Bowel obstruction in patients with Alpers-Huttenlocher syndrome.

Alpers-Huttenlocher syndrome (AHS) is a very rare autosomal recessive disorder. AHS is caused by homozygous or compound heterozygous mutations in the nuclear gene encoding mitochondrial DNA polymerase gamma (POLG, chromosome 15q25). Most patients become symptomatic before the age of 2 years. We report 3 patients who were treated in our clinic between 2007 and 2010. All patients suffered from myoclonic seizures and had at least one refractory convulsive status which led to the diagnosis. All of them had varying degrees of developmental delay, 2 of them additionally ataxia. Gastrointestinal motility problems were severe in all patients despite only mildly deranged liver function. While in most aspects our patients present with typical AHS features, they also share intestinal problems, a feature that has not been recognized as typical for AHS before. AHS is a multisystem disorder that does affect all cell systems. Liver and brain are organs with the highest energy demand and are therefore usually affected early in the disease course of AHS. However, constipation and bowel obstruction should be regarded as typical complications in AHS and patients should be monitored and treated to improve quality of life. Regarding treatment options for epilepsy in AHS ketogenic diet as well as lacosamide might be considered.

Merosin-positive congenital muscular dystrophy with transient brain dysmyelination, pontocerebellar hypoplasia and mental retardation.

The congenital muscular dystrophies (CMDs) are a heterogeneous group of disorders. Among these, the laminin alpha 2 chain 'merosin' deficient CMD is caused by mutations of the LAMA2 gene on chr 6q2 and Fukuyama CMD is linked to chr 9q31. We report a 7-year-old boy who was born to consanguineous healthy parents. His motor and mental development were slow. Creatine kinase (CK) was elevated (2.100 U/l), and the muscle biopsy was dystrophic. He sat unsupported at 12 months and took his first steps at 3 years of age. At 6 years of age he could walk up to 500 m. He was mentally retarded and spoke single words only. At 1 year, MR imaging of the brain showed abnormal increased periventricular T2-signal, consistent with dysmyelination as well as pontocerebellar hypoplasia and several cerebellar cysts. The pattern of gyration was normal. Follow-up at 4 years showed normalization of the previously abnormal periventricular T2-signal. Immunohistochemical analysis of the skeletal muscle showed normal expression of laminin alpha 2 for a C-terminal antibody and antibodies to the 300 and 150 kDa fragments, as well as of laminins alpha 5, beta 1, beta 2 and gamma 1. The boy has two healthy younger brothers. Linkage analysis excluded the candidate loci on chromosomes 6q2 and 9q31. As such, the patient's data are suggestive of a new form of laminin alpha 2 positive CMD characterized by transient brain dysmyelination, pontocerebellar hypoplasia and mental retardation.

Familial pontocerebellar hypoplasia type I with anterior horn cell disease.

We report the association of pontocerebellar hypoplasia and anterior horn cell disease in three female siblings. One child presented with the classical clinical and neuropathological features of pontocerebellar hypoplasia with associated anterior horn cell disease, described by Barth as pontocerebellar hypoplasia type I. This patient showed polyhydramnios, congenital contractures, respiratory insufficiency, hypotonia, areflexia, listlessness and myoclonic seizures. Postmortem examination revealed a loss of neurons and reactive gliosis in the pontocerebellum and in addition anterior horn cell atrophy resembling Werdnig-Hoffmann disease. Another sibling demonstrated the same clinical symptoms. However neuropathological findings showed evidence for pontocerebellar hypoplasia only. The third sibling was examined after induced fetal abortion because of prenatally diagnosed arthrogryposis. Anterior horn cell disease was obvious histologically whereas pontocerebellar hypoplasia could not be demonstrated due to cerebral autolysis. The similar clinical and neuropathological findings in the three reported siblings suggest a common genetic defect with different patterns of pontocerebellar hypoplasia and associated anterior horn cell disease. The gene defect of this rare disorder is still unknown. The 'survival motor neuron' gene of spinal muscular atrophy was not found in these three siblings.

31Phosphorus magnetic resonance spectroscopy in late-onset Tay-Sachs disease.

The late-onset form of GM2 gangliosidosis (Tay-Sachs disease) is an autosomal-recessive disorder with progressive neurologic disease, mainly characterized by motor neuron and spinocerebellar dysfunction. The majority of patients are of Ashkenazi Jewish origin. 31Phosphorus magnetic resonance spectroscopy of the brain was performed to study the metabolic changes of a 16-year-old patient with late-onset Tay-Sachs disease who had a heterozygous Gly269-->Ser mutation in the hexosaminidase A encoding gene in compound heterozygosity with another, yet unidentified mutation. Severe changes in phosphorus metabolism with a decreased amount of phosphodiesters and membrane-bound phosphates were demonstrated, suggesting an activation of phosphodiesterases by accumulating gangliosides. The clinical findings were well related to the changes in spectroscopically determined metabolites.

Lissencephaly: diagnosis by computed tomography and magnetic resonance imaging.

A patient with Miller-Dieker-Syndrome, which is associated with lissencephaly, was examined by Computed Tomography (CT) and Magnetic Resonance Imaging (MRI). While CT demonstrated the main features of lissencephaly, MRI detected disturbed myelination and cell migration in the cerebral hemispheres and a normal appearance of the cerebellum. MRI provides more accurate information of the pathomorphologic changes of lissencephaly and is thus superior to CT.

[Magnetic resonance tomography of laminar heterotopia]. / Kernspintomographie bei laminärer Heterotopie.

In one baby and 2 infants who presented with psychomotor retardation and epilepsy laminar heterotopic grey matter was demonstrated via magnetic resonance imaging. Laminar heterotopia is a rare migrational disorder with bilateral symmetric ribbons of grey matter within the centrum semiovale, separated from ventricular walls and from obviously normal-sized cortex by broad layers of white matter. The heterotopic grey matter has a signal intensity which is isointense compared with that of normal cortex irrespective of image weighting. On account of this signal behaviour differentiation against other white matter diseases is easy. The knowledge of these pathognomonic findings facilitates correct diagnosis, especially during the first and the second year of life, when signal intensities of white and grey matter differ from normal findings because of the occasionally delayed myelination process. Therefore, further diagnostic procedures can be avoided and early counseling of parents is possible.

FLIP&FLAP-a training programme for children and adolescents with epilepsy, and their parents.

OBJECTIVE: The objective of this article is to present the development, contents and efficacy of the FLIP&FLAP programme for children and adolescents with epilepsy, and their parents. INTERVENTION: The programme is mainly directed at age-appropriately developed children and adolescents between 6 and 16 who take antiepileptic drugs. It is conducted as a 2.5-day group training programme; children and parents are grouped separately. The main focuses are: EVALUATION STUDY: We performed a multi-centre non-randomised two-group pre-/post-trial using a waiting-list control group design. 10 German epilepsy centres participated. The intervention group, IG (21 children 8-11 years, 44 adolescents 12-16 years, 72 parents) completed standardised questionnaires immediately before the FLIP&FLAP course and 6 months later; the waiting control group, WCG (31 children, 39 adolescents, 72 parents) 6 months before and immediately before the course. Compared to the WCG, the children and parents of the IG showed significantly improved knowledge of epilepsy, with medium to large effect sizes (univariate analysis of variance with repeated measurements, d=0.6-1.4). Parents of the IG reported improved self-management skills (d=0.7) and communication skills (d=0.8) of their child and fewer epilepsy-related worries (d=0.5). Children and adolescents of the IG reported improved HRQOL in the Social Exclusion dimension (d=0.3). CONCLUSION: FLIP&FLAP is an effective child- and family-centred programme. It is currently being established in Northern Germany to test its usefulness in routine care.

Functional MRI reveals activation of a subcortical network in a 5-year-old girl with genetically confirmed myoclonus-dystonia.

We investigated a five-year-old girl suffering from genetically confirmed, action-induced myoclonus-dystonia (M-D) with functional magnetic resonance imaging (MRI). We compared the activation pattern by movements of her right hand as if drawing a picture, which elicited M-D, with simple snapping movements (without overt M-D). The drawing and snapping conditions resulted in activation of a motor network including the motor cortex, the putamen, and the cerebellar hemispheres. The direct comparison of the drawing condition with snapping as control revealed specific activations within the thalamus and the dentate nucleus. An age matched healthy control did not show significant activation within the thalamus or dentate nucleus.

[Magnetic resonance tomography of adrenoleukodystrophy]. / MRT der Adrenoleukodystrophie.

Adrenoleucodystrophy (ALD) is an uncommon, sex-linked disease, characterised by the accumulation of very long-chain fatty acids in various tissues. There is a great predilection for young boys between the age of three and ten years. The disease ends fatally after a clinical course of several years. The clinical and MR findings of a child with typical ALD are presented. T2-weighted MR demonstrates confluent, symmetrical, hyperintense lesions of the occipital white matter bilaterally. After the application of Gd-DTPA, contrast enhancement is seen in the margins of the lesions indicating active demyelination. MR is recommended as imaging modality of choice in patients with suspected or confirmed diagnosis of adrenoleucodystrophy.

The spreading of focal brain edema induced by ultraviolet irradiation.

Focal brain edema limited to one cerebral hemisphere was produced by ultraviolet irradiation of the exposed cortex. Tissue water content was determined by the gravimetric method which allows microsampling. Therefore, the spread of edema around the small necrotic area could be mapped more precisely than by determination of dry weight which calls for larger samples. As early as 30 min following irradiation, hyperemia and swelling of the brain are observed under the operating microscope. This correlates with venous stasis, hyperemia, and broadened perivascular spaces around venules and large capillaries accompanied by a marked rise in the specific weight of the tissue. After 4 h an edema front can be observed spreading from the perinecrotic zone in which there is a marked rise in endothelial cell vesicular activity. Edema reaches maximum levels in the deep white matter at 48 h post irradiation with normalisation of the tissue water content after 96 h. The velocity at which the edema front spreads from the cortex to the periventricular area lies in the range of 0.25 mm/hr. Edema reabsorption coincides with signs of retrograde micropinocytosis in endothelial cells.

The clinical outcomes of neonatal and childhood stroke: review of the literature and implications for future research.

A detailed assessment of clinical outcomes after ischemic stroke in childhood is necessary to evaluate prognostic factors. Previous studies are difficult to compare because of differences in test instruments, study design, heterogeneity of cohorts and number of included cases. Depending on neurodevelopmental assessment methods, major and subtle/minor disabilities, especially in infants, may not have been detected. Most outcome studies reveal only limited information about behavioral changes and quality of life in children with ischemic stroke. Thus the assumption that children make a better recovery from stroke than adults due to the immature brain's capacity to reorganize function is not evidence-based. We systematically review the current literature with regard to the neurological and psychosocial development of affected children as well as their quality of life. Implications for future research strategies follow the review to encourage further clinical study of the neurobehavioral trajectory of childhood stroke.

Ultrastructure of the neuroglial fatty metamorphosis (Virchow) in the perinatal period.

The ultrastructure of neuroglial fatty metamorphosis (GFM) has been investigated in the telencephalic white matter of 12 premature and mature infants (gestational age 22-40 weeks; survival 0-96 days). GFM was found in all cases apart from a 22-week-old fetus, and involves predominantly astrocytic cells (68.8%), then glioblasts (43.5%), but only 7.4% of oligodendrocytes. GFM, therefore, seems to be independent of the myelination process and indicates the vulnerability of the immature neuroglial population in the metabolic and circulatory disorders of the perinatal period. Since GFM is found in almost all children dying within the early postnatal period, this subtle alteration reflects a special form of minimal brain damage. The relationship between GFM, astrocytic hypertrophy and periventricular leucomalacia and their role in the telencephalic leucoencephalopathy are discussed.

[Prenatal diagnosis of fetal polymicrogyria--case report]. / Pränatale Diagnose einer fetalen Polymikrogyrie--Fallbericht.

Migration disorders of foetal neurons are rare conditions which are normally diagnosed after birth and may be followed by severe alterations of neurological development. We describe a case of foetal hemilateral polymicrogyria in combination with hemihypoplasia of the brain, the symptoms of which were diagnosed in the 23rd week of pregnancy, leading to termination of pregnancy. To the best of our knowledge, this is the first case report of antenatal diagnosis of this disorder by vaginal sonography.

Clinical, radiological and histological findings in desmoplastic infantile ganglioglioma.

The clinical course and radiological and histological findings in a 30-month-old boy suffering from desmoplastic infantile ganglioglioma are reported. The child's development was normal until a series of complex partial seizures occurred at the age of 7 months. Cranial computed tomography and magnetic resonance imaging revealed a cystic mass with intensive ring-shaped contrast enhancement in the right temporal fossa without shift of intracranial structures. Histologically, the firm, grayish tumor showed an enormous amount of connective tissue, cystic areas, and some mitoses. Glial and neuronal cell lines were identified by immunocytochemical methods. Eighteen months after surgery the boy had developed well without any neurological dysfunction; no radiation or chemotherapy was given. For the first time a synopsis of radiological findings in this rare brain tumor is correlated with the results of multiple histological and immunocytochemical studies. Despite some malignant characteristics, the prognosis of this dysontogenetic brain tumor is good.

Variable course of Canavan disease in two boys with early infantile aspartoacylase deficiency.

This is a report of two patients with Canavan disease from the Federal Republic of Germany. One is a severely retarded, macrocephalic boy, who had the characteristic laboratory findings of Canavan disease and progressive leucodystrophy on neuro-imaging. The other is retarded, with signs of a cerebral movement disorder showing no deterioration during the first 15 months. The significance of aspartoacylase deficiency in Canavan disease for differential diagnosis, genetic counselling and prenatal diagnosis of leucodystrophy is discussed.

[Sturge-Weber syndrome. Diagnostic imaging relative to neuropathology]. / Die Sturge-Weber-Erkrankung. Bildgebende Diagnostik in bezug zur Neuropathologie.

Clinical presentation of a child with port-wine stain and seizures leads to the suspicion of Sturge-Weber disease (SWD). This diagnosis can be confirmed by the detection of a meningeal angiomatosis. In rare cases, early detection of meningeal pathology by ultrasound has been reported. Key findings are brain atrophy, gyriform cortical calcifications demonstrated by skull radiographs after the first year of life or earlier by cranial CT, and dys- or aplasia of the deep cerebral veins on angiography. Radionuclide imaging shows focal or diffuse tracer accumulation over the affected brain regions. MR demonstrates an abnormal appearance of the affected meninges, especially thickening and pathologically increased signal intensity after Gd-DTPA application. This, in association with the demonstration of abnormal enhancement in deep medullary veins, is the most characteristic finding. Contrast-enhanced MR allows early and non-invasive diagnosis of SWD, mainly by revealing leptomeningeal angiomatosis and abnormal venous vessels.

Severe transitory encephalopathy with reversible lesions of the claustrum.

Reversible bilateral lesions of the claustrum and external capsule in a 12-year-old girl suffering from a severe, transitory encephalopathy are reported. After a prodromal stage of feeling uncomfortable a sudden onset of status epilepticus occurred, followed by recurrent complex partial and myoclonic seizures for 3 weeks, with psychotic symptoms and temporary loss of vision, speech and hearing. After treatment with phenytoin the patient became free of seizures and recovered completely without neurological deficit. The initial cranial CT was normal; however, cranial MRI 7 days later showed bilateral selective lesions of the claustrum and external capsule, which disappeared completely 5 weeks later. The aetiology of these lesions remains obscure; repeated cerebrospinal fluid and blood tests were negative for herpes simplex virus and other infectious agents. The clinical and radiological improvement were concomitant. This may indicate a functional disturbance of the claustrum grey matter, rather than lesions of the white matter of the external and extreme capsules.