Neuroradiological Investigations Research Articles

Further Characterization of the Neuroendocrine Phenotype Associated With the PPOX-Related Variegate Porphyria

BackgroundVariegate porphyria is caused by mutations in the PPOX gene; it usually presents in adolescents and adults as an autosomal dominant condition, with cutaneous features or acute peripheral and/or central nervous system crises. A rarer variant, homozygous variegate porphyria, presents in childhood with cutaneous manifestations as well as neurophenotypes. This study sought to further characterize the homozygous PPOX-related neuroendocrine phenotype. MethodsThis study is a retrospective review of the patients’ charts, including their clinical evaluation and molecular genetics, neurodiagnostic, and neuroradiological investigations. ResultsWe describe here three children from a consanguineous family who presented with nystagmus, developmental delay and ataxia, photosensitive skin manifestations, and adrenal insufficiency. Analysis of porphyrins in plasma, urine, and stool together with a genetic study of the PPOX gene confirmed the diagnosis. Interestingly, brain MRI showed severe hypomyelination, a finding rarely reported in variegate porphyria, together with adrenal insufficiency. ConclusionWe recommend analysis of porphyrins in unexplained hypomyelination disorders. Patients with variegate porphyria should be tested for adrenal insufficiency.

Ocular morbidity and co-morbidities in children attending a nodal district early intervention center in Uttar Pradesh.

To obtain epidemiological data on children with ocular morbidity attending a nodal district early intervention center (DEIC). : After parental consent, we recruited children with ocular morbidity. After detailed history and clinical evaluation, along with pediatric consultation and relevant neuro-radiological and ancillary investigation, information was entered in a pretested proforma: especially looking for perinatal morbidity, including developmental delay (DD). Visual acuity (VA) was assessed by age-appropriate means by an ophthalmic assistant trained to work with children with special needs. We diligently looked for strabismus and performed dilated ophthalmoscopy. Using JASP, we summarized data as means and proportions and reported 95% CIs. We explored the association of disability percentage with possible predictor variables using regression. We enrolled 320 children, with a mean age of 34.43 ± 31.35 months; two-thirds were male; one-third belonged to lower socioeconomic status (36%), with most parents being illiterate. The mean presenting VA was 1.8 logMAR for both eyes, range: 0 to 3. Sixty-one percent were hyperopic and 27% were myopic. High refractive error, (>±6D) occurred in nine; anisometropia in one; strabismus in 149, mostly esotropia; congenital cataract in 25, whereas 63 had abnormal fundus. Seventy-six received a diagnosis of cerebral visual impairment (CVI). On multivariate linear regression (MLR), younger age, presence of DD, and CVI significantly predicted a higher disability percentage. Logistic regression revealed that statutory disability is likely associated with DD (odds ratio [OR]:13.43); whereas older age was protective (OR: 0.977). Our study suggests that in DEIC children with ocular morbidity, younger children, and the presence of DD significantly predict both greater disability and the likelihood of statutory levels.

Spectrum of EEG Findings in Patients with Leptomeningeal Carcinomatosis and Seizures: Correlation with Neurodiagnostic Results and Outcome.

Purpose: Leptomeningeal carcinomatosis (LC) is a devastating condition in patients with systemic malignancies or primary brain tumors. Although much is known about neuro-radiologic investigations, there is very little information about EEG findings in these patients. Whether EEG is correlated with cranial magnetic resonance imaging (MRI) results and survival has not been investigated. Methods: Medical records of 2340 adult patients with the diagnosis of brain tumor, either metastatic (Group 1) or primary (Group 2), between 2000-2021 were reviewed for the presence of LC and seizures. Demographic and clinical features, laboratory results and Karnofsky performance scores of included patients were noted. Available routine EEG recordings were re-evaluated. Any possible correlation between EEG findings-MRI and EEG findings-survival were investigated statistically. Results: Sixty-six patients with LC and seizures were identified. The most common malignancies were lung cancer and glioblastoma multiforme. Twenty-six EEG recordings of 17 patients in Group 1, and 13 EEGs of 9 patients in Group 2 were available for final analysis. The most common EEG characteristic was background slowing (73%). The most frequent findings were rhythmic periodic patterns or spike wave activity (27%). Sporadic epileptiform discharges (8%) or ictal recordings (4%) were very rare. None of the EEG features correlated with MRI results or survival. Conclusion: There are various EEG patterns in patients with LC and seizures. The most common findings are related to background activity, with rhythmic periodic patterns or spike wave activity being observed less commonly. EEG characteristics do not predict MRI findings or survival.

Spheno-orbital Meningioma Presenting with Mild Proptosis and Visual Loss: A Case Report and Literature Review

Sphenoid wing meningiomas commonly present with headaches and visual changes. Some presentations may vary depending on the meningioma’s site of growth. Here we present a gentleman with no headaches, a very mild proptosis that went unnoticed, together with a rapid visual loss that progressed over 4 months. Prior to presenting at the eye casualty, he has been assessed by other doctors and opticians, who diagnosed his fundal toxoplasmosis scar as the cause of his visual loss. Only through a thorough examination and measurement, did the mild proptosis become a significant part of the investigations and diagnosis. Neuroradiological investigations confirmed a diagnosis of spheno-orbital meningioma, for which he underwent 2 surgeries to achieve satisfactory debulking of the mass. This case report is to highlight the importance of having a systematic approach when reviewing patients with proptosis, and to always explore other potential causes for visual loss. A brief review of literature looking at the various causes of unilateral proptosis and different presentations of spheno-orbital meningiomas is included.

Toxin-associated infectious diseases: tetanus, botulism and diphtheria.

The incidence rates of the toxin-related infectious diseases, tetanus, diphtheria and botulism declined dramatically over the past decades mainly because of the implementation of immunization programs also in low-and-middle-income countries (LAMICs) and by improving hygiene conditions. But still, single cases occur, and they need fastest possible recognition and management. Over the past 20 years, the incidence of neonatal tetanus has declined by more than 90%. This success was achieved by immunizing women in reproductive age in areas of high risk as sub-Saharan Africa and parts of Asia. Larger regional outbreaks of diphtheria have been reported from the former Soviet Union in the 1990s and from India in 2017. Botulism is still rare, mainly seen in infants and, in recent years, in intravenous drug abusers. Tetanus, diphtheria and botulism are rarities in high-income countries (HICs) with unlimited access to immunization programs and standard hygiene procedures. The diagnosis of all three diseases is still, even in the 21st century, based upon patient's history and clinical signs and symptoms. Neither biochemical bedside tests nor neuroradiological investigations help to confirm the diagnosis in an emergency situation.

Coexistence of Autism with Neurofibromatosis type 1

Autism is a developmental disorder that usually appears during the first three years of childhood. It results from a nervous system disorder, which affects brain functions. Neurofibromatosis 1 (NF 1) is a group of genetic diseases that mainly affect the growth of neural tissue cells. This alteration is also known as von Recklinghausen's disease. The objective of this study is to highlight a case of this neurocutaneous alteration (NF 1) which was associated with autism spectrum disorders at the age of eight years. The data for this study are extracted from the medical file of a 12-year-old boy with confirmed autism who has been taken care of by the "Applied Behavioral Analysis" (ABA) center in Morocco since the age of three. At the age of eight, the appearance of numerous café-au-lait spots on his body led the center to conduct neuroradiological investigations (T1, T2 and Flair). The examinations had revealed T2 hyper intensity signals involving several unidentified bright objects (UBO) and the globus pallidus was the most affected area. With ASD alone, the child faces various disorders of the nervous system and many difficulties in his socio-communicative life. The onset of NF1 gave rise to additional complications.

Management of haemorrhagic stroke secondary to arteriovenous malformations in childhood.

The aim of this study is to describe the outcome and management of all children who have presented with haemorrhagic stroke (HS) secondary to an arteriovenous malformation (AVM) at a single UK centre over a 13-year period. All children with HS managed at our institution (2005-2018) were identified and those with underlying AVMs were studied. Clinical and imaging data were obtained from medical records. Outcome was scored using the Recovery and Recurrence Questionnaire. Ninety-three children (median age 8.8years; 56 males; 8 neonates) presented with both global and focal features (28 had Glasgow Coma Score < 8). Haemorrhage was intraparenchymal in 72; prior risk factors present in 14. An underlying vascular lesion was identified in 68/93, most commonly AVM (n= 48). A systemic cause was found in 10, cerebral venous thrombosis in three, and 9 remain unidentified despite neuroradiological investigation. Median follow-up was 2.4years, six died, and one was lost to follow-up. Outcome was rated as good in 60/86. Of the 48 AVMs, 3 were Spetzler-Martin (SM) grade 1, 21 SM 2, 21 SM3 and 3 SM4. One patient was treated conservatively as the AVM was too high risk to treat. At follow-up, 19 with AVM were angiographically cured, all with low SM grade and with the use of a single modality in 9 cases (all low SM grade). Although children with acute HS are extremely unwell at presentation, supportive care results in a good outcome in the majority. Complete obliteration for childhood AVMs is challenging even with low-grade lesions with multimodal treatment.

Lissencephaly in an epilepsy cohort: Molecular, radiological and clinical aspects.

Lissencephaly is a rare malformation of cortical development due to abnormal transmantle migration resulting in absent or reduced gyration. The lissencephaly spectrum consists of agyria, pachygyria and subcortical band heterotopia. In this study we compared genetic aetiology, neuroradiology, clinical phenotype and response to antiepileptic drugs in patients with epilepsy and lissencephaly spectrum malformations. The study group consisted of 20 patients - 13 males and 7 females, aged 18 months to 21yearsat the time of data collection. Genetic testing was performed by oligonucleotide array comparative genomic hybridization (microarray), multiplex ligation-dependent probe amplification (MLPA), targeted gene panels and whole exome/genome sequencing. All neuroradiological investigations were re-evaluated and the malformations were classified by the same neuroradiologist. Clinical features and response to anti-epileptic drugs (AEDs) were evaluated by retrospective review of medical records. In eleven patients (55%) mutations in PAFAH1B1 (LIS1) or variable microdeletions of 17p13.3 including the PAFAH1B1 gene were detected. Four patients (20%) had tubulin encoding gene mutations (TUBA1A, TUBG1 and TUBGCP6). Mutations in DCX, DYNC1H1, ADGRG1 and WDR62 were identified in single patients. In one patient, a possibly pathogenic intragenic deletion in TRIO was detected. A clear radiologic distinction could be made between tubulinopathies and PAFAH1B1 related lissencephaly. The majority of the patients had therapy resistant epilepsy and epileptic spasms was the most prominent seizure type. The best therapeutic response to seizure control in our cohort was obtained by the ketogenic diet, vigabatrin, clobazam, phenobarbital and valproate. The most common genetic aetiologies in our cohort of 20 individuals with epilepsy and lissencephaly spectrum were intragenic deletions or single nucleotide mutations in PAFAH1B1 or larger deletions in 17p13.3, encompassing PAFAH1B1, followed by mutations in tubulin encoding genes. Radiological findings could reliably predict molecular results only in agyria with a posterior to anterior gradient. Radiological and molecular findings did not correlate consistently with severity of clinical outcome or therapeutic response.

Clinicopathologic Features of Thoracolumbar Interdural Disc Herniations: A Retrospective Case Series with a Systematic Literature Review

Transdural disc herniations represent about 0.3% of all herniated discs. Preoperative imaging rarely demonstrates this condition. Therefore, diagnosis of transdural disc herniation is usually made intraoperatively. We describe the clinicopathologic features of extremely rare cases of thoracic and lumbar interdural disc herniations mimicking spinal intradural en plaque tumors. This is a retrospective case series with a systematic literature review. Clinical presentation, imaging, differential diagnosis, intraoperative microsurgical findings, and possible pathogenesis were reviewed according to published guidelines. All patients underwent a posterior approach for microsurgical excision of disc herniation, but no epidural lesion was found. At intradural exploration, a tumor-like en plaque lesion was discovered. The surface of the lesion was incised, and multiple friable, cartilaginous white-yellow fragments were removed to achieve complete intralesional excision. The postoperative course was characterized by progressive neurologic improvement in all cases. In peculiar anatomic (adhesions between the anulus fibrosus, posterior longitudinal ligament, and ventral surface of dura mater) and pathologic (calcified giant disc herniation, spinal canal stenosis, previous lumbar spine surgery) conditions, penetration of disc fragment in the thickness of spinal dura mater can occur. Interdural disc herniations constitute a rare pathologic condition characterized by the migration of the herniated disc in neither the epidural nor the subdural spinal space, but rather in the thickness of the spinal dura mater. Further advances are necessary in neuroradiologic investigations to achieve a correct preoperative diagnosis, which is essential, as spine surgeons must be aware of these rare pathologies.

Gerstmann-Sträussler-Scheinker disease (PRNP p.D202N) presenting with atypical parkinsonism.

The p.D202N mutation in PRNP is a rare variant associated with Gerstmann-Straussler-Scheinker disease (GSS), a genetic form of prion cerebral amyloidosis. To date, there have been only 4 reports of this mutation worldwide and only one detailed clinical study (table e-1, [links.lww.com/NXG/A223][1]).1–4 Here, we describe the clinical phenotype and the results of neuroradiologic and laboratory investigations in an Italian patient carrying this genetic variant. [1]: http://links.lww.com/NXG/A223

Imaging findings in hypophysitis: a review.

Hypophysitis (HP) is a rare acute or chronic inflammatory condition of the pituitary gland. The greatest challenge in the management of HP is establishing a diagnosis through clinical criteria and non-invasive methods and predicting the patients' clinical outcome. The aim of this review is to describe the neuroradiological findings of this rare disease, providing some information regarding the possible differential diagnosis in order to avoid unnecessary surgery. Gadolinium-enhanced pituitary magnetic resonance imaging (MRI) is considered the neuroradiological investigation of choice. The features suggestive for HP include an enlarged triangular- or dumbbell-shaped gland with a thickened and not obviously deviated stalk, further supported by the absence of posterior pituitary bright spot on T1weighted images, particularly in patients presenting with diabetes insipidus. Contrast enhancement pattern is quite variable; dural enhancement has been reported in some cases after intravenous contrast administration. The characterization of the unusual sellar mass is not straightforward and generally results in a wide differential. HP should be primarily differentiated from pituitary adenomas (including pituitary apoplexy), from pituitary metastases, and from other sellar and parasellar tumors, e.g., craniopharyngiomas, germinomas, gliomas, lymphomas, meningiomas, pituicytomas, chordomas, teratomas, dermoids and epidermoids, Rathke's cleft cysts, and abscesses. In patients suspected for secondary forms related to systemic pathology, additional imaging is helpful in identifying other involved sites. Neuroradiologists need to know MRI appearance of this rare disease, as well as its typical symptoms and serological markers. A strict collaboration with endocrinologists and neurosurgeons is mandatory in order to reach a definitive diagnosis, allowing to promptly initiating an appropriate treatment.

Clinical and cytogenetic assessment of a cohort of Egyptian patients with Neurofibromatosis 1

IntroductionNeurofibromatosis 1 (NF1) is an autosomal dominant disorder characterized by the presence of certain clinical manifestation. The most common clinical features are, hyperpigmented areas, neurofibromas and Lisch nodules of the iris. The diagnosis is usually based on the clinical finding. The NF1 is caused by heterozyous mutations of the NF1 gene. It was suggested that individuals with inherited NF1 microdeletion usually have a more severe phenotype compared with those harboring intragenic mutations. AimThe aim of the study is to evaluate the clinical and cytogenetic findings of NF1 patients referred to the Dermatology and Neurology clinics at NRC. Patients and methodsThis study included 30 NF1 patients, 7 patients were from 3 families and the others were sporadic cases. All patients were subjected to thorough clinical examination, pedigree construction, various neuro-radiological investigation, and G-Banding and FISH using NF1 probe to detect deletion. ResultsAll patients had the characteristic clinical manifestations including the multiple skin hyperpigmented areas >0.5 cm, axillary and/or inguinal freckling and neurofibroma. Karyotype was normal for all patients but one has 45,XX,rob(13;14)(q10;q10). FISH results showed positive deletion for NF1 locus in 5 patients including two sibs (6y and 4mon), both and their mother have multiple neurofibromas. ConclusionOur patients exhibited the common features for the NF1. All young children below 10 years did not show any neurofibromas lesions. However the neurofibromas lesions were unusually developed early in 3patients, this could be explained by the presence of NF1 deletion that was detected by FISH, which underscores the impact of this deletion on the early development of neurofibromas.

Characteristics and outcome of influenza-associated encephalopathy/encephalitis among children in a tertiary pediatric hospital in Italy, 2017\u20132019

BackgroundInfluenza is the most frequent cause of acute upper respiratory tract infections during winter season. Although rare, neurological manifestations are known to occur during influenza infection and approximatively three-quarters of cases are in children. In this study, we aimed to characterize the burden and clinical spectrum of influenza-associated encephalopathy and encephalitis in children admitted at a tertiary pediatric hospital in Italy over two influenza seasons (2017–2019).MethodsWe retrospectively analyzed clinical, laboratory, instrumental data and outcome of patients discharged with ICD9-CM 487.0 code.ResultsFifteen children (13.1% of those discharged with a diagnosis of influenza infection in the study period), had influenza-associated central nervous system (CNS) manifestations. Eight patients (53.3%) were diagnosed as influenza encephalitis, 7 (46.7%) as influenza encephalopathy. Median age was 27 months. In children under 2 years of age (40% of all cases) altered consciousness was the most frequent neurological manifestation while respiratory symptoms were present at admission in all cases. Younger children also required intensive care support more frequently. Five subjects (33.3%) presented comorbidity. None of the patients had received seasonal influenza vaccination. The median time from onset of respiratory signs to onset of neurological manifestations was 24 h. Cerebrospinal fluid (CSF) analysis was normal in most patients and polymerase chain reaction for influenza virus RNA on CSF, when performed, was negative in all samples. Neuroradiological investigations, performed in 5 children, reported cortical and subcortical white matter signal alterations. Oseltamivir was administered only in 2 cases. Fourteen patients recovered without sequelae, and only a 2-year-old girl had minimal impairment in fine motor skills at discharge.ConclusionsAll children presenting acute neurological features during influenza season should be evaluated for influenza-associated CNS complications even if the respiratory involvement is mild. Absence of underlying diseases or other risk factors are not protective factors against CNS influenza-associated complications. The lack of CSF pleocytosis does not exclude CNS involvement. Children under 2 years of age are at higher risk of requiring intensive care support.

Long-term EEG monitoring and positron emission tomography in evaluating patients with drug-resistant epilepsy

BackgroundDrug-resistant epilepsy (DRE) is a commonly faced problem in epilepsy practice associated with great psychosocial consequences. This work aimed to study the role of seizure semiology analysis (SSA), long-term EEG monitoring, high field strength MRI, and positron emission tomography (PET) scan of the brain to confirm the diagnosis of true-RDE cases as well as seizure onset zone (SOZ) localization.MethodsThis study was conducted on 67 DRE patients subjected to SSA, long-term video EEG, 3-Tesla MRI brain, and 18-FDG PET scan of brain.ResultsForty-three patients had true-DRE and 24 had non-epileptic episodic events (NEEE). The former group consisted of 23 patients with temporal lobe, 17 with frontal lobe, and 3 with occipital lobe epilepsies. Forty-eight patients had abnormal EEG included all patients with true-DRE and 5 patients with NEEE. Thirty patients had abnormal MRI brain findings in the form of mesial temporal sclerosis and/or focal cortical dysplasia. Sixteen true-DRE patients with normal 3-T MRI underwent PET scan of the brain where regional hypometabolism was detected in 14 (87.5%) of them.ConclusionPracticing with DRE patients’ needs meticulous assessment through detailed SSA, adequate neurophysiological long-term video EEG monitoring, and thorough neuroradiological investigation (structural and/or functional) to confirm the diagnosis of true-DRE and localize the SOZ as well as identification of patients with NEEE.

Manganese-Enhanced MRI of the Brain in Healthy Volunteers.

The manganese ion is used as an intracellular MR imaging contrast agent to study neuronal function in animal models, but it remains unclear whether manganese-enhanced MR imaging can be similarly useful in humans. Using mangafodipir (Teslascan, a chelated manganese-based contrast agent that is FDA-approved), we evaluated the dynamics of manganese enhancement of the brain and glandular structures in the rostral head and neck in healthy volunteers. We administered mangafodipir intravenously at a rate of 1 mL/minute for a total dose of 5 μmol/kg body weight. Nine healthy adult volunteers (6 men/3 women; median age, 43 years) completed baseline history and physical examination, 3T MR imaging, and blood work. MR imaging also followed mangafodipir administration at various time points from immediate to 7 days, with delayed scans at 1-3 months. The choroid plexus and anterior pituitary gland enhanced within 10 minutes of infusion, with enhancement persisting up to 7 and 30 days, respectively. Exocrine (parotid, submandibular, sublingual, and lacrimal) glands also enhanced avidly as early as 1 hour postadministration, generally resolving by 1 month; 3 volunteers had residual exocrine gland enhancement, which resolved by 2 months in 1 and by 3 months in the other 2. Mangafodipir did not affect clinical parameters, laboratory values, or T1-weighted signal in the basal ganglia. Manganese ions released from mangafodipir successfully enable noninvasive visualization of intra- and extracranial structures that lie outside the blood-brain barrier without adverse clinical effects, setting the stage for future neuroradiologic investigation in disease.

Effectiveness of care in acute dizziness presentations

PurposeThis study aims to evaluate whether a management algorithm has improved the effectiveness of care for dizzy patients at Umeå University Hospital.MethodsThis was an interventional study using medical records to collect data for acute dizziness presentations before (period 1, 2012–2014) and after (period 2, 2016–2017) the implementation of a management algorithm. Outcomes were changes in a set of pre-defined effectiveness markers and health economic effects.ResultsTotal n = 2126 and n = 1487 acute dizziness presentations were identified in period 1 and 2, respectively. Baseline characteristics were similar. The proportion of patients undergoing Dix–Hallpike testing increased, 20.8% [95% confidence interval (CI) 18.8–23.0%] vs. 37.7% (95% CI 35.2–40.2%), as did BPPV diagnoses, 7.6% (95% CI 6.6–8.8%) vs. 15.3% (95% CI 13.6–17.3%). Hospitalization became less common, 61.5% (95% CI 59.4–63.6%) vs. 47.6% (95% CI 45.1–50.2%). The proportion undergoing any neuroradiological investigation decreased, 44.8% (95% CI 42.7–47.0%) vs. 36.3% (95% CI 33.8–38.7%) with a shift from CT to MRI, with unchanged sensitivity for diagnosing cerebrovascular causes. The average cost for the care of one dizzy patient decreased from $2561 during period 1 to $1808 during period 2.ConclusionsThis study shows that the implementation of a management algorithm for dizzy patients was associated with improved effectiveness of care.

Isolated neonatal bilateral vocal cord paralysis revealing a unilateral medullary defect: a case report

BackgroundCongenital bilateral vocal cord paralysis is a rare occurrence. Approximately half the cases are associated with a major comorbidity, usually neurological, neuromuscular or malformative.Case presentationIn a male newborn, respiratory distress syndrome and stridor were observed immediately following birth. The cause was bilateral vocal cord paralysis in the adducted position. Neuroradiological investigation revealed a unilateral discontinuity between the upper pons and the right medulla oblongata. Hypoplasia of the right posterior hemiarches of C1-C2 and the right exo-occipital bone was observed, as was a small clivus. MR angiography showed the absence of the distal right vertebral artery, with hypoplasia and parietal irregularities of the proximal segments. Respiratory autonomy was not obtained despite endoscopic laser cordotomy, corticosteroid therapy and nasal continuous positive airway pressure. The infant died at the age of 4 weeks after treatment was limited to comfort care.ConclusionsA medullary lesion is an exceptional cause of congenital bilateral vocal cord paralysis. The strictly unilateral neurological and vascular defect and the absence of associated intracranial or extracranial malformation make this clinical case unique and suggest a disruptive mechanism. This case also highlights the help provided by advanced neuroimaging techniques, i.e. fibre tracking using diffusion tensor imaging, in the decision-making process.

Reliability of clonidine testing for the diagnosis of growth hormone deficiency in children and adolescents.

The diagnosis of growth hormone deficiency (GHD) is currently based on clinical, auxological, biochemical and neuro-radiological investigation. Provocative tests of GH secretion using physiological/pharmacological stimuli are required to confirm GHD. The clonidine test (CT) is widely used to assess GH secretory status. In this retrospective study, we analyzed the reliability of CT and the effect of puberty in a large number of children with short stature who had been evaluated for suspected GHD. Data were collected retrospectively from 327 children and adolescents with short stature (204 boys and 123 girls, median age 10.5years (IQR 7.90-12.40) followed in four Italian Paediatric Endocrine Units (Cagliari, Genova, Napoli and Roma) between 2005 and 2013. All children underwent CT as the first GH stimulation test after exclusion of other known cause of their short stature. In 73 prepubertal children and 25 pubertal children, the GH peak after CT was <7μg/L. GHD was confirmed in 87 (37 organic, 50 idiopathic). Six prepubertal and five pubertal patients showed false positive responses. The median BMI-SDS in these children was similar to that of children with GH peak ≥7μg/L, and none were obese. Overall, the prevalence of false-positive responses was 3.3%. The median (IQR) peak GH after CT was similar between prepubertal and pubertal GHD (3.80μg/L [1.7-6.00] vs 3.51μg/L [0.76-5.74]) and non-GHD (13.70μg/L [10.70-18.40] vs 12.40μg/L [9.90-19.25]) children. Our results show that CT is a reliable and safe GH-releasing agent in both prepubertal and pubertal children.

Novel Homozygous Mutation of the AIMP1 Gene: A Milder Neuroimaging Phenotype With Preservation of the Deep White Matter

BackgroundMutations in AIMP1, which plays an important role in the development and maintenance of axon-cytoskeleton integrity and regulating neurofilaments, cause neurodegeneration of variable severity and white matter abnormalities. MethodsFrom the patient records we analyzed the clinical evaluation, molecular genetics, neurodiagnostic, and neuroradiological investigations. ResultsWe describe six members of a large consanguineous family with a phenotype of severe neurodegeneration in the form of developmental delays, progressive microcephaly, epilepsy, and failure to thrive. MRI showed callosal atrophy and T2 hyperintensity in the superficial white matter. The periventricular and deep white matter structures were, however, preserved. MR spectroscopy demonstrated N-acetylaspartate preservation without evidence of neuroinflammation. Exome sequencing showed a novel homozygous mutation of the AIMP1 gene in all individuals: c.917A>G (p.(Asp306Gly)). ConclusionsThis novel homozygous mutation of the AIMP1 gene is characterized by preserved development of the periventricular and deep white matter structures as demonstrated by MRI and MR spectroscopy correlation.

Non-operative meningiomas: long-term follow-up of 136 patients.

Improving access to neuroradiology investigations has led to an increased rate of diagnosis of incidental meningiomas. A cohort of 136 incidental meningioma patients collected by a single neurosurgeon in a single neurosurgical centre is retrospectively analysed between 2002 and 2016. Demographic data, imaging and clinical features are presented. The radiological factors associated with meningiomas progression are also presented. The mean age at diagnosis was 65 (range, 33-94) years. Univariate analysis showed oedema was most strongly correlated with progression (p = 0.010) followed by hyperintensity in T2-weighted (T2W) MRI (p = 0.029) and in Flair-T2W MRI (p = 0.017). Isointensity in Flair-T2W MRI (0.004) was most strongly correlated with non-progression of the meningioma followed by calcification (p = 0.007), older age (p = 0.087), hypointensity in Flair-T2W MRI (p = 0.014) sequences and in T2W MRI (p = 0.096). In multivariate analysis, the strongest radiological factor predictive of progression was peritumoural oedema (p = 0.016) and that of non-progression was calcification (p = 0.002). At the end of the median follow-up (FU) of 43 (range, 4-150) months, 109 (80%) patients remained clinically stable, 13 (10%) became symptomatic and 14 (10%) showed clinical and radiological progression. One hundred and nine (80%) patients remained stable at the end of FU. Peritumoural oedema was predictive of meningiomas progression. Further prospective study is needed to identify the combination of factors which can predict the meningioma progression for an early surgery or early discharge.