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Peripheral neuropathy and Parkinson’s disease

Today I will address the potential link between Parkinson’s disease and a common neurologic condition called peripheral neuropathy. This topic was submitted via the Suggest a Topic portal. I am grateful for your suggestions so please continue to let us know what you’d like to learn more about!
In order to understand what peripheral neuropathy is and what symptoms it can cause, we will briefly review the components of the nervous system.
Central nervous system vs. peripheral nervous system
Neurologic control of the body is very broadly divided into two systems – the central nervous system which consists of the brain and the spinal cord – and the peripheral nervous system which consists of the network of nerves that are outside the brain and spinal cord, and innervate the limbs and the organs of the body.
The peripheral nervous system is composed of three types of nerves: autonomic nerves, sensory nerves and motor nerves. Different types of nerves have varying diameters and are generally divided into those that are small and those that are large.

Autonomic nerves exert control over functions that are not under conscious direction such as respiration, heart function, blood pressure, digestion, urination, sexual function, pupillary response, and much more. This information is conveyed on small fibers.
Motor nerves carry information on limb movement from the brain and spinal cord to the limbs. This information is conveyed on large fibers.
Sensory nerves carry information on the various sensations felt by the limb to the brain and spinal cord. There are two main types of sensory nerves:

Pain and temperature fibers which are small fibers
Vibration and joint position sense fibers which are large fibers

The peripheral nervous system and Parkinson’s disease

It is well-established that the autonomic nervous system can be significantly affected in PD causing symptoms such as constipation, urinary dysfunction and orthostatic hypotension. The autonomic nerves that bring signals to the gut for example, can be directly affected by Lewy body-like accumulations and neurodegeneration. (This is not the only way that automatic functions of the body are affected in PD however. There can also be Lewy bodies and neurodegeneration in the parts of the brain that control these functions.)
What remains unclear is if motor and sensory nerves are also affected in PD.
What is peripheral neuropathy?
Peripheral neuropathy (PN) is a condition in which there is damage to peripheral nerves. Symptoms depend on which type of nerves are affected and can result in:

Weakness
Imbalance with walking
Numbness
Pain or paresthesias (sensations such as burning or tingling) in the limbs

The legs are more commonly affected than the arms because the nerves to the legs are longer than the arms and therefore more prone to damage.
Symptoms of peripheral neuropathy
The symptoms of PN can be non-specific, and a person therefore may not be able to distinguish on their own whether his/her symptoms are due to PN or another condition. PN, however, often results in specific findings on a neurologic exam, such as decreased sensation to pin prick or vibration or the lack of ability to discern which way a toe is being pointed without looking.

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Drug-induced parkinsonism

I’m so thankful to those of you who submit potential topics for my blog as it helps me understand what you would like to know more about. A frequent topic that I am asked about is symptoms of Parkinson’s disease (PD) that are caused by medications. So today, I will address drug-induced parkinsonism.
Common symptoms of drug-induced parkinsonism
The motor features of PD are often (but not always) very easy to see via a neurologic exam in a doctor’s office. Rest tremor (which is a tremor that goes away with movement, but often returns when the limb is at rest) for example, is seen in virtually no other illness and can therefore be very important in diagnosing PD. But there is one other common condition that induces the symptoms of PD, including a rest tremor, which must be considered every time PD is being considered as a diagnosis, and that is drug-induced parkinsonism.
Parkinsonism is not technically a diagnosis, but rather a set of symptoms including slowness, stiffness, rest tremor, and problems with walking and balance. This set of symptoms can be caused by PD, but also can occur as a side effect of certain prescription medications (that have nothing to do with PD).
A number of medications can cause parkinsonism because they block the dopamine receptor and thereby mimic the symptoms of PD that are caused by loss of dopamine neurons in the brain. Reviewing a patient’s medications is therefore a critical step for a neurologist when seeing someone with parkinsonism. Anti-psychotics and anti-nausea treatments make up the bulk of the problematic medications, although there are other medications that can also cause parkinsonism. The primary treatment for this type of parkinsonism is weaning off of the offending medication, if possible.
For some people, it is not possible to stop the problematic medication. For example, some people with bipolar disorder or schizophrenia have tried multiple medications to control their mental health issues and the one that works best also causes parkinsonism. In these difficult situations, some amount of parkinsonism might be tolerated in order to maximize the person’s mental health. This is a tricky clinical situation, and one that typically requires the psychiatrist and neurologist to work together to optimize the circumstances.
The connection between PD and drug-induced parkinsonism
In addition to potentially causing parkinsonism in the general population, these medications should definitely be avoided in people who have parkinsonism from other causes, such as PD. APDA has created a list of Medications to be Avoided or Used With Caution in Parkinson’s Disease. It is important to note that there are anti-psychotics and anti-nausea medications which do not cause parkinsonism and can be used safely by people with PD.
Sometimes, a person without a diagnosis of PD is prescribed a medication which leads to a side effect of drug-induced parkinsonism. The prescribing physician may stop the new medication, but the parkinsonism does not resolve. The patient remains off the medication with continuing symptoms, and eventually is given a diagnosis of PD. In this scenario, that person most likely had dopamine depletion in the brain (prior

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Planning for the What-Ifs: Sleep disorders in Advanced Parkinson’s Disease

Planning for the What-Ifs, Part Five: Sleep Disorders & Advanced Parkinson’s Disease
 Today we continue Parkinson’s Disease: Planning for the What-Ifs, a special series of posts to address both motor and non-motor issues of people with advanced Parkinson’s disease (PD). We are defining advanced PD as those who are no longer independent in their activities of daily living and require help for their self-care such as eating, bathing, dressing and toileting. Remember, PD is a very variable condition and many never reach the advanced stages. Additional background and the full introduction to the series is still available if you missed it.
In previous blogs, we’ve addressed the mental health issues in relation to advanced PD which include: cognitive decline/dementia, depression, anxiety, apathy, psychosis, mania and behavioral problems. We also addressed other topics of advanced PD including falls, extreme immobility, and drooling and swallowing difficulties and urinary and gastro-intestinal issues.
Today we will focus on sleep issues in advanced PD.
Sleep and Parkinson’s Disease
There are many sleep disorders that are associated with PD and that can be problematic throughout the disease course. These include:

Rapid eye movement (REM) behavior sleep disorder (RBD) – a sleep disorder in which the affected person is not paralyzed during dreaming (which is normally what occurs) and can therefore act out his/her dreams
Insomnia – an inability to fall asleep at the beginning of the night or in the middle of the night upon awakening
Restless leg syndrome – uncomfortable sensations, usually in the legs, which are temporarily relieved by movement of the legs
Sleep apnea – a disorder in which breathing stops and starts through the night, leading to periods of low oxygenation in the blood and frequent awakenings
Sleep fragmentation – brief arousals during sleep cause sleep to be less restful

PD medications can interfere with sleep by causing:

Nightmares and vivid dreams
Sleep attacks (falling asleep without warning)

Finally, there are motor and non-motor symptoms of PD that interfere with sleep. These include:

Anxiety
Hallucinations
Urinary frequency
Pain
Tremor
Stiffness

In addition to all the sleep issues listed above, people with PD often have fatigue, a complicated non-motor symptom of PD, characterized by a general lack of energy, which is sometimes present even in the face of what seems like intact and restful sleep. This can be due to many causes including PD medications, but can also be independent of medication use.
All of these sleep issues can continue to be problematic for the person with advanced PD. In addition, an extreme form of fatigue, or excessive daytime sleepiness (EDS), can develop. EDS is defined as an inability to maintain wakefulness during the waking day which leads to lapses into drowsiness or sleep. Care partners often report that the person with PD will sleep for large parts of the day and care partners are not sure whether or how to intervene.
Possible causes of Excessive Daytime Sleepiness:

Poor nighttime sleep – all the sleep disorders and PD symptoms that interfere with sleep that were mentioned above can lead to non-restorative sleep at night. This can in turn lead to an overwhelming urge to sleep during the day
Medication side effect (both

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Restless Leg Syndrome and Parkinson’s Disease

Restless Legs Syndrome (RLS) is a neurologic and sleep-related condition characterized by an irresistible urge to move the legs. The symptoms respond to dopaminergic medications such as dopamine agonists or levodopa, which are also used to treat Parkinson’s disease (PD), making an association between RLS and PD likely. Here we explore RLS and its potential connections with PD. This post was adapted from content originally written by Dr. J Steven Poceta, neurologist and sleep medicine specialist.

What is Restless Leg Syndrome (RLS)?

Characteristics of Restless Leg Syndrome

There are certain features of RLS that make it a unique and specific disorder.

  1. The hallmark of RLS is a feeling of restlessness, usually in the legs. The restlessness is often accompanied by additional sensations such as tingling, “creepy-crawly” or electric sensations, usually located in the legs. The symptoms are usually not restricted to the toes or feet, as in peripheral neuropathy, but rather are present more generally in the legs, often the calves or thighs.
  2. The restlessness is worse when the person is at rest or not moving. This feature makes it hard for people with RLS to get to sleep and can also interfere with the ability to sit still in order to read, relax, or do desk work.
  3. Symptoms are improved with moving, particularly walking. Unfortunately, the relief lasts only as long as the movement continues, which makes some people “pace the floor” for hours when the condition is severe. Besides walking, sometimes providing other stimuli to the legs is helpful, such as rubbing, massage, or stretching.
  4. RLS symptoms usually occur in the evening and night and are absent in the daytime. This is the reason that RLS is considered a sleep disorder. If the symptoms are present in the daytime, the intensity of the sensations are usually less than in the evening and night. Most people with the condition have the onset of the feeling in the hours after dinner and before bedtime. The restlessness might impede the onset of sleep or cause the person to wake up frequently, but usually the restlessness goes away during the latter portion of the night and is gone by morning. RLS can cause significant sleep deprivation and anxiety related to trying to fall asleep — and poor sleep can have significant ramifications on health and wellbeing.
  5. RLS can be accompanied by a related disorder called Periodic Limb Movements of Sleep (PLMS) which are repetitive leg movements that occur during sleep.

Causes of Restless Leg Syndrome

  1. Although the cause of RLS in many people remains unknown, about half of people with RLS have a family history of the condition. Despite this, no specific gene has been identified.
  2. RLS can also be secondary to other medical conditions such as iron deficiency, neuropathy and renal failure.

Parkinson’s & Restless Leg Syndrome: Using Dopaminergic Medication

Because RLS is well-treated by medications that also treat PD, it is likely that some aspect of brain dopamine function is altered in RLS. However, unlike in PD, in which the deficit in substantia nigra dopamine-producing cells can be proven in many ways, no such abnormality has been shown in RLS. For example, studies show that DaTscan results are not abnormal in RLS.

Using dopaminergic medications to treat RLS however can be tricky. In some people they can lead to a phenomenon known as augmentation, in which long term use of dopaminergic medications can worsen the symptoms – making them appear earlier in the day or migrating to the upper body in addition to the legs.

Does having RLS increase the risk of developing PD?

Since RLS affects as much as 4-10% of the US adult population, it is clear that the vast majority of those with RLS do not ever develop PD.

Despite this, it still might be the case that RLS increases the risk of subsequently developing PD. There have been many studies trying to figure this out – with conflicting results. Some studies show that there is no increased risk and others show that having RLS confers about a two-fold increased risk of developing PD over the general population.

Is RLS more common in PD?

But what about the other possibility? Do patients with PD have an increased risk of RLS over the general population? Is it the same RLS as the person without PD has, or is it different? These questions have been difficult to answer. Of course, since PD affects about 1.5% of the elderly, and RLS in about 4-10% of the population, there will be some coincidental overlap. In addition to this however, patients with PD can have sensations that feel like RLS when their dose of dopamine medication is wearing off. These sensations are not truly RLS since they do not have the key features of RLS described above (more common at night, improves with movement, etc) and fluctuate with medication timing, but they can be easily confused with RLS by the person with PD.

Studies of people with PD that assess for RLS and compare to a control group are hindered by the fact that the majority of patients with significant PD are under treatment with medications that affect RLS. Over the years, there have been multiple studies investigating whether RLS is more common in PD than in the general population. Different studies come to different conclusions. Studies conducted in which a group of people with PD are directly compared to a group of people without PD (case-control study) typically show that RLS is more common in PD than the general population.

To complicate matters, some researchers of this topic explain that the experience of people with PD is not actually RLS but rather something else called leg motor restlessness (LMR).  The difference between the two is that RLS is worse when the legs are not moving and temporarily relieved by movement whereas leg motor restlessness is not worse when the legs are not moving and not relieved by movement. LMR may be increased in people with PD, whereas true RLS may not be.

Treatment of RLS in PD

Regardless of the above discussion, it is clear that many people with PD have difficulty falling asleep because of annoying sensations in the legs accompanied by a sometimes unbearable sense of restlessness in the legs. For these people, taking dopamine agonists before bed can be helpful. Caution is in order, of course, because in some patients with PD, especially older or more advanced patients, these medications can cause confusion and hallucinations and are thus not well-tolerated. A long-acting levodopa formulation or medications such as gabapentin, gabapentin enacarbil and pregabalin can also be effective. Trying to address sleep issues such as RLS in patients who have sleep complaints can be an important aspect of maximizing therapy for PD.

Tips and Takeaways

  • Restless leg syndrome (RLS) causes a feeling of restlessness in the evening hours, usually in the legs, when the limbs are at rest. The restlessness is relieved by movement.
  • RLS is a common condition in the general population and may have an increased incidence among people with PD, but studies have been inconsistent.
  • Dopamine agonists, levodopa, gabapentin, gabapentin enacarbil, and pregabalin, can be tried to help relieve RLS symptoms, but should be used with caution (as with all medications) due to potential side effects.
  • Sleep disorders including RLS are very common in PD and often interfere with getting a restful night sleep. Poor sleep can have significant impacts on your health and wellbeing, so talk with your doctor about these symptoms or any symptoms that interfere with your sleep.

The post Restless Leg Syndrome and Parkinson’s Disease appeared first on APDA.

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