In a patient with a low symptomatic COPD that could probably be classified as GOLD 2, the starting treatment can be either with inhaled tiotropium or with a long-acting beta two. Therefore there is no doubt in the correct answer.

In a patient with a low symptomatic COPD that could probably be classified as GOLD 2, the starting treatment can be either with inhaled tiotropium or with a long-acting beta two. Therefore there is [HIDDEN].

A 67-year-old man consults for moderate exertional dyspnea of progressive onset in recent years. He has daily whitish expectoration and sometimes breath sounds, especially in winter with respiratory infections. He has been a smoker of about 20 cigarettes a day for the last 45 years. On examination he is eupneic, normocolored, with an oxygen saturation of 94%, and has generalized decreased vesicular murmur on chest auscultation as the only findings of interest. Chest X-ray shows an elongated cardiac silhouette, with signs of hyperinflation or pulmonary air trapping, without other alterations. Spirometry was performed with the following result: FVC 84%, FEV1 58%, FEV1/FVC 61%, unchanged after bronchodilator. Among those indicated, indicate the most appropriate treatment for this patient:

Home oxygen therapy with portable oxygen source for ambulation.

Obstructive lung disease

The diagnosis of COPD is established through spirometry although other pulmonary function tests can be helpful. A chest X-ray is often ordered to look for hyperinflation and rule out other lung conditions but the lung damage of COPD is not always visible on a chest x-ray. Emphysema, for example, can only be seen on CT scan. The main form of long term management involves the use of inhaled bronchodilators (specifically beta agonists and anticholinergics) and inhaled corticosteroids. Many patients eventually require oxygen supplementation at home. In severe cases that are difficult to control, chronic treatment with oral corticosteroids may be necessary, although this is fraught with significant side effects.

[Clinical examinations for COPD].

The natural history of COPD such as pulmonary emphysema demonstrates that FEV1 rapidly declines in smokers who are susceptible to cigarette smoke. The susceptible smokers who quit smoking do not regain only a little, but the rate of the FEV1 decline is no longer steep. These have been interpreted that early detection of this obstructive impairment is the most important issue to prevent the progression to severe emphysema. Pulmonary function tests, at least a measure of FEV1, in the all middle-aged smokers have been particularly recommended. The smokers with abnormal FEV1 defect should be advised to quit smoking. In moderate and severe cases, after staging of the disease by pulmonary function and exercise tests, assessments of complicated factors such as eosinophilic bronchitis are clinically important for constructing therapeutic strategies. Asthmatic component can be assessed by eosinophil count in the sputum and/or reversibility of the pulmonary function after challenging of bronchodilater inhalations. In the severe stage of the disease, examinations such as arterial blood gas analysis and pulse oxymetric measure are critical because oxygen therapy for the patients with respiratory failure has been known to improve survival prognosis. Portable devices which can assess arterial oxygen saturation during daily activity will be useful to decide its indication or to titrate oxygen. In conclusion, clinical examination in COPD, particularly in pulmonary emphysema in this paper, should appropriately be planned in each stage of the disease, or in each clinical purpose.

[Acute exacerbations of chronic obstructive pulmonary disease].

Acute exacerbation of chronic obstructive pulmonary disease (COPD) is defined by modification of the usual COPD symptoms, dyspnea, coughing and sputum, beyond daily variations, with a sudden onset, and requiring modification of the usual treatment. Exacerbations stud the course of COPD. Their frequency is variable, averaging 1-2 per year. Their frequency generally increases with COPD severity. Exacerbations impair patients' quality of life and aggravate disease prognosis by accelerating the decline in FEV1, the primary indicator of respiratory function. The most frequent causes of exacerbations are viral and bacterial respiratory infections and pollution. No cause is identified for nearly one third of all exacerbations. Most exacerbations can be treated at home, if a careful search for signs of clinical severity is negative. Treatment combines inhaled bronchodilator agents (beta-2 agonists, combined if necessary with anticholinergics) and oral corticosteroid therapy (prednisone: 0.5 mg/kg/d for 1 week) when the COPD is severe or signs of severity accompany the exacerbation. Antibiotic therapy is justified when the sputum appears purulent. Severe exacerbation may require oxygen therapy in cases of severe hypoxemia (PaO(2)<60 mm Hg) or mechanically assisted ventilation, essentially by noninvasive ventilation in cases of respiratory acidosis (pH<7.35). Noninvasive ventilation improves dyspnea and respiratory acidosis, diminishes respiratory frequency, intubation, duration of hospitalization, nosocomial infections, and mortality. Pulmonary follow-up is necessary after an exacerbation, especially to prevent the recurrence of exacerbations by measures that have been demonstrated to be effective, including help in smoking cessation, adaptation of COPD treatment, vaccination against influenza and pneumonia (pneumococci), and respiratory rehabilitation. Early diagnosis and rapid treatment of exacerbations can limit their impact, improve quality of life, and reduce the risk of hospitalization.

Chronic obstructive pulmonary disease

Spirometry measures the amount of airflow obstruction present and is generally carried out after the use of a bronchodilator, a medication to open up the airways. Two main components are measured to make the diagnosis, the forced expiratory volume in one second (FEV1), which is the greatest volume of air that can be breathed out in the first second of a breath, and the forced vital capacity (FVC), which is the greatest volume of air that can be breathed out in a single large breath. Normally, 75–80% of the FVC comes out in the first second and a FEV1/FVC ratio less than 70% in someone with symptoms of COPD defines a person as having the disease. Based on these measurements, spirometry would lead to over-diagnosis of COPD in the elderly. The National Institute for Health and Care Excellence criteria additionally require a FEV1 less than 80% of predicted. People with COPD also exhibit a decrease in diffusing capacity of the lung for carbon monoxide due to decreased surface area in the

Respiratory Conditions Update: Chronic Obstructive Pulmonary Disease.

Chronic obstructive pulmonary disease (COPD) is defined as persistent airflow limitation due to irritant-induced chronic inflammation. A postbronchodilator forced expiratory volume in 1 second to forced vital capacity (FEV1/FVC) ratio of 0.7 or less is diagnostic in a patient with dyspnea, chronic cough or sputum production, and a history of irritant exposure. Tobacco smoking is the most significant etiology, and smoking cessation is the only intervention shown to slow disease progression. Long-acting beta2-agonists and long-acting muscarinic antagonists are first-line treatments for patients with persistently symptomatic COPD with an FEV1 of 80% or less of predicted. When COPD is uncontrolled with a long-acting bronchodilator, combination therapy with a long-acting muscarinic antagonist-long-acting beta2-agonist or long-acting beta2-agonist-inhaled corticosteroid should be prescribed. Patients with COPD and reduced exercise tolerance should undergo pulmonary rehabilitation and be evaluated for supplemental oxygen therapy. Other treatment options for persistently symptomatic COPD include inhaler triple therapy (ie, long-acting muscarinic antagonist, long-acting beta2-agonist, inhaled corticosteroid), phosphodiesterase type 4 inhibitors, oxygen, and surgical interventions.

Obstructive lung disease

In COPD, there is an increase in airway resistance, shown by a decrease in the forced expiratory volume in 1 second (FEV1) measured by spirometry. COPD is defined as a forced expiratory volume in 1 second divided by the forced vital capacity (FEV1/FVC) that is less than 0.7 (or 70%). The residual volume, the volume of air left in the lungs following full expiration, is often increased in COPD, as is the total lung capacity, while the vital capacity remains relatively normal. The increased total lung capacity (hyperinflation) can result in the clinical feature of a barrel chest – a chest with a large front-to-back diameter that occurs in some individuals with emphysematous COPD. Hyperinflation can also be seen on a chest X-ray as a flattening of the diaphragm. The most common cause of COPD is cigarette smoking. COPD is a gradually progressive condition and usually only develops after about 20 pack-years of smoking. COPD may also be caused by breathing in other particles and gases.

Clinical Significance of Symptoms in Smokers with Preserved Pulmonary Function.

Currently, the diagnosis of chronic obstructive pulmonary disease (COPD) requires a ratio of forced expiratory volume in 1 second (FEV1) to forced vital capacity (FVC) of less than 0.70 as assessed by spirometry after bronchodilator use. However, many smokers who do not meet this definition have respiratory symptoms. We conducted an observational study involving 2736 current or former smokers and controls who had never smoked and measured their respiratory symptoms using the COPD Assessment Test (CAT; scores range from 0 to 40, with higher scores indicating greater severity of symptoms). We examined whether current or former smokers who had preserved pulmonary function as assessed by spirometry (FEV1:FVC ≥0.70 and an FVC above the lower limit of the normal range after bronchodilator use) and had symptoms (CAT score, ≥10) had a higher risk of respiratory exacerbations than current or former smokers with preserved pulmonary function who were asymptomatic (CAT score, <10) and whether those with symptoms had different findings from the asymptomatic group with respect to the 6-minute walk distance, lung function, or high-resolution computed tomographic (HRCT) scan of the chest. Respiratory symptoms were present in 50% of current or former smokers with preserved pulmonary function. The mean (±SD) rate of respiratory exacerbations among symptomatic current or former smokers was significantly higher than the rates among asymptomatic current or former smokers and among controls who never smoked (0.27±0.67 vs. 0.08±0.31 and 0.03±0.21 events, respectively, per year; P<0.001 for both comparisons). Symptomatic current or former smokers, regardless of history of asthma, also had greater limitation of activity, slightly lower FEV1, FVC, and inspiratory capacity, and greater airway-wall thickening without emphysema according to HRCT than did asymptomatic current or former smokers. Among symptomatic current or former smokers, 42% used bronchodilators and 23% used inhaled glucocorticoids. Although they do not meet the current criteria for COPD, symptomatic current or former smokers with preserved pulmonary function have exacerbations, activity limitation, and evidence of airway disease. They currently use a range of respiratory medications without any evidence base. (Funded by the National Heart, Lung, and Blood Institute and the Foundation for the National Institutes of Health; SPIROMICS ClinicalTrials.gov number, NCT01969344.).

Pulmonology

Surgical procedures Major surgical procedures on the heart and lungs are performed by a thoracic surgeon. Pulmonologists often perform specialized procedures to get samples from the inside of the chest or inside of the lung. They use radiographic techniques to view vasculature of the lungs and heart to assist with diagnosis. Treatment and therapeutics Medication is the most important treatment of most diseases of pulmonology, either by inhalation (bronchodilators and steroids) or in oral form (antibiotics, leukotriene antagonists). A common example being the usage of inhalers in the treatment of inflammatory lung conditions such as asthma or chronic obstructive pulmonary disease. Oxygen therapy is often necessary in severe respiratory disease (emphysema and pulmonary fibrosis). When this is insufficient, the patient might require mechanical ventilation.

InternalMed_Harrison

The diagnosis of asthma is usually apparent from the symptoms of variable and intermittent airways obstruction, but must be confirmed by objective measurements of lung function. Lung Function Tests Simple spirometry confirms airflow limitation with a reduced FEV1, FEV1/FVC ratio, and PEF (Fig. 309-6). Reversibility is demonstrated by a >12% and 200-mL increase in FEV1 15 min after an inhaled short-acting β2-agonist or in some patients by a 2to 4-week trial of oral corticosteroids (OCS) (prednisone or prednisolone 30–40 mg daily). Measurements of PEF twice daily may confirm the diurnal variations in airflow obstruction. Flow-volume loops show reduced peak flow and reduced maximum expiratory flow. Further lung function tests are rarely necessary, but whole-body plethysmography shows increased airway resistance and may show increased total lung capacity and residual volume. Gas diffusion is usually normal, but there may be a small increase in gas transfer in some patients.

Chronic obstructive pulmonary disease

Management of exacerbations People with COPD can experience exacerbations (flare-ups) that are commonly caused by respiratory tract infections. The symptoms that worsen are not specific to COPD and differential diagnoses need to be considered. Acute exacerbations are typically treated by increasing the use of short-acting bronchodilators including a combination of a short-acting inhaled beta agonist and short-acting anticholinergic. These medications can be given either via a metered-dose inhaler with a spacer or via a nebulizer, with both appearing to be equally effective. Nebulization may be easier for those who are more unwell. Oxygen supplementation can be useful. Excessive oxygen; however, can result in increased levels and a decreased level of consciousness. Corticosteroids given orally can improve lung function and shorten hospital stays but their use is recommended for only five to seven days; longer courses increase the risk of pneumonia and death.

Shortness of breath

Asthma Asthma is the most common reason for presenting to the emergency room with shortness of breath. It is the most common lung disease in both developing and developed countries affecting about 5% of the population. Other symptoms include wheezing, tightness in the chest, and a non productive cough. Inhaled corticosteroids are the preferred treatment for children, however these drugs can reduce the growth rate. Acute symptoms are treated with short-acting bronchodilators. Pneumothorax Pneumothorax presents typically with pleuritic chest pain of acute onset and shortness of breath not improved with oxygen. Physical findings may include absent breath sounds on one side of the chest, jugular venous distension, and tracheal deviation.

Chronic Obstructive Pulmonary Disease: Diagnosis and Management.

The diagnosis of chronic obstructive pulmonary disease (COPD) should be suspected in patients with risk factors (primarily a history of smoking) who report dyspnea at rest or with exertion, chronic cough with or without sputum production, or a history of wheezing. COPD may be suspected based on findings from the history and physical examination, but must be confirmed by spirometry to detect airflow obstruction. Findings that are most helpful to rule in COPD include a smoking history of more than 40 pack-years, a self-reported history of COPD, maximal laryngeal height, and age older than 45 years. The combination of three clinical variables-peak flow rate less than 350 L per minute, diminished breath sounds, and a smoking history of 30 pack-years or more-is another good clinical predictor, whereas the absence of all three of these signs essentially rules out airflow obstruction. Pharmacotherapy and smoking cessation are the mainstays of treatment, and pulmonary rehabilitation, long-term oxygen therapy, and surgery may be considered in select patients. Current guidelines recommend starting monotherapy with an inhaled bronchodilator, stepping up to combination therapy as needed, and/or adding inhaled corticosteroids as symptom severity and airflow obstruction progress.

InternalMed_Harrison

Airflow limitation, also known as airflow obstruction, is typically determined by spirometry, which involves forced expiratory maneuvers after the subject has inhaled to total lung capacity. Key parameters obtained from spirometry include the volume of air exhaled within the first second of the forced expiratory maneuver (FEV1) and the total volume of air exhaled during the entire spirometric maneuver (forced vital capacity [FVC]). Patients with airflow obstruction related to COPD have a chronically reduced ratio of FEV1/FVC. In contrast to asthma, the reduced FEV1 in COPD seldom shows large responses to inhaled bronchodilators, although improvements up to 15% are common. Asthma patients can also develop chronic (not fully reversible) airflow obstruction.

World Trade Center dyspnea: bronchiolitis obliterans with functional improvement: a case report.

Bronchiolitis obliterans is a severe, often progressive, lung disease characterized by cough, exertional dyspnea, and airflow obstruction. It has been ascribed to specific causes such as lung or bone marrow transplant, medications for rheumatoid disease, and most recently in association with exposure to environmental agents. A 42-year-old, previously healthy New York City Highway Patrol officer who arrived at the World Trade Center (WTC), "ground zero," early on September 11, 2001 was evaluated. He has been followed for over 2 years with serial chest radiographs, CT scans, and pulmonary function studies. He eventually underwent an open lung biopsy. His dyspnea started on September 12, 2001 and progressed despite aggressive therapy with inhaled bronchodilator as well as oral and inhaled corticosteroids. At no time did he have any radiographic evidence of pulmonary disease. His forced vital capacity (FVC) decreased from 5.32 L in October 2001 to 2.86 L in January 2003. He underwent an open lung biopsy because of the persistent exertional dyspnea coupled with the loss of over 2 L of lung volume. The pathological findings were chronic bronchiolitis with focal obliterative bronchiolitis and rare non-necrotizing granuloma. Symptoms and pulmonary function improved after therapy with Azithromycin was added to his treatment. This process is believed to be secondary to his massive exposure to the cloud of dust that followed the collapse of the WTC. It is our conviction that many of those present at the WTC on September 11 who have persistent dyspnea and deterioration of pulmonary function may have a similar pathologic process despite absence of abnormalities on CT of the chest. In view of the many signs and symptoms seen in first responders we feel that these findings provide important information about the pathophysiology and treatment of progressive disease resulting from this exposure.

The Changes of Pulmonary Function in COPD During Four-Year Period.

none declared. COPD (chronic obstructive pulmonary disease) is characterized by airflow limitation that is not fully reversible. to show the changes of pulmonary function in COPD during the 4 -year evolution of illness. The research was done on patients suffering from COPD treated at the Clinic "Podhrastovi" during 2006 and 2007. The tested parameters were examined from the date of receiving patient with COPD to hospital treatment in 2006 and 2007 and then followed prospectively until 2010 or 2011 (the follow-up period was 4 years). There were total 199 treated patients who were chosen at random and regularly attended the control examinations. The study was conducted on adult patients of both sexes, different age group. In each patient the duration of illness was recorded so is sex, age, data of smoking habits, information about the regularity of taking bronchodilator therapy during remissions of disease, about the treatment of disease exacerbations, results of pulmonary functional tests as follows: FVC (forced vital capacity), FEV1 (forced expiratory volume in one second) and bronchodilator reversibility testing. All these parameters were measured at the beginning and at the end of each hospital treatment on the apparatuses of Clinic "Podhrastovi". We took in elaboration those data obtained in the beginning of the first hospitalization and at the end of the last hospitalization or at the last control in outpatient department when patient was in stable state. Patients were divided into three groups according to the number of exacerbations per year. airflow limitation in COPD is progressive; both FVC and FEV1 shows the statistically significant decrease during follow-up period of 4 years (p values / for both parameters/ =0.05) . But in patients regularly treated in phases of remission and exacerbations of illness the course of illness is slower. The fall of FVC and FEV1 is statistically significantly smaller in those received regular treatment in phases of remissions and exacerbations of illness (p values / for both parameters/ =0.01). The number of patients responding properly to bronchodilators decreased statistically significantly in patients with COPD during follow-up period (p=0.05). COPD is characterized with airflow limitation which is progressive in the course of illness, but that course may be made slower using appropriate treatment during remission and exacerbations of diseases.

InternalMed_Harrison

Clinical Features Patients are aware of increasing chest tightness, wheezing, and dyspnea that are often not or poorly relieved by their usual reliever inhaler. In severe exacerbations, patients may be so breathless that they are unable to complete sentences and may become cyanotic. Examination usually shows increased ventilation, hyperinflation, and tachycardia. Pulsus paradoxus may be present, but this is rarely a useful clinical sign. There is a marked fall in spirometric values and PEF. Arterial blood gases on air show hypoxemia, and PCO2 is usually low due to hyperventilation. A normal or rising PCO2 is an indication of impending respiratory failure and requires immediate monitoring and therapy. A chest roentgenogram is not usually informative but may show pneumonia or pneumothorax.

The symptoms of acute exacerbations are treated using short-acting bronchodilators. A course of corticosteroids, usually in tablet or intravenous rather than inhaled form, can speed up recovery. The IV and oral forms of steroids have been found to be equivalent. Antibiotics are often used but will only help if the exacerbation is due to an infection. Antibiotics are indicated when a patient notes increased sputum production, purulent sputum, increased dyspnea, has an elevated white count, or is febrile. Examples of first-line antibiotics are amoxicillin, doxycycline, and co-trimoxazole. Mechanical ventilation Severe exacerbations can require hospital care where treatments such as oxygen and mechanical ventilation may be required. Mechanical ventilation can be invasive (endotracheal intubation) or non-invasive forms of ventilation such as continuous positive airway pressure (CPAP) or bilevel positive airway pressure (BiPAP).

Shrinking lung syndrome treated with rituximab in pediatric systemic lupus erythematosus: a case report and review of the literature.

Shrinking lung syndrome (SLS), a rare complication of systemic lupus erythematosus (SLE) characterized by dyspnea, low lung volumes, and a restrictive pattern on pulmonary function tests (PFTs), has only been reported in a few children. Given the rarity of SLS there is a paucity of literature regarding its optimal treatment. Outcomes are variable, with case reports documenting some improvement in most patients treated with corticosteroids, with or without additional immunosuppressive agents. However, most reported patients did not recover normal lung function. We report full recovery of a child with SLE and SLS following treatment with rituximab and review the current literature. An 11-year-old boy presented with a malar rash, myositis, arthritis, oral ulcers, leukopenia, anemia, positive lupus autoantibodies and Class II nephritis. He was diagnosed with SLE and treated with corticosteroids, hydroxychloroquine, azathioprine, and subsequently mycophenolate with symptom resolution. At age 14, his SLE flared coincident with a viral chest infection. He presented with a malar rash, polyarthritis, increased proteinuria and pleuritis which all improved with corticosteroids and ongoing treatment with mycophenolate. Six weeks later he presented with severe dyspnea, markedly decreased lung volumes, but otherwise normal chest X-ray (CXR) and high-resolution chest computed tomography (HRCT). He was found to have severely restricted PFTs (FEV1 27%, FVC 29%; TLC 43%). After additional investigations including echocardiography, pulmonary CT angiography, and diaphragmatic fluoroscopy, he was diagnosed with SLS and treated with rituximab and methylprednisolone. At 1 month his symptoms had improved, but he still had dyspnea with exertion and severely restricted PFTs. At 6 months his FVC and TLC had improved to 51 and 57% respectively, and were 83 and 94% respectively at 4 years. He had returned to all baseline activities, including competitive hockey. Although extremely rare, it is important to recognize SLS as a possible cause of dyspnea and chest pain in a child with SLE. Optimal treatment strategies are unknown. This is the second reported case of a child treated with rituximab for SLS who recovered normal lung function. International lupus registries should carefully document the occurrence, treatment and outcome of patients with SLS to help determine the optimal treatment for this rare complication.

COPD--moving beyond bronchodilation.

The burden of chronic obstructive pulmonary disease (COPD) remains very high. Till recently clinical approach of COPD patients was focused on measuring airflow limitation during exercise and treating airway obstruction with inhaled bronchodilators and corticosteroids. This approach stems from an old definition of COPD, mainly consisting of airflow limitation with poor reversibility after bronchodilation. The concept of COPD has changed strikingly in the last years. Many recent studies have shown that COPD is a systemic disease affecting not only the lungs but many other organs of the patient. Laboratory cardiopulmonary exercise testing assesses physiological and biological reserves. However, it is not the most suitable test to assess the functional state of a systemic disease such as COPD. We need simpler exercise tests that can be used on larger scales. The 6-minute walk test has been shown to be highly reproducible and reflects real life limitations of these patients better. It allows precise measurements of medical intervention and is a good predictor of mortality, provided clinicians respect the defined standards of this test. It should be associated with a more systemic index such as the BODE index to better find disease-modifying interventions and improve the outcome of COPD patients. On the other hand routine measurement of spirometry in the general population by primary care physicians should be promoted as it decreases smoking habits and helps better detecting and management of COPD patients. Specialists should support primary care physicians to spread these new concepts of COPD throughout the medical community.

Airway obstruction

Lower airway obstruction Lower airway obstruction is mainly caused by increased resistance in the bronchioles (usually from a decreased radius of the bronchioles) that reduces the amount of air inhaled in each breath and the oxygen that reaches the pulmonary arteries. It is different from airway restriction (which prevents air from diffusing into the pulmonary arteries because of some kind of blockage in the lungs). Diseases that cause lower airway obstruction are termed obstructive lung diseases. Lower airway obstruction can be measured using spirometry. A decreased FEV1/FVC ratio (versus the normal of about 80%) is indicative of airway obstruction, as the normal amount of air can no longer be exhaled in the first second of expiration. An airway restriction would not produce a reduced FEV1/FVC ratio, but would reduce the vital capacity. The ventilation is therefore affected leading to a ventilation-perfusion mismatch and hypoxia. Consequences

[Diagnosis and therapy of COPD exacerbation].

The acute exacerbation of COPD (AECOPD) is a life-threatening clinical situation. This review summarizes the definition of AECOPD, the severity assessment, typical clinical signs and symptoms, and refers to clinical pitfalls of diagnosis and therapy. Important aspects of clinical history and physical examination in severe exacerbations are reported. The necessary accompanying examinations like chest X-ray, blood gas analysis, ECG and echocardiography and their differential diagnosis as well as therapeutic significance are described. The most important lab examinations are summarized and controversial parameters, e.g., procalcitonin, are commented upon. The differentiated need for a microbiological sputum screening is emphasized. The authors place special weight on the essential components of the therapeutic management of severe AECOPD. Practical aspects of uncontrolled oxygen therapy, drug selection, and application form of inhalative acute therapy, dose, and duration of glucocorticoids, the indication for antibiotics, mechanical ventilation, and also opiates are summarized.

Tiotropium bromide. A review of its use as maintenance therapy in patients with COPD.

Tiotropium bromide (Spiriva) is a long-acting anticholinergic bronchodilator that maintains bronchodilation for at least 24 hours, allowing once-daily administration. The active moiety is the tiotropium cation (tiotropium); tiotropium bromide 22.5 micrograms is equivalent to 18 micrograms of tiotropium cation. Greater improvements in lung function from baseline (primary endpoint mean trough FEV(1)) were observed with inhaled tiotropium 18 micrograms once daily than with placebo in 6-month and 1-year randomized, double-blind trials in patients with COPD. Tiotropium improved lung function (trough FEV(1) response) more effectively than ipratropium bromide (ipratropium) 40 micrograms four times daily in 1-year clinical trials, and was at least as effective as salmeterol 50 micrograms 12-hourly in 6-month trials. Preliminary data suggest that tiotropium alone or in combination with once-daily formoterol has a greater bronchodilator effect than twice-daily formoterol in patients with COPD. Improvements in patients' perception of health-related quality of life (HR-QOL) or dyspnea were greater with tiotropium than with placebo or ipratropium, and were similar to those with salmeterol. Reductions in the frequency and severity of acute exacerbations and in the use of rescue medication were also greater with tiotropium than with ipratropium or placebo. There was no evidence of tachyphylaxis with tiotropium during 1-year clinical trials. Inhaled tiotropium was generally well tolerated in clinical trials. Apart from dry mouth, the type and incidence of adverse events with tiotropium were similar to those with ipratropium, salmeterol or placebo in patients with COPD. In conclusion, inhaled tiotropium 18 micrograms once daily improved lung function, dyspnea, and HR-QOL, and decreased the incidence of acute COPD exacerbations and the use of rescue medication relative to placebo or ipratropium in clinical trials in patients with COPD. Tiotropium was at least as effective as salmeterol in terms of bronchodilator efficacy and improvements in dyspnea or HR-QOL. With the exception of dry mouth, the tolerability profile of tiotropium was similar to that with placebo, ipratropium, or salmeterol. Consequently, inhaled tiotropium is likely to be a valuable option for first-line, long-term maintenance therapy in the management of bronchoconstriction in patients with symptomatic COPD. Tiotropium bromide has a quaternary ammonium structure and acts as an anticholinergic bronchodilator; the active moiety is the tiotropium cation (tiotropium). A 22.5 micrograms dose of tiotropium bromide provides 18 micrograms of tiotropium. Orally inhaled tiotropium bromide antagonizes the muscarinic M(1), M(2), and M(3) receptors located in airway smooth muscle, reversing vagally mediated bronchoconstriction. Receptor binding assays and in vitro tests indicate that tiotropium bromide is kinetically selective for M(1) and M(3) receptors over the M(2) receptor, unlike ipratropium bromide, which is nonselective. Animal and in vitro studies showed that tiotropium bromide was more potent ( approximate, equals 20-fold) than ipratropium bromide in displacing [(3)H]N-methylscopolamine (NMS) from muscarinic receptors, and had a more sustained protective effect (>70% inhibition) against NMS binding. Tiotropium bromide was a more potent inhibitor of bronchial contraction than atropine ( approximate, equals 23-fold), and had a slower onset and markedly longer duration of action than atropine or an equipotent dose of ipratropium bromide. Aerosol particle penetration is improved with tiotropium, without delaying mucus clearance from the lungs. Tiotropium 4.5-36 micrograms once daily for 4 weeks increased mean trough and average FEV(1) and FVC and mean PEFR values from baseline compared with placebo, with no evidence of tachyphylaxis. Improvements in trough FEV(1) from baseline with tiotropium 4.5-36 micrograms were not dose dependent. Based on a lack of dose response, the optimal once-daily tiotropium dosage is 18 micrograms. Steady-state trough FEV(1) values are achieved within 48 hours of commencing tiotrochodilation (for >/=24 hours) and an attenuation of the nocturnal decline in FEV(1) that were unaffected by timing of the daily tiotropium dose were seen in randomized, double-blind, placebo-controlled studies in patients with stable COPD. The drug improved static and dynamic lung hyperinflation (evidenced by reduced trapped air volume and increased tidal volume and end-of-exercise inspiratory capacity), and improved exertional dyspnea (during activities of daily living and exertion) and exercise tolerance compared with placebo in randomized, double-blind studies. In patients with stable COPD, improved sleep-related oxygen desaturation that was unaffected by the timing of the daily dose was seen with tiotropium but not with placebo. Clinically significant treatment-related disorders of conduction or rhythm, or changes in heart rate were not observed with tiotropium in this patient group. Mean maximal plasma concentrations (C(max)) were observed within 5 minutes of inhalation of a single dose of tiotropium 18 micrograms in patients with COPD. Plasma drug levels declined to minimum concentrations (C(min)) within 1 hour of treatment in healthy volunteers. Mean steady-state C(max) concentrations (16 ng/L) were achieved after 2-3 weeks of once-daily inhaled tiotropium 18 micrograms in elderly patients with COPD; tiotropium does not appear to accumulate once steady-state has been achieved.The estimated absolute bioavailability of tiotropium at steady state in healthy volunteers was approximately 20-25%, and approximately 72% of the drug is bound to plasma proteins. Excretion of tiotropium is predominantly renal (through active secretion by the kidneys), although in vitro studies suggest that cytochrome P450 (CYP) oxidation (possibly involving CYP2D6 and CYP3A4 enzymes) may have a minor role. In patients with COPD, renal excretion of the unchanged drug at 24 hours (Ae(24)) was approximately 7%. The mean plasma elimination half-life after single or multiple doses in healthy volunteers and elderly patients with COPD was approximately 5-6 days. The renal clearance and urinary excretion of tiotropium decrease with increasing age; however, these changes are not considered to be clinically significant. Because of altered steady-state C(max), C(min), area under the concentration-time curve, and Ae(24) values, caution is required with tiotropium administration in patients with moderate-to-severe renal impairment. The pharmacokinetics of tiotropium in patients with severe renal or hepatic impairment have not been studied. Tiotropium does not interact with drugs such as cimetidine or ranitidine, which are also eliminated by active renal secretion. Orally inhaled tiotropium bromide has been evaluated as a bronchodilator for the management of patients with COPD in randomized, double-blind 6-month and 1-year trials, and in several shorter studies. In clinical trials, COPD was diagnosed according to the American Thoracic Society guidelines. The bronchodilator effect was expressed as the trough FEV(1) response (the mean change in FEV(1) from baseline measured 1 hour prior to and immediately before a scheduled dose), and was the primary endpoint in all but two clinical trials. The bronchodilator effect with tiotropium 18 micrograms once daily was superior to that with placebo in several well designed trials in patients with COPD. Moreover, greater improvements in mean peak and average FEV(1) responses occurred with tiotropium but not with placebo. Mean trough, peak, and average FVC responses, and weekly mean morning and evening PEFR values were also improved to a greater extent with tiotropium than with placebo. Tiotropium demonstrated a greater bronchodilator effect than ipratropium bromide (hereafter referred to as ipratropium when used at approved dosages) 40 micrograms four times daily in two 1-year trials in patients with COPD. Mean peak and average FEV(1), mean trough FVC responses, and weekly mean morning and evening PEFR values were also increased to a greater extent with tiotropium than with ipratropium. In one of the two 6-month trials that compared the efficacy of tiotropium with that of inhaled salmeterol 50 micrograms twice daily, greater improvements from baseline in mean trough, peak, and average FEV(1) and FVC responses were seen with tiotropium than with salmeterol. Increases in weekly mean evening, but not morning, PEFR values were generally greater with tiotropium than salmeterol. In the second trial, improvement in the primary endpoint (mean trough FEV(1) response from baseline) with tiotropium or salmeterol was similar, although peak and average responses were superior with tiotropium. Preliminary results from a 6-week crossover study in patients with COPD suggested that tiotropium alone or in combination with once-daily formoterol improved mean trough and average FEV(1) and trough FVC values from baseline to a greater extent than twice-daily formoterol. More patients achieved a clinically important improvement (increase of >/=1 unit) in the transitional dyspnea index focal score (a measure of dyspnea-related impairment) with tiotropium than with placebo in the 1-year trials. Tiotropium was superior to ipratropium in 1-year trials, and was at least as effective as salmeterol in 6-month trials, in achieving a clinically important improvement in focal scores. Tiotropium recipients experienced fewer COPD exacerbations than placebo or ipratropium recipients and had fewer and shorter COPD-related hospitalizations compared with placebo recipients. Unlike salmeterol, tiotropium lengthened the time to onset of the first exacerbation and decreased the number of exacerbations compared with placebo in two 6-month trials. Similar proportions of tiotropium, salmeterol, and placebo recipients required COPD-related hospitalizations. (ABSTRACT TRUNCATED)

Asymptomatic Unilateral Hyperlucent Lung in a Prospective Kidney Donor.

A 50 year old lady, prospective kidney donor was referred to our department for opinion in view of abnormal clinical findings during preoperative evaluation. She was asymptomatic from respiratory point of view. Her vital parameters were normal and on auscultation found to have decreased breath sounds and fine crackles throughout left hemithorax. Chest x-ray (CXR) showed left sided hyperlucency with small hilum (Figure 1). High resolution computed tomography (HRCT) showed scattered areas of bronchiectasis with associated air trapping throughout left lung with small left pulmonary artery (Figure 2). Sputum for acid fast bacilli (AFB) was negative. Spirometry showed moderate obstructive abnormality with forced expiratory volume in one second (FEV1) - 51% predicted, forced vital capacity (FVC) - 60% and FEV1/FVC - 76% with no bronchodilator reversibility. On post bronchodilator study there was paradoxical fall in FEV1/FVC to 72% consistent with small airway disease. Arterial blood gas analysis was normal. Technetium (Tc) 99m MAA lung perfusion scan (Figure3) showed normal perfusion of right lung contributing 75.4% of relative function and left lung contributing only 24.6%. Diagnosis of Swyer-James-MacLeod syndrome (SJMS) probably due to a childhood viral infection was made. Operative complications in such cases like difficult weaning and extubation, post-operative respiratory infections, collapse and respiratory failure are likely. However, our patient had an uneventful operative and post-operative course. SJMS is characterized by unilateral hyperlucency of a part of or the entire lung which was first described in 1953 by Swyer and James and later in 1954 by Macleod.1,2 It is considered to be an acquired disease as a result of post-infectious obliterative bronchiolitis. Productive cough, shortness of breath and sometimes hemoptysis are presenting symptoms. Some patients are asymptomatic and not diagnosed until they are adults.3 Radiologically it presents as predominant unilateral hyperlucency. Hence other causes of unilateral hyperlucent lung like pneumothorax, idiopathic giant bullae, congenital lobar emphysema, pulmonary artery hypoplasia, pulmonary embolism and bronchial obstruction due to foreign body or mucus plugs should be considered. Treatment is supportive with early control of super-added infections along with influenza and pneumococcal vaccination. Bronchodilators can be useful, especially if the spirometry shows obstructive abnormality.

[COPD: Guidelines for primary care physicians].

Chronic obstructive pulmonary disease (COPD) is common and should be suspected in any patient with chronic dyspnea, cough, or sputum with a history of exposure to tobacco or harmful particles. Spirometry is used for diagnosis. Full evaluation includes the severity of obstruction and clinical data, following the Global Initiative for Chronic Obstructive Lung Disease guidelines. Although the only treatments that have an impact on mortality are tobacco cessation, pulmonary rehabilitation and, for advanced disease, oxygen therapy, new symptomatic treatment have recently been made available. The duration of antibiotic and corticosteroid treatment for exacerbations has been shortened. The new diagnostic and management recommendations are summarized in this article.

[Combined pulmonary fibrosis and emphysema - case report and literature review].

We describe the case of a 61-year-old male patient, in which the search for the cause of chronic respiratory failure, severe pulmonary hypertension and secondary erythrocytosis resulted in a diagnosis of combined pulmonary fibrosis and emphysema (CPFE). This is a unique, recently characterised syndrome with upper-lobe emphysema and pulmonary fibrosis of the lower lungs. The cause is unknown, but one of the main risk factor remains smoking. The patient was a heavy smoker (over 40 pack-years). He complained of dyspnoea on exertion and cough. Physical examination revealed basal crackles and cyanosis. The patient had severe reduction in diffusing capacity, out of proportion to his lung volumes (DLCO 27% of predicted value, FEV1 2.95 l (100%), FVC 4.41 l (118%), FEV1/FVC (66%). The blood gas showed hypoxemia (pO2 37 mm Hg), hypocapnia and respiratory alkalosis. Diagnosis was based on chest computer tomography, which revealed upper lobe emphysema and lower lobe ground glass changes and honeycombing. Severe pulmonary hypertension (SPAP 80 mm Hg) was confirmed by echocardiography and right cardiac catherisation. The patient received long-term oxygen therapy, inhaled corticosteroid and Ca-blocker.

Shortness of breath--is it chronic obstructive pulmonary disease?

Of all the major diseases, chronic obstructive pulmonary disease (COPD) is the one for which the burden is increasing the fastest. This article discusses the diagnoses and assessment of COPD, and provides management guidelines including smoking cessation, bronchodilator therapy, the use of inhaled corticosteroids, combination therapies, oxygen therapy, and rehabilitation. Diagnosis is by clinical suspicion in patients with an appropriate clinical history and airflow obstruction is confirmed using spirometry. Although smoking cessation and oxygen in selected individuals are the only interventions known to alter the natural history of COPD, many other treatments can significantly lessen breathlessness, reduce exacerbations, and improve exercise and quality of life.

Pneumocystis Carinii pneumonia in an AIDS patient with dramatic response to inadvertent steroid therapy--a case report.

A 28 year-old homosexual man had one month history of intermittent high fever, nonproductive cough and progressive shortness of breath. He not only had immunity deficits, with decrease CD4 cells decreased CD8 cells and inverted CD4/CD8 ratio, but also presented with evidence of human immunodeficiency virus infection (positive ELISA antibody tests and Western blot tests). Chest X-ray showed diffuse pulmonary infiltration. The arterial blood gases revealed hypoxemia. The PaO2 was 69 mmHg. Spirometry showed FVC 2.28 L (45% predicted), FEV1 2.21 L (49% predicted), FEV1/FVC 93%, and MMEF 4.41 L/sec (90% predicted). The configuration of the Flow-Volume loop was consistent with a restrictive ventilatory defect. Transthoracic lung biopsy demonstrated pneumocystis carinii pneumonia (PCP). He had inadvertent steroid therapy and showed some clinical, pulmonary function and chest X-ray improvement before the diagnosis was established. Steroids might be as adjunctive therapy for a short period of time in treatment of PCP associated with acquired immunodeficiency syndrome (AIDS) at respiratory failure.

Respiratory Conditions: Chronic Obstructive Pulmonary Disease.

Chronic obstructive pulmonary disease (COPD) is a progressive respiratory disease characterized by cough, dyspnea, and sputum production caused by inhalation of harmful chemicals, such as tobacco smoke. COPD should be suspected in patients with a significant smoking history, shortness of breath, and sputum production. The diagnosis is made by spirometry. A forced expiratory volume in the first second of expiration to forced vital capacity (FEV<sub1</sub/FVC) ratio of less than 0.7 after bronchodilator administration confirms the diagnosis. Therapy for patients with stable COPD should include a bronchodilator, either a long-acting beta<sub2</sub-agonist (LABA) or a long-acting muscarinic antagonist (LAMA). For patients who continue to experience dyspnea with a single bronchodilator, dual therapy with a LABA and LAMA is appropriate. For patients with continued exacerbations, inhaled corticosteroids can be added to LABA-LAMA therapy. Acute exacerbations are characterized by a worsening of symptoms that requires additional therapy. Short-acting beta2-agonists with or without short-acting muscarinic antagonists are the basic therapy for acute exacerbations of COPD. Systemic glucocorticoids have been shown to shorten exacerbations and improve lung function. Antibiotics have been shown to reduce rates of treatment failure and sputum purulence. Noninvasive mechanical ventilation is preferred for patients with respiratory failure.

Traumatic Inhalation due to Merapi Volcanic Ash.

Pneumonoultramicroscopicsilicovolcanoconiosis is fibrotic lung diseases of the pulmonary parenchyma following chronic inhalation of inorganic dusts containing crystalline silicon dioxide. The acute manifestations observed after heavy ashfalls include attacks of asthma and bronchitis, with an increased reporting of cough, breathlessness, chest tightness, and wheezing due to irritation of the lining of the airways. The chronic health condition of most concern is silicosis, a diffuse nodular fibrosis of the lungs, develops slowly, usually appearing 10 to 30 years after first exposure. A 35 years old male was admitted to Sardjito Hospital, Yogyakarta with complaints of progressive dyspnoea, right side chest pain since last 3 month and periodic episodes of dry cough. He had history of exposure to volcanic ash at the location around volcano eruption for about 10 month. Examination revealed hyperresonant note, diminished vesicular breath sounds in lower right side of the chest. The chest X-ray presence leads to bleb. Based on the clinical and radiological suspicion of pneumoconiosis the patient was submitted to computed tomography of the chest and revealed bilateral multiple bullae mainly at the right lung field. The biopsy specimen verified the diagnosis of anthrocosilicosis. There is no proven specific therapy for any form of silicosis. Symptomatic therapy should include treatment of airflow limitation with bronchodilators, aggressive management of respiratory tract infection with antibiotics, and use of supplemental oxygen (if indicated) to prevent complications of chronic hypoxemia.

Emphysema -- History and Physical

Most patients present with very nonspecific symptoms of chronic shortness of breath and cough with or without sputum production. As the disease process advances, the shortness of breath and cough progressively get worse. Initially, there is exertional dyspnea with significant physical activity, especially arm work at or above shoulder level, with progression to dyspnea with simple daily activities and even at rest. Some patients may present with wheezing because of airflow obstruction.

Pediatrics_Nelson

Initial assessment Brief history, physical examination (auscultation, use of accessory muscles, heart rate, respiratory rate), PEF or FEV1, oxygen saturation, and other tests as indicated Severe exacerbation FEV1 or PEF <40% predicted/personal best Physical exam: severe symptoms at rest, accessory muscle use, chest retraction History: high-risk patient No improvement after initial treatment  Oxygen  Nebulized SABA plus Ipratropium, hourly or continuous  Oral systemic corticosteroids  Consider adjunct therapies Moderate exacerbation FEV1 or PEF 40–69% predicted/personal best Physical exam: moderate symptoms  Inhaled SABA every 60 minutes  Oral systemic corticosteroid  Continue treatment 1–3 hours, provided there is improvement; make admit decision in <4 hours

Predictors of treatment with antibiotics and systemic corticosteroids for acute exacerbations of asthma and chronic obstructive pulmonary disease in primary care.

Antibiotic and oral corticosteroid prescribing rate in patients suffering from acute exacerbations of chronic obstructive pulmonary disease (COPD) or asthma in general practice are only sparsely described. Our aim was to identify predictors for such prescribing when results from CRP testing, spirometry, and pulse oximetry are available. Patients aged 40 years or more diagnosed with asthma, COPD or both, the previous five years from seven general practice offices in Norway, were invited to a baseline examination and asked to visit their GPs during exacerbations the following 12 months. At all visits, symptoms, chest findings, and results from spirometry, pulse oximetry and CRP testing were registered. Out of the 376 who took part in baseline examination, 95 patients with an exacerbation were included in the analysis. Based on the diagnosis made by GPs, 46 patients (48.4%) were only registered with asthma, and 49 (51.6%) with COPD (or both diagnosis). 11 patients had taken antibiotics and 16 had taken systemic corticosteroids prior to their visit to their GPs. After excluding those already treated, antibiotics were prescribed in 34.9% and systemic corticosteroids in 42.5% of patients diagnosed with COPD compared to 14.6% and 30.8% respectively in patients only diagnosed with asthma (P = 0.02, P = 0.2). In the COPD group, antibiotic prescribing was not significantly associated with purulence or other respiratory symptoms, but increased phlegm was a significant predictor of antibiotic prescribing in the whole sample (P = 0.04). Prolonged expiration, wheezes and diminished breath sounds also predicted the prescribing of both antibiotics and systemic corticosteroids in the whole sample with P values < 0.01. The prescribing rate of antibiotics and systemic corticosteroids also increased with increasing CRP value (P = 0.001 and P = 0.01, respectively) and with decreasing oxygen saturation (P = 0.01 and P = 0.003, respectively). FEV1/FVC < 0.7 at baseline was as significant predictor in patients with COPD and in the whole sample of patients regarding treatment with antibiotics (P = 0.004 and P = 0.001, respectively) and treatment with systemic corticosteroids (P = 0.004 and P = 0.001, respectively). Chest findings, raised CRP value and decreased oxygen saturation were stronger predictors of prescribing of antibiotics and systemic corticosteroids than were respiratory symptoms. Further evaluation of the importance of these findings to guide treatment of asthma and COPD exacerbations is warranted.


The correct answer is 3. It defines a typical cerebrospinal fluid of tuberculosis. In clinical practice things might not be so simple......

[HIDDEN] It defines a typical cerebrospinal fluid of tuberculosis. In clinical practice things might not be so simple......

Given a 7-month-old child with fever and irritability, bulging fontanel and a cerebrospinal fluid study with 110 cells/mm3 (75% lymphocytes), protein 120 mg/dl and glucose 28 mg/dl (serum glycemia 89 mg/dl), what is the most reasonable diagnostic suspicion?

Viral meningitis

The diagnosis of viral meningitis is made by clinical history, physical exam, and several diagnostic tests. Kernig and Brudzinski signs may be elucidated with specific physical exam maneuvers, and can help diagnose meningitis at the bedside. Most importantly however, cerebrospinal fluid (CSF) is collected via lumbar puncture (also known as spinal tap). This fluid, which normally surrounds the brain and spinal cord, is then analyzed for signs of infection. CSF findings that suggest a viral cause of meningitis include an elevated white blood cell count (usually 10-100 cells/µL) with a lymphocytic predominance in combination with a normal glucose level. Increasingly, cerebrospinal fluid PCR tests have become especially useful for diagnosing viral meningitis, with an estimated sensitivity of 95-100%. Additionally, samples from the stool, urine, blood and throat can also help to identify viral meningitis. CSF vs serum c-reactive protein and procalcitonin have not been shown to elucidate

[Laboratory and clinical variables in the differential diagnosis of aseptic and pyogenic meningitis in children].

We reviewed the charts of 573 children with a final diagnosis of pyogenic or aseptic meningitis, who were hospitalized in a large reference hospital for the treatment of infectious disease, from January 1990 to December 1992. Seizures, decreased consciousness, nuchal rigidity were more frequent in bacterial than in aseptic meningitis. A cerebrospinal fluid (CSF) glucose level lower than 45 mg/dL, a protein level equal or greater than 140 mg/dL and cell count greater than 600/mm3 were predictors of pyogenic meningitis. Receiver operating characteristic curve analysis was used to assess the best point in CSF measures of leukocytes, glucose and protein that could predict bacterial meningitis. These results suggest that clinicians should differentiate bacterial from aseptic meningitis in children with greater accuracy utilizing only clinical and simple CSF data.

C-reactive protein is useful in distinguishing Gram stain-negative bacterial meningitis from viral meningitis in children.

To clarify to what extent Gram stain-negative bacterial meningitis can be distinguished from viral meningitis by assessment of cerebrospinal fluid (CSF) and blood indices and serum C-reactive protein (CRP) in children over 3 months of age. Common CSF indices, blood leukocyte counts, and serum CRP values were compared between patients with bacterial meningitis who had a positive CSF bacterial culture but a negative Gram stain and patients with viral meningitis. Three hundred twenty-five consecutive patients with CSF culture-proven bacterial meningitis, for whom Gram stain was negative in 55 cases, and 182 children with proven or presumed viral meningitis. Significant differences between patients with bacterial and viral meningitis were found in all indices with large overlap in all except serum CRP. In patients with bacterial meningitis, the mean CSF glucose concentration, protein concentration, leukocyte count, blood leukocyte count, and serum CRP were 2.9 mmol/L (52 mg/dL), 1.88 g/L, 4540 x 10(6)/L, 18.0 x 10(9)/L, and 115 mg/L; and in those with viral meningitis, mean values were 3.3 mmol/L (59 mg/dL), 0.52 g/L, 240 x 10(6)/L, 10.6 x 10(9)/L, and <20 mg/L, respectively. Of the tests investigated in this study, only serum CRP was capable of distinguishing Gram stain-negative bacterial meningitis from viral meningitis on admission with high sensitivity (96%), high specificity (93%), and high negative predictive value (99%). Exclusion of bacterial meningitis with only the conventional tests is difficult. Combined with careful physical examination and CSF analyses, serum CRP measurement affords substantial aid.

Meningitis

The concentration of glucose in CSF is normally above 40% of that in blood. In bacterial meningitis it is typically lower; the CSF glucose level is therefore divided by the blood glucose (CSF glucose to serum glucose ratio). A ratio ≤0.4 is indicative of bacterial meningitis; in the newborn, glucose levels in CSF are normally higher, and a ratio below 0.6 (60%) is therefore considered abnormal. High levels of lactate in CSF indicate a higher likelihood of bacterial meningitis, as does a higher white blood cell count. If lactate levels are less than 35 mg/dl and the person has not previously received antibiotics then this may rule out bacterial meningitis.

Neurology_Adams

The protein content of the CSF in bacterial meningitis may reach 500 mg/dL or more. Viral infections induce a less intense and mainly lymphocytic reaction and a lesser elevation of protein—usually 50 to 100 mg/dL but sometimes up to 200 mg/dL; in some instances of viral meningitis and encephalitis the protein content is normal. Brain tumors, by opening the blood–CSF barrier, can raise the total protein. Protein values as high as 500 mg/dL are found in exceptional cases of the Guillain-Barré syndrome and in chronic inflammatory demyelinating polyneuropathy. Values in the lumbar CSF of 1,000 mg/dL or more usually indicate a block to CSF flow, typically in the spinal canal; the fluid is then deeply yellow and clots readily because of the presence of fibrinogen, a phenomenon called Froin syndrome. Partial CSF blocks by ruptured discs or tumor may elevate the protein to 100 to 200 mg/dL. Low CSF protein values are sometimes found in meningismus (a febrile illness in children with signs of

Aseptic meningitis in a large MMR vaccine campaign (590,609 people) in Curitiba, Paraná, Brazil, 1998.

The aseptic meningitis after Measles-Mumps-Rubella vaccine (MMR) is a well recognized complication, and different incidences have been observed in several studies. We retrospectively analyzed forty cases of aseptic meningitis, during a large public immunization campaign (1998) in Curitiba, Southern Brazil (590,609 people), admitted in our Service. The vaccine utilized was Leningrad-3-Zagreb mumps strain, Edmonston-Zagreb measles strain, and RA 27#3 rubella strain. In all county, a total number of 87 cases were reported, resulting in a incidence of 1.7 cases per 10,000 given doses. The mean age was 23.7 +/- 12.8 years. The female:male ratio was 1.35:1. Severe headache with meningismus (92.5%), fever (87.5%), nausea/vomiting (82.5%) were the most common clinical findings. Three cases (7.5%) developed mild mumps. All patients underwent cerebrospinal fluid (CSF) tap with the following findings: mononuclear pleocytosis from 100 to 500 cells/mm(3) in 17 cases (42.5%; 257.5 +/- 260.6 cells/mm3); increased protein 28 cases (67.5%; 92.1 +/- 76.9 mg/dL); glucose was normal in all cases (56.8 +/- 11.2 mg/dL) except in 4 (10%) cases, which presented less than 44 mg/dL. All serological tests (latex to bacterial meningitis, Cryptococcus, cysticercosis, VDRL) and bacteriological cultures were negative. Virus identification were also negative in 8 samples. None of the patients had neurological deficits or related symptoms after one year of onset. We believe the benefit of vaccination clearly outweighs the incidence of benign vaccine-associated meningitis.

CSF albumin

CSF albumin is a measurement used to determine the levels of albumin in cerebrospinal fluid. A closely related test, CSF total protein is a measurement used to determine the levels of protein in cerebrospinal fluid. It combines the albumin, IgG, and other proteins. It can be useful in distinguishing among causes of Meningitis. It is more likely to be elevated in bacterial meningitis than in viral meningitis. The upper normal range is 150 mg/dl in neonates, and 50 mg/dl in adults. References Body fluids CSF tests

Neonatal meningitis

Laboratory features Laboratory features that are characteristic of neonatal bacterial meningitis include: Isolation of a bacterial pathogen from the cerebrospinal fluid by culture and/or visualization by Gram stain Increased cerebrospinal fluid white blood cell count (typically >1000 white blood cells/μL, but may be lower, especially with Gram-positive bacteria), usually with a predominance of neutrophils Elevated cerebrospinal fluid]] protein concentration (>150 mg/dL in preterm (premature birth) and >100 mg/dL in term infants) Decreased cerebrospinal fluid glucose concentration (<20 mg/dL [1.1 mmol/L] in preterm (premature birth) and <30 mg/dL [1.7 mmol/L] in term (on time) infants) Causes

Clinical prediction rule for differentiating tuberculous from viral meningitis.

The Professor Dr Matei Bals National Institute of Infectious Diseases, Bucharest, Romania. To create a prediction rule to enable clinicians to differentiate patients with tuberculous meningitis (TBM) from those with viral meningitis. We retrospectively  analysed patients admitted to a tertiary care facility between 2001 and 2011 with viral meningitis and TBM. Patients were defined as having TBM according to a recently published consensus definition, and as viral meningitis if a viral aetiology was confirmed, or after ruling out bacterial,  fungal and non-infectious causes of meningitis. We identified 433 patients with viral meningitis and 101 TBM patients and compared their clinical and laboratory features. Multivariable analysis showed a statistically significant association between TBM and the following variables:  duration of symptoms before admission of ≥5 days, presence of neurological impairment (altered consciousness, seizures, mild focal signs, multiple cranial nerve palsies, dense hemiplegia or paraparesis), cerebrospinal fluid/blood glucose ratio < 0.5 and cerebrospinal fluid protein level  > 100 mg/dl. We propose a diagnostic score based on the coefficients derived from the logistic regression model with a sensitivity and specificity for TBM of respectively 92% and 94%. Our study suggests that easily available clinical and laboratory data are very useful for  differentiating TBM from other causes of meningitis.

Accuracy and test characteristics of ancillary tests of cerebrospinal fluid for predicting acute bacterial meningitis in children with low white blood cell counts in cerebrospinal fluid.

To determine whether ancillary tests of cerebrospinal fluid (CSF), specifically, the total protein concentration, glucose concentration, and percent neutrophils, provide information for diagnosing acute bacterial meningitis among children with low white blood cell (WBC) count in CSF. The authors retrospectively reviewed CSF from children aged 1 month to 18 years undergoing lumbar puncture at Children's Hospital in Boston from 1993 to 1999. Data were supplemented with CSF test results obtained from children with 0-30 WBCs/mm(3) in CSF diagnosed with acute bacterial meningitis at the same institution from 1984 to 1992. For each test, the incremental value of ancillary tests was estimated by calculating indices of performance such as the area under receiver operator characteristic curves (AUC) and interval likelihood ratios that are relatively insensitive to disease prevalence. Among children with 0-30 WBCs/mm(3) in CSF who met study criteria, acute bacterial meningitis was identified in ten of 7,701 (0.1%) for the period from 1993 to 1999 and supplemented with 11 additional cases for the period from 1984 to 1992. AUC values for ancillary tests were 0.61 for total protein concentration, 0.69 for glucose concentration, and 0.90 for percent neutrophils. Interval likelihood ratios were unremarkable for mildly abnormal test results. In contrast, interval likelihood ratios for markedly abnormal test results were higher: 22 for total protein concentration >120 mg/dL, 57 for neutrophils >75%, 15 for glucose concentration <20 mg/dL, and 20 for glucose concentration >120 mg/dL. When markedly abnormal, results of CSF total protein concentration, glucose concentration, and percent neutrophils have value for diagnosing acute bacterial meningitis, even among children with a low WBC count in CSF.

Viral Meningitis -- Evaluation

In adults, researchers have studied individual predictors of bacterial rather than viral meningitis. In one study, these predictors included CSF glucose less than 34 mg/dL, CSF WBC over 2000 cells/mm3, CSF neutrophils greater than 1180, CSF protein over 220 mg/dL, and a ratio of CSF to blood glucose less than 0.23.15. [17] CSF lactate has been shown to be a good indicator to differentiate bacterial from aseptic meningitis. [18] [19] The combination of CSF results, such as enterovirus and lactate, with the BMS, can increase sensitivity and specificity. [20] [21]

Neurology_Adams

Laboratory findings suggest certain organisms as the cause of aseptic meningitis. Most cases of infectious mononucleosis can be identified by the blood smear and specific serologic tests (heterophil or others). LCM should be suspected if there is an intense lymphocytic pleocytosis. Counts above 1,000 cells/mm3 in the spinal fluid, particularly if the cells are all lymphocytes, are most often due to LCM but may occur occasionally with mumps or echovirus 9. In the last of these agents, neutrophils may predominate in the CSF for a week or longer. Slightly depressed glucose in the spinal fluid is consistent with mumps meningitis and with the viruses mentioned earlier, but it is more often indicative of bacterial or fungal infection.

Neurology_Adams

The CSF contains a moderate number of white blood cells, mostly lymphocytes and mononuclear cells, and the protein content is in the range of 100 to 400 mg/dL (i.e., a higher protein content than all other neonatal infections except bacterial meningitis). The glucose values are normal. Fewer than 10 percent of infected children recover; the others are developmentally delayed to varying degrees, with seizures and paralysis. In those without symptoms of infection at birth, the outcome is better.

InternalMed_Harrison

LABORATORY DIAGNOSIS CSF Examination The most important laboratory test in the diagnosis of viral meningitis is examination of the CSF. The typical profile is a pleocytosis, a normal or slightly elevated protein concentration (0.2–0.8 g/L [20–80 mg/dL]), a normal glucose concentration, and a normal or mildly elevated opening pressure (100–350 mmH2O). Organisms are not seen on Gram’s stain of CSF. The total CSF cell count in viral meningitis is typically 25–500/μL, although cell counts of several thousand/μL are occasionally seen, especially with infections due to lymphocytic choriomeningitis virus (LCMV) and mumps virus. Lymphocytes are typically the predominant cell. Rarely, PMNs may predominate in the first 48 h of illness, especially with infections due to echovirus 9, West Nile virus, eastern equine encephalitis (EEE) virus, or mumps. A PMN pleocytosis occurs in 45% of patients with West Nile virus (WNV) meningitis and can persist for a week or longer before shifting to a

Viral Meningitis -- Evaluation

Because of the lack of clinical findings to help distinguish between viral and bacterial meningitis and the risk of untreated bacterial meningitis, there has been much interest in identifying predictors of bacterial meningitis. The bacterial meningitis score (BMS) was originally developed for and validated in children with meningitis. The score is comprised of four laboratory predictors (positive Gram stain, CSF protein over 80 mg/dL, peripheral absolute neutrophil count greater than 10000 cells/mm3, CSF absolute neutrophil count over 1000 cells/mm3) and one clinical predictor (seizure at or before the presentation). A positive Gram stain is worth 2 points, and the other predictors are worth 1 point each if present. The negative predictive value for a score of 0 was 100%; a score of more than 2 predicted bacterial meningitis with 87% sensitivity. [15] The BMS has also undergone validation in adults with meningitis. [16]

Aseptic Meningitis -- Evaluation

Typical CSF results in patients with aseptic meningitis include: Opening pressure either normal (<180 mmH2O) or slightly elevated, glucose normal to mildly decreased, protein normal to mildly elevated (<200mg/dL), cell count of 10-1000 cells per microliter (initially neutrophils (>50%) may predominate with a gradual shift toward lymphocytes (>80%). [2] [3] [6] Numerous differences have been found between adults and children concerning their presentation and their laboratory findings. [6]

Mumps meningo-encephalitis.

Between July 1981 and June 1985, 49 cases (36 boys (73%) and 13 girls (27%] of mumps meningo-encephalitis confirmed by culture of the virus from the cerebrospinal fluid (CSF) were seen. Patients presented particularly in the late spring and early summer. A CSF cell count greater than 500 X 10(6)/l was obtained in 14 cases (28%), a total CSF protein greater than 0.8 g/l in 6 cases (12%) and a CSF glucose of less than 2.2 mmol/l in 2 cases (4%). Two cases are reported to illustrate the diagnostic problems which the infection may cause, particularly when the CSF changes resemble those of tuberculous meningitis. In 1 case neurogenic pulmonary oedema developed after a convulsion; this caused further diagnostic uncertainty.

[Guillain-Barré syndrome as a rare cause of acute respiratory insufficiency].

Guillain-Barré syndrome (GBS) is an acute inflammatory demyelinating disease of peripheral nerves. Antibodies acting against antigens on the myelin or the axons seem to play a causative role. In up to 80 % the onset of GBS follows an antecedent respiratory or gastrointestinal infection. An 20 month old boy was referred to our hospital because of meningism and aspiration pneumonia. 10 days earlier the patient had experienced a period of fever. Because of respiratory insufficiency the patient was intubated, sedated and received mechanical ventilation. That's why a major neurological examination was not possible. The patient demonstrated a flaccid tetraplegic paralysis and autonomic dysfunction with elevated blood pressure, tachycardia, elevated ADH level and hyperglycaemia. Decreased motor nerve conduction and an increased CSF protein with normal CSF cell count confirmed diagnosis of GBS. Active CMV infection was diagnosed by PCR as the possible trigger factor. Intravenous immunoglobulins were given and the patient reached a complete remission except a slight disturbance of peroneal nerve. IVIG and PP therapy are equally effective in GBS. In contrast corticosteroids are not of benefit. Prognosis of childhood GBS is good. Only 4 % of affected children demonstrate persistent muscular weakness. The long interval between admission and diagnosis in the reported case emphasized the importance of neurological examination especially in sedated patients.

First_Aid_Step2

TABLE 2.8-4. CSF Prof les Normal < 10 < 5 ∼2/3 of serum 15–45 10–20 Clear 3–12 Bacterial meningitis ↔ ↑ (> 1000 PMNs) ↓ ↑ ↑ Cloudy ↔ or ↑ Viral meningitis ↔ ↑ (monos/ lymphs) ↔ ↔ or ↑ ↔ or ↑ Most often clear ↔ or ↑ Aseptic meningitis ↔ ↑ ↔ ↔ or ↑ ↔ Clear ↔ SAH ↑↑ ↑ ↔ ↑ ↔ or ↑ Yellow/red ↔ or ↑ Guillain-Barré syndrome ↔ ↔ ↔ or ↑ ↑↑ ↔ Clear or yellow (high protein) ↔ MS ↔ ↔ or ↑ ↔ ↔ ↔ Clear ↑↑ Pseudotumor cerebri ↔ ↔ ↔ ↔ ↑↑↑ Clear ↔ Antibiotics should be administered rapidly (see Table 2.8-5) and may be given empirically up to two hours before an LP is performed. Some cases of viral meningitis can be treated with supportive care and close follow-up. Close contacts of patients with meningococcal meningitis should receive rifampin, ciprofoxacin, or ceftriaxone prophylaxis.

Ranson criteria

Acute pancreatitis not secondary to gallstones At admission: Blood glucose > 11.11 mmol/L (> 200 mg/dL) Age > 55 years Serum LDH > 350 IU/L Serum AST > 250 IU/L WBC count > 16000 cells/mm3 Within 48 hours: Serum calcium < 2.0 mmol/L (< 8.0 mg/dL) Hematocrit decreased by > 10% Oxygen (hypoxemia with PaO2 < 60 mmHg) BUN increased by 1.8 or more mmol/L (5 or more mg/dL) after IV fluid hydration Base deficit (negative base excess) > 4 mEq/L Sequestration of fluids > 6 L Acute pancreatitis secondary to gallstones At admission: Glucose > 220 mg/dl Age > 70 years LDH > 400 IU/L AST > 250 IU/ 100 ml WBC count > 18000 cells/mm3 Within 48 hours: Serum calcium < 8 mg/dL Hematocrit decreased by > 10% Base deficit > 4 mEq/L BUN increased by > 2 mg/dL Sequestered fluid > 6L

InternalMed_Harrison

pleocytosis; the CSF cell count shows a shift from neutrophil to lymphocyte predominance within 1 day of presentation, and the total cell count does not exceed 1000/μL. The CSF glucose level is usually normal (in contrast to the low CSF glucose level in mumps), with a normal or slightly elevated protein concentration. Partially treated bacterial meningitis may be particularly difficult to exclude in some instances. Enteroviral meningitis is more common in summer and fall in temperate climates, while viral meningitis of other etiologies is more common in winter and spring. Symptoms ordinarily resolve within a week, although CSF abnormalities can persist for several weeks. Enteroviral meningitis is often more severe in adults than in children. Neurologic sequelae are rare, and most patients have an excellent prognosis.

Neurology_Adams

children younger than 2 years of age; in older children, it is more likely to develop in recurrent and less severe episodes. This clinical syndrome must be distinguished from tuberculous meningitis, viral meningoencephalitis, and the various conditions causing acute increased intracranial pressure. Usually, in lead encephalopathy, the CSF is under increased pressure with manifest papilledema, and there may be a slight lymphocytic pleocytosis and elevated protein but normal glucose values. It follows that lumbar puncture should be done with caution and only if it is essential for diagnosis.

Viral Meningitis -- Evaluation

A lumbar puncture is necessary unless there are contraindications such as focal neurologic deficits, papilledema, recent seizures, age 60 or greater. [1] [11] Indications for imaging before performing a lumbar puncture include focal neurological signs, papilledema, continuous or uncontrolled seizures, or a Glasgow Coma Score less than 12. [12] Cerebrospinal fluid (CSF) analysis, including cell count and differential, glucose, protein, culture, and molecular diagnostics as available, should be performed. Viral meningitis characteristically has a CSF mononuclear pleocytosis, although there may initially be a neutrophilic predominance. [1] This neutrophilic predominance is not limited to the first 24 hours of illness and is not a reliable indicator between viral and bacterial meningitis. [1] [13] Polymerase chain reaction (PCR) tests can be used to diagnose some causes of viral meningitis, such as enterovirus, VZV, and HSV. Serum white blood cell count and C-reactive protein do not reliably distinguish viral and bacterial meningitis. [1] CSF C-reactive protein and procalcitonin have not been shown to differentiate viral vs. bacterial meningitis compared to serum levels. [14]

Neurology_Adams

The CSF is typically under increased pressure and almost invariably shows a pleocytosis (range 10 to 200 cells/mm3; infrequently greater than 500 cells/mm3). The cells are mostly lymphocytes, but there may be a significant number of neutrophils early on. In a few cases, 3 to 5 percent in some large series, the spinal fluid was normal in the first days of the illness, only to become abnormal when reexamined. The hemorrhagic nature of brain tissue destruction with this infection is infrequently reflected in the spinal fluid. In fact, in only a minority of cases, red cells, sometimes numbering in the thousands but usually far fewer, and xanthochromia are found. The protein content is increased in most cases. Rarely, the CSF glucose levels may be reduced to slightly less than 40 mg/dL, creating confusion with tuberculous and fungal meningitides. The cerebral imaging appearance, giving highly characteristic features, is discussed later in the section on “Diagnosis.”

[Nested polymerase chain reaction for the diagnosis and follow-up of tuberculous meningitis: a case report].

We presented a case of tuberculous meningitis in which a nested polymerase chain reaction was useful for its rapid diagnosis and follow-up. A 5-month-old girl was hospitalized for gastrointestinal complaints of 4 days' duration. She initially had no meningeal signs, but showed a bulging of the anterior fontanel on the 10th day of her illness. Cerebrospinal fluid examination revealed a cell count of 886/3 microliters (80% lymphocytes), protein of 20 mg/dl, and glucose of 27 mg/dl. Tuberculous meningitis was suspected clinically and an antituberculous therapy was commenced on the 13th day. Although repeated attempts to culture Mycobacterium tuberculosis were negative, the DNA of the organism was detected sequentially from the cerebrospinal fluid of the 13th and 16th day by the method of a nested polymerase chain reaction. The final diagnosis of tuberculous meningitis was established on the basis of the positive results of the nested polymerase chain reaction, a positive tuberculin test, and typical cerebrospinal fluid findings. She recovered rapidly in response to the therapy and was discharged from the hospital without any neurological sequelae on the 89th day. The follow-up samples of the nested polymerase chain reaction resulted as negative after the 26th day of the illness.

[The value of C-reactive protein for the differentiation of bacterial meningitis from viral meningitis].

In order to differentiate bacterial meningitis versus viral meningitis, we have comparatively tested the efficacy of the following tests: C-reactive protein (CRP), erythrocytes sedimentation rate (ESR), fever, level of glucose in cerebro-spinal fluid (CSF), glucose in CSF/glycemia ratio, number of white blood cells in peripheric blood, percentage of neutrophils in peripheric blood, level of proteins in CSF and number of nucleated cells in CSF for a group of 49 patients, both children and adults with central nervous system infection (37 patients with bacterial meningitis and 12 with viral meningitis) hospitalised between May 1993 and July 1994 in Clinical Hospital for Infectious Diseases in Iaşi. The mean value of CRP in bacterial meningitis patients was 8.78 mg%, contrasting with the mean value of CRP = 1.92 mg% recorded in patients with viral meningitis. Ten out of 37 bacterial meningitis patients presented a CRP concentration < 1.85 mg%. All these 10 patients have already had an antibiotic treatment at the moment of the assay. One out of 12 cases of viral meningitis had a value of CRP = 3.3 mg%, all the remainder cases having values under 1.85 mg%. We recorded highly significant differences between the two patient groups for CRP (p < 0.001), ESR (p < 0.01), protein concentration in CSF (p < 0.001) and number of nucleated cells in CSF (p < 0.001). Differences recorded for fever, concentration of glucose in CSF, glucose in CSF/glycemia ratio, number of leucocytes in peripheric blood and percentage of neutrophils in peripheric blood, were not significant (p > 0.5). Data were analysed also by box-plot method which facilitates the visual appraisal of the differences recorded between the two aetiological groups. In conclusion, assays of CRP and ESR may be used as differentiation tests for bacterial meningitis versus viral meningitis, when assay is done before the antibiotic treatment, being sufficient sensitive, and easy to perform.

[Tuberculoma and tuberculous meningitis mimicking metastatic brain tumor and meningeal carcinomatosis--case report].

A 45-year-old man was well until February 1986, when he experienced gait disturbance and psychiatric symptoms. On February 11 he fell down several times and developed generalized convulsion on the following day. He was admitted to a hospital in a delirious condition. The chest X-ray film showed infiltration in the left upper lobe, but computed tomographic (CT) scan of the head revealed no abnormality. Cerebrospinal fluid obtained by lumbar puncture contained 155 cells/mm3, all of which were lymphocytes, and protein and glucose concentrations were 372 mg/dl and 68 mg/dl respectively. In spite of negative smear tests of sputum and cerebrospinal fluid for tubercle bacilli he was administered antituberculosis drugs on the suspicion of pulmonary tuberculosis and tuberculous meningitis. His level of consciousness gradually returned to normal but the follow-up CT scans showed a low density area with contrast enhancement in the right thalamus and obliteration of the right quadrigeminal cistern which was also enhanced with contrast medium. He was transferred to our hospital on March 28 for further evaluation. On admission to our hospital he was alert and oriented, his pupils were equal and reactive to light and he had mild left hemiparesis, left hyperreflexia and left hemihypesthesia. Cell count of the cerebrospinal fluid was 243/mm3, 90% of which were lymphocytes and protein and glucose contents were 340 mg/dl and 42 mg/dl respectively. Both smear and culture of the cerebrospinal fluid were negative for tubercle bacilli and other organisms. Cytological examination of the cerebrospinal fluid demonstrated clusters of cells of various sizes with high N/C ratio which suggested these cells were malignant.(ABSTRACT TRUNCATED AT 250 WORDS)

[Clinical and laboratory characteristics of 62 tuberculous meningoencephalitis cases].

The authors present clinical, demographic and laboratory characteristics of 62 patients with proven tuberculous meningoencephalitis admitted at Couto Maia Hospital, reference for patients with infectious diseases in the State of Bahia. The patients' age varied from 2 months to 50 years, 59.7% of the cases with ages ranging from 0 to 4 years, no sex predominance. The time length for the disease varied from 0 to 90 days, average around 13 days. The most common signs and symptoms were fever and neck stiffness in 86.7 and 81.8% of the cases respectively. The cerebrospinal fluid showed cells varying from 4 to 1549/mm3, average of 406; glucose from 20 to 70 mg/dL, average of 37.3, protein from 30 to 500 mg/dL, average of 203; lymphocyte predominance occurred in most cases, however in 21.3% there was predominance of neutrophils.

Leptospirosis

For those with liver involvement, transaminases and direct bilirubin are elevated in liver function tests. The Icterohaemorrhagiae serogroup is associated with jaundice and elevated bilirubin levels. Hemolytic anemia contributes to jaundice. A feature of leptospirosis is acute haemolytic anaemia and conjugated hyperbilirubinemia, especially in patients with glucose-6-phosphate dehydrogenase deficiency. Abnormal serum amylase and lipase levels (associated with pancreatitis) are found in those who are admitted to hospital due to leptospirosis. Impaired kidney function with creatinine clearance less than 50 ml/min is associated with elevated pancreatic enzymes. For those with severe headache who show signs of meningitis, a lumbar puncture can be attempted. If infected, cerebrospinal fluid (CSF) examination shows lymphocytic predominance with a cell count of about 500/mm3, protein between 50 and 100 mg/ml and normal glucose levels. These findings are consistent with aseptic meningitis.

Neurology_Adams

The CSF glucose concentration is normally in the range of 45 to 80 mg/dL, that is, about two-thirds of that in the blood (0.6 to 0.7 of serum concentrations). Higher levels parallel the blood glucose in this proportion; but with marked hyperglycemia, the ratio of CSF to blood glucose is reduced (0.5 to 0.6). With extremely low serum glucose, the ratio becomes higher, approximating 0.85. In general, CSF glucose values below 35 mg/dL are abnormal. After the intravenous injection of glucose, 2 to 4 h is required to reach equilibrium with the CSF; a similar delay follows the lowering of blood glucose. For these reasons, samples of CSF and blood for glucose determinations should ideally be drawn simultaneously in the fasting state or the serum should be obtained a few hours before the puncture but (this is often not practical). Low values of CSF glucose (hypoglycorrhachia) in the presence of pleocytosis usually indicate bacterial, tuberculous, or fungal meningitis, although similar

An infant in whom contrast-enhanced fluid attenuated inversion recovery (FLAIR) MRI was useful for the diagnosis of meningitis and devising a treatment strategy.

A 3-month-old male was brought to our hospital due to fever, poor sucking, and a bulging anterior fontanel. His general condition was poor. Analysis of the cerebrospinal fluid (CSF) showed increases in the cell count (8/μl) and the polymorphonuclear leukocyte count (2/μl) but normal sugar (66 mg/dl) and protein (28 mg/dl) levels. A CSF smear showed no bacterial cells. The administration of antibacterial drugs was initiated, and head MRI was performed on the next day. Plain images revealed no abnormalities. However, contrast-enhanced fluid-attenuated inversion recovery (FLAIR) MRI showed clear contrast enhancement along the brain surface in the meninges of the left and right frontal and left parietal lobes and fluid retention accompanied by contrast enhancement in a part of the adjacent subdural space. These findings could be confirmed only by contrast-enhanced FLAIR MRI. A diagnosis of bacterial meningitis with an unknown cause was made, and the administration of 2 antibacterial drugs was continued. MRI on day 8 of the illness showed the disappearance of contrast enhancement, and plain FLAIR also facilitated a diagnosis of a subdural hygroma. The treatment was effective. At present, the patient is 1 year and 6 months old without sequelae. The diagnosis of bacterial meningitis in infants is difficult based on only symptoms. In its early stage with few abnormal findings in the CSF, diagnosis is sometimes difficult. Antibacterial drug administration should be immediately initiated. However, definite findings are necessary for the continuation of large amounts of antibacterial drugs. Contrast-enhanced FLAIR allows the sensitive visualization of meningeal inflammation and is useful as a complementary diagnostic method for meningitis. In addition, this technique can reveal marked inflammatory lesions such as a subdural hygroma in the early stage, providing information useful for making a diagnosis of bacterial meningitis.

Pediatrics_Nelson

Table 100-2 Cerebrospinal Fluid (CSF) Findings in Various Central Nervous System Disorders CONDITION PRESSURE LEUKOCYTES (/µL) PROTEIN (mg/dL) GLUCOSE (mg/dL) COMMENTS Normal 50–180 mm H2O <4; 60%–70% lymphocytes, 30%–40% monocytes, 1%–3% neutrophils 20–45 >50% of serum glucose HSV, Herpes simplex virus; IGRA, interferon gamma release assay for tuberculosis; PCR, polymerase chain reaction; PMNs, polymorphonuclear leukocytes; TST, tuberculin skin test.