The use of EEG in aircrew selection.

The value of the electroencephalograph (EEG) as a screening device in aviation medicine is questioned, because few subjects are disqualified on grounds of an EEG exam. At the Netherlands Aeromedical Institute, pilot applicants are rejected with a diagnosis of epilepsy or with severe EEG abnormalities (including epileptiform patterns where epilepsy is highly suspected). Although several studies have shown a low incidence of epileptiform EEG abnormalities in candidate pilots, subjects with an epileptiform EEG have a substantially increased risk of sudden incapacitation during their flying careers. In this review, we calculate the probability that a candidate with epileptiform EEG, but no history of epileptic seizures, will develop seizures during his flying career. This probability is about 25%, more than 12 times higher than for subjects with normal EEG and no history of epileptic seizures (2%). Subjects with epileptiform EEGs not only have increased risk of future epileptic seizures, but additionally it is recognized that epileptiform EEG discharges may be associated with episodic functional impairment, which can be a danger when a subject is flying. Taking this into account, one should consider rejecting all candidates with epileptiform EEGs in the future. This is at the expense of a small group of subjects with false-positive EEGs, but we believe that concern for public safety must override other considerations in these rare cases. To improve the understanding of the usefulness of the EEG in pilot screening procedures, an international classification and coding system should be developed, so that data from different countries can be compared.

Von Hippel-Lindau disease: new strategies in early detection and treatment.

UNLABELLED: Von Hippel-Lindau disease is an autosomal dominant inherited disorder causing hemangioblastomas of the central nervous system (CNS), retinal hemangiomas, renal cell carcinomas, pheochromocytomas, pancreatic and liver cysts, and epididymal cystadenomas. PURPOSE: Since 1976, we have periodically screened for the lesions in a large affected family and were able to evaluate new strategies in detection and treatment. PATIENTS AND METHODS: A total of 23 individuals underwent the screening program. A multidisciplinary team of physicians was involved. RESULTS: In 13 patients (7 females and 6 males), a total of 31 tumors was detected; hemangioblastoma of the CNS (9), retinal angioma (4), renal involvement (8), pheochromocytoma (4), pancreatic lesions (4), and liver lesions (2) were diagnosed by periodic family screening. On the basis of more than 10 years of experience and current literature, new criteria for diagnosis and treatment have been proposed. CONCLUSION: The von Hippel-Lindau disease gene appears to be a tumor suppressor gene, and its absence or a defect in its structure is responsible for the predisposition to the disease. Tumor development depends on a somatic second mutation in the homologous allele. That means, in disease-gene carriers, tumor growth may begin at any age. Most of the lesions can be treated successfully when diagnosed in time. Periodic screening by a multidisciplinary team has to be continued lifelong.

Prevention of cisplatin neurotoxicity with an ACTH(4-9) analogue in patients with ovarian cancer.

In a randomized, double-blind, placebo-controlled study, we assessed the efficacy of an ACTH(4-9) analogue, Org 2766, in the prevention of cisplatin neuropathy in 55 women with ovarian cancer. The analogue was given subcutaneously in a dose of 0.25 mg (low dose) or 1 mg (high dose) per square meter of body-surface area before and after treatment with cisplatin and cyclophosphamide (75 and 750 mg per square meter every three weeks). The threshold of vibration perception was used as the principal measure of neurotoxicity. After four cycles of chemotherapy, the mean (+/- SEM) threshold value for vibration perception in the placebo group increased from 0.67 +/- 0.12 to 1.61 +/- 0.43 microns of skin displacement (P less than 0.0001). In the high-dose treatment group, there was no increase in the threshold value after four cycles (from 0.54 +/- 0.12 to 0.50 +/- 0.06 micron). After six cycles of chemotherapy, the threshold value was 5.87 +/- 1.97 microns in the placebo group (more than an eight-fold increase from base line), as compared with 0.88 +/- 0.17 micron (less than a twofold increase) in the high-dose treatment group (P less than 0.005). In the high-dose group, fewer neurologic signs and symptoms were recorded than in the placebo group. With the lower dose of the analogue, these protective effects were less prominent. No side effects were seen after treatment with Org 2766. The rates of clinical response to chemotherapy were similar in all groups. These results suggest that Org 2766 can prevent or attenuate cisplatin neuropathy without adversely affecting the cytotoxic effect of the drug.

Vibration perception and thermoperception as quantitative measurements in the monitoring of cisplatin induced neurotoxicity.

In 20 ovarian cancer patients treated by cisplatin-based chemotherapy quantitative investigations of the vibration and the thermoperception were performed. Following the administration of cisplatin of 300 mg/m2 and more the vibration perception threshold (VPT) was shown to be significantly elevated in all patients, despite the absence of clinical symptoms and signs in a number of patients. The VPT returned within 8 months to its original level in the 2 patients who were followed after cessation of therapy (cumulative dose of cisplatin 450-525 mg/m2). The changes seen in hands and in feet were comparable. There was no significant difference between the left and the right hand side. Thermoperception thresholds did not change during the treatment period. This study shows that quantitative measurement of vibration perception thresholds in patients treated with cisplatin is a relatively simple, accurate and reliable technique. Measurement is only required at the hand. It is concluded that this technique is a valuable tool in the assessment of cisplatin neurotoxicity and may be used in the monitoring of drugs that claim to be of benefit in the prevention and treatment of this affliction.

Chronic forms of Borrelia burgdorferi infection of the nervous system.

Three European patients had chronic active forms of Borrelia burgdorferi infection of the nervous system, with high titers of antibodies to this spirochete in serum and CSF. Two patients had meningitis for 3 to 4 years, with remissions in one and slowly progressive symptoms in the other. Both had CT lucencies in the basal ganglia. The third patient had lumbosacral plexus neuropathy for 1 year. All three patients responded to intravenous penicillin treatment.

Meningeal involvement in patients with acute nonlymphocytic leukemia. Incidence, management, and predictive factors.

Between 1977 and 1983, symptomatic meningeal leukemia was diagnosed in 9 of 93 adult patients with acute nonlymphocytic leukemia (10%). All cases occurred after complete remission had been achieved (46 patients), either as the only site of relapse (3 patients), or together with a first bone marrow relapse (3 patients), or after a bone marrow relapse (3 patients). Extramedullary involvement at initial diagnosis was the only independent predictive factor (P = 0.005), the number of patients with initial hyperleukocytosis being too small (three) for evaluation. Remission of the meningeal leukemia was obtained after treatment in four of eight patients. The presence of meningeal leukemia and the response to therapy had no influence on survival. However, the morbidity and therapy related toxicity of meningeal leukemia were impressive. Some recommendations for prophylactic treatment are suggested.

Nonsurgical treatment of subdural empyema. Case report.

The nonsurgical treatment of a case of interhemispheric subdural empyema is reported. At the time of diagnosis, the patient had a mild decrease in consciousness and only moderate focal neurological deficits. Computerized tomography (CT) confirmed the limited (interhemispheric) extent of the intracranial infection. After drainage of the nasal sinuses and antibiotic treatment, the patient recovered, although the lesion was initially increased in size on CT scanning.

Albumin and immunoglobulin-G in the cerebrospinal fluid and the diagnosis of multiple sclerosis.

Multiple sclerosis (MS) remains a diagnosis based mainly on clinical criteria. Definitive diagnostic tests are, despite numerous attempts, not available. However, some laboratory tests like electrophoresis of the cerebrospinal fluid proteins or the determination of immunoglobulin G in cerebrospinal fluid have proved useful in increasing the probability of MS. This paper describes how these laboratory tests have to be interpreted in relation to pathophysiological phenomena and how they correlate with each other. The electrophoresis of CSF proteins and the diagnostic quotients (Ralb and CSF-IgG-index) are valuable aids to the clinician. It especially can substantiate the diagnosis MS. The magnitude of the index cannot be correlated with the clinical stage of MS. The usefulness of these tests in terms of a possible gain of information in the diagnostic process is discussed.