Table 1.
Patient characteristics and important assessments. The seven adult SMA patients exhibit high demographic and clinical heterogeneity. Patient 3 was the only patient who could walk unassisted; thus, he was the only patient who could perform the 6MWT. As the 10-month 6MWT could not be evaluated due to an error in documentation, data from the 14-month assessment are presented. Patient 4 received only four applications of Nusinersen due to a sacral pressure ulcer, and subsequent withdrawal from treatment. As patient 4 is bedridden, no spirometry could be performed in our pulmonary unit. Six patients reported subjective improvements in symptom severity that partly coincided with the assessed scores. Clinically meaningful improvements in the assessments are indicated, with the absolute value of increased points between baseline and last assessment (as RULM and HFMSE scores are on an ordinal scale, no percentage is calculated); improvement in the 6MWT is indicated as a percentage.
| Patient 1 | Patient 2 | Patient 3 | Patient 4 | Patient 5 | Patient 6 | Patient 7 | ||||
|---|---|---|---|---|---|---|---|---|---|---|
| Demographics | ||||||||||
| Sex | Male | Female | Male | Male | Male | Female | Male | |||
| Age at baseline | 45 years | 50 years | 20 years | 57 years | 68 years | 31 years | 22 years | |||
| Clinical characteristics | ||||||||||
| SMA type | III | II | III | II | III | II | II | |||
| SMN2 copy number | Not known | 2 | >4 | Not known | 4 | 3 | 2 | |||
| Type of mutation in SMN1 as stated in genetic report | Homozygote deletion exon 7, heterozygote deletion exon 8 | Homozygote deletion exons 7 and 8 | Homozygote deletion exons 7 and 8 | Homozygote deletion exons 7 and 8 | Homozygote deletion exon 7, heterozygote deletion exon 8 | Homozygote deletion (no further details stated) | Deletion exons 7 and 8 (no further details stated) | |||
| Age at onset | 7–8 years | 9 months | 14 years | 1–1.5 years | 14 years | 9 months | 1 year | |||
| Best motor milestone in patient history | Unassisted walking | Assisted walking | Unassisted walking | Assisted walking | Unassisted walking | Unassisted sitting | Assisted standing | |||
| Mobility and dependence at baseline | Wheelchair-bound, unassisted transfers | Wheelchair-bound, 24 h assistance | Ambulatory | Mostly bedridden, 24 h assistance | Wheelchair-bound, unassisted transfers | Wheelchair-bound, 24 h assistance | Wheelchair-bound, 24 h assistance | |||
| Need for ventilatory support | No | Indication at night since age 49, not frequently used | No | 8–10 h a day, since age 53 | At night since age 50 (concurrent obstructive sleep apnea) | Indication at night since age 31, not frequently used | No | |||
| Gastrostomy | No | No | No | After 4th application | No | No | No | |||
| Scoliosis | Yes | Yes | No | Severe | No | Yes, posterior spinal fusion since childhood | Yes, posterior spinal fusion since childhood | |||
| Drug administration | ||||||||||
| Lumbar puncture on ward | Fluoroscopic guidance, since 4th application CT-guided, transforaminal | Lumbar puncture on ward | CT-guided, interlaminar | Lumbar puncture on ward | CT-guided, transforaminal | CT-guided, transforaminal | ||||
| Assessments during treatment with Nusinersen (excerpt) | ||||||||||
| RULM (total score of 37 points), assessed by physical therapist | ||||||||||
| Baseline | 15 | 4 | 37 | 1 | 17 | 5 | 3 | |||
| At 2nd month | 16 | 7 | 37 | 0 | 35 | 18 | 12 | |||
| At 6th month | 15 | 5 | 35 | n/a | 35 | 10 | 12 | |||
| At 10th month | 15 | 5 | 35 | n/a | 37 | ⇧ +20/37 | 16 | ⇧ +11/37 | 19 | ⇧ +16/37 |
| Elbow contracture | No | Yes | No | Yes | No | Yes | Yes | |||
| Limitation by contracture | No | No | No | No | No | No | No | |||
| HFMSE (total score of 66 points), assessed by physical therapist | ||||||||||
| Baseline | 29 | 0 | 60 | 0 | 6 | 2 | 0 | |||
| At 2nd month | 28 | 0 | 60 | 0 | 10 | 2 | 3 | |||
| At 6th month | 28 | 0 | 56 | n/a | 11 | 0 | 3 | |||
| At 10th month | 28 | 0 | 63 | n/a | 23 | ⇧ +17/66 | 7 | ⇧ +5/66 | 6 | ⇧ +6/66 |
| Limitation by contracture | No | No | No | No | No | No | No | |||
| 6MWT (meters walked), assessed by physical therapist | ||||||||||
| Baseline | 275 m | |||||||||
| At 2nd month | 305 m | |||||||||
| At 6th month | 327 m | |||||||||
| At 10th month | n/a | |||||||||
| At 14th month | 343 m ⇧ +25% | |||||||||
| ALSFRS-R (total score of 48 points), subscores: (bulbar/upper limb/lower limb/respiratory), assessed by neurologist | ||||||||||
| Baseline | 36 (12/ 8/ 4/ 12) | 19 (10/ 1/ 0/ 8) | 45 (11/ 12/ 10/ 12) | 15 (9/ 0/ 0/ 6) | 24 (8/ 4/ 2/ 10) | 30 (12/ 6/ 0/ 12) | 27 (12/ 3/ 0/ 12) | |||
| At 2nd month | 35 (11/ 9/ 5/ 10) | 20 (10/ 2/ 0/ 8) | 44 (11/ 12/ 9/ 12) | 15 (9/ 0/ 0/ 6) | 26 (8/ 6/ 2/ 10) | 30 (11/ 7/ 0/ 12) | 27 (12/ 3/ 0/ 12) | |||
| At 6th month | 33 (11/ 7/ 3/ 12) | 21 (10/ 3/ 0/ 8) | 44 (11/ 12/ 9/ 12) | n/a | 28 (11/ 5/ 2/ 10) | 32 (12/ 8/ 0/ 12) | 29 (12/ 3/ 2/ 12) | |||
| At 10th month | 35 (11/ 8/ 4/ 12) | 21 (10/ 3/ 0/ 8) | 44 (11/ 12/ 9/ 12) | n/a | 27 (9/ 5/ 3/ 10) | n/a | 29 (12/ 3/ 2/ 12) | |||
| Spirometry: FVC (% of predicted), assessed by pulmonary unit | ||||||||||
| Baseline | n/a | 44 | 111 | n/a | 101 | 31 | 15 | |||
| At 2nd month | 86 | n/a | n/a | n/a | n/a | 30 | 27 | |||
| At 6th month | 79 | 45 | 115 | n/a | 105 | 31 | 25 | |||
| At 10th month | 81 | 43 | 110 | n/a | 93 | 32 | 24 | |||
| EUROQoL EQ-5D-5L Index, self-evaluated by patient | ||||||||||
| Baseline | 0.39 | –0.02 | 0.60 | 0.06 | 0.06 | 0.18 | 0.18 | |||
| At 2nd month | 0.49 | 0.06 | 0.81 | 0.18 | 0.15 | 0.18 | 0.18 | |||
| At 6th month | 0.43 | 0.09 | 0.81 | n/a | 0.13 | 0.06 | 0.18 | |||
| At 10th month | 0.77 | 0.09 | 0.81 | n/a | 0.13 | n/a | 0.18 | |||
| Subjective changes of symptoms and motor function after 10 months of treatment with Nusinersen, as reported by patient | ||||||||||
| ⇧ | ⇧ | ⇧ | ⇧ | ⇧ | ⇧ | |||||
| At 10th month | Strength of arms ↑; facilitation of transfers, sitting, unsupported standing, regain of walking with walking frame up to 10 m | Strength of hands, forearms, and chewing muscles
↑; neck stability ↑; less dysphagia; louder voice, clearer speech |
Total walking distance ↑; less fatigability |
After 2 months: Strength of right hand ↓ (last remaining
motor function in extremities); less dysphagia |
Strength of shoulders and arms ↑; facilitation of transfers and rolling over; regain of unassisted standing | Strength of arms, hands, right knee extension
and flexion ↑; less assistance needed for eating |
Strength of right hand ↑; neck stability ↑; stronger cough; regain of unsupported sitting; less dysphagia, louder voice; less fatigue |
|||
| Further assessments | Validated German version of the MYMOP-D, peak cough flow (both self-assessed, weekly) | |||||||||
marks a tendency of improvement over the 10 months of treatment with Nusinersen, ↑ and ↓ mark increase/improvement and decrease/deterioration, respectively.
ALSFRS-R, Revised Amyotrophic Lateral Sclerosis Functional Rating Scale; CT, computed tomography; FVC, forced vital capacity; HFMSE, Hammersmith Functional Motor Scale Expanded; MYMOP-D, Measure Yourself Medical Outcome Profile; 6MWT, 6-minute Walk Test; RULM, Revised Upper Limb Module; SMA, spinal muscular atrophy; SMN, spinal motor neural protein.