Dementia Syndromes

1. Alzheimer's disease: A very common form of dementia in elderly patients. Characterized by progressive short term memory loss and cognitive decline. It is a clinical diagnosis, however classic histology reveals amyloid deposition in the brain (in beta-pleated sheets) and neurofibrillary tangles. A great link on AD here.

2. Vascular dementia: Manifested by cognitive decline after a stroke. There is a "stepwise" deterioration in function with subsequent ischemic injuries. Imaging of the brain will reveal ischemic changes.

3. Fronto-Temporal dementia: Atrophy of frontal and temporal lobes, but without histologic evidence of Alzheimer disease. This classically occurs in a slightly younger cohort...50-60 year old males and females. One of the hallmarks of this disease are personality changes - inappropriate personal or social behaviours. Aphasia may also be seen. You may hear of "Pick's Disease", a subset of fronto-temporal dementia with a progressive, non-fluent aphasia component to it.

4. Lewy-Body dementia: manifested by progressive cognitive decline, vivid visual hallucinations, delusions, syncope, and occasionally Parkinson-like symptoms (see below).

5. Dementia associated with Parkinsonism: This is an umbrella term for dementia associated with primary Parkinson's disease, and the Parkinson Plus Syndromes. Note that the Parkinson Plus syndromes typically have a poor response to dopaminergic therapy - that with their individual clinical features, this often helps clinicians distinguish them from primary Parkinson's disease.

• 
  Progressive supranuclear palsy: Parkinsonian symptoms, dementia, syncope, and vertical gaze abnormalities. Many have bulbar symptoms like dysarthria and dysphagia. It is sometimes referred to as the Steele-Richardson-Olszewski syndrome.


• 
  Multisystem Atrophy: A more mild progressive dementia, with mild features of Parkinson's disease (although tremor is mostly absent), and autonomic dysfunction manifested by syncope. You may also hear this condition referred to as the Shy-Drager syndrome. An excellent link here.
  
• 
  Corticobasilar Degeneration: A progressive dementia, with motor features of bradykinesia, rigidity, and postural instability. Patients may have sensory disturbances, apraxia, aphasia, or even alien limb syndrome.

6. Reversible Dementias: these include conditions where we can remove/modify an offending agent. Think about drug/toxin exposure, space occupying lesion, depression, or a metabolic abnormality.

Well's Criteria for DVT/PE

When we are clinically suspecting a deep vein thrombosis or pulmonary embolism we need to use a composite of clinical findings to estimate our pre-test probability of having the event - this is because no single finding is sensitive enough on it's own. As thromboembolic disease can have catestophic results, we want to ensure that the sensitivity of our composite of tests is high. The name "Wells" appears frequently...

Deep Vein Thrombosis: Wells Scoring System
[JAMA 1998; 279: 1094 – 1099]

• Active Cancer (on treatment/within 6 months/palliative): 1
• Paralysis, paresis, or recent plaster immobilization of the lower extremities: 1
• Recently bedridden for >3 days or major surgery within 4 weeks: 1
• Localized tenderness along the distribution of the deep venous system: 1
• Entire leg swelling: 1
• Calf swelling > 3 cm compared to asymptomatic leg (measured 10 cm below tibial tuberosity): 1
• Pitting edema (greater in the symptomatic leg): 1
• Collateral superficial veins (nonvaricose): 1
• Alternative diagnosis as more likely than that of deep vein thrombosis: -2

DVT Clinical Pretest Probability
Is the score...

A. Greater than/equal to 2? DVT Likely
B. Less than 2? DVT unlikely

Pulmonary Embolism: Modified Wells’ criteria
[Ann Intern Med 2001; 135: 98 – 107]

• Clinical findings suggestive of DVT: 3
• No other more likely alternative diagnosis: 3
• Immobilization (bedridden ³ 3 days) or major surgery within past 4 wks: 1.5
• HR > 100: 1.5
• Previous DVT/PE: 1.5
• Active malignancy: 1
• Hemoptysis: 1
  

Simplified Wells Criteria Scoring System [JAMA 2006; 295: 172-179]
Is the score...

A. Greater than 4? PE Likely
B. Less than 4? PE Unlikely

Your choice of investigations will be determined from the above scoring systems - whether thromboembolic disease is "likely" or "unlikely". More on this soon.

It is also important to ask yourself why this person his having thromboembolic disease in the first place?

(Get it? Get it? There's a picture of a well. Well's criteria? Yeah - that's terrible, I know.)

Cirrhosis - etiology

Cirrhosis - what are the causes?

1. Drug/Toxin: Alcohol, prescribed and non-prescribed medications

2. Chronic viral hepatitis - Hep B, C, and D

3. Metabolic diseases: Non-alcoholic fatty liver disease, hemochromatosis, alpha 1 antitrypsin deficiency, Wilsons disease

4. Autoimmune hepatitis

5. Vascular processes: Right sided heart failure, Budd-Chiari Syndrome

6. Diseases of the Biliary Tract: Primary Sclerosing Cholangitis, Primary Biliary Cirrhosis, Tumor

7. Cryptogenic

-Here is a great NEJM article on the management of cirrhosis and ascites
-We discussed the evaluation of Ascites here.
-We looked at peripheral stigmata of liver disease here.

Pneumocystis carinii (or P. jirovecii) pneumonia

PCP is a common respiratory opportunistic infection in HIV+ individuals. Those with a CD4 count less than 200 are at the greatest risk. It is a protozoa, and is found ubiquitously in soil - we are all exposed, but this organism poses few problems to healthy immune systems.

The classic clinical presentation is dyspnea with subacute onset, and a dry cough. Patients may have a low-grade fever, tachycardia, and tachypnea. The chest exam is variable - you may hear crackles...you may have a normal exam (in up to 50% of cases). The Chest X-ray often reveals bilateral interstitial infiltrates, but virtually any abnormality may be seen.

Remember, we can make the diagnosis roughly 90% of the time with history and physical exam alone. Still, it is nice to confirm your diagnosis by politely acknowledging the presence of an organism. Methenamine silver (photo above) or Immunofluorescent (photo below) stains on induced sputum (or bronchoalveolar lavage) has a high sensitivity and specificity.

Treatment: TMP-SMX in high doses. This has some interesting complications associated with it. If people are allergic to sulfa drugs or have complications, other agents can be used, such as TMP-Dapsone, or Atovaquone.

Steroids? Yep. If the PaO2 is less than 70, this is very helpful. Of note, this was a major breakthrough in medicine and was discovered here at the Toronto Western Hospital.

What else? Watch these patients closely. There is often a profound inflammatory reaction to the dying organisms, and patients often get worse on day 2-ish of treatment. That is why the steroids are added in severe disease.

Acid Base Approach...and Metabolic Acidosis

Acid-Base Problems...

Step 1: look at the pH. Whichever side of 7.4 the pH is on will be your Primary abnormality. Eg. if the pH is less than 7.4, you have a primary acidemic issue.

Step 2: find out if this is a metabolic or respiratory disorder (see flow chart below).

normal values:
pH 7.4
HC03 25
pCO2 40

Step 3: Look for “Compensation”
The body’s goal is to attain a pH of 7.4, this is a pH which our enzymes, muscles, nerves, etc. function at their best. The direction of compensation is almost always the same as the primary disorder to help the pH get back to normal.

Eg.1. you have a primary metabolic acidosis (low pH, low HCO3), you would expect your pCO2 to also fall, hence the direction of compensation of pCO2 is in the same direction as the primary disorder, they are both lowered.

Eg.2. if you have a primary respiratory alkalosis (high pH, low pC02), you would expect your HCO3 to fall as well.

Step 4: Look at the magnitude of compensation (discussed below).

What is the mechanism of compensation?
respiratory disorders: the kidneys increase their rate of HCO3 production in response to respiratory acidosis, and decrease their rate of HCO3 production in response to respiratory alkalosis
↑ pCO2 → HCO3↑
↓ pCO2 → HCO3 ↓

metabolic disorders: Patients hyperventilate in response to metabolic acidosis, and hypoventilate in response to metabolic alkalosis.
↓ HCO3 → pCO2 ↓
↑ HCO3 → pCO2 ↑


Metabolic Acidosis

Today we discussed a case of Diabetic Ketoacidosis. We talked about precipitants of DKA earlier and you can read about it here, we have also discussed the management of DKA here. There are some good links on both pages.

Ask yourself a few questions:

1. Firstly: Is this an anion gap, or non-anion gap metabolic acidosis? See below for details.

2. What is the etiology? you can use your “mudpiles,” but I find this a simpler way…you only have to remember 4 things...

1. Lactic acidosis: hypoperfusion of tissue vs Liver disease and cannot metabolize lactate.
2. Ketones: from Diabetes, alcohol, starvation
3. Uremia
4. Poisons/Toxins: ethanol, methanol, ethylene glycol, ASA, isopropyl alcohol, etc.

3. Is there compensation? for each 1 mmol/L fall in HCO3, you would expect a 1 mmHg drop in pCO2

4. Calculate the Anion Gap: AG = Na – [Cl + HCO3], a normal value is 12 or less

Remember to correct for Albumin: for every drop of albumin by 10, add 3 to your AG. So if you calculate your AG to be 12 (seemingly normal), but your albumin is 30, you must add 3 to your AG, making it 15… now start looking for excess anions (see above etiologies).

5. The Delta Delta: Delta what? Not to worry, it's pretty straight forward, and it adds some valuable information. Compare the change in anion gap to the change in HC03. What does this mean? Let’s say our patient has an AG of 20 and a HCO3 of 17. Well, compared to our normal values, the delta AG is 8 (20 – 12), and the delta HCO3 is 8 (25 – 17), so the delta AG is equal to the delta HCO3. We would expect the change in AG and the change in HC03 to be similar in a pure metabolic acidosis. If the delta AG is bigger than the delta HCO3, there is also a concurrent metabolic alkalosis present. If the delta AG is less than the delta HCO3, there is a concurrent AG metabolic acidosis, and non-AG metabolic acidosis.

6. Calculate the Osmolar Gap:

OG = [2x Na] + Urea + Glucose ....Remember "two salts and a sugar-bun"

Measured OG – Calculated OG should be less than 10.

Is this greater than 10? think about EtOH, methanol, ethylene glycol, isopropyl alcohol

Non-AG Metabolic Acidosis? think about diarrhea, and renal tubular acidosis. You can read more about RTA's here.

Respiratory Arrest in Pregnancy

Yikes. We have to be very careful in these situations and consider the heath of both the mother and unborn child. A critical question is if the shortness of breath is pregnancy related, not pregnancy related, or from a pre-existing condition.

Pre-existing conditions/Not pregnancy related:
Think about asthma, pneumonia, COPD, and previous cardiac conditions. The clinical manifestations of valvular abnormalities like mitral or aortic stenosis will be accentuated during pregnancy because of an increased cardiac output - normal physiologic changes. You can read more about valvular abnormalities in pregnancy here.

Pregnancy Related Conditions:
Pulmonary Edema: may be secondary to a few things. Eclampsia or Preeclampsia can cause this. Also, think about Pregnancy Associated Cardiomyopathy - this presents at 8 months gestation up to 5 months post partum. Salient features include a reduced left ventricular ejection fraction (less than 45%), the timing when cardiomyopathy develops, and ruling out other etiologies. Finally, tocolytic therapy may be associated with pulmonary edema.

Pulmonary embolism is about 5 times more common during pregnancy. Why? likely from a combination of venous stasis from the gravid uterus intermittently compressing the inferior vena cava, and from alterations of clotting factors (remember Virchow's Triad). Finally, if severe respiratory symptoms develop during labour and delivery, consider an amniotic fluid embolus - which unfortunately tends to be catastrophic.

ACLS guidelines in pregnancy can be found here.

Rhabdomyolysis

First, think about the underlying etiology:
1. Trauma: this can be overt, like a crush injury or a bit more subtle, like immobilization in an elderly person who falls and is unable to get up for some time. Also think about immobilization in patients with a decreased level of consciousness or during prolonged operation.

2. Physical activity: rhabdo may occur in those who either perform excessive physical activity (eg. marathons), in those who are doing significantly more physical activity than they are used to (eg. couch potato who goes on run for 1st time in 10 years), or in situations where hyperthermia may occur (eg. jogging in the Sahara). Also, don't forget seizures as a common etiology.

3. Drugs/Toxins: as always, we should consider prescribed drugs (eg statins, colchicine), and non-prescribed drugs (eg. alcohol, cocaine, ecstasy). There are always a few cases per year of rhabdomyolysis from wild mushroom poisoning.

4. Infections: many viruses (eg. cytomegalovirus, Coxsackievirus, Epstein-Barr, Influenza, adenovirus, HIV), bacteria (eg. pyomyositis), sepsis, and parasitic (Falciparum malaria).

5. Electrolyte: primarily hypokalemia and hypophosphatemia from any cause.

6. Endocrinopathy: mostly in hypothyroidism, but may also be seen in DKA/HONK - probably from hypophosphatemia.

7. Those who are more prone: people who have myopathies may be more prone to developing rhabomyolysis. Think about those with poly/dermatomyositis, malignant hyperthermia, or rare congenital myopathies

What should I watch out for?
1. Hyperkalemia: lots of potassium can be released from muscle cells. Monitor this and the ECGs closely.
2. Renal failure: watch out. Myoglobin is toxic to the renal tubules and can cause acute tubular necrosis.
3. Other electrolytes: hyperphosphatemia (released from muscle cells), hypocalcemia.

Treatment:
This primarily revolves around finding and reversing precipitants, and aggressive fluid administration to prevent myoglobin-induced ATN. There is debate whether the best fluids are saline or if sodium bicarbonate added to D5W works best. Also, keep a close eye on the potassium.

Some good links:
Here's an interesting case
Here's a strange case of Rhabdo from the CMAJ

Tastes like chicken...

HoPingKong-isms

1."...What was discovered here in Toronto?...don't be nervous...you don't have to sweat here..." Referring to Professor Lap-Chee Tsui, who discovered the Cystic Fibrosis Transmembrane Regulator (CFTR) genetic mutation responsible for Cystic Fibrosis. "Don't sweat" hints towards the Sweat Chloride Test for the diagnosis of Cystic Fibrosis.

2. "...To diagnose amyloidosis, do you go to India? Noooooo, you go to Africa..." Referring to the Congo Red stain that is helpful in the diagnosis of amyloidosis. If amyloid protein is present you will see an apple-green birefringence under polarized light. Check out the picture below of renal amyloidosis stained with Congo Red under polarized light....looks 'apple green' to me.

3. "...There are some genetic causes of liver disease....think about a leader of Germany, no bagels, no doughnuts, no buns..." Hmmm, tricky. There is a Kaiser in Germany, but really he is referring to Keiser-Fleisher rings seen in Wilson's disease. You can see a good picture of these KF rings and read more here.

4. "...A surgical problem? I don't think they will operate...they will probably give you the finger...". Get it? Get it? (I sure didn't). He was referring to Inglefinger's sign, seen in pancreatitis. This is when epigastric pain is diminished when patients sit up and lean forward. You can read more about issues in pancreatitis here.

5. "...Think about a medical liver problem from East Asia...you may get it right, but it may be a fluke..." Okay, sure...we all know he is referring to a liver fluke...but which one? It's Clonorchis sinensis, a cute little tramatode that can cause some serious damage. Those who eat fish are at risk. Adult worms live in the distal biliary ducts for years, and can cause fibrosis, cirrhosis, and cholangiocarcinoma. Check out a glamor shot of one of these worms at the top of the page.

mmmmh....apples.

Approach to Headaches

History and physical examination are vital. Most diagnoses can be made by history. It is important to rule out "red flags" that may indicate a headache secondary to something more ominous.

Red Flags:
1. Neck stiffness: possible meningitis
2. Focal neurologic deficits: mass lesion or infarction
3. Evidence of elevated intracranial pressure: headache worse in AM or on exertion, papilledema
4. Visual changes: think about temporal arteritis or elevated intracranial pressures
5. Constitutional symptoms: is there a malignant, inflammatory, or chronic infection causing this?

Based on History and Physical Exam, try determine whether you are dealing with a Primary or Secondary headache

Primary Headaches:
Migraine
Tension
Cluster

Secondary Headaches:
1. Infectious: think about meningitis, encephalitis, abscess
2. Vascular: hemorrhage (epidural, subdural, subarachnoid, intraparenchymal), arterio-venous malformations, sinus venous thrombosis, unruptured aneurysms
3. Mass effect: such as tumour, abscess, blood
4. Trigeminal neuralgia
5. Temporal Arteritis
6. Other: sinusitis, Temporal-Mandibular Joint pain, hydrocephalus, referred pain,

1. Here is a link to a good rational clinical exam on Meningitis
2. Here's another link written by local talent on the evaluation of headaches