TIA Management

Today we reviewed the approach to a patient presenting with symptoms suggestive of a Transient Ischemic Attack (TIA).

A TIA is defined as an abrupt focal loss of neurologic function caused by reduction in blood flow that persists less than 24 hours and clears without residual disability.

Diagnosis is made with a thorough history and physical examination, where the latter can be normal in many patients.

The patient's risk for progression to stroke can be assessed by the ABCD score, which helps to guide the clinician on the need for admission:

A: Age - 1-pt if over 60 years old; 0-pt if less than 60

B: Blood Pressure - 1-pt if SBP greater than 140 OR 1-pt if DBP greater than 90

C: Clinical symptoms - 2-pts if unilateral weakness; 1-pt if language disturbance but no weakness; 0-pt for other symptoms

D: Diabetes - 1-pt if patient has diabetes; 0-pt if not

D: Duration - 2-pts if more than 60 min; 1-pt if 10-59 min; 0-pt if less than 10 min

Score 0-3: low risk, 2-day stroke risk 1%

Score 4-5: moderate risk, 2-day stroke risk 4%

Score 6-7: high risk, 2-day stroke risk 8%

Low risk patients don't need to be admitted for stroke work-up; however, they do require expedited investigations which sometimes warrant an admission. Moderate risk patients and High risk patients generally warrant an admission and investigations and monitoring for stroke.

Current Canadian Stroke Guidelines recommend rapid turn around times for investigations in a patient presenting with a TIA. Patients are categorized into Emergent, Urgent, and Semi-urgent; and based on these 3 categories, their stroke work-up is recommended to be performed within the given timeline.

Emergent: investigations within 24-hrs

• Symptoms within the previous 24-hrs with 2 or more high-risk clinical features (ABCD criteria)
• Acute persistent or fluctuating stroke symptoms
• One positive investigation (evidence of acute infarct on CT/MRI; evidence of carotid artery stenosis > 50%)
• Other factors based on individual presentation and clinical judgment

Urgent: investigations within 72-hrs

• TIA within the previous 72-hrs

Semi-urgent: investigations within 30-days

• Does not meet urgent or emergent criteria

Investigations include standard screening blood work, an assessment by a neurologist or stroke specialist, brain CT or MRI, carotid imaging (doppler, CT angio, or MR angio), and ECG.

Management should include initiation of an anti-platelet agent, once confirmation that there is no intracranial hemorrhage. If not already on ASA, start with 160-mg followed by 81-mg daily. If failing ASA treatment, then change to either Clopidogrel (load with 300-mg followed by 75-mg daily) or Aggrenox (1-tab BID).

Those with 70 - 99% blockages in their carotid arteries (matching their TIA symptom pattern)should undergo endarterectomy within 2-weeks.

If Atrial Fibrillation is discovered the patient should be initiated on anti-coagulation therapy immediately after their event, once an intracranial hemorrhage has been ruled out.

All modifiable risk factors should be addressed by way of smoking cessation, blood glucose control (HbA1C less than 7%), lipid management (LDL less than 2), and blood pressure reduction (less than 140/90).

The complete Current Canadian Stroke and TIA guidelines can be found here.

Pulmonary-Renal Syndromes

Yesterday we discussed a case of hemoptysis NYD and today we reviewed an elderly gentleman with acute renal failure who was diagnosed with Goodpasture's syndrome.

Yesterday's differential diagnosis for hemopytsis included vasculitis. In particular one always needs to consider pulmonary-renal syndromes in the differential for hemoptysis, including Wegener's Granulomatosis (WG) and Goodpasture's syndrome.

WG's can present in many ways, but often involves a history or sinusitis or rhinitis, along with constitutional symptoms, hemoptysis, renal failure, and occassionally polyarthralgias. Patients can develop a "saddle nose" due to collapse of their nasal support.

The pathological triad of WG includes:
1) systemic necrotizing angiitis
2) necrotizing granulomatous inflammation of the respiratory tract
3) necrotizing glomerulonephritis

Diagnosing Wegener's requires a detailed history and physical exam as well as blood work, looking for evidence of c-ANCA or anti-PR3, a urinalysis looking for RBC casts, chest imaging, and often a biopsy of either the kidney or lung. Lung biopsies frequently reveal evidence of vasculitis and granulomatous inflammation. Renal biopsies demonstrate a Pauci Immune picture (i.e.: no deposition of immunoglobulin or complement) with segmental crescentic necrotizing glomerulonephritis.

Treatment includes pulsed steroids and often cyclophosphamide urgently as this is a rapidly progressive disease. Involvement of a rheumatologist and nephrologist for management and follow-up is usually warranted.

Goodpasture's disease is a triad of pulmonary hemorrhage, glomerulonephritis (GN), and circulating anti-glomerular basement membrane (anti-GBM) antibodies in the blood. However, not all patients present with the triad, but anti-GBM antibodies is a distinguishing feature of Goodpasture's. Most patients (~60 - 80%) present with both pulmonary and renal disease, 20 -40% have only renal disease, and less than 10% have only pulmonary disease.

Diagnosis, like WG, involves a thorough history and physical exam as well as blood work looking for anti-GBM antibodies, chest imaging, and usually a renal or lung biopsy. Direct immunofluorescence of the renal biopsy will light up and stain along the basement membrane, reflecting the deposition of IgG.

Treatment again, requires rapid aggressive management; however, in the setting of Goodpasture's there is a role for plasmapheresis to remove any circulating anti-GBM antibodies. This occurs in conjunction with immunosuppression with pulsed steroids and often cyclophosphamide. Again, consultation with a nephrologist is often warranted!

Here is a review on the differential diagnosis of hemoptysis and here is a brief case report and review of Goodpasture's from The Lancet.

Lymphadenopathy

Today we discussed the unfortunate case of a 25 year old young man presenting with a multitude of complaints, including 4-weeks of right shoulder pain, 8-months of lower back pain, head ache, RUQ pain, dyspnea, non-productive cough, night sweats, and an "intentional" weight loss of ~30 pounds over 2 months. He had recently returned from South America, where he had spent the past few months.

We generated a broad differential diagnosis for this diffuse constellation of complaints. The 3 main categories we reviewed were:

1) Neoplasm - hematologic vs. solid organ (ie: testicular, given his gender and age)

2) Infectious - TB, liver abscess, amoebic infection, liver fluke, malaria, infectious endocarditis

3) Inflammatory - inflammatory bowel disease, SLE, sarcoidosis

A CT scan revealed multiple lesions within the liver as well as porta hepatis and para-aortic lymphadenopathy. Large volume lymphadenopathy was also seen in the chest, along with some lytic bone lesions. The clinical picture, along with these imaging findings, raise the most likely diagnosis to lymphoma.

Lymphomas are a heterogeneous group of cancers arising from the reticuloendothelial and lymphatic systems, which often present as solid tumors of lymphoid cells. Historically lymphomas have been categorized as Hodgkins Lymphoma (HL) or Non-Hodgkin Lymphoma (NHL), but as we learn more and more about these cancers the classifications are constantly being upgraded. Currently lymphomas are still broadly categorized as HL and NHL, with the latter group being further subclassified based on the type of cell from which they originate: B-cell, T-cell, or Natural Killer cell.

HL results from clonal transformation of cells of B-cell origin, giving rise to the pathognomic Reed-Sternberg cells. The cause is unknown, but genetic susceptibility and environmental associations are thought to play a role. HL is slightly more common in patients with immunosuppression secondary to post-transplant drugs, congenital immunodeficiency, HIV, and autoimmune diseases (SLE, RA, Sjogren's, etc.). Patients often present with painless lymphadenopathy, that can become painful after consumption of alcohol... for no clear reason! Usually the lymphadenopathy arises in one area and spreads in a contiguous manner. The classic "B symptoms" are often described: fever, night sweats, and unintentional weight loss. Diagnosis requires a lymph node core biopsy +/- a fine needle biopsy. Depending on the specific type of HL identify on pathology, and the stage at diagnosis, treatment usually involves chemotherapy +/- radiation therapy, surgery, or stem cell transplant.

NHL is also a disease of clonal transformation, most often of B-cells, but different subtypes of NHL can develop as a result of clonal transformation of T-cells or Natural Killer cells; classification depends on immunophenotyping, genotyping, and cytogenetics. NHL is much more common than HL. Immunosuppressed patients are also at risk for NHL. The exact etiology of NHL is yet to be discovered, but it is hypothesized that a viral cause may be at play. Patients often present again with painless lymphadenopathy; however, in NHL they can often have multiple areas of involvement. Occasionally patients can present with SVC syndrome secondary to compression of the SVC from nodal enlargement, or acute renal failure secondary to obstruction of the ureters from retroperitoneal or pelvic lymph nodes.

Diagnosis requires a lymph node core biopsy for nodal architecture as well as immunophenotyping and cytogenetics for subclassification of the lymphoma. Full imaging with CT of the chest/abdo/pelvis and a BM biopsy is required for staging +/- a PET scan (this image shows lymphoma with increased uptake of 18-FDG in the brain, chest, and spleen). Although not fully validated in clinical settings, PET scans can be used in the proper setting, as determined by the oncologist and the radiologist.

Staging of NHL follows the Cotswold Modified Ann Arbour Staging. Prognosis is generally better for those with B-cell NHL compared to T-cell NHL. The International Prognostic Index (IPI) is used to help guide clinicians and patients with aggressive lymphomas. There are 5 risk factors with the IPI, and outcomes deteriorate as the number of risk factors increases.

1) Age over 60

2) Poor performance status measured by the ECOG (Eastern Cooperative Oncology Group)

3) Elevated LDH

4) More than 1 extranodal site

5) Stage III or IV disease

Patients in the highest IPI risk group (4-5 risk factors) have a 50% survival rate at 5-years, whereas those in the lowest IPI risk group (no risk factors) have a very high cure rate. Modifications to the IPI have been made to account for diffferent NHL, including the FLIPI (follicular lymphoma) and the R-IPI (diffuse large B-cell lymphoma).

Treatment for NHL is again specific to the subtype of lymphoma and the stage at diagnosis; however, it generally incorporates chemotherapy "R-CHOP" (rituximab (anti-CD20 monoclonal antibodies), cyclophosphamide, doxorubicin, vincristine, prednisone), radiation therapy, or both +/- stem cell transplantation.

Here is a great review article on the approach to a patient with lymphadenopathy.

Welcome to the Horses & Zebras of TGH

Welcome to GIM at TGH and this, the official blog of the TGH CMR!

This is my first posting and I will try to update the blog every few days with summaries from morning report, noon rounds, physical exam rounds, etc. as well as links to articles and web sites that provide excellent reviews of the topics at hand. Today's post will be a brief summary of the past week's salient teaching points!

Last week we discussed an interesting case of seizure in a patient with a recent history of malaria, travel, and fever. We reviewed the general breakdown of the most common causes of seizure by age category:

Children:
-febrile seizure, seizure disorder
Adults (~20 - 50):
-trauma, toxic, alcohol withdrawal, metabolic, seizure disorder/idiopathic
-less likely stroke or tumour
Older Adults (>50):
-more likely stroke or tumour
-could still be one of the other causes


Last Friday we discussed a great case of HCV cirrhosis and SBP, spontaneous bacterial peritonitis. Here is a NEJM review article on the management of cirrhosis and ascites. There is also a very helpful video on NEJM demonstrating how to perform a paracentesis found here. And this all links in well with Physical Exam Rounds yesterday, where we examined a patient with ascites. You should all have received the JAMA Rational Clinical Exam paper entitled "Does this patient have ascites?" in your inbox (it is not possible to link to the website!). Key points to remember for physical examination of ascites:
1) Most sensitive findings are ANKLE EDEMA and INCREASED GIRTH
2) Most specific finding is FLUID WAVE


During our Emergency Lecture Series we have had a variety of excellent topics covered, including a review of atrial and ventricular arrhythmias. Here you will find the 2006 ACC/AHA guidelines for patients with Atrial Fibrillation as well as the 2003 guidelines for patients with SVT. Here you will find the ACC Pocket Guide for ventricular arrhythmias. And on that note, here is a link to drugs that can induce Torsades de Pointes.



Today's Morning Report discussed a fascinating case of SOB, muscle weakness, swollen joints, and weight loss. The patient was found to have an elevated CK and a small pericardial efffusion on 2D Echo, but normal inflammatory markers (ESR and CRP). There were no sensory findings and only mild objective muscle weakness on exam.

During our discussion the topic of Constrictive Pericarditis came up and how to make the diagnosis; which requires a right and left heart catheterization to compare pressures across the septum. Constrictive pericarditis is a relatively rare diagnosis that is often caused by tuberculosis or other infections agents such as fungi and parasites. Here is a great article, as mentioned in Morning Report, describing a case of constrictive pericarditis!

For our case, there is no diagnosis as of yet - hopefully Team 5 will keep us all posted! However, as we discussed, our differential for this case includes (but is not limited to):

1. Malignancy with associated Polymyositis/Dermatomyositis
2. Rheumatoid arthritis
3. Inclusion body polymyositis
4. Mixed connective tissue disorder

Dermatomyositis (DM) is less likely given that the patient has no skin manifestations. The classic skin features of DM include:

Gottron's papules: lacy, pink/violaceous, raised or macular lesions, symmetric over the dorsal interphalangeal joints, elbows, and knees
Heliotrope rash: a violaceous discolouration of the eyelids with periorbital edema
Shawl sign/V-sign: erythematous rash over the shoulders/neck (in the pattern of a shawl) OR neck/chest (V-sign)
Periungual telangiectasias: nail changes (cuticular hypertrophy) with or without Raynaud's
Mechanic's hands: coarse, fissured, scaly, hyperkeratotic hands

Thanks to former CMR David Frost for the DM links! For a complete review of DM please see this great review article in American Family Physician and a previous Blog by David Frost.