Routine Cerebrospinal Fluid (CSF) Parameters in Patients With Spinal Muscular Atrophy (SMA) Treated With Nusinersen.

Claudia D Wurster,Markus Otto,Hayrettin Tumani,Patrick Weydt,Michael Schocke,Jan C Koch,Zeljko Uzelac,Isabell Cordts,Tugrul Kocak,Simon Witzel,Jens Dreyhaupt,Albert C Ludolph,Paul Lingor,Marcus Deschauer,René Günther,Kurt Wollinsky,Benedikt Winter,Andreas Hermann

doi:10.3389/fneur.2019.01179

Abstract

Background: Nusinersen is an antisense-oligonucleotide (ASO) approved for treatment of 5q-spinal muscular atrophy (SMA). Since the drug cannot cross the blood-brain barrier (BBB), it must be administered into the cerebrospinal fluid (CSF) space repeatedly by lumbar puncture. However, little is known whether ASOs have an impact on CSF routine parameters that may yield information on CSF flow and/or intrathecal inflammation. The objective of this study was to examine CSF routine parameters in SMA patients treated with nusinersen.Methods: Routine CSF parameters [white cell count, total protein, CSF/serum quotients of albumin (Qalb), lactate, and oligoclonal IgG bands (OCB)] of 60 SMA patients (type 1, 2, and 3, aged 7–60 years) were retrospectively analyzed.Results: White cells ranged from 0 to 4/μL in CSF; a singular case of pleocytosis (8/μL) was observed in a patient in parallel with a systemic infection. Total protein and Qalb showed a mild increase from baseline to the following lumbar punctures (except for total protein in CSF at the fourth injection of nusinersen). Lactate levels revealed a stable course. In one patient, positive OCB in CSF were transiently observed. The slight change in total CSF protein and Qalb may be caused by repeated lumbar puncture and/or intrathecal administration of the drug.Conclusion: Our data suggest that a regular examination of routine CSF parameters in patients in which intrathecal ASOs are administered is important to obtain information on possible side effects and to gain further insights into intrathecal processes.

Highlights

Spinal muscular atrophy (SMA) is a rare neuromuscular disease caused by homozygous deletion or point mutation in the survival of motoneuron (SMN) 1 gene on chromosome 5 leading to muscle weakness and muscle atrophy [1]
cerebrospinal fluid (CSF) of 63 SMA patients was collected; CSF samples of 3 patients were excluded from analysis due to massive contamination of erythrocytes in baseline CSF (T1), analysis included CSF of 60 patients
Two samples of one patient were excluded in the following (CSF of T6 and T7) because of massive contamination of erythrocytes during lumbar puncture T6, which was performed intraoperatively during change of growing rods. Another sample of a second patient was excluded from analysis at T5 due to massive contamination of erythrocytes caused by a traumatic lumbar puncture

Summary

Introduction

Spinal muscular atrophy (SMA) is a rare neuromuscular disease caused by homozygous deletion or point mutation in the survival of motoneuron (SMN) 1 gene on chromosome 5 leading to muscle weakness and muscle atrophy [1]. Nusinersen is an antisense-oligonucleotide (ASO) approved for treatment of 5qassociated SMA [2]. Since there is limited experience in clinical practice with ASOs so far, not much is known whether ASOs have an impact on blood-CSF barrier (BCB) function or CSF flow [assessed by albumin CSF/serum quotient (Qalb)] [7] and on other CSF routine parameters. The objective of this study was to examine CSF routine parameters [white cells, total protein, Qalb, lactate, and oligoclonal IgG bands (OCB)] in 60 SMA patients (type 1, 2, and 3, aged 7–60 years) treated with nusinersen. Nusinersen is an antisense-oligonucleotide (ASO) approved for treatment of 5q-spinal muscular atrophy (SMA). The objective of this study was to examine CSF routine parameters in SMA patients treated with nusinersen

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Methods

Results

Conclusion