8B. Parkinson’s disease

Parkinsonism is the clinical triad of bradykinesia, resting tremor, and rigidity. Parkinson disease (PD) is the idiopathic cause of parkinsonism when a person has parkinsonism without an underlying cause. It’s a chronic neurogenerative disorder which mostly affects adults > 50 years, and men more often than women.

Etiology of parkinsonism

• Parkinson disease (most common)
• Drug-induced (antipsychotics)
• Parkinson-plus syndromes
  • Multiple system atrophy
  • Lewy body dementia
  • Corticobasal degeneration
  • Progressive supranuclear palsy

Pathomechanism

There is idiopathic progressive degeneration of dopaminergic neurons in the substantia nigra, which leads to a dopamine deficiency in the CNS. In the later stages, pathways other than dopaminergic pathways are also degenerated.

Clinical features

In Parkinson disease the classic parkinsonism symptoms of bradykinesia, resting tremor, and rigidity, begin unilaterally and are asymmetric, i.e. beginning on one side and always being worse on that side, even as it progresses.

Bradykinesia involves slow onset of voluntary movement and that movements which are repeated continuously quickly develop a reduction in amplitude or frequency. Rigidity can be leadpipe (continuous throughout passive movement) or cogwheel (passive movements become jerk-like). The resting tremor is often nicknamed a “pill-rolling tremor” because the tremor movements resembles the movement which you’d make when rolling a pill between your finger and thumb.

Parkinson disease is also associated with many other symptoms:

• Motor symptoms
  • Hypokinetic gait (freezing, en bloc turning (using many steps to turn), hesitation to begin, reduced arm swinging on the affected side, and taking short steps when walking)
  • Postural instability
  • Small handwriting
  • Mask face (reduced emotional expression on the face)
  • Weak, monotonous voice
• Non-motor symptoms
  • Stooped posture (camptocormia)
  • Anosmia
  • Neuropsychiatric symptoms (depression, delusions, hallucinations, dementia)
  • Sleep problems
  • Drooling

Some non-motor symptoms often develop before the motor symptoms, including anosmia, depression, and constipation. Dementia develops late.

Diagnosis and evaluation

Diagnosis is based on typical clinical features as well as ruling out secondary causes of parkinsonism with the help of MRI or scintigraphy.

Froment manoeuvre can be helpful to evaluate rigidity. While examining rigidity in the ipsilateral extremity, ask the patient to perform a repetetive movement in the contralateral extremity. This makes the rigidity more pronounced and more easily detected.

The pull test can be used to evaluate postural instability. While standing behind the patient (and while ensuring patient safety), pull on their shoulders. The test is positive if the patient requires two or more steps to correct their balance after the pull.

To evaluate bradykinesia, it’s helpful to ask the patient to make continuous repeated movements, like stomping their foot, tapping their fingers, etc. The patient’s gait should also be assessed. The glabellar tap test involves repetetively tapping the glabella. A healthy person blinks in response to the first few taps, but soon stops blinking with each next tap. Persistent blinking with each tap is typical for Parkinson disease.

Differential diagnosis and parkinson-plus syndromes

The other causes of parkinsonism have symmetric symptoms, as opposed to PD. Poor response to levodopa means that another diagnosis than Parkinson disease is likely.

Parkinson-plus syndromes are neurological symptoms which have parkinsonism as well as other neurological features which differentiate them from Parkinson disease. These are:

• Lewy body dementia  – early dementia, visual hallucinations
• Multiple system atrophy – cerebellar symptoms, autonomic symptoms, pyramidal symptoms
• Corticobasal degeneration – dystonia, alien limb phenomenon
• Progressive supranuclear palsy – vertical gaze palsy, postural instability

Treatment

All treatments for Parkinson disease involve increasing the availability of dopamine. The best treatment for Parkinson disease is levodopa plus a peripherally acting DOPA decarboxylase inhibitor, either carbidopa or benserazide. The combination tablet is administered multiple times a day to ensure sufficient dopamine supply during the day. This is very effective initially, but each dose lasts shorter and shorter as the disease progresses. The “on” periods, where the patient has effect of the treatment and has few/no symptoms, become shorter and shorter, and the “off” periods, where the patient has parkinson symptoms, become longer.

Other options include dopamine agonists, COMT inhibitors, MAO-B inhibitors, levodopa-carbidopa intestinal gel infusion (LCIG), and deep brain stimulation of subthalamic nuclei. Physiotherapy and psychosocial support are also important.