Acute pulmonary oedema: presenting symptom of multiple sclerosis.

Objective To investigate the significance of matrix metalloproteinase-9 (MMP-9) and tissue inhibitor of metalloproteinase-1 (TIMP-1) in serum and cerebrospinal fluid for evaluation of severe hand, foot, and mouth disease (HFMD) complicated with neurogenic pulmonary edema (NPE). Methods A total of 140 patients diagnosed with HFMD in Henan Children′s Hospital were enrolled and divided into three groups including mild group, severe HFMD group without NPE , severe HFMD group with NPE .These severe HFMD patients were also divided into survival group and death group according to the 28-day prognosis. Meanwhile, 50 age-matched healthy children were selected as controls. Serum MMP-9 and TIMP-1 levels were measured in all enrolled children. At the same time, MMP-9, TIMP-1 and ratio of MMP-9/TIMP-1 in cerebrospinal fluid were measured in the severe HFMD group with and without NPE. Quantitative data were compared using one-way analysis of variance, and means comparisons between samples were conducted using LSD- t test. Results Among 140 children with HFMD, 66 were in mild group, 42 in severe HFMD without NPE group, and 32 in severe HFMD with NPE group. And 50 healthy children were in control group. After 28 days, 14 cases died in severe HFMD groups. MMP-9, TIMP-1 and MMP-9/TIMP-1 in serum of severe HFMD group with NPE increased significantly greater than those in the other three groups (F=269.356, 121.301 and 101.502, respectively, all P <0.05). MMP-9, TIMP-1 and MMP-9/TIMP-1 in cerebrospinal fluid of severe HFMD group with NPE were (57.24±8.92) μg/L, (35.26±8.14) μg/L and (1.66±0.23) μg/L, respectively, while those in cerebrospinal fluid of severe HFMD group without NPE were (30.57±3.89) μg/L, (26.25±0.32) μg/L and (1.17±0.61) μg/L, respectively. The differences between the two groups were all statistically significant (t=62.485, 37.680 and 169.387, respectively, all P<0.01). MMP-9, TIMP-1 and MMP-9/TIMP-1 in serum and cerebrospinal fluid of death group increased significantly greater than those in survival group, the difference were statistically significant (all P<0.01). The maximum area under curve (AUC) was reached when the MMP9/TIMP-1 ratio in cerebrospinal fluid was 0.890 (95% CI: 0.801-0.978). Conclusions MMP-9 and TIMP-1 may be involved in the pathogenesis of HFMD complicated with NPE. The detection of MMP-9 and TIMP-1 levels may be beneficial for the early diagnosis of severe HFMD with NPE. The imbalance of MMP-9/TIMP-1 ratio can be used as one of the predictors of severe HFMD combined with NPE. Key words: Matrix metalloproteinase 9; Hand, foot and mouth disease; Pulmonary edema; TIMP-1

Introduction: Multiple sclerosis (MS) is a demyelinating disease of the central nervous system that predominantly affects young women. Its clinical manifestations include sensory–motor relapses, monocular optic neuritis, and brainstem syndrome, which may follow a relapsing–remitting, primary, or secondary progressive course. Recently, prodromal symptoms, such as psychiatric alterations, have been described, adding complexity to the initial diagnosis. Objective: The aim of this study was to report a clinical case of MS with an atypical presentation, characterized by acute behavioral changes with fluctuating infantilization, highlighting the importance of an interdisciplinary approach and early diagnosis. Methods: A 23-year-old female patient was referred due to acute behavioral changes. During hospitalization, the mental health team ruled out a primary psychiatric disorder. Neurological investigation included imaging exams, such as computed tomography and brain magnetic resonance imaging, along with cerebrospinal fluid (CSF) analysis for oligoclonal bands. Results: The exams revealed hyperintense lesions in T2 and FLAIR sequences located in the periventricular and subcortical white matter and the posterior fossa, some with peripheral contrast enhancement, in addition to positive oligoclonal bands in the CSF. Despite initial treatment, the patient experienced repeated sensory–motor relapses, requiring plasmapheresis due to high disease activity. Conclusion: MS presents with a wide range of manifestations, with acute psychiatric symptoms being a less common initial presentation. This case highlights the importance of early recognition of atypical presentations for proper diagnosis and treatment, reducing disease progression and functional impairment in the patient.

Vestibular evoked myogenic potentials and MRI in early multiple sclerosis: Validation of the VEMP score

A 39-year-old woman was admitted to hospital because of a sensory hemisyndrome caused by a contrast-enhancing demyelinating lesion of the cervical cord. MRI, CSF examination and subsequent clinical and neuroradiological follow-up led to the diagnosis of multiple sclerosis. The patient had noticed an involuntary contraction of a small muscle fascicle on the right side of the chin for a year. Electromyographic and video recordings confirmed the synkinesis between the orbicularis oculi and lower facial muscles, a finding distinct from the myokymic discharges reported in multiple sclerosis and more similar to the synkinesis associated with hemifacial spasm.

Serum markers of multiple sclerosis - a new approach

Sirs: Acute transverse myelitis is a spinal cord inflammatory process of unknown aetiology. Involvement of an autoimmune response is the most widely accepted mechanism [1, 2, 3]. Some cases have been reported concomitantly or after a viral infection [4]. In some patients it can be the first symptom of multiple sclerosis [5]. The severity of the neurological symptoms and sequelae depend on the location of the lesion and on the severity of the underlying lesions, oedema, demyelination and/or axonal lesions. The spinal cord clinical syndrome includes autonomous, motor and sensory disorders either in isolation or in combination. The experience of illusory symptoms or phantom limb movement during transverse myelitis or as a symptom of multiple sclerosis is exceptional [6, 7]. A 50-year-old female with a two-week history of flu-like symptoms and with no previous history of systemic, neurological or vaccination-related illness was evaluated on 20 October 1998 because of a progressive one-week clinical picture of severe predominantly right sided proprioceptive ataxia, dysaesthesia in the legs which were painful to touch, sensation of submammary pressure, continuous icy coldness and roughness in the legs, as if the skin were covered in horsehair, and roughness on the soles of the feet. Physical examination confirmed the presence of a thoracic D2-4 sensory level for all sensory modalities, absence of weakness and extensor plantar responses in the right leg. During admission the patient began to experience vivid, spontaneous episodes of sensation as if her right leg were rising from the bed or crossing over the other leg. These intermittent episodes resolved without treatment after seven days. The following serological tests were negative: hepatitis B and C, rheumatoid factor, ANA, p-cANCA, anticardiolipin autoantibodies, lues, borrelia, Brucella mellitensis, Lyme disease, Mycoplasma pneumoniae, varicella zoster, Epstein-Barr and herpes simplex virus. MRI of the dorsal spinal cord revealed a highintensity lesion on T-2 weighted images at D2-D4 levels, which, after administration of gadolinium, showed irregular uptake with hypodense areas. It was suggested that this could be a glial expanding process. An open biopsy revealed an extensive sharply-demarcated demyelinated area (Fig. 1). Cranial MRI was normal. A 99mTc-HMPAOSPECT (23 November 1998), LETTER TO THE EDITORS

Multiple sclerosis (MS) is a chronic inflammatory disease of the central nervous system (CNS) [1]. In the majority of patients, MS begins with a relapsing–remitting course. It is characterized by unpredictable relapses followed by periods of months to years of clinical remission. MS relapses entail various clinical symptoms depending on the location of the inflammatory lesion within the CNS. Besides the common symptoms of optic neuritis, paresis, paraesthesia, and ataxic gait disorders, in some rare cases a relapse may alter cardiovascular and autonomic function [1]. Clinical studies have shown that acute cerebral lesions (e.g., stroke, hemorrhage) may induce changes in cardiac and respiratory function including hypertension, arrhythmias, myocardial necrosis, and sudden death [2, 3]. Moreover, experimental and clinical studies indicate that damage of the brainstem is likely to cause disturbances in either sympathetic or parasympathetic autonomic function with subsequent cardiac and respiratory dysfunction [4–6]. Neurogenic pulmonary edema (NPE) is usually defined as an acute pulmonary edema occurring shortly after various injuries of the central nervous system [7]. The most important vasomotor centers for NPE development are nuclei of the solitary tract, the dorsal motor vagus nucleus in the medulla oblongata and the medial reticulated nucleus. On the other hand, brainstem damage in the region of the solitary tract nuclei may result in a transient cardiomyopathy [8]. The exact mechanisms remain poorly understood because of the complexity of its pathophysiologic mechanisms, involving both hemodynamic and inflammatory aspects. There are two possible explanations: one presumes that neurological damage directly involves the pulmonary and cardiac vascular bed with disconnection of the central nervous system vasomotor centers. However, there are also data that brainstem dysfunction can cause changes of sympathetic vasomotor tone [7]. This case study describes a rare initial presentation of a MS relapse with pulmonary edema caused by left ventricular failure. A 48-year-old woman, diagnosed with clinically definite relapsing–remitting MS 3 years previously with a preexisting expanded disability status scale (EDSS) of 3.5, presented with increasing dyspnea and cough without chest pain to a department of internal medicine. She was on immunomodulatory treatment with glatiramer acetate. No clinically apparent atherosclerotic disease was known. On admission, laboratory testing showed that high-sensitivity troponin T was slightly elevated. An electrocardiogram showed no signs of myocardial infarction. In a coronary computed tomography angiogram, no significant changes in the coronary arteries were found. The next day, increases in high-sensitivity troponin T, C-reactive protein (CRP), and a massive increase of B-type natriuretic peptide (proBNP) were observed (Table 1). Pulmonary edema was initially not diagnosed (Fig. 1a) and according to the assumption of pneumonia the patient was treated with antibiotic therapy (amoxicillin) and furosemide. Due to the further worsening of respiratory conditions, intubation and mechanical respirator treatment became necessary. An echocardiogram showed acute left ventricular failure with apical wall motion abnormalities and a left ventricular ejection fraction of 35% in this patient without a history of cardiac disease. No abnormalities concerning the right ventricle and the atria were seen. With regard to her P. Wipfler (&) G. Pilz E. Broussalis S. M. Golaszewski A. Kunz E. Trinka J. Kraus Christian-Doppler-Klinik, University Hospital of Neurology, Paracelsus Medical University and Salzburger Landesklinken, Ignaz Harrerstrasse 79, 5020 Salzburg, Austria e-mail: p.wipfler@salk.at

PERIOPERATIVE hiccups in children are usually not associated with significant morbidity. We report a case of massive pulmonary edema that occurred after inhalational induction of general anesthesia, which was complicated by vigorous regular hiccups.An 8-yr-old, 20-kg girl was scheduled to undergo dental restorations and extractions as an outpatient. The patient had a history of seizures and multiple ischemic strokes secondary to Moyamoya disease. She had undergone three previous operations during general anesthesia, without anesthesia-related difficulties.At the preoperative visit, she was aphasic and drooling. Significant left lower extremity weakness and diffuse fine motor deficits were also present, but the patient was ambulatory.The patient received 10 mg midazolam via G-tube as premedication. After application of electrocardiogram leads and pulse oximetry, inhalational induction with 70% nitrous oxide in oxygen and halothane was begun. Within seconds after the start of induction, vigorous hiccups, which were accompanied by tracheal tugging, developed in the patient. Pulse oximetry showed a stable arterial saturation of 99–100% throughout induction, and capnography did not show impairment of gas exchange. Therefore, inhalational induction was continued, with the child breathing spontaneously. The strong hiccups never ceased during approximately 10 min of induction.Finally, intravenous access was obtained and 20 mg rocuronium was administered intravenously. As neuromuscular blockade occurred, spontaneous ventilation and the hiccups stopped, and positive pressure ventilation of the lungs was applied without difficulty. The trachea was intubated with an uncuffed 5.5-mm nasotracheal tube. Subsequently, the patient underwent mechanical ventilation with 1% isoflurane in an air–oxygen mixture. Fentanyl, 2μg/kg, and 0.1 mg glycopyrrolate were administered intravenously, and the table was turned 90° for the dental procedure.During the next 20 min, blood pressure readings by Dinamapp (Critikon, Tampa, FL) were erratic. The Dinamapp intermittently displayed unexpectedly high pressures between 165/100 and 130/100 mmHg but eventually failed after prolonged cycling. Peripheral pulses could not be palpated, but a Doppler probe placed over the left posterior tibial artery finally gave reproducible systolic readings between 90 and 120 mmHg. During the period of hemodynamic lability, increased oxygen requirements developed in the patient. Repeated chest auscultations revealed no evidence of wheezing or decreased or asymmetric breath sounds. The capnogram remained unchanged with end-tidal carbon dioxide values of 36–40 mmHg. After the oxygen requirements reached 100%, the dental procedure was interrupted. Endotracheal suction revealed more than 100 ml frothy pink fluid. Chest radiography confirmed moderate pulmonary edema with a central pattern and normal heart size (fig. 1B) . No effusions or focal consolidations were present. Intraoperative transthoracic echocardiography showed good biventricular function but mild mitral regurgitation (+1) and mild pulmonary insufficiency. The patient was administered a second dose of 15 mg rocuronium, and reintubation was performed with a cuffed tube. The patient was sedated with 2 mg lorazepam and 60 μg fentanyl and transferred to the intensive care unit for postoperative ventilation with positive end-expiratory pressure. No inotropic or vasoactive agents were administered at any time. A total volume of 800 ml lactated Ringer’s solution was infused over 4 h. The patient was extubated on the first postoperative day. Chest radiography showed almost complete resolution of the pulmonary edema and no focal areas of consolidation. The inspiratory oxygen requirement normalized. A neurologic examination did not show new deficits. Follow-up echocardiography showed resolution of all intraoperative abnormalities. Results of an allergy workup were negative for latex and ethylene oxide, but a skin-prick test showed a mild reaction to a 1:100 dilution of rocuronium (roc 1+, histamine 3+).This child presented with fulminant pulmonary edema that was most likely postobstructive and related to vigorous hiccups during inhalation induction.Negative-pressure pulmonary edema (NPPE) occurs soon after relief of acute or chronic obstruction of the upper airway. It is commonly reported after laryngospasm during induction or emergence from anesthesia. 1Markedly negative intrapleural pressures during airway occlusion cause increased venous return and increased left ventricular afterload. The increased hydrostatic pressure gradient in the pulmonary capillaries leads to transsudation of fluid into the alveoli. Hypoxemia and a hypoxia-induced hyperadrenergic state further promote edema formation. 1,2In this patient, the rapid appearance and resolution of edema with supportive respiratory therapy alone make NPPE likely.Lack of acidity of the suctioned fluid (pH 7.0) and the centrally and bilaterally symmetric pattern of the edema on the chest radiograph argue against any significant aspiration of gastric contents. The initial hypertensive phase and the complete absence of wheezing and other signs of anaphylaxis are inconsistent with an allergic reaction. In addition, results of the allergy workup for latex were negative and a second dose of rocuronium before reintubation was tolerated well.The most important differential diagnosis to NPPE in this patient seems to be neurogenic pulmonary edema. Moyamoya disease is characterized by symmetric narrowing of the anterior and middle cerebral arteries and the formation of hemodynamically insufficient collateral networks. 3,4We were initially concerned that the hemodynamic lability in this patient with intracranial malformations could have caused cerebral edema and subsequent neurogenic pulmonary edema. Intraoperative hypertension in the absence of strong surgical stimuli has been described in patients with Moyamoya disease. 5,6Neurogenic pulmonary edema, however, usually has a prolonged course with high mortality, 7and our patient did not show any deterioration in neurologic status or evidence of cerebral edema after extubation.However, the observed hemodynamic instability with peripheral vasoconstriction may be explained by a hyperadrenergic state that is associated with the development of postobstructive pulmonary edema. 2Hypoxia of the central nervous system is an important mediator for this reaction, and some central nervous system tissue hypoxia may have been present in this patient because Moyamoya disease impairs cerebral blood circulation.Negative-pressure pulmonary edema has been described without any clinical evidence of airway obstruction, which suggests that obstructive events can be subtle. 1Our patient had vigorous hiccups during 10 min of spontaneous breathing that only ceased with neuromuscular blockade. Hiccups are brief, powerful inspiratory efforts synchronous with glottic closure. 8Studies in cats have shown that hiccups can cause negative intrathoracic pressures that are four times greater than during normal inspiration. 8Because NPPE can develop even after minor airway obstruction, 1we suggest that, in our patient, the continuous, forceful hiccups were sufficient to cause NPPE.We believe this is the first reported case of NPPE associated with hiccups during inhalational induction of anesthesia. It is likely that more cases of unexplained perioperative hypoxemia are related to unrecognized NPPE. We suggest that prolonged vigorous hiccups in anesthetized, spontaneously breathing patients who are not intubated may not always be benign.

Neurogenic pulmonary edema (NPE) is an increase in interstitial and alveolar lung fluid that occurs as a direct consequence of acute or subacute central nervous system (CNS) injury. In this review we describe a patient who developed hypoxemic respiratory failure as a result of NPE following catastrophic subarachnoid hemorrhage (SAH). The patient displayed many of the characteristic symptoms, signs, and physiologic aberrations associated with NPE, including an altered level of consciousness, dyspnea, cyanosis, crackles, hypoxemia, and diffuse pulmonary infiltrates. These clinical features can be mistaken for other causes of pulmonary edema and may lead to confusion in the diagnosis and therapeutic approach of hypoxemic respiratory failure in the setting of CNS injury. Although NPE is thought to be due to a combination of pulmonary capillary leakage and elevated intravascular pressures, many questions about its pathophysiology remain unanswered. Data from animal models using therapeutic trials of antiadrenergic agents suggest a significant role for sympathetic nervous system activation and massive catecholamine release in the pathogenesis of this disorder. The most common causes of NPE include head trauma, seizures, cerebral hemorrhages, subarachnoid bleeds, and increased intracranial pressure of any etiology. As is generally observed with this disorder, conservative and supportive management of our patient's respiratory failure led to complete resolution of the NPE within 96 hours. Although NPE is an infrequent phenomenon, it should be considered in the differential diagnosis of all patients who develop respiratory complications soon after CNS injury.

Two cases of ruptured intracranial aneurysm associated with neurogenic pulmonary edema are described. One patient, a 53-year-old female, was Hunt and Kosnik grade 4 on admission and was expressing pinkish, foamy sputum. A ruptured aneurysm in the anterior communicating artery was clipped 3 hours later. The second patient, a 55-year-old female, was also grade 4 on admission and she, too, exhibited signs of pulmonary edema. A ruptured aneurysm at the junction of the right internal carotid-posterior communicating arteries was clipped 4 hours later. In both cases, intraand postoperative respiratory maintenance with positive end-expiratory pressure was successfully carried out. Both patients were discharged without major neurological deficits. The optimal timing of surgery for ruptured cerebral aneurysms associated with neurogenic pulmonary edema has not been clearly determined. In these two cases, very early surgery combined with aggressive management of the pulmonary edema was successful. The importance of early diagnosis and treatment of pulmonary edema is stressed, and the timing of surgery after subarachnoid hemorrhage is discussed.

Objective To investigate the positive end-expiratory pressure (PEEP) ventilation in the treatment of neurogenic pulmonary edema. Method 64 patients with neurogenic pulmonary edema were treated with the timely use of positive end-expiratory pressure(PEEP) ventilation. Then the curative effect was observed. Result The symptoms of hypoxia, pulmonary edema were had a rapid improvement in ventilation with PEEP. the improvementof heart rate, respiratory rate, oxygen saturation, partial pressure of oxygen, carbon dioxide partial pressure had significant difference compared with that before treatment(P ＜ 0.01). Conclusion Neurogenic pulmonary edema patients treated with PEEP therapy had goved clinical effect. Key words: Pulmonary edema; Continuous positive airway pressure; Ventilators,mechanical

McAlpine's Multiple Sclerosis

Application of transpulmonary thermodilution monitoring (PiCCO) in patient with neurogenic pulmonary edema and acute obstructive hydrocephalus due to a central neurocytoma: A case report

Bilateral injections of aconitine in the preoptic-anterior hypothalamic area in rats produces pulmonary edema that is mediated by neurogenic mechanisms. The aim of the present study was to determine the efficacy of hypovolemia or intravenous methylprednisolone on preventing aconitine-induced pulmonary edema. Rats made hypovolemic before or after injection of aconitine or treated with 40 mg/kg methylprednisolone had normal lung weight-to-body weight ratios (LW/BW) and normal pulmonary ultrastructure. In contrast, high LW/BW and gross ultrastructural alterations were noted in rats injected with aconitine only. These findings suggest that hypovolemia was effective in preventing aconitine-induced neurogenic pulmonary edema (NPE) because it lowered the pulmonary blood volume and that methylprednisolone provided a beneficial effect by suppressing the hemodynamic response involved in NPE or by directly stabilizing the cell membranes.

GRAZ-01-26 Introduction: Sympathetic over-activity may mediate neurogenic pulmonary oedema. It has been reported that vagotomy may also cause neurogenic pulmonary oedema. Thus, vagotomy might be attributed to the lack of afferent nerves or to uncontrolled sympathetic nerve activity. This study evaluates the role of nitric oxide in the central nervous system on the development of neurogenic pulmonary edema. Methods: Neurogenic pulmonary oedema was induced by injection of fibrinogen and thrombin into the cisterna magna. The physiological role of nitric oxide was evaluated using N-nitro-L-arginine methyl ester or L-arginine. Vagus nerves were either left intact or bilaterally severed. The concentration of neuropeptide Y, a neurotransmitter, in oedema fluid was measured using enzyme-linked immunosorbent assay. Lung water content and protein concentration in oedema fluid were analysed. Results: With an intact vagus, injection of N-nitro-L-arginine methyl ester worsened pulmonary oedema, whereas L-arginine had no effect. Likewise, the ratio of oedema fluid protein to serum protein was, 6.02 ± 0.25, increased by N-nitro-L-arginine methyl ester in rats with the vagus nerve intact, and diminished, 4.57 ± 0.47, by L-arginine in vagotomized rats. Furthermore, neuropeptide Y concentration in oedema fluid was elevated, −6.77 ± 0.13, by N-nitro-L-arginine methyl ester in rats with the vagus nerve intact, and was decreased with L-arginine, −7.51 ± 0.16, in vagotomized rats. Conclusions: Neurogenic pulmonary oedema is characterized by elevated pulmonary vascular permeability and may be inhibited by nitric oxide production in vagal nerve cells.