Bilateral loss of cortical SEPs predict severe MRI lesions in neonatal hypoxic ischemic encephalopathy treated with hypothermia.

OBJECTIVE: The introduction of therapeutic hypothermia for neonatal hypoxic-ischemic encephalopathy calls for reevaluation of the prognostic role of somatosensory evoked potentials (SEPs). METHODS: Among 80 consecutive neonates undergoing hypothermia for hypoxic-ischemic encephalopathy, 58 performed SEPs and MRI at 4-14 days of life and were recruited in this multicenter study. SEPs were scored as: 0 (bilaterally/unilaterally recorded N20) or 1 (bilaterally absent N20). The severity of brain injury was scored using MRI. RESULTS: Bilaterally absent N20 was observed in 10/58 neonates (17%); all had moderate/severe MRI abnormalities; 36/48 neonates (75%) with score 0 at SEPs had normal MRI. The positive predictive value of SEPs on MRI outcome was of 1.00, while the negative predictive value 0.72, sensitivity 0.48, specificity 1.00, with an accuracy of 0.78 (p < .001). CONCLUSIONS: Bilateral absence of cortical SEPs predicts moderate/severe MRI pattern of injury. SIGNIFICANCE: Therapeutic hypothermia does not seem to significantly affect prognostic reliability of SEPs.

Salivary glands abnormalities in oculo-auriculo-vertebral spectrum.

BACKGROUND: Feeding and swallowing impairment are present in up to 80% of oculo-auriculo-vertebral spectrum (OAVS) patients. Salivary gland abnormalities have been reported in OAVS patients but their rate, features, and relationship with phenotype severity have yet to be defined. MATERIAL AND METHODS: Parotid and submandibular salivary gland hypo/aplasia was evaluated on head MRI of 25 OAVS patients (16 with severe phenotype, Goldenhar syndrome) and 11 controls. RESULTS: All controls disclosed normal salivary glands. Abnormal parotid glands were found exclusively ipsilateral to facial microsomia in 21/25 OAVS patients (84%, aplasia in six patients) and showed no association with phenotype severity (14/16 patients with Goldenhar phenotype vs 7/9 patients with milder phenotype, p = 0.6). Submandibular salivary gland hypoplasia was detected in six OAVS patients, all with concomitant ipsilateral severe involvement of the parotid gland (p < 0.001). Submandibular salivary gland hypoplasia was associated to Goldenhar phenotype (p < 0.05). Parotid gland abnormalities were associated with ipsilateral fifth (p < 0.001) and seventh cranial nerve (p = 0.001) abnormalities. No association was found between parotid gland anomaly and ipsilateral internal carotid artery, inner ear, brain, eye, or spine abnormalities (p > 0.6). CONCLUSIONS: Salivary gland abnormalities are strikingly common in OAVS. Their detection might help the management of OAVS-associated swallowing and feeding impairment.

Natural history of optic pathway gliomas in a cohort of unselected patients affected by Neurofibromatosis 1.

Optic pathway glioma (OPG) represents the most common central nervous system tumor in children with Neurofibromatosis type-1 (NF1). Although overall survival is usually good, no clear prognostic factors have been identified so far. We assessed the natural history of OPG in a cohort of unselected patients affected by NF1. We retrospectively evaluated 414 consecutive patients affected by NF1 and referred to our NF1 clinic before age 6. Average follow-up was 11.9 years: 52 out of 414 patients had OPG with a total cumulative incidence of 15.4% at age 15 (Kaplan-Meier estimate) and a statistically significant difference according to sex. Brain and orbit MRI was performed in 44.7% of patients: 34.6% for screening purposes and 65.4% because of the presence of neurological, ocular or other symptoms. OPG was diagnosed in 12.5% of cases in the first group, whereas in 36.4% in the latter group (p = 0.001). Clinical management was conservative in most patients, while 8 of them underwent therapy mainly because of visual deterioration. OPG was diagnosed earlier in treated patients, but the difference was not statistically significant. Conversely, all patients who underwent screening MRI had normal visual outcome. In conclusion, OPG location does not correlate with need for treatment; female patients were more frequently affected by OPG but not more frequently treated. OPG diagnosis by screening MRI does not affect the natural history of the tumor.

Second-line tests in the differential diagnosis of ACTH-dependent Cushing's syndrome.

INTRODUCTION: Diagnosing Cushing's syndrome (CS) can be a challenge, especially in ACTH-dependent CS, when it comes to detecting the origin of ACTH secretion. MATERIALS AND METHODS: Retrospective data were collected on 170 patients with ACTH-dependent CS (149 CD, 21 EAS) referring to two endocrinology units, focusing on three non-invasive tests: dexamethasone 8 mg overnight challenge (HDDST); corticotrophin-releasing hormone (CRH) assay and the desmopressin (DDAVP) test. RESULTS: Patients with EAS were slightly older and had higher ACTH, serum and urinary cortisol levels than patients with CD (p < 0.01). CD patients had a stronger ACTH and cortisol response after CRH injection (p < 0.0001), and a more pronounced reduction in cortisol levels after HDDST (p < 0.0001). A threshold percentage ACTH increase after CRH stimulation of 72.4 % was able to identify CD with a sensitivity (SE) of 76 % (95 % CI 68-83) and a specificity (SP) of 100 % (95 % CI 83-100). As for HDDST, a cortisol suppression >52.7 % below the basal level suggested a pituitary origin with a SE of 88 % (95 % CI 81-93) and a SP of 90 % (95 % CI 68-99). There were no cases of EAS with positive responses to both these tests. Increases in ACTH and cortisol levels after the DDAVP test were also higher in CD than in EAS (p < 0.01), though the SE and SP were lower. CONCLUSIONS: Patients with CD showed a stronger response to HDDST and CRH, and the adopted cut-offs showed a good SE and SP in discriminating them from patients with EAS. Concordant tests indicated CD when positive, whereas no response to either test was highly suggestive of EAS. The DDAVP test was of limited utility in the diagnostic phase. In conclusion, the choice of tests may play an important part in the differential diagnosis of ACTH-dependent CS.

Facial asymmetry quantitative evaluation in oculoauriculovertebral spectrum.

OBJECTIVES: Facial asymmetries in oculoauriculovertebral spectrum (OAVS) patients might require surgical corrections that are mostly based on qualitative approach and surgeon's experience. The present study aimed to develop a quantitative 3D CT imaging-based procedure suitable for maxillo-facial surgery planning in OAVS patients. MATERIALS AND METHODS: Thirteen OAVS patients (mean age 3.5 ± 4.0 years; range 0.2-14.2, 6 females) and 13 controls (mean age 7.1 ± 5.3 years; range 0.6-15.7, 5 females) who underwent head CT examination were retrospectively enrolled. Eight bilateral anatomical facial landmarks were defined on 3D CT images (porion, orbitale, most anterior point of frontozygomatic suture, most superior point of temporozygomatic suture, most posterior-lateral point of the maxilla, gonion, condylion, mental foramen) and distance from orthogonal planes (in millimeters) was used to evaluate the asymmetry on each axis and to calculate a global asymmetry index of each anatomical landmark. Mean asymmetry values and relative confidence intervals were obtained from the control group. RESULTS: OAVS patients showed 2.5 ± 1.8 landmarks above the confidence interval while considering the global asymmetry values; 12 patients (92%) showed at least one pathologically asymmetric landmark. Considering each axis, the mean number of pathologically asymmetric landmarks increased to 5.5 ± 2.6 (p = 0.002) and all patients presented at least one significant landmark asymmetry. CONCLUSIONS: Modern CT-based 3D reconstructions allow accurate assessment of facial bone asymmetries in patients affected by OAVS. The evaluation as a global score and in different orthogonal axes provides precise quantitative data suitable for maxillo-facial surgical planning. CLINICAL RELEVANCE: CT-based 3D reconstruction might allow a quantitative approach for planning and following-up maxillo-facial surgery in OAVS patients.

Cognitive dysfunctions and cerebral microbleeds in adult patients with haemophilia A: a clinical and MRI pilot-study.

BACKGROUND: Studies providing information about the cognitive profile of adult haemophiliacs are lacking. AIMS: To assess the neuropsychological profile in a group of Haemophiliac patients; to detect asymptomatic cerebral microbleeds (CMBs) and any correlation between CMBs and cognitive dysfunctions; to verify how several contributing factors may determine cognitive dysfunctions and/or Magnetic Resonance Imaging (MRI) findings. METHODS: Adult haemophiliacs without history of brain bleeding were prospectively enrolled on Padua Haemophilia Centre. Patients underwent: i) "Short Neuropsychological Test" assessing cognitive functions (Short Neuropsychological Examination) to obtain an overall cognitive performance (OCP) profile standardised on a cohort matched for age, sex, cultural profile; ii) MRI of the brain to evaluate areas of brain atrophy or haemorrhagic lesions. We collected information on anti-haemorrhagic treatment, cardiovascular risk profile, viral infections, birth trauma. RESULTS: 49 adults with haemophilia (31 severe-moderate, 18 mild) were enrolled. 73% of patients presented a reduction in OCP. According to OCP, no significant difference between severe and mild haemophilia was observed though scores tended to be worse in severe haemophilia (mean Z score 0.20 ± 0.10 vs s0.15 ± 0.11). Considering risk factors, OCP correlated significantly with coronary artery disease (p=0.02). MRI findings in 44 patients, indicated CMBs were inversely related to OCP (R=-0.32 p<0.05). CMBs were associated with cardiovascular risk factors (p=0.018). CONCLUSIONS: Adult haemophiliacs seem to present high prevalence of mild cognitive dysfunctions that doesn't correlate with the severity of haemophilia probably for the few number of patients evaluated. OCP impairment seems to be related to the presence of CMBs and of risk factors for cardiovascular disease.

Headache in children with Chiari I malformation.

BACKGROUND: Headache is the most common symptom of Chiari 1 malformation, a condition characterized by the herniation of cerebellar tonsils through the foramen magnum. However, the headache pattern of cases with Chiari 1 malformations is not well defined in the literature, especially in children. OBJECTIVE: The aim of this retrospective chart review was to evaluate the frequency and the characteristics of headache in children with Chiari 1 malformation at initial evaluation and during follow up. METHODS: Forty-five cases with tonsillar ectopia were selected among 9947 cases under 18 years of age who underwent neuroimaging between 2002 and 2010. A semistructured clinical interview (mean follow-up: 5.2 years) was conducted. Headache was classified according to the second edition of the International Classification of Headache Disorders. RESULTS: Possible associations between clinical picture, in particular headache pattern, but also other signs and symptoms attributable to Chiari 1 malformation, and the extent of tonsillar ectopia were found for 3 different groups: those with borderline (<5 mm, N = 12), mild (5-9 mm, N = 27), and severe tonsillar ectopia (≥10 mm, N = 6), respectively. Twenty-four out of 33 (73%) cases with Chiari 1 malformation complained of headache, and 9/33 (27%) of those patients (5 with mild and 4 with severe tonsillar ectopia) reported headache attributed to Chiari 1 malformation. CONCLUSIONS: In our studied pediatric population, the most common symptom for cases diagnosed with Chiari 1 malformation was headache, and headache attributed to Chiari 1 malformation was the most common headache pattern in patients with Chiari 1 malformation. The presence of headache attributed to Chiari 1 malformation along with 3 other signs or symptoms of Chiari 1 malformation were highly predictive of severe tonsillar ectopia.

Delayed myelination is not a constant feature of Allan-Herndon-Dudley syndrome: report of a new case and review of the literature.

INTRODUCTION: Allan-Herndon-Dudley syndrome is an X-linked condition caused by mutations of the monocarboxylate transporter 8 gene. This syndrome is characterized by axial hypotonia, severe mental retardation, dysarthria, athetoid movements, spastic paraplegia, and a typical thyroid hormone profile. In most of the cases reported so far, brain magnetic resonance imaging showed delayed myelination of the central white matter and this finding greatly affects the diagnosis of the syndrome. CASE REPORT: We present a new case studied with magnetic resonance imaging and spectroscopy and we reviewed all the articles published between 2004 and 2012 containing information on brain neuroimaging in this syndrome. An Italian boy, showing a classical phenotype of the syndrome, was diagnosed at 17months of age. Genetic analysis revealed a new frameshift mutation of the monocarboxylate transporter 8 gene. His brain magnetic resonance imaging and spectroscopy, performed at the age of 14months, were normal. DISCUSSION: Among the 33 cases reported in the literature, 3 cases had normal neuroimaging and in 7 of 14 cases, having a longitudinal follow-up, the initial finding of delayed myelination gradually improved. Our case and the review of the pertinent literature suggest that Allan-Herndon-Dudley syndrome should be suspected in males with the typical neurological and thyroid profile, even in cases with normal brain myelination.

Short lasting activity-related headaches with sudden onset in children: a case-based reasoning on classification and diagnosis.

BACKGROUND: Short lasting headaches related to activity or cough are rare, particularly in childhood, and can be difficult to diagnose, especially in young children who are not able to describe their symptoms. In the literature there are few data on this topic in adults and the paediatric cases reported are even more rare. FINDINGS: We present the clinical history of a 7-year-old child and a 3-year-old child both diagnosed as having activity-related headaches, characterized by sudden onset of short lasting (few seconds) attacks, that were triggered by cough or exercise. There were no accompanying symptoms and the neurological examination was normal in both cases. Brain magnetic resonance imaging showed, in the first case, a cerebellar pilocytic astrocytoma and, in the second case, a Chiari 1 malformation. Both cases received an early diagnosis, were surgically treated and had a good prognosis at follow-up. CONCLUSIONS: When headache has a recent onset, it presents suddenly, and it is triggered by strain, even with normal neurological examination, neuroimaging is mandatory in order to exclude secondary headaches, especially in children.

Early developmental outcomes in children following convulsive status epilepticus: a longitudinal study.

PURPOSE: Convulsive status epilepticus (CSE) is the most common pediatric neurologic emergency and is often associated with unfavorable neurodevelopmental outcomes. The early developmental trajectory of children following CSE has not been previously investigated, leaving a gap in our understanding of how these adverse long-term outcomes emerge. METHODS: We prospectively recruited children aged between 1 and 42 months from a predefined geographic region of North London who had at least one episode of CSE and classified them as prolonged febrile seizures (PFS) or nonfebrile CSE. Neuropsychological and imaging investigations were conducted within 6 weeks of CSE (baseline) and were repeated a year later (follow-up). Neurodevelopment was assessed using the Bayley Scales of Infant Development III and compared to normally developing children. Predictors of neurodevelopmental scores at baseline and follow-up were investigated using regression analyses. KEY FINDINGS: Of the 54 children that underwent investigations a mean of 38 days following CSE, 27 had PFS (mean age 18.4 months) and 27 had nonfebrile CSE (mean age 15.5 months). In addition, 17 healthy controls were assessed (mean age 20.49 months). Children with nonfebrile CSE had a worse developmental outcome than children with PFS (p < 0.002), despite there being no differences in seizure characteristics. In contrast to expectations, the PFS group had a worse developmental outcome than controls (p = 0.002). There were no significant differences in performance from baseline to 1-year follow-up for the 70.4% of children who provided data. Seizure characteristics were not shown to be significant predictors of performance. SIGNIFICANCE: CSE is associated with developmental impairments within 6 weeks of the acute event that continue to be present a year onward. This is also true of PFS cases that under-perform relative to controls despite mean scores within the clinically normal range. The absence of a change in performance from baseline to follow-up as well as the lack of a relationship between seizure characteristics and developmental outcomes supports the notion that premorbid abilities may be overshadowing any direct effects of CSE itself on outcome.

A 14-year-old girl with multiple tumors.

Pleomorphic xanthoastrocytoma (PXA) is a rare astrocytic tumor that usually occurs in the superficial cerebral hemispheres of children and young adult and has a favorable prognosis. We report a case of a 14-year-old girl with a recent history of sciatica and ataxic gait. Pre- and post-contrast brain and spinal MRI revealed the presence of multiple solid lesions with a cystic component in the cerebellum and the spinal cord with a concomitant massive leptomeningeal involvement Histological and immunohistochemical findings were concordant with a final diagnosis of WHO grade II PXA. Even the biological indolent PXAs' behavior, this is the third report in the literature of such an unusual multicentric PXA with leptomeningeal dissemination.

Brain and spine MRI features of Hunter disease: frequency, natural evolution and response to therapy.

BACKGROUND: Hunter disease is a rare X-linked mucopolysaccharidosis. Despite frequent neurological involvement, characterizing the severe phenotype, neuroimaging studies are scarce. OBJECTIVES: To determine frequency and severity of neuroradiological mucopolysaccharidosis-related features; to correlate them with clinical phenotype; to evaluate their natural evolution and the impact of intravenous enzymatic replacement therapy (ERT). METHODS: Sixty nine brain MRI examinations of 36 Italian patients (mean-age 10.4 years; age-range 2.2-30.8; severe phenotype in 22 patients) were evaluated. Twenty patients had multiple MRIs (median follow-up 3.1 years, range 1-16.9): among them 15 had MRIs before and after ERT, six had repeated MRIs without being on ERT and five while on ERT. Perivascular, subarachnoid and ventricle space enlargement, white matter abnormality (WMA) burden, pituitary sella/skull/posterior fossa abnormalities, periodontoid thickening, spinal stenosis, dens hypoplasia, myelopathy, vertebral and intervertebral disc abnormalities were graded by means of dedicated scales. RESULTS: Perivascular spaces enlargement (89%), WMAs (97%), subarachnoid space enlargement (83%), IIIrd-ventricle dilatation (100%), pituitary sella abnormalities (80%), cranial hyperostosis (19%), craniosynostosis (19%), enlarged cisterna magna (39%), dens hypoplasia (66%), periodontoid thickening (94%), spinal stenosis (46%), platyspondylia (84%) and disc abnormalities (79%) were frequently detected. WMAs, IIIrd-ventricle dilatation and hyperostosis correlated with the severe phenotype (p < 0.05). Subarachnoid spaces and ventricle enlargement, WMAs and spinal stenosis progressed despite ERT, while other MR features showed minimal or no changes. CONCLUSIONS: The spectrum of brain and spine MRI abnormalities in Hunter disease is extremely wide and requires a thorough evaluation. WMAs, atrophy/communicating hydrocephalus and spinal stenosis progress over time and might represent possible disease severity markers for new treatment efficacy assessment.

Pontocerebellar angle aspergillosis: clinical and radiological findings.

INTRODUCTION: Cerebral aspergillosis is a rare and severe condition mostly affecting immunocompromised patients. The lesions are usually intra-axial and supratentorial; several radiologic patterns have been reported. CASE REPORT: A 65-year-old patient with chronic lymphocytic leukemia presented with fever, headache, and a pontocerebellar syndrome. A brain magnetic resonance imaging (MRI) showed a ring-enhancing left pontocerebellar mass consistent with an infectious disease. Despite broad-spectrum antibiotic therapy, the patient worsened. A follow-up MRI examination disclosed a concomitant acute ischemic lesion in the ipsilateral thalamus and an irregular narrowing of the posterior cerebral artery close to the lesion. A retrospective analysis of the first MRI revealed a small mesencephalic ischemic lesion, contiguous to the extra-axial pontocerebellar mass. At surgical inspection the mass was found to be an extra-axial granuloma, with purulent components, attached to the petrous-tentorial angle, surrounded by a thick capsule. The lesion was only partially removed because of the tight relationship with the leptomeninges of the brain stem. Cerebral aspergillosis was the final histologic and microbiological diagnosis. CONCLUSION: In immunocompromised patients, the coexistence of an infectious lesion with involvement of contiguous vessels and consequent ischemic infarction should raise the suspicion of aspergillosis, even in unusual locations such as the pontocerebellar angle.

Bilateral perisylvian polymicrogyria with cerebellar dysplasia and ectopic neurohypophysis.

Polymicrogyria (involving or not the sylvian scissure) with cerebellar cortical dysplasia or vermis hypoplasia has been reported in few cases. In addition, the association between ectopic neurohypophysis and other cortical malformations, including bilateral perisylvian polymicrogyria, has been documented. We describe a girl affected by focal epilepsy since the age of 2 years. Magnetic resonance imaging (MRI) at 11 and 22 years of age showed bilateral perisylvian polymicrogyria, dysplasia of the left cerebellar hemisphere, and ectopic neurohypophysis. Genetic tests, including fluorescent in situ hybridization 22q11.2 and array-comparative genomic hybridization, and pituitary hormones (at the age of 20 years) were normal. The patient is now 22 years old, and she is seizure free under therapy with lamotrigine and levetiracetam. To the best of our knowledge, this is the first description of this complex cerebral malformation. This finding confirms that bilateral perisylvian polymicrogyria can be associated with other cerebral malformations; cerebellum and neurohypophysis must be carefully evaluated in patients with polymicrogyria.

Multimodal neuroimaging in a child with sporadic hemiplegic migraine: a contribution to understanding pathogenesis.

BACKGROUND: Hemiplegic migraine (HM) is a rare variety of migraine with aura, characterized by motor deficits during the aura, often beginning in childhood. The hemiplegic attacks can be severe and prolonged but the prognosis is usually good. Data on neuroimaging, including diffusion-weighted imaging (DWI) and spectroscopy, during prolonged attacks of HM are quite limited, particularly in children. CASE: An eight-year-old female had a prolonged attack of sporadic HM characterized by right-sided hemiplegia, global aphasia, fever and impairment of consciousness. MRI nine hours after hemiplegia onset was negative, while the following MRI scans (days 4 and 11) documented a progressive increase in cortical swelling in the left hemisphere with mild hyperintensity on DWI and mild reduction of apparent diffusion coefficient values. Proton MRI spectroscopy (MRS) (day 15) showed a decrease in the N-acetylaspartate/creatine ratio in the left hemisphere. (99m)Tc-ECD single-photon emission tomography (SPET) (day 27) showed marked left hemispheric hypoperfusion. The patient recovered completely after 40 days and neuroimaging follow-up (MRI and SPET) after six months was normal. The patient carried a missense mutation of the ATP1A2 gene. CONCLUSION: Multimodal neuroimaging (MRI, DWI, MRS, SPET) in a prolonged HM attack supports evidence for a primary neuronal dysfunction.

Hunter syndrome in an 11-year old girl on enzyme replacement therapy with idursulfase: brain magnetic resonance imaging features and evolution.

Mucopolysaccharidosis type II (MPS-II, Hunter disease) is a X-linked recessive disorder. Affected females are extremely rare, mostly due to skewed X chromosome inactivation. A few papers outline MPS-II brain magnetic resonance imaging (MRI) "gestalt" in males, but neuroradiological reports on females are still lacking. We present an 11-year-old girl affected by the severe form of MPS-II who was followed up over a time span of 8 years, focusing on clinical and brain MRI evolution. In the last 2.5 years, the patient has been treated with enzyme replacement therapy (ERT) with idursulfase (Elaprase™, Shire Human Genetic Therapies AB, Sweden). On brain and cervical MRI examination, abnormalities in our patient did not differ from those detected in male patients: J-shaped pituitary sella, enlargement of perivascular spaces, brain atrophy, mild T2-hyperintensity in the paratrigonal white matter, diffuse platyspondylia, and mild odontoid dysplasia with odontoid cup. Brain atrophy progressed despite ERT introduction, whereas perivascular space enlargement did not change significantly before and after ERT. Cognitive impairment worsened independently from the course of white matter abnormality. Despite a profound knowledge of genetic and biochemical aspects in MPS-II, neuroradiology is still poorly characterized, especially in female patients. Spinal and brain involvement and its natural course and evolution after ERT introduction still need to be clarified.