“MND mimic syndromes”: the main differential diagnoses of MND (modified from Kato et al, 2003, with permission)
| Final diagnosis | Characteristic features | Distinguishing diagnostic features and investigations |
|---|---|---|
| Cerebral lesions | Focal motor cortex lesions very rarely mimic MND, but frontal lesions with co-existent cervical or lumbosacral 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 |
| Cervical spondylotic myelopathy | Progressive limb weakness, but often stabilises, or may be variably progressive; 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; evidence of brachial (localised to 1 or 2 segments) CPD on EMG (but patients may have co-existent lumbosacral motor radiculopathy with lower limb CPD) |
Other cervical myelopathies
| 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 lumbosacral radiculopathy; spinal dural fistula Inclusion body myositis (IBM) | Progressive mixed UMN and LMN syndrome | Usually significant sensory symptoms if not signs; bladder involvement; MRI thoracic and lumbosacral region |
| Progressive weakness; bulbar symptoms; sometimes respiratory muscle weakness | Characteristic pattern of weakness and wasting (deep fibres of finger flexors, quadriceps femoris); EMG evidence of myopathy; muscle biopsy definitive test (rimmed vacuoles) | |
| Multifocal motor neuropathy (MMN) | 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; positive anti-ganglioside (GM1) antibodies in ,70%; improvement with intravenous immunoglobulin (IVIG) in ,70% |
| Myasthenia gravis | Bulbar involvement usually (not always) associated with fatiguability, diplopia, ptosis; no wasting; no UMN signs | Anti-acetylcholine or anti-MuSK antibodies; EMG (repetitive stimulation, single fibre EMG) |
| Benign fasciculation syndrome | Benign fasciculations common in calf muscles; fasciculations elsewhere often felt rather than seen and described as localized twitching lasting few seconds; no weakness; patients often health professionals or relatives of people with MND | EMG shows fasciculations without denervation; CPK normal |
| 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 CAG repeat mutation in exon 1 of androgen receptor gene |