Parkinson’s Disease – Causes, Symptoms, Diagnosis, Treatment & Pathology

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Introduction:

Parkinson’s disease, which is sometimes called Parkinson’s disease, Parkinson’s, or PD, is a movement disorder where the dopamine-producing neurons in the substantia nigral of the brain undergo degeneration. Parkinson’s is one of the most common neurological disorders. It’s a progressive, adult-onset disease, and it gets more common with age, affecting about 1% of people over 60.

Parkinson's Disease
Parkinson’s Disease

Causes, Symptoms, Diagnosis, Treatment & Pathology:

Here are the Causes, Symptoms, Diagnosis, Treatment & Pathology

Parkinsons_Disease_sympyoms

Causes:

  • Most of the time, there’s no known cause. But in a few cases, there might be a genetic cause, like mutations in the PINK1, Parkinson’s, or alpha-synuclein genes, and in rare cases, Parkinsonian symptoms may be caused by MPTP, a toxic impurity that can be found in the recreational drug MPPP or desmethylprodine, which is a synthetic opioid.
  • In other people, one or more risk factors, rather than a single outright cause, might contribute to Parkinson’s, for example, pesticide exposure or DNA variants in genes like LRRK2.
  • No matter the cause, Parkinson’s derives from the death of dopamine-producing, or dopaminergic, neurons in the substantia nigra. The name substantia nigra means black substance since it is darker than other brain regions when you look at a slice of the brain during an autopsy.
  • We usually refer to the substantia nigra as if it’s in a single location, but there are two of these regions in the brain, one on each side of the midbrain. The substantia nigra is a part of the basal ganglia, a collection of brain regions that control movement through their connections with the motor cortex.
  • In Parkinson’s, these darkened areas of substantia nigra gradually disappear. Under a microscope, Lewy bodies, which are eosinophilic, round inclusions made of alpha-synuclein protein are present in the sympathetic substantia nigra neurons before they die.
  • The function of alpha-synuclein is unknown, as well as the significance of Lewy bodies, and they are both found in other diseases like Lewy body dementia and multiple system atrophy.
  • The substantia nigra actually can be split into two sub-regions. First, there’s the pars reticulata, which receives signals from another part of the basal ganglia called the striatum, which is a term for the caudate and putamen put together, and relays messages to the thalamus via neurons rich in the neurotransmitter GABA, also known as gamma-aminobutyric acid. Second, there are the pars compacta, which is the part of the substantia nigra affected by Parkinson’s.
  • The pars compacta send messages to the striatum via neurons rich in the neurotransmitter dopamine, forming the nigrostriatal pathway, which helps to stimulate the cerebral cortex and initiate movement. Therefore, when substantia nigra pars compacta neurons die, the individual may be in a hypokinetic or low movement state which is commonly seen in Parkinson’s.
  • In addition to simply initiating movements, the substantia nigra helps to calibrate and fine-tune the way that movements happen, which leads to the clinical features of Parkinson’s. First, there’s tremor, which is an involuntary shakiness most noticeable in the hands characteristically called a pill-rolling tremor because it looks like someone rolling a pill between their thumb and index finger.

Symptoms:

  • This is a resting tremor, meaning it is present at rest and diminishes with voluntary movement. Next, there’s rigidity, which refers to the stiffness that can appear as cogwheel rigidity, which is when there are a series of catches or stalls as a person’s arms or legs are passively moved by someone else.
  • Rigidity is also responsible for the stooped posture and an almost expressionless face that some individuals with Parkinson’s might have. Next up is Bradykinesia is a slow movement, hypokinesia is lessened movement, and akinesia an absence of movement, and all three result from difficulty initiating movements. Examples are having the legs freeze up when trying to walk and walking with a shuffling gait, or small steps.
  • Finally, a late feature of the disease is postural instability which causes problems with balance and can lead to falls. Despite these multiple effects on movement, Parkinson’s Disease does not produce weakness. This helps differentiate it from diseases that affect the motor cortex or corticospinal pathway.
  • Also, the resting tremor of Parkinson’s Disease helps to differentiate it from cerebellar diseases, which might result in an action or intention tremor, which is a tremor that’s essentially the opposite of a resting tremor, where the tremor gets worse with movement. Also, both bradykinesia and postural instability help differentiate Parkinson’s from essential tremors Action tremor is also a hallmark feature. Non-motor brain functions can be affected in Parkinson’s as well, leading to additional common symptoms including depression, dementia, sleep disturbances, and difficulty smelling.
  • These are thought to come about because of dysfunction in dopaminergic signaling in other parts of the brain beyond the substantia nigra, for example in the prefrontal cortex leading to cognitive symptoms, and also possibly from issues with other neurotransmitters like acetylcholine.

Treatment:

  • Fortunately, some treatments help with Parkinson’s symptoms, although nonstop the progressive neurodegeneration. The main strategy here is to increase the amount of dopamine signaling in the brain. Dopamine itself can’t cross the blood-brain barrier, but its precursor levodopa can, and once in the brain, levodopa is converted to dopamine by dopa decarboxylase, most importantly within the remaining nigrostriatal neurons.
  • Peripheral dopa decarboxylase also exists, which can metabolize levodopa into dopamine before it gets through the blood-brain barrier, and via additional enzymes metabolize it into other catecholamines like epinephrine, which can cause unwanted side effects like arrhythmias. This is precisely why levodopa is administered with carbidopa, a dopa decarboxylase inhibitor that isn’t able to cross the blood-brain barrier. Another strategy is using amantadine, which is also an antiviral medication that increases endogenous dopamine production, although the mechanism here is still being worked out.
  • A different strategy is to use dopamine agonists that can stimulate dopamine receptors and trick the brain into thinking there’s more dopamine than there is, like bromocriptine, which is an ergot or fungal derivative, as well as pramipexole and ropinirole, which are not ergot derivatives.
  • Alright, the next dopamine-directed class of therapies is COMT inhibitors, catecholamine-O-methyltransferase, an enzyme that degrades dopamine. COMT inhibitors like entacapone and tolcapone prevent the enzyme from degrading dopamine and therefore allow more dopamine to hang around.
  • Very similarly, there are medications like selegiline which inhibits monoamine oxidase-B, also known as MAO-B, which is another enzyme that metabolizes dopamine. Since usually there’s this balance of signaling between dopamine and acetylcholine, a loss of dopamine reaching the striatum increases the relative amount of acetylcholine signaling there. Therefore anticholinergics can be given to restore the balance of cholinergic and dopaminergic signaling, benztropine, which improves the tremor of PD. A special treatment available to help treat PD is deep-brain stimulation.
  • This involves an implantable device that directly sends electrical signals to the basal ganglia which counteracts the aberrant signaling in Parkinson’s. The term parkinsonism is sometimes used to describe symptoms of Parkinson’s that are seen in other nervous system diseases like Lewy body dementia, Wilson disease, and pick disease, as well as side effects of a medication, like antipsychotics such as haloperidol, which blocks dopamine receptors, and metoclopramide, a dopamine antagonist sometimes used to treat vomiting.

Pathology

Alright, as a quick recap, Parkinson’s is a progressive movement disorder caused by degeneration of dopamine-producing neurons in the substantia nigra, specifically in the pars compacta, which leads to resting tremor, rigidity, problems initiating movement, and postural instability, and for which therapy primarily focuses on increasing brain dopamine.

FAQS

What is Parkinson’s Disease?

Parkinson’s Disease is a progressive neurological disorder that affects movement. It occurs when there is a loss of dopamine-producing cells in the brain, leading to motor symptoms like tremors, stiffness, and difficulty with balance and coordination.

What causes Parkinson’s Disease?

The exact cause is not known, but a combination of genetic and environmental factors is believed to contribute. Certain genetic mutations and exposure to environmental toxins may increase the risk of developing Parkinson’s Disease.

What are the common symptoms of Parkinson’s Disease?

Common symptoms include tremors, bradykinesia (slowness of movement), muscle stiffness, impaired balance, and changes in handwriting. Non-motor symptoms such as mood changes, sleep disturbances, and cognitive impairment may also occur.

How is Parkinson’s Disease diagnosed?

Diagnosis is typically based on a thorough medical history, neurological examination, and assessment of symptoms. There is no definitive test for Parkinson’s Disease, so a diagnosis is often made by a neurologist based on clinical findings.

What treatments are available for Parkinson’s Disease?

Treatment aims to manage symptoms and improve quality of life. Medications like levodopa, dopamine agonists, and other drugs may be prescribed. Physical therapy, speech therapy, and in some cases, surgical interventions like deep brain stimulation, may also be recommended.

Note:

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