Table 2.
Clinical, electrophysiological, and neuroradiological characteristics of ALS patients carrying rare heterozygous deleterious SPG7 variants
| Patient | MD087 | VALS008 | TALS012-01 | VALS020 | VALS125 | TALS002-01 | MD075 | VALS093 | MD018 |
|---|---|---|---|---|---|---|---|---|---|
| SPG7 variant | c.1045G > A | c.1198C > T | c.1457G > A | c.1457G > A | c.1457G > A | c.1529C > T | c.1529C > T | c.1529C > T | c.1552 + 1G > T |
| Sex | F | M | F | M | M | M | M | M | M |
| Diagnosis | sALS-FL | sALS | sALS | sALS | sALS-FA | sALS-FA | sALS | sALS-FA | sALS-UMN |
| Age at onset, years | 55 | 73 | 48 | 64 | 70 | 38 | 71 | 66 | 52 |
| Site of onset | Spinal (LL) | Spinal (LL) | Spinal (UL) | Spinal (LL) | Spinal (UL) | Spinal (UL) | Bulbar | Spinal (UL) | Spinal (LL) |
| Disease duration, yearsa | 3.17 | 1.33 | 7.00 | 5.08 | 2.58 | 9.42 | 1.17 | 3.33 | 11.25 |
| Last ALSFRS-R | 32 | 17 | 2 | 29 | 32 | 25 | 39 | 23 | 20 |
| Mean ALSFRS-R-PR | 0.43 | 1.76 | 0.38 | 0.61 | 0.85 | 0.38 | 0.90 | 0.54 | 0.33 |
| Bulbar involvement | – | + | + | + | + | + | + | – | + |
| UL-spasticity | – | – | – | – | – | – | – | – | + |
| UL-DTR | ↑ | ↑ | ↑ | ↑ | ↓ | ↑ | ↑ | ↓ | ↑ |
| UL-atrophy/fasciculation | –/– | +/+ | +/+ | +/+ | +/+ | +/+ | +/+ | +/+ | +/+ |
| UL-weakness | + | + | + | + | + | + | + | + | + |
| LL-spasticity | – | – | – | – | – | – | – | – | + |
| LL-DTR | ↑ | ↑ | ↑ | ↑ | ↑ | ↑ | ↑ | ↓ | ↑ |
| Babinski (right/left) | –/– | –/– | –/– | –/– | –/– | +/+ | –/– | +/− | +/+ |
| LL-atrophy/fasciculation | +/− | +/+ | –/+ | +/+ | –/+ | –/ + | +/+ | +/+ | +/+ |
| LL-weakness | + | + | + | + | + | + | – | + | + |
| Respiratory insufficiency | – | NIV | NIV | IV | – | IV | – | NIV | NIV |
| Pallhypaesthesia | + | + | – | – | + | – | + | + | + |
| Cerebellar dysfunction | – | IT | – | IT | SP | AG | – | – | SP/N |
| Bladder dysfunction | – | – | – | – | – | – | – | – | + |
| Cognitive impairment | + | n.a. | n.a. | n.a. | + | n.a. | n.a. | + | n.a. |
| Environmental factors | n.a. | n.a. | Smoking | n.a. | TBI | Smoking | Smoking | n.a. | Smoking |
| CK (U/L) | 164 | 98 | 267 (↑) | 398 (↑) | 197 (↑) | n.a. | 100 | 119 | 279 (↑) |
| NCS | AMN | AMN | AMN | AMN | ASMN | AMN | ASMN | AMN | ASMN |
| EMG | ACD | ACD | ACD | ACD | ACD | ACD | ACD | ACD | ACD |
| Brain MRI | + | + | + | + | + | – | + | + | – |
| TCC (mm2) | 570 (↓) | 496 (↓) | n.a. | 542 (↓) | 482 (↓) | n.a. | 621 | 448 (↓) | n.a. |
| TA | – | + | – | – | + | n.a. | – | + | n.a. |
| Structural cerebellar abnormalities | VA | VA | CA | CA | - | n.a. | – | – | n.a. |
| CST | – | – | – | – | – | n.a. | – | – | n.a. |
Clinical features are given that were diagnosed until the last follow-up visit
+ present, – absent, ↑ increased, ↓ decreased, ACD acute and chronic denervation, AG ataxic gait, ALSFRS-R amyotrophic lateral sclerosis functional rating scale–revised (range 0–48 points), ALSFRS-R-PR ALSFRS-R-progression rate (low numbers indicate slow progression), AMN axonal motor neuropathy, ASMN axonal sensorimotor neuropathy, CA cerebellar atrophy, CK creatine kinase (increased level > 171U/L), CST corticospinal tract T2 hyperintensity, DTR deep tendon reflex, EMG electromyography, F female, FA flail arm, FL flail leg, IT intention tremor, IV invasive ventilation, LL lower limb, M male, MRI magnetic resonance imaging, N nystagmus, n.a. not available, NCS nerve conduction studies, NIV non-invasive ventilation, sALS sporadic amyotrophic lateral sclerosis, SP saccadic pursuit, TA temporal atrophy, TBI traumatic brain injury, TCC total corpus callosum area: decrease determined by comparison to anatomical references (normal range 580–1040 mm2) [20], UL upper limb, UMN upper motor neuron, VA vermis atrophy
aUntil last follow-up (VALS020, TALS002-01, MD018) or death (MD087, VALS008, TALS012-01, VALS125, MD075, VALS093)