​Kembara Xtra - Medicine - Parkinson Disease

​Kembara Xtra - Medicine - Parkinson Disease
A progressive neurodegenerative disorder characterized by resting tremor, stiffness, bradykinesia, and postural instability that is brought on by the death of dopaminergic neurons in the substantia nigra and other dopaminergic regions of the brain.

Epidemiology 
Average age of onset: 60 years; incidence: 21 per 100,000 person-years; slightly more common in men than in women
Second most prevalent neurological disease after Alzheimer's disease; affects 1 million people in the United States and 5 million people globally; prevalence: 1 to 2/1,000 people; 0.3% of the general population; 1-2% of those under 60; and up to 4% of those over 80;

Pathophysiology and Etiology 

The primary motor difficulties of PD are caused by dopamine depletion in the substantia nigra and nigrostriatal pathways.
Selective loss of dopamine-containing neurons in the pars compacta of the substantia nigra is a pathologic characteristic.
 Lewy bodies (hyaline inclusion bodies) and Lewy neuritis present along with neuronal loss
Genetics
Particularly when the age at symptom start reaches 50 years, mutations in many autosomal dominant and autosomal recessive genes are associated to PD/parkinsonian syndrome.

A farmer's lifetime usage of pesticides, particularly rotenone and other carbamates, is linked to an increased chance of acquiring Parkinson's disease (PD).
 Consistent head trauma, rural living, well water use, and employment in a wood pulp mill

Prevention 

Weight training, running, dance, yoga, and traditional Chinese martial arts are among the physical activities that have been associated to a lower chance of developing PD.


Accompanying Conditions 

Alterations in mental status (depression, psychosis, hallucinations, dementia), sleep problems, autonomic dysfunction (e.g., constipation, urine urgency), orthostatic hypotension, and pain

The diagnosis is made based on clinical characteristics and the patient's reaction to dopaminergic medication.
The neuropathologic examination is the gold standard for diagnosis.
Typically, idiopathic PD can only be diagnosed if bradykinesia and either tremor or stiffness are present.
When compared to their white counterparts, African American patients with Parkinson's disease (PD) are less likely to receive standard therapy. Idiopathic rapid eye movement sleep behavior disorder is thought to be a potential prodrome for PD.
HISTORY
symptoms that are frequently mild or linked to aging
 Less emotion was visible in the facial features.
 Slowing and stiffening of the entire body (either one or both arms do not swing when walking).
Resting tremors, usually in one hand at first, slurred speech, falling or having trouble balancing as the disease progresses
• Urinary symptoms such as increased frequency and urgency • Psychiatric symptoms such as anxiety, hallucinations, and dementia


clinical assessment 

Tremor: A resting tremor (4 to 6 Hz), frequently asymmetrical, that vanishes with voluntary movement; it frequently manifests as pill-rolling while walking; it can also affect the jaw, chin, lips, and tongue.
Bradykinesia Rigidity: lead pipe (constantly rigid) or cogwheel (catching and releasing) Postural instability


Multiple Diagnoses 
Essential tremor: Bradykinesia is absent; it frequently occurs symmetrically, mainly when moving or holding outstretched hands, and it is unresponsive to levodopa.
Psychomotor slowness brought on by depression might resemble Parkinson's disease (PD) bradykinesia in appearance.
Visual hallucinations, erratic cognition, and parkinsonism are the hallmarks of dementia with Lewy bodies, which can develop concurrently with or before parkinsonism.
Multiple system atrophy: parkinsonism, different degrees of dysautonomia, cerebellar involvement, and pyramidal signs are the most common symptoms.
Progressive supranuclear palsy: pseudobulbar palsy, hyperextension of the neck, and difficulties in vertical eye movements, notably down gaze.
 Associated neurodegenerative conditions include frontotemporal dementia, spinocerebellar ataxias, late stages of Alzheimer disease, Huntington disease, and
Secondary parkinsonism, which is generally bilateral in nature and is caused by drugs, is reversible but may take weeks or months to manifest.
- Neuroleptics (the most prevalent factor)
- Antiemetics, including metoclopramide and prochlorperazine.
- SSRIs
- Amiodarone - Calcium channel blockers (such as flunarizine and cinnarizine) - Lithium/valproic acid
- Estrogens with Amphotericin B

Initial test results from the laboratory and imaging
No physiologic or blood tests are performed to confirm the diagnosis, which is primarily made clinically.
DJ-1 and -synuclein protein reduction can be used as a qualitative feature in the diagnosis of Parkinson's disease.
However, it can be used to rule out structural problems. MRI of the brain is nondiagnostic.

Tests in the Future & Special Considerations
Be aware that PD and parkinsonism can be distinguished from one another using single-photon emission computed tomography (SPECT).
Other PET and MR spectroscopy diagnostic procedures are not advised.
Test Interpretation The diagnosis of Parkinson's disease is clinical, and no tests are advised to support this conclusion.

Management 

To improve functional outcomes, multidisciplinary rehabilitation should include elements of traditional physical and occupational therapy.

Medication 
The agents are chosen according on the patient's age and the symptoms they are currently experiencing. PD goal: Improve motor and nonmotor impairments.
When symptoms (typically dyskinesias) appear while a patient is taking PD medication, this is referred to as having "off" periods. Patients who are elderly and on levodopa drugs particularly experience this.

Initial Line
Levodopa, dopamine agonists, and monoamine oxidase B (MAO-B) inhibitors are first-line treatments for early Parkinson's disease.
- The most effective treatment for PD symptoms, notably bradykinesia, is still levodopa plus carbidopa.
- There is debate concerning levodopa versus dopamine agonist:
The majority of levodopa patients eventually experience involuntary motor fluctuations or dyskinesias.
Older people may have a lower tolerance for the side effects of dopamine agonists.
Levodopa will eventually be needed by all patients.
- Consider MAO-B inhibitors (rasagiline) or catechol O-methyltransferase (COMT) inhibitors (entacapone) as adjuvants for patients who have dyskinesias when on levodopa. Carbidopa plus levodopa (Carbidopa prevents levodopa's peripheral conversion).
Carbidopa, levodopa, and entacapone (Stalevo) - Addition of entacapone as a single drug should be commenced before to administration of this combination: - Immediate release (Sinemet) - Orally disintegrating (Parcopa)
Once the appropriate daily dose of carbidopa/levodopa has been established, the patient may switch to Stalevo; the side effects are the same, in addition to diarrhea and brownish-orange urine.
Dopamine-receptor agonists (nonergot) can cause hallucinations, nausea, vomiting, hypotension, drowsiness, edema, vivid dreams, obsessive behavior, disorientation, and lightheadedness.
- Ropinirole (Requip) with pramipexole (Mirapex)
Selective MAO-B inhibitors can cause sleeplessness, jitteriness, and hallucinations; these side effects are typically associated with selegiline. In clinical trials, rasagiline showed identical adverse effects to placebo. Rasagiline is metabolized by CYP1A2; use cautious when taking other drugs (such as ciprofloxacin) that use this enzyme system:
Rasagiline (Azilect) and selegiline (Eldepryl) are second-line drugs.
Second-line treatments for early Parkinson's disease include -adrenergic antagonists (for postural tremor), amantadine, and anticholinergics (for young individuals with tremor); there isn't much evidence to support symptom management.[A]
Dopamine agonists (ergot): Due to their higher risk of side effects, these medications are not as popular as nonergot dopamine agonists as bromocriptine (Parlodel). Management of levodopa-related motor side effects
- The effects of the final dose wearing off (i.e., a decrease in responsiveness to PD medicine that causes a recurrence of PD symptoms)
- Rasagiline or entacapone (with each dosage of levodopa) preferable
Dyskinesias generally happen at dopamine peak levels. Amantadine may be taken into consideration, however its effectiveness is debatable.
- The first oral adenosine A2A receptor antagonist to receive FDA approval in the United States for treatment in adults with Parkinson's disease (PD) who have "off" episodes istradefylline (Nourianz).
Anticholinergic medications should be avoided since they are ineffective (helpful only for tremor) and have a higher risk of unwanted events.
- Benztropine (Trihexyphenidyl; Cogentin)
 N-methyl-D-aspartic acid antagonist: unclear mechanism and potential benefit for dyskinesias. Confusion, drowsiness, dry mouth, livedo reticularis, and hallucinations are some of the side effects.
- Symmetrel, or amantadine
Entacapone is favored over tolcapone as a COMT inhibitor because of the latter's potential hepatotoxicity. Orthostatic hypotension and nausea are undesirable effects:
Tolcapone (Tasmar) and entacapone (Comtan)
 Demands LFT surveillance
 Apomorphine (Apokyn) is a nonergot-derived dopamine agonist that is administered subcutaneously (SC) for off-episodes in advanced disease; side effects include nausea, vomiting, dizziness, hallucinations, orthostatic hypotension, and somnolence.
Levodopa therapy is only used for "off" episodes.
QUESTIONS FOR REFERENCE
Patients with suspected PD should be referred to neurology as soon as possible for a more thorough clinical evaluation and therapy suggestions.

Further Therapies 
The emotional and mental support of the patient's family
It has been demonstrated that physical therapy and endurance training can enhance balance, muscle strength, and walking speed.
Speech therapy may be useful for maintaining voice quality and enhancing speech volume.
 Psychosis treatment for non-motor symptoms
The FDA authorized pimavanserin (Nuplazid) in 2016 as the first medication created exclusively to treat Parkinson disease psychosis.
Before pimavanserin, quetiapine (Seroquel) was frequently used for PDP patients.
Sleep issues
FDA-approved transdermal version of rotigotine for treating insomnia in PD
Orthostatic hypotension: Droxidopa, an FDA-approved medication, can be used in conjunction to increasing salt and fluid consumption.
 May also take into account midazolam, fludrocortisone, and wearing compression stockings (3).
Memory loss
For cognitive impairment (such as mild to moderate dementia in PD), rivastigmine can be investigated.
Depression in PD: Pramifexole, Nortriptyline, Desipramine, Venlafaxine, and CBT may be considered. 


Surgical Techniques 

For individuals with motor problems unresponsive to best medical care who are healthy, free of substantial comorbidities, responsive to levodopa, and without depression or dementia, deep brain stimulation is a viable therapeutic alternative.

Alternative Therapies 

In PD patients, music therapy may help to lessen their motor symptoms and overall quality of life.


Admission When admitted, take the fall risk precaution Keep in mind that even a slight change in medication dosage might have an impact on PD symptoms. Inspect the patient's residence for PD meds.

Follow-Up – If the patient is experiencing levodopa "off" periods, avoid medication holidays.
If a patient experiences dyskinesias while on levodopa/carbidopa, you might want to switch to a dopamine agonist (nonergot is recommended), an MAO-B inhibitor, or a COMT inhibitor.
Significant motor symptoms. The patient shouldn't be permitted to drive themselves at this point. This needs to be taken note of and reported to the licensing body.
patient observation
If using dopamine agonists, keep an eye out for the emergence of impulse control issues.

Diet – Soft food, a swallowing evaluation, and more time spent eating are all options for dysphagia.
 Steer clear of hefty, high-fat meals because they cause delayed digestion and affect how well drugs are absorbed.

PD is a chronic, progressive condition, and the prognosis varies depending on the symptoms of the individual patient.
 An increase in PD mortality; on average, survival declines by 5% year.