Acute necrotizing encephalopathy associated with RANBP2 mutation: value of MRI findings for diagnosis and intervention.

INTRODUCTION: Acute necrotizing encephalopathy (ANEC) is a rare entity characterized by encephalopathy following a febrile illness. Most patients are sporadic; however, recurrent and familial cases have been associated with RAN-binding protein 2 (RANBP2) mutation. Well-defined MRI findings can even be life-saving with early diagnosis and treatment. METHODS: In this article, nine pediatric cases diagnosed with ANEC1 both clinically and radiologically, and with least one variation in the RANBP2 gene, are presented. RESULTS: All patients were previously healthy and presented with encephalopathy after an acute febrile infection. The patients of 44% had a similar attack history in their family. Influenza A/B was detected in 7 patients (78%). One patient was admitted at age 32 years old. The first clinical findings of patients were encephalopathy (100%), seizure (44%), vision problems (33%), ataxia (11%), and monoplegia (11%). Recurrent attacks were seen in two (22%) patients. Brain MRI findings including bilateral thalamus, external capsules, and brainstem involvements were highly suggestive for RANBP2 mutation. Based on MRI findings, genetic analyses were quickly performed and confirmed. All of the patients were treated with empirical encephalitis treatment, oseltamivir, intravenous immunoglobulin (IVIG), high-dose steroid and, if necessary, plasmapheresis, but three (33%) patients died despite treatment. CONCLUSION: ANEC associated with RANBP2 mutation may occur early or late-onset and can be recurrent and fatal. Therefore, early diagnosis and treatment have the potential to modify the severity of this encephalopathy. Well-defined MRI findings are highly instructive for early diagnosis.

Evaluation of the risk factors for recurrence and the development of epilepsy in patients with febrile seizure.

BACKGROUND: Although febrile seizure (FS) is generally considered benign and self-limiting, there are differences regarding the risk factors, the prognosis, and the development of epilepsy. OBJECTIVE: To examine the clinical and sociodemographic characteristics of patients diagnosed with FS, and to determine the risks of recurrence and the development of epilepsy. METHODS: Between 2015 and 2019, we performed a retrospective evaluation of 300 patients with FS followed for at least 24 months. RESULTS: The first episode of FS was simple in 72.7% of the patients and complex in 27.3%, and it recurred in 40%. Age under 12 months in the first FS, complex FS, and neurodevelopmental delay were found to statistically increase the risk of recurrence (p < 0.05). A total of 7% of the patients developed epilepsy, and this rate was found to be higher in patients with neurodevelopmental delay and long-term use of antiepileptic drugs (p < 0.001). The development of epilepsy was also observed in 77.8% of the patients with abnormal electroencephalogram (EEG). Epilepsy developed more frequently in those with abnormal EEG (p<0.001). CONCLUSIONS: Neurodevelopmental delay was an important risk factor for FS recurrence and the development of epilepsy. Abnormality in the EEG is an important risk factor for the development of epilepsy. We found that the long-term prophylactic treatment did not cause decreases in the recurrence of FS nor in the development of epilepsy.

ANTECEDENTES: Embora a convulsão febril (CF) seja geralmente considerada benigna e autolimitada, existem diferenças nos fatores de risco, prognóstico e desenvolvimento de epilepsia. OBJETIVO: O objetivo foi examinar as características clínicas e sociodemográficas de pacientes diagnosticados com CF e determinar os riscos de recorrência e desenvolvimento de epilepsia. MéTODOS: Trezentos pacientes com CF, acompanhados por pelo menos 24 meses, foram avaliados retrospectivamente entre 2015 e 2020. RESULTADOS: A primeira CF foi simples em 72,7% dos pacientes e complexa em 27,3%. CS foi recorrente em 40% dos pacientes. Encontrou-se que a idade da primeira CF inferior a 12 meses, CF complexa e atraso no neurodesenvolvimento aumentaram estatisticamente o risco de recorrência (p < 0,05). Epilepsia se desenvolveu em 7% dos pacientes. A epilepsia foi maior em pacientes com atraso no desenvolvimento neurológico e uso prolongado de drogas antiepilépticas (p < 0,001). A epilepsia se desenvolveu em 77,8% dos pacientes com eletroencefalograma (EEG) anormal. Uma diferença estatisticamente significativa foi determinada em pacientes com EEG anormal em risco de epilepsia (p < 0,001). CONCLUSõES: O atraso no neurodesenvolvimento foi um importante fator de risco para recorrência de CF e epilepsia. A anormalidade do EEG é um importante fator de risco para o desenvolvimento de epilepsia. O tratamento de profilaxia a longo prazo não diminuiu a recorrência de CS e o desenvolvimento de epilepsia.

Clinical, radiological, and genetic variation in pontocerebellar hypoplasia disorder and our clinical experience.

Pontocerebellar hypoplasia (PCH) constitutes a heterogeneous neurodegenerative/neurodevelopmental disorder of the pons and cerebellum with onset in the prenatal period. Our study aimed to present different clinical and radiological manifestations of our genetically diagnosed PCH patients. METHOD:  Six patients were enrolled in this study from September 2018 to March 2021. All the clinical radiological and genetic investigations were done at Cukurova University Medical School. RESULTS: Five children were diagnosed genetically and categorized under one of the types of PCH (type 10,7,11). Homozygous mutations in CLP1 In PCH type 10, TOE1 in PCH type 7, and TBC1D23 in PCH type 11 were respectively detected. Pateint with PCH type 11 and female patient with PCH type 7 could walk and speak few words. Male patient with PCH type 7 had disorder of sex development. CONCLUSION: According to our study, PCH is a rare neurodegenerative disease, although some types are static as PCH11 male gender and PCH7 female gender. Some clinical features are specific to a definite type. PCH7 express disorders of sex development most apparent in 46 XY. Some ethnic groups could express distinct subtypes. PCH10 is seen in the Turkish population. Radiological imaging is beneficial in pre-diagnosis; all the patients had different pons and cerebellar hypoplasia degrees. Genetic testing like whole exome sequencing -next-generation sequencing is essential in setting the definite diagnosis and determining the type/subtype of PCH.

Evaluation of the risk factors for recurrence and the development of epilepsy in patients with febrile seizure / Avaliação de fatores de risco para recorrência e desenvolvimento de epilepsia em pacientes com convulsões febris

Abstract Background Although febrile seizure (FS) is generally considered benign and self-limiting, there are differences regarding the risk factors, the prognosis, and the development of epilepsy. Objective To examine the clinical and sociodemographic characteristics of patients diagnosed with FS, and to determine the risks of recurrence and the development of epilepsy. Methods Between 2015 and 2019, we performed a retrospective evaluation of 300 patients with FS followed for at least 24 months. Results The first episode of FS was simple in 72.7% of the patients and complex in 27.3%, and it recurred in 40%. Age under 12 months in the first FS, complex FS, and neurodevelopmental delay were found to statistically increase the risk of recurrence (p< 0.05). A total of 7% of the patients developed epilepsy, and this rate was found to be higher in patients with neurodevelopmental delay and long-term use of antiepileptic drugs (p< 0.001). The development of epilepsy was also observed in 77.8% of the patients with abnormal electroencephalogram (EEG). Epilepsy developed more frequently in those with abnormal EEG (p<0.001). Conclusions Neurodevelopmental delay was an important risk factor for FS recurrence and the development of epilepsy. Abnormality in the EEG is an important risk factor for the development of epilepsy. We found that the long-term prophylactic treatment did not cause decreases in the recurrence of FS nor in the development of epilepsy.

Resumo Antecedentes Embora a convulsão febril (CF) seja geralmente considerada benigna e autolimitada, existem diferenças nos fatores de risco, prognóstico e desenvolvimento de epilepsia. Objetivo O objetivo foi examinar as características clínicas e sociodemográficas de pacientes diagnosticados com CF e determinar os riscos de recorrência e desenvolvimento de epilepsia. Métodos Trezentos pacientes com CF, acompanhados por pelo menos 24 meses, foram avaliados retrospectivamente entre 2015 e 2020. Resultados A primeira CF foi simples em 72,7% dos pacientes e complexa em 27,3%. CS foi recorrente em 40% dos pacientes. Encontrou-se que a idade da primeira CF inferior a 12 meses, CF complexa e atraso no neurodesenvolvimento aumentaram estatisticamente o risco de recorrência (p< 0,05). Epilepsia se desenvolveu em 7% dos pacientes. A epilepsia foi maior em pacientes com atraso no desenvolvimento neurológico e uso prolongado de drogas antiepilépticas (p< 0,001). A epilepsia se desenvolveu em 77,8% dos pacientes com eletroencefalograma (EEG) anormal. Uma diferença estatisticamente significativa foi determinada em pacientes com EEG anormal em risco de epilepsia (p< 0,001). Conclusões O atraso no neurodesenvolvimento foi um importante fator de risco para recorrência de CF e epilepsia. A anormalidade do EEG é um importante fator de risco para o desenvolvimento de epilepsia. O tratamento de profilaxia a longo prazo não diminuiu a recorrência de CS e o desenvolvimento de epilepsia.

Case series of arginase 1 deficiency: Expanding the spectrum in hyperargininemia.

BACKGROUND: Arginase-1 deficiency is a rare, autosomal recessively inherited disorder of the urea cycle. In this study, we describe the clinical and molecular details of six patients who were diagnosed with argininemia, and we describe two of the patients with hyperargininemia who carried two novel variations of the Arginase-1 gene. METHODS: The clinical and demographic characteristics of the patients were retrospectively evaluated. RESULTS: The ages of the six patients ranged from 1 day to 20 years, and each patient had consanguineous parents. Neuromotor retardation and spastic paraparesis were found in all patients except one, who was diagnosed prenatally. Hyperargininemia was present in all patients. Urinary orotic acid excretion was increased in four of the six patients. The diagnosis was confirmed by genetic analysis in all the patients. Elevated liver enzymes were detected in three patients and blood urea nitrogen levels were normal in each of the six patients. CONCLUSIONS: In this study, we describe the two patients with hyperargininemia who carried two novel variations of the ARG1 gene. Also, we present a patient with normal neurodevelopment who was diagnosed prenatally and treated at an early stage of the disease.

The management of elevated intracranial pressure and sinus vein thrombosis associated with mastoiditis: the experience of eighteen patients.

PURPOSE: Cerebral sinus vein thrombosis (CSVT) associated with acute mastoiditis is a rare complication of acute otitis media. Elevated intracranial pressure (ICP) frequently occurs secondary to CSVT. The study aims to review the 5 years of experience of four medical centres to treat sigmoid sinus thrombosis and elevated intracranial pressure in children. METHODS: Patients with CSVT that developed secondary mastoiditis from 2016 through 2021 were evaluated in four centres from Turkey. Patients diagnosed with a preceding or synchronous mastoiditis and intracranial sinus thrombosis were included in the study. Magnetic resonance imaging (MRI), magnetic resonance venography (MRV), ICP measurements, ophthalmological examinations, thrombophilia studies and treatments for increased ICP have also been recorded. RESULTS: The study group comprises 18 children. Twelve patients were diagnosed with right-sided, six patients with left-sided sinus vein thrombosis. All of the patients had ipsilateral mastoiditis. The most common presenting symptoms were fever, ear pain, headache, visual disorders and vomiting. The most encountered neurologic findings were papilledema, strabismus and sixth cranial nerve palsy. ICP was over 20 cm H2O in eleven patients. Anticoagulant treatment, antibiotics, pressure-lowering lumbar puncture and lumboperitoneal shunt were among the treatment modalities. CONCLUSION: Elevated ICP can damage the brain and optic nerve irreversibly, without treatment. For treating elevation of ICP associated with cerebral sinus thrombosis, pressure-lowering lumbar puncture (LP), acetazolamide therapy, optic nerve sheath fenestration (ONSF) and cerebrospinal fluid (CSF)-shunting procedures are suggested in case of deteriorated vision.

Newly defined peroxisomal disease with novel ACBD5 mutation.

Peroxisomal disorders are a heterogeneous group of diseases caused by mutations in a large number of genes. One of the genetic disorders known to cause this situation is ACBD5 (Acyl-CoA binding-domain-containing-5) gene mutations that have been described in recent years. Here, we report two siblings with a novel homozygous nonsense variation (c.1297C>T, p.Arg433*) in ACBD5 (NM_145698.4) gene using Clinical Exome Sequencing (Sophia Genetics).

Approaches for diagnosis and treatment in neurotransmitter disorders of childhood.

Neurotransmitter disorders are a group of neurometabolic syndromes caused by disturbances of neurotransmitter metabolism. The primary aim of this retrospective study is to present patients with disturbances of monoamine neurotransmitter metabolism. Cerebrospinal fluid (CSF) neurotransmitter measurements and genetic analysis were performed on five patients. Five patients who had various movement disorders and motor and cognitive disabilities were included. Four patients were diagnosed with sepiapterin reductase (SR) deficiency, and one was diagnosed with aromatic L-amino acid decarboxylase (AADC) deficiency. Different treatment responses appeared in patients with SR and AADC deficiency. The responses to drug treatment ranged from good to weak in our patients. The diagnosis process is challenging in patients with SR and AADC deficiency, which present similar clinical features to other neurological and metabolic diseases. Investigations of neurotransmitters in CSF and analysis of related genes are essential to differentiate disturbances of monoamine neurotransmitter metabolism from other neurometabolic diseases. For patients with monoamine neurotransmitter disorders, drugs that target these disturbances should be combined as necessary to produce the appropriate response.

Recently defined epileptic encephalopathy related to WWOX gene mutation: six patients and new mutations.

Purpose: Pathogenic variants of the WWOX gene have been linked to sexual differentiation disorders, spinocerebellar ataxia, and epileptic encephalopathy (EE). We evaluated the clinical and molecular data from six newly diagnosed patients with WWOX-related EE.Methods: Clinical and molecular findings in six patients with EE were investigated, and biallelic pathogenic variants in the WWOX gene were identified. Clinical exome sequencing and Sanger sequencing were performed.Results: Three variations, as well as two novel mutations, in the WWOX gene were detected.Conclusion: Pathogenic WWOX mutations are associated with early-onset EE. Here, we report the case of six children with WWOX-related EE.

Magnetic resonance imaging patterns of subacute sclerosing panencephalitis may mimic metabolic disorders: clinical, electroencephalographic and imaging features of six cases.

Subacute sclerosing panencephalitis is a rare, devastating neurodegenerative encephalitis whose diagnosis and therapy are still in question. Atypical clinical presentation and heterogeneity of neuroimaging findings that have been initially confused with metabolic disorders have hampered early diagnosis. To describe a series of patients with subacute sclerosing panencephalitis with imaging findings mimicking metabolic disorders. A total of six patients with subacute sclerosing panencephalitis were diagnosed from January 2012 to December 2016 in whom a metabolic disorder was suspected on initial clinical and MRI findings. Detailed laboratory investigation was performed in all patients. All patients presented with atypical neurologic manifestations, including dystonia, syncopal attacks, involuntary limb movements, meaningless speech and ataxia. Magnetic resonance imaging abnormalities included bilateral putaminal, bilateral posterior periventricular white matter and diffuse or splenial corpus callosum involvement which are particularly unusual in SSPE and mostly observed in metabolic disorders. All patients had elevated cerebrospinal fluid Ig G measles antibodies. The diagnosis of subacute sclerosing panencephalitis through clinical and imaging features can be considerably challenging. It is crucial to differentiate it from metabolic disorders, since the management and clinical outcome are different.

A rare pediatric case of neurobrucellosis with bilateral optic neuritis.

BACKGROUND: The estimated incidence of central nervous system involvement in brucellosis ranges between 0 and 17.8%. Optic neuritis is infrequently seen in the clinical presentation of neurobrucellosis. Only six cases of neurobrucellosis manifesting with optic neuritis have been previously reported in the literature during childhood. Moreover, four of these were isolated optic neuritis. CASE: An 11-year-old boy presented with the complaint of bilateral visual loss which was more prominent in the left eye than the right. He was diagnosed with brucellosis two months prior. His fundus examination revealed mild papilledema of the right eye and remarkable papilledema of the left eye. Brucella agglutination titer of serum was 1/640. Cerebrospinal fluid (CSF) cultures were negative, but polymerase chain reaction (PCR) examination in CSF was positive for Brucella melitensis. Antibiotic and pulse methylprednisolone treatments were administered. The visual acuity returned incompletely within the 12-month follow-up period. CONCLUSION: Isolated optic neuritis is a rare manifestation of neurobrucellosis in children.

MRI in CLN2 disease patients: Subtle features that support an early diagnosis.

Neuronal ceroid lipofuscinosis type 2 (CLN2) disease is a rare, paediatric-onset, neurodegenerative disorder characterised in its early stages by language delay, seizures and loss of motor function. It is rapidly progressive and ultimately results in the premature death of patients. We aim to highlight common magnetic resonance imaging (MRI) features seen in early CLN2 disease and increase disease awareness among clinicians in order to facilitate early diagnosis and treatment of patients with disease-modifying enzyme replacement therapy. We obtained MRI scans from 12 Turkish children with CLN2 disease, at symptom onset or time of diagnosis, and at various times during disease progression. Patient details including age at onset of symptoms, age at diagnosis and clinical presentation were collected. MRIs were analysed to identify common features present in patients with CLN2 disease. The median diagnostic delay in this cohort was 2 years, highlighting the need for increased disease awareness among clinicians. Key MRI features suggestive of CLN2 disease that were identified included cerebellar atrophy in 11 patients, linear hyperintensity of central white matter in 10 patients, cerebral atrophy in 8 patients and thinning of the corpus callosum in 6 patients. Thalamic hypointensity was seen in 1 patient and may also indicate CLN2 disease. It is important to consider the presenting symptoms alongside clinical test results in order to support early diagnosis of CLN2 disease. Clinical suspicion of CLN2 disease accompanied by the detection of any of the above-mentioned features on MRI should encourage healthcare professionals to test for CLN2 disease.

Two patients with glutaric aciduria type 3: a novel mutation and brain magnetic resonance imaging findings.

BACKGROUND: Glutaric Aciduria Type 3 (GA-3) is a rare metabolic disease which is inherited autosomal recessively and characterized by isolated glutaric acid excretion. To date, a limited number of cases have been reported in the literature. We present two patients with GA3 who were diagnosed with the isolated increased level of glutaric acid in urine. CASE: Glutaric aciduria type 1 and type 2 were excluded by genetic analysis and other laboratory and clinical findings. One of our patients had a homozygous mutation p.Arg322Trp (c.964C > T) of SUGCT (NM_001193311) gene. To the best of our knowledge this mutation has not been reported in the literature previously. Symmetrical periventricular and deep cerebral white matter abnormalities were detected on his brain magnetic resonance imaging (MRI). CONCLUSION: We present two patients with GA-3 and a novel mutation in the SUGCT gene. Our findings expand the spectrum of causative mutations and clinical findings in GA-3.

Two different missense mutations of PEX genes in two similar patients with severe Zellweger syndrome: an argument on the genotype-phenotype correlation.

Background Peroxisomal biogenesis disorders (PBDs) include a miscellaneous group of diseases which cause serious multisystem disease. Mutations of 13 different PEX genes lead to PBDs including Zellweger syndrome (ZS). Different types of mutations of PEX1 and PEX10 genes are correlated with broad-range phenotypes of PBDs. Case presentation Patient 1 is a 4-month-old boy who was affected by myoclonic seizures, poor oral feeding since birth. The patient was hypotonic and had hepatosplenomegaly. Patient 2 is a 2-month-old boy who presented with decreased movement, severe hypotonia and failure to thrive. The laboratory studies of the patients revealed increased plasma very-long-chain fatty acids (VLCFAs). The genetic analyses of patient 1 demonstrated the first homozygous missense mutation in the PEX10 gene. A novel homozygous missense mutation was found in the PEX1 gene in patient 2. Conclusions This report highlights that the detected homozygous missense mutations of PEX10 and PEX1 genes and the substitutions of specific amino acids lead to the severe form of PBDs.

Cerebral neoplasm in L-2-hydroxyglutaric aciduria: two different presentations.

BACKGROUND: L-2-hydroxyglutaric aciduria (L2HGA) is a rare neurometabolic disorder characterized by a slowly progressive clinical course, psychomotor and mental retardation, macrocephaly, dysarthria, seizures, and cerebellar and extrapyramidal findings. The diagnosis depends on the presentation of increased levels of L-2-hydroxyglutaric acid in the urine, plasma, and cerebrospinal fluids. Patients with L2HGA have an increased risk for the development of cerebral neoplasms which, though rarely, can be the initial presentation of the disease. Moreover, patients with L2HGA have an increased risk for the development of cerebral neoplasms. CASES PRESENTATION: Although psychomotor and mental retardation, macrocephaly, dysarthria, seizures, and cerebellar and extrapyramidal findings are the most common characteristics of the disease, we present two rare cases admitted with tumoral symptoms. CONCLUSION: Patients with L2HGA have an increased risk for the development of cerebral neoplasms.

Temporary Seizure in an Infant Who Had Been Exposed to G-Amino Butyric Acid Receptor Antagonist Thiocolchicoside.

Seizure is the most common presentation of neurological disorder in the pediatric emergency care setting. In evaluating the child after a first seizure, the first consideration should be determining if the seizure was provoked or unprovoked. Investigation listing the causes of the first seizure is considerably long, and adverse drug reactions must be in mind. Epileptic seizures after using thiocolchicoside (TCC) have been reported in several adult patients with epilepsy and acute brain injury. We present a previously healthy 3-month-old female infant who was admitted to the emergency department with a generalized seizure after exposure to TCC. To the best of our knowledge, this is the first case of a child who had an epileptic seizure after TCC intake via breastfeeding in the literature.

Are diagnostic magnetic resonance patterns life-saving in children with biotin-thiamine-responsive basal ganglia disease?

BACKGROUND: Biotin-thiamine responsive basal ganglia disease (BTBGD) is an autosomal recessive disorder caused by mutations in the SLC19A3 gene and characterized by recurrent sub-acute episodes of encephalopathy that typically starts in early childhood. This study describes characteristic clinical and magnetic resonance imaging (MRI) findings of six cases of BTBGD diagnosed with newly identified mutations and genetically confirmed, with very early and different presentations compared to cases in the previous literature. METHODS: Six patients referred from different centers with similar clinical findings were diagnosed with BTBGD with newly identified mutations in the SLC19A3 gene. Two novel mutations in the SLC19A3 gene were identified in two patients at whole exome sequencing analysis. The clinical characteristics, responses to treatment, and electroencephalography (EEG) and MRI findings of these patients were examined. The other four patients presented with similar clinical and cranial MRI findings. These patients were therefore started on high-dose biotin and thiamine therapy, and mutation analysis concerning the SLC19A3 gene was performed. Responses to treatment, clinical courses, EEG findings and follow-up MRI were recorded for all these patients. RESULTS: Age at onset of symptoms ranged from 1 to 3 months. The first symptoms were generally persistent crying and restlessness. Seizures occurred in five of the six patients. Cranial magnetic resonance imaging revealed involvement in the basal ganglia, brain stem, and the parietal and frontal regions in general. The first two patients were siblings, and both exhibited a novel mutation of the SLC19A3 gene. The third and fourth patients were also siblings and also exhibited a similar novel mutation of the SLC19A3 gene. The fifth and sixth patients were not related, and a newly identified mutation was detected in both these subjects. Three novel mutations were thus detected in six patients. CONCLUSION: BTBGD is a progressive disease that can lead to severe disability and death. Early diagnosis of treatable diseases such as BTBGD is important in order to prevent long-term complications and disability.

A child with atypically subtle clinical presentation of acute arterial ischaemic stroke in the middle cerebral artery.

Arterial ischaemic stroke in the paediatric population is considered a rare disease, and its diagnosis is often delayed due to the subtlety and variability of clinical symptoms, especially in younger patients. The clinical presentation and imaging features of ischaemic stroke in the paediatric population are variable depending on the underlying cause, affected artery and patient's age. Literally, acute occlusion of the middle cerebral artery shows significant clinical signs and symptoms, and riotous imaging findings due to the size of the territory. Here, we present a case of a 15-year-old boy who unusually had subtle and intermittent clinical symptoms in spite of a complete acute occlusion in his right middle cerebral artery.

The efficacy of orbital ultrasonography and magnetic resonance imaging findings with direct measurement of intracranial pressure in distinguishing papilledema from pseudopapilledema.

INTRODUCTION: The goal of this study was to evaluate the utility of orbital ultrasonography and magnetic resonance imaging in the diagnosis of idiopathic intracranial hypertension (IIH). METHOD: We reviewed the medical records of patients referred to our department for suspected IIH. RESULTS: Seven children were diagnosed with IIH. Nine children revealed pseudopapilledema by optic coherence tomography and/or orbital ultrasonography. When the axial sequences were reexamined, patients with papilledema had optic nerve sheath (ONS) enlargement (6.62 ± 0.70 mm); patients with pseudopapilledema had ONS diameter as 4.62 ± 0.64 mm. There was a significant correlation between the CSF opening pressure and ONS diameter (p < 0.005, r = 0.661). In the papilledema group, the presence of proposed subtle markers as increased tortuosity in the optic nerve was found in six patients. Five of seven patients had a target sign, intraocular protrusion of the optic nerve, and posterior globe flattening. DISCUSSION: Ophthalmological review is important to avoid unnecessary procedures for detection of true papilledema. ONS diameter is a reliable neuroimaging marker as other subtle markers.