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Biomedical subjects

Eugen Boltshauser

Publications and source records attributed to Eugen Boltshauser.

35 records · Page 2Linked to original sources
PubMed2004

Novel mutation in the tyrosine kinase domain of FGFR2 in a patient with Pfeiffer syndrome.

Mutations in the fibroblast growth factor receptor 2 (FGFR2) cause a variety of craniosynostosis syndromes. The mutational spectrum tends to be narrow with the majority of mutations occurring in either exon IIIa or IIIc or in the intronic sequence preceding exon IIIc. Mutations outside of this hotspot are uncommon and the few identified mutations have demonstrated wide clinical variability, making it difficult to establish a clear-cut genotype-phenotype correlation. To better delineate the clinical picture associated with these unusual mutations, we describe a severely affected patient with Pfeiffer syndrome and a missense mutation in the tyrosine kinase (TK) domain of FGFR2.

Acrocephalosyndactylia↗
PubMed2004

Natural history of twin disruption sequence.

Intrauterine death of one fetus in a monochorionic twin pregnancy is associated with high morbidity and mortality in the surviving co-twin. Thromoboplastic material from the dead twin may pass to the circulation of the living twin via placental anastomoses and cause tissue necrosis by direct embolization or by activating intravascular coagulation. Alternatively, acute blood loss into the dying twin through placental anastomoses may result in hypotension and hypoxic-ischemic damage to cerebral and visceral tissue in the surviving twin. The resulting clinical picture is referred to as twin disruption sequence. Affected twins have rarely been followed beyond the neonatal period and the long-term development of such children is unknown. Here, we present a natural history and neurological assessment of 18 patients with twin disruption sequence, whom we have followed over several months to years.

Abnormalities, Multiple↗
PubMed2004

Cerebellum-small brain but large confusion: a review of selected cerebellar malformations and disruptions.

Defining and classifying congenital disorders of the cerebellum can be difficult and confusing. One reason is that some abnormalities called "malformations" are not truly (primary) developmental malformations. This applies to Chiari I "malformations" as well as to Chiari II "malformations." The latter results mainly from a prenatal cerebrospinal fluid (CSF) leak. Also disruptive cerebellar lesions are not uncommon, examples being the "vanishing cerebellum" in myelomeningocele, cerebellar lesions in very low birth weight prematurely born infants, unilateral cerebellar hypoplasia/aplasia, and probably some instances of cerebellar agenesis (CA). The cerebellar hypoplasias consist of a heterogeneous group of inherited and prenatally acquired conditions. The concept of pontocerebellar hypoplasias will need to be expanded beyond the two main types (PCH-1 and PCH-2), and demonstrate that a classification system of cerebellar malformations cannot be based on neuroimaging criteria only. Additional studies are expected to show that this also applies to the molar tooth sign, which was initially described in Joubert syndrome (JS). The JS is the prototype of midhindbrain malformation, but its delineation is still unsolved. JS may well be an overdiagnosed entity; many cases likely not having JS are on record. Rhombencephalosynapsis (RS) has been increasingly diagnosed with the advent of neuroimaging. No familial cases have been observed. Although many affected individuals have variable impairments, RS can be found in children with normal cognitive function. In this review, some of the cerebellar anomalies are briefly discussed.

Arnold-Chiari Malformation↗
PubMed2004

Severe neurological impairment in hereditary methaemoglobinaemia type 2.

UNLABELLED: Recessive congenital methaemoglobinaemia (RCM) due to NADH-cytochrome b5 reductase (cytb5r) deficiency is a very rare disorder. We report on two unrelated patients (4 and 2.5 years old) with RCM type 2. Developmental delay was obvious at the age of 4 months. On follow-up, both children showed severe tetraspastic cerebral palsy, profound cognitive impairment, strabismus, impressive secondary microcephaly and failure to thrive. One novel mutation in the DIA1gene was identified. Prenatal diagnosis was successfully done in both families by mutation analysis in chorionic villi or measurement of cytb5r in fetal amniotic cells. CONCLUSION: Due to the severity of this disease and its 25% recurrence risk, prenatal diagnosis should be made available to all affected families.

Child, Preschool↗
PubMed2004

Progressive encephalopathy with edema, hypsarrhythmia and optic atrophy (PEHO) syndrome in a Swiss child.

Progressive encephalopathy with edema, hypsarrhythmia and optic atrophy (PEHO) syndrome is a rare neurodegenerative syndrome first reported in 1991. Most patients described are of Finnish descent and very few patients have been reported in other countries. We report the first Swiss patient who fulfils the criteria of the PEHO syndrome. The course of the epilepsy is less severe than previously reported. Our patient developed a severe dystonic state after a febrile gastrointestinal infection, with a hypotonic state that may have been a dysregulation of brainstem origin. The diagnosis was made because of marked cerebellar atrophy in the repeated MRI. In patients with infantile spasms and severe developmental delay PEHO syndrome should be considered; it is not confined to Finnish heritage. Optic atrophy should be looked for and repeat MRI is indicated.

Atrophy↗
PubMed2004

Outcome of craniopharyngioma in children: long-term complications and quality of life.

Childhood craniopharyngiomas are histologically benign tumours arising from remnants of Rathke's pouch in the hypothalamic-pituitary region. The two common treatment approaches are primary total resection or limited resection followed by radiotherapy. To study the outcome after a primary surgical approach, we followed 25 consecutive patients (10 females, 15 males) under 16 years of age who were treated in a single institution with a management policy of radical tumour excision (mean age at diagnosis 9 years 2 months, SD 4 years 3 months; range 2 years 9 months to 15 years 11 months). Mean follow-up after primary surgery was 11 years 3 months (SD 7 years 7 months). Tumour control, and neurological, endocrine, and hypothalamic complications and their impact on health-related quality of life were assessed (medical follow-up, semi-structured interview, and questionnaires). Results of tumour control were generally good, however, local failure was observed in 6 of 25 patients, and severe late-treatment complications decreased quality of life for many long-time survivors. Endocrine deficiency occurred in 24/25, visual complications in 16/24, neurological complications in 8/24, obesity in 14/23, increased daytime sleepiness in 6/21, and significant school problems in 10/20. Patients with craniopharyngioma rated their health-related quality of life as considerably lower than healthy controls; the domains of social and emotional functioning were particularly affected. Parents' ratings were considerably lower than those of the patients. Poor functional outcome was associated with large tumours infiltrating or displacing the hypothalamus, the occurrence of hydrocephalus, and young age at diagnosis, but also with multiple operations due to tumour recurrence. Alternative treatment strategies should be considered, especially in very young patients with large tumours.

Activities of Daily Living↗
PubMed2003

eIF2B-related disorders: antenatal onset and involvement of multiple organs.

Leukoencephalopathy with vanishing white matter, also called "childhood ataxia with central nervous system hypomyelination," is the first human disease related to mutations in any of the five genes encoding subunits of eukaryotic initiation factor eIF2B or any translation factor at all. eIF2B is essential in all cells of the body for protein synthesis and the regulation of this protein synthesis under different stress conditions. It is surprising that mutations in the eIF2B genes have been reported to lead to abnormalities of the white matter of the brain only, although it has been shown recently that ovarian failure may accompany the leukoencephalopathy. Another surprising observation is that the onset of the disease varies from early childhood to adulthood, with the exception of Cree leukoencephalopathy, a disease related to a particular mutation in one of the eIF2B genes, which invariably has its onset within the first year of life. We analyzed the eIF2B genes of nine patients with an antenatal- or early-infantile-onset encephalopathy and an early demise and found mutations in eight of the patients. In addition to signs of a serious encephalopathy, we found oligohydramnios, intrauterine growth retardation, cataracts, pancreatitis, hepatosplenomegaly, hypoplasia of the kidneys, and ovarian dysgenesis. Until now, no evidence had been found for a genotype-phenotype correlation, but the consistently severe phenotype in affected siblings among our patients and in Cree encephalopathy patients suggests an influence of the genotype on the phenotype.

Abnormalities, Multiple↗
PubMed2003

Neuropsychological long-term sequelae after posterior fossa tumour resection during childhood.

The importance of the cerebellum for non-motor functions is becoming more and more evident. The influence on cognitive functions from acquired cerebellar lesions during childhood, however, is not well known. We present follow-up data from 24 patients, who were operated upon during childhood for benign cerebellar tumours. The benign histology of these tumours required neither radiotherapy nor chemotherapy. Post-operatively, these children were of normal intelligence with a mean IQ of 99.1, performance intelligence quotient (PIQ) of 101.3 and verbal intelligence quotient (VIQ) of 96.8. However, 57% of patients showed abnormalities in subtesting. In addition, more extensive neuropsychological testing revealed significant problems for attention, memory, processing speed and interference. Visuo-constructive problems were marked for copying the Rey figure, but less pronounced for recall of the figure. Verbal fluency was more affected than design fluency. Behavioural deficits could be detected in 33% of patients. Attention deficit problems were marked in 12.5%, whereas others demonstrated psychiatric symptoms such as mutism, addiction problems, anorexia, uncontrolled temper tantrums and phobia. Age at tumour operation and size of tumour had no influence on outcome. Vermis involvement was related to an increase in neuropsychological and psychiatric problems. The observation that patients with left-sided cerebellar tumours were more affected than patients with right-sided tumours is probably also influenced by a more pronounced vermian involvement in the former group. In summary, this study confirms the importance of the cerebellum for cognitive development and points to the necessity of careful follow-up for these children to provide them with the necessary help to achieve full integration into professional life.

Adolescent↗
PubMed2003

Spontaneous intracranial haemorrhage in children: aetiology, presentation and outcome.

We are aware of only few reports addressing spontaneous intracranial haemorrhage (SICH) in non-selected series of children. This is a retrospective analysis of clinical presentation and outcome in 34 children with SICH seen in the period 1990-2000 in our hospital. Traumatic, neonatal and subdural haemorrhages were excluded. The majority (47%, 16/34) of SICH was caused by an arteriovenous malformation (AVM). SICH was presented as an acute event in 53% (17/32) of patients. Forty-seven percent (15/32) of the cases had protracted courses, which made the diagnosis difficult. In our series, younger children had less specific symptoms. Mortality (25%, 8/32) and morbidity were considerable, particularly in infratentorial haemorrhages, in aneurysms, in children younger than 3 years and in those with underlying haematological disorders.

Adolescent↗
PubMed2003

Cervical myelomeningocele--follow-up of five patients.

Only a few series of patients with cervical myelomenigocele (cMMC) and cervical meningocele (cMC) have been published. Interventions as well as the neurologic, orthopaedic, urologic and intellectual outcomes were analysed in this retrospective description of five patients with cMMC and cMC diagnosed in the period 1984-1999. Four patients suffered from cMMC, one from cMC. The average duration of follow-up was 9.5 years. None of the patients had periconceptual prevention with folic acid. Three had a Chiari II malformation and two a hydrocephalus. Tethering of the cervical cord was demonstrated in three patients at follow-up. All children achieved an independent ambulatory function and urinary continence. Incomplete sensorimotor hemiparesis was present in two children, and a mild unilateral arm paresis in one. Two of five patients had age appropriate cognitive functions. Three patients with mild mental retardation or behavioural problems had to be placed in special classes. The outcome of patients with cMMC is favourable regarding to the neurologic, orthopaedic and urologic problems compared with lower neural tube defects. However, the burden of repeated examinations and therapies is considerable and induces high costs, therefore prevention with periconceptual folic acid is a crucial issue also in cMMC. Spinal cord dysfunction has to be considered in growing children due to persistent tethering or re-tethering, therefore regular neurologic and urodynamic investigations are of particular importance.

Activities of Daily Living↗
PubMed2003

Diffusion tensor imaging in cases of adrenoleukodystrophy: preliminary experience as a marker for early demyelination?

BACKGROUND AND PURPOSE: Diffusion tensor imaging measures the proton diffusivity and preferential orientation of the diffusion tensor. X-linked adrenoleukodystrophy is a demyelinating disease for which therapy depends on the onset and extension of demyelination. We investigated the ability of diffusion tensor imaging to detect changes in the demyelinated lesions and in the normal appearing white matter. METHODS: Diffusion tensor imaging of three related boys with X-linked adrenoleukodystrophy and seven age-matched control participants was performed. Isotropic diffusion (D') and fractional anisotropy (FA) values were determined in 18 regions of interest in the white matter of both hemispheres. RESULTS: In all the demyelinated white matter areas, a pattern with increased D' and loss of FA was found. For example, mean D' was 1.772 x 10(-3)mm(2)/s in patient 2 with blindness and extensive demyelination of the occipital white matter and was 0.693 x 10(-3)mm(2)/s in control participants (P =.01). In the same region, mean FA was 0.103 (0.464 in control participants, P <.0001). Significant alterations of D' and FA were also observed in normal appearing white matter. For example, mean D' was 0.802 x 10(-3)mm(2)/s in the parietal white matter of patient 1 with no visible alterations on T2-weighted images (0.715 x 10(-3) mm(2)/s in control patients, P =.03), whereas mean FA was 0.320 (0.400 in control participants, P =.003). CONCLUSION: Elevated D' and loss of FA revealed by diffusion tensor imaging are consistent with severe demyelination in patients with X-linked adrenoleukodystrophy. Significant alterations of D' and FA in normal appearing white matter may indicate early demyelination in areas that are not yet visibly altered on conventional MR images. Further evaluation in a larger series of patients and long-term study are needed.

Adolescent↗
PubMed2002

Delay in the diagnosis of paediatric brain tumours.

UNLABELLED: The pre-diagnostic period of 252 children (median age 6.3 years, range 0-16.9 years) with primary brain tumours was assessed to analyse their clinical presentation and reasons for any delay in diagnosis. The median pre-diagnostic symptomatic interval (PSI) was 60 days (range 0-3010 days) with a parental delay of 14 days (range 0-2310 days) and a doctor's delay of 30 days (range 0-3010 days). Only 33% of brain tumours were diagnosed within the 1st month after the onset of signs/symptoms. PSI correlated significantly with patients' age and tumour histology, but not with gender, year of diagnosis or tumour location (supratentorial hemispheric, supratentorial midline, infratentorial). In children older than 2 years, most common initial signs/symptoms were headache, nausea/vomiting, seizures, squint/diplopia, ataxia and behavioural changes. In children younger than 2 years, most common initial signs/symptoms were seizures, vomiting, head tilt and behavioural changes. These signs/symptoms are by no means pathognomonic features of brain tumours, making the diagnosis in the early course often difficult. CONCLUSION: given the fact that the vast majority of patients (88% in the present study) develop further signs/symptoms, a high level of awareness, a detailed medical history and repeated correctly interpreted neurological examinations should lead to an earlier diagnosis and to a higher probability of total tumour resection.

Adolescent↗
PubMed2002

Vanishing cerebellum in myelomeningocoele.

Reduced hindbrain herniation observed after intrauterine myelomeningocoele repair suggests that posterior fossa changes in myelomeningocoele are secondary results of prolonged prenatal spinal cerebrospinal fluid leak. Exceptionally, this transforaminal herniation results in 'degeneration' of cerebellar tissue, presumably due to mechanically induced ischaemia. This phenomenon was called 'vanishing cerebellum in Chiari II malformation'. We report three similar cases of this apparently rare finding. Pregnancies were normal. Cerebellar hypoplasia was already recognized in one instance by prenatal ultrasound at gestational week 25. Postnatal imaging was similar in all three patients showing small posterior fossa, beaked midbrain tectum, small brainstem without pontine prominence, reduced cerebellar tissue with virtual absence of one hemisphere and supratentorial hydrocephalus. Our series is too small to draw firm conclusions about predisposing risk factors for and consequences of vanishing cerebellum. Cerebellar damage can interfere with cognitive development, as shown in children with cerebellar agenesis/ hypoplasia, congenital ataxia and small cerebellum following prematurity. A final conclusion on the cognitive consequence of vanishing cerebellum cannot be drawn on the available literature and our limited observations, as one of our patients died at 3 months and another is still too young for appropriate testing. However, the third (aged 15 years) is very severely retarded.

Adolescent↗
PubMedDate not supplied

Association of lentiginous mosaicism and congenital cataract in a girl.

Partial unilateral lentiginosis (PUL) is a rare pigmentary disorder characterized by multiple lentigines on otherwise normal skin affecting one side of the body. We report on a girl with an extensive form of bilateral lentiginosis with systematized segmental distribution and a unilateral congenital cataract. The arrangement of the lentigines is reminiscent of a checkerboard pattern. The benign condition is discussed in the context of systemic diseases with lentigines.

Cataract↗