M. Xhelili1,2, J. Kruja2,3, Z. Ilirjana2,3 1Regional Hospital Center “Shefqet Ndroqi”, Neurology, Tirana, Albania; 2University of Medicine, Faculty of Medicine, Tirana, Albania; 3UHC “Mother Teresa”, Head of Neurology Service, Tirana, Albania Correspondence: M. Xhelili

The Journal of Headache and Pain 2025, 26(Suppl 2):LP080

Objective: Headache is one of the most common neurological disorders, affecting approximately 40% of the population1. Crouzon syndrome (CS), first described in 19122, is a rare autosomal dominant syndrome caused by mutations in the FGFRII gene located on chromosome 10q3. CS has a neuro-ophthalmologic clinical picture characterized by craniosynostosis, hypertelorism, headache, exophthalmos, strabismus, hydrocephalus, sleep apnea, and epileptic seizures. Escobar Syndrome (ES), also known as nonfatal multiple pterygium syndrome (MPS)4, is a very rare autosomal recessive disorder characterized by congenital pterygium, arthrogryposis, and spinal malformations. Mutations in the gamma subunit of the acetylcholine receptor (AChR) gene CHRNG, are found in this disorder. Escobar syndrome was first described by Bussiere et al. in 1902 and again by Escobar et al. in 19785. Langerhans cell histiocytosis (LCH) is a localized form of histiocytosis X6, characterized by osteolytic lesions and involvement of many organs, including the lungs, spleen, liver, lymph nodes, gastrointestinal tract, and pituitary gland. Langerhans cell histiocytosis infiltrates the hypothalamic-pituitary axis in 5–50% of cases, causing diabetes insipidus7.

To present three clinical cases in which headache was the symptom leading to a neurological consultion.

Methods: 1. Crouson Syndrome~ We present the case of a 30-year-old female patient who presented with a seven- year history of daily moderate frontal headache and vertigo. Eight months later, she developed blurred vision and significant hearing loss on both sides. The patient complained of nocturnal dyspnea consistent with sleep apnea. Recurrent episodes of keratoconjunctivitis were also noted. Neurological examination revealed no motor or sensory deficits or clinical signs of increased intracranial pressure. Normal psychomotor development. Examination: multiple malformations of the dental arches without facial dysmorphism, exophthalmos and syndactyly. General metabolic and hematological tests are normal. Normal electroencephalography. Panoramex has identified numerous orthodontic abnormalities. MRI of the head shows scaphocephalic prominence of the skull and enlargement of the optic nerve sheath without signs of hydrocephalus.

2. Escobar Syndrome~ A 26-year-old female patient presented with severe daily frontotemporal headache and anxiety. Examination revealed severe muscle wasting and hypotonia, cervical and popliteal pterygium, hypertrichosis, severe scoliosis, and left upper syndactyly. The patient also had a flat face with micrognathia, hypertelorism, and mild bilateral ptosis. Clinically, Escobar syndrome was suspected, which has been genetically confirmed.

3. Langerhans cell histiocytosis~ A 33-year-old patient presented with a 3-month history with progressive moderate-intensity headaches and psychomotor agitation. In addition, she has memory and concentration difficulties, behavioral disturbances, and increased emotional instability. She was consulted several times by her physician and was taking analgesic drugs. She has been reported to have had severe dysphagia since 10 weeks, drinking more than 10 liters of water per day. The patient was admitted and underwent the necessary laboratory and imaging tests. MRI of the skull showed an increase in the size of the pituitary infundibulum, which was homogeneously enlarged after the injection of contrast, suggesting an eosinophilic granuloma.

Results: Headache is the most common neurological symptom and may be a spontaneous or physiopathological sign of many rare systemic diseases. For this reason, attention should be paid to all details of the patient's history and general examination, because through routine patient complaints, we can diagnose rare syndromes.

Conclusion: Headaches are often not something that can be addressed by a neurologist alone. An interdisciplinary approach is needed to identify these syndromes and provide the most appropriate treatment for the patient.

The patients gave their explicit informed consent to publish their information in an open access journal.

Keywords: headache, general inspection, challenge, syndrome, further evaluation

Abbreviations:

CS- Crouzon Syndrome

ES- Escobar Syndrome

FGFRII- fibroblast growth factor receptor II

LCH- Langerhans cell Histiocytosis

MRI= Magnetic Resonance Imaging

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