| Disease | Upper motor neuron signs | Peripheral neuropathy | Cognitive dysfunction | Cerebellar ataxia | Other |
| HSP (Hereditary Spastic Paraparesis) | • | • | | | Bilateral symmetric lower extremity spasticity, gait disturbance, urinary urgency, sparing of craniobulbar function, and abnormal SSEP’s |
| MTHR (methylene tetrahydrofolate reductase) deficiency | • | • | • | | Behavior changes, seizures, and leukoencephalopathy |
| Multiple sclerosis | • | | | • | Wide range: dysarthria, dysphagia, optic neuritis, nystagmus, chronic pain, fatigue, weakness, and bladder/bowel difficulties |
| Spinocerebellar ataxia | | | | • | Dysarthria, nystagmus, intentional tremor, and hyporeflexia |
| Cervical or lumbar spondylosis | • | | | | Neck or back pain, leg or arm weakness, abnormal gait, loss of bowel/bladder control, and MRI imaging of the spine will be abnormal |
| Arginase deficiency | • | | • | • | Seizures and tremor, usually evident by age 3 |
| Vitamin B-12 deficiency | • | • | • | | Macrocytic anemia |
| Vitamin E deficiency | | • | | • | Retinitis pigmentosa |
| Copper deficiency | • | • | | | Optic neuropathy, anemia, and neutropenia |
| Lathyrism | • | | | | From excessive consumption of the chickling pea; restricted to India, Bangladesh, and Ethiopia; it results in an irreversible, nonprogressive spastic paraparesis |
| HTLV-1 (human T lymphocytic virus-1) | • | • | | | More frequent in IV drug users, weakness, nocturia, arthralgia, gingival bleeding, dry oral mucosa, and erectile dysfunction |
| Friedreich’s ataxia | | • | | • | Usually no spasticity (although it can develop later); pes cavus, scoliosis, cardiomyopathy, and arrhythmias |
| Krabbe’s disease | • | • | • | • | Loss of vision is also seen. |
| ALS (amyotrophic lateral sclerosis) | • | | | | ALS is typically more rapidly progressive and not limited to legs as seen in HSP. Symptoms include upper and lower motor neuron signs, weakness, fasciculations, cramps, dysarthria, dysphagia, dyspnea, muscle spasms, sialorrhea, emotional lability, and cognitive difficulties. |
| PLS (primary lateral sclerosis) | • | | | | Not limited to legs as seen in HSP; weakness, dysarthria, dysphagia, emotional lability, and bladder urgency can be seen. |
| Metachromatic leukodystrophy | • | | • | | Seizures, optic atrophy, and tremors can be seen. |
| Adrenal leukodystrophy | • | | • | • | Vision loss, seizures, adrenal insufficiency, dysphagia, dysarthria, deafness, weakness, vomiting, or aggression can be seen. |
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