Managing Cognitive Load to Uncover an Unusual Cause of Syncope: Exercises in Clinical Reasoning
KEY WORDS: clinical reasoning; cognitive load; hyperviscosity syndrome;
J Gen Intern Med
Managing Cognitive Load to Uncover an Unusual Cause of Syncope: Exercises in Clinical Reasoning
Andrew M. Land
Steven A. Haist
Carlos A. Estrada
Erin D. Snyder
0 Birmingham Veterans Affairs Medical Center , Birmingham, AL , USA
1 National Board of Medical Examiners , Philadelphia, PA , USA
2 Tinsley Harrison Internal Medicine Residency Program, University of Alabama at Birmingham , Birmingham, AL , USA
3 University of Alabama at Birmingham , Birmingham, AL , USA
I diagnostic approach (regular text) to sequentially presented n this series, a clinician extemporaneously discusses the clinical information (bold). Additional commentary on the diagnostic reasoning process (italics) is integrated throughout the discussion. CLINICAL INFORMATION A 72-year-old man presented to the emergency department after a syncopal episode at home. For the past 2 months, he had syncope and near syncope with associated generalized weakness, nausea, scotomas, and subjective hearing loss. He sustained multiple falls during the episodes. His symptoms come on without warning, usually when he is changing positions. He did not describe vertigo or dizziness. A month prior, he was prescribed meclizine for these episodes, without any benefit.
Any time I think about a diagnosis with multiple potential
etiologies, like syncope, I try to put possibilities in large and
small Bbuckets.^ For example, the cardiovascular system is
one of those Blarge buckets,^ in which one may find a lot of
different causes of syncope. Some specific diagnoses include
tachy- or brady-arrhythmias, along with etiologies related to
valvular heart disease. Neurally induced causes are another
Blarge bucket^; examples would include situational
micturition and cough syncope. Finally, orthostatic syncope, due to
obstruction or reduction of blood flow, would fall into a third
My next inquiries would include asking about the
circumstances surrounding the syncope and presyncope. For
example, was he urinating; did he exert himself beforehand; did he
have any palpitations? Neurally induced causes such as
vasovagal syncope often have associated dizziness or nausea. I
would also want to know what he was like when he awoke
from his episode.
Syncope carries with it a long differential diagnosis that can
sometimes seem overwhelming as a clinician gets started with
a case. This overwhelming sensation is a symptom of excess
cognitive load when faced with a complex problem.
Shortterm memory, can only hold 5–9 pieces of information at once,
which are then presented to working memory.1 However,
longterm memory capacity is nearly unlimited. Our clinician
quickly deals with the complexity of the problem by utilizing
a schema from his long-term memory to evaluate syncope.
This schema, organizing potential diagnoses into Bbuckets,^
allows him to chunk multiple pieces of information together,
thereby reducing the number of elements that his short term
memory must hold at the same time.2 Each bucket becomes a
separate element that is presented to working memory. The
clinician can then focus on each bucket individually, in order
to get a grasp of the overall problem at hand.
The discussant tries here to gather more information to
better understand this patient’s syncope as cardiogenic or
neurally mediated, so as to know which Bbucket^ is more
likely to hold the correct diagnosis.
He was sitting at the time of the most recent event and
sustained no injuries as a result of his fall. His roommate,
who witnessed the event, saw no jerking or twitching.
Afterward, the patient was mildly confused for 1–2 min
and did not recall the events preceding the episode. During
his prior episodes, he was not urinating, defecating, or
straining. He reported no palpitations or chest pain.
He reported a 40-pound weight loss during the six
months prior to this episode. A month prior, he suffered
a gastrointestinal bleed. A colonoscopy demonstrated
internal hemorrhoids. He had no evidence of malignancy on
either colonoscopy or upper endoscopy.
He has a history of diet-controlled diabetes mellitus,
hypertension, hyperlipidemia, chronic kidney disease
(stage IIIB), anemia from iron deficiency, insomnia, and
long-standing B-12 deficiency. His home medications are
losartan, ferrous sulfate, omeprazole, trazodone, monthly
B-12 injections, and meclizine. He lives with three
roommates locally. He smokes an occasional cigar but
denies alcohol use. He has no known history of coronary
artery disease, heart failure, or cardiac arrhythmia.
Certainly orthostasis from anemia due to his gastrointestinal
bleeding becomes a possibility. Did his syncope precede the
admission for gastrointestinal bleeding? When performing the
physical examination, I would do a thorough cardiac exam,
looking for signs of aortic stenosis, including non-valvular
outflow obstruction. A thorough neurologic exam is also
required in this setting. A focused evaluation directed by the
history and physical exam can be much more efficient and
cost-effective than the diagnostic testing typically
recommended for patients with syncope, as it is expensive and often
Cognitive load theory proposes three types of load; intrinsic,
extraneous, and germane. The complexity of the problem and
the expertise of the problem solver, or learner, are the main
elements that make up intrinsic load. In clinical medicine, one
cannot change the intrinsic nature of the problem presented or
the expertise of the clinician at that time in that particular
area; thus, the intrinsic load is fairly immutable in the short
term. However, in instructional design, an educator may
decide to present a simpler problem in order to reduce overall
The second type of cognitive load is extraneous load, which
is increased by processes that are potentially irrelevant or
superfluous and do not contribute to learning. This load is
related to how the problem is presented, along with other
things that may be distracting during a case presentation
(pagers, other patient needs, lack of sleep). Commonly in case
presentations, a lot of data is provided at once, and the
challenge for the clinician is to prioritize and categorize the
information. Our clinician has already prepared himself for
this with the creation of his Bbuckets.^ This allows him to
manage cognitive load and minimize extraneous load as the
problem is presented.
The final type of cognitive load is germane load. This
describes the working memory processes that are necessary
for acquiring new knowledge, or expanding upon existing
knowledge. The three types of load are additive, and as
working memory is not unlimited, our clinician and his audience
must manage the intrinsic and extraneous load in order to
learn from this case. As the intrinsic load is difficult to change,
clinicians primarily manage extraneous load by avoiding
distractions, thus allowing optimum conditions within
working memory. Similarly, in instructional design, the timing of
concepts and format in which material is presented can
optimize germane load.
At this time, our expert clinician has gathered more
information about the syncope and about the patient himself. This
information, particularly the recent gastrointestinal bleeding,
seems to fit into the bucket for orthostatic hypotension. He has
not forgotten about his other buckets, however, as he plans to
focus on the cardiovascular and neurologic exams.
He also makes no attempt to place into context the
significant weight loss, other past medical history, or medications.
Our clinician has a well-developed schema for diagnosing
syncope, and he is looking for specific details to sort into his
Bbuckets.^ Those details that do not seem immediately
relevant may be tabled, at least initially. This helps to manage his
extraneous load, by initially focusing only on certain pieces of
information provided. Of course, this is also a potential source
of error, if the clinician does not return to all of the information
presented, and place it into context with the physical exam
findings. His schema will help prevent this, as he can return to
each of the buckets to be sure that they have been adequately
assessed to rule in or out the correct diagnosis.
On physical exam, the patient’s vital signs were heart rate of
92 bpm, blood pressure of 157/91 mmHg, respiratory rate
of 18 rpm, and temperature of 97.5 °F. Orthostatic vital
signs were normal. Cardiac auscultation revealed a regular
rate and rhythm without murmurs or gallops. Detailed
abdominal, pulmonary, vascular, skin, lymph node, and
genitourinary exams were normal. His neurological exam
revealed intact strength, normal gait, normal cranial nerves,
and no sensory deficits. He had a normal Romberg test.
Laboratory data on admission were notable for a
hematocrit of 24.6 %, hemoglobin of 7.8 g/dL, MCV of
90.6 fL, BUN of 27 mg/dL, creatinine of 1.9 mg/dL, glucose
of 286 mg/dL, calcium of 9.1 mg/dL, total protein of
9.5 mg/dL, albumin of 2.8 mg/dL, and venous lactic acid
of 5.2 mg/dL. Urinalysis demonstrated 2+ protein. The
remainder of the patient’s basic metabolic panel,
urinalysis, and complete blood count were normal. An ECG was
notable only for sinus tachycardia at 100 bpm.
A magnetic resonance imaging and angiogram of the
brain and neck demonstrated no abnormalities. Similarly,
a carotid Doppler and transthoracic echocardiogram were
There are several findings of interest from the initial laboratory
evaluation, including renal insufficiency, proteinuria, anemia,
an elevated lactic acid level, and elevated protein with
hypoalbuminemia. I would be interested in obtaining information
on his prior renal function, including prior urinalysis and (if
previously performed) a measure of albumin in his urine. As is
often the case, the imaging studies were not helpful; although
the normal ECG and echocardiogram are somewhat
reassuring. I would also suspect that this patient was on
telemetry during the hospitalization, and significant
arrhythmias would have been detected.
An interesting observation is that the gap between the total
protein and the albumin is high. In a 70-year-old, one would
need to consider multiple myeloma, which may or may not be
related to the syncope. I would check serum protein
electrophoresis (SPEP), serum immunofixation and free light chain
assay to further evaluate the protein gap. If results suggest a
monoclonal gammopathy, other valuable studies would
include quantitative immunoglobulins, a bone survey, and a
bone marrow aspiration and biopsy as well as a measure of
Now our clinician returns to the information presented earlier
to place it into context with the physical exam and results of
testing. His initial concern for orthostatic hypotension
becomes less likely in the setting of normal vital signs. The next
consideration, of a cardiogenic etiology for syncope, also
becomes less likely with a normal exam and ECG. Rather
than ignoring these pieces of data that conflict with his
expectations, our expert broadens his differential diagnosis. He is
careful to review all pieces of data, even those that may not
initially seem relevant.
Here, we see the clinician return to his initial schema of
large Bbuckets^ in order to be sure that a broad differential
diagnosis is considered. He reframes the long list of
laboratory values and test results into potential diagnoses, which he
can then sort into each of these buckets as a test for which
might hold the final diagnosis. He notes the renal
insufficiency, elevated lactic acid, and the protein gap. He focuses
particularly on the protein gap in the setting of anemia and
renal dysfunction, which highlights the potential for myeloma.
Lactic acidosis without evidence of hypoperfusion could
suggest malignancy. He is not yet sure how to tie this to the
presenting complaint, but is sure to pursue further evaluation
and look for more information.
Further work-up of the globulin gap was undertaken. An
SPEP demonstrated the presence of an IgM kappa
monoclonal band, with IgM level at 7030 mg/dL.
This information definitely helps. Waldenström’s
macroglobulinemia is associated with a high IgM level. IgM is a
pentamer and is much more likely to cause symptoms related
to hyperviscosity, compared with an elevated IgG of the same
level. This patient has a fairly large IgM spike. Elevation of
IgM levels leads to an increase in serum viscosity, which can
cause neurologic symptoms, often involving the posterior
circulation, including vertigo, hearing loss, blurred or double
vision, and ataxia. Other, more generalized neurologic
symptoms, such as headache, alterations in consciousness, and
seizures, can occur. Less frequently, hyperviscosity can result
in syncope or stroke. These neurologic symptoms of
Waldenström’s would fall into a new Bbucket^ for syncope
as these symptoms are not caused by the cardiovascular
system, neural reflexes, or orthostasis. Instead, slow vascular flow
and anemia contribute to global cerebral hypoperfusion. We
might call this the Bother^ bucket, which could also could hold
diagnoses like polycythemia vera or cryoglobulinemia.
In addition, gastrointestinal bleeding, as seen in this patient,
can be caused by elevated M protein, presumably related to
hyperviscosity in intestinal/colonic small vessels with
associated bleeding or with amyloid infiltration into the intestinal or
Hyperviscosity is a clinical diagnosis, and treatment should
be started without waiting on a test result. However, the
diagnosis is confirmed by measuring serum viscosity.
Viscosity is measured in centipoises, with water being 1.0 and normal
serum being 1.4–1.8 centipoises. My hypothesis is that this
patient had a markedly elevated serum viscosity.
Our clinician utilized the creation of chunks or Bbuckets^ of
potential diagnoses that he could consider in turn, so as to
more efficiently process the information as it was delivered,
allowing him to focus on the pertinent clinical information.
This allowed him to remain facile enough to consider the
protein gap, even though it did not seem immediately related
to the syncope. By following that evaluation to its conclusion,
our expert clinician found a potential diagnosis. Had he been
overwhelmed by excess cognitive load, he may have elected to
defer evaluation to a later setting. Instead, as the results
returned, he compared the data that he had to potential
etiologies, and uncovered a rare diagnosis with overlap
between the two.
Hyperviscosity as an etiology of syncope was not previously
considered by our clinician, but now can be added into his
schema, in a new Bother^ bucket, which also reminds him of
other unusual causes of syncope. Similarly, the learners in our
audience now have a new schema for thinking about syncope,
which can be applied to other cases. As new diagnoses for
syncope are taught, the learners can determine into which
bucket they might fit, or add new buckets as our clinician did.
The cognitive load needed for germane load in this situation is
only available to learners if the intrinsic and extraneous loads
are sufficiently managed.
The patient’s bone marrow biopsy was consistent with
lymphoplasmacytic lymphoma. Serum viscosity was
measured at 8.9 centipoises. Given the clinical manifestations,
bone marrow biopsy, and cytogenetics analysis, the
diagnosis of Waldenström’s macroglobulinemia was made.
The patient was started on plasmapheresis before
beginning chemotherapy with cyclophosphamide, bortezomib,
and dexamethasone. At 6-month follow-up, his symptoms
were improved, and he had not experienced further
syncope or near syncope.
This case highlights cognitive load theory, as it can be applied
to clinical medicine. Cognitive load theory discusses how
working memory is strained by a particular problem, and
outlines three types of load: intrinsic, extraneous, and
germane.3 Intrinsic load relates to the nature of the problem and
the expertise of the problem solver. Extraneous load relates to
how the problem is presented and increases with distractions
from potentially irrelevant information; the vast amount of
laboratory data in the case is an example. Finally, germane
load is the necessary working memory power that is required
for learning. These types of cognitive load may be considered
to be additive, and each learner has a maximum amount of
cognitive load possible that will still give room for the work
required for learning, or germane load, to occur. To give a
different clinical example, a woman with recurrent urinary
tract infections who now presents with fever and dysuria
represents a case with low intrinsic load, as the diagnosis is
not particularly challenging when the patient returns with the
same problem they had before. If the presentation was clouded
with a variety of extra details in history or physical exam, or if
it presented in the midst of a busy clinic day, that would
increase the extraneous load. However, when the problem is
more complex, or the problem solver has less expertise in an
area, the intrinsic load increases, and the clinician must find a
way to reduce extraneous load so that learning can occur.
In this case of syncope, intrinsic cognitive load is high, as
the case is complex. The discussant minimizes extraneous
load by starting with a schema that he has previously utilized,
placing differential diagnoses inside larger Bbuckets^ of
cardiogenic, neurally mediated, or orthostatic diagnoses. He can
then easily Bchunk^ several pieces of information together,
allowing his working memory to treat each chunk as a single
piece. He can return to his larger schema throughout the case
to be sure that he has not forgotten a potential diagnosis or
ignored a piece of data.
This schema also helps to focus his germane load, as he has
a clear system for thinking about new diagnoses related to
syncope, and he can further refine his approach as he learns
more and faces more cases with new diagnoses. By adequately
managing the extraneous load in this case, he has the power
within working memory to learn.
CLINICAL TEACHING POINTS
1. Syncope is a common complaint with a broad differential
diagnosis. One framework for working through this
diagnosis is to group potential diagnoses into categories
of neurally mediated, cardiovascular, orthostatic, or other
2. Waldenstrom’s Macroglobulinema (WM) is an
infrequently occurring B cell lymphoma. It is a lymphoplasmacytic
leukemia, in which there is an overproduction of IgM.4,5
Patients with WM may have neurologic manifestations
either from hyperviscosity or related to direct infiltration
of lymphoplasmacytic cells into the CSF; the latter
manifestations are known as the Bing Neel syndrome.6
Neurologic manifestations include visual and auditory
disturbances, headache, confusion, dizziness, vertigo, and
rarely syncope or stroke.
3. Serum viscosity is measured by comparing the patient’s
serum viscosity with that of water. The result is expressed
in centipoises. About one-third of patients with WM will
have serum viscosity over four centipoises. Almost all
patients will be symptomatic at or above a level of eight
4. Hyperviscosity due to WM is treated with
plasmapheresis to remove IgM protein, followed by chemotherapy to
treat the underlying malignancy. Hyperviscosity should
be treated when patients have symptoms attributable to
hyperviscosity, not purely based on a particular viscosity
Contributor: Dr. Yvette Cua-Ramirez for providing the video of the live
session. Dr. Bob Means for insight into the Bing Neel syndrome and
neurologic sequlae of hyperviscosity.
Corresponding Author: Erin D. Snyder, M.D.; University of Alabama
at Birmingham, Birmingham, AL, USA (e-mail: ).
Compliance with Ethical Standards:
Prior Presentations: The case presented here was presented as a
Clinical Vignette Unknown at the Southern Society of General Internal
Medicine, New Orleans, February 20–22, 2014. The clinical
information and case discussion closely reflect the topics discussed. The case
description was modified slightly for instructional purposes.
Conflicts of Interest: The authors declare that they do not have a
conflict of interest.
Disclosures: The opinions expressed in this article are those of the
authors alone and do not reflect the views of the Department of
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