Case report: Concordant traumatic brainstem contusion delayed diagnosis in a young man with Wilson's disease

Wilson's disease is a hereditary autosomal recessive disorder of copper metabolism. The corresponding gene locus has been localized on the long arm of chromosome 13. Three different clinical variants of the disease can be distinguished: hepato-cerebral, abdominal/hepatic, and central nervous type. The heterogeneity of symptoms can cause problems in differential diagnosis, especially when another concordant disorder can also explain the pathogenesis of symptoms. The case report of a young man who suffered from brainstem contusion demonstrates the possibilities of misinterpretation because presenting symptoms could be attributed either to traumatic brain injury followed by adjustment disorder or Wilson's disease. Clinical signs included leftsided hemiparesis, bilateral gaze direction nystagmus, marked dysarthria with consecutive pervasive mutism, choreo-athetoid movements, spasmodic torticollis and diplopia dependent on gaze direction. Slit lamp examination showed Kayser-Fleischer's corneal ring. EEG- and computer assisted tomography investigations revealed non-specific findings. The patient was treated with D-Penicillamine. Alternative treatment with oral zinc preparations is discussed.

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Zusammenfassung Beim Morbus Wilson handelt es sich um eine autosomal rezessiv vererbte Störung des Kupferstoffwechsels. Der Genort konnte auf dem langen Arm des Chromosoms 13 lokalisiert werden. Klinisch können aufgrund ihrer Symptomatik drei Verlaufsformen (hepato-zerebraler, abdominalhepatischer und zerebraler Typ) unterschieden werden. Die Vielfalt der Symptome kann differentialdiagnostische Schwierigkeiten bereiten. Das Beispiel eines jungen Mannes mit einer traumatischen Hirnstammkontusion zeigt, wie die Diagnose der hepato-lentikulären Erkrankung dadurch erschwert wurde, daß die Pathogenese der Symptome durch die Hirnstammkontusion und darauf folgende Anpassungsstörungen erklärt worden war. Die Symptomatik bestand aus linksseitiger Hemiparese, lateralem Blickrichtungsnystagmus, Dysarthrie mit nachfolgendem universalem Mutismus, choreo-athetodischen Bewegungsstörungen, Torticollis spasmoidicus und blickrichtungsabhängigem Auftreten von Doppelbildern. Bei der Spaltlampenuntersuchung stellte sich der Kayser-Fleischer Ring dar. EEG- und computertomographische Untersuchungen erbrachten nur unspezifische Befunde. Die Behandlung erfolgte mit D-Penicillamin. Die alternative Behandlung mit oraler Gabe von Zinksalzen wird diskutiert.

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Résumé La maladie de Wilson est une affection héréditaire autosomale recessive concernant le métabolisme cuivré. Le locus du gène a été situé sur le bras long du chromosome 13. Du point de vue clinique on distingue trois formes symptomatologiques: le type hepato-cérébral, hepato-abdominal et cérébral. La diversité des signes cliniques peut poser des problèmes de diagnostic différentiel, car d'autres affections peuvent se présenter avec cette même Symptomatologie. Nous rapportons ici l'exemple d'un homme jeune, porteur d'une maladie de Wilson et victime d'une contusion traumatique du tronc cérébral, dont les signes cliniques ainsi que les troubles du comportement pouvaient été autant rapportés à la contusion du tronc cérébral qu'à l'affection métabolique.La Symptomatologie comprenait une hemiparesie gauche, un nystagmus lateralisé, une dysarthrie avec mutisme secondaire universel, des mouvements choréo-athétosiques, un torticolis spasmodique et une diplopie dépendante de la direction du regard. L'examen à la lampe à fente permettait à mettre en evidence un anneau de Kayser Fleischer. L'EEG et le scanner cérébral ne montraient pas d'anomalies specifique.Le traitement a consisté en l'administration de D-Penicillamine. Traitment alternative avec les sels de zinc est discuté.

     

Clonidine in the treatment of brainstem spasticity. Case report.

This report describes a patient who developed spasticity after a medullary infarct. No improvement in her spasticity was achieved by baclofen therapy and the side effects of the drug necessitated its gradual withdrawal. Recent reports of the success of clonidine in the management of spasticity due to spinal cord injury prompted an attempt at clonidine therapy. When clonidine therapy was initiated, the patient responded rapidly with both subjective and objective improvements in her spasticity. This case suggests a potential role for clonidine in the treatment of spasticity resulting from brainstem infarction.     

Parenting stress among caregivers of children with congenital cataracts.

OBJECTIVE: To examine parenting stress among caregivers of young children with congenital cataracts and to assess whether diagnostic and/or treatment differences are associated with differences in perceived parenting stress. METHODS: Parents of 41 preschool-age children with congenital cataracts (13 with bilateral cataracts [BCCs] and 28 with unilateral cataracts [UCCs], of whom 14 were aphakic and 14 were pseudophakic) completed the Parenting Stress Index (PSI) and/or a disease-specific parental stress measure, ie, the Ocular Treatment Index (OTI). RESULTS: The 28-item OTI had excellent internal consistency (alpha = 0.94) and supported three of four a priori validity hypotheses. Parents of children with congenital cataracts reported normal parenting stress levels on the PSI. Parents of children with UCCs tended to report higher levels of stress, but not significantly so, than did parents of children with BCCs. Among parents of children with UCCs, those whose children were aphakic reported higher levels of stress on the OTI and all of the PSI subscales than did parents of pseudophakic children. These differences were statistically significant for two subscales (Adaptability [P =.03] and Mood [P =.01]). CONCLUSIONS: Although parents of children with congenital cataracts generally did not report increased parenting stress levels, clinicians should be aware that parenting stress can adversely impact patients' families. We did observe higher stress levels in parents with children who had UCCs and did not receive an intraocular lens-particularly stress related to their child's reaction to sensory stimulation and mood-compared with parents of pseudophakic children. Thus, clinicians may want to consider parenting stress levels when choosing a treatment for children with UCCs, especially because such stress has been associated with poor treatment compliance for children with other chronic conditions.     

Evidence for persistence of adenovirus in the tear film a decade following conjunctivitis

Chronic papillary conjunctivitis has been described following adenoviral conjunctivitis. It is unknown however, how long adenovirus is able to persist in the tear film and conjunctiva. To determine if adenovirus persists in the ocular surface following adenoviral conjunctivitis, 304 patients with a history of adenovirus conjunctivitis from whom an adenovirus had been isolated 10 years previously were sent a questionnaire regarding persistent or recurrent symptoms and were invited to attend. Patients were examined and samples of tears and conjunctival cells were collected from both eyes using tear film washes, filter paper, and swabs, the latter for virus isolation. Extracted DNA from the ocular samples was amplified using primers for herpes simplex virus (thymidine kinase) and adenovirus (hexon) genes. Adenovirus amplicons were sequenced and compared to original serotype. Thirty patients attended, 19 of whom had persistent papillary conjunctivitis. Evidence of adenovirus DNA was detected in 17 of 30 patients, 15 of whom also had evidence of a chronic papillary conjunctivitis. Adenovirus DNA was significantly associated with papillary conjunctivitis (P = 0.03). Adenovirus amplicons were successfully sequenced from six patients. Four patients harbored type 3 adenovirus, the same serotype with which they were infected originally 10 years previously. Two patients were infected originally with adenovirus serotype 3 but the current serotype was type 4. Infection of the ocular surface with adenovirus may predispose to the development of a persistent or recurrent conjunctivitis, the presence of which, appears to be associated with evidence of long term persistence of adenovirus DNA.     

Receptive field scatter,topography and map variability in different layers of the hindpaw representation of rat somatosensory cortex

We recorded neurons extracellularly in layers II/III, IV, and V of the hindpaw representation of primary somatosensory cortex in anesthetized rats and studied laminar features of receptive fields (RFs) and representational maps. On average, RFs were smallest in layer IV and largest in layer V; however, for individual penetrations we found substantial deviations from this rule. Within the hindpaw representation, a distinct rostrocaudal gradient of RF size was present in all layers. While layer V RFs were generally largest independent of this gradient, layer IV RFs recorded caudally representing the proximal portions of the paw were larger than layer II/III RFs recorded rostrally representing the digits. The individual scatter of the locations of RFs across laminar groups was in the range of several millimeters, corresponding to about 25% of the average RF diameter. The cutaneous representations of the hindpaw in extragranular layers were confined to the areal extent defined by responsive sites in layer IV. Comparison between RFs determined quantitatively and by handplotting showed a reliable correspondence. Repeated measurements of RFs revealed spontaneous fluctuations of RF size of no more than 5% of the initial condition over an observation period of several hours. The topography and variability of cortical maps of the hindpaw representation were studied with a quantitative interpolation method taking into account the geometric centers of RFs and the corresponding cortical recording sites. On average, the overall topography in terms of preservation of neighborhood relations was present in all layers, although some individual maps showed severe distortions of topography. Factors contributing to map variability were overall position of the representation on the cortical surface, internal topography and spatial extent. Interindividual variability of map layout was always highest in the digit representations. Local topographic orderliness was lowest in layer V, but comparable in layers II/III and IV. Within layer IV, the lowest orderliness was observed in the digit representations. Our data emphasize a substantial variability of RF size, overlap and position across layers and within layers. At the level of representational maps, we found a similar degree of variability that often co-varied across layers, with little evidence for significant layer specificity. Laminar differences are likely to arise from the specific input-output pattern, layer-specific cell types and the connectivity between different layers. Our findings emphasizing similarities in the variability across layers support the notion of tightly coupled columnar interactions between different layers.     

Assessment of class-specific antibodies against denatured DNA in patients with systemic lupus erythematosus

In this retrospective study 103 serum samples from 16 females with systemic lupus erythematosus (SLE), obtained during a mean follow-up time of 2 years, were investigated for the presence of anti-denatured [single-stranded (ss)] DNA antibodies of the IgG, IgM, and IgA classes. The anti-ssDNA antibodies were determined by an enzyme-linked immunosorbent assay (ELISA), and the results were expressed in three ways: as units derived from a single serum dilution and as two parameters,E andA, calculated from the dose-response curve,E being an estimate of the effective amount of antibodies andA a function of the reaction constant between the antigen and the antibody. The simultaneous occurrence of anti-ssDNA antibodies of all three immunoglobulin classes was seen most often in the patients with the shortest duration of the disease. Clinically active disease was found to correlate with high reaction constants of the IgA anti-ssDNA antibodies. There was also an association between the IgA anti-ssDNA antibody levels and the presence of nephritis. Great fluctuations in the amounts of effective antibodies of the IgG class were seen in seven patients, in six of whom changes in the disease activity also were seen. Changes in the disease activity were unaccompanied by fluctuations in the IgG anti-ssDNA levels in four patients; two of these patients were positive for antibodies against extractable nuclear antigens. We conclude that it is of value to express the results of the anti-ssDNA ELISA as a function of the dose-response curve when monitoring patients with SLE and that immunoglobulin class-specific determinations of anti-ssDNA antibodies may provide information about the disease activity in many patients with SLE.     

Using simulation to instruct emergency medicine residents in cognitive forcing strategies.

PURPOSE: Recent literature defines certain cognitive errors that emergency physicians will likely encounter. The authors have utilized simulation and debriefing to teach the concepts of metacognition and error avoidance. METHOD: The authors conducted a qualitative study of an educational intervention at Lehigh Valley Hospital during academic year 2002-03. Fifteen emergency medicine residents--eight from postgraduate year three (PGY3) and seven from postgraduate year two (PGY2)--experienced a difficult simulator lab scenario designed to lead them into a cognitive error trap. The debriefing was a PowerPoint with audio format CD-ROM with a didactic on succinylcholine (15 minutes) and cognitive forcing strategies (30 minutes). After debriefing, residents were interviewed by an ethnographer with an 11-question (15-minute) interview and completed an eight-question written survey. RESULTS: The residents ranked this experience second only to direct patient care for educational effectiveness. Survey results (Likert scale, 1 = disagree completely to 5 = agree completely) included "Improved my ability to use succinylcholine" (mean = 4.73), "Improved my ability to diagnose and treat hyperkalemia" (mean = 4.6), and "Cognitive forcing strategies is a useful educational effort" (mean = 4.33). The major interview themes that evolved were that the simulation lab was a positive experience; succinylcholine knowledge was gained; mistakes caused reflection/motivation; the lab was stressful; attending feedback was desired; the lab was realistic; and cognitive forcing strategies were discussed. When asked what they learned, more of the PGY3s commented on cognitive strategies or heuristic techniques (six out of eight), whereas the PGY2s commented on knowledge gained about succinylcholine (five out of seven) and only one PGY2 mentioned cognitive strategies. CONCLUSION: Pilot data suggest that metacognitive strategies can be taught to residents, though they may be better understood by upper-level residents.     

Molecular epidemiology of hepatitis B virus infections in Denmark.

BACKGROUND: Denmark has a low incidence of acute hepatitis B (HBV) infections but the impact of an increasing number of immigrants with chronic HBV infection on HBV transmission is unknown. OBJECTIVES: To characterise individuals with chronic and acute HBV infection in a defined region and to examine the importance of different risk groups for the current HBV transmission. METHODS: During 2000-2001 all consecutive HBV infected individuals routinely diagnosed through the regional HBV serology laboratory in the County of Funen were classified according to ethnicity, presumed route of transmission and stage of infection based on clinical data mainly supplied by the requesting physician. HBV DNA was sequenced and subjected to phylogenetic analysis. RESULTS: Of 309 identified cases, 91 (29%) were classified as acute infection. HBV DNA sequencing was possible in 54 (59%) of these cases. Phylogenetic analysis showed that HBV isolated from injecting drug users (IDUs) was identical or closely related. Among acute cases acquired in Denmark 89% (74/83) were seen in IDUs (65) or in individuals presumably exposed to IDUs (nine) and phylogenetic analysis corroborated the assumption of IDU related transmission in every case with available sequence data. Among 83 ethnic Danes who acquired their HBV infection in Denmark, no new cases of transmission from immigrants were detected. CONCLUSION: Injecting drug use was the single most important factor for hepatitis B transmission in Denmark. The current Danish vaccination strategy is unable to protect IDUs from HBV infection and IDUs pose a greater risk of HBV transmission to the general population than immigrants.     

A genomic analysis of chicken cytokines and chemokines.

As most mechanisms of adaptive immunity evolved during the divergence of vertebrates, the immune systems of extant vertebrates represent different successful variations on the themes initiated in their earliest common ancestors. The genes involved in elaborating these mechanisms have been subject to exceptional selective pressures in an arms race with highly adaptable pathogens, resulting in highly divergent sequences of orthologous genes and the gain and loss of members of gene families as different species find different solutions to the challenge of infection. Consequently, it has been difficult to transfer to the chicken detailed knowledge of the molecular mechanisms of the mammalian immune system and, thus, to enhance the already significant contribution of chickens toward understanding the evolution of immunity. The availability of the chicken genome sequence provides the opportunity to resolve outstanding questions concerning which molecular components of the immune system are shared between mammals and birds and which represent their unique evolutionary solutions. We have integrated genome data with existing knowledge to make a new comparative census of members of cytokine and chemokine gene families, distinguishing the core set of molecules likely to be common to all higher vertebrates from those particular to these 300 million-year-old lineages. Some differences can be explained by the different architectures of the mammalian and avian immune systems. Chickens lack lymph nodes and also the genes for the lymphotoxins and lymphotoxin receptors. The lack of functional eosinophils correlates with the absence of the eotaxin genes and our previously reported observation that interleukin- 5 (IL-5) is a pseudogene. To summarize, in the chicken genome, we can identify the genes for 23 ILs, 8 type I interferons (IFNs), IFN-gamma, 1 colony-stimulating factor (GM-CSF), 2 of the 3 known transforming growth factors (TGFs), 24 chemokines (1 XCL, 14 CCL, 8 CXCL, and 1 CX3CL), and 10 tumor necrosis factor superfamily (TNFSF) members. Receptor genes present in the genome suggest the likely presence of 2 other ILs, 1 other CSF, and 2 other TNFSF members.