Choosing Wisely Campaign - Part I

I am on outpatient this month. The questions I find myself asking on most of the patients are focused on the type of health maintenance that the patient needs. I understand that medical care is ever evolving and changing but I find that preventative medicine, in my very limited experience, seems to change faster, more often. I came across the AAFP's recent release of the Choosing Wisely Campaign. It was released just last week and I thought it would be good to summarize a few (the table is 89 pages long) recommendations on topics I know I will deal with frequently in the clinical setting. 

Allergy/Immunology 

• Don’t perform screening panels, IgE panels, for food allergies without previous consideration of medical history -It is important to use clinical correlation when considering allergen testing. For example, only consider testing a patient specifically for peanut allergy if the patient endorses symptoms after ingestion of peanuts. Studies have shown that about 8% of the population tests positive to peanuts but only approximately 1% are truly allergic and exhibit symptoms upon ingestion. When symptoms suggest a food allergy, tests should be selected based on a careful medical history. 

Cardiovascular

• Don't order annual electrocardiography or any other cardiac screening for asymptomatic, low-risk patients - Who is considered low risk? Risk factors can be combined in many ways to allow classification of a person's risk for a CHD event as low, intermediate, or high. Several calculators and models are available to quantify a person's 10-year risk for CHD events. The Framingham Adult Treatment Panel III calculator (http://hp2010.nhlbihin.net/atpiii/calculator.asp) performs well for the U.S. population. Persons with a 10-year risk greater than 20% are generally considered high-risk, those with a 10-year risk less than 10% are considered low-risk, and those in the 10% to 20% range are considered intermediate-risk.
• Don’t perform stress cardiac imaging or advanced noninvasive imaging in the initial evaluation of patients without cardiac symptoms unless high risk markers are present - Asymptomatic, low-risk patients account for up to 45% of unnecessary “screening.” Testing should be performed only when the following findings are present: diabetes in patients older than 40 years; peripheral arterial disease; or greater than 2% yearly risk of coronary heart disease events.
• Avoid using stress echocardiograms on asymptomatic patients who meet "low-risk" scoring criteria for coronary disease -Stress echocardiography is mostly used in symptomatic patients to assist in the diagnosis of obstructive CAD. There is very little information on using stress echocardiography in asymptomatic individuals for the purposes of cardiovascular risk assessment, as a stand-alone test or in addition to conventional risk factors. 
• Don't repeat echocardiograms in stable, asymptomatic patients with a murmur or click when no pathology has been previously found and there has been no clinical change in the patient’s condition - Trace mitral, tricuspid, and pulmonic regurgitation can be detected in 70% to 90% of normal individuals and has no adverse clinical implications. Aortic stenosis is an exception. The 2014 American Heart Association/American College of Cardiology valvular guideline recommends serial echocardiography in patients with aortic stenosis. In patients with Stage B mild AS (transvalvular velocity 2 to 2.9 m/s), echocardiography is recommended every three to five years. In patients with Stage B moderate AS (transvalvular velocity 3 to 3.9 m/s), echocardiography is recommended every one to two years. In patients with asymptomatic Stage C1 severe AS (transvalvular velocity 4 m/s or higher), echocardiography is recommended every 6 to 12 months. Echocardiography is indicated earlier if there is a change in symptoms or signs suggestive of worsening cardiac status. 
• Don't perform routine annual stress testing after coronary artery revascularization - Routine annual stress testing in patients without symptoms does not usually change management. This practice may lead to unnecessary testing without any proven impact on patient management

Asthma

Definition - A common chronic disorder of the airways that is complex and characterized by variable and recurring symptoms, airflow obstruction, bronchial hyperresponsiveness, and an underlying inflammation. The latter definition of asthma has features that overlap with the description of COPD. Besides historic features (such as the onset of disease in middle age/older, history of cigarette smoking), the characteristic that best distinguishes COPD from asthma is the degree of reversibility of airflow obstruction.

Clinical Features

•  Asthma is diagnosed before the age of seven years in approximately 75 percent of cases and may resolve when the patient begins puberty. Asthma may reoccur later in adulthood. 
• A pattern of respiratory symptoms that occur with exposure to triggers (such as a allergen, exercise, viral infection) and resolve with trigger avoidance or asthma medication is typical of asthma. 
• Patients often report 2 out of 3 of the following symptoms
• Wheezing
• Coughing (often worse at night)
• Shortness of Breath or difficulty breathing

Diagnosis - A history of intermittent symptoms typical of asthma plus the finding on physical examination of characteristic musical wheezing, when patient is symptomatic, strongly point to a diagnosis of asthma. Diagnosis is confirmed by evaluating the following...

• Pulmonary function test - will tell you if the lung disease is a obstructive pattern (FEV1/FVC < 0.7) and what the response after bronchodilator therapy
• Response to bronchodilator - The presence of a bronchodilator response, in isolation, is not enough to diagnose asthma. Asthma is typically distinguished from these other conditions (COPD, bronchiectasis, cystic fibrosis, and bronchiolitis) by the large response as at least 15 to 20 percent. 

Treatment - Once you have diagnosed Asthma, what are the goals of management and treatment options? The goals of chronic asthma management may be divided into two domains...

•  Reduction in impairment - Specific goals for reducing impairment include..
• Freedom from frequent or troublesome symptoms of asthma
• Minimal need (≤2 days per week) of inhaled short acting beta agonists to relieve symptoms
• Few night-time awakenings (<2 nights per month) due to asthma
• Oral glucocorticoid courses and/or urgent care visits should be needed no more than once per year
• Maintenance of normal daily activities, including work or school attendance and participation in athletics and exercise
• Satisfaction with asthma care on the part of patients and families
• Reduction in risk 
• Prevention of recurrent exacerbations and need for emergency department or hospital care
• Prevention of reduced lung growth in children, and loss of lung function in adults
• Optimization of pharmacotherapy with minimal or no adverse effects

Treatment - First, you want to categorize the patient's report of symptoms into a category (See figure below)

Once you have the patient's symptom categorized, you can chose a treatment plan. 

• Mild Intermittent - Patients with mild intermittent asthma are best treated with a quick-acting inhaled beta-2-selective adrenergic agonist, taken PRN for relief of symptoms.
• Mild Persistent - distinction between intermittent and mild persistent asthma is important, because current guidelines for mild persistent asthma call for initiation of daily long-term controller medication, a low dose inhaled glucocorticoid.
• Moderate Persistent - the preferred therapies are either low-doses of an inhaled glucocorticoid plus a long-acting inhaled beta agonist, or medium doses of an inhaled glucocorticoid
• Severe Persistent - medium or high doses of an inhaled glucocorticoid, in combination with a long-acting inhaled beta-agonist

Management of Diabetic Ketoacidosis (DKA) and Hyperosmolar Hyperglycemic State (HHS) in Adults

This is the common internal medicine problem that will keep me quite busy if it rolls in on night float...or anytime of the day, I suppose.

Definitions 

• DKA - metabolic acidosis, secondary to ketones, is often the major finding, while the serum glucose concentration is generally below 800 mg/dL. 
• In HHS, there is little or no ketoacid accumulation, the serum glucose concentration frequently exceeds 1000 mg/dL, the serum osmolality may reach 380 mosmol/kg.

Initial Evaluation

• Take care of your ABCs first! (Airway,Breathing and Circulation)
• Establish a diagnosis with CBC, BMP, UA for ketones, ABG, plasma osmolality
• Try to find the underlying etiology of the DKA or HHS and treat that. Most are secondary to infection (pneumonia and UTI) so obtain blood cultures, chest xray and EKG

Monitoring

Once you have established the diagnosis, how should you monitor?

•  Serum glucose should initially be measured every hour until stable, while serum electrolytes, blood urea nitrogen, creatinine, osmolality, and venous pH, which is about 0.03 units lower than arterial blood gas, should be measured every two to four hours, depending upon disease severity and the clinical response. 
• Monitor the acidosis by either directly measuring beta-hydroxybutyrate or the anion gap.

Treatment

• FLUIDS!! - Fluids should be given first as it increases the effectiveness of the insulin therapy to come. Initial fluid therapy in DKA and HHS is directed toward expansion of the intravascular volume and restoration of renal perfusion. The average fluid loss is 3 to 6 L in DKA and up to 8 to 10 L in HHS, due largely to the glucose osmotic diuresis . Start with NS and switch over to D5NS when the serum glucose is <250. As mentioned below, if the patient is hemodynamically stable, then you will want to switch to 1/2NS when adding potassium to the fluid.
• Replenish the Potassium - To prevent hypokalemia, potassium chloride (20 to 30 meq/L) is generally added to the replacement fluid once the serum potassium concentration falls below 5.3 meq/L. If the patient is hemodynamically stable, one-half isotonic saline is preferred since the addition of potassium to isotonic saline will result in a hypertonic solution that will delay correction of the hyperosmolality.
• Insulin of course!! - After you have given fluids and serum potassium is > 3.5, you may give insulin. A continuous IV administration of regular insulin is the treatment of choice. DKA and HHS can be treated either with an IV bolus (0.1 U/kg body weight), followed by a continuous infusion of regular insulin at a dose of 0.1 U/kg per hour or with an intravenous infusion alone at a rate of at least 0.14 U/kg per hour.
• Sodium Bicarbonate - We recommend administering bicarbonate if the arterial pH is less than 6.90. UptoDate recommends giving 100 meq of sodium bicarbonate in 400 mL sterile water with 20 meq of potassium chloride, if the serum potassium is less than 5.3 meq/L, administered over two hours. 

Chronic Obstructive Pulmonary Disease (COPD) Exacerbation 

Introduction - The Global Initiative for Chronic Obstructive Lung Disease (GOLD), a report produced by the National Heart, Lung, and Blood Institute and the World Health Organization defines a Chronic Obstructive Pulmonary Disease Exacerbation as an acute increase in symptoms beyond normal day-to-day variation [1]. This generally includes an acute increase in one or more of the following cardinal symptoms...

• Cough increases in frequency and severity
• Sputum increases in volume or changes in character
• Dyspnea increases from baseline (using inhalers/breathing treatments more often, increase in O2 use at home)

Etiology - Most precipitants of COPD exacerbations are secondary to viral and bacterial respiratory infections (estimated as 70-80% of the time). The other 20% is secondary to environmental pollution or unknown etiology. 

Risk of Exacerbations - The GOLD guidelines suggest using a combination of an individual’s FEV1 and history of exacerbations to assess the exacerbation risk. The severity of lung function impairment is stratified based on the postbronchodilator FEV1, using the GOLD classification of airflow limitation (see table below). These components are combined into the following risk stratification...

• Low risk: Typically GOLD 1 or 2 (mild to moderate airflow limitation) and/or 0 to 1 exacerbation per year. 
• High risk: Typically GOLD 3 or 4 (severe or very severe airflow limitation) and/or ≥2 exacerbations per year

Initial Evaluation - Initial evaluation of a patient with a suspected exacerbation of COPD includes a medical history, physical examination, chest xray, sputum culture and routine laboratory studies. Arterial blood gas analysis should be performed in most patients to assess the severity of the exacerbation and to establish a baseline from which improvement or deterioration can be measured. Patients with COPD who present to the hospital with acute worsening of dyspnea should be evaluated for potential alternative diagnoses, such as heart failure, pulmonary thromboembolism, and pneumonia.

Treatment - Supplemental oxygen is a critical component of acute therapy. It should target an O2 saturation of 90 to 94 percent. The major pharmacologic components of managing an acute exacerbation of COPD include inhaled short-acting bronchodilators (beta adrenergic agonists and anticholinergic agents), glucocorticoids, and antibiotics. 

• Beta adrenergic agonists - Inhaled short-acting beta adrenergic agonists (albuterol) are the mainstay of therapy for an acute exacerbation of COPD because of their rapid onset of action and efficacy in producing bronchodilation.
• Anticholinergics - Inhaled short-acting anticholinergic agents (ipratropium) may be used in combination with inhaled short-acting beta adrenergic agonists. 
• Glucocorticoids - Systemic glucocorticoids, when added to the bronchodilator therapies described above, improve symptoms and lung function, and decrease the length of hospital stay. The route used depends on the stability of the patient. Oral glucocorticoids are rapidly absorbed and appear equally efficacious as intravenous glucocorticoids. In fact, a randomized trial assigned 210 patients hospitalized with a COPD exacerbation to receive oral or IV steroids for five days and found no difference between the two groups in the rate of treatment failure, length of hospital stay, improvement in spirometry, or improvement in quality of life. However, intravenous glucocorticoids are typically administered to patients who present with a severe exacerbation, who respond poorly to oral glucocorticoids or who are unable to take oral medication. 
• Antibiotics - The optimal antibiotic regimen for the treatment of exacerbations of COPD has not been determined. UpToDate recommends a "risk stratification" approach when selecting initial antibiotic therapy (see algorithim below). Specifically, they recommend prescribing a broader antibiotic regimen for patients who have risk factors for a poor outcome.

Hypertensive Urgency and Emergency

My last post was on defining hypertension and secondary causes of hypertension. Continuing with the theme, I wanted to refresh myself on this common inpatient problem.

Definitions

• Hypertensive Emergency - Severe hypertension in adults (systolic blood pressure ≥180 mmHg and/or diastolic blood pressure ≥120 mmHg) associated with symptoms that signal end-organ damage (hypertensive encephalopathy, subarachnoid or intracerebral hemorrhage, retinal hemmorrhage, kidney injury, acute pulmonary edema, aortic dissection, and rebound after withdrawal of antihypertensive medications).
• Hypertensive Urgency - Severe hypertension in adults (systolic blood pressure ≥180 mmHg and/or diastolic blood pressure ≥120 mmHg) associated with none or mild symptoms, often a mild headache, but no signs of acute end-organ damage.

Etiology - often occurs in patients who have been non adherent with either their antihypertensive drug regimen or their low-sodium diet. Severe hypertension can also develop in patients who are adherent to their medications and following ingestion of large quantities of salt and can be controlled by resuming a low-salt diet.

Treatment

Hypertensive Urgency - The blood pressure should be reduced over a period of hours to days. The blood pressure should usually be lowered to <160/<100 mmHg. However, the mean arterial pressure should not be lowered by more than 25 to 30 percent over this relatively short period of time. This means that patient's who have very elevated blood pressures, the goal may be a little higher than 160/100. The choice of therapy depends on the timeline. If the blood pressure needs to be lowered over a period of hours (Patients judged to be at high risk for imminent cardiovascular events due to severe hypertension, including those with known aortic or intracranial aneurysms), UptoDate recommends oral furosemide, oral clonidine, or oral captopril. If the blood pressure needs to be lowered over a period of days, resumption of antihypertensive therapy, initiation of antihypertensive therapy, or the addition of another antihypertensive drug is adequate.

Hypertensive Emergency - Nitroprusside dilates both arterioles and veins and is generally considered to be the most effective parenteral drug for most hypertensive emergencies. Nitroprusside acts in less than one minute and its effects disappear within 1 to 10 minutes, thereby minimizing the risk of hypotension. Nitroprusside's major limitation is its metabolism to cyanide which could lead to the development of cyanide or rarely thiocyanate toxicity. Nitroglycerine, CCB, Labetalol (a combined beta-adrenergic and alpha-adrenergic blocker with a rapid onset of action, 5 min, makes it useful in the treatment of hypertensive emergencies), Esmolol, Hydralazine and Phentolamine (good in catecholamine excess). On my ward rotations, the most common drugs I see used in Hypertensive Emergencies are Nitro drips and Labetolol.

Hypertension

First, some definitions...

• Normal blood pressure: systolic <120 mmHg and diastolic <80 mmHg
• Prehypertension: systolic 120 to 139 mmHg or diastolic 80 to 89 mmHg
• Hypertension:
• Stage 1: systolic 140 to 159 mmHg or diastolic 90 to 99 mmHg
• Stage 2: systolic ≥160 or diastolic ≥100 mmHg

Primary (Essential) Hypertension 

Pathogenesis - poorly understood for but the following have been implicated in primary HTN

• Increased sympathetic neural activity
• Increased Ang II and mineralcorticoid activity
• Genetic predisposition
• Reduced nephron mass

Risk Factors 

• Excess Na or ETOH intake
• Obesity and weight gain
• Physical inactivity
• dyslipidemia
• Depression
• Vitamin D deficiency

Secondary causes of HTN

• Medications - chronic NSAIDs, oral contraceptives and antidepressants. 
• Primary renal disease - vascular and glomerular
• Hyperaldosteronism - the presence of primary mineralocorticoid excess, primarily aldosterone, should be suspected in any patient with the triad of hypertension, unexplained hypokalemia, and metabolic alkalosis.
• Cushing's syndrome
• Hyper/Hypothyroidism and Hyperparathyroidism
• Obstructive sleep apnea
• Coarctation of the aorta

When should you start working up secondary causes of HTN?

It is not cost effective to perform a complete evaluation for secondary hypertension in every hypertensive patient. Thus, it is important to be aware of the clinical clues that suggest secondary hypertension. Clinical clues include...

• Severe or resistant hypertension. Resistant hypertension is defined as the persistence of hypertension despite concurrent use of adequate doses of three antihypertensive agents from different classes, including a diuretic.
• An acute rise in blood pressure developing in a patient with previously stable values.
• Age < 30 years of age in non-obese, non-black patients with a negative family history of and no other risk factors (obesity, HLD) for hypertension.
• Malignant or accelerated hypertension (patients with severe hypertension and signs of end-organ damage such as retinal hemorrhages or papilledema, heart failure, neurologic disturbance, or acute kidney injury). 
• Proven age of onset before puberty.

Tests to order and Physical Exam findings

• BMP to look at the BUN and CR and assess for primary renal disease
• US of the renal vasculature to search for RAS or Fibromuscular Dysplasia 
• On physical exam, carotid, abdominal, or femoral bruits suggest atherosclerotic disease and possible renal artery stenosis, diminished femoral pulses and/or a discrepancy between arm and thigh blood pressures suggest aortic coarctation or significant aortoiliac disease
• Screening for primary aldosteronism begins with a paired, morning measurement of the plasma aldosterone concentration (PAC) and plasma renin activity (PRA) to determine whether the patient has an elevated or high-normal PAC, suppressed PRA, and elevated PAC/PRA ratio
• If the patient is showing clinical clues for pheochromocytoma (episodic headache, sweating, and tachycardia) then measuring fractionated metanephrines and catecholamines in a 24-hour urine collection is the intial step. 
• For Cushing disease workup, UptoDate recommends two first-line tests should be abnormal to establish the diagnosis of Cushing's syndrome. First line tests include...late night salivary cortisol, urinary cortisol, and the low-dose dexamethasone suppression tests
• Sleep study for OSA
• TSH and PTH levels

Acute Pancreatitis

Introduction -The most common cause of pancreatitis is gallstones. The second most common cause if alcohol. Pancreatitis can be divided into two categories. 

1. Edematous acute pancreatitis, which is characterized by acute inflammation of the pancreatic parenchyma and peripancreatic tissues, but without recognizable tissue necrosis
2. Necrotizing acute pancreatitis, which is characterized by inflammation associated with pancreatic parenchymal necrosis and/or peripancreatic necrosis

Clinical Features - Most patients with acute pancreatitis have acute onset of persistent, severe epigastric abdominal pain. In approximately 50 percent of patients, the pain radiates to the back. Approximately 90 percent of patients have associated nausea and vomiting which may persist for several hours.

Diagnosis - The diagnosis of acute pancreatitis requires the presence of two of the following three criteria

1. Acute onset of persistent, severe, epigastric pain often radiating to the back
2. Elevation in serum lipase or amylase to three times or greater than the upper limit of normal
3. Characteristic findings of acute pancreatitis on imaging (focal or diffuse enlargement of the pancreas on contrast-enhanced abdominal CT or MRI is suggestive of acute pancreatitis. Check out the image below...P is for pancreas and it is quite large in that picture)

Management

• Fluid replacement - Up to Date recommends aggressive hydration at a rate of 5 to 10 mL/kg per hour of isotonic crystalloid solution (NS or LR) to all patients with acute pancreatitis. Fluid management needs to be reassessed frequently during the hospital stay. Monitor the vital signs, keep HR <120 and MAP between 65-89 and monitor the BUN as both the BUN at the time of admission and the change in 24 hours since admission can predict mortality. Watch the urine output (should be >0.5 to 1 cc/kg/hour) and try to achieve a reduction in hematocrit with a goal of 35 to 44 percent
• Pain control - Abdominal pain is often the predominant symptom in patients with acute pancreatitis and should be treated with analgesics. Hydromorphone and Fetanyl are recommended. I remember while studying for the boards that Merperidine was recommended over Morphine because it is believed that Morphine will cause contraction of the Sphincter of Oddi which would exacerbate the pancreatitis. However, Merperidine has a very short half life and can be cumbersome to manage the patient's pain adequately. 
• Nutrition - In mild pancreatitis, in the absence of nausea or vomiting, oral feeds can be initiated as soon as the pain is decreasing and inflammatory markers are improving (about 24-48 hours). A low fat, soft diet is recommended. In moderately severe to severe pancreatitis, oral feeding is frequently not tolerated. Patients usually require enteral or parenteral feeding.  Early enteral nutrition (within 24 to 48 hours) should be initiated when a patient is transferred to the ICU, or has the development of organ failure, or systemic inflammatory response syndrome (SIRS) persisting for 48 hours. Enteral feeding requires the placement of a jejunal feeding tube beyond the ligament of Treitz. The reason it needs to be beyond the ligament of Trietz is to avoid the duodenal release of cholecystokinin, the hormone that will activate the pancreas. A feed that is high protein and low fat is best to avoid little activation of the pancreas. 

Upper GI Bleed

The Common Internal Medicine posts continue. I have two patients with upper GI bleeds (UGIB) on my census this week. One patient has a large antral ulcer and another patient has a varicele bleed from cirrhosis of the liver.

Introduction - An upper gastrointestinal bleeding includes hemorrhage originating from the esophagus to the ligament of Treitz. Peptic ulcer bleeding causes more than 60 percent of cases of upper gastrointestinal bleeding, whereas esophageal varices cause approximately 6 percent. Other etiologies of upper gastrointestinal bleeding include arteriovenous malformations, Mallory-Weiss tear, gastritis and duodenitis, and malignancy.

Management 

Triage the patient - Patients with acute upper gastrointestinal (GI) bleeding commonly present with hematemesis or melena. The very first thing you should do when evaluating a patient with an UGIB is ask if they are hemodynamically stable and order a type and cross in case the patient will need a transfusion.

General Support - The patient recieve supplemental oxygen and be kept NPO for 24 hours or as long as an active bleed is occuring. If hemodynamic instability is occurring or suspected, the patient should have two large bore IV catheters or a central line for rapid fluid resuscitation.

Fluid Resuscitation - Patients with active bleeding should receive intravenous fluids, about 500 mL of normal saline or lactated Ringer's solution over 30 minutes, while being typed and cross-matched for blood transfusion.

Blood Transfusion - The decision on whether to transfuse or not depends on the patient's medical history. Do they have and co-morbid condition such as unstable angina that make them more susceptible to hypoxemia. Up to Date recommends that you should try to keep the patient's hemoglobin > 7, including patients with stable CAD. In patients with unstable CAD, the recommendation is > 9. However, patients with active bleeding and hypovolemia may require blood transfusion despite an apparently normal hemoglobin. In one of my patients, he became tachycardiac with a HR of 120 and so we transfused two PRBC eventhough his hemoglobin was >7. One should also avoid over transfusing (Hg>10) the patient as it may precipitate the bleeding.

Medications 

Acid suppression - Patients admitted to the hospital with acute upper GI bleeding are typically treated with a proton pump inhibitor (PPI). We started my patients on IV Protonix for 72 hours. PPIs may also promote hemostasis in patients with lesions other than ulcers secondary to the neutralization of gastric acid which leads to the stabilization of blood clots.

Prokinetics - The goal of using a prokinetic agent (erythromycin and metoclopramide) is to improve gastric visualization at the time of endoscopy by clearing the stomach of blood, clots, and food residue. We suggest that erythromycin be considered in patients who are likely to have a large amount of blood in their stomach, such as those with severe bleeding.  Erythromycin is a motilin agonist and will promote gastric motility. My patient with an antral ulcer may have benefited from this as the endoscope report read that "stomach difficult to fully visualize due to the large amount of blood".

Octreotide - Somatostatin, or its analog octreotide, is used in the treatment of variceal bleeding and may also reduce the risk of bleeding due to nonvariceal causes. In patients with suspected variceal bleeding, octreotide is given as an intravenous bolus of 20 to 50 mcg, followed by a continuous infusion at a rate of 25 to 50 mcg per hour. My patient with a varicele bleed and cirrhosis is on octreotide.
Octreotide is not recommended for routine use in patients with acute nonvariceal upper GI bleeding, but it can be used as adjunctive therapy in some cases, such as when the patient needs to be stabilized before an endoscopy. My patient with an antral ulcer is currently not on octreotide.

Antibiotics - Antibiotics are considered in the patient with an UGIB and cirrhosis. Bacterial infections are present in up to 20 percent of patients with cirrhosis who are hospitalized with gastrointestinal bleeding and up to an additional 50 percent develop an infection while hospitalized. The most common infections include spontaneous bacterial peritonitis, UTI, respiratory infections and septicemia. Studies have shown that by giving patients with a varicele bleed and cirrhosis prophylactic antibiotics, you will decrease mortality, hospital stay and recurrence of bleeding. The most common antibiotics used are the fluoroquinolones and ceftriaxone. Ceftriaxone is used on patients with severe cirrhosis or if the patient is in a hospital setting where there is a high resistance to the flouroquinolones. My patient with a varicele bleed and cirrhosis is on 1 gm/day of IV ceftriaxone X 5 days.

Anticoagulants - hold any anticoagulant medication (plavix, aspirin or coumadin) that the patient may be on.

Procedures - upper endoscopy is diagnostic test of choice for patients with UGIB.

Syncope

It is almost the 2 month countdown to the beginning of my Internal Medicine residency. I am looking forward to not being a medical student anymore but, naturally, I am terrified at the idea of being a physician. It has been very busy around here. We are in the process of sorting and packing up our home while trying to go to our everyday jobs as well. Still, I want to stay true to the spirit of my blog and continue to learn and read no matter how busy life gets. I thought that it would be appropriate to start focusing on common Internal Medicine admission problems to prep for the upcoming excitement! Today's topic...Syncope!

Introduction - Syncope is the abrupt and transient loss of consciousness associated with absence of postural tone, followed by complete and often rapid spontaneous recovery.

There are many causes of syncope but one can sort differentials into most likely vs least likely by taking a detailed history. Questions I ask all of my syncope patients include...

• What were you doing before it happened (laying to sitting to standing position? stressful event? Prolonged standing?)?
• Did you have any flushing, lightheadedness diaphoresis or nausea?
• Did you feel any palpitations?
• Did you lose bowel of bladder control?
• Did you have tremors/shaking?
• Were you short of breath?
• Did you have any chest pain?
• Was it witnessed? If so, what did the patient look like or do when they passed out? How long were they unconscious? Were they confused when they woke up? How long were they confused?
• Did the patient experience any auras before they passed out?
• Patients past medical history (panic attacks with hyperventilation, cardiac conditions or diabetes)
• Any new medications (antiarrhythmics or antihypertensives) or illicit drugs/etoh?
• Recent illness?
• Decreased oral intake?
• Has this ever happened before and if so, what was the circumstance?

Physical Exam

• Blood pressure obtained in the supine, sitting, and erect position may detect orthostatic hypotension
• Heat rate - is it tachy, brady or irregular?
• Resp rate - is the patient hyperventilating?
• Cardiac ascultation
• Neurologic findings such as unilateral neurologic defecits

Causes of Syncope

Vasovagal - Vasovagal syncope (also known as neurocardiogenic syncope) is the most common cause of syncope. Vasovagal syncope may be caused by autonomic cardioinhibitory and/or vasodilator responses. It is likely that sensory inputs through vagal afferents, pain pathways, and central pathways to cause inhibition of the sympathetic nervous system and vagal activation. The most frequent mechanism for vasovagal syncope is a cardioinhibitory response and the most common abnormality was prolonged asystolic pauses and bradycardia. 

Situational - Situational syncope refers to syncope associated with specific scenarios.

Some situations  (postmicturition, cough, or post-tussive) appear to trigger a neural reflex causing a vagal response others (eg, straining, squatting) may cause syncope via mechanisms unrelated to neural reflexes. Several forms of situational syncope are associated with gastrointestinal stimuli (swallowing, defecation, visceral pain).

Orthostatic (Postural) - When autonomic reflexes are impaired or intravascular volume is decreased, a significant reduction in blood pressure occurs upon standing, a phenomenon termed orthostatic hypotension. Orthostatic hypotension can cause dizziness, syncope, and even angina or stroke. Many disorders can cause orthostatic hypotension (Parkinsons, dementia with Lewy bodies and Multiple System Atrophy), volume depletion (blood loss or decreased oral intake) and medications (antihypertensives) are all common causes.

Cardiogenic - Cardiac causes of syncope include structural heart disease leading to abrupt episodic drops in cardiac output by various mechanisms and thus, decreased cerebral perfusion. These conditions may include an abnormal heart rhythm (arrhythmia), obstructed blood flow in the heart or blood vessels, valve disease, aortic stenosis, blood clot, or heart failure

Neurologic - Neurologic syncope is the loss of consciousness due to a neurological condition such as seizure, stroke, transient ischemic attack or other rare causes including migraines and normal pressure hydrocephalus.

What tests should you order?

• Orthostatic Blood Pressures
• Echocardiogram when there is previous known heart disease or data suggestive of structural heart disease or syncope secondary to cardiovascular cause
• Immediate EKG monitoring when there is a suspicion of arrhythmia
• Blood glucose
• CBC/CMP
• In hospital monitoring is recommended if patient has structural heart disease and is determined to be at risk for arrhythmia 
• If a neurologic cause is suspected should get CT or head without contrast or EEG if patient had suspected seizure activity 
• Exercise if exercise induced syncope is suspected
• Psychiatric consult if pseudosyncope is suspected
• Tox screen is high suspicion of drug/alcohol abuse

Meningitis

Introduction - Meningitis is an inflammatory disease of the leptomeninges, the tissues surrounding the brain and spinal cord, and is defined by an abnormal number of white blood cells in the cerebrospinal fluid.

Clinical Manifestations - Patients with bacterial meningitis are often so ill that they will present soon after symptom onset. The classic triad of acute bacterial meningitis consists of fever, nuchal rigidity, and a change in mental status. The headache is another common symptom and is usually worse than the patients usual headache. Nuchal rigidity can be demonstrated by the following physcial examiniation techniques.

• Brudzinski sign (figure B) - spontaneous flexion of the hips during attempted passive flexion of the neck.
•  Kernig sign (figure A) - inability or reluctance to allow full extension of the knee when the hip is flexed 90 degrees.

Aseptic meningitis often has a similar presentation to bacterial meningitis (eg, fever, headache, altered mental status, stiff neck, photophobia), which can be a life-threatening illness. However, in contrast to bacterial meningitis, the majority of patients with aseptic meningitis have a self-limited course that will resolve without specific therapy. In my experience, patients with bacterial meningitis are very sick and will seek medical attention quickly after the onset of symptoms.

Diagnosis - Lumbar puncture!!! Examination of the cerebrospinal fluid is crucial for establishing the diagnosis of bacterial meningitis. There are situations where you need to get a CT of the head before you get an LP. CT of the head is indicated if the patient has one or more of the following...

• Immunocompromised state (eg, HIV infection, immunosuppressive therapy, solid organ or hematopoietic stem cell transplantation)
• History of central nervous system (CNS) disease (mass lesion, stroke, or focal infection)
• New onset seizure (within one week of presentation)
• Papilledema or any signs of raised intracranial pressure
• Abnormal level of consciousness
• Focal neurologic deficit

If LP is delayed needs to be delayed while the patient is getting a CT of the head, blood cultures should be obtained and antimicrobial therapy should be administered empirically before the patient goes for the CT and the LP should be done as soon as possible when the patient is cleared from the CT of the head. Dexamethasone may be given before or at the same time as the antimicrobials if the labs and clinical picture is highly suspicious of bacterial meningitis. Empiric antibiotics will not effect the cytology of the CSF but it may effect the gram stain and culture.

CSF Analysis

Opening pressure -The opening pressure is typically elevated in patients with bacterial meningitis (>200 mmH2O).

False-positives - It is important to note that a false-positive elevation of the CSF white blood cell count can be found after traumatic lumbar puncture or in patients with intracerebral or subarachnoid hemorrhage in which both red blood cells and white blood cells are introduced into the subarachnoid space. Generalized seizures may also induce a transient CSF pleocytosis mainly neutrophils.
A Gram stain of the CSF should be obtained whenever there is suspicion of bacterial meningitis. It has the advantage of suggesting the bacterial etiology one day or more before culture results are available .

•  Gram-positive diplococci suggest pneumococcal infection
• Gram-negative diplococci suggest meningococcal infection
• Small pleomorphic gram-negative coccobacilli suggest Haemophilus influenzae infection
• Gram-positive rods and coccobacilli suggest Listeria infection

 Treatment

If the patient has no immunodeficiency

Ceftriaxone or Cefotaxime - 2 g IV every 12 hours

PLUS

Vancomycin - 15 to 20 mg/kg IV every 8 to 12 hours

PLUS

Ampicillin (in adults greater than 50yrs of age) - 2 g IV every four hours

If the patient has an immunodeficiency

Vancomycin - 15 to 20 mg/kg IV every 8 to 12 hours

PLUS

Ampicillin - 2 g IV every four hours

PLUS

Cefepime/Meropenem - 2 g IV every eight hours


If the patient is allergic to Beta-Lactams

Vancomycin - 15 to 20 mg/kg IV every 8 to 12 hours

PLUS

Moxifloxacin -  400 mg IV once daily

PLUS

Trimethroprim-Sulfamethoxazole (if the patient is older than 50 years of age and needs covereage for Listeria) - 5 mg/kg IV every 6 to 12 hours

Transverse Myelitis

Introduction - Acute transverse myelitis is a spinal cord disorder that may present with the rapid onset of weakness, sensory alterations, and bowel or bladder dysfunction. TM can occur as an independent entity, most often a postinfectious complication, but TM may occur along with neuro-inflammatory disorders such as acute disseminated encephalomyelitis, multiple sclerosis, and neuromyelitis optica. It is important in the evaluation of patients with acute myelopathies to exclude compressive and noninflammatory causes of myelopathy because the treatment options will vary depending on the etiology. Compressive etiology may require urgent neurosurgery!

Differentiating TM from acute inflammatory demyelinating polyneuropathy (AIDP) - Patients with acute inflammatory demyelinating polyneuropathy (AIDP, Guillain-Barre syndrome) may also present with progressive sensory and motor dysfunction. There are several features that may be used to rapidly discriminate patients with AIDP from those with acute myelopathies.

• Patients who have AIDP often have both upper and lower extremity involvement. In contrast, patients with myelopathy will have dysfunction that is specific to the level of myelopathy. 
• Patients with myelopathy are more likely to have urinary or bowel urgency or retention, while those with AIDP are more likely to have cardiovascular instability. 
• A sensory level is often definable in patients with acute myelopathy but is never present in AIDP. 
• Cerebrospinal fluid analysis in AIDP usually shows an elevated protein with few white cells (this is known as cyto-albuminologic dissociation) whereas patients with TM may have an inflammatory cerebrospinal fluid with an elevated number of white blood cells and IgG index. 
• Spinal MRI imaging often shows a discrete lesion in myelopathy, whereas spinal MRI is normal in AIDP. 
• Electrodiagnostic studies may show conduction block or slowed conduction of peripheral nerves in AIDP and are usually normal in myelopathies.

Etiology

In 30 to 60 percent of the idiopathic TM cases, there is an antecedent respiratory, gastrointestinal, or systemic illness. In parainfectious TM, the injury may be associated with direct microbial infection of the central nervous system, or with the systemic response to infection by a variety of agents such as varicella zoster virus, herpes virus, and Listeria. TM may be associated with central nervous system vasculitis or infarction/ischemia of the spinal cord.  Alternatively, TM can be directly associated with infectious, systemic inflammatory, or multifocal central nervous system disease.

Although idiopathic TM usually occurs as a postinfectious complication that appears to result from an autoimmune process, TM can be directly associated with infectious, systemic inflammatory, or multifocal central nervous system disease.
Acquired central nervous system autoimmune disorders that can cause TM include multiple sclerosis, neuromyelitis optica, and acute disseminated encephalomyelitis.

• Multiple Sclerosis - TM can occur as part of the spectrum of multiple sclerosis. 
• Neuromyelitis Optica - TM manifesting as a longitudinally extensive spinal cord lesion spanning three or more vertebral segments is one of the characteristic findings of neuromyelitis optica. NMO antibodies may be ordered if this is suspected. 
• Disseminated Encephalomyelitis - TM may be seen in patients with acute disseminated encephalomyelitis, a demyelinating disease of the central nervous system.

Other central nervous system conditions that can cause TM are as follows:
- Infections including but not limited to West Nile virus, herpes viruses, HIV, HTLV-1, Lyme, Mycoplasma, Syphilis, Paraneoplastic syndromes and Neurosarcoidosis

 Systemic inflammatory autoimmune disorders that are associated with TM include the following:
-Ankylosing spondylitis
-Antiphospholipid antibody syndrome
-Behcet disease
-Mixed connective tissue disease
-Rheumatoid arthritis
-Scleroderma
-Sjogren syndrome
-Systemic lupus erythematosus

CLINICAL FEATURES — The onset of TM is characterized by motor, sensory and/or autonomic dysfunction (bowel, bladder, and sexual dysfunction). Motor symptoms include a rapidly progressing paraparesis with initial flaccidity followed by spasticity. The patient may describe sensory symptoms such as pain, dysesthesia, and paresthesia. Autonomic symptoms include increased urinary urgency, bladder and bowel incontinence, difficulty or inability to void, constipation, and sexual dysfunction.

MRI of the spinal cord typically shows a gadolinium-enhancing signal abnormality (seen in the image below), usually extending over one or more cord segments. The cord often appears swollen at the affected levels.



-Cerebrospinal fluid (CSF) is abnormal in approximately one-half of patients, with a moderate lymphocytosis and an elevated protein level

The diagnosis of TM is suspected when there are acute or subacute signs and symptoms of motor, sensory and/or autonomic dysfunction that localize to one or more contiguous spinal cord segments in patients with no evidence of a compressive cord lesion. Thus, the diagnosis of TM requires exclusion of a compressive cord lesion, usually by MRI, and confirmation of inflammation by either gadolinium-enhanced MRI or lumbar puncture.


Diagnostic criteria
Sensory, motor or autonomic dysfunction attributable to the spinal cord
Bilateral signs and/or symptoms
Clearly defined sensory level
No evidence of compressive cord lesion
Inflammation defined by cerebrospinal fluid pleocytosis or elevated IgG index or gadolinium enhancement



Treatment
Steroids
IVIG
Plasmapharesis

Wernike-Korsakoff syndrome - or Wernicke's encepatholopathy and Korsakoff's syndrome

 

I am now on the General Neurology service which has been very interesting compared to the stroke service. I had a patient with transverse myelitis and another with Wernike-Korsakoff syndrome today! Pretty interesting for my first day!

 

Introduction - Wernicke-Korsakoff syndrome is the best known neurologic complication of thiamine/vitamin B1 deficiency. The term is a combination of two different syndromes, each representing a different stage of the disease. Wernicke's encephalopathy is the acute syndrome which requires emergent treatment (thiamine and glucose) to prevent death and neurologic morbidity. Korsakoff's syndrome refers to a chronic neurologic condition that usually occurs as a consequence of WE.

 

Etiology - Although Wernike-Korsakoff is most often associated with chronic alcoholism, it can also occur in the setting of poor nutrition caused by malabsorption, poor dietary intake, increased metabolic requirement (cancer or systemic illness/inflammation) or increased loss of the water-soluble vitamin thiamine (eg, in renal dialysis). My patient has both a history of chronic ETOH abuse as well as a gastric bypass 8 years ago. Causes of Wernike-Korsakoff are listed below.

 

-Chronic alcoholism

-Anorexia nervosa or dieting

-Hyperemesis of pregnancy

-Prolonged intravenous feeding without proper supplementation

-Prolonged fasting or starvation, or unbalanced nutrition, especially with refeeding

-Gastrointestinal surgery (including bariatric surgery)

-Systemic malignancy

-Transplantation

-Hemodialysis or peritoneal dialysis

-Acquired immunodeficiency syndrome

 

Pathophysiology - It is unclear how thiamine deficiency causes brain lesions. Thiamine is a cofactor for several key enzymes important in energy metabolism such as transketolase, alpha-ketoglutarate dehydrogenase, and pyruvate dehydrogenase (You need to give thiamine before you give glucose in these patients). Because of its role in cerebral energy utilization, it has been proposed that its deficiency initiates neuronal injury by inhibiting metabolism in brain regions with high metabolic requirements and high thiamine turnover. 

 

Pathology - Acute lesions are characterized by vascular congestion, microglial proliferation, and petechial hemorrhages. In chronic cases, there is demyelination and gliosis. You will see neuronal loss most prominently in the unmeylinated areas of the medial thalamus. Necrosis/Atrophy of the mamillary bodies is a highly specific finding in chronic WE and Korsakoff syndrome and is present in up to 80 percent of cases. The lesions of WE occur in a characteristic, symmetrical distribution in structures surrounding the third ventricle, aqueduct, and fourth ventricle.

 

Clinical Manifestations

 

The classic triad of WE is encepthalopathy, gait ataxia and oculomotor dysfunction.

 

- Encepathopathy - characterized by profound disorientation, indifference, and inattentiveness. If these are less severe and permit higher cognitive testing, impaired memory and learning are also evident. My patient was attentive but didn't know where she was exactly and didn't have any insight as to why she was in the hospital. She seemed to think it was about 20 years ago when she still lived with her mom and dad (who had passed 15 years ago).

 

-Oculomotor dysfunction - Nystagmus, lateral rectus palsy, and conjugate gaze palsies reflect lesions of the oculomotor, abducens, and vestibular nuclei. Nystagmus is the most common finding and is typically evoked by horizontal gaze to both sides. My patient had horizontal nystagmus that was evident when she looked both to the right and to the left.

 

-Gait ataxia - When the WE is severe, walking is impossible. Less affected patients walk with a wide-based gait and slow, short-spaced steps. The portion of the cerebellum often affected is the vermis so you will see more truncal ataxia and less ataxia of the arms and the legs.

 

Treatment

 

Immediate parenteral administration of thiamine is the course of treatment in any patient that has suspected WE. A recommended regimen is 500 mg of thiamine intravenously, infused over 30 minutes, three times daily for two consecutive days and 500 mg intravenously or intramuscularly once daily for an additional five days, in combination with other B vitamins. Daily oral administration of 100 mg of thiamine should be continued after the completion of parenteral treatment and after discharge from the hospital until patients are no longer considered at risk. My patient has finished her IV thiamine and is now on 100mg PO daily. She will continue this regimen as an outpatient. 

Multiple sclerosis

Multiple sclerosis is the most common autoimmune inflammatory demyelinating disease of the central nervous system. It tends to affect women of the Northern European descent in their 20-40s. The pathologic feature of MS is multifocal areas of demyelination with loss of oligodendrocytes and astroglial scarring as well as axonal injury.

Diagnosis - MS is a clinical diagnosis. The typical patient is a young adult with either focal or multifocal neurologic deficit that often follow a relapsing remitting pattern. There are no distinct symptoms that are only seen with MS but there are classic clinical findings listed below.

Optic neuritis - is the most common type of involvement of the visual pathways. It usually presents as acute or subacute unilateral eye pain that is accentuated by movement of the eye. This is followed by a variable degree of visual loss affecting mainly central vision. Physical examination of patients with Optic Neuritis reveals a relative afferent pupillary defect (Marcus Gunn pupil). Desaturation of color (particularily red) is a common finding as well.

Internuclear ophthalmoplegia -  Internuclear ophthalmoplegia refers to abnormal horizontal ocular movements with lost or delayed adduction and horizontal nystagmus of the abducting eye. It is caused by a lesion of the medial longitudinal fasciculus on the side of diminished adduction. Convergence is preserved.

Sensory symptoms - Sensory symptoms are a common in MS. Symptoms are commonly described as numbness, tingling, pins-and-needles, tightness, coldness, or swelling of the limbs or trunk. Radicular pains also can be present, particularly in the low thoracic and abdominal regions. An intensely itching sensation, especially in the cervical dermatomes and usually unilateral, is suggestive of MS.

Lehermitte Phenomenon - Described as transient sensory/pain symptom that can be described as radiating down the spine or into the limbs with flexion of the neck and is commonly seen in MS

Vertigo - Vertigo is a reported symptom in 30 to 50 percent of patients with MS.

Motor symptoms - Paraparesis or paraplegia is more common than significant upper extremity weakness in patients with MS due to the lesions in the descending motor tracts of the spinal cord. Severe spasticity can occur when attempts to move the extremities occurs such as getting out of bed or a chair.

Coordination - Gait imbalance, difficulty in performing coordinated actions with the arms, and slurred speech may occur as a result of impairment of cerebellar pathways. Physical examination typically reveals dysmetria, decomposition of complex movements, and hypotonia, most often observed in the upper extremities. An intention tremor may be noted in the limbs and in the head. Walking is impaired by truncal ataxia.

Bowel/bladder/sexual function - Bowel, bladder, and sexual dysfunction are common in MS. The extent of sphincter and sexual dysfunction often parallels the degree of motor impairment in the lower extremities. The most common urinary complaint is urgency. Urinary incontinence becomes more common as the disease progresses, and an atonic dilated bladder that empties by overflow can be the end result.

Fatigue - Fatigue is a characteristic finding in MS, usually described as physical exhaustion that is unrelated to the amount of activity performed. Many patients complain of feeling exhausted on waking, even if they have slept soundly. Fatigue can also occur during the day but may be partially or completely relieved by rest. In addition, there appears to be a correlation between fatigue and disrupted sleep in MS patients.

Depression - depression is the most affective disturbance in MS. Depression may be more common in patients with MS than in others with chronic medical conditions. It is not known whether depression in MS patients reflects a comorbid association with bipolar illness or an effect of frontal or subcortical white matter disease.

Epilepsy - Epilepsy is more common in patients with MS than in the general population, occurring in 2 to 3 percent of patients. Convulsions may be either tonic-clonic in nature or partial complex.


McDonald criteria - The McDonald criteria can only be applied after careful clinical evaluation of the patient. The core requirement of the diagnosis is the objective demonstration of dissemination of central nervous system (CNS) lesions in both space and time, based upon either clinical findings alone or a combination of clinical and MRI findings.

• Dissemination in space - demonstrated on MRI by one or more T2 lesions in at least two of four MS-typical regions of the CNS (periventricular, juxtacortical, infratentorial, or spinal cord) or by the development of a further clinical attack implicating a different central nervous system site. For patients with brainstem or spinal cord syndromes, symptomatic MRI lesions are excluded from the criteria and do not contribute to lesion count.

• Dissemination in time - demonstrated on MRI by the simultaneous presence of gadolinium-enhancing and nonenhancing lesions at any time, or a new T2 and/or gadolinium-enhancing lesion on follow-up MRI, irrespective of its timing with reference to a baseline scan, or by the development of a second clinical attack.

Lesion characteristics - The characteristic lesion demonstrated on MRI is the cerebral or spinal plaque. Histological examination of active plaques reveals perivascular infiltration of lymphocytes and macrophages.

Cerebrospinal fluid analysis -  Qualitative assessment of cerebrospinal fluid for oligoclonal IgG bands using electrophoresis is an important diagnostic CSF study when determining a diagnosis of MS. The immunoglobulin increase is predominantly IgG.

Treatment - A number of medications are available as disease modifying therapy which includes interferon beta drugs, glatiramer acetate, fingolimod, teriflunomide, mitoxantrone. Natalizumab  is approved as monotherapy only.

Imaging in stroke setting

CT without contrast- the large benefit of ordering this test is that it is very fast at determining if there was any intracranial hemorrhage which is important because the management of a stroke secondary to intracranial hemorrhage is very different than the management of an ischemic stroke. CT angiography and CT perfusion study has been added to the work up of stroke and has been shown to improve the detection of an acute infarction than using CT without contrast alone. In addition, the CTA and CTP may indicate the status of the vasculature and may show an occlusion in the vessel.

CT angiography — CT angiography (CTA) is performed by administering a bolus of standard intravenous CT contrast. The helical CT scan is timed to capture the arrival of dye into the brain. For the detection of intracranial large vessel stenosis and occlusion, CTA in various studies had sensitivities of 92 to 100 percent and specificities of 82 to 100 percent when compared with conventional angiography.

MRI - Has the advantage for further categorizing the stroke patients that may benefit from TPA and intravascular treatments. Studies that combines conventional MRI with diffusion-weighted imaging (DWI), perfusion-weighted imaging (PWI) can reliably diagnose both acute ischemic stroke and acute hemorrhagic stroke in emergency settings

Diffusion-weighted imaging (DWI)— DWI is based upon the capacity of fast MRI to detect a signal related to the movement of water molecules and  can detect abnormalities due to ischemia within 3 to 30 minutes of onset. In acute stroke, swelling of the ischemic brain parenchymal cells follows failure of the energy-dependent Na+/K + – ATPase pumps and is believed to increase the ratio of intracellular to extracellular volume fractions which will cause the DWI to detect abnomalities.

Perfusion Weighted Image - Diffusion-weighted imaging reveals evidence of ischemic injury, not ischemia itself which PWI will aid in. Perfusion-weighted imaging (PWI) uses fast MRI techniques to quantify the amount of MR contrast agent reaching the brain tissue after a fast intravenous bolus. Integration of the amount of gadolinium entering the brain on first pass allows construction of maps of cerebral blood volume as well as the transit time that it takes for the dye to reach and wash out of the tissue.

MR Angiogram - MR angiography (MRA) to detect vascular stenosis or occlusion is done at many centers as part of a fast MRI protocol for acute ischemic stroke. Results from a case series showed that the combined use of DWI with MRA within 24 hours of hospitalization substantially improved the early diagnostic accuracy of ischemic stroke subtypes. Most of my patients on the stroke service will get a MRA of the head and neck.

Peripheral Neuropathy

Definition - A disease process affecting many peripheral nerves (nerves outside the CNS), with the distal nerves affected most prominently. The clinical presentation is typically characterized by symmetric distal sensory loss, burning, or weakness.

Etiology - The peripheral nerves are susceptible to a variety of toxic, inflammatory, hereditary, infectious, and parainfectious factors that can impair their function, leading to polyneuropathy. 

• Diabetic - Poor glycemic control leads to the accumulation of advanced glycosolation products which, simply, produce an inflammatory state and can cause damage to blood vessels, organs nerves (peripheral nerve in the case of diabetic peripheral neuropathy)
• Uremia
• Long-standing HIV infection
• Amyloidosis 
• Vitamin deficiency such as B12 and folate 
• Long-standing hypothyroidism
• Lyme Disease
• Guillian-Barre Syndrome -  an acute neuropathy, usually provoked by a preceding infection. The preceding infection causes autoantibodies to form and are directed towards the myelin sheath or axon of the peripheral nerves causing inflammation and damage. 
• Toxic exposure - history of chemotherapy, alcoholism or heavy toxic metals
• Hereditary - Charcot-Marie-Tooth is an X linked genetic disorder causing demyelination of the peripheral nerves. Other genetic diseases include metabolic diseases of childhood, such as Krabbe's disease, metachromatic leukodystrophy, and adrenoleukodystrophy
• Environmental - prolonged cold exposure and hypoxemia
• Idiopathic

History of Illness

• Chronic Polyneuropathies are slow in progression. Injury tends to be related to axon length. The longer axons are affected first, resulting in symptoms that begin in the lower extremities. Sensory symptoms usually precede motor symptoms. Patients will present with progressive sensory loss and complain of  numbness, a burning sensation and pain in the feet. As the syndrome progresses, the motor function begins to be affected and the patient will complain of mild weakness of the lower legs and hand.
• Acute Polyneuropathies - usually secondary to toxic exposures such as metals and pophyrias. The predominant symptom is pain over numbness and tingling and the symptoms are more fulminant and rapidly progressive 2-3 weeks often followed by a period of recovery follows in a few months. 

Physical Examination

Motor and sensory deficits will predominate depending on if the neuropathy is secondary to axonal damage or demyelination. In patients with axonal neuropathy, there may be intrinsic muscle wasting of the hands and feet as well as decreased sensation to light touch, pinprick, vibration and proprioception. In the case of neuropathy secondary to demyelination, generalized weakness is the more common physical exam finding and the distal muscles are more commonly affected. 

Diagnosis

EMG or nerve conduction studies are a good first diagnostic test in patients where there is not a clear etiology. Lab tests such as A1C, thyroid and B12/Folate are useful. Nerve biopsy is reserved for patients in the situation where it is difficult to diagnose whether the disease is demyelinating versus axonal. 

Seizure

This is a very large topic and an important one! I am currently on the stroke service right now but will be starting the general neurology service in one week so I wanted to attempt to get a solid foundation of seizures before jumping in.

Definition - A seizure is a sudden change in behavior that is the consequence of brain dysfunction. Seizures can be divided into different categories…

-Epileptic Seizures - result from electrical hyper synchronization of neurons in the cerebral cortex. There are different classes of epileptic seizures and are named according to how they present such as simple partial (consciousness not impaired), complex partial (consciousness impaired) and generalized (involving the entire cortex). Epilepsy the disease is characterized by recurrent epileptic seizures due to a genetically determined or acquired brain disorder. Approximately 0.5 to 1 percent of the population has epilepsy.

-Provoked seizures - some seizures are provoked and occur secondary to alcohol or drug withdrawl, metabolic derangements, strokes or encephalitis. These patients are not considered to have epilepsy because the seizure would not occur in the absence of any of the above situations.

-Nonepileptic seizures - sudden changes in behavior that appear to be epileptic in nature (epileptic imitators) but are not associated with the same neurophysiologic changes seen in epilepsy

After looking at the groupings of seizures, one can see that a primary goal when assessing the cause of the patient’s seizure, is to understand whether it occurred secondary to a treatable systemic process (provoked) or if this is secondary to a true dysfunction of the neuronal network (epilepsy). If it is due to a dysfunction of the CNS, the nest step would be to figure out the underlying brain pathology. These are all important steps when decided the treatment plan.

Etiologies

Epilepsy

-Head trauma

-Brain tumors

-intracranial infection

-cerebral degeneration

-stroke

-congenital malformation

-inborn errors of metabolism

Nonepileptic seizures (imitators or epileptic seizures) – etiologies divided into age groups

Neonates – apnea, jitterinus, hyperplexia and benign neonatal sleep myoclonus

Infants – breath holding spells, benign myoclonus of infancy, shuddering attacks, torticollis and rhythmic movement disorder.

Children - Breath-holding spells, Vasovagal syncope, Migraine, Benign paroxysmal vertigo, Staring spells, Tic disorders and stereotypies, Rhythmic movement disorder, Parasomnias

Adolesence - Vasovagal syncope, Narcolepsy, Periodic limb movements of sleep, Sleep starts, Paroxysmal dyskinesia, Tic disorders, Hemifacial spasm, Stiff person syndrome, Migraine, Psychogenic nonepileptic pseudoseizures, Hallucinations

Adults - Cardiogenic syncope, Transient ischemic attack, Drop attacks, Transient global amnesia, Delirium or toxic-metabolic encephalopathy, Rapid eye movement sleep disorder

Clinical Features

As always, a good history and physical is important to formulate a diagnosis. Questions to ask…

Triggers?  Strong emotions, intense exercise, loud music or flashing lights? Interestingly, in 1997 the cartoon Pokemon caused in Japan 685 children out of 7 million viewers to seek medical attention for neurological symptoms and about 80% of the cases were diagnosed as seizures. Three fourths of the cases included first time seizure activity. The stimuli that caused these photic-induced seizures appear to be identifiable because the British and Japanese government have guidelines restricting the use of certain signals on television.

Auras? An aura (sound, light, smell and sensation distortion) is something that occurs when enough of the brain has been affected to cause it but not affected enough to cause loss of consioucness. Auras fall under the category of simple-partial seizures.

Loss of Consciousness? Loss of consciousness occurs in complex partial seizures and generalized seizures. Complex partial seizures are the most common type of seizure in epileptic adults. Patients often appear to be awake but are not consciousness. They often seem to stare into space and either remain motionless or engage in repetitive behaviors, called automatisms, such as facial grimacing, gesturing, chewing, lip smacking, snapping fingers, repeating words or phrases, walking, running, or undressing. Patients may become hostile or aggressive if physically restrained during complex partial seizures. Generalized seizures involve more than one portion of the brain rather than a focal portion and include absence seizures and generalized tonic-clonic seizures. Absence seizures can cause impaired consicouness along with staring spells. They occur in clusters, are short in duration (usually less than 10 seconds) and can happen multiple times a day. Tonic clonic siezures are the most dramatic type of seizure. They being with an abrupt loss of consciousness often in conjunction with a scream or a shriek. All of the muscles of the arms and legs as well as the chest and back then become stiff which is considered to be the tonic phase. After approximately one minute, the muscles begin to jerk and twitch for an additional one to two minutes. During this clonic phase the tongue can be bitten, and frothy and bloody sputum may be seen coming out of the mouth. The postictal phase begins once the twitching movements end. In the post-ictal state, the patient returns to consciousness and is groggy, confused and may have some residual aphasia or sensory loss.

Other questions to ask…

Medication history?

Family history of neurologic disease?

Drug or alcohol use?

History of head trauma?

History of intracranial infection?

Acute management of seizure

Most seizures do not need medical intervention and remit on their own. If the seizures are lasting 5-10 minutes or are occurring in close enough proximity and prevent the patient from returning to interictal baseline, then benzos or anti-epileptic drug (AED) is warranted. The first episode of a seizure, especially if it was provoked, is not enough to consider starting an AED. After the second seizure, AED is usually started. 

All of this research came from UptoDate

Toxic-Metabolic Encephalopathy

Acute toxic-metabolic encephalopathy (TME) is an acute condition of global cerebral dysfunction in the absence of primary structural brain disease.  There are many canuses of TME, however, it is usually secondary to a systemic illness. Most TME is reversible, making prompt recognition and treatment important because there are specific metabolic encephalopathies, such as thiamine deficiency (Wernicke's encephalopathy), that may result in permanent structural brain damage if untreated. Alcohol withdrawal syndromes must be excluded in patients with suspected TME

 

Pathology - All the etiologies of acute toxic-metabolic encephalopathy (TME) interfere in some way with the function of the ascending reticular activating system and/or its projections to the cerebral cortex which then causes a problem with the patient's consciousness/awareness. The pathophysiology behind the TME differs depending on the underlying etiology such as...

 

- Cerebral edema occurs in the setting of acute fulminant hepatic encephalopathy and hypoossmolar encephalopathies.

 

- Disruption of the balance of neurotransmitters (dopamine, serotonin, GABA and acetylcholine) can cause drug-induced delirium.

 

-Neuronal death can occur from nutritional disorders which can impair normal cellular metabolism

 

-Exogenous toxins such as CO and CN can lead to impairment of mitochrondrial function and decrease delivery of O2 to the brain.

 

-Increased blood-brain barrier permeability may lead to an increase in systemic toxins leading to impariement in neuronal function. Patients who have increased permeability in the BBB may have a larger amount of protein in the CSF fluid.

 

Clinical Manifestations - The manifestations are varied and generalized depending on the etiology. The symptoms can be broken down into categories.

 

-Mental status - impaired attention and fluctuation in attention, disturbed sleep-wake cycle, decreased alertness, hypervigilance, hallucinations, sensory misperceptions, impaired memory,apathy, mania and disorientation

 

-Seizures - usually are generalized clonic-tonic but can also be focal, multifocal or partial complex

 

-Cranial nerve examination - Almost all the causes of TME will leave the patient with intact pupillary function except in the cases of anticholinergic or glutethimide ingestion. Other brainstem reflexes such as gag, oculocephalic or corneal reflex typically remain intact and are only affected in severe TME

 

-Motor examination - a variety of motor abnormalities can be see in TME such as tremor, as

terixis, multifocal myoclonus, primitive reflexes, brinsk deep tendon reflexes and extensor plantar reflexes.

 

-Autonomic instability such as tachycardia, hypertension, fever, diaphoresis is characteristic in delirium

Specific Etiologies

-Septic Encephalopathy - This is THE MOST COMMON CAUSE of acute TME

 

-Hepatic encephalopathy - normal ammonia levels does not exclude the diagnosis

 

-Uremic encephalopathy

 

-Hyponatremia - Hypernatremia

 

-Hypoglycemia

 

-Hyperosmolar hyperglycemia and diabetic ketoacidosis

 

-Wernicke's Encephalopathy - secondary to a thiamine deficiency and may see the classic triad of confusion, ataxia and opthalmoplegia

 

-Hypoxic-ischemic encephalopathy - Hypoxic-ischemic encephalopathy is usually a straightforward diagnosis that follows an obvious precipitating event such as cardiac arrest with prolonged resuscitation efforts

 

-Post-transplantation encephalopathy - Encephalopathy following transplantation may be due to underlying conditions, operative procedures, immunosuppressive medications, cranial radiation, or opportunistic infections

 

Medications - Most immunosuppressant medications used following transplantation are capable of producing encephalopathy: Cyclosporin, steroids, tacrolimus.

 

Diagnsosis - TME is a diagnosiss of exclusion. Tests that would be helpful would be...

 

Laboratory studies - complete blood count, coagulation studies, electrolyte panel, and examination of calcium, magnesium, phosphate, glucose, blood urea nitrogen, creatinine, bilirubin, liver enzymes, ammonia, serum osmolality, and arterial blood gases, toxicologic screening should be performed for suspected intoxications, and blood and CSF cultures obtained if infection appears present. Thyroid function tests, vitamin B12 and serum cortisol concentrations should be assessed if endocrinopathy is in the differential diagonosis.  

 

Neuroimaging - CT or MRI of the head is indicated when focal signs are present on physical examination or when subdural hematoma is suggested by the history.

 

Electroencephalography — The electroencephalogram (EEG) can both confirm global cerebral dysfunction and exclude subclinical seizures with greater sensitivity than clinical examination alone

 

Treatment - the best treatment is to treat the underlying cause of the TME. A thourough check of the medication list would be helpful. Give thiamine for patient's suspicious of wernickes encephalopathy as well as patients on hemodialysis, malnutrition, cancer and hyperemesis gravidarum. Can give haloperidol for agitation but avoid halopaeridol in cases of alcohol withdrawal, anticholinergic toxicity, and benzodiazepine withdrawal, and also in patients with parkinsonism

Cerebral Amyloid Angiopathy

In the Neuro ICU, cerebral amyloid angiopathy (CAA) gets blamed a lot in elderly patients as a cause of their hemorrhagic stroke. Although I am familiar with the disease, I thought I should revisit it.

 CAA is characterized by amyloid beta peptide deposits in the blood vessels of the brain. The deposits weaken the blood vessel wall and makes it prone to bleeding.  It can occur as a sporadic disorder, in association with Alzheimer’s disease or as a familial syndrome. CAA can cause intracerebral hemorrhage, transient neurological symptoms, hemosiderosis, incidental microhemorrhages or cognitive impairment.

 Epidemiology – the incidence is largely age dependent and is uncommon at ages younger than 60-65.


Pathogenesis – The vascular deposits in CAA consist of an amyloid beta-peptide. There has been an APP mutation identified which has been shown to cause AD CAA. Other side effects of the mutated APP is producing an amyloid protein that is unable to be degraded by proteasomes or producing an amyloid protein that has more of a toxic effect on the vascular wall. There is growing evidence from studies that support a link between CAA and the alleles of the Apolipoprotein E gene. Patients who carry the APO epsilon 2 or epsilon 4 allele correlate with a higher risk for CAA. Other factors likely contributing to CAA include pt’s who over express cytokines such as TGF.


Presenting Features – The most common presenting feature of CAA is spontaneous lobar hemorrhage which is located in the cortex and subcortical white matter and sparing of the areas that are affected more by hypertensive hemorrhages such (basal ganglia, thalamus or the pons).  Spontaneous hemorrhage secondary to CAA is more likely to happen in the posterior portion of the brain. A reason for this particular deposition of the amyloid proteins in the posterior circulation is unknown, but may be due to an undiscovered characteristic of the posterior circulation that would decrease the elimination of the beta amyloid deposits. Other clinical manifestations include seizure, headache, hemiplegia and depressed consciousness. Patients may also complain of transient symptoms such  as a recurrent, brief (about 10 minutes) episodes of weakness, numbness or paresthesias.


Diagnostic criteria – CAA should be suspected in patients over the age of 60 who have multiple lobar hemorrhages in the absence of an obvious cause. The true diagnosis can only be definitive with a post-mortem autopsy but there are two approaches to give a probable diagnosis during life such as a gradient-echo MRI and an examination of the tissue (brain biopsy which is rarely done). A gradient-echo MRI will accentuate the signal dropout caused specifically by iron-containing deposits left by old hemorrhages.


Treatment – similar to the treatment of other acute intracerebral hemorrhages by paying attention to the ICP and controlling the blood pressure and surgical hematoma resection.  After diagnosis, patients are to avoid anticoagulation medication such as Warfarin and Aspirin.


Other bits I learned today…

 -Primary Lateral Sclerosis (PLS) is similar to ALS but only involves the upper motor neuron and survival is better than ALS

 - A Jannetta procedure is something that can be done for trigeminal neuralgia. It involves a craniotomy and the removal or separation of various vascular structures, often an ectatic superior cerebellar artery, away from the trigeminal nerve.