Relationship between temperature variability and brain injury on magnetic resonance imaging in cooled newborn infants after perinatal asphyxia.

OBJECTIVE: The objective of the study was whether temperature management during therapeutic hypothermia correlates with the severity of brain injury assessed on magnetic resonance imaging in term infants with hypoxic-ischemic encephalopathy. STUDY DESIGN: Prospectively collected register data from the National Asphyxia and Cooling Register of Switzerland were analyzed. RESULT: Fifty-five newborn infants were cooled for 72 h with a target temperature range of 33 to 34 °C. Individual temperature variability (odds ratio (OR) 40.17 (95% confidence interval (CI) 1.37 to 1037.67)) and percentage of temperatures within the target range (OR 0.95 (95% CI 0.90 to 0.98)) were associated with the severity of brain injury seen on magnetic resonance imaging (MRI). Neither the percentage of measured temperatures above (OR 1.08 (95% CI 0.96 to 1.21)) nor below (OR 0.99 (95% CI 0.92 to 1.07) the target range was associated with the severity of brain injury seen on MRI. CONCLUSION: In a national perinatal asphyxia cohort, temperature variability and percentage of temperatures within the target temperature range were associated with the severity of brain injury.

Diagnostic accuracy and limitations of post-mortem MRI for neurological abnormalities in fetuses and children.

AIM: To compare the diagnostic accuracy of non-invasive cerebral post-mortem magnetic resonance imaging (PMMRI) specifically for cerebral and neurological abnormalities in a series of fetuses and children, compared to conventional autopsy. MATERIALS AND METHODS: Institutional ethics approval and parental consent was obtained. Pre-autopsy cerebral PMMRI was performed in a sequential prospective cohort (n = 400) of fetuses (n = 277; 185 ≤ 24 weeks and 92 > 24 weeks gestation) and children <16 years (n = 123) of age. PMMRI and conventional autopsy findings were reported blinded and independently of each other. RESULTS: Cerebral PMMRI had sensitivities and specificities (95% confidence interval) of 88.4% (75.5 to 94.9), and 95.2% (92.1 to 97.1), respectively, for cerebral malformations; 100% (83.9 to 100), and 99.1% (97.2 to 99.7) for major intracranial bleeds; and 87.5% (80.1 to 92.4) and 74.1% (68 to 79.4) for overall brain pathology. Formal neuropathological examination was non-diagnostic due to maceration/autolysis in 43/277 (16%) fetuses; of these, cerebral PMMRI imaging provided clinically important information in 23 (53%). The sensitivity of PMMRI for detecting significant ante-mortem ischaemic injury was only 68% (48.4 to 82.8) overall. CONCLUSIONS: PMMRI is an accurate investigational technique for identifying significant neuropathology in fetuses and children, and may provide important information even in cases where autolysis prevents formal neuropathological examination; however, PMMRI is less sensitive at detecting hypoxic-ischaemic brain injury, and may not detect rarer disorders not encountered in this study.

RYR1-related congenital myopathy with fatigable weakness, responding to pyridostigimine.

The spectrum of RYR1 mutation associated disease encompasses congenital myopathies, exercise induced rhabdomyolysis, malignant hyperthermia susceptibility and King-Denborough syndrome. We report the clinical phenotype of two siblings who presented in infancy with hypotonia and striking fatigable ptosis. Their response to pyridostigimine was striking, but genetic screening for congenital myasthenic syndromes was negative, prompting further evaluation. Muscle MRI was abnormal with a selective pattern of involvement evocative of RYR1-related myopathy. This directed sequencing of the RYR1 gene, which revealed two heterozygous c.6721C>T (p.Arg2241X) nonsense mutations and novel c.8888T>C (p.Leu2963Pro) mutations in both siblings. These cases broaden the RYR1-related disease spectrum to include a myasthenic-like phenotype, including partial response to pyridostigimine. RYR1-related myopathy should be considered in the presence of fatigable weakness especially if muscle imaging demonstrates structural abnormalities. Single fibre electromyography can also be helpful in cases like this.

A Clinically Severe Variant of ß-Mannosidosis, Presenting with Neonatal Onset Epilepsy with Subsequent Evolution of Hydrocephalus.

ß-Mannosidosis results from a functional deficiency of the lysosomal enzyme, ß-mannosidase. While being a well recognised, naturally occurring disease in both goats and cattle, it is an extremely rare disorder in humans with the first cases only being recorded in 1986. Until now the severity of the human disease has not mirrored that of its bovine or caprine counterparts, whose presentation is typically in the neonatal period with both altered skull morphology and seizures. Human ß-mannosidosis has previously appeared to be a more indolent disease, with its only consistent phenotypic feature being developmental delay of varying severity. We report a patient, homozygous for a private mutation, who presented in the immediate perinatal period with seizures and who subsequently developed communicating hydrocephalus at 2 years of age.These are two new phenotypic features for ß-mannosidosis. The first being the neonatal onset of the seizures, for while seizures have been seen in 3 out of the previous 20 documented cases, they have never before manifested prior to 6 months of age. However, as in the previous documented cases, the seizures were difficult to control and were associated with severe developmental delay.The second unique feature about this case was the development of communicating hydrocephalus. We discuss the possible mechanisms of its development.In summary, ß-mannosidosis must thus now be considered in the differential diagnosis of neonatal onset seizures, and the potential for the development of hydrocephalus should be monitored during subsequent clinical follow-up.

Severe iron deficiency anaemia and ischaemic stroke in children.

Iron deficiency anaemia (IDA) has a peak prevalence of 4-8% in children aged 1-3 years of age and is known to be associated with developmental delay, lethargy, irritability and cognitive problems. Rarely, IDA has also been reported as a risk factor for stroke in otherwise healthy children. We report a series of four young children aged 14 months to 48 months with significant IDA. Three children had venous sinus thrombosis and one had arterial ischaemic stroke, without other risk factors. We discuss the potential underlying mechanisms and review the relevant literature. This report further consolidates the evidence for a strong association between IDA and childhood stroke and highlights an easily treatable (and preventable) risk factor.

Spontaneous rapid resolution of acute basal ganglia changes in an untreated infant with propionic acidemia: a clue to pathogenesis?

Basal ganglia lesions are a well reported feature of acute decompensation in propionic acidemia; however, their underlying causation still needs to be fully elucidated. We report an 8-month-old infant whose lesions had almost completely resolved radiologically within 3 weeks of initial presentation without specific metabolic management and in light of this, we discuss the current thinking on their pathogenesis.

CT and MRI appearances of inflammatory pseudotumour of the cervical lymph nodes.

Inflammatory pseudotumour (IPT), also known as plasma cell granuloma and inflammatory myofibroblastic tumour, is a rare cause of benign cervical lymphadenopathy which mimics malignant causes of cervical lymphadenopathy. The imaging features of IPT affecting the cervical lymph nodes have not previously been described. We present cross sectional imaging in a case of IPT occurring in a 42-year-old African-Caribbean man, from his initial presentation to a subsequent spontaneous reduction in the extent of lymphadenopathy.

Spontaneous regression of supratentorial intracerebral Langerhans' cell histiocytosis.

Langerhans' cell histiocytosis (LCH) describes a group of conditions affecting the reticuloendothelial system. It includes the subtypes of Letterer-Siwe disease, Hand-Schuller-Christian disease and eosinophilic granuloma and most often presents in childhood. Intracranial involvement in LCH is usually restricted to the hypothalamic-pituitary axis or involves extra-axial extension from skull vault lesions. Supratentorial intracerebral lesions with mass effect and enhancement have rarely been described and are not included in the magnetic resonance based classification system of neurological LCH. We present the MRI of a patient with multisystem LCH with spontaneous resolution of enhancing temporal lobe lesions.

Magnetic resonance image registration and subtraction in the assessment of minor changes in low grade glioma volume.

The purpose of this study was to apply image registration and subtraction to standard T2-weighted (T2-W) and FLAIR magnetic resonance imaging (MRI) protocols in an attempt to improve the detection of minor changes in low grade glioma volume. Thirteen patients with low grade glial tumours and minimal or no apparent change on serial MRI scans were prospectively recruited for the study. Forty-two pairs of images were compared (T2-W sequences in 27/27 and FLAIR sequences in 15/27). The image pairs were registered, subtracted and randomised. Three independent raters assigned non-parametric ratings according to the dominant volume change for unregistered, registered and subtracted image sets. There was a statistically significant improvement in the detection of tumour volume change using T2-W registration and T2-W and FLAIR registration/subtraction relative to unregistered images. The reproducibility and increased sensitivity of FLAIR images relative to T2-W images were most apparent when registration was applied. Smaller degrees of low grade glioma tumour volume change are detectable using image registration and subtraction techniques that can be applied successfully to images acquired with standard clinical protocols.