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Background/objective: The use of natalizumab (NAT) in multiple sclerosis (MS) may be complicated by progressive multifocal leukoencephalopathy (PML), a rare and life-threatening opportunistic brain infection. We aimed to analyze the course of MS after PML recovery together with the long-term outcome of NAT-associated PML (NAT-PML) in Austria. Methods: Retrospective study based on identification of cases in the nationwide Austrian MS treatment registry (AMSTR) and MS centers with review of patient records. The expanded disability status scale (EDSS) was used to measure neurological disability and outcome. Results: As of December 2022, we identified 15 NAT-PML cases in Austria; only 20% occurred after 2016, when increased vigilance commenced. Two patients did not survive acute PML, and an additional patient died five years later, yielding a mortality rate of 20%. Seizures occurred exclusively in patients with pronounced EDSS increase. Gadolinium (Gd)-enhancement on brain magnetic resonance imaging (MRI) on PML suspicion was associated with minor changes of post-PML neurological disability. Long-term follow-up of up to 132 months (median 76 months) was available in 11/15. The overall median EDSS increased from 3.5 at pre-PML to 6.5 at the last assessment. Regarding inflammatory MS-related disease activity during the observation period, one single individual experienced an MS relapse and another patient had two Gd-enhancing brain lesions. Three patients converted to progressive MS within three years from PML and the EDSS further increased in 6/11. Conclusions: The number of NAT-PML cases is decreasing over time. While many patients accumulated severe persistent neurological deficits compared to pre-PML, inflammatory MS-related disease activity after PML recovery was rare. [ABSTRACT FROM AUTHOR]

This report presents the case of a 47-year-old male patient who worked as a mathematics teacher and experienced the sudden onset of disorientation, aphasia, and acalculia during an online class. The current study reveals the first documented case of HIV and progressive multifocal leukoencephalopathy with the detection of SARS-CoV-2 and human polyomavirus 2 (previously known as John Cunningham virus) in the cerebrospinal fluid. Furthermore, serum analysis revealed elevated concentrations of interleukin (IL)-6, IL-17, and IL-8, which are potential factors known to reduce the expression of tight junctions and adhesion molecules in the extracellular matrix, thereby affecting the permeability of the blood-brain barrier. Finally, the study discusses whether SARS-CoV-2 triggers or exacerbates progressive multifocal leukoencephalopathy.

Progressive multifocal leukoencephalopathy (PML) is one of the most severe opportunistic diseases of the central nervous system, which leads to multiple demyelination of brain structures, neurological symptoms and frequent death or disability of the patient. The etiological factor of this disease is Human polyomavirus 2 (JCPyV).This pathogen is widespread – antibodies are found in 80% of the world›s population. However, the clinical symptoms of this infection appear only in people with a pronounced decline in cellular immunity. Until 1980 progressive multifocal leukoencephalopathy was extremely rarely diagnosed. Now days the main cause of the clinical symptoms of PML is immunodeficiency caused by HIV infection. Clinical manifestations of PML are characterized by various non-specific neurological symptoms, similar to other lesions of the central nervous system, the symptoms progress slowly over several months, and usually lead to death. Diagnosis of PML is based on laboratory and instrumental methods, such as DNA JCPyV detection in the cerebrospinal fluid, brain biopsy, and radiation diagnostic methods. There is no effective prevention and etiotropic therapy for PML. Improved parameters of cellular immunity and antiretroviral treatment in HIV positive patients significantly increase the life expectancy of patients with PML. Despite the ability of drugs to prevent the progression of the disease, pathological changes in the brain are irreversible and lead to persistent disability of patients, therefore, it is necessary to diagnose PML in the early stages of the disease.