Early changes on electroencephalography in natalizumab-associated progressive multifocal leucoencephalopathy

Abstract

Progressive multifocal leucoencephalopathy has become a growing concern in natalizumab-treated multiple sclerosis patients. Here, we describe a 35-year-old patient who was treated with 34 infusions of natalizumab before complaining about visual deterioration. MRI was non-diagnostic and JC virus testing initially was negative. Electroencephalography showed severe slowing of the right hemisphere, and neuropsychological testing revealed right frontal and temporal deficits. The diagnosis of progressive multifocal leucoencephalopathy was established 2 months later by typical MRI presentation and detection of JC virus DNA in the cerebrospinal fluid. Functional neurological deficits may precede imaging features and should prompt early consideration of progressive multifocal leucoencephalopathy.

Drug-associated progressive multifocal leukoencephalopathy: a clinical, radiological, and cerebrospinal fluid analysis of 326 cases

“…Because of the frequently grim prognosis and lethal outcomes, it is of paramount importance to consider the diagnosis of medication-associated PML at an early stage during treatment with immunosuppressive drugs. The clinical phenotype in the articles reviewed, however, was not seldom initially misinterpreted as an exacerbation or the cerebral manifestations of the underlying disease, i.e., an MS relapse, neuropsychiatric lupus, or central nervous system vasculitis [ 23 , 28 , 50 , 67 , 78 , 101 , 103 , 117 , 122 , 149 , 158 , 185 , 201 , 213 , 223 , 224 , 226 , 233 , 235 , 236 ]. It was only after further clinical and radiological worsening upon high doses of immunosuppressive therapies that the possibility of PML was considered in these cases.…”

Efficacy and Side Effects of Natalizumab Therapy in Patients with Multiple Sclerosis

“…Interictal EEG recording demonstrated focal slowing in seven and epileptic discharges in two of the eight patients 65. EEG changes in terms of focal slowing were described in one patient prior to MRI and CSF alterations 66. We also demonstrated the temporal association of seizures with immune reconstitution inflammatory syndrome (IRIS, which will be discussed subsequently) 65.…”

“…65 EEG changes in terms of focal slowing were described in one patient prior to MRI and CSF alterations. 66 We also demonstrated the temporal association of seizures with immune reconstitution inflammatory syndrome (IRIS, which will be discussed subsequently). 65 This led to the conclusion that more frequent occurrence of seizures in Nat-PML than in non-Nat-PML patients might be due to the more frequent and severe IRIS in Nat-PML patients.…”

Prophylactic antiepileptic treatment reduces seizure frequency in natalizumab-associated progressive multifocal leukoencephalopathy

“…Little is known about seizure frequency, clinical presentation and treatment in NAT-PML [Kleiter et al 2010]. In non-NAT-PML, seizures occur in 18% of the cases [Lima et al 2006], whilst Clifford and colleagues, focusing on the general clinical description of NAT-PML, reported seizures in 36% (10/28) of NAT-PML cases [Clifford et al 2010].…”