Epub: Dahlhaus et al. Disease course and outcome of 15 monocentrically treated natalizumab-associated progressive multifocal leukoencephalopathy patients. J Neurol Neurosurg Psychiatry. 2013 Apr.
OBJECTIVE: Although the prognosis of natalizumab-associated progressive multifocal leukoencephalopathy (PML) seems to be better than HIV-associated PML, little is known about the long-term functional outcome in multiple sclerosis (MS) patients and the subsequent return of MS disease activity. We evaluated retrospectively 15 patients with natalizumab-associated PML treated at our centre.
PATIENTS AND METHODS: Fifteen MS-PML patients (nine women, six men) were referred to us from adjacent local centres. The patients had a median (middle item) natalizumab exposure of 34 months at PML diagnosis. They received standardised treatment as described in previous work. Expanded Disability Status Scale (EDSS) and Karnofsky score in the year pre-PML, at PML-diagnosis (pre-immune reconstitution inflammatory syndrome (IRIS)) and post-PML were determined in 3-6 monthly intervals.
RESULTS: The median follow-up of these 15 patients was 21.5 months. None of the 15 patients died. Three patients had a Karnofsky score of 80 or higher, nine patients between 50-70 and three patients of 40 or lower at latest examination. Eight of the 15 patients developed seizures (fit) during acute PML phase. Fifty percent of those patients were not seizure-free one year post PML, despite continuation of anti-epileptic treatment. The median EDSS in the year pre-PML was 2.5, 4.5 at PML diagnosis, 6.5 post-IRIS and 5.5 at latest examination. CSF became virus-free in eight of the 15 patients after a median time of 4.5 months. In nine patients, disease reappeared after a median time of seven months from PML diagnosis.
CONCLUSIONS: Although the clinical outcome of natalizumab-treated PML patients is much better than in patients with HIV-associated PML, this may be further improved by treatment at reference centres using standardised therapy regimens and transient intensive care if needed. Systematic studies of appropriate MS immunotherapies after PML are critically needed.
The Karnofsky score runs from 100 to 0, where 100 is "perfect" health and 0 is death. The initialpurpose of its development was to allow doctors to evaluate the ability of the pateint to survive chemotherapy for cancer.
100% – normal, no complaints, no signs of disease
90% – capable of normal activity, few symptoms or signs of disease
80% – normal activity with some difficulty, some symptoms or signs
70% – caring for self, not capable of normal activity or work
60% – requiring some help, can take care of most personal requirements
50% – requires help often, requires frequent medical care
40% – disabled, requires special care and help
30% – severely disabled, hospital admission indicated but no risk of death
20% – very ill, urgently requiring admission, requires supportive measures or treatment
10% – moribund, rapidly progressive fatal disease processes
0% – death.
In this case it was used to score for the effect of PML. As we have reported previously currently JC virus, which causes PML is currently untreatable and the development of PML has a death rate of about 20-25%. In the survivors there is damage due to the PML and also when Tysabri therapy is stopped anti-viral cells invade the CNS and destroy the infected oligodendrocytes this is called the "immune reconstitution inflammatory syndrome or IRIS". The surviving MSers in this study were much more disabled after PML had occurred. We really need to find a way to stop this problem.