Distress and post-traumatic stress in parents of patients with congenital gastrointestinal malformations: a cross-sectional cohort study.

BACKGROUND: Congenital gastrointestinal malformation (CGIM) require neonatal surgical treatment and may lead to disease-specific sequelae, which have a potential psychological impact on parents. The aim of this study is to assess distress and symptoms of post-traumatic stress disorder (PTSD) in parents of patients with CGIM. In this cross-sectional study, seventy-nine parents (47 mothers and 32 fathers) of 53 patients with CGIM completed the Distress Thermometer for Parents (DT-P) and the Self Rating Scale for Posttraumatic Stress Disorders (SRS-PTSD) as part of the multidisciplinary follow-up of their children (aged 5-35 months). Group differences were tested between parents and representative Dutch reference groups with regard to rates of (clinical) distress and PTSD, and severity of overall distress and PTSD, for mothers and fathers separately. Mixed model regression models were used to study factors associated with the risk of (clinical) distress, PTSD and with severity of symptoms of PTSD (intrusion, avoidance and hyperarousal). RESULTS: Prevalence of clinical distress was comparable to reference groups for mothers (46%) and fathers (34%). There was no difference in severity of overall distress between both mothers as well as fathers and reference groups. Prevalence of PTSD was significantly higher in mothers (23%) compared to the reference group (5.3%) (OR = 5.51, p < 0.001), not in fathers (6.3% vs 2.2.%). Symptoms of intrusion were commonly reported by all the parents (75%). Longer total length of child's hospital stay was associated with more severe symptoms of intrusion, avoidance and hyperarousal. Child's length of follow-up was negatively associated with severity of intrusion. CONCLUSIONS: Having a child with CGIM has a huge impact on parents, demonstrated by a higher prevalence of PTSD in mothers, but not fathers, compared to parents in the general population. Monitoring of symptoms of PTSD of parents in follow-up is necessary.

Frontal ataxia in childhood.

Frontal ataxia may be the result of a unilateral frontal lesion. In this report three cases are presented with ataxia due to right frontal lesions. One case concerns a boy presenting with an unsteady gait and titubation of the trunk, mimicking developmental disequilibrium and with complex partial seizures. It proved to be caused by a small right-sided cavernoma in the middle frontal gyrus. After surgical intervention the symptoms and the seizures disappeared. Two subsequent cases concern teenage patients presenting with headache after an ENT infection and on physical examination mild dysmetric function of the upper limbs and slight disequilibrium, due to right-sided frontal lobe abscesses. After neurosurgical and antibiotic therapy the symptoms were relieved. The frontal origin of ataxia should be considered in children presenting with a "cerebellar syndrome". Frontal gait disorders consist of a clinical pattern of different gait disorders. The syndrome has been mentioned in the literature under different names. Our patients show signs compatible with the term frontal disequilibrium, a clinical pattern of frontal gait disorder. This assumes walking problems characterized by loss of control of motor planning, leading to imbalance. Remarkably, frontal ataxia may mimic developmental delay as demonstrated in the first case and may be the leading mild symptom in extensive frontal lobe damage as demonstrated by the two other cases. We suppose that frontal ataxia is the result of a disturbance in the cerebellar-frontal circuitries and an impairment of executive and planning functions of the basal ganglia-frontal lobe circuitry.

Hormonal determinants of pubertal growth.

Pubertal growth results from increased sex steroid and growth hormone (GH) secretion. Estrogens appear to play an important role in the regulation of pubertal growth in both girls and boys. In girls, however, estrogens cannot be the only sex steroids responsible for pubertal growth, as exogenous estrogens do not initiate a complete growth spurt. We therefore investigated the levels of the different sex steroids and GH, and related them to pubertal growth. In addition, we studied the process of bone maturation and mineralization during this period. Levels of both estrogens and androgens were found to increase at the start of the female pubertal growth spurt, and it was demonstrated that height velocity is related to levels of GH, estradiol and androstenedione, but not dehydroepiandrosterone sulfate. In boys, GH, testosterone and estradiol increased at the time of peak height velocity. Bone mineralization increased as puberty began, and was associated with the increase in height velocity. Osteocalcin, a marker of bone formation, declined when height velocity decreased, although bone maturation progressed at a steady rate. We conclude, therefore, that in girls, the concerted actions of estradiol, GH and androstenedione play a role in the pubertal growth spurt, whereas in boys this role is fulfilled by testosterone, GH and estradiol. During puberty, an advanced rate of bone maturation with respect to cross-sectional standards is a physiological phenomenon.

Clinical and biochemical effects of zileuton in patients with the Sjögren-Larsson syndrome.

UNLABELLED: The Sjögren-Larsson syndrome (SLS) is an inborn error of lipid metabolism, characterised clinically by congenital ichthyosis, mental retardation and spasticity. Patients also suffer from severe pruritus. The degradation of leukotriene (LT) B4 is one of the defective metabolic routes in SLS. Zileuton inhibits the synthesis of LTB4 and the cysteinyl leukotrienes. Five SLS patients were treated with zileuton for 3 months. Favourable effects were found on pruritus score (P = 0.006), general well-being, and background activity of electroencephalographic studies. Neuropsychological test results did not change significantly. There was, however, a clinically important trend towards improvement in the speed of information processing. Results of cerebral MRI and proton magnetic resonance spectroscopy did not change during therapy. Urinary concentrations of LTB4 and omega-OH-LTB4 decreased significantly (P=0.02 and P=0.003 respectively), while their concentrations in CSF were normal at baseline and remained so after therapy. CONCLUSION: Patients with Sjögren-Larsson syndrome might benefit from treatment with zileuton, especially with respect to the agonising pruritus. The findings reported here, point to a crucial role for leukotriene B4 in the pathogenesis of pruritus.

Recurrent alternating facial paralysis and malignant hypertension.

A previously healthy 11-year old girl with three episodes of alternating facial palsy is described. On examination during the third relapse a severe essential hypertension was diagnosed, accompanied by abnormalities on cerebral imaging, cardiac and fundoscopic investigations. Antihypertensive treatment normalized the hypertension. No relapse of the facial palsy occurred since. The objective of this communication is to draw the attention to hypertension as a possible cause of recurrent facial paralysis in children, to stress the importance of measuring the blood pressure and taking a thorough family history in every patient presenting with facial palsy.

Chemotherapy with Adriamycin (doxorubicin) and CCNU (lomustine) in four children with recurrent craniopharyngioma.

BACKGROUND: The prognosis of craniopharyngioma in children after subtotal surgical removal, followed by irradiation of remaining tumour with 50 Gy, is better than usually reported. In our subjects we found a relapse rate of 5% in the last 20 years. The treatment of recurrences forms a special problem because the possibilities of adjuvant radiotherapy are restricted. We report on a chemotherapeutic treatment after multiple or very rapid recurrences of craniopharyngioma in four children. METHODS: Four children experienced their first tumour recurrence at respectively 3, 8, 50 and 59 months after the initial treatment. New neurosurgical attempts to remove the recurring tumour, and in one patient a second course of radiotherapy, were performed, but there were two or more recurrences in these children, resulting in further restriction of surgical or radiotherapeutical possibilities. Chemotherapy was given, consisting of five intravenous ambulatory courses of Adriamycin (doxorubicin) (33 mg/m2/day, continuously over 3 days) together with oral CCNU (lomustine) (80 mg/m2 at day 1) at 6-weeks intervals. RESULTS: After the chemotherapy there was no further tumour recurrence after 12, 10, 3 and 3 years respectively. In the third patient a cystic relapse occurred after 3 years' remission. In the fourth patient a complete regression was observed of the cystic part of the tumour. The side-effects of the chemotherapy consisted of alopecia and bone marrow depression. No signs of cardiomyopathy have been found. CONCLUSION: Treatment of recurrent craniopharyngioma in children by chemotherapy with anthracyclines and nitrourea-derivates may be effective.

The Aircardi-Goutières syndrome: variable clinical expression in two siblings.

We report 2 siblings with the Aicardi-Goutières syndrome (encephalopathy, basal ganglia calcifications, and persistent cerebrospinal fluid pleiocytosis). The eldest sibling is severely retarded; his younger brother has only mild, slowly progressive neurological deficits. To our knowledge, such a striking difference in clinical expression has not been reported previously.

A new leukoencephalopathy with vanishing white matter.

We identified nine children with a leukoencephalopathy of similar type according to clinical and MRI findings. The patients included three affected sibling pairs. The age range was 3 to 19 years. The onset of the disease was in childhood; the course was both chronic-progressive and episodic. There were episodes of deterioration following infections and minor head traumas, and these could results in unexplained coma. In eight patients with advanced disease, MRI revealed a diffuse cerebral hemispheric leukoencephalopathy, in which increasing areas of the abnormal white matter had a signal intensity close to that of CSF on all pulse sequences. In one patient in the early stages of disease, initial MRI showed diffusely abnormal cerebral white matter, which only reached the signal characteristics of CSF at a later stage. In the patients in whom the disease was advanced, magnetic resonance spectroscopy (MRS) of the white matter showed an almost complete disappearance of all normal signals and the presence of glucose and lactate, compatible with the presence of mainly CSF and little brain tissue. Spectra of the cortex were much better preserved. However, in addition to the normal resonances, there were signals representing lactate and glucose. MRS of the white matter in the patient whose disease was at an early stage was much less abnormal. Autopsy in one patient confirmed the presence of extensive cystic degeneration of the cerebral white matter with reactive change and a preserved cortex. Typical involvement of pontine tegmental white matter was suggested by MRI and confirmed by autopsy. The disease probably has an autosomal recessive mode of inheritance, but the basic metabolic defect is not known.

Dihydropyrimidinase deficiency, a progressive neurological disorder?

A case of a child presenting with congenital abnormalities at birth is reported. The early development remained severely retarded and acquired skills minimally. The head circumference centile decreased. Magnetic resonance imaging showed progressive neuronal atrophy and secondary delay in myelination. Dihydropyrimidine concentrations in body fluids were quantitated by NMR spectroscopy. Enzymatic assay in the liver biopsy revealed total deficiency of dihydropyrimidinase (DHP) (5,6-dihydropyrimidine amidohydrolase; EC 3.5.2.2). As such, the patient is the first with enzymatically proven DHP deficiency. Thus far dihydropyrimidinuria has been reported in three other patients with a variety of neurological abnormalities. A relation of the enzyme deficiency with the neurodegenerative clinical course in our patient is suggested.

Serum procollagen I carboxyterminal propeptide (PICP) levels through puberty: relation to height velocity and serum hormone levels.

The synthesis of type I collagen, the major component of the organic bone matrix, is reflected by procollagen I carboxyterminal propeptide (PICP) levels. Conflicting reports have been made about the relationship between PICP levels and puberty. We have studied PICP levels in serum in relation to pubertal stage, height velocity, oestradiol, testosterone, androstenedione, dehydroepiandrosterone sulphate, insulin-like growth factor I and growth hormone levels in 32 healthy boys aged 7.2-15.8 years and 32 healthy girls aged 7.2-14.8 years. The PICP levels in girls tended to be higher during midpuberty: in boys the levels were higher at the end of puberty. The PICP levels correlated strongly with height velocity in boys and girls. In conclusion, PICP correlates especially with height velocity. The variation of PICP between subjects during puberty is considerable. The PICP levels may predict growth at a certain moment, especially in cases where only one height measurement is available.

Androstenedione, dehydroepiandrosterone sulfate, and estradiol levels throughout female puberty: relation to height velocity.

Sex steroids are important contributors to the pubertal growth spurt. Both androgens and estrogens have been related to this moment of rapid growth, but the role of estrogens is thought to be the most important one. Since exogenous estrogens are not capable to induce an appropriate growth spurt in girls, there might be an additional contributing factor involved. In a recent pilot study of 32 healthy pubertal girls, we found that the peak height velocity (HV) is preceded by relatively high levels of dehydroepiandrosterone sulfate and androstenedione (delta4A) as compared with the end-pubertal level. In the present study we evaluated HV in relation to dehydroepiandrosterone sulfate and delta4A levels in 149 healthy girls of various Tanner stages. HV was correlated with delta4A and estradiol levels in Tanner stages I-III. These results suggest that, like estrogens, delta4A might be an important stimulator of the female growth spurt.

Acute transverse myelopathy as the initial manifestation of probable systemic lupus erythematosus in a child.

A 10-year-old girl was presented with acute transverse myelopathy. She had three mild relapses within one year. Systemic lupus erythematosus (SLE) was suspected on the basis of positive antinuclear antibodies (ANA), moderately decreased total hemolytic complement, antibodies to histone, immunological abnormalities of kidney and skin biopsy. Symptoms of SLE involving other organs were absent.

Abnormal EMG and SSEP in a young child with an ependymoma.

We report our findings on a case of ependymoma in a one-year-old boy. A partial paresis of the left arm was found but the EEG and BAEP were normal. The EMG showed fibrillations and positive sharp waves in the paretic muscles and the SSEP showed a far field negativity. After removal of the cerebral process all neurophysiologic findings normalized. We discuss a hypothesis for the established clinical neurophysiological findings.

Occurrence of an astrocytoma in a patient with Williams syndrome.

The Williams elfin facies syndrome (Williams-Beuren syndrome) is a disorder characterized by a typical facies, supravalvular aortic stenosis and mental retardation. Its coexistence with a brain tumor has, so far, never been described. Recently, we treated a patient who was previously diagnosed as having Williams syndrome for a cerebral astrocytoma. In view of the incidence of astrocytomas in children and the occurrence of Williams syndrome, we want to report this coincidence.

The application of evoked potentials in the diagnosis and follow-up of children with intracranial tumors.

Somatosensory and brainstem auditory evoked potentials (SSEPs and BAEPs) provide sensitive measures of the central conduction functions of the auditory and somatosensory input systems at different levels of the central nervous system. The contribution of SSEPs and BAEPs in the primary diagnosis and follow-up of 26 children with infra- and supratentorial tumors were reviewed. The SSEPs, especially the specific complex, showed a latency increase in patients with supratentorial and brainstem mass lesions involving directly or distantly the somatosensory tracts. The BAEPs were sensitive for supratentorial pressure effects and for local and distant posterior fossa tumor effects. In the follow-up of children, evoked potentials offer a good method of detecting tumor recurrence, whereas neuroradiological procedures may be obscured by surgical or radiation artifacts.

Ultrasound detection of congenital arteriovenous aneurysm of the great cerebral vein of Galen.

Using combined echoencephalography and Doppler flow determination the diagnosis Arteriovenous aneurysm of the great cerebral vein of Galen could be made in two infants. Without vascular surgery one patient died, the other recovered completely. CT scanning confirmed the diagnosis. Invasive methods such as cerebral angiography were avoided. Case histories, neuropathological findings, ultrasound method and results are presented. Pathogenesis, clinical signs, treatment and prognosis are discussed. With the ultrasound method presented, the nature and location of the vascular anomaly were demonstrable, thus additional higher risk diagnostic methods could be avoided or planned more purposefully.

A new variant of glucosephosphate isomerase deficiency.

A new variant of glucose-6-phosphate isomerase deficiency is described. The enzyme kinetics and properties were studied. Genetic and electrophoretic data pointed to a double heterozygous state in the patient. These data are compared to the other variants described in the literature until now.