ULTRA-MICRONIZED PALMITOYLETHANOLAMIDE IN THE MANAGEMENT OF SEVERE HEADACHE: THE COMPLEX CASE OF A 13-YEAR-OLD GIRL WITH MULTIPLE NEURODEVELOPMENTAL DISORDERS

I. Turrini¹, C. Monaco¹, I. Contaldo¹, C. Veredice¹, C. Brogna¹, D. Rigante² | ¹Pediatric Neurology Unit, Policlinico Universitario A. Gemelli IRCCS, Roma; ²Department of Life Sciences and Public Health, Policlinico Universitario A. Gemelli IRCCS, Roma

INTRODUCTION
Headache is a common and disabling condition affecting children and adolescents. Its unclear pathogenesis has led to high rates of misdiagnosis and limited available treatment options¹. Neurogenic inflammation is a major contributor to painful conditions, including headache², and mast cells (MCs) - nerve interaction plays a key role in its onset and maintenance, fueled by uncontrolled MCs degranulation and the consequent release of inflammatory mediators³. Palmitoylethanolamide (PEA) is an endogenous lipid mediator with neuroprotective, anti-inflammatory and analgesic properties attributable to its ability to modulate MCs reactivity⁴. Given the recognized beneficial role of ultra-micronized PEA (um-PEA) formulation in managing pediatric migraine⁵, we reported the case of a young girl suffering from episodes of severe headache successfully controlled by um-PEA administration.
METHODS
The case of a 13-year-old girl diagnosed with Kabuki syndrome and attention-deficit/hyperactivity disorder (ADHD), with expressive and receptive language as well as developmental coordination disorders, who suffered from high-intensity headaches since the age of four. The girl came to our attention presenting pulsating frontal headaches associated with nausea and vomiting, triggered by stress or physical exercise, with an average monthly frequency of 3-4 episodes in the previous 4 months, each lasting about 3 days. Symptoms were poorly responsive to oral ibuprofen and unresponsive to paracetamol suppositories. For headache control, the girl was prescribed um-PEA 5 ml/day (Paidinil® HD 12% oral suspension), plus ibuprofen oral suspension or tablets as needed. The frequency of headaches (number of attacks/month) and treatment safety were monitored over time.
RESULTS
Um-PEA allowed a gradual reduction in the frequency of headaches, which decreased from 3-4 episodes/month to 2-3 attacks/month during the first 5 months, up to 1 attack/month in the next 11 months of um-PEA supplementation. Attacks became shorter (lasting one day), persistent especially in stressful situations, occasionally associated with vomiting and responsive to ibuprofen therapy. Interestingly, upon episodes reduction, the patient self-discontinued um-PEA treatment, experiencing over the following 2 months an increase in headache frequency (3 attacks/month) while maintaining a positive response to ibuprofen. Three um-PEA cycles then followed, showing a significant reduction in headache frequency from 3 attacks/month during the discontinuation period to 1 episode every two months during um-PEA administration (Figure 1). No adverse effects were reported throughout the observation.
CONCLUSIONS
To date, only a single pilot study evaluated the efficacy of um-PEA in pediatric patients with migraine, demonstrating a decrease in pain intensity and attack frequency after three months of treatment [5]. This case confirms the beneficial effect of um-PEA in reducing headache frequency and shows its good tolerability even in the long-term use, in a young girl with a complex clinical condition. Furthermore, um-PEA administration seems to have improved the response to ibuprofen therapy, allowing optimal control of acute attacks.

Figure 1. Change in headache frequency during different um-PEA supplementation cycles.