Clinical Implication of Dosimetry of Computed Tomography- and Fluoroscopy-Guided Intrathecal Therapy With Nusinersen in Adult Patients With Spinal Muscular Atrophy

Abstract

Background: Spinal muscular atrophy (SMA) is a genetic disorder that leads to progressive tetraparesis. Nusinersen is the first approved drug for the treatment of SMA and is administered via intrathecal injections. Neuromyopathic scoliosis and spondylodesis can impede lumbar punctures, thus necessitating the use of radiological imaging. Furthermore, dosimetry of this potentially lifelong therapy should be supervised.Methods: Fluoroscopy-assisted or computed tomography (CT)-guided intrathecal injections of nusinersen were performed in adult patients with SMA type 2 and 3. The mean effective dose was compared in patients with and without spondylodesis as well as in those with SMA type 2 and 3. The dosimetry was analyzed in relation to the motor function evaluated with the Revised Upper Limb module (RULM) score and the Hammersmith Functional Motor Scale-Expanded (HFMSE) score.Results: Fifteen patients with SMA type 2 and 3 underwent radiological imaging-assisted intrathecal injections. The mean effective dose per CT-guided injection per patient was 2.59 (±1.67) mSv (n = 12). The mean dose area product (DAP) per fluoroscopy-guided injection per patient was 200.48 (±323.67) μGym2 (n = 3). With increase in the number of injections, the effective dose (r = −0.23) (p < 0.05) and the DAP (r = −0.09) (p > 0.05) decreased. The mean effective dose in 4 patients without spinal fusion (SMA type 2) was 1.39 (±0.51) mSv, whereas that in 8 patients with spondylodesis (SMA type 2 and 3) was 3.21 (±1.73) mSv. The mean effective dose in 5 SMA type 2 patients with spondylodesis was 2.68 (±1.47) mSv (n = 5) and in 3 SMA type 3 patients was 4.00 (±1.82) mSv. Dosimetry did not show significant correlation with the clinical severity of the disease (RULM score: r = −0.045, p > 0.05 and HFMSE score: r = −0.001, p > 0.05).Conclusions: In SMA type 2 and 3 patients undergoing radiological imaging-assisted injections, the effective dose and DAP decreased during therapy with nusinersen. The mean effective dose in patients with spondylodesis was higher than that in patients without spondylodesis. Dosimetry should be monitored carefully in order to detect and prevent unnecessary radiation exposure.

Intrathecal delivery of nusinersen in individuals with complicated spines

“…Previous studies have specifically examined radiation exposure during nusinersen injection using fluoroscopy and CT guidance and have found similar results to our estimation. Repeated radiation exposure for the delivery of nusinersen is a risk that needs to be balanced with the benefit of the treatment, and further research into this topic is needed 2–4 …”

Health, wellbeing and lived experiences of adults with SMA: a scoping systematic review

“…Five randomized placebo controlled clinical trials and three open label trials evaluated medications (valproic acid, gabapentin, salbutamol, hydroxyurea and nusinersen) in adults with SMA type II and III (n = 362 participants, follow up 6-12 months), using different measures of muscle strength and function: four showed no statistically significant effects on the outcome measures, and an open label study of nusinersen showed mean improvement of 8.25 m in the 6 min walk test (p = 0.01), Taken together these were rated as providing Level 1-4 evidence (Table 2) on the Oxford Centre for Evidencebased Medicine scale. Seven case series reported administration of intrathecal nusinersen, with radiological guidance an option for administration, using transforaminal or interlaminar approaches +/− laminotomy [89][90][91][92][93][94][95]. Lumbar punctures were mostly well tolerated, adverse events included post lumbar headache and subarachnoid haemorrhage.…”

Radiation dose reduction for CT-guided intrathecal nusinersen administration in adult patients with spinal muscular atrophy

“…The technical procedure of CT-guided LP for intrathecal nusinersen administration is well described in the literature; however, details on the radiation exposure are often excluded 6 . Recent studies showed that radiation exposure during nusinersen administration in SMA patients is generally not higher compared to those for patients with normal spine anatomy 6,15 . Interestingly, a decrease of the radiation dose during therapy with nusinersen has been demonstrated, probably due to decreased frequency of imaging, data from successful previous injections, and a learning effect of the interventionalists 3,7,15 .…”

“…Recent studies showed that radiation exposure during nusinersen administration in SMA patients is generally not higher compared to those for patients with normal spine anatomy 6,15 . Interestingly, a decrease of the radiation dose during therapy with nusinersen has been demonstrated, probably due to decreased frequency of imaging, data from successful previous injections, and a learning effect of the interventionalists 3,7,15 . Direct comparisons of radiation dosage or patient exposure between the studies is limited because different units (mSv vs. mGy•cm 15 ) and different statistical values (median vs. mean 2 ) were used.…”

“…Interestingly, a decrease of the radiation dose during therapy with nusinersen has been demonstrated, probably due to decreased frequency of imaging, data from successful previous injections, and a learning effect of the interventionalists 3,7,15 . Direct comparisons of radiation dosage or patient exposure between the studies is limited because different units (mSv vs. mGy•cm 15 ) and different statistical values (median vs. mean 2 ) were used. However, the median DLP of 100 to 120 mGy•cm given in previous studies -with values being even increased in patients with spinal fusion 6,7 -is considerably higher compared to the median DLP of 34.5 mGy•cm for the whole session according to our study.…”