Day #92 - "I don't know"

Wow. What a great case. It isn't often that I truly throw my hands up and say that "I don't know" but this was one of them.

But I hope the exercise in reasoning was useful for you. I think we demonstrated an approach that was safe, cost-effective, and broad in going through the history and physical exam.

Dr. Gold previously spoke about meningitis (bacterial) and that talk is available here.

In approaching a patient with multiple infarcts we need to consider the following differential:

• Emboli - Arising from the heart or great vessels. One possibility is subacute bacterial endocarditis, particularly given the history of night sweats. I think this patient needs blood cultures drawn with blind subculturing (endocarditis blood cultures) to look for unusual pathogens like brucella. I also think he needs a trans-esophogeal echo looking for a cardiac source including a bubble study to exclude PFO. This can also look at the aortic arch.
  
• Ischemia -- Either bad luck from uncontrolled risk factors, or genetic stroke syndrome like CADASIL, Fabry's or MELAS, or thrombophilia like antiphospholipid antibody syndrome, ATIII deficiency or hyperhomocysteinemia. I would exclude thrombophilia. As a last resort I would look into genetic testing. Night sweats don't fit with ischemia.
  
• Vasculitis (Night Sweats would fit with this too)
  
  • Primary:
    
    • Primary CNS angiitis
    • GCA/Takayatsu, polyarteritis nodosa (patient has Hep B!)
      
  • Secondary due to:
    
    • Infection:
      
      • Syphilis always needs to be considered in young patients who present with stroke like syndromes.
      • HIV can do this -- though he is suppressed.
        
      • CNS TB can cause this also (usually have CNS pleocytosis).
        
      • Fungal infections like cryptococcus can do this too.
        
    • Malignancy -- Angioinvasive lymphoma or lymphovascular lymphamatosis
      
• Other

If the echo is clean, I would consequently perform angiography (MRA possibly conventional) in this patient and look for evidence of vasculitis. I think given the night sweats and epidemiology that TB needs to be excluded prior to high dose steroids. I would repeat the lumbar puncture to ensure that it is still acellular (early TB can be acellular) and again send TB studies.

I would confirm whether or not he has had a mantoux. He should have one prior to immunosuppression anyways and should be treated for latent TB if this does not represent CNS TB.

I would probably scan his chest/abdomen/pelvis to look for evidence of malignancy, lymphoma or TB disease -- or something safer than the brain to biopsy and make a diagnosis.

Ultimately he may require a stereotactic brain biopsy to exclude TB and make a diagnosis. In a young man, with progressive infarcts and no other cause, I would discuss this with the patient.

TB is treatable, thrombophilia and emboli preventable, and lymphoma may be cured but CADASIL can not so we had better be sure!

Day #87 - Post Influenza Sepsis

This was one of my most memorable cases I presented to the discussant today. The article he asked me to send you is here.

Teaching Points:

• Influenza presents year-round but with a predominantly seasonal distribution. It is a highly transmissible virus with droplet (and possibly airborne particle) spread. Patients present with fever, malaise, lassitude, cough, myalgias, arthralgias and headache. The illness is usually self-limiting lasting approximately 1 week.
• Patients with underlying cardiac disease, respiratory disease, diabetes, or immunosuppression are at high risk of developing severe disease. Pregnant women, in the third trimester are also at risk compared to age-matched controls.
• Vaccines have been shown to have mortality and morbidity benefit, particularly amongst high risk groups. But vaccination of healthy individuals is proposed to have indirect benefit to these high-risk groups as well.
  
• A study done here in Toronto has shown that admitted patients with influenza, particularly those who are critically ill should be treated with oseltamivir. There is a reduction in mortality.
• Other notable sequelae:
  • Primary viral pneumonia or bacterial superinfection -- Most commonly streptococcus pneumoniae or staphylococcus aureus (including community acquired MRSA). This can be severe.
    
  • Viral myocarditis (rare)
  • myositis with possible rhabdomyolysis
    
  • Guillain-Barre syndrome, Influenza meningoencephalitis, Transverse myelitis

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In this case, the patient likely had a secondary bacterial infection with lobar pneumonia, sepsis and eventually multiorgan failure. Early recognition and treatment of sepsis is important. The principle is called "Early Goal Directed Therapy". This is a protocol of interventions designed to maximize tissue perfusion and interventions in a rational way.

Essentially this means:

• IV crystalloids to maintain central venous pressure of 8-12 (JVP 3-7cm is about that if you don't have a CVP line), normal blood pressure (MAP >=65) and mixed venous oxygen saturation of >=70%
• If still not at goal with crystalloids add vasopressors (i.e. norepinephrine)
  
• If still not at goal with this and hematocrit <30%,>
• If still not at goal with this, add positive inotrope dobutamine.
  
• Early appropriate antibiotic therapy
  
• Source control -- removal of septic focus, drainage of pus, etc --> this is often the neglected step....
  
• NB: pentastarch may be harmful and so I don't use it. The use of albumin is also contraversial -- an ongoing clinical trial hopes to solve this.
  

The protocol from Rivers et. al is below:

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Notable people affected by the 1918 pandemic:

• • Woodrow Wilson -- allegedly had meningoencephalitis while signing the treaty of Versailles
  • Harvey Cushing -- developed Guillain-Barre post-influenza
  • William Osler -- died of empyema (post influenza superinfection)
    

Day 85 - "That sounds bad"

Back pain is one of the most frequent complaints in medicine. Today's case highlighted why it always needs to be taken seriously.

Back Pain:

• Mechanical: Classically worsens with movement, better with rest. Can be referred down to bilateral hips, thighs.
  
  • Patterns:
    
    • Radiculopathy (classically sciatica): pain radiates in dermatome of nerve root impingement. May be associated with neurologic symptoms (weakness or numbness) in the affected area
    • Spinal Stenosis: pain radiates to legs. Worse with activity. Predictably improves with leaning forward, rest
      
  • RED FLAGS:
    
    • Night pain
    • B-Symptoms (fever, sweats, weight loss)
    • Neurological symptoms including numbness, weakness, bladder incontinence (overflow), fecal incontinence (loss of sphincter tone)
      
    • Known history of malignancy
      
• Inflammatory: associated with morning stiffness, aggravated by rest, possibly extra-axial symptoms of connective tissue disease.
• Referred pain

The examination should include a general exam looking for signs of systemic disease. A focussed exam should look for focal bony or paraspinal tenderness, and neurological findings (including rectal tone if appropriate), and associated MSK findings.

---

In the case today the patient had progressive, severe back pain in the context of 2 months of B-symptoms. He presented with cord compression.

Differential:

• Malignancy:
  
  • Most commonly prostate, breast, lung. Then RCC, lymphoma and myeloma
  • Pain (present in 95%) is often the first symptom, usually preceeding neurologic symptoms by several weeks
  • Weakness (up to 85%) and sensory losses follow. Can also have bowel/bladder dysfunction and gait ataxia.
  • Patients should get steroids (dexamethasone 10mg IV x 1 then 16mg/day in divided doses tapered over 2 weeks), intravenous pamidronate, and either neurosurgery or radiation.
    
  • This trial showed that for metastatic disease in a single area, surgery +RT was superior to RT alone for solid tumors.
• Infection:
  
  • Spinal epidural abscess
  • Vertebral osteomyeltis including Pott's disease.
• Other:
  
  • Traumatic, vertebral compression fracture

Diagnosis is best made with MRI. If MRI is not an option, the next best test would be a CT myelogram.

Day #77 - Malaria

Today we talked about a case of a new immigrant to Canada who presented with cyclical fever and anemia. She had emigrated from a malaria endemic country and had had plasmodium malariae.

JAMA has a great article on malaria available here.

NEJM has a great article on malaria prevention available here.

Also, see my previous approach to anemia and thrombocytopenia.

Day #80 - Diarrhea

Today we talked about a case of acute diarrhea. The discussant took us through an excellent approach to acute diarrhea. Some highlights below:

Etiology:

• Infection (great article -- also IDSA diarrhea guidelines)
  
  • Viral: rotavirus, enterovirus, norovirus, etc. (CMV in immunocomprimized)
    
  • Bacterial: shigella, yersinia, e. coli, salmonella, campylobacter, C. difficile, TB (usually chronic), atypical mycobacterial (immunocomprimised)
    
  • Protozoal/Parasitic: Giardia, amebiasis, etc.
    
• Inflammatory
  
  • UC/Crohn's
• Ischemic
  
  • Small bowel -- pain out of proportion, post prandial pain
  • Large bowel -- bloody stool, colitis
• Osmotic
  
  • Laxatives, chewing gum diarrhea (xylulose), sorbitol, sucrose, post-surgical "dumping"
    
• Endocrine
  
  • Hyperthyroidism, carcinoid syndrome, VIPoma

Day #72 - Acute Cognitive Decline

We had actually discussed this case before in early August. At that time there were no myoclonic jerks, mri abnormalities, or eeg triphasic spikes suggestive of the diagnosis (now presumed) of CJD (from nejm or here from CID).



The previous discussion points on acute confusion, aphasia, and neurosyphilis are available here.

Day #70 - Fever of Unknown Origin III

I missed the rounds -- but have discussed pyrexia of unknown origin twice before. #1 and #2. Probably not as good as the discussant, but I referenced the article they were referring to.

"Special Guest Blog" by the discussant:

• Even in the "modern era", up to 1/3 of cases may go undiagnosed -these cases carry a good prognosis.
• Infections only account for 1/4 of all diagnoses.
• In certain cases without diagnosis, the benefits of liver biopsy outweigh the risks.
• Bone marrow cultures are of low diagnostic yield. Bone marrows should be performed only when there are other indications to do so ie unexplained cytopenias.
• I recently cared for a patient with FUO whose Hodgkin's disease was diagnosed on liver biopsy alone. Patients with FUO are challenging to investigate, are rewarding by virtue of the enigmatic causes that are may be found and reinforce the importance of basic principles like the careful history and physical examination.

Day #65 - Endocarditis

A confession -- today's case was "recycled" for your benefit -- and so is today's blog.

I have previously blogged on endocarditis, renal failure, and hyperkalemia and direct you to those sections.