Valproic acid induced encephalopathy--19 new cases in Germany from 1994 to 2003--a side effect associated to VPA-therapy not only in young children.

Valproic acid (VPA) is a broad-spectrum antiepileptic drug and is usually well-tolerated. Rare serious complications may occur in some patients, including haemorrhagic pancreatitis, bone marrow suppression, VPA-induced hepatotoxicity and VPA-induced encephalopathy. The typical signs of VPA-induced encephalopathy are impaired consciousness, sometimes marked EEG background slowing, increased seizure frequency, with or without hyperammonemia. There is still no proof of causative effect of VPA in patients with encephalopathy, but only of an association with an assumed causal relation. We report 19 patients with VPA-associated encephalopathy in Germany from the years 1994 to 2003, none of whom had been published previously.     

Routine diagnostics for neural antibodies,clinical correlates,treatment and functional outcome

Objective

To determine frequencies, interlaboratory reproducibility, clinical ratings, and prognostic implications of neural antibodies in a routine laboratory setting in patients with suspected neuropsychiatric autoimmune conditions.

Methods

Earliest available samples from 10,919 patients were tested for a broad panel of neural antibodies. Sera that reacted with leucine-rich glioma-inactivated protein 1 (LGI1), contactin-associated protein-2 (CASPR2), or the voltage-gated potassium channel (VGKC) complex were retested for LGI1 and CASPR2 antibodies by another laboratory. Physicians in charge of patients with positive antibody results retrospectively reported on clinical, treatment, and outcome parameters.

Results

Positive results were obtained for 576 patients (5.3%). Median disease duration was 6 months (interquartile range 0.6–46 months). In most patients, antibodies were detected both in CSF and serum. However, in 16 (28%) patients with N-methyl-d-aspartate receptor (NMDAR) antibodies, this diagnosis could be made only in cerebrospinal fluid (CSF). The two laboratories agreed largely on LGI1 and CASPR2 antibody diagnoses (κ = 0.95). The clinicians (413 responses, 71.7%) rated two-thirds of the antibody-positive patients as autoimmune. Antibodies against the α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor (AMPAR), NMDAR (CSF or high serum titer), γ-aminobutyric acid-B receptor (GABABR), and LGI1 had ≥ 90% positive ratings, whereas antibodies against the glycine receptor, VGKC complex, or otherwise unspecified neuropil had ≤ 40% positive ratings. Of the patients with surface antibodies, 64% improved after ≥ 3 months, mostly with ≥ 1 immunotherapy intervention.

Conclusions

This novel approach starting from routine diagnostics in a dedicated laboratory provides reliable and useful results with therapeutic implications. Counseling should consider clinical presentation, demographic features, and antibody titers of the individual patient.

     

Apocrine mixed tumor

We report on an apocrine mixed tumor. There are two essential elements that are characteristic of well-circumscribed, benign tumor: 1. Nests of epithelial cells, 2. Variously structured glandular pattern of the apocrine type embedded in a chondroid or mucoid. matrix.     

Protoporphyrin IX occurs naturally in colorectal cancers and their metastases

Colorectal cancers exhibit a red fluorescence. The nature of the responsible fluorophore and its eventual diagnostic potential were investigated. Thirty-three consecutive colorectal resection specimen, 32 of which with histologically confirmed cancer, and a total of 1053 palpable mesenteric nodes were fluorimetrically characterized ex vivo. Furthermore, frozen material from 28 patients was analyzed, selected for the availability of primary tumor material and metastatic tissue, e.g., lymphatic and liver metastases from the same patient. Biochemical characterization was carried out through chemical extraction and reversed phase high-performance liquid chromatography. The fluorescence spectra of tissues, tissue extracts, and standard solutions of porphyrins were determined using a pulsed solid-state laser system for excitation and an imaging polychromator, together with an intensified CCD camera for time-delayed observation. Protoporphyrin IX (PpIX) was identified as the predominant fluorophore in primary tumors and their metastases. The fluorophore occurred in the absence of necrosis and in sterile locations. In untreated cases (n = 24), PpIX fluorescence discriminates metastatically involved lymph nodes from all other palpable nodes with a sensitivity of 62% at a specificity of 78% (P < 0.0001). After neoadjuvant treatment of rectal cancer, the PpIX fluorescence level of the primary tumors was reduced and a discrimination of lymph nodes based on PpIX-fluorescence was impossible. We conclude that colorectal cancer metastases accumulate diagnostic levels of endogenous PpIX as a result of a tumor-specific metabolic alteration.     

Bowenoid papulosis of the genito-anal region

Bowenoid papulosis is a new and rather frequent entity affecting young men and women. Clinically, the lesions consists of multiple red or brown papules in the genitoanal region. Histologically, the papules shows alterations of the epidermis similar to those in Bowen's disease. The course of the disease, however, is benign. Recent investigations by zur Hausen, Ikenberg et al. have demonstrated the presence of HPV type 16-DNA in bowenoid papulosis.     

Diagnostischer und prognostischer Wert neurologischer Zusatzdiagnostik beim Alkoholdelir

Der Verlauf intensivmedizinisch behandelter Alkoholdelirien ist in 28% der F?lle durch eine begleitende ZNS-Erkrankung erschwert. Durch das Delir mitigierte neurologische Begleiterkrankungen, wie Meningoenzephalitiden, intrakranielle H?matome oder eine zentrale pontine Myelinolyse k?nnen bei Vorliegen einer atypischen deliranten Symptomatik durch eine neurologische Zusatzdiagnostik mit Hilfe von CCT/MRT und Liquoranalyse ausreichend diagnostiziert werden. Der diagnostische und prognostische Wert dieser Zusatzdiagnostik wurde an 32 neurologisch-intensivmedizinisch behandelten Alkoholikern im Delir untersucht. Das Auftreten zerebraler Komplikationen korreliert dabei ebenso wie ein initialer Grand-mal-Anfall mit einem protahierten Verlauf und Beatmungspflichtigkeit. Eine Blut-Liquor-Schrankenst?rung lie? sich bei 70% nachweisen. Es finden sich Hinweise für einen verl?ngerten Krankheitsverlauf dieser Patienten. Dem alleinigen Nachweis einer zerebralen Atrophie im CCT/MRT kommt dagegen kein prognostischer Wert hinsichtlich des Delirverlaufes zu. Ein Alkoholdelir mit jedoch typischem klinischem Bild erfordert nach unseren Ergebnissen keine bildgebende oder liquoranalytische Untersuchung.     

Cardiac denervation in postural tachycardia syndrome

Myocardial 123I-Meta-iodobenzylguanidine uptake was markedly reduced in a patient with postural tachycardia syndrome (POTS). This finding suggests that loss of sympathetic autonomic neurons in the heart may play a role in the etiology of POTS.     

Autonomic nervous system laboratories: a European survey

We present a questionnaire-based survey on methods adopted in European autonomic nervous system (ANS) laboratories in the year 2002. Seventy-nine laboratories from 16 countries in Western and Eastern Europe provided information on test methods, equipment, staff, educational programme and research activities. The results confirmed the anticipated heterogeneity of techniques used to investigate ANS disorders. However, cardiovascular (84.8%) and sudomotor (43.0%) tests were the most common. There were no standards regarding equipment, but devices used varied widely, in part commercially available, in part self-developed. Some ANS laboratories performed cardiovascular tests using standard EMG devices with implemented routines to measure heart rate variability. Many investigators used published normative data (75.4%). Most of the responders were involved in scientific work, half were active in education of trainees. A wide variation was found in number and profession of staff members. As more than 60% of questionnaires were returned by neurologists our results may be limited to neurological ANS laboratories. Given the wide variation of methods and equipment used in European ANS laboratories, minimal standards for routine ANS testing are desirable. Standards may help to compare results of diagnostic tests, evaluate equipment and test laboratory methods and commercial devices and set-up educational programmes.     

Pemphigus herpetiformis

Pemphigus herpetiformis is a separate form of pemphigus with its own features. Clinically it resembles dermatitis herpetiformis Duhring. Periodically there is an extraordinary violent itching. Histologically pemphigus herpetiformis shows an eosinophilic spongiosis. The important acantholysis can only be found by repeated biopsies. Because of the acantholysis and the intercellular autoantibodies, demonstrated by direct and indirect immunfluorescence, this dermatosis belongs to the group of pemphigus. The therapeutical response to 4,4'-diaminodimethyl-diphenylsulfone (DDS)--a similarity to dermatitis herpetiformis Duhring--is especially characteristic. Our own observation gives occasion to characterize this pemphigus variant, which is repeatedly described in the literature under different designations, as pemphigus herpetiformis.