Please confirm that you would like to log out of Medscape.
If you log out, you will be required to enter your username and password the next time you visit.
Log outCancel
Parkinsonism: Not Just a Motor Problem
Sumaira Nabi, MBBS, FCPS | June 12, 2020
| Contributor Information
Swipe to advance
Image by Nejron | Dreamstime.
Parkinsonism: Not Just a Motor Problem
Sumaira Nabi, MBBS, FCPS | June 12, 2020 | Contributor Information
Parkinson disease (PD) is the second most common neurodegenerative disorder, after Alzheimer disease. Its incidence and prevalence rise with advancing age. PD typically affects individuals older than 60 years; approximately 1% of individuals in this age group are affected by the disease, and the rate is almost 3% in those older than 80 years.[1] The hallmark features of PD are progressively worsening disability and increasing dependence. A wide range of medications and therapies are capable of slowing down the progression of disability and controlling the symptoms to some extent; unfortunately, there is no well-established cure. Monoamine oxidase (MAO)-B inhibitors are thought to have a neuroprotective role, but substantial evidence is lacking, and no disease-modifying agent has yet been found.
Image courtesy of Waleed Shahzad, MBBS.
Parkinsonism: Not Just a Motor Problem
Sumaira Nabi, MBBS, FCPS | June 12, 2020 | Contributor Information
PD is a complex clinical disorder characterized by a variety of features, including both motor and nonmotor symptoms.[1,2] It was first described as the "shaking palsy" by James Parkinson in 1817. It was then further elaborated by Jean-Martin Charcot.
The cardinal findings involve the motor system. In 70% of patients, the presenting feature is the characteristic asymmetric distal 4- to 6-Hz resting tremor (shown), also known as the pill-rolling tremor, which progressively spreads to involve the other extremities as well.
Other features include bradykinesia or poverty of movement, lead pipe and cogwheel rigidity, postural instability and falls, motor blocks, and freezing. The gait is short-stepped and festinating, with a stooped posture and poor arm swing.
Image courtesy of Waleed Shahzad, MBBS.
Parkinsonism: Not Just a Motor Problem
Sumaira Nabi, MBBS, FCPS | June 12, 2020 | Contributor Information
Persons with PD have reduced facial expression, also known as hypomimia, which produces the characteristic "masklike" facies. They have poor expression of happiness, anger, and surprise. They also have reduced eye blinking and sometimes have a fixed stare. In addition, they have difficulty interpreting the emotional facial expressions produced by others around them.
(The image was taken with the permission of the patient.)
Image courtesy of Medscape.
Parkinsonism: Not Just a Motor Problem
Sumaira Nabi, MBBS, FCPS | June 12, 2020 | Contributor Information
Although the exact cause of PD remains unknown, various genetic and environmental factors are thought to be implicated in the pathogenesis. Pathologically, PD is marked by the loss of pigmented dopaminergic neurons in the pars compacta substantiae nigrae and the locus caeruleus in the midbrain and by the presence of Lewy bodies.
The loss of dopamine neurons leads to bradykinesia and poverty of movement. Excessive unopposed production of acetylcholine by the caudate nucleus and consequent increased acetylcholine action leads to tremors. By the time motor symptoms begin, nearly 60-80% of dopaminergic neurons may have degenerated. The image shows the gross appearance of the substantia nigra in a normal brain (left) compared with that of a brain affected by PD (right), in which loss of pigmentation in the substantia nigra can be seen.
Image courtesy of Medscape.
Parkinsonism: Not Just a Motor Problem
Sumaira Nabi, MBBS, FCPS | June 12, 2020 | Contributor Information
On histopathologic examination, in addition to the loss of melanin-containing neurons in the substantia nigra and the locus caeruleus (left), the presence of Lewy bodies (eosinophilic cytoplasmic inclusions with halos containing alpha-synuclein) may be noted in the remaining neurons (right, arrow).
Image courtesy of Wikipedia.
Parkinsonism: Not Just a Motor Problem
Sumaira Nabi, MBBS, FCPS | June 12, 2020 | Contributor Information
The basal ganglia (red highlight) are a group of nuclei in the subcortical area that are involved in control of motor movement and have extensive connections with other areas of the brain. A complicated interplay of neurotransmitters modulates motor activity, with dopamine acting as the inhibitory neurotransmitter while acetylcholine has an excitatory role. Dopamine depletion, as occurs in PD, results in bradykinesia and poverty of movement.[2] In addition, loss of dopamine's inhibitory signals leads to unopposed excitation mediated by acetylcholine. The resulting overstimulation of the neurons of the basal ganglia causes tremors and rigidity.
Image courtesy of Sumaira Nabi, MBBS, FCPS.
Parkinsonism: Not Just a Motor Problem
Sumaira Nabi, MBBS, FCPS | June 12, 2020 | Contributor Information
Levodopa, a dopamine precursor, is the gold standard for symptomatic treatment of PD. It is combined with carbidopa, a peripheral decarboxylase inhibitor. Other dopamine agonists (eg, ropinirole) also provide symptomatic improvement, crossing the blood-brain barrier to reduce motor symptoms. Levodopa is now also available in inhaler form (Inbrija). These drugs provide adequate improvement in PD features for 4-6 years. In March 2017, safinamide was approved by the US Food and Drug Administration (FDA) for use as an add-on treatment for PD. It has multiple modes of action, including inhibition of MAO-B.[3] Another drug, istradefylline, was approved by the FDA in 2019. To date, no disease-modifying therapy has been established. Surgery is another option for controlling motor signs.
Image courtesy of Wikipedia.
Parkinsonism: Not Just a Motor Problem
Sumaira Nabi, MBBS, FCPS | June 12, 2020 | Contributor Information
A 67-year-old man who has had PD for 7 years presents with increased urinary frequency and urgency. Urinalysis and culture yield unremarkable results. Ultrasonograms of the kidneys, ureters, bladder, and prostate are also normal.
Which of the following is the most likely cause of these symptoms?
Benign prostatic hyperplasia
Urinary tract infection
Autonomic dysfunction
Nephrolithiasis
Image courtesy of Carloscastilla | Dreamstime.
Parkinsonism: Not Just a Motor Problem
Sumaira Nabi, MBBS, FCPS | June 12, 2020 | Contributor Information
Answer: C. Autonomic dysfunction.
As discussed earlier, PD is primarily a disorder of motor dysfunction, traditionally characterized by tremor, bradykinesia, and rigidity. Being a neurodegenerative disease, it follows a progressive and protracted course that gives rise to significant disability. However, the disease is also characterized by a wide spectrum of nonmotor symptoms (shown), which are present in almost every patient. These symptoms may start as early as 12-14 years before the onset of motor symptoms. Depression is the most common of these nonmotor symptoms; others that may be noted include cognitive impairment, sleep disorders, dysautonomia (orthostatic hypotension, constipation, and urinary dysfunction), hyposmia, pain, and fatigue.[2] These complications contribute to disease severity and lead to deterioration in the patient's quality of life. Accordingly, they must be properly evaluated and appropriately managed.
Image by William Richard Gowers after St Leger, courtesy of Wikipedia.
Parkinsonism: Not Just a Motor Problem
Sumaira Nabi, MBBS, FCPS | June 12, 2020 | Contributor Information
A 70-year-old man presents with a 1-year history of left shoulder pain and gait difficulty. He does not swing his left arm when he walks and has had difficulty using this hand to manipulate buttons. The patient also reports constipation and falling out of bed during vivid dreams for 6 years before the onset of gait difficulty.
Which of the following is the most likely imaging finding in this patient, given the probable diagnosis?
Normal results on magnetic resonance imaging (MRI) of the brain
Increased uptake of dopamine on a dopamine transporter (DaT) scan
Contrast enhancement of basal ganglia on MRI of the brain
Bilateral T2 hyperintensities in the periventricular white matter on MRI
Image courtesy of Medscape.
Parkinsonism: Not Just a Motor Problem
Sumaira Nabi, MBBS, FCPS | June 12, 2020 | Contributor Information
Answer: A. Normal results on magnetic resonance imaging (MRI) of the brain.
PD has long been a clinical diagnosis, and until relatively recently, there were no diagnostic investigations thought to be specific for diagnosing this condition. Even today, the true diagnosis can be made only from postmortem examination of the affected brain tissue. Computed tomography (CT) and MRI of the brain usually yield normal findings and are performed to exclude conditions that can mimic PD but are potentially treatable, such as stroke, normal-pressure hydrocephalus, Wilson disease, and tumors. MRI of the brain is particularly helpful in PD surgery to identify sites for electrode placement and to ensure the accuracy of placement. The cross in the slide marks the position for placement of a thalamic stimulator. Positron emission tomography (PET) may show a decrease in fluorodopa.
The DaTscan single-photon emission CT (SPECT) imaging technique is now approved in the United States for assessing patients with PD symptomatology. DaT has the function of reuptaking dopamine from the synaptic cleft. DaTscan imaging uses iodine-123 ioflupane, which binds to the DaT in the striatum. SPECT is then used to visualize the quantity of transporters present. DaT has an important function in maintaining the presynaptic neuron and is reduced to 50-70% in patients with PD. DaTscan has a high specificity for PD and detects nigrostriatal dopaminergic degeneration.[4]
Image courtesy of Medscape.
Parkinsonism: Not Just a Motor Problem
Sumaira Nabi, MBBS, FCPS | June 12, 2020 | Contributor Information
A 62-year-old patient with an 8-year history of PD treated with levodopa presents with a significant wearing-off effect and dyskinesia despite initial good response to medication. On examination, the patient has a masklike facies and marked resting tremor in both upper extremities. There is no rigidity or cognitive impairment.
For which of the following treatments should this patient now be considered a candidate?
Deep brain stimulation (DBS)
Thalamotomy
Pallidotomy
Stem-cell transplant
Image courtesy of Medscape.
Parkinsonism: Not Just a Motor Problem
Sumaira Nabi, MBBS, FCPS | June 12, 2020 | Contributor Information
Answer: A. Deep brain stimulation (DBS).
Surgical options in PD include thalamotomy, pallidotomy, and DBS. All levodopa-responsive features of PD can improve with DBS; however, this procedure is not curative and does not alter the course of the disease.[5] Patients who have had levodopa-responsive idiopathic parkinsonism for 5 years or longer and are experiencing disabling side effects should be considered candidates for DBS. Dementia and depression must be excluded clinically. The medication dosage may be reduced after surgery. DBS is a stereotactic procedure during which electrodes are placed in the subthalamic nuclei or the globus pallidus and are connected to a pulse generator below the clavicles. Electrostimulation is used to overcome the abnormal currents generated in the circuitry involved in PD.
Images courtesy of Sumaira Nabi, MBBS, FCPS (left, center), and Cenorman | Dreamstime (right).
Parkinsonism: Not Just a Motor Problem
Sumaira Nabi, MBBS, FCPS | June 12, 2020 | Contributor Information
Parkinson-Plus Syndromes
A 62-year-old woman presents with a 3-year history of bradykinesia and rigidity of all four extremities. She was diagnosed with parkinsonism and has been taking levodopa-carbidopa. For the past 6 months, she has been experiencing hyperhidrosis and urinary incontinence. On examination, the patient has significant orthostatic (postural) hypotension. T2-weighted MRI of the brain (axial view) shows the so-called hot cross bun sign in the pons.
Which of the following is the most likely diagnosis?
Progressive supranuclear palsy (PSP)
Shy-Drager syndrome
Stroke
Central nervous system tuberculosis
Images courtesy of Sumaira Nabi, MBBS, FCPS.
Parkinsonism: Not Just a Motor Problem
Sumaira Nabi, MBBS, FCPS | June 12, 2020 | Contributor Information
Answer: B. Shy-Drager syndrome.
Parkinson-plus syndromes are a set of disorders characterized by parkinsonian features in conjunction with additional signs and symptoms, such as dementia, early onset of falls, and eye signs.[6] Another typical finding is poor response to standard antiparkinsonian medications such as levodopa and ropinirole. Clinically, there are five Parkinson-plus syndromes, each of which has its characteristic features: (1) multiple system atrophy (MSA), (2) PSP, (3) parkinsonism–dementia–-amyotrophic lateral sclerosis complex, (4) corticobasal degeneration (CBD), and (5) dementia with Lewy bodies (DLB). MSA has been used as a common term for a set of syndromes that includes olivopontocerebellar atrophy (OPCA), striatonigral degeneration (SND), and Shy-Drager syndrome. (According to a current consensus, MSA can be divided into two main categories, MSA with predominant parkinsonism [MSA-P] and MSA with cerebellar features [MSA-C].[7]) Shy-Drager syndrome is a combination of parkinsonism with autonomic dysfunction (eg, orthostatic hypotension or hyperhidrosis). T2-weighted MRI of the brain in patients with MSA shows the hot cross bun sign in axial views of the pons (see slide 14). Selective degeneration of pontocerebellar tracts gives rise to a hyperintense cross, which is the source of the comparison to the well-known pastry.[8]
Image courtesy of Haralur SB | NLM NIH.
Parkinsonism: Not Just a Motor Problem
Sumaira Nabi, MBBS, FCPS | June 12, 2020 | Contributor Information
A 65-year-old man presents with a 10-year history of progressively worsening generalized body stiffness, recurrent falls, visual disturbance, and slurred speech. On examination, besides bradykinesia and rigidity, the patient also has retrocollis and vertical gaze palsy. His face is masklike, and his speech is monotonous. Glabellar tap is present. He has been using levodopa-carbidopa for 5 years without any significant improvement in his clinical condition. T1-weighted MRI of the brain (sagittal view) shows the so-called hummingbird (or penguin) sign.
Which of the following is the most likely diagnosis?
PSP
Stroke
Motor neuron disease
Paralysis agitans
Images courtesy of Medscape / Howard Cheek | Dreamstime.
Parkinsonism: Not Just a Motor Problem
Sumaira Nabi, MBBS, FCPS | June 12, 2020 | Contributor Information
Answer: A. PSP.
PSP (also known as Steele-Olszewski-Richardson disease) has features of idiopathic PD with marked postural instability, axial rigidity, vertical gaze dysfunction (especially of downgaze), and pseudobulbar palsy.[9] Patients with PSP respond poorly to antiparkinsonian treatment. They have a characteristic look, with masked facies, lid retraction, and axial rigidity yielding a startled appearance (see slide 16). The appearance of the brainstem on T1-weighted brain MRI (sagittal view) resembles that of a hummingbird (or, in the eyes of some viewers, a penguin).[10] Atrophy of the midbrain is seen, with preservation of the pons.
Image courtesy of Medscape.
Parkinsonism: Not Just a Motor Problem
Sumaira Nabi, MBBS, FCPS | June 12, 2020 | Contributor Information
A 71-year-old man presents with a 4-year history of memory impairment and recurrent visual hallucinations. Since being diagnosed 5 years ago as having PD with bradykinesia and rest tremors, he has been taking medications daily, including levodopa-carbidopa and ropinirole. His Mini-Mental Status Examination (MMSE) score is 14 (out of a maximum of 30). MRI of the brain reveals global cerebral atrophy. Administration of rivastigmine yields improvement with respect to the visual hallucinations and memory loss.
Which of the following is the most likely diagnosis?
Alzheimer disease
Vascular dementia
Parkinson disease dementia
Normal-pressure hydrocephalus
Image courtesy of Sumaira Nabi, MBBS, FCPS.
Parkinsonism: Not Just a Motor Problem
Sumaira Nabi, MBBS, FCPS | June 12, 2020 | Contributor Information
Answer: C. Parkinson disease dementia.
Dementia is another nonmotor complication encountered in patients with PD.[11] Two forms of dementia are seen in association with PD: Parkinson disease dementia (PDD) and Lewy body dementia (dementia with Lewy bodies [DLB]). In PDD, the signs and symptoms of PD precede the onset of dementia by at least 1 year. In DLB, the onset of dementia is almost simultaneous with the onset of parkinsonian features. In PDD, MRI of the brain may show nonspecific cortical atrophy. Several different scales are used to diagnose and grade the severity of dementia. Of these, the MMSE (shown) is the most commonly employed tool.
Image courtesy of Wikipedia.
Parkinsonism: Not Just a Motor Problem
Sumaira Nabi, MBBS, FCPS | June 12, 2020 | Contributor Information
Other Conditions
An 18-year-old male presents with history of manic episodes, hand tremors, and gait disorder. On examination, he has cogwheel rigidity, pill-rolling tremors, and slightly icteric sclerae. Slit-lamp examination reveals Kayser-Fleischer (K-F) rings in the superior margins of both corneas.
Which of the following is the likely diagnosis?
Sydenham chorea
Wilson disease
Huntington disease
Systemic lupus erythematosus
Image courtesy of Soban Khan, MBBS.
Parkinsonism: Not Just a Motor Problem
Sumaira Nabi, MBBS, FCPS | June 12, 2020 | Contributor Information
Answer: B. Wilson disease.
Wilson disease generally presents at an early age and is characterized by psychiatric, neurologic, and hepatic features, alone or in combination. It is one of the causes of parkinsonian features in the young age group. The gait is irregular and interrupted, like that of a marionette. Each step is accompanied by different movements involving the limbs, trunk, and neck, with jerking and twisting.[11]
The above T2-weighted MRI brain images show the "double panda sign" characteristic of Wilson disease. The abnormalities in the midbrain constitute the "face of the giant panda" (left) while a second "miniature panda" can be seen in the high-signal abnormality in the pons (right).
Image courtesy of Wikipedia | NEUROtiker.
Parkinsonism: Not Just a Motor Problem
Sumaira Nabi, MBBS, FCPS | June 12, 2020 | Contributor Information
Advances in Management
A pump device has been devised to provide jejunal delivery of levodopa via direct infusion. A long-acting formulation of levodopa has also been developed. Both of these aim at improving the symptomatic control of motor manifestations of PD. Opicapone and safinamide have been approved for management of the "off" phenomenon seen in patients on levodopa. For motor wearing-off, the adenosine 2A receptor antagonist istradefylline was approved in Japan in 2015 and subsequently by the FDA in 2019. The hardware and software of DBS are constantly being improved. Multiple trials of potential disease-modifying agents are being conducted. Immune therapy and stem cell therapy are also being evaluated.
E-Cigarettes: What Healthcare Professionals Need to Know
Since 2007, e-cigarettes and novel nicotine products have significantly shifted the US tobacco/nicotine market and how tobacco products are used. Improve your understanding of e-cigarettes and vaping, as well as how patients use these products and how to talk to patients about them.Medscape Reference Slideshow, June 2020
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.Medscape Drugs & Diseases, June 2020
Commenting is limited to medical professionals. To comment please Log-in.
Comments on Medscape are moderated and should be professional in tone and on topic. You must declare any conflicts of interest related to your comments and responses. Please see our Commenting Guide for further information. We reserve the right to remove posts at our sole discretion.
Comments on Medscape are moderated and should be professional in tone and on topic. You must declare any conflicts of interest related to your comments and responses. Please see our Commenting Guide for further information. We reserve the right to remove posts at our sole discretion.
Close
Contributor Information
Author
Sumaira Nabi, MBBS, FCPS
Assistant Professor and Consultant Neurologist Department of Neurology
Pakistan Institute of Medical Sciences
Islamabad, Pakistan
Disclosure: Sumaira Nabi, MBBS, FCPS, has disclosed no relevant financial
relationships.
Editors
Olivia Wong, DO
Section Editor
Medscape Drugs & Diseases
New York, New York
Disclosure: Olivia Wong, DO, has disclosed no relevant financial relationships.
John Heinegg, RN
Section Editor
Medscape Drugs & Diseases
New York, New York
Disclosure: John Heinegg, RN, has disclosed no relevant financial
relationships.
Ceravolo R et al. Nonmotor symptoms in Parkinson's disease: the dark side of the moon. Future Neurology. 2010;5(6):851-71. Available at http://www.medscape.com/viewarticle/734227.
De Cock VC et al. Sleep disturbances in patients with parkinsonism. Nat Clin Pract Neurol. 2008 May;4(5):254-66. [PMID: 18398415]
Melville NA. FDA approves DaTscan for imaging of dopamine transporters. Medscape Medical News. January 18, 2011; Accessed: June 8, 2020. Available at https://www.medscape.com/viewarticle/735875.
Eggenberger ER et al. Progressive supranuclear palsy. Medscape Drugs & Diseases. October 17, 2018; Accessed: June 8, 2020. Available at http://emedicine.medscape.com/article/1151430.
Um YH et al. Visual hallucinations and amyloid deposition in Parkinson's disease dementia: a case report. Psychiatry Investig. 2016 May;13(3):364-9. [PMID: 27247605]
Please do not use this form to submit personal or patient medical information or to report adverse drug events. You are encouraged to report adverse drug event information to the FDA.
Comments