In this post, we will discuss the etiology and clinical features of restless legs syndrome, essential tremor, and Parkinson’s disease.
Introduction to Movement Disorders
Anyone can exhibit a physiologic tremor. Typically, these are not persistent. Tremors become abnormal when they are persistent and affect normal functioning. Abnormal tremors can be a sign of many diseases, not just neurological disorders.
Restless Leg Syndrome (RLS)
This is typically characterized by restlessness in the lower extremities, especially during inactivity (at night), but this is not always so. Symptoms can vary a lot from patient to patient. The treatment of RLS is mainly symptomatic.
The pathogenesis of RLS is unclear. There are no structural changes in nerves or nerve endings that can identify RLS. The low iron level has been associated with RLS, but not always. Current RLS hypotheses suggest abnormalities in the central dopaminergic, opiate, or GABA activities, which is why medications that target DA and GABA are the mainstay treatments of RLS.
RLS affects up to 3% of the general population. It tends to affect women more than men. Having a family history of RLS is associated with an earlier onset of RLS, and being older is associated with neuropathic pain RLS.
Diagnosing Restless Leg Syndrome
The diagnosis is made based on the clinical history of restlessness, compelling urge to move, and peripheral sensation. In some patients, there may be involuntary rhythmic brief contractions of the legs during sleep (periodic limb movement.)
There are four elements for diagnosing RLS: a compelling urge to move limbs, motor restlessness, circadian variation, and worsening symptoms.
Many patients also experience insomnia and daytime fatigue due to poor sleep quality, which leads to reduced quality of life and increase risk of suicide.
There are two types of RLS: primary (idiopathic) and secondary RLS (iron deficiency, pregnancy, ESRD, alcohol, and caffeine.) Primary RLS is more common than secondary RLS.
There are medications that can worsen RLS, such as diphenhydramine, phenytoin, SSRI, beta-blockers, lithium, H2-blockers, and neuroleptics.
It is important to note that RLS is not the same as nocturnal leg cramps, akathisia, and peripheral neuropathy.
Essential Tremor
Essential tremor is a pathologic tremor of the upper extremities, head, and voice. Like restless leg syndrome, mortality is unaffected, but there can be social and functional disabilities.
The incidence increases with older age, and it affects males and females equally. The average onset is 45 years of age. 50-70% have relatives with essential tremors, which is why it is also known as “familial tremors.” 20% of individuals with essential tremors will go on to develop Parkinson’s.
The etiology is unknown, and it is not secondary to other conditions. There is no structural lesion of the brain, but neuroimaging studies support the theory that abnormal tremorogenic activity originates in the cerebellum. While it is not yet confirmed, it is thought that adrenergic and GABA systems are involved.
Diagnosing Essential Tremor
Similar to RLS, the diagnosis is made based on clinical findings, which include family history and tremor assessment (bilateral action tremor of upper extremities – hallmark symptom).
The head and voice can sometimes be affected. The disease starts as intermittent but becomes persistent over time.
The core criteria include bilateral postural tremor, isolated head tremor, and absence of other neurologic signs.
The secondary criteria include a duration greater than 3 years, positive family history, and a positive response to alcohol.
Lab and imaging are not routinely recommended unless the presentation is suggestive of other conditions.
When the individual is diagnosed, they are usually given a disability scoring that ranges from absent to severe.
Parkinson’s Disease (PD)
PD is the 2nd most common chronic neurodegenerative disorder and the 3rd most common movement disorder. The onset is usually between 55-65 years and is more prevalent in males than females.
Like Alzheimer’s, there is neuronal toxicity with oxidative stress, environmental toxins, viral infection, and some genetic predisposition.
Interestingly, nicotine and caffeine may confer some protective property against developing Parkinson’s Disease.
Parkinson’s Disease Pathophysiology
The loss of dopaminergic neurons in the substantial nigra leads to DA depletion in the striatum. This disrupts the balance between DA and ACh where DA decreases and ACh increases. This also disrupts the balance between DA and adenosine where there is overactive adenosine as well. Adenosine works to suppress the movement, and dopamine helps initiates movement.
The threshold for the onset of symptoms is over 80% loss of functioning neurons. There are also a loss of pigment in the substantial nigra and the presence of Lewy bodies.
Diagnosing Parkinson’s Disease
The only way to diagnose PD for certain is with an autopsy, but clinically, it can also be made with the presence of cardinal features, such as bradykinesia with tremor or rigidity.
It is important to rule out other diagnoses, such as drug-induced parkinsonism, essential tremor, Wilson’s disease, and Huntington’s disease.
Drug-Induced Parkinsonism
This is a reversible condition that occurs within 3 months of the insults, such as antipsychotics, metoclopramide, methyldopa, and anti-emetics. It is known as “pseudo parkinsonism.” Older women are at the greatest risk. When this happens, discontinue the agent and switch to another.
If the agent cannot be discontinued, benztropine and trihexyphenidyl can be used to help combat the ADRs.
The symptoms generally resolve within 2 weeks to months.
PD Clinical Presentation
The early symptoms include fatigue, malaise, and mild shakiness. Family members may notice hypophonia, micrographia (writing becomes small), and bradykinesia. This early period may last for a long time.
Bradykinesia may eventually progress to become dyskinesia.
Parkinson’s Disease will lead to complete incapacitation.
The cardinal features of PD are TRAP: Tremor, Rigidity, Akinesia, and Postural Instability.
Tremor (40-70%) – PD tremors are characterized by unilateral, pin-rolling tremors. PD tremors occur at rest, which is why it’s called resting tremors, but it is absent during sleep.
Rigidity – This is characterized by ratchet-like, short, jerky movement. This is also known as cogwheel rigidity. Some patients experience loss of tonic reflexes, such as diminished facial expression (masking), infrequent blinking, and drooling.
Akinesia/Bradykinesia – Akinesia is the absence of movement that is generally preceded by bradykinesia (the slowing down.)
Postural Instability – This is an impaired balance and coordination characterized by shuffling gait and start hesitation. This increase the risk of fall.
Other symptoms include depression, loss of smell, memory loss, autonomic disturbances, skin problems, and sleep problems.
The Hoehn and Yahr Staging System and UPDRS
This is a staging system ranging from 0 (no signs of PD) to stage 5 where the disease has fully -developed and the patients are in wheelchairs or bed restricted.
The Unified Parkinson Disease Rating Scale (UPDRS) is now being used in place of the Hoehn and Yahr Staging.