Patient characteristics and routine CSF parameters
In total, the CSF results of 108 patients from four centers were analyzed. The patients’ mean age was 48 years, with a range from 19 to 81 years. The underlying diagnoses included multiple sclerosis treated with natalizumab (MS/NTZ, n=54), HIV infection (n=25), and hematological diseases (n=19) such as B-cell non-Hodgkin lymphoma (n=10), multiple myeloma (n=2), chronic lymphocytic leukemia (n=6), and acute myeloid leukemia (n=1) (referred to collectively as lymphoma group). Ten patients of the lymphoma group were treated with rituximab mono- or combination-therapy. Other chemotherapy regimens included bendamustine, melphalane, mitoxantrone, or methotrexate. In four of the patients an organ transplant had been performed and they received immunosuppressive therapy with tacrolimus, mycophenolate mofetil, or ciclosporin. One patient each suffered from bronchial carcinoma, sarcoidosis, microscopic polyangiitis and common variable immunodeficiency (CVID). In two cases no explanatory underlying disease was found. Detailed information about the individual patients can be found in additional file 1. Compared to the routine CSF parameters (table 1), 24/108 patients (22%) had an elevated cell count and 35/108 patients showed an elevated Qalbumin indicating a disturbed blood-CSF-barrier. The mean lactate content was 1.64 mmol/l (range: 0.99 - 2.8 mmol/l), whereby 6/108 (6%) subjects presented with increased lactate levels.
Comparison of PML cohort and control group
Routine CSF parameters of the whole PML cohort were compared with CSF results of an aged matched control group (suppl. table 2) consisting of patients with NPH (n=8) or IIH (n=13). In the case of CSF lactate, Qalbumin, and CSF protein there was no difference between the two groups. In contrast, the CSF mean cell count of the PML cohort was significantly higher compared with the control group (p< 0.001, Fig. 1).
Comparison of different PML subgroups regarding routine CSF parameters at diagnostic lumbar puncture
We then compared the PML patients with different underlying diagnoses (Fig. 2). Patients with PML together with HIV infection showed a higher cell count, CSF lactate, CSF protein, and Qalbumin level in comparison with the control group. Other PML subgroups compared among each other and compared with the control group were not significantly different from the routine CSF parameters. The HIV PML patients exhibited a higher cell count, CSF protein, Qalbumin, and CSF lactate compared to MS patients who had PML because of natalizumab treatment.
Comparison between HIV control group and HIV-PML group
To investigate whether the differences between HIV PML patients and the other subgroups regarding routine CSF parameters were caused by either the HIV infection itself or by the PML, the HIV PML patients were compared with an HIV control group without PML (suppl. table 3). While there was no significant difference concerning CSF lactate, HIV-PML patients showed a significantly higher CSF cell count (P<0.05, CSF protein (P<0.05) and Qalbumin (P<0.01) compared with the non-PML control group (Fig. 3A). MS/NTZ PML patients were also compared with a respective control group (Fig. 3B). MS control patients exhibited a significantly higher CSF cell count (P<0.001). This is most likely explained by the fact that control group patients were mostly untreated, as the lumbar puncture was performed during the diagnostic process for MS. CSF lactate concentration was also significantly higher in the control group compared with the MS/NTZ PML group (P<0.001) while there was no difference between MS/NTZ PML and control group patients regarding CSF protein or albumin quotient.
CSF cell distribution in PML patients
In 80 patients of the total cohort a differentiation of cell distribution was performed during CSF analysis. Sixty-seven patients (79%) showed a lymphocytic predominance while in 10 patients (12%) the majority of cells was monocytic. Six patients (7%) exhibited a mixed cell distribution and only two patients (2%) demonstrated mainly granulocytes within the CSF. The latter is best explained by blood contamination. Considering the individual subgroups, patients of the MS/NTZ-, the HIV-, the lymphoma-, and the transplant-group all showed a lymphocytic predominance (table 2) as did all the control groups. Some of the HIV patients showed a mixed cell distribution, however, all of these had blood contaminations in the lumbar puncture.
Analysis of oligoclonal bands of PML patients
At diagnostic lumbar puncture, oligoclonal bands (OCB) were analyzed in 58 patients. In 22 cases (38%) OCB type 2 (OCB in CSF only) were found, of which 18 patients belonged to the MS/NTZ group and one patient each to the HIV-, lymphoma-, and transplant-group. Nine patients (16%) exhibited OCB type 3 (identical OCB in CSF and serum and additional OCB in CSF only). The majority of patients (n=5) suffered from HIV as underlying disease, two patients had MS/NTZ and one patient each belonged to the lymphoma and transplant group. Oligoclonal bands were negative in 27 patients, with 13 patients (22%) showing type 1 OCB (no OCB) and 14 patients (24%) showing type 4 OCB (identical OCB in CSF and serum). Seven patients (26%) of the MS/NTZ group exhibited negative oligoclonal bands. This effect might be due to the natalizumab treatment which is known to modify oligoclonal bands [25, 26].