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.

     

Excess of DD homozygotes in haemodialysed patients with type II diabetes. The Diabetic Nephropathy Study Group

The role of the insertion/deletion polymorphism of the angiotensin- converting enzyme (ACE) gene in the genesis of diabetic nephropathy has been controversial. It has recently been proposed that progression occurs more rapidly in individuals with diabetic and non-diabetic renal disease who are homozygous for the D allele. We studied 658 patients with type II diabetes, 347 without diabetic nephropathy and 311 with various stages of diabetic nephropathy, and determined the I/D polymorphism of the ACE gene. Patients at the extremes of renal risk, i.e. normotensive patients without antihypertensive treatment and without nephropathy (n = 144), vs patients on dialysis (n = 61), differed with respect to genotype (DD 36.8% vs 57.4%; P = 0.007) and allele frequencies (D 0.59 vs 0.76; P < 0.001). In contrast, patients with and without presumed nephropathy as assessed by albuminuria did not differ with respect to DD genotype. In conclusion, in this study, which was limited by sample size, patients with the highest renal risk more frequently had the DD genotype. This would be compatible with a greater risk of (or rate of) progression to end-stage renal failure.      

Investigations of the acute toxic, cytogenetic, and embryotoxic activity of buminafos.

The organophosphorus herbicide buminafos (O,O-dibutyl-(1-butylaminocyclohexyl)-phosphonate) was tested for its acute toxic, cytogenetic, and embryotoxic activity on different strains of mice. The oral LD50 value for male NMRI mice was determined to be 3500 mg/kg. Single oral doses of 175, 1000, and 2000 mg/kg did not cause any significant enhancement in the percentage of chromosome aberrations in bone marrow cells of male NMRI mice. After oral administration of 500 and 1000 mg/kg buminafos to pregnant Halle:DBA and Halle:AB mice at Days 6-15 of gestation no embryotoxic effects were observed. The cytogenetic inactivity of buminafos in the bone marrow chromosome assay corresponds to negative findings in other mutagenicity tests.     

Tyramine neurotoxicity and first-pass brain technetium-99m-diethylenetriamine penta-acetic acid

Tyramine induces coma in phenelzine-treated dogs with liver disease. The objective of the present investigation was to examine the influence of tyramine in these monoamine oxidase-inhibited dogs on the kinetics of Tc-99m-diethylenetriamine penta-acetic acid (Tc-99m-DTPA) during its first passage through the brain by nuclear imaging techniques. The study began with anesthetized mongrel dogs (n = 10) in a supine position over the camera detector. Data acquisition was started simultaneously after the rapid intracarotid injection of Tc-99m-DTPA (5 mCi) and 60 0.5-sec images of the brain were taken. Tyramine induced increased uptake with a concomitant impairment in the elimination of Tc-99m-DTPA from the brain of these phenelzine-treated animals with hepatic injury (n = 5) as compared to pretreated animals serving as a control group or phenelzine-treated animals without liver disease. This was accompanied by an appreciable reduction in hemispheric cerebral blood flow (50.5 +/- 19.3 vs. 110 +/- 16 ml/100 g/min), respectively. Increased cerebrovascular permeability of Tc-99m-DTPA and decreased cerebral blood flow occurred concomitantly with increased cerebrospinal fluid pressure and elevation in cerebrospinal fluid catecholamines of monoamine oxidase-inhibited animals with hepatic injury.     

Suitability and durability of multiple internal thoracic artery coronary artery bypasses.

OBJECTIVE: The authors evaluate operative and extended outcomes of coronary artery bypass surgery using the bilateral internal thoracic arteries (ITAs) as bypass grafts. The authors conclude that the procedure is viable and of long-term benefit to most patients. SUMMARY BACKGROUND DATA: Multiple ITA grafting was met with early enthusiasm by the surgical profession, but skepticism and controversy arose with reports of increased operative morbidity, insufficient graft blood flow, a high incidence of failure of the right ITA, and uncertainty about durability and long-term benefits. METHODS: To assess the actual incidence and impact of these complications and long-term results, the authors prospectively studied 500 consecutive patients with multiple ITA bypasses, constituting the closely observed and carefully documented experience of one surgeon over an 11-year period. RESULTS: Operative mortality in the series of 500 patients was 1.8%, perioperative myocardial infarction (new Q wave) rate was 0.6%, and deep sternal wound infection occurred in 1%. Six patients (1.2%) had strokes, and nine patients (1.8%) were returned to the operating room to control bleeding. One hundred ninety-eight patients who had abnormal stress test results before surgery were retested within 3 months of surgery. Ninety-four percent of these were normal, 3% were nondiagnostic, and 3% were abnormal. After a mean follow-up of 7.1 years (mode, 7.2 years), 87.5% of patients in the sample were alive, and 93.2% of this group have experienced continuing good clinical results (New York Heart Association class I or II). Eighty-nine patients who underwent an angiogram had 90.8% patency rates of ITA bypasses and 84.5% patency of vein grafts. Only two patients required repeat operations. CONCLUSIONS: The operative results did not support the contention that the coronary artery bypass using ITA procedure produces higher than acceptable mortality and morbidity rates. Multiple ITA bypasses can be performed without excessive morbidity, with low reoperation rates and long-term outcomes that should encourage skeptics to reconsider the procedure's clinical value.     

Use of naturally enriched mixed food in 13C breath tests applied in young suckling calves.

Utilization of three milk diets including cream, casein or whey, each naturally labelled with 13C (1 mmol 13C excess) from C4 sources, by six young male calves of the Deutsche Fleckvieh breed was investigated in a Latin-square split-plot design. Each milk diet was examined under resting conditions and during a short period of physical exercise on a treadmill. Delta 13C values (/1000) in carbon dioxide in expired air were measured at intervals of about 1 h during 6.5 h after food intake. Expired air samples for CO2 isolation, subsequent isotopic analysis, measurement of CO2 production and respiratory quotient were taken at about hourly intervals and 13C recovery rates over 6.5 h were calculated. Feeding milk containing enriched milk casein, cream, or whey resulted in maximal significant 13C enrichments over background (delta 13C) in CO2 of +1, +2.4 and +2.2 /1000, and recovery rates of 3.6, 9.9 and 12.2% respectively. This comparison shows the different kinetic behaviour of the main nutrients during the oxidation in tissues. The short exercise period (5 min at 1 J/s per kg body-weight +5 min at 2 J/s per kg body-weight) did not influence the recovery rates significantly. However, after 10 min of muscular exercise there was a brief decrease in delta 13C value of expired air which disappeared within the first 5 min of rest. These experiments demonstrate for the first time the applicability of the 13C breath test with naturally enriched diets in animal nutrition research and that quantitative results may be obtained.     

Quantification of tricuspid insufficiency--comparison of Doppler echocardiography and radionuclide ventriculography]

In 40 patients (pts) (ages 34-83 years) the severity of tricuspid regurgitation (TR) was graded by pulsed Doppler echocardiographic determination of regurgitant jet extension. Mild TR was assessed in seven pts (group I), mode-rate TR in 20 pts (group II), and severe TR in 13 pts (group III). The enddiastolic diameter of the left ventricle as measured by M-mode-echocardiography was 55 +/- 16 mm in group I, 48 +/- 6 mm in group II, and 50 +/- 10 mm in group III. The regurgitant index (RI), i.e., the ratio of left-to-right-ventricular stroke counts (normal range 0.89-1.97) and the time-activity curve over the liver area were measured by equilibrium radionuclide ventriculography (RNV). The RI differed significantly between group I (1.6 +/- 0.5), II (1.0 +/- 0.3), and III (0.8 +/- 0.3) (p less than 0.01). An RI-value below 0.89 as an index of right-ventricular volume overload was found in 14% (group I), 45%, (group II) and 77% (group III). The time-activity curve over the liver area, as graded by count variation in phase with the right atrium from 1 (no count variation) to 4 (typical count variation) showed all grades in groups I and II, but only grade 2 to 4 in group III. The RI resp. the time-activity curve over the liver is a sensitive parameter for the detection of moderate to severe TR. If TR is ascertained, severe regurgitation can be differentiated from mild regurgitation by RNV-derived RI as an index of right-ventricular volume overload.     

Prevalence of post-traumatic stress disorder symptoms in orofacial pain patients.

OBJECTIVE: There is a high comorbidity between symptoms of post-traumatic stress disorder (PTSD) and chronic pain incidence. The objective of this investigation was to determine the prevalence of PTSD symptoms in chronic orofacial pain patients. STUDY DESIGN: The study included 1478 adult patients (mean age 36.4 +/- 12.7 years) with primary diagnoses of masticatory/cervical muscle pain or temporomandibular joint pain. Patients completed a battery of psychometric questionnaires including a screening for PTSD symptoms. The sample was divided into a PTSD-positive group (n=218, 15%) a PTSD-negative group (n=551, 37%), and a no-stressor group (n=709, 48%) according to stressor incidence and symptom severity. RESULTS: The current prevalence of PTSD symptomatology was considerably higher than that reported in surveys from the general population. Patients in the PTSD-positive symptom group reported significantly higher psychological distress, sleep dysfunction, and pain severity compared to patients in the other groups. Psychological distress as measured by the SCL-90-R reached clinically significant levels only in those patients with PTSD symptomatology. CONCLUSIONS: The results of this study performed at a tertiary care center suggest that TMD patients without PTSD symptomatology show low levels of psychological distress, if any. Clinically significant levels of psychological distress are likely indicators for PTSD. PTSD screening should be included as part of a routine psychometric test battery in TMD patients.