Repeated bilateral retrobulbar injection of botulinum toxin in a blind patient with retinitis pigmentosa and incapacitating nystagmus.

Pronounced visual loss can lead to nystagmus, provoking oscillopsia and distressing ocular sensations. The treatment of acquired nystagmus remains difficult and various therapeutic options are attempted with limited results. We report the case of a man with acquired nystagmus and excessive ocular discomfort, successfully treated with repeated retrobulbar injections with botulinum toxin.

Expanded motor and psychiatric phenotype in autosomal dominant Segawa syndrome due to GTP cyclohydrolase deficiency.

BACKGROUND: Segawa syndrome due to GTP cyclohydrolase deficiency is an autosomal dominant disorder with variable expression, that is clinically characterised by l-dopa responsive, diurnally fluctuating dystonia and parkinsonian symptoms. OBJECTIVE: To delineate the neurological and psychiatric phenotype in all affected individuals of three extended families. METHODS: GTP cyclohydrolase deficiency was documented by biochemical analyses, enzymatic measurements in fibroblasts, and molecular investigations. All affected individuals were examined neurologically, and psychiatric data were systematically reviewed. RESULTS: Eighteen affected patients from three families with proven GTP cyclohydrolase deficiency were identified. Eight patients presenting at less than 20 years of age had typical motor symptoms of dystonia with diurnal variation. Five family members had late-presenting mild dopa-responsive symptoms of rigidity, frequent falls, and tendonitis. Among mutation carriers older than 20 years of age, major depressive disorder, often recurrent, and obsessive-compulsive disorder were strikingly more frequent than observed in the general population. Patients responded well to medication increasing serotonergic neurotransmission and to l-dopa substitution. Sleep disorders including difficulty in sleep onset and maintenance, excessive sleepiness, and frequent disturbing nightmares were present in 55% of patients. CONCLUSION: Physicians should be aware of this expanded phenotype in affected members of families with GTP cyclohydrolase deficiency.

Surgical treatment outcomes of congenital and juvenile cataracts.

PURPOSE: Evaluation of visual outcome after lens aspiration with or without intraocular lens implantation for isolated congenital and juvenile cataract in children aged 6 years and younger. MATERIAL AND METHODS: Retrospective review of 48 children with isolated congenital and juvenile cataract who were surgically treated between January 1993 and December 2002 and had a minimal follow-up of 12 months. RESULTS: In the group of children with unilateral cataract, 33% (3 out of 9 children) of aphakic children and 45.5% (5 out of 11 children) of pseudophakic children attained a final best corrected visual acuity of 20/200 and 20/60 respectively. In the group of children with bilateral involvement, 35% (6 out of 17 children) of aphakic children have a final best corrected visual acuity of 20/30 and 63.7% (7 out of 11 children) of pseudophakic children have a final best corrected visual acuity of 20/25 or more. CONCLUSION: The results of this study emphasize the need for early surgery and good organisation of postsurgical care in patients with pediatric cataract to optimise visual outcome. Furthermore patients with isolated unilateral congenital cataract surgically treated at an average age of 15 months without primary lens implantation and with variable and low compliance have suboptimal results. The effect of early surgery with primary lens implantation on the long term visual outcome in pediatric cataract needs to be further evaluated.

Rett syndrome in females with CTS hot spot deletions: a disorder profile.

From a series of 107 females with Rett syndrome (RTT), we describe the long-term history of ten females with a deletion in the C-terminus of the MECP2 gene. We observed that their disorder profile is clinically recognizable with time and different from other atypical and milder RTT phenotypes. In females with hot spot deletions in the C-terminus, dystonia is present from childhood and results in a serious spine deformation in spite of preventive measures. Their adaptive behavior is surprisingly better preserved and in contrast with the typical decline in motor functioning. The delineation of disorder profiles by long-term clinical observation can teach us about genotype/phenotype relationships and eventually about the effect of epigenetic phenomena on the final phenotype.

House dust mite-specific T cells in healthy non-atopic children.

BACKGROUND: T-helper type 2 (Th2) cells play an important role in the pathogenesis of allergic diseases. Recent studies have demonstrated that allergen-specific T cells can also be found in the blood of healthy individuals. Both IL-10 and IFN-gamma might modulate the induction and maintenance of allergen-specific tolerance. AIM: To study the phenotype and functional characteristics of allergen-specific T cells in healthy non-atopic children. METHODS: Peripheral blood mononuclear cells (PBMC) from 13 symptomatic house dust mite (HDM)-allergic children and from nine matched healthy control children were stimulated with recombinant (r)Der p 2, a major allergen from HDMs. RESULTS: Stimulation with rDer p 2 resulted in Th2 cytokine production in cultures of PBMC from allergic but not from healthy children. In contrast, IL-10 and IFN-gamma were induced in PBMC cultures from both healthy and HDM-allergic children. Intracellular staining revealed that IL-10 and IFN-gamma are largely produced by the same T cells. Stimulation of T cells from healthy children with rDer p 2 also induced expression of inducible costimulator (ICOS) on a small T cell subset. CONCLUSION: Allergen-specific memory T cells from healthy non-atopic children produce IL-10 and IFN-gamma (but not Th2 cytokines) and express ICOS upon stimulation. These cells might be responsible for a normal immune balance after allergen encounter in non-atopics.

Ibuprofen and cerebral oxygenation and circulation.

The effect of prophylactic administration of ibuprofen on the cerebral circulation in preterm babies was measured with near infrared spectroscopy. No significant difference in the change in cerebral blood volume, change in cerebral blood flow, or tissue oxygenation index was found between administration of ibuprofen or placebo.

Continuous measurement of cerebral blood volume and oxygenation during rewarming of neonates.

AIM: To investigate the effect of rewarming in preterm infants presenting with hypothermia at admission. METHODS: The tissue oxygenation index (TOI), changes in cerebral blood volume (DeltaCBV) and changes in intravascular oxygenation (DeltaHbD) were measured in eight preterm infants, presenting with a temperature less than 35 degrees C at admission. RESULTS: A significant increase in HbD and TOI was seen in four patients (group A), while a significant increase in CBV and a decrease in HbD was seen in four other patients (group B). Retrospective analysis showed that group A had important signs of peripartal asphyxia. CONCLUSION: While infants with peripartal asphyxia showed an important increase in oxygenation during rewarming, no significant changes were seen in the non-asphyxiated infants.

Long chain polyunsaturated fatty acid supplementation in infant formula and blood pressure in later childhood: follow up of a randomised controlled trial.

OBJECTIVE: To determine whether supplementation of infant formula milk with long chain polyunsaturated fatty acids (LCPUFAs) influences blood pressure in later childhood. DESIGN: Follow up of a multicentre, randomised controlled trial. SETTING: Four study centres in Europe. PARTICIPANTS: 147 formula fed children, with a reference group of 88 breastfed children. INTERVENTION: In the original trial newborn infants were randomised to be fed with a formula supplemented with LCPUFAs (n=111) or a formula without LCPUFAs but otherwise nutritionally similar (n=126). In the present follow up study the blood pressure of the children at age 6 years was measured. MAIN OUTCOME MEASURES: Systolic, diastolic, and mean blood pressure. RESULTS: 71 children in the LCPUFA supplementation group (64% of the original group) and 76 children in the non-supplementation group (60%) were enrolled into the follow up study. The LCPUFA group had significantly lower mean blood pressure (mean difference -3.0 mm Hg (95% confidence interval -5.4 mm Hg to -0.5 mm Hg)) and diastolic blood pressure (mean difference -3.6 mm Hg (-6.5 mm Hg to -0.6 mm Hg)) than the non-supplementation group. The diastolic pressure of the breastfed children (n=88 (63%)) was significantly lower than that of the non-supplemented formula group but did not differ from the LCPUFA formula group. CONCLUSIONS: Dietary supplementation with LCPUFAs during infancy is associated with lower blood pressure in later childhood. Blood pressure tends to track from childhood into adult life, so early exposure to dietary LCPUFAs may reduce cardiovascular risk in adulthood.

The value of fast MR imaging as an adjunct to ultrasound in prenatal diagnosis.

The aim of this study was to evaluate the role of MR imaging of the fetus to improve sonographic prenatal diagnosis of congenital anomalies. In 40 fetuses (not consecutive cases) with an abnormality diagnosed with ultrasound, additional MR imaging was performed. The basic sequence was a T2-weighted single-shot half Fourier (HASTE) technique. Head, neck, spinal, thoracic, urogenital, and abdominal fetal pathologies were found. This retrospective, observational study compared MR imaging findings with ultrasonographic findings regarding detection, topography, and etiology of the pathology. The MR findings were evaluated as superior, equal to, or inferior compared with US, in consent with the referring gynecologists. The role of these findings in relation to pregnancy management was studied and compared with postnatal follow-up in 30 of 40 babies. Fetal MRI technique was successful in 36 of 39 examinations and provided additional information in 21 of 40 fetuses (one twin pregnancy with two members to evaluate). More precise anatomy and location of fetal pathology (20 of 40 cases) and additional etiologic information (8 of 40 cases) were substantial advantages in cerebrospinal abnormalities [ventriculomegaly, encephalocele, vein of Galen malformation, callosal malformations, meningo(myelo)cele], in retroperitoneal abnormalities (lymphangioma, renal agenesis, multicystic renal dysplasia), and in neck/thoracic pathology [cervical cystic teratoma, congenital hernia diaphragmatica, congenital cystic adenomatoid lung malformation (CCAM)]. This improved parental counseling and pregnancy management in 15 pregnancies. In 3 cases, prenatal MRI findings did not correlate with prenatal ultrasonographic findings or neonatal diagnosis. The MRI provided a more detailed description and insight into fetal anatomy, pathology, and etiology in the vast majority of these selected cases. This improved prenatal parental counseling and postnatal therapeutic planning.

Cerebral tissue oxygenation index in very premature infants.

AIM: To describe normal values of the cerebral tissue oxygenation index (TOI) in premature infants. METHODS: TOI was measured by spatially resolved spectroscopy in preterm infants on the first 3 days of life. Infants with an abnormal cranial ultrasound were excluded. Other simultaneously measured variables were PaO(2), PaCO(2), pH, mean arterial blood pressure, heart rate, haemoglobin, glycaemia, and peripheral oxygen saturation. RESULTS: Fifteen patients with a median postmenstrual age of 28 weeks were measured. There was a significant increase in median TOI over the first 3 days of life: 57% on day 1, 66.1% on day 2, and 76.1% on day 3. Multiple regression analysis showed no correlation between TOI and postmenstrual age, peripheral oxygen saturation, mean arterial blood pressure, PaO(2), PaCO(2), and haemoglobin concentration. CONCLUSION: Cerebral TOI increases significantly in the first 3 days of life in premature babies. This increase probably reflects the increase in cerebral blood flow at this time.

Effects of non-nutritive sucking on heart rate, respiration and oxygenation: a model-based signal processing approach.

Several studies support the idea that the use of pacifiers can reduce the risk of Sudden Infant Death Syndrome. To investigate the effect of non-nutritive sucking (NNS), we measured heart rate, abdominal respiration, EMG and arterial oxygen saturation of 20 neonates. Also, in 10 of these neonates, changes in cerebral hemoglobin concentrations were acquired by means of near-infrared spectroscopy. Using a parametric technique to model the heart rate as a sum of exponentially damped sinusoids, two main frequency components were found in the heart rate during NNS: a frequency of approximately 0.08 Hz due to the alternation of sucking bursts and pauses, and a frequency of approximately 0.8 Hz that reflects the influence of the respiration. Our analysis shows that it is the alternation of bursts and pauses itself that causes the increased heart rate variability, and that this is not due to increased effort. This suggests that the neuronal mechanism regulating NNS also stimulates the heart rate. From our measurements, no effect of NNS on cerebral or peripheral oxygenation could be found. Furthermore, we show that our model-based signal processing technique is well suited for the analysis of non-stationary biomedical signals.

Effects of preterm extrauterine visual experience on the development of the human visual system: a flash VEP study.

To compare the functional maturation of the human visual system between intra- and extrauterine course flash visual evoked potentials (VEPs) in preterm infants (gestational age 24 to 36 weeks). Previously established normal values, with special reference to the two components of the N1 wave, were employed (Tsuneishi 1995). A cross-sectional analysis of 124 infants at 36 weeks postmenstrual age (PMA), showed that there are no differences in the absolute values of VEP peak latencies depending on the postnatal age (PNA). Conversely, the N1 wave form changes with increasing PNA from a wave in which the early peak (N1a) has a higher amplitude than the late peak (N1b) into the reverse situation with a higher amplitude of the N1b as compared to N1a. This observation may correlate with the maturation of the neuronal networks in the visual cortex. In a longitudinal analysis of 50 infants followed for more than 5 sessions of weekly recordings, we found that the individual rapid decrease in the N1a latency, which may reflect the initiation of myelination in the optic radiation, most frequently occurs at around 37 weeks PMA, regardless of PNA. Preterm extrauterine visual experience has little effect on the myelination process in the visual pathway, but has a marked effect on the developmental changes in VEP wave form which reflect the developmental changes of the neuronal networks in the visual cortex.

Septo-optic dysplasia in combination with a pigmented skin lesion: a case report with nosological discussion.

In this case report a patient with bilateral optic nerve hypoplasia, schizencephaly and a pigmented skin lesion is described. The diagnosis of de Morsier syndrome or septo-optic dysplasia is put forward on the basis of the diagnosis of optic nerve hypoplasia. The differential diagnosis with Jadassohn's naevus phakomatosis is discussed. The importance of direct ophthalmoscopy of optic nerve abnormalities is stressed, as well as of magnetic resonance imaging, which has become a guideline in the classification of this syndrome.

Long-term external drainage for subdural collections in infants.

The treatment of subdural collections in infants remains controversial. In order to evaluate the treatment guidelines that we developed on the basis of our earlier experience, we have reviewed the results obtained in 31 consecutive infants with symptomatic chronic and subacute subdural collections treated with external drainage. Using our guidelines for removal of the drains, there was only a very low rate of permanent shunting (4/31), with a low complication rate and good clinical results. However, the long period of external drainage, and therefore of hospitalization, might make if general application of these guidelines problematic.

Acquired microcephaly after low Apgar score in Zimbabwe.

Serial head circumference measurements were made on 165 African babies born with a 5 min Apgar score of 5 or less. Measurements were taken at birth and at 4, 9, and 12 months of age. In the majority of infants the onset of microcephaly could be diagnosed as early as 4 months of age. Twenty-five of the 142 infants were microcephalic at 1 year. Neurological development was impaired in 19 of the 25 (76 per cent) microcephalic infants and in 18 of the 117 (15 per cent) normocephalic infants. Fourteen of the 16 (88 per cent) infants with severe quadriplegia developed microcephaly before the age of 4 months. A decreased rate of head growth during the first 4 months of life in African infants born with a low Apgar score correlates closely with the development of microcephaly. Infants with an acquired microcephaly have a high probability of developing neurologic impairment by the age of 1 year. Serial head circumference measurement in low Apgar score babies in developing countries is an easy, simple, and inexpensive method to detect microcephaly.

Results after surgery for lumbosacral lipoma: the significance of early and late worsening.

We retrospectively reviewed 32 patients operated on for lipoma of the conus and lipomyeloschisis, the two main anatomical subtypes of congenital lumbosacral lipomas associated with tethered cord syndrome. Surgery was proposed to patients when they were symptomatic, and in most cases for progressive symptoms. The evolution of the different symptoms was studied separately. In most patients, symptoms improved or stabilized after surgery; in some, however, postoperative worsening, at least of some of the symptoms, was seen. This postoperative worsening became apparent either early or late after the operation, and was not associated with surgical trauma or postoperative complications. We suggest it was caused mainly by the natural course of the disease (especially in the case of the orthopedic deformities), and in some cases by retethering. Our series is not large enough to detect statistical significance for the different symptoms or for the anatomical subgroups. Importantly, according to our analysis by the different symptoms, the operation did not seem to protect the patients from later development of new deficits. This can be interpreted as an argument against prophylactic surgery in asymptomatic patients.

Treatment of a symptomatic posterior fossa subdural effusion in a child.

We describe the first observation of a child with a posterior fossa subdural effusion with secondary hydrocephalus and tonsillar herniation. We diagnosed this entity in a 14-month-old girl with no history of trauma or coagulation disorder. The patient presented in our emergency department with opisthotonus and raised intracranial pressure resulting from supratentorial hydrocephalus. An emergency ventriculo-peritoneal shunt was placed, which resolved the symptoms only temporarily. Eventually external drainage of the subdural fluid was performed. The collection gradually disappeared, and both the external subdural shunt and the ventriculo-peritoneal shunt were removed. The patient made a complete neurological recovery. We review the physiopathology and treatment of subdural effusions in general, and propose some guidelines for the management of symptomatic effusions occurring in the posterior fossa in particular.

Neurodevelopmental outcome at 1 year in Zimbabwean neonates with extreme hyperbilirubinaemia.

UNLABELLED: The study concentrates on estimating the magnitude of the effect of a single risk factor, maximum total serum bilirubin (TSB) in excess of 400 micromol/l (23.4 mg/dl), on the neurodevelopmental outcome of 50, singleton, Zimbabwean neonates at 1 year of age. At 1 year corrected age the Bayley Scales of Infant Development (BSID) was administered. Two infants died and five were lost to follow up. TSB was neither associated with birth weight nor with gestational age. Of 43 infants with a TSB > 400 micromol/l (23.4 mg/dl),11(26%) scored abnormal on the BSID at 1 year of age and 5 (12%) infants developed the choreoathetoid type of cerebral palsy. CONCLUSION: Infants with bilirubin levels between 400 and 500 micromol/l (23.4 and 29.2 mg/dl) who scored abnormal or suspect on the Bayley Scales of Infant Development were preterm or had haemolytic disease. All term infants without haemolysis and with bilirubin levels between 400 and 500 micromol/l (23.4 mg/dl-29.2 mg/dl) were normal at 1 year of age.

PIP: The effect of maximum total serum bilirubin (TSB) in excess of 400 mcgmol/l (23.4 mg/dl) on neurodevelopmental outcome at 12 months was assessed in a follow-up study of 50 infants admitted to the Special Baby Care Unit of Mpilo Central Hospital in Bulawayo, Zimbabwe. There were 26 preterm infants (52%) in this series. 2 infants died before they reached 12 months of age and 5 were lost to follow-up. TSB levels were not associated with either birth weight or gestational age. Overall, 32 infants (74%) had Bayley Scales of Infant Development scores within the normal range. 11 (26%) of the 43 infants with extreme TSB (above 482 mcgmol/l) had suspect or abnormally low scores on the Bayley Scales and 5 of these infants (12%) developed the choreo-athetoid type of cerebral palsy. The infants with TSB levels of 400-500 mcgmol/l who had suspect or abnormal Bayley scores either had hemolytic disease or were premature. Finally, infants treated with exchange transfusion had higher TSB levels and 67% of transfused newborns demonstrated delayed development at 12 months of age.

Neuropathological findings in Moebius syndrome.

Pathological findings in two patients with Moebius syndrome and lethal fetal akinesia sequence are described. In both patients a congenital brain stem malformation with neuronal loss in the cranial nerve nuclei and tegmental microcalcifications was observed. In one patient, the association with splenogonadal fusion was observed, whilst in the second patient, the association with tetraperomelia was present. As the association of peromelia and splenogonadal fusion is a well-known association, the different combination of splenogonadal fusion, peromelia and Moebius syndrome due to congenital brain stem anomalies with necrosis might be the result of a disruptive phenomenon during a prolonged vulnerable critical period in the 5th and 6th week of embryonic life. The finding of olivary dysplasia in one case, reminiscent of olivary dysplasia in Zellweger syndrome and in Miller Dieker syndrome, might suggest a primary malformation underlying Moebius syndrome due to brain stem defects.