Introduction :
Parkinson's Disease (PD), Idiopathic Primary Parkinsonism, Hypokinetic rigid syndrome(HRS), or paralysis
agitans is a degenerative disorder of the Central Nervous System mainly affecting the Motor System.
The cause of this cell death is poorly understood in the early course of the disease. The most obvious symptoms
are Movement Related; these include shaking, rigidity, slowness of movements and difficulty with walking and gait.
Thinking and behavioral problems may arise, with dementia in the advanced stages of disease; Depression is the
most common Psychiatric Symptom. The sensory symptoms include Sleep and Emotional problems.
Parkinson's disease is more Common in older people after the age of 50.
When it is seen in young adults it is called young-onset PD (YOPD). The main motor symptom is called Parkinsonism
or a Parkinsonian Syndrome. The disease may be primary or secondary; Primary Parkinson's Disease is referred to as
Idiopathic (Having no known cause). Some typical causes have a genetic origin, while secondary Parkinsonism is due
to known causes like toxins. Many risks and protective factors have been investigated.
The pathology of the disease is characterized by the accumulation of a protein into Lewy
Bodies in the neurons and from insufficient formation and activity of the Dopamine in certain parts of the
midbrain, where the Lewy bodies are located, is often related to the expression and degree of the symptoms of an
individual. Diagnosis of the typical cause is mainly based on symptoms, with tests such as Neuroimaging being used
for confirmation.
Causes For Parkinsons Disease
PD is a degenerative disorder of the central nervous system. Most of the PD cases are idiopathic(no cause).
A small proportion of cases can be attributed to known genetic factors.
Other factors such as environmental toxins, herbicides, pesticides, and fungicides have been associated with the
risk of developing PD no cause is proven.
Genetic Factors :
PD is a non-genetic disorder.
15% of individuals with PD have a first-degree relative who has the disease.
At least 5% of people are now known to have forms of the disease that occur because of a mutation of one of the
severe specific genes.
These genes code for alpha-synuclein(SNCA). Leucine-rich repeat kinase 2(LLRK 2 or Dardar in), PTEn induced
putative kinase 1 (PINK 1) DI-1 and ATPI3A2. In most cases, people with these mutations will develop PD. Except
for LRRK2, they account for only a small minority of cases of PD. The most extensively studied PD related genes
are SNCA and LRRK2 and Glucocerebrosidase(GBA) be risk factors for PD-Mutations in GBA are known to cause
Gaucher's disease.
Genome-wide association studies that search for PD mutated alleles with low penetrance in sporadic PD- Mutations
in GBA are known to cases have now yielded many positive results.
SNCP Gene
The role of SNCA Gene is important in PD because the alpha-synuclein protein is the main component of Lewy
bodies.
SNCA is expressed throughout the mammalian brain, and enriched in presynaptic nerve terminals. Missense Mutations
of the gene(in which a single nucleoid is changed) and duplications are triplications of the locus containing it
have been found in different groups with familial PD.
Missense mutations in SNCA are rare.
Multiplications of SNCA locus account for around 2% of familial cases. Multiplications of the SNCA have been
found in asymptomatic carriers, which indicate that penetrance is incomplete or age-dependent.
Level of alpha-synuclein expression correlates with disease onset and progression with SNCA gene triplication
advancing earlier and faster than duplication.
Sign & Symptoms For Parkinson's Disease
Parkinson's Disease :
Affects movement, producing motor symptoms, non-motor symptoms, which include autonomic dysfunction,
neuro-psychiatric (mood, cognition, behavior or throughout alterations) and sensory and sleep difficulties are
also common.
Motor Symptoms :
There are four motor symptoms that are considered cardinal in Parkinson’s disease.
These four symptoms are:
- Tremor
- Rigidity
- Slowness of movement
- Postural instability
1) Tremor :
This symptom is most apparent and well-known in 30% of patients with PD don’t have tremors at disease onset.
Most develop as the disease progresses. It is usually a rest tremor. Maximal when the limb is at rest and
disappearing with voluntary movement and sleep.
It affects to a greater extent the most Distal part of the limb and at the onset typically appears in only a
single arm or leg, becoming bilateral later. The frequency of PD tremor is between 4-6 hertz cycles per second.
Pill rolling tremor the tendency of the index finger and to get into contact with the thumb and perform together
with a circular movement.
2) Rigidity :
It is stiffness and resistance to limb movement caused by increased Muscle Tone, excessive and continuous
contraction of muscles. Rigidity is uniform (Lead-pipe rigidity) or ratchet (Cogwheel rigidity). The combination
of tremor and increased tone are considered to be at the origin of cogwheel rigidity. It may be associated with
joint pains, frequent. In the beginning, it is asymmetrical rigidity, the neck is affected shoulder muscles before
the muscles of the face and extremities. Rigidity affects the whole body and reduces the ability to move.
3) Hypokinesia :
It is associated with difficulties along the whole course of the movement process, from planning to initiation
and finally execution of a movement. The performance of sequential and simultaneous movements is hindered.
Bradykinesia is a very disabling symptom in the early stages of the disease. Initial complaints are performing
daily tests that require fine motor control like writing, sewing or getting dressed.
Clinical evaluation is based on similar tasks such as alternating movements between both hands / both feet.
Bradykinesia is not equal for all movements or times.
4) Postural Instability :
It is seen in the last stage of the disease, leading to impaired balance and frequent falls, then to bone
fractures. Up to 40% may experience falls and around 10% may have falls weekly, with several falls being related
to severity.
Festinating (rapid shuffling steps and forward flexed posture when walking, speech, swallowing disturbances,
including voice disorders)may be seen. Mask like face expression or small handwriting may be seen.
Classification Of Parkinson's Disease :
Classification:
Parkinsonism word is used for a motor syndrome. The main symptoms are tremor at rest, stiffness, slowing of
movement and postural instability.
Parkinsonian syndromes can be divided into four subtypes according to their origin:
- Primary / Idiopathic
- Secondary / Acquired
- Hereditary
- Parkinson Plus Syndrome/ Multiple Degenration
Primary Parkinsonism :
It means Parkinsonism with no external identifiable cause. In recent years several genes that are directly
related to some causes of Parkinson’s Disease have been discovered.
The term Familial Parkinson’s Disease and Sporadic Parkinson’s Disease can be used to differentiate genetic
from truly idiopathic forms of the disease.
Usually classified as a movement disorder PD also gives rise to many non-motor types of symptoms like sensory
deficits cognitive difficulties or sleep problems.
Parkinson’s Plus Disease are primary Parkinsonism’s which present additional features. They include Multiple
System Atrophy, progressive supranuclear palsy, corticobasal degeneration and dementia with Lewy Bodies.
In terms of pathophysiological part, PD is considered a Synucleiopathy due to abnormal accumulation of
alpha-synuclein protein in the brain in the form of Lewy Bodies, as opposed to other diseases such as
Alzheimer’s Disease, where the brain accumulates Tan Protein in the form of Neurofibrillary Tangles.
The most typical symptoms of Alzheimer’s Disease, dementia, occurs in advanced stages of PD, while it is common
to find neurofibrillary tangles in brains affected by PD.
Dementia with Lewy Bodies (DLB) is another synuclein that has similarities with PD and especially with subsets
of PD cases with dementia.
Treatments are effective at improving the early motor symptoms of the disease. Treatment is typical with
medications L-DOPA and Dopamine Agonists.
As the disease progresses and Dopaminergic Neurons continue to be lost, these drugs eventually become ineffective
at treating the symptoms and the same time produce a complication marked by involuntary writing movement.
The primary symptoms of Parkinson's Disease are all related to voluntary and involuntary motor
symptoms.
Tremors : Trembling in fingers, hands arms, feet, legs, jaw or head.
Rigidity : Stiffness of the limbs and trunk, which may increase during movement.
Bradykinesia : Slowness of voluntary movement.
