Showing posts with label Levodopa. Show all posts
Showing posts with label Levodopa. Show all posts

Wednesday, 22 March 2023

Parkinson Disease

Parkinson disease (PD) is one of the most common neurologic disorders, affecting approximately 1% of individuals older than 60 years and causing progressive disability that can be slowed, but not halted, by treatment. The 2 major neuropathologic findings in Parkinson disease are loss of pigmented dopaminergic neurons of the substantia nigra pars compacta and the presence of Lewy bodies and Lewy neurites.


Signs and symptoms
https://drive.google.com/uc?export=view&id=1kEMxO4RssoNR94qTF5velJErtk-kw_S5



Initial clinical symptoms of Parkinson disease include the following:

  • Tremor
  • Subtle decrease in dexterity
  • Decreased arm swing on the first-involved side
  • Soft voice
  • Decreased facial expression
  • Sleep disturbances
  • Rapid eye movement (REM) behavior disorder (RBD; a loss of normal atonia during REM sleep)
  • Decreased sense of smell
  • Symptoms of autonomic dysfunction (eg, constipation, sweating abnormalities, sexual dysfunction, seborrheic dermatitis)
  • A general feeling of weakness, malaise, or lassitude
  • Depression or anhedonia
  • Slowness in thinkin

Onset of motor signs include the following:

  • Typically asymmetric
  • The most common initial finding is a resting tremor in an upper extremity
  • Over time, patients experience progressive bradykinesia, rigidity, and gait difficulty
  • Axial posture becomes progressively flexed and strides become shorter
  • Postural instability (balance impairment) is a late phenomenon

Nonmotor symptoms

Nonmotor symptoms are common in early Parkinson disease. Recognition of the combination of nonmotor and motor symptoms can promote early diagnosis and thus early intervention, which often results in a better quality of life.

Diagnosis

Parkinson disease is a clinical diagnosis. No laboratory biomarkers exist for the condition, and findings on routine magnetic resonance imaging and computed tomography scans are unremarkable.

Clinical diagnosis requires the presence of 2 of 3 cardinal signs:

  • Resting tremor
  • Rigidity
  • Bradykinesia

Management

The goal of medical management of Parkinson disease is to provide control of signs and symptoms for as long as possible while minimizing adverse effects.

Symptomatic drug therapy

  • Usually provides good control of motor signs of Parkinson disease for 4-6 years
  • Levodopa/carbidopa: The gold standard of symptomatic treatment
  • Monoamine oxidase (MAO)–B inhibitors: Can be considered for initial treatment of early disease
  • Other dopamine agonists (eg, ropinirole, pramipexole): Monotherapy in early disease and adjunctive therapy in moderate to advanced disease
  • Anticholinergic agents (eg, trihexyphenidyl, benztropine): Second-line drugs for tremor only

Treatment for nonmotor symptoms

  • Sildenafil citrate (Viagra): For erectile dysfunction
  • Polyethylene glycol: For constipation
  • Modafinil: For excessive daytime somnolence
  • Methylphenidate: For fatigue (potential for abuse and addiction)

Deep brain stimulation

  • Surgical procedure of choice for Parkinson disease
  • Does not involve destruction of brain tissue
  • Reversible
  • Can be adjusted as the disease progresses or adverse events occur
  • Bilateral procedures can be performed without a significant increase in adverse events

Prognosis

Before the introduction of levodopa, Parkinson disease caused severe disability or death in 25% of patients within 5 years of onset, 65% within 10 years, and 89% within 15 years. The mortality rate from Parkinson disease was 3 times that of the general population matched for age, sex, and racial origin. With the introduction of levodopa, the mortality rate dropped approximately 50%, and longevity was extended by many years. This is thought to be due to the symptomatic effects of levodopa, as no clear evidence suggests that levodopa stems the progressive nature of the disease.

The American Academy of Neurology notes that the following clinical features may help predict the rate of progression of Parkinson disease :
Older age at onset and initial rigidity/hypokinesia can be used to predict (1) a more rapid rate of motor progression in those with newly diagnosed Parkinson disease and (2) earlier development of cognitive decline and dementia; however, initially presenting with tremor may predict a more benign disease course and longer therapeutic benefit from levodopa
A faster rate of motor progression may also be predicted if the patient is male, has associated comorbidities, and has postural instability/gait difficulty (PIGD)
Older age at onset, dementia, and decreased responsiveness to dopaminergic therapy may predict earlier nursing home placement and decreased survival
Patient Education

Patients with Parkinson disease should be encouraged to participate in decision making regarding their condition. In addition, individuals and their caregivers should be provided with information that is appropriate for their disease state and expected or ongoing challenges. Psychosocial support and concerns should be addressed and/or referred to a social worker or psychologist as needed.

Prevention of falls should be discussed. The UK National Institute for Health and Clinical Excellence has several guidance documents including those for patients and caregivers.

Other issues that commonly need to be addressed at appropriate times in the disease course include cognitive decline, personality changes, depression, dysphagia, sleepiness and fatigue, and impulse control disorders. Additional information is also often needed for financial planning, insurance issues, disability application, and placement (assisted living facility, nursing home).