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Biomedical subjects

F Kirkham

Publications and source records attributed to F Kirkham.

11 recordsLinked to original sources

Which paediatric head injured patients might benefit from decompression? Thresholds of ICP and CPP in the first six hours.

Severe head injury in childhood continues to be associated with considerable mortality and morbidity. Early surgical decompression may be beneficial and the objective of this study was to examine the relationship between age-related thresholds of mean intracranial pressure (ICP) and cerebral perfusion pressure (CPP) over the first 6 hours and age outcome in paediatric head injury patients. A total of 209 head injured children admitted to five UK hospitals were studied. Patients aged 2 to 16 years were included if they had a minimum of six hours of invasive pressure monitoring. Mean values of ICP and CPP over this period were calculated and compared to those with independent (good recovery and moderate disability) and poor outcome (severe disability, and death) for different age groups. There were 148 children with independent outcome (92 good recovery, 56 moderately disabled), and 61 with poor outcome (30 severely disabled, 31 deaths). There was a significant difference between those with independent compared to poor outcome in relation to ICP (p < 0.001) and CPP (p < 0.001). Patients were divided into three groups according to age. The sensitivity of ICP and CPP in predicting outcome was similar for all groups but the specificity differed between groups. At a CPP of 50 mmHg the specificity varied between the age groups (2 to 6 years: 0.47, 7 to 10 years: 0.28 and 11 to 16 years: 0.10) and similarly for an ICP of 25 mmHg (2 to 6 years: 0.53, 7 to 10 years: 0.44 and 11 to 16 years: 0.38). Younger children may be able to tolerate lower perfusion pressures and still have an independent outcome. Our threshold values for young children are likely to be important in the identification of patients who might benefit from new treatments such as surgical decompression.

Adolescent↗

Cardiopulmonary bypass temperature and brain function.

A debate has emerged in recently published studies about the optimum cardiopulmonary bypass temperature for good neurological outcome - warm vs. cold, i.e. normothermic vs. hypothermic. Although many comparative studies have been performed, the results of these studies are inconclusive and are difficult to interpret. Brain function has been studied in terms of neurological and neuropsychological outcome, protein S100beta levels as a marker of brain damage, and cerebral oxygenation using jugular bulb oximetry and near-infrared spectroscopy. The studies produce no conclusive proof of the superiority of warm or cold cardiopulmonary bypass. However, it appears that any degree of bypass hypothermia (< 35 degrees C) may protect the brain. On the other hand, even a slight increase in bypass temperature to > 37 degrees C may cause marked brain injury.

Brain↗

A pilot study of evaluation of cerebral function by S100beta protein and near-infrared spectroscopy during cold and warm cardiopulmonary bypass in infants and children undergoing open-heart surgery.

Cerebral injury in children undergoing cardiopulmonary bypass (CPB) remains a major source of morbidity. The effect of cardiopulmonary bypass temperature on cerebral function in terms of serum S100beta protein level and cerebral oxygenation monitored by near infrared spectroscopy (NIRO-300) in children is not known. In this study, 18 children undergoing open-heart surgery at the Hospital for Sick Children in London were equally assigned by minimisation to warm (35 +/- 1 degrees C) or cold (25 +/- 1 degrees C) CPB. Changes in S100beta protein and cerebral oxygenation were studied in both groups. S100beta protein serum level increased significantly after CPB in both groups. There was no significant difference in serum S100beta protein concentrations between the two groups. However, cerebral oxygenation in terms of tissue oxygen index (TOI) was significantly impaired during rewarming from cold CPB. Five patients were desaturated (TOI < 50%) during rewarming in the cold bypass group compared to two in the warm patients. This study supports the use of warm CPB in children undergoing open-heart surgery, although further studies recruiting more patients are warranted.

Biomarkers↗

Homozygous thermolabile variant of the methylenetetrahydrofolate reductase gene: a potential risk factor for hyperhomocysteinaemia, CVD, and stroke in childhood.

In this study of 118 children (median age 5.1 years; range 6 months to 17 years) with ischaemic stroke or transient ischaemic attack (TIA), 22 children (19%) were homozygous for the thermolabile variant of the methylenetetrahydrofolate reductase allele (t-MTHFR), compared with nine of 78 (12%) of a reference population (p=0.18, OR 1.76, 95% CI 0.76 to 4.04). Of those with cerebrovascular disease (CVD), 17 of 84 were homozygous for the t-MTHFR allele (p=0.13 compared with the reference population (OR 1.95, 95% CI 0.81 to 4.65). There was a significant (p<0.025) increment of plasma total homocysteine concentration in homozygotes for the t-MTHFR allele compared with heterozygotes, negatives for the t-MTHFR allele, and control children with no history of stroke. In four of 12 homozygotes for the t-MTHFR allele, plasma homocysteine levels were raised, compared with three of 38 of those who were negative or heterozygous (p=0.047; OR 5.8, 95% CI 1.1 to 31.2). Homozygotes for the t-MTHFR allele were significantly more likely to have a recurrent event than those who were negative or heterozygous (Cox regression p=0.031, hazard ratio 2.18, 95% CI 1.08 to 4.42). These data suggest that homozygosity for the t-MTHFR allele is associated with raised homocysteine levels in children and is a risk factor for primary and secondary stroke and TIA.

Adolescent↗

Electroencephalographic and clinical features of cerebral malaria.

BACKGROUND: Seizures are a prominent feature of childhood cerebral malaria, and are associated with an increased risk of death and neurological sequelae. We present the electroencephalographic (EEG) findings from a detailed clinical and electrophysiological study. METHODS: Children with cerebral malaria had EEGs recorded within six hours of admission, and at 12 hourly intervals until recovery of consciousness. Ten deeply comatose children underwent intracranial pressure monitoring. Children were not mechanically ventilated, which made it possible to directly correlate the clinical and EEG findings. RESULTS: Of 65 children aged 9 months and above, 40 had one or more seizures, and 18 had an episode of status epilepticus. Most seizures were partial motor, and spike wave activity consistently arose from the posterior temporo-parietal region, a border zone area lying between territories supplied by the carotid and vertebrobasilar circulations. Fifteen children had seizures that were clinically subtle or electrographic. Clinical seizures were associated with an abrupt rise in intracranial pressure. Fifty children recovered fully, seven died, and eight had persistent neurological sequelae. Initial EEG recordings of very slow frequency, or with background asymmetry, burst suppression, or interictal discharges, were associated with an adverse outcome. CONCLUSIONS: Serial EEG recording has uncovered a range of clinical, subtle, and electrographic seizures complicating childhood cerebral malaria, and has emphasised their importance in the pathogenesis of coma. Further work is required to determine the most appropriate regimen for the prophylaxis and treatment of seizures in cerebral malaria, in order to improve outcome.

Analysis of Variance↗

Hyponatraemia associated with lamotrigine in cranial diabetes insipidus.

We report the cases of two children with cranial diabetes insipidus who were treated with lamotrigine for seizures and who had accompanying changes in desmopressin requirements. Lamotrigine is a new anticonvulsant chemically unrelated to other existing antiepileptic drugs. Studies suggest it acts at voltage-sensitive sodium channels and also decreases calcium conductance. Both of these mechanisms of action are shared by carbamazepine, which can cause hyponatraemia secondary to inappropriate secretion of antidiuretic hormone. It is possible that the effect of lamotrigine on fluid balance in the cases described is also centrally mediated.

Adolescent↗

Fatal haemorrhagic infarct in an infant with homocystinuria.

Thrombotic and thromboembolic complications are the main causes of morbidity and mortality in patients with homocystinuria. However, it is unusual for thrombosis and infarction to be the presenting feature leading to investigation for homocystinuria and cerebrovascular lesions in the first year of life. We describe a previously healthy 6-month-old infant who presented with a large middle-cerebral-artery territory infarction and died of massive brain swelling. Homocystinuria due to cystathionine beta-synthase (CBS) deficiency was diagnosed by metabolite analysis and confirmed by enzymatic activity measurement in a postmortem liver biopsy. Homocystinuria should be considered in the differential diagnosis of venous or arterial thrombosis, regardless of age, even in the absence of other common features of the disease. We recommend systematic metabolic screening for hyperhomocysteinemia in any child presenting with vascular lesions or premature thromboembolism.

Brain Edema↗

[The role of resistance to C active protein (R-APC) in a pediatric stroke].

INTRODUCTION: Activated protein C resistance is a recently identified thrombophylic state which results from a mutation in the factor V gene and has been shown to be an important risk factor for peripheral venous thrombosis. We report a case of paediatric stroke in whom we have identified APC resistance. CLINICAL CASE: A boy presented acutely at the age of 6 years with a severe right sided headache, vomiting, unsteadiness and drowsiness which worsened over a period of 40 hours. Prior to this episode, he was neurologically and developmentally normal except for occasional headaches. CT showed low attenuation in the left cerebellar hemisphere, and occipital lobe associated with acute hydrocephalus. Excision biopsy of the left cerebellar cortex revealed inflammation and possible infarction. Although he remained in a 'locked-in' state with a flaccid quadriparesis for six months, he improved and was left with a left side hemiplegia, multiple cranial nerve palsies and a visual field defect. He represented at the age of thirteen years with transient ischaemic attacks and was found be heterozygous for the factor V Leiden mutation. Since he has been warfarinised, his symptoms have improved. CONCLUSIONS: Although cerebellar stroke in childhood is rare, it has been underdiagnosed in the past. As recurrence is common, patients should be fully investigated and followed up long term. Screening for new factor such as APC-resistance is recommended.

Adolescent↗

Seizures and status epilepticus in childhood cerebral malaria.

Prolonged, multiple seizures complicate a high proportion of cases of childhood cerebral malaria, and several studies have shown an association between these and neurological sequelae. We prospectively studied 65 patients (38 female) admitted to Kilifi Hospital in 1994. Electroencephalographic recordings (EEGs) were made at 12-hourly intervals, with continuous recordings made on a cerebral function analysing monitor (CFAM). Survivors were seen one month after discharge. Cerebral computerized tomography was performed on children with neurological sequelae. Sixty-two percent of patients had seizures following admission, of whom half had an episode of status epilepticus. Fifty-two percent of seizures were partial motor, 34% generalized tonic-clonic, and 14% partial with secondary generalization. In 22%, coma appeared to be due to a prolonged postictal state. Ten children had subtle motor seizures. Posterior parieto-temporal discharges were the most common EEG finding. Seven children died, eight developed neurological sequelae, and 50 (77%) recovered fully. Status epilepticus was associated with the development of neurological sequelae. Prolonged, multiple seizures may play an important part in the pathogenesis of coma in childhood cerebral malaria, and are likely to contribute to both the morbidity and mortality of this disease.

Brain↗

Peripheral neuropathy and neuromuscular blockade presenting as prolonged respiratory paralysis following critical illness.

We report two patients who following critical illness presented with generalised paralysis associated with persistent failure to breathe. Both patients eventually recovered and were weaned from the ventilator. The cause of the paralysis was an unusual peripheral neuropathy in the first patient and persistent neuromuscular blockade secondary to vecuronium in the second. It is important to consider a reversible, possibly even iatrogenic, cause of this type of complication.

Acute Disease↗