Infantile spasms: does season influence onset and long-term outcome?

To study whether onset of infantile spasms manifests seasonal variation, as previously reported, and whether any such seasonality is associated with treatment response and long-term outcome, data for 57 patients were retrospectively reviewed. The data were collected from hospital files and through a mail survey of children with infantile spasms born from 1980 to 2002 and monitored at the University Children's Hospital of Berne, Switzerland. The mean age at time of onset of infantile spasms was 7 months (range, 0.75-40), at diagnosis 8 months (range, 1-42) and at follow-up 11.3 years (range, 1-23 years). In 77% of participants, the etiology of infantile spasms was known (symptomatic); in the remaining 23% it was not known (nonsymptomatic). In contrast to previous findings, onset of infantile spasms was not associated with calendar month, photoperiod, or global solar radiation. Long-term prognosis was poor: 4 of the 57 (7%) children died; 49 (86%) had cognitive impairment and 40 (70%) had physical impairment; 31 (54%) had cerebral palsy, 37 had (65%) persistent seizures, and 9 (16%) had Lennox-Gastaut syndrome. Symptomatic infantile spasms were associated with worse cognitive outcome (P < 0.001), but treatment modality and overall duration of infantile spasms were not. There was no association of calendar month or photoperiod at onset with cognitive outcome or treatment response.

Infantile hypophosphatasia due to a new compound heterozygous TNSALP mutation - functional evidence for a hydrophobic side-chain?

BACKGROUND: Infantile hypophosphatasia (IH) is an inherited disorder characterized by defective bone mineralization and a deficiency of alkaline phosphatase activity. OBJECTIVE/DESIGN: The aim of the study was to evaluate a new compound heterozygous TNSALP mutation for its residual enzyme activity and localization of the comprised amino acid residues in a 3D-modeling. PATIENT: We report on a 4-week old girl with craniotabes, severe defects of ossification, and failure to thrive. Typical clinical features as low serum alkaline phosphatase, high serum calcium concentration, increased urinary calcium excretion, and nephrocalcinosis were observed. Vitamin D was withdrawn and the patient was started on calcitonin and hydrochlorothiazide. Nonetheless, the girl died at the age of 5 months from respiratory failure. RESULTS: Sequence analysis of the patient's TNSALP gene revealed two heterozygous mutations [c.653T>C (I201T), c.1171C>T (R374C)]. Transfection studies of the unique I201T variant in COS-7 cells yielded a mutant TNSALP protein with only a residual enzyme activity (3.7%) compared with wild-type, whereas the R374C variant was previously shown to reduce normal activity to 10.3%. 3D-modeling of the mutated enzyme showed that I201T resides in a region that does not belong to any known functional site. CONCLUSION: We note that I201, which has been conserved during evolution, is buried in a hydrophobic pocket and, therefore, the I>T-change should affect its functional properties. Residue R374C is located in the interface between monomers and it has been previously suggested that this mutation affects dimerization. These findings explain the patient's clinical picture and severe course.

Vulnerabilitäts- und Resilienzfaktoren in der Psychopathologie und deren Einfluss im Umgang mit Stressoren: drei empirische Artikel als Beitrag zum erweiterten Verständnis des Vulnerabilität-Resilienz Modells

Das Vulnerabilität-Resilienz Modell dient in der folgenden Arbeit als theoretischer Rahmen, um die Entstehung von Psychopathologie zu verstehen. Es handelt sich um ein Schwellenmodell, bei dem angenommen wird, dass Vulnerabilitäts- und Resilienzfaktoren die Schwelle bestimmen, ab der ein Individuum unter Belastung (Stress) eine psychische Störung entwickelt. In dieser Arbeit werden unterschiedliche Vulnerabilitätsfaktoren (Emotionsregulation, Schmerz) sowie Resilienzfaktoren (Selbstwirksamkeit, soziale Unterstützung) bei unterschiedlichen Stichproben und Designs untersucht und in Form von drei veröffentlichten Artikeln präsentiert. Im ersten Artikel wurde ein Screening-Fragebogen (RS-8), welcher Rumination und Suppression erfasst, validiert. Die Resultate zeigen, dass der RS-8 ein valides, reliables und ökonomisches Messinstrument ist, welches bei klinischen und nicht-klinischen Stichproben eingesetzt werden kann. Im zweiten Artikel wurde in einem längsschnittlichen Design untersucht, welchen Einfluss Selbstwirksamkeit und soziale Unterstützung auf die Beziehung zwischen Schmerz und Depressivität bei Unfallpatienten haben. Die Resultate ergaben, dass Schmerz und soziale Unterstützung signifikante Prädiktoren für Depressivität darstellten. Selbstwirksamkeit wirkte als Moderator zwischen Schmerz und Depressivität. Tiefere Selbstwirksamkeit in Zusammenhang mit Schmerz hatte einen stärkeren Einfluss auf die Depressivität als höhere Selbstwirksamkeit und Schmerz. Die Resultate weisen darauf hin, dass Selbstwirksamkeit im Umgang mit Schmerz und in der Entwicklung von Depression zentral ist. Im dritten Artikel wurde der Zusammenhang zwischen kompensatorischem Gesundheitsverhalten (z.B. langsamer fahren) und Selbstwirksamkeit bei Fahrradfahrern, welche einen Fahrradhelm entweder gelegentlich oder nie trugen, untersucht. Die Resultate ergaben eine signifikante Interaktion zwischen Selbstwirksamkeit und der Häufigkeit des Fahrradhelmtragens auf das kompensatorische Gesundheitsverhalten. Individuen, die gelegentlich einen Fahrradhelm trugen und hohe Selbstwirksamkeit aufwiesen, zeigten mehr kompensatorisches Gesundheitsverhalten als jene mit tiefer Selbstwirksamkeit. Eine mögliche Erklärung könnte sein, dass bei den gelegentlichen Helmträgern eine höhere Risikowahrnehmung vorhanden ist. Die Ergebnisse dieser drei Artikel belegen die Relevanz von Vulnerabilitäts-und Resilienzfaktoren in klinischen und nicht-klinischen Stichproben.

Insights into post-translational processing of beta-galactosidase in an animal model resembling late infantile human G-gangliosidosis

G(M1)-gangliosidosis is a lysosomal storage disorder caused by a deficiency of ss-galactosidase activity. Human GM1-gangliosidosis has been classified into three forms according to the age of clinical onset and specific biochemical parameters. In the present study, a canine model for type II late infantile human GM1-gangliosidosis was investigated 'in vitro' in detail. For a better understanding of the molecular pathogenesis underlying G(M1)-gangliosidosis the study focused on the analysis of the molecular events and subsequent intracellular protein trafficking of beta-galactosidase. In the canine model the genetic defect results in exclusion or inclusion of exon 15 in the mRNA transcripts and to translation of two mutant precursor proteins. Intracellular localization, processing and enzymatic activity of these mutant proteins were investigated. The obtained results suggested that the beta-galactosidase C-terminus encoded by exons 15 and 16 is necessary for correct C-terminal proteolytic processing and enzyme activity but does not affect the correct routing to the lysosomes. Both mutant protein precursors are enzymatically inactive, but are transported to the lysosomes clearly indicating that the amino acid sequences encoded by exons 15 and 16 are necessary for correct folding and association with protective protein/cathepsin A, whereas the routing to the lysosomes is not influenced. Thus, the investigated canine model is an appropriate animal model for the human late infantile form and represents a versatile system to test gene therapeutic approaches for human and canine G(M1)-gangliosidosis.

Floppy Baby mit makrozytärer Anämie und veganischer Mutter

We report the case of a 7 month-old girl that presented with acute anemia, generalized muscular hypotonia and failure to thrive. Laboratory evaluation revealed cobalamin deficiency, due to a vegan diet of the mother. The clinical triad of an acquired floppy baby syndrome with megaloblastic anemia and failure to thrive is pathognomic for infantile cobalamin deficiency. Neurological abnormalities are often irreversible and may be associated with delayed myelinization in the MRI. A normal cobalamin level in maternal serum and absence of anemia do not exclude subclinical deficiency. If cobalamin deficiency is suspected, e.g. in pregnant women on vegan diet, urinary methylmalonic acid excretion and plasma homocysteine levels should be determined and cobalamin substitution should be started at an early stage to avoid potentially irreversible damage of the fetus.

Chronic stimulation of the globus pallidus internus for treatment of non-dYT1 generalized dystonia and choreoathetosis: 2-year follow up

OBJECT: The authors studied the long-term efficacy of deep brain stimulation (DBS) of the posteroventral lateral globus pallidus internus up to 2 years postoperatively in patients with primary non-DYT1 generalized dystonia or choreoathetosis. The results are briefly compared with those reported for DBS in DYT1 dystonia (Oppenheim dystonia), which is caused by the DYT1 gene. METHODS: Enrollment in this prospective expanded pilot study was limited to adult patients with severely disabling, medically refractory non-DYT1 generalized dystonia or choreoathetosis. Six consecutive patients underwent follow-up examinations at defined intervals of 3 months, 1 year, and 2 years postsurgery. There were five women and one man, and their mean age at surgery was 45.5 years. Formal assessments included both the Burke-Fahn-Marsden dystonia scale and the recently developed Unified Dystonia Rating Scale. Two patients had primary generalized non-DYT1 dystonia, and four suffered from choreoathetosis secondary to infantile cerebral palsy. Bilateral quadripolar DBS electrodes were implanted in all instances, except in one patient with markedly asymmetrical symptoms. There were no adverse events related to surgery. The Burke-Fahn-Marsden scores in the two patients with generalized dystonia improved by 78 and 71% at 3 months, by 82 and 69% at 1 year, and by 78 and 70% at 2 years postoperatively. This was paralleled by marked amelioration of disability scores. The mean improvement in Burke-Fahn-Marsden scores in patients with choreoathetosis was 12% at 3 months, 29% at 1 year, and 23% at 2 years postoperatively, which was not significant. Two of these patients thought that they had achieved marked improvement at 2 years postoperatively, although results of objective evaluations were less impressive. In these two patients there was a minor but stable improvement in disability scores. All patients had an improvement in pain scores at the 2-year follow-up review. Medication was tapered off in both patients with generalized dystonia and reduced in two of the patients with choreoathetosis. All stimulation-induced side effects were reversible on adjustment of the DBS settings. Energy consumption of the batteries was considerably higher than in patients with Parkinson disease. CONCLUSIONS: Chronic pallidal DBS is a safe and effective procedure in generalized non-DYT1 dystonia, and it may become the procedure of choice in patients with medically refractory dystonia. Postoperative improvement of choreoathetosis is more modest and varied, and subjective ratings of outcome may exceed objective evaluations.

Long-term follow-up in patients with Lennox-Gastaut syndrome. Epileptological aspects, psychomotor development and social adaptation

In 1989/90 a follow-up was made possible on 72 of 78 patients who have been treated for the supposed or confirmed diagnosis of a Lennox-Gastaut-Syndrome at the university children hospital of Berne between 1964 and 1978. Nine patients were excluded of this study because the diagnosis was proved wrong retrospectively, leaving 63 cases. Of these, eleven patients (17.5%) have died. The remaining 52 (82.5%) were evaluated regarding their epilepsy, psychomotor development and social adaptation. The follow-up was good for 14.3%, intermediate for 23.8% and poor for 44.4%. Bad prognostic factors were found to be: first manifestation of epilepsy during the first year of life, occurrence of infantile spasms or hypsarrhythmia in the EEG and pathological neurological signs at the beginning of the disease. In the course of illness a change of seizure phenomenology was observed. The infantile spasms were seen only during the first three years of epilepsy. After the second year of disease psychomotor seizures became more and more frequent. Atypical absences, already seen at the beginning, were the most frequent form of seizure from the third year of epilepsy until the end of our observations. During the course of disease the frequency of generalized tonic and tonic-clonic seizures decreased little.

Psychoedukative und bewältigungsorientierte Gruppentherapie für SchizophreniepatientInnen

Anliegen: Es sollte evaluiert werden, in wieweit Patienten mit Schizophrenie oder einer schizoaffektiven Erkrankung von einem psychoedukativen, bewältigungsorientierten Therapieprogramm profitieren können. Methode: Für die Evaluation wurde ein kontrolliertes prospektives Studiendesign herangezogen. Zum Einsatz kam in der Experimentalgruppe das “Therapiemanual zur Psychoedukation und Krankheitsbewältigung” (PKB), das neben gezielter Information über die Erkrankung und die Pharmakotherapie Strategien vermittelt, wie Frühwarnsignale erkannt und der Umgang mit ihnen erlernt werden können. Darüber hinaus werden auch Aspekte zu „gesundem“ Verhalten behandelt. Als Kontrollgruppe diente eine Patientengruppe mit supportiven Gesprächen bzw. eine Gruppe mit dem Schwerpunkt der Arbeitsrehabilitation. Um die Effekte der PKB zu evaluieren, wurden der psychopathologische Status, wissensbezogene sowie soziale Variablen zu verschiedenen Messzeitpunkten (vor der Therapie, nach Therapieende, 12 Monate nach Therapieende) erhoben. Als abhängige Variablen dienten der Wissensstand über die Erkrankung, Rehospitalisierungen, soziale Integration und Bewältigungsstrategien. Ergebnisse: 82 Patienten nahmen an der Studie teil. Sowohl in der Experimentalgruppe als auch in der Kontrollgruppe wurde eine signifikante Verbesserung des Allgemeinzustandes und der Psychopathologie beobachtet. Die Ergebnisse der Gruppen unterschieden sich insofern, dass in der Experimentalgruppe weniger Rehospitalisierungen im ersten Jahr nach Studienende vermerkt wurden und die Teilnehmer sich anderer Copingstrategien bedienten (signifikant weniger depressive Krankheitsverarbeitung und Bagatellisierung). Schlussfolgerungen: In der Behandlung von Schizophrenie können unterschiedliche Interventionen wirksam sein. Fragestellungen, welche Patienten von welcher Art der therapeutischen bzw. rehabilitativen Intervention profitieren können, sollten weiterhin Gegenstand intensiver Forschung sein.

Fibromatosis in a young Bernese Mountain Dog: clinical, imaging, and histopathological findings

A young, intact, male Bernese Mountain Dog was presented to the animal hospital for lameness and diffuse thickening of the soft tissue in the right hind limb. Magnetic resonance imaging revealed multiple, multilobular, space-occupying lesions within and between the muscles of the right femur. Biopsies taken from the lesions revealed an infiltrative mass composed mainly of collagen fibers and a low density of benign-appearing fibroblasts. These findings were compatible with a diagnosis of a fibromatosis. Taking the age of onset into account, infantile fibromatosis was most likely. A deep fibromatosis, similar to that seen in adults, could not be excluded based on histology.