Table 1.

Differential diagnoses of primary lateral sclerosis.

Disease	Etiology	Clinical Hallmarks
Hereditary spastic paraparesis (most commonly type 4 or 7 for late-onset)	Genetic disorders	Symmetric paresis usually limited to lower limbs Slower progression Presence of family history or genetic variant
UMN-predominant ALS	Degenerative disorders	Faster progression Progressive development of clinical LMN involvement
Adrenomyeloneuropathy	Metabolic disorders	Impaired sensory vibration Elevated blood levels of adrenocorticotropic hormone Elevated serum levels of very long chain fatty acids Cerebral MRI white matter abnormalities Pathogenic variants in ABCD1 gene
Primary progressive multiple sclerosis	Neuroinflammatory disorders	Presence of other neurological deficits (cerebellar dysfunction, brainstem syndromes, and visual loss) Demyelinating lesions of brain and cord Possible CSF oligoclonal bands
Progressive solitary sclerosis		Single demyelinating lesion in CNS Possible CSF oligoclonal bands
Anti-amphiphysin syndrome		Limbic encephalitis Dysautonomia Cerebellar dysfunction Positive anti-amphiphysin antibodies Presence of tumour
Tropical spastic paraparesis (HTLV-1 and -2 myelopathy)	Infectious diseases	Sphincter dysfunction Sensitive dysfunctions Positive serology
Neurosyphilis		Positive VDRL and TPHA Multisystemic involvement
Vascular and ischemic lesions	Brain and spine structural abnormalities	Imaging findings
Cervical spondylosis
Syringomyelia
Chiari malformation
Compressive foramen magnum lesions
Spinal cord tumours

Abbreviations: CNS, central nervous system; CSF, cerebrospinal fluid; LMN, lower motor neuron; UMN, upper motor neuron; VDRL, venereal disease research laboratory; TPHA, treponema pallidum hemagglutination test.