Jerzy Hildebrand

Epileptic seizures during follow-up of patients treated for primary brain tumors

Objective: To determine the presentation, incidence, and severity of seizures in follow-up of patients treated for primary brain tumors. Methods: A total of 234 consecutive patients attending an outpatient clinic for chemotherapy of a supratentorial brain tumor were examined. Results: Seizures occurred in 183 patients. All patients with epilepsy were on antiepileptic drugs (AEDs). Compared with patients without epilepsy, patients with epilepsy had a higher proportion of low-grade gliomas (p < 0.001) and cortical tumor location (p < 0.001). In 158 (86.4%) patients, seizures were an early manifestation of the disease, and epilepsy developed in only 25 (13.6%) individuals in the course of the malignant disease. Generalization occurred in 50% of early seizures, but in only 19.1% of patients with seizures persisting after the initiation of AEDs and specific antitumor therapies. The reduction in seizure generalization was significant (p = 0.001). Despite AED and various antitumor treatments, one-half of the patients had a seizure within 1 month and two-thirds within 3 months before the last evaluation. Conclusions: Most tumor-related seizures first appear early in the course of disease, usually as a presenting manifestation. Antiepileptic drugs combined with specific antitumor treatments significantly reduce the rate of seizure generalization. However, most patients continue to have focal epilepsy during follow-up.

Skull-base metastases

SummaryMetastasis to the skull-base particularly affects patients with carcinoma of the breast and prostate. Clinically, the key feature is progressive ipsilateral involvement of cranial nerves. Five syndromes have been described according to the metastatic site including the orbital, parasellar, middle-fossa, jugular foramen and occipital condyle syndromes. Magnetic resonance imaging (MRI) is nowadays the most useful examination to establish the diagnosis but plain films, CT scans with bone windows and isotope bone scans remain helpful to demonstrate bone erosion. Normal imaging studies do not exclude the diagnosis. The treatment depends on the nature of the underlying tumor. Radiotherapy is generally the standard treatment, while some patients with chemosensitive or hormonosensitive lesions benefit from chemotherapy or hormonotherapy and selected patients from surgical removal. Gamma Knife radiosurgery is sometimes a useful alternative, particularly for previously irradiated skull-base regions, and for small tumors (diameter < 30 mm). The overall prognosis is poor, with an overall median survival of about 2.5 years, probably because skull-base metastases appear late in the course of the disease.

Regional glucose metabolism and histopathology of gliomas: A study based on positron emission tomography‐guided stereotactic biopsy

Positron emission tomography (PET) with 18F‐2‐fluoro‐2‐deoxy‐D‐glucose (FDG) is widely applied to the study of gliomas. The histology of most gliomas is regionally heterogeneous. The relationship between histologic features and glucose metabolism evaluated by PET with FDG may therefore vary within the limits of the tumor. PET with FDG integrated in the planning of stereotactic brain biopsy allows precise comparison between local FDG uptake and histology. Using this approach, the authors investigated whether glucose metabolism of gliomas is related to anaplasia, and whether PET with FDG detects metabolic heterogeneity that parallels histologic heterogeneity of gliomas.

Affinity of adriamycin to phospholipids a possible explanation for cardiac mitochondrial lesions

Abstract Two thirds or more of adriamycin (ADM) is found in the hydrophilic phase when the drug is dissolved in the two-phase system of Folch. This distribution is changed dramatically by the presence of all the negatively charged phospholipids, which form an electrostatic complex with the drug in the lower lipophilic phase. The molar ratio of ADM to phospholipids in the lower phase is 2 to 1 with cardiolipin, which has 2 phosphate molecules, and 1 to 1 with phosphatidic acid which has only one. ADM is recovered from lipophilic phase by acidification. No complex was obtained with sulfatides or ADM-ADN complex. The relevance of these data to the pathogenesis of ADM induced cardiac mitochondrial lesions is discussed.

Adjuvant Therapy With Dibromodulcitol and Bcnu Increases Survival of Adults With Malignant Gliomas

Objective: We tested adjuvant chemotherapy combining dibromodulcitol (DBD) and bischloroethyl-nitrosourea (BCNU) given postoperatively to adults with newly diagnosed supratentorial malignant gliomas. Methods: We enrolled 269 patients, 255 of whom were eligible. After surgery, we treated all patients with radiation therapy, using a median dose of 60 Gy given in 30 fractions. After randomization, patients in the chemotherapy group also received (1) six weekly courses, administered during irradiation, of DBD 700 mg/m2 and (2) one to nine (median, four) courses, administered during the first year following radiation therapy, of DBD 1,000 mg/m2 on day 1 and BCNU 150 mg/m2 on day 2, with the course being repeated every 6 weeks. Results: Patients treated with radiation therapy along with DBD plus BCNU (group 2) had significantly longer survival time (p = 0.044) and time to progression (p = 0.003) than did those treated with radiation therapy alone (group 1). The median survival time was 13.0 months for group 2 and 10.4 months for group 1; the median time to progression was 8.1 months for group 2 and 6.7 months for group 1. The percentage of patients alive at 18 and 24 months was 34% and 21% in group 2 compared with 21% and 12% in group 1. Conclusion: DBD plus BCNU is an effective adjuvant therapy for malignant glioma.

Glucocorticoid-induced long-term remission in primary cerebral lymphoma: Case report and review of the literature

We report a 25-year old immunocompetent woman with a high grade primary non-Hodgkin‘s lymphoma of the central nervous system (PNHL-CNS) in whom the administration of dexamethasone alone during three months produced a complete clinical and radiological response lasting over four years. If complete remission of PNHL-CNS induced by glucocorticoids are well known, the opportunity to observe glucocorticoid-induced remission for a long period oftime without radio- and chemotherapy is rare. Only nine othercases of PNHL-CNS with complete remission induced by glucocorticoidslasting from 6 to 60 months, were found in the literature and aresummarized here. Duration of glucocorticoids therapeutic effect inPNHL-CNS is probably underestimated. Glucocorticoids cannotbe recommended as sole initial treatment for PNHL-CNS. However, we suggest standard therapies to be delayed in thosepatients responding completely to glucocorticoids where radio-and chemotherapy should be contraindicated (kidney, liver, bonemarrow failure, pregnancy).

Positron Emission Tomography-Guided Stereotactic Brain Biopsy

We describe a technique that allows target definition for stereotactic brain biopsy using coordinates calculated on stereotactic positron emission tomographic (PET) images. In this study, PET images were obtained using [18F]-labeled fluorodeoxyglucose, a marker for glucose metabolism. The difference between PET-calculated and actual stereotactic coordinates of simulated targets is within PET spatial resolution. Combined computed tomography- and PET-guided stereotactic biopsies were performed in 11 patients with brain tumors. In this report, we describe two representative patients who underwent stereotactic brain biopsy using the present technique. Because of the complementary role of PET and computed tomography, their integration in multimodality planning might optimize the target selection for stereotactic brain biopsies.

PET findings in a brain abscess associated with a silent atrial septal defect

Brain abscesses are classical complications of congenital heart disease (CHD) in children and adolescents. This association is rarely observed in adults. We report a 46-year-old man presenting a fronto-parietal abscess associated with an asymptomatic atrial septal defect. Positron emission tomography (PET) study revealed high uptake of L-[methyl-11C]methionine ([11C]methionine) and 2-[18F]fluoro-2-deoxy-D-glucose (FDG) around the brain abscess. We suggest (1) to exclude a silent cardiac malformation in the presence of a cerebral abscess of unknown source occurring in adults; (2) to consider the diagnosis of brain abscess in cases of high uptake of [11C]methionine and FDG in relation to a brain lesion.

Neuroradiologic findings in leptomeningeal carcinomatosis: the value interest of gadolinium-enhanced MRI

SummaryFour patients with leptomeningeal metastases documented by neuroradiological examinations are reported. All had central nervous system or systemic neoplasms and showed clinical signs of carcinomatous meningitis. Gadolinium-enhanced MRI (Gd-MRI) disclosed for each patient pathological foci, allowing delineation of the extent of meningeal disease. Although non-specific, these findings, combined with the clinical context and CSF analysis, may lead to a rapid diagnosis and treatment of carcinomatous meningitis, even when malignant cells are not detected in the cerebrospinal fluid.

Acute ischemic brachial plexus neuropathy following radiation therapy

Breast carcinoma is prominent among cancers where brachial plexopathy commonly occurs. Tumor invasion or postradiation fibrosis are the most common etiologies,’.* and both produce slowly progreesive neurologic symptoms and signs. Acute ischemia due to occlusion of the subclavian artery is an extremely rare cause of postradiation brachial plexopathy. Case report. In 1967, a 34-year-old woman developed a left areolar mammary carcinoma and was treated by a 4,000-rad irradiation of the breast and axillary area, followed by a radical mastectomy. Both treatments were well tolerated. Eight yeare later, a recurrence (or a second carcinoma) was found in the right breast and treated by mammectomy followed by a 4.000-rad irradiation of the breast area. This treatment was followed by a lymphedema of the right upper limb. In February 1988, &r carrying heavy objects and holding the left arm outstretched above her shoulder, she noted painlese weaknees of the left arm; decreased temperature sense of the left hand and fingers developed within a few days. Except for slight eeneory improvement in the third and fourth fingers, the manifestations remained unchanged until we first examined her in April 1988. Neurologic abnormalities, which were confined to the left upper limb, consisted of attophy and fasciculations of interosseous muscles; distal weakness grade 315 of the entire hand and the flexor of wrist and fingers; weakness grade 415 of the extenmr of wrist and proximal muscles of the arm (MRC scale); reduction of pinprick, touch, and thermic perception in the hand and touch perception in the entire forearm and aboli’ion of all tendon reflexes in the limb. There was painlese induration of the left supraclavicular fossa, and humeral, radial, and cubital pulse were absent. Blood preaeure was 140/80 on the right and 80/? on the left side. General examination findings were normal except for the lymphedema of the right upper limb. EMG showed fibrillations and resting positive sharp waves in distal muscles, and giant motor unit potentials in both distal and proximal segments of the left upper limb. No myokymic discharges were observed left paracervical muscles were normal. Sensory nerve potentials recorded at the wrist were 3.5