Subacute fever and torpor in a hematological patient revealing atypical CLIPPERS with supratentorial involvement: a case report

Abstract

Case report: A 62-year-old patient was transferred from another hospital with complaints of subacute torpor and fever two months after an allogeneic bone marrow transplant. He had the diagnosis of chronic myelomonocytic leukemia type 2 four years before the beginning of the neurological symptoms. The disease remained stable for two years after the diagnosis, but progressed and he was submitted to a bone marrow transplant. The complications during the procedure were a febrile neutropenia, that resolved with a cycle of antibiotics, and a reactivation of cytomegalovirus (CMV) infection (he had a high risk to reactivation due to the status of antibodies of the donator, that was negative, and he had positive antibodies). He remained stable and was discharged from the hospital 30 days after the transplant. Two months after the transplant, the fever and torpor began, and he went to the emergency department in his hometown. There, he was diagnosed with a positive coronavirus disease 2019 (COVID-19) infection and reactivation of cytomegalovirus, with prescription of endovenous ganciclovir, without clinical improvement. His clinical symptoms evolved to loss of balance and progressive torpor, and was transferred to our hospital for clinical evaluation. In the initial examination, he was febrile, torporous, he was not collaborative to the neurological examination due to the level of consciousness. He was hypotonic and had withdrawal from a painful stimulus on four limbs. His tendinous reflexes were hyperactive and symmetrical. Due to his level of consciousness, the cerebellar maneuvers were not testable. He was then submitted to orotracheal intubation due to neurological deterioration. In his complementary investigation, the serum polymerase chain reaction (PCR) for CMV was already negative and his PCR for COVID-19 was also negative. The electroencephalogram showed slow generalized periodic discharges. His computerized tomography showed no abnormalities, so he was submitted to a lumbar puncture that showed 8 cells, with 97% lymphocytes, 74 mg/dL of protein, 26 mg/dL of glucose with no neoplasic cells and a positive PCR for Toxoplasma gondii. The PCR for mycobacterium tuberculosis, cryptococcosis, and viruses were negative. After the results, we started sulfadiazine and pyrimethamine and he was submitted to a magnetic resonance imaging that showed multiple nodular foci of hypersignal in T2/FLAIR (T2-weighted-Fluid-Attenuated Inversion Recovery) and diffusion abnormalities on the cortical surface of the cerebellar hemispheres, thalamus, basal ganglia and subcortical white matter of the cerebral hemispheres, being more evident in the cerebellum and basal ganglia. Besides the atypical radiological findings for neurotoxoplasmosis, his serologic testing on the serum showed an positive immunoglobulin M and immunoglobulin G for Toxoplasma gondii. He had no clinical improvement with the antibiotics, and so, ten days after he was submitted to a new magnetic resonance imaging showing increase in the size and number of multiple small focal lesions with hypersignal on T2/FLAIR in the brain parenchyma, highlighting confluent lesions in the basal ganglia and focal lesions in the cerebellar hemispheres, which show contrast uptake, as well as in the thalamus and midbrain. His neurological symptoms evolved and he showed a minimally conscious state, with spasticity in the four limbs. He was submitted to a new lumbar puncture that showed 1 cell, 78 mg/dL of protein and 50 mg/dl of glucose, an improvement, despite clinical and radiological worsening. Because of the clinical worsening, he was submitted to a brain biopsy. His cerebral biopsy was negative for neoplasic infiltration of the cerebral nervous system, viral infections, cryptococcus and toxoplasmosis. It showed an interstitial CD3 lymphocytic inflammation with vasculitis and frequent macrophages, very rare CD20 lymphocytes and p24 and SV-40 negative. His neuropathological criteria were compatible with CLIPPERS (chronic lymphocytic inflammation with pontine perivascular enhancement responsive to steroids). The patient was submitted to five days of metilprednisolone and with oral prednisone after, with slow clinical improvement, but probably due to the lack of systemic clinical status of the patient and delayed diagnosis because of the atypical presentation, the patient died of pneumonia.