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.     

Inhaled iloprost to control residual pulmonary hypertension following pulmonary endarterectomy

Objective: Pulmonary endarterectomy (PEA) is the standard therapy for patients with chronic thromboembolic pulmonary hypertension (CTEPH). In the immediate postoperative period, persistent pulmonary hypertension increases the risk of acute respiratory or right heart failure. In pulmonary arterial hypertension, prostanoid inhalation has been found to improve pulmonary hemodynamics, right ventricular function, gas exchange, and clinical outcome. We report the results of a double-blinded randomized trial with the aerosolized prostacyclin analogue iloprost in patients with residual pulmonary hypertension after PEA. Methods: Twenty-two patients (age, 55 ± 13 years; 8 females; propofol- and sufentanil-based anesthesia; pressure-controlled mechanical ventilation) were randomized to receive either a single dose of 25 μg aerosolized iloprost (iloprost group; n = 11) or normal saline (placebo group; n = 11) immediately after postoperative ICU admission. Primary endpoints were changes in gas exchange, pulmonary and systemic hemodynamics, and clinical outcome. Results: Iloprost significantly enhanced cardiac index (CI) and reduced mean pulmonary arterial pressure (mPAP) and pulmonary vascular resistance [PVR (dyn s cm⁻⁵)] in contrast to placebo. Placebo: pre-inhalation 413 ± 195 versus post-inhalation 404 ± 196 at 30 min (p = 0.051), 415 ± 189 at 90 min (p = 0.929). Iloprost: pre-inhalation 503 ± 238 versus post-inhalation 328 ± 215 at 30 min (p = 0.001), 353 ± 156 at 90 min (p = 0.003). Blood oxygenation remained unchanged. Conclusion: In addition to the effect of PEA, iloprost reduces residual postoperative pulmonary hypertension, decreases right ventricular afterload and may facilitate the early postoperative management after PEA.     

A note on paternity computation in cases lacking a mother

When the mother is unavailable for parentage testing, a calculation must usually be based on types determined for the child and the alleged father. Particularly in the case of DNA typing, the formula is easy to derive. The correct formula is apparently not widely known, however, and in fact, a formula that is obviously incorrect seems often to be used and quoted. The correct method of derivation is indicated, and formulae are given for the various possibilities for patterns of gene- sharing between child and alleged father. In most cases paternity = 1/4Pr(shared allele) is an adequate formula.     

HELLP syndrome associated with factor V R506Q mutation

The pathogenesis of HELLP (haemolysis, elevated liver enzyme and low platelet count) syndrome, a severe presentation of pre-eclampsia, is still an enigma. Activated protein C resistance resulting from a mutation in coagulation factor V has recently emerged as the leading cause of thrombosis in pregnancy. We report on two patients with HELLP syndrome who were found to be heterozygous for factor V R506Q mutation, leading to activated protein C resistance. These findings suggest that the pathogenesis of HELLP syndrome is associated with a thrombotic process, and point to the potential benefit of anti-thrombotic therapy in this condition.     

Concentric sclerosis (Baló): Morphometric and in situ hybridization study of lesions in six patients

Brain tissues from 6 patients with concentric sclerosis (Baló) were examined by in situ hybridization, immunocytochemistry, morphometry, and histological methods. The patients were 24 to 48 years old and had progressive cerebral symptoms and signs that lasted 15 to 100 days. Large demyelinative lesions, most frequent in the frontal white matter, contained alternating bands of demyelinated and partly myelinated white matter that were arranged in concentric or mosaic patterns. In the areas of demyelination, axons were relatively well preserved and there were perivascular inflammatory infiltrates. In 2 specimens, lesions contained regions with the characteristic appearance of actively demyelinating multiple sclerosis plaques. Oligodendroglial densities were highest in normal-appearing white matter, lower in partially myelinated areas, and lowest in demyelinated areas, which also contained many hypertrophic astrocytes closely associated with oligodendroglia. Messenger RNA levels for myelin-related proteins followed the same pattern; they were lowest in demyelinated areas, higher in partially myelinated areas, and highest in normal-appearing white matter beyond lesion margins. Our findings suggest that concentric sclerosis is a variant of multiple sclerosis, that oligodendroglial loss is important in the pathogenesis of demyelination, and that partially myelinated areas probably represent stages of ongoing myelin breakdown rather than remyelination of previously demyelinated areas.     

A case of area-specific stimulus-sensitive postanoxic myoclonus.

The authors report a case of area-specific stimulus-sensitive postanoxic myoclonus and discuss possible pathophysiology. A 71-year-old man sustained cardiorespiratory arrest that lasted 10 minutes and remained unresponsive. On the first EEG obtained 8 hours after the arrest there was no cerebral electrical activity before stimulation of the trigeminal-innervated areas. Periorbital stimulation was associated with bursts of spike-wave activity and generalized myoclonic jerks, whereas other types of stimulation did not elicit any response. A second EEG obtained 32 hours later showed a nonreactive alpha coma pattern. The patient died 7 days after the arrest. Area-specific stimulus-sensitive postanoxic myoclonus is very rare. The regularity of generalized bursts of spike-wave activity (cortical response) in response to stimulation of trigeminal-innervated areas suggests that the resting EEG electrocerebral silence may have been a result of cortical suppression with disinhibition of stimulus-sensitive brainstem-generated myoclonus.     

Detection of primary breast cancer in women with known adenocarcinoma metastatic to the axilla: Use of MRI after negative clinical and mammographic examination

The purpose of this study was to evaluate the ability of MRI to identify a primary site of malignancy in the breast of patients who present clinically with ipsilateral lymph nodes containing metastatic carcinoma but whose physical and mammographic examination are negative. MRI of the breast was performed on four patients using a variety of imaging parameters, all with and without gadolinium contrast. All patients had biopsy-proven adenocarcinoma of the ipsilateral axilla, with negative physical and mammographic examinations. Foci of enhancement assessed visually on precontrast and postcontrast scans (n = 1) and on substraction studies (n = 3) were considered suspicious under the clinical circumstances defined for this study. Lesions identified on MRI were re-identified on ultrasound examination and either preoperative localization for excisional biopsy or tissue sampling was performed. Surgery was performed and histopathologic correlation was obtained in all cases. Primary sites of breast carcinoma were identified in all four patients, with multiple sites of malignancy identified in three of four patients. Breast conservation therapy was made possible for three of four patients based on the results of the MRI study showing sites of malignancy and no features of cancer elsewhere in the breast. Follow-up data of 1, 2, and 5 years of these patients show no evidence of recurrent disease. MRI of the breast is a useful technique for identifying primary sites of malignancy in patients presenting with ipsilateral lymph nodes positive for metastatic adenocarcinoma when the physical and mammographic examinations are negative.