Toxoplasmic Encephalitis

Dr. Xu presented an interesting case of a gentleman without significant past medical history presenting with fevers and headaches, found to have a solitary ring-enhancing brain mass on MRI. He was subsequently diagnosed with toxoplasmic encephalitis after a brain biopsy stained positively for toxoplasmosis. Further evaluation revealed that the patient was HIV+ and had AIDS with a CD4 count <35 data-preserve-html-node="true" with a viral load of 400k. The case prompted several interesting points:

  • The differential for a ring-enhancing mass is affected dramatically by the hosts immunocompetency; thus it is worth screening every individual with a ring enhancing mass for HIV
  • In immunocompetent individuals, consider benign tumors, malignant tumors, or brain abscesses
  • In the immunocompromised, the differential expands considerably and should include toxoplasmic encephalitis, primary CNS lymphoma, and PML

A review on Toxoplasmosis, courtesy of of Dr. Xu

Epidemiology

  • Toxoplasmosis gondii is a protozoan parasite acquired through ingestion of oocysts by way of food or environment
  • Primary infection typically consists of a subacute, influenza-like illness prior to entering a quiescent stage
  • Infection can reactivate with Reactivates with severe impairment of host cell-mediated immunity causing severe disease, most commonly as toxoplasmic encephalitis

Transmisssion

  • Obligate intracellular protozoan parasite
  • Typically transmitted to humans by eating food/water contaminated by cat feces or blood/organ transplantation
  • Definitive host is cats, where it replicates in the intestines and oocytes shed in feces
  • Humans are an accidental, dead-end host for toxoplasma. Oocytes transform into tachyzoites and encyst in neural and muscle tissue
Kittens

Kittens

Tachyzoites

Tachyzoites

Clinical Presentation

  • Primary infection
  • Asymptomatic latent infx
  • Reactivation

Most common signs/symptoms:

  • Headache (55%), encephalopathy (52%), fever (46%), seizures (29%)
  • Focal neurologic deficits (69%), hemiparesis (39%), ataxia (30%), cranial nerve palsies (28%)

Diagnosis

  • CT or MRI with contrast
    • Ring-enhancing lesions (not always)
    • Most common lesions in basal ganglia, frontal or parietal lobes
  • Toxo IgG (+)

    • Negative IgG does not exclude
  • Presumptive diagnosis:

    • CD4 <100 data-preserve-html-node="true"
    • Neurologic symptoms
    • Focal brain lesion
Ring-enhancing Toxoplasma

Ring-enhancing Toxoplasma

Treatment

  • Empirically treat with the following drugs that target folate synthesis:
    • Pyrimethamine
    • Sulfadiazine
    • Clindamycin
    • Atovaquone
    • TMP-SMX
  • Few head to head trials
  • Early ART
  • A lack of clinical or radiologic improvement after two weeks of treatment should prompt pursuit of biopsy and workup for other opportunistic disease or non-Hodgkin’s lymphoma

Key Points

  • Screen for HIV in patients presenting with neurologic symptoms + focal brain lesions
  • Empiric treatment for TE should not be delayed if there is high clinical suspicion
  • When pyrimethamine based regimens become cost-prohibitive, alternative regimens, such as atovaquone-sulfadiazine or TMP-SMX can be considered

Thanks so much to Dr. Xu for such an interesting presentation and thorough review!

Hip pain, auto-SCT

Thanks Kaleb for a great case! This is a case of a young man with a history of Hodgkin Lymphoma (sp ABVD and autoSCT) presenting to an outpatient clinic with hip pain found to have avascular necrosis likely from high dose steroids used to treat bleomycin-induced pneumonitis.

temp faber.jpg

Main points:

  1. ) Hodgkin lymphoma is generally treated with combination chemotherapy and radiation with a high cure rate. Some complications to consider include chemo and XRT related including heart failure (doxorubicin), ILD (bleomycin), neuropathy (vinblastine), early onset CAD, constrictive pericarditis (XRT) and secondary malignancies.
  2. ) Localization is helpful for the diagnosis of hip pain. Posterior pain can be referred lumbrosacral disease, sacroiliac pain or bursitis. Lateral hip pain should make someone consider trochanteric bursitis or meralgia paresthetica. Anterior hip pain is more consistent with hip joint pathology. The differential should also include pathology outside of the MSK hip region including a retroperitoneal and intraabominal process especially if the patient has a normal gait or symptoms that point against an MSK etiology.
  3. ) A dedicated hip exam should include inspection, palpation, range of motion, strength, specific maneuvers to help logalize the pathology, and gait. See this great Stanford 25 page that illustrates various aspects of the hip exam to localize pathology.

Want to learn more?

Hip pain differential

One way to formulate a differential is based on where the pain is located.

  • Posterior

    • referred lumbrosacral – if suspected, perform back exam
    • piriformis syndrome – specific maneuvers to isolate the piriformis
    • sacroiliac – suspected with positive FABER test (Flexion, ABduction, External Rotation)
    • bursitis – usually pain with palpation of iliopsoas or ischiogluteal bursae
  • Lateral

    • meralgia paresthetica – usually presents with neuropathy symptoms in the thigh
    • IT band syndrome
    • trochanteric bursitis – pain with palpation of the greater trochanter
  • Anterior

    • hip joint pathology – suspect in pain with passive ROM maneuvers
    • meralgia paresthetica
    • hernia
  • Extra MSK

    • retroperitoneal/ intraabdominal pathology
    • nephrolithiasis

Autologous Hematopoietic Stem Cell Transplant (Auto HSCT)

Autologous hematopoietic stem cell transplant is indicated for multiple malignancies (eg some lymphomas, myeloma, testicular cancer) and involves harvesting the patient’s own stem cells to be returned to reconstitute the bone marrow after intensive chemotherapy +/- radiation to treat the malignancy. Advantages include fewer side effects than allogeneic (donor derived stem cells) due to lack of GVHD and being in an immunosuppressed state only peri-transplant. However, patients do not get the benefit of graft versus tumor that allogeneic transplants confer. Here is a chart on complications to watch out for after an autoSCT from a great overview review article on autologous stem cell transplant.

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Chest Pain + Bezold-Jarisch Reflex

Thanks to Dr. Levin today for her case of chest pain which reminded us of coronary anatomy distribution on ECGs and post-MI complications. It also highlighted the importance of good sign-out during transitions of care.

Image adopted from ecgwaves.com for reference. 

Image adopted from ecgwaves.com for reference. 

Remember to correlate the ST changes on the ECG to the myocardial territory and the coronary anatomy. This will help you think through complications and what other tests may be useful (i.e. posterior or right sided ECG).

ecg.PNG

One complication of myocardial ischemia is arrhythmia. Many may recall that the SA node is supplied by the RCA (60%) or LCX (40%) and, the AV node is supply by the RCA (90%) or LCX (10%). Thus, RCA infarcts can lead to bradycardia via loss of blood supply to those regions. However, another physiologic response called the Bezold-Jarisch Reflex (BJR) is another explanation for arrhythmias. The BJR plausits that myocardial ischemia results in hypotension and bradycardia via stimulation of the cardioinhbitory C fiber afferent receptors in the myocardium. The greatest concentration of these fibers are in the inferior and posterior wall of the heart which just so happen to be supplied by the RCA and LCX. This reflux was thought to be the result of the transient bradycardia and hypotension in this patient who had a distal RCA occlusion on coronary angiogram. For more information of the BJR take a look at this review article in Anesthesiology from 2003.

For additional review on chest pain and CAD diagnosis, evaluation and treatment, please see Dr. Lesselroth's handy pocket cards.

W.O.W. Peer Scholarship Mentors!

WOW scholarship.PNG

Introducing the NEW peer-to-peer scholarship mentorship initiative, available at imscholarship@ohsu.edu

This group is formed of IM residents who have made themselves available as a resource to answer any and all questions their peers may have about accessing or participating in the scholarship process, and to help serve as a link between residents and various faculty!

They plan to circulate a survey this week to ascertain a "state of scholarship" newsletter in conjunction with Dr. O'Glasser, so be on the lookout!

Contact Jeff Bien (bien@ohsu.edu) or imscholarship@ohsu.edu with any questions, suggestions, or ideas!

Vent management: Auto-PEEP and peak pressures, acid-base

Thanks for presenting a great case Kathy! This is a case of a middle age person with persistent asthma and a history of an extensive unprovoked DVT (sp IVC filter placement), who developed hypercarbic hypoxic respiratory failure requiring intubation secondary to an acute bacterial necrotizing pneumonia who presented to our ICU for hemoptysis s/p bronchial blocker placement. The patient was hypercarbic at presentation, which was thought 2/2 auto-PEEP. The hospital course was complicated by spontaneous pneumothorax thought multifactorial 2/2 underlying lung disease, the bronchial blocker, and necrotizing pneumonia.

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Main points:

  1. ) We briefly discussed the differential of hemoptysis which includes categories such as oropharyngeal/ airways, parenchyma (infectious vs inflammatory vs malignancy), vasculature, drug/ toxins, and misc. See this great blog from Monday on the differential.
  2. ) In a patient with underlying obstructive lung disease, ventilated with a high RR, and persistent hypercarbia, consider auto-PEEP as the cause.
  3. ) A stepwise approach that Sharon Anderson teaches to evaluate a blood gas includes the components:
    1. ) acidosis or alkalosis? (pH >/< 7.4)
    2. ) respiratory or metabolic? (pH and PaCO2 deranged in same way = metabolic; opposite = respiratory)
    3. ) appropriate compensation or underlying second disorder? (various formulae and shortcuts)
    4. ) concurrent AGMA? Concurrent simultaneous non-gap and gap acidosis?
    5. ) does this result fit with the clinical picture?

Want to learn more?

Auto PEEP

  • Auto-PEEP occurs when expiratory time is not long enough to fully exhale, leading over time to more and more air trapping
  • This can lead to high intrathoracic pressures, hypotension and PEA arrest if not noticed
  • Patients with obstructive lung disease are more prone to auto PEEP
  • Ways to evaluate for auto PEEP include: visualization of incomplete return to baseline of the expiratory flow curve (above), “shark finning” on waveform capnography (EtCO2; 2/2 slower rate at exhaling CO2), and diagnostically & therapeutically disconnecting the ETT from the vent to observe for prolonged exhalation and wheezing.
  • Here's a great Life in the Fast Lane (awesome blog by some ICU/EM docs down under) entry on this topic

PIP and Pplat

  • In a patient with acute alarms for high peak pressures, consider whether this is an airways, compliance or PEEP problem
  • Recall:

    • PIP/ peak inspiratory pressure/ peak pressure ~ flow x resistance + alveolar pressure
    • Pplat/ plateau pressure ~ alveolar pressure ~ volume/ compliance + PEEP
  • PIP is displayed on the ventilator
  • Pplat can be measured via a button on the vent that initiates an inspiratory breath hold (aka flow = 0) to isolate alveolar pressure

  • In patients with only a high PIP and normal Pplat this is most likely an airways/ tubing problem and consider tube kinking, bronchospasm, mucus plugging, and compression

  • In patients with a high PIP and Pplat, consider acute problems with lung compliance/ PEEP including pneumothorax, right mainstem bronchus intubation, worsening effusion

The OHSU library has an e-subscription to the Marino ICU book as a good reference for these topics and more.

Foreign Body Ingestion

Today, Dr. Jason Mannion presented an interesting case of a young male with sickle cell anemia and Cluster B personality disorder who presented with sharp, substernal chest pain concerning initially for acute chest syndrome, but was found on CXR to have swallowed a foreign body.

Learning Points: The diagnostic criteria for acute chest syndrome include:

  • A new segmental radiographic pulmonary infiltrate AND at least one of the following:
  • Temperature > 38.5C
  • A >2% decrease in SpO2
  • PaO2 <60 data-preserve-html-node="true" mmHg
  • Tachypnea
  • Intercostal retractions, nasal flaring, or use of accessory muscles of respiration
  • Chest pain
  • Cough
  • Wheezing
  • Rales

Management of ACS includes: adequate and immediate pain control, fluid management to prevent hypovolemia, supplemental oxygen and IS, blood transfusion, antibiotics, and VTE prophylaxis.

Check out this excellent article in Gastroenterology & Hepatology. The highlights of the article are below:

  • Intentional foreign body ingestion is most commonly seen in adults with intellectual or mental disabilities, significant substance abuse, psychiatric disorders, or external motivations (such as avoidance of a jail sentence).
  • The management protocol of foreign body ingestions depends on the object type, shape, location, associated symptoms, time course, and complications.
  • Treatment should include a multidisciplinary team including endoscopists, surgeons, and psychiatrists.

Primary CNS lymphoma, HIV + AMS

Thanks to Jack Shuler for presenting a great case! And thanks to Joe Shatzel and Sven Olson for coming and sharing some pearls. This is a case of a young MSM male who has a history of HIV presenting with altered mental status and gait instability found to have a new diagnosis of primary CNS lymphoma (DLBCL).

N Engl J Med 2014; 371:447-456

N Engl J Med 2014; 371:447-456

Main Points

  1. ) The gait exam can be extremely useful in the neurological exam. There are several classic gaits to be aware of. See the Stanford 25 page for a great video of Abraham Verghese demonstrating them.

  2. ) The CD4 nadir is useful for prognostication but also a guess at what the CD4 becomes when a patient stops ART.

  3. ) The treatment for CNS DLBCL includes a methotrexate based-regimen since R-CHOP has difficulty penetrating the BBB. It is important to monitor for drug-drug interactions with ART.


Want to learn more?-

HIV associated neurocognitive disorder

This consists of a wide spectrum of conditions from asymptomatic changes to dementia. HIV neurocognitive disorder should be considered as the diagnosis when infections (opportunistic + atypical presentation of common), mass effect, vasculidities, IRIS, and malignancies have been ruled out. Here is a great JAMA article about this.

HIV defining malignancies

Here is a great JCO review article on AIDS defining malignancies which classically includes Kaposi’s, NHL, HL and cervical cancer. However HIV also increases the risk of many cancers (eg synergy with HCV leading to HCC). The thought is HIV invades the immune system and establishes latency in multiple organs which predisposes individuals to developing cancers.

SLE Presenting with Hemoptysis

Today Dr. Bien presented a very interesting case of a young man presenting with hemoptysis and acute respiratory failure in the setting of a month course of fevers, malaise and weight loss. In addition to hemoptysis, exam was notable for developing alopecia, ulcers on the hard palate and a S3. Labs were noted pancytopenia, elevated LDH, elevated CK and hematuria. After exploring the differential for hemoptysis, rheumatologic disorders were highest on the differential. However, his initial ANA was negative. On repeat he had a floridly positive ANA, ant-dsDNA and very low complements (C3 and C4) consistent with systemic lupus erythematosis (SLE) complicated by diffuse alveolar hemorrage (DAH) and myocarditis. The Prozone Effect was felt to be the reason why the initial ANA was negative.

CT scan with lobular GGOs and "crazy paving" concerning for DAH as referenced in the recent case report from Respiratory Medicine. 

CT scan with lobular GGOs and "crazy paving" concerning for DAH as referenced in the recent case report from Respiratory Medicine

1) Hemoptysis can be streaks of blood to gross blood. Massive hemoptysis is defined as 100-600ml of blood within 24 hours. Once you determine that the hemoptysis is coming from the airway (not the mouth, stomach, etc) the differential can be built around the location with a few additions.

  • Airway: bronchitis, bronchiectasis (CF), emphysema, fistula formation, bronchial adenocarcinoma, Dieulofoy lesion, metastasis
  • Pulmonary Parenchyma:
    • Infectious: anthrax, abscess, fungus, parasite (strongyloides), TB, tuleremia, virual (HSV, flu), yersinia
    • Rheumatologic: amyloid, anti-GBM (formally Goodpasture's), Behcet's, collagen vascular disease (Ehlers-Danlos), granulomatosis with polyangiitis formally Wegener's), APLA, SLE
  • Vascular: congential heart disease, heart failure, mitral stenosis, hereditary hemorrhagic telangiectasia, tricuspid endocarditis, pulmonary AVMs, PE with or without infarction, pulmonary veno-occlusive disease
  • Drugs/Toxins: bevalizumab, cocaine, nitrogen dioxide
  • Misc: celiac with idiopathic pulmonary hemosiderosis, catamenial hemoptysis with menses and endometriosis
  • Trauma: blunt force, ETT placement, bronch etc.
  • Coagulation Disorders: DIC, TTP, HUS, vWD

2) ANA is 93-95% sensitive and 57% specific. However, the Prozone Effect is a false negative response resulting from high antibody titer which interferes with the formation of antigen-antibody formation necessary for the positive ELISA.

prozone effect.png

3) DAH is a rare and life threatening complication of SLE. It is traditionally managed with high dose IV corticosteroids first line. Cyclophosphomide use has been associated with improved survival. Plasmapheresis on the other hand shows no difference. Use of Rituximab is up and coming with case reports. For additional reading, see the systematic review from 2015 in the Journal of Clinical Rheumatology and the recent case report in Respiratory Medicine using rituximab.