Investigations to exclude secondary causes of parkinsonism in atypical cases28 40
| Category | Test | Rationale/differential |
| Blood tests | Serum electrolytes, caeruloplasmin, thyroid function tests, parathyroid hormone, blood film, HIV and syphilis serology, autoantibodies (NMDAR, LGI1, CRMP5, Ri, DPPX, Ma2) | Wilson disease, hyper and hypothyroidism, hypoparathyroidism and pseudohypoparathyroidism, neuroacanthocytosis, HIV and neurosyphilis, autoimmune encephalitis |
| Urine | 24 hour urine copper | Wilson disease |
| CSF | Viral PCR, syphilis, autoantibodies, 14-3-3 | Encephalitis, neurosyphilis, autoimmune encephalitis, prion disease |
| Imaging | MRI brain | Structural brain lesions (normal pressure hydrocephalus, chronic subdural haematoma, tumours), stroke, evidence of previous head trauma, encephalitis, manganese intoxication, specific atrophy patterns in atypical parkinsonian syndromes, for example midbrain predominant atrophy in PSP |
| CT brain | Calcium deposition in the basal ganglia (Fahr disease) | |
| Genetic testing | DCTN1 | Perry syndrome |
| ATP13A2 | Kufor-Rakeb syndrome | |
| FMR1 | Fragile X-associated tremor/ataxia syndrome | |
| HTT | Huntington’s disease with parkinsonism | |
| CSF1R | Adult-onset leukoencephalopathy with axonal spheroids and pigmented glia | |
| POLG | Mitochondrial disorder with parkinsonism | |
| GBA | Gaucher’s disease | |
| NPC1 and NPC2 | Niemann-Pick C disease | |
| CYP27A1 | Cerebrotendinous xanthomatosis |
anti-Ri, anti-neuronal nuclear antibody type 2; ATP13A2, Gene, locus PARK9; CRMP5, collapsin response-mediating protein 5; CSF, cerebrospinal fluid; CSF1R, colony stimulating factor 1 receptor; CT, computed tomography; CYP27A1, cytochrome P450 family 27 subfamily A member 1; DCTN1, Gene encoding the dynactin subunit p150; DPPX, dipeptidyl-peptidase-like protein 6; FMR1, fragile x mental retardation 1; GBA, glucosidase beta acid; HIV, human immunodeficiency virus; HTT, Huntingtin gene; LGI1, leucine-rich glioma inactivated 1; Ma2, anti-Ma2; MRI, magnetic resonance imaging; NMDAR, N-methyl-D-aspartate receptor; NPC1, Niemann-Pick disease, type C1; NPC2, Niemann-Pick disease, type C2; PCR, polymerase chain reaction; POLG, DNA polymerase gamma gene; PSP, progressive supranuclear palsy.