Background There is insufficient knowledge about how aerobic exercise impacts the disease process of multiple sclerosis, which is characterized by accumulation of white matter lesions and accelerated brain atrophy. Objective To examine the effect of aerobic exercise on neuroinflammation and neurodegeneration by magnetic resonance imaging and clinical measures of disease activity and progression in persons with multiple sclerosis. Patients and methods An exploratory 12-week randomized control trial including an intervention group ( n = 14, 12 weeks of aerobic exercise twice weekly) and a control group ( n = 14, continuation of usual lifestyle). Primary outcomes were magnetic resonance imaging measures (lesion load, brain structure volume change), while secondary outcomes included disability measures, blood cytokine levels, cognitive tests and patient-reported outcomes. Results The effects of aerobic exercise on whole brain and grey matter atrophy were minor. Surprisingly, the observed effect on volume (atrophy) in selected brain substructures was heterogeneous. Putaminal and posterior cingulate volumes decreased, parahippocampal gyrus volume increased, thalamus and amygdala volume remained the same, and active lesion load and count decreased. However, apart from weak improvements in walking speed and brain-derived neurotrophic factor levels, there was no effect of aerobic exercise on other clinical, cognitive or patient-reported outcomes. Conclusion These results suggest that aerobic exercise in persons with multiple sclerosis has a positive effect on the volume of some of the substructures of the brain, possibly indicating a slowing of the neurodegenerative process in these regions, but a negative impact on the volume of some other substructures, with unclear implications. Further research is needed to determine whether the slight decrease in active lesion volume and count implies an anti- inflammatory effect of aerobic exercise, and the exact significance of the heterogeneous results of volumetric assessments. LAY ABSTRACT The aim of this study was to evaluate the effects of aerobic exercise (physical exercise in the form of aerobics) on people with multiple sclerosis who were being treated with fingolimod. Two groups of patients with multiple sclerosis were studied: an intervention group ( n = 14) who undertook 12 weeks of exercise training, and a control group ( n = 14) who continued with their usual lifestyle. Magnetic resonance imaging, bloodwork analysis and some other clinical assessments were performed before and after the 12-week period, and the patients completed several questionnaires about their wellbeing and accompanying symptoms of multiple sclerosis. The results suggest that aerobic exercise (combined with appropriate phar...

BackgroundToxoplasmosis is an opportunistic protozoal infection that has, until now, probably been an underestimated cause of encephalitis in patients with hematological malignancies, independent of stem cell or bone marrow transplant. T and B cell depleting regimens are probably an important risk factor for reactivation of a latent toxoplasma infection in these patients.Case reportWe describe a 62-year-old HIV-negative right-handed Caucasian female with systemic diffuse large B cell lymphoma who presented with sudden onset of high fever, headache, altered mental status, ataxia and findings of pancytopenia, a few days after receiving her final, 8th cycle of rituximab, cyclophosphamide, vincristine, doxorubicin, prednisolone (R-CHOP) chemotherapy regimen. A progression of lymphoma to the central nervous system was suspected. MRI of the head revealed multiple on T2 and fluid attenuated inversion recovery (FLAIR) hyperintense parenchymal lesions with mild surrounding edema, located in both cerebral and cerebellar hemispheres that demonstrated moderate gadolinium enhancement. The polymerase chain reaction on cerebrospinal fluid (CSF PCR) was positive for Toxoplasma gondii. The patient was diagnosed with toxoplasmic encephalitis and successfully treated with sulfadiazine, pyrimethamine and folic acid. Due to the need for maintenance therapy with rituximab for lymphoma remission, the patient now continues with secondary prophylaxis of toxoplasmosis.ConclusionsWith this case report, we wish to emphasize the need to consider cerebral toxoplasmosis in patients with hematological malignancies on immunosuppressive therapy when presenting with new neurologic deficits. In such patients, there are numerous differential diagnoses for cerebral toxoplasmosis, and the CNS lymphoma is the most difficult among all to distinguish it from. If left untreated, cerebral toxoplasmosis has a high mortality rate; therefore early recognition and treatment are of essential importance.

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Disclosure: No potential conflicts of interest were disclosed.Background. Toxoplasmosis is an opportunistic protozoal infection that has, until now, probably been an underestimated cause of encephalitis in patients with hematological malignancies, independent of stem cell or bone marrow transplant. T and B cell depleting regimens are probably an important risk factor for reactivation of a latent toxoplasma infection in these patients.Case report. We describe a 62-year-old HIV-negative right-handed Caucasian female with systemic diffuse large B cell lymphoma who presented with sudden onset of high fever, headache, altered mental status, ataxia and findings of pancytopenia, a few days after receiving her final, 8 th cycle of rituximab, cyclophosphamide, vincristine, doxorubicin, prednisolone (R-CHOP) chemotherapy regimen. A progression of lymphoma to the central nervous system was suspected. MRI of the head revealed multiple on T2 and fluid attenuated inversion recovery (FLAIR) hyperintense parenchymal lesions with mild surrounding edema, located in both cerebral and cerebellar hemispheres that demonstrated moderate gadolinium enhancement. The polymerase chain reaction on cerebrospinal fluid (CSF PCR) was positive for Toxoplasma gondii. The patient was diagnosed with toxoplasmic encephalitis and successfully treated with sulfadiazine, pyrimethamine and folic acid. Due to the need for maintenance therapy with rituximab for lymphoma remission, the patient now continues with secondary prophylaxis of toxoplasmosis.Conclusions. With this case report, we wish to emphasize the need to consider cerebral toxoplasmosis in patients with hematological malignancies on immunosuppressive therapy when presenting with new neurologic deficits. In such patients, there are numerous differential diagnoses for cerebral toxoplasmosis, and the CNS lymphoma is the most difficult among all to distinguish it from. If left untreated, cerebral toxoplasmosis has a high mortality rate; therefore early recognition and treatment are of essential importance.

The most accurate diagnosis of clinically suspected progressive multifocal leukoencephalopathy (PML) is made by neuronavigated needle brain biopsy and microscopic examination of the specimen confirming typical morphological features of the disease and, additionally, using immunohistochemistry (IHC) for detection of early viral proteins of the etiologic agent - polyoma virus JC (JCV). Due to the small biopsy volume, this approach can sometimes fail to confirm the clinical diagnosis of PML, as demonstrated by the presented clinical case. To check the reliability of using only IHC, we additionally tested 6 archival cases from our institute using IHC, in-situ hybridization (ISH) and real-time polymerase chain reaction (PCR). In the presented case, both biopsy and autopsy material were tested, in three archival cases only biopsy material and in the remaining cases post-mortem brain tissue was available. IHC (Anti-SV40 T antigen, mAb Pab416) was negative in 3 samples, in another 3 fewer than 10 cells per one ×20 microscopic field were positive. In our study, ISH proved to be a more sensitive method for JCV detection than IHC, being positive in all cases. Out of 7 tested specimens, realtime PCR failed to confirm the presence of JCV in 1 specimen, which was the oldest brain autopsy of an AIDS patient. Our study demonstrated that, especially when confronted with borderline clinical suspicion of PML and when only a small biopsy specimen is available, a combination of at least two different methods for JCV detection should be considered, preferably IHC with one of the available molecular methods.