Finding comfort in complexity: The role of palliative care in children with leukodystrophy

Abstract

Introduction:

Children with leukodystrophy experience progressive physical and cognitive decline, which can lead to suffering. Palliative care consultation can help with multimodal symptom management, building trust with medical teams, and managing advanced care planning in children with severe neurological impairment.

Objectives:

To evaluate palliative care’s role, timing, and impact on end-of-life for children with leukodystrophy.

Methods:

Single-center retrospective chart review conducted on patients (0–18 years) with leukodystrophy at Children’s Healthcare of Atlanta from 2016 to 2023.

Results:

206 patient charts were included. Of all patients with leukodystrophy, 26% (53/206) had a palliative care consultation. It took average interval of 2.4 years from date of diagnosis to palliative care consultation. The hospitalist team (38%) and ICU team (26%) placed most referrals. Of the cohort, 20% (41/206) of the patients had died, average age of death 5.2 years. Of deceased, 63% (27/41) had a palliative care consult. 54% (22/41) of the deceased were enrolled in hospice. 29% (11/41) of deceased had full code status, 42% (16/41) were DNR/DNI, and 29% (11/41) were exclusively DNR. Most patients with leukodystrophy who died did so in the hospital, 37% (n = 13) of whom died in the ICU and 17% (n = 6) on the acute care floors. More than a quarter of those that died, 40% (n = 14), died at home. In the deceased, those enrolled in hospice were more likely DNR/DNI and to die at home instead of the hospital (p = 0.019, p < 0.001). In the deceased, there was no statistical difference in number of days admitted nor in number of hospitalizations in the last year of life between those enrolled and not enrolled in hospice (p = 0.871, p = 0.077).

Conclusion:

Pediatric patients and caregivers can benefit from goals of care conversations and advanced care planning while navigating the neurodegenerative disease process. There are unique psychosocial and medical needs in leukodystrophy population, and many opportunities to improve neuro-palliative integration early in the disease course for children with leukodystrophy.

1. Introduction

Leukodystrophies are a group of rare, inherited disorders that primarily affect the myelin sheath of the brain and spinal cord. More than 100 distinct leukodystrophies have been described, each with varying prognoses and illness trajectories [1]. Children with leukodystrophy experience physical and cognitive decline over their lifetime, which can cause considerable suffering. According to the American Academy of Pediatrics’ 2021 policy statement on leukodystrophy, inherited leukodystrophies have a 30% mortality rate by 8 years of age [1]. Palliative care can be valuable in supporting children and families through symptom management, medical decision-making, and end-of-life care as they cope with the progressive, debilitating effects of these illnesses.

Adult palliative care literature has increasingly focused on neuropalliative care, recognizing it as a growing field aimed at improving the quality of life for patients with serious neurological injuries [2]. This improvement is achieved through various models of integrating palliative care into the treatment plan and interdisciplinary teamwork [3]. Literature on palliative care for children with severe neurological impairments is also growing. Research emphasizes that early and ongoing palliative care can help in various domains, including multimodal symptom management, building trust with the medical team, psychosocial support, advanced care planning, and care coordination [4,5]. In children with neuromuscular conditions, such as Duchenne muscular dystrophy, there is evidence that early integration of palliative care introduces a framework to guide clinicians and families on advance care planning, concurrent provision of disease-focused care and palliation, enhanced communication and decision-making, and improved quality of life by reducing pain and suffering [6].

Emerging work describes palliative care needs in inherited metabolic diseases, many of which present with leukodystrophy. Prior studies have highlighted trigger points for palliative assessment across the disease course [7], underutilization of palliative services in metabolic conditions [8], and long-term outpatient palliative care experiences in this population [9]. Families caring for children with leukodystrophies face substantial and sustained challenges, with documented impacts on caregiver well-being, family relationships, and parental employment, including in conditions such as metachromatic leukodystrophy [10–12]. These studies highlight the complexity of care and caregiver burden, reinforcing the need for integrated, multidisciplinary care across the illness trajectory.

When looking specifically at the pediatric leukodystrophy population, there is a paucity of literature on the integration of pediatric palliative care and outcomes of palliative care involvement. The aim of this study is to investigate the role of pediatric palliative care within the leukodystrophy population and to better understand both utilized and missed opportunities. This study examines palliative care utilization, timing, and end-of-life outcomes in children with leukodystrophy to clarify how pediatric palliative care subspecialty services can support patients and families across the illness trajectory.

2. Materials and methods

This retrospective study was conducted following approval from the Institutional Review Board (IRB) of Children’s Healthcare of Atlanta. A comprehensive chart review was performed on pediatric patients aged 0–18 years with a diagnosis of leukodystrophy who were followed at the leukodystrophy clinic at Children’s Healthcare of Atlanta from January 2016 to December 2023. Data collected included patient demographics, disease characteristics, palliative care consultation details, and end-of-life care outcomes.

Descriptive statistics were calculated for the sample overall and by identified subgroups. Categorical variables were described with frequencies and percentages, while continuous variables were described with median and interquartile ranges. Differences between subgroups were tested using chi-square and Fisher’s exact tests for categorical variables and Wilcoxon rank sum test for continuous variables. The threshold for statistical significance was p < 0.05.

3. Results

A total of 206 patient charts were included in the analysis. Overall, 61% of patients were male, 61% were white, and 55% were covered by Medicaid insurance (Table 1). Our cohort included multiple types of leukodystrophy, with the most common specific diagnoses being X-linked adrenoleukodystrophy (13%) and Pelizaeus–Merzbacher disease (8%). Thirty-four percent of patients were categorized as having “other” leukodystrophies, which included genetic leukoencephalopathies with white matter changes such as Sanfilippo, Cockayne, Batten, and Allen–Herndon–Dudley syndromes, among others. In 10% of the cohort, the underlying cause of leukodystrophy was not specified in the medical record.

Table 1.

Descriptive statistics of the sample overall and by palliative referral (N = 206).

Variable	Overall, N = 2061	Palliative referral placed		p-value2
		No, N = 1531	Yes, N = 531
Age at Diagnosis (yrs)	2.23 (0.66, 5.14)	2.22 (0.74, 5.15)	2.52 (0.54, 5.08)	0.959
Sex				0.264
Male	126 (61%)	97 (63%)	29 (55%)
Female	80 (39%)	56 (37%)	24 (45%)
Race				0.131
White	122 (61%)	93 (62%)	29 (57%)
Black	51 (25%)	40 (27%)	11 (22%)
Asian	15 (7.5%)	11 (7.3%)	4 (7.8%)
Other	13 (6.5%)	6 (4.0%)	7 (14%)
(Missing)	5	3	2
Hispanic Ethnicity	43 (21%)	26 (17%)	17 (32%)	0.023
(Missing)	2	2	0
Primary Insurance				0.403
Medicaid	114 (55%)	82 (54%)	32 (60%)
Private Insurance	79 (38%)	62 (41%)	17 (32%)
Tricare/Military	10 (4.9%)	6 (3.9%)	4 (7.5%)
Other	0 (0%)	0 (0%)	0 (0%)
Uninsured	3 (1.5%)	3 (2.0%)	0 (0%)
Secondary Insurance				0.348
None	158 (77%)	120 (78%)	38 (72%)
Medicaid	48 (23%)	33 (22%)	15 (28%)
Private Insurance	0 (0%)	0 (0%)	0 (0%)
Tricare/Military	0 (0%)	0 (0%)	0 (0%)
Other	0 (0%)	0 (0%)	0 (0%)
Diagnosis				–
Unspecified Leukodystrophy	20 (9.7%)	18 (12%)	2 (3.8%)
Krabbe	14 (6.8%)	7 (4.6%)	7 (13%)
Metachromatic Leukodystrophy	15 (7.3%)	10 (6.5%)	5 (9.4%)
X-linked Adrenoleukodystrophy	27 (13%)	25 (16%)	2 (3.8%)
Alexander Disease	8 (3.9%)	6 (3.9%)	2 (3.8%)
Fucosidosis	3 (1.5%)	2 (1.3%)	1 (1.9%)
Aicardi–Goutières Syndrome	10 (4.9%)	7 (4.6%)	3 (5.7%)
Pelizaeus–Merzbacher Disease	17 (8.3%)	16 (10%)	1 (1.9%)
Multiple Sulfatase Disease	3 (1.5%)	3 (2.0%)	0 (0%)
Canavan Disease	1 (0.5%)	1 (0.7%)	0 (0%)
4H Syndrome‡	5 (2.4%)	2 (1.3%)	3 (5.7%)
H-ABC†	1 (0.5%)	1 (0.7%)	0 (0%)
Vanishing White Matter Disease	3 (1.5%)	1 (0.7%)	2 (3.8%)
Zellweger Spectrum	8 (3.9%)	3 (2.0%)	5 (9.4%)
Other	71 (34%)	51 (33%)	20 (38%)
Patient Status				<0.001
Alive	145 (78%)	123 (90%)	22 (44%)
Deceased	41 (22%)	13 (9.6%)	28 (56%)
(Missing)	20	17	3
Code Status				0.003
Full Code	144 (97%)	125 (99%)	19 (86%)
DNR/DNI	1 (0.7%)	1 (0.8%)	0 (0%)
DNR	3 (2.0%)	0 (0%)	3 (14%)
DNI	0 (0%)	0 (0%)	0 (0%)
(Missing)	58	27	31
Hospice Involvement	34 (18%)	11 (7.9%)	23 (44%)	<0.001
(Missing)	14	13	1
Signed POLST	14 (7.8%)	0 (0%)	14 (30%)	<0.001
(Missing)	26	19	7

Abbreviations: DNR/DNI: do not resuscitate/do not intubate; POLST: Physician Orders for Life-Sustaining Treatment.

¹Median (IQR); n (%).

²Wilcoxon rank-sum test; Pearson’s chi-squared test; Fisher’s exact test.

^‡4H Syndrome = hypomyelination with hypogonadotropic hypogonadism and hypodontia.

^†H-ABC = hypomyelination with atrophy of the basal ganglia and cerebellum.

We examined palliative care referral patterns by insurance type and race. The proportion of patients who received a palliative care referral did not differ significantly between those with Medicaid versus private insurance, nor between white and non-white patients (Table 1; p > 0.05 for all comparisons).

Among all patients with leukodystrophy, 26% (n = 53) received a palliative care referral during their illness course. Palliative care referrals were initiated exclusively during inpatient admissions, as our institution only had inpatient pediatric palliative care services and no outpatient palliative services during the study period. Of the 53 referrals placed, 85% (n = 45) resulted in a completed palliative care consult. Referrals that did not result in a completed consultation were most often due to the patient being discharged before the consult could be performed or to limitations in inpatient palliative care staffing. There were no clinically meaningful differences in demographic or disease characteristics between patients who did and did not receive a completed consultation following referral.

Referrals were most often placed by inpatient hospitalists (38%), followed by intensive care unit (ICU) teams (26%). The most common reasons for referral included disease-related issues (96%), such as assistance with diagnosis, prognosis, and goals-of-care discussions, followed by symptom-related needs (13%), including pain, dyspnea, dysautonomia, and neuro-irritability. The average interval from leukodystrophy diagnosis to the initial palliative care consultation was 2.4 years (median 1.5 years).

Among the cohort of patients who received a palliative care referral (n = 53), there was a statistically significant association between having a completed palliative care consult and vital status (alive or deceased) at last follow-up. Specifically, 63% of patients who received a consult were deceased at the end of the study period, compared with 14% of those who did not receive a consult (p = 0.034). This likely reflects a pattern of later referral during more advanced stages of illness.

Overall, 20% of the cohort (n = 41) had died by the end of the study period, with the average age of death being 5.2 years (Table 2). Within the deceased cohort, the most common diagnoses were Zellweger spectrum (n = 5), Krabbe disease (n = 4), and Aicardi–Goutières syndrome (n = 4). Among the 26 deceased patients for whom both the date of diagnosis and date of death were available, the mean time from palliative care consultation to the child’s death was 1.1 years. Approximately one-third of deceased patients (34%, 13/41) did not have any documented palliative care consultation.

Table 2.

Among deceased (N = 41), comparing patients who did not and did receive hospice.

Variable	Overall, N = 411	Hospice		p-value2
		No, N = 191	Yes, N = 221
Age at Diagnosis (yrs)	1.39 (0.45, 3.97)	2.20 (0.61, 4.87)	1.02 (0.43, 2.49)	0.460
Age at Referral (yrs)	2.7 (0.6, 6.6)	5.5 (2.2, 6.8)	1.4 (0.6, 6.0)	0.510
(Missing)	13	8	5
Age at Consult (yrs)	1.6 (0.6, 6.2)	5.5 (2.2, 6.8)	1.3 (0.6, 4.4)	0.451
(Missing)	14	8	6
Age at Death (yrs)	5.2 (1.4, 9.1)	6.8 (4.0, 9.3)	1.8 (1.3, 8.6)	0.258
(Missing)	1	0	1
Sex				0.397
Male	23 (56%)	12 (63%)	11 (50%)
Female	18 (44%)	7 (37%)	11 (50%)
Race				0.059
White	18 (46%)	5 (26%)	13 (65%)
Black	9 (23%)	5 (26%)	4 (20%)
Asian	5 (13%)	3 (16%)	2 (10%)
Other	7 (18%)	6 (32%)	1 (5.0%)
(Missing)	2	0	2
Hispanic Ethnicity	13 (32%)	6 (32%)	7 (32%)	0.987
Primary Insurance				0.279
Medicaid	22 (54%)	10 (53%)	12 (55%)
Private Insurance	16 (39%)	9 (47%)	7 (32%)
Tricare/Military	3 (7.3%)	0 (0%)	3 (14%)
Other	0 (0%)	0 (0%)	0 (0%)
Uninsured	0 (0%)	0 (0%)	0 (0%)
Diagnosis				–
Unspecified Leukodystrophy	0 (0%)	0 (0%)	0 (0%)
Krabbe	4 (9.8%)	0 (0%)	4 (18%)
Metachromatic Leukodystrophy	2 (4.9%)	1 (5.3%)	1 (4.5%)
X-linked Adrenoleukodystrophy	0 (0%)	0 (0%)	0 (0%)
Alexander Disease	2 (4.9%)	1 (5.3%)	1 (4.5%)
Fucosidosis	3 (7.3%)	2 (11%)	1 (4.5%)
Aicardi–Goutières Syndrome	4 (9.8%)	4 (21%)	0 (0%)
Pelizaeus–MerzbacZbr Disease	2 (4.9%)	2 (11%)	0 (0%)
Multiple Sulfatase Disease	2 (4.9%)	2 (11%)	0 (0%)
Canavan Disease	0 (0%)	0 (0%)	0 (0%)
4H Syndrome‡	1 (2.4%)	0 (0%)	1 (4.5%)
H-ABC†	0 (0%)	0 (0%)	0 (0%)
Vanishing White Matter Disease	0 (0%)	0 (0%)	0 (0%)
Zellweger Spectrum	5 (12%)	1 (5.3%)	4 (18%)
Other	16 (39%)	6 (32%)	10 (45%)
Palliative Referral Placed	28 (68%)	11 (58%)	17 (77%)	0.184
Team Placing Referral				0.400
Neurology	2 (7.1%)	1 (9.1%)	1 (5.9%)
ICU	8 (29%)	4 (36%)	4 (24%)
Hospitalist	11 (39%)	2 (18%)	9 (53%)
Specialty service – GI	2 (7.1%)	1 (9.1%)	1 (5.9%)
Specialty service – Pulm	5 (18%)	3 (27%)	2 (12%)
Specialty service – Heme/Onc	0 (0%)	0 (0%)	0 (0%)
Other	0 (0%)	0 (0%)	0 (0%)
(Missing)	13	8	5
Completed Palliative Care Consultation	27 (96%)	11 (100%)	16 (94%)	>0.999
Reasons for Palliative Care* (Missing N = 13)
Disease	27 (96%)	11 (100%)	16 (94%)	>0.999
Symptom	4 (14%)	1 (9.1%)	3 (18%)	>0.999
End of Life	2 (7.1%)	0 (0%)	2 (12%)	0.505
Intensive Care	3 (11%)	1 (9.1%)	2 (12%)	>0.999
Palliative Involvement* (Missing N = 14)
Symptoms	14 (52%)	5 (45%)	9 (56%)	0.581
Goals of Care	27 (100%)	11 (100%)	16 (100%)
Hospice Enrollment	9 (33%)	0 (0%)	9 (56%)	0.003
Care Coordination	8 (30%)	4 (36%)	4 (25%)	0.675
Signed POLST	13 (37%)	1 (5.6%)	12 (71%)	<0.001
(Missing)	6	1	5
Place of Death				<0.001
Acute Care Floors	6 (17%)	5 (31%)	1 (5.3%)
ICU	13 (37%)	10 (63%)	3 (16%)
Home	14 (40%)	0 (0%)	14 (74%)
Hospice house	1 (2.9%)	0 (0%)	1 (5.3%)
Local Hospital	1 (2.9%)	1 (6.3%)	0 (0%)
(Missing)	6	3	3
Cause of Death* (Missing N = 8)
Disease Progression	17 (52%)	4 (24%)	13 (81%)	<0.001
Infectious	4 (12%)	2 (12%)	2 (13%)	>0.999
Therapy/treatment-related	0 (0%)	0 (0%)	0 (0%)
Sudden Event	9 (27%)	8 (47%)	1 (6.3%)	0.017
Withdrawal of Life-Sustaining Technology	10 (30%)	7 (41%)	3 (19%)	0.259
Withdrawal of Artificial Hydration/Nutrition	2 (6.1%)	0 (0%)	2 (13%)	0.227
Unknown	8 (20%)	2 (11%)	6 (27%)	0.249
Resuscitation Status at Death*(Missing N = 3)
Full Code	11 (29%)	8 (44%)	3 (15%)	0.046
DNR/DNI	16 (42%)	4 (22%)	12 (60%)	0.019
DNR	11 (29%)	6 (33%)	5 (25%)	0.572
DNI	0 (0%)	0 (0%)	0 (0%)
Unknown	3 (7.3%)	1 (5.3%)	2 (9.1%)	>0.999
Technological Support*
None	2 (4.9%)	2 (11%)	0 (0%)	0.209
Tracheostomy and ventilator	6 (15%)	3 (16%)	3 (14%)	>0.999
ETT and ventilator	4 (9.8%)	3 (16%)	1 (4.5%)	0.321
Nasogastric feeding tube	6 (15%)	2 (11%)	4 (18%)	0.668
Enteral feeding	30 (73%)	13 (68%)	17 (77%)	0.524
Dialysis	0 (0%)	0 (0%)	0 (0%)
ECMO	0 (0%)	0 (0%)	0 (0%)
VP Shunt/EVD	1 (2.4%)	0 (0%)	1 (4.5%)	>0.999
Unknown	3 (7.3%)	2 (11%)	1 (4.5%)	0.588
Years from Diagnosis to Referral	0.67 (0.24, 2.26)	1.77 (0.94, 5.28)	0.48 (0.02, 1.53)	0.024
(Missing)	13	8	5
Years from Diagnosis to Consult	0.75 (0.27, 1.88)	1.77 (0.94, 5.30)	0.50 (0.08, 1.08)	0.011
(Missing)	14	8	6
Years from Consult to Death	1.15 (0.27, 2.64)	2.17 (0.29, 3.11)	0.87 (0.27, 2.62)	0.721
(Missing)	15	8	7
Number of Hospitalizations in Last Year of Life	3 (2, 4)	2 (2,3)	4 (2, 5)	0.077
(Missing)	1	0	1
Number of Admitted Days in Last Year of Life	25 (7, 43)	17 (8, 47)	28 (7, 42)	0.871
(Missing)	1	0	1

Abbreviations: DNR/DNI, do not resuscitate/do not intubate; ICU, intensive care unit; GI, gastroenterology; Pulm, pulmonology; Heme/Onc, hematology/oncology; POLST, Physician Orders for Life-Sustaining Treatment; ETT, endotracheal tube; ECMO, extracorporeal membrane oxygenation; VP shunt, ventriculoperitoneal shunt; EVD, external ventricular drain.

¹Median (IQR); n (%).

²Wilcoxon rank-sum test; Pearson’s chi-squared test; Fisher’s exact test.

^‡4H Syndrome = hypomyelination with hypogonadotropic hypogonadism and hypodontia.

^†H-ABC = hypomyelination with atrophy of the basal ganglia and cerebellum.

^*Response options are not mutually exclusive; more than one category could be selected per patient.

Of the total sample, 18% (n = 34) were enrolled in hospice at some point (Table 1). Within the deceased cohort, 54% (n = 22) had hospice enrollment (Table 2). When comparing deceased patients who were enrolled in hospice with those who were not, hospice enrollment was associated with a higher likelihood of having a completed Georgia Advance Directive Form/Physician Orders for Life-Sustaining Treatment (POLST) form (71% vs. 6%, p < 0.001), and of dying at home (74% vs. 0%, p < 0.001). Hospice enrollment was not associated with a difference in the number of hospitalizations or total days admitted in the last year of life.

Most patients with leukodystrophy who died did so in the hospital: 37% (n = 13) died in the intensive care unit and 17% (n = 6) on acute care floors. Forty percent (n = 14) died at home, and all patients who died at home were enrolled in hospice.

Twenty-nine percent (n = 11) had a full code order at the time of death, and 42% (n = 16) had chart documentation of limitations on cardiopulmonary resuscitation and/or intubation (documented as ‘do not resuscitate’/’do not intubate’ [DNR/DNI] orders). Those who died with hospice involvement were more likely to have such limitations documented than those who died without hospice involvement (60% vs. 22%, p = 0.019).

Among deaths with documented circumstances (Table 2), nearly one in three (30%, n = 10) occurred following withdrawal of life-sustaining technology, while slightly more than a quarter (27%, n = 9) were attributed to a sudden event.

4. Discussion

Children with leukodystrophy and their families benefit from comprehensive palliative care to address goals of care, advance care planning, and multimodal symptom management, as well as spiritual and emotional support. One of the challenging aspects of caring for patients with leukodystrophies is addressing the progressive nature of these illnesses. The impact of the diagnosis on patients and families can be difficult to navigate and evolves over time. Our findings, together with prior leukodystrophy guidance and qualitative work describing high care complexity and caregiver burden, support the importance of multidisciplinary care and suggest a key role for palliative care in supporting these families [1,10–12].

Our data demonstrate substantial unmet palliative needs in this cohort: 20% of the sample had died by the end of the study period, yet only 26% ever received a palliative care referral, and roughly one-third of deceased patients never had palliative involvement. Among patients who did receive a palliative care consultation, a significantly higher proportion were deceased at last follow-up compared with those without consultation (63% vs. 14%). This association likely reflects a pattern of late referral, often when illness is in its advanced stages or death is anticipated. Similar patterns of under-utilization and late referral have also been described in inherited metabolic diseases, in which only 20% of deceased patients received palliative care support before death [7,8].

There are patients in the deceased cohort who may have benefitted from a palliative care referral but did not have the opportunity to be seen in the inpatient setting. Not all placed referrals resulted in a completed consultation because patients were discharged before the inpatient palliative team could see them or because of staffing limitations. This highlights the need to consider earlier and more systematic referral points, adequate inpatient staffing, and development of outpatient palliative services or partnerships to ensure timely access.

The timing for engaging palliative care for patients and families can vary depending on the type and trajectory of leukodystrophy. For instance, many patients with X-linked adrenoleukodystrophy are diagnosed through newborn screening while they are still presymptomatic. These patients may not require hospital care for many years, if at all, and often do not receive a palliative care consultation until much later in their illness course. However, if signs of early cerebral disease appear, interventions such as hematopoietic stem cell transplantation or gene therapy may be offered. These disease-modifying treatments can be highly stressful, risky, and symptom-laden, making early palliative involvement beneficial for assisting families with symptom management, decision-making, and emotional coping throughout the treatment process. Similarly, for other leukodystrophies such as Krabbe disease (identified on newborn screening and treated with early bone marrow transplant) and metachromatic leukodystrophy (for which gene therapy may be offered early), palliative care remains valuable. Even when trajectory- altering treatments exist, they involve substantial risk, prolonged hospitalizations, and ongoing disease burden. These experiences parallel those of children with other complex chronic conditions, in whom early palliative care has been shown to support symptom control, communication, and coping alongside disease-directed therapies [4,5].

Despite ongoing efforts to clarify the distinction between palliative care and hospice care, the term “palliative care” often carries a stigma for many parents. They may fear that engaging with palliative care signifies giving up on their child or accepting the inevitability of death. Primary teams play a key role in reframing palliative care as an added layer of support focused on quality of life, symptom control, and shared decision-making throughout the illness course, regardless of prognosis or concurrent disease-directed treatments.

Within our cohort, hospice involvement appeared to influence certain aspects of end-of-life care. Deceased patients enrolled in hospice were more likely to have a completed advance directive/Physician Orders for Life-Sustaining Treatment (POLST) form and to die at home, compared with those not enrolled in hospice. These findings suggest hospice may facilitate advance care planning and support death at home when aligned with family goals. At the same time, it is important to recognize that “measurable” palliative care outcomes such as hospice enrollment, POLST completion, and death at home are meaningful only insofar as they reflect individual family goals. For some families, pursuing intensive treatment and ongoing life-prolonging interventions is consistent with their values and hopes for their child, and high-intensity care can be aligned with good palliative care when it is informed, intentional, and well supported.

Our abstraction of code status relied on chart terminology such as “do not resuscitate” and “do not intubate” (DNR/DNI), which we report to accurately reflect the retrospective data. In clinical practice, however, these orders are embedded within broader goals-of-care discussions that focus on allowing natural death and tailoring the level of cardiopulmonary resuscitation and respiratory support to the child’s best interests and family values. Future work should explore how families of children with leukodystrophies understand and experience these decisions and how palliative care can best support nuanced, longitudinal conversations about treatment intensity and end-of-life preferences.

As pediatric palliative care expands into outpatient and integrated clinic settings, future work should evaluate specific models of neuropalliative integration (e.g., embedded palliative clinicians in leukodystrophy and neurology clinics, co-visits with neurology, home-based services) and identify practical referral triggers, such as diagnosis of rapidly progressive leukodystrophies or initiation of high-intensity therapies. Prior work in inherited metabolic diseases has proposed structured trigger points for palliative assessment across the disease course [7]; adapting similar approaches to leukodystrophy programs may help normalize early palliative involvement and reduce reliance on crisis-driven referrals during acute hospitalizations.

There are certain inherent limitations to our study. This was a single-center retrospective chart review at an institution where pediatric palliative care was available only as an inpatient consultation service during the study period. If outpatient or home-based palliative care services had been available and systematically integrated into leukodystrophy care pathways, the overall rate and timing of palliative involvement in this cohort would likely have differed. Approximately 10% of the cohort was lost to follow-up, defined as an absence of patient records in our charts for a period of 3 or more years from their last visit, and this may bias estimates of mortality and service use. Our findings may not be generalizable to other settings, particularly centers with established outpatient neuropalliative programs or different models of hospice and home care. Multicenter studies are needed to better characterize neuropalliative care patterns and outcomes in leukodystrophy, to compare different models of integration (inpatient-only vs. combined inpatient–outpatient approaches), and to understand family experiences and perceived benefits of palliative consultation across diverse healthcare systems.

5. Conclusion

Palliative care plays a crucial role in supporting children with leukodystrophy, providing care that addresses medical, psychosocial, and spiritual needs. In this single-center cohort, many children died without ever receiving palliative care, and most palliative involvement occurred late in the illness course, underscoring missed opportunities for earlier support.

Early integration of palliative care can prevent and relieve suffering in physical, psychosocial, and spiritual spheres, facilitate advance care planning, and enhance support for end-of-life care when it becomes relevant. Further work is needed to define optimal referral points and models of neuropalliative integration. Studies are also needed to better understand family experiences and perceived benefits of palliative care across the illness trajectory.

6. Implications for practice

Our findings suggest several practical steps for leukodystrophy care:

• Use structured referral triggers. Programs should consider routine palliative care referrals at defined milestones, such as rapidly progressive diagnoses, early neurologic decline, initiation of high-intensity or disease-modifying therapies, or recurrent/prolonged hospitalizations, paralleling proposed trigger points in inherited metabolic diseases [7–9].

• Develop integrated neuropalliative models. Where feasible, embedding palliative clinicians in leukodystrophy or neurology clinics and building outpatient or home-based services may improve access to longitudinal support and advance care planning.

Data availability

The data that has been used is confidential.