Table 3.
Clinical and pathology features in patients with NEFL-related neuropathy (n=173)*
| All n=173 (%) |
P8R n=23 (%) |
P22S n=28 (%) |
N98S n=12 (%) |
E396K n=43 (%) |
|
|---|---|---|---|---|---|
| Clinical features | |||||
| Ataxia† | 22 (13) | 4 (17) | 3 (11) | 5 (42) | 4 (9) |
| Sensory ataxia‡ | 8 (5) | 1 (4) | – | 3 (25) | 1 (2) |
| Diagnosed with SCA/FRDA§ | 7 (4) | 1 (4) | – | 3 (25) | 1 (2) |
| Motor developmental delay | 18 (10) | – | – | 11 (92) | 1 (2) |
| Hearing loss/deafness | 17 (10) | – | – | 8 (67) | 4 (9) |
| Pyramidal signs/brisk reflexes | 13 (8) | – | – | – | 4 (9) |
| Head/limb tremor¶ | 11 (6) | 3 (13) | – | 3 (25) | – |
| Hypotonia in infancy | 8 (5) | – | – | 4 (33) | – |
| Claw hands/finger contractures | 9 (5) | – | 6 (21) | 2 (17) | 1 (2) |
| Dysarthria/abnormal speech | 6 (3) | 1 (4) | – | 3 (25) | 2 (5) |
| Early upper limb involvement | 5 (3) | – | – | 1 (8) | 1 (2) |
| Waddling gait | 5 (3) | – | – | 1 (8) | 3 (7) |
| Facial weakness | 3 (2) | – | – | 1 (8) | – |
| Scoliosis/hyperlordosis | 3 (2) | 2 (9) | – | 1 (8) | – |
| Broken-up smooth pursuits | 4 (2) | 1 (4) | – | 3 (25) | – |
| Nystagmus | 4 (2) | 1 (4) | – | 3 (25) | – |
| Intellectual impairment | 3 (2) | – | – | 2 (17) | – |
| Delayed/poor growth | 2 (1) | – | – | 2 (17) | – |
| Scapular winging | 2 (1) | – | – | 2 (17) | – |
| Laboratory | |||||
| Raised CK (≤1414 IU/L) | 14 (9) | – | – | 1 (10) | 10 (23) |
| Raised CSF protein (≤0.76 g/L) | 2 (1) | – | – | 1 (10) | – |
| Neurophysiology | |||||
| BAEP abnormal/absent | 20 (12) | – | – | 3 (30) | 11 (26) |
| VEP delayed | 3 (2) | – | – | – | – |
| MEP abnormal | 7 (4) | – | – | – | 7 (16) |
| MR imaging (n=17) | |||||
| Cerebellar volume loss | 4 (24) | – | – | 3 (75) | 1 (33) |
| Spinal cord volume loss | 3 (18) | – | – | 3 (75) | – |
| Thinning of corpus callosum | 2 (12) | – | – | – | – |
| Dilation of fourth ventricle | 1 (6) | – | – | – | 1 (33) |
| Sural nerve biopsy (n=21) | |||||
| Loss of large-myelinated fibres | 21 (100) | 1 (100) | 2 (100) | 2 (100) | 6 (100) |
| Regenerating clusters | 17 (81) | 1 (100) | 1 (50) | 1 (50) | 5 (83) |
| Onion bulbs | 12 (57) | – | 1 (50) | 1 (50) | 3 (50) |
| Thin myelin sheaths | 7 (33) | – | – | 1 (50) | 3 (50) |
| Irregularly shaped nerve fibres | 7 (33) | 1 (100) | – | 1 (50) | 1 (17) |
| Giant axons ± thin myelin sheaths | 6 (29) | – | 2 (100) | – | – |
| Irregularly folded myelin sheaths | 5 (24) | – | – | – | 3 (50) |
| Axonal degeneration | 4 (19) | – | – | – | 2 (33) |
| Muscle biopsy (n=4) | |||||
| Neurogenic features | 4 (100) | – | – | 2 (100) | 2 (100) |
| Myopathic features | 2 (50) | – | – | – | 2 (100) |
*
Features observed in two or more patients.
†
Any ataxia, including gait ataxia/imbalance, limb ataxia or ataxia not otherwise specified.
‡
Described as sensory ataxia or positive Romberg’s test.
§
Diagnosed with or tested for spinocerebellar ataxia or Friedreich’s ataxia.
¶
Any tremor, including head tremor, limb tremor or tremor not otherwise specified.
BAEP, brainstem auditory evoked potentials; CK, plasma creatine kinase; FRDA, Friedreich’s ataxia; MEP, motor evoked potentials; SCA, spinocerebellar ataxia; VEP, visual evoked potentials.
Values in brackets indicate percentages.