Medical Management
Medical management of severe pediatric ME/CFS follows similar principles to adult management (Chapter Urgent Action Plan for Severe Cases) but requires pediatric-specific dosing and heightened attention to developmental effects. The CDC recommends extra caution with pediatric ME/CFS medications, starting at lowest possible doses (Centers for Disease Control and Prevention 2024).
1 Orthostatic Intolerance (Priority)
Orthostatic intolerance (OI) affects 70–90% of pediatric ME/CFS patients, compared to approximately 40–70% of adults (Rowe et al. 2017). This higher prevalence makes OI management the single most important intervention in pediatric ME/CFS. Treatment of orthostatic intolerance improves not only cardiovascular symptoms but also fatigue, cognitive function, and overall wellbeing (Ojha, McNeeley, et al. 2024).
1.1 Non-Pharmacological Interventions
Non-pharmacological measures should be implemented first and continued even if medications are added:
Hydration Targets (age-adjusted):
- Ages 4–8 years: 1.5–2 liters/day
- Ages 9–13 years: 2–2.5 liters/day
- Ages 14–18 years: 2.5–3 liters/day
- Note: These targets exceed standard pediatric recommendations because ME/CFS patients have reduced plasma volume; adequate hydration is therapeutic, not merely maintenance
- Timing: Spread throughout day; concentrated fluid intake before upright activities
- Type: Water, oral rehydration solutions, dilute juice; avoid excessive caffeine
Salt Supplementation (pediatric dosing):
- Children \(<\) 30 kg: 2–3 grams sodium/day (from dietary sources plus salt tablets if needed)
- Children 30–50 kg: 3–5 grams sodium/day
- Adolescents \(>\) 50 kg: 5–8 grams sodium/day
- Implementation: Salt tablets (0.5–1 g each) with meals and snacks; salted foods; oral rehydration solutions
- Monitoring: Blood pressure should be monitored; reduce salt if sustained hypertension develops
- Contraindications: Reduce dose in renal or cardiac disease
Compression Garments (sizing for children):
- Waist-high compression: Most effective; 20–30 mmHg compression
- Pediatric sizing: Measure carefully; adult sizes often too large
- Alternative: Abdominal binder if full-leg compression not tolerated
- Tolerance: Start with shorter wear times (1–2 hours); increase gradually
- Application: Put on while lying down, before rising
Positioning Strategies:
- Elevate head of bed: 10–15 degrees (blocks under head of bed, not pillows) to maintain blood volume training
- Avoid prolonged standing: Sit or lie whenever possible
- Lower extremity movement: Fidgeting, ankle pumping, crossing legs when must stand
- Squat when symptomatic: If feeling faint, squat immediately (raises blood pressure)
- Avoid warm environments: Heat worsens vasodilation and OI symptoms
1.2 Pharmacological Interventions
When non-pharmacological measures are insufficient, medications may be needed. Pediatric POTS studies demonstrate high response rates to standard OI medications (Ojha, McNeeley, et al. 2024).
First-Line: Fludrocortisone (Florinef)
Mineralocorticoid that expands plasma volume by promoting sodium and water retention.
Pediatric Dosing:
- Starting dose: 0.05 mg (50 mcg) once daily (half of the standard 0.1 mg tablet)
- Titration: Increase by 0.05 mg weekly if tolerated and symptoms persist
- Target dose: 0.1–0.2 mg daily (rarely exceeds 0.2 mg in pediatrics)
- Timing: Morning, with breakfast
- Response timeline: 1–2 weeks for initial effect; full effect may take 4–6 weeks
Monitoring Requirements:
- Blood pressure: Weekly initially; must catch hypertension early
- Potassium: Baseline and at 2–4 weeks; fludrocortisone can cause hypokalemia
- Weight: Weekly; excessive weight gain suggests fluid retention beyond therapeutic
- Edema: Ankle swelling indicates dose may be too high
- Growth: Long-term corticosteroid effects on growth are theoretical but monitor height velocity
Side Effects and Management:
- Hypokalemia: Supplement with potassium-rich foods or potassium chloride if levels fall
- Hypertension: Reduce dose or discontinue
- Headache: Often transient; reduce dose if persistent
- Edema: Mild ankle edema may be acceptable; reduce dose if significant
Second-Line: Midodrine (ProAmatine)
Alpha-1 agonist that causes vasoconstriction, increasing blood pressure and reducing venous pooling. Pediatric POTS studies report 78% response rate (Ojha, McNeeley, et al. 2024).
Pediatric Dosing:
- Starting dose: 2.5 mg (half tablet) once or twice daily
- Titration: Increase by 2.5 mg every 3–7 days as tolerated
- Target dose: 5–10 mg three times daily (maximum 40 mg/day in adolescents)
- Timing: Upon waking, midday, mid-afternoon; do not give within 4 hours of bedtime (supine hypertension risk)
- Response timeline: Hours to days; relatively rapid onset
Critical Warnings:
- Supine hypertension: Most important side effect; patient must be upright when taking medication and should not lie flat for 4 hours after dose
- Last dose timing: No later than 4–6 PM to avoid nocturnal hypertension
- Scalp tingling: Common (piloerection); not dangerous but can be bothersome
- Urinary retention: Rare in pediatrics; more common in older patients
Monitoring Requirements:
- Supine blood pressure: Check BP lying down periodically; if systolic \(>\) 150 while lying, reduce dose
- Standing blood pressure: Should improve with treatment; document response
Third-Line: Pyridostigmine (Mestinon)
Acetylcholinesterase inhibitor that enhances autonomic function and may improve orthostatic tolerance.
Pediatric Dosing:
- Starting dose: 15–30 mg twice to three times daily
- Titration: Increase gradually based on response
- Target dose: 30–60 mg three times daily
- Timing: With meals to reduce GI side effects
Side Effects:
- GI symptoms: Nausea, diarrhea, abdominal cramping (most common; often dose-limiting)
- Increased salivation/sweating: Cholinergic effects
- Bradycardia: Monitor heart rate, especially in combination with beta-blockers
Fourth-Line: IV Fluids
For severe OI unresponsive to oral measures and medications.
Indications:
- Syncope or near-syncope despite adequate oral hydration, salt, and medications
- Unable to maintain adequate oral intake due to nausea or gastroparesis
- Severe dehydration from illness exacerbation
- Acute severe crashes requiring rapid support
Implementation:
- Typical regimen: Normal saline 1–2 liters, 1–3 times weekly
- Access: Peripheral IV for intermittent use; PICC line or port for frequent/regular infusions
- Setting: May be given at infusion center, at home by visiting nurse, or by trained parent
- Risks: Line infection (PICC/port), volume overload, electrolyte disturbance
Note on IV access: Decisions about central access (PICC, port) in pediatric ME/CFS require careful risk-benefit analysis. Line infections are serious complications. IV fluids should be reserved for patients with clearly documented benefit from fluid loading who cannot achieve equivalent benefit orally.
2 Sensitization Prevention Protocol
Severe pediatric ME/CFS patients are vulnerable to progressive sensitization—the phenomenon where increasing numbers of triggers (infections, environmental exposures, activities) progressively reduce symptom tolerance. Early intervention to prevent sensitization can preserve quality of life and potentially prevent further deterioration.
Anti-Neuroinflammatory Foundation
A multi-component approach targets neuroinflammatory activation, which underlies both PEM and progressive sensitization. The goal is to interrupt the cycle where each crash and each infection creates lasting sensitization (see Chapter Neurological and Neurocognitive Dysfunction for discussion of and Chapter Immune System Dysfunction for discussion of ).
Low-Dose Naltrexone (LDN):
Dosing: Weight-adjusted: 0.1 mg/kg daily, maximum 4.5 mg
Age-adjusted examples:
- Child 20 kg: 2 mg daily
- Child 40 kg: 4 mg daily
- Adolescent 45+ kg: 4.5 mg daily
Timing: Evening (bedtime) for better efficacy
Onset: 2–8 weeks for measurable effect
Mechanism: Low doses activate microglia inhibition, reducing neuroinflammation that perpetuates PEM cycles
Safety: Generally well-tolerated in pediatrics; reversible if discontinued
Palmitoylethanolamide (PEA):
Dosing: Age-adjusted based on published pediatric data
- Younger children (6–10 years): 600 mg daily
- Older children (11–14 years): 900 mg daily
- Adolescents (15–18 years): 1200 mg daily
Type: Enteric-coated formulations improve absorption
Mechanism: Endocannabinoid system modulation; reduces neuroinflammation and neuropathic sensitization
Timing: Can be taken with meals
Omega-3 Fatty Acids (EPA/DHA):
Dosing: Age-appropriate targets for anti-inflammatory benefit
- Children \(<\) 30 kg: 500–1000 mg EPA/DHA daily
- Children 30–50 kg: 1000–1500 mg EPA/DHA daily
- Adolescents \(>\) 50 kg: 1500–2000 mg EPA/DHA daily
Form: Liquid or chewable formulations often better tolerated than capsules
Benefits: Anti-inflammatory, supports cardiovascular health, may improve mood
Comprehensive Sleep Assessment and Treatment
Sleep deprivation perpetuates neuroinflammation. Severe cases warrant sleep medicine evaluation:
- Sleep study: Polysomnography to rule out sleep apnea (higher prevalence in ME/CFS)
- Aggressive apnea treatment: If present, treating sleep apnea often improves overall ME/CFS symptoms
- Optimization: Melatonin, trazodone, or low-dose amitriptyline (see Protocol Avoid in Pediatrics) as needed to ensure adequate sleep quality
Activity Monitoring with Wearable Alerts
Preventing overexertion is critical to preventing sensitization cascade:
- Heart rate monitoring: Continuous or frequent monitoring using wearables appropriate for the child’s age
- Threshold definition: Establish safe heart rate ceiling based on aerobic threshold calculation: \((220 - \text{age}) \times 0.55\) to $ 0.60$
- Parent/caregiver alerts: Configure wearable to alert parents when child approaches or exceeds threshold
- Purpose: Prevent parent-blind overexertion (activity the child’s caregiver cannot directly observe, or where child underestimates intensity)
- Example: Bedbound child who engages in sustained conversation or cognitive activity without realizing intensity until crash occurs next day
Infection Prevention as Sensitization Prevention
Each infection causes both acute PEM and lasting sensitization increases. Aggressive prevention is sensitization prevention:
- Masking protocol: FFP2 or N95 masks during any household illness; consider seasonal masking during high-transmission periods
- Isolation: If possible, isolate severely ill child from sick household members (separate room, bathroom if feasible)
- Hand hygiene: Frequent handwashing after any contact with potentially infected persons
- Prompt treatment: Antivirals if viral infection suspected; antibiotics for bacterial infections
- Prophylaxis consideration: During high-risk periods (siblings in school with active outbreaks), discuss prophylactic antivirals with physician
Educational Continuity as Health Protection
While not a direct medical intervention, preventing crash-induced educational disruption protects developmental trajectory and reduces secondary psychological harm that perpetuates neuroinflammation:
- Homebound instruction: Maintain some educational engagement without requiring school attendance that triggers crashes
- Avoid education-forced crashes: Never pressure school attendance for academic reasons when doing so will trigger PEM
- Each prevented crash: Each crash not occurring is a sensitization cascade prevented
Severe pediatric ME/CFS differs from adult disease in one critical dimension: the developing nervous system and the developing life trajectory. Each crash during childhood does not merely reduce current function—it may have lasting effects on neurological development, educational progress, and identity formation. Sensitization prevention is not mere symptom management; it is developmental protection. Prevention of a single crash during a critical developmental window may have lifelong implications for the child’s ultimate prognosis and capacity.
3 Pain Management
Pain is common in pediatric ME/CFS, including widespread musculoskeletal pain, headaches, and abdominal pain. Pain management in developing nervous systems requires particular caution.
3.1 Non-Pharmacological Approaches
Non-pharmacological strategies should be first-line:
- Positioning: Supportive pillows, position changes to relieve pressure
- Heat/cold: Heating pads for muscle pain; cold packs for acute inflammation or headaches
- Gentle massage: Light massage by caregiver (not deep tissue; avoid triggering PEM)
- TENS units: Transcutaneous electrical nerve stimulation for localized pain
- Distraction: Audio content (audiobooks, music, podcasts) at tolerable volumes
3.2 Analgesic Medications
Tier 1: Acetaminophen and NSAIDs
Acetaminophen (Tylenol):
- Dose: 10–15 mg/kg every 4–6 hours as needed
- Maximum: 75 mg/kg/day (up to 4 grams/day in adolescents)
- Advantages: No anti-inflammatory effects that might mask fever; low GI risk
- Caution: Hepatotoxicity at high doses; avoid in liver disease
Ibuprofen (Advil, Motrin):
- Dose: 5–10 mg/kg every 6–8 hours as needed
- Maximum: 40 mg/kg/day (up to 2.4 grams/day in adolescents)
- Advantages: Anti-inflammatory effects helpful for musculoskeletal pain
- Caution: GI irritation, renal effects with chronic use; take with food
Naproxen (Aleve):
- Dose: 5–7 mg/kg every 12 hours
- Maximum: 1 gram/day in adolescents
- Advantages: Longer duration; twice-daily dosing
- Caution: Same NSAID precautions as ibuprofen
Tier 2: Neuropathic Pain Agents
For neuropathic pain characteristics (burning, tingling, shooting, allodynia), consider agents targeting neuropathic pathways. These require specialist consultation in pediatrics.
Gabapentin:
- Starting dose: 5 mg/kg/day divided into 3 doses (e.g., 100 mg TID for 60 kg adolescent)
- Titration: Increase by 5 mg/kg/day every 5–7 days
- Target: 15–35 mg/kg/day divided TID (typical adolescent dose 900–1800 mg/day)
- Side effects: Sedation, dizziness, peripheral edema
- Advantages: Generally well-tolerated; no significant drug interactions
Amitriptyline (low-dose):
- Starting dose: 0.1 mg/kg at bedtime (typically 5–10 mg for child, 10–25 mg for adolescent)
- Titration: Increase by 0.1 mg/kg weekly if tolerated
- Target: 0.5–1 mg/kg at bedtime (rarely exceeds 50 mg in pediatrics)
- Side effects: Anticholinergic effects (dry mouth, constipation, urinary retention), sedation, QTc prolongation
- Dual benefit: May help pain AND sleep
Tricyclic antidepressants (amitriptyline) and SSRIs/SNRIs carry FDA black box warnings for increased suicidal thinking and behavior in children and adolescents. Low-dose amitriptyline for pain is typically below antidepressant doses, but families should be counseled about warning signs and patients should be monitored for mood changes, particularly during dose initiation and adjustments.
Tier 3: Specialist Pain Management
Referral to pediatric pain specialist is indicated for:
- Pain refractory to Tier 1–2 interventions
- Pain significantly limiting function beyond ME/CFS baseline
- Complex regional pain syndrome (CRPS) features
- Need for opioid consideration (rarely appropriate in pediatric ME/CFS)
4 Sleep Optimization
Sleep dysfunction is nearly universal in ME/CFS. Children with ME/CFS experience unrefreshing sleep regardless of duration, along with difficulty falling asleep, maintaining sleep, or both. The severely ill child may sleep 12–16 hours yet feel exhausted.
4.1 Sleep Hygiene for Bedbound Children
Standard sleep hygiene recommendations require modification for bedbound patients who cannot leave their beds:
- Bed association: When child is in bed 20+ hours/day, the bed becomes associated with wakefulness. Mitigation: different positions, blankets, or pillow arrangements for “sleep time” versus “awake time”; different lighting (lamp on for awake, off for sleep)
- Light exposure: Attempt some natural light during “daytime” hours, even if from window while lying down; complete darkness for sleep periods
- Screen timing: Reduce screens 1–2 hours before intended sleep; blue-light filtering if screens are used
- Consistent schedule: Maintain regular sleep and wake times even when homebound; circadian rhythm disorders are common in ME/CFS
- Temperature: Cooler room temperatures (65–68{}F) facilitate sleep
4.2 Sleep Medications
First-Line: Melatonin
Melatonin is the preferred first-line sleep aid for pediatric ME/CFS due to safety profile and documented efficacy (Castro-Marrero et al. 2021).
Dosing:
- Starting dose: 0.5–1 mg, 30–60 minutes before desired sleep time
- Titration: Increase by 0.5–1 mg every 3–7 days if ineffective
- Target dose: 1–5 mg for most children; some adolescents may need up to 10 mg
- Timing is critical: Must be taken at consistent time; efficacy depends on circadian timing, not just sedation
- Extended-release formulations: May help with sleep maintenance (waking in night)
Important Considerations:
- Quality matters: Pharmaceutical-grade melatonin is preferable; supplement quality varies widely
- Not purely sedating: Melatonin works by signaling circadian timing; some children feel more alert initially before sleep onset
- Long-term safety: Generally regarded as safe for extended use in pediatrics, though long-term studies are limited
Second-Line: Low-Dose Trazodone
Serotonin antagonist and reuptake inhibitor with sedating properties; commonly used off-label for pediatric insomnia.
Dosing:
- Starting dose: 12.5–25 mg at bedtime
- Titration: Increase by 12.5–25 mg weekly if needed
- Target dose: 25–100 mg at bedtime (rarely exceeds 100 mg for sleep in pediatrics)
Side Effects:
- Morning sedation: Most common; may need dose reduction
- Orthostatic hypotension: Caution in patients with OI (may worsen or improve—varies by patient)
- Priapism: Rare but serious; educate male adolescents to seek immediate care
Third-Line: Low-Dose Amitriptyline
As above for pain, low-dose amitriptyline at bedtime can improve sleep quality. Dosing: 5–25 mg at bedtime. Dual benefit for patients with pain plus sleep dysfunction.
Other Options (Specialist Consultation Recommended):
- Clonidine: 0.05–0.1 mg at bedtime; alpha-2 agonist with sedating effects
- Hydroxyzine: 12.5–50 mg at bedtime; antihistamine with sedating effects
- Mirtazapine: 7.5–15 mg at bedtime; antidepressant with sedating effects at low doses
- Benzodiazepines: Risk of dependence, cognitive effects, respiratory depression; avoid except for acute crisis management under specialist supervision
- Z-drugs (zolpidem, eszopiclone): Not FDA-approved for pediatrics; limited safety data; complex sleep behaviors reported
4.3 Circadian Rhythm Disorders
Delayed sleep phase disorder (DSPS) is common in adolescents with ME/CFS—the natural sleep-wake cycle shifts later, making it difficult to fall asleep before 2–4 AM and wake before noon. This overlaps with but is distinct from ME/CFS sleep dysfunction.
Management of DSPS:
- Chronotherapy: Gradual advance of sleep time (15–30 minutes earlier every few days)
- Light therapy: Bright light exposure (10,000 lux light box) immediately upon waking for 20–30 minutes; helps advance circadian phase
- Melatonin timing: Low-dose melatonin (0.5–1 mg) 4–6 hours before desired sleep time (not at bedtime) can help advance circadian phase
- Evening light restriction: Minimize bright light exposure, especially blue light, in evening hours
4.4 Circadian Light Therapy for Energy and Sleep Alignment
The selective energy dysfunction hypothesis (Chapter Selective Energy Dysfunction Hypothesis, lines 628–645) proposes that circadian dysregulation impairs energy budget allocation, explaining why pediatric patients often have evening energy spikes despite daytime exhaustion.
Mechanism: Morning bright light exposure (10,000 lux) resets the suprachiasmatic nucleus (SCN), improving alignment of circadian energy distribution with sleep-wake cycle. Particularly effective for children with delayed sleep phase or energy crashes mid-afternoon followed by evening “second wind.”
Pediatric Protocol:
Equipment: 10,000 lux light therapy box ($\(25\)–100). Child-friendly options: Some have adjustable arms or can be positioned at varied angles for bedbound use.
Timing: 20–30 minutes immediately upon waking (within 30 minutes of desired wake time)
- Consistency crucial: Same wake time every day (even weekends) for circadian effectiveness
- NEVER use after 3pm (will delay sleep further and worsen late-evening sleep phase issues)
Position: Light box 16–24 inches from child’s face. For bedbound children, can be positioned on bedside table or stand at angle allowing light exposure while lying down.
Safety:
- Safe for all ages
- Very low risk of adverse effects (occasional mild eye strain if too close)
- DO NOT stare directly at bulb
- Discontinue if triggers mood elevation or anxiety (rare)
Expectation setting: Benefits emerge over 2–4 weeks; earlier bedtime and more consistent daytime energy are typical outcomes.
Evidence level: Moderate (circadian disruption documented in pediatric ME/CFS; light therapy established for circadian disorders; pediatric ME/CFS-circadian-energy specific RCTs pending)
Expected outcomes:
- More predictable sleep onset at night
- Reduced late-evening “second wind” phenomenon
- Better energy consistency throughout day
- Timeline: 2–4 weeks
4.5 Sleep Spindle Enhancement via Acoustic Stimulation (Low Priority, Experimental)
Mechanism: Sleep spindles (brief high-frequency brain activity during sleep) are reduced in ME/CFS. Acoustic stimulation during sleep may enhance spindle production, improving sleep architecture coordination (Chapter Selective Energy Dysfunction Hypothesis, lines 552–569).
Pediatric Protocol (Simple, Non-Pharmacological):
Equipment: White or pink noise machine ($15–50) or free app
- White noise: Constant frequency; easier to find
- Pink noise: Lower frequencies enhanced; some literature suggests better sleep effects
- Apps: myNoise.net (free, customizable), YouTube brown noise videos
How to use:
- Play throughout entire sleep period (all night)
- Volume: Low (30–50 dB, quiet background level); NOT disruptive
- Placement: Bedside speaker positioned where child can hear but not blasted
- Start time: Can use during naps and nighttime sleep
Parent tracking:
- Sleep quality rating (child report: more rested vs. unchanged vs. worse)
- Duration of trial: Minimum 2–4 weeks to assess benefit
- Expected benefit timeline: 3–4 weeks if spindles improve
Integration:
- Adjunctive to sleep medications (melatonin, trazodone)
- Can be combined with other sleep strategies
- Non-pharmacological option for families preferring fewer medications
Evidence level: Speculative (spindle deficits documented in ME/CFS; acoustic enhancement effect unproven in pediatric ME/CFS)
Expected outcomes: Modest improvement in subjective sleep quality if spindles enhance. Not expected to directly improve daytime fatigue or activity tolerance.
Positioning: Very low priority. Sleep medications have stronger evidence. Consider only if child has difficulty with medications or if medications provide insufficient benefit.
5 Cognitive Support
Cognitive dysfunction (“brain fog”) significantly impacts educational progress. In severe cases, children may be unable to read, follow conversations, or retain information.
5.1 Cognitive Function Assessment
Formal neuropsychological testing is often not feasible for severely ill children (the testing itself may trigger PEM). Instead, functional assessment through observation:
- Reading tolerance: How long can child read or be read to before cognitive fatigue?
- Conversation tolerance: How long can child participate in conversation before losing comprehension?
- Information retention: Can child recall content from previous day? Previous hour?
- Word-finding: Does child frequently lose words or use wrong words?
- Processing speed: Is there noticeable delay between question and response?
5.2 Maintaining Developmental Progress
Even during severe illness, maintaining some cognitive engagement is important for developmental trajectory:
- Match modality to capacity: Audiobooks if reading is impossible; dictated responses if writing is impossible
- Micro-learning: 5–10 minute educational activities with breaks, rather than extended lessons
- Interest-driven: Children may tolerate more cognitive effort for topics of personal interest
- No pressure: Removing academic pressure paradoxically often improves cognitive function
- Social connection: Even brief social interaction (texting friends, short video calls) maintains developmental skills
5.3 When Cognitive Symptoms May Improve
Cognitive function often improves with OI treatment. If orthostatic intolerance is inadequately treated, cerebral hypoperfusion (reduced blood flow to brain) contributes significantly to brain fog (see Chapter Cardiovascular Dysfunction, Section Blood Pressure Regulation). Many children experience noticeable cognitive improvement within 1–2 weeks of effective OI management. Always optimize OI treatment before assuming cognitive dysfunction is irreversible.
5.4 Intranasal Delivery for CNS-Targeted Cognitive Support
The selective energy dysfunction hypothesis (Chapter Selective Energy Dysfunction Hypothesis, lines 238–257) proposes that the blood-brain barrier may be compromised in ME/CFS, limiting delivery of cognitive support compounds. Intranasal delivery bypasses the BBB via olfactory nerve pathways.
For severe pediatric cases with refractory brain fog:
Intranasal formulations: If oral cognitive support proves insufficient, ask your child’s neurologist or ME/CFS specialist about intranasal options. Examples include intranasal insulin (being studied for cognitive support in neurodegenerative disease) or dopamine precursors.
Caution with children: Intranasal medications require cooperation and proper technique. May be difficult in very young or severely ill children.
Current status: NOT standard pediatric ME/CFS care. EXPERIMENTAL. Only pursue with specialist guidance.
Evidence level: Speculative (established for other neurological conditions; no pediatric ME/CFS trials)