Incidence of neurocutaneous melanosis in Japanese pediatric patients with congenital melanocytic nevi.

Neurocutaneous melanosis (NCM) is a rare, non-hereditary neurocutaneous disorder characterized by excessive melanocytic proliferation in the skin and central nervous system. As no major studies have covered the incidence of NCM among Japanese patients with congenital melanocytic nevi (CMN), we prospectively investigated the incidence of NCM among Japanese patients who underwent initial treatment for CMN. The relationship of CMN and NCM was also investigated. Japanese pediatric patients with CMN under 1 year of age were included between January 2020 and November 2022, and all patients underwent brain MRI to check for NCM in this study. NCM lesions were most frequently seen in the amygdala, followed by the cerebellum, brainstem, and cerebral hemispheres. NCM was diagnosed on brain MRI in 31.6% of the 38 patients with CMN and in 25.0% of patients with no prior examination or treatment. Distribution and size of CMN, number of satellite nevi, rugosity and nodules were strongly associated with the existence of NCM, and these findings may guide a future registry study with a large cohort of CMN patients.

Congenital melanocytic naevus syndrome and Dandy-Walker malformation - a mistaken association: case report and literature review.

Congenital melanocytic naevus (CMN) syndrome, previously termed neurocutaneous melanosis, is a rare disease caused by postzygotic mosaic mutations occurring during embryogenesis in precursors of melanocytes. The severity of neurological manifestations in CMN patients is related to central nervous system abnormalities found at magnetic resonance imaging. The association between CMN and Dandy-Walker malformation (DWM) has been described in the literature, but recent advances in imaging and genetics lead to diagnostic criteria revision. In this paper, we aim to re-evaluate the proposed association by reviewing the available literature and present a patient with CMN and a large posterior fossa cyst.

Congenital Melanocytic Nevi Syndrome With Leptomeningeal Melanoma.

ABSTRACT: The incidence of congenital melanocytic nevi (CMNs) is 1% to 6% for small- to intermediate-size nevi to 1 in 500,000 for giant size nevi. Large and satellite CMNs are known to be associated with neurocutaneous melanosis and central nervous system malformations such as Dandy-Walker malformation, defects of the vertebra-skull, and intraspinal lipomas. We hereby present a case of CMN syndrome in an 18-year-old girl with leptomeningeal melanoma, evaluated with MRI, adequately staged, and screened with FDG PET.

Neurosurgical management of patients with neurocutaneous melanosis: a systematic review.

OBJECTIVE: Neurocutaneous melanocytosis (NCM), also referred to as neurocutaneous melanosis, is a rare neurocutaneous disorder characterized by excess melanocytic proliferation in the skin, leptomeninges, and cranial parenchyma. NCM most often presents in pediatric patients within the first 2 years of life and is associated with high mortality due to proliferation of melanocytes in the brain. Prognosis is poor, as patients typically die within 3 years of symptom onset. Due to the rarity of NCM, there are no specific guidelines for management. The aims of this systematic review were to investigate approaches toward diagnosis and examine modern neurosurgical management of NCM. METHODS: A systematic review was performed using the PubMed database between April and December 2021 to identify relevant articles using PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines. Search criteria were created and checked independently among the authors. Inclusion criteria specified unique studies and case reports of NCM patients in which relevant neurosurgical management was considered and/or applied. Exclusion criteria included studies that did not report associated neurological diagnoses and neuroimaging findings, clinical reports without novel observations, and those unavailable in the English language. All articles that met the study inclusion criteria were included and analyzed. RESULTS: A total of 26 extracted articles met inclusion criteria and were used for quantitative analysis, yielding a cumulative of 74 patients with NCM. These included 21 case reports, 1 case series, 2 retrospective cohort studies, 1 prospective cohort study, and 1 review. The mean patient age was 16.66 years (range 0.25-67 years), and most were male (76%). Seizures were the most frequently reported symptom (55%, 41/74 cases). Neurological diagnoses associated with NCM included epilepsy (45%, 33/74 cases), hydrocephalus (24%, 18/74 cases), Dandy-Walker malformation (24%, 18/74 cases), and primary CNS melanocytic tumors (23%, 17/74 cases). The most common surgical technique was CSF shunting (43%, 24/56 operations), with tethered cord release (4%, 2/56 operations) being the least frequently performed. CONCLUSIONS: Current management of NCM includes CSF shunting to reduce intracranial pressure, surgery, chemotherapy, radiotherapy, immunotherapy, and palliative care. Neurosurgical intervention can aid in the diagnosis of NCM through tissue biopsy and resection of lesions with surgical decompression. Further evidence is required to establish the clinical outcomes of this rare entity and to describe the diverse spectrum of intracranial and intraspinal abnormalities present.

Fetal neuroimaging findings in PHACE syndrome: case report and review of the literature.

OBJECTIVE: To describe the main prenatal sonographic and magnetic resonance imaging (MRI) features leading to the diagnosis of Posterior fossa malformations, Hemangiomas of the face, Arterial anomalies, Coarctation of the aorta and cardiac defects, and Eye abnormalities (PHACE) syndrome. The literature was also reviewed in order to determine the main neuroimaging features of fetuses with this condition. RESULTS: The index case was referred at 24 weeks' gestation with the probable diagnosis of Dandy-Walker malformation. Prenatal sonographic examination revealed hypoplasia of the left cerebellar hemisphere, hypoplasia of the cerebellar vermis, and enlarged cisterna magna (the "tilted telephone receiver sign"). Fetal MRI at 30 weeks confirmed the findings and also revealed an ipsilateral retrocerebellar cyst communicating with the asymmetrical dilated fourth ventricle, upward displacement of the left cerebellar hemisphere, and elevation of the ipsilateral tentorium. Postnatally, a large left facial segmental hemangioma as well as ipsilateral vascular intracranial malformations were identified, confirming the diagnosis of PHACE syndrome. A review of the literature revealed 11 reports describing 22 fetuses with prenatal imaging studies, including ours, confirming the high prevalence of specific posterior fossa abnormalities associated with PHACE syndrome. CONCLUSION: Our case and those reported in the literature support the observation that PHACE syndrome presents with characteristic features affecting the posterior fossa, which can be identified through prenatal sonography and fetal MRI.

The Forgotten Phacomatoses: A Neuroimaging Review of Rare Neurocutaneous Disorders.

Phakomatoses, or neurocutaneous syndromes, are a heterogeneous group of rare genetic disorders that predominantly affect structures arising from the embryonic ectoderm, namely the skin, eye globe, retina, tooth enamel, and central nervous system. Other organs are also involved in some syndromes, mainly cardiovascular, pulmonary, renal, and musculoskeletal systems. Currently, more than sixty distinct entities belonging to this category have been described in the literature. Common phakomatoses include conditions like Neurofibromatosis and Tuberous sclerosis. Several review papers have focused on various aspects of these common conditions, including clinical presentation, genetic and molecular basis, and neuroimaging features. In this review, we focus on rare neurocutaneous syndromes: Melanophakomatoses (Ie, Neurocutaneous Melanosis, and Incontinentia Pigmenti), Vascular Phakomatoses (Ie, Ataxia Telangiectasia and PHACE Syndrome), and other conditions such as Cowden Syndrome, Basal Nevus Syndrome, Schwannomatosis, Progressive Facial Hemiatrophy, Gomez-Lopez-Hernandez Syndrome, Wyburn-Mason Syndrome, CHILD Syndrome, and Proteus Syndrome. We also review the neuroradiologic manifestations of these conditions as a guide for neurologists and neuroradiologists in their daily practice.

Care of Congenital Melanocytic Nevi in Newborns and Infants: Review and Management Recommendations.

A pediatric dermatology expert working group performed a narrative review to describe care related to congenital melanocytic nevi (CMN) in neonates and infants. There are no published guidelines for most aspects of care, including routine skin care and visit intervals. Few guidelines exist for surgical management; newer recommendations favor conservative practice. Emerging evidence contributes to recommendations for screening MRI to evaluate for neural melanosis and related central nervous system complications, however, more research is needed. Risk for melanoma is generally low, but those with large, giant, or multiple CMN have a higher risk. Multidisciplinary care, with a focus on family and patient preferences, is of paramount importance. Without standardized screening and management guidelines, questions abound regarding appropriate physical examination intervals, potential treatment including full or partial excision, timing and frequency of imaging, melanoma risk, and assessment for neural melanosis. This review highlights the current state of knowledge concerning care of patients with CMN, reveals gaps in the literature surrounding skin care, and provides management recommendations. We additionally discuss cutaneous complications of CMN, such as pruritus, hypertrichosis, and wound healing. Resources and references for families and providers can help patients navigate this sometimes challenging diagnosis. Finally, we contribute expert care recommendations to the current body of literature as a foundation for the development of future, more comprehensive care guidelines.

Neuroaxial Infantile Hemangiomas: Imaging Manifestations and Association with Hemangioma Syndromes.

BACKGROUND AND PURPOSE: Infantile hemangiomas are common lesions in the pediatric population; in rare cases, an infantile hemangioma can be detected along the neural axis. The purposes of our study included determination of the incidence, location, and imaging appearance of neuroaxial infantile hemangiomas and their syndromic association. We also assessed additional features of cerebral and cardiovascular anomalies that may be associated with neuroaxial lesions. MATERIALS AND METHODS: A retrospective cohort study was performed, searching the radiology database for patients with segmental infantile hemangiomas referred for assessment of possible hemangioma syndromes. We retrospectively reviewed brain and spine MR imaging studies, with particular attention paid to neuroaxial vascular lesions, as well as the relevant clinical data. Neuroaxial hemangioma imaging findings were described, and comparison of segmental cutaneous infantile hemangioma location with the imaging findings was performed in patients with confirmed hemangioma syndromes and in patients with isolated skin infantile hemangioma. RESULTS: Ninety-five patients with segmental infantile hemangioma were included in the study, 42 of whom had a hemangioma syndrome; of those, 41 had posterior fossa brain malformations, hemangioma, arterial lesions, cardiac abnormalities, and eye abnormalities (PHACE) syndrome and 1 had diffuse neonatal hemangiomatosis. Neuroaxial involvement was detected in 20/42 patients (48%) with hemangioma syndromes and in no subjects with isolated segmental infantile hemangioma (P < .001). The most common intracranial hemangioma location was within the ipsilateral internal auditory canal (83%). CONCLUSIONS: Many pediatric patients with segmental infantile hemangioma in the setting of hemangioma syndromes, especially those with PHACE, had neuroaxial hemangiomas. This finding may potentially lead to requiring additional clinical evaluation and management of these patients.

Imaging and Clinical Features of Neurocutaneous Melanosis in the Pediatric Population.

BACKGROUND: Neurocutaneous Melanosis (NCM) is a rare nonfamilial phakomatosis characterized by the presence of congenital melanocytic nevi and abnormal melanocyte infiltration of the leptomeninges. OBJECTIVE AND METHODS: This paper shows the importance of early diagnosis and the most important imaging features of the disease on CT and MR scans. PubMed database was searched from January 1972 to September 2020. Papers including imaging findings of NCM, clinical, follow-up, and treatment features were collected, selecting only 89 studies. DISCUSSION: NCM is a term used for the first time by van Bogaert in 1948. It refers to a condition caused by an error during morphogenesis and migration leading to leptomeningeal melanocytic accumulation. Although histological findings are the gold standard for diagnosis confirmation, neuroimaging and clinical features strongly support the suspect of NCM. Localization and extension of the lesions are predictive of neurological manifestations related to increased intracranial pressure, mass lesions, or spinal cord compression. CT demonstrates sites of increased density in the anterior temporal lobe, mainly the amygdala, thalami, cerebellum, and frontal lobes base. However, MRI is the best imaging method to diagnose central nervous system lesions, often appearing as T1-short signal areas of the cerebral parenchyma, indicative of central nervous system melanosis. MRI can also reveal associated intracranial and intraspinal abnormalities. CONCLUSION: Early imaging, when available, is helpful if NCM suspect is raised and may be of guidance in comparing later studies. NCM requires a multidisciplinary approach since it is a multisystem disease with a genetic component.

Clinical and molecular evaluation of 13 Brazilian patients with Gomez-López-Hernández syndrome.

We aim to characterize patients with Gomez-López-Hernández syndrome (GLHS) clinically and to investigate them molecularly. A clinical protocol, including a morphological and neuropsychological assessment, was applied to 13 patients with GLHS. Single-nucleotide polymorphism (SNP) array and whole-exome sequencing were undertaken; magnetic resonance imaging was performed in 12 patients, including high-resolution, heavily T2-weighted sequences (HRT2) in 6 patients to analyze the trigeminal nerves. All patients presented alopecia; two did not present rhombencephalosynapsis (RES); trigeminal anesthesia was present in 5 of the 11 patients (45.4%); brachycephaly/brachyturricephaly and mid-face retrusion were found in 84.6 and 92.3% of the patients, respectively. One patient had intellectual disability. HRT2 sequences showed trigeminal nerve hypoplasia in four of the six patients; all four had clinical signs of trigeminal anesthesia. No common candidate gene was found to explain GLHS phenotype. RES does not seem to be an obligatory finding in respect of GLHS diagnosis. We propose that a diagnosis of GLHS should be considered in patients with at least two of the following criteria: focal non-scarring alopecia, rhombencephalosynapsis, craniofacial anomalies (brachyturrycephaly, brachycephaly or mid-face retrusion), trigeminal anesthesia or anatomic abnormalities of the trigeminal nerve. Studies focusing on germline whole genome sequencing or DNA and/or RNA sequencing of the alopecia tissue may be the next step for the better understanding of GLHS etiology.

Clinical Follow-Up of Patients with Neurocutaneous Melanosis in a Tertiary Center; Proposed Modification in Diagnostic Criteria.

INTRODUCTION: Neurocutaneous melanosis (NCM) is a rare congenital syndrome. Except for some retrospective studies, information on clinical follow-up and management of these patients are limited. This study aimed to review our experience on diagnostic protocol and clinical follow-up of patients with NCM in a referral children's hospital in Iran. METHODS: Between 2012 and 2019, eight patients with NCM were consecutively managed in our center. Brain magnetic resonance imaging and cutaneous biopsy were done in all patients at diagnosis. Follow-up surveillance and characteristics of the disease are described. RESULTS: The mean follow-up period was 25.75 ± 13.81 months, and 75% of patients were male. Most magnetic resonance imaging findings were hypersignal lesions in the temporal lobe (75%), cerebellum (62.5%), brainstem (50%), and thalamus (12.5%). Dandy-Walker syndrome was found in 4 patients (50%), and shunt-dependent hydrocephalus was found in 3 patients (37.5%). Cutaneous malignant melanoma and malignant involvement of the central nervous system were found in 2 (25%) and 3 cases (37.5%), respectively. The mortality rate was 37.5%. CONCLUSIONS: There are no specific guidelines for management of NCM due to the rarity of the disease. This study proposed modifications in diagnostic criteria, as well as recommendations for follow-up surveillance.

Arterial Spin-Labeling Perfusion for PHACE Syndrome.

BACKGROUND AND PURPOSE: Arterial stroke is a rare-but-reported complication in patients with posterior fossa brain malformations, hemangiomas, arterial anomalies, coarctation of the aorta and cardiac defects, and eye abnormalities (PHACE) syndrome. Currently, stroke risk is inferred by the severity of arterial anomalies identified on MRA, though no evidenced-based data exist. The purpose of our study was to determine whether arterial spin-labeling MR imaging perfusion can detect alterations in CBF in patients with PHACE syndrome. MATERIALS AND METHODS: Records were reviewed from 3 institutions for all patients with PHACE syndrome who underwent arterial spin-labeling from 2000 to 2019. CBF was qualitatively investigated with arterial spin-labeling to determine whether there was decreased or normal perfusion. Arterial anomalies were characterized on MRA imaging, and parenchymal brain findings were evaluated on conventional MR imaging sequences. RESULTS: Forty-one patients with PHACE syndrome had arterial spin-labeling imaging. There were 30 females and 11 males (age range, 7 days to 15 years). Of the 41 patients, 10 (24%) had decreased CBF signal corresponding to a major arterial territory. Ten of 10 patients had decreased CBF signal in the anterior circulation, 2/10 had decreased anterior and posterior circulation CBF signal, 2/10 had decreased bilateral anterior circulation CBF signal, and 1/10 had globally decreased CBF signal. Forty of 41 (97.5%) patients had at least 1 arteriopathy, and in those with decreased CBF signal, the arteriopathy corresponded to the CBF signal alteration in 10/10 patients. CONCLUSIONS: Arterial spin-labeling can potentially characterize hemodynamic changes in patients with PHACE syndrome.