Parkinson’s Disease Symptoms: Early Signs and Symptoms of Parkinson’s Disease

Neurodegenerative diseases are commonly described as progressive and irreversible, an example of this is Parkinson’s disease. In spite of improved pharmacological option in management, current treatment has not been able to reverse or even stop the progression of this illness. This has made an early diagnosis essential in order improve probabilities of better results in patient management.

Parkinson’s Disease Symptoms

Parkinsons Symptoms

Parkinsons Symptoms

The problem is that early signs and symptoms of Parkinsons disease are subtle, can be confused with other disease and are still not researched enough. An early diagnosis of Parkinson’s disease requires proper comprehension of the disease and clinical experience in the evaluation of patients. In other words, an early diagnosis of Parkinson’s disease requires knowledge of the temporal basis of the histopathologic lesions and its association to the understanding of risk factors, signs and symptoms of Parkinson’s disease in the pre-clinical, prodromal and clinical phases of the illness.

The histopathological lesions are the basis of the progression of the signs and symptoms Parkinson’s disease. The typical description of histological studies describes Parkinson’s alterations macroscopically as a depigmentation process in the substancia nigra and the locus coeruleus. Related to this is one of the main microscopic findings, neuronal cell death. Finding accompanied by the precedence of protein intracellular inclusions called “Lewy bodies”. However, neurodegeneration is not exclusive to the previously mentioned regions. Other regions affected by neurodegeneration include the olfactory bulb, substancia nigra, raphe nuclei, dorsal nucleus of the vagus, and cortical areas.

The site of the lesion can have a direct association with the signs and symptoms of Parkinson’s disease. This association is particularly strong with lesions in the substancia nigra, whose function is associated with neuronal motor systems. Another The alteration of this brain structure helps explain the cardinal signs of Parkinson’s disease, bradykinesia, rest tremor, rigidity and postural instability. Also, the degree of neuronal loss in the substancia nigra determines the severity of symptoms. Other histopathological findings with strong clinical correlation are found in the hippocampus and cholinergic cortical structures. Degeneration in these brain regions strongly contributes to the appearance of dementia in patients with Parkinson’s disease. In the other hand brain, regions with poor clinical correlation include as the serotonin and noradrenaline pathways.

Another way histopathology is relevant to the signs and symptoms is in the clinical differences in the two subtypes of Parkinson’s disease. The subtypes are tremor-dominant Parkinson’s disease and postural instability and gait difficulty Parkinson’s disease.  Histopathological alterations in tremor-dominant Parkinson’s disease are found in the retrorubral A8 field in the midbrain. In the other hand posture instability and gait difficulty, Parkinson’s disease have a greater histopathological lesion in the substancia nigra and the locus coeruleus.

Finally, histopathology has been linked to the temporal order in the appearance of symptoms of Parkinson’s disease. Some studies, the following order of histopathological findings has been proposed. First lesions appear on the dorsal nucleus of the vagus and the olfactory bulb. Later degeneration affects the substancia nigra and the locus coeruleus. Finally, there is a lesion of the cortical areas (particularly the entorhinal and cingulate cortices). Another pattern of degeneration, in general, described as cephalic progression, starting from the peripheral and autonomic nervous system in the first stage. Later in the second and third stage reaches the brainstem and reaching superior cortical areas in the fourth and fifth stage. These can help conceptualize and perhaps explain the order of appearance of signs of Parkinson’s disease in the context of the terminology recommended by the Motor Disorders Society.

The Movement Disorders society has recommended the following terminology:

  1. Preclinical Parkinson’s disease

This phase can be described by the presence of neurodegeneration processes without the signs and symptoms of Parkinson’s disease. In this stage, we can only study the patient for possible risk factors.

  1. Prodromal Parkinson’s disease

This phase can be described by the presence of early signs and symptoms of Parkinson’s disease. Signs and symptoms in this phase tend to be mild and subtle. Also, they are classically divided into motor and non-motor. It is important to note that this phase was termed the “pre-motor” phase.

  1. Clinical Parkinson’s disease.

In this phase, the diagnosis of Parkinson’s disease is possible due to the presences of the classical motor signs.

In order to achieve an early diagnosis of Parkinson’s disease, it is important to study the possible risk factors. The first of which is the patient’s age, as Parkinson’s disease tends to manifest in the 5th and 7th decade of life. (It is relevant to recall the subtypes as tremor-dominant Parkinson’s disease develops earlier in the 2nd and 4th decade of life. While posture instability and gait difficulty Parkinson’s disease tends to develop later, after the 6th decade of life.) Another risk factor is being a male due to the 3:2 males to female ratio in Parkinson’s disease.

The rest of risk factors can be classified into hereditary and environmental risk factors. Among the hereditary risk factors are having a history of Parkinson’s disease in their family and specific genetic alterations. If a patient has a family history of the disease his risk increases to be three times higher than average. Also, genetic alterations put patients at higher risk than others. Some of the specific gene alteration include SNCA, LRRK2, GBA, PARK2, PINK1, and DJ1.  In addition, environmental factors such as head trauma and intoxication (in particular organophosphates and 1-methyl-1-phenyl-1,2,3,6-tetrahidropiridine) have been known to increase the risk. In contrast, smoking, caffeine, alcohol and elevate urate have shown to decrease risk.

Currently, during the preclinical phase, only risk factors can be studied in patients. Therefore, the identification of the illness will only be possible in the prodromal phase.  It is essential for the clinician to be meticulous while studying the patient to observe the subtle early signs and symptoms of Parkinson’s disease. There is still lots of research going on with respects as to which signs are useful in this phase. But the following have been shown to be useful in the early diagnosis of Parkinson’s disease, anosmia, sleep disturbances (Rapid Eye Movement sleep behavior disorder), constipation, dysautonomies and mild motor disorders (micrographia). It must be noted that even though the signs and symptoms of Parkinson’s disease are not as severe in this phase; the quality of life can be quite significant in the prodromal phase.

Olfactory dysfunction is one of the earliest signs and symptoms of Parkinson’s disease.  There is no definite pathophysiological explanation currently. However, neurodegeneration of the olfactory bulb, olfactory nucleus, the amygdala and olfactory cortex could explain this disorder. Depending on its severity it is labeled as hyposmia or anosmia which refer to a partial or complete loss of the sense of smell. It can be identified through the patient’s medical history or certain medical test. Currently, it has been pointed out that it is a nonspecific sign and does not imply a neurodegenerative process. But its relevance has not diminished because of its high prevalence in Parkinson’s disease patient. Its prevalence, ranging from 60 to 90%, is even higher than the cardinal motor signs of Parkinson’s disease.

Another useful sign is Rapid Eye Movement sleep behavior disorder. Like anosmia and hyposmia, the pathophysiological mechanism of this symptom has not been identified yet. However, it could be explained by lesions in the following structures, locus coeruleus, raphe nuclei, the thalamus and the hypothalamus.  Rapid Eye Movement sleep behavior disorder is characterized by violent dreams, vocalization, loss of regular sleep atony and dangerous behaviors during sleep. This sign is quite useful because it is highly specific to neurodegenerative processes. Studies have shown that in patients with Rapid Eye Movement sleep behavior disorder have a risk of 50-70% of present neurodegenerative disease and at least 38% will be diagnosed with Parkinson’s disease. However, it does not distinguish specifically which neurodegenerative disease is present. Clinically it can be identified through patient history or an assessment questionnaire.

An additional sign of Parkinson’s disease is constipation. It is another key sign in the early detection of Parkinson’s disease. This sign can be identified from 2 months up to 24 years before the appearance of the motor signs required for Parkinson’s disease diagnosis. Constipation is an interesting sign because it could be perhaps the result of the initial neurodegeneration in the autonomic nervous system. In about 60-70% of patients, the autonomic nervous system has alfa-synuclein inclusions.

Finally, there are motor signs that could aid an early diagnosis of Parkinson’s disease. Micrographia has been a minor sign in the clinical phase for a long time but recently it also has been considered a tool to identify patients in the Prodromal phase. Micrographia is defined as progressively small handwriting that continues de diminish until it is unreadable. In a recent paper, it has been suggested that patients be studied for dysgraphia rather than micrographia because this would allow a richer exploration of the patient condition. When examining a patient for dysgraphia, more components would be analyzed, size, duration, speed, and fluency. It is important to note that micrographia or dysgraphia is associated to one of the cardinal signs of Parkinson’s disease, bradykinesia.

Parkinsons Disease Symptoms

Other Parkinsons Disease Symptoms

However, bradykinesia, strictly speaking, does not appear until the clinical phase begins along with the other cardinal signs. Parkinson’s cardinal signs are bradykinesia, rest tremor, rigidity, and postural instability, determined by the degeneration in the substancia nigra. Also in the clinical phase, non-motor signs can be displayed. These include psychiatric manifestations (apathy, depression,and anxiety), autonomic dysfunction (constipation, orthostatic hypotension and genitourinary disturbances), sleep disorders, olfactory dysfunction, pain and cognitive impairment (ranging from mild reduction in functional capacity to severe impairment in dementia.)

Bradykinesia is a very frequent manifestation among the diverse signs and symptoms of Parkinson’s disease. Bradykinesia, hypokinesia, and akinesia are symptoms characterized by slowness or failure performing motor functions in general. However, it is important to note that each has a precise clinical definition. Bradykinesia is defined as the slowness of movement, while akinesia is defined as the absence of movements (voluntary or spontaneous) and hypokinesia is described as smaller movements than what was expected by the patients. These motor symptoms can manifest also in day to day activities. These include partial or complete loss of facial expression (hypomimia or amimia), reduced volume of speech (hypophonia), alteration of writing (micrographia or agraphia) and drooling (sialorrhea). It could be said that these manifestations are the best understood signs and symptoms of Parkinson’s disease, as they are explained by the simple direct and indirect motor control pathways.

Another cardinal sign of Parkinson’s disease is rest tremor. Even though there are several types of tremors, rest tremor stands out to its frequency in the disease. Rest tremor is defined as an asymmetric tremor of moderate amplitude in agonist-antagonist alternating contractions. Common movements in rest tremor include hand movements (sometimes called the pill rolling tremor), leg abduction-adduction tremors, and head movement (movements resembling yes or no gestures).

Rigidity is another common sign of Parkinson’s disease and it is defined as the increase in muscle tone identified upon palpation of the muscle at rest and resistance to passive movements. A remarkable clinical finding is the cogwheel phenomena. This sign is the consequences of two overlapping cardinal signs, rigidity, and tremor. The cogwheel phenomena can be described as the resistance in passive movement.

The last cardinal sign of Parkinson’s disease is postural instability in which physiological posture neurological systems are deficient due to decreased or loss of postural reflexes. It is of great clinical relevance because it is associated with falls in the elderly patients. Other signs associated with this cardinal sign are gait disturbances. Among these are, freezing of gait and shuffling gait, both which have been associated to previously mention signs (akinesia and hypokinesia). Freezing of gait is defined by the difficulty of gait initiation and unintentional motor blocks during walking. In the other hand shuffling gait is characterized by short and quickly alternating steps.

Other common manifestationsare described as non-motor, among which psychiatric manifestations and cognitive impairment need special considerations. These symptoms are diverse and need to be referred with other specialists to distinguish non-motor manifestation of Parkinson’s from coexisting neuropsychiatric diseases. Also, it is important to know that these signs are evidence of progression final stages of Parkinson’s disease. They are easily identified as they are incapacitating and severely detrimental to quality of life of patient.

Due to Parkinson’s disease progressive and irreversible in nature, currently, the best option is a precise and early diagnosis of this illness. Essential is knowing the underlying physiopathological mechanisms going on during the time course of the progression of the disease.  It is evident that our current understanding is lacking. This could explain the lack of testing technologies for early diagnosis most cases which could aid the clinical study of patients at risk. Also, it explains the difficulty of understanding the heterogeneity in the signs and symptoms of Parkinson’s disease. However, until more research is done it is the signs and symptoms of Parkinson’s disease and the detailed study of patients in the three phases (preclinical, prodromal and clinical phases) which will provide the best outcomes for patients.