By Marcello Cherchi, MD PhD
For patients
Parkinson’s disease causes slowness of movement, a particular pattern of tremor, muscle stiffness and imbalance. The diagnosis is based on a patient’s history and physical examination. Parkinson’s disease needs to be distinguished from other parkinsonian disorders (that may look similar to Parkinson’s disease, but are not actually Parkinson’s disease), and this distinction is not always obvious early in the disease course. Parkinson’s disease usually starts slowly and progresses gradually. Onset of symptoms is usually after age 50 years. Remaining physically active helps a person’s level of function. The initial treatment for Parkinson’s disease includes medications. If those fail, then some patients may be candidates for invasive treatments such as deep brain stimulation. A general neurologist or a movement disorders specialist usually diagnoses and manages Parkinson’s disease.
For clinicians
Overview
Idiopathic Parkinson’s disease (IPD) is the most common movement disorder. It results from cell death of dopamine-producing neurons in the substantia nigra. Symptoms start insidiously and progress gradually. The stereotypical presentation on physical examination includes bradykinesia, tremor, rigidity and postural instability. Ocular motor examination may identify convergence insufficiency. The differential diagnosis includes other parkinsonian disorders. The most common pharmacotherapy is carbidopa-levodopa; less common approaches include amantadine and COMT inhibitors. Invasive therapies include deep brain stimulation and ablative procedures (thalamotomy, pallidotomy). With treatment, many patients can maintain an acceptable level of function with nearly normal life expectancy. The management of Parkinson’s disease is often initiated by a general neurologist, and if it proves difficult to control, then referral to a movement disorders specialist is appropriate.
The role of otoneurology is limited in idiopathic Parkinson’s disease (IPD). If a patient originally suspected of having IPD is failing to respond to therapy, then they are sometimes referred to otoneurology. In this situation, the role of the otoneurologist is usually to help distinguish IPD from other parkinsonian syndromes. The usual example in this circumstance is when the appearance of specific ocular motor findings begins to increase the suspicion for progressive supranuclear palsy and lower the suspicion for IPD.
Introduction
In 1817 the English physician, Dr. James Parkinson (1755 – 1824), published, “An essay on the shaking palsy” (Parkinson 1817), and this is usually credited as the first clinical description of this entity. During life this is a clinical diagnosis, based on the history (gradually progressive symptoms), cardinal physical examination findings (bradykinesia, tremor, rigidity, and postural instability) and the absence of evidence for an alternative cause of parkinsonism. This is called idiopathic Parkinson’s disease (IPD).
Epidemiology
IPD is the most common movement disorder. The prevalence of IPD is 1 – 2 per 1000 people (von Campenhausen, Bornschein et al. 2005). The onset of IPD younger than age 50 years is uncommon. IPD affects 1% of the population age 60 years and up (de Lau and Breteler 2006) and up to 4% in the highest age groups (de Rijk, Launer et al. 2000).
Etiology
The majority of cases of Parkinson’s disease have no identifiable underlying cause, and these cases are classified as idiopathic.
Perhaps 5% of cases have genetic causes. Mutations in the LRRK2 (leucine-rich repeat kinase) account for the bulk of genetic cases (Gilks, Abou-Sleiman et al. 2005).
Pathophysiological mechanism of disease
IPD is due to cell death of dopamine-producing neurons in the substantia nigra pars compacta.
Clinical presentation
Symptoms start insidiously and progress gradually.
Some familial forms of parkinsonism may present at an earlier age.
Some non-motor symptoms of IPD may occur years prior to the onset of motor symptoms. The main prodromal symptoms include hyposmia (Haehner, Hummel et al. 2007) and REM sleep behavior disorder (Haehner, Hummel et al. 2007).
Physical examination
Classically patients with IPD exhibit:
- Bradykinesia, meaning that their movements are reduced in velocity and amplitude; this applies to appendicular movements (e.g., small handwriting), pharyngeal movements (e.g., reduced volume of voice), facial movements (masked facies), stance (narrow base), ambulation (e.g., reduced stride length, reduced arm swing, shuffling).
- Tremor. This is present to varying degrees. It often presents asymmetrically. The appendicular tremor is present at rest (e.g., when a patient is sitting quietly, or when walking with arms at the sides), and is often described as a “pill rolling tremor,” referring to the regular oscillatory pronation-supination movement of the forearm. Vocal tremor and head tremor may also be present.
- Rigidity. This refers to resistance to passive movement detected on physical examination. So-called “cogwheel rigidity” can be detected as rhythmic intermittent resistance to passive rotation at the wrists and is due to underlying tremor.
- Postural instability. This is due in part to bradykinesia, and in part to reduced reflex postural adjustments in response to unexpected perturbations. It can be detected on the “pull test,” in which an examiner gently but quickly pulls the patient backwards at the shoulders; in response to this a healthy person will usually place one heel further backwards for support, whereas a patient with IPD will fail to make this postural adjustment and will simply fall backwards.
Posture is usually stooped.
The diagnostic criteria for IPD have evolved. At one point postural instability was considered one of the cardinal symptoms (Gelb, Oliver et al. 1999), but this was subsequently relegated to a “supportive” finding (Postuma, Berg et al. 2015).
Ocular motor examination
Patients with IPD often exhibit convergence insufficiency to variable degrees.
Testing: ocular motor
Instrumented ocular motor testing, such as videonystagmography (VNG), may show findings not detectable on face-to-face examination. Compared to controls, IPD patients have prolonged saccadic latency, decreased saccadic accuracy, and reduced gain on smooth pursuit (Zhou, Wang et al. 2022). Some research has also explored whether the degree of square wave jerks can help distinguish IPD from other parkinsonian disorders (Rascol, Sabatini et al. 1991).
Testing: video head impulse testing (vHIT)
Research on video head impulse testing (vHIT) in IPD has provided conflicting results. Some investigators find no difference in the vestibulo-ocular reflex (VOR) gain on vHIT (Hawkins, Rey-Martinez et al. 2021, Hawkins, Chiarovano et al. 2022), while other researchers report reduced VOR gain (Lv, Guan et al. 2017, Berkiten, Tutar et al. 2023). Other vHIT protocols, such as the SHIMP (suppression head impulse) paradigm, are reportedly abnormal in IPD patients (Hawkins, Rey-Martinez et al. 2021).
Testing: vestibular evoked myogenic potentials (VEMPs)
Vestibular evoked myogenic potentials (VEMPs) may be abnormal in IPD.
Scarpa and colleagues (Scarpa, Cassandro et al. 2020) studied 15 IPD patients and found cVEMPs responses were absent bilaterally in 47% and absent unilaterally in 13%. Bertiken and colleagues (Berkiten, Tutar et al. 2023) studied 40 IPD patients and found cVEMPs responses generally had lower amplitudes; responses were absent bilaterally in 20% and unilaterally in 15%.
IPD patients may have abnormal cVEMP latencies, but not in a consistent pattern. For example, Scarpa and colleagues (Scarpa, Cassandro et al. 2020) reported that the p13 latency was significantly increased, whereas Bertiken and colleagues (Berkiten, Tutar et al. 2023) reported that the p13 latency was decreased.
Berkiten and colleagues (Berkiten, Tutar et al. 2023) studied 40 IPD patients and reported that oVEMP responses generally had lower amplitudes; responses were oVEMPs were absent bilaterally in 15% and unilaterally in 13%.
Testing: computerized dynamic posturography (CDP).
Computerized dynamic posturography (CDP) often quantifies postural instability in IPD patients (Visser, Oude Nijhuis et al. 2010, Ebersbach and Gunkel 2011, Lee, Koh et al. 2012, Johnson, James et al. 2013, Nonnekes, de Kam et al. 2013, Rossi-Izquierdo, Basta et al. 2014, Souza, Voos et al. 2019), but the pattern is not specific for IPD.
Testing: other
The sense of smell is often reduced in IPD (Haehner, Hummel et al. 2007).
Autonomic testing may show some degree of dysfunction. For example, tilt table test may show orthostatic hypotension in patients with IPD.
Imaging
A standard brain MRI will not confirm IPD, but may help exclude competing diagnoses; for example, infarctions involving the basal ganglia may suggest vascular parkinsonism; midbrain atrophy (sometimes called the “hummingbird sign”) suggests progressive supranuclear palsy.
In 2011 the FDA approved the radiopharmaceutical agent ioflupane I 123 for SPECT (single photon emission computed tomography) scans; this agent contains a radioactive isotope of iodine (I‑123) which has a high binding affinity for presynaptic dopamine transporters, and its decay can be detected by a gamma camera. This nuclear medicine procedure can visualize striatal dopamine transporter uptake, and thus is known as a DaT scan (dopamine transporter scan). It can help distinguish some parkinsonian syndromes (idiopathic Parkinson’s disease, progressive supranuclear palsy and multiple systems atrophy) from others.
Histopathology
Histopathology shows Lewy bodies (accumulation of alpha synuclein) and loss of dopaminergic cells in the substantia nigra. With disease progression, the Lewy bodies spread outside of the substantia nigra towards the cerebral cortex.
Differential diagnosis
The differential diagnosis of IPD is that of other parkinsonian disorders. Early in these diseases they can be difficult to distinguish.
A favorable (and sustained) response to levodopa is strongly suggestive of IPD, as other parkinsonian disorders do not respond to that medication.
Exclusion criteria (Tysnes and Storstein 2017) for IPD are the presence of prominent cerebellar abnormalities (which suggests olivopontocerebellar atrophy), the presence of supranuclear gaze palsy (which suggests progressive supranuclear palsy), the presence of frontotemporal cognitive changes (which suggests Lewy body disease) and other cognitive findings such as apraxia (which suggests corticobasal ganglionic degeneration), absence of any response to levodopa therapy, and a normal DaT scan.
“Red flag” criteria which lower the suspicion for IPD (Tysnes and Storstein 2017)are early gait impairment, absence of progression, early bulbar dysfunction, inspiratory respiratory dysfunction, severe autonomic failure during the virst year of the disease, recurrent falls due to reduced balance, early antecollis, pyramidal tract signs, bilateral symmetric parkinsonism, and the absence of any of the common non-motor features of PD (such as sleep disturbances, autonomic dysfunction or hyposmia).
Treatment
The most widely used treatment for IPD is carbidopa-levodopa. Other pharmacologic agents used include amantadine and inhibitors of COMT (catechol‑O‑methyltransferase). Problems with pharmacologic treatment of IPD include that (1) the efficacy of these drugs tends to decrease as the disease progresses; (2) the drugs are associated with symptom fluctuation; (3) the drugs often have side effects.
If pharmacotherapy fails, then invasive treatments may be considered in selective patients. These include deep brain stimulation, and ablative procedures (thalamotomy, pallidotomy).
Unfortunately, the postural instability is the feature that tends to be least responsive to treatment.
There is evidence that physical activity may help preserve the level of function for a patient with IPD.
Prognosis
The treatment of IPD has improved over the years, and most patients can preserve a reasonable level of function with nearly normal life expectancy.
References
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