Kortikosteroidi (KS) se že desetletja uspešno uporabljajo za zmanjševanje obtumorskega edema pri bolnikih z možganskimi tumorji, tako primarnimi kot metastatskimi. Kljub dolgi uporabi niso povsem ...znani mehanizmi njihovega delovanja v smislu na biološko in klinično učinkovitost. Deksametazon je najbolj uporabljen KS v nevroonkologiji zaradi njegovih ugodnih farmakokinetičnih, farmakodinamičnih in drugih lastnosti. Zaradi številnih možnih neželenih učinkov KS, ki lahko močno okrnijo kakovost bolnikovega življenja, uporabljamo čim nižje še učinkovite odmerke čim krajši možni čas. Številna nova tarčna zdravila za zdravljenje raka, ki zavirajo poti v procesu angiogeneze, izkazujejo učinkovitost tudi v zmanjšanju obtumorskega edema pri bolnikih z možganskimi tumorji.
Neželeni učinki radioterapije na možgane so številni in pogosto nepredvidljivi. Lahko gre za neposredno ali posredno okvaro možganov. Okvara se lahko pojavi akutno ali več tednov, mesecev ali celo ...let po končani radioterapiji. Ločevanje med temi oblikami je pomembno, saj so zgodnji zapleti navadno reverzibilni, pozni pa se večinoma ne popravijo. Incidenco neželenih učinkov radioterapije na možgane je težko oceniti. Razlogi za to so v različnih opredelitvah in metodoloških razlikah v raziskavah ter v klinični sliki, ki se pogosto prekriva z napredovanjem osnovne maligne bolezni. Med mehanizmi radiacijske okvare možganov je v ospredju okvara celic glije in možganskih endotelijskih celic. Za radiacijsko okvaro je zlasti občutljiv hipokampus. Obseg okvare možganov je odvisen od številnih dejavnikov. Dodatna sistemska ali intratekalna kemoterapija pomembno poveča nevrotoksičnost. Diagnosticiranje neželenih učinkov radioterapije na možgane je težavno, saj je časovni interval med radioterapijo in pojavom nevroloških simptomov precej variabilen, klinična slika pa lahko posnema metastatsko, paraneoplastično ali drugo nevrološko bolezen. Zavedati se je treba, da klinično sliko lahko pripišemo neželenim učinkom radioterapije na možgane šele po izključitvi drugih vzrokov. V članku opisujeva različne klinične oblike neposredne in posredne radiacijske okvare možganov. Pri akutni encefalopatiji ima pomembno vlogo okvara krvno-možganske pregrade. Pri zgodnji odloženi encefalopatiji je pomembna demielinizacija, pri pozni odloženi encefalopatiji pa radiacijska nekroza. O kognitivnem upadu kot posledici radioterapije so mnenja še vedno deljena.
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.
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.
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.
Progresivna multifokalna levkoencefalopatija (PML) je redko in običajno smrtno demielinizacijsko obolenje možganov, ki se razvije skoraj izključno pri bolnikih z imunsko pomanjkljivostjo in je ...posledica reaktivacije latentne okužbe s polioma virusom JC. V zadnjih letih so opisani tudi primeri PML po zdravljenju z rituksimabom. Predstavljamo naš prvi potrjeni primer PML pri 55-letnem HIV-negativnem bolniku z recidivnim limfomom plaščnih celic, pri katerem smo raka uspešno zdravili s kemoterapijo in rituksimabom ter z avtologno presaditvijo perifernih krvotvornih matičnih celic (PKMC). S primerom želimo opozoriti na pomembnost PML v diferencialni diagnozi pri bolnikih z napredujočo nevrološko simptomatiko in imunsko pomanjkljivostjo po zdravljenju limfoma z rituksimabom ter pomembnost zgodnjega prepoznavanja te bolezni z dokazom JC-virusne okužbe v likvorju ali v vzorcu stereotaktične biopsije možganov.
Abstract
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, 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.
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.
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