Nonmotor problems in Parkinson disease

Pain

Many textbooks do not list pain and the other sensory complaints in Table 8.2 as a part of PD, and they may be erroneously omitted as symptoms of the disease ( ; ; ; ; ; ). A constant, boring pain in the initially affected limb may be the first complaint. Aching in the shoulder and arm is also a common earlier symptom in PD and may be incorrectly attributed to a bursitis or a frozen shoulder. When pain occurs in the hip or leg, it is often attributed to arthritis. That such pain is due to PD is most supported by the observation that there is relief with antiparkinsonian medication, though in many cases there may be only partial relief or even no relief. Once adequate dosing is achieved, whether or not mobility is restored, such pain may improve. Of course, patients with PD may also have coincidental joint disease, so if the pain persists, patients require appropriate investigation.

Another initial complaint, particularly in younger patients, may be painful dystonic foot cramps, especially on walking. Rarely, similar painful cramps may occur in the hands. An extended big toe or curling of small toes may be observed with the cramping. In surveys conducted in 2008, about two-thirds of patients experience chronic pain ( ; Nègre-Pagès et al., 2008).

When patients with PD develop motor fluctuations and dyskinesias, pain may become a major feature. Additionally, “off-period” dystonia may be frequently painful. This issue may manifest as early morning painful cramps, particularly affecting the feet ( ). Similar painful dystonic cramps may emerge during “off” periods and can be very distressing ( ). Some patients may experience more generalized excruciating pain during “off” periods, often a deep-seated aching, but sometimes accompanied by a superficial burning quality. In many cases, such pains disappear when the patient is switched “on” by appropriate medication. An “off-period” pain may be an indication for the use of rapidly acting water-soluble preparations of levodopa or apomorphine rescue injections.

Burning, numbness, and paresthesia

Other specific sensory symptoms, such as burning, numbness, and paresthesia, are less common in PD. Some patients may describe nonspecific paresthesia in the affected limbs; however, objective sensory signs are absent ( ; ). A rare patient may have sensory complaints from levodopa therapy, unaccompanied by dystonia. Electroconvulsive therapy (ECT) has been reported in some cases as effective in alleviating the problem, though this would not be a first-line therapy. If parkinsonian pain occurs during an “off” or as a result of parkinsonism, one should first try to increase medications to avoid “offs.” (Sensory “offs” are considered later in this chapter.) If pain occurs during peak-dose dystonia, one needs to consider lowering the dose. If pain is secondary to levodopa or a dopamine agonist, one needs to reduce or eliminate the causal agent. Occasionally, the ergot dopamine agonists bromocriptine and pergolide may cause a burning pain with inflammatory changes in the skin. This condition has been referred to as St. Anthony’s fire. If this issue emerges, the agonist needs to be discontinued.

A recent review of pain by Jost and colleagues (2019) revealed that there is an appreciation for both nociceptive and neuropathic pain in PD. Data on drug therapy are limited and not specific. Medications used include dopaminergic drugs, opioids, nonopioid analgesics, anticonvulsives, antidepressants, and cannabinoids. Pain may be resistant to many of these therapies.

Akathisia

A more common sensory symptom is akathisia, or a sense of inner restlessness. This symptom may be focused on the legs with uncomfortable paresthesias and the need to move the legs to gain relief, in which the condition may be termed a true restless legs syndrome (RLS) ( ). More often, there is a sense of generalized inner restlessness and discomfort, demanding walking for relief; akathisia is the more appropriate description ( ). Akathisia may be a presenting feature of PD. The symptoms of both restless legs and akathisia may respond to dopamine replacement therapy. Akathisia may also occur during the “off” period ( ). It may be difficult for the patient and the clinician to distinguish between akathisia and RLS in select patients.

Akathisia probably occurs more often in PD than is commonly recognized. It can be a sensory complaint of the disease and also an adverse effect from levodopa. asked patients with PD specifically for complaints of restlessness and found that 86% had this subjective complaint. Most patients with PD who complained of an inner feeling of restlessness did not overtly manifest any signs such as moving about. From Lang and Johnson’s study it was not clear whether akathisia represented an adverse effect from levodopa or was a feature of the disease. In most of their patients it appeared only after the introduction of antiparkinsonian drugs, but a small number had this symptom early in the course of PD, before receiving any medication. It is likely that levodopa and other antiparkinsonian agents may also contribute to this complaint. Restlessness has been reported to occur in patients with primary torsion dystonia after starting these drugs.

Restless legs syndrome

RLS is encountered frequently in patients with PD. In one study, 24% of patients with PD had RLS ( ). The symptoms are described in Chapter 23 . Briefly, it consists of unpleasant crawling sensations in the legs, particularly when sitting and relaxing in the evening, and disappears on walking. Whether RLS is an epiphenomenon of PD, because both respond to dopaminergics, is not clear. Like PD, dopamine transporter binding is reduced in the striatum in sporadic RLS ( ). Sporadic and familial RLS respond to dopamine agonists and levodopa, but these drugs can cause augmentation, a worsening of the restless legs symptoms—more severe unpleasant sensations, occurring earlier in the day, and spread to involve other body parts. This raises the possibility that some cases of RLS in patients with PD may be the result of dopaminergic medications used to treat PD. Fortunately, opioids are effective in treating RLS and periodic movements in sleep, whether in patients with PD or in sporadic and familial RLS ( ; ), and these can be used safely in PD. Propoxyphene 65 mg late in the day before the onset of symptoms is usually effective. Start with a half-tablet, and titrate up to two tablets if necessary. Other opioids such as oxycodone ( ), tramadol (Lauerma and Markkula, 1999), and methadone ( ) are effective without the augmentation problem. Finally, pregabalin and gabapentin have both been used to treat restless legs ( ).

Meta-analysis revealed that the prevalence of restless legs is higher in PD. It was also higher among patients who had previously received PD treatment (15%) than among drug-naive patients (11%). Overall, the RLS prevalence was higher among PD patients than controls (odds ratio [OR], 2.86; 95% confidence interval [CI], 2.10–3.90; P < 0.001) ( ).

Hyposmia

Decreased sense of smell is not a common PD complaint; however, if olfaction is tested, decreased smell is detected in most patients with PD. In one study, 45% of patients were functionally anosmic, 51.7% were hyposmic, and only 3.3% were normosmic ( ). This indicates that 96.7% of PD patients presented with significant olfactory loss compared with young normosmic subjects. This figure fell to 74.5% when adjusted to age-related norms.

Hyposmsia often precedes the onset of motor symptoms ( ; ) and is now being studied to determine whether it can predict future PD. Hyposmia is more predictive than is executive dysfunction ( ). One study indicated that hyposmia could predict PD in men up to 4 years before the onset of motor features ( ), and an autopsy study showed that those with the greatest reduction of smell were more likely to have incidental Lewy bodies at autopsy ( ). One problem is that hyposmia is not selective; it is decreased in other neurodegenerative disorders, including corticobasal degeneration ( ). Hyposmia has been associated with striatal dopamine deficiency ( ) but showed a better correlation with decreased cholinergic activity in the cortical and limbic areas ( ).