Abstract
Introduction
Encephalocraniocutaneous lipomatosis (ECCL) is a rare congenital syndrome with complex skin, eye, and central nervous system (CNS) symptoms. Diagnosis and treatment are challenging due to its rarity and diverse manifestations. It often involves issues like porencephalic cysts, cortical atrophy, and low-grade gliomas in the CNS, resulting in developmental delays. The spinal cord is frequently affected, leading to problems like medullary compression and radiculopathy, causing back pain and sensory/motor deficits. Surgical interventions are reserved for symptomatic cases to address hydrocephalus or alleviate spinal lipomas. This article reviews a case series to assess surgical risks and neurological outcomes.
Case series
We present a case series ECCL, focusing on the diffuse lipomatosis of the spinal cord and the intricate surgical procedures involved. A multi-stage surgical approach was adopted, with continuous neuromonitoring employed to safeguard motor pathways. We discuss clinical characteristics, imaging studies, and indications for neurosurgical interventions.
Discussion
ECCL is a complex syndrome. Diagnosis is challenging and includes clinical evaluation, neuroimaging, and genetic testing. Treatment targets specific symptoms, often requiring surgery for issues like lipomas or cerebral cysts. Surgery involves laminectomies, spinal fusion, and motor pathway monitoring. Thorough follow-up is crucial due to potential CNS complications like low-grade gliomas. Hydrocephalus occurs in some cases, with endoscopic third ventriculostomy (ETV) preferred over ventriculoperitoneal shunt placement.
Conclusion
Neurosurgery for ECCL is for symptomatic cases. ETV is preferred for hydrocephalus, while the treatment for lipoma is based on the presence of symptoms; the follow-up should assess growth and prevent deformities.
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Introduction
Encephalocraniocutaneous lipomatosis (ECCL) is a rare congenital syndrome characterized by signs and symptoms involving the skin, eyes, and central nervous system (CNS) [1]. This disease, of unknown origin, poses a challenge both for diagnosis and treatment due to its rarity and the complexity of its manifestations [2]. Reported CNS manifestations include porencephalic cysts, cortical atrophy, and low-grade gliomas (LGG), which are consistently associated with developmental delay and mental retardation. Most problems focus on the spinal cord with diffuse lipomatosis. Specifically, clinical presentations can be compressive medullary or radiculopathy, resulting in consequences such as back pain, radiculopathy, or motor or sensory deficits. Neurosurgical interventions are complex and reserved for symptomatic cases. In this article, we analyze our series and reviews to evaluate the risk of surgery and neurological outcomes.
Case series
We present a series of three patients with ECCL treated at our institute between 2008 and 2023 (Table 1).
Patient A had scoliosis and a congenital lipoma in the right eye. Magnetic resonance imaging (MRI) revealed obstructive hydrocephalus and a spinal lipoma extending into the cervical-dorsal region (Fig. 1A), leading to the development of spastic tetraparesis and neurogenic bladder. Consequently, the patient underwent ventriculocisternostomy and later had two surgical procedures to remove the spinal lipoma. Following the surgical removal of the spinal lipoma, the patient developed kyphosis, requiring stabilization with spinal fusion. During follow-up, the patient developed a diffuse low-grade glioneuronal neoplasm throughout the brain, ultimately resulting in death.
Patient B presented with scoliosis and psychomotor delay. MRI revealed a spinal lipoma extending into the bulbo-dorsal region, along with hydrobulbia and hydromyelia (Fig. 1B). Surgical treatment was performed in two stages. After the first debulking surgery, the patient developed obstructive hydrocephalus, necessitating external ventricular drainage. The follow-up was concluded due to the patient’s death.
Patient C presented with lower back pain, motor disturbances, pigmented skin lesions, and attention deficits. MRI showed a cervical-lumbar spinal lipoma associated with kyphosis (Fig. 1C). The patient underwent three-stage surgical removal of the spinal lipoma, which included laminotomies and spinal stabilization. The patient’s follow-up is ongoing and has revealed an increase in kyphosis, requiring the use of a brace and rehabilitative therapy.
In all patients, surgical treatment was performed using a multi-step approach to better control the sequelae. Continuous neuromonitoring was applied during surgical procedures, including electroencephalogram (EEG), electromyogram (EMG), somatosensory evoked potentials (SSEPs), and motor evoked potentials (MEPs). Neuronal integrity was assessed through wake-up tests during surgery. This strategy was particularly crucial in the case of Patient C, as a loss of motor potentials in the lower limbs was detected during surgery (Fig. 2), allowing for immediate resolution of the complication.
Discussion
ECCL is a multisystemic syndrome that involves three main components: cutaneous involvement is often one of the most apparent signs with various skin defects, including superficial lipomas, pigmented skin lesions, and facial angiofibromas [3, 4]. Central nervous system (CNS) involvement is the most severe component and the most important prognostic factor [5]. The distribution of lipomas is often widespread along the spinal cord, typically remaining stable throughout a patient’s life. Diagnosing ECCL can be challenging due to its clinical variability and similarity to other neurocutaneous diseases. Typically, it is made through a detailed clinical evaluation, neuroimaging studies, and sometimes genetic tests to identify specific genetic mutations associated [6]. ECCL is primarily associated with mosaic mutations in the FGFR1 gene as revealed by exome sequencing. The connection between mosaic mutations and developmental pathologies, with potential overlap in tumorigenesis-related signaling pathways like RAS-MAPK, is highlighted. However, not all ECCL cases are linked to identifiable FGFR1 mutations, suggesting the possibility of other genetic factors or mechanisms at play [4, 7, 8]. The treatment of ECCL is complex and aimed at managing the specific manifestations of the disease. In symptomatic cases, surgical removal may be necessary [9]. In particular, in patient with joint cervicomedullary involvement, posterior fossa craniectomy with cervical laminectomies is reserved for sleep apnea and upper deficits. Extensive laminectomy can lead to progressive kyphosis, necessitating consideration of surgical atlantoaxial transarticular screw fixation. In pre-operative scoliosis cases where debulking occurs in multiple steps, a complete posterior arthrodesis is indicated. Authors recommend subpial excision of lipomas, although intramedullary invasiveness may prevent complete removal [10]. Motor evoked potentials monitoring provides real-time feedback on the integrity of motor pathways, reducing the risk of neurological injury. Another reason for rigorous follow-up is that CNS malformations may increase morbidity and mortality [11]. We analyzed clinical cases of ECCL with spinal cord lipoma described in the literature (Table 2), and we found descriptions of 7 cases of ECCL with spinal cord lipoma. The extent of the lipoma ranged from involvement of only the dorsal portion to the entire spinal cord. Four patients underwent a surgical laminectomy with resection of the spinal lipoma [5, 10, 12, 13], but only one case was the procedure performed in two stages [10]. Of the cases described in the literature, only two presented obstructive hydrocephalus [10, 14], and in both cases, the patients underwent surgical treatment. In one case, an endoscopic third ventriculostomy (ETV) was performed [10], while in the other, a ventriculo-peritoneal shunt (VPS) was placed [14]. In fact, ventriculomegaly and macrocephaly are common findings in ECCL patients, but not all of them develop hydrocephalus. Hydrocephalus was diagnosed in approximately one-third of patients with ECCL, and ETV should be considered as the first option instead of VPS placement.
Conclusion
Early identification of ECCL is crucial for accurate diagnosis, effective symptomatic management, and better patient care, ultimately improving the quality of life for affected individuals [4]. In terms of treatment, the approach varies. In cases of associated hydrocephalus, ETV is usually preferred to alleviate intracranial pressure. The surgical approach for spinal cord lipomas is recommended in symptomatic cases and involves the removal of the lipoma, sometimes in multiple stages, to preserve nerve function. In our experience, we believe it is appropriate to perform surgical procedures in symptomatic cases, and we consider follow-up crucial not only to assess the growth of lipomatous lesions but also to prevent vertebral deformities; specifically, we anticipate cervical stabilization to prevent the development of kyphosis.
Data availability
No datasets were generated or analysed during the current study.
References
Biesecker LG (2006) The challenges of Proteus syndrome: diagnosis and management. Eur J Hum Genet 14(11):1151–1157
Klein S, Hamerschmidt R, Waissmann W (2009) Encephalocraniocutaneous lipomatosis. Revista brasileira de neurologia (Rev Bras Neurol) 45(3):69–72
Herrera-Gómez Á, Carrasco-Rozas A, Sánchez-Romero F, Herrera-Gómez FJ (2019) Encephalocraniocutaneous lipomatosis: clinical, neuroimaging, and genetic features. A review of 32 cases. Neurologia 34(1):46–54
Karaman ZF, Özüdoğru ŞE (2021) Encephalocraniocutaneous lipomatosıs (Haberland syndrome) in a newborn baby: a case report with review of literature. Child’s nervous system : ChNS : official journal of the International Society for Pediatric Neurosurgery 37(12):3951–3955. https://doi.org/10.1007/s00381-021-05099-7
Moog U, Jones MC, Bird LM et al (2005) Encephalocraniocutaneous lipomatosis plus: a syndrome including intracranial lipomas, uveal colobomas, and complex vascular anomalies. Report of two patients and review of the literature. Neuropediatrics 36(6):347–352
Slavotinek AM, Garcia ST, Chandratillake G, Bardakjian T, Ullah E, Wu D et al (2015) Exome sequencing in 32 patients with anophthalmia/microphthalmia and developmental eye defects. Clin Genet 88(5):468–473
Bennett JT, Tan TY, Alcantara D, Tétrault M, Timms AE, Jensen D, Collins S, Nowaczyk MJ, Lindhurst MJ, Christensen KM, Braddock SR, Brandling-Bennett H, Hennekam RCM, Chung B, Lehman A, Su J, Ng S, Amor DJ, University of Washington Center for Mendelian Genomics, Care4Rare Canada Consortium, ... McDonell LM (2016) Mosaic activating mutations in fgfr1 cause encephalocraniocutaneous lipomatosis. Am J Hum Genet 98(3):579–587
Kordacka J, Zakrzewski K, Gruszka R, Witusik-Perkowska M, Taha J, Sikorska B, Liberski PP, Zakrzewska M (2019) Sensitive detection of FGFR1 N546K mosaic mutation in patient with encephalocraniocutaneous lipomatosis and pilocytic astrocytoma. Am J Med Genet A 179(8):1622–1627. https://doi.org/10.1002/ajmg.a.61256
Caro-Domínguez P, Esteban-Sanchis A, Gomis-Couto A, Mínguez-Martínez I, Mata-Gregori J, Sanahuja-Martínez A et al (2020) Encephalocraniocutaneous lipomatosis: a case report and review of literature. Case Rep Med 2020:9056079
Ayer REZA (2011) Encephalocraniocutaneous lipomatosis: a review of its clinical pathology and neurosurgical indications. J Neurosurg Pediatr 8(3):316–320
Brassesco MS, Valera ET, Becker AP, Castro-Gamero AM, de Aboim MA, Santos AC et al (2010) Low-grade astrocytoma in a child with encephalocraniocutaneous lipomatosis. J Neurooncol 96:437–441
Deda G, Caksen H, Yavuzer G, Arasil T (2001) Encephalocraniocutaneous lipomatosis associated with iris coloboma, chorioretinitis and spinal cord involvement: a case report. Brain Dev 23(5):355–358. https://doi.org/10.1016/s0387-7604(01)00219-4. PMID: 11504608
Chiang CC, Lin SC, Wu HM, Wang JC, Yang TF, Chen HH, Ho DM, Wong TT (2014) Clinical manifestation and neurosurgical intervention of encephalocraniocutaneous lipomatosis–a case report and review of the literature. Childs Nerv Syst 30(1):13–17. https://doi.org/10.1007/s00381-013-2252-z. Epub 2013 Aug 24 PMID: 23974968
Naous A, Shatila AR, Naja Z, Naja AS, Rajab M (2015) Encephalocraniocutaneous lipomatosis: a rare association with tethered spinal cord syndrome with review of literature. Child Neurol Open 2(1):2329048X14553297. https://doi.org/10.1177/2329048X14553297. PMID: 28503585; PMCID: PMC5417016
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Pavanello, M., Piro, L., Roggero, A. et al. Navigating the complexities of encephalocraniocutaneous lipomatosis: a case series and review. Childs Nerv Syst 40, 1251–1258 (2024). https://doi.org/10.1007/s00381-024-06279-x
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DOI: https://doi.org/10.1007/s00381-024-06279-x