Parkinson’s Disease: Definition, Symptoms, Clinical Features, Causes, Risk Factors and Diagnosis

Parkinson's disease (PD) is the second age-related neurodegenerative disease (Nervous system), second only to Alzheimer's disease (AD). The average age of onset of PD is around 60 years and the risk for life is ~ 2% for men and 1.3% for women. The frequency of PD increases with aging, but cases can be observed in subjects of twenty years or even younger, particularly in association with a genetic mutation

Parkinson's disease is a progressive neurological disorder with bradykinesia, resting tremor, stiffness and postural reflex. The disturbance is due to the progressive loss of pigmented neurons associated with the loss of dopamine. The beginning is insidious, the progression tends to be gradual and the course of the disease is generally prolonged. Diagnosis is based on clinical criteria that have changed over time due to changes in clinical practice. Misdiagnosis of depression and involvement of multiple systems lead to variable case determinations

Parkinson's Disease Definition 

Parkinson's disease (PD) is a disorder of the motor system caused by the chronic and progressive degeneration of neurons (nerve cells) in the regions of the brain that control movement. PD causes a decrease in the onset, speed and smoothness of movements. Over time it can affect many bodily functions

Etiology

The pathogenesis of PPE is unknown. The highly selective neurotoxins for the nigra pars compact (SNc) dopaminergic neurons are instructive because animal models of parkinsonism can be created with 6-hydroxydopamine and 1-methyl-4-phenyl-1,2,3,6 tetrahydropyridine (MPTP) . The latter compound is converted from type B monoamine oxidase (MAO) to the toxic ion 1-methyl-4-phenylpyridinium (MPP +). Inhibition of MAO-B by selegiline eliminates the toxicity of the MPTP. MPP + is toxic to neurons by interfering with mitochondrial metabolism

Another toxicity mechanism that has received consideration for the pathogenesis of IPD is cellular damage from oxiradics. Dopamine generates free radicals from auto-oxidation and MAO metabolism. There are various antioxidant mechanisms inside and outside neurons to limit the damage that a free radical can cause attack, but one possibility is that such protection may be overwhelmed or damaged in IPD. Excitotoxicity, programmed activation of cell death and chronic infection are also considered for the etiology of IPD

Physiopathology

• The two distinctive features of the noun nigra pars compact are the loss of neurons and the presence of Lewy bodies. There is a positive correlation between the degree of nigrostriatal dopamine loss and the severity of motor symptoms. PD is relatively asymptomatic until a depletion of substantial compact nigra neurons occurs (70% to 80%)

• Decreased dopamine-1 and dopamine-2 receptor activation causes greater inhibition of the thalamus. Clinical improvement may be more related to the repair activity on the dopamine-2 receptor than the dopamine-1 receptor. The loss of presynaptic neurons of nigrostriatal dopamine causes the inhibition of thalamic activity and activity in the motor cortex

• Degeneration of nigrostriatal dopaminergic neurons produces a relative increase in striatal cholinergic activity, contributing to PD tremor

Parkinson's Disease Symptoms and Clinical Features

Motor symptoms

The patient experiences reduced manual dexterity, difficulties resulting from a sitting position, decreased arm swing during ambulation, dysarthria (difficulty speaking), dysphagia (difficulty swallowing), festive gait (tendency to move from a rhythm to running feet), flexed posture (axial, upper / lower extremities), "freezing" at the beginning of the movement, hypomimia (reduced facial animation), hypophony (reduced volume of the voice) and photomicrograph (decrease of handwritten letters / symbols) )

Autonomic and sensory symptoms

The patient experiences bladder and anal sphincter disorders, constipation, diaphoresis, fatigue, olfactory disorders, changes in orthostatic blood pressure, pain, paraesthesia, paroxysmal vascular redness, seborrhea, sexual dysfunction and sialorrhea (drooling)

Changes in mental state

The Patients suffers from:

• Anxiety and apathy 
• Bradyphrenia (slow thinking processes)
• Confusional state and dementia 
• Depression and hallucinosis 
• Psychosis (typically drug-induced)  
• Sleep disturbances (excessive daytime sleepiness, insomnia, obstructive sleep apnea and behavioral disorder)

Others

Fatigability, oily skin, pedal edema, seborrhea, weight loss

Parkinson's Disease Causes

The cause of Parkinson's disease (PD) is unknown, it occurs as the result of a combination of environmental and hereditary factors, and also the  oxidative damage and aging. Factors for PD can include:

• exposure to herbicides and pesticides

• an unidentified toxin or virus Cell damage by oxidation from free radicals (atoms or molecules with an unpaired electron)

• with age, especially with accelerated aging there is a loss of dopamine-secreting cells

• Fewer cells that secrete dopamine at birth

Parkinson's Disease Risk factors and Preventive measures

Examination of the brain decades of drug addicts after exposure to MPTP shows activated microglia (cells in areas of damage and neuronal inflammation), suggesting that even brief toxic exposure to the brain can produce long-term damage. Some pesticides are postulated to produce direct toxic action on substantial dopaminergic traits and contribute to the development of Parkinson's in humans based on:

• Sex (being Male)

• Age

• Genetic variants

• Ethnicity (higheste in whites)

• Exposure to toxins

• Family history 

• Head Trauma

• Medications and other drugs 

The silent neurotoxicity produced by developmental insults can be unmasked by subsequent challenges throughout life, as well as by the potential for lifelong cumulative neurotoxicity

Researchers don't know what causes Parkinson's disease, although it appears to work in some families. The most significant risk factor for Parkinson's disease is advanced age, as neurologists diagnose the condition more frequently in people aged 60 and over.There are no known measures to prevent Parkinson's disease

Parkinson's Disease Diagnosis

There is no definitive diagnostic test for Parkinson's disease, so the diagnostic pathway considers, both personal medical history and clinical results. The neurologist can take photos procedures such as Computer Tomography (TAC) Scan and Magnetic Resonance Image (MRI) to rule out other causes of symptoms, such as the Brain Tumor or Stroke 

Idiopathic parkinsonism (Parkinson's disease, parkinsonism with Lewy bodies)

Secondary parkinsonism
   
   Induced drug:

•   Antipsychotics (phenothiazines, butyrophenones, risperidone, others)
•   Antiemetics (metoclopramide, proclorperazine)
•   Other drugs (reserpine, alpha-methyldopa)

   Toxic:

•   Carbon monoxide poisoning
•   Hydrogen sulfide
•   Manganese
•   Methanol
•   MPTP (1-methyl-4-phenyl-1-2-5-6-tetrahydropyridine)
•   Petrochemical

• Neoplasms or brain attack (stroke) in the regions of the nigrostriatal pathways

• Traumatic injuries that interrupt the projections of the noun nigra 

• Normal pressure hydrocephalus

Parkinsonism with other degenerations of the neuronal system

• Wilson's disease (copper deposition in the brain)

• Progressive supranuclear palsy

• Paledigital degeneration

• Corticobasalganglionic degeneration

• Alzheimer's disease

• Multisystemic atrophy

•   Striatonigral degeneration
•   Shy-Drager syndrome
•   Olivopontocerebellar atrophy