Neurosyphilis (in non-HIV patient)

This morning we discussed a case of rapidly progressive dementia, likely secondary to neurosyphilis.

Neurosyphilis can occur early or late. It may occur with primary, secondary, or tertiary syphilis. Early neurophysilis can present as stroke, meningitis, meningoencephalitis, cranial nerve deficits, hearing loss (otosyphilis), or visual loss (oculosyphilis). Late neurosyphilis occur decades later and can presents as general paresis, dementia with psychosis (rapidly progressive), or tabes dorsalis (posterior column involvement, bowel, bladder dysfunction).

Syphilis Screen:
CMIA-Chemiluminescent Microparticle Immunoassay (serum)- T.pallidum (IgG/IgM)
VDRL-Venereal Disease Research Laboratory-no longer done at UHN labs.
RPR - Rapid Plasma Reagin Test. Detects total IgG/IgM antibody to syphilis (T. pallidum). Automatically done by lab if CMIA is reactive.

CMIA and PRP are called “syphilis screen” in EPR

Confirmatory Tests:
TP.PA- Treponema pallidum particle agglutination.
FTA.ABS- fluorescent treponemal antibody. Positive confirmatory test(s) are often reactive for life

CSF examination (not done at UHN lab, sent to PHL):
• CSF VDRL is specific but not sensitive
• CSF FTA-ABS is sensitive but not specific

Here is a review of syphilis.

Click here for the Ontario Public Health Lab algorithm for interpreting the MANY permutations and combinations of lab results

* A U.S. Army Educational Commission Poster about Neurosypilis, 1918.

Epidural Abcess

This morning we discussed a case of fever with back pain and our differential included epidural abscess.

If you're thinking about an epidural abscess, you need to image the spine. MRI is the best modality as it is sensitive to pick early signs of inflammation. CT with IV contrast is an acceptable alternative if MRI is not available. Plain X-ray may show changes of advanced osteomyelitis or discitis but is not used to diagnose an epidural abscess.

Here is a previous post and a reference on Epidural Abscesses.

Once in a while my heart flutters really fast...

This morning we discussed a case of CHF decompensation secondary to atrial flutter with rapid ventricular response.

Atrial flutter is an arrhythmia of organized atrial activity that is not a sinus rhythm. It can be seen its own or sometime as a transition arrhythmia between sinus rhythm and atrial fibrillation.

Any disorders predisposing to atrial fibrillation can cause atrial flutter including thyrotoxicosis, obesity, the sick sinus syndrome, pericarditis, pulmonary disease, and pulmonary embolism. Mitral valve prolapse and cardiac surgery are also risk factors for developing atrial flutter.

Atrial flutter is very similar to atrial fibrillation its clinical presentation and should be treated the same in terms of rate control and anticoagulation. Ablations therapy is very successful for atrial flutter, however, so long-term antiarrhythmic medications are infrequently used.

Here is review on managment of Atrial Flutter.

* the hallmark of atrial flutter on ECG is the saw-tooth pattern (also referred as a picket fence pattern).

Light's Criteria for Pleural Effusion

Today at morning report we discussed the Light's Criteria.

Light's criteria for exudative effusion are any of
protein level pleural:serum over 0.5
LDH pleural:serum of over 0.6
pleural LDH over 2/3 upper limit of normal for serum

The combination of the three criteria has a higher sensitivity, but a lower specificity, than each individual criterion. Light's criteria are sensitive for exudate; may have transudates falsely called exudates. If clinical appearance suggests transudate but Light's criteria says exudate, measure albumin in serum vs. pleural fluid. If serum albumin is over 12 greater than pleural fluid almost all have transudative.

Our case had a bloody effusion, which narrows Ddx somewhat to cancer, PE, trauma, infection (inc. pneumonia, TB)

Here is a review of Pleural Effusion by Dr. Light himself!

*A large left sided pleural effusion as seen on an upright chest X-ray.

Ascites

At Gel Rounds we discussed ascites.

Some key points:

Most sensitive findings (i.e. make it unlikely if not present):
1) flank dullness
2) bulging flanks
3) shifting dullness
4) peripheral edema
-history of increased girth, weight gain, ankle swelling

Most specific findings (i.e. make it likely if present)
1) fluid wave
2) shifting dullness

An approach to the examination in liver disease (besides examining the liver itself)

1) Signs of decompensated liver disease
-jaundice, scleral icterus, dark urine (high bilirubin)
-petechiae, ecchymoses (coagulopathy)
-edema (hypoalbuminemia)
-asterixis, level of consciousness (encephalopathy)

2) Signs of portal hypertension
-ascites
-splenomegaly
-dilated abdominal veins (extreme of this is caput medusae)
-hemorrhoids

Reference:

Click here for JAMA rational clinical exam on ascites.

* using the ultrasound, we looked at the Pouch of Morrison, which is a potential space between the liver and the right kidney. This is the first spot to check if you suspect a small amount of ascites. The picture shows Morison's pouch with fluid present (red arrows).

Pericarditis

At physical exam rounds today, we reviewed Pericarditis.

Clinical presentation: usually a sudden onset of retrosternal chest pain with a pleuritic component to it, often relieved by sitting up. You may hear a pericardial rub - this is classically described as a triphasic high-pitched sound. The 'tri' refers to 1. atrial systole, 2. ventricular systole, and 3. ventricular diastole.

ECG: may show diffuse, concave ST elevations that do not fit any particular vascular territory. PR depression is also seen.

Treatment: In most cases of idiopathic pericarditis, high dose NSAIDS are effective. Steroids and colchicine also may have a role.


Here is a review article on the topic.

Rhabdomolysis

This morning we discussed a case of rhabdomyolysis.

Here is a previous blog post on the topic.

*myoglobinuria

Miller Fisher Syndrome

Guillain-Barré syndrome (GBS) is an immune-mediated polyneuropathy characterized classically by ascending weakness and absent reflexes. GBS is a heterogeneous disease with several variants. Miller Fisher Syndrome (MFS) is a variant that presents with opthalmoplegia, ataxia and areflexia.

In patients with GBS, CSF has elevated protein and normal WBC. In about 85% of patients with MFS antibodies against GQ1b (a ganglioside component of nerve) is positive, though this testing is not routinely performed.

Here is review of Guillain-Barre Syndrome.

* Dr. C. Miller Fisher, Canadian neurologist who first described the MFS variant of GBS in 1956. He was a stroke neurologist who contributed greatly to our understanding of lacunar stroke, and strokes related to atrial fibrillation.

SSRI and SIADH

This morning we talked about the association between SSRIs and SIADH.

The article we talked about was a review, by Dr. Liu, of case reports involving various SSRIs and hyponatremia. This study found that the majority (83%) of patients with this complication were over the age of 65. The average time to onset of hyponatremia was 13 days (range 3 to 120 days). This finding has since been confirmed through a prospective study.

Take home message is that elderly patients are at increased risk of hyponatremia associated with SSRIs.

Here is the abstract for the above article.

Here is a great review article about SAIDH.

Mitral Regurgitation

In physical exam rounds yesterday, we examined a patient with mitral regurgitations.
Here is a previous post on Mitral Regurgitation.

*Doppler ultrasound of the heart showing mitral regurgitation: there is abnormal leakage of blood backward (blue is flow away from the probe) through the mitral valve during systole.

Antimitochondrial antibody

Antimitochondrial antibody is present in 95% patients with Primary Billiary Cirrhosis. The antibody assay is 95% sensitive and 98% specific for PBC (except if it's done by indirect immunoflorescence).

There has been suggestion that the presence of antimitochondrial antibodies may predict the eventual development of PBC in asymptomatic people based on a small study. About 13% of first-degree relatives of patients with PBC have circulating antimitochondrial antibodies, suggesting they may be susceptible to developing PBC. The clinical significance of this finding remains to be determined.

Here is a great review on Primary Billiary Cirrhosis.

*Immunofluorescent stain shows antimitochondrial antibodies on a liver biopsy specimen.

Endocarditis

This morning we discussed a case of subacute bacterial endocarditis secondary to Strep viridans.

Here is a previous post on endocarditis with some great review referrences.

* Viridans Streptococcus is a term for a large group of commensal streptococcal bacteria that are either α-hemolytic, producing a green coloration on blood agar plates (hence the name "viridans", from Latin "vĭrĭdis", green), or nonhemolytic.

Hypertension

This morning we discussed a case of Hypertensive Emergency.

Here is a previous post on this topic.

* William Harvey (1578–1657)the first physician who described the systemic circulation of blood being pumped around the body by the heart in his book "De motu cordis" which became the basis for our current understanding of hypertension.

Hypophosphatemia

Hypophosphatemia is secondary to decreased intestinal absorption (such as in Vit D deficiency), increased urinary excretion (such as in hyperparathyroidism), or shift into the cells (such as in refeeding syndrome).

Symptomatic hypophosphatemia occur when serum phosphate concentration reaches 0.64 mmol/L. Worrisome symptoms of hypophosphatemia are related to ATP depletion, causing metabolic encephalopathy, impaired myocardial contractility, respiratory failure due to weakness of the diaphragm, a proximal myopathy, Rhabdomyolysis, dysphagia, ileus, and hematologic abnormalities.

Hypophosphatemia should be replaced aggressively even if the patient is not overtly symptomatic, since develop myopathy and weakness.

IV phosphate is potentially dangerous, since it can precipitate with calcium causing hypocalcemia, renal failure due to calcium phosphate precipitation in the kidneys, and possibly fatal arrhythmias. So, if IV therapy is necessary in the patient with severe symptomatic hypophosphatemia, it should be given by slow infusions (over a long period of 4-12hrs).

Paraneoplastic Erythrocytosis

There are 5 types of tumor commonly associated with the overproduction Epo:

1. Hepatocellular carcinoma: Epo elevation doesn’t always cause erythropoiesis because of RBC production inhibition by malignancy.

2. Renal cell carcinoma: In about 1-5% of patients.

3. Hemangioblastoma

4. Pheochromocytoma

5. Uterine myomata: clue will be absence of anemia in patients with menorrhagia. RBC overproduction is reversed following myomectomy.

*Contrast-enhanced MRI image of a patient with Hb=194, showing renal cell carcinoma(arrow).

HIV and Pneumococcal Disease

Although we automatically think about opportunistic and atypical infections in immunocompromised patients, it is important to note that , similar to non-HIV infected patients, Streptococcus pneumoniae, is the most common bacterial pathogens of CAP in patients with HIV.

As was discussed this morning, HIV infection substantially increases the risk of invasive pneumococcal infection, particularly among those patients with a low CD4 count <200, and those not on therapy. This increased risk may be partially explained by the observation that HIV infected individuals have a predisposition for pneumococcal nasopharyngeal colonization.

For this reason, the Centers for Disease Control and Prevention (CDC) recommends that all HIV–infected patients be vaccinated (preferably early in the disease while they still have the ability to mount an effective antibody response).

Here is a review on the topic.

Invasive pneumococcal disease in patients infected with HIV: still a threat in the era of highly active antiretroviral therapy. Jordano et al. Clin Infect Dis.38(11):1623.

* Chest radiograph of an HIV positive individual with a CD4 cell count above 200 cells/mm3, revealing right upper lobe consolidation. Sputum and blood cultures were positive for Streptococcus pneumoniae.

Hypercalcemia associated with Malignancy

We discussed a case of hypercalcemia this morning and reviewed the mechanisms by which malignancy can cause hypercalcemia.

1. Direct metastases to bone: These mets trigger the production of inflammatory cytokines and stimulate ostoclasts. Sometimes osteoclasts are directly stimulated by tumor cells via Osteoclast Activating Factors (eg IL6) in multiple myeloma or lymphoma.

2. PTH related peptide: this is the most common cause of hypercalcemia from non-metastatic solid tumors. Classically in squamous cell lung Ca

3. PTH: this is rare! only a few case reports of PTH being released from tumors

4. Calcitriol: a very common mechanism for hypercalcemia in the lymphomas.

Here is a great review article.
*CT scan of a patient presenting with Ca=3.1, who subsequently was found to hav have small cell lung cancer.

This morning we talked about a variety of different cases. One of them, involved a patient with a presentation of swollen warm painful knee. Here is a previous morning repot blog post on approach to monoarthritis.

*The Gout by James Gillray. Published May 14th 1799.

Hormone Replacement Therapy

This morning we briefly talked about the Women’s Health Initiative (WHI)and hormone replacement therapy. WHI was a set clinical trials including two hormone trials in healthy postmenopausal woman 50-70. The hormone trials were stopped early due to increased risk of cardiac events, VTE, stroke and breast cancer. The study did show benefits in reducing fracture and colorectal cancer risk.

Subsequent analysis of the WHI noted that the increased risk of CHD tended to depend on the timing of exposure, with no excess risk observed in younger menopausal women.

Current recommendations are as follows:

Moderate to severe menopausal symptoms can be treated with short term HRT in peri- or postmenopausal women (and no contraindications to estrogen). HRT should be stopped before five years. HRT should not be used as primary or secondary prevention of CAD.


Here is Endocrine Society’s statement on HRT.

Lets SIGN OUT? at TWH!

Handing over. We do it often. And the information we transfer is critical to patient safety. This morning we talked about SIGN OUT? as a template for our signovers.

S: Is the patient sick? Code status!!!
I: Identifying data
G: General hospital course
N: New events
O: Overall health status right now
U: Upcoming possibilities (if and then statements)
T: Tasks to complete overnight
?: Questions

Every team will function differenly, but sticking to consisten hand over template an style keeps communication flowing, and patients safe.

* it's 5pm...have you Singed Out yet?!

VTE and Malignancy

The questions of screening for an occult malignancy comes up often when a patient presents with unprovoked VTE. There are multiple observational studies that have confirmed the increased incidence of malignancy among those with VTE, however, none has shown improved survival with aggressive diagnostic testing. None of these studies are prospective.

As a result, the current recommendations is that all patients with idiopathic DVT should be evaluated with careful history. A past history of cancer should be a red flag. Other symptoms such as loss of appetite, weight loss, fatigue, pain, hematochezia, hemoptysis, and hematuria should also raise suspicion about cancer.

A complete physical examination (including digital rectal examination and testing for fecal occult blood, pelvic examination in women), and routine laboratory testing (complete blood count, chemistry panel including electrolytes, calcium, creatinine, and liver function tests), urinalysis and CXR should also be performed. Furthermore, age-appropriate cancer screening (PSA, FOB and C-scope, mammogram) should be offered.

Any abnormality observed on initial testing should then be investigated aggressively.

HCV-associated Cryoglobulinemia

Cryoglobulins are immunoglobulins that precipitate in cold and dissolve with warming.

HCV infections is associated with Type II or essential mixed cryoglobulinemia (polyclonal IgG and a monoclonal IgM rheumatoid factor directed against the IgG) and Type III or mixed cryoglobulin (polyclonal IgG and rheumatoid factor IgM).

Deposition of antigen-antibody complexes in small and medium-sized arteries leads to the clinical findings of cyroglobulinemia. It is unclear, however, why cryoglobulins are produced and which antigen triggers this process. HCV RNA itself may serve as the inciting agent.

Clinical features include palpable purpura, nonspecific systemic symptoms, arthralgias, lymphadenopathy, hepatosplenomegaly, peripheral neuropathy, and hypocomplementemia (low C4).

Here is a review on the topic.

*image is papable purpura (non-blanching erythematosus papules) found in a patient with chronic HCV infection with mixed cryoglobulinemia.

"Did the green onion make me yellow"?

Hep A is an RNA virus that spreads by the fecal-oral route. HAV is more prevalent in low socioeconomic areas with lack of adequate sanitation and poor hygienic practices. International travel is the most common risk factor in USA (and Canada).

HAV infection usually results in an acute, self-limited illness and only rarely leads to fulminant hepatic failure in those with underlying liver disease, especially chronic hepatits C infection.

The manifestations also vary with age: HAV is usually silent or subclinical in children. In contrast, infection in adults can vary in severity from a mild flu-like illness to fulminant hepatitis. The incubation period averages 30 days (range 15 to 49 days). Symptoms include fatigue, malaise, nausea, vomiting, anorexia, fever, and right upper quadrant pain followed by dark urine, light stools, jaundice, and pruritus. Lab investigations show marked elevations of serum aminotransferases (usually >1000 IU/dL), bilirubin, and alkaline phosphatase.

Acute HAV infection is diagnosed by the detection IgM anti-HAV in serum.

The treatment is supportive care.

* image: the most widespread hepatitis A outbreak in USA affected 640 people (killing 4) ,in late 2003, was blamed on tainted green onions at a restaurant.

Statin-induced muscle injury

Muscle injury with statin therapy can range from myalgias to myositis to rhabdomyolysis. Muscle symptoms usually begin within weeks to months after starting statins and usually return to normal over days to weeks after drug discontinuation.

You should warn your patients about new onset muscle pain and weakness when you start a statin. A CK level should be obtained at baseline, but routine monitoring of serum CK levels is not recommended.

Patients with acute or chronic renal failure, liver disease, and hypothyroidism are at higher risk of developing muscle injury. Clinical symptoms or a CK level >10X the upper limit of normal should prompt a drug discontinuation.

Pravastatin and fluvastatin appear to have much less intrinsic muscle toxicity than other statins. After the CK has returned to baseline, patients may be tried on a statin less likely to cause muscle toxicity with careful monitoring.

Here is review on the topic.

An assessment of statin safety by muscle experts. Thompson PD, Clarkson PM, Rosenson RS, National Lipid Association Statin Safety Task Force Muscle Safety Expert Panel. Am J Cardiol. 2006;97(8A):69C.

Antibiotics in COPD exacerbation

The use of antibiotics in exacerbations of COPD is based on small placebo-controlled trials and large retrospective population studies. They found that antibiotics improve clinical outcomes in severe COPD exacerbations. There is little evident for the use of antibiotics in mild exacerbation.

A recent cochrane review on the topic concluded that "in COPD exacerbations with increased cough and sputum purulence antibiotics, regardless of choice, reduce the risk of short-term mortality by 77%, decrease the risk of treatment failure by 53% and the risk of sputum purulence by 44%; with a small increase in the risk of diarrhoea These results should be interpreted with caution due to the differences in patient selection, antibiotic choice, small number of included trials and lack of control for interventions that influence outcome, such as use of systemic corticosteroids and ventilatory support. Nevertheless, this review supports antibiotics for patients with COPD exacerbations with increased cough and sputum purulence who are moderately or severely ill".


Choice of antibiotics is an area where not a great deal of evidence exists. Most initial trials were with Amoxicillin, Doxycyclin and Septra. However, these antibiotics are no longer considered first-line for treatment of pathogens such as H.Flu and M. catarrhalis that maybe responsible for COPD exacerbations. When deciding on the antibiotic choice, risk factors such as older age (>65 years), comorbid conditions (especially cardiac disease), severe underlying COPD (defined as FEV1 <50 percent), frequent exacerbations (three or more per year), and antimicrobial therapy within the past three months should be taken into account.

The GOLD guidelines recommend antibiotic therapy for patients with:

1) Severe exacerbation requiring mechanical ventilation
2) With three cardinal symptoms of increased sputum purulence plus either increased dyspnea or increased sputum volume
(thought they don’t provide any guidance regarding the choice of antibiotics)

WITHDRAWN: Antibiotics for exacerbations of chronic obstructive pulmonary disease.
Ram FS, Rodriguez-Roisin R, Granados-Navarrete A, Garcia-Aymerich J, Barnes NC. Cochrane Database Syst Rev. 2011 Jan 19;(1):CD004403.