Sickle Cell Disease in Social Security Disability Evaluations (2025)
Chapter: 5 Effects of Sickle Cell Disease on the Central Nervous System
5
Effects of Sickle Cell Disease on the Central Nervous System
Sickle cell disease (SCD) reduces access to oxygen for tissue and organs throughout the body, including those of the central nervous system (CNS). This persistent hypoxia, combined with a higher risk for recurring cerebral infarcts such as strokes, can cause significant damage to the brain. This in turn can create significant impairment in people with SCD, regardless of whether the infarct is clinically detectable or a more “silent” stroke. This impairment occurs across motor, cognitive, behavioral, and a variety of other functional domains.
Beyond the structural damage to the brain, SCD is a chronic disease with recurring, painful vaso-occlusive crises. The stressors associated with this can be traumatizing. As a result, people with SCD are at increased risk of experiencing anxiety, mood, and behavioral disorders, including depression. Poor treatment in the health care system can also create further trauma. These disorders, like those caused by infarction and hypoxia, can cause impairment along a variety of functional areas.
The Social Security Administration (SSA) generally considers neurological, neurocognitive, and mood or anxiety disorders to be separate; in fact, the latter two categories are under a different body system in the SSA listings from the first. However, these disorders are all interrelated in terms of both cause and symptoms. The brain injury associated with SCD, whether caused by overt or silent stroke, can also be a direct etiological component of the other disorders discussed in this chapter.
It is similarly arbitrary to separate conditions of the CNS and those of other organ systems. While this report will consider them in separate chapters for ease of organization and readability, it should be noted that
all organ systems are part of a single body, and disorders in one can affect others. For example, stroke can affect motor functions related to maintaining good health in other organ systems, and traumatic experiences in the health care system can delay seeking further care for such issues. This relationship is bidirectional. The health effects of SCD across the body can lead to anxiety or mood disorders, negative effects on development, and other complications discussed in this chapter.
A more concrete example is pica, or the compulsive ingestion of nonnutritive substances. While the etiology of pica is generally unknown, various behavioral and mood disorders have been associated with the condition, and pica in turn has negative effects on digestion, development, and overall health. Similarly, chronic kidney disease associated with SCD substantially affects daily functioning in many ways but is also often concomitant with mood disorders such as anxiety and depression. Pica and other non-CNS complications are primarily discussed in Chapter 6, but these examples illustrate that CNS complications are often associated with such conditions.
This chapter provides an overview of selected health effects of SCD related to end-organ damage in the CNS, as well as other SCD-related conditions the committee considered within the “CNS umbrella.” The discussion of each condition briefly describes the condition, its pathogenesis and risk factors, and its functional implications. In addition, the committee reviewed the relevant SSA listing criteria. In most cases the committee found that the criteria in the listings would apply in the same way to individuals with and without SCD, while in other cases the committee found differences in the way that listing criteria might apply to someone with SCD. These considerations are included in separate sections entitled “Implications for SSA Listings.”
Three annex tables are included at the end of this chapter, after the references. Annex Table 5-1 lists selected CNS conditions associated with SCD. The table includes a summary of the potential functional implications of each of the conditions and, for children, the potential functional equivalence domains affected. Where applicable, it also includes SSA listings that may be relevant to the condition in question. For functional implications, the committee chose to focus on the kind of information that SSA considers about functioning in children and adults, which comes from a variety of sources, including the applicant, medical providers, educators, employers, and other third parties with knowledge of the applicant. Annex Table 5-2 lists the six functional equivalence domains considered by SSA when evaluating children for disability. Annex Table 5-3 lists the physical activities; vision, hearing, and speaking activities; and mental activities the committee considered in populating the tables, along with their definitions. The committee populated the columns on potential functional limitations
and potential functional equivalence domains affected based on the members’ collective expertise.
STROKE AND SILENT CEREBRAL INFARCT
Stroke is a broad term used to identify neurologic dysfunction resulting from abnormal cerebral blood flow (Sacco et al., 2013). Among people with SCD, this can include injury resulting from ischemia, silent cerebral ischemia, or hemorrhage.
Pathogenesis and Risk Factors
Sickled red blood cells can cause vascular occlusion in cerebral arteries, blocking blood flow to the brain and causing a stroke. When vascular occlusion is temporary, it can cause transient ischemic attacks, also known as ministrokes, which have similar symptoms to overt strokes but resolve within 24 hours. Also common are silent strokes, which can also be caused by severe anemia or otherwise inadequate blood flow and oxygenation to the brain.
An overt stroke is caused by occlusion in areas of the brain that result in motor, sensory, or verbal deficits. Overt stroke is one of the most devastating complications of SCD, and without primary prevention, 11 percent of children with SCD will have an overt stroke by age 18 (Ohene-Frempong et al., 1998; Powars et al., 1978).
In contrast to overt strokes, silent strokes are caused by vaso-occlusion in areas of the brain that do not cause obvious neurologic deficits that are detectable via physical exam (DeBaun et al., 2012; Kwiatkowski et al., 2009). Silent strokes are common, affecting 20 to 50 percent of people with hemoglobin (Hb) SS or HbSβ0 (beta-zero) thalassemia and about 10 percent of people with HbSC and HbSβ+ (beta-plus) thalassemia (Houwing et al., 2020). Diagnosis is based on neuroimaging. While such occurrences were previously considered incidental and largely asymptomatic, the neurocognitive impairment resulting from silent strokes in people with SCD is increasingly being recognized as an etiological component of significant disability.
In addition to the basic pathophysiology of SCD, children with evidence of cerebral vasculopathy—a range of disorders characterized by changes in the structure and function of blood vessels in the brain—are at greater risk for stroke compared to children in general (Fasano et al., 2015). In adults with SCD, the risk for overt stroke is compounded by the same modifiable and nonmodifiable risk factors relevant to stroke in adults without SCD, such as hypertension, hyperlipidemia, and tobacco use (Jordan et al., 2024; Oluwole et al., 2024). On the other hand, the evidence suggesting risk factors for silent stroke is weaker. Only a few studies have examined risk
factors for silent stroke, and they enrolled relatively small samples (DeBaun et al., 2012).
In an effort to prevent devastating functional and neurologic complications related to SCD, children are screened from ages 2 to 16 years with transcranial Doppler ultrasounds to detect abnormal cerebral blood flow and intervene with prophylactic exchange transfusions to minimize the risk of overt stroke (Lee et al., 2006). Recommendations for stroke screening in adults with SCD remain limited, with most current guidelines recommending screening via magnetic resonance imaging (MRI) once in adulthood (DeBaun et al., 2020; Ohene-Frempong et al., 1998; Powars et al., 1978).
In patients who do not receive prophylaxis, population-level studies have estimated the prevalence of overt stroke at approximately 3 to 5 percent (Kirkham and Lagunju, 2021). As stated above, an estimated 11 percent of children with SCD will have an overt stroke by age 18 (DeBaun and Kirkham, 2016). Moreover, approximately 67 percent of people with SCD who have had one stroke will have recurrent strokes (Powars et al., 1978).
Functional Implications
The functional implications of stroke and silent cerebral infarct will vary based upon the vascular territory involved in the infarct. The resulting limitations could include loss of motor function; changes in speech, communication, and other issues related to sensory or motor aphasia; and neurocognitive functional deficits. Annex Table 5-1 lists the functional limitations and functional equivalence domains that stroke and silent cerebral infarct may affect. The neurocognitive functional limitations are characterized more specifically in later sections within this chapter.
Prophylaxis for stroke can also inhibit function, including in areas related to employment, for people with SCD. Prophylactic treatment most commonly takes the form of chronic blood transfusions, which are given monthly. The landmark Stroke Prevention Trial in Sickle Cell Anemia (STOP trial) demonstrated that children with abnormal cerebral flow velocities who started such chronic blood transfusions had a 90 percent reduction in the risk of primary stroke compared with standard of care (Lee et al., 2006). Similarly, the Transcranial Doppler with Transfusions Changing to Hydroxyurea (TWiTCH) trial demonstrated that after 4 years of chronic transfusions, children with SCD and abnormal transcranial doppler velocities could transition off transfusions and onto hydroxyurea without increased risk of primary stroke (Ware et al., 2016). Transfusions are particularly beneficial in preventing recurrent strokes in people with SCD who have had strokes before; in one study, only 10 percent of enrolled participants with SCD with one prior stroke had a second after beginning transfusion therapy (Pegelow et al., 1995).
Given that trials attempting to discontinue transfusions (Adams et al., 2005) or to transition to hydroxyurea (Ware et al., 2012) did not meet their primary endpoints, the evidence-based recommendations to prevent recurrent stroke in someone with SCD who has had a stroke is to continue lifelong blood transfusions (DeBaun et al., 2020). In addition, chronic blood transfusions can reduce the incidence of silent strokes, as the Silent Cerebral Infarct Transfusion trial demonstrated (DeBaun et al., 2014).
Whether the transfusions are indicated for a few years (i.e., for primary prevention) or lifelong (i.e., for secondary prevention), transfusions are burdensome to people with SCD and their caregivers, disrupting participation in school and work and often requiring an entire day at the hospital or clinic. There are additional medical risks of chronic transfusion programs, including iron overload and red blood cell alloimmunization. The risk of alloimmunization is increased in people with SCD compared with other populations. Many patients require port placement for chronic blood transfusion programs, with associated risks of line complications and infections.
Implications for Social Security Administration Listings
Adults with SCD who have had an overt stroke may qualify for Social Security disability benefits under Listing 11.04, “vascular insult to the brain.” Children with SCD may qualify under the parallel listing for children, Listing 111.04. The SSA-relevant functional limitations and functional equivalence domains affected by these conditions are listed in Annex Table 5-2.
Unfortunately, silent infarcts may not readily fall under this listing given the lack of overt symptomatology involving motor or speech functions. Moreover, it is especially difficult to diagnose silent infarcts in pediatric patients because of the complexity of obtaining a brain MRI in younger children, particularly without sedation. People with SCD have a higher risk of complications from surgeries involving sedation; while more recent evidence suggests that deep sedation can be safely administered to children with SCD, this risk may make it harder to diagnose and document silent stroke in this group (Belmont et al., 2015; Firth et al., 2004; Koshy et al., 1995). As such, consideration of listings related to neurocognitive or mental–behavioral health disorders may also be relevant for people with SCD and may be particularly helpful in pediatric populations.
NEUROCOGNITIVE DISORDERS
Persons with SCD are at risk for neurodevelopmental and neurocognitive disorders, as well as intellectual developmental disorder. These are secondary to the pathophysiology of SCD, reflecting the effect of disease
across the lifespan. While neurodevelopmental challenges focus on pathology occurring during the developmental period and neurocognitive deficits are thought to occur later in life, complications related to SCD can occur at any time along this continuum.
Separating neurodevelopmental disorders, neurocognitive disorders, and intellectual developmental disorder is somewhat arbitrary and semantic in nature. The specific characterization of the type of cognitive deficit and its resulting functional limitations are imperative, and one individual may meet listing criteria across these various criteria over their lifetime.
Pathogenesis and Risk Factors
Regardless of whether or not an overt stroke occurs, abnormal cerebral blood flow can cause damage to the brain. Such brain injury can occur through severe vascular occlusions resulting in encephalomalacia, the loss or softening of brain tissue. However, neurocognitive disorders can occur even without infarction. Brain injury in SCD may also result from persistent hypoxia secondary to the decreased oxygen carrying capacity of sickled red blood cells or anemia.
Research has shown that anemia severity is associated with poorer cognitive function in children with SCD (Schatz et al., 2004). This association was shown to be an interdependent risk factor with socioeconomic status. In adults, hemoglobin level, age, and education were associated with lower neurocognitive performance (Vichinsky et al., 2010). As with cerebral infarction, people with a higher concentration of hemoglobin S (HbS percent) are at greater risk for neurocognitive complications; as a result, people with the HbSS genotype are thought to be at greatest risk.
Children with SCD also often experience nocturnal hypoxemia, which further complicates the neurodevelopmental trajectory (Hogan et al., 2006). Sleep-disordered breathing, nocturnal hypoxemia, and fragmented sleep have been associated with neurocognitive deficits (Rice et al., 2025; Tucker et al., 2022). These include reductions in verbal comprehension, executive function, and working memory.
Functional Implications
Overt stroke has been associated with a 10- to 15-point decline in intelligence quotient (IQ) scores from expected levels in children (Schatz and McClellan, 2006), particularly when the overt stroke occurs earlier in life (Couette et al., 2023). Even though a standardized assessment of IQ has historically been the gold standard metric for cognitive impairment, there are systemic limitations to the applicability of IQ for measuring function in the SCD population as shown by research indicating a strong association
between the education level of the head of household and the child’s IQ (King et al., 2014). Although a lower IQ score can indicate functional limitations, contextual and systemic factors in addition to SCD must be considered (Kawadler et al., 2016). Beyond IQ scores, studies examining specific cognitive domains such as attention, processing speed, executive functioning, language, visual–spatial processing, and memory have demonstrated neurodevelopmental effects on each, depending on the location of the overt stroke (Couette et al., 2023).
Even subclinical infarcts can severely affect neurocognition. In fact, screening of neurocognitive functioning may be the most effective way outside of brain MRI to identify individuals with silent infarct (DeBaun et al., 1998). The effect of silent infarcts is particularly relevant in pediatric populations, where early and compounded cerebrovascular insults throughout life can affect development, educational attainment, and work productivity, with functional impairment worsening with age as vascular insults related to SCD continue. Some studies have reported neurodevelopmental delay in children with SCD even younger than 1 year old (Berkelhammer et al., 2007). Much of this can be attributed to subclinical or overt cerebral infarct, which will affect the developmental trajectory that follows (Berkelhammer et al., 2007; Schatz et al., 2002).
These general cognitive deficits may result in a clinical diagnosis of intellectual developmental disorder or global developmental delay. However, it can often be difficult for people with SCD or their parents to document such delay; this is especially true when it is caused by silent stroke or by insufficient blood flow to the brain unrelated to infarction. Such disability often develops relatively slowly, with one study associating SCD of the HbSS phenotype with drops of approximately 1 IQ point per year (King et al., 2014). As a result, disability may not be evident until later in a child’s life rather than during early childhood when systems of care and education are most attuned to developmental concerns.
Cognitive deficits, which can be experienced alongside or in the absence of cerebral infarction, can also affect attention and executive function. In fact, research has shown that persons without visible tissue injury most often have deficits in verbal ability, verbal working memory, and processing speed (Schatz and McClellan, 2006). This illustrates the broad and variable effect that SCD can have on neurologic function. These specific cognitive deficits may result in symptoms consistent with clinical diagnoses of attention deficit/hyperactivity disorder, language disorders, specific learning disabilities, or cognitive disorders (Bills et al., 2025).
Individuals with cognitive deficits resulting from SCD have a higher risk of poor academic performance (Heitzer et al., 2021, 2023; Karkoska et al., 2021). They will likely also have difficulties in instrumental activities of daily living that will further affect functioning in school and vocational
settings, as well as general functional independence. Finally, research has shown that individuals with cognitive deficits resulting from SCD have limited health literacy, further affecting their ability to be functionally independent while living with a chronic, complex, multisystemic health condition (Bhatt et al., 2023).
Implications for Social Security Administration Listings
On the basis of known neurodevelopmental and neurocognitive deficits observed in individuals with SCD, the following additional SSA listings for adults and children respectively may be relevant:
- 12.02, 112.02 (Neurocognitive Disorders)
- 12.05, 112.05 (Intellectual Disorder)
- 12.11, 112.11 (Neurodevelopmental Disorders)
The SSA-relevant functional limitations and functional equivalence domains affected by these conditions are listed in Annex Table 5-1.
Notably, the SSA listings for intellectual disorder (12.05, 112.05) require an applicant to submit results from IQ testing. While SSA does not require any specific IQ test, such tests may be limited, as stated earlier. However, the listings for neurocognitive disorders (12.02, 112.02) and neurodevelopmental disorders (12.11, 112.11) define impairment in terms of function. Disability across cognitive functional areas can be documented via domain-specific neuropsychological testing. To the extent that all these conditions are related, applicants may qualify for Social Security disability benefits via those listings as well.
However, even while receiving specialist treatment, people with SCD do not always receive neurodevelopmental or neurocognitive screening (Afranie-Sakyi et al., 2024). The accumulative nature of these conditions means that without early detection, they will often progress and worsen before they are diagnosed. These difficulties in identifying and documenting disability will also impede applicants’ ability to demonstrate eligibility for Social Security benefits.
DEPRESSION, ANXIETY, AND TRAUMA
Depression
Depression is a common psychiatric disorder defined by the primary symptoms of depressed mood or anhedonia, which is a loss of interest or pleasure. Secondary symptoms include appetite changes, sleep difficulties,
psychomotor agitation or retardation, fatigue or loss of energy, difficulty with concentration, feelings of worthlessness, and suicidality (APA, 2013).
Pathogenesis and Risk Factors
People living with SCD are at increased risk for experiencing depressive symptoms. A summary of lifetime prevalence estimates for depression in different regions approximated the median estimate at 10 percent for the general population (Kessler and Bromet, 2013). By contrast, several reviews of the published literature have found wide variance in individual studies’ prevalence estimates for depression in people with SCD. While these estimates often cluster from 20 to 40 percent, some are as low as 2 percent and others are as high as 85 percent (Jonassaint et al., 2016; Leite et al., 2022; Moody et al., 2019; Oudin Doglioni et al., 2021). Some researchers suggest that this variance results from the many cultural and clinical contexts in which depression is measured, as well as the wide array of methodologies used to measure it (Oudin Doglioni et al., 2021). However, even Oudin Doglioni and colleagues (2021) “tentatively” estimated the prevalence of depression in people with SCD globally is approximately 29 to 36 percent. Moreover, 39 percent of respondents in a global survey of people with SCD reported depressive symptoms, including 47 percent of patients in high-income settings and 39 percent of patients in low- and middle-income settings (Osunkwo et al., 2021). This study used the economic status designations defined by the World Bank.
This increased risk comes primarily from the emotional stress of pain episodes, which can be frequent, severe, and unpredictable. Previous research has demonstrated that having more frequent or severe pain episodes predicts having more depressive symptoms (Jonassaint et al., 2024; Moody et al., 2019). Other pain-related outcomes associated with more depressive symptoms include higher interference of pain in daily life, catastrophizing, and a higher likelihood of opioid misuse (Jonassaint et al., 2024).
People with SCD commonly report secondary symptoms of depression as well. For example, the aforementioned global survey of this population found that 65 percent of respondents reported experiencing fatigue, and most of these individuals indicated that reducing fatigue was a priority treatment goal (Osunkwo et al., 2021).
Functional Implications
Depression can affect daily functioning, including tasks at school, job functions, and adherence to treatment. Effects on the instrumental activities of daily living have been found to be associated with depression, pain, sleep, attention, and executive functioning (Longoria et al., 2025). A recent systematic review demonstrated that chronic pain was associated with
depression, anxiety, pain outcomes, executive functioning, and functional impairment in youth living with SCD (Coco et al., 2024). Research has also identified relationships between fatigue and poor social functioning and depression in adults living with SCD (Knisely et al., 2020). Depression may reduce motivation to adhere to medication or self-management regimens. Mood disorders may be accompanied by fatigue, which in turn can affect activities of daily living, including, potentially, academic achievement and employment engagement (Ameringer et al., 2014).
Sleep disorders and sleep disturbances are highly prevalent in individuals with SCD. As patients age, total sleep time decreases, and sleep onset latency—the time it takes to fall asleep—increases (Koelbel and Kirkham, 2024). The sleep–pain relationship is cyclical; poor sleep quality is associated with high pain severity the next day, while high pain severity during the day is associated with poor sleep quality at night. Poor sleep quality has also been associated with other functional outcomes that influence the sleep–pain relationship (Evans et al., 2017). For example, a high degree of negative affect strengthens the relationship between pain severity and poor sleep quality (Valrie et al., 2021). Fatigue, in particular, is common in SCD and negatively affects health-related quality of life (Lanzkron et al., 2024), as it is associated with stress, mood, poor sleep quality, and lower working memory and executive functioning (Anderson et al., 2015; Cheminet et al., 2024). Sleep and fatigue have a similar bidirectional relationship; poor sleep predicts increases in next-day fatigue, and fatigue disrupts sleep patterns (Johnston et al., 2023).
Anxiety Disorders
Individuals with SCD may experience elevated levels of anxiety, including generalized anxiety disorder, social anxiety, and procedural anxiety. Anticipatory anxiety about pain crises or hospitalization is especially prevalent.
Pathogenesis and Risk Factors
In a global sample of people with SCD, 38 percent of enrolled individuals reported anxiety symptoms, with 39 percent of patients in high-income settings and 36 percent of patients in low- and middle-income settings reporting such symptoms (Osunkwo et al., 2021).
Research has demonstrated associations between pain frequency in SCD and anxiety (Reader et al., 2020). More severe pain was associated with greater social anxiety in older youth with SCD (Wagner et al., 2004). In addition, being hospitalized after prior negative health care experiences can be an anxiety trigger for patients (Drahos et al., 2025).
Functional Implications
Given the occurrences of poor hospital experiences and being perceived as drug-seeking by health care providers, some individuals with SCD report hesitancy in seeking care because of concern about being hospitalized (Drahos et al., 2025). Furthermore, anxiety affects their academic and vocational functioning, such that they fear consequences related to missing school and work.
Trauma
Individuals with SCD may experience trauma symptoms resulting from recurrent medical events and systemic health inequities. Some may meet the criteria for posttraumatic stress disorder (PTSD), triggered by exposure to a traumatic event with symptoms including reexperiencing the event, heightened arousal, negative thoughts or feelings, and avoidance of reminders of the trauma (APA, 2013).
Pathogenesis and Risk Factors
Trauma symptoms can be caused by the intense emotional toll of chronic medical events, such as those experienced by many people with SCD. A set of semistructured interviews and questionnaires given to 11 children with SCD and their parents in France found that 27 percent of enrolled children and 40 percent of enrolled parents met the criteria for PTSD. While not correlated with disease severity, PTSD among caregivers was correlated with a feeling of powerlessness over their child’s illness (Hofmann et al., 2007). Disease severity and education level were found to be associated with trauma ratings among caregivers in Saudi Arabia—longer hospital stays were associated with increased distress, and caregivers with higher education levels were less likely to report severe trauma (Alsaad et al., 2024).
As discussed earlier, trauma can also come from inequitable or otherwise unacceptable interactions with the health care system. One qualitative study exploring the effects of experienced discrimination from the perspective of caregivers and providers revealed that health care system factors underlie discrimination, with families’ challenging interactions with providers leading to perceptions of discrimination and experiences of discrimination affecting the caregiver–provider interactions. As stated elsewhere in the report, the SCD experience needs to be viewed in the context of historic and current racism within the United States and the health care system (Power-Hays and McGann, 2020), with patients and their families experiencing stigma and differential treatment within the health care system (Bulgin et al., 2018; Goddu et al., 2018).
Functional Implications
Trauma can affect daily functioning in social, occupational, and educational settings in several ways. First, its primary symptoms, such as intrusive memories, avoidance, heightened arousal, disordered sleep, and fatigue, can directly impede functioning. Trauma is also associated with higher rates of other mood and behavioral conditions such as depression or anxiety, both of which have functional implications themselves, as discussed above.
As discussed earlier, people with SCD also report higher rates of negative experiences with the health care system. These events can include longer wait times in the clinic, inadequate pain management, and medical professionals discounting complaints of pain; such insufficient treatment is likely to worsen the physical symptoms of SCD. However, the trauma from these events can also cause people with SCD to delay seeking medical care, which can worsen the effect of their symptoms on functioning and quality of life (Haywood et al., 2013; Jenerette et al., 2014; Stanton et al., 2010).
Implications for Social Security Administration Listings
Depressive, bipolar, and related disorders (12.04, 112.04); anxiety disorders (12.06, 112.06); and trauma (12.15, 112.15) are all included in the Mental Disorders sections of the SSA listings for both adults and children. The SSA-relevant functional limitations and functional equivalence domains affected by these conditions are listed in Annex Table 5-1. However, all three listings require formal medical documentation of the disorder in question. Given the complex diagnostic processes associated with these disorders, this may make it difficult for people with SCD who have limited access to specialist care to acquire the necessary documentation.
SUMMARY AND CONCLUSIONS
As in other body systems, SCD and its physiological effects reduce CNS access to oxygen. This includes stroke and silent stroke, which can cause significant damage to the brain and functional impairment in people with SCD. Moreover, SCD is associated with an increased risk of anxiety, mood, and behavioral disorders such as depression. Finally, both the complications of SCD and poor treatment in the health care system can cause trauma in people with SCD.
These conditions are all associated with one another, causing compounding functional impairment across motor, cognitive, and behavioral domains. For example, injury to the brain caused by stroke or silent stroke can cause other complications in the CNS; experiencing one stroke also increases the risk of further cerebral infarcts. Similarly, the effects of SCD
on the CNS are associated with impairments in other body systems. For example, depression, anxiety, and trauma are often associated with non-CNS complications such as those discussed in Chapter 6. Disorders of the CNS also often affect people’s ability to care for themselves and navigate the health care system. More generally, this illustrates the common reality of SCD as a disease with chronic, cumulative effects beyond the intermittent, acute pain crises.
Based on its review of the literature, the committee reached the following conclusions:
Conclusion 5-1: The central nervous system (CNS) effects of sickle cell disease (SCD) may lead to significant functional impairment, limiting the ability for school or work.
Conclusion 5-2: Because SCD is a multisystem disorder, the effects of SCD on the CNS often do not occur in isolation. SCD-related complications in the CNS and associated impairment are often cyclical and cumulative, both in terms of further complication in the CNS and in other body systems.
People with SCD are at increased risk of stroke, a broad term used to identify neurologic dysfunction resulting from abnormal blood flow to the brain. Some cerebral infarcts are not immediately clinically detectable, but even these “silent strokes” can cause significant brain injury. Recurring cerebral infarction affects motor, cognitive, behavioral, and other functional domains, and in children with SCD, strokes and silent strokes can profoundly alter the neurodevelopmental trajectory. Importantly, however, cognitive and developmental impairments are also observed in individuals with SCD in the absence of overt or silent strokes, suggesting that other SCD-related mechanisms can affect the brain.
This means that the impairments caused by subclinical—silent—strokes can still be assessed under SSA listings related to neurocognitive function; in fact, screening in this way is typically how silent strokes are detected. Even so, the difficulty of directly observing these silent strokes may make it difficult for people with SCD to qualify for disability benefits based on subclinical infarcts. This is especially true of pediatric patients, since it is often difficult to obtain MRIs in younger children without sedation.
This illustrates a common difficulty in applying for disability benefits on the basis of CNS-related impairments caused by SCD. Complications of the CNS can be difficult to detect and diagnose. Often, it requires specialist care, which may not be available in all care settings. The stressors posed by finding adequate care and diagnosis, as well as those caused by the
comorbidities associated with SCD, can be traumatizing. This can be further compounded by poor treatment while pursuing care.
Based on its review of the literature, the committee reached the following conclusions:
Conclusion 5-3: Limited access to specialists restricts diagnosis of CNS complications of SCD, including silent stroke, neurocognitive disorders, and mental or behavioral health disorders.
Conclusion 5-4: Poor experiences while pursuing care for SCD may negatively affect psychological well-being, compounding the physiological effects of damage to the CNS and increasing the risk of anxiety, mood, and behavioral disorders.
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ANNEX TABLE 5-1 Selected Central Nervous System Conditions Associated with SCD
| Health Effect | Potential Functional Limitations | Potential Functional Equivalence Domains Affected | Related SSA Listings |
|---|---|---|---|
| Stroke | Sitting; standing; walking; strenuous physical activity; lifting; carrying; pushing/pulling; reaching; gross and fine manipulation; foot/leg controls; climbing; low work; vision; hearing; speaking; understanding, remembering, and applying information; concentrating, persisting, or maintaining pace; problem solving; adapting or managing oneself; interacting with others | Acquiring and using information, attending and completing tasks, moving about and manipulating objects, caring for oneself, and health and physical well-being | 11.04, 111.04 |
| Neurocognitive disorders | Speaking; gross and fine manipulation; understanding, remembering, and applying information; concentrating, persisting, or maintaining pace; problem solving; adapting or managing oneself; interacting with others | Acquiring and using information, attending and completing tasks, interacting and relating with others, moving about and manipulating objects, and caring for oneself | 12.02, 112.02 |
| Health Effect | Potential Functional Limitations | Potential Functional Equivalence Domains Affected | Related SSA Listings |
|---|---|---|---|
| Intellectual disorder | Speaking; gross and fine manipulation; understanding, remembering, and applying information; concentrating, persisting, or maintaining pace; problem solving; adapting or managing oneself; interacting with others | Acquiring and using information, attending and completing tasks, interacting and relating with others, moving about and manipulating objects, and caring for oneself | 12.05, 112.05 |
| Neurodevelopmental disorder | Speaking; gross and fine manipulation; understanding, remembering, and applying information; concentrating, persisting, or maintaining pace; problem solving; adapting or managing oneself; interacting with others | Acquiring and using information, attending and completing tasks, interacting and relating with others, moving about and manipulating objects, and caring for oneself | 12.11, 112.11 |
| Depressive, bipolar, and related disorders | Understanding, remembering, and applying information; interacting with others; concentrating, persisting, or maintaining pace; adapting or managing oneself | Acquiring and using information, attending and completing tasks, interacting and relating with others, caring for oneself, and health and physical well-being | 12.04, 112.04 |
| Anxiety disorders | Understanding, remembering, and applying information; interacting with others; concentrating, persisting, or maintaining pace; adapting or managing oneself | Attending and completing tasks, interacting and relating with others, caring for oneself, and health and physical well-being | 12.06, 112.06 |
| Health Effect | Potential Functional Limitations | Potential Functional Equivalence Domains Affected | Related SSA Listings |
|---|---|---|---|
| Trauma | Understanding, remembering, and applying information; interacting with others; concentrating, persisting, or maintaining pace; adapting or managing oneself | Attending and completing tasks, interacting and relating with others, caring for oneself, and health and physical well-being | 12.15, 112.15 |
| Disordered sleep | Understanding, remembering, and applying information; concentrating, persisting, or maintaining pace; problem solving; interacting with others; adapting or managing oneself | Acquiring and using information, attending and completing tasks, caring for oneself, and health and physical well-being | None |
ANNEX TABLE 5-2 SSA’s Functional Equivalence Domains for Children
| Domain | Description |
|---|---|
| Acquiring and using information |
A child’s ability to learn information and to think about and use the information. Children acquire and use information at all ages for many different purposes.…[T]his domain considers more than just assessments of cognitive ability as measured by intelligence tests, academic achievement instruments, or grades in school. Learning and thinking begin at birth.…Throughout the learning process, children have to think about and use the information they have learned. Thinking involves being able to perceive relationships (for example, over/under and near/far), reason, and make logical choices.…Eventually, children should be able to use language to think about the world, understand others, and express themselves. As they learn more complex language, children should be able to combine ideas to solve problems and perform more complex tasks. (SSA, 2019a) |
| Domain | Description |
|---|---|
| Attending and completing tasks | A child’s ability to focus and maintain attention, and to begin, carry through, and finish activities or tasks…the child’s ability to initiate and maintain attention, including the child’s alertness and ability to focus on an activity or task despite distractions, and to perform tasks at an appropriate pace…the child’s ability to change focus after completing a task and to avoid impulsive thinking and acting…a child’s ability to organize, plan ahead, prioritize competing tasks, and manage time. (SSA, 2019b) |
| Interacting and relating with others |
A child’s ability to initiate and respond to exchanges with other people and to form and sustain relationships with family members, friends, and others. This domain includes all aspects of social interaction with individuals and groups at home, at school, and in the community. Important aspects of both interacting and relating are the child’s response to persons in authority, compliance with rules, and regard for the possessions of others. In addition, because communication is essential to both interacting and relating, [SSA] considers in this domain the speech and language skills children need to speak intelligibly and to understand and use the language of their community. This ability is involved in a broad range of childhood activities, such as playing, learning, and working cooperatively with others, either one-on-one or in groups. To interact and relate effectively in any activity, a child must be able to recognize, understand, and respond appropriately to emotional and behavioral cues from other people. (SSA, 2019c) |
| Moving about and manipulating objects |
The physical ability to move one’s body from one place to another and to move and manipulate things. These activities may require gross or fine motor skills or a combination of both. All of these physical actions require children to exhibit varying degrees of strength, coordination, dexterity, and pace to accomplish a given task or activity…to have a sense of where their bodies are in relation to the environment and an understanding of how their bodies move in space.…In addition, gross and fine motor skills require the integration of sensory input with motor output…[and] the capacity for motor planning and motor memory, that is, the ability to plan, remember, and execute controlled movement. (SSA, 2019d) |
| Domain | Description |
|---|---|
| Caring for [oneself] |
A child’s ability to maintain a healthy emotional and physical state. This includes:
The focus [is] on how well a child relates to self by maintaining a healthy emotional and physical state in ways that are age-appropriate and in comparison to other same-age children who do not have impairments. (SSA, 2019e) |
| Health and physical well-being |
The cumulative physical effects of physical and mental impairments and their associated treatments on a child’s health and functioning. Unlike the other five domains of functional equivalence (which address a child’s abilities), this domain does not address typical development and functioning. Rather, the health and physical well-being domain addresses how such things as recurrent illness, the side effects of medication, and the need for ongoing treatment affect a child’s body; that is, the child’s health and sense of physical well-being. Some physical effects that we consider in this domain can result directly from a physical or mental impairment(s).… These and other physical effects can also be the consequence of treatment a child receives. (SSA, 2019f) |
ANNEX TABLE 5-3 Physical Activities; Vision, Hearing, and Speaking Activities; and Mental Activities
| Activity | Definition |
|---|---|
| Physical Activities | |
| Sitting |
For the purpose of collecting occupational data, the U.S. Bureau of Labor Statistics (BLS) considers sitting to be present when any of the following conditions exists:
From a functional perspective, however, sitting as a physical activity involves resting one’s lower body (buttocks) on a seat or the ground, while maintaining one’s upper body (torso, neck, head) in an upright position. In addition to strong neck, shoulder, and core muscles, sitting requires balance and good proprioception. Although lying on a raised surface (e.g., a bed) may be grouped with sitting, sitting is distinct from lying down on the ground (e.g., lying on a dolly underneath a vehicle), which this report groups under low work. |
| Standing | For the purpose of collecting occupational data, the Occupational Requirements Survey distinguishes only between sitting (as defined previously) and standing/walking defined as “whenever workers are not sitting or lying down,” including “time spent stooping, crawling, kneeling, crouching, or climbing” (BLS, 2025, p. 94). In other words, “a worker is always either sitting or standing/walking” (BLS, 2025, p. 94). From a functional perspective, standing is distinct from walking, which in turn is distinct from low work (stooping, crawling, kneeling, crouching), or climbing. |
| Walking | Moving along on foot or advancing by steps, with one foot always on the ground. Distance (long or short) and surface type (uneven, rough) can affect an individual’s ability to walk. |
| Strenuous physical activity | Strenuous physical activity captures activities that require exertion and stamina—for example, running, jumping, swimming, throwing, catching, and the like. It potentially includes all other physical activities, in addition to running and other impact activities. |
| Lifting (floor to waist and overhead) | Raising or lowering an object from one level to another, including upward pulling (BLS, 2025, p. 99). |
| Activity | Definition |
|---|---|
| Carrying | “[T]ransporting an object, usually by holding it in the hands or arms, or wearing it on the body, usually around the waist or upper torso” (BLS, 2025, p. 99). Carrying usually also requires the ability to stand, lift, and walk. |
| Pushing/pulling | Exerting force upon an object so the object moves away from or toward the origin of the force, respectively (BLS, 2025, p. 106). |
| Reaching | “Extending the hand(s) and arm(s) in any direction, requiring the straightening and extending of the arm(s) and elbow(s) and the engagement of the shoulder(s)” (BLS, 2025, p. 110). Reaching may require standing. |
| Overhead reaching | Extending the arm(s) with the hand(s) higher than the head and (1) the elbow is bent and the angle at the shoulders is about 90 degrees or more or (2) the elbow is extended and the angle at the shoulder is about 120 degrees or more (BLS, 2025, p. 110). Overhead reaching requires neck extension and may require standing. |
| At/below the shoulder reaching | Reaching that does not meet the threshold for overhead reaching described above (BLS, 2025, p. 110). At/below the shoulder reaching may require standing. |
| Gross manipulation | Gross manipulation involves “seizing, holding, grasping, turning, or otherwise working with the hand(s)…fingers are involved only to the extent that they are an extension of the hand to hold or operate an object or tool, such as a hammer” (BLS, 2025, p. 112). It includes handling of large objects. |
| Fine manipulation | Fine manipulation involves “touching, picking, pinching, or otherwise working primarily with fingers rather than with the whole hand or arm” (BLS, 2025, p. 112). It includes writing, typing, or handling small objects, though keyboarding has its own additional coding that should be used along with other fine manipulation. |
| Foot/leg controls | Refers to the “use of one or both feet or legs to move controls on machinery or equipment. Controls include, but are not limited to, pedals, buttons, levers, and cranks” (BLS, 2025, p. 112). |
| Climbing | “The act of ascending or descending stairs, ramps, ladders, ropes, or scaffolding and similar structures using feet, legs, hands, and/or arms” (BLS, 2025, p. 142). |
| Activity | Definition |
|---|---|
| Low postures |
Low postures are those that include stooping, crouching, kneeling, or crawling.
Stooping is the act of “bending the body forward and down while bending the spine at the waist 45 degrees or more either over something below waist level or down towards an object on or near the ground” (BLS, 2025, p. 116). Stooping must be performed standing. Crouching is “bending the body downward and forward by bending the legs and spine” (BLS, 2025, p. 116). Kneeling is “bending the legs at the knees to come to rest on the knee or knees” (BLS, 2025, p. 116). Crawling is “moving about on hands and knees or hands and feet” (BLS, 2025, p. 116). Clustering activities done in low postures is appropriate because one generally has to be able to stoop, crouch, and kneel to be able to crawl. There might be an occasion when someone only has to kneel momentarily (e.g., to lift a child) that might be less difficult for some people, but most of the difficulties are shared among these activities. From a functional perspective, lying on the ground has more in common with other low work activities in that it includes the need to get up and down from the ground and potentially squirming around to do work while on the ground. These are difficult tasks that are equivalent to the other low work activities. |
| Vision, Hearing, and Speaking Activities | |
| Near visual acuity | “Clarity of vision at approximately 20 inches or less, as when working with small objects or reading small print” (BLS, 2025, p. 128), including the use of a computer in support of a critical job function, regardless of distance. |
| Far visual acuity | “Clarity of vision at a distance of 20 feet or more, involving the ability to distinguish features of a person or objects at a distance” (BLS, 2025, p. 128). |
| Peripheral vision | “What is seen above, below, to the left or right by the eye while staring straight ahead” (BLS, 2025, p. 128). |
| Hearing | “Ability to hear, understand, and distinguish speech” (BLS, 2025, p. 124). Includes hearing in-person one-on-one and group or conference communication; telephones and similar devices, such as radios, walkie-talkies, intercoms, and public address systems; and other such sounds as machinery alarms and equipment sounds. Passing a hearing test may be required for certain jobs. |
| Activity | Definition |
|---|---|
| Speaking | “Expressing or exchanging ideas by means of the spoken word to impart oral information to clients or the public and to convey detailed spoken instructions to other workers accurately, loudly, or quickly” (BLS, 2025, p. 124). |
| Mental Activities | |
| Understand, remember, and apply information | The abilities to learn, recall, and use (apply) information (SSA, n.d.-a,n.d.-b). |
| Concentrate, persist, or maintain pace | The abilities to focus attention on work/school activities and stay on task at a sustained rate (SSA, n.d.-a,n.d.-b). |
| Interact with others | The abilities to relate to and work with supervisors, coworkers, the public, teachers, peers, and others—for example, cooperating with others; asking for help when needed; handling conflicts with others; stating [one’s] point of view; initiating or sustaining conversation; understanding and responding to social cues (physical, verbal, emotional); responding to requests, suggestions, criticism, correction, and challenges; and keeping social interactions free of excessive irritability, sensitivity, argumentativeness, or suspiciousness (SSA, n.d.-a; see also SSA, n.d.-b). |
| Adapt or manage oneself | The abilities to “regulate emotions, control behavior, and maintain well-being” in a work or school setting—for example, responding to demands; adapting to changes; managing [one’s] psychologically based symptoms; distinguishing between acceptable and unacceptable work performance; setting realistic goals; making plans for [oneself] independently of others; maintaining personal hygiene and [appropriate attire]; and being aware of normal hazards and taking appropriate precautions (SSA, n.d.-a; see also SSA, n.d.-b). |
SOURCES: BLS, 2025; SSA, n.d.-a,n.d.-b; table is an updated version of a table originally printed in NASEM, 2022, p. 197.
