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Introduccion. El metronidazol es un antibiotico ampliamente conocido y utilizado. En casos excepcionales puede producir como efecto adverso un cuadro de encefalopatia con unas lesiones caracteristicas en la resonancia magnetica, localizadas generalmente en el cerebelo y el esplenio del cuerpo calloso. La incidencia y la patogenia se desconocen. La suspension del tratamiento habitualmente resuelve los sintomas y normaliza la resonancia magnetica en pocas semanas. Debido al habitual buen pronostico, los hallazgos anatomopatologicos son excepcionales. Se presenta un caso clinico con los hallazgos radiologicos sugestivos de la encefalopatia inducida por metronidazol y, de forma excepcional, se aportan los hallazgos anatomopatologicos. Caso clinico. Mujer de 72 anos, con enfermedad de Crohn grave, que meses mas tarde de iniciar tratamiento con metronidazol presento de forma lentamente progresiva bradipsiquia y dificultad para caminar hasta llegar al coma. En la resonancia magnetica mostraba caracteristicas imagenes hiperintensas en T2 en el cuerpo calloso, y los nucleos rojos y dentados. Mejoro al suspender el metronidazol, pero posteriormente desarrollo una sepsis y fallecio. En la autopsia se observo reblandecimiento del nucleo rojo y, microscopicamente, necrosis celular y desmielinizacion. Conclusion. Con la publicacion de la informacion clinica, radiologica y anatomopatologica de este caso se pretende fomentar el conocimiento de esta infrecuente causa tratable de encefalopatia subaguda y aportar datos que ayuden a aclarar su patogenia.

The value of hyperthermia as an adjuvant to radiotherapy in patients with malignant melanoma was studied in a European multicentre trial. 134 metastatic or recurrent lesions of malignant melanoma in 70 patients were randomly assigned to receive radiotherapy (three fractions of 8 Gy or 9 Gy in 8 days) alone or followed by hyperthermia (43 degrees C for 60 min). Overall, the 2-year actuarial local tumour control was 37 (SE 5)%. Univariate analysis showed a beneficial effect of hyperthermia (radiation alone 28% vs combined treatment 46%, p = 0.008) and radiation dose (24 Gy 25% vs 27 Gy 56%, p = 0.02), but no effect of tumour size ( 4 cm 29%, p = 0.21). Cox multivariate regression analysis showed the most important prognostic variables to be hyperthermia (odds ratio for 2-year local control 1.73 [95% CI 1.07-2.78], p = 0.023), tumour size (0.91 [0.85-0.99], p = 0.05), and radiation dose (1.17 [1.01-1.36], p = 0.05). Addition of heat did not significantly increase acute or late radiation reactions. Heating was well tolerated, but because of difficulties with equipment only 14% of treatments achieved the protocol objective. The overall 5-year survival rate was 19%, but 38% of the patients for whom all known disease was controlled survived 5 years. Adjuvant hyperthermia significantly improved local tumour control when applied in association with radiation in treatment of malignant melanoma. Successful local treatment of patients with a single or a few metastatic malignant melanoma lesions has significant curative potential.

Hyperthermia was applied in the region of the vertebral column from the second to the fifth lumbar vertebra using a ring-shaped 434 MHz microwave radiator. In all experiments temperatures were measured at a 'reference' thermocouple which was placed against the fourth lumbar vertebra. After 60 min of heat treatment at 'reference' temperatures of 43.0 degrees C, 44.0 degrees C and 45.0 degrees C (+/- 0.05 degrees C) the average maximal temperature inside the vertebral canal were 42.6 degrees C, 43.0 degrees C and 43.8 degrees C (+/- 0.3 degrees C), respectively. At all 'reference' temperatures the maximal core temperature of the animal did not exceed 40.5 +/- 0.3 degrees C after 60 min of heat treatment. Dorsal skin and muscle temperatures in the treatment area reached 'reference' temperature, and transient skin and muscle necrosis was observed after treatment for 1 h at 'reference' temperatures at 44 degrees C and 45 degrees C. Temperatures in the peritoneal cavity approximately 1 mm ventrally of the vertebral column rose to 41.8 degrees C after 60 min at reference 43.0 degrees C. Treatment at spinal cord temperature 42.6 degrees C for 60 min did not induce any significant neurological effects. Motoric dysfunction of the hind legs, such as difficulties with walking, was observed after 60 min treatment at spinal cord temperatures of 43.0 degrees C or 43.8 degrees C. In addition, 24 h after treatment at 43.8 degrees C for 60 min loss of tail tonus was observed, as well as loss of sensory function in the hind limbs. Recovery from the neurological disorders, except for the loss of tail tonus, occurred within 2 weeks after treatment. Histopathological examination revealed necrosis in the central areas of the spinal cord at 3 days and complete necrosis at 7 days after treatment at 43.8 degrees C for 60 min.

Primary non-Hodgkin's lymphoma (NHL) of the central nervous system is a rare disease. The number of cases reported in the literature does not exceed 200. The current series comprises 15 cases of primary NHL of the CNS. In 12 cases material for pathology was obtained at surgery. In the other three cases the diagnosis was established by cytologic examination of the cerebrospinal fluid (CSF). The type of lymphoma was predominantly the diffuse lymphocytic type. All the patients received irradiation on the whole brain by means of two opposite lateral fields. The administered total doses were 40 Gy in four weeks in ten cases, 50 to 60 Gy in 5 to 6 weeks in four cases and 30 Gy in three weeks in one case. All but three patients are dead although initially a good tumor response was obtained as confirmed in most of the cases by CT scan. The mean survival of the dead patients was 14.5 months. No relationship was found between the administered dose and the relapse-free time. In six cases (40%) evidence of seeding was observed. Because of the poor results obtained with irradiation either of only the tumor bearing area or whole brain and because of the high risk of seeding through the CSF, the irradiation of the entire CNS is recommended in patients with primary NHL of the brain.

Effects of different fractionation schedules of irradiation were studied in an experimental mammary adenocarcinoma transplanted in the back of mice. The number of fractions per day varied from one to three, keeping the daily dose constant. It was found that an increase of the number of fractions per day did not necessarily lead to a decrease in the tumour response, as might be expected for the same total dose. At a twelve-day overall time, three fractions per day did not give such a good result as one fraction per day, but at a nineteen-day overall time three fractions per day were about as good as one fraction per day; and below 45 Gy total dose, the result with three fractions per day even seemed to be better. The effects of actinomycin D administered during the irradiation treatment show that schedules with three fractions per day possibly take better advantage of repair of sublethal and potentially lethal damage than schedules with one fraction per day. Administration of misonidazole during the irradiation treatment led to a dose-modifying effect of 1.2 in one fraction per day schedules but had no significant effect in three fractions per day schedules. The present results may provide guidelines for clinical application of irradiation schedules with more than one fraction per day.