lesion. Surgical difficulty of the latter group can be correlated with the increased frequency of neurological deterioration occurring just after the operation, but not of delayed one. Concerning prophylactic surgery for asymptomatic patients, the former group of patients are obviously good candidates, but the latter group is not.

Successful transarterial glue embolisation by wedged technique for a tentorial dural arteriovenous fistula presenting with a conjunctival injection.

Many tentorial dural arteriovenous fistulae (TDAVF) present with intracranial haemorrhage. We report a patient who presented with conjunctival injection. Transarterial embolisation of the TDAVF was undertaken with a wedged injection of a low concentration of N-butyl cyanoacrylate, arresting the flow next to the proximal segment of the venous outlet. After three sessions, a complete cure was achieved. We present a useful method which has not been reported previously.

Endodermal cyst of the quadrigeminal cistern: case report.

BACKGROUND: Endodermal cysts usually develop in the subdural space in the anterior spinal cord and rarely occur inside the cranium. Most intracranial endodermal cysts develop in the posterior fossa. We report the first case of an endodermal cyst in the quadrigeminal cistern. CASE DESCRIPTION: The patient was a 71-year-old man who suffered from gait disturbance for 6 months. Although head computed tomography (CT) scanning 4 years previously did not show any cystic lesion, CT and magnetic resonance imaging (MRI) on admission showed a cystic lesion extending from the quadrigeminal cistern to the right ambient cistern. The cyst was subtotally removed via a suboccipital transtentorial approach. The cyst wall consisted of a layer of columnar epithelium and connective tissue. Based on the results of immunostaining, it was diagnosed as an endodermal cyst. CONCLUSIONS: It is possible that the increase of secretion from the cells lining the cyst may have caused a difference in osmotic pressure between the cerebrospinal fluid and the cyst contents, leading to rapid enlargement of the cyst. An endodermal cyst should be removed as completely as possible because its cells have the ability to grow and produce secretions.

Transcranial transsphenoidal approach for tuberculum sellae meningiomas.

OBJECTIVE: A series of 21 patients with tuberculum sellae meningioma who received surgical treatment is reported. PATIENTS AND METHODS: All 9 females and 12 males (mean age 49 years) presented visual disturbances of varying degrees in either one or both eyes. Eighteen of the tumours were less than 3 cm in size, and 3 were larger. Tumour resection of uniform surgical technique was performed in all cases. Following a bicoronal scalp incision, bifrontal craniotomy combined with removal of the orbital rim bilaterally was performed. The frontal dura was opened bilaterally, and the most anterior portion of the superior sagittal sinus was transected. Bifrontal retraction and arachnoid dissection along the proximal olfactory tracts brought the tumour into view. Additional dissection of the interhemispheric fissure extended the operative field to the anterior communicating artery. The anterior skull base was drilled out to resect the basal part of the tumour. In all cases, the optic canal and sphenoid sinus, and additionally in some cases the ethmoid sinus were opened. The tumour uniformly extended inferomedially to the optic nerve, and direct visualization of this portion of the tumour was possible with our approach. The opened paranasal sinuses were reconstructed with adipose tissue harvested from the patient's abdomen and the pericranial flap. RESULTS: In all patients, total or almost total resection of the tumour was accomplished. Postoperatively, visual function was improved in 11 patients, was unchanged in 8, and worsened in 2. There were no operative deaths. Cerebrospinal fluid leakage was occurred in two patients but could be conservatively managed. In a mean 3-year follow-up, tumour recurrence was observed in only one patient who presented a malignant histology. CONCLUSIONS: We are confident that our surgical approach has great clinical value in surgical resection of tuberculum sellae meningioma. The good accessibility to a tumour extending inferomedially to the optic nerve should, in particular, be stressed.

Possible origin of suprasellar arachnoid cysts: neuroimaging and neurosurgical observations in nine cases.

OBJECT: In this study the authors identify and investigate two new classifications of suprasellar arachnoid cysts. METHODS: The authors used computerized tomography cisternography, magnetic resonance (MR) imaging, and neuroendoscopy to investigate nine cases of suprasellar arachnoid cysts. A communicating cyst with early filling and early clearance of a radioopaque tracer was found in seven of nine cases; a communicating cyst with delayed filling and delayed clearance of the tracer was observed in one case; and a noncommunicating cyst was observed in the other. The MR findings indicated a variation in the position of the basilar artery (BA) bifurcation in relation to the ventral surface of the midbrain. A distance existed between the BA bifurcation and the ventral surface of the midbrain in a communicating cyst with early filling, whereas the BA bifurcation was posteriorly displaced in a communicating cyst with delayed filling and also in a noncommunicating cyst, leaving little space between the bifurcation and the ventral surface of the midbrain. Endoscopic observation revealed, in the case of communicating cysts with early filling and early clearance of tracer, that the BA bifurcation is located inside the cyst with no overlying membrane, whereas in a noncommunicating cyst, the BA and its branches can be observed through the transparent membrane of the lesion. CONCLUSIONS: The authors postulate two different types of suprasellar arachnoid cysts: a noncommunicating intraarachnoid cyst of the diencephalic membrane of Liliequist and a communicating cyst that is a cystic dilation of the interpeduncular cistern.

Early experience with poly L-lactic acid bioabsorbable fixation system for paediatric craniosynostosis surgery. Report of 3 cases.

OBJECTIVE: The authors describe early experience in the use of bioabsorbable fixation devices for cranial reconstruction of paediatric craniosynostosis patients. METHODS: Three patients, individually respectively presenting sagittal synostosis, metopic synostosis, and clover leaf skull deformity, underwent cranial reconstruction using poly L-lactic acid (PLLA) plates and screws. The patients ranged in age from 2 to 10 months at the time of surgery. The postoperative clinical follow-up ranged from 16 to 18 months. All patients showed satisfactory wound healing without signs of infection or local inflammation. The plates provided satisfactory fixation and were not palpable through the skin after 16 to 18 postoperative months. CONCLUSION: Our experience demonstrated the efficacy of PLLA bioabsorbable plates and screws for cranial reconstruction in cases of infant craniosynostosis. Prospective studies and longer follow-up of a larger number of patients is desirable for confirmation of these findings.

Melanoma antigen recognition by tumour-infiltrating T lymphocytes (TIL): effect of differential expression of melan-A/MART-1.

We have isolated, from an individual patient with metastatic melanoma, a series of eight TIL clones capable of lysing autologous melanoma cell targets. Six of the eight clones expressed TCRAV2S1 and lysed targets expressing HLA-A2 and the Melan-A/MART-1 peptide: AAGIGILTV. Polymerase chain reaction-single stranded conformational polymorphism (PCR-SSCP) analysis showed that the Melan-A/MART-1-specific clones were predominant in the bulk culture prior to cloning. However, the tumour progressed in vivo even in the presence of these tumour cell-lytic clones. Using the anti-Melan-A/MART-1 MoAb (A-103), we noted that Melan-A/MART-1 expression on three melanoma cell lines varied considerably during in vitro culture, in the absence of T cell immunoselection, relative to cell density. Tumour cells which spontaneously decreased Melan-A/MART-1 expression were less susceptible to specific TIL lysis. Melan-A/MART-1 expression and susceptibility to lysis increased in cells cultured at lower density. These data suggest that modulation of tumour antigen may account for tumour progression in the presence of tumour cell-lytic T lymphocytes. The observations suggest a possible explanation for the common finding of Melan-A/MART-1-specific lytic TIL in clinically progressing melanomas, as well as a possible pathway for therapeutic intervention.

Studies of the mechanism of cytolysis by tumour-infiltrating lymphocytes.

In order to determine the mechanism of tumour destruction by tumour-infiltrating lymphocytes (TIL), we examined the ability of both CD4+ and CD8+ effector TIL, and TIL clones, to manifest granzyme-mediated and Fas-mediated destruction of tumour targets. In many in vitro studies TIL have been shown to manifest anti-tumour reactivity, yet many tumours escape immunological destruction. To investigate the role of Fas expression and the concomitant sensitivity to the inducibility of apoptotic death, we derived TIL from four melanomas and one glioma. The glioma, and all but one of the melanomas, expressed Fas, but Fas-mediated apoptosis could only be detected if the targets were treated with cyclohexamide. The melanomas and the glioma all expressed detectable cytoplasmic Bcl-2 protein, known to exert anti-apoptotic activity. Lysis of tumours by CD8-enriched cultures and CD8+ clones was Ca2+-dependent and could not be modified by an anti-Fas MoAb. In CD4-enriched cultures or CD4+ clones with cytotoxic potential against tumour cells, cytotoxicity was also Ca2+-dependent. As Ca2+-dependent cytotoxicity is usually the result of secretion of perforin/granzyme-B, we investigated the presence of perforin in cytotoxic CD4+ clones and demonstrated the presence of granular deposits of this enzyme in some of the CD4+ clones. Although an anti-Fas MoAb did not block the lysis of melanoma targets by CD4+ clones, the examination of Fas-dependent targets demonstrated that these clones also had the potential to kill by the Fas/Fas ligand system. These data suggest that the predominant mechanism in tumour killing by TIL appears to be perforin-granzyme-dependent, and that the solid tumour cell lines we studied are less susceptible to Fas-mediated apoptosis. As non-apoptotic pathways may enhance tumour immunogenicity, exploitation of the perforin-granzyme-dependent cytotoxic T lymphocyte (CTL) pathways may be important for achieving successful anti-tumour responses.

In vivo accumulation of the same anti-melanoma T cell clone in two different metastatic sites.

In a patient with progressing metastatic melanoma, we showed that the same autologous tumor-cytolytic CD8+ tumor infiltrating lymphocyte (TIL) clone accumulated in two separate metastatic sites. This clone, which represented three of eight independently derived clones from a tumor deposit on the skin of the abdomen, also represented two of eight clones derived from a skin lesion on the shoulder. This clone could be identified by its use of a unique TCRBV2-nD1n-J1S6 sequence, and could also be detected by single-stranded conformational polymorphism (SSCP) as the dominant TCRBV2-expressing clone among CD8+ TILs propagated from both shoulder and abdominal lesions. Using SSCP analysis, we also demonstrated that this clone was dominant in the fresh tumor tissue and in all TILs in which CD8+ were strongly represented, including several separate but parallel cultures. The SSCP pattern for this clone was not apparent among CD4+ TILs or CD8+ peripheral blood mononuclear cells. The SSCP analysis of the tumor tissue prior to in vitro culture is an indication that the selection for this anti-tumor cytotoxic T cell clone was a reflection of its in vivo accumulation. Thus, we provide evidence that melanomas are immunogenic and able to select for cytotoxic antitumor-specific TIL clones that are expanded in vivo and can circulate to accumulate in different tumor sites. However, because these clones were isolated from progressing tumor metastases, the accumulation of these specific cytotoxic T cells was not sufficient to contain tumor growth.

Human glioma-derived interleukin-10 inhibits antitumor immune responses in vitro.

Intracranial malignant gliomas are sequestered from the immune system yet are associated with broad suppression of host immunocompetence. Immune system dysfunction in patients with gliomas seems to be related to inhibitory mediators produced by glioma cells. We investigated the physiological roles of glioma-derived interleukin (IL)-10 in Class II expression of monocytes, cytokine secretion from lymphocytes, and T cell proliferation in vitro. We could detect the messenger ribonucleic acid transcript of IL-10 in four gliomas by the reverse-transcribed polymerase chain reaction. Glioma-derived IL-10 greatly down-regulated human lymphocyte antigens-DR expression on monocytes. The inhibitory effect of IL-10 on interferon-gamma and tumor necrosis factor-alpha was neutralized by the anti-IL-10 monoclonal antibody; however, the inhibitory effect on IL-2 was not neutralized. Next, supernatants of glioma cells remarkably suppressed T cell proliferation in a dose-dependent fashion; however, this inhibitory effect was not restored by adding anti-IL-10 monoclonal antibodies. The supernatant also inhibited the allocytolytic activity of lymphocytes that were not neutralized by anti-IL-10 monoclonal antibody. IL-10 plays an important role in cytokine synthesis; nevertheless, impaired T cell responsiveness cannot be solely explained by glioma-derived IL-10.

Immunohistochemical characterization of 'small, lymphoid-like cell populations' within germinomas: immunologic and molecular approaches to diagnosis.

Little is known to date about the biological and molecular characteristics of 'small lymphoid cells' within intracranial germinomas. Frozen sections from three germinoma specimens were evaluated immunohistochemically in order to identify phenotypic markers expressed on human lymphoid cells as well as intercellular adhesion molecules. In addition, T-cell receptor (TCR) variable alpha- and beta-chain mRNA expression was analyzed by polymerase chain reaction (PCR). The small cells stained faintly with anti-CD5 in two specimens, but were negative for the T cell specific markers, CD2, CD3, CD7, and CD8. In addition, these cells were weakly positive for CD11b (Mac-1) and CD54 (ICAM-1), but were negative for lymphocyte-specific CD11a (LFA-1) and CD11c (p150,95). No TCR V alpha or V beta gene expression was detected by PCR within these germinoma specimens. The small cells of germinomas with the cytologic appearance of lymphocytes are not derived from T-cells or other lymphocytic lineages.

Surgical management of comatose patients with cerebellar infarction.

A series of 20 patients with cerebellar infarction were classified into four groups based on the clinical and CT findings. Two comatose patients who developed acute hydrocephalus (Group 2) are presented and were successfully treated with external ventricular drainage (EVD) alone. Continuous post-operative monitoring of intracranial pressure (ICP) demonstrated that EVD had sufficiently controlled ICP and therefore suboccipital decompression of the cerebellum was not indicated even though the patients were not immediately responsive to EVD. Both patients made a gradual recovery: a 57-year-old woman, independently ambulatory, was discharged to her home and a 76-year-old woman, ambulatory with assistance, was discharged to a rehabilitation hospital. The results of our two cases suggest that EVD should be the first treatment in cases of cerebellar infarction with cerebellar swelling or oedema accompanied by hydrocephalus. Posterior fossa decompression and removal of infarcted cerebellar tissue should be indicated only in cases where ICP can not be controlled by EVD, even if there is no immediate recovery of the patient's impaired consciousness. Reviewing the literature pertinent to our two cases, the use of ventricular drainage alone in the management of cerebellar infarction with ischaemic cerebellar swelling is discussed.

Targeting therapy for glioma by LAK cells coupled with bispecific antibodies.

Targeting of T cells or natural killer (NK) cells to tumours by using bispecific antibodies has attracted increasing interest in the past few years. We treated 31 patients with malignant glioma using adoptive transfer of lymphokine-activated killer (LAK) cells coupled to a bispecific antibody (anti-CD3+anti-glioma) as post-operative adjuvant therapy. Although this study excluded patients with deeply-seated tumours or a poor performance status, approximately 50% of the patients remained alive after 3 years, and 40% were free of recurrence. Serial CT scans revealed disappearance of remnant tumours in some patients. In addition, CT-guided stereotactic biopsy of the tumour in 3 patients showed extensive necrosis and degeneration after specific targeting therapy (STT). Five patients developed acute infection, and one of them died of bacterial meningitis. Our results suggest that antibody-targeted LAK therapy can achieve a higher response rate in patients with standard LAK therapy or any type of conventional treatment.

Interleukin regulation of prolactin and corticotropin from pituitary adenoma.

Recent findings indicate that lymphokines, leukocyte-derived hormones, interact with the hypothalamic-pituitary axis. We examined the role of neurotrophic lymphokines in the neuroendocrine system. Specifically, the action of Interleukin (IL)-1b, IL-2 and IL-6 upon the anterior pituitary hormones, growth hormone (GH), prolactin (PRL) and adrenocoticotropic hormone (ACTH) were studied in rodent pituitary adenoma cell lines. Hormone release by GH and PRL-producing rat adenoma cells (GH3) and ACTH-producing mouse adenoma cells (AtT-20) was analyzed by radioimmunoassay (RIA). Recombinant (r) IL-1beta decreased PRL release from GH3 in a dose-dependent fashion. IL-1 inhibition of PRL production occurred in parallel with IL-1 inhibition of DNA synthesis in GH3 as measured by [(3)H] thymidine incorporation. This result strongly indicates that IL-1 alters PRL production by adenoma cells at the translational level. Low dose IL-2 (10 U/ml) enhanced ACTH production from AtT-20, but higher concentrations of IL-2 failed to affect the release of ACTH. IL-2 did not change the incorporation of [(3)H] thymidine in AtT-20. Previous studies showed that IL-1 and IL-6 induce a significant secretion of ACTH via the hypothalamic-pituitary axis. However, IL-1 and IL-6 failed to affect ACTH secretion by AtT-20. Blood-derived cytokines have direct effects on hormone secretion by pituitary adenoma cells in vitro.

Selective expression of interleukin-10 gene within glioblastoma multiforme.

Little information exists regarding which glioma cells are able to escape immune system detection and progress within the host. In order to elucidate some of the mediators which facilitate the growth and spread of glioma cells, the expression of cytokines, TNF-alpha, IL-6, gamma-IFN, IL-10, and GM-CSF, within 12 human glioma specimens was investigated by the polymerase chain reaction. The twelve patients with malignant glioma were categorized into a localized (n = 4) and an invasive glioma (n = 8) groups, mostly glioblastoma multiforme, based upon the CT and MRI scans. We examined the correlation between specific cytokine gene expression and the clinical category of each patient. The results showed that while IL-10 mRNA transcripts were expressed in most of the tumors from the invasive glioma group (7/8), they were not expressed in tumors from the localized group. On the other hand, gamma-IFN gene expression was more frequent in tumors from the localized group (3/4 vs 1/8 from the invasive group). The mRNA transcripts of IL-6 and GM-CSF were more frequently expressed in tumors from the localized group. No consistent pattern was seen in TNF-alpha gene expression between the two groups. Among the five cytokines studied, IL-10 mRNA was selectively expressed within invasive gliomas compared to less malignant, localized glioma group. Our results demonstrate specific cytokine mRNA profiles in glioma patients, which might have prognostic significance for immunotherapy.

[Unilateral supranuclear abducens palsy in a pineal tumor].

A 13-year-old boy complained of frequent headaches and diplopia on rightward gaze. A CT scan demonstrated hydrocephalus and a non-homogeneous enhancing mass in the pineal area, leading to a diagnosis of pineal tumor. The physical examination revealed no abnormalities. On neurological examination, there were a right homonymous hemianopsia and slight choked disc in both optic fundi. His right eye was slightly adducted on primary gaze. On right lateral gaze, his right eye could not move beyond the midline and showed gaze paretic nystagmus, whereas his left eye could move fully in all directions. The abducens palsy could be overcome by the oculocephalic maneuver or caloric test. Interestingly, his right eye could abduct when his left eye was covered. From these finding, this was labelled a supranuclear abducens palsy. The convergent nystagmus was observed. Rightward OKN (quick phase to right) of the right eye was abolished with and without the left eye covered, while leftward OKN of the right eye was preserved. Pursuit to right was disturbed. After removal of the tumor, the gaze palsies disappeared. It is postulated that the supranuclear lateral gaze palsy was caused by impairment of supranuclear control by involvement of lateral gaze pathways to gaze center coursing near the oculomotor nucleus.