Parkinson's disease is the second most common chronic neurodegenerative disease, after Alzheimer's disease, and it is important to know how it can present itself and how to detect its symptoms how it can present.
Currently, the diagnosis of Parkinson's disease is clinical, based on an interview and physical examination of the patient. This requires the presence of several symptoms and signs (e.g., slowed movement, tremor of hands and feet, rigidity and alteration of gait, among others). However, attempts have been made to identify Parkinson's disease according to so-called prodromal symptoms for years. These precede the cardinal symptoms - which are those that can be diagnosed - that are seen when the disease is in its full expression.
Prodromal symptoms are highly variable, differ among patients and, above all, do not guarantee 100% that the person will end up developing the disease.
The list of these symptoms is extensive, but some of the most documented are:
- Mild and isolated tremor.
- Loss of smell (hyposmia or anosmia) not explained by another disease.
- Behavioural disorder during REM sleep, consisting of vigorous movements or vocalisations during vivid dreams, usually of a violent nature.
- Constipation.
- Depression.
In recent years, in addition to prodromal symptoms, some biomarkers have been developed as additional diagnostic criteria. An example is dopamine transporter SPECT imaging, which is used to determine the reduction in the amount of dopamine in the striatum (the part of the basal ganglia that receives dopamine from the substantia nigra), as an indirect measure of decreased dopamine in this substantia nigra. If this is normal, it excludes the diagnosis of the disease.
SPECT imaging has been used for years. It is popularly known as the “Parkinson's test”, but technically it is not considered a specific diagnostic test, since it can be found altered in any neurodegenerative type parkinsonism. In other words, it must be reserved for cases in which a differential diagnosis has to be made between Parkinson's disease and non-degenerative secondary parkinsonism or essential tremor.
However, an altered dopamine transporter SPECT image in the presence of few or a single prodromal Parkinson's symptom is associated with a greater risk of imminent progression towards the full form of this disease.
In 2016, two independent research groups demonstrated that aggregation of the protein alpha-synuclein, can be detected in the cerebrospinal fluid of patients with Parkinson's and those at risk of having it. In 2018, the Parkinson's disease and other neurodegenerative movement disorders: clinical and experimental research group at the Hospital Clínic Barcelona – IDIBAPS launched a technique that has been incorporated into clinical practice as a routine diagnostic care service since 2021.
The difference between these two tests (SPECT and αSyn RT-QuIC) is found in the fact that although SPECT can detect incipient alterations in people who only have prodromal symptoms, it implies that there is already a degeneration of the dopaminergic neurons; while RT-QulC is capable of detecting alpha-synuclein alteration, even before neuron degeneration - that is, earlier in cases where the dopaminergic neurons has not yet been altered.
In short, it seems that the combination of prodromal symptoms and biomarkers such as SPECT and RT-QulC could allow early detection that would theoretically benefit future neuroprotective treatments more than cases diagnosed later with traditional clinical criteria. This will all have to be evaluated in corresponding clinical trials, which will also have to address several bioethical and public health challenges.
INFORMATION DOCUMENTED BY:
Dr. Yaroslau Compta, neurologist in the Neurology Service at the Clínic Barcelona hospital.
