Table 3.
Diagnostic errors and most common 'ALS mimic syndromes'. (Modified from Kato et al., with permission)
| Final diagnosis | Characteristic features | Distinguishing diagnostic features and investigations |
| Cerebral lesions | Focal motor cortex lesions very rarely mimic ALS, but frontal lesions with co-existent cervical or lumbo-sacral root damage may cause confusion. | MRI/CT; no EMG evidence of widespread chronic partial denervation (CPD) in limbs |
| Skull base lesions | Lower cranial nerve signs (bulbar symptoms and signs; wasting of tongue, often asymmetrical); seldom significant long tract signs unless foramen magnum involved in addition | MRI; CT with bone windows; no EMG evidence of CPD in limbs unless wasting of C8/T1 muscles (rare, but present in some lesions at foramen magnum or high cervical level) |
| Cervical spondylotic myelopathy | Progressive limb weakness. Asymmetrical onset; combined UMN and LMN signs in arm(s); spastic paraparesis; occasionally fasciculations in arms. | Pain in root distribution, but pain may not be severe and may resolve quickly; often progression followed by clinical stabilisation; no bulbar involvement; MRI evidence of spinal cord and root compression; no evidence of CPD on EMG (NB: patients may have co-existent lumbo-sacral motor radiculopathy with lower limb denervation) |
| Other cervical myelopathies • Foramen magnum lesions • Intrinsic and extrinsic tumours • Syringomyelia |
Progressive weakness; foramen magnum lesions and high cervical cord lesions may be associated with focal (C8/T1) wasting; syringomyelia usually associated with LMN signs and dissociated sensory loss | Usually involvement of cerebellar and/or sensory pathways; MRI of head and cervical spine reveal pathology |
| Conus lesions and lumbo-sacral radiculopathy | Progressive mixed UMN and LMN syndrome | Usually significant sensory symptoms if not signs; bladder involvement; MRI thoracic and lumbo-sacral region; EMG evidence of radiculopathy |
| Inclusion body myositis (IBM) | Progressive weakness; bulbar symptoms; sometimes respiratory muscle weakness | Characteristic wasting and weakness of deep finger flexors and quadriceps femoris; EMG evidence of myopathy; muscle biopsy as definitive test (rimmed vacuoles) |
| Cramp/fasciculation/myokymia syndromes | Cramps, undulating muscle contractions, +/- weakness, stiffness (Isaac's syndrome; peripheral nerve hyper-excitability syndrome) | EMG evidence of myokymia; ~30% VGKC antibodies; ~20% associated with thymoma or lung cancer; association with other autoimmune diseases |
| Multifocal motor neuropathy (MFMN) | Focal asymmetrical onset, often upper limb; pure LMN syndrome; may stabilise for months or years; M:F 4:1; | Conduction block on nerve conduction studies (NCS); weakness often out of proportion to wasting; improvement with intravenous immunoglobulin (IVIG) in ~70% |
| Kennedy's disease (X-linked bulbar and spinal muscular atrophy) | Males symptomatic; slowly progressive bulbar and limb weakness | Family history; fasciculations of facial muscles; gynaecomastia; proximal symmetrical weakness in addition to foot drop; mild sensory neuropathy on NCS; positive DNA test for CAG repeat mutation in exon 1 of androgen receptor gene |