Contributions
Abstract: P1253
Type: Poster
Abstract Category: Therapy - disease modifying - Risk management for disease modifying treatments
Background: The diagnosis of natalizumab-associated progressive multifocal leukoencephalopathy (NTZ-PML) is, if not biopsy proven, based on the combination of PML lesion identification on magnetic resonance imaging (MRI), presence of clinical PML symptoms, and detection of JC virus (JCV) DNA by polymerase chain reaction (PCR) in cerebrospinal fluid (CSF). In 2013, the AAN Neuroinfectious Disease Section introduced PML diagnostic criteria proposing categories of diagnostic certainty depending on the presence or absence of these features. However, at the time of NTZ-PML suspicion, patients often lack PML symptoms due to early PML lesion detection on MRI (as recommended recently by the European Medicines Agency), and JCV DNA can be undetectable in their CSF, hampering the diagnosis of NTZ-PML.
Objective: To investigate the diagnostic performance of the AAN PML diagnostic criteria in early NTZ-PML patients.
Methods: For all patients in the Dutch-Belgian NTZ-PML cohort, data on the presence or absence of the diagnostic features were collected from the time of the first NTZ-PML diagnostic work-up. Diagnosis was based on JCV DNA detection in CSF or PML lesion evolution on MRI, including PML immune reconstitution inflammatory syndrome at later stages. The AAN PML diagnostic categories are: “definite PML” (PML lesion on MRI, PML symptoms, and positive JCV PCR), “probable PML” (PML lesion on MRI and positive JCV PCR, but no PML symptoms), “possible PML” (PML lesion on MRI and PML symptoms, but negative JCV PCR), “not PML” (PML lesion on MRI, but no PML symptoms and negative JCV PCR). Frequencies and percentages of the patients for each category are presented.
Results: Of the 28 NTZ-PML patients included, 10 patients (35.7%) met the criteria for “definite PML”, 8 patients (28.6%) met the criteria for “probable PML”, 6 patients (21.4%) met the criteria for “possible PML”, and 4 patients (14.3%) met the criteria for “not PML”, at the time of first diagnostic work-up. There were no significant differences between the categories in terms of age, gender, or natalizumab treatment duration.
Conclusion: A larger proportion of NTZ-PML patients of our cohort did not fulfil diagnostic criteria for “definite PML” or even “probable PML” at the time of first PML suspicion, which is likely the result of early PML lesion detection on MRI. Thus, the AAN PML diagnostic criteria may not be applicable to early NTZ-PML patients, and a revision of the NTZ-PML case definition may be warranted.
Disclosure: Potential conflict of interest
MTW does not report any competing interest.
CW has received consultancy or speaking fees from Novartis, Bayer, Biogen and Teva.
JK has received consultancy fees from Merck-Serono, Teva, Biogen, Genzyme and Novartis.
MPW has received consultancy fees from Biogen and Roche.
Abstract: P1253
Type: Poster
Abstract Category: Therapy - disease modifying - Risk management for disease modifying treatments
Background: The diagnosis of natalizumab-associated progressive multifocal leukoencephalopathy (NTZ-PML) is, if not biopsy proven, based on the combination of PML lesion identification on magnetic resonance imaging (MRI), presence of clinical PML symptoms, and detection of JC virus (JCV) DNA by polymerase chain reaction (PCR) in cerebrospinal fluid (CSF). In 2013, the AAN Neuroinfectious Disease Section introduced PML diagnostic criteria proposing categories of diagnostic certainty depending on the presence or absence of these features. However, at the time of NTZ-PML suspicion, patients often lack PML symptoms due to early PML lesion detection on MRI (as recommended recently by the European Medicines Agency), and JCV DNA can be undetectable in their CSF, hampering the diagnosis of NTZ-PML.
Objective: To investigate the diagnostic performance of the AAN PML diagnostic criteria in early NTZ-PML patients.
Methods: For all patients in the Dutch-Belgian NTZ-PML cohort, data on the presence or absence of the diagnostic features were collected from the time of the first NTZ-PML diagnostic work-up. Diagnosis was based on JCV DNA detection in CSF or PML lesion evolution on MRI, including PML immune reconstitution inflammatory syndrome at later stages. The AAN PML diagnostic categories are: “definite PML” (PML lesion on MRI, PML symptoms, and positive JCV PCR), “probable PML” (PML lesion on MRI and positive JCV PCR, but no PML symptoms), “possible PML” (PML lesion on MRI and PML symptoms, but negative JCV PCR), “not PML” (PML lesion on MRI, but no PML symptoms and negative JCV PCR). Frequencies and percentages of the patients for each category are presented.
Results: Of the 28 NTZ-PML patients included, 10 patients (35.7%) met the criteria for “definite PML”, 8 patients (28.6%) met the criteria for “probable PML”, 6 patients (21.4%) met the criteria for “possible PML”, and 4 patients (14.3%) met the criteria for “not PML”, at the time of first diagnostic work-up. There were no significant differences between the categories in terms of age, gender, or natalizumab treatment duration.
Conclusion: A larger proportion of NTZ-PML patients of our cohort did not fulfil diagnostic criteria for “definite PML” or even “probable PML” at the time of first PML suspicion, which is likely the result of early PML lesion detection on MRI. Thus, the AAN PML diagnostic criteria may not be applicable to early NTZ-PML patients, and a revision of the NTZ-PML case definition may be warranted.
Disclosure: Potential conflict of interest
MTW does not report any competing interest.
CW has received consultancy or speaking fees from Novartis, Bayer, Biogen and Teva.
JK has received consultancy fees from Merck-Serono, Teva, Biogen, Genzyme and Novartis.
MPW has received consultancy fees from Biogen and Roche.