3. Factors associated with long-term survival, mortality risk, and thus with life expectancy in CP

In the preceding section, we provided a general introduction to the concept of life expectancy and touched upon the idea that persons with various medical conditions may have life expectancies lower than those of age- and gender-matched general populations. In this section we identify the main factors associated with longevity and life expectancy in CP. We will delineate these factors roughly in order of importance, beginning with those having the greatest potential impact on life expectancy. The reader should keep in mind, however, that everything is relative in this regard. Thus, while gross motor functioning may rightly be identified as a major factor, and often the most significant factor effecting life expectancy in CP, for those with only minor deficits in gross motor functioning, another factor may in fact be more relevant. Thus, for any given individual or group, the factors identified in this section may need to be re-ordered for importance.

#### 3.1. Gross motor functioning

"The contraction of the muscle…causes dilation of the arterioles, capillaries, and lymph spaces, allowing more oxygenized blood to flow to the muscular fibers, which abstract from it what they require for their nutrition and let the remainder, together with used-up material, pass partly into the veins, partly into the lymph spaces and the lymphatic vessels. By this process the muscle is nourished, the products of decomposition are removed, metabolism is promoted, and heat is produced. …

The most natural of all muscular exercises, as pointed out by Hippocrates, is walking exercise. A great part of all the muscles in the body is activated by it; the action of the heart and respiratory organs is increased; the blood is passed with greater force from the heart into the blood vessels of the body, which are obliged to contract more vigorously, carry more blood to the different organs of the body, nourish the latter, and are themselves nourished through their work." Sir Herman Weber, On the Influence of muscular exercise on longevity. 1918 [13].

It has long been understood that voluntary physical activity helps promote health and longevity, and that, conversely, a sedentary lifestyle leads to elevated risk of morbidity and mortality [8–13]. The negative consequences of involuntary inactivity, after injury, illness, or surgery, have also been documented [14]. That the limitations in volitional gross motor functioning that often manifest in persons with CP might negatively impact survival and life expectancy should therefore come as no surprise. Nevertheless, clear evidence of this association for CP and other encephalopathies affecting gross and fine motor functioning was not published before 1990.

In 1990, a Special Article published in the New England Journal of Medicine reported on the life expectancy of severely neurologically disabled people [15]. Drawing on the recent work that had identified severe intellectual disability (or mental retardation, as it was called at the time) as a marker for mortality rates far exceeding those of age- and gender-matched GPs [16], the study provided life tables stratified by level of disability. For the first time in a major medical journal, level of gross motor functioning emerged as a profound indicator of elevated mortality risk: Life expectancy for immobile children were reported to be less than 10% of age-matched GP life expectancy, and less than 20% that of ambulatory children with comparable levels of intellectual disability. Unfortunately, the article had a serious flaw that rendered all actual life expectancy figures too low, and all mortality rates too high by something on the order of a factor of 3.

Subsequent evaluations of life expectancy of CP specifically based on the same source of data (but without errors of arithmetic) have subsequently been reported and have confirmed what was perhaps the primary finding in the NEJM Special Article: life expectancy varies on a seeming continuum with level of independent gross motor functioning. Evidence in support of this hypothesis is abundant now, coming from numerous countries around the globe. Examples are easily found in the references at the end of this chapter. A summary of life expectancy estimates per se will be found in a recent review of literature from 1990 to 2014 [7]. Life expectancy for young children range from as low as 15 remaining years for those with little or no purposeful gross motor functional ability, to nearly as high as that of their peers in the GP for those who are able to walk without difficulty (and who have no other significant comorbidities related to their CP).

#### 3.2. Fine motor functioning and feeding ability

from age 5 to 35 years. On the same figure, we include the corresponding GP survival curve over the same ages. One can immediately see that the area under the CP curve has to be less than that below the GP curve, and this would be true even if both curves extended to ages over 100 years. Published studies of survival of CP (or almost any medical condition) provide estimates of survival across a limited age span - but survival to all ages is needed to estimate life expectancy. Thus some method of extrapolating information to ages 100 or beyond is necessary to use such

An in-depth explanation of the issues involved in such extrapolations is beyond the scope of this chapter. Descriptions and comparisons of various methods may be found in the references cited below [3, 5–7]. In the next section, we review the factors that have been shown to be

3. Factors associated with long-term survival, mortality risk, and thus with

In the preceding section, we provided a general introduction to the concept of life expectancy and touched upon the idea that persons with various medical conditions may have life expectancies lower than those of age- and gender-matched general populations. In this section we identify the main factors associated with longevity and life expectancy in CP. We will delineate these factors roughly in order of importance, beginning with those having the greatest potential impact on life expectancy. The reader should keep in mind, however, that everything is relative in this regard. Thus, while gross motor functioning may rightly be identified as a major factor, and often the most significant factor effecting life expectancy in CP, for those with only minor deficits in gross motor functioning, another factor may in fact be more relevant. Thus, for any given individual or group, the factors identified in this section may

"The contraction of the muscle…causes dilation of the arterioles, capillaries, and lymph spaces, allowing more oxygenized blood to flow to the muscular fibers, which abstract from it what they require for their nutrition and let the remainder, together with used-up material, pass partly into the veins, partly into the lymph spaces and the lymphatic vessels. By this process the muscle is nourished, the products of decomposition are removed, metabolism is

The most natural of all muscular exercises, as pointed out by Hippocrates, is walking exercise. A great part of all the muscles in the body is activated by it; the action of the heart and respiratory organs is increased; the blood is passed with greater force from the heart into the blood vessels of the body, which are obliged to contract more vigorously, carry more blood to the different organs of the body, nourish the latter, and are themselves nourished through their work." Sir Herman Weber, On the Influence of muscular exercise on longevity. 1918 [13].

empirical evidence to estimate life expectancy.

50 Cerebral Palsy - Clinical and Therapeutic Aspects

life expectancy in CP

need to be re-ordered for importance.

promoted, and heat is produced. …

3.1. Gross motor functioning

strongly associated with long-term survival in CP.

In published studies, the ability to dress independently and to feed oneself have served as surrogates for overall fine motor functioning, and the connection to longevity is again straightforward: The greater the independent abilities in these areas, the longer the life expectancy. Numerous studies from California have focused on feeding ability [17–21]. Studies from England have focused on combinations of self-feeding and dressing abilities [22–27], and one study from Israel accounted for independent/non-independent feeding ability [28]. The association of mortality risk with fine motor functioning is not nearly as strong as with gross motor functioning, and a number of studies have not addressed this factor at all. Thus, if one is able to account for a specific category of gross motor functioning, a further adjustment for precise levels of fine motor functioning would be expected to have a smaller impact, all else being equal.

As we have alluded to above, the issue of enteral nutrition (via gastrostomy or otherwise) deserves special attention, and a number of studies have addressed this to one degree or another [17–20, 28–32]. Taken as a whole, these studies provide evidence of a strong association between placement of (and need for) a feeding tube with elevated mortality risk, all else being equal. Of course, association is not causation, and a number of reviews have pointed out the difficulties in interpretation of this association [33–37]. As one noted, "Mortality rates range from 7 to 29% but there is no way to ascertain the degree to which mortality can be attributed to the intervention" [33].

#### 3.3. Intellectual disability

Historically, level of intellectual disability has been considered a strong driver of mortality rates and survival of people with a wide variety of neurological disabilities. Within the category of CP, level of intellectual disability may be of great importance for those whose gross and fine motor functional abilities are high; for those who are immobile and unable to feed themselves, the further impact of level of intellectual disability is small.

> accounting for level of gross motor impairment [43]. A number of studies from the UK identified severe visual disability as marker for elevated mortality [23, 25–27]. It may be that these disabilities are more common among more severely disabled people, and thus they may

> Table 2. Other issues that may be associated with excess mortality risk beyond the major factors discussed in preceding

Hydrocephalus Level of risk diminishes with age but risk of infection and malfunction of ventriculoperitoneal shunt

Decubitus ulcers Pose infection risk. More common among less mobile, and are part of the reason for excess mortality

Tracheostomy Poses infection risk. At least one study of people with developmental disabilities reported an excess

reflux; leading to aspiration pneumonia or other respiratory infections. Contractures May impact negatively on survival given that they can further limit volitional movement.

Severe cases may impact heart and lung function; surgical intervention is relatively safe and effective in

Survival, Mortality, and Life Expectancy http://dx.doi.org/10.5772/intechopen.80293 53

Related to swallowing dysfunction, dysphagia, paletopharyngeal incoordination, or gastroestophageal

There are any number of additional factors relative to survival and mortality of persons with CP that have, to date, not been studied extensively. Factors that may well have some further impact on life expectancy, beyond the major known factors discussed above, are listed in

Life expectancy in CP is lower than expected in age- and gender-matched GPs. The question naturally arises as to what causes of death are driving the higher mortality rates and lower life expectancies, in this population? A number of studies have addressed this question, most focusing on either underlying cause of death or immediate (principal, primary) cause of death [24, 27, 42, 46–51]. At least two studies were vague as to whether an immediate cause or underlying cause was identified [52, 53]. Most of these studies relied on information reported in death certificates, [24, 27, 42, 46–51, 54] with at least one basing cause of death on a review of medical records from the time of death [53]. An underlying cause of death is meant to be the medical condition or other event that started a chain of events ending in death due to an immediate cause. In this section we will highlight some of the main underlying and immediate causes of death that have been found to be more common in CP than in the GP, and a few that

serve as a marker for overall level of brain injury.

may persist across the lifespan.

risk associated with immobility.

Ventilator Poses risk independent of tracheostomy.

mortality risk of about 1% across all ages.

such cases.

3.6. Other issues

Factor Comment

Scoliosis, kyphosis

Frequent aspiration

sections.

4. Causes of death in CP

are in fact less common.

Table 2.

#### 3.4. Epilepsy/seizures

Many studies have addressed the association of epilepsy, including remote symptomatic epilepsy, with elevated risk of mortality as a general medical condition, irrespective of any underlying disability [38, 39]. For remote symptomatic epilepsy, comparisons of mortality with the GP may be misleading, as some of the excess may be associated with an underlying brain injury or other neurological condition precipitating the seizures. A California study attempted to measure excess mortality risk associated with seizures by focusing on people with mild developmental disabilities and comparing mortality among those with and without a history of seizures [40, 41]. In studies of CP seizures have also been shown to be markers for excess mortality, above and beyond the excess mortality risk associated with limitations in mobility or feeding ability and other CP-associated disabilities [17, 18, 42, 43]. The relative impact of epilepsy on life expectancy is greater for those with greater levels of independent gross motor functioning.

The reason for the elevated risk of mortality in CP associated with seizures is likely multifactorial. First, as we will see in a subsequent section, seizures and convulsions do manifest as a cause of death in CP, and thus a direct link with mortality is evident. The presence of seizures may also be a marker for overall more involved brain injuries, which in turn may be associated with greater risk of long-term morbidity and mortality. And finally, some anti-epileptic drugs are associated side-effects that can be life threatening, including toxicities, liver failure, anemia, metabolic acidosis, and thrombocytopenia, among others [44, 45].

#### 3.5. Visual and auditory disability

There is little evidence to suggest that auditory or visual disabilities impact directly on mortality risk in cerebral palsy. One Australian study did include deafness and blindness among five "additional impairments" that they found to have a significant impact on mortality rates after


Table 2. Other issues that may be associated with excess mortality risk beyond the major factors discussed in preceding sections.

accounting for level of gross motor impairment [43]. A number of studies from the UK identified severe visual disability as marker for elevated mortality [23, 25–27]. It may be that these disabilities are more common among more severely disabled people, and thus they may serve as a marker for overall level of brain injury.

#### 3.6. Other issues

As we have alluded to above, the issue of enteral nutrition (via gastrostomy or otherwise) deserves special attention, and a number of studies have addressed this to one degree or another [17–20, 28–32]. Taken as a whole, these studies provide evidence of a strong association between placement of (and need for) a feeding tube with elevated mortality risk, all else being equal. Of course, association is not causation, and a number of reviews have pointed out the difficulties in interpretation of this association [33–37]. As one noted, "Mortality rates range from 7 to 29% but there is no way to ascertain the degree to which mortality can be

Historically, level of intellectual disability has been considered a strong driver of mortality rates and survival of people with a wide variety of neurological disabilities. Within the category of CP, level of intellectual disability may be of great importance for those whose gross and fine motor functional abilities are high; for those who are immobile and unable to feed

Many studies have addressed the association of epilepsy, including remote symptomatic epilepsy, with elevated risk of mortality as a general medical condition, irrespective of any underlying disability [38, 39]. For remote symptomatic epilepsy, comparisons of mortality with the GP may be misleading, as some of the excess may be associated with an underlying brain injury or other neurological condition precipitating the seizures. A California study attempted to measure excess mortality risk associated with seizures by focusing on people with mild developmental disabilities and comparing mortality among those with and without a history of seizures [40, 41]. In studies of CP seizures have also been shown to be markers for excess mortality, above and beyond the excess mortality risk associated with limitations in mobility or feeding ability and other CP-associated disabilities [17, 18, 42, 43]. The relative impact of epilepsy on life expectancy is greater for those with greater levels of independent gross motor

The reason for the elevated risk of mortality in CP associated with seizures is likely multifactorial. First, as we will see in a subsequent section, seizures and convulsions do manifest as a cause of death in CP, and thus a direct link with mortality is evident. The presence of seizures may also be a marker for overall more involved brain injuries, which in turn may be associated with greater risk of long-term morbidity and mortality. And finally, some anti-epileptic drugs are associated side-effects that can be life threatening, including toxicities, liver failure, anemia,

There is little evidence to suggest that auditory or visual disabilities impact directly on mortality risk in cerebral palsy. One Australian study did include deafness and blindness among five "additional impairments" that they found to have a significant impact on mortality rates after

themselves, the further impact of level of intellectual disability is small.

metabolic acidosis, and thrombocytopenia, among others [44, 45].

3.5. Visual and auditory disability

attributed to the intervention" [33].

52 Cerebral Palsy - Clinical and Therapeutic Aspects

3.3. Intellectual disability

3.4. Epilepsy/seizures

functioning.

There are any number of additional factors relative to survival and mortality of persons with CP that have, to date, not been studied extensively. Factors that may well have some further impact on life expectancy, beyond the major known factors discussed above, are listed in Table 2.

#### 4. Causes of death in CP

Life expectancy in CP is lower than expected in age- and gender-matched GPs. The question naturally arises as to what causes of death are driving the higher mortality rates and lower life expectancies, in this population? A number of studies have addressed this question, most focusing on either underlying cause of death or immediate (principal, primary) cause of death [24, 27, 42, 46–51]. At least two studies were vague as to whether an immediate cause or underlying cause was identified [52, 53]. Most of these studies relied on information reported in death certificates, [24, 27, 42, 46–51, 54] with at least one basing cause of death on a review of medical records from the time of death [53]. An underlying cause of death is meant to be the medical condition or other event that started a chain of events ending in death due to an immediate cause. In this section we will highlight some of the main underlying and immediate causes of death that have been found to be more common in CP than in the GP, and a few that are in fact less common.

Figure 3. Top four broad categories and corresponding subcategories of immediate cause of death among deaths with a mention of CP on the death certificate.

of causes of death as classified by the World Health Organization's International Statistical Classification of Diseases and Related Health Problems, tenth revision (ICD 10) [57], though in

Figure 4. Top five broad categories and corresponding subcategories of underlying cause of death among deaths with a

Survival, Mortality, and Life Expectancy http://dx.doi.org/10.5772/intechopen.80293 55

As Figure 3 (immediate causes of death) illustrates, CP (ICD 10 G80) was identified in US national death records as being the immediate cause of death in a substantial number of cases (19.5% of the leading causes, or 14.5% of all deaths). CP was far more common as an underlying cause of death among deaths including CP as any cause or contributing factor: initially, 59% of underlying causes of death were attributed to CP. We recoded these, when possible, to be (a) the last cause listed in Part 1 of a death certificate if that cause was not CP; or (b) the penultimate cause in Part 1 if one existed. After recoding, CP accounted for 10% of all underlying causes, or 13.8% of the top 5 leading causes (Figure 4). Many studies of causes of death in CP that have relied on death certificate information have reported CP itself to be among the most common underlying causes [24, 27, 46, 47, 49, 50]. Some authors have considered CP to

some of the studies to be referenced, an earlier revision of the ICD was employed.

4.1. Cerebral palsy as immediate or underlying cause of death in CP

mention of CP on the death certificate.

Figures 3 and 4 shows the distribution of the leading immediate and underlying causes of death among 26,677 deaths in the US from 2005 to 2014 that mentioned CP anywhere on the death certificate (immediate cause of death, underlying cause, contributing cause, or other significant condition).<sup>2</sup> Figure 3 shows the top 4 broad categories of immediate cause of death (accounting for 73% of all 26,677 deaths) as originally reported on death certificates [55], and as coded in the National Center for Health Statistics (NCHS) Multiple Cause of Death Records [56]. Figure 4 similarly reports the distribution of the leading underlying causes of death (top 5 broad categories, accounting for 74% of all 26,677 deaths), but recoding some underlying causes originally attributed to CP on death certificates and in the NCHS death records (see next section for details on the recoding). Figures 3 and 4 both report primarily broad categories

<sup>2</sup> Such analyses of death certificate information do not capture all deaths of people with CP, of course, as in some cases (cases of very mild CP, or when a death clearly had no connection to CP) CP is not mentioned on the death certificate. Other studies have estimated that approximately 40-50% of deaths of people with CP include no mention of CP on the death certificate [24, 43, 47].

Figure 4. Top five broad categories and corresponding subcategories of underlying cause of death among deaths with a mention of CP on the death certificate.

of causes of death as classified by the World Health Organization's International Statistical Classification of Diseases and Related Health Problems, tenth revision (ICD 10) [57], though in some of the studies to be referenced, an earlier revision of the ICD was employed.

#### 4.1. Cerebral palsy as immediate or underlying cause of death in CP

Figures 3 and 4 shows the distribution of the leading immediate and underlying causes of death among 26,677 deaths in the US from 2005 to 2014 that mentioned CP anywhere on the death certificate (immediate cause of death, underlying cause, contributing cause, or other significant condition).<sup>2</sup> Figure 3 shows the top 4 broad categories of immediate cause of death (accounting for 73% of all 26,677 deaths) as originally reported on death certificates [55], and as coded in the National Center for Health Statistics (NCHS) Multiple Cause of Death Records [56]. Figure 4 similarly reports the distribution of the leading underlying causes of death (top 5 broad categories, accounting for 74% of all 26,677 deaths), but recoding some underlying causes originally attributed to CP on death certificates and in the NCHS death records (see next section for details on the recoding). Figures 3 and 4 both report primarily broad categories

Such analyses of death certificate information do not capture all deaths of people with CP, of course, as in some cases (cases of very mild CP, or when a death clearly had no connection to CP) CP is not mentioned on the death certificate. Other studies have estimated that approximately 40-50% of deaths of people with CP include no mention of CP on the

Figure 3. Top four broad categories and corresponding subcategories of immediate cause of death among deaths with a

mention of CP on the death certificate.

54 Cerebral Palsy - Clinical and Therapeutic Aspects

2

death certificate [24, 43, 47].

As Figure 3 (immediate causes of death) illustrates, CP (ICD 10 G80) was identified in US national death records as being the immediate cause of death in a substantial number of cases (19.5% of the leading causes, or 14.5% of all deaths). CP was far more common as an underlying cause of death among deaths including CP as any cause or contributing factor: initially, 59% of underlying causes of death were attributed to CP. We recoded these, when possible, to be (a) the last cause listed in Part 1 of a death certificate if that cause was not CP; or (b) the penultimate cause in Part 1 if one existed. After recoding, CP accounted for 10% of all underlying causes, or 13.8% of the top 5 leading causes (Figure 4). Many studies of causes of death in CP that have relied on death certificate information have reported CP itself to be among the most common underlying causes [24, 27, 46, 47, 49, 50]. Some authors have considered CP to be "uninformative", or "not valid", as an underlying or principal cause of death [46, 58], and various methods of recoding such deaths have been undertaken [47, 51, 58]. That CP is often recorded as the underlying cause of death on death certificates may be unfortunate, as it is indeed somewhat uninformative.

infection, according to specific organism, sepsis is spread throughout its hierarchy, and across many of the broad categories of causes of death illustrated in Figures 3 and 4. Among the 26,677 deaths in the US from 2005 to 2014 that included CP anywhere on the death certificate, sepsis was noted to be the immediate cause in 1628 deaths (6.1%). Among these deaths, 98% were coded as ICD 10 A41 (other sepsis), of which most (97%) were coded as A41.9 (sepsis,

Survival, Mortality, and Life Expectancy http://dx.doi.org/10.5772/intechopen.80293 57

Cancers, including both malignant and benign tumors, were an underlying cause of death in only 924 records out of the 26,677 deaths contributing to the analyses of Figures 3 and 4, thus not a leading immediate or underlying cause of death, and not included in those figures. Nevertheless, some interesting results have been reported regarding cancer mortality in CP. A large California study reported that those with CP were at greater risk of death due to cancer of the esophagus (SMR = 5.4, 95% CI 3.1–8.8), colon (2.2, 1.4–3.3), liver (2.2, 1.1–4.1), breast (1.8, 1.2–2.6), and bladder (4.6, 2.1–8.7); but at a five-fold decreased risk of death due to cancer of the trachea, bronchus and lung (SMR = 0.2, 0.1–0.4) [59]. The number of cancer deaths is likely small due primarily to its typical manifestation in older ages, ages to which many with more

Another category of causes that appears frequently on deaths certificates of persons with CP is "symptoms, signs, and abnormal results of clinical and laboratory tests, not classified elsewhere," (ICD 10 R00–R99). These causes have been considered to be uninformative (or perhaps uninteresting) [46]. Referring again to Figure 4, we see that this category was the second leading underlying cause in US deaths from 2005 to 2014 (after recoding as described above), accounting for 22.2% of the top five leading cause categories, or 16.3% of all 26,677 deaths. However, given that this category includes "convulsions, not elsewhere classified," (ICD 10 R56) which in some cases account for up to half of deaths in this category, and also includes deaths related to unspecified respiratory and circulatory system problems, which in one study accounted for more than half of all deaths in this category (ICD 10 R56) [51, 58], more careful scrutiny of this broad category may be warranted. When comparing results from various studies as to the most common underlying or immediate cause of death in CP, it should be

borne in mind that some studies omit this, and other, categories from consideration.

The studies cited and discussed in the foregoing sections of this chapter provide a wealth of information about long-term survival, mortality, and life expectancy of people with cerebral palsy. Many questions remain to be answered, however, and more studies will undoubtedly be carried out in the future in an attempt to answer them. The questions such researchers will face in planning and executing their studies will be many and complex, and a full discussion of all

5. Methodological considerations for future research

unspecified organism).

4.6. Neoplasms, cancer (C00–D46)

severe levels of CP do not live owing to competing risks.

4.7. Other "uninformative" causes of death

#### 4.2. Respiratory diseases (ICD 10 J00–J99)

Respiratory diseases have consistently been reported to be among the leading causes of death among children and adults with CP [24, 27, 43, 46–53]. Figures 3 and 4 shows that, among deaths with any mention of CP on a death certificate, respiratory diseases were the most common immediate cause of death (39.7% of the top 4 causes of death, 29.5% of all deaths) and also the most common underlying cause after recoding many deaths originally attributed to CP (32.4% of the top 5 causes, 23.7% of all deaths).

Those with more severe levels of disability are at greater risk of mortality due to respiratory diseases. Standardized mortality ratios (SMRs) have been reported from as low as 10 or below in older ages for those with less severe disability, to as high as 600 or more at younger ages for those with more severe levels of disability [46]. Among respiratory diseases, pneumonias, and in particular pneumonia related to aspiration of solids or liquids, are common [24, 42, 43, 46– 49, 52, 53] and the excess in observed deaths due to this cause is again more pronounced in those with greater levels of disability [46].

#### 4.3. Circulatory diseases (I00–I99)

Circulatory diseases are also elevated in frequency as a cause of death in CP, and is a common cause of death in this population, though this is primarily evidenced in deaths that occur at older ages (as is the case in the GP as well) [27, 46, 47, 51]. Figures 3 and 4 show circulatory diseases to be the second leading immediate cause of death, and the fourth leading underlying cause (the latter after recoding of underlying causes of death with underlying cause originally attributed to CP).

#### 4.4. Diseases of the nervous system (G00–G99)

The broad category of diseases of the nervous system includes CP itself (G80), as we have discussed above. Even after recoding deaths that are attributed to CP, it remains as a significantly common underlying cause of death (Figure 4), but other nervous system diseases become more prominent. Among the most common underlying causes of death within this broad category other than CP itself are seizures and hydrocephalus [51, 52].

#### 4.5. Sepsis

Sepsis is an often life threatening condition caused by the body's system-wide inflammatory response to infection. Sepsis is a common cause of death in CP and in the GP, particularly in the elderly, the very young, or in those with severe disabilities or compromised immune systems. Because the ICD 10 classifies disease according to body system or, in the case of infection, according to specific organism, sepsis is spread throughout its hierarchy, and across many of the broad categories of causes of death illustrated in Figures 3 and 4. Among the 26,677 deaths in the US from 2005 to 2014 that included CP anywhere on the death certificate, sepsis was noted to be the immediate cause in 1628 deaths (6.1%). Among these deaths, 98% were coded as ICD 10 A41 (other sepsis), of which most (97%) were coded as A41.9 (sepsis, unspecified organism).

#### 4.6. Neoplasms, cancer (C00–D46)

be "uninformative", or "not valid", as an underlying or principal cause of death [46, 58], and various methods of recoding such deaths have been undertaken [47, 51, 58]. That CP is often recorded as the underlying cause of death on death certificates may be unfortunate, as it is

Respiratory diseases have consistently been reported to be among the leading causes of death among children and adults with CP [24, 27, 43, 46–53]. Figures 3 and 4 shows that, among deaths with any mention of CP on a death certificate, respiratory diseases were the most common immediate cause of death (39.7% of the top 4 causes of death, 29.5% of all deaths) and also the most common underlying cause after recoding many deaths originally attributed

Those with more severe levels of disability are at greater risk of mortality due to respiratory diseases. Standardized mortality ratios (SMRs) have been reported from as low as 10 or below in older ages for those with less severe disability, to as high as 600 or more at younger ages for those with more severe levels of disability [46]. Among respiratory diseases, pneumonias, and in particular pneumonia related to aspiration of solids or liquids, are common [24, 42, 43, 46– 49, 52, 53] and the excess in observed deaths due to this cause is again more pronounced in

Circulatory diseases are also elevated in frequency as a cause of death in CP, and is a common cause of death in this population, though this is primarily evidenced in deaths that occur at older ages (as is the case in the GP as well) [27, 46, 47, 51]. Figures 3 and 4 show circulatory diseases to be the second leading immediate cause of death, and the fourth leading underlying cause (the latter after recoding of underlying causes of death with underlying cause originally

The broad category of diseases of the nervous system includes CP itself (G80), as we have discussed above. Even after recoding deaths that are attributed to CP, it remains as a significantly common underlying cause of death (Figure 4), but other nervous system diseases become more prominent. Among the most common underlying causes of death within this

Sepsis is an often life threatening condition caused by the body's system-wide inflammatory response to infection. Sepsis is a common cause of death in CP and in the GP, particularly in the elderly, the very young, or in those with severe disabilities or compromised immune systems. Because the ICD 10 classifies disease according to body system or, in the case of

broad category other than CP itself are seizures and hydrocephalus [51, 52].

indeed somewhat uninformative.

56 Cerebral Palsy - Clinical and Therapeutic Aspects

4.2. Respiratory diseases (ICD 10 J00–J99)

those with greater levels of disability [46].

4.4. Diseases of the nervous system (G00–G99)

4.3. Circulatory diseases (I00–I99)

attributed to CP).

4.5. Sepsis

to CP (32.4% of the top 5 causes, 23.7% of all deaths).

Cancers, including both malignant and benign tumors, were an underlying cause of death in only 924 records out of the 26,677 deaths contributing to the analyses of Figures 3 and 4, thus not a leading immediate or underlying cause of death, and not included in those figures. Nevertheless, some interesting results have been reported regarding cancer mortality in CP. A large California study reported that those with CP were at greater risk of death due to cancer of the esophagus (SMR = 5.4, 95% CI 3.1–8.8), colon (2.2, 1.4–3.3), liver (2.2, 1.1–4.1), breast (1.8, 1.2–2.6), and bladder (4.6, 2.1–8.7); but at a five-fold decreased risk of death due to cancer of the trachea, bronchus and lung (SMR = 0.2, 0.1–0.4) [59]. The number of cancer deaths is likely small due primarily to its typical manifestation in older ages, ages to which many with more severe levels of CP do not live owing to competing risks.

#### 4.7. Other "uninformative" causes of death

Another category of causes that appears frequently on deaths certificates of persons with CP is "symptoms, signs, and abnormal results of clinical and laboratory tests, not classified elsewhere," (ICD 10 R00–R99). These causes have been considered to be uninformative (or perhaps uninteresting) [46]. Referring again to Figure 4, we see that this category was the second leading underlying cause in US deaths from 2005 to 2014 (after recoding as described above), accounting for 22.2% of the top five leading cause categories, or 16.3% of all 26,677 deaths. However, given that this category includes "convulsions, not elsewhere classified," (ICD 10 R56) which in some cases account for up to half of deaths in this category, and also includes deaths related to unspecified respiratory and circulatory system problems, which in one study accounted for more than half of all deaths in this category (ICD 10 R56) [51, 58], more careful scrutiny of this broad category may be warranted. When comparing results from various studies as to the most common underlying or immediate cause of death in CP, it should be borne in mind that some studies omit this, and other, categories from consideration.

#### 5. Methodological considerations for future research

The studies cited and discussed in the foregoing sections of this chapter provide a wealth of information about long-term survival, mortality, and life expectancy of people with cerebral palsy. Many questions remain to be answered, however, and more studies will undoubtedly be carried out in the future in an attempt to answer them. The questions such researchers will face in planning and executing their studies will be many and complex, and a full discussion of all factors that ought to be considered is beyond the scope of this chapter. In this section, we mention a few of the most important methodological considerations for future studies in the broad context of questions about CP survival and life expectancy. We will also point to a few areas of research that remain poorly explored but important.

things: (a) how much of the increase in mortality for people with a gastrostomy tube is caused by the need for a tube versus the placement and presence of the tube itself; (b) what if all children with CP of a given functional profile were given a gastrostomy tube; or (c) what if no children with CP of a given profile were given gastrostomy tubes? Given the right data and careful analysis, even in the absence of an ethically impractical randomized clinical trial [35], the causal inference framework could help answer these and other important questions.

Survival, Mortality, and Life Expectancy http://dx.doi.org/10.5772/intechopen.80293 59

In this chapter we have reviewed the general concepts of life expectancy, life tables, and survival curves. We reviewed the important predictors of mortality and life expectancy in CP,

Mobility is a strong predictor of mortality in CP, and as a consequence, a strong predictor of cause of death; in young and old with CP, respiratory diseases figure prominently as a cause of death, and circulatory diseases become more relevant in older ages. Neurologic disorders are also a major category of cause of death, even after reclassifying underlying causes initially attributed to CP to more informative causal categories. Seizures and hydrocephalus are impor-

Future research in the mortality and life expectancy of CP should focus on analyzing data using as many of the previously-identified risk factors as possible and should stratify patients using widely replicable scales of those factors, such as GMFCS. New tools of causal inference

Though much has been learned about life expectancy and causes of death in CP, there is undoubtedly much to be learned. It is our hope that this review and our recommendations will help guide future research in its quest to answer the many open questions related to long-

[1] The Economist. Life Expectancy in America Has Declined for Two Years in a Row. 2018 [2] Arias E, Heron M, Xu J. United States life tables, 2013. National Vital Statistics Reports.

should be employed to help control bias and confounding in observational studies.

term mortality and survival, and life expectancy in cerebral palsy.

\*Address all correspondence to: sday@mortalityresearch.com

Mortality Research and Consulting, Inc., City of Industry, California, USA

6. Conclusions

Author details

References

2017;66(3):1-63

as well as the major causes of death common in CP.

tant causes in this category as well.

Steven M. Day\* and Robert J. Reynolds

#### 5.1. External validity

In previous sections of this chapter, we have identified a number of risk factors that are known to be strongly associated with survival and life expectancy in CP. One of the most important factors is gross motor functioning, and any study of survival in CP must account for this. However, as the literature to date has demonstrated, there are many ways to form cohorts based on combinations of this and other functional abilities. Therefore, for the sake of comparing results across time and place, we advise forming cohorts according to Gross Motor Function Classification System (GMFCS) [60] level or other commonly employed measures of gross motor functioning. For similar reasons, when possible, scales such as the Manual Ability Classification System (MACS) [61], the Communication Function Classification System (CFCS) [62], and the Eating and Drinking Ability Classification System (EDACS) [63] should be utilized. Other factors to account for can be gleaned from Section 4, perhaps chief among them gastrostomy status. Some studies will be limited by data that has been collected historically, but prospective studies should seize the opportunity to measure and report results in a more standardized fashion.

#### 5.2. Time-based biases

Consider the 2000 UK study by Hutton et al. [24] Figure 1D in this study illustrates survival for children with severe ambulatory disability (i.e., no independent walking ability) and for children without severe ambulatory disability. The survival curves begin at age 0. This is problematic. Was walking ability really measured at age 0? Surely all children would be considered to have severe ambulatory disability at age 0, by the definition employed in this study. Furthermore, CP is rarely diagnosed in any child before a year or two of age. These issues are important: be as precise as possible with regard to when any time varying covariates are measured, and also as to precisely when (at what age) CP was diagnosed. Failure to do so can lead to a phenomenon known as immortal time bias, a surprisingly common error in reports of survival in a variety of populations, [64] including at least one study of survival of children with neurological disabilities [65].

#### 5.3. Methods for causal inference

Researchers in the fields of Epidemiology, Biostatistics, and Computer Science have collaborated in recent years to develop a framework for robust causal inference [66]. This framework provides the analytic techniques and needed assumptions for interpreting results obtained from observational (i.e. non-experimental) studies in a causal way. The framework also provides tools for thinking more clearly about hypotheses and identifying potential sources of bias and confounding in conventional analyses. Applying these methods to studies of mortality in CP may help to unravel complex questions which have thus far been impossible to address [67]. For example, on the subject of gastrostomy feeding, we might wonder several things: (a) how much of the increase in mortality for people with a gastrostomy tube is caused by the need for a tube versus the placement and presence of the tube itself; (b) what if all children with CP of a given functional profile were given a gastrostomy tube; or (c) what if no children with CP of a given profile were given gastrostomy tubes? Given the right data and careful analysis, even in the absence of an ethically impractical randomized clinical trial [35], the causal inference framework could help answer these and other important questions.

### 6. Conclusions

factors that ought to be considered is beyond the scope of this chapter. In this section, we mention a few of the most important methodological considerations for future studies in the broad context of questions about CP survival and life expectancy. We will also point to a few

In previous sections of this chapter, we have identified a number of risk factors that are known to be strongly associated with survival and life expectancy in CP. One of the most important factors is gross motor functioning, and any study of survival in CP must account for this. However, as the literature to date has demonstrated, there are many ways to form cohorts based on combinations of this and other functional abilities. Therefore, for the sake of comparing results across time and place, we advise forming cohorts according to Gross Motor Function Classification System (GMFCS) [60] level or other commonly employed measures of gross motor functioning. For similar reasons, when possible, scales such as the Manual Ability Classification System (MACS) [61], the Communication Function Classification System (CFCS) [62], and the Eating and Drinking Ability Classification System (EDACS) [63] should be utilized. Other factors to account for can be gleaned from Section 4, perhaps chief among them gastrostomy status. Some studies will be limited by data that has been collected historically, but prospective studies should

seize the opportunity to measure and report results in a more standardized fashion.

Consider the 2000 UK study by Hutton et al. [24] Figure 1D in this study illustrates survival for children with severe ambulatory disability (i.e., no independent walking ability) and for children without severe ambulatory disability. The survival curves begin at age 0. This is problematic. Was walking ability really measured at age 0? Surely all children would be considered to have severe ambulatory disability at age 0, by the definition employed in this study. Furthermore, CP is rarely diagnosed in any child before a year or two of age. These issues are important: be as precise as possible with regard to when any time varying covariates are measured, and also as to precisely when (at what age) CP was diagnosed. Failure to do so can lead to a phenomenon known as immortal time bias, a surprisingly common error in reports of survival in a variety of populations, [64] including at least one study of survival of

Researchers in the fields of Epidemiology, Biostatistics, and Computer Science have collaborated in recent years to develop a framework for robust causal inference [66]. This framework provides the analytic techniques and needed assumptions for interpreting results obtained from observational (i.e. non-experimental) studies in a causal way. The framework also provides tools for thinking more clearly about hypotheses and identifying potential sources of bias and confounding in conventional analyses. Applying these methods to studies of mortality in CP may help to unravel complex questions which have thus far been impossible to address [67]. For example, on the subject of gastrostomy feeding, we might wonder several

areas of research that remain poorly explored but important.

5.1. External validity

58 Cerebral Palsy - Clinical and Therapeutic Aspects

5.2. Time-based biases

children with neurological disabilities [65].

5.3. Methods for causal inference

In this chapter we have reviewed the general concepts of life expectancy, life tables, and survival curves. We reviewed the important predictors of mortality and life expectancy in CP, as well as the major causes of death common in CP.

Mobility is a strong predictor of mortality in CP, and as a consequence, a strong predictor of cause of death; in young and old with CP, respiratory diseases figure prominently as a cause of death, and circulatory diseases become more relevant in older ages. Neurologic disorders are also a major category of cause of death, even after reclassifying underlying causes initially attributed to CP to more informative causal categories. Seizures and hydrocephalus are important causes in this category as well.

Future research in the mortality and life expectancy of CP should focus on analyzing data using as many of the previously-identified risk factors as possible and should stratify patients using widely replicable scales of those factors, such as GMFCS. New tools of causal inference should be employed to help control bias and confounding in observational studies.

Though much has been learned about life expectancy and causes of death in CP, there is undoubtedly much to be learned. It is our hope that this review and our recommendations will help guide future research in its quest to answer the many open questions related to longterm mortality and survival, and life expectancy in cerebral palsy.

## Author details

Steven M. Day\* and Robert J. Reynolds

\*Address all correspondence to: sday@mortalityresearch.com

Mortality Research and Consulting, Inc., City of Industry, California, USA

#### References


[3] Singer RB. Methodology article 003M1 a method of relating life expectancy in the U.S. population life table to excess mortality. Journal of Insurance Medicine, 1992;24(1):32-41

[18] Strauss DJ, Shavelle RM, Anderson TW. Life expectancy of children with cerebral palsy.

Survival, Mortality, and Life Expectancy http://dx.doi.org/10.5772/intechopen.80293 61

[19] Brooks JC, Strauss DJ, Shavelle RM, Tran LM, Rosenbloom L, Wu YW. Recent trends in cerebral palsy survival. Part I: Period and cohort effects. Developmental Medicine and

[20] Brooks JC, Strauss DJ, Shavelle RM, Tran LM, Rosenbloom L, Wu YW. Recent trends in cerebral palsy survival. Part II: Individual survival prognosis. Developmental Medicine

[21] Brooks J, Tran L, Shavelle R, Strauss D. Concordance of survival models for children with cerebral palsy: A 24-year follow-up in the California database. In: 66th Annual Meeting of the American Academy for Cerebral Palsy and Developmental Medicine; Toronto. 2012.

[22] Hutton JL, Cooke T, Pharoah PO. Life expectancy in children with cerebral palsy. BMJ.

[23] Hemming K. Regional variation in survival of people with cerebral palsy in the United

[24] Hutton JL, Colver AF, Mackie PC, Rosenbloom L. Effect of severity of disability on survival in north East England cerebral palsy cohort. Archives of Disease in Childhood.

[25] Hutton JL. Life expectancy in severe cerebral palsy. Archives of Disease in Childhood.

[26] Hutton JL, Pharoah POD, Rosenbloom L. Effects of cognitive, motor, and sensory disabilities on survival in cerebral palsy. Archives of Disease in Childhood. 2002;86(2):84-90 [27] Hemming K, Hutton JL, Pharoah POD. Long-term survival for a cohort of adults with cerebral palsy. Developmental Medicine and Child Neurology. 2006;48(02):90

[28] Cohen A, Asor E, Tirosh E. Predictive factors of early mortality in children with develop-

[29] Westbom L, Bergstrand L, Wagner P, Nordmark E. Survival at 19 years of age in a total population of children and young people with cerebral palsy. Developmental Medicine

[30] Wockenforth R, Gillespie CS, Jaffray B. Survival of children following Nissen fundoplication.

[31] McGrath SJ, Splaingard ML, Alba HM, Kaufman BH, Glicklick M. Survival and functional outcome of children with severe cerebral palsy following gastrostomy. Archives of Phys-

[32] Smith SW, Camfield C, Camfield P. Living with cerebral palsy and tube feeding: A population-based follow-up study. The Journal of Pediatrics. 1999;135(3):307-310

mental disabilities. Journal of Child Neurology. 2008;23(5):536-542

Pediatric Neurology. 1998;18(2):143-149

Child Neurology. 2014;56(11):1059-1064

pp. 46-47

1994;309(6952):431-435

2000;83(6):468-474

2006;91(3):254-258

and Child Neurology. 2014;56(11):1065-1071

Kingdom. Pediatrics. 2005;116(6):1383-1390

and Child Neurology. 2011;53(9):808-814

The British Journal of Surgery. 2011;98(5):680-685

ical Medicine and Rehabilitation. 1992;73:133-137


[18] Strauss DJ, Shavelle RM, Anderson TW. Life expectancy of children with cerebral palsy. Pediatric Neurology. 1998;18(2):143-149

[3] Singer RB. Methodology article 003M1 a method of relating life expectancy in the U.S. population life table to excess mortality. Journal of Insurance Medicine, 1992;24(1):32-41

[4] Day SM, Reynolds RJ, Kush SJ. The relationship of life expectancy to the development and

[5] Anderson TW, Marion SA. Estimating mortality rates: The role of proportional life expec-

[6] Strauss DJ, Vachon PJ, Shavelle RM. Estimation of future mortality rates and life expectancy in chronic medical conditions. Journal of Insurance Medicine. 2005;37(1):20-34

[7] Day SM, Reynolds RJ, Kush SJ. Extrapolating published survival curves to obtain evidence-based estimates of life expectancy in cerebral palsy. Developmental Medicine

[8] Haskell WL, Lee IM, Pate RR, Powell KE, Blair SN, Franklin BA, et al. Physical activity and public health: Updated recommendation for adults from the American College of Sports

[9] Katzmarzyk PT, Lee IM. Sedentary behaviour and life expectancy in the USA: A cause-

[10] Jonker JT, De Laet C, Franco OH, Peeters A, Mackenbach J, Nusselder WJ. Physical activity and life expectancy with and without diabetes: Life table analysis of the Framingham

[11] Janssen I, Carson V, Lee IM, Katzmarzyk PT, Blair SN. Years of life gained due to leisuretime physical activity in the U.S. American Journal of Preventive Medicine. 2013;44(1):23-29

[12] Warburton DER, Nicol CW, Bredin SSD. Health benefits of physical activity: The evidence.

[13] Weber H. On the influence of muscular exercise on longevity. British Medical Journal.

[14] Halar, Eugen M. Bell KR. Physical inactivity: Physiological and functional impairments and their treatment. In: Frontera WR, DeLisa JA, Gans BM, Walsh NE, Robinson LR, editors. De Lisa's Physical Medicine & Rehabilitation Principles and Practice. 5th ed.

[15] Eyman RK, Grossman HJ, Chaney RH, Call TL. The life expectancy of profoundly handicapped people with mental retardation. The New England Journal of Medicine.

[16] Eyman RK, Grossman HJ, Tarjan G, Miller CR. A longitudinal study in a state residential facility. Monograph of the American Association of Mental Deficiency. 1987;7:1-73

[17] Strauss D, Shavelle R. Life expectancy of adults with cerebral palsy. Developmental

Philadelphia: Lippincott Williams & Wilkins; 2010. pp. 1249-1272

Medicine and Child Neurology. 1998;40(6):369-375

Medicine and the American Heart Association. Circulation. 2007;116(9):1081-1093

valuation of life care plans. NeuroRehabilitation. 2015;36(3):253-266

and Child Neurology. 2015;57(12):1105-1118

deleted life table analysis. BMJ Open. 2012;2(4):1-8

heart study. Diabetes Care. 2006;29(1):38-43

CMAJ. 2006;174(6):801-809

1918;1(2982):228-229

1990;323(9):584-589

tancy. 2005;35-41

60 Cerebral Palsy - Clinical and Therapeutic Aspects


[33] Ferluga ED, Sathe NA, Krishnaswami S, Mcpheeters ML. Surgical intervention for feeding and nutrition difficulties in cerebral palsy: A systematic review. Developmental Medicine and Child Neurology. 2014;56(1):31-43

[48] Evans PM, Alberman E, Street T, El L. Certified cause of death in children and young adults with cerebral palsy. Archives of Disease in Childhood. 1990;65:325-329

Survival, Mortality, and Life Expectancy http://dx.doi.org/10.5772/intechopen.80293 63

[49] Blair E, Watson L, Badawi N, Stanley FJ. Life expectancy among people with cerebral palsy in Western Australia. Developmental Medicine and Child Neurology. 2001;43(08):508

[50] Williams K, Alberman E. Survival in cerebral palsy: The role of severity and diagnostic

[51] Day SM, Reynolds RJ. Mortality related to cerebral palsy in the United States: Analysis of multiple causes of death and comparison with deaths in the general population from 2005 to 2014. In: Society for Pediatric and Perinatal Epidemiologic Research 31st Annual Meet-

[52] Himmelmann K, Sundh V. Survival with cerebral palsy over five decades in western

[53] Reddihough DS, Baikie G, Walstab JE. Cerebral palsy in Victoria, Australia: Mortality and

[54] Reid SM, Carlin JB, Reddihough DS. Reid et al. Reply. Developmental Medicine and Child

[55] CDC. U.S. Standard Certificate of Death, 2003 Revision [Internet]. Centers for Disease Control and Prevention; 2003 [cited 2018 Jul 3]. Available from: https://www.cdc.gov/

[56] NCHS. The National Center for Health Statistics Multiple Cause of Death Data [Internet]. [cited 2018 Jul 3]. Available from: ftp://ftp.cdc.gov/pub/Health\_Statistics/NCHS/Datasets/

[57] World Health Organization. International Statistical Classification of Diseases and Related

[58] Duruflé-Tapin A, Colin A, Nicolas B, Lebreton C, Dauvergne F, Gallien P. Analysis of the medical causes of death in cerebral palsy. Annals of Physical and Rehabilitation Medicine.

[59] Day SM, Brooks J, Strauss D, Shumway S, Shavelle RM, Kush S, et al. Cancer mortality in cerebral palsy in California, 1988–2002. International Journal on Disability and Human

[60] Palisano R, Rosenbaum P, Bartlett D, Livingston M. Gross motor function classification system expanded and revised. Developmental Medicine and Child Neurology. 2007:1-4. Available from: http://motorgrowth.canchild.ca/en/GMFCS/resources/GMFCS-ER.pdf

[61] Eliasson AC, Krumlinde-Sundholm L, Rosblad B, Beckung E, Arner M, Ohrvall AM, et al. The manual ability classification system (MACS) for children with cerebral palsy: Scale development and evidence of validity and reliability. Developmental Medicine and Child

Sweden. Developmental Medicine and Child Neurology. 2015;57(8):762-767

causes of death. Journal of Paediatrics and Child Health. 2001;37(2):183-186

labels. Developmental Medicine and Child Neurology. 1998;40(6):376-379

ing. 2018. p. 22

DVS/mortality/

2014;57(1):24-37

Development. 2008;7(4):425-432

Neurology. 2012;54(9):867-868

nchs/data/dvs/death11-03final-acc.pdf

Health Problems. Vol. 1. Tenth revision. 2016


[48] Evans PM, Alberman E, Street T, El L. Certified cause of death in children and young adults with cerebral palsy. Archives of Disease in Childhood. 1990;65:325-329

[33] Ferluga ED, Sathe NA, Krishnaswami S, Mcpheeters ML. Surgical intervention for feeding and nutrition difficulties in cerebral palsy: A systematic review. Developmental Medicine

[34] Cowen ME, Simpson SL, Vettese TE. Survival estimates for patients with abnormal swal-

[35] Samson-Fang L, Butler C, O'Donnell M. Effects of gastrostomy feeding in children with cerebral palsy: An AACPDM evidence report. Developmental Medicine and Child Neu-

[36] Srivastava R, Downey EC, O'Gorman M, Feola P, Samore M, Holubkov R, et al. Impact of fundoplication versus gastrojejunal feeding tubes on mortality and in preventing aspiration pneumonia in young children with neurologic impairment who have gastroesopha-

[37] Dahlseng MO, Andersen GL, Da Graca Andrada M, Arnaud C, Balu R, De La Cruz J, et al. Gastrostomy tube feeding of children with cerebral palsy: Variation across six European

[38] Nevalainen O, Sander JW, Ansakorpi H, Bell GS, Keezer MR. Cause of death and predictors of mortality in a community-based cohort of people with epilepsyAuthor response. Neu-

[39] Granbichler CA, Zimmermann G, Oberaigner W, Kuchukhidze G, Ndayisaba JP, Taylor A, et al. Potential years lost and life expectancy in adults with newly diagnosed epilepsy.

[40] Strauss DJ, Day SM, Shavelle RM, Wu YW. Remote symptomatic epilepsy: Does seizure

[41] Day S, Strauss D, Shavelle R, Wu YW. Excess mortality in remote symptomatic epilepsy.

[42] Baird G, Allen E, Scrutton D, Knight A, McNee A, Will E, et al. Mortality from 1 to 16-18 years in bilateral cerebral palsy. Archives of Disease in Childhood. 2011;96(11):1077-1081

[43] Reid SM, Carlin JB, Reddihough DS. Survival of individuals with cerebral palsy born in Victoria, Australia, between 1970 and 2004. Developmental Medicine and Child Neurol-

[44] Forsgren L, Edvinsson SO, Nyström L, Blomquist HK. Influence of epilepsy on mortality in mental retardation: An epidemiologic study. Epilepsia. 1996;37(10):956-963 [45] Chen AH. Update on pediatric epilepsy. Advances in Pediatrics. 2011;58(1):259-276

[46] Strauss D, Cable W, Shavelle R. Causes of excess mortality in cerebral palsy. Developmen-

[47] Maudsley G, Hutton JL, Pharoah POD. Cause of death in cerebral palsy: A descriptive

countries. Developmental Medicine and Child Neurology. 2012;54(10):938-944

low studies. Journal of General Internal Medicine. 1997;12(2):88-94

and Child Neurology. 2014;56(1):31-43

geal reflux disease. Pediatrics. 2009;123(1):338-345

severity increase mortality? Neurology. 2003;60(3):395-399

Journal of Insurance Medicine. 2003;35(3–4):155-160

tal Medicine and Child Neurology. 1999;41(9):580-585

study. Archives of Disease in Childhood. 1999;81(2):390-394

rology. 2003;45:415-426

62 Cerebral Palsy - Clinical and Therapeutic Aspects

rology. 2016;87(8):852.2-852.85853

Epilepsia. 2017;58(11):1939-1945

ogy. 2012;54(4):353-360


Neurology. 2006;48(7):549-554. Available from: http://www.ncbi.nlm.nih.gov/pubmed/ 16780622

**Chapter 4**

**Provisional chapter**

**Cerebral Palsy and Epilepsy**

**Cerebral Palsy and Epilepsy**

http://dx.doi.org/10.5772/intechopen.79565

condition of the patient.

**1. Introduction**

as nonprogressive process.

Additional information is available at the end of the chapter

Additional information is available at the end of the chapter

DOI: 10.5772/intechopen.79565

The frequency of epilepsy in children with cerebral palsy is 40 times higher than the common population rate. The presence of epilepsy aggravates the clinical course of cerebral palsy, complicates the rehabilitation, affects the prognosis of motor and intellectual functions, and could be life-threatening. Another problem is the possibility of aggravation of epileptic seizures and their appearance de novo due to application of some neurorehabilitation methods (electrophoresis, acupuncture, nootropic drugs, brain stimulators, etc.). Children with cerebral palsy have a broad spectrum of epilepsies—varying from favorable combinations with benign idiopathic forms to extremely severe epileptic encephalopathies. Frequent combination of epileptic and non-epileptic paroxysms causes difficulty in their interpretation and differential diagnosis. Video-EEG monitoring is the "golden standard" for differential diagnostic of epileptic and non-epileptic events, and it is very useful for investigation of patients with cerebral palsy. Treatment of epilepsy in combination with cerebral palsy strictly requires an individual approach due to the form of epilepsy, seizure types, age of the patient, comorbidity, and somatic and mental

The actual problem is the presence of epileptic seizures in children with cerebral palsy that caused deterioration of disease, complicates the rehabilitation, affects the prognosis of motor and intellectual functions, and could be life-threatening. Also, the presence of epileptiform discharges with high index can cause progression of cognitive defects and also with possible increasing of motor deficits. These phenomena violate such a core criterion of cerebral palsy

**Keywords:** cerebral palsy, epilepsy, epileptic seizures, EEG, AEDs

© 2016 The Author(s). Licensee InTech. This chapter is distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

© 2018 The Author(s). Licensee IntechOpen. This chapter is distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use,

distribution, and reproduction in any medium, provided the original work is properly cited.

Alexey Kholin

Alexey Kholin

**Abstract**


#### **Chapter 4 Provisional chapter**

#### **Cerebral Palsy and Epilepsy Cerebral Palsy and Epilepsy**

#### Alexey Kholin Alexey Kholin

Neurology. 2006;48(7):549-554. Available from: http://www.ncbi.nlm.nih.gov/pubmed/

[62] Hidecker MJC, Paneth N, Rosenbaum PL, Kent RD, Lillie J, Eulenberg JB, et al. Developing and validating the communication function classification system for individuals with

[63] Tschirren L, Bauer S, Hanser C, Marsico P, Sellers D, van Hedel HJA. The eating and drinking ability classification system: Concurrent validity and reliability in children with

[64] Day SM, Reynolds RJ. Immortal Time Bias: A Source of Bias in Estimating Life Expectancy and Other Measures [Internet]. Mortality Research & Consulting: Musings, Revelations,

[65] Plioplys AV, Kasnicka I, Lewis S, Moller D. Survival rates among children with severe

[66] Pearl J. The art and science of cause and effect. In: Causality: Models, Reasoning, and Inference. 2009. pp. 401-428. Available from: https://ecampus.uni-bonn.de/goto\_ecampus\_

[67] Day SM, Reynolds RJ. Risk factors for cerebral palsy: Current knowledge and future causal inference. Developmental Medicine and Child Neurology. 2013;55(6):490

cerebral palsy. Developmental Medicine and Child Neurology. 2011;53(8):704-710

cerebral palsy. Developmental Medicine and Child Neurology. 2018;60(6):611-617

Reviews. 2013. Available from: http://www.mortalityresearch.com/main/post/221

neurologic disabilities. Southern Medical Journal. 1998;91(2):161-172

16780622

64 Cerebral Palsy - Clinical and Therapeutic Aspects

file\_1046817\_download.html

Additional information is available at the end of the chapter Additional information is available at the end of the chapter

http://dx.doi.org/10.5772/intechopen.79565

#### **Abstract**

The frequency of epilepsy in children with cerebral palsy is 40 times higher than the common population rate. The presence of epilepsy aggravates the clinical course of cerebral palsy, complicates the rehabilitation, affects the prognosis of motor and intellectual functions, and could be life-threatening. Another problem is the possibility of aggravation of epileptic seizures and their appearance de novo due to application of some neurorehabilitation methods (electrophoresis, acupuncture, nootropic drugs, brain stimulators, etc.). Children with cerebral palsy have a broad spectrum of epilepsies—varying from favorable combinations with benign idiopathic forms to extremely severe epileptic encephalopathies. Frequent combination of epileptic and non-epileptic paroxysms causes difficulty in their interpretation and differential diagnosis. Video-EEG monitoring is the "golden standard" for differential diagnostic of epileptic and non-epileptic events, and it is very useful for investigation of patients with cerebral palsy. Treatment of epilepsy in combination with cerebral palsy strictly requires an individual approach due to the form of epilepsy, seizure types, age of the patient, comorbidity, and somatic and mental condition of the patient.

DOI: 10.5772/intechopen.79565

**Keywords:** cerebral palsy, epilepsy, epileptic seizures, EEG, AEDs

#### **1. Introduction**

The actual problem is the presence of epileptic seizures in children with cerebral palsy that caused deterioration of disease, complicates the rehabilitation, affects the prognosis of motor and intellectual functions, and could be life-threatening. Also, the presence of epileptiform discharges with high index can cause progression of cognitive defects and also with possible increasing of motor deficits. These phenomena violate such a core criterion of cerebral palsy as nonprogressive process.

© 2016 The Author(s). Licensee InTech. This chapter is distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. © 2018 The Author(s). Licensee IntechOpen. This chapter is distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

The frequency of neonatal seizures in children with cerebral palsy in 17 times is higher than common population rate, febrile seizures (2.5 times), and epilepsy (more than 40 times higher) [1].

**3.** Non-rare cerebral palsy is combined with epileptic encephalopathies of infancy and early childhood (Ohtahara, West, Markand-Blume-Ohtahara, Lennox-Gastaut syndromes, etc.).

Cerebral Palsy and Epilepsy

67

http://dx.doi.org/10.5772/intechopen.79565

**4.** The prevalence of the clinical picture of complex focal, secondarily generalized, and socalled pseudo-generalized epileptic seizures (atypical absence, tonic spasms, and bilateral

**5.** Frequent combination of epileptic and non-epileptic paroxysms, as well as possible similarity of their kinematics, causes difficulty in their interpretation and differential diagnosis. For example, the "dystonic attacks" with kinetic type of asymmetric tonic neck reflex

**6.** The presence of epilepsy aggravated motor and cognitive impairment in cerebral palsy. Frequently, epileptic seizures and epileptiform discharges with high index caused cognitive epileptiform disintegration or partial cognitive defects, as well as a possible increase

**7.** Frequent combination of cerebral palsy and benign epileptiform discharges of childhood (BEDC) on the EEG. Children with periventricular leukomalacia (PVL) and diffuse myelination defects had favorable prognosis for epileptic seizures but in combination with drug-resistant epileptiform discharges (including BEDC) and disintegrative epileptiform

**8.** In children with cerebral palsy (unless caused by cerebral dysgenesis) may not be a correlation between the sites of epileptiform activity and the area most pronounced structural

**9.** There is often a reflex provocation under the influence of audiogenic seizures and somatosensory stimulation (including epilepsy of feeding). The problem of differential diagno-

**10.** Increased risk of recurrence of epilepsy in children with cerebral palsy after antiepileptic

Children with cerebral palsy have a wide spectrum of epilepsies which varies from favorable combinations with benign idiopathic forms to extremely severe epileptic encephalopathies.

So, in the total of 231 pediatric cases of cerebral palsy observed and treated on the Department of Psychoneurology N2 Russian Children Clinical Hospital (Moscow) at 2007–2012 years, 84

The following forms of epilepsy were fixed: symptomatic focal frontal lobe epilepsy (25 patients (29.7%)), temporal lobe epilepsy (15 patients (17.9%)), parietal lobe epilepsy (3 patients (3.6%)), occipital lobe epilepsy (8 patients (9.5%)), SE-MISF (severe epilepsy with multifocal independent spike foci or Markand-Blume-Ohtahara syndrome) (7 patients (8.3%)), other multifocal epilepsies (4 patients (4.8%)), West syndrome (5 patients (6%)), focal epilepsy

of motor deficits and progressive loss of certain motor and speech skills.

sis of startle reflex and startle epilepsy in children with cerebral palsy.

children (36.4%) had a combination of cerebral palsy and epilepsy [3].

myoclonic seizures with focal origin).

processes.

changes in neuroimaging.

drug (AED) discontinuation.

(ATNR) and versive tonic epileptic seizures.

Epilepsy in cerebral palsy occurs according to different authors data in 28% [2], 36.4% [3], 44% [4], 43.2% [1], 62% [5], and even 75% [6].
