Parkinson’s Disease Diagnosis and Test

As a person grows old, their susceptibility to disease increases. In particular, neurodegenerative processes become relatively common and many can overlap in their clinical and histopathologic characteristics. Because of this sometimes diagnosing a patient with neurodegenerative affection can be quite challenging. However, as research is performed and technology develops, an accurate and precise diagnosis is possible. This is because it is frequently required to perform a differential diagnosis. In Parkinson’s disease, one must differentiate from a primary and a secondary cause of parkinsonism. Also, it is essential to distinguish it from other neurodegenerative diseases that could resemble Parkinson’s disease.

Parkinson's disease diagnosis

Early diagnosis of Parkinson’s disease is essential

Also, apart from an accurate and precise diagnosis, an early one is essential for improving patient outcome. Parkinson’s disease is defined by it progressive and irreversible nature. Therefore, an early diagnosis is essential to increase the patient’s quality of life. It is also essential, in order to delay its progression as long as possible. Even if in the future technology could reverse the disease, an early diagnosis will remain essential to increase therapeutical efficacy.

Parkinson’s Disease Diagnosis

Parkinson’s disease diagnosis currently is clinical but there are numerous testing technologies being developed. Additionally, the definite diagnosis can be performed posthumously following a pathological study. Finally, Parkinson’s disease diagnosis should be organized around the phases defined by the Motor Disorders Society. These are the three phases of Parkinson’s disease.

  1. Preclinical phase

This phase is characterized by the lack of clinical manifestations but the underlying histopathological lesions are present in their initial steps.

  1. Prodromal phase

This phase is defined by the presence of prodromal clinical manifestations which usually include mild non-motor and motor signs and symptoms.

  1. Clinical phase

In this phase the characteristic signs and symptoms of Parkinson’s make an accurate diagnose possible.

Parkinson’s clinical diagnosis requires a detailed examination of the patient in order to identify subtle clinical manifestations in the prodromal phase and later, in the clinical phase, to distinguish Parkinson’s disease from another disease that can produce similar manifestations. In both phases, signs and symptoms can be classified into two categories: motor and non-motor.

In the prodromal phase, a diagnosis is extremely challenging making the detailed study of risk factors along with non-motor and motor manifestations even essential. Risk factors for Parkinson’s disease are extremely varied and include the following age, sex, family history, head trauma, environmental exposition to neurotoxins. When considering age, the risk is having a direct relation with age. This is observed by the higher prevalence of Parkinson’s disease in old age. Sex also has a considerable effect on risk, seen in 3:2 males to female ratio in patients diagnosed with the disease. Head trauma is another important risk factor. Even in general culture, the association of sports involving head trauma and Parkinson’s disease is seen.

Certain of these risk factors need to be studied with special considerations, one of these is the family history of the illness. Research shows that most patients diagnosed with Parkinson’s disease do not have the family history of the illness. However, the presence of family history can increase a patient’s risk to 3 times higher than average. Additionally, this risk, in some cases, is related to specific genetic modifications associated with Parkinson’s disease. Other risk factors that needs special considerations are the expositions to neurotoxins. This is because if the clinical manifestations are solely explained by neurotoxins, this can exclude a Parkinson’s diagnostic. This is because the diagnosis would involve parkinsonism secondary to these neurotoxins. However, if the exposition is not recent and the patient did not present parkinsonism after the initial exposition it can be considered as a risk factor only. Among the substances with neurotoxic effects are particular organophosphates and 1-methyl-1-phenyl-1,2,3,6-tetrahidropiridine, rotenone and several other chemicals.

Apart from risk factors, there are “protective factors”. These include caffeine, alcohol, and smoking. (The category of protective factors are placed between quotation marks because there is not enough research and their potential to be risk factor for other.)

Only when the prodromal phase has begun, a physician could attempt to diagnose Parkinson’s disease. However, it is important to emphasize that this is highly unlikely because Parkinson’s disease diagnosis has certain criteria that in almost all cases, if not all, are only met in the clinical phase. Like it has been previously mentioned, in the prodromal phase symptoms can be classified into non-motor and motor manifestation. The non-motor manifestations include olfactory dysfunction, sleep alterations and mild autonomic symptoms.

Olfactory dysfunction is one of the most studied manifestations used for an early diagnosis of Parkinson’s disease. Olfactory dysfunction is called either hyposmia or anosmia, these terms merely identify the severity of the dysfunction. In hyposmia is defined by a partial dysfunction, while anosmia is defined by a complete loss of olfactory function. This is one of the most common symptoms of Parkinson’s disease (60-90% of prevalence), even rivaling the cardinal signs of Parkinson’s disease. However, it is important to note that olfactory dysfunction is highly unspecific, and patients with this sign do not necessarily develop any kind of neurodegenerative process.

Clinical evaluation of the olfactory dysfunction could be identified through patient’s history or more objectively through several test techniques, which include the University of Pennsylvania Smell Identification Scale or the Phenyl Ethyl Alcohol or Detection Threshold. The University of Pennsylvania requires the patient to smell and identify 40 items, resulting in a range of scores from 0-40. Later the result is compared to normal results of other patients the same age and gender. This will provide the patient with a result of a regular olfactory function, anosmia or hyposmia. The degree of hyposmia can also be identified as “severe”, “moderate” or “mild.

Other useful manifestations are sleep alterations, frequently as Rapid Eye Movement behavior disorder. Rapid Eye Movement behavior disorder is defined by the presence of violent dreams, vocalization, loss of regular sleep atony and dangerous behaviors during sleep. In contrast to olfactory dysfunction, Rapid Eye Movement behavior disorder is highly specific to neurodegenerative diseases. Present with this manifestation has a 50-70% risk of being diagnosed with a neurodegenerative disease and a 38% risk of being diagnosed with Parkinson’s disease.

Like olfactory dysfunction, Rapid Eye Movement behavior disorder can be identified through the patient’s history or medical test. Medical testing for this manifestation is done through a polysomnography. The results of the polysomnography will show abnormal muscle tone during REM sleep. Contrasting with regular atonia, characteristically of REM sleep.

Also, there can be autonomic manifestations, specifically constipations predominate in the prodromal phase. A particular characteristic of this symptom is the earliness of its appearance. It has been observed that constipation can appear from 2 years to 24 years before the onset of the disease. One must be aware, however, that it is an unspecific symptom because it occurs relatively frequently.

Finally, during the prodromal phase, motor signs could be key to the identification of patients developing Parkinson’s disease. Micrographia, defined as the progressive decrease in handwriting to the point it becomes illegible, has been a minor sign in Parkinson’s disease diagnosis for a long time. Now, research has observed that observing other characteristics might be useful in order to identify alterations in the motor systems of patients. These characteristics include size, duration, speed and fluency, which can define the general alteration of handwriting or dysgraphia.

After the prodromal phase, the patient’s illness progress and the manifestations that will permit Parkinson’s disease diagnosis will appear. The signs and symptoms useful in the diagnosis of Parkinson’s disease are briefly reviewed in the diverse diagnosis criteria established. Even though these are numerous, they share properties such as a general description of the progression of the disease, a certain amount of cardinal and minor signs, and the absences of exclusion criteria.

Criteria for Parkinson’s disease diagnosis requires certain characteristics in the progression of the disease. First, of the clinical manifestation must develop in a progressive manner. If they appear otherwise they could point to another disease with an acute or subacute presentation. Additionally, symptoms should appear unilaterally initial. As the disease progresses the patient might develop bilateral affection.  The acute and bilateral development of parkinsonism are indicative that disease is drug induced and could exclude the diagnosis of Parkinson’s disease.

Another aspect in the criteria for diagnosing Parkinson’s disease is the presence of cardinal signs and minor signs. The exact number of signs needed from each category vary, yet the signs of each group remain the same. All cardinal signs of Parkinson’s Disease are motor signs  and include the following bradykinesia, rest tremor, cogwheel rigidity and postural instability. Minor signs include both motor and non-motor signs, such as hypophonia, drooling, olfactory dysfunction, autonomic, and neuropsychiatric manifestations.

During the evaluation, the physician needs to consider excluding criteria that might suggest another diagnosis. For example, if a patient presents with parkinsonism along with early dementia manifestations and hallucination this suggest Dementia with Lewy Bodies. Other exclusion criteria include supranuclear gaze palsy, abnormal imaging results or history of repeated strokes. But one of the most important exclusion criteria is a negative response to levodopa. Parkinson’s disease is highly responsive to levodopa, therefore if a patient has a negative result physicians are recommended to investigate for a different diagnosis.

Finally, after diagnosing a patient with Parkinson’s disease it could be useful to evaluate its severity. For which numerous scales have been developed. One of the most commonly used is the Unified Parkinson’s disease severity scale, which is evaluated in 199-point scale. Points are added from three subscales and indicate the severity which varies from 0 (meaning no disability) to (199 total disability). Other scales for evaluating the severity include Webster Parkinson’s disease scale and the Activities of Daily Living.

In many diseases, physicians can rely on a variety of testing technologies to confirm a diagnosis. This is not the case in Parkinson’s disease diagnosis, as testing technology is not as useful and physician mainly relies on clinical evaluations. However numerous are studies being made in researching imaging, biological markers, and mechanosensor technologies in order to study the disease.

Imaging is one the cornerstones in the development of Parkinson’s test. Currently, research is focused in functional imaging technology (PET and SPECT), MRI and transcranial sonography. Some will reveal abnormal results not compatible with the diagnosis of Parkinson’s disease, while others will reveal findings associated with Parkinson’s disease. Functional imaging technology can reveal findings associated with Parkinson’s disease due to their use of tracers that measure dopaminergic cell function. Dopaminergic malfunction, in Parkinson’s disease, is commonly described as striatal dopamine deficiency. This deficiency can define the severity of the disease in most case. Transcranial sonography can also be used as Parkinson’s disease testing, to identify midbrain hyperechogenicity.  This study, however, does not correlate with severity and remains static after 5 years of the progression of the disease.

In the other hand, MRI technology is used to identify the disease that excludes the diagnosis of Parkinson’s disease.  In regular MRI studies, evidence of secondary causes of parkinsonism can be found, such as hydrocephalus, neoplasms, granuloma or traumatic brain injury. Other studies such as the diffusion-weighted MRI imaging can be evidence of atypical neurodegenerative causes of parkinsonism.

Other testing technologies currently being developed are the biological markers. Biomarkers could be used in either studying the risk of patients in the preclinical or prodromal phase. Or, they could be used as the diagnosis tool. These markers are extracted from body fluids such as urine, blood, or cerebrospinal fluid. However, biological markers from the cerebrospinal fluid are thought to be of greater utility due to its location in the body. The biomarkers include a great diversity of biological molecules which include alfa-synuclein protein, DJ-1 protein, inflammatory markers and many more molecules involved in the development of the disease.

Finally, an innovating Parkinson’s diagnosis technology is the use of mechanosensor wearable technology. In an attempt to identify motor signs as early as possible, many devices are being developed. Among the devices being developed are, keyboard test, gait sensors, voice analyzers and much more. They seek to gather detailed information that would be invisible to eye for long periods of time.

These tools in diagnosis of Parkinson’s disease seek to identify abnormal findings in patients to aid in an early diagnosis. However, it is important to consider the practicality and cost of each.  Functional studies are not widely spread in medical facilities and are quite expensive. In contrast, the mechanosensor technology could be relatively cheap to implement however until they are in the market no one can tell. Until the moment Parkinson’s disease testing technologies are developed and approved, Parkinson’s disease diagnosing will remain clinical, based upon the cardinal signs of Parkinson’s disease.