Search

Patients who undergo salivary gland, neck, or facelift surgery or suffer from diabetes mellitus often develop Frey syndrome (also known as auriculotemporal syndrome or gustatory sweating). Frey syndrome has been occasionally reported to occur in subjects without history of surgery or diabetes but this variant of Frey syndrome has not been systematically investigated. We searched for original articles of Frey syndrome unrelated to surgery or diabetes without date and language restriction. Article selection and data extraction were performed in duplicate. Our systematic review included 76 reports describing 121 individual cases (67 males and 54 females) of Frey syndrome not associated with surgery or diabetes. The age at onset of symptoms was ≤ 18 years in 113 (93%) cases. The time to diagnosis was 12 months or more in 55 (45%) cases. On the other hand, an allergy evaluation was performed in half of the cases. A possible cause for Frey syndrome was detected in 85 (70%) cases, most frequently history of forceps birth (N = 63; 52%). The majority of the remaining 22 cases occurred after a blunt face trauma, following an auriculotemporal nerve neuritis or in association with a neurocutaneous syndrome. The cause underlying Frey syndrome was unknown in 36 cases. Conclusion: Frey syndrome not associated with surgery or diabetes almost exclusively affects subjects in pediatric age and is uncommon and underrecognized. Most cases occur after forceps birth. There is a need to expand awareness of this pseudo-allergic reaction among pediatricians and allergists. What is Known:• Pre-auricular reddening, sweating, and warmth in response to mastication or a salivary stimulus characterize Frey syndrome.• It usually occurs after salivary gland surgery and in diabetes. What is New:• In children, Frey syndrome is rare, and most cases occur after a forceps-assisted birth.• In childhood, this condition is often erroneously attributed to food allergy.

Background Valproic acid is prescribed for epilepsy and as prophylaxis for bipolar disorder and migraine headaches. It has also been implicated as a cause of a kidney tubular injury. Methods We undertook a review of the literature to characterize the biochemical and histopathological features of the overt kidney tubular injury and to evaluate the possible existence of a pauci-symptomatic injury. The pre-registered review (CRD42022360357) was performed following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) methodology. Searches were conducted in Excerpta Medica, the National Library of Medicine, and Web of Science. The gray literature was also considered. Results For the final analysis, we retained 36 articles: 28 case reports documented 48 individuals with epilepsy on valproic acid for 7 months or more and presenting with features consistent with an overt kidney tubular injury. The following disturbances were noted: hypophosphatemia (N = 46), normoglycemic glycosuria (N = 46), total proteinuria (N = 45), metabolic acidosis (N = 36), hypouricemia (N = 27), tubular proteinuria (N = 27), hypokalemia (N = 23), and hypocalcemia (N = 8). A biopsy, obtained in six cases, disclosed altered proximal tubular cells with giant and dysmorphic mitochondria. Eight case series addressed the existence of a pauci- or even asymptomatic kidney injury. In the reported 285 subjects on valproic acid for 7 months or more, an isolated tubular proteinuria, mostly N-acetyl-β-glucosaminidase, was often noted. Conclusions Valproic acid may induce an overt kidney tubular injury, which is associated with a proximal tubular mitochondrial toxicity. Treatment for 7 months or more is often associated with a pauci- or oligosymptomatic kidney tubular injury. Graphical abstract

We aimed to assess the association of diabetes mellitus (DM) and admission hyperglycaemia (AH), respectively, and outcome in patients with acute ischaemic stroke with large vessel occlusion in the anterior circulation treated with endovascular therapy (EVT) in daily clinical practice.Consecutive EVT patients admitted to our stroke centre between February 2015 and April 2020 were included in this observational cohort study. Patients with versus without DM and with versus without AH (glucose ≥ 7.8 mmol/L) were compared.We included 1020 patients (48.9% women, median age = 73.1 years); 282 (27.6%) had DM, and 226 (22.2%) had AH. Patients with versus without DM less often showed successful reperfusion (odds ratio [OR]subadjusted/sub = 0.61, p = 0.023) and worse 3-month functional outcome (modified Rankin Scale [mRS] = 0-2: 31.3% vs. 48%, ORsubadjusted/sub = 0.59, p = 0.004; death: 38.9% vs. 24.1%, ORsubadjusted/sub = 1.75, p = 0.002; mRS shift: psubadjusted/sub lt; 0.0001; if moderate/good collaterals and mismatch, mRS = 0-2: ORsubadjusted/sub = 0.52, p = 0.005; death: ORsubadjusted/sub = 1.95, p = 0.005). If analysis was additionally adjusted for AH, only mRS shift was still significantly worse in patients with DM (psubadjusted/sub = 0.012). Patients with versus without AH showed similar successful reperfusion rates and worse 3-month functional outcome (mRS = 0-2: 28.3% vs. 50.4%, ORsubadjusted/sub = 0.52, p lt; 0.0001; death: 40.4% vs. 22.4%, ORsubadjusted/sub = 1.80, p = 0.001; mRS shift: psubadjusted/sub lt; 0.0001; if moderate/good collaterals and mismatch, mRS = 0-2: ORsubadjusted/sub = 0.38, p lt; 0.0001; death: ORsubadjusted/sub = 2.39, p lt; 0.0001). If analysis was additionally adjusted for DM, 3-month functional outcome remained significantly worse in patients with AH (mRS = 0-2: ORsubadjusted/sub = 0.58, p = 0.004; death: ORsubadjusted/sub = 1.57, p = 0.014; mRS shift: psubadjusted/sub = 0.004). DM independently predicted recurrent/progressive in-hospital ischaemic stroke (OR = 1.71, p = 0.043) together with admission National Institutes of Health Stroke Scale score (OR = 0.95, p = 0.005), and AH independently predicted in-hospital symptomatic intracranial haemorrhage (OR = 2.21, p = 0.001). The association of admission continuous glucose levels and most outcome variables was (inversely) J-shaped.Hyperglycaemia more than DM was associated with worse 3-month outcome in the patients studied, more likely so in the case of moderate/good collaterals and mismatch in admission imaging.

Background Kidney diseases are a recognized cause of posterior reversible leukoencephalopathy syndrome, usually abbreviated as PRES. The purpose of this review was to systematically address the association between acute postinfectious glomerulonephritis and PRES. Methods We performed a systematic review of the literature on acute postinfectious glomerulonephritis associated with PRES. The principles recommended by the Economic and Social Research Council guidance on the conduct of narrative synthesis and on the Preferred Reporting Items for Systematic Reviews and Meta-analyses were used. Databases searched included Excerpta Medica, US National Library of Medicine, and Web of Science. Results For the final analysis, we evaluated 47 reports describing 52 cases (32 males and 20 females). Fifty patients were ≤ 18 years of age. Blood pressure was classified as follows: normal-elevated (n = 3), stage 1 hypertension (n = 3), stage 2 hypertension (n = 5), and severe hypertension (n = 41). Acute kidney injury was classified as stage 1 in 32, stage 2 in 16, and stage 3 in four cases. Neuroimaging studies disclosed a classic posterior PRES pattern in 28 cases, a diffuse PRES pattern in 23 cases, and a brainstem-cerebellum PRES pattern in the remaining case. Antihypertensive drugs were prescribed in all cases and antiepileptic drugs in cases presenting with seizures. A resolution of clinical findings and neuroimaging lesions was documented in all cases with information about follow-up. Conclusions The main factor associated with PRES in acute postinfectious glomerulonephritis is severe hypertension. Prompt clinical suspicion, rapid evaluation, and management of hypertension are crucial. Graphical abstract A higher resolution version of the Graphical abstract is available as Supplementary information

Background and Purpose— Pediatric arterial ischemic stroke (AIS) is a rare disease leading to long-lasting neurological sequelae. Little is known about the long-term health-related quality of life (HRQoL) of these patients. The study aims to compare HRQoL in young adults who have had pediatric AIS with a healthy control group. Methods— A cross-sectional study compared self-rated HRQoL, depression, fatigability, and behavior in pediatric stroke survivors to healthy controls. Patients with a confirmed diagnosis of pediatric AIS who were ≥18 years at the time of recruitment and ≥2 years after acute AIS, as well as healthy controls ≥18 years matched for age, sex, and socioeconomic status were included. Primary outcome was HRQoL measured with the Short Form Health Survey. Results— Thirty-three patients (median [interquartile range] aged 22 years [20–26]; 22 males, 67%) and 71 controls (median [interquartile range] aged 23 years [21–25]; 41 males, 58%) were included. Overall, HRQoL, depression, or fatigability did not differ between the patients and the control group. Patients rated themselves lower on the disinhibition scale ( P =0.049) and tended to rate themselves lower on the executive dysfunction scale ( P =0.076). Patients with a poor outcome 24 months after AIS showed a clear trend toward impairment of executive functioning ( P =0.056) and work/productivity in the stroke-specific QoL ( P =0.05). Conclusions— Self-rated HRQoL, depression, and fatigability in adult pediatric stroke survivors are comparable to healthy adult peers. A poor outcome 24 months after acute stroke might affect work performance and executive functioning in adulthood.

Background: Cervical artery dissection is a major cause of stroke in young people (aged

A holocord syringomyelia due to Chiari 1.5 malformation (CM) in a 12-year-old girl was serially imaged with 3 T MRI over 4 years. The serial MRI showed reduction in size of the syrinx, without any surgical intervention or CM improvement, but rather due to spontaneous spinal cord tear. The tear was clearly demonstrated by evidence of flow signal across the tear between syrinx and subarachnoid space at the upper thoracic level. The tear showed spontaneous closure at follow-up. A medullary tear has been described in the adult population as one of the putative causes of spontaneous syringomyelia reduction, but its clear demonstration with modern high-resolution MRI has not been reported in the paediatric population. Moreover, this is the first reported case of syrinx reduction due to spontaneous fissuration in a paediatric patient.

ObjectiveTo compare risk factors, clinical presentation, and outcomes after posterior circulation arterial ischemic stroke (PCAIS) and anterior circulation arterial ischemic stroke (ACAIS) in neonates and children.MethodsIn this international multicenter observational study including neonates and children up to 18 years of age with arterial ischemic stroke (AIS), we compared clinical and radiologic features according to stroke location.ResultsOf 2,768 AIS cases, 507 (18%) were located in the posterior circulation, 1,931 (70%) in the anterior circulation, and 330 (12%) involved both. PCAIS was less frequent in neonates compared to children (8.8% vs 22%, p < 0.001). Children with PCAIS were older than children with ACAIS (median age 7.8 [interquartile range (IQR) 3.1–14] vs 5.1 [IQR 1.5–12] years, p < 0.001), and more often presented with headache (54% vs 32%, p < 0.001) and a lower Pediatric NIH Stroke Scale score (4 [IQR 2–8] vs 8 [IQR 3–13], p = 0.001). Cervicocephalic artery dissections (CCAD) were more frequent (20% vs 8.5%, p < 0.001), while cardioembolic strokes were less frequent (19% vs 32%, p < 0.001) in PCAIS. Case fatality rates were equal in both groups (2.9%). PCAIS survivors had a better outcome (normal neurologic examination at hospital discharge in 29% vs 21%, p = 0.002) than ACAIS survivors, although this trend was only observed in children and not in neonates.ConclusionPCAIS is less common than ACAIS in both neonates and children. Children with PCAIS are older and have a higher rate of CCAD, lower clinical stroke severity, and better outcome than children with ACAIS.

Purpose Knowledge about the localization and outcome of iatrogenic dissection (ID) during endovascular treatment of acute ischemic stroke (AIS) is limited. We aimed to determine the frequency, clinical aspects and morphology of ID in endovascular AIS treatment and to identify predictors of this complication. Methods Digital subtraction angiography (DSA) of ID carried out during endovascular treatment between January 2000 and March 2012 have been re-evaluated. The ID localization and morphology were analyzed and related to the interventional techniques. Baseline clinical and radiological findings, treatment modality and outcome were compared with patients without ID. Results Out of 866 patients 18 (2%) suffered an ID (44% female, median age 64 years). Localization was extracranial in 15 (83%, 14 internal carotid artery and 1 vertebral artery) and intracranial in 3 (17%; 1 vertebrobasilar dissection and 2 in the anterior circulation). Of the IDs 5 (28%) resulted in a high-degree, 3 (17%) in a moderate, 5 (28%) in a mild and 5 (28%) in no stenosis and 8 IDs were stented in the acute phase. At 3 months 7 (42%) patients had a favorable outcome (modified Rankin score mRS ≤ 2) and 6 (33%) patients had died. Patients with ID had a different stroke etiology (p = 0.041), were more likely to be smokers (44% versus 19%, p = 0.015) and were more likely to be treated with mechanical thrombectomy (100% versus 60%, p < 0.001). Although two ID patients had relevant complications, the outcome did not differ between the groups. Conclusion The occurrence of ID is a rare complication of endovascular AIS treatment associated with smoking and mechanical thrombectomy. Electronic supplementary material The online version of this article (10.1007/s00062-017-0639-z) contains supplementary material, which is available to authorized users.

Serum neurofilaments are markers of axonal injury. We addressed their diagnostic and prognostic role in acute ischemic stroke (AIS) and transient ischemic attack (TIA).Nested within a prospective cohort study, we compared levels of serum neurofilament light chain (sNfL) drawn within 24 h from symptom onset in patients with AIS or TIA. Patients without magnetic resonance imaging on admission were excluded. We assessed whether sNfL was associated with: (i) clinical severity on admission, (ii) diagnosis of AIS vs. TIA, (iii) infarct size on admission magnetic resonance diffusion-weighted imaging (MR-DWI) and (iv) functional outcome at 3 months.We analyzed 504 patients with AIS and 111 patients with TIA. On admission, higher National Institutes of Health Stroke Scale (NIHSS) scores were associated with higher sNfL: NIHSS score7, 13.1 pg/mL [interquartile range (IQR), 5.3-27.8]; NIHSS score 7-15, 16.7 pg/mL (IQR, 7.4-34.9); and NIHSS score15, 21.0 pg/mL (IQR, 9.3-40.4) (P = 0.01). Compared with AIS, patients with TIA had lower sNfL levels [9.0 pg/mL (95% confidence interval, 4.0-19.0) vs. 16.0 pg/mL (95% confidence interval, 7.3-34.4), P0.001], also after adjusting for age and NIHSS score (P = 0.006). Among patients with AIS, infarct size on admission MR-DWI was not associated with sNfL, either in univariate analysis (P = 0.15) or after adjusting for age and NIHSS score on admission (P = 0.56). Functional outcome 3 months after stroke was not associated with sNfL after adjusting for established predictors.In conclusion, among patients admitted within 24 h of AIS or TIA onset, admission sNfL levels were associated with clinical severity on admission and TIA diagnosis, but not with infarct size on MR-DWI acquired on admission or functional outcome at 3 months.

Background: Data on endovascular therapy (EVT) in patients with stroke attributable to CeAD is scarce. We performed a systematic review and meta-analysis of all studies comparing EVT to intravenous thrombolysis (IVT) in CeAD-patients and compared EVT to IVT with regard to 3-month outcome and complications. Additionally, we included data of IVT-/EVT-treated CeAD-patients from a Swiss multicenter IVT-/EVT registry based cohort study. Methods: We systematically searched the pubmed® database to identify all existing studies comparing IVT to EVT in CeAD-patients. Studies were eligible if IVT-treated CeAD- patients were compared to EVT-treated patients, and 3-month outcomes were reported as modified Rankin Scale (mRS) score. Outcome measures in this study were favorable 3-month outcome (i.e. mRS 0-2), excellent 3-month outcome (i.e. mRS 0-1), symptomatic intracranial hemorrhage (sICH) and death. Additionally, in a Swiss multicenter IVT-/EVT registry based cohort-study (SWISS) we identified all consecutive patients with ischemic stroke attributable to CeAD and included outcome data of these patients in our analyses. In a meta-analysis across all studies, we compared EVT to IVT with regard to primary and secondary outcome measures using a fixed-effect Mantel-Haenszel model. Results: The literature search yielded 388 results. We identified 7 eligible studies for a systematic comparison of EVT versus IVT. Data on 62 patients from the SWISS cohort were included as an additional study. In total, we compared EVT (n=102) versus IVT (n=110) in 212 CeAD-patients. With regard to the occurrence of mRS 0-2, there was no significant difference between both treatment groups (OR 1.04 (95% CI 0.57-1.88)). Separate Data on mRS 0-1 was available in 5 studies (OR 0.88 (95% CI 0.39-2.00)). There was no difference between groups with regard to death at 3 months (OR 0.66 (0.22-1.94)) which was separately reported in 6 studies. For sICH there were too few data (n=5 patients) available for meta-analysis. Conclusion: In this systematic review and meta-analysis of all existing studies comparing EVT to IVT in CeAD patients there was no clear signal of superiority of EVT. Further investigation of EVT with up-to-date devices is warranted.

Introduction In patients with stroke attributable to cervical artery dissection, we compared endovascular therapy to intravenous thrombolysis regarding three-month outcome, recanalisation and complications. Materials and methods In a multicentre intravenous thrombolysis/endovascular therapy-register-based cohort study, all consecutive cervical artery dissection patients with intracranial artery occlusion treated within 6 h were eligible for analysis. Endovascular therapy patients (with or without prior intravenous thrombolysis) were compared to intravenous thrombolysis patients regarding (i) excellent three-month outcome (modified Rankin Scale score 0–1), (ii) symptomatic intracranial haemorrhage, (iii) recanalisation of the occluded intracranial artery and (iv) death. Upon a systematic literature review, we performed a meta-analysis comparing endovascular therapy to intravenous thrombolysis in cervical artery dissection patients regarding three-month outcome using a random-effects Mantel–Haenszel model. Results Among 62 cervical artery dissection patients (median age 48.8 years), 24 received intravenous thrombolysis and 38 received endovascular therapy. Excellent three-month outcome occurred in 23.7% endovascular therapy and 20.8% with intravenous thrombolysis patients. Symptomatic intracranial haemorrhage occurred solely among endovascular therapy patients (5/38 patients, 13.2%) while four (80%) of these patients had bridging therapy; 6/38 endovascular therapy and 0/24 intravenous thrombolysis patients died. Four of these 6 endovascular therapy patients had bridging therapy. Recanalisation was achieved in 84.2% endovascular therapy patients and 66.7% intravenous thrombolysis patients (odds ratio 3.2, 95% confidence interval [0.9–11.38]). Sensitivity analyses in a subgroup treated within 4.5 h revealed a higher recanalisation rate among endovascular therapy patients (odds ratio 3.87, 95% confidence interval [1.00–14.95]), but no change in the key clinical findings. In a meta-analysis across eight studies (n = 212 patients), cervical artery dissection patients (110 intravenous thrombolysis and 102 endovascular therapy) showed identical odds for favourable outcome (odds ratio 0.97, 95% confidence interval [0.38–2.44]) among endovascular therapy patients and intravenous thrombolysis patients. Discussion and Conclusion In this cohort study, there was no clear signal of superiority of endovascular therapy over intravenous thrombolysis in cervical artery dissection patients, which – given the limitation of our sample size – does not prove that endovascular therapy in these patients cannot be superior in future studies. The observation that symptomatic intracranial haemorrhage and deaths in the endovascular therapy group occurred predominantly in bridging patients requires further investigation.

Ischaemic stroke (IS) in young adults has been increasingly recognized as a serious health condition. Stroke aetiology is different in young adults than in the older population. This study aimed to investigate aetiology and risk factors, and to search for predictors of outcome and recurrence in young IS patients. We conducted a prospective multicentre study of consecutive IS patients aged 16-55 years. Baseline demographic data, risk factors, stroke aetiology including systematic genetic screening for Fabry disease and severity were assessed and related to functional neurological outcome (modified Rankin Scale, mRS), case fatality, employment status, place of residence, and recurrent cerebrovascular events at 3 months. In 624 IS patients (60 % men), median age was 46 (IQR 39-51) years and median NIHSS on admission 3 (IQR 1-8). Modifiable vascular risk factors were found in 73 %. Stroke aetiology was mostly cardioembolism (32 %) and of other defined origin (24 %), including cervicocerebral artery dissection (17 %). Fabry disease was diagnosed in 2 patients (0.3 %). Aetiology remained unknown in 20 %. Outcome at 3 months was favourable (mRS 0-1) in 61 % and fatal in 2.9 %. Stroke severity (p

Aims The use of topiramate, which is prescribed for the management of epilepsy, for migraine headache prophylaxis and as a weight-loss agent, has been associated with the development of metabolic acidosis, hypokalaemia and renal stone disease. We systematically reviewed all the literature.

Background and Purpose— To compare potential risk factors, clinical symptoms, diagnostic delay, and 3-month outcome between spontaneous internal carotid artery dissection (sICAD) and spontaneous vertebral artery dissection (sVAD). Methods— We compared patients with sICAD (n=668) and sVAD (n=302) treated in 3 university hospitals. Results— Patients with sICAD were older (46.3±9.6 versus 42.0±10.2 years; P P =0.004), and presented more frequently with tinnitus (10.9% versus 3.4%; P s of Health Stroke Scale, 10±7.1 versus 5±5.9; P P P =0.007). Thunderclap headache (9.2% versus 3.6%; P =0.001) and neck pain were more common (65.8% versus 33.5%; P P P P =0.21), and all other variables remained significant. Time to diagnosis was similar in sICAD and sVAD and improved between 2001 and 2012 compared with the previous 10-year period (8.0±10.5 days versus 10.7±13.2 days; P =0.004). In sVAD, favorable outcome 3 months after ischemic stroke (modified Rankin Scale, 0–2: 88.8% versus 58.4%; P P =0.001), and recurrent ischemic stroke (2.8% versus 0.7%; P =0.02) within 3 months were more frequent. Conclusions— sICAD and sVAD patients differ in many aspects. Future studies should perform separate analyses of these 2 entities.

Aim Little is known about basilar artery stroke (BAS) in children. The objective of this study was to calculate the incidence of BAS in children and to analyse the clinical presentation, risk factors, radiological findings, therapeutic approaches, and outcome of BAS in childhood. Method A prospective, population-based study including children with arterial ischaemic stroke and a systematic review of the literature was undertaken. Results Seven children with BAS were registered at the Swiss Neuropaediatric Stroke Registry between January 2000 and June 2011 (incidence 0.037 per 100 000 children per year, 95% confidence interval [CI] 0.013–0.080). A further 90 cases were identified through the literature search. The majority of patients were male (73 males, 24 females) and the median age was 9 years (interquartile range [IQR]=6–13y). The median Pediatric National Institutes of Health Stroke Scale (PedNIHSS) score was 15 (IQR=4–27). Presenting signs and symptoms comprised impaired consciousness (n=64), quadri- or hemiparesis (n=58), bulbar dysfunction (n=46), vomiting, nausea (n=43), and headache (n=41). Prodromes occurred in 43% of cases. Aetiology was largely vasculopathic (n=38), but often unknown (n=40). Time to diagnosis varied from hours days; six patients received antithrombotic, thrombolytic, or mechanical endovascular treatment 12 hours or less after symptom onset. Outcome was good (modified Rankin Scale 0–2) in 45 patients; eight died. PedNIHSS score of up to 17 was a prognostic factor for good outcome. Interpretation BAS is rare in children. Compared with adults, outcome is more favourable despite a considerable delay in diagnosis and treatment. Outcome was better in children with a PedNIHSS score of 17 or less.

Sodium channel gene aberrations are associated with a wide range of seizure disorders, particularly Dravet syndrome. They usually consist of missense or truncating gene mutations or deletions. Duplications involving multiple genes encoding for different sodium channels are not widely known. This article summarizes the clinical, radiologic, and genetic features of patients with 2q24 duplication involving the sodium channel gene cluster.

Objective: To describe a novel pattern of magnetic resonance imaging (MRI) abnormalities as well as the associated clinical and laboratory findings. Design: The MRIs of more than 3000 patients with an unclassified leukoencephalopathy were systematically reviewed. Clinical and laboratory data were retrospectively collected. Setting: University hospital. Patients: Seven patients (3 male) shared similar MRI abnormalities and clinical features. Main Outcome Measures: Pattern of MRI abnormalities and clinical and laboratory findings. Results: The MRIs showed signal abnormalities of the deep cerebral white matter, corpus callosum, thalamus, basal ganglia, brainstem, and cerebellar white matter between the ages of 9 months and 2 years. On follow-up, abnormalities gradually improved. Clinical regression occurred in the second half-year of life with spasticity and loss of milestones. From the second year on, clinical improvement occurred. So far, no second episode of regression has happened. Lactate levels were elevated during clinical regression. Conclusion: These patients represent a single novel leukoencephalopathy, probably caused by a mitochondrial defect. Arch Neurol. 2012; 69(6): 718-722. Published online February 6, 2012. doi:10.1001/archneurol.2011.1048

OBJECTIVE This study explored whether acute serum marker S100B is related with post-concussive symptoms (PCS) and neuropsychological performance 4 months after paediatric mild traumatic brain injury (mTBI). RESEARCH DESIGN AND METHODS This prospective short-term longitudinal study investigated children (aged 6-16 years) with mTBI (n = 36, 16 males) and children with orthopaedic injuries (OI, n = 27, 18 males) as a control group. S100B in serum was measured during the acute phase and was correlated with parent-rated PCS and neuropsychological performance 4 months after the injury. MAIN OUTCOMES AND RESULTS The results revealed no between-group difference regarding acute S100B serum concentration. In children after mTBI, group-specific significant Spearman correlations were found between S100B and post-acute cognitive PCS (r = 0.54, p = 0.001) as well as S100B and verbal memory performance (r = -0.47, p = 0.006). In children after OI, there were insignificant positive relations between S100B and post-acute somatic PCS. In addition, insignificant positive correlations were found between neuropsychological outcome and S100B in children after OI. CONCLUSIONS S100B was not specific for mild brain injuries and may also be elevated after OI. The group-specific association between S100B and ongoing cognitive PCS in children after mTBI should motivate to examine further the role of S100B as a diagnostic biomarker in paediatric mTBI.

PURPOSE OF REVIEW Although arterial hypertension is less common in children than in adults, there is growing concern about elevated blood pressure (BP) in children and adolescents not only because of the association of elevated values with the overweight epidemic, but also as cardiovascular functions are determined in childhood and track into adulthood. The purpose of the review is to discuss new aspects of childhood hypertension. RECENT FINDINGS Guidelines advocate determining BP in children as part of routine health maintenance. This recommendation was recently subject to review by the US Preventive Services Task Force. It was concluded that evidence is insufficient to assess the benefits of this screening. In our opinion, however, assessing BP is part of any thorough physical examination.Sophisticated approaches demonstrate the role of sympathetic nervous system overdrive in the field of sympathetic cardiovascular modulation of childhood arterial hypertension. SUMMARY Elevated BP in children is increasing in frequency and is now recognized as having relevant short-term and long-term consequences. Although efforts to address the childhood overweight epidemic may eventually reduce the number of young patients with hypertension, improved therapies for childhood hypertension also offer the potential for preventing or ameliorating early cardiovascular disease.

International audience; Spontaneous intracranial artery dissection is an uncommon and probably underdiagnosed cause of stroke that is defined by the occurrence of a haematoma in the wall of an intracranial artery. Patients can present with headache, ischaemic stroke, subarachnoid haemorrhage, or symptoms associated with mass effect, mostly on the brainstem. Although intracranial artery dissection is less common than cervical artery dissection in adults of European ethnic origin, intracranial artery dissection is reportedly more common in children and in Asian populations. Risk factors and mechanisms are poorly understood, and diagnosis is challenging because characteristic imaging features can be difficult to detect in view of the small size of intracranial arteries. Therefore, multimodal follow-up imaging is often needed to confirm the diagnosis. Treatment of intracranial artery dissections is empirical in the absence of data from randomised controlled trials. Most patients with subarachnoid haemorrhage undergo surgical or endovascular treatment to prevent rebleeding, whereas patients with intracranial artery dissection and cerebral ischaemia are treated with antithrombotics. Prognosis seems worse in patients with subarachnoid haemorrhage than in those without.

In 2006, hypomagnesemia was first described as a complication of proton-pump inhibitors. To address this issue, we systematically reviewed the literature. Hypomagnesemia, mostly associated with hypocalcemic hypoparathyroidism and hypokalemia, was reported in 64 individuals on long-term proton-pump inhibitors. Hypomagnesemia recurred following replacement of one proton-pump inhibitor with another but not with a histamine type-2 receptor antagonist. The association between proton-pump inhibitors and magnesium metabolism was addressed in 14 case-control, cross-sectional studies. An association was found in 11 of them: 6 reports found that the use of proton-pump inhibitors is associated per se with a tendency towards hypomagnesemia, 2 found that this tendency is more pronounced in patients concurrently treated with diuretics, carboplatin, or cisplatin, and 2 found a relevant tendency to hypomagnesemia in patients with poor renal function. Finally, findings likely reflecting decreased intestinal magnesium uptake were observed on treatment with proton-pump inhibitors. Three studies did not disclose any relationship between magnesium metabolism and treatment with histamine type-2 receptor antagonists. In conclusion, proton-pump inhibitors may cause hypomagnesemia. In these cases, switching to a histamine type-2 receptor antagonist is advised.

Erratum in: Familial occurrence and heritable connective tissue disorders in cervical artery dissection. [Neurology. 2016]; International audience; In a large series of patients with cervical artery dissection (CeAD), a major cause of ischemic stroke in young and middle-aged adults, we aimed to examine frequencies and correlates of family history of CeAD and of inherited connective tissue disorders. We combined data from 2 large international multicenter cohorts of consecutive patients with CeAD in 23 neurologic departments participating in the CADISP-plus consortium, following a standardized protocol. Frequency of reported family history of CeAD and of inherited connective tissue disorders was assessed. Putative risk factors, baseline features, and 3-month outcome were compared between groups. Among 1,934 consecutive patients with CeAD, 20 patients (1.0%, 95% confidence interval: 0.6%-1.5%) from 17 families (0.9%, 0.5%-1.3%) had a family history of CeAD. Family history of CeAD was significantly more frequent in patients with carotid location of the dissection and elevated cholesterol levels. Two patients without a family history of CeAD had vascular Ehlers-Danlos syndrome with a mutation in COL3A1. This diagnosis was suspected in 2 additional patients, but COL3A1 sequencing was negative. Two patients were diagnosed with classic and hypermobile Ehlers-Danlos syndrome, one patient with Marfan syndrome, and one with osteogenesis imperfecta, based on clinical criteria only. In this largest series of patients with CeAD to date, family history of symptomatic CeAD was rare and inherited connective tissue disorders seemed exceptional. This finding supports the notion that CeAD is a multifactorial disease in the vast majority of cases.

OBJECTIVE To compare long-term outcome of children and young adults with arterial ischemic stroke (AIS) from 2 large registries. METHODS Prospective cohort study comparing functional and psychosocial long-term outcome (≥2 years after AIS) in patients who had AIS during childhood (1 month-16 years) or young adulthood (16.1-45 years) between January 2000 and December 2008, who consented to follow-up. Data of children were collected prospectively in the Swiss Neuropediatric Stroke Registry, young adults in the Bernese stroke database. RESULTS Follow-up information was available in 95/116 children and 154/187 young adults. Median follow-up of survivors was 6.9 years (interquartile range 4.7-9.4) and did not differ between the groups (p = 0.122). Long-term functional outcome was similar (p = 0.896): 53 (56%) children and 84 (55%) young adults had a favorable outcome (modified Rankin Scale 0-1). Mortality in children was 14% (13/95) and in young adults 7% (11/154) (p = 0.121) and recurrence rate did not differ (p = 0.759). Overall psychosocial impairment and quality of life did not differ, except for more behavioral problems among children (13% vs 5%, p = 0.040) and more frequent reports of an impact of AIS on everyday life among adults (27% vs 64%, p < 0.001). In a multivariate regression analysis, low Pediatric NIH Stroke Scale/NIH Stroke Scale score was the most important predictor of favorable outcome (p < 0.001). CONCLUSION There were no major differences in long-term outcome after AIS in children and young adults for mortality, disability, quality of life, psychological, or social variables.

Objective: There is evidence that children after mild traumatic brain injuries (mTBI) suffer ongoing post-concussive symptoms (PCS). However, results concerning neuropsychological outcome after mTBI are controversial. Thus, our aim was to examine group differences regarding neuropsychological outcome and PCS. Additionally, we explored the influence of current and pre-injury everyday attention problems on neuropsychological outcome in children after mTBI. Method: In a prospective short-term longitudinal study, 40 children (aged 6–16 years) after mTBI and 38 children after orthopedic injury (OI) underwent neuropsychological, socio-behavioral and PCS assessments in the acute stage and at 1 week, at 4 weeks, and 4 months after the injury. Results: Parents of children after mTBI observed significantly more PCS compared to parents of children after OI, especially in the acute stage. Our results revealed no neuropsychological or socio-behavioral differences over time between both groups. However, in children after mTBI, we found negative correlations between elevated levels of everyday attention problems and reduced neuropsychological performance. Furthermore, there was a negative influence of pre-injury everyday attention problems on neuropsychological performance in children after mTBI. Conclusion: In accordance with earlier studies, parents of children after mTBI initially observed significantly more PCS compared to parents of children after OI. There were no neuropsychological or socio-behavioral group differences between children after mTBI and OI in the post-acute period. However, our exploratory findings concerning the influence of everyday attention problems on neuropsychological outcome indicate that current and pre-injury everyday attention problems were negatively associated with neuropsychological performance in children after mTBI. (JINS, 2014, 20, 1–12)

Ein hoher Konsum von Kochsalz ist ein Risikofaktor fur ein Schlaganfall-Erstereignis, ein Schlaganfall-Rezidiv und eine erhohte Mortalitat bei Schlaganfall.

The use of topiramate, which is prescribed for the management of epilepsy, for migraine headache prophylaxis and as a weight-loss agent, has been associated with the development of metabolic acidosis, hypokalaemia and renal stone disease. We systematically reviewed all the literature.The systematic review of the literature was realized using the principles underlying the UK Economic and Social Research Council guidance on the conduct of narrative synthesis and the Preferred Reporting Items for Systematic Reviews and Meta-Analyses statement.Fourty-seven reports published between 1996 and 2013 were retained for the final analysis. Five case-control studies and six longitudinal studies addressed the effect of topiramate on acid-base and potassium balance. A significant tendency towards mild-to-moderate hyperchloraemic metabolic acidosis (with bicarbonate ≤21.0 mmol l(-1) in approximately every third case) and mild hypokalaemia (with potassium ≤3.5 mmol l(-1) in 10% of the cases) was noted on treatment with topiramate, which was similar in children and adults. A single study observed that topiramate causes mild hyperuricaemia in male adults. A tendency towards hypocitraturia, a recognized promoter of renal stone formation, was noted in all patients on topiramate.Increasing evidence supports the use of topiramate. Topiramate is generally well tolerated, and serious adverse events are rare. Nonetheless, the present systematic review of the literature indicates that its use is linked with the development of acidosis, hypokalaemia, hyperuricaemia and hypocitraturia.

BACKGROUND Signs of nervous system dysfunction such as headache or convulsions often occur in severe systemic hypertension. Less recognized is the association between severe hypertension and peripheral facial nerve palsy. The aim of this study was to systematically review the literature on the association of peripheral facial palsy with severe hypertension. METHODS Systematic review of Medline, Embase, Web of Science, and Google Scholar from 1960 through December 2011 and report of two cases. RESULTS The literature review revealed 24 cases to which we add two cases with severe hypertension and peripheral facial palsy. Twenty-three patients were children. Palsy was unilateral in 25 cases, bilateral in one case, and recurred in nine. The time between the first facial symptoms and diagnosis of hypertension was a median of 45 days (range, 0 days-2 years). In five case series addressing the complications of severe hypertension in children, 41 further cases of peripheral facial palsy were listed out of 860 patients (4.8%). CONCLUSIONS The association between severe hypertension and peripheral facial palsy is mainly described in children. Arterial hypertension is diagnosed with a substantial delay. Outcome is favorable with adequate antihypertensive treatment. The pathophysiology is still debated

Little is known about basilar artery stroke (BAS) in children. The objective of this study was to calculate the incidence of BAS in children and to analyse the clinical presentation, risk factors, radiological findings, therapeutic approaches, and outcome of BAS in childhood.A prospective, population-based study including children with arterial ischaemic stroke and a systematic review of the literature was undertaken.Seven children with BAS were registered at the Swiss Neuropaediatric Stroke Registry between January 2000 and June 2011 (incidence 0.037 per 100,000 children per year, 95% confidence interval [CI] 0.013-0.080). A further 90 cases were identified through the literature search. The majority of patients were male (73 males, 24 females) and the median age was 9 years (interquartile range [IQR]=6-13y). The median Pediatric National Institutes of Health Stroke Scale (PedNIHSS) score was 15 (IQR=4-27). Presenting signs and symptoms comprised impaired consciousness (n=64), quadri- or hemiparesis (n=58), bulbar dysfunction (n=46), vomiting, nausea (n=43), and headache (n=41). Prodromes occurred in 43% of cases. Aetiology was largely vasculopathic (n=38), but often unknown (n=40). Time to diagnosis varied from hours days; six patients received antithrombotic, thrombolytic, or mechanical endovascular treatment 12 hours or less after symptom onset. Outcome was good (modified Rankin Scale 0-2) in 45 patients; eight died. PedNIHSS score of up to 17 was a prognostic factor for good outcome.BAS is rare in children. Compared with adults, outcome is more favourable despite a considerable delay in diagnosis and treatment. Outcome was better in children with a PedNIHSS score of 17 or less.

Sodium channel gene aberrations are associated with a wide range of seizure disorders, particularly Dravet syndrome. They usually consist of missense or truncating gene mutations or deletions. Duplications involving multiple genes encoding for different sodium channels are not widely known. This article summarizes the clinical, radiologic, and genetic features of patients with 2q24 duplication involving the sodium channel gene cluster.A systematic review of the literature and report of two cases.Nine individuals with 2q24 duplication involving the sodium channel gene cluster are described (seven female, two male). All presented with severe seizures refractory to anticonvulsant drugs. Seizure onset was in the neonatal period in eight patients with SCN1A-involvement, in infancy in one patient with SCN2A and SCN3A, but no SCN1A involvement. Seizure activity decreased and eventually stopped at 5-20 months of age. Seizures recurred at the age of 3 years in the patient with SCN2A and SCN3A, but no SCN1A involvement. Eight patients had a poor neurodevelopmental outcome despite seizure freedom.This article describes a distinct seizure disorder associated with a duplication of the sodium gene cluster on 2q24 described in otherwise healthy neonates and infants with severe, anticonvulsant refractory seizures and poor developmental outcome despite seizure freedom occurring at the age of 5-20 months.

Purpose: Optic pathway gliomas, which occur in 15-20% of paediatric patients with neurofibromatosis type 1, are the most common central nervous system tumour associated with this neurocutaneous disorder. The detection of optic pathway gliomas is essential for further management but is often delayed in infancy due to oligosymptomatic progression and difficulties in clinical detection. Therefore, the aim of our study was to find a clinical indicator for the presence of optic pathway gliomas in children with neurofibromatosis type 1 in order to facilitate early diagnosis and initiate further ophthalmological and neuroimaging investigations. Methods: We retrospectively evaluated 70 patients (mean age of 10.5years; SD of 4.3years; range of 0.5-19.6years; 35 females) with neurofibromatosis type 1 seen at the University Children's Hospital of Bern, Switzerland, between January 1998 and December 2008 regarding clinical features of neurofibromatosis type 1 in relation to the presence of optic pathway gliomas. Results: Fifty-seven of the 70 patients (81.4%) had no clinical or radiological signs of optic pathway gliomas [magnetic resonance imaging (MRI) of the brain in 26/57], whereas 13/70 patients (18.6%) were diagnosed with optic pathway gliomas by MRI. Patients with optic pathway gliomas showed macrocephaly significantly more often compared to patients without optic pathway gliomas (8/13 vs. 9/57, respectively; p = 0.004). Conclusion: Macrocephaly significantly correlates with the incidence of optic pathway gliomas in children with neurofibromatosis type 1. We therefore hypothesise that in otherwise asymptomatic patients, macrocephaly is an additional indicator for performing MRI to detect optic pathway gliomas

OBJECTIVE: CNS or peripheral nervous system dysfunction sometimes occurs in Henoch-Schönlein patients. METHODS: We review all Henoch-Schönlein cases published after 1969 with CNS dysfunction without severe hypertension and neuroimaging studies (n = 35), cranial or peripheral neuropathy (n = 15), both CNS and peripheral nervous system dysfunction without severe hypertension (n = 2) or nervous system dysfunction with severe hypertension (n = 2). Forty-four of the 54 patients were