Evangelos Markakis

Localized proton NMR spectroscopy of brain tumors using short-echo time STEAM sequences.

Recent progress in localized proton NMR spectroscopy has been utilized to improve the spatial resolution and the metabolic specificity in a study of 19 patients with intracranial tumors. Selected examples demonstrate that short echo time stimulated echo acquisition mode sequences are able (a) to account for macroscopic tissue heterogeneity by reducing the volume of interest to 2-8 ml and (b) to facilitate a reasonable characterization of tumor metabolism by increasing the number of accessible metabolites. Proton NMR spectra were acquired within measuring times of 6.5 min on a 2.0 T whole-body system using the imaging headcoil.

Cisternal S100 protein and neuron-specific enolase are elevated and site-specific markers in intractable temporal lobe epilepsy.

In the brain, S100 protein and neuron-specific enolase (NSE) are mainly found in glial cells and neurons, respectively. We investigated concentrations of S100 protein and NSE in cisternal cerebrospinal fluid obtained during implantation of foramen ovale electrodes in eight patients with temporal lobe epilepsy (TLE). In addition, the meningeal markers cystatin-C and beta-trace as well as total protein were measured. Patients with trigeminal neuralgia (TN) undergoing glycerol rhizotomy served as controls. S100 protein and NSE levels ipsilateral to the site of seizure onset were significantly higher than in TN. Contralateral TLE values were also markedly but not significantly elevated. The meningeal markers cystatin-C and beta-trace protein as well as total protein did not differ in TLE and TN. We conclude that interictal temporal lobe dysfunction corresponds with neuronal and glial marker elevations in the extracellular space and that site-specific elevations may predict the site of seizure origin biochemically.

Quantitative proton magnetic resonance spectroscopy of focal brain lesions

The diagnostic value of single-voxel proton magnetic resonance spectroscopy (2 T, stimulated echo acquisition mode, TR = 6,000 ms, TE = 20 ms, 4-5 mL volumes-of-interest) was assessed for a differentiation of focal brain lesions of unknown etiology in 17 patients 1-14 years of age. Absolute metabolite concentrations were compared with age-matched control subjects and an individual control region. Most of the brain tumors were characterized by strongly reduced total N-acetylaspartyl compounds and marked increases of myo-inositol and choline-containing compounds, consistent with a lack of neuroaxonal tissue and a proliferation of glial cells. Lactate was elevated in only four patients. When using this pattern for a metabolic discrimination of brain tumors from other focal lesions, proton spectroscopy correctly identified 14 of 17 abnormalities, as confirmed by histologic examination after neurosurgical intervention. One false-positive tumor diagnosis was a severe reactive gliosis mimicking a typical tumor spectrum. Two inconclusive cases comprised an astrocytoma with moderately elevated myo-inositol but reduced choline-containing compounds and a patient with an abscess leading to a marked reduction of all metabolites but strong contributions from mobile lipids. In summary, quantitative proton spectroscopy has considerable clinical value for preoperative characterization of focal brain lesions.

c-myc oncogene family expression in glioblastoma and survival

BACKGROUND In gliomas, c-myc proto-oncogene expression has been found to correlate with the grade of malignancy, with low expression in Grade I and II and high expression in Grade III and IV tumors. We aimed to discover if myc expression is of prognostic significance in glioblastomas. METHODS Expression of the c-myc, N-myc, and L-myc proto-oncogenes and of the max gene was investigated in 46 supratentorial glioblastomas from adult patients using in situ hybridization. RESULTS Seventy-eight percent of the tumors expressed c-myc m-RNA, 84% max m-RNA, 57% N-myc m-RNA, and 57% L-myc m-RNA. The postoperative survival of patients over 60 years of age and that of patients under 60 years of age were analyzed separately, since advancing age was found to be negatively correlated with the duration of postoperative survival (p = 0.004). There was no significant difference in postoperative survival in either age group between patients whose tumors expressed either c-myc, N-myc, or L-myc, respectively, and those whose tumors did not exhibit this characteristic. A difference in postoperative survival, however, was found in the over 60-year age group between patients whose tumors expressed max to an equal or lesser extent than c-myc and those whose tumors expressed max to a greater extent than c-myc or neither max nor c-myc. CONCLUSION The biologic behavior of glioblastomas in older patients may depend on the relative, but not on the absolute content of the c-myc protein and interacting proteins.

Hemicranial attacks or permanent hemicrania--a sequel of upper cervical root compression.

After many years of unsuccessful conservative treatment 16 patients suffering from hemicrania are relieved of their pain or are improved by operative treatment. Hemicranial attacks or permanent hemicrania is found to be caused by upper cervical nerve root compression. Vascular compression of C2 (n = 9) or scar tissue surrounding C2 (n = 1) or C3 (n = 1) is the pathology identified in cases of cervicogenic headache or “cluster headache-like” headache. Compression attributable to tumor, prolapsed disc, or spondylotic changes is found to be a cause of permanent headache. Only in those patients with permanent headache are radiological or electrophysiological findings helpful for diagnosis. In patients with hemicranial attacks and compression of nerve root C2 (n = 10) or C3 (n = 1), only vasoactive tests (provoking or relieving pain) or local anaesthesia prove to be helpful in diagnosing and localizing the origin of pain. The operation involves freeing the nerve roots from vascular compression. In two patients the C2 ganglion is resected. Thirteen patients subsequently become pain free. In three patients, hemicrania improves. Four of the 16 patients experience a recurrence of pain after the decompressive operation. After additional thermorhizotomy two patients have no further complaints and one patient has improved. One patient can tolerate his pain with occasional analgesics. The problem of referred pain into the fronto-ocular region is discussed.

Potential prognostic value of C-erbB-2 expression in medulloblastomas in very young children.

Purpose The expression of the c-erbB-2 oncogene was studied in childhood medulloblastoma to evaluate its prognostic value, which has been claimed previously. Patients and Methods Tumor material from 45 patients <15 years old at diagnosis was studied using 3 monoclonal antibodies against the internal and external domains of the c-erbB-2 oncogene product. Results Six of the 45 (13%) tumor specimens were found to be positive. C-erbB-2 expression was found more often in patients <3 years old at diagnosis (4 of 15 patients, 27%) than in older patients (2 of 30, 6.6%). During the follow-up period (5.8±2.8 years) all patients with c-erbB-2 expression died of disease (after 1.2±0.7 years). Kaplan-Meier estimation revealed a highly significant correlation of c-erbB-2 expression and survival (p = 0.002). A further study of the expression of synaptophysin and the glial fibrillary acidic protein (GFAP) in the 45 tumors revealed a negative correlation of the expression of c-erbB-2 and these proteins. Conclusion C-erbB-2, which may be predominantly expressed by less differentiated tumors, was found to delineate a poorer prognostic subgroup, especially when diagnosed in patients <3 years old.

Visually Evoked Potentials in 52 Children Requiring Operative Repair of Craniosynostosis

We evaluated the prevalence of pathological visually evoked potentials (VEP) before the apppearance of papilledema or other signs of elevated intracranial pressure in children suffering from craniosynostosis. In 52 children (19 girls, 33 boys, median age 7.6 months, mean age 7.6 months, range from 3 to 34 months) preoperative VEP were analyzed. In 13 patients, pathological VEP were observed. In all children, both eyes were involved. Only 1 child suffered from papillar anomalies. Latency was pathological in 12 children, whereas the amplitude was suppressed in only 2 children. In all children with preoperative pathological VEP, postoperative controls (n = 4) were improved or normal. Thus, VEP may be the first test for neuronal damage in craniosynostosis.

Atypical and Malignant Meningiomas: Evaluation of Different Radiological Criteria Based on CT and MRI

The following are our results of a retrospective analysis of 214 patients, operated on meningiomas, in order to investigate radiological criteria of malignancy. Among these cases there were 31 patients with a histologically confirmed diagnosis of malignant subtypes. As uncertain signs of malignancy of ensuing radiological features are an irregular enhancement of contrast-media and the size of cerebral edema. Based upon CT and MR images we have developed a standardised, computerised evaluation method which enables us to study in detail the internal architecture of meningiomas.

Intra-axial endophytic tumors in the pons and/or medulla oblongata I. Symptoms, neuroradiological findings, and histopathology in 30 children

Abstract Between August 1987 and June 1994 we operated upon 30 consecutive children suffering from endophytic intra-axial tumors located in the pons and/or medulla oblongata. We present the clinical findings, neuroradiological aspects and histopathological results recorded in these cases. Diagnostic tests included clinical examinations, neurophysiological tests and neuroradiological imaging [magnetic resonance tomography (MRT) in all cases, often combined with cranial computer tomography (CCT)]. The diagnosis was confirmed by histopathological examination of the tumor material obtained by open surgical exploration in all cases. We conclude that a short history and more horizontal growth within the pons are more valuable predictors of the histopathology than dif-ferentiation between focal or diffuse growth patterns. MRT has little predictive value for histopathological diagnosis in intra-axial brain stem tumors.

Surgical treatment of intramedullary tumors (spinal cord and medulla oblongata) : analysis of 16 cases

From February 1987 to July 1988, 16 patients of our clinic with intramedullary tumors (seven astrocytomas, six ependymomas, two angiomas with intramedullary hematomyelia, and one angioblastoma of the medulla oblongata) underwent surgery. Radical excision was possible in six cases with tumors in the cervical and/or thoracic region as well as in two cases with tumors in the medulla oblongata. In the group of patients with cervical and/or thoracic tumors, seven showed improvement, up to complete remission of the neurological symptoms. From eight patients with tumors of the medulla oblongata, one patient showed an invasive tumor of the medulla oblongata and pons with corresponding extensive neurological deficits, and died six weeks after surgery. The neurologic symptoms of the other seven patients improved after a postoperative interval of at least six weeks.The surgical approach to tumors of the medulla oblongata or spinal cord was performed by midline incision. Occasionally, a dorsal root entry zone (DREZ) incision was used when the tumor showed strictly unilateral localization. Tumors of the rhomboid fossa were approached by a lateral incision to avoid damage to nuclear structures. The more rostral the tumor localization (medulla oblongata, pons), the less complete was the surgery: only one ependymoma of the medulla oblongata was accessible to total extirpation. The tumor dignity worsened with ascending level of tumor localization. As described generally in the literature, neurological deficits of those patients with tumors in the medulla oblongata increased in the first few postoperative weeks before they began to improve.Chemotherapy, radiation therapy or decompressive laminectomy by themselves only lead to an improvement and are, therefore, not recommended.