Diagnosis of Parkinson’s Disease

Blood tests. There is currently no blood test that can help diagnose Parkinson’s disease. However, in cases where tremor predominates, it is recommended to perform a thyroid profile in order to rule out thyroid disorders. It is also recommended in cases when the disease starts when the person is young, to determine copper metabolism to help rule out Wilson’s disease, which has a specific treatment. In some centers, neurofilament light chain (NfL) level testing is already available and, if elevated, should suggest an atypical and aggressive parkinsonism rather than Parkinson’s disease. It is still preferable to study it in a research context, as diagnostic cut-off points are not well established.

Cerebrospinal fluid (CSF) analysis. In recent years, there has been a revolution in this field. Currently, some centers already have alpha-synuclein SAA assays in cerebrospinal fluid, which allow for the diagnosis of underlying synucleinopathy, supporting clinical diagnosis and aiding in the differential diagnosis of other parkinsonian syndromes. Its disadvantage is that it requires a lumbar puncture, which is relatively invasive but safe. A modification of this technique is currently being researched to provide reliable results in peripheral blood, which is much more accessible, although at present this technique is still experimental. Other CSF studies include the measurement of tau and amyloid-beta proteins, which are established diagnostic biomarkers for Alzheimer’s disease, but are also associated with the risk or presence of dementia in Parkinson’s disease.

Structural Neuroimaging. If symptoms are atypical and, as is usually the case at onset, occur on only one side, a structural imaging test (CT scan or MRI) can be carried out to rule out structural lesions in one cerebral hemisphere, explaining symptoms limited to the opposite side of the body and ruling out other structural alterations (vascular lesions, hydrocephalus) that may occur with parkinsonism.

• Magnetic resonance imaging (MRI) can show signs of atypical parkinsonism that might suggest an alternative diagnosis to Parkinson’s disease. For example, the putaminal rim and the cross sign are indicators of multiple system atrophy, while the hummingbird sign is associated with progressive supranuclear palsy. Finally, other MRI markers are under investigation (such as iron and neuromelanin content in the substantia nigra) that could differentiate Parkinson’s disease from other conditions, but these are still experimental techniques.
• Iron accumulation detection via ultrasound has proven useful in various studies, but is not used routinely due to the variability of results.

Functional neuroimaging. Single photon emission computed tomography (SPECT) imaging of dopamine transporter is available in order to determine the reduction in the amount of dopamine in the striate (part of the basal ganglia that receives the dopamine of the black substance), as an indirect measurement of the decrease of dopamine in the black substance. It is not a specific diagnostic test of Parkinson’s disease, since it is altered by any neurodegenerative type Parkinsonism. It should be reserved for cases in which it may be used to make a differential diagnosis between Parkinson’s disease and secondary non-degenerative type Parkinsonism (vascular, pharmacological), or essential tremor. In cases in which the Parkinsonism is associated with significant cognitive impairment and there is a doubt between dementia of Parkinson’s disease and Alzheimer’s disease, an altered SPECT of dopamine transporter confirms the possibility of Parkinson’s dementia.  These are nuclear medicine techniques such as SPECT and PET that can detect abnormal protein deposits in different areas of the brain. Reliable PET tracers are already available for tau and beta-amyloid in Alzheimer's disease; however, in Parkinson's disease, the detection of alpha-synuclein using PET is still purely experimental.

Molecular neuroimaging. These are nuclear medicine techniques such as SPECT and PET, which can detect abnormal protein deposits in different areas of the brain. Reliable PET tracers are already available for tau and amyloid-beta in the case of Alzheimer’s disease, but in the field of Parkinson’s, PET detection of alpha-synuclein is still purely experimental.