Table 3 Diagnostic errors and most common 'ALS mimic syndromes'. (Modified from Kato et al., with permission)

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