Abstract Body

Patients affected by hematological disorders, and especially hematopoietic stem cell transplant recipients, have a lifelong risk of developing neurological complications. Despite their low incidence, neurological complications are associated with high morbidity, and early diagnosis and treatment are essential to reduce the risk of permanent sequelae. Among neurological complications, acute encephalitis is one of the most fearful due to its high short-term mortality. Diagnosing this condition can be challenging in patients with hematological disorders, as they are exposed to uncommon pathogens, they can have atypical clinical presentations or lack inflammatory findings in the CSF. Whereas clear recommendations exist for immunocompetent patients, indications for patients with hematological disorders are necessarily loose due to the complexity of this clinical setting, and physicians must heavily rely on their personal expertise to guide diagnostic testing and result interpretation. Hence, a high risk of misdiagnosis exists even in Centers with a longstanding experience in this field. A number of viruses can induce life threatening encephalitis in these patients. We report here our recent experience about the following topics: a diagnostic work-up performed at our Center in a cohort of patients affected by hematological disorders presenting with a suspicion of acute viral encephalitis, a retrospective analysis of clinical, biological features of suspected encephalitis due to HHV6 (Fig 1-2, Neurol Neuroimmunol Neuroinflammation. 2021), a brief report of specific T-cell treatment against non-HIV Progressive Multifocal Leukoencephalopathy mainly induced by biological therapy for various autoimmune diseases (Fig 3, Ann Neurol. 2021).

Abstract Body

Progressive multifocal leukoencephalopathy (PML) is a rare demyelinating disease caused by the polyomavirus JC (JCV), which affects persons with an impaired immune system, such as in HIV infection, congenital immunodeficiencies or during immunosuppressive or immunomodulant therapies. Currently, there is no effective antiviral treatment for PML and its remission can only be achieved by reversing immune suppression, e.g., by starting antiretroviral treatment in patients with HIV-associated PML or by withdrawing immunosuppressive drugs in other conditions. Additional approaches to increase host responses have included the administration of interleukin-7 (IL-7), programmed cell death protein-1 (PD1) blockers and JCV or BK virus (BKV)-specific T-cells.

IL-7 is a homeostatic cytokine that increases proliferation and functional responses of naïve and memory T-cells. The administration of recombinant human IL-7 has been associated with increased T-cell number and function and PML remission in a few patients with CD4+ cell lymphopenia. PD-1 acts as a negative regulator of immune responses and its engagement leads to loss of T-cell functions and, indeed, PD-1 expression is upregulated in CD4+ and CD8+ cells in PML. PD-1 blockade by administration of either nivolumab or pembrolizumab has also been associated with a survival benefit in some PML cases. Another promising strategy is the adoptive transfer of virus-specific T-cells that are generated from related or unrelated donors, or available as ‘off-the-shelf’ products. Infusion of BKV or JCV-specific T-cells has also been shown to enhance JCV-specific immune responses in association with PML remission.

In summary, immune therapeutical interventions for PML are feasible and the observations from small patient series my provide the background for designing larger controlled studies.

Abstract Body

Viral infections of the spinal cord are associated with inflammatory changes preferentially affecting the grey matter (poliomyelitis), the white matter (leukomyelitis), nerve roots and spinal cord (radiculomyelitis), or inducing extensive damage of the grey and white matter. Common pathogens include DNA and RNA neurotropic viruses such as herpesviruses, enteroviruses, flaviviruses and retroviruses. Clinical features vary according to host-specific factors, time course and progression of symptoms, spinal cord syndrome, site and area of spinal cord pathology. Spinal cord and brain MRI, CSF examination, serologic and PCR testing, and electrophysiological investigations are of great help in providing diagnostic clues or confirmation.

Enteroviruses EV-D68 and EV-A71 have recently emerged as the agents likely responsible for clusters of acute flaccid myelitis, a disabling polio-like condition affecting children, characterized by longitudinally extensive involvement of of the gray matter of the spinal cord.

Viral myelitis is a major cause of disability and death and a prompt recognition of distinct spinal cord syndromes and related pathogens is required in the clinical setting.