Inflammatory Type Focal Cerebral Arteriopathy of the Posterior Circulation in Children: A Comparative Cohort Study.

BACKGROUND: Inflammatory type focal cerebral arteriopathy (FCA-i) in the anterior circulation (AC) is well characterized, and the focal cerebral arteriopathy severity score (FCASS) reflects the severity of the disease. We identified cases of FCA-i in the posterior circulation (PC) and adapted the FCASS to describe these cases. METHODS: In this comparative cohort study, patients from the Swiss NeuroPaediatric Stroke Registry with ischemic stroke due to FCA-i between January 2000 and December 2018 were analyzed. A comparison between PC and AC cases regarding pediatric National Institutes of Health Stroke Scale score and pediatric stroke outcome measure and FCASS was performed. We estimated infarct size by the modified pediatric Alberta Stroke Program Early Computed Tomography Score in children with AC stroke and the adapted Bernese posterior diffusion-weighted imaging score in the PC. RESULTS: Thirty-five children with a median age of 6.3 (interquartile range, 2.7-8.2 [95% CI, 0.9-15.6]; 20 male; 57.1%) years with FCA-i were identified. The total incidence rate was 0.15/100 000/year (95% CI, 0.11-0.21). Six had PC-FCA-i. Time to final FCASS was longer in the PC compared with AC; the evolution of FCASS did not differ. Initial pediatric National Institutes of Health Stroke Scale score was higher in children with FCA-i in the PC with a median of 10.0 (interquartile range, 5.75-21.0) compared with 4.5 (interquartile range, 2.0-8.0) in those with AC-FCA-i. Different from the anterior cases, PC infarct volume did not correlate with higher discharge, maximum, or final FCASS scores (Pearson correlation coefficient [r], 0.25, 0.35, and 0.54). CONCLUSIONS: FCA-i also affects the PC. These cases should be included in future investigations into FCA-i. Although it did not correlate with clinical outcomes in our cohort, the modified FCASS may well serve as a marker for the evolution of the arteriopathy in posterior FCA-i.

Amplitude-Integrated EEG for Neurological Assessment and Seizure Detection in a German Pediatric Intensive Care Unit.

Objective: The aim of our study was to assess the use of aEEG in our pediatric intensive care unit (PICU), indications for neuromonitoring and its findings, utility for seizure detection, and associations with outcome. Design: We retrospectively analyzed non-neonates who were treated in our PICU and received amplitude-integrated EEG (aEEG). Patients: 27 patients aged between 29 days and 10 0/12 years (median 7.3 months) were included, who received a total of 35 aEEGS. Measurements: aEEG tracings were assessed for background (BG) pattern and its evolution, seizures, and side differences using a visual classification (Hellström-Westas). Clinical data were collected from patients' histories and analyzed for correlation with aEEG findings. Main results: While rare in early years, there was an increase in use over time. Most aEEGs were conducted because of (suspected) seizures or for management of antiepileptic treatment. aEEG had low sensitivity but high specificity for recognition of pathological BG pattern with reference to conventional EEG. Worsening of BG pattern or failure to improve was associated with death. Seizure detection rates by aEEG were higher than by clinical observation, especially for identification of non-convulsive epileptic state (ES). Side differences in aEEG were rare, but if present, they were associated with unilateral brain injury. Conclusions: aEEG is useful for the detection of seizures and ES in pediatric intensive care patients. Abnormal BG pattern and poor evolution of BG are negatively associated with survival. aEEG is a potential supplement to conventional EEG, facilitating long-term surveillance of cerebral function when continuous full-channel EEG is not available. Further investigation is needed.

Hemodialysis in MNGIE transiently reduces serum and urine levels of thymidine and deoxyuridine, but not CSF levels and neurological function.

Mitochondrial neurogastrointestinal encephalomyopathy (MNGIE) is a rare, autosomal-recessive mitochondrial disorder caused by TYMP mutations presenting with a multisystemic, often lethal syndrome of progressive leukoencephalopathy, ophthalmoparesis, demyelinating neuropathy, cachexia and gastrointestinal dysmotility. Hemodialysis (HMD) has been suggested as a treatment to reduce accumulation of thymidine and deoxyuridine. However, all studies so far have failed to measure the toxic metabolites in cerebrospinal fluid (CSF), which is the crucial compartment for CNS damage.Our study is the first prospective, longitudinal investigation, exploiting detailed serial testing of predefined clinical and molecular outcome parameters (including serial CSF assessments) in a 29-year-old MNGIE patient undergoing 1 year of extensive HMD. We demonstrate that HMD only transiently restores increased serum and urine levels of thymidine and deoxyuridine, but fails to reduce CSF levels of the toxic metabolites and is ineffective to influence neurological function. These findings have direct important implications for clinical practice: They prevent a burdensome, long-term invasive, but ultimately probably ineffective procedure in future MNGIE patients.

Brain morphometry in Pontocerebellar Hypoplasia type 2.

BACKGROUND: Pontocerebellar hypoplasia type 2 (PCH2) is caused by a defect in the TSEN54-gene and leads to severe and early disruption of brain development, especially of cerebellum and pons. The aim of this work was to quantify the infra- and supratentorial brain growth during postnatal brain development in children with PCH2. METHODS: MRI data of 24 children with PCH2 (age 0.02-17 years., 13 females) were analysed volumetrically and compared to images of 24 typically developing age- and gender-matched children. All children with PCH2 had the homozygous p.A307S mutation in the TSEN54-gene. In 5 patients follow-up MRI investigations were available. Images of the children with PCH2 were available either on film (n = 12) or in digital format (n = 21). Images on film were digitalized. Brain structures were manually masked and further adjusted semi-automatically using intensity thresholding to exclude CSF. Volumes of cerebellum, brain stem, and pons were measured, as well as supratentorial brain and frontal lobe volume. For validation of the method part of the digital images were processed as images on film. In addition, intra- and inter-rater variabilities were tested. RESULTS: Children with PCH2 showed reduced volumes of all measured brain structures compared to healthy controls. Severely hypoplastic cerebellum, pons and brain stem only slightly increased in size postnatally. Supratentorial brain volume also showed reduced growth compared to the healthy controls. Differences between patients and controls could already be seen at birth but became more significant during childhood. Validation of the method showed high precision and reproducibility. CONCLUSIONS: In a genetically very homogenous group of children with PCH2 severely hypoplastic infratentorial structures, the hallmark of the disease, showed only slight increase in volume postnatally. Supratentorial brain structures, which are considered normal at birth, also showed smaller volumes neonatally and a lower growth rate compared to controls, leading to severe microcephaly. Volume loss, however, could not be observed during the first years of life. This argues for a severe disruption of the cerebellar-cerebral networks during pre- and postnatal development caused by a primary cerebellar dysfunction, rather than postnatal neurodegeneration. The developmental progress in these children, although little, further supports this.

Nosological delineation of congenital ocular motor apraxia type Cogan: an observational study.

BACKGROUND: The nosological assignment of congenital ocular motor apraxia type Cogan (COMA) is still controversial. While regarded as a distinct entity by some authorities including the Online Mendelian Inheritance in Man catalog of genetic disorders, others consider COMA merely a clinical symptom. METHODS: We performed a retrospective multicenter data collection study with re-evaluation of clinical and neuroimaging data of 21 previously unreported patients (8 female, 13 male, ages ranging from 2 to 24 years) diagnosed as having COMA. RESULTS: Ocular motor apraxia (OMA) was recognized during the first year of life and confined to horizontal pursuit in all patients. OMA attenuated over the years in most cases, regressed completely in two siblings, and persisted unimproved in one individual. Accompanying clinical features included early onset ataxia in most patients and cognitive impairment with learning disability (n = 6) or intellectual disability (n = 4). Re-evaluation of MRI data sets revealed a hitherto unrecognized molar tooth sign diagnostic for Joubert syndrome in 11 patients, neuroimaging features of Poretti-Boltshauser syndrome in one case and cerebral malformation suspicious of a tubulinopathy in another subject. In the remainder, MRI showed vermian hypo-/dysplasia in 4 and no abnormalities in another 4 patients. There was a strong trend to more severe cognitive impairment in patients with Joubert syndrome compared to those with inconclusive MRI, but otherwise no significant difference in clinical phenotypes between these two groups. CONCLUSIONS: Systematical renewed analysis of neuroimaging data resulted in a diagnostic reappraisal in the majority of patients with early-onset OMA in the cohort reported here. This finding poses a further challenge to the notion of COMA constituting a separate entity and underlines the need for an expert assessment of neuroimaging in children with COMA, especially if they show cognitive impairment.

Natural course of pontocerebellar hypoplasia type 2A.

INTRODUCTION: Pontocerebellar hypoplasia Type 2 (PCH2) is a rare autosomal recessive condition, defined on MRI by a small cerebellum and ventral pons. Clinical features are severe developmental delay, microcephaly and dyskinesia.Ninety percent carry a p.A307S mutation in the TSEN54-gene. Our aim was to describe the natural course including neurological and developmental features and other aspects of care in a homogeneous group of PCH2 patients all carrying the p.A307S mutation. PATIENTS AND METHODS: Patients were recruited via the German patients' organizations. Inclusion criteria were imaging findings of PCH2 and a p.A307S mutation. Data were collected using medical reports and patient questionnaires discussed in a standardized telephone interview. RESULTS: Thirty-three patients were included. When considering survival until age 11 years, 53% of children had died Weight, length and head circumference, mostly in the normal range at birth, became abnormal, especially head circumference (-5.58 SD at age 5 yrs). Neurologic symptoms: Choreathetosis was present in 88% (62% with pyramidal signs), 12% had pure spasticity. Epileptic seizures were manifest in 82%, status epilepticus in 39%. Non-epileptic dystonic attacks occurred in 33%. General symptoms: feeding difficulties were recorded in 100%, sleep disorder in 96%, apneas in 67% and recurrent infections in 52%; gastroesophageal reflux disease was diagnosed in 73%, 67% got percutaneous endoscopic gastrostomy and 36% a Nissen-fundoplication. Neurodevelopmental data: All children made progress, but on a low level: such as fixing and following with the eyes was seen in 76%, attempting to grasp objects (76%), moderate head control (73%), social smile (70%), rolling from prone to supine (58%), and sitting without support (9%). Ten percent lost achieved abilities on follow-up. The presence of prenatal symptoms did not correlate with outcome. CONCLUSION: Phenotype of this genetically homogeneous group of PCH2 children was severe with reduced survival, but compatible with some developmental progress. Our data support the hypothesis of an early onset degeneration which thereafter stabilizes.

Possible effect of corticoids on hemiplegic attacks in severe hemiplegic migraine.

BACKGROUND: Sporadic and familial hemiplegic migraines are rare paroxysmal disorders characterized by transient hemiparesis and headache. The distinction is based on whether other family members are affected. In 50% of cases, these migraines are caused by CACNA1 A missense mutations. PATIENTS: We describe a boy with a particularly severe phenotype and a de novo R1349Q mutation of the CACNA1 A gene. RESULTS: The patient suffered from early-onset profound mental retardation, epileptic seizures, cerebellar ataxia, and progressive cerebellar atrophy. He experienced prolonged attacks of migraine with hemiparesis, seizures, altered consciousness, and fever resulting from minor head traumas. A prolonged hemiplegic attack improved following a 5-day treatment of 100 mg/d methylprednisolone. CONCLUSION: R1349Q mutation of the CACN1 A gene may be associated with a severe phenotype. Corticoids might be beneficial in prolonged hemiplegic attacks.

Twenty years of pulmonary tuberculosis in children: what has changed?

OBJECTIVES: To compare the frequency, clinical and radiologic manifestations and source of infection of pulmonary tuberculosis in children treated in our hospital during two decades (1978 through 1987 and 1988 through 1997) and to evaluate the influence of the emergence of HIV infection (since 1985) and the effect of the discontinuation of Calmette-Guérin bacillus (BCG) vaccination (since 1987) on childhood tuberculosis. METHODS: We reviewed 324 children diagnosed with pulmonary tuberculosis in our hospital during the 20 years (1978 through 1997). The data from 2 decades, 1978 through 1987 and 1988 through 1997, were compared. BCG vaccination in Spain was discontinued in 1987, and HIV infection emerged significantly as a public health problem. RESULTS: An increase in the number of children with single hilar adenopathy was observed (32.2% in 1978 through 1987 vs. 43.4%, in 1988 through 1997, P < 0.05) in comparison with those with parenchymal involvement or a mixed pattern (62.4% in 1978 through 1987 vs. 45.7% in 1988 to 1997). Frequency in extrapulmonary manifestations in both periods was similar, with a nonsignificant trend toward a lower rate of tuberculous meningitis in the latter decade (10.4 vs. 5.6%, P = 0.07). We were able to identify an adult source case for 67.1% of the children (100 of 149) in the first decade vs.58.3% (102 of 175) in the second (P = NS); 10.8% of adult contacts but only 2.3% of children (all of them in the second period) were HIV-positive. CONCLUSIONS: Discontinuation of BCG vaccination and emergence of HIV infection have had little influence on childhood tuberculosis in our area.