What’s up fellow AMBOSSians! I’m Dr. Zeb with another question walkthrough. Today we’re going to
review an important condition involving recurring neurological symptoms that you need to know for
your board exams. You can follow along by clicking this link to the question, so let’s check it out!
We should start with reading the lead-in to figure out what the question is asking us to do.
“Which of the following is the most appropriate next step in diagnosis?”
Ok, so we’re going to have to come up with a hypothesis of the most likely diagnosis first.
Normally I’d see if the sentence before gives any confirmatory findings, but
because I already know it doesn’t, let’s jump straight to the top to save some time.
“A 30-year-old woman comes to the physician for the evaluation of increasing weakness
and numbness of the upper extremities for 5 days.” So some motor and sensory dysfunction.
“During this time, she has also had urinary incontinence unrelated to sneezing or laughing.”
Ok, this is important to consider in combination with the other neurological symptoms,
as it could be due to autonomic dysfunction or nerve damage.
“She reports that last summer during a vacation in Mexico she had weakness and numbness of her
right lower extremity that was worse when she was outside; she regained her strength 3 weeks later.”
Alright, this is what we’re looking for:
Does she have a history of similar events that had resolved?
What is the main differential I should be thinking of with relapsing motor and sensory neurological
symptoms involving different areas of the body and also urinary incontinence in a 30-year-old woman,
especially if associated with warm weather? That’s right, multiple sclerosis, so MS, a condition
that causes symptoms of demyelination, axonal degeneration, and resulting conduction issues due
to immune-mediated inflammation. In particular, the past exacerbation of neurological symptoms
during her summer vacation could fit the so-called Uhthoff phenomenon, which is a transient worsening
of MS symptoms triggered by an increase in body temperature, as with, for example, hot weather,
a warm bath, physical exertion, or fever. For Uhthoff think “you hot.” Got it?
With that said, MS can be a tricky diagnosis and there are a lot of differentials to keep in mind,
such as neoplasms, acute disseminated encephalomyelitis,
vitamin B12 deficiency causing subacute combined degeneration, or infectious-related etiologies
like neuroborreliosis, neurosyphilis, HIV encephalopathy, or PML. However,
these are generally progressive and not associated with a remitting and relapsing course.
Given their potential recurring nature, we should still consider however other causes of transverse
myelitis, sarcoidosis, vasculitides, and neuromyelitis optica spectrum disorders!
And by the way, you can read all about these conditions and much
more in AMBOSS for free for 5 days with the link in the description.
So let’s read further to solidify our hypothesis.
“She has no history of serious illness. She has had 10 male sexual partners in her lifetime and
uses condoms inconsistently. Vital signs are within normal limits. Examination shows an
impaired tandem gait. There is mild spasticity and muscle strength is decreased in both
upper extremities. Deep tendon reflexes are 4+ bilaterally.” So enhanced with clonus.
“Abdominal reflex is absent.” This is an early sign of MS that is seen in about 70% of patients.
“Muscle strength in the right lower extremity is mildly decreased.
Sensation to vibration and fine touch is decreased over the upper extremities.”
Alright, given the complete remittance between exacerbations of symptoms that correspond to
demyelinating lesions in different locations throughout the pyramidal tracts (so weakness,
spasticity, increased deep tendon reflexes, and impaired gait), the dorsal spinal column (so loss
of vibration and fine touch), and the autonomic nervous system (so urinary incontinence) in
this younger woman, relapsing-remitting MS should be at the top of our differentials.
Now to answer the question, what is the next step in diagnosis?
That’s right, MRI of the brain and spine is the imaging study of choice
for diagnosing and setting a baseline for the monitoring of MS. We would expect to
see multiple sclerotic plaques related to demyelination and reactive gliosis.
These are most commonly found in the periventricular white matter and are
accompanied by finger-like radial extensions known as Dawson fingers.
Since her reported symptoms from last summer were not confirmed clinically to meet the
revised McDonald criteria, and no, this has nothing to do with hamburgers, but is, roughly,
two episodes of central neurological symptoms that occurred 30 days or more apart and involve lesions
in different regions of the CNS, an MRI both with and without gadolinium should be ordered
to confirm the diagnosis. An MRI with gadolinium has the advantage of enhancing active lesions.
With an explanation of the best answer covered, let’s check out the other options to briefly
consider what we can learn or reinforce. As with many board questions, especially for Step 2 and 3,
note that we can’t completely rule out some of these differentials. The exam writers expect
you to differentiate what is most likely. So they are essentially requiring you to
make a clinical judgment call, which actually reflects what you have to do as a physician.
Remember, especially for test purposes, if it looks like a duck,
swims like a duck, and quacks like a duck, it’s probably… a duck.
Or in other words, for diagnostic medicine and especially for board exams,
when you hear hoofbeats, look for horses, not zebras.
But enough with the animal analogies, sorry I was just at the zoo last weekend with my kids, so…
Serum vitamin B12 level would be obtained for suspected deficiency, which can cause
demyelination of the spinal cord that manifests as subacute combined degeneration. This condition
could explain many of this patient's symptoms, such as her sensory abnormalities, muscle
spasticity and weakness, impaired tandem gait, and urinary incontinence. But symptoms of subacute
combined degeneration are generally symmetrical and involve the legs more than the arms. This
patient also doesn’t have a history of a vegan diet or risky alcohol use or any other signs of
vitamin B12 deficiency, such as fatigue, pallor, or glossitis related to megaloblastic anemia.
Antinuclear antibody testing was a very good consideration as it screens for
numerous rheumatic diseases, including systemic lupus erythematosus (SLE)
or Sjögren syndrome, which are important differentials of MS.
Neurologic involvement is common in patients with SLE. However, the very common signs of SLE,
including skin and joint involvement, are not present. Although SLE may manifest
before the onset of other systemic findings, typical findings are cognitive dysfunction,
strokes, seizures, and headaches, none of which are present in this patient.
Sjögren syndrome can manifest with a variety of focal and/or diffuse neurological abnormalities,
for example, impaired motor control, paresis, seizures, or peripheral neuropathy,
making it an important differential. But this patient's primary symptoms became
worse in the summer heat and demonstrated complete remission, which is not expected
with Sjögren syndrome. She also doesn’t report any symptoms of gland destruction,
such as dry eyes or mouth. In addition, most patients with CNS Sjögren syndrome also have
signs of peripheral vasculitis affecting the skin and muscles such as ulcers or pain.
However, in a clinical setting, if a diagnosis of MS was unclear, ANA testing may be considered.
Rapid plasma reagin, or RPR, test is used to screen for syphilis, which is of course more
common in individuals like this patient who don’t always use barrier contraception and can
also manifest with neurological symptoms. A late stage of neurosyphilis known as tabes dorsalis is
also associated with sensory disturbances, impaired gait, and bladder dysfunction.
But these findings typically occur about 20 years after primary infection,
making it an unlikely diagnosis in this younger patient with no history of syphilis. In addition,
tabes dorsalis often presents with paresthesias and signs of lower motor neuron injury,
including diminished deep tendon reflexes, the opposite of her exam finding. Early manifestations
of neurosyphilis also include acute meningitis and ischemic stroke, neither of which are seen here.
Electromyography, or EMG, can be helpful in diagnosing amyotrophic lateral sclerosis, or ALS.
While this patient has symptoms of upper motor neuron injury, again,
she doesn’t have signs of lower mot... lower m... lower bah...
(beep)
Again, she doesn't have signs of lower motor neuron injury like absent or diminished deep
tendon reflexes, flaccid paralysis, atrophy, or fasciculations, which would be expected for ALS.
Patients with ALS also don’t experience symptom remission. We don’t have time to cover all the
differences between upper and lower motor neuron injury in more depth in this video,
but it's very high yield, so I recommend checking them out in this AMBOSS table.
Lumbar puncture was good to consider because it is can help in diagnosing MS!
But it’s first indicated for suspected MS when an MRI is inconclusive. In patients with MS,
the CSF analysis typically shows lymphocytic pleocytosis and oligoclonal bands.
To get the most out of this question,
let’s continue with our reflective practice by briefly thinking about what other questions
we could get for this vignette. The question writers could have asked for:
An expected finding, such as the multiple sclerotic plaques on MRI
or lymphocytic pleocytosis and oligoclonal bands in CSF analysis as we just discussed.
Had they given us confirmatory diagnostic findings, they might have
just gone with a first-order question and asked the diagnosis of MS itself.
Then they could have asked for the best next step of management, which would be?
That’s right, high-dose glucocorticoids such as methylprednisolone for the management of
acute exacerbation. Should that fail, then plasmapheresis would be indicated.
They might have asked what would help prevent this patient’s exacerbations in terms of
long-term management. In this case, there are a number of so-called disease-modifying drugs that
could be correct, including the more high-yield ones of interferon beta, glatiramer acetate,
and monoclonal antibodies such as natalizumab and ocrelizumab. Vitamin D supplementation may
also be beneficial since MS is associated with low vitamin D levels and locations with less sunlight.
Lastly, the vignette could have included many other clinical features like impaired
vision due to optic neuritis (often the first manifestation) or internuclear ophthalmoplegia.
You can strengthen your understanding of these details and many more high-yield
concepts in the Multiple Sclerosis AMBOSS article
So to recap, the key takeaways of this question are:
Suspect MS based on typical relapsing symptoms, separated by time and space,
that correspond to demyelinating lesions in the pyramidal tracts (such weakness, spasticity,
increased deep tendon reflexes, and impaired gait), the dorsal spinal column (so loss of
vibration and fine touch), and the autonomic nervous system (such as urinary incontinence),
especially in a woman of childbearing age. Also, remember visual symptoms due to optic
neuritis or internuclear ophthalmoplegia, as they are often the first manifestation.
Know the diagnostic steps of MS, including confirming with MRI, often with gadolinium,
which shows new and old white matter lesions in multiple areas.
(Clap.)
And that’s it for this question walkthrough! Let me know with a thumbs up if you found it helpful
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I wish you all good luck on your exams. Remember:
hard work pays off, so keep it up and stay positive. You’ve got this!