Natalizumab-associated PML identified in the presymptomatic phase using MRI surveillance

Blair, Nicholas F.; Brew, Bruce J.; Halpern, Jean-Pierre

doi:10.1212/wnl.0b013e318246d6d8

Cited by 54 publications

(40 citation statements)

References 4 publications

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“…The utility of routine MRI for monitoring natalizumab-treated patients has been highlighted in several recent case reports and case series 15,17–25. In some reports, patients were diagnosed with PML in the absence of clinical symptoms when radiologic signs of PML were detected on routine MRI and confirmed by JCV DNA detection in the CSF by polymerase chain reaction 17,18,21,23,24. In others, MRI findings consistent with PML were retrospectively identified on MRI scans obtained several months before clinical symptoms of PML were apparent 19,20,25…”

Section: Introductionmentioning

confidence: 99%

Outcome and survival of asymptomatic PML in natalizumab‐treated MS patients

Dong‐Si

Richman

Wattjes

et al. 2014

Ann Clin Transl Neurol

117

104

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ObjectiveAs of 3 September 2013, 399 cases of natalizumab-associated progressive multifocal leukoencephalopathy (PML) were confirmed in multiple sclerosis (MS) patients. We evaluated outcomes of natalizumab-treated MS patients who were asymptomatic at PML diagnosis.MethodsAnalyses included data available as of 5 June 2013. Asymptomatic patients diagnosed with PML by magnetic resonance imaging (MRI) findings and JC virus DNA detection in the central nervous system were compared with patients presenting with symptoms at diagnosis. Demographics, MRI, and survival over 12 months were analyzed. Expanded Disability Status Scale (EDSS) and Karnofsky Performance Scale (KPS) scores were recorded pre-PML, at diagnosis, and at 6 and 12 months post-diagnosis.ResultsA total of 372 PML cases were analyzed; 30 patients were asymptomatic and 342 were symptomatic at PML diagnosis. Classifications of PML lesions on MRI in asymptomatic versus symptomatic patients were unilobar in 68% versus 37%, multilobar in 21% versus 24%, and widespread in 11% versus 40%. In both groups with unilobar lesions, frontal lobe lesions predominated. Prior to PML, mean EDSS and KPS scores were similar for asymptomatic and symptomatic patients. At diagnosis, mean EDSS score was significantly lower for asymptomatic patients (4.1; n = 11) than for symptomatic patients (5.4; n = 193; P = 0.038). Six months after PML diagnosis, asymptomatic patients had less functional disability than symptomatic patients. As of 5 June 2013, 96.7% of asymptomatic patients and 75.4% of symptomatic patients were alive.InterpretationPML patients asymptomatic at diagnosis had better survival and less functional disability than those who were symptomatic at diagnosis.

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Section: Introductionmentioning

confidence: 99%

Outcome and survival of asymptomatic PML in natalizumab‐treated MS patients

Dong‐Si

Richman

Wattjes

et al. 2014

Ann Clin Transl Neurol

117

104

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“…Although there was only a mild change in patient’s neurological status, MRI scan was suspicious for PML. The repeated PCR for JCV at different time intervals as well as the clinical improvement of the patient’s clinical status excludes the diagnosis of PML with low JCV DNA copies [7]. …”

Section: Discussionmentioning

confidence: 99%

“…However, clinical vigilance of patients under prolonged NTM is necessary to access any change in neurological status since in the presymptomatic phase of PML, the presentation may be atypical [7]. A follow-up from the same neurologists might permit the evaluation of even slight changes of patient’s clinical status, suspicious of PML.…”

Section: Discussionmentioning

confidence: 99%

Immune Reconstitution Inflammatory Syndrome Mimicking Progressive Multifocal Leucoencephalopathy in a Multiple Sclerosis Patient Treated With Natalizumab: A Case Report and Review of the Literature

et al. 2015

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Natalizumab (NTM) represents an effective drug for the treatment of relapsing-remitting multiple sclerosis (RRMS). Progressive multifocal leucoencephalopathy (PML) is a potential life-threatening complication of NTM treatment. A close follow-up and MRI monitoring of patients under NTM are required to avoid such devastating complications. The case of a 47-year-old woman with RRMS (EDSS 1.5) treated with NTM for 44 months is reported. The patient had a relapse with mild cerebellar symptomatology and visual complaints. MRI revealed a new area of abnormal signal intensity in the subcortical white matter of the right parietal lobe with mild peripheral enhancement. Visual fields showed scotomata mostly of the left eye. NTM was discontinued. JC virus (JCV) polymerase chain reaction (PCR) in cerebrospinal fluid was negative. The patient received IV corticosteroids for 5 days and then monthly for 2 months with subsequent clinical and MRI improvement. On month 4, she presented with a new relapse with severe ataxia, mild behavioral change, increase of cerebellar symptoms and internuclear opthalmoplegia (EDSS 3.5). MRI showed reappearance of the right parietal lobe lesion, with decreased size and less pronounced contrast enhancement. A new 2-cm lesion was noted in the left cerebellar hemisphere with a speckled pattern of contrast enhancement. JCV PCR was negative and the patient was treated with IV corticosteroids. On month 12, she demonstrated clinical and MRI improvement. Although initially PML was highly suspected in this patient, the clinical and MRI findings were supportive of the presence of immune reconstitution inflammatory syndrome (IRIS).

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“…unilobar vs. multilobar or widespread lesions) [44]. Recently, several cases have been reported in which PML has been detected by MRI in asymptomatic patients [45,46]. In a study of patients with natalizumab-associated PML, 7% (21/298) were asymptomatic at the time of diagnosis [14].…”

Section: Benefits Of Early Pml Detection and Treatmentmentioning

confidence: 99%

Natalizumab treatment for multiple sclerosis: Middle East and North Africa regional recommendations for patient selection and monitoring

Alroughani¹,

Aref²,

Bohlega³

et al. 2014

Multiple Sclerosis and Related Disorders

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Background: Natalizumab, a highly specific α4-integrin antagonist, , has recently been registered across the Middle East and North Africa region. It improves clinical and magnetic resonance imaging (MRI) outcomes and reduces the rate of relapse and disability progression in relapsing-remitting multiple sclerosis (MS). Natalizumab is recommended for patients who fail first-line disease-modifying therapy or who have very active disease. Progressive multifocal leukoencephalopathy is a rare, serious adverse event associated with natalizumab. We aim to develop regional recommendations for the selection and monitoring of MS patients to be treated with natalizumab in order to guide local neurological societies. Methods: After a review of available literature, a group of neurologists with expertise in the management of MS met to discuss the evidence and develop regional recommendations to guide appropriate use of natalizumab in the region. Results: Disease breakthrough is defined as either clinical (relapse or disability progression) or radiological activity (new T2 lesion or gadolinium-enhancing lesions on MRI), or a combination of both. Natalizumab is recommended as an escalation therapy in patients with breakthrough disease based on its established efficacy in Phase III studies. Several factors including prior immunosuppressant therapy, anti-John Cunningham virus (JCV) antibody status and patient choice will affect the selection of natalizumab. In highly active MS, natalizumab is considered as a first-line therapy for naive patients with disabling relapses in association with MRI activity. The anti-JCV antibody test is used to assess anti-JCV antibody status and identify the risk of PML. While seronegative patients should continue treatment with natalizumab, anti-JCV antibody testing every 6 months and annual MRI scans are recommended as part of patient monitoring. In seropositive patients, the expected benefits of natalizumab treatment have to be weighed against the risks of PML. Clinical vigilance and follow-up MRI scans remain the cornerstone of monitoring. After 2 years of natalizumab therapy, monitoring should include more frequent MRI scans (every 3-4 months) for seropositive patients, and the risk-benefit ratio should be reassessed and discussed with patients. Conclusions: Recommendations have been developed to guide neurologists in the Middle East and North Africa on patient selection for natalizumab treatment and monitoring.

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Natalizumab-associated PML identified in the presymptomatic phase using MRI surveillance

Cited by 54 publications

References 4 publications

Outcome and survival of asymptomatic PML in natalizumab‐treated MS patients

Outcome and survival of asymptomatic PML in natalizumab‐treated MS patients

Immune Reconstitution Inflammatory Syndrome Mimicking Progressive Multifocal Leucoencephalopathy in a Multiple Sclerosis Patient Treated With Natalizumab: A Case Report and Review of the Literature

Natalizumab treatment for multiple sclerosis: Middle East and North Africa regional recommendations for patient selection and monitoring

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