Enlargement Of Subarachnoid Spaces Research Articles

Prevalence of Fecal Incontinence in Normal Pressure Hydrocephalus: A Prospective Evaluation of 100 Patients

Normal pressure hydrocephalus (NPH) is a frequent disease in elderly patients. The main symptoms are gait disturbance, urine incontinence, and cognitive decline. Fecal urgency and incontinence are described as rare additional symptoms; however, no exact numbers are known. The aim of this study was to investigate the prevalence of fecal disturbances in NPH patients. Patients who presented to our department with confirmed diagnosis of NPH between January and December 2021 were interviewed prospectively about fecal function. Additionally, the extent of gait disturbance, cognitive decline, ventriculomegaly (EvansIndex), disproportionate enlarged subarachnoid space hydrocephalus (DESH presence), age, gender, and length of history were documented. In those who were operated with a hydrocephalus shunt postoperative development of stool incontinence was followed up. One hundred patients were evaluated (67 males, 33 females, medium age 77.5years, medium Evans Index: 0.37; 87 with disproportionate enlarged subarachnoid space hydrocephalus). 97 patients showed gait disturbance, 84 cognitive decline, and 87 bladder dysfunctions. 78 patients had the complete Hakim triad. 32 patients complained about fecal incontinence (20 with urge incontinence, 12 with complete incontinence). Twenty nine patients were shunted, of which 17 (57%) recovered completely, 9 (31%) partially, and 3 (10%) did not show any change. Fecal urgency and incontinence is a frequent finding in NPH (32%) and is essential for the quality of life. In the general population, fecal incontinence in elderly is found in up to 15%. The more than two-fold higher prevalence in NPH patients and the high percentage of postshunted improvement suggests that NPH causes often directly fecal disturbance.

Quantitative assessment of cerebrospinal fluid flow and volume in enlargement of the subarachnoid spaces of infancy using MRI.

The etiology of enlarged subarachnoid spaces of infancy is unknown; however, there is radiologic similarity with normal pressure hydrocephalus. Adults with normal pressure hydrocephalus have been shown to have altered cerebrospinal (CSF) flow through the cerebral aqueduct. To explore potential similarity between enlarged subarachnoid spaces of infancy and normal pressure hydrocephalus, we compared MRI-measured CSF flow through the cerebral aqueduct in infants with enlarged subarachnoid spaces of infancy to infants with normal brain MRIs. This was an IRB approved retrospective study. Clinical brain MRI examinations including axial T2 imaging and phase contrast through the aqueduct were reviewed for infants with enlarged subarachnoid spaces of infancy and for infants with a qualitatively normal brain MRI. The brain and CSF volumes were segmented using a semi-automatic technique (Analyze 12.0) and CSF flow parameters were measured (cvi42, 5.14). All data was assessed for significant differences while controlling for age and sex using analysis of covariance (ANCOVA). Twenty-two patients with enlarged subarachnoid spaces (mean age 9.0months, 19 males) and 15 patients with normal brain MRI (mean age 18.9months, 8 females) were included. Volumes of the subarachnoid space (P < 0.001), lateral (P < 0.001), and third ventricles (P < 0.001) were significantly larger in infants with enlarged subarachnoid spaces of infancy. Aqueductal stroke volume significantly increased with age (P = 0.005), regardless of group. CSF volumes were significantly larger in infants with enlarged subarachnoid spaces of infancy versus infants with a normal MRI; however, there was no significant difference in CSF flow parameters between the two groups.

BENIGN ENLARGEMENT OF SUBARACHNOID SPACES IN INFANTS

Benign enlargement of subarachnoid spaces (BESS) constitutes is one of the most frequent neurosonographic findings in infancy and is considered to regress spontaneously by the age of 2 years. Although the majority of children with BESS demonstrate normal developmental milestones, some patients may experience a transient psychomotor delay under the age of 2 year. Besides clinical andneuroimaging findings, the long-term impact of BESS is of great interest (learning difficulties at school, language delay, impairmentsin social-cognitive abilities, reduced quality of life, decreased attention skills and poor visual-motor performance, increased risk ofautism spectrum disorders as well as a higher incidence of epilepsy). It is considered that the risk of long-term consequences may be associated with pathogenetic features of dilation of extra-axial cerebrospinal fluid spaces. In this review, we describe potentialpathogenetic mechanisms of dilatation of the subarachnoid space and its pathological sequelae in children. Generally, numerous pathogenetic hypotheses about developing BESS have been proposed as follows: remarkable physiological imbalance between the skull and brain growth in infants aged from three months to one year; manifestation of cerebral trophy; communicating hydrocephalus due to a distal block with a valve mechanism; a delay in maturation of arachnoid villi/granulations until two years of age; the result of abusive head trauma in infants. However, the hypothesis about pathological consequences of BESS in the long run due to abnormalvenous hemodynamics has emerged in recent years. Impaired venous outflow is the main driving factor of subarachnomegaly and the more severe pathological changes the more significant symptoms of subarachnomegaly. We also highlight the role of impaired cerebralvenous circulation in the development of subarachnomegaly. Further studies are needed to investigate the clinical relevance of chronic increased intracranial pressure due to venous outflow disturbance in infants with enlarged subarachnoid spaces.Тhe subject for future research should be to determine a diagnostic algorithm to help distinguish patients with BESS from those who are at risk of impairedneurological development and require additional diagnostic and therapeutic interventions.

Genetics and clinical phenotypes of epilepsy associated with chromosome 2q24.3 microdeletion

Objective: To summarize the genetics and clinical phenotypes of epilepsy children with 2q24.3 microdeletion. Methods: All the patients with 2q24.3 microdeletion were retrospectively collected at the Pediatric Department of Peking University First Hospital from March 2017 to July 2022. The features of clinical manifestations, electroencephalogram (EEG), and neuroimaging were analyzed. Results: There were 13 patients with 2q24.3 microdeletion were included. All 13 patients had de novo copy number variation (CNV) with a deletion size ranged 0.18-7.31 Mb. The main pathogenic genes in the region were SCN3A, SCN2A, TTC21B, SCN1A and SCN9A genes. Among the 13 patients, 7 were boys, and 6 were girls. The onset age of epilepsy was 3.3(2.5, 6.0) months. Multiple seizure types were observed, including focal seizures in 13 patients, generalized tonic-clonic seizures (GTCS) in 6 patients, myoclonic seizures in 3 patients, epileptic spasm in 2 patients, and tonic seizures in 2 patients. Seizures were fever sensitivity in 9 patients. Status epilepticus was observed in 6 patients. One case had normal mental motor development and 12 cases had different degrees of developmental delay. Six patients had craniofacial abnormality, 1 had six-finger deformity of the right thumb, and 1 had multiple system abnormalities. EEG showed focal discharge in 3 cases, multifocal discharges in 5 cases, multifocal and generalized discharges in 1 case. Brain magnetic resonance imaging (MRI) showed enlargement of subarachnoid spaces in the frontal and temporal region in 4 patients, enlargement of lateral ventricle in 4 patients and delayed myelination of white matter in 1 patient. Dravet syndrome was diagnosed in 5 cases. The age at the last follow-up were 2.5(1.4,5.5) years, 1 patient was seizure free longer than 1 year, and 12 patients still had seizures. Conclusions: The epilepsy associated with 2q24.3 microdeletion is mainly induced by the deletion of SCN3A, SCN2A and SCN1A genes. The seizure onset age of 2q24.3 microdeletion related epilepsy was in infancy. Multiple seizure types are observed and the common seizure types include focal seizures and GTCS. Most patients have fever sensitivity and status epilepticus. Most patients have developmental delay. The phenotype of patients with deletion of SCN3A and SCN2A gene is more severe than that of patients with deletion of SCN1A gene only.

Multiple Machine Learning Approaches for Morphometric Parameters in Prediction of Hydrocephalus.

The diagnosis of hydrocephalus is mainly based on imaging findings. However, the significance of many imaging indicators may change, especially in some degenerative diseases, and even lead to misdiagnosis. This study explored the effectiveness of commonly used morphological parameters and typical radiographic findings in hydrocephalus diagnosis. The patients' imaging data were divided into three groups, including the hydrocephalus group, the symptomatic group, and the normal control group. The diagnostic validity and weight of various parameters were compared between groups by multiple machine learning methods. Our results demonstrated that Evans' ratio is the most valuable diagnostic indicator compared to the hydrocephalus group and the normal control group. But frontal horns' ratio is more useful in diagnosing patients with symptoms. Meanwhile, the sign of disproportionately enlarged subarachnoid space and third ventricle enlargement could be effective diagnostic indicators in all situations. Both morphometric parameters and radiological features were essential in diagnosing hydrocephalus, but the weights are different in different situations. The machine learning approaches can be applied to optimize the diagnosis of other diseases and consistently update the clinical diagnostic criteria.

The impact of telephone consultations due to COVID-19 on paediatric neurosurgical health services.

PurposeThe aim of the study was to evaluate the role of telephone consultations due to the pandemic in the management of paediatric neurosurgical patients and, furthermore, to examine the proportion of patients who eventually needed a face-to-face appointment and assess the underline reasons for that.MethodsThis retrospective study included all the paediatric neurosurgical patients who had a telephone appointment during a 3-month lockdown period. Overall, 319 patients (186 males and 133 females) aged 8.36 ± 4.88 (mean ± SD) had a consultation via telephone. Two hundred fifty-one (78.7%) patients had a follow-up assessment and 68 (21.3%) were new appointments.ResultsPatients were divided between two main groups. Group A included 263 patients (82.4%) whose consultation was adequate via telephone, and Group B included 56 patients (17.6%) who required a complementary face-to-face appointment. Patients who were more likely to require a supplementary appointment were patients with either dysraphism or ventriculomegaly and benign enlarged subarachnoid spaces (BESS) (43.3% and 36.4%, respectively). Interestingly, most children with hydrocephalus who underwent a cerebrospinal fluid (CSF) diversion procedure and children with Chiari I malformation were appropriately assessed via telephone (85.1% and 83.3%, respectively). Finally, children aged < 2 years (55.2%) were better managed with face-to-face appointments. No difference was noticed regarding follow-up and new appointments.ConclusionAlthough telemedicine was not unknown to neurosurgical services, the actual application of telephone or video consultations remained quite limited. It was COVID-19 pandemic who reinforced the use of telemedicine, and taking into consideration its promising results, we can safely assume that it can be incorporated into neurosurgical health care even once the pandemic crisis has resolved.

Change in Morphological Features of Enlarged Subarachnoid Spaces Following Treatment in Idiopathic Normal Pressure Hydrocephalus.

Focally enlarged sulci (FES) are areas of proposed extraventricular fluid entrapment that may occur within idiopathic normal pressure hydrocephalus (iNPH) with radiographic evidence of disproportionately enlarged subarachnoid-space hydrocephalus (DESH), and should be differentiated from atrophy. To evaluate for change in FES size and pituitary height after shunt placement in iNPH. Retrospective. A total of 125 iNPH patients who underwent shunt surgery and 40 age-matched controls. 1.5 T and 3T. Axial T2w FLAIR, 3D T1w MPRAGE, 2D sagittal T1w. FES were measured in three dimensions and volume was estimated by assuming an ellipsoid shape. Pituitary gland height was measured in the mid third of the gland in iNPH patients and controls. Wilcoxon signed-rank test for comparisons between MRI measurements; Wilcoxon rank sum test for comparison ofcases/controls. Significance level was P < 0.05. Fifty percent of the patients had FES. FES volume significantly decreased between the pre and first postshunt MRI by a median of 303 mm3 or 30.0%. Pituitary gland size significantly increased by 0.48 mm or 14.4%. FES decreased significantly by 190 mm3 or 23.1% and pituitary gland size increased significantly by 0.25 mm or 6% between the first and last postshunt MRI. Decrease in size of FES after shunt placement provides further evidence that these regions are due to disordered cerebrospinal fluid (CSF) dynamics and should not be misinterpreted as atrophy. A relatively smaller pituitary gland in iNPH patients that normalizes after shunt is a less-well recognized feature of altered CSF dynamics. 3 TECHNICAL EFFICACY: Stage 2.

Diagnostic Approach to Macrocephaly in Children.

Macrocephaly affects up to 5% of the pediatric population and is defined as an abnormally large head with an occipitofrontal circumference (OFC) >2 standard deviations (SD) above the mean for a given age and sex. Taking into account that about 2–3% of the healthy population has an OFC between 2 and 3 SD, macrocephaly is considered as “clinically relevant” when OFC is above 3 SD. This implies the urgent need for a diagnostic workflow to use in the clinical setting to dissect the several causes of increased OFC, from the benign form of familial macrocephaly and the Benign enlargement of subarachnoid spaces (BESS) to many pathological conditions, including genetic disorders. Moreover, macrocephaly should be differentiated by megalencephaly (MEG), which refers exclusively to brain overgrowth, exceeding twice the SD (3SD—“clinically relevant” megalencephaly). While macrocephaly can be isolated and benign or may be the first indication of an underlying congenital, genetic, or acquired disorder, megalencephaly is most likely due to a genetic cause. Apart from the head size evaluation, a detailed family and personal history, neuroimaging, and a careful clinical evaluation are crucial to reach the correct diagnosis. In this review, we seek to underline the clinical aspects of macrocephaly and megalencephaly, emphasizing the main differential diagnosis with a major focus on common genetic disorders. We thus provide a clinico-radiological algorithm to guide pediatricians in the assessment of children with macrocephaly.

Coronal T2-weighted imaging improves the measurement accuracy of the subarachnoid space in infants: a descriptive study

The subarachnoid space width (SASw) is part of crucial neuroimaging criteria for the diagnosis of subarachnoid space enlargement in infants. In addition to indicating the presence of these diseases, SASw can be used to assess their severity. Therefore, it is important to be able to measure the SASw accurately. This study aimed to compare the accuracy of measurements made from axial and coronal T2-weighted imaging (T2WI) and to establish a consentaneous measurement scheme of SASw in infants. A total of 63 infants (31 males and 32 females) aged 4 days to 24 months were enrolled in this study. The supratentorial subarachnoid space volume (SASv) and corrected SASv (cSASv) were used as the gold standard reference. The SASw (including interhemispheric width and bilateral frontal craniocortical width) was measured on axial and coronal T2WI. The intra- and inter-observer reproducibility and agreement of the SASw were assessed by the intraclass correlation coefficient (ICC) and Bland-Altman analysis. A paired t-test was used to compare SASw measured on axial and coronal images. The accuracy of SASw measurements made from axial and coronal T2WI was evaluated by the relationships between the SASw and supratentorial SASv and between the SASw and supratentorial cSASv, and the relationships were examined by multivariate linear regression. The intra- and inter-observer ICC values of the three SASw measurements were greater on coronal T2WI than on axial T2WI. Bland-Altman analysis confirmed that the SASw values measured on coronal T2WI had better intra- and inter-observer agreement than axial T2WI. According to the multivariate linear regression results, model 4 (the SASw measured in coronal T2WI) was the best predictor of supratentorial cSASv (R2 = 0.755). The SASw measured on coronal T2WI was more repeatable and accurate than axial T2WI and was more representative of the actual cerebrospinal fluid accumulation in the supratentorial subarachnoid space. The SASw has been found to be a simple and essential substitution for supratentorial SASv, which can be measured on both axial T2WI passing through the bodies of the bilateral ventricles and coronal T2WI at the level of the foramen of Monro. The SASw measured on coronal T2WI was more beneficial to the diagnosis and severity assessment of subarachnoid space enlargement in infants.

Abstracts from Hydrocephalus 2021: The Thirteenth Meeting of the International Society for Hydrocephalus and Cerebrospinal Fluid Disorders

Abstracts from Hydrocephalus 2021: The Thirteenth Meeting of the International Society for Hydrocephalus and Cerebrospinal Fluid Disorders

Infantile Macrocephaly: Complicated Familial Benign Enlargement of Subarachnoid Space in Twins of Suspected Nonaccidental Injury

A 3-month-old first of dizygotic male twins, born at 34+ 5 weeks gestational age, presented with a 4-week history of increasing head circumference and vomiting. He had a tense anterior fontanelle and a head circumference above the 97th percentile. Magnetic resonance imaging showed large bilateral subdural collection with hemosiderin deposits suggestive of hemorrhage. Nine days of bilateral subdural drainage reduced the collection size and blood load. On postoperative day 16, magnetic resonance imaging confirmed persistent but smaller subdural collections, unmasking the underlying subarachnoid space enlargement. On day 18, a right subdural-peritoneal valveless shunt was inserted as definitive treatment. As part of a nonaccidental injury investigation, Twin 2 was also found to have macrocephaly secondary to benign enlargement of subarachnoid space, which was managed conservatively. Benign enlargement of subarachnoid space has an assumed autosomal/multifactorial inheritance and predisposes to subdural hemorrhage. Ultimately, no safeguarding issues were raised. Both twins continued to be neurologically stable at 2-year follow-up with head circumferences between the 98th and 99th percentiles.

The diagnostic value of cranial MRI findings in idiopathic intracranial hypertension: evaluating radiological parameters associated with intracranial pressure.

Idiopathic intracranial hypertension (IIH) is a disease that can result in blindness if there is a delay in diagnosis. Although it is stated that cranial imaging should be normal among the diagnostic criteria, we know that some radiological parameters can be used for the pre-diagnosis of IIH. To determine the predictive value of radiological parameters for the diagnosis of IIH with cranial magnetic resonance imaging (MRI). The study included a group of 19 patients with IIH ("IIH Group"), a group of 34 patients with hyperintensity around the optic nerve in cranial MRI ("Radiological Increased Intracranial Pressure Group"), and a "Control Group" consisting of 45 healthy individuals. All patients were evaluated using cranial MRI with respect to the presence/absence of empty sella, flattening of the posterior globe, hyperintensity around the optic nerve, optic nerve tortuosity, and optic nerve protrusion. In addition, optic nerve sheath diameter measurement was performed in all patients using cranial axial T2 sequence. It was found that optic nerve tortuosity (P = 0.002), flattening of the posterior globe (P = 0.013), and optic nerve protrusion (P = 0.033) were the best parameters to distinguish patients with IIH and those with optic nerve subarachnoid space enlargement. A scoring system was developed according to these data. In the presence of hyperintensity around the optic nerve, it may be possible to evaluate optic nerve tortuosity, flattening of the posterior globe, and optic nerve protrusion using cranial MRI in order to come upon a preliminary diagnosis of IIH.

Editors' note: Cerebrospinal fluid dynamics disorders: Relationship to Alzheimer biomarkers and cognition

High-convexity tight sulci (HCTS) has emerged in the last decade as a radiographic biomarker among cognitively impaired individuals with enlarged subarachnoid spaces, with most of the literature reporting an association with normal pressure hydrocephalus (NPH) and responsiveness to CSF shunting. Using their previously validated, automated imaging analysis of HCTS—which was further validated by a neuroradiologist in this investigation—Drs. Graff-Radford and colleagues explored the relationships between HCTS and various cognitive and radiographic parameters in a cohort of 684 patients aged ≥50 years. Patients with HCTS had more frequent cognitive impairment, subcortical microvascular ischemic disease with lower white matter and cortical volumes, and (most importantly) lower Tau burden. The investigators reported that the lower Tau burden in patients with HCTS indicated that subarachnoid space enlargement could not be related to Alzheimer pathology. Furthermore, the fact that HCTS correlated strongly with less cortical volume (which might otherwise suggest an underlying tauopathy) suggests that this imaging signature could be used to identify a subgroup of cognitively impaired patients without Alzheimer pathology and who may not respond to targeted Alzheimer therapeutics. Drs. Alali and Laticevschi recall their related observations from the Geneva NPH cohort, which further validate HCTS as a radiographic indicator of a nontauopathy condition. Together, these studies typify biomarkers like HCTS as indicators of a nontauopathy state, which could be useful in future clinical trials enrolling patients with neurodegenerative conditions. High-convexity tight sulci (HCTS) has emerged in the last decade as a radiographic biomarker among cognitively impaired individuals with enlarged subarachnoid spaces, with most of the literature reporting an association with normal pressure hydrocephalus (NPH) and responsiveness to CSF shunting. Using their previously validated, automated imaging analysis of HCTS—which was further validated by a neuroradiologist in this investigation—Drs. Graff-Radford and colleagues explored the relationships between HCTS and various cognitive and radiographic parameters in a cohort of 684 patients aged ≥50 years. Patients with HCTS had more frequent cognitive impairment, subcortical microvascular ischemic disease with lower white matter and cortical volumes, and (most importantly) lower Tau burden. The investigators reported that the lower Tau burden in patients with HCTS indicated that subarachnoid space enlargement could not be related to Alzheimer pathology. Furthermore, the fact that HCTS correlated strongly with less cortical volume (which might otherwise suggest an underlying tauopathy) suggests that this imaging signature could be used to identify a subgroup of cognitively impaired patients without Alzheimer pathology and who may not respond to targeted Alzheimer therapeutics. Drs. Alali and Laticevschi recall their related observations from the Geneva NPH cohort, which further validate HCTS as a radiographic indicator of a nontauopathy condition. Together, these studies typify biomarkers like HCTS as indicators of a nontauopathy state, which could be useful in future clinical trials enrolling patients with neurodegenerative conditions.

Non-Invasive Estimation of Intracranial Pressure by Diffuse Optics: A Proof-of-Concept Study.

Intracranial pressure (ICP) is an important parameter to monitor in several neuropathologies. However, because current clinically accepted methods are invasive, its monitoring is limited to patients in critical conditions. On the other hand, there are other less critical conditions for which ICP monitoring could still be useful; therefore, there is a need to develop non-invasive methods. We propose a new method to estimate ICP based on the analysis of the non-invasive measurement of pulsatile, microvascular cerebral blood flow with diffuse correlation spectroscopy. This is achieved by training a recurrent neural network using only the cerebral blood flow as the input. The method is validated using a 50% split sample method using the data from a proof-of-concept study. The study involved a population of infants (n = 6) with external hydrocephalus (initially diagnosed as benign enlargement of subarachnoid spaces) as well as a population of adults (n = 6) with traumatic brain injury. The algorithm was applied to each cohort individually to obtain a model and an ICP estimate. In both diverse cohorts, the non-invasive estimation of ICP was achieved with an accuracy of <4 mm Hg and a negligible small bias. Further, we have achieved a good correlation (Pearson's correlation coefficient >0.9) and good concordance (Lin's concordance correlation coefficient >0.9) in comparison with standard clinical, invasive ICP monitoring. This preliminary work paves the way for further investigations of this tool for the non-invasive, bedside assessment of ICP.

A variety of abnormal movements in 13 cases with nutritional cobalamin deficiency in infants

HypothesisAbnormal movements such as tremor, myoclonus, and choreoathetosis due to infantile nutritional vitamin B12 (Cbl, cobalamin) deficiency or after Cbl injection have been recognized for many years. However, nutritional Cbl deficiency may be more common than recognized and a variety of the abnormal movements may be beyond our estimates. ObjectiveTo define the relationship between a large variety of abnormal movements in infants and vitamin B12 deficiency even if serum vitamin B12 levels and/or examination are normal. Materials and methodsThis study analyzed a variety of abnormal movements such as involuntary eye movements, limb and body contractions, and gasping as well as clinical, metabolic, radiologic, and treatment results in 13 infants with nutritional Cbl deficiency. This is a retrospective study based on observation and experience. ResultsThis study included 13 infants (11 boys and 2 girls) with a large spectrum of abnormal movements, the mean age at admission was 8.3 months with a range of 3–22 months. All patients were breastfeeding. In seven cases and their mothers serum vitamin B12 levels were below 200 pg/ml. About one-third of cases serum vitamin B12 levels were over 200 pg/ml. Clinically, mild hypotonia was present in 5 cases, inadequate social interactions in 2 cases, and sensorineural hearing loss in one case. Brain MRI showed frontotemporal enlarged subarachnoid spaces and thinning of the corpus callosum in two cases. EEG examinations were normal in all cases at admission. All cases recovered rapidly within one month with treatment. ConclusionNutritional Cbl deficiency is a treatable disease that should be considered in the etiology of a variety of movement abnormalities in infants even if serum vitamin B12 values and neurological development are normal.

Novel compound heterozygous mutation in NPC1 gene cause Niemann–Pick disease type C with juvenile onset

Niemann-Pick disease type C (NPC) is a progressive lysosomal storage disorder caused by mutations in the NPC1 (in 95% of cases) or NPC2 (in ~5% of cases) genes, inherited in an autosomal recessive manner. We report the case of a 38-year-old woman with learning disorder from her first year of schooling, and could notice slow progressed cognitive impairment, social withdrawal, apathy, handwriting alterations, deterioration of language skills and dysphagia. Brain magnetic resonance imaging showed severe cerebellar atrophy, hypoplasia of the corpus callosum, asymmetric lateral ventricular enlargement, and severe enlargement of frontal and parietal subarachnoid spaces. Next generation sequencing for NPC genes (NPC1 and NPC2) detected compound heterozygous mutations in NPC1 gene, including c.1553G[A (p.Arg518Gln), paternally inherited, and c.1270C[T (p.Pro424Ser) maternally inherited. The first mutation has been already described in literature and correlated to NPC, while the second mutation is still unknown. Moreover, filipin test and quantification of plasma oxysterols confirmed NPC diagnosis. We can suggest the missense mutation c.1270C[T (p.Pro424Ser) as a new causative mutation of NPC.

Enlarged subarachnoid space on cranial ultrasound in preterm infants: Neurodevelopmental implication

The role of enlarged subarachnoid space (ESS) in preterm infants has not been described in concrete. We aimed to evaluate whether ESS should be considered a risk factor potentially associated with adverse neurodevelopmental outcomes in prematurity. Electronic medical records of 197 preterm infants (median 32.1 weeks' gestation) including cranial ultrasound (cUS) images, head circumferences, and Korean Developmental Screening Tests for Infants and Children (K-DST) results at 18–24 months corrected age were reviewed. The clinical characteristics and K-DST results were compared in infants with and without ESS (sinocortical width > 3.5 mm). A multivariable logistic regression analysis was performed to identify potential risk factors associated with positive K-DST results. At a median corrected age of 39.0 weeks, 81/197 (41.1%) infants presented ESS. A significantly greater percent of infants in the ESS group screened positive on the K-DST than in the no ESS group (27.2% vs 12.1%, p = 0.007). Within the ESS group, micro-/macrocephaly at term-equivalent age was not different with regard to the K-DST results. From the multivariable logistic regression analysis, gestational age (p = 0.016, OR = 0.855, 95% CI = 0.753–0.971) and ESS (p = 0.019, OR = 1.310, 95% CI = 1.046–1.641) were two significant risk factors associated with positive K-DST results. ESS identified on cUS at term-equivalent age in preterm infants is associated with possible developmental delays. Macrocephaly at term-equivalent age does not guarantee a benign prognosis. Future studies are required to verify ESS as a potential marker for neurodevelopmental delay in preterm infants.

Linear vs volume measures of ventricle size: Relation to present and future gait and cognition.

To compare the clinical utility of volume-based ratios with the standard linear ratio of Evans index (EI) by examining their associations with gait, cognition, and other patient and imaging variables. From MRI scans of 1,774 participants in the Mayo Clinic Study of Aging, we calculated 3 ventricle size measures: Evan index (frontal horn width divided by widest width of skull inner table), total ventricular volume, and frontal horn volume as ratios of total intracranial volume. Gait was measured by a timed 25-foot walk and cognition by a composite of psychometric tests. We also evaluated variables associated with the measures of ventricular size. Further, we evaluated gait and cognition associations with MRI of extraventricular findings seen in normal-pressure hydrocephalus: disproportionate enlargement of subarachnoid space (DESH) and focal sulcal dilations (FSD). Ventricular volume measures had stronger association with gait and cognition measures than EI. In decreasing order of strength of association with ventricle size were DESH, FSD, white matter hyperintensity volume ratio, age, male sex, cortical thickness, and education. Modest evidence was observed that FSD was associated with future decline in gait and cognition. Ventricular volume measures are clinically more useful than EI in indicating current and future gait and cognition. Multiple factors are associated with ventricle volume size, including FSD and DESH, suggesting that changes in CSF dynamics may go beyond simple ventriculomegaly.

Nasal fistula, epidermal cyst and hypernatremia in a girl presenting holoprosencephaly due to a rare ZIC2 point mutation

Holoprosencephaly is the most common brain malformation in humans and it is a complex genetic disorder. We report on a patient with holoprosencephaly caused by a rare ZIC2 mutation presenting a bifid nose associated with a nasal fistula and an epidermal cyst, besides hypernatremia. The patient was a 1 year and 4 months old girl that developed an important neuropsychomotor delay. Currently, she uses a wheelchair to move around and only emits sounds. Computed tomography (CT) scan revealed a semilobar holoprosencephaly and a Dandy-Walker variant. Head magnetic resonance imaging also disclosed corpus callosum agenesis and prefrontal subarachnoid space enlargement. On physical examination at 1 year and 4 months of age, we verified growth retardation, microcephaly, bilateral epicantic fold, upslanting palpebral fissures, bifid nose, and limbs spasticity secondary to hypertonia. Later, she began to present hypernatremia; however, its precise cause was not identified. At 6 years and 10 months of age, a nasal fistula was suspected. Facial CT scan showed an epidermal cyst at cartilaginous portion of the nasal septum. High resolution GTG-Banding karyotype was normal. However, molecular analysis through direct sequencing technique showed a mutation at regulatory region of the ZIC2 gene: c.1599*954T > A, a genetic variation previously described only in a Brazilian patient. Our patient presented findings still not reported in literature among patients with holoprosencephaly, including those with ZIC2 mutations. Thus, the spectrum of abnormalities associated to ZIC2 mutations may be broader and include other defects as those observed in our patient.

Impact factor analysis of cerebrospinal fluid tap test response in patients of idiopathic normal pressure hydrocephalus

Objective To facilitate diagnosis and predict the outcome of shunting surgery in idiopathic normal pressure hydrocephalus (iNPH) and to explore the influence of clinical and neuroimaging factors on cerebrospinal fluid (CSF) tap test response in Han Chinese patients with iNPH. Methods Forty-three patients with possible clinical diagnosis of iNPH at neurology clinic and neurology inpatient at Department of Peking Union Medical College Hospital, Chinese Academy of Medical Sciences from March 2013 to January 2017 were recruited and underwent CSF tap test. Patients were categorized into CSF tap test responders (24 patients) and non-responders (19 patients) justified by two iNPH professional neurologists. The clinical parameters in those 2 groups including gender, age onset, duration, walking ability, neuropsychological testing result, clinical scores were analyzed. The neuroimaging parameters including Evan's index, callosum corpus angle, sign of disproportion of enlarged subarachnoid space and white matter lesion (WML) Fazekas rating score were also analyzed. Results The univariate analysis showed that compared with CSF tap test negative group, the proportion of males in the positive group was significantly higher (male ∶female 20 ∶4 vs. 9 ∶10, P=0.03), the duration of walking disturbance was longer [M (QR): 30(17) months vs. 12(20) months, P=0.04], Z score of executive function was lower [M(QR): -10.3(25.0) vs. -4.8(11.3), P=0.04], Fasekas score of paraventricular white matter lesions was higher[M (QR): 2.5 (1.0) vs. 1.0 (1.0), P=0.03]. However, those factors had no statistical correlation with the CSF tap test response by multivariate logistic regression analysis(all P>0.05). Conclusions Longer disease duration, worse walking ability, worse executive function test performance and prominent white matter lesions might be the impact factors of CSF tap test. Further research of large sample size is needed in the future. Key words: Hydrocephalus, normal pressure; Factor analysis, statistical; Idiopathic; Cere-brospinal fluid tap test