Clinical, immunological and molecular profiles of DOCK8 deficiency in six patients from a tertiary care centre in North India.

BACKGROUND: Dedicator of cytokinesis protein 8 (DOCK8) deficiency is an autosomal recessive form of combined immunodeficiency. This rare disorder is characterized by an increased predisposition to allergy, autoimmunity and malignancies. OBJECTIVES: To analyse clinical, immunological and molecular profiles of patients with DOCK8 deficiency. METHODS: Clinic records of all patients attending the primary immunodeficiency clinic from 2018 to 2021 were reviewed. Six patients from five families were found to have DOCK8 deficiency. RESULTS: Median age at diagnosis was 7.5 years (range 2-13), with a male/female ratio of 5 : 1. Among the six patients, recurrent eczematous skin lesions were the predominant cutaneous manifestation, present in five patients (83%). Warts and molluscum contagiosum were evident in two patients (33%) and one patient (16%), respectively. Two patients had recalcitrant prurigo nodularis lesions and two had epidermodysplasia verruciformis-like lesions. Food allergies and asthma were reported by one patient each. Of the six patients, recurrent sinopulmonary infections were detected in five (83%). Epstein-Barr virus-driven non-Hodgkin lymphoma with liver metastases was the only case of malignancy, in a 4-year-old boy. IgE was elevated in all patients. Lymphopenia and eosinophilia were observed in three patients (50%) and five patients (83.3%), respectively. Genetic analysis showed DOCK8 pathogenic variants in all patients: homozygous deletion mutations in two patients, compound heterozygous deletion mutations in one, and homozygous nonsense mutations in two. A novel pathogenic homozygous missense variant in the DOCK8 gene was identified in one patient. CONCLUSIONS: DOCK8 deficiency should be considered as a possibility in any patient with early onset eczema, cutaneous viral infections and increased predisposition to allergy, autoimmunity and malignancy.

Neurodevelopmental Outcomes of a Cohort of Children with Tuberous Sclerosis Complex with Epileptic Spasms.

The neurodevelopmental outcomes in children with tuberous sclerosis complex (TSC) with epileptic spasms remain underdiagnosed and might be responsible for significant morbidity and mortality burdens, even after spasms abate. The study was a cross-sectional study over 18 months at a tertiary care pediatric hospital, involving 30 children with TSC who had epileptic spasms. They were assessed with Diagnostic and Statistical Manual of Mental Disorders-5 criteria for autism spectrum disorder (ASD), attention deficit hyperactivity disorder (ADHD), and intellectual disability (ID), and childhood psychopathology measurement schedule (CPMS) for behavioral disorders. The median age at onset of epileptic spasms was 6.5 (1-12) months, and the age at enrolment was 5 (1-15) years. Of 30 children, 2 (6.7%) had only ADHD, 15 (50%) had only ID/GDD (global developmental delay), 4 (13.3%) had ASD and ID/GDD, 3 (10%) had ADHD and ID/GDD, and 6 (20%) had none. The median intelligence quotient/development quotient (IQ/DQ) score was 60.5 (20-105). CPMS assessment revealed significant behavioral abnormalities in almost half the children. Eight (26.7%) patients were completely seizure-free for at least 2 years, 8 (26.7%) had generalized tonic-clonic seizures, 11 (36.6%) had focal epilepsy, and 3 (10%) had evolved into Lennox-Gastaut syndrome. A high proportion of neurodevelopment disorders, including ASD, ADHD, ID/GDD, and behavioral disorders were seen in this pilot study with a small cohort of children with TSC with epileptic spasms.

An Observational Study on Pattern of Empirical Acyclovir Therapy in Children With Acute Encephalitis From Northern India.

OBJECTIVES: To identify the prevalence of herpes simplex encephalitis (HSE), factors influencing the duration of empirical acyclovir and frequency of acute kidney injury (AKI) in children with acute encephalitis syndrome (AES). DESIGN: Prospective observational study. SETTING: Pediatric Emergency Department and PICU of a tertiary hospital in Northern India. PATIENTS: All consecutive, eligible children between 1 month and 12 years old presenting with AES, defined as altered consciousness for greater than 24 hours (including lethargy, irritability, or a change in personality) and two or more of the following signs: 1) fever (temperature ≥ 38°C) during the current illness, 2) seizures or focal neurological signs, 3) cerebrospinal fluid (CSF) pleocytosis, 4) electroencephalogram, and/or 5) neuroimaging suggesting encephalitis, who received at least one dose of acyclovir. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Of the 101 children screened, 83 were enrolled. The median (interquartile range [IQR]) age was 3 years (1-6 yr). Thirty-one children (37.3%) were diagnosed with AES, of which four were labeled as probable HSE (three based on MRI brain, one based on serology). Scrub typhus, dengue, Japanese encephalitis, and mumps were the other infective causes. The median (IQR) duration of acyclovir therapy was 72 hours (24-264 hr); 21 children (25.3%) received acyclovir for less than 24 hours and 11 (13.3%) for greater than or equal to 14 days. New-onset AKI was seen in 18 children (21.7%) but was mostly transient. Death ( n = 8, 9.6%) and discontinuation of care due to futility or other reasons ( n = 15, 18%) were noted in 23 children (28%). Factors associated with duration of acyclovir greater than 7 days, on univariable analysis, were lower modified Glasgow Coma Score at admission, requirement of invasive ventilation, invasive intracranial pressure monitoring, and CSF pleocytosis (5-500 cells). On multivariable analysis, only CSF pleocytosis of 5-500 cells was associated with duration of acyclovir greater than 7 days. CONCLUSIONS: Given the low prevalence of HSE, and the risk of AKI, this study sensitizes the need to review our practice on initiation and stopping of empirical acyclovir in children with acute encephalitis.

Nutritional Recovery Batwing Dystonia in Infantile Vitamin B12 Deficiency.

The neurocutaneous syndrome of infantile B12 deficiency, more commonly called the infantile tremor syndrome, typically is characterized by developmental delay, sparse hair, hyperpigmentation, and tremors. When treated with injectable B12, the affected babies can develop a peculiar transient "batwing dystonia." This dystonia is possibly a nutritional recovery movement disorder due to basal ganglia dysfunction.

Seroprevalence of MOG and AQP4 Antibodies and Outcomes in an Indian Cohort of Pediatric Acquired Demyelinating Syndromes.

This study aimed to determine the seropositivity of myelin oligodendrocyte glycoprotein antibodies (MOG-Ab) and aquaporin-4 antibodies (AQP4-Ab) and outcomes in children with acquired demyelinating syndromes (ADSs). Children (6 months-15 years) with suspected ADS were enrolled and tested for MOG-Ab and AQP4-Ab prospectively over 18 months at a tertiary care hospital in North India. Children with proven nonimmune-mediated neurological disorders were enrolled as controls. Of 79 children with suspected ADS, 66 were enrolled. Among the enrolled children with ADS, acute demyelinating encephalomyelitis (ADEM) (25) was the most common first clinical event followed by optic neuritis (ON) (20) and transverse myelitis (TM) (19; one child had ON and TM simultaneously [neuromyelitis optica spectrum disorders [NMOSDs]]), while two children had clinically isolated syndrome (CIS) apart from ON and TM. Fourteen (21.2%, confidence interval [CI] 11.3-31.1) tested positive for one antibody (12 [18.1%; 95% CI 10.5-25.5%] for MOG-Ab and 2 [3%; 95% CI 0-7.2%] for AQP4-Ab). None of the 62 controls tested positive for any antibody. The final diagnosis in those with the monophasic ADS was ADEM (21), ON (13), TM (16), and other CIS (1) while that in children with recurrent events was multiphasic disseminated encephalomyelitis (MDEM) (2), NMOSD (3), ADEM-ON (4), recurrent ON (4), and MS (2). Among those with the first event, 4/51 (7.8%; 95% CI 0.5-15.2%) were MOG-Ab positive and 2 AQP4-Ab positive, whereas 8/15 (53.3% [95% CI 28.1-78.6%]) with recurrent events (MDEM [2], ADEM-ON [4], recurrent ON [1], and recurrent TM [1]) were MOG-Ab positive. Hence, MOG-Abs are the most common antibodies detected in one in five children with pediatric ADS, especially in relapsing disease. AQP4-Abs are rare in children with ADS.

MR vessel wall imaging in cerebral bacterial and fungal infections.

PURPOSE: Central nervous system (CNS) bacterial and fungal infections can cause secondary vasculitis which worsens the prognosis due to development of complications like infarctions or hemorrhages. In this prospective study, we aim to study intracranial vessel wall imaging findings in bacterial and fungal infections. METHODS: We included 12 cases of nontubercular bacterial and fungal CNS infections each, in whom definitive microbiological diagnosis could be made. High-resolution vessel wall imaging (VWI) and time of flight MR angiography (TOF MRA) were incorporated in the routine imaging protocol. All cases were evaluated for the presence of vascular enhancement, pattern of enhancement, and stenosis on VWI. Statistical analysis was done to evaluate association between findings of vessel wall imaging and infarctions. RESULTS: We found infarctions in 5 out of 12 cases (41.7%) of the bacterial group and 7 out of 12 cases (58.3%) of the fungal group. Vessel wall enhancement was seen in 5 cases (41.7%) of the bacterial group and 9 cases (75%) of the fungal group. There was a significant association between infarctions and vessel wall enhancement in the fungal group. However, pattern of enhancement or stenosis on VWI was not significantly associated with presence of infarction. VWI detected more cases of vascular involvement than TOF MRA. CONCLUSION: Secondary infectious vasculitis in bacterial and fungal infections can be detected by VWI, which can play an important role in better patient management as detection of vascular involvement can prompt early treatment to prevent complications like infarctions or hemorrhages.

High-resolution intracranial vessel wall imaging in cerebral viral infections evaluations.

PURPOSE: Vascular complications can be seen in various viral CNS infections. Variable neuro-imaging findings have been described in the literature elucidating the parenchymal changes with vascular involvement. Vessel wall imaging (VWI) can help to detect these vascular involvements. We aimed to describe the role and usefulness of VWI in the evaluation of various viral CNS infections. METHODS: In this prospective study, we included 15 cases of various diagnosed viral CNS infections (varicella, HIV encephalopathy, HSV encephalitis, Japanese encephalitis, dengue, COVID-19). VWI and time-of-flight MR angiography (TOF MRA) were included in imaging protocol. All cases were evaluated for the presence of cerebral parenchymal changes, vascular enhancement, and vascular stenosis. RESULTS: We found infarctions in all 5 cases of varicella, 1 case of HIV encephalopathy, and 1 case of COVID-19 encephalopathy. All these cases also showed vascular enhancement and stenosis on VWI. The rest of the cases, including 1 case of HIV encephalopathy, 3 cases of herpes encephalitis, 2 cases of dengue, and 2 cases of Japanese encephalitis did not have any vascular complication, and also did not show vascular enhancement or stenosis. CONCLUSION: VWI can be useful in the detection of vascular involvement in various viral infections of CNS which show a relatively higher cerebrovascular complication rate like varicella, HIV encephalopathy, and COVID-19. However, VWI may not be useful in the routine evaluation of other viral infections like herpes, dengue, and Japanese encephalitis, which have a very low rate of cerebrovascular complication rate.

Clinical Features Associated With Need for Mechanical Ventilation in Children With Guillain-Barré Syndrome: Retrospective Cohort From India.

OBJECTIVES: To analyze the clinical features associated with the need for mechanical ventilation (MV) in children with Guillain-Barré syndrome (GBS). DESIGN: Retrospective cohort study, 2010-2019. SETTING: PICU. PATIENTS: All children, 1 month to 12 years old, diagnosed with GBS in our single-center PICU. INTERVENTION: Retrospective chart and data review. MEASUREMENTS AND MAIN RESULTS: Out of 189 children identified with a diagnosis of GBS, 130 were boys (69%). The median (interquartile range [IQR]) age was 6 years (3-9 yr). At admission, the Hughes disability score was 5 (4-5), and cranial nerve palsies were present in 81 children (42%). Autonomic instability subsequently occurred in a total of 97 children (51%). In the 159 children with nerve conduction studies, the axonal variant of GBS (102/159; 64%) predominated, followed by the demyelinating variant (38/189; 24%). All children received IV immunoglobulins as first-line therapy at the time of admission. The median (IQR) length of PICU stay was 12 days (3-30.5 d). Ninety-nine children (52%) underwent invasive MV, and median duration of MV was 25 days (19-37 d). At admission, upper limb power less than or equal to 3 (p = 0.037; odds ratio (OR), 3.5 [1.1-11.5]), lower limb power less than or equal to 2 (p = 0.008; OR, 3.5 [1.4-8.9]), and cranial nerve palsy (p = 0.001; OR, 3.2 [1.6-6.1]) were associated with subsequent need for MV. Prolonged (> 21 d) MV was associated with more severe examination findings at admission: upper limb power less than or equal to 2 (p < 0.0001; OR, 4.2 [2.5-6.9]) and lower limb power less than or equal to 1 (p < 0.0001; OR, 4.5 [2.6-7.9]). CONCLUSIONS: In children with GBS, referred to our center in North India, severe neuromuscular weakness at admission was associated with the need for MV. Furthermore, greater severity of this examination was associated with need for prolonged (> 21 d) MV. Identification of these signs may help in prioritizing critical care needs and early PICU transfer.

Aetiological Profile and Short-Term Neurological Outcome of Haemorrhagic Stroke in Children.

BACKGROUND: Haemorrhagic stroke (HS) accounts for nearly half of the paediatric strokes. The aetiology of HS in childhood is not well defined in the Indian context. OBJECTIVES: To study the aetiological profile and short-term neurological outcome of children with HS from North India. METHODS: In a prospective observational study, consecutive patients >28 days to <12 years of age admitted with a diagnosis of HS were enrolled. Demography, clinical, radiological details and investigations were recorded. Short-term outcomes were assessed at three months follow-up with the Paediatric Cerebral Performance Category scale and Paediatric Stroke Outcome Measure (PSOM). RESULTS: A total of 48 children with HS were enrolled. The median age was 6 months (1-58 months), and 33 (69%) were <2 years old. Vitamin K deficiency-related bleeding disorder (VKDB, 44%), central nervous system infections (19%), arteriovenous malformations (13%) and inherited coagulation disorders (8%) were the most common risk factors for HS. VKDB and inherited coagulation disorders were more frequent in children <2 years of age, and arteriovenous malformations were more frequent in children >2 years of age (p = 0.001). During hospitalization, 21 (44%) children died. Older age, low Glasgow coma score (<8) at admission and paediatric intracerebral haemorrhage score ≥2 were associated with mortality at discharge (p = <0.05). Among survivors, 15 (56%) children had neurological deficits (PSOM >0.5) at three month follow-up. CONCLUSION: VKDB, inherited coagulation disorders, central nervous system infections and arteriovenous malformations were the most common risk factors for HS. VKDB is the single most important preventable risk factor for HS in infants.

A high frequency and geographical distribution of MMACHC R132* mutation in children with cobalamin C defect.

Cobalamin C defect is caused by pathogenic variants in the MMACHC gene leading to impaired conversion of dietary vitamin B12 into methylcobalamin and adenosylcobalamin. Variants in the MMACHC gene cause accumulation of methylmalonic acid and homocysteine along with decreased methionine synthesis. The spectrum of MMACHC gene variants differs in various populations. A total of 19 North Indian children (age 0-18 years) with elevated methylmalonic acid and homocysteine were included in the study, and their DNA samples were subjected to Sanger sequencing of coding exons with flanking intronic regions of MMACHC gene. The genetic analysis resulted in the identification of a common pathogenic nonsense mutation, c.394C > T (R132*) in 85.7% of the unrelated cases with suspected cobalamin C defect. Two other known mutations c.347T > C (7%) and c.316G > A were also detected. Plasma homocysteine was significantly elevated (> 100 µmol/L) in 75% of the cases and methionine was decreased in 81% of the cases. Propionyl (C3)-carnitine, the primary marker for cobalamin C defect, was found to be elevated in only 43.75% of cases. However, the secondary markers such as C3/C2 and C3/C16 ratios were elevated in 87.5% and 100% of the cases, respectively. Neurological manifestations were the most common in our cohort. Our findings of the high frequency of a single MMACHC R132* mutation in cases with combined homocystinuria and methylmalonic aciduria may be proven helpful in designing a cost-effective and time-saving diagnostic strategy for resource-constraint settings. Since the R132* mutation is located near the last exon-exon junction, this is a potential target for the read-through therapeutics.

Diagnostic values of 68Ga-labelled DOTANOC PET/CT imaging in pediatric patients presenting with paraneoplastic opsoclonus myoclonus ataxia syndrome.

OBJECTIVES: Opsoclonus myoclonus ataxia (OMA) syndrome, also known as "Kinsbourne syndrome" or "dancing eye syndrome," is a rare, paraneoplastic entity which may be associated with pediatric neuroblastic tumors and carry a grave prognosis. We aimed to evaluate the role of 68Ga DOTANOC PET/CT for detecting neuroblastic tumors in patients with OMA syndrome. METHODS: We retrospectively evaluated the 68Ga-DOTANOC PET/CT data of pediatric patients presenting with OMA syndrome from March 2012 to November 2018. A somatostatin receptor (SSTR)-expressing lesion with corresponding morphological change on CT image was considered PET-positive, while no abnormal SSTR expression or lesion was noticed in PET-negative patients. Histopathology and/or clinical/imaging follow-up (minimum one year) was considered a reference standard for comparing the PET/CT findings. The results of 68Ga-DOTANOC PET/CT were also compared with 131I MIBG whole-body scintigraphy, which was available in five patients. RESULTS: Of 38 patients (13 males, 25 females, aged 3-96 months), 18 (47.3%) had SSTR-expressing lesions (PET-positive), and histopathology revealed neuroblastic tumors in 17/18 lesions (neuroblastoma 14, ganglioneuroblastoma 2, and ganglioneuroma 1) and reactive hyperplasia in 1/18. The remaining 20/38 (52.6%) patients did not demonstrate SSTR-expressing lesions (PET-negative) and had an uneventful follow-up. The average SUVmax of the PET-positive lesions was 10.3 (range 2.8-34.5). The PET/CT results revealed 17 true-positive, one false-positive, 20 true-negative, and zero false-negative. The sensitivity, specificity, positive predictive value, negative predictive value, and accuracy were 100%, 95.2%, 94.4%, 100%, and 97.3% respectively. CONCLUSIONS: 68Ga-DOTANOC PET/CT identified neuroblastic tumors with a high diagnostic accuracy in our cohort compared to histology and follow-up. KEY POINTS: • Opsoclonus myoclonus ataxia (OMA) syndrome or "dancing eye syndrome" is a rare paraneoplastic entity which may be associated with pediatric neuroblastic tumors with a grave prognosis. • 123I/131I MIBG imaging has a proven role for functional imaging in neuroblastoma or patients with OMA, but the role of 68Ga-DOTANOC PET/CT is not yet studied. • 68Ga-labelled DOTANOC PET/CT (SSTR) imaging, in our cohort, was able to positively identify neuroblastic tumors with high diagnostic accuracy when compared with histology.

MR vessel wall imaging in tubercular meningitis.

PURPOSE: Tubercular meningitis (TBM) has the propensity to cause secondary vasculitis through various mechanisms leading to development of cerebrovascular complications. These vascular involvements can be detected by vessel wall imaging (VWI). In this study, we aimed to study detailed findings of vessel wall imaging in cases of tubercular meningitis. METHODS: All consecutive patients of suspected tubercular meningitis in whom diagnosis of TBM could be made according to diagnostic criteria given by Ahuja et al. were included in the study. High-resolution MR VWI and time of flight (TOF) magnetic resonance angiography (MRA) were done along with routine MRI sequences. Arteries up to second-order branches were studied, and statistical analyses were done with respect to stage of tubercular meningitis, infarctions and TOF MRA findings. RESULTS: Out of all 101 cases of TBM, infarctions were found in 49 cases (48.5%), and vessel wall enhancement was seen in 67 cases (66.3%). With increasing severity of disease, more severe vascular involvement was seen on VWI. There was significant association between enhancement of individual arteries and infarctions in their territories. VWI had better sensitivity than the MRA, while MRA had better specificity than VWI for detection of vascular complications. CONCLUSION: Tubercular vasculitis can be detected by VWI in the form of nodular or smooth segmental enhancement of vessel wall with or without stenosis. Incorporation of VWI in routine MR imaging can play a greater role in early detection and management of cerebrovascular complications which can help to improve prognosis of the disease.

Intensive Care Unit-Acquired Weakness in Children: A Prospective Observational Study Using Simplified Serial Electrophysiological Testing (PEDCIMP Study).

BACKGROUND: To study the incidence and time of onset of intensive care unit-acquired weakness in a prospective cohort of children (2-12 years) by serial simplified electrophysiological assessment (Pediatric Critical Illness Myopathy Polyneuropathy study, PEDCIMP). METHODS: A single-center, prospective cohort study (Trial Registry Number: NCT02763709; PEDCIMP2016) was conducted at the pediatric intensive care unit of a tertiary care hospital in North India. A complete electrophysiological evaluation (4 motor nerves and 2 sensory nerves) was performed at baseline in children (2-12 years) admitted to the ICU with a pediatric risk of mortality (PRISM) of > 20 with more than 24-h stay. Following the entry evaluation, a minimal alternate day simplified electrophysiological testing of the unilateral common peroneal nerve and the sural nerve was assessed. A 25% reduction in compound muscle action potential (CMAP) and sensory nerve action potential from baseline was considered significant for ICUAW and was confirmed by complete electrophysiological re-evaluation. RESULTS: Of the total 481 children assessed for eligibility, 97 were enrolled. The median age of the cohort was 7 years. Sepsis (81%); need for vasoactive support (43%); multiorgan dysfunction (26%) were the common reasons for admission. Of the 433 eligible patient ICU days, 380 electrophysiological observations were done. A significant decrease of > 25% in CMAP of common peroneal nerve was not detected in any of the 380 observations. However, two children unfit for inclusion were diagnosed with ICUAW during the study period. CONCLUSIONS: Children admitted with PRISM > 20 have a very low incidence of intensive care unit-acquired weakness by serial clinical and abbreviated electrophysiological evaluation.

Plasma and Urinary Amino Acid Profile in Children with Infantile Tremor Syndrome.

BACKGROUND: Infantile Tremor Syndrome (ITS) is a disorder of infancy, and characterized by developmental delay and/or regression, pallor, skin hyperpigmentation and hypopigmented hair. It is commonly seen in infants in whom exclusive breastfeeding is given inappropriately for longer durations than recommended. ITS is predominantly reported from the Indian subcontinent and in children from a lower socioeconomic background. It is a clinical diagnosis and vitamin B12 deficiency is the most commonly accepted etiology of this entity. OBJECTIVES: The primary objectives of study were to compare the plasma and urine amino acid levels among children with ITS spectrum with those of healthy children. The secondary objectives were to compare the plasma and urine amino acid levels among children with ITS and Pre-ITS. STUDY DESIGN: This cross-sectional, observational study was carried out at a tertiary care hospital in North India. PARTICIPANTS: A total of 50 children aged < 36 months with ITS/Pre-ITS were enrolled. Children with Pre-ITS and ITS were compared with healthy age-matched study subjects. RESULTS: Thirty-nine (78%) cases and twelve (24%) healthy children had low serum vitamin B12 levels. Folate levels were normal in all the controls, while only one case had folate deficiency. There were significant differences (p < 0.05) in the values of 32 amino acids in plasma. Among 44 urinary amino acids, levels of 30 amino acids were significantly different in the cases compared with the controls (p < 0.05). CONCLUSIONS: Several changes in amino acids in the children suffering from ITS were observed. These changes may be a reflection of the metabolic derangements in ITS.

Evaluation of Optic Nerve Sheath Diameter and Transcranial Doppler As Noninvasive Tools to Detect Raised Intracranial Pressure in Children.

OBJECTIVES: To compare the diagnostic accuracy of the ultrasonography-guided optic nerve sheath diameter with transcranial Doppler-guided middle cerebral artery flow indices against the gold standard invasive intraparenchymal intracranial pressure values in children. DESIGN: A single-center prospective cohort study. SETTING: PICU of a tertiary care teaching hospital in North India. PATIENTS: Eligible children (2-12 yr) are admitted to ICU and are undergoing intracranial pressure monitoring using an intraparenchymal catheter. Observations with a parallel measured intracranial pressure greater than or equal to 20 mm Hg were included as case-observations. Children with an invasive intracranial pressure of less than or equal to 15 mm Hg were taken as neurologic-control-observations and healthy children served as healthy-control-observations. INTERVENTIONS: The horizontal and vertical diameters of the optic nerves were measured, and averages were calculated and compared. Middle cerebral artery flow indices (pulsatility index and resistive index) were measured bilaterally and averages were calculated and compared in the three groups. Twenty-two measurements of optic nerve sheath diameter were assessed by two different observers in quick succession for interrater reliability. MEASUREMENTS AND MAIN RESULTS: A total of 148 observations were performed in 30 children. Four observations were excluded (intracranial pressure between 16 and 19 mm Hg). Of the 144 observations, 106 were case-observations and 38 were neurologic-control-observations. Additional 66 observations were healthy-control-observations. The mean optic nerve sheath diameter was 5.71 ± 0.57 mm in the case-observations group, 4.21 ± 0.66 mm in the neurologic-control-observations group, and 3.71 ± 0.27 mm in the healthy-control-observations group (p < 0.001 for case-observations vs neurologic-control-observations/healthy-control-observations). The mean pulsatility index in case-observations was 0.92 ± 0.41 compared with controls 0.79 ± 0.22 (p = 0.005) and the mean resistive index was 0.56 ± 0.13 in case-observations compared with 0.51 ± 0.09 (p = 0.007) in controls (neurologic-control-observations and healthy-control-observations). For the raised intracranial pressure defined by intracranial pressure greater than or equal to 20 mm Hg, the area under the curve for optic nerve sheath diameter was 0.976, while it was 0.571 for pulsatility index and 0.579 for resistive index. Furthermore, the optic nerve sheath diameter cutoff of 4.0 mm had 98% sensitivity and 75% specificity for raised intracranial pressure, while the pulsatility index value of 0.51 had 89% sensitivity and 10% specificity by middle cerebral artery flow studies. The sensitivity and specificity of 0.40 resistive index value in the raised intracranial pressure were 88% and 11%, respectively. Kendall correlation coefficient between intracranial pressure and optic nerve sheath diameter, pulsatility index, and resistive index was 0.461, 0.148, and 0.148, respectively. The Pearson correlation coefficient between two observers for optic nerve sheath diameter, pulsatility index, and resistive index was 0.98, 0.914, and 0.833, respectively. CONCLUSIONS: Unlike transcranial Doppler-guided middle cerebral artery flow indices, ultrasonography-guided optic nerve sheath diameter was observed to have a good diagnostic accuracy in identifying children with an intracranial pressure of greater than or equal to 20 mm Hg.

Role of Plasma Exchange in a Steroid- and IVIG-Refractory Patient with Acute Disseminated Encephalomyelitis: A Case Report.

BACKGROUND: Acute disseminated encephalomyelitis (ADEM) is a demyelinating disease usually affecting children and is treated with high-dose steroid therapy. CASE REPORT: An 8-year boy presented with limbs weakness and complete loss of vision and was resistant to steroid therapy. He was further treated with plasma exchange and showed full recovery from the neurological deficit. CONCLUSION: Therapeutic plasma exchange appears to be effective in ADEM patients in reversing the neuropathological process especially refractory to steroids and intravenous immunoglobulin.

Perfusion magnetic resonance imaging in differentiation of neurocysticercosis and tuberculoma.

PURPOSE: Tuberculoma and neurocysticercosis (NCC) are two of the most common intracranial infections in developing countries and cause of seizures or focal neurological deficit. They often present on neuroimaging as ring-enhancing lesions, and in absence of typical imaging features, can cause significant diagnostic dilemma. Differentiation is extremely important to avoid empirical exposure to anti-tubercular treatment or nonspecific treatment causing disease progression. The aim our study was to evaluate the MR perfusion characteristics of brain tuberculoma and NCC and to assess the potential role of the perfusion in differentiating the two entities. METHODS: Fifty untreated patients (20 tuberculoma and 30 NCC) were prospectively evaluated by using conventional imaging and dynamic susceptibility contrast (DSC) MR perfusion. Relative cerebral blood volume (rCBV) values were calculated from the wall and core of the lesion and were compared with contralateral normal white matter. RESULTS: rCBV values from the wall of the lesion were significantly different in tuberculoma and NCC (P < 0.05). Tuberculomas showed high mean rCBV values than NCC (3.3 and 1.3 respectively). The core of these lesions showed lower rCBV values in both the lesions which were lower than normal white matter. A cutoff value of rCBV from the wall of the lesion 1.965 for tuberculoma showed 90% sensitivity and 100% specificity. CONCLUSION: Perfusion MRI in combination with conventional sequences can better characterize and differentiate similar-appearing tuberculoma and NCC and may be incorporated in routine protocol which may help in avoiding brain biopsy and empirical therapy.

Isolated Congenital Absence of Cranial Nerves: Report of Two Cases.

Isolated cranial nerve absence is a rare condition that can be diagnosed using high-resolution cranial nerve magnetic resonance (MR) imaging. Thorough clinical examination with proper knowledge of the course of cranial nerves may help diagnose this rare condition. We describe two cases, one each of, isolated congenital absence of the third and seventh cranial nerve with their clinical presentation. High-resolution T2-weighted MR imaging was done in both patients which revealed absence of cisternal segment of the right-sided third nerve and cisternal with canalicular segment of the right-sided facial nerve.