Transverse myelitis associated with restless legs syndrome and periodic movements of sleep responsive to an oral dopaminergic agent but not to intrathecal baclofen.

Periodic limb movement disorder (PLMD) and restless legs syndrome (RLS) are related sleep disorders that occur with increased frequency in spinal cord disease. Effective treatment may be obtained with dopaminergic or opioid drugs, while anticonvulsants, benzodiazepines, and possibly baclofen may be helpful. This report describes a patient who developed RLS and PLMD after acute transverse myelitis associated with infectious mononucleosis, and failed to respond to intrathecal baclofen. All symptoms of RLS/PLMD resolved after treatment with pergolide.

Treatment of malignant gliomas with interstitial irradiation and hyperthermia.

A Phase I study of interstitial thermoradiotherapy for high-grade supratentorial gliomas has been completed. The objective of this trial was to test the feasibility and toxicity of hyperthermia induced by ferromagnetic implants in the treatment of intracranial tumors. The patient population consisted of 16 males and 12 females, with a median age of 44 years and a median Karnofsky score of 90. Nine patients had anaplastic astrocytoma while 19 had glioblastoma multiforme. Twenty two patients were treated at the time of their initial diagnosis with a course of external beam radiotherapy (median dose 48.4 Gy) followed by an interstitial implant with Ir-192 (median dose 32.7 Gy). Six patients with recurrent tumors received only an interstitial implant (median dose 40 Gy). Median implant volume for all patients was 55.8 cc and median number of treatment catheters implanted per tumor was eighteen. A 60-minute hyperthermia treatment was given through these catheters just before and right after completion of brachytherapy. Time-averaged temperatures of all treatments were computed for sensors located within the core of (> 5 mm from edge of implant), and at the periphery of the implant (outer 5 mm). The percentage of sensors achieving an average temperature > 42 degrees C was 61% and 35%, respectively. Hyperthermia was generally well tolerated; however, there have been 11 minor toxicities, which resolved with conservative management, and one episode of massive edema resulting in the death of a patient. In addition, there were three major complications associated with the surgical implantation of the catheters. Preliminary survival analysis shows that 16 of the 28 patients have died, with a median survival of 20.6 months from diagnosis. We conclude that interstitial hyperthermia of brain tumors with ferromagnetic implants is feasible and carries significant but acceptable morbidity given the extremely poor prognosis of this patient population.

Neurotoxicity of intraventricularly administered alpha-interferon for leptomeningeal disease.

Nine patients with leptomeningeal disease are reported who were treated with intraventricular alpha-interferon (alpha-IFN). In seven of these patients, a progressive vegetative state developed during treatment. The patients became unresponsive to verbal commands but opened their eyes with auditory or tactile stimulation. It took an average of 3 weeks for these patients to become verbally responsive after treatment was discontinued. Electroencephalographic findings showed evidence of irritative involvement of the deep midline nuclei in 80% of patients. Periventricular white matter changes developed during treatment in three of six patients who underwent computed tomographic scans. All patients with this severe neurotoxicity received whole-brain irradiation before treatment. Possible mechanisms for the development of this neurotoxic syndrome are discussed. The neurotoxicity of alpha-IFN and brain irradiation may be additive, suggesting a cautious approach when using this combination for treatment.

Treatment of malignant brain tumors with focused ultrasound hyperthermia and radiation: results of a phase I trial.

Hyperthermia delivered by scanned focused ultrasound was combined with external beam radiation to treat 15 patients with primary malignant tumors of the brain. A preliminary craniectomy was performed to avoid attenuation of the ultrasound beam by the skull, and multiple thermal sensors were employed to ascertain intratumoral temperatures. The target temperature was 42.5 degrees C at the tumor boundary. This was attained at more than one point during every complete treatment, while a mean temperature in excess of 42 degrees C was achieved within the scanned tumor volume during at least 1 treatment in 11 patients. Technical problems and toxicities are described.

Interstitial thermoradiotherapy of brain tumors: preliminary results of a phase I clinical trial.

A Phase I clinical trial has been initiated to determine the feasibility, tolerance, and toxicity of interstitial thermoradiotherapy in the treatment of high-grade supratentorial brain gliomas. Hyperthermia was delivered by means of thermally-regulating ferromagnetic implants afterloaded into stereotactically placed plastic catheters. Heat treatments were given immediately before interstitial irradiation; in addition, five patients received a second heat treatment at the completion of brachytherapy. The desired target temperature for the 60-minute hyperthermia session was between 42 degrees C and 45 degrees C. Following hyperthermia, the catheters were afterloaded with Ir-192, which delivered a variable radiation dose of 14-50 Gy depending on the clinical situation. Interstitial irradiation was supplemented with external beam radiotherapy (40-41.4 Gy) in patients with previously untreated tumors. A total of 14 patients (4 males, 10 females) have been treated to date on this protocol. Eleven of the patients had a diagnosis of glioblastoma multiforme, whereas three had anaplastic astrocytoma. The mean implant volume was 61.5 cm3 (range: 9-119 cm3); the median number of interstitial treatment catheters implanted was 19 (range: 7-33). Continuous temperature monitoring was performed by means of multisensor thermocouple probes inserted in the center as well as in the periphery of the tumor. Of the 175 monitored intratumoral points, 83 (47%) had time-averaged mean temperatures of greater than 42 degrees C, and only 12 sensors (7%) exceeded a temperature of 45 degrees C. Among the 19 heat treatments attempted, there have been four minor acute toxicities, all of which resolved with conservative medical management and one major complication resulting in the demise of a patient. These preliminary results indicate that ferromagnetic implants offer a promising new approach to treating brain tumors with hyperthermia.

Internuclear ophthalmoplegia in acquired immunodeficiency syndrome.

We describe the case of a patient with acquired immunodeficiency syndrome (AIDS) who had internuclear ophthalmoplegia (INO) and subsequent rapid neurologic deterioration. To our knowledge, this is the first report of a patient with AIDS and INO.

Ommaya reservoirs in 387 cancer patients: a 15-year experience.

We reviewed records of 387 patients with cancer who had Ommaya reservoirs placed between October 1967 and December 1982. Complications of reservoir placement were reported in 27 patients, including intracranial hemorrhage (5 patients) and reservoir malfunction (15 patients). In 15 of 19 patients with meningitis, the infection was linked to the reservoir. The organism most frequently implicated was Staphylococcus epidermidis. Seizures, leukoencephalopathy, and pericatheter necrosis were seen in 10 patients who had received intraventricular chemotherapy.

Phase I clinical trial of intralesional or intraventricular leukocyte interferon for intracranial malignancies.

Eight patients were treated with leukocyte interferon for a variety of neurological malignancies that had failed or recurred after conventional therapy. Three patients with malignant astrocytoma received intratumoral interferon in dosages up to 9 million units 3X/week, with total dosages of up to 160 million units. Interferon was administered intraventricularly in 4 patients with leptomeningeal metastases and one patient with multiple brain metastases. Dosages increased from 1 to 10 million units 3X/week, and total dosages of up to 113 million units were given intraventricularly. Acute side effects of fever, nausea, vomiting, and headache occurred almost exclusively with intraventricular injections, and these subsided after the initial injection. Fatigue, loss of appetite, weight loss, and hematologic toxicity developed a few weeks after onset of treatment, independent of the dose given. A modest tumor regression was seen on CT scans of one patient with a malignant astrocytoma, who was treated with interferon for 8 months. In all 4 patients with leptomeningeal metastases, the CSF became free of malignant cells for 6 to 10 weeks, while clinical improvement was less dramatic.

Successful treatment of leptomeningeal relapse of epithelial ovarian cancer.

A case of isolated leptomeningeal recurrence of an epithelial ovarian cancer was recently diagnosed and treated successfully with methotrexate placed via an Ommaya reservoir in combination with radiation therapy. A review of the literature revealed no other cases of epithelial ovarian leptomeningeal malignancy similarly treated.

A phase II trial of 2,5,-diaziridinyl 3,6-bis (carboethoxy amino) 1,4-benzoquinone (AZQ, NSC 182986) in recurrent primary brain tumors.

Forty-one patients with recurrent primary malignant brain tumors were treated with 2,5-diaziridinyl 3,6-bis (carboethoxyamino), 1,4-benzoquinone (AZQ) at an initial dose of 6-8 mg/m2/day X 5 days. Courses were repeated monthly upon recovery of myelosuppression. Six of 25 evaluable patients (24%) showed definite tumor regression, and 7 (28%) showed disease stability as determined by monthly CT scans and neurologic examination. For all patients receiving one course of AZQ, the response rate was 16% (6 of 37 patients) and the stable disease rate 19%. The estimated median time to tumor progression with AZQ was 54 weeks for the responding patients and 36 weeks for the stable patients. Toxicity consisted of myelosuppression, primarily thrombocytopenia, which was delayed and cumulative. Other toxicities were uncommon. Further clinical trials in patients with malignant primary brain tumors, including combination studies with other drugs, are indicated.