Neurocutaneous Syndrome Research Articles

Facing PHACES Syndrome; Anesthesiologist’s Point of View

Introduction: PHACES syndrome is a neurocutaneous syndrome that consists of posterior fossa brain malformation, hemangiomas of the face, arterial cerebrovascular malformation, cardiovascular anomalies (Coarctation of the aorta), eye anomaly, and sternal defect or supraumbilical raphe. Most of these manifestations would interfere with anesthesia and hence need major considerations. Case Presentation: A 2.5-month-old female weighing 2100 gr was a candidate for laser therapy due to retinopathy of prematurity. She was diagnosed with PHACES syndrome. Her anesthesia was induced and maintained with sevoflurane. LMA #1 was used for airway management. No complications occurred during or after anesthesia, and she was discharged the next day. Conclusions: PHACES syndrome interacts with numerous anesthesia-related characteristics, such as airway management, cardiovascular disease, and CNS malformations. Based on the accompanying characteristics, perioperative care for these patients should be tailored.

The role of cranial magnetic resonance imaging findings in pediatric epilepsy: A single-center experience.

The aim of this study was to investigate cranial magnetic resonance imaging (MRI) findings in different age groups and genders in pediatric epilepsy, to determine the percentages of etiologic factors, and to evaluate the association between MRI positivity and treatment resistance. Cranial MRIs of 359 patients with epilepsy aged 1 month to 18 years were retrospectively evaluated. Etiologic factors as an underlying cause of epilepsy were classified as previous parenchymal damage, hippocampal sclerosis, malformations of cortical development, tumor, neurocutaneous syndrome, myelination disorder, vascular anomaly, metabolic/genetic/neurodegenerative diseases, encephalitis, and an uncategorized "other" group. Data were transferred to IBM SPSS Statistics 25.0 (SPSS Inc., Chicago, IL, USA), and descriptive statistics, correlation analyses, chi-square, and t-tests were performed. Among the patients included in the study, 141 (39.3%) had pathological findings on MRI related to the etiology. Previous parenchymal damage (39.7%) was the most common etiologic cause in all age groups. Regarding the relationship between drug resistance and MRI positivity, MRI positivity was observed in 72% of drug-resistant cases, while a complete response to therapy was found in 67.6% of MRI-negative cases. MRI guides clinicians to determine the presence of an etiologic factor as the underlying cause of childhood epilepsy before treatment planning. MRI positivity is a remarkable indicator of response to antiseizure drug treatment and drug resistance.

The role of scoliosis on the comorbidity and demographics of neurofibromatosis type 1 patients: A retrospective analysis of the National Inpatient Sample database.

Neurofibromatosis type 1 (NF1) is the most common neurocutaneous syndrome in the United States, affecting every 1 in 3000 individuals. NF1 occurs due to non-functional mutations in the NF1 gene, which expresses neurofibromin, a protein involved in tumour suppression. As a result, NF1 typically presents with non-cancerous neoplasm masses called neurofibromas across the body. Out of all NF1 abnormalities, the most common skeletal abnormality seen in around 10%-30% of NF1 patients is scoliosis, an improver curvature of the spine. However, there is a lack of research on the effects of scoliosis on demographics and morbidities of NF1 patients. We performed a national analysis to investigate the complex relationship between NF1 and scoliosis on patients' demographics and comorbidities. We conducted a retrospective cross-sectional analysis of the 2017 US National Inpatient Sample database using univariable Chi-square analysis and multivariable binary logistic regression analysis to determine the interplay of NF1 and scoliosis on patients' demographics and comorbidities. Our query resulted in 4635 total NF1 patients, of which 475 (10.25%) had scoliosis and 4160 (89.75%) did not. Demographic analysis showed that NF1 patients with scoliosis were typically younger, female and white compared to NF1 patients without scoliosis. Comorbidity analysis showed that NF1 patients with scoliosis were more likely to develop malignant brain neoplasms, epilepsy, hydrocephalus, pigmentation disorders, hypothyroidism, diabetes with chronic complications and coagulopathy disorders. NF1 patients with scoliosis were less likely to develop congestive heart failure, pulmonary circulation disease, peripheral vascular disease, paralysis, chronic pulmonary disease, lymphoma and psychosis. NF1 patients with scoliosis were predominantly younger, female, white patients. The presence of scoliosis in NF1 patients increases the risks for certain brain neoplasms and disorders but serves a protective effect against some pulmonary and cardiac complications.

Tuberous sclerosis complex, Clinic and pathology manifestations, Mini -review

Tuberous sclerosis complex (TSC) is an autosomal dominant neurocutaneous syndrome that affects almost all of the organs of the body, including the brain, heart, lungs, liver, and kidneys. Brain tumors in TSC patients include cortical tubers, subependymal nodules (SENs), and Subependymal giant cell astrocytomas (SEGAs). Seizures that occur in 92% of patients with TSC are an important cause of sudden deaths in them. Other organ involvement includes renal angiomyolipomas, lymphangioleiomyomatosis, cardiac rhabdomyomas, and cutaneous manifestations (hypomelanotic macules, angiofibroma, ungual fibromas, shagreen patch, and ‘confetti’ skin lesions). There is a criterion for tuberous sclerosis complex that consists of 11 major and 6 minor clinical features that diagnosis occurs based on it. The best way for a definitive diagnosis of TSC in a patient is by using genetic tests and histopathology. Immunohistochemistry is a helpful method in confirming the diagnosis of brain tumors in TSC. Immunostaining of SEGA shows positivity for GFAP and S-100 protein while neurofilament and synaptophysin are negative. Ki-67, which indicates nuclear proliferation, has a low proliferation index in immunostain. In an aggressive tumor, hydrocephalus, rising intracranial pressure and focal neurologic deficit, surgery is a necessity and can improve outcomes. Brain and kidney involvement in this disease is life-threatening. Brain involvement in these patients can lead to extensive neuropsychological complications, so the aim of this study is a concise review of the variable manifestations of this disease with a focus on the histopathological findings of brain involvement.

10141-GMC-13 MULTIREGIONAL GENOMIC ANALYSIS: A NOVEL APPROACH FOR DETECTING PATHOGENIC DRIVER MUTATION ASSOCIATED WITH MALIGNANT PROGRESSION IN NEUROCUTANEOUS MELANOSIS

Abstract Neurocutaneous melanosis (NCM) is a rare congenital neurocutaneous syndrome characterized by congenital melanocytic nevus of skin and abnormal proliferation of leptomeningeal melanocytes. Early acquisition of post-zygotic somatic mutations has been postulated to underlie the pathogenesis of NCM. The pathogenesis of NCM remains to be fully elucidated and treatment options have not been established. Here, we report for the first time, multiregional genomic analyses in a 3-year-old autopsied girl with leptomeningeal melanomatosis associated with NCM, in which a ventriculo-peritoneal shunt was inserted for the treatment of hydrocephalus. The patient expired six months after the onset due to respiratory failure caused by abdominal dissemination via ventriculo-peritoneal shunt. We performed multiregional exome sequencing to identify genomic differences among brain and abdominal tumors, nevus, and normal tissues. A total of 87 somatic mutations were found in 71 genes, with a significantly large number of gene mutations found in the tumor site. The genetic alterations detected in the nevus were only few and not shared with other sites. Three pathogenic mutations, GNAQ R183Q, S1PR3 G89S and NRAS G12V were found. GNAQ and S1PR3 mutations were shared in both tumor and normal sites. Moreover, the mutant allele frequencies of the two mutations were markedly higher in tumor sites than in normal sites. NRAS mutation was found only in the abdominal tumor and was thought to be responsible for malignant progression in the present case. Multiregional comprehensive genetic analysis may lead to discover novel driver mutations associated with tumorigenesis and targeted therapy.

Photogallery. Genodermatoses. Part I

Genodermatoses are skin diseases caused by the inheritance of a pathological gene responsible for the formation of a particular skin structure.
 Hereditary diseases can be monogenic, polygenic and chromosomal. Genodermatoses follow Mendelian inheritance (autosomal dominant, autosomal recessive or sex-linked). Some genodermatoses appear as a result of genetic mosaicism (parts of two different chromosomes exchange their fragments).
 Autosomal dominant disorder manifest in every generation in women and men with the same frequency. Recessive genodermatoses are usually more severe and rarer. In this case, both parents are carriers of the pathological gene, but are clinically (phenotypically) healthy. The risk of developing of autosomal recessive pathology increases highly in closely related marriages.
 We present a gallery of the hereditary dermatoses.
 Neurofibromatosis is a neurocutaneous syndrome characterized by the formation of benign tumors in the skin, soft tissues, nervous system and internal organs.
 Congenital epidermolysis bullosa is a group of genodermatoses with the development of intraepidermal blisters that arise spontaneously or as a result of minor trauma.
 Tuberous sclerosis (Bourneville–Pringle disease) is a hereditary disease characterized by hyperplasia of ectodermal and mesodermal derivatives, leading to disruption of embryonic differentiation. It damages the skin, central nervous system and other organs.
 Pseudoxanthoma elasticum is characterized by calcification of elastic fibers of the skin with damage to the vision organ, cardiovascular system and reproductive function.

Retinal Tumors Associated with Phacomatoses and Isolated Retinal Hamartoma

The phacomatoses or neurocutaneous syndromes are a heterogeneous group of genetic disorders arising from the embryonic ectoderm, characterized by multiple congenital anomalies affecting the eye, skin, and central nervous system. Two of the most common phacomatoses are neurofibromatosis and tuberous sclerosis, and retinal manifestations may be seen in both these entities. Retinal astrocytic hamartomas are benign glial tumors that originate from astrocytes in the retinal nerve fiber layer. While they are classically associated with systemic phacomatoses such as tuberous sclerosis complex and neurofibromatosis, these lesions can also present as incidental findings in otherwise healthy individuals. It should be kept in mind that retinal involvement may accompany phacomatoses and detailed ophthalmological evaluation should be performed in these patients.

The profile of epilepsy and its characteristics in children with neurocutaneous syndromes.

The profile of seizures in neurocutaneous syndromes is variable. We aimed to define the characteristics of epilepsy in children with neurocutaneous syndromes. Cross-sectional study over 18 months at a tertiary care pediatric hospital, including children with neurocutaneous syndromes aged between 1 and 15 years, using the 2017-International League Against Epilepsy classification. In 119 children with neurocutaneous syndromes, 94 (79%) had epilepsy. In eight children with neurofibromatosis one with epilepsy, 5 (62.5%) had generalized motor tonic-clonic seizures, 1 (12.5%) had generalized motor epileptic spasms, 1 (12.5%) had generalized motor automatism, and 1 (12.5%) had a focal seizure. In 69 children with tuberous sclerosis complex with epilepsy, 30 (43.5%) had generalized motor epileptic spasms, 23 (33.3%) had focal seizures, and nine (13.0%) had generalized motor tonic-clonic seizures. In 14 children with Sturge-Weber syndrome with epilepsy, 13 (92.8%) had focal seizures, and 1 (7.2%) had generalized motor tonic seizures. Statistically significant associations were found between epilepsy and intellectual disability (P = 0.02) and behavioral problems (P = 0.00). Profiling seizures in children with neurocutaneous syndromes are paramount in devising target-specific treatments as the epileptogenesis in each syndrome differs in the molecular pathways leading to the hyperexcitability state. Further multicentric studies are required to unravel better insights into the epilepsy profile of neurocutaneous syndromes.

Evaluation of Molecular and Clinical Findings in Children With Neurofibromatosis Type 1: Identification of 15 Novel Variants

BackgroundNeurofibromatosis type 1 (NF1) is the most common neurocutaneous disease and is caused by mutations in the NF1 gene. The most common clinical features of NF1 are pigmentary abnormalities such as café-au-lait spots and inguinal or axillary freckling, cutaneous and plexiform neurofibromas, hamartomas of the iris, optic gliomas, and bone lesions. The aim of this retrospective study was to define the clinical and molecular characteristics of a pediatric sample of NF1, as well as the mutational spectrum and genotype-phenotype correlation. MethodsThe study included 40 children with clinically suspected NF1. The patients were screened for NF1 mutations by DNA-based sequencing. In addition, all the patients were studied by multiplex ligation-dependent probe amplification (MLPA) to identify any duplications or deletions in NF1. The demographic, clinical, and genetic features of the children were characterized. ResultsA total of 40 children with NF1 were included. Of those, 28 were female and 12 were male. The mean age was 8.91 years. An NF1 variant was discovered in 28 of 40 patients (70%). Among these mutations, intronic mutations were the most frequently detected mutations; 15 of these variants had not been previously reported. Only one patient had a whole NF1 gene deletion. ConclusionsThis study expands the spectrum of mutations in the NF1 gene. This study also showed that genetic screening using both next-generation sequencing and MLPA had a positive effect on diagnosis and genetic counseling in patients with suspected NF1.

Sjogren-Larsson syndrome brain volumetric reductions demonstrated with an automated software.

Sjogren-Larsson syndrome (SLS) is a neurocutaneous disease with an autosomal recessive inheritance, caused by mutations in the gene that encodes fatty aldehyde dehydrogenase (ALDH3A2), clinically characterized by ichthyosis, spastic diplegia, and cognitive impairment. Brain imaging plays an essential role in the diagnosis, demonstrating a nonspecific leukoencephalopathy. Data regarding brain atrophy and grey matter involvement is scarce and discordant. We performed a volumetric analysis of the brain of two siblings with SLS with the aim of detecting deep grey matter nuclei, cerebellar grey matter, and brainstem volume reduction in these patients. Volume data obtained from the brain magnetic resonance imaging (MRI) of the two patients using an automated segmentation software (Freesurfer) was compared with the volumes of a healthy control group. Statistically significant volume reduction was found in the cerebellum cortex, the brainstem, the thalamus, and the pallidum nuclei. Volume reduction in grey matter leads to the hypothesis that SLS is not a pure leukoencephalopathy. Grey matter structures affected in the present study suggest a dysfunction more prominent in the thalamic motor pathways.

Update in the Understanding, Diagnosis, and Management of Sturge Weber Syndrome: Case Report

Sturge-Weber Syndrome (SWS) is a congenital, vascular, neurocutaneous, uncommon disease associated with facial angiomas port wine birthmark (PWB) or “nevus flammeus”, cerebral vascularity alterations (leptomeningeal vascular malformation), and ocular disorders. It is the third most common neurocutaneous syndrome after neurofibromatosis and tuberous sclerosis. GNAQ R183Q is the most frequent related mutation, caused by a postzygotic, somatic, gain-of-function. 75% of patients present seizures during the first year of life, mainly focal motor seizures, with or without consciousness impairment. We present the case of a 33-year-old female with a diagnosis of SWS, with refractory seizures that started at 4 months of age. In this admission, she presented upper and lower respiratory tract infections that culminated in a convulsive status epilepticus (CSE), the reason for which she required sedation and advanced airway management with adjustment of the anti-seizure medication (ASM). An electroencephalogram (EEG) was performed that reported epileptic activity, as well as an imaging study with data suggestive of calcification in the frontal and right parietal region, compatible with vascular malformation.

Right sided facial nevus with contralateral cavernous angioma in a child with Sturge Weber syndrome

Sturge Weber syndrome is a rare sporadic neurocutaneous syndrome. It has extra -oral manifestations mostly in form of unilateral port wine stain on face that are ipsilateral to intra-cranial lesions (mostly lepto-meningeal angioma), seizures, glaucoma and intra-orally by hemangioma of ipsilateral gingiva. We case report a child with Sturge Weber syndrome with facial nevus opposite to intra-cranial lesion, intra-oral port wine stain and gum hypertrophy. Other than contralateral intracranial lesion and facial nevus, challenge was whether to see gingival manifestations as part of syndrome or as drug side effect, as child was also on phenytoin, an anti-epileptic drug widely related to this condition.

Neurocutaneous Syndromes, Perinatal Factors, and the Risk of Childhood Cancer in Sweden

Neurocutaneous syndromes are associated with cancer predisposition and sometimes associated with perinatal factors. A better understanding of the association between neurocutaneous syndromes, perinatal factors, and childhood cancer is key for earlier cancer detection. To evaluate the association of neurocutaneous syndromes and perinatal factors with childhood cancer risk in a cohort of Swedish children. In this nationwide cohort study, all children and adolescents up to age 20 years, from 1973 to 2015, were identified through the Swedish National Medical Birth Register (MBR), provided they had information on both biological parents. Analyses were conducted from April 2021 through May 2023. Diagnoses of neurocutaneous syndromes were obtained from the MBR, National Patient Register, and Cause of Death register. Perinatal factors (birth weight, gestational age, birth weight by gestational age, 5-minute Apgar score, and head circumference) were obtained from the MBR. Childhood cancer risk (<20 years at diagnosis; identified from the National Cancer Register), including leukemia, lymphoma, and central nervous system (CNS) tumors. Among 4 173 108 included children (2 143 133 [51.4%] male, median [IQR] follow-up 20 [9.7-20] years), 1783 had neurofibromatosis type 1 (NF1), 444 tuberous sclerosis, 63 von Hippel-Lindau disease, and 39 ataxia-telangiectasia. An increased cancer risk was observed among children with any neurocutaneous syndrome (HR, 34.9; 95% CI, 30.8-39.6) and was particularly pronounced for CNS tumors (HR, 111.7; 95% CI, 96.8-128.8), except among children with ataxia-telangiectasia, where the increased risk was associated with lymphomas (HR, 233.1; 95% CI, 75.0-724.1). Leukemia risk was increased only among children with NF1 (HR, 4.1; 95% CI, 1.7-9.8). Several perinatal factors, including high birth weight, being born large for gestational age, preterm birth, low 5-minute Apgar score, and large head circumference had lesser associations with childhood cancer. Adjusting for neurocutaneous syndromes did not affect these associations. In this nationwide cohort study, neurocutaneous syndromes were associated with an increased risk of childhood cancer, especially CNS tumors. Several perinatal factors had lesser associations with childhood cancer, independently of the presence of neurocutaneous syndromes. Other biological mechanisms likely underlie the association between perinatal factors and childhood cancer.

Isolated diffuse choroidal hemangioma without systemic symptoms: a case report

BackgroundSturge-Weber syndrome is a nonhereditary congenital neurocutaneous syndrome characterized by a distinctive facial capillary malformation,neurological abnormalities, and ocular abnormalities such as glaucoma and choroidal hemangioma.It can be divided into different subtypes according to different clinical manifestations. It is rare for a patient to present with isolated difuse choroidal hemangioma and ipsilateral abnormal conjunctival and episcleral vessels without other systemic symptoms.Case presentationWe report a 30-year-old man with isolated diffuse choroidal hemangioma in his right eye without systemic symptoms, such as vascular malformations in the skin or leptomeningeal angiomatosis. The only additional ophthalmic finding was ipsilateral abnormal conjunctival and episcleral vessels without glaucoma. However, there was no evidence of leptomeningeal angiomatosis or port-wine stain on the right side of the face, or glaucoma, which are common clinical manifestations of the Sturge-Weber syndrome (SWS).The absence of these characteristic symptoms did not preclude the diagnosis, and the patient could be diagnosed with a particular subtype of SWS.ConclusionsThis is a rare case of documented isolated difuse choroidal hemangioma with ipsilateral abnormal conjunctival and episcleral vessels without glaucoma which we think it is belonging to a particular subtype of SWS.In addition to the traditional clinical manifestations, more and more atypical clinical manifestations are also accompanied by SWS, which requires our clinicians to continuously discover and report, so as to help more clinicians understand this disease.

A Call for Discovery and Therapeutic Development for Cutaneous Neurofibromas

A Call for Discovery and Therapeutic Development for Cutaneous Neurofibromas

Multidisciplinary Outpatient Clinic of Neurocutaneous Diseases: Five-year Experience of a Pediatric Tertiary Hospital in Portugal.

Neurocutaneous syndromes (NCS) are a heterogeneous group of conditions with multiorgan involvement and diverse manifestations, evolving throughout life with significant morbidity. A multidisciplinary approach to NCS patients has been advocated, although a specific model is not yet established. The aim of this study was 1) to describe the organization of the recently created Multidisciplinary Outpatient Clinic of Neurocutaneous Diseases (MOCND) at a Portuguese pediatric tertiary hospital; 2) to share our institutional experience focusing on the most common conditions, neurofibromatosis type 1 (NF1) and tuberous sclerosis complex (TSC); 3) to analyze the advantages of a multidisciplinary center and approach in NCS. Retrospective analysis of 281 patients enrolled in the MOCND over the first five years of activity (October 2016 to December 2021), reviewing genetics, family history, clinical features, complications, and therapeutic strategies for NF1 and TSC. The clinic works weekly with a core team of pediatricians and pediatric neurologists supported by other specialties as needed. Of the 281 patients enrolled, 224 (79.7%) had identifiable syndromes such as NF1 (n = 105), TSC (n = 35), hypomelanosis of Ito (n = 11), Sturge-Weber syndrome (n = 5), and others. In NF1 patients, 41.0% had a positive family history, all manifested café-au-lait macules, 38.1% neurofibromas with 45.0% being large plexiform neurofibromas. Sixteen were under treatment with selumetinib. Genetic testing was performed in 82.9% of TSC patients with pathogenic variants found in TSC2 gene in 72.4% patients (82.7% if considered contiguous gene syndrome). Family history was positive in 31.4%. All TSC patients presented hypomelanotic macules and fulfilled diagnostic criteria. Fourteen patients were being treated with mTOR inhibitors. Offering a systematic and multidisciplinary approach to NCS patients enables timely diagnosis, promotes a structured follow-up, and encourages discussion to outline management plans for optimal care to every patient, with significant impact on the quality of life of patients and families.

Spinal Surgery in Patients with Type-1 Neurofibromatosis: A Comprehensive Review

AbstractType-1 neurofibromatosis (NF1) is a neurocutaneous syndrome classically known as peripheral NF to distinguish it from type-2 NF (central NF). Its main characteristic is the high predisposition to the growth of multiple tumors, which specially arouses the interest of spinal surgeons due to the presence of spinal cord compression and spinal deformities.Considering this, we have performed a comprehensive review, with illustrative cases of the main manifestations of NF1, focusing on the perspective of the spine surgeon. Articles were grouped according to the following subjects: diagnosis, skeletal complications, spinal deformity, and spinal tumors. For all of them, a detailed discussion on pearls for practice was presented.The diagnosis of NF1 is based on the presence of at least two out of seven criteria. Cutaneous findings are very common in NF1, and the most usual tumor is cutaneous neurofibroma (NFB). Plexiform neurofibromas are also found and present a high risk of becoming malignant peripheral nerve sheath tumors (MPNSTs), reducing life expectancy. Astrocytomas, especially pilocytic astrocytomas, are the most common central nervous system tumor, including in the spinal cord. Surgery is necessary to resect as much as possible without adding new neurological deficits. Spinal deformities are also commonly found (in 30–70% of the cases), potentially associated with dystrophic changes, which may result in acute and rapid progression.In the present review, we discuss specific characteristics found in this group of patients which are of paramount importance to properly manage this challenging disease.

Is neurofibromatosis type 1 diagnosed in every patient who presents with café au lait macules? A single-center experience

Objective: Neurofibromatosis type 1 (NF1) is the most common hereditary neurocutaneous syndrome. The most crucial morbidity of&#x0D; NF1 is tumors that may develop. Cases with café-au-lait macules (CALMs) which is the first clinical finding of NF1, due to the anxiety&#x0D; of its associated morbidity, are referred to the pediatric oncology clinic. In this study, we aimed to examine the characteristics of the&#x0D; patients who applied to our outpatient clinic with CALMs.&#x0D; Patients and Methods: The data of 157 pediatric patients who applied to our institution with the diagnosis of CALMs between June&#x0D; 2010 and November 2020 were analyzed retrospectively.&#x0D; Results: There were 157 pediatric cases referred to us for CALMs. According to the National Institutes of Health (NIH) diagnostic&#x0D; criteria, 109 (69.4%) cases were diagnosed with NF1. The diagnosis of 22 cases with NF1 were supported by genetic examination.&#x0D; Optic glioma was detected in 39 (24.8%) cases. In 15 (38.4%) of cases with optic glioma, visual functions were also affected. Second&#x0D; diagnostic criterion did not develop during the follow-up period, except for macules, in 48 cases (30.5%).&#x0D; Conclusion: In cases with multiple CALMs, the probability of NF1 diagnosis is high, and close and regular follow-up is of great&#x0D; importance in catching the development of the second clinical criterion and minimizing its morbidity.

Rare Case of C4 Perineurinoma with Lambdatic Parieto-occipital Neuroma in Von Recklinghausen Disease in a 5 Years Old Child: A Case Report

Neuro fibromatosis groups together distinct diseases that most often share only certain cutaneous signs. Neurofibromatosis (NF) is a neurocutaneous syndrome characterized by the development of tumors of the central or peripheral nervous system including the brain, spinal cord, organs, skin, and bones. Prineurinoma is a relatively rare tumour that has been shown to be a proliferation of perineural cells with an incomplete basal lamina and no onion bulb appearance. Neuroma also known as traumatic neuroma or amputation neuroma or stump neuroma, is a focal non-neoplastic area of proliferative hyperplastic reaction secondary to peripheral nerve damage that commonly occurs after a focal trauma (acute or chronic) or surgery, such as amputation or partial transection; We report an extremely rare clinical case of a 5 year old child with neurfibromatosis congenita type 1 with asyntomatic medullary comrepssion and incidental discovery of a left intraductal C4 perineurinoma during the exploration of an occipital-parietal neuroma associated with a dehiscence of the lambda suture. He was operated on, with the postoperative course marked by paresis of the cervical muscles, which was in the process of recovery by physiotherapy.

Untargeted Metabolomic Analysis of Sjögren-Larsson Syndrome Reveals a Distinctive Pattern of Multiple Disrupted Biochemical Pathways.

Sjögren-Larsson syndrome (SLS) is a rare inherited neurocutaneous disease characterized by ichthyosis, spastic diplegia or tetraplegia, intellectual disability and a distinctive retinopathy. SLS is caused by bi-allelic mutations in ALDH3A2, which codes for fatty aldehyde dehydrogenase (FALDH) and results in abnormal lipid metabolism. The biochemical abnormalities in SLS are not completely known, and the pathogenic mechanisms leading to symptoms are still unclear. To search for pathways that are perturbed in SLS, we performed untargeted metabolomic screening in 20 SLS subjects along with age- and sex-matched controls. Of 823 identified metabolites in plasma, 121 (14.7%) quantitatively differed in the overall SLS cohort from controls; 77 metabolites were decreased and 44 increased. Pathway analysis pointed to disrupted metabolism of sphingolipids, sterols, bile acids, glycogen, purines and certain amino acids such as tryptophan, aspartate and phenylalanine. Random forest analysis identified a unique metabolomic profile that had a predictive accuracy of 100% for discriminating SLS from controls. These results provide new insight into the abnormal biochemical pathways that likely contribute to disease in SLS and may constitute a biomarker panel for diagnosis and future therapeutic studies.