Parkinson's Disease (PD)

Parkinson's disease (PD) is a progressive neurodegenerative disease. Although historically considered a motor disorder, there are many neuropsychiatric symptoms associated with the disease, and the majority of diagnoses will progress to Parkinsons's Disease Dementia (PDD).


Parkinson's disease affects 1–2% of individuals over 60 years of age.


Often, patients may have prodromal symptoms that occur decades before the classic symptoms present. This includes restless legs, REM sleep behaviour disorders (always think about Parkinson's or Lewy Body Dementia in the patients!), autonomic dysfunction, obstructive sleep apnea, and late onset depression. Loss of smell (hyposmia) is an important preclinical sign of PD as well.[1]

Classic Motor

The classic motor features of PD include rigidity, asymmetric resting tremors, bradykinesia, shuffling gait (festination, falls, block turn, freezing), and postural instability. In addition, patients may develop hypophonia (soft/hoarse voice), dysphagia, and drooling, micrographia, and seborrhea. As the disease progresses, patients may developing orthostatic hypotension due to progressive destruction of dopaminergic neurons. Patients may also report a general “slowing down” of their day-to-day movements, and have difficulty getting or rolling out of bed in the mornings.

Impulsive Control Disorders

Impulse control disorders (ICDs) such as compulsive gambling, buying, sexual, and eating behaviours, are a serious and increasingly recognized complication in Parkinson's disease (PD), occurring in up to 20% of PD patients over the course of their illness. Related behaviours include punding (stereotyped, repetitive, purposeless behaviours), dopamine dysregulation syndrome (DDS) (compulsive medication overuse), and hobbyism (e.g., compulsive internet use, artistic endeavours, and writing). These disorders have a significant impact on quality of life and function, strain interpersonal relationships, and worsen caregiver burden, and are associated with significant psychiatric comorbidity. ICDs have been most closely related to the use of carbidopa-levodopa and dopamine agonists.[2]


Anxiety is a common non-motor comorbidity in Parkinson’s disease that contributes to reductions in quality of life, higher levels of care dependency and increased caregiver distress. A combination of medical, neurochemical and psychosocial phenomena contribute to anxiety in Parkinson's. The degeneration of subcortical nuclei and ascending dopamine, norepinephrine and serotonin pathways within the basal ganglia–frontal circuits may be responsible for symptoms of anxiety.[3] There are a few studies on treatment of anxiety in Parkinson's. SSRIs and SNRIS in particular have been used, with citalopram having the most evidence.


Psychotic symptoms in Parkinson's disease (PD) are relatively common. PD psychosis has unique clinical features, in that patients are usually aware and have insight. The use of Parkinson's medications (particularly dopamine receptor agonists) has been the most widely identified risk factor for psychosis. The psychosis most commonly involves visual hallucinations, which progresses over time. Other symptoms may include auditory hallucinations, delusions, and illusions.

Clozapine is the most effective treatment for Parkinson's-related psychosis,[4] and should be used if patients can tolerate the required blood monitoring. There is actually limited positive evidence for the use of quetiapine in Parkinson's-related psychosis.[5] However, it is often clinically used due to the lack of need for regular bloodwork. Anticholinesterase inhibitors are also efficacious in the treatment of psychosis, with rivastigmine having the most evidence, followed by donepezil.[6] More recently, pimavanserin was approved for the treatment of PD psychosis in the USA.

Though not present in early stages, the majority of patients with Parkinson's Disease will have cognitive impairment and subsequently develop dementia.

To diagnose Parkinson's Disease, the patient must present first with features of parkinsonism. However, this only means the have parkinsonism, and not Parkinson's Disease itself (for example they could have other neurodegnerative disorders such as progressive supranuclear palsy [PSP] or multisystem atrophy [MSA]). In order for Parkinson's Disease to be confirmed, at the vey least there needs to be an improvement/resolution of symptoms when patients are put on a trial of Sinemet (carbidopa-levodopa). The latest diagnostic criteria is based on the 2015 Movement Disorder Society Clinical Diagnostic Criteria for Parkinson's disease.[7]

If the patient meets the absolute exclusion criteria, this immediately argues against the diagnosis of PD.

Diagnostic Criteria for PD

Postuma, Ronald B., et al. MDS clinical diagnostic criteria for Parkinson's disease. Movement Disorders 30.12 (2015): 1591-1601.
Essential Criterion
Must have parkinsonism, which is defined as bradykinesia, in combination with at least 1 of rest tremor or rigidity. Examination of all cardinal manifestations should be carried out as described in the MDS–Unified Parkinson Disease Rating Scale
Clinically established PD requires
1. Absence of absolute exclusion criteria
2. At least two supportive criteria
3. No red flags
Clinically probable PD requires
1. Absence of absolute exclusion criteria
2. Presence of red flags counterbalanced by supportive criteria (i.e. - if one red flag is present there must also be at least one supportive criterion; if two red flags, at least two supportive criteria are needed. If there are more than two red flags, clinically probable PD cannot be diagnosed).

Supportive Criteria for PD

Supportive Criteria
1. Clear and dramatic beneficial response to dopaminergic therapy. During initial treatment, patient returned to normal or near-normal level of function.
2. Presence of levodopa-induced dyskinesia
3. Resting tremor of a limb, documented on clinical examination (in past, or on current examination)
4. The presence of either olfactory loss or cardiac sympathetic denervation on MIBG scintigraphy

Absolute Exclusion Criteria

The presence of any of these features rules out PD
1. Unequivocal cerebellar abnormalities, such as cerebellar gait, limb ataxia, or cerebellar oculomotor abnormalities (e.g. - sustained gaze evoked nystagmus, macro square wave jerks, hypermetric saccades)

2. Downward vertical supranuclear gaze palsy, or selective slowing of downward vertical saccades

3. Diagnosis of probable behavioral variant frontotemporal dementia or primary progressive aphasia, defined according to consensus criteria within the first 5 years of disease

4. Parkinsonian features restricted to the lower limbs for more than 3 years

5. Treatment with a dopamine receptor blocker (e.g. - antipsychotic) or a dopamine-depleting agent in a dose and time-course consistent with drug-induced parkinsonism

6. Absence of observable response to high-dose levodopa despite at least moderate severity of disease

7. Unequivocal cortical sensory loss (i.e. - graphesthesia, stereognosis with intact primary sensory modalities), clear limb ideomotor apraxia, or progressive aphasia

8. Normal functional neuroimaging of the presynaptic dopaminergic system

9. Documentation of an alternative condition known to produce parkinsonism and plausibly connected to the patient’s symptoms, or, the expert evaluating physician, based on the full diagnostic assessment feels that an alternative syndrome is more likely than PD

Red Flags

Red flags rule out probable PD diagnosis only when they cannot be counterbalanced by supportive criteria.
1. Rapid progression of gait impairment requiring regular use of wheelchair within 5 years of onset

2. A complete absence of progression of motor symptoms or signs over 5 or more years unless stability is related to treatment

3. Early bulbar dysfunction: severe dysphonia or dysarthria (speech unintelligible most of the time) or severe dysphagia (requiring soft food, NG tube, or gastrostomy feeding) within first 5 years

4. Inspiratory respiratory dysfunction: either diurnal or nocturnal inspiratory stridor or frequent inspiratory sighs

5. Severe autonomic failure in the first 5 y of disease.

6. Recurrent (> 1 per year) falls because of impaired balance within 3 years of onset

7. Disproportionate anterocollis (dystonic) or contractures of hand or feet within the first 10 years

8. Absence of any of the common nonmotor features of disease despite 5 years of disease duration. These include sleep dysfunction (sleep-maintenance insomnia, excessive daytime somnolence, symptoms of REM sleep behavior disorder), autonomic dysfunction (constipation, daytime urinary urgency, symptomatic orthostasis), hyposmia, or psychiatric dysfunction (depression, anxiety, or hallucinations)

9. Otherwise-unexplained pyramidal tract signs, defined as pyramidal weakness or clear pathologic hyperreflexia (excluding mild reflex asymmetry and
isolated extensor plantar response)

10. Bilateral symmetric parkinsonism. The patient or caregiver reports bilateral symptom onset with no side predominance, and no side predominance is observed on objective examination

Parkinson's Rating Scales

Name Rater Description Download
Unified Parkinson's Disease Rating Scale (UPDRS) Clinician The UPDRS is a comprehensive 50 question assessment of both motor and non-motor symptoms associated with Parkinson's Download

The exact pathogenesis of Parkinson’s disease is not known. The disease may have multiple causes, including both genetic and sporadic causes. The motor impairments of the disease are due to selective loss of pigmented midbrain neurons in the substantia nigra pars compacta. These neurons project to the putamen and caudate (the striatum), where dopamine is released. When more than half the dopaminergic nerve terminals in the striatum are lost, Parkinsonian symptoms begin to emerge.

Many neurodegenerative disorders are on the differential diagnosis. These disorders may first present with neuropsychiatric symptoms, and patients may see a psychiatrist before any other specialist. A differential diagnosis for Parkinson's includes:

  • Progressive Supranuclear Palsy (PSP)
    • First signs include early falls and swallowing difficulties
    • Later, look for saccadic breakdown, downgaze palsy > upgaze vertical palsy, axial rigidity (in PD, this only happens in severe stages)
    • “Surprised look” on face
  • Corticobasal Degeneration (CBD)
    • Apraxia, aphasia, neglect, dystonia, and other cortical features, and striking asymmetry
  • Huntington disease
  • Normal Pressure Hydrocephalus (NPH may exhibit a classic triad of clinical findings (known as the Adams/Hakim's triad) of urinary incontinence, gait disturbance, and dementia (commonly referred to as “wet, wacky and wobbly” or “weird walking water”)
  • Tremor syndrome unrelated to Parkinson's
  • Substance Use Disorders (e.g. - alcohol withdrawal)
  • Brain lesions or mass effects

Atypical Parkinson's

Don't forget that there are atypical features in some Parkinson's patients, including:
  • Symmetry at on set
  • Lack of resting tremor
  • Dysautonomia such as urinary symptoms, retention, and erectile dysfunction
  • Poor response to levodopa (some patients may need to hit 900mg/day of Carbidopa/levodopa before their symptoms resolve)

How do we determine whether parkinsonism is due to the use of antipsychotics or Parkinson disease?

It could be both! Especially in the case in geriatric populations. If older patients have been receiving antipsychotics and develop parkinsonism, these patients may have been developing idiopathic Parkinson disease and the psychiatric symptoms may have been related. It is not always easy to tell the difference between the disease and its adverse effects. The first thing to do, if possible, is to stop the antipsychotic agent and wait 1 to 3 months to see if the symptoms resolve. In most cases, patients with parkinsonism will have a tremor of one or both hands. If it is unilateral, a resting tremor suggests idiopathic Parkinson disease, but if it is symmetric, it is difficult to determine whether it is idiopathic or medication-induced.
  • Observe for reduced facial and limb expressions and gestures (e.g. - decreased smiling and decreased affect), PD pati

ents will have fewer eye blinks the tendency to stare

  • Check for primitive reflexes
  • Check for cogwheeling (rotate the wrists) bilaterally
    • In patients with a unilateral tremor, that same wrist will have rigidity, while the other one will not.
    • Use activation techniques (tell your patient to “open and close your (contralateral) hand” and then examine the ipsilateral side for rigidity and cogwheeling)
Special Tests
  • “Chair Test” - get patient to stand up from a chair without using their arms
  • “Pull Test” - with the patient standing, the examiner stands behind the patient (with a wall behind the examiner!), put hands on the patient’s shoulders, and say “At the count of three, I’m going to pull you back a little.”
    • Normal exam: patient will take a step or two back or bend the shoulders backwards to keep maintain balance when pulled back.
    • Parkinson's: patient will either take many steps backwards (“retropulsion”), or fall over like a statue (“falling en bloc”).
Gait and Motor
  • Observe for normal arm swing - a lack of normal swinging on one or both sides is consistent with parkinsonism
  • Motor Exam
    • Check for decreased amplitude or fatiguability (meaning the patient can start with fast movements, but then the movements slow down considerably)
    • Check for foot tap, finger tap, axial rigidity
  • Festination - a gait disturbance characterized by short rapid steps
  • Check for hidden tremors using distraction techniques (ask patient to count the months backwards, or subtracting numbers - this can often bring out resting tremors)
  • Is there any reemergence of tremor when someone goes from resting their hands on their palms to moving it forward with hands facing forward in a pronator drift position?

Levodopa-induced Dyskinesia

Dyskinesia is not caused by Parkinson's Disease. Long‐term use of levodopa often results in significantly disabling fluctuations and dyskinesias known as levodopa-induced dyskinesia (LID).[8] Different types of movement disorders are seen in LID, including chorea, ballism, dystonia, myoclonus, or combination of any of these movements. These dyskinesias are seen in the neck, facial muscles, jaw, tongue, hip, shoulder, trunk, and limb or may appear as involuntary flexion of toes. These dyskinesias can often be very debilitating, and even more so than the original Parkinson's symptoms.

The main treatment for PD is levodopa, a dopamine precursor (since dopamine itself cannot cross the blood–brain barrier). When taken orally, levodopa is rapidly converted to dopamine outside the CNS. Thus carbidopa, a DOPA decarboxylase inhibitor (DDCI), is added to inhibit the conversion of levodopa to dopamine outside the CNS.

The on-off phenomenon is a consequence of sustained levodopa treatment in patients with Parkinson's disease. It is characterized by a switch between mobility and immobility, which occurs as an end-of-dose or “wearing off” worsening of motor function or, much less commonly, as sudden and unpredictable motor fluctuations.[9]

Dopamine agonists include the ergot derivatives: bromocriptine, cabergoline, dihydroergocryptine, lisuride, and pergolide. There are also the non-ergot derivatives: apomorphine, piribedil, pramipexole, ropinirole, rotigotine.

Dopamine agonist withdrawal syndrome (DAWS) is a complication that affects up to 19% of PD patients who undergo a dopamine agonist taper. It was initially described in 2010 as a severe stereotypical cluster of psychiatric and physical symptoms occurring with dopamine agonist withdrawal.[10][11] The symptoms of DAWS include anxiety, panic attacks, dysphoria, depression, agitation, irritability, suicidal ideation, fatigue, orthostatic hypotension, nausea, vomiting, diaphoresis, generalized pain, and drug cravings.

For Providers