The chemotherapy long-term effect on cognitive functions and brain metabolism in lymphoma patients.

AIM: A growing number of neuropsychological studies reported that chemotherapy may impair brain functions, inducing persistent cognitive changes in a subset of cancer survivors. The aim of this paper was to investigate the neural basis of the chemotherapy induced neurobehavioral changes by means of metabolic imaging and neuropsychological testing. METHODS: We studied the resting brain [¹8F]FDG-PET/CT images of 50 adult cancer patients with diagnosis of lymphoma: 18 patients were studied prior and 32 after to chemotherapy. All patients underwent to a neuropsychological examination assessing cognitive impairment (tests for shifting attention, verbal memory, phonemic fluency), depression, anxiety and distress. RESULTS: Compared to no chemotherapy patients, the treated group showed significant bilateral lower rate of glucose metabolism in prefrontal cortices, cerebellum, medial cortices and limbic brain areas. The metabolism of these regions negatively correlated with number of cycles and positively with post-chemotherapy time. The treated group showed a poorer performance in many frontal functions, but similar level of depression, anxiety and distress. CONCLUSIONS: Chemotherapy induced significant long-term changes in metabolism of multiple regions with a prevailing involvement of the prefrontal cortex. The observed cognitive dysfunctions could be explained by these changes. The recovery from chemotherapy is probably affected by treatment duration and by the time elapsed after its end. We speculated that the mechanism could be an accelerating ageing / oxidative stress that, in some patients at risk, could result in an early and persistent cognitive impairment.

Persistence of sialodacryoadenitis virus in athymic rats.

To determine whether SDAV infection persists in athymic rats, weanling athymic rats and euthymic rats were inoculated intranasally with 10(4) TCID50 of SDAV and examined periodically for up to 90 days. Viral antigen and lesions characteristic of acute SDAV infection, including rhinotracheitis, bronchitis and sialodacryoadenitis, were detected in both groups of rats during the first week. In euthymic rats, tissues were under repair and viral antigen was undetectable by day 17, and tissues were histologically normal by day 31 except for mild focal dacryoadenitis. In athymic rats, viral antigen and chronic active inflammation of respiratory tract, salivary and lacrimal glands persisted through day 90. Inflammation and viral antigen also were observed in the transitional epithelium of the renal pelvis and urinary bladder as late as day 90. Virus was isolated from nasopharynx, lung, salivary gland and Harderian gland of athymic rats through day 90. All euthymic rats seroconverted to SDAV by day 6, whereas all athymic rats remained seronegative through day 31, and two of six were seropositive by day 90. As judged by seroconversion of contact sentinels, six of six athymic rats shed virus through 6 weeks, and five of six through 10 weeks. These results indicate that SDAV persists in athymic rats, and that normal T cell function is required for host defenses against SDAV.

Persistence of rat parvovirus in athymic rats.

Euthymic (SD or outbred rnu/+) and athymic (rnu/rnu) rats were inoculated oronasally or intraperitoneally with the RV-Y strain of rat virus when they were 2 days or 4 weeks old. Clinical signs of infection in athymic infants were similar to those in euthymic infants, but significantly more athymic infants died. Some infants developed anemia and thrombocytopenia. After inoculation of infants. RV-Y was detected in surviving euthymic rats for 7 weeks and in surviving athymic rats for at least 10 weeks. After oronasal inoculation of 4 week-old rats no clinical illness was observed. RV-Y persisted less than 6 weeks in juvenile euthymic rats but at least 12 weeks in athymic juvenile rats. Intraperitoneal inoculation of juveniles resulted in infection for at least 6 weeks. The antibody response of athymic rats to RV-Y was significantly reduced compared to that of euthymic rats. These studies indicate that T cell deficiency increases the severity and duration of RV infection and imply that T cells are required for the full expression of resistance to RV infection. They also suggest that RV-Y induced anemia could serve as a model for human parvovirus-induced anemia.

Persistence of rat virus in seropositive rats as detected by explant culture. Brief report.

Rat virus (RV) was detected by explant culture for up to 14 weeks in rats inoculated as infants and for up to 7 weeks in rats inoculated as juveniles, although both groups were seropositive by 3 weeks post-inoculation.