**4. Diagnosis**

*Updates in Sleep Neurology and Obstructive Sleep Apnea*

sion and poor nocturnal mobility [12, 17, 19].

requested to confirm its diagnosis.

breathing [11]. Therefore, when OSA is suspected a polysomnogram should be

In regard to the effects of sleep-disordered breathing on quality of life, ALS patients often complain of excessive daytime sleepiness resulting from nocturnal sleep fragmentation and insomnia. Nocturnal hypoventilation results in orthopnea, morning headaches, excessive daytime sleepiness, and cognitive dysfunction [12, 17]. A study showed the most common nocturnal complaints in ALS patients were nocturia, sleep fragmentation, and cramps (each seen in about half of the patients) [19]. **Table 1** shows the common sleep disturbances seen in ALS.

Nocturnal restlessness, sleep fragmentation with multiple awakening, snoring, and apneas leads to excessive daytime sleepiness, difficulties to arouse in the morning, difficulties to arouse from sleep, cognitive problems and poor work performance. In severe cases when insomnia and sleep continuity is severely impaired patients develop lethargy, cyanosis, early morning headaches, nausea and vomiting and leg edema. **Table 2** shows the most common sleep features in ALS patients. Patients with ALS suffer from other conditions that also affect the sleep such as restless leg syndrome (RLS), REM-sleep behavior disorder (RBD), cramps, immobility-associated discomfort, pain, depression-related sleep disorders and dementia-related sleep disorders which may affect the sleep continuity. Even patients newly diagnosed with ALS have shown poor sleep quality related to depres-

There are important secondary cardiopulmonary effects of chronic nocturnal hypoxemia that should not be overlooked. These include pulmonary hypertension, right heart failure and arrhythmia. There is also an increased risk of stroke, myocardial infarction and lethal cardiac arrhythmias. This highlights the critical

> Excessive daytime sleepiness Increase daytime napping

Fatigue

Poor concentration Poor work performance Morning lethargy Morning headaches Cognitive dysfunction

**Nocturnal features Daytime features**

**54**

**Table 2.**

Nocturnal restlessness Sleep fragmentation Increase WASO Insomnia Apneas/hypopneas Snoring/snorting Orthopnea

*Sleep disturbances in ALS.*

Excessive daytime sleepiness Sleep fragmentation Sleep related hypoventilation Sleep breathing disorders

Insomnia

**Table 1.**

Respiratory interruptions Difficulty to aroused in the morning

Nocturnal cyanosis Choking Nocturia Nocturnal cramps Nightmares

*WASO: wake after sleep onset.*

*Sleep-related features in ALS.*

Essential to the identification of ALS patients with sleep abnormalities is maintaining a high index of suspicion and taking a detailed sleep history. This ideally takes place with a family member or caregiver present (or anyone who may share a bed with the patient). This second party can provide history regarding the patient's behaviors during sleep and functioning in the daytime (some of which the patient himself/herself may not be aware of). Specific questions regarding the presence of excessive daytime sleepiness, cognitive dysfunction, orthopnea, apneas and snoring are essential. Frequent awakenings, snoring and choking are clues for suspecting obstructive sleep apnea. Nocturnal orthopnea is often an early sign of respiratory dysfunction causing hypoventilation. Commonly used screening tools for sleep disorders include STOP-BANG, Epworth Sleepiness Scale and Pittsburgh Sleep Quality Index Scale [3]. All patients with respiratory dysfunction or bulbar weakness should be screened for sleep disorders. Close attention should be placed on examining for signs of respiratory dysfunction such as accessory muscle use (particularly when supine). Increased work of breathing can result in weight loss and cachexia. Patients with bulbar dysfunction progressively develop changes in their voice, difficulty clearing secretions, weak cough and difficulty swallowing [21].

There are multiple modalities that can be utilized in the diagnostic evaluation of respiratory muscle weakness and sleep disorders in ALS. The use of more than one modality increases the precision and accuracy of the diagnosis and prevents over- or underestimation of respiratory muscle strength [20]. **Table 3** outlines the different laboratory investigations used to diagnose sleep disorders in ALS.

If hypoventilation is suspected, then spirometry should be requested. Clinical indicators include excessive daytime sleepiness, morning headaches, frequent nocturnal waking, and vivid dreams [22]. Forced vital capacity (FVC) has long been used to predict survival and disease progression in ALS patients. Faster progression of disease has been associated with FVC < 75 percent of predicted value. A more accurate measure of weakness of the diaphragm is supine FVC however this can be difficult to evaluate [21, 22]. The difference between standing and supine FVC correlates with orthopnea and a fall from sitting to supine >20 percent has a sensitivity of 90 percent for identifying diaphragmatic weakness [12], whereas sitting FVC < 50 percent has only a sensitivity of 58 percent. Despite wide availability in obtaining FVC it is not as sensitive for early respiratory dysfunction and values may be inaccurate in patients with bulbar dysfunction who cannot maintain a tight seal on the mouth piece [21].

Arterial Blood Gas (ABG) Pulmonary Function Tests


Sniff Nasal Pressure (SNP) Overnight Pulse Oximetry Polysomnography (PSG)

#### **Table 3.**

*Investigations commonly used to detect sleep disorders in amyotrophic lateral sclerosis.*

#### **Figure 1.**

*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].*

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 sufficiency such as MIP and FVC [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 patient [21].

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

**57**

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

in diagnosing hypoventilation by measuring a nocturnal transcutaneous carbon dioxide [PtcC02] increment of >10 mm Hg above 50 mm Hg for >10 min. This is performed with simultaneous pulse oximetry recording to compensate for possible

Nocturnal and daytime arterial blood gases (ABG) is another tool that can be used to predict nocturnal hypoventilation resulting in hypoxia (PaO2 < 60 mm Hg) and hypercapnia (PaCO2 > 45 mm Hg). Nocturnal hypoventilation is suggested by an increase of PaCO2 by 10 mm Hg when comparing nocturnal to daytime values. This method is more invasive, and disparities can sometimes only be seen late in the disease [20]. Hypoventilation can also be diagnosed by ABG with hypercapnia defined as a cut off of PCO2 > 45 mm Hg while resting in a seated position for 15 min [26].

In-laboratory overnight polysomnography is the gold standard for the diagnosis of hypoventilation and OSA. At home tests are not recommended for patients with neuromuscular disease as these are limited studies. The standard polysomnogram consists of at least 3 electroencephalography (EEG) channels, chin and leg electromyography (EMG), 2 eye (electrooculogram) leads, effort channels, flow channels, electrocardiography and SaO2. This allows for tracking and monitoring the stages of sleep, SaO2 abnormalities and any abnormal movements [20]. Polysomnography [PSG] with capnography [transcutaneous PCO2] detects sleep-related hypoventilation [PCO2 increment more than 10 mmHg during sleep versus wakefulness, especially during REM] and is more sensitive than oximetry. One third of the patients with confirmed sleep hypoventilation have normal oxygenation [12, 19]. Using PSG, the etiologies of sleep disturbances can be distinguished using analysis of this multimodal test and patterns of SaO2 abnormalities. This allows for recognition of hypoxemia that is event related (obstructive sleep apnea) or due to hypoventilation

The measurement of diaphragmatic thickening using ultrasound is a new developing technique that predicts hypoventilation, though no cut off value has

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 hypothy-

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

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

falls below 40 cm H2O, FVC < 50%, or in the setting of abnormal nocturnal

roidism, depression or obesity should also be addressed.

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

(or a combination of both) [20].

been established [19].

**5. Treatment**

oximetry [22].

aberrant valuates seen at times with PtCO2 [25].

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

in diagnosing hypoventilation by measuring a nocturnal transcutaneous carbon dioxide [PtcC02] increment of >10 mm Hg above 50 mm Hg for >10 min. This is performed with simultaneous pulse oximetry recording to compensate for possible aberrant valuates seen at times with PtCO2 [25].

Nocturnal and daytime arterial blood gases (ABG) is another tool that can be used to predict nocturnal hypoventilation resulting in hypoxia (PaO2 < 60 mm Hg) and hypercapnia (PaCO2 > 45 mm Hg). Nocturnal hypoventilation is suggested by an increase of PaCO2 by 10 mm Hg when comparing nocturnal to daytime values. This method is more invasive, and disparities can sometimes only be seen late in the disease [20]. Hypoventilation can also be diagnosed by ABG with hypercapnia defined as a cut off of PCO2 > 45 mm Hg while resting in a seated position for 15 min [26].

In-laboratory overnight polysomnography is the gold standard for the diagnosis of hypoventilation and OSA. At home tests are not recommended for patients with neuromuscular disease as these are limited studies. The standard polysomnogram consists of at least 3 electroencephalography (EEG) channels, chin and leg electromyography (EMG), 2 eye (electrooculogram) leads, effort channels, flow channels, electrocardiography and SaO2. This allows for tracking and monitoring the stages of sleep, SaO2 abnormalities and any abnormal movements [20]. Polysomnography [PSG] with capnography [transcutaneous PCO2] detects sleep-related hypoventilation [PCO2 increment more than 10 mmHg during sleep versus wakefulness, especially during REM] and is more sensitive than oximetry. One third of the patients with confirmed sleep hypoventilation have normal oxygenation [12, 19]. Using PSG, the etiologies of sleep disturbances can be distinguished using analysis of this multimodal test and patterns of SaO2 abnormalities. This allows for recognition of hypoxemia that is event related (obstructive sleep apnea) or due to hypoventilation (or a combination of both) [20].

The measurement of diaphragmatic thickening using ultrasound is a new developing technique that predicts hypoventilation, though no cut off value has been established [19].
