**5. Treatment**

*Updates in Sleep Neurology and Obstructive Sleep Apnea*

sufficiency such as MIP and FVC [24].

The sniff nasal transdiaphragmatic pressure (SNIP) is a strong predictor of diaphragmatic muscle strength. It is a non-invasive inspiratory volitional test. It can also be used to monitor progression of disease [21]. In addition, SNIP testing is not limited by the requirement of securing an adequate seal over the instrument's mouthpiece, rendering it advantageous for evaluation of patients with prominent cranio-bulbar weakness. The sniff test has a sensitivity of 97 percent for a sniff value <40 cm H2O for predicting six-month mortality, compared to 58 percent sensitivity of VC < 50 percent [23, 24]. SNIP value <40 cm H2O is strongly correlated with nocturnal hypoxemia in ALS patients [24] (see **Figure 1**). This predictive value for nocturnal hypoxemia was not seen with other measures of respiratory

*Scatterplot of the proportion of the night spent with nocturnal hypoxemia (defined as oxygen saturation < 90* 

*percent) in ALS patients with SNIF <40 cm H2O compared to those with SNIF >40 cmH2O [24].*

Maximal inspiratory pressure (MIP) and maximal expiratory pressures (MEP) are useful for predicting early respiratory muscle weakness. MIP is done by inspiring from residual lung volume. MEP is done by having the patient maximally expire against a closed airway. MIP > 80 cm H2O or MEP > 90 cm H2O excludes significant respiratory muscle weakness [21]. MIP < 40 cmH2O also identifies people at risk of hypoventilation. This test may underestimate the degree of respiratory muscle weakness as it involves a mouthpiece and those with facial or bulbar weakness may not form a tight seal around it. This test does require effort on the part of the

Nocturnal pulse oximetry and capnography can also be used for screening for hypoventilation. Nocturnal pulse oximetry is often the first test ordered when sleep disturbance is suspected as it is inexpensive and non-invasive [20]. Nocturnal desaturation <90 percent for >5–10 percent of the time may suggest hypoventilation [23]. A nocturnal desaturation to less than 90 percent for one minute is also helpful to diagnose hypoventilation [22]. Patterns seen in early disease suggestive of hypoventilation are cyclical desaturations with low baseline oxygen saturation. This pattern is also seen in COPD or interstitial lung disease and nocturnal pulse oximetry cannot distinguish between these conditions. There are also some technical problems with nocturnal pulse oximetry as the oximeter can become dislodged or readings can be inaccurate in the setting of anemia. [20] Capnography is utilized

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patient [21].

**Figure 1.**

Basic sleep hygiene should always be emphasized with the patient and family as the usefulness of these interventions is often overlooked. Treatment of comorbid conditions that may be contributing to sleep disorders or fatigue such as hypothyroidism, depression or obesity should also be addressed.

The mainstay of treatment of sleep-disordered breathing in ALS is through assistance of the weakened respiratory muscles with positive upper airway pressurization [20]. Non-invasive positive pressure upper airway ventilation [NIV] should be considered when hypoventilation is clinically suspected and confirmed with spirometry [19]. Practice parameters recommend initiation of NIV when SNIP falls below 40 cm H2O, FVC < 50%, or in the setting of abnormal nocturnal oximetry [22].

It is well established, that NIV improves symptoms of sleep disturbance, quality of life and cognitive function and is primarily indicated in sleep-disordered breathing and inspiratory muscle dysfunction. NIV may also prolong tracheostomy -free survival [19]. Studies have shown a slower rate of decline of FVC and pulmonary function with use of NIV in ALS patients. Benefit in survival correlated with at least 4 hours of NIV use at night [20]. Most patients with ALS will need NIV at first while sleeping, but later as symptoms progress with more dyspnea and hypercapnia/hypoxemia-related-symptoms NIV will be required for longer periods of ventilation and then continuously [12, 19]. They are at first treated with NIV and

finally with tracheostomy with total ventilator support, if elected by the patient, or with supportive measures in hospice until death.

The aim of NIV is normalization of hypercapnia, hypoxia, and the apneahypopnea index. This results in improvement of the sleep architecture and prolonged survival up to one year [19]. NIV is divided in pressure-assisted control where partial pressure is provided and volume-assisted control where the patient receives a predefined gas volume. Volume-assisted control has the advantage of overcoming airflow obstruction and being effective in obstructive events, but it has the disadvantage of an uncomfortable feeling caused by the ventilation and no compensation for leaks [27]. The pressure assisted control is more comfortable and it compensates for leaks. One study showed greater survival with pressure-assisted over volume-assisted ventilation [28]. NIV using nasal ventilation is preferred because it allows speech and induces a lower rate of OSA. Patients require close surveillance in the first few days of use to determine proper the settings and then monthly or quarterly evaluations thereafter. NIV failure is most commonly caused by leaks [29] and the coexistence of untreated OSA that increases mortality.

Bronchial congestion caused by weak coughing and excessive sialorrhea may also cause failure of NIV therapy. Sialorrhea may be treated with drugs [atropine, scopolamine, belladone tincture], and if these drugs fail with salivary glands radiation; Botox injections are not recommended. Keeping the head up to avoid supine position, cervical collars, or mandibular advancement may also be helpful in addition to NIV [19].

To assist cough, mechanical insufflation-exsufflation (MI-E) devices can be prescribed to patients in order to clear airway secretions and prevent development of pneumonia. These devices administer pressure (both positive and negative, as might be done in a voluntary cough) artificially and can be used via face mask or tracheostomy [30].

It is important to mention, that bulbar dysfunction poses some management challenges in regard to the use of NIV. Compliance with use of NIV in these patients is lower due to decreased tolerance. As previously mentioned, hypersalivation in these patients worsens prognosis with NIV and requires symptomatic treatment. The initial study that showed increased survival with use of NIV [31] in patients with ALS did not show benefit in patients with severe bulbar symptoms however more recent studies have contradicted this. For this reason, treating symptoms that limit NIV usage in these patients is essential. Full face masks rather than the nasal mask are necessary for patients with bulbar dysfunction due to incomplete mouth closure [32].

### **6. Sleep disorders in Parkinson disease**

Parkinson Disease [PD] is the second most common neurodegenerative disorder after Alzheimer's disease [33]. PD occurs as a result of chronic, progressive decrease in dopamine levels of the substantia nigra, secondary to loss of dopaminergic neurons in the pars compacta and the occurrence of Lewy bodies in the cytoplasm of remaining neurons [34]. It is primarily diagnosed clinically and patients may present with the characteristic motor deficits, which include the resting tremor, bradykinesia, rigidity and postural instability. However, most will have both motor and nonmotor symptoms. The nonmotor symptoms cause disturbances, which affect sleep, mood, cognition, sensation and autonomic function. Among the nonmotor symptoms in PD, sleep disorders are second in frequency only to neuropsychiatric disorders [35]**.**

It is estimated that between 55 to 80 percent of PD patients suffer from sleep disorders [SD] [36, 37]. Sleep can be affected in a multitude of ways with the most common SD displayed in **Table 4**. Some disturbances will precede the disease, while others are indicators of disease progression. In many cases, more than one sleep

**59**

*The Relationship between Amyotrophic Lateral Sclerosis and Parkinson's Disease and Sleep…*

**Nocturnal sleep disorders Diurnal sleep disorders**

Excessive daytime sleepiness

Sleep attacks

disorder may coexist in the same patient. Poor sleep, particularly if chronic, will have an impact on daily activities causing excessive daytime sleepiness [EDS] and sleep attacks [SA]. The neurodegenerative process caused by PD itself will exacerbate daily drowsiness, as well as certain medications [38]. Therefore, a detailed sleep history in a patient with PD is imperative to identify symptoms in order to treat accordingly and monitor their progression. There is evidence to suggest that improving a patient's quality of sleep not only will improve their quality of life, but

Another important consideration for patients with bradykinesia and rigidity, who may have trouble turning in bed at night or getting to the bathroom - is using an extended release formulations as their last dose of the day that might disrupt

Two validated scales were created to assess the severity of the impact of PD [Parkinson Disease Sleep Scale (PDSS) and Scales for Outcome in PD Sleep

Patients with PD often have many sleep architecture changes, the most common ones are shown in **Table 5**. The sleep architecture abnormalities include intrinsic brain changes caused by the underlying neurodegenerative disorder, co-existent sleep disorders, nocturnal motor symptoms, and dopaminergic medications.

Insomnia affects approximately 50 to 60% of patients with PD, making it the most common sleep disorder and perhaps the most complex to treat given its multifaceted basis [42]. When it lasts for more than three months, it is considered

• Sleep-maintenance insomnia, also referred as sleep fragmentation: when the

• Terminal insomnia: when the patient awakens involuntarily earlier than usual

• Sleep-onset insomnia: when the patient has difficulty falling asleep

It can be further classified into the following patterns:

patient has difficulty staying asleep

can also lead in an improvement of their motor symptoms.

their sleep or, even worse, lead to falls.

**7. Sleep architecture changes in PD**

**8. Nocturnal sleep disorders**

**8.1 Insomnia**

chronic insomnia [43].

[SCOPA-S] [39, 40].

*DOI: http://dx.doi.org/10.5772/intechopen.98934*

Rapid Eye Movement (REM) sleep behavior disorder

Insomnia

Nocturia

*Sleep disorders in PD.*

**Table 4.**

Circadian rhythm disorders Sleep breathing disorders Restless leg syndrome

Periodic limb movements of sleep

*The Relationship between Amyotrophic Lateral Sclerosis and Parkinson's Disease and Sleep… DOI: http://dx.doi.org/10.5772/intechopen.98934*


#### **Table 4.** *Sleep disorders in PD.*

*Updates in Sleep Neurology and Obstructive Sleep Apnea*

with supportive measures in hospice until death.

finally with tracheostomy with total ventilator support, if elected by the patient, or

Bronchial congestion caused by weak coughing and excessive sialorrhea may also cause failure of NIV therapy. Sialorrhea may be treated with drugs [atropine, scopolamine, belladone tincture], and if these drugs fail with salivary glands radiation; Botox injections are not recommended. Keeping the head up to avoid supine position, cervical collars, or mandibular advancement may also be helpful in addition to NIV [19]. To assist cough, mechanical insufflation-exsufflation (MI-E) devices can be prescribed to patients in order to clear airway secretions and prevent development of pneumonia. These devices administer pressure (both positive and negative, as might be done in a voluntary cough) artificially and can be used via face mask or

It is important to mention, that bulbar dysfunction poses some management challenges in regard to the use of NIV. Compliance with use of NIV in these patients is lower due to decreased tolerance. As previously mentioned, hypersalivation in these patients worsens prognosis with NIV and requires symptomatic treatment. The initial study that showed increased survival with use of NIV [31] in patients with ALS did not show benefit in patients with severe bulbar symptoms however more recent studies have contradicted this. For this reason, treating symptoms that limit NIV usage in these patients is essential. Full face masks rather than the nasal mask are necessary for

Parkinson Disease [PD] is the second most common neurodegenerative disorder after Alzheimer's disease [33]. PD occurs as a result of chronic, progressive decrease in dopamine levels of the substantia nigra, secondary to loss of dopaminergic neurons in the pars compacta and the occurrence of Lewy bodies in the cytoplasm of remaining neurons [34]. It is primarily diagnosed clinically and patients may present with the characteristic motor deficits, which include the resting tremor, bradykinesia, rigidity and postural instability. However, most will have both motor and nonmotor symptoms. The nonmotor symptoms cause disturbances, which affect sleep, mood, cognition, sensation and autonomic function. Among the nonmotor symptoms in PD, sleep disorders are second in frequency only to neuropsychiatric disorders [35]**.** It is estimated that between 55 to 80 percent of PD patients suffer from sleep disorders [SD] [36, 37]. Sleep can be affected in a multitude of ways with the most common SD displayed in **Table 4**. Some disturbances will precede the disease, while others are indicators of disease progression. In many cases, more than one sleep

patients with bulbar dysfunction due to incomplete mouth closure [32].

**6. Sleep disorders in Parkinson disease**

The aim of NIV is normalization of hypercapnia, hypoxia, and the apneahypopnea index. This results in improvement of the sleep architecture and prolonged survival up to one year [19]. NIV is divided in pressure-assisted control where partial pressure is provided and volume-assisted control where the patient receives a predefined gas volume. Volume-assisted control has the advantage of overcoming airflow obstruction and being effective in obstructive events, but it has the disadvantage of an uncomfortable feeling caused by the ventilation and no compensation for leaks [27]. The pressure assisted control is more comfortable and it compensates for leaks. One study showed greater survival with pressure-assisted over volume-assisted ventilation [28]. NIV using nasal ventilation is preferred because it allows speech and induces a lower rate of OSA. Patients require close surveillance in the first few days of use to determine proper the settings and then monthly or quarterly evaluations thereafter. NIV failure is most commonly caused by leaks [29] and the coexistence of untreated OSA that increases mortality.

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tracheostomy [30].

disorder may coexist in the same patient. Poor sleep, particularly if chronic, will have an impact on daily activities causing excessive daytime sleepiness [EDS] and sleep attacks [SA]. The neurodegenerative process caused by PD itself will exacerbate daily drowsiness, as well as certain medications [38]. Therefore, a detailed sleep history in a patient with PD is imperative to identify symptoms in order to treat accordingly and monitor their progression. There is evidence to suggest that improving a patient's quality of sleep not only will improve their quality of life, but can also lead in an improvement of their motor symptoms.

Another important consideration for patients with bradykinesia and rigidity, who may have trouble turning in bed at night or getting to the bathroom - is using an extended release formulations as their last dose of the day that might disrupt their sleep or, even worse, lead to falls.

Two validated scales were created to assess the severity of the impact of PD [Parkinson Disease Sleep Scale (PDSS) and Scales for Outcome in PD Sleep [SCOPA-S] [39, 40].
