Neurological Symptoms

19 Neurological Symptoms

Shih-Ning Liaw, Jenna E. Freitas, and Julie Hauer

We could not foresee what we might meet upon our road. Torment in the dark was the danger that I feared, and it did not hold me back. But I would not have come, had I known the danger of light and joy.

gimli, in the Lord of the Rings by J. R. R. Tolkien

Children with neurological conditions comprise one of the largest populations of individuals who receive pediatric palliative care (PPC). In a multicenter demographic study of hospital-based PPC programs in North America, nearly half of all children enrolled in palliative care were identified as having cognitive impairment, with the most common categories of principal diagnoses being genetic/congenital and neuromuscular conditions.¹ Other serious illnesses, such as primary brain tumors and malignancies with metastatic brain disease (discussed in Chapter 33), place children at risk for neurological symptoms. PPC clinicians should be familiar with management strategies of common neurological symptoms, which can be a major source of distress for these patients and their families.

This chapter addresses symptoms that arise due to impairment of the central nervous system (CNS). These symptoms may manifest from a variety of conditions that cause dysfunction of the CNS, including congenital anomalies, genetic/metabolic conditions that cause degenerative CNS disease, and brain lesions or injury acquired after birth. Neurological symptoms present particular difficulties for PPC clinicians for multiple reasons. Regardless of etiology, these symptoms are often difficult to treat, are sometimes intractable, and may evolve over time. Furthermore, children with severe neurological impairment (SNI) are at risk for more than one CNS etiology for observed symptoms. For example, a child with SNI who experiences dystonia is also at risk for central neuropathic pain, which can trigger and worsen dystonic features. The evidence base is limited for symptom interventions among children with SNI, and the complex clinical presentation of neurological symptoms makes assessment and management an inexact science that may require trials of pharmacological treatment for multifactorial causes. This chapter presents a general treatment approach for all neurological symptoms, followed by management strategies for specific symptoms, such as seizures, spasticity, dystonia, chorea, myoclonus, autonomic dysfunction, and central neuropathic pain.

General Approach to Care

The most important principle in providing palliative care for children with SNI is an effective partnership among the caregivers and members of the healthcare team. Families caring for children with SNI often rely on multiple pediatric providers, including primary care clinicians and pediatric subspecialists, to identify, evaluate, and manage chronic neurological symptoms. Neurologists, physiatrists, and palliative care clinicians have complementary yet distinct skill sets to promote comfort and optimize management of distressing neurological symptoms. Subspecialists in gastroenterology, orthopedics, pulmonology, complex care, and pain medicine may serve crucial roles in addressing comorbidities that contribute to increased symptomatology. Comprehensive care of children with neurological conditions also includes an array of clinicians in the home and community setting, and an interdisciplinary approach will provide the most holistic support for a child with SNI (Table 19.1).

Table 19.1 Interdisciplinary approaches to management of neurological symptoms

Physicians and advanced practice providers (nurse practitioners, physician assistants)	Physicians and advanced practice providers play an integral role in caring for children with SNI. Given the complex nature of neurological symptoms, many subspecialties are often involved in management, including neurology, physiatry, orthopedics, gastroenterology, pulmonology, complex care, pain medicine, and palliative care. Providers work together to manage seizures, spasticity, dystonia, autonomic dysfunction, neuro-irritability, and pain
Nurses	Nurses play a crucial role in caring for children with SNI across healthcare settings (e.g., home, clinics, schools, hospitals, long-term care). Nurses are often the first-line providers who can assess a child’s symptomatology and offer immediate, hands-on support through nonpharmacologic and pharmacologic interventions. Nurses can work with a child and family to recognize pain behaviors and identify the appropriate pain assessment tool that can be implemented across settings to identify and treat discomfort.
Social workers	Social workers support children with SNI and their families in a variety of ways. Social workers can help to identify psychosocial factors that may contribute to symptomatology. They can also assess the impact of challenging symptoms on the psychosocial functioning of the family, assisting with caregiver coping and anticipatory grief.
Psychologists	Psychologists perform focused assessments that allow families and teams to understand a child’s neurocognitive abilities. This sets the stage for the multidisciplinary team to best support a child’s development considering the level of neurologic impairment. An evaluation by a psychologist is often required for a child with SNI to receive appropriate community services. Psychologists may also assist with the assessment and management of behavioral issues and delirium.
Child life specialists	Child life specialists (CLS) are trained to support a child coping with illness. CLS are usually available in inpatient pediatric settings and are commonly members of home-based palliative care services. CLS implement developmentally appropriate, nonpharmacologic interventions to improve comfort and enhance quality of life for children with SNI.
Other: Chaplains, music therapists, integrative therapy providers, bereavement counselors	Various other specialists play important roles in supporting the physical, psychosocial, and spiritual needs of children with SNI and their families.

Open communication is an essential element of effective palliative care for children with SNI. Family members and caregivers have an intimate knowledge of their child’s likes, dislikes, behavioral patterns, and rhythms of daily life and are the most reliable reporters of any symptoms that deviate from their child’s norm. Healthcare providers attending to concerns raised by families must consider the broader impact of these symptoms on the child’s relational and emotional well-being within the context of the family’s psychosocial health.

An important dimension of open communication with a trusted clinician is anticipatory guidance about what to expect in the future. Many families report greater peace of mind and increased hopefulness when provided honest prognostic information, even if the news is difficult to hear.²^,³ In any discussion about prognostication, clinicians must acknowledge the inherent uncertainty that exists as they provide guidance about potential outcomes, complications, and decisions that may arise in the future. For families who find advance care planning helpful, clinicians can offer the approach of “hoping for the best while preparing for the worst” to aid in developing plans for potential clinical scenarios.⁴

Effective collaboration and open communication empower families of children with SNI and their healthcare teams to develop a proactive approach to managing neurological symptoms. This entails having a shared understanding about anticipated symptoms and the goals of treatment for each of these symptoms. In most situations, a reasonable goal for treatment is to achieve an acceptable level of symptom control with a tolerable level of medication side effects. For every neurological symptom, a comprehensive management plan should include nonpharmacological and pharmacological interventions that address both maintenance of symptom control and treatment of breakthrough symptoms. This often requires a scheduled medication regimen to decrease the frequency and severity of symptom episodes and a plan to treat breakthrough symptoms (Box 19.1).⁵

Box 19.1 Example of a Neurological Symptom Management Plan

Interventions for persistent crying and increased tone above baseline:

1. Utilize nonpharmacological strategies:

a. Swaddle tightly with legs flexed toward abdomen

b. Apply vibratory mat, 15 minutes on followed by 15 minutes off

c. Apply weighted blanket, 30 minutes on followed by 30 minutes off

2. If pain is suspected, administer as-needed dose of acetaminophen or ibuprofen via gastrostomy tube

3. If no benefit from the above, administer as-needed dose of diazepam via gastrostomy tube

4. Continue nonpharmacological strategies, and, if no relief after 30 minutes, notify provider

Acute changes in symptomatology should prompt consideration of a new nociceptive trigger. Neurological symptoms are often exacerbated by any cause of discomfort, including acute illness, pain, constipation, poor sleep, and medication toxicity. Given the nonspecific clinical presentation and the broad range of possible triggers, a thoughtful evaluation that incorporates a detailed history of new symptoms, a careful consideration of previous exacerbation patterns, and a thorough physical examination is imperative to establishing a reasonable evaluation and treatment plan that effectively addresses safety concerns without overly burdensome diagnostic testing. Clinicians can also engage families in other helpful strategies, such as maintaining a symptom diary, recording videos of symptom episodes, and reviewing medication side effects, to better characterize the symptoms.⁶

Children who receive nutrition and fluids by feeding tubes are at high risk for overfeeding when there is a gradual decline in health and function, as there is no easy way to measure this gradual decline in metabolic expenditure.⁷ Palliative care teams should remain vigilant to the risk of symptoms arising from overfeeding, such as pain, emesis, retching, and respiratory symptoms. Children with SNI may exhibit an increase in neurological symptoms, including spasticity and dystonic movements. Palliative care teams can guide families in the reduction of feeds while attending to worries about such plans, as illustrated in the Family Vignette. A 25–30% reduction of enteral feeds and fluids may be suggested as a trial to assess for symptom improvement.⁷

Family Reflection

We were told of Grace’s medical issues when she was 5 months old. We will never forget hearing, “Kids like Grace typically don’t live to their first birthday, and we never see them live past their second birthday.” Given the numerous health issues Grace would endure due to an undiagnosed disorder of her brain, our goal became one of living the best life possible in the short one we were going to have with her. This is why palliative care became so important to us! This was the team that helped not only to manage Grace’s symptoms and comfort, but also to support our whole family emotionally. We were blessed to make it past both those 1- and 2-year marks relatively smoothly. With the exception of a couple of short hospital stays for illness and surgeries to aid in her care, such as G-tube placement and orthopedic surgery, Grace was doing well! It was in Grace’s fourth year that things really started to change. We noticed her respiratory needs changing, resulting in more interventions to help maintain health and treat acute illness. Her irritability really increased with what we believed to be nerve pain. After some long stays in the hospital trying to understand the cause, we decided it was time to take her home and do what we could to make her comfortable. Palliative care worked with us to adjust and add to her medications so that Grace could be comfortable at home over the next year. Due to this support, we were also able to do things our family loved, like travel and spend time at the lake, valuing every precious moment. The following spring, we noticed another change; Grace’s body was becoming puffier, and she was having vomiting spells. Again, palliative care helped make adjustments to medications, and we decreased her feedings. Grace was showing us signs that her body was no longer able to process what she was given. The palliative care team was amazing at helping us understand what this all meant. Soon we were having more discussions as decreasing the formula seemed to play a big part in improving her comfort. While this was easy to identify, it was also heartbreaking to see and accept as a parent. Eventually, stopping feeds entirely was the best way to ensure her comfort. Two days later, our Gracie passed away in our arms surrounded by all her favorite people. To this day, we attribute her ability to enjoy those 5 and a half years of living, with an impaired nervous system, to the care and support we were provided through palliative care and all those people we will always affectionately refer to as “Team Grace.”

Optimizing overall comfort through nonpharmacological interventions is important in maintaining a holistic approach to symptom management. Just as adjuvant medications are used synergistically with opioids to treat pain, nonpharmacologic strategies and integrative therapies work together with pharmacologic management to address distressing symptoms.⁸ Nonpharmacological options that may provide benefit for children with SNI include comfort strategies, positional support, sensory interventions, and integrative therapies (Table 19.2). Simple strategies such as repositioning, rocking, swaddling, and light massage can be easily utilized by parents, caregivers, and bedside nurses. While there is a paucity of published data regarding the use and efficacy of integrative therapy in children with SNI, families often report benefits from these types of interventions. When thinking about which strategies to try, considerations should include sources of discomfort, developmental level of the child, potential physical limitations, and replicability of the intervention.⁹

Table 19.2 Nonpharmacological strategies to promote comfort in children with severe neurological impairment (SNI)

Comfort strategies	Cuddling, rocking, massage, warm baths, music Adjusting enteral feed rate, venting gastrostomy tube
Positional support	Repositioning, supportive seating systems, supportive bedding/mattresses
Sensory interventions	Weighted blankets, vibratory mats and pillows
Integrative therapies	Essential oils, aromatherapy, Reiki, craniosacral therapy, acupuncture/acupressure

Unfortunately, each of the neurological symptoms discussed in this chapter has the potential to become persistent and intractable despite best attempts to address contributing factors, enhance comfort, and treat with multiple medications. Children with intractable symptoms are at risk for experiencing undesirable adverse effects from polypharmacy, and these situations should prompt families and healthcare teams to weigh the anticipated benefits and burdens of escalation of pharmacological treatment. Open communication within a trusted therapeutic relationship allows for exploration of values that are most important to the family and shared decision-making about goals of treatment. For example, if a family is worried that their child who is receiving multiple medications for treatment of intractable seizures is too sedated to interact and participate in activities, clinicians can partner with the family to develop a shared understanding about the desired functional goals of treatment (e.g., ability to engage with therapies), the potential tradeoffs (e.g., increased risk of breakthrough seizures), and the changes needed in the management plan to achieve these goals.

Management of Neurological Symptoms at the End of Life

Children with neurological conditions may experience intensification of neurological symptoms as they near the end of life. This may be particularly marked in children with progressive neurological conditions, such as a neurodegenerative disorder or brain malignancy. Determination of whether symptomatic changes represent irreversible progression of the underlying disease requires careful consideration of the trajectory of a child’s condition and compassionate communication with the family. Escalation of medications may be necessary to treat distressing neurological symptoms at the end of life, and ongoing conversations with the family are important to establish shared prognostic understanding and modified treatment goals. In these situations, the family and healthcare team may agree that prioritizing comfort allows for intensifying pharmacological treatment with the expectation of increased somnolence. Because this plan of care may also diminish respiratory function and the effectiveness of respiratory clearance, clinicians must engage the family in considering the potential role and impact of advanced respiratory technologies, hospitalizations, intensive care, and resuscitative efforts in the care of their child. In addition to managing distressing symptoms, interdisciplinary palliative care clinicians serve a crucial role in supporting the family through difficult decisions, attending to anticipatory grief, and providing bereavement care.

Neurological Symptoms

The following sections describe management strategies for specific symptoms, such as seizures, spasticity, dystonia, chorea, myoclonus, autonomic dysfunction, central neuropathic pain, visceral hyperalgesia, and neuro-pain (neuro-irritability). For a summary of doses and indications of medications in this chapter, see Table 19.3.

Table 19.3 Medications for neurological symptoms (maximum weight of 50 kg for dosing)

Medications	Mechanisms of action	Initial starting dose (maximum starting dose)
Autonomic Dysfunction/Dysautonomia
Clonidine	Centrally acting alpha-2-adrenergic receptor agonist, reducing sympathetic outflow	Days 1–4: 0.002 mg/kg PO TID Days 5–8: 0.004 mg/kg PO TID Option to start with once a day dose to minimize sedation, then increase to BID, then TID Option to increase further: 0.02 mg/kg per day was the average dose identified for spasticity⁵ Autonomic storm: 0.003–0.006 mg/kg q4h prn Sleep: 0.003–0.006 mg/kg nightly
Gabapentin	Inhibit excitation by binding to alpha-2-delta protein of the voltage-gated calcium channels in the CNS	Day 1–3: 2 mg/kg (100 mg), PO TID Day 4–5: 4 mg/kg PO TID Increase every 2–4 days by 5–6 mg/kg/day until: Effective analgesia reached (may be noted at 30–45 mg/kg/day) Side effects experienced (nystagmus, sedation, tremor, ataxia, swelling) Maximum total dose of 50–72 mg/kg/day reached (2,400–3,600 mg/day) Younger children (<5 years) may require a 30% higher dose, such as a total dose of 45–60 mg/kg/day Half of the total daily dose may be given as the evening dose if symptoms occur more in the evening Titrate more rapidly for severe pain or as tolerated, titrate more gradually if sedation noted
Morphine	CNS opioid receptors	Autonomic storm: 0.2–0.3 mg/kg (10–15 mg) PO q4h prn
Propranolol	Beta-1 adrenergic receptor antagonist	0.2–0.4 mg/kg PO q8h (20 mg), increase every 3–4 days up to 1.6 mg/kg q8h (80 mg)
Bromocriptine	D2 receptor agonist	0.025 mg/kg (1.25 mg) PO q12h
Central Neuropathic Pain/Visceral Hyperalgesia
Gabapentin	See above	See above
Pregabalin	See gabapentin	Day 1–3: 1 mg/kg (50mg) PO nightly Day 4–5: 1 mg/kg PO BID Increase every 2–4 days up to 3 mg/kg/dose PO given BID or TID (maximum 6 mg/kg/dose)
Nortriptyline Amitriptyline	Presynaptic reuptake inhibition in the CNS of norepinephrine and serotonin	Day 1–4: 0.2 mg/kg (10 mg) PO nightly Day 5–8: 0.4 mg/kg PO nightly Increase every 4–5 days by 0.2 mg/kg/day until: Effective analgesia, side effects (constipation, dry mouth, urinary retention, sedation), or dosing reaches 1–1.5 mg/kg/day (50–75 mg/day maximum) Obtain ECG before further dose escalation up to 1.5–2 mg/kg/day (100 mg/day maximum); higher rate of side effects with higher doses including anticholinergic Consider plasma level if concerns with GI tract absorption Option of twice-daily dosing, giving 25–30% in the morning and 70–75% in the evening
Methadone	NMDA receptor antagonist, mu-opioid receptor agonist	0.1 mg/kg (5 mg) PO q8h; titrate slowly due to long biphasic half–life, monitor for cumulative effects in first 3–7 days
Spasticity
Baclofen	Modulates GABA-B receptors	2.5–5 mg PO TID; increase every 3 days by 5–15 mg/day up to a maximum of 60–80 mg/day
Tizanidine	See clonidine above	0.04–0.08 mg/kg (2–4 mg) PO nightly, increase up to 0.16 mg/kg q8h (max 8–12 mg q8h)
Clonidine	See clonidine above	See dysautonomia above
Diazepam	Increases affinity of GABA for GABA-A receptor	0.03–0.05 mg/kg (2 mg) PO/IV q6–8 hr, titrate to effect (max 10 mg)
Dystonia
Trihexylphenidyl	Anticholinergic	1 mg/day PO, increase every 3–5 days up to 4–5 mg TID; some children will benefit from and tolerate up to 60–100 mg/day (side effects may be managed with pyridostigmine)
Tetrabenazine	Dopamine depletion	12.5 mg/day PO, increase weekly up to 25 mg q12h
Clonidine	See clonidine above	Status dystonicus: 0.003–0.006 mg/kg q3–4h prn¹⁷
Myoclonus
Clonazepam	See diazepam above	0.005–0.01 mg/kg PO q8–12h (0.25–0.5 mg)
Seizures (acute therapy for prolonged seizure)
Lorazepam	See diazepam above	0.1 mg/kg (4–6 mg) PO/SL/PR/IV every 15 min × 2
Midazolam	See diazepam above	0.2 mg/kg SL, intranasal, or IV (10 mg)
Diazepam rectal gel	See diazepam above	2–5 years: 0.5 mg/kg every 15 min × 3 6–11 years: 0.3 mg/kg every 15 min × 3 >12 years: 0.2 mg/kg every 15 min × 3 Round dose to 2.5, 5, 10, 15, or 20 mg/dose
Fosphenytoin Phenytoin	Sodium-channel modulator	15–20 mg/kg IV loading dose followed by maintenance dose of 4–10 mg/kg/day (age-dependent dosing)
Seizures at end of life
Phenobarbital	Enhances inhibition at GABA-A receptor	15–20 mg/kg IV/SC/PO/PR loading dose for seizures, followed by maintenance dose 4–6 mg/kg/day IV/SC/PO/PR
Clonazepam	See diazepam above	0.005–0.01 mg/kg PO q8–12h (0.25–0.5 mg), increase up to 0.05–0.1 mg/kg PO q8–12h
Midazolam infusion	See diazepam above	Loading dose of 0.03–0.04 mg/kg (maximum 2 mg) followed by 0.03–0.1 mg/kg/hour IV or SC infusion titrated to effect

5HT, serotonin; ACh, acetylcholine; CNS, central nervous system; D2, dopamine; H, histamine; hr, hours; IV, intravenous; min, minutes; NMDA, N-methyl-D-aspartate; PO, by mouth (also enteral by feeding tube); PR, per rectum; PRN, as needed; q, every; SC, subcutaneous; SL, sublingual.

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