Biomedical subjects

Jerzy Hildebrand

Publications and source records attributed to Jerzy Hildebrand.

6 recordsLinked to original sources

PubMed2006

Neurological complications of cancer chemotherapy.

PURPOSE OF REVIEW: To update central and peripheral nervous system neurological manifestations caused by anticancer agents. RECENT FINDINGS: Mostly unpredictable encephalopathy continues to be sporadically reported even in patients treated systemically with conventional chemotherapy doses. Recently, capecitabine, a 5-fluorouracil prodrug, has been added to the list. Magnetic resonance diffusion-weighted and fluid-attenuated inversion-recovery imaging are useful in demonstrating chemotherapy-induced central nervous system lesions. The pathogenesis of these lesions is often poorly understood, and is probably multifactorial. A recent observation indicates that genetic polymorphism for methionine is a potent risk factor for methtrexate-induced central nervous system toxicity. Chronic peripheral neuropathy still represents a major limiting factor in a series of chemotherapeutic drugs, and the neuroprotective effect of several older and newer agents is either deceptive or insufficiently proven. In addition to chronic neuropathy, oxaliplatine causes a unique acute syndrome which may respond to calcium plus magnesium infusion. SUMMARY: Neurotoxicity remains a major limitation of many drugs used in cancer patients. Their list grows steadily, and magnetic resonance imaging makes easier the recognition of central nervous system toxicity. Synthesis and thorough clinical testing of neuroprotective molecules remain a major challenge.

Antineoplastic Agents↗

PubMed2006

Treatment of central nervous system metastases: parenchymal, epidural, and leptomeningeal.

PURPOSE OF REVIEW: With prolonged survival from systemic therapies in the adjuvant and salvage setting, and because these agents cannot cross the intact blood-brain barrier, central nervous system metastases are becoming a therapeutic challenge in oncology. RECENT FINDINGS: Recent therapeutic achievements include an extended use of surgery and radiosurgery. Although each of these treatment modalities has its own indications, in patients eligible for both treatments the upfront comparison of these two techniques has not been performed yet. Systemic chemotherapies and biotherapies may be effective in the management of central nervous system metastases as they may act on both neurologic and extra-central nervous system lesions. In the treatment of epidural metastases, a surgical procedure providing immediate direct circumferential decompression of the spinal cord followed by local irradiation has been demonstrated in a prospective randomized trial. The management of leptomeningeal metastases remains controversial and of limited efficacy especially in chemoresistant tumours and still relies on the combination of chemotherapy (intrathecal and intravenous) and focal radiotherapy. SUMMARY: Aggressive treatments in patients with early diagnosis and in whom central nervous system metastases are the life-threatening location may provide a substantial increase in survival and favourably affect quality of life.

Antineoplastic Agents↗

PubMed2005

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.

Adult↗

PubMed2005

Dural metastases.

Dural metastases are found at autopsy in 8-9% of patients with advanced systemic cancer. They arise either by direct extension from skull metastases or by hematogeneous spread. Dural metastases are often clinically asymptomatic but they may produce progressive neurological deficits and sometimes subdural hematomas. MRI may be misleading when the metastasis simulates a meningioma or when a subdural hematoma masks the underlying tumor. Whenever possible, surgical removal is the most appropriate treatment. The prognosis is poor because of the progressive systemic cancer but prolonged survival has been reported in operated patients, when the systemic cancer was controlled.

Dura Mater↗

PubMed2005

Skull-base metastases.

Metastasis 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.

Humans↗

PubMed2004

Management of epileptic seizures.

PURPOSE OF REVIEW: Acquired epileptic seizures are common in cancer patients. They heavily impact on the quality of life and may affect survival. Most patients are medically treated, but the use of antiepileptic drugs (AEDs) in neuro-oncology is complicated by serious specific side effects and interference of AEDs with other commonly prescribed drugs such as chemotherapeutic agents and corticosteroids. The main purpose of this review is to help the clinician to select the most appropriate drug or drug combination, and to minimize drug side effects and drug interactions in epilepsy treatment of cancer patients. RECENT FINDINGS: Considerable progress has been achieved recently in epileptology. They include the development of new AEDs and better understanding of their subcellular mechanism of action and of drug interactions. Most studies concerning the efficacy of AEDs have not been performed specifically in neuro-oncological patients, and the extrapolation of their results to tumor-related epilepsy requires some caution. The most significant findings specific to tumor-related epilepsy are (a) the indication that their pathogenesis may be due to a decrease of focal GABA-ergic inhibition, and (b) the guidelines for prophylaxis based on a report by a subcommittee of the American Academy of Neurology. SUMMARY: The quality of life of epileptic patients has been improved by both a better control of seizures and the use of drugs with fewer side effects. Cancer patients probably benefit from this progress. However, treatment of tumor-related epilepsy faces several specific problems, and there is a real need for conducting clinical trials restricted to cancer patients.

Anticonvulsants↗