Cerebrospinal Fluid Parameters in Antisense Oligonucleotide-Treated Adult 5q-Spinal Muscular Atrophy Patients

Abstract

Approval of nusinersen, an intrathecally administered antisense oligonucleotide, for the treatment of 5q-spinal muscular atrophy (SMA) marked the beginning of a new therapeutic era in neurological diseases. Changes in routine cerebrospinal fluid (CSF) parameters under nusinersen have only recently been described in adult SMA patients. We aimed to explore these findings in a real-world setting and to identify clinical and procedure-associated features that might impact CSF parameters. Routinely collected CSF parameters (leukocyte count, lactate, total protein, CSF/serum albumin quotient (QAlbumin), oligoclonal bands) of 28 adult SMA patients were examined for up to 22 months of nusinersen treatment. Total protein and QAlbumin values significantly increased in the first 10 months, independent of the administration procedure. By month 14, no further increases were detected. Two patients developed transient pleocytosis. In two cases, positive oligoclonal bands were found in the beginning and in four patients throughout the whole observation period. No clinical signs of inflammatory central nervous system disease were apparent. Our data confirm elevated CSF total protein and QAlbumin during nusinersen treatment. These alterations may be caused by both repeated lumbar punctures and the interval between procedures rather than by the medication itself. Generally, there were no severe alterations of CSF routine parameters. These results further underline the safety of nusinersen therapy.

Increased Chitotriosidase1 Concentration Following Nusinersen Treatment in Spinal Muscular Atrophy

“…We therefore hypothesize that CHIT1 dynamics under nusinersen treatment may occur as a response of nusinersen-exposed circulating monocytes in the CSF. In addition, we found a mild increase of Qalb and total protein during therapy ( tting to (32,33,49)), which underline the occurrence of a low unspeci c in ammatory reaction following treatment initiation.…”

“…Motor neurons were colocalized with an increased number of microglial cells in SMA mice which indicates a certain degree of neuroin ammation (31). Increased risk of hydrocephalus in untreated SMA patients and a marginal but signi cant increase of the serum / CSF albumin ratio (Qalb) with rare cases of communicating hydrocephalus during treatment with the ASO nusinersen were reported (32)(33)(34)(35).…”

Increased chitotriosidase 1 concentration following nusinersen treatment in spinal muscular atrophy

“…We therefore hypothesize that CHIT1 dynamics under nusinersen treatment may occur as a response of nusinersen-exposed circulating monocytes in the CSF. In addition, we found a mild increase of Qalb and total protein during therapy (fitting to [32,33,49]), which underline the occurrence of a low unspecific inflammatory reaction following treatment initiation.…”

“…Motor neurons were colocalized with an increased number of microglial cells in SMA mice which indicates a certain degree of neuroinflammation [31]. Increased risk of hydrocephalus in untreated SMA patients and a marginal but significant increase of the serum/CSF albumin ratio (Qalb) with rare cases of communicating hydrocephalus during treatment with the ASO nusinersen were reported [32][33][34][35].…”

CSF Diagnostics: A Potentially Valuable Tool in Neurodegenerative and Inflammatory Disorders Involving Motor Neurons: A Review

“…Both values are measures of an intact blood–CSF barrier [ 133 ]. Both parameters were found to be increased in several studies in patients with SMA type 2, 3, or 4 at until up to 10 months of treatment compared to baseline values [ 134 , 135 , 136 ]. Total protein levels in CSF were not increased in SMA patients compared to healthy controls and changes in total protein levels during the time of observation did not correlate with changes in HFMSE score, which is a common criterion for motor function in SMA patients [ 134 ].…”