Most work has been undertaken in the more common neurodegenerative conditions (i.e., MS and PD), although the results may be applied to other diseases.
Breathlessness
Breathlessness (or dyspnea) is well recognized in MND due to progressive respira- tory muscle weakness. However, it has also been demonstrated that respiratory problems can occur in movement disorders (such as PD, PSP, MSA) [ 25 ] and in MS [ 26 ] .
Dyspnea is de fi ned as the “subjective experience of breathing discomfort”
and encompasses not just physiological parameters but also psychological, social, and environmental factors [ 27 ] . Higher rates of “perceptions of dyspnea”
(despite normal lung function) have been described in PD when compared to controls [ 28 ] .
Multiple pathophysiological mechanisms are involved in the development of breathlessness in neurological conditions. They can be related primarily to the neu- rological disease (central or peripheral) or to other coexisting factors (e.g., heart or lung disease).
One mechanism common to all the neurodegenerative conditions (especially when advanced) is the risk of pneumonia (both aspiration and hypostatic). In advanced disease, the risk of pneumonia is increased by:
Dysphagia
•
Weight loss and nutritional issues
•
Increasing immobility
•
Progressive muscle weakness which can diminish the ability to cough and clear
•
bronchial secretions effectively
The treatment of dyspnea will require a broad approach following a full assess- ment of physical, psychological, social, and environmental aspects.
Management
Nondrug Physical
Physiotherapy input can be employed in neurodegenerative conditions in order
•
to improve ventilation and help clear secretions.
Positional changes, such as sitting upright, can help. Indeed, some patients may
•
need postural aids/supports to maintain an optimum position, especially as the disease progresses.
In those patients with MND who have an ineffective cough due to respiratory
•
muscle weakness, the use of mechanical insuf fl ation/exsuf fl ation or manually assisted cough can be helpful in clearing upper airway secretions [ 29 ] . This may be particularly helpful in acute infections.
A systematic review [
• 30 ] looking at nondrug interventions for breathlessness, mainly in COPD, demonstrated bene fi cial effect from:
The use of walking aids –
Neuromuscular electrical stimulation –
Chest wall vibration –
Breathing training –
The review did not recommend the use of fans, acupuncture, or relaxation, but
•
they may prove helpful in individual patients.
Psychological
Exploring anxieties, fears, or panic associated with breathlessness is important.
•
Drug
Treat any underlying cause (e.g., infection or airway reversibility).
•
Optimize parkinsonian medication in PD.
•
Opioids:
•
The precise mechanism of how opioids help breathlessness is unclear; however, –
a systematic review of their use via the oral or parenteral route to palliate breath- lessness (mainly in COPD) demonstrated a signi fi cantly positive effect [ 31 ] . Benzodiazepines:
•
The results from a systematic review of the use of benzodiazepines for breath- –
lessness in cancer and COPD reported a slight but nonsigni fi cant trend toward a bene fi cial effect. They recommended benzodiazepines (such as diazepam or lorazepam) for third-line use after nondrug therapies and opioids [ 32 ] .
In refractory cases, mechanical ventilation may be required. This most often
•
occurs in MND patients after multidisciplinary discussions with patient and family (see section “ Sleep Disorders ”).
Constipation
Constipation is very common in all neurodegenerative conditions and may be related to the primary disease or to secondary causes such as existing comorbidi- ties, decreased activity levels, poor fl uid intake, and/or medications (levodopa, dopamine agonists, anticholinergics, or opioids). Constipation has been de fi ned by a number of criteria which include symptoms of straining, hard or lumpy stool, sensation of anorectal obstruction, sensation of incomplete evacuation, manual maneuvers to facilitate defecation, and fewer than three defecations per week [ 33 ] .
The links between the primary neurological disease and constipation have not been fully elucidated; however, a number of mechanisms may be involved, includ- ing autonomic dysfunction and altered gut motility.
Management
Nondrug
Increased dietary fi ber/ fl uid intake
•
Increased exercise
•
Drug
Review of medications
•
Stool softener (e.g., docusate)
•
Stool stimulants (e.g., senna or bisacodyl)
•
Polyethylene glycol solutions [
• 34 ]
Enema or suppositories
•
Prokinetics (5HT4 agonists):
•
Prucalopride at doses of 1–4 mg once daily has proved ef fi cacious in elderly –
patients with chronic constipation [ 35 ] .
Mosapride citrate has also shown positive effects in MSA and PD in case –
series [ 36 ] .
Drooling
Drooling is a common problem in neurological disease (e.g., MND = 50–70 % [ 37 ] , PD = 56 % [ 38 ] ) and can have a huge negative impact on patients’ quality of life.
Normal daily salivary production is between 1 and 1.5 l/day. Drooling is the over fl owing of saliva from the mouth and, in the context of neurological dis- ease, may be the result of swallowing dysfunction, excess saliva (or sialorrhea), poor oral control of saliva, or a combination of all three. The evidence in patients with MND [ 39 ] suggests that they actually produce decreased amounts of saliva when compared to controls, and therefore, the drooling is thought primarily to be due to dysphagia [ 40 ] . In PD, decreased swallowing frequency is also a fac- tor [ 41 ] .
Management
Nondrug
Address any underlying cause of increased salivation, such as oral thrush, ill-
•
fi tting dentures, or poor oral hygiene.
Early involvement of speech and language therapy.
•
In the context of PD, preliminary work has also been undertaken on a portable
•
metronome broach which alerts at set intervals in order to remind patients to swallow [ 42 ] .
Other authors have suggested that chewing gum can also improve the swallow
•
frequency in PD [ 43 ] .
Drug
Drug therapies for drooling have largely focused on the use of anticholinergics, yet much of the initial data of their ef fi cacy was gained from studies in children with neurodisabilities [ 44 ] .
Atropine eye drops given sublingually have shown equivocal results [
• 45 ] .
Transdermal scopolamine has been shown to be effective for drooling in severely
•
disabled patients [ 46 ] , but side effects were commonly reported.
Oral glycopyrrolate (a quaternary amine drug that does not cross the blood-brain
•
barrier) has been shown ef fi cacy in studies in adults with PD [ 47 ] . The side effects are generally mild (dry mouth/thick secretions) but may necessitate stop- ping treatment in some cases.
Injection of botulinum toxin into the salivary glands can temporarily reduce the
•
volume of saliva between 2 and 6 months. A 2010 international consensus state- ment concluded that botulinum toxin in adults and children not only improved drooling but had positive impacts on psychosocial aspects of care [ 48 ] .
External beam radiotherapy has been used in small studies of MND patients with
•
good effect [ 49 ] . Given the irreversible nature of this treatment, it is probably best reserved for refractory cases.
Dysarthria
Dysarthria is de fi ned as dif fi culty in articulating words and may be a consequence of weakness, incoordination, or spasticity of speech muscles. The social and psy- chological rami fi cations of speech dif fi culties can often be more important than the speech problem itself. Furthermore, the ability to communicate one’s wishes is a key part of determining whether a patient has the capacity to make decisions and exercise autonomy.
Dysarthria is common in all neurological conditions (e.g., MND = 77 % [ 50 ] , PD = 38–69 % [ 51 ] ), but the cause of the problem can vary between different dis- eases. For example, in MND, dysarthria results from weakness or spasticity of the bulbar muscles whereas, in PD, it can result from incoordination of oral and respira- tory elements.
In neurodegenerative conditions, dysarthria often coexists with other neurologi- cal lesions which can further affect communication. For example:
Dysphasia (expressive or receptive)
•
Bradyphrenia (slow thought processes)
•
Cognitive impairment
•
In advanced disease, communication can be challenging, frustrating, and time consuming for both patients and health-care staff.
Treatment strategies are based on a full assessment of the patient by an experi- enced speech and language therapist (SALT). Goals and therapies are then tailored to the patients needs.
Management
Time to speak:
•
As speech slows or quietens, patients with neurological conditions often need –
more time to express themselves.
All patients with dysarthria should have a SALT assessment.
•
Exercises:
–
Lee Silverman Voice Treatment (LSVT) is one treatment designed for use in PD patients and has been shown to improve voice volume for up to 6 months [ 52 ] .
Augmentative and alternative communication devices:
–
Voice ampli fi ers Alphabet boards Pacing boards
Electronic speaking devices (e.g., Lightwriter or iPad).
Dysphagia
Swallowing is a complex neuromuscular process which involves around 50 pairs of muscles and nerves. The overall coordination of the sequential muscle activation is thought to arise from the brainstem [ 53 ] . Once activated, there are three phases involved in normal swallowing:
• The oral phase – The mouth, through chewing and bolus formation, makes the food or liquid ready for swallowing.
• The pharyngeal phase – Begins when the tongue pushes the food or liquid to the back of the mouth. This triggers a swallowing response which passes the bolus through the pharynx while at the same time covering the airway with the epiglot- tis. This phase is an involuntary re fl ex.
• The esophageal phase – Carries the food bolus from the pharynx to the stomach.
This phase is also involuntary, but voluntary swallowing can be triggered from the cerebral cortex.
In neurodegenerative conditions, these phases can be affected even in early disease.
Management
Given the complexity of the de fi cits in neurodegenerative conditions, the key rec- ommendation in guidelines is early referral to and assessment by an experienced speech and language therapist [ 12, 54 ] . Treatments then need to be decided on a case by case basis.
Nondrug
Speech and language therapy (SALT):
•
In broad terms, the approaches used in SALT are rehabilitative (e.g., post –
stroke where some recovery may occur), compensatory (where recovery is not likely), or a combination of the two:
Rehabilitative (or facilitatory) approaches include muscle strengthening exer- cises and electrical stimulation.
Compensatory techniques include dietary modi fi cation and use of postures/
maneuvers.
Drug
No drug therapies have been shown to reliably help dysphagia in neurodegenera-
•
tive conditions; however, in parkinsonian conditions, optimizing levodopa ther- apy may help in a small number of patients [ 55 ] .
Enteral Feeding
In patients where there is symptomatic dysphagia with weight loss due to reduced calorie intake, dehydration, or ending meals because of choking, a nasogastric tube (NGT) or percutaneous endoscopic gastrostomy (PEG) might be considered for feeding. The use of NGT or PEG in neurological conditions involves a multidisci- plinary assessment and a full discussion with the patient and family. It is seldom a clear-cut decision but rather involves weighing up issues of risks, bene fi ts, auton- omy, capacity, culture, prognosis, and expected outcomes.
A systematic review of the use of NGT versus PEG demonstrated that in neuro- logical conditions (mainly stroke) ( n = 109), PEG had signi fi cantly fewer treatment failures. However, in the group as a whole (both neurological and non-neurologi- cal), there were no signi fi cant differences in mortality rates, complications, or pneu- monia. The review suggested that overall survival improved (4.3 months) with PEG use [ 56 ] .
In MND, some authors suggest that PEG tubes improved nutrition and perhaps prolonged survival, but it is unlikely to prevent aspiration [ 57 ] .
Nasogastric Tube Feeding
A role for NGT feeding has been suggested for short-term use, and therefore, it
•
may have more of a role in acute neurological de fi cits which may recover (e.g., in stroke).
Short-term use of nasogastric tubes (NGT) has also been suggested in PD in
•
order to deliver dopaminergic medications where there is a temporary loss of swallow. This can be considered when reversible causes (e.g., pneumonia) and an inability to take regular dopaminergic drugs have contributed to the dysphagia.
Percutaneous Endoscopic Gastrostomy
Recommendations for the use of gastrostomy in MND suggest that an individu-
•
alized approach should be used looking at the following:
Bulbar symptoms –
Weight loss (>10 %) –
Patient’s overall condition –
It is suggested that in MND, a PEG should be considered early, but if there are
•
increased risks (i.e., FVC <50 % of predicted), then a percutaneous radiologi- cally inserted gastrostomy (PRG) is recommended [ 57 ] . A PRG can be placed without any sedation or general anesthetic and is less likely to compromise respi- ratory function.
The use of PEGs for nutrition in other neurological conditions has not been
•
clearly de fi ned and hence should be assessed on a case by case basis.
PEGs and percutaneous endoscopic jejunostomies (PEJ) have been used in
•
advanced PD with success in order to provide continuous infusions of levodopa leading to more stable drug levels and improved motor symptoms [ 58 ] .
Fatigue
Fatigue is probably one of the most common symptoms experienced by patients with chronic neurological diseases. There is no universally accepted de fi nition of fatigue, and as such, the estimated prevalence in neurological diseases is extremely variable (e.g., MS = 39–78 % [ 12 ] ). Currently, the causes of fatigue are thought to be multifactorial – some are primarily related to the neurological disease (e.g., dis- ruption of central neural connections [ 59 ] ) and others to secondary causes (e.g., depression, disability) [ 60 ] . Regardless of the cause, it is a symptom which can have a signi fi cant negative impact on quality of life.
Management
Nondrug
Exclude secondary causes of fatigue (e.g., depression).
•
Fatigue management such as the use of exercise or of energy conservation/activ-
•
ity pacing is recommended. Good evidence of their ef fi cacy in neurological con- ditions is lacking.
In MS, structured “mindfulness-based intervention” has been used in a random-
•
ized study with improvements reported for up to 6 months in health-related qual- ity of life, depression, and fatigue [ 61 ] .
Drug
Stopping medications which may cause fatigue (e.g., riluzole).
•
Fatigue is one of the non-motor symptoms of PD, and as such, optimizing the
•
dopaminergic treatment can help.
The use of medicines which directly target fatigue should not be used routinely
•
but may be helpful in refractory cases. For example, case series in PD [ 62 ] and MS [ 63 ] suggest there may be a role for moda fi nil.
Immobility
The progressive nature of the neurodegenerative conditions means that in many cases mobility will be adversely affected at some point in the disease trajectory. In those conditions where progression is generally slower (e.g., MS, PD, HD, and stroke), there may be opportunities for a rehabilitative approach. In those with more rapidly progressive diseases (e.g., MND) a traditional neurorehabilitative approach is more dif fi cult to apply. However, as one author has stated:
“There are few people with any form of neurological disability who would not bene fi t from at least some exposure to a team skilled in the basic principles of neu- rological rehabilitation” [ 64 ] .
The rami fi cations of worsening mobility are considerable, and therefore, assess- ing each of the affected domains is vital in facilitating adjustment to the progressive losses which many patients face. These rami fi cations include:
Physical – falls, injury (e.g., fractures), pressure sores, the effect on eliminations,
•
muscle weakness, and inability to carry out activities of daily living Psychological – fear, loss of con fi dence, and loss of independence
•
Social – isolation, housebound, and increasing carer strain
•
Spiritual – decreased sense of worth, purpose, or meaning
•
Environmental – adaptations to home, accepting of external carers, or even
•
a change in care setting
Mobility issues are more common as neurodegenerative diseases progress; how- ever, they often occur at presentation or in early disease. Therefore, early assess- ment by and involvement of specialist multidisciplinary teams are vital fi rst steps in trying to facilitate maximal mobility (and independence) for as long as possible [ 65 ] .
Management
Recommendations speci fi c for mobility problems in patients with MS provide a useful model with which to approach mobility issues in general in neurological conditions [ 12 ] .
Physiotherapy treatments should be offered in order to improve mobility:
•
In parkinsonian disorders, freezing of gait is a common problem being pres- –
ent in around 50 % of patients [ 66 ] . Physiotherapy in general and the use of auditory or visual cueing techniques in particular may be helpful [ 67 ] .
Consider assessment by a specialist neurological rehabilitation service for:
•
Identi fi cation and treatment of the impairment –
Task-related practice of mobility activities (e.g., transferring) –
Use of equipment –
Adaptations to environment –
Teaching others how to safely help –
Regular reviews are important given the progressive nature of the conditions.
•
Planning ahead also needs to be sensitively explored with patients and families.
•
Pain
Gagliese and Melzack [ 68 ] highlighted that pain is a “multidimensional experience with sensory, affective, and cognitive-evaluative components” and, as such, requires a holistic approach to its management. Pain is very common in the general popula- tion. In one study, its prevalence in all ages in the community setting was 50 % [ 69 ] ; however, in elderly patients, pain was present in 70 % [ 70 ] .
It is on this backdrop that we need to consider the management of pain in neuro- degenerative diseases. In particular, our assessment needs to consider not simply the neurological causes of the pain but also the non-neurological causes. In one study in patients with PD, pain related to PD was as common as pain unrelated to PD (62.6 % vs. 64.2 %). Moreover, the pain in the latter group was rated by patients as signi fi cantly more severe and constant [ 71 ] .
The pathogenesis of pain related to neurological conditions is complex. The basal ganglia have a crucial role in processing pain, and other somatosensory inputs and damage to these areas may affect how pain is perceived [ 72 ] . The basal ganglia can be affected in a number of neurodegenerative conditions (e.g., PD, PSP, MSA, HD, and stroke) and as such has been implicated as a mechanism for pain in these conditions.
As a whole, pain is common in neurodegenerative diseases:
PD – Estimates of the frequency of pain in PD range from 40 to 85 % [
• 71, 73 ] . It
is more frequent when compared to an age-matched control group [ 74 ] . PD-related pains (such as cramps or dystonias) may worsen at “wearing off” times and improve with dopaminergic therapy. Other pains were thought to be non-PD related (mainly osteoarthritis). In all the studies, neuropathic pain was uncom- mon (<10 %).
MS – The frequency of pain ranges from 29 to 86 % [
• 75, 76 ] . The MS-related
pains appear to be commonly due to neuropathic phenomenon but can also be related to spasticity.
MND – Pain in MND tends to be more of an issue in later disease, and the preva-
•
lence has been estimated between 40 and 73 % [ 77 ] . It can be caused by cramps, spasticity, joint stiffness, or skin pressure due to immobility.
Stroke – Pain post stroke has been shown to change with time. One population-
•
based study demonstrated a prevalence of moderate/severe pain in 32 % of patients at 4 months and 21 % at 16 months [ 78 ] . They highlight the wide varia- tions in estimates of pain post stroke (19–74 %) and that shoulder pain (on the affected side) and central post-stroke pain are most commonly reported.
MSA/PSP – Pain in MSA has been reported in 47 % of patients in one retrospec-
•
tive study [ 79 ] . The pain was classi fi ed as “rheumatic,” sensory, or dystonic with some evidence of exacerbation on “wearing off.” Pain seems to affect patients with MSA much more commonly than patients with PSP (78 % vs. 56 %, respec- tively) [ 80 ] .
The prevalence of pain in HD is unknown, but one study found increased levels
•
of bodily pain when compared to control norms [ 81 ] . The nature of the pain was not reported.
Management
The key element to optimal pain control is optimal pain assessment. All patients should have thorough assessments of each pain, and then treatments should be pre- scribed accordingly.
Nondrug
Physiotherapy.
•
Walking aids may help where pain is exacerbated by mobilization.
•
Pressure-relieving devices (e.g., high-speci fi cation foam mattresses and cush-
•
ions) to help treat or reduce risk of pressure sores.
Transcutaneous electrical nerve stimulation (TENS) machine may be useful for
•
some patients with chronic pain [ 82 ] .
Small bene fi ts to chronic pain have also been demonstrated using psychological
•
therapies [ 83 ] .
Drug
Robust interventional studies looking at the drug treatments of pain in neurological conditions are lacking. However, evidence does suggest that analgesics are under- used in patients with neurological conditions who have pain [ 71, 84 ] .
In considering drug treatments, we will consider interventions under the pro- posed mechanism of the pain:
Nociceptive pain:
•
In PD, optimizing dopaminergic therapy may help to alleviate pain in some –
patients.