To review 2 cases of symptomatic arachnoiditis in nusinsersen-treated SMA.

Nusinersen is an antisense oligonucleotide therapy approved for SMA delivered via intrathecal (IT) injection. Adverse events are limited and typically result from the procedure itself. In patients with SMA2, scoliosis surgeries are common and can complicate IT injections. Lumbosacral arachnoiditis is a rare, inflammatory condition that can occur following an insult to the spinal leptomeninges. The inflammatory response triggers fibrinous adhesions, causing clumping of nerve roots that can result in sensory and motor symptoms, and bowel and bladder dysfunction. Etiologies of arachnoiditis include spinal post-surgical and degenerative changes. We present 2 patients with SMA2 and prior spinal surgeries who developed symptomatic arachnoiditis after nusinersen infusions.

Patient 1 was 20 yo and within 18 mo of starting nusinersen developed lower extremity (LE) hypesthesia, which progressed to involve saddle anesthesia, incontinence, rectal prolapse, and progressive distal extremity weakness. Imaging revealed the empty sac sign below L1; patient received steroids without clear benefit. Patient 2 was 18 yo and reported progressive LE pain, paresthesias and demonstrable hypesthesia within 18 mos of starting nusinersen; imaging showed L2-L4 arachnoid adhesions. After initial symptoms both patients stopped nusinersen and switched to risdiplam.

Although arachnoiditis is rarely associated with SMA, this unfavorable outcome should be considered when prescribing IT therapies. Both patients reported here had spinal fusions before starting nusinersen. The incidence of post-spinal fusion arachnoid adhesions is unknown but is a likely contributing factor in both cases. We hypothesize that nusinersen may cause or exacerbate arachnoiditis in patients with prior spinal surgery. MRI investigation of pre-existing arachnoid adhesions may be warranted before initiating nusinersen, and MRI is recommended if patients develop symptoms suggestive of arachnoiditis, with consideration for switching to risdiplam.