Rethinking Microvascular Disease

Case courtesy of A.Prof Frank Gaillard, From the case rID: 25641

The image above shows extensive cerebral white matter hyperintensities (WMH). We commonly call this “microvascular disease” with the notion, implicit or explicit, that they are caused by the usual vascular risk factors of hypertension, diabetes, dyslipidemia, etc. This past January, Dr. Joanna Wardlaw, receiving the the William M. Feinberg Award for Excellence in Clinical Stroke, delivered a very interesting lecture arguing against this. Citing evidence that less than 2% of the variance in WMH burden is attributable to the usual risk factors, she advanced several other possibilities. One is that the findings are due to blood-brain barrier disruption, allowing water to leak into the perivascular space. Other associations / possible contributing factors include increased arterial pulse pressure and decreased vascular reactivity. She goes on to show that the lesions aren’t always permanent and she describes some promising treatment modalities.

It’s an informative article, and I recommend it in particular because it forces us to get back to basics in a few ways. First, this common and sometimes vexing problem of WMH serves as a reminder that clinical, radiological, and pathological diagnoses are not identical. A stroke is a clinical event. A focus of restricted water diffusion (high DWI signal) is a radiological finding. An infarct is a pathological finding. Conflating these, such as by saying, “We saw the stroke on MRI”, can lead to misdiagnosis, since not everything that appears bright on DWI is an infarct. And even if the lesion seen on MRI is an infarct, it may or may not be the cause of the patient’s presenting symptoms. That’s why residency training programs (should) emphasize the traditional neurological formulation: First, frame the problem succinctly (e.g., “This is an elderly woman presenting with the sudden onset of left hemiparesis”). Second, localize the lesion. Third, develop a differential diagnosis. Having the formulation clearly in mind will guide both the selection and the interpretation of imaging and other diagnostic testing.

Further, Dr. Wardlaw’s paper provides an impetus to review the classic literature on the subject of microvascular disease. As she states in her talk, “Reading original observations is always valuable because subsequent interpretations may drift from the original over time”. In this case, the must-read papers are by C. Miller Fisher, who, in the 1950s and 1960s, painstakingly made thousands upon thousands of ~ 10 micron thick sections of autopsied brains, starting at the “softening” (lacunar infarct) and tracing the feeding vessel back to find the point of occlusion. One was not always apparent (present in 45/50 lesions in his classic, “The Arterial Lesions Underlying Lacunes“). Most occlusions were caused by what he termed “segmental arterial disorganization”, and he noted that “Others have termed this condition hyalinosis, angionecrosis with aneurysm formation, plasmatic destruction, fibrinoid necrosis, fibrinoid arteritis, etc.” It’s a great paper–I highly recommend it.

Other classics by Fisher include:

Posted in Uncategorized | Tagged | Comments Off on Rethinking Microvascular Disease

Reclaiming the Medical Record

Electronic medical documentation is horrendous. Notes are usually very light on narrative regarding the patient’s illness and the physician’s assessment thereof. I’ve read more than a few that have almost none at all–just page upon page of data copied from one part of the electronic health record into another part of the record. These notes serve several constituencies–payors, quality analysts, regulatory bodies, attorneys, etc.–but not clinicians. I think a big reason that electronic record-keeping drives burnout is that it shifts the work of documentation from an important, but small, part of the physician-patient relationship into, arguably, the central part. We no longer write notes to remind ourselves later of what the exam showed, or to clearly explain our assessments to referring physicians. Instead, we’re now in the business of note construction. Note construction is very, very different from note writing; the former is highly laborious and dissatisfying.

I will say, however, that we bear a little of the blame ourselves. It’s not necessary, for example, to copy the entire HPI from the admission H&P into the discharge summary. I’ve seen many d/c summaries where the “Hospital Course” is actually 80% HPI and only 20% about what happened thereafter. That is absurd; we have to get our own house in order too.

Anyway, here’s a little essay on this topic from an executive with the American College of Physicians. The website is one of the messiest I’ve ever seen, but the essay is worthwhile. (“The bottle was dusty, but the liquor was clean . . .”)

Posted in Uncategorized | Comments Off on Reclaiming the Medical Record

Empathy: Peds Neurology Edition

I have mentioned before that I often find patients’ writings about their neurological conditions to be quite valuable. Reading them can be humanizing, and at the same time efficiently augment one’s clinical knowledge. For example, every resident will have a case where NMDA encephalitis was on the differential; many will see a case. But reading a personal narrative about one’s experience with the disease can really sear it into your memory.

Here’s a short New York Times piece about a pediatric neurology resident’s reflections on her experiences as both a person who’s suffered a neonatal stroke and as a physician needing to counsel families about the condition. It’s a short read, but I think worthwhile.

Posted in Uncategorized | Tagged | Comments Off on Empathy: Peds Neurology Edition

Podcasts of Note

Good news: Subscriptions to Continuum now include access to the accompanying podcasts, and they are excellent. They consist of 10-15 minute interviews by prominent neurological educators such as Dr. Ralph Jozefowicz with the author of each chapter in the issue. These provide a concise summary of each topic and allow those who have difficulty finding time to read the issue to digest the content. Bad news: The only way to access the content is via the Continuum or Audio Digest app. The app is a bit frustrating at times, for example signing you out seemingly randomly. I do like the brief written summaries of each interview, which boils the chapter down even further to its essentials. There are a couple of pre- and post-test questions; answering them and a brief survey allows you to claim CME credit (irrelevant to residents, but useful for the rest of us). Overall, I find this a useful way to keep up with Continuum, especially the issues that I don’t want to read deeply but just want to sample.

I was recently reading something about lipid metabolism and atherosclerosis and stumbled upon Dr. Peter Attia’s podcast, The Drive, where he has quite a few episodes on that topic. Dr. Attia has an interesting bio–his training is in surgical oncology, but it appears that at some point he re-oriented towards the study of metabolic health as it relates to longevity and well-being. I’m plus / minus on the overall genera of performance optimization and the quantified life, but I found some of these to be informative, digestible refreshers on topics learned early in medical school. They may not be of interest to every neurologist, but they’re certainly pertinent to stroke and arguably other areas such as dementia. Poking around Dr. Attia’s blog, I also found a bunch of posts on clinical trial design and other topics that would be of interest to neurologists. Here are links to some of the podcast episodes I enjoyed:

I should include a caveat here, which is that some of the ideas discussed are a bit outside of the mainstream. For example, the just-released lipid guidelines from the American College of Cardiology aren’t quite on board with the conclusion that LDL particle concentration (LDL-P) needs to be measured in every patient rather than, or in addition to, LDL cholesterol concentration (LDL-C). I do think there’s a compelling case to be made that it is indeed the number of circulating atherogenic particles that most directly drives plaque formation, but the extent to which there is discordance between LDL-C and LDL-P is a matter of controversy; my understanding is that it’s more of an issue in patients with the metabolic syndrome. On the other hand, that population is growing rapidly . . .

I think some of the variance between the guidelines and the views of particular experts may be attributable to their target populations. The guidelines need to account for the additional cost of testing for biomarkers such as LDL-P, ApoB, Lp(a), etc. and the extent to which they improve health in the broad population of primary care patients. Dr. Attia has botique practices in San Diego and NYC, where I hypothesize that he cares for many like-minded patients–those who are very interested in the fine details of their metabolic profiles, optimizing their risk modification regimens, and willing to pay out of pocket for such. Eventually, of course, the hope is that such precision medicine will become fully-validated and deployed to the entire population.

Finally, longtime readers may recall that I have an interest in the psychology of decision-making. Kahneman, Slovic, and Tversky’s Heuristics and Biases: Judgment under Uncertainty is a volume I keep on the shelf, and many people are familiar with Prof. Kahneman’s more publicly-oriented work, Thinking, Fast and Slow.

Recently, Prof. Kahneman was interviewed by the economist Tyler Cowan on his excellent podcast, Conversations with Tyler. One of the main themes in this conversation was the difference between bias, which was a major focus of the books mentioned above, and noise. Concluding that your patient has Ménière’s disease rather than a posterior circulation stroke may be due to a representativeness bias, which I’ve written about before. Rendering an incorrect diagnosis because you failed to take a complete history because you were hungry is an example of noise.

They also talk about artificial intelligence, the replication problem in medicine and psychology, and other interesting topics. I like Cowan’s style–he’s a no-nonsense interviewer and I enjoyed many of his other interviews as well.

Posted in Uncategorized | Comments Off on Podcasts of Note

New Links for the New Year

It’s been a long hiatus, and I’m finally trying to catch up with some things I wanted to post on the blog. To start, I re-organized the menu a bit and added a bunch of links that may be of interest:

Under General Medicine is a link to the Stanford Medicine 25 video series. It’s a set of videos that demonstrate various aspects of physical examination–cardiac, pulmonary, musculoskeletal, neurologic, etc.

Under General Neurology is a link to a more in-depth treatment of the reflex exam by Dr. Abraham Verghese. It includes an overview of the kinds of hammers and their histories in addition to technical tips. Many of you will recognize Dr. Verghese as the Stanford internist who authored Cutting for Stone–a beautifully written novel about life, loss, medicine, and reconciliation, set in Ethiopia and New York. I highly recommend it for my own residents taking our global health elective in Addis. While I’m on this tangent about Dr. Verghese, I also recommend an essay he wrote about a decade ago, titled Culture Shock–Patient as Icon, Icon as Patient.

Also under General Neurology is a link to Neurosigns, a Wikipedia-like site with a bunch of entries on neurological exam findings. The most recent entry, for example, is on myokymia; it includes a short embedded video of this in a quadriceps muscle with an EMG needle inserted. Neurosigns is a creation of Dr. William Campbell, who has had a long career in academic, military, and private practice. Among several other books and many articles, he is the primary author on the most recent editions of the classic DeJong’s the Neurologic Examination. It’s actually Dr. Campbell who recommended some of these links that I’m writing about here, so I’d like to extend my thanks for the helpful recommendations.

Dr. Josiah just gave us a very nice grand rounds on functional neurological disorders and I’ve added the links she had on one of her slides to the relevant sub-menu under Neurological Disorders. I read through a bit of each of the sites and found the information mostly reasonable / potentially helpful for patients. I do, however, question the advice on the FND Hope website that “Patients experiencing neurological symptoms should receive therapeutic doses of B-12 until symptoms are no longer responsive and/or test result is below [I assume they mean above] 550.” Really? Every patient with “neurological symptoms” needs B12 shots?

Finally, I added, again at Dr. Campbell’s suggestion, a link to the Canadian Neuro-Ophthalmology Group. Their website has an embedded textbook and a bunch of teaching cases.

Happy reading!

Posted in Uncategorized | Comments Off on New Links for the New Year

The Origin of the DNR Order

By MTSOfan on flickr; click for original

I recently came across an interesting podcast interview with Dr. Mitchell Rabkin, a distinguished internist and former president of Beth Israel Hospital. The interview was conducted in the context of the 40th anniversary of his landmark paper, Orders Not to Resuscitate. Dr. Rabkin discusses the historical context–how medicine was practiced in the 1960s, when he was a resident at MGH–along with the development of DNR orders and the ethical discussions (and lack thereof) surrounding it.

Neurologists are often called upon to prognosticate with the intent to use our assessments to justify, if not a transition to comfort-oriented cares, at least implementation of DNR orders. Occasionally, there is pressure to render a grim prognosis when prudence would require acknowledgment of a bit more uncertainty. I liked this interview because it serves as a reminder that medical practices change dramatically over time–what we take for granted today was once novel. This perspective can be helpful when navigating the challenging clinical and ethical situations that arise in our specialty.

The video interview (41 min), along with a transcript and podcast link, can all be found here.

Posted in Medical Knowledge | Tagged , | 1 Comment

Novel Research Methods

Here’s two interesting articles I’ve been saving up, both on the theme of studying the brain from an unusual perspective:

1. Could a Neuroscientist Understand a Microprocessor?

This is a fun and controversial (among neuroscientists) paper. The authors reverse-engineered an old microprocessor–the ones used in the Atari Video Game System and the old Apple 1 and Commodore 64 computers and then subjected it to various investigations such as “lesion studies”, connectomics, and tuning properties of the type commonly used in neuroscience. The “behaviors” being studied were whether the system would successfully boot up Donkey Kong, Pitfall!, or Space Invaders–very old friends of mine. Their premise is that their model system is one in which they know with perfection the electrical state of every transistor and the entire pattern of connections (its “connectome”). They were unable to predict the behavior of this perfectly-understood system using neuroscience methods, and raised the question of whether that has any implication for the validity of contemporary methods in neuroscience research, such as the study of EEG spectra, fMRI, etc.

2. To Unlock the Brain’s Mysteries, Purée It

This is a New York Times piece about Suzana Herculano-Houzel, a Brazilian neuroscientist now at Vanderbilt. She had the brilliant idea to ascertain the number of neurons and glia in brains not by counting them up on small histological slices, but by puréeing them, staining the neuronal and glial nuclei with different stains and counting the nuclei. She thereby arrived at very different estimates about the number of neurons and glia than was previously reported, and she has interesting ideas about brain size and neuron counts in humans vs. other animals.

Posted in Medical Knowledge | Tagged | Comments Off on Novel Research Methods

Humanism in Neurology

Whenever I find myself growing grim about the mouth; whenever it is a damp, drizzly November in my soul; whenever I find myself involuntarily pausing before coffin warehouses, and bringing up the rear of every funeral I meet; and especially whenever my hypos get such an upper hand of me, that it requires a strong moral principle to prevent me from deliberately stepping into the street, and methodically knocking people’s hats off—then, I account it high time to get to sea as soon as I can.

—Ishmael, Moby-Dick

Or, if one happens to be a neurologist feeling mired in ACGME, GMEC, TJC, LCME, OSCE, and other such things, it’s high time to reconnect with the humanistic aspects of our venerable specialty. I recently came across an oldish (2001) “special article” published by the AAN’s Ethics, Law, and Humanities committee: Humanistic Dimensions of Professionalism in the Practice of Neurology. This short paper is well-worth reading; it might even count as a “wellness activity!” Below I’ve quoted a few choice passages (emphasis added):

To encourage neurologists to resolve time pressures in their patients’ favor, and to help dispel the false and destructive notion that humanistic practices are now expendable inefficiencies, the AAN Ethics, Law, and Humanities Committee here summarizes humanistic professional attributes we consider intrinsic to good neurologic practice.

1. Developing an understanding of the complex and elegant workings of the human nervous system in health and disease.

3. Appreciating the necessity to approach the whole patient, rather than focus exclusively on what ostensibly is the “presenting” problem.

4. Recognizing that understanding the patient’s narrative—as told by the patient or, if necessary, by others—is essential to successful treatment. The neurologist should strive to understand the inner experience of patients, the meanings they attach to illness, and their personal values.

5. Appreciating that a precise and detailed neurologic examination personally performed can create a strong bond between patient and doctor.

6. Remaining sensitive to the perceptions of neurologic disorders that exist in the minds of patients and their families. Patients and families often respond with dread and a sense of helplessness to the disability produced by these disorders, and their uncertain implications for the future.

10. Understanding that neurologists should play a pivotal role in defining and administering high-quality palliative and end-of-life care.

Coincidentally, with respect to that last point about palliative and end-of-life care, ” . . . the AAN has decided to retire its 1998 position on ‘Assisted suicide, euthanasia, and the neurologist’ and to leave the decision of whether to practice or not to practice LPHD [lawful physician-hastened death] to the conscientious judgment of its members acting on behalf of their patients. The Ethics, Law and Humanities Committee and the AAN make no attempt to influence an individual member’s conscience in consideration of participation or nonparticipation in LPHD.” Here’s the link to this new position. I’m thinking that this topic would make for an excellent journal club: Is physician participation in hastening death indeed humanistic?

Let’s not end on a heavy note, however. Each year, the AAN gives out an Award for Creative Expression of Human Values in Neurology.  This year’s winner is a former mentor of mine, Dr. Madaline Harrison at the University of Virginia. She wrote a sweet essay, The 9 o’clock patient, that nicely shows her understanding not only of her patients’ neurological conditions, but also of their relationships and sources of meaning in their lives. Some of my other favorites from this past year follow:

Posted in Interpersonal and Communication Skills | Tagged | Comments Off on Humanism in Neurology

A Claw (Hand) by Any Other Name


By Photo: Myrabella / Wikimedia Commons, Public Domain,

A timely Christmas blog post! At an MS2 session yesterday, we discussed the following practice question:

Blunt trauma to the elbow may lead to the development of:
a) Wrist drop
b) Weakness of the abductor pollicis brevis
c) Claw hand or benediction sign
d) Ulnar deviation of the hand
e) Poor pronation of the forearm

There ensued a somewhat confusing (because of my own confusion) discussion of what exactly is a benediction sign, is it different from a claw hand, what specific muscles are involved, etc. We’ll take a deep dive into that below, but first let’s just address the test question itself.

Blunt trauma to the elbow will most often injure the ulnar nerve. The ulnar nerve lies in a little groove between the medial humeral epicondyle and the olecranon. Partially flex your elbow to stretch the nerve a bit and then run your fingers in there and tap on the nerve; you’ll feel a little zinger in the medial hand. The median and radial nerves run deeper in the arm and aren’t typically injured by minor elbow (“funny bone”) trauma. So, we know that we’re looking at the answer choices for an ulnar nerve lesion.

When caused by a peripheral nerve lesion, wrist drop is due to injury of the radial nerve, so a) is out.

Abductor pollicis brevis is innervated by the median nerve, so b) is out.

Ulnar deviation of the hand (most apparent upon attempted flexion at the wrist) would also be due to a median nerve injury. Why? In a (proximal) median nerve lesion, there is unopposed action of flexor carpi ulnaris (ulnar nerve), pulling the wrist medially / to the ulnar side. In contrast, an ulnar lesion would result in unopposed action of flexor carpi radialis (median nerve) and would pull the wrist laterally / to the radial side. Thus, d) is out.

Finally, weakness of pronation is also a median nerve lesion, because pronators teres and quadratus are from the median and anterior interosseus nerves, respectively (the latter is a branch of the former). So that rules out e), leaving the answer as c) Claw hand or benediction sign.

So now let’s talk about the claw hand: Continue reading

Posted in Medical Knowledge | Tagged | 2 Comments


I’ve always had a place in my heart for pathology—the fundamental basis for allopathic medicine. By this I mean that in diagnosing and treating disease, we’re concerned with the structure and function of the body’s organs and systems, their pathological disruptions, and the biochemical and genetic bases for such. I don’t mean to downplay the importance of patients’ emotional experiences, existential challenges, family dynamics, and other personal and social aspects of health and disease; these are important too. But what we are not concerned with is balancing the four humors or regulating the flow of qi.

Even in psychiatric practice, one of the first tasks in any diagnostic evaluation is to rule out an “organic” cause of the patient’s mental or behavioral dysfunction. This raises extremely interesting questions about structure-function relationships in the brain—is there truly a difference between “organic” and “psychiatric” disease, or is the latter just a brain disorder where the underlying structure-function relationships haven’t been fully elucidated? These sorts of questions are in part what drew me, and many others, to neurology, but that’s a topic for another day.

The bottom line is that if one is going to diagnose and treat disease in the allopathic paradigm, one must have at least some grasp of pathology. I actually spent a year as a pathology “fellow” between my M2 and M3 years and can attest that it was very helpful in understanding the diseases I later saw on the wards. There’s a huge difference between say, reading about congestive heart failure vs. actually squeezing with one’s own fingers the edema fluid from the lungs of a deceased CHF patient, or feeling and hearing the scalpel scrape and cut through his atherosclerotic coronaries. Similarly, directly inspecting a brain’s purulent meninges, its atrophic gyri, its depigmented midbrain, its foci of infarction, etc. brings a greater depth of understanding than simply reading about these conditions or viewing the pathologies on MRI.

To that end, I want to encourage residents to take advantage of learning opportunities in neuropathology. At our institution, we’re fortunate to have a neuropathologist with over 30 years of experience teaching residents. He has dozens of gross “museum cases” and clinico-pathological case reports and hundreds of slides, all with accompanying explanatory material for self-study. And we have brain cutting twice each week, which also serves as a reminder that we should refer our deceased patients for autopsy when appropriate—again, MRI doesn’t have all of the answers.

The specific purpose of this post is to bring to the residents’ attention an outstanding web resource for neuropathology. It’s an online textbook / lecture series / self-assessment tool developed by Dr. Dimitri Agamanolis of Akron Children’s Hospital and Northeast Ohio Medical University. The meat of it is a series of chapters on neurocytology, hypoxic / ischemic injury, CNS infections, demyelinating diseases, etc. Most of the chapters have an embedded video lecture that’s also accessible on Vimeo, but the material can be perused by reading alone if desired. Clicking on the thumbnail photomicrographs reveals enlargements with detailed captions. Most chapters have an associated quiz, and I think that working through all of the chapters and all of the quizzes would be great preparation for the RITE and boards. This is a very high-quality resource that Dr. Agamanolis has graciously published to the web for free; I wish to extend to him my thanks!

(I added a link to the site in the main menu above, under Clinical Neurology Resources→General Neurology).

Posted in Medical Knowledge | Tagged , | Comments Off on Neuropathology