Neurological presentations of the antiphospholipid syndrome: three illustrative cases.

The antiphospholipid syndrome (APS) is defined by the association of high titers of antiphospholipid antibodies (aPLs) with thrombotic events and/or obstetrical problems. APS can be isolated or associated with immune system diseases. Several central nervous system (CNS) manifestations have been reported in APS, but are still not included in the international diagnostic criteria. We present here three cases of APS revealed by CNS manifestations. The first patient had a primary APS with stroke, dementia, epilepsy and the "so-called" Liebman-Sacks disease, a subacute thrombotic non-bacterial valvulopathy. The second one developed a primary APS with a Sneddon syndrome, while the third case is a neurolupus-associated APS with subacute encephalopathy, chorea, stroke, and epilepsy. The pathogenesis of the APS is related to both prothrombotic and immunologic effects of the aPLs. Long-term anticoagulation by low-weight heparin or warfarin is currently recommended in APS. We propose to search the presence of aPLs in any case of young adults' stroke, unexplained dementia, and acquired chorea.

Posterior reversible encephalopathy syndrome as a revealing manifestation of Guillain-Barré syndrome.

We report a patient with a Guillain-Barré syndrome (GBS) revealed by a posterior reversible encephalopathy syndrome (PRES). The PRES is typically associated with bilateral parieto-occipital T2 and FLAIR hyperintense MRI lesions and observed in various etiologic conditions leading to acute arterial hypertension. PRES results from a breakdown of the circulatory autoregulation, many in the posterior cerebral territories. GBS can be considered as an independent risk factor of PRES, due to acute dysautonomia and pain with consecutive arterial hypertension, as well as to cytokine production changing capillary permability. Such patients with PRES-revealed GBS may be treated with intravenous immunoglobulin therapy only after exclusion of any ischemic or hemorrhagic cerebral complications, and after control of the blood pressure and of the encephalopathic signs and symptoms.

[Neurosyphilis revealed by a multiple cranial neuropathy: magnetic resonance imaging findings]. / Neurosyphilis révélée par une atteinte multiple des nerfs crâniens: apport de l'imagerie par résonance magnétique nucléaire.

INTRODUCTION: We report the magnetic resonance imaging (MRI) findings in a case of neurosyphilis revealed by the involvement of two cranial nerves. CASE REPORT: A 41-year-old man developed a right cochleovestibular and left trigeminal neuropathy, associated with high serum titers of VDRL and TPHA, high titers of TPHA in the cerebrospinal fluid (CSF) and several CSF oligoclonal IgG bands. On MRI, hypertrophy and gadolinium contrast enhancement of these cranial nerves were associated with several supratentorial cortical nodules surrounded by marked cerebral edema, corresponding to syphilitic gummas. One of these cortical nodules was biopsied. Microscopic examination showed lesions of meningoencephalitis with necrosis and granulomatous vasculitis. After penicillin therapy, the serum VDRL titers and the MRI abnormalities disappeared, a partial clinical recovery was observed and a significant reduction of the serum TPHA titers was found. DISCUSSION: Such MRI abnormalities are not specific and can be observed in various tumoral, auto-immune and infectious diseases. They can also mimic neurofibromatosis type II. Cranial nerve involvements in neurosyphilis can result from nerve inflammation in basal meningitis, nerve ischemia in meningovasculitis or from compression by an adjacent gumma. In our case, the cranial neuropathy was related to a mixed meningovascular and parenchymatous form of neurosyphilis.

Mitoxantrone-related acute leukemia in two MS patients.

We report two new cases of mitoxantrone-related leukemia occurring in two patients with multiple sclerosis (MS), 14 and 18 months after the last infusion of the drug. One patient was successfully treated. We were able to collect 29 other cases in the literature. Most of them were single reports but some were described within cohorts of mitoxantrone-treated MS patients. The incidence rate was 0.65% from all cohorts totalizing 2299 patients. Acute promyelocytic leukemia with the translocation t(15;17) was over-represented in the MS population in comparison with cancer patients also treated with mitoxanrone. The occurrence of leukemia was dose-independent and appeared with a mean delay of 20 months after the end of the treatment.

[Wernicke's encephalopathy associated with chronic disulfiram intoxication]. / Encéphalopathie de Gayet-Wernicke associée a une intoxication chronique au disulfiram.

INTRODUCTION: We report the case of a patient with an unusual association of Wernicke encephalopathy and chronic disulfiram intoxication. CASE REPORT: A 41-year-old man presented with progressive frontal decline and akineto-rigid parkinsonism under chronic disulfiram therapy. He also developed acute confusion with ataxia, blepharospasm, and supranuclear ophthalmoplegia following a severe malnutrition due to refusal of food intake. Brain MRI revealed symmetrical and reversible hyperintense lesions on T2 and FLAIR in the posterior putaminal regions, dorso-medial thalamic and subthalamic nuclei, the periaqueducal gray matter, the cerebellar peduncles, and the pontine tegmentum. A slow partial clinical recovery with persistent frontal syndrome was observed after discontinuation of disulfiram and parenteral administration of thiamine. DISCUSSION: The symmetry and reversibility of the MRI lesions in the basal ganglia and brain stem were suggestive of a deficiency, a toxic or a metabolic neurological disease. The dorso-medial thalamo-subthalamic and brainstem localizations, as well as their occurrence in a state of malnutrition, were consistent with Wernicke encephalopathy. Moreover, chronic disulfiram intoxication might explain the frontal syndrome and the akineto-rigid parkinsonism, associated with MRI putaminal lesions. Similar MRI lesions have been described in the so-called "energy deprivation syndromes", which are toxic, genetic or nutritional disorders that disrupt enzymes involved in energy generating metabolic pathways such as glycolysis and pyruvate oxidation.

[Acute pain management in proximal femoral fractures: femoral nerve block (catheter technique) vs. systemic pain therapy using a clinic internal organisation model]. / Akutschmerztherapie bei Patienten mit hüftgelenknahen Frakturen : N.-femoralis-Katheter-Analgesie vs. systemische Schmerztherapie unter Anwendung eines klinikinternen Organisationsmodells.

BACKGROUND: The aim of this study was to compare safety and efficacy of catheter-mediated femoral nerve block analgesia with systemic pain therapy in patients with proximal femoral fractures in the pre-operative and post-operative setting using a protocol for coordinating pain management. METHODS: In a prospective randomised trial of patients attending the emergency department, 100 individuals were selected with a clinically diagnosed proximal femoral fracture. Patients were divided into two equal groups A and B. Group A (n=50) received a catheter-mediated femoral nerve block with 1% prilocaine (40 ml) and post-operatively 0.2% ropivacaine (30 ml) 6 hourly. Group B (n=50) initially received intravenous metamizol (1 g) and a fixed combination of oral tilidine (100 mg) + naloxone (8 mg). Patients aged 90 years or more received a reduced dose (tilidine 75 mg + naloxone 6 mg). In the post-operative period regular oral ibuprofen (400 mg, 8 hourly) in addition to oral tilidine (50 mg) + naloxone (4 mg) was given as required for break through pain. Pain intensity was measured using a verbal rating scale (VRS) from 1 to 5: pain free (=1), mild pain (=2), moderate pain (=3), severe pain (=4), excruciating pain (=5). Pain scores were recorded at rest (R), during passive anteflection (30 degrees) of the hip (PA) on arrival and at 15 and 30 min after initial administration of analgesia. Thereafter, recordings were made 4 times a day up to the third post-operative day. RESULTS: Pain scores were comparable for both groups on admission (VRS in R 2.50 vs. 2.46; VRS during PA 4.30 vs. 4.34). Significant pain relief was achieved in both groups following initial administration of analgesia, but the total pain scores in group A were significantly lower than in group B (VRS in R 1.22 vs. 1.58, p<0.01 and VRS during PA 2.66 vs. 3.26; p<0.001). No difference was noted between the two groups during the first 3 post-operative days. No severe complications occurred as a result of analgesia, however, the catheter was dislodged in 20% of patients in group A resulting in the need for systemically administered analgesia. CONCLUSION: All patients presenting with proximal femoral fractures should receive adequate analgesia within the emergency department even prior to radiographic imaging. Femoral nerve block should be considered as the method of choice. The insertion of a femoral nerve block catheter has the dual advantage of early analgesia permitting repeated clinical examination in addition to continued post-operative pain management. The cumbersome logistics inherent in this technique within the clinical setting limits its practical application. An initial single-shot regional nerve block followed by a systemic post-operative analgesia protocol was considered an appropriate alternative. The execution of safe, consistent and appropriate regional nerve block anaesthesia is reliant on formal guidelines and protocols as agreed by the multidisciplinary teams involved with patient-directed pain management and good clinical practice.

The scoliosis (sco) mouse: a new allele of Pax1.

We describe the spontaneous mutant mouse scoliosis (sco) that carries a new allele of Pax1 (un-i, undulated intermediate). The Pax1(un-i) allele is lacking the 5'-flanking region and exon 1 to 4 which is mapped to nt -2636 to -640 and -272 to 4271 of the Pax1 gene. Homozygous mice show a mild form of the known phenotypes of other Pax1 mutants. Adult mice have a lumbar scoliosis and kinky tails. In homozygous embryos the skeleton ossifies early, ossification centers of the vertebral bodies are fused with the ossification centers of the pedicles. Neural arches and spinous processes are underdeveloped but the pedicles and transverse processes are overdeveloped which is in contrast to other Pax1 mutants. In the scapula, the acromion is missing and the deltoid tuberosity of the proximal humerus is shortened and thickened. Among the inner organs the thymus development is affected. In late embryos, the thymus is small and thymocyte numbers are reduced. T-cell development from CD4- and CD8- double negative (DN) to CD4+ and CD8+ double positive (DP) is decelerated. The percentage of CD90+ cells is also reduced but in contrast to other Pax1 mutants no alteration of the expression level of the CD90 (Thy-1) could be found.