Lower cranial nerve motor function in unilateral vascular lesions of the cerebral hemisphere.

Motor function subserved by cranial nerves V, VII, X, XI, and XII was assessed in 100 patients with hemiparesis due to a unilateral vascular lesion of the cerebral hemisphere. Several of the findings were not described clearly in many of the standard textbooks of neurology. Weakness of sternomastoid when present was always contralateral to the hemiparesis. This emphasises the principle that the cerebral hemisphere controls movement of the body parts in or towards the contralateral half of the body rather than simply the contralateral muscle groups. An apparent exception to this was seen, however, in the small group of patients who had unilateral weakness of the tongue. In those patients deviation of the tongue was towards the hemiparetic side--that is, the cerebral hemisphere controlled the contralateral half of the tongue and hence protrusion towards the ipsilateral side. Mild dysarthria was common with both right and left sided hemiparesis.     

A case of hypokalemic myopathy associated with transient hypothyroidism

A case of transient hypothyroidism in the course of hypokalemic myopathy is reported. A 69-year-old woman had severe muscle weakness and marked potassium deficiency associated with alkalosis during treatment with thiazide diuretics. The cause of muscle weakness proved to be hypokalemic myopathy confirmed by clinical findings and muscle biopsy. After the episode of hypokalemic myopathy, serum levels of thyroid hormone were lowered (T4; 3.8 micrograms/dl, T3; 54 ng/dl) and that of TSH was elevated (25.1 microU/ml). Antithyroid microsomal antibody was positive (1:25600) and anti-thyroglobulin antibody was negative. About one month after potassium supplement, her thyroid functions returned to normal, along with normalization of serum potassium level. This is the first documented case report of hypokalemic myopathy accompanied by transient hypothyroidism in a patient with autoimmune thyroiditis. We suggest that this transient hypothyroidism might be induced by hypokalemia during the course of autoimmune thyroiditis.     

Brugada syndrome manifested by the typical electrocardiographic pattern both in the right precordial and the high lateral leads

We identified a patient with the Brugada syndrome and frequent episodes of the traumatic syncope. This patient presented with alternating ST-segment elevation in the right precordial and the high lateral leads. The signal-averaged ECG was positive for the late potentials and electrophysiology study revealed no inducible supraventricular or ventricular tachycardias. Because of the frequent traumatic syncope, a dual-chamber implantable cardioverter-defibrillator was implanted. This report suggests that the Brugada syndrome may have different electrocardiographic presentations within a single individual over a short period of time. The significance of these changes needs to be assessed in a prospective long term study.     

Effect of Methylguanidine in a Model of Septic Shock Induced by LPS

Septic shock, a severe form of sepsis, is characterized by cardiovascular collapse following microbial invasion of the body. The progressive hypotension, hyporeactivity to vasopressor agents and vascular leak leads to circulatory failure with multiple organ dysfunction and death. Many inflammatory mediators (e.g. TNF-α, IL-1 and IL-6) are involved in the pathogenesis of shock and, among them, nitric oxide (NO). The overproduction of NO during septic shock has been demonstrated to contribute to circulatory failure, myocardial dysfunction, organ injury and multiple organ failure. We have previously demonstrated with in vitro and in vivo studies that methylguanidine (MG), a guanidine compound deriving from protein catabolism, significantly inhibits iNOS activity, TNF-α release and carrageenan-induced acute inflammation in rats. The aim of the present study was to evaluate the possible anti-inflammatory activity of MG in a model of septic shock induced by lipopolysaccharide (LPS) in mice. MG was administered intraperitoneally (i.p.) at the dose of 30 mg/kg 1 h before and at 1 and 6 h after LPS-induced shock. LPS injection (10 mg/kg in 0.9% NaCl; 0.1 ml/mouse; i.p.) in mouse developed a shock syndrome with enhanced NO release and liver, kidney and pancreatic damage 18 h later. NO_x levels, evaluated as nitrite/nitrate serum levels, was significantly reduced in MG-treated rats (78.6%, [Formula: See Text]). Immunohistochemistry revealed, in the lung tissue of LPS-treated group, a positive staining for nitrotyrosine and poly(adenosine diphosphate [ADP] ribose) synthase, both of which were reduced in MG-treated mice. Furthermore, enzymatic evaluation revealed a significant reduction in liver, renal and pancreatic tissue damage and MG treatment also improved significantly the survival rate. This study provides evidence that MG attenuates the degree of inflammation and tissue damage associated with endotoxic shock in mice. The mechanisms of the anti-inflammatory effect of MG is, at least in part, dependent on the inhibition of NO formation.     

Insertion of the Impella 5.0 left ventricular assist device via right anterior mini-thoracotomy: a novel practical approach

The Impella 5.0 microaxial pump is a miniaturized left ventricular assist device commonly used for circulatory support in acute cardiogenic shock. The catheter-based pump is designed to be inserted either into a peripheral artery or directly into the ascending aorta. We report the first case in which the Impella 5.0 device was placed directly into the ascending aorta via a small right anterior thoracotomy in a patient following acute myocardial infarction complicated by cardiogenic shock.     

Distinct functional defect of three novel Brugada syndrome related cardiac sodium channel mutations

The Brugada syndrome is characterized by ST segment elevation in the right precodial leads V1-V3 on surface ECG accompanied by episodes of ventricular fibrillation causing syncope or even sudden death. The molecular and cellular mechanisms that lead to Brugada syndrome are not yet completely understood. However, SCN5A is the most well known responsible gene that causes Brugada syndrome. Until now, more than a hundred mutations in SCN5A responsible for Brugada syndrome have been described. Functional studies of some of the mutations have been performed and show that a reduction of human cardiac sodium current accounts for the pathogenesis of Brugada syndrome. Here we reported three novel SCN5A mutations identified in patients with Brugada syndrome in Taiwan (p.I848fs, p.R965C, and p.1876insM). Their electrophysiological properties were altered by patch clamp analysis. The p.I848fs mutant generated no sodium current. The p.R965C and p.1876insM mutants produced channels with steady state inactivation shifted to a more negative potential (9.4 mV and 8.5 mV respectively), and slower recovery from inactivation. Besides, the steady state activation of p.1876insM was altered and was shifted to a more positive potential (7.69 mV). In conclusion, the SCN5A channel defect related to Brugada syndrome might be diverse but all resulted in a decrease of sodium current.     

Patient with pontine warning syndrome and bilateral posterior internuclear ophthalmoplegia: case report

Background

Capsular warning syndrome was first described in 1993, featured with repetitive episodes of motor and/or sensory dysfunction without cortical signs. Recently, it has been demonstrated that clinically typical capsular warning syndrome can be associated with pontine infarct and the term �pontine warning syndrome� was coined.

Case Presentation

A 54-year-old woman with a history of hypertension was seen with profound left-sided hemiplegia. She had had 3 episodes of left-sided weakness before complete hemiplegia. Her speech was slurred. Left central facial palsy and hemiglossoplegia were presented. Her left plantar response was extensor and bilateral posterior internuclear ophthalmoplegia was seen on neurologic examination. Biochemical tests revealed hyperglycemia and dyslipidemia on the next day. MRI demonstrated an acute right paramedian pontine infarct. The patient was commenced on oral clopidogrel, atorvastatin and acarbose. After 23 days of hospitalization, she was discharged with severe left hemiplegia.

Conclusions

1) Pontine warning syndrome may be underestimated and understudied. 2) Posterior internuclear ophthalmoplegia is a rare clinical sign in cerebrovascular diseases, while it can help to locate a brainstem lesion rather than an internal capsular one. 3) Blood pressure lowing administration may be improper for patients with pontine warning syndrome.

     

Effect of methylguanidine in a model of septic shock induced by LPS

Septic shock, a severe form of sepsis, is characterized by cardiovascular collapse following microbial invasion of the body. The progressive hypotension, hyporeactivity to vasopressor agents and vascular leak leads to circulatory failure with multiple organ dysfunction and death. Many inflammatory mediators (e.g. TNF-alpha, IL-1 and IL-6) are involved in the pathogenesis of shock and, among them, nitric oxide (NO). The overproduction of NO during septic shock has been demonstrated to contribute to circulatory failure, myocardial dysfunction, organ injury and multiple organ failure. We have previously demonstrated with in vitro and in vivo studies that methylguanidine (MG), a guanidine compound deriving from protein catabolism, significantly inhibits iNOS activity, TNF-alpha release and carrageenan-induced acute inflammation in rats. The aim of the present study was to evaluate the possible anti-inflammatory activity of MG in a model of septic shock induced by lipopolysaccharide (LPS) in mice. MG was administered intraperitoneally (i.p.) at the dose of 30 mg/kg 1 h before and at 1 and 6 h after LPS-induced shock. LPS injection (10 mg/kg in 0.9% NaCl; 0.1 ml/mouse; i.p.) in mouse developed a shock syndrome with enhanced NO release and liver, kidney and pancreatic damage 18 h later. NOx levels, evaluated as nitrite/nitrate serum levels, was significantly reduced in MG-treated rats (78.6%, p < 0.0001; n = 10). Immunohistochemistry revealed, in the lung tissue of LPS-treated group, a positive staining for nitrotyrosine and poly(adenosine diphosphate [ADP] ribose) synthase, both of which were reduced in MG-treated mice. Furthermore, enzymatic evaluation revealed a significant reduction in liver, renal and pancreatic tissue damage and MG treatment also improved significantly the survival rate. This study provides evidence that MG attenuates the degree of inflammation and tissue damage associated with endotoxic shock in mice. The mechanisms of the anti-inflammatory effect of MG is, at least in part, dependent on the inhibition of NO formation.     

The serpentine mitral valve and cerebral embolism

Valvular strands, well-delineated filiform masses, attached to cardiac valve edges are associated with cerebral embolism and stroke. Strokes, caused by emboli from valvular strands, tend to occur among younger persons. In this case report a valvular strand, giving a peculiar serpentine appearance to the mitral valve is described. This mitral valvular strand was the only explanation for an episode of cerebral embolism, presenting with a transient right sided hemiparesis. It is proposed that a randomized study involving combined treatment with aspirin and clopidogrel is warranted in young patients with valvular strands, presenting with a first episode of cerebral embolism.     

Heat Shock Stress Induces Cleavage and Activation of PAK2 in Apoptotic Cells

Heat shock induces a stress response in mammalian cells and can also lead to apoptotic cell death. Here we report that a 36-kDa myelin basic protein (MBP) kinase detected by an in-gel kinase assay can be drastically activated in several cell types by heat shock. Immunoblot analysis revealed that this 36-kDa MBP kinase can be recognized by an antibody against the C-terminal region of a family of p21^Cdc42/Rac-activated kinases (PAKs). By using this antibody and a PAK2-specific antibody against the N-terminal region of PAK2 as tools, we further demonstrated that heat shock can induce cleavage of PAK2 to generate a 36-kDa C-terminal catalytic fragment in mouse Balb/c 3T3 and human Hep 3B cells. The kinetic profile of appearance of the 36-kDa C-terminal catalytic fragment of PAK2 matched exactly with the activation of the 36-kDa MBP kinase in these cells induced by heat shock. In addition, the heat shock-induced cleavage and activation of PAK2 was found to be closely associated with both DNA fragmentation and activation of an ICE/CED-3 family cysteine protease termed caspase-3 in heat shock-treated Hep 3B cells. Moreover, blockage of the activation of caspase-3 by pretreating the cells with two specific tetrapeptidic inhibitors of caspases (Ac-DEVD-cho and Ac-YVAD-cmk) could substantially diminish the extent of heat shock-induced cleavage/activation of PAK2. Overall, our results point out that PAK2 is cleaved and activated during the heat shock-induced apoptotic cell death process and suggest that caspase-3 is involved in this process.     

Lack of effect of thyrotropin releasing hormone (TRH) in circulatory shock

Thyrotropin releasing hormone (TRH) has been reported to reverse hypotension induced by a variety of agents and thus it has been suggested to be of therapeutic value in circulatory shock. We have investigated TRH (2 mg/kg bolus plus 2 mg/kg/hr infusion) in both hemorrhagic (cats) and traumatic shock (rats). TRH induced a pressor effect of 23 +/- 8 mm Hg (p less than 0.05) in cats and 19 +/- 3 mm Hg (p less than 0.01) in rats during hypotension. However, this transient (10-15 min) response did not result in any sustained improvement in the cardiovascular status of the animals in either shock model when compared to the vehicle. In addition, TRH did not attenuate any of the biochemical indices of the severity of the shock state (i.e., plasma amino-nitrogen concentrations, or plasma cathepsin D and MDF activities) nor did it improve survival time in traumatic shock (2.8 +/- 0.4 vs. 2.0 +/- 0.2 hours). Furthermore, TRH resulted in a significant blunting of the maximum post-reinfusion superior mesenteric artery flow and enhanced beta-glucuronidase release from liver lysosomal preparations in vitro. These potentially detrimental effects in conjunction with the lack of any overt protective effect under the conditions existing in these two shock models, do not provide evidence that TRH is beneficial as a therapeutic agent in circulatory shock.     

Fine needle aspiration diagnosis of lymphangiomyomatosis. A case report

BACKGROUND: Lymphangiomyomatosis is a rare disease of females, usually of reproductive age. There is a proliferation of lymphatic smooth muscle in mediastinal, retroperitoneal and often pulmonary lymphatics and lymph nodes. CASE: A 45-year-old female presented with a right pleural effusion and increasing retroperitoneal adenopathy with palpable left inguinal adenopathy. Three months previously she had undergone a right salpingo-oophrectomy for an ovarian fibroma with concomitant left ovarian wedge biopsy, myomectomy for leiomyomas and partial omentectomy. Three years previously, at age 42, she had experienced two transient episodes of chylous pleural effusion with no sequelae. She underwent computed tomography-guided fine needle aspiration of a 4-cm inguinal lymph node to rule out lymphoma. CONCLUSION: Fine needle aspiration of lymphangiomyomatosis yields distinctive cytologic morphology. This characteristic morphology, in combination with the appropriate history, permits a minimally invasive, timely and in this particular case, entirely unexpected diagnosis.     

Confirmation of the mapping of the Camurati-Englemann locus to 19q13. 2 and refinement to a 3.2-cM region

Camurati-Englemann syndrome (DPD1) is an autosomal dominant condition associated with progressive cortical sclerosis of the diaphyses of all the long bones. Clinical features include abnormal gait, muscle weakness and wasting, and generalized fatigue. The DPD1 gene was recently mapped to a 15.1-cM region on chromosome 19q13.2. We have narrowed the region containing the DPD1 gene to a 3.2-cM region flanked by short tandem repeat markers, D19S881 and D19S718. TGFB1, a candidate gene mapped within this region, was excluded.     

Interactions between platelet activating factor and eicosanoids during endotoxic shock in anaesthetized pigs

The effects of platelet activating factor (PAF) on eicosanoid release during endotoxic shock was investigated in anaesthetized pigs receiving 5 mug kg(-1) Escherichia coli endotoxin (LPS) into the superior mesenteric artery over a 60 min period, by measuring plasma levels of a variety of mediators. Fifteen of the 31 animals infused with LPS and not treated with BN 52021, a PAF receptor antagonist, died within 30 min after the commencement of LPS infusion (non-survivors), while the other 16 survived the experimental period of 3 h, though in a state of shock (survivors). No alterations were observed in plasma concentrations of eicosanoids in the non-survivors. A significant, though transient, increase in eicosanoid concentrations occurred only in the survivors. Treatment with BN 52021 (4 mg kg-1, i.v.) injected 5 min prior to LPS infusion, failed to exert any effect on the survival rate. However, pretreatment with BN 52021 prevented circulatory collapse in the survivors and reduced the concentration of cyclooxygenase enzyme products, without affecting LTB(4) release. Exogenous administration of PAF (0.01 mug kg(-1)) caused hypotension and increased TXB(2) levels although 6-keto PGF(1alpha) and LTB(4) concentrations were unchanged. The data suggest that prostanoid formation may be secondary to PAF release in circulatory collapse evoked by LPS infusion in survivors, and give further support to the suggestion that PAF prostanoid interaction is important during endotoxic shock. However, their role in early death seems to be negligible, indicating the importance of other mediators.     

Subcutaneous immunoglobulin therapy in a patient with myopathic dropped head syndrome and common variable immunodeficiency

Prominent neck extension weakness is an uncommon clinical entity, also termed dropped-head syndrome, that may be part of a generalized neuromuscular disorder. We report here the case of a woman with dropped-head syndrome and pulmonary arterial hypertension secondary to systemic sclerosis. Subsequently, she developed common variable immunodeficiency and subcutaneous immunoglobulin therapy was started. After two months from the start of therapy we did not observe any improvement in the degree of flexion of the head, although the clinical examination shows an improvement in neck extensor muscle strength. Subcutaneous immunoglobulin therapy could be a possible therapeutic option for the treatment of myopathic neck extensor weakness.     

Long QT syndrome with AV Wenckebaching & bundle branch block in a neonate

We present a case of 21-day-old neonate brought with history of 3 episodes of syncope. Evaluation revealed congenital long QT syndrome associated with long cycle atypical AV Wenkebaching with a long short cycle sequence related left bundle branch aberrancy. Syncope was attributed to multiple episodes of Torsades de Pointes, necessitating emergency epicardial pacemaker implantation. In addition, child was started on oral propranolol therapy. On 2 months follow up, child was stable with no ventricular high rate episodes during pacemaker interrogation.     

Enhanced survival of skeletal muscle myoblasts in response to overexpression of cold shock protein RBM3

Cold-inducible RNA-binding protein (RBM3) is suggested to be involved in the regulation of skeletal muscle mass. Cell death pathways are implicated in the loss of muscle mass and therefore the role of RBM3 in muscle apoptosis in C(2)C(12) myoblasts was investigated in this study. RBM3 overexpression was induced by either cold shock (32°C exposure for 6 h) or transient transfection with a myc-tagged RBM3 expression vector. Cell death was induced by H(2)O(2) (1,000 μM) or staurosporine (StSp, 5 μM), and it was shown that cold shock and RBM3 transfection were associated with attenuation of morphological changes and an increase in cell viability compared with normal temperature or empty vector, respectively. No changes in proliferation were observed with either cold shock or RBM3 transfection. DNA fragmentation was not increased in response to H(2)O(2), and a cell permeability assay indicated that cell death in response to H(2)O(2) is more similar to necrosis than apoptosis. RBM3 overexpression reduced apoptosis and the collapse of the membrane potential in response to StSp. Moreover, the increase in caspase-3, -8, and -9 activities in response to StSp was returned to control levels with RBM3 overexpression. These results indicate that increased RBM3 expression decreases muscle cell necrosis as well as apoptosis and therefore RBM3 could potentially serve as an intervention for the loss of muscle cell viability during muscle atrophy and muscle diseases.     

POLG mutation in a patient with cataracts, early-onset distal muscle weakness and atrophy, ovarian dysgenesis and 3-methylglutaconic aciduria

Mutations in POLG account for one of the most frequent nuclear encoded causes of mitochondrial disorders to date. Individuals harboring POLG mutations exhibit fairly heterogeneous clinical presentations leading to increasing difficulties in classifying these patients into defined clinical phenotypes. This study aims to investigate the molecular basis of a mitochondrial cytopathy in a patient with 3-methylglutaconic aciduria and to expand the clinical phenotype associated with POLG mutations. Clinical, molecular and genetic analyses as well as neurophysiological examinations were carried out for a 23-year-old woman of mixed Caucasian and Latin American ancestry with a history of cataracts diagnosed at age 1 year, she had onset of distal muscle weakness at age 2 years progressing to atrophy and ovarian dysgenesis at puberty. The patient was found to have 3-methylglutaconic acid with normal 3 hydroxyisovaleric acid on urine organic acid analysis. POLG sequencing was done and a heterozygous variant, c.2851T>A (p.Y951N) was found which is predicted to be deleterious. There are limited reports of POLG mutations in individuals with 3-methylglutaconic aciduria. This case report of a young woman with a heterozygous mutation in POLG, presenting with muscle weakness and atrophy at a young age aims to aid clinicians in similar challenging diagnostic situations as well as enhances our understanding of POLG-related disease phenotypes.     

Heteroplasmic m.1624C>T mutation of the mitochondrial tRNAVal gene in a proband and his mother with repeated consciousness disturbances

Homoplasmic m.1624C>T mutation of the mitochondrial tRNA^Val gene was previously demonstrated to cause fatal neonatal Leigh syndrome. Here, we report the clinical phenotypes of a Japanese male and his mother with heteroplasmic m.1624C>T mutation. The 36-year-old male presented with repeated episodes of consciousness disturbance since the age of 25, cognitive decline, and personality change. Cerebrospinal fluid levels of lactate and pyruvate were elevated. His mother showed similar symptoms and course. The mutation m.1624C>T was identified heteroplasmically in the proband's muscle and leukocytes and in the mother's leukocytes. The heteroplasmy load decreased with age.