Diplopia and dysconjugate gaze, ptosis

Today we discussed an approach to ptosis, diplopia and dysconjugate gaze. A few points:

An approach to diplopia: A useful first step is to break down between monocular (i.e. present with 1 eye closed) and binocular (far more common). If binocular, run through the potential causes anatomically from the central to peripheral.

Monocular: Consider ophthalmological causes

Binocular:
If changes through the day, consider myasthenia gravis
If thyroid disease present, consider Graves ophthalmopathy
If facial trauma, consider orbital fracture (most likey to cause inferior oblique palsy because of orbital floor fracture) other orbital diseases (e.g. tumor, infiltration, etc)

Once neurological:
1) Cerebral hemisphheres- gaze palsy/preference from frontal lesion (e.g. stroke), progressive supranuclear palsy (vertical then horizontal palsy with dementia, parkinsonism)
2) Brainstem- III, IV, or VI nuclei, internuclear ophthalmoplegia (can't adduct eye)- ipsilateral median longitudinal fasciculus (MLF)- leaves convergence intact. Brainstem causes include ischemic stroke, tumor, bleed, infection, demyelination
3) Nerves exiting the brainstem- compression (tumor, aneurysm), infarction or inflammation(e.g. DM2, vasculitis). REMEMBER WERNICKE'S! (thiamine deficiency), Miller-Fisher variant of Guillan-Barre (would have areflexia, ataxia),
4) Meninges- meningitis, neurosarcoid, leptomeningeal spread of cancer
5) Cavernous sinus thrombosis- III, IV, V1, V2, VI pass through; often associated with facial infections
6) NMJ- myasthenia as above

In someone with diplopia, how do you figure out which eye is the problem (if it's not obvious)?
A couple of pearls:
1) If someone complains of diplopia on looking in one diagonal direction, it is either the same-sided and oriented rectus muscle or the other-sided oppositely-oriented oblique muscle (e.g. diplopia on looking up and right, it is either R superior rectus or L inferior oblique. Diplopia on looking down and L is either L inferior rectus or R superior oblique)
2) If you cover up an eye when the patient is having diplopia, the eye that, when covered, takes away the most peripheral image is the problem

Ptosis:
Some considerations:
CN III palsy- should have ocular movement abnormalities, may have pupillary involvement (would be mydriasis from loss of parasympathetics)
Horner's syndrome- miosis (from loss of sympathetics), anhydrosis
Neuromuscular junction disorders- myasthenia gravis, botulism

Links:

Click here for a review from Neurology on evaluation of diplopia (need subscription to get)

Click here for a review of the link between migraine and stroke (a controversial, hot topic)

Pleural effusions

Today we discussed pleural effusions

Most common causes of effusion in North America are CHF, pneumonia and cancer.

Indication for thoracentesis: Clinically significant effusion (i.e. over 10mm thick on u/s or lateral decubitus) with no clearly known cause.
If CHF with bilateral effusions, trial of diuresis first. 80% of CHF effusions are bilateral. If unilateral, should be tapped. 75% of CHF effusions resolve within 48h of diuresis.
If over 3d, thoracentesis is indicated.
If pt has SOB at rest, therapeutic in addition to diagnostic tap should be done (i.e. up to 1-1.5L).

No need to do routine CXR post except if air is obtained, c/p, cough, dyspnea.

Bloody effusion narrows Ddx somewhat to cancer, PE, trauma, infection (inc. pneumonia, TB)

Transudative: leading causes are CHF, cirrhosis, PE.
Exudative: leading causes are pneumonia, cancer, PE.


Light's criteria for exudative effusion:
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

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. This criterion is more specific for transudate, because it calls some exudates transudates.

If transudative effusion, determine which of CHF, cirrhosis, PE exists.
If exudative, further workup is needed, including cell counts, culture, glucose, cytology, TB studies.

Cell count:
Predominence of PMNs (over 50%) suggests acute process (parapneumonic, PE, pancreatitis). Only ~15% of malignant, and almost no tuberculous effusions have PMN over 50%.
Mononuclear predominance (lymphocytic) suggests chronic process; cancer, tuberculous, post-CABG.
Eosinophils (over 10%) is usually blood or air in pleural space. Unusual causes are Churg-Strauss, drugs (dantrolene, bromocripine, nitrofurantoin), asbestosis, parasitic infections.
Basophils: leukemic infiltration

Culture: yield is higher if also blood C+S.

Glucose: low glucose suggests empyema or malignant. Less commonly, hemothorax, TB, parasitic (e.g. paragonimiasis), primary inflammatory (e.g. RA, SLE, Churg-Strauss)

Cancer: cytology yield is highest for adenoca. Less useful for mesothelioma, squamous, lymphoma, sarcoma. VATS is choice if suspected ca but negative cytology. If lymphoma suspected, flow cytometry can show pleural fluid clonal population.

TB: tuberculous pleuritis effusions resolve, but pulmonary or extrapulm TB develop in >50%. Investigate for TB if lymphocytosis. Less than 40% have positive pleural cultures.

pH: indicated if parapneumonic or malignant suspected.

PE: Suspect if dyspnea out of keeping with size of effusion, pleuritic c/p, hemoptysis.

"Complicated pleural effusion"- i.e. an indication for drainage (pigtail or surgical chest tube) Any of
1) cloudy fluid
2) pH less than 7.2
3) Glucose less than 2.2
4) Pleural to serum glucose ratio less than 0.5
5) LDH over 1000
6) Neutrophils over 25000
7) effusion occupying 50% of hemithorax (relative indication)

Links
Click here for NEJM review of pleural effusions by Dr. Light himself
Click here for an excellent review from Clinical Infectious Diseases on empyema and parapneumonic effusions

Ileitis

Ruptured terminal ileum from intestinal TB


Today we discussed ileal inflammation (AKA 'terminal ileitis') and some related issues. A few points:

In any patient presenting with RLQ pain, always exclude life-threatening conditions:
-Appendicitis, diverticulitis with or without abscess
-Strangulated hernia
-Ectopic pregnancy
-Pelvic inflammatory disease
-Others presenting atypically (e.g. ruptured AAA, bowel obstruction, etc)

Specific causes of ileitis:
Infectious:
Bacterial: yersinia, campylobacter, typhoid (from Peyer's patch enlargement), actinomyces Mycobacterial: TB, or non-tuberculous mycobacteria
Parasitic: amebiasis- can present exactly like Crohn's
Viral: CMV
Typhlitis (aka neutropenic enterocolitis or ileocecal syndrome)- seen in immunocompromised pts

Inflammatory:
Crohn's disease
Microscopic colitis

Neoplastic:
Small bowel lymphoma

Vasculitic:
Henoch-Schonlein purpura (rarely!)


Intestinal TB
Difficult to diagnose; need high index of suspicion;
non-specific chronic abdominal pain is the most common symptom, with constitutional symptoms. Palpable mass in 25-50% of patients. May see ascites, which helps to distinguish from some of the above causes of ileitis. Treatment is similar to pulmomary TB, and usually responds well

Links:
Click here for a CMAJ review of extrapulmonary TB
Click here for a NEJM clinical pathological conference where the differential of ileitis is discussed

Mitral stenosis

Today we discussed mitral stenosis. A few issues that came up about this big topic:

Predominant cause is rheumatic. Many pts with rheumatic heart disease have multiple valve lesions (25% have isolated MS; 40% have MS+MR; ~35% have aortic valve involvement)

Primary problem in MS is insufficient flow across the MV that leads to LA enlargement and high LA pressures to compensate. Remember that the pressure gradient for given valve area varies with square of flow (i.e. doubling flow requires 4x higher pressure gradient- this is also important in aortic stenosis).

Therefore, situations that increase flow (usually from tachycardia) cause dyspnea -
A-fib, infection, pregnancy, exercise are common ones

Tachycardia also decreases diastolic filling time, decreasing forward flow.

The high LA pressures needed to compensate for decreased diastolic filling time in tachycardia can lead to flash pulmonary edema. Atrial fibrillation is even worse because the atrial kick is relatively more important.

LA enlargement from elevated pressures predisposes to AF

Important complications of MS: pulmonary edema, atrial fibrillation, cardio-embolic stroke (from stasis and A-fib- very high risk of stroke in this setting), pulmonary HTN, endocarditis

Symptoms:
1) Dyspnea: most common, esp with exertion. Any situation causing increased flow across valve brings on (esp. tachycardia).
2) Hemoptysis: May occur from rupture of dilated bronchial veins
3) Chest pain: uncommon; often from secondary pulmonary HTN
4) Palpitations: A-fib
5) Other: Hoarseness (Ortner's sign for medical jeopardy fans), edema

Physical:
General- May see obvious resp distress, mitral facies (i.e. pink-purple patches from vasoconstriction on face)
Pulse: May see A-Fib. Usually normal, but may see low volume.
JVP: May see signs of pulmonary HTN as consequence of MS
Palpation: may have tapping S1 (pliable anterior leaflet). In LLD, may palpate diastolic thrill. May have RV heave and palpable P2 from pulm HTN.

Heart sounds:
Major findings are
1) loud S1 early, soft late in course
2) opening snap- early diastolic sound of MV opening; moves closer to S2 with more severe
3) diastolic rumble (murmur) post- opening snap
4) late diastolic murmur with presystolic accentuation from atrial kick

Others:
1) ECG- L atrial enlargement- 'p-mitrale'
2) CXR- splayed carina, double R heart border, flat or everted L heart border from LA enlargement

Link:

Click here for a nice website from the Cleveland Clinic summarizing MS

Thrombocytopenia and ITP

Today we discussed an approach to a bleeding diathesis, and issues related to thrombocytopenia and ITP. A few key points:

General approach to bleeding history:
Try to differentiate primary hemostasis problem (vascular response and platelet plug) vs. secondary hemostasis problem (fibrin clot, or resolution phases)

Clues:
Primary- excessive immediate post-traumatic bleeding usually. Petechiae, purpura, mucosal bleeds: nose, mouth, gums, GI, uterine
Secondary- delayed, subcutaneous, deep tissues, joints, GI/GU, post-op.
Acquired vs. inherited: new-onset vs. lifelong, new medical problem or drug, FHx.


General approach to thrombocytopenia

3 major categories
1. Decreased platelet production
2. Increased platelet destruction or platelet consumption
3. Sequestration

Decreased PLT production: Bone marrow problem; marrow shows decreased megakaryocytes
Aplastic anemias (congenital or acquired)
Myelophthisic anemia - i.e. marrow replacement (malignancy, granulomatous, etc)
Megaloblastic anemias (B12, folate deficiency)
Marrow suppression from drugs, toxins, infection, etc)

Peripheral destruction or consumption
Immune-mediated: ITP- Primary (idiopathic) or secondary (SLE, HIV, EBV B-cell disorders), drug-induced, post-transfusion
Non-immune: Thrombotic thrombocytopenia purpura- TTP, disseminated intravascular clotting

Sequestration:
Usually portal hypertension, hypersplenism

ITP specifics

Most cases are idiopathic.
In adults, it is generally chronic, the onset is often insidious. Approximately
twice as many women as men are affected

If all these conditions are met, bone marrow bx (gold standard) is not required
-age less than 60
-isolated TCP
-no splenomegaly
-no lymphadenopathy

To exclude before calling "idiopathic ITP":
-non-immune causes of TCP (primary marrow problem, TTP, HIT, DIC, etc)
-infection- HIV especially, EBV
-inflammatory disorders, esp. SLE
-malignancy, esp. B-cell disorders (CLL, myeloma, etc)
-drug induced (for immune-mediated, B-lactams, quinine, vancomycin, others)

Therapy:
In serious bleeding
1) hemodynamic and RBC transfusion support
2) platelet transfusion
3) steroid
4) IVIG
5) some evidence for factor VII in life-threatening bleeding

Most pts require therapy; those who do not are those with mild (over around 50), asymptomatic, incidentally discovered thrombocytopenia. Otherwise, options are:
-Steroids (prednisone 1mg/kg, tapered over 4-6 weeks depending on response or dexamethasone 40mg PO x 4d). 50% have relapse. RCT underway comparing these regimens
-IVIG; indicated for severe bleeding, pre-operatively or pre-delivery, and in steroid-refractory cases
-Splenectomy (need appropriate vaccinations first)
-Rituximab (controversial whether should be tried before splenectomy)

In chronic refractory cases, there may be a role for vincristine, azathioprine and cyclophosphamide, and thrombopoeitin agonists

Links:
Click here for a NEJM review of ITP

Click here for a series demonstrating effect of short course of dexamethasone described above

Hypocalcemia

Today we discussed hypocalcemia. A few points:

Clinical manifestations:
-Paresthesias
-Lethargy
-Seizures
-possibly arrhythmias (lengthens QT)

-Chvostek's sign:
Tap cheek 2cm anterior to tragus, look for ipsilateral upper lip twitch

www.youtube.com/watch?v=CVpWhiQNwGc

NB- this video is freely available on YouTube, and is not a patient cared for in this hospital

-Trousseau's sign:
Inflate BP cuff above systolic pressure for 3 minutes, look for painful carpal spasm (shown above)

An approach to causes of hypocalcemia (which drives appropriate history, physical, and investigations):

Think of major determinants of calcium handling, and what can affect each:

Low PTH:
-iatrogenic (most common cause); e.g. post-thyroidectomy
-autoimmune (can be part of autoimmune polyendocrine syndrome with vitiligo and candidiasis)
-infiltration of the parathyroids (sarcoid, hemochromatosis)
-hypomagnesemia (alters PTH receptor sensitivity)

Low Vitamin D:
-malabsorption of fat-soluble vitamins (ADEK)
-liver disease
-kidney disease
-inadequate sun exposure

GI tract:
-malabsorption of calcium (proximal small bowel): celiac, Crohn's, others in addition to vit D malabsorption

Kidneys:
-Loop diuretics
-Calcium wasting: Fanconi's syndrome (proximal tubular reabsorption problem; causes hypocalcemia, hypophosphatemia, non-anion gap metabolic acidosis, hypoglycemia, hypoalbuminemia)

Bone:
-"Hungry bone syndrome"- post parathyroidectomy after hyperparathyroidism, increased bone uptake of calcium after prolonged calcium "leaching"
-osteoblastic metastases (esp. prostate, breast)

Intravascular Ca binding:
-citrate (e.g. in dialysis or massive transfusion)- binds ca
-hyperphosphatemia

Calcium deposition sites:
-severe pancreatitis
-rhabdomyolysis

Others:
-secondary hyperparathyroidism; often have normal or low Ca in renal failure for many reasons
-DiGeorge syndrome- affects PTH receptor
-Bartter's syndrome- acts like a loop diuretic causing calciuresis
-"pseudohypoparathyroidism"- looks like hypoparathyrodism, except PTH is high; receptor mutation

Tip: The phosphate level can be quite helpful in sorting out causes; PTH increases calcium and decreases phosphate. Vitamin D increases both calcium and phosphate.

Link:

Click here for a NEJM review of hypoparathyroidism that discusses much of above

Peripheral neuropathy

Today we discussed peripheral neuropathy. A few points on this very broad topic:

Important differential: 'THIN'
1) Toxic, Metabolic- medications, DM2, EtOH, metals, B12
2) Hereditary- Charcot-Marie-Tooth and variants
3) Inflammatory and infectious- Guillain-Barre, CIDP (chronic inflammatory demyelinating polyneuropathy), vasculitis, and HIV, HTLV, leprosy
4) Neoplastic/paraneoplastic: multiple myeloma

Important points on history:
1) Temporal course- acute (days to weeks), subacute (4-8 weeks), chronic (>8 weeks); relapsing? progressive?
2) Proximal vs. distal motor and sensory symptoms (trouble reaching overhead, climbing stairs vs. opening jars, picking things up)
3) What are the sensory symptoms? negative- e.g. numbness or positive- e.g. paresthesias, burning, throbbing, etc.
4) Questions around above differential

Important physical exam:
Atrophy, fasiculations for LMN lesion
Distribution of weakness- nerve vs. plexus vs. root
Reflexes
Sensory- pin prick, vibration (named nerve vs. nerve root vs. length-dependent)

Important investigations:
FBG, HbA1C
CBC, Cr, Vitamin B12, TSH, serum and urine electrophoresis, HIV

Multiple named nerve palsies = mononeuritis multiplex
Essentially diabetes-related vs. vasculitis.
Common nerves involved in DM2: CN III, IV, VI, median nerve, peroneal nerve.
Vasculitides that commonly cause mononeuritis multiplex: Churg-Strauss, polyarteritis nodosa, rheumatoid arthritis with vasculitic component

Link:
Click here for an excellent review of peripheral neuropathy from Lancet

Pancreatitis

Indeed...

Today we discussed an approach to pancreatitis. A few points:

Acute = no pre-existing pancreatic pathology; usually resolves without permanent damage.
Chronic = pre-existing fibrosis/scarring/calcification. EtOH-induced is often acute on chronic.

Pancreatitis is essentially autodigestion, release of zymogens, and in severe cases, a retroperitoneal chemical burn injury.

Etiologies:
-EtOH
-Gallstone
-Drugs (commonly reported include some HIV medications, HRT, azathioprine, tetracycline, 5'ASA, sulfasalazine)
-Metabolic- hypertriglyceridemia, hypercalcemia
-Iatrogenic (esp. post-ERCP)
-Autoimmune
-Others- anatomic (pancreas divisum), scorpion bites (everyone's favourite), cystic fibrosis, infection

Symptoms: Epigastric abdo pain, better leaning forward (Ingelfinger's sign for medical jeopardy fans), radiating to back, N+V

Things to look for on exam:
Vitals: Tachypnea, tachycardia, fever
-jaundice
-abdominal distension, absent bowel sounds (ileus)
-cullen/grey turner signs
-dull lung bases from pleural effusion
-abdominal tenderness.

Lab: Lipase/amylase (NB- macroamylasemia, salivary gland pathology, and tubo-ovarian pathology give high amylase but normal lipase). Lipase and amylase support the dx, not make it. The levels fall off in days.

Imaging:

AXR: may show colon-cutoff sign or ileus

CT may show pseudocyst or necrosis in addition to stranding, inflammation

Prognostic factors: Development of organ failure, SIRS (look for ARF-most common, ARDS), necrosis, abscess, pseudocyst. Others: Ranson criteria, APACHE score, etc.

Therapy:

Largely supportive; monitor closely for complications.

Principles of managment:
1) Fluid resuscitate aggressively as needed
2) Watch respiratory status, and intervene if necessary (ABG's, etc)
3) Watch for other organ involvement (AKI, DIC, etc)
4) Nutrition: Do not rest the pancreas; start enteral nutrition (increased metabolic requirements, decreased bacterial translocation) - evidence for early PO feeding.
5) Pain managment
6) Antibiotics- very controversial; only convincing evidence is in pancreatitis with necrosis (there are scoring systems based on CT), in which case meropenem has proven benefit. In some cases, a fine needle aspirate of a collection is done to determine whether infected and only treated if positive.
7) If gallstone-related, ERCP and cholecystectomy (during current admission if mild or delayed if severe) reduces recurrence risk from 25% to 8%.

If severe deterioration, consider surgery for debridement, but this is high-risk.

Links:

Click here for an interesting paper highlighting common problems and pitfalls in pancreatitis management

Click here for a Cochrane review of antibiotics in pancreatitis

Click here for a trial comparing symtom-drive vs. standing benzos for alcohol withdrawal

Brugada syndrome and Arrhythmogenic RV cardiomyopathy

V1 leads in Brugada syndrome (left) and ARVC (right)

Today we discussed syncope. For a discussion of an approach to syncope with a link to an excellent review from Circulation, click here

The topics of the Brugada syndrome and arrhythmogenic right ventricular cardiomyopathy -ARVC (aka ARVD, d for 'dysplasia') came up. A few points on these rare, but important causes of syncope:

Brugada syndrome:

Characterized by "pseudo-RBBB", with ST elevation in R precordial leads and high incidence of sudden death in patients with structurally normal hearts (up to 4% of all sudden deaths, 20% of cases with structurally normal heart). Typically presents in adulthood.

Prevalence is unknown; estimated to be 5/10,000 but may be as high as 50/10000 in Asian populations.

May be associated with either atrial or ventricular arrhythmias.

Diagnosis:
Classic ("type 1") ECG is "coved" ST eleation over 2mm in one or more of V1-V3 with T-inversion (shown above).

There are less classic ECG changes in Brugada syndrome, including "saddlebacked" ST elevation in same leads.
Many other conditions can mimic the R-sided ST changes seen in Brugada syndrome, including RBBB, LVH, early repolarization, MI, PE, hyperkalemia, ARVD, hypothermia, and Duchenne's muscular dystrophy.

The use of a sodium channel blocker like procainamide can bring out the ECG changes, and this type of "challenge" can be helpful diagnostically (obviously needs to be done in appropriate setting...)

Therapy may consist of antiarrhythmic therapy (quinidine) or implantation of a defibrillator (ICD). General indications for an ICD include aborted arrest, inducible VT on EP study, and suggestive ECG with otherwise unexplained syncope or family history.

ARVC:

This is a genetic condition (autosomal dominant with variable penetrance) characterized by progressive replacement of RV myocardium with fibro-fatty infiltration, which predisposes to ventricular arrhythmia.

Prevalance is estimated to be 1-5 per 1000; highest prevalence in southern European populations (especially Italian). Typically presents from teens to 30s, and affects more males than females.

Diagnosis should be considered in adolescents or young adults presenting with palpitations, syncope, or aborted sudden death. ECG may show T-inversion in R precordial leads (shown above), possibly with "epsilon wave"- small "saddle" in ST segment in V1-V3.

Imaging modalities sigh as 2D echo (most commonly used) and cardiac MRI (becoming more common) may show RV structural changes, and are part of the diagnostic criteria. Family members should be screened.

Therapy:
ICD is indicated for similar indications to above for Brugada syndrome (aborted sudden death, inducible VT).
There is a role for pharmacologic therapy (B-blocker like sotalol antiarrhythmic like amiodarone) in supprssing arrhythmias.
Participation in sports increases the risk of sudden death 5-fold; 24 years of a screening programs in Italy has led to a significant decline in sudden death in athletes.

There is no well-validated risk stratification tool to assess which patients are most likely to benefit from which therapies.

Links:

Click here for a 2005 review from Circulation on Brugada syndrome

Click here for a 2009 review from Lancet on ARVC

Click here for a JAMA paper showing the mortality reduction in Italy from screening for ARVC in competitive athletes

Pericarditis

Today we discussed pericarditis. A few key points:

Causes of pericarditis:
Vast majority are viral/idiopathic (90%).
Long list of other causes includes
-other infections (purulent pericarditis- H.Flu, pneumococcal, many others), TB
-aortic dissection, trauma
-uremia
-malignancy (although more commonly effusion than pericarditis)- breast, lung, esophageal, hematologic malignancies
-primary autoimmune of inflammatory disorders (esp. SLE, RA, mixed CTD, many others)
-post radiation
-drugs

Pain in pericarditis is usually retrosternal, acute onset, and pleuritic. Often worse supine, improves leaning forward

Physical exam may show pleural rub (mono, bi, or tri-phasic)- each phase corresponds to movement of pericardium. Triphasic rub has 2 diastolic components (early and late diastolic filling) and 1 systolic component. Differentiate pleural vs. pericardial rub by having pt stop breathing. Also look for signs of effusion and tamponade or constrictive pericarditis- JVP findings, pulsus paradoxus, etc.

ECG in pericarditis: 4 stages described
1) diffuse ST elevation (concave up; not dome-shaped) and PR depression
2) normalization of ST and PR changes
3) diffuse T-wave inversions
4) normalization of T changes
ECG in pericarditis vs. MI: In MI, uncommon to have diffuse STE, concave up ST segments, PR depression. T-inversions in MI usually happen before ST segments return to baseline (as opposed to above sequence).

Poor prognostic factors- consider 2D echo +/- admission:
-fever
-subacute onset
-immunosuppression
-trauma-associated
-anticoagulation
-elevated troponin (implies myocardial involvement)
-tamponade suspected (no kidding...)

Every pt should have CBC, troponin., Other tests are guided by evaluation.

Treatment:
If no specific cause found (majority of cases), options include
-high dose ASA (2-4g/day)
-ibuprofen (1600-3200mg/day) or other high dose NSAID

In recurrent pericarditis, colchicine or prednisone are often effective.

Complications of pericarditis:
-cardiac tamponade
-constrictive pericarditis

Link:

Click here for a NEJM review of pericarditis

Click here for JAMA Does this patient have cardiac tamponade?