Tag Archives: MRI

Biden’s cerebral aneurysm

A friend sent me a semi-hysterical rant from a neurosurgeron about the dangers of President Biden’s cerebral aneurysm. Not to worry. This happened in 1988 and was successfully clipped although it ruptured during surgery. The only possible complication at this point is normal pressure hydrocephalus (occult hydrocephalus). That’s a medical mouthful so here’s some background to put it all into context.

If you’ve ever seen a blister on an inner tube, that’s what a cerebral aneurysm looks like. They usually look like a round ball on the side of an artery in the brain. They look nothing like an aneurysm of the aorta. To treat them, one puts a clip around the neck of the aneurysm, so to prevent the pressure in the adjacent artery from bursting it. As Dr. Tom Langfitt, the neurosurgeon who taught medical students, interns and residents at Penn Med in the 60’s said “they’ll stare you down every time”. To put a clip around the neck of the aneurysm you have to jiggle and move it, which may cause it to break. This happened during surgery on President Biden in 1988.

Remarkably, Neal Kassell, the neurosurgeon operating on President Biden was an undergraduate at Penn when I was a neurology resident there in ’67 – ’68. Even before med school (graduating Penn Med in’72) he was vitally interested in neurosurgery and hung around the hospital and would observe Langfitt in action in the OR.

What is there to worry about? Relatively little. It is possible that Biden is developing another aneurysm. One well known complication of a ruptured intracranial aneurysm is something called occult hydrocephalus (or normal pressure hydrocephalus). Blood is extremely inflammatory, and the inflammation can resolve causing scarring (fibrosis) of the linings of the brain. This can impede the flow of spinal fluid.

What are the symptoms? Cognitive decline for one, something that’s been endlessly discussed by pundits, politicians and the voters. The other symptom which even you can look for is difficulty walking, in particular beginning to walk. People with this seem to have feet glued to the floor and have problems initiating walking.

Diagnosis — in Biden’s case, a CAT scan to see if the cerebral ventricles are larger than they should be — https://en.wikipedia.org/wiki/Ventricular_system has great pictures and explanation.

Why not an MRI — because the clips used back in 1988 contain magnetizable material, and entering the strong magnetic fields of an MRI scanning would rip the clips off the aneurysm and kill Biden.

I think the chances of occult hydrocephalus developing 32 years after the aneurysm are remote. If it were going to happen it would have already. In the meantime, watch him start to walk.

Two disconcerting papers

We all know that mutations cause cancer and that MRI lesions cause disability in multiple sclerosis. We do, don’t we? Maybe we don’t, say two papers out this October.

First: cancer. The number of mutations in stem cells from 3 organs (liver, colon, small intestine) was determined in biopsy samples from 19 people ranging in age 3 to 87 [ Nature vol. 538 pp. 260 – 264 ’16 ].th How did they get stem cells? An in vitro system was sued to expand single stem cells into epithelial organoids, and then the whole genome was sequenced of each. Some 45 organoids were used. Some 79,790 heterozygous clonal mutations were found. They then plotted the number of mutations vs. the age of the patient. When you have a spread in patient ages (which they did) you can calculate a tissue mutation rate for its stem cells. What is remarkable, is that all 3 tissues had the same mutation rate — about 40 mutations per year. Not bad. That’s only 4,000 if you live to 100 in your 3.2 BILLION nucleotide genome.

This is so  remarkable because the incidence of cancer is wildly different in the 3 tissues, so if mutations occurring randomly cause cancer, all 3 tissues should have the same cancer incidence (and there is much less liver cancer than gut cancer).

Of course there’s a hooker. The numbers are quite small, only 9 organoids from liver with a relatively small age range spanning only 25 years. There were more organoids from colon and small and the age ranges was wider but, clearly, the work needs o be replicated with a lot more samples. However, a look at figure one shows that the slope of the plot of mutation number vs. age is quite similar.

Second: Multiple sclerosis. First, some ancient history. I started in neurology before there were CAT scans and MRIs. All we had to evaluate the MS patient was the neurologic exam. So we’d see if new neurologic signs had developed, or the old ones worsened. There were all sorts of clinical staging scores and indices. Not terribly objective, but at least they measured function which is what physician and patient cared about the most.

The MRI revolutionized both diagnosis and our understanding of MS. We quickly found that even when the exam remained constant, that new lesions appeared and disappeared on the MRI totally silent to both patient and physician. I used to say that prior to MRI neurologists managed patients the way a hematologist would manage leukemics without blood counts, by looking at them to see how pale they were.

In general the more lesions that remained fixed, the worse shape the patient was in. So new drugs against MS could easily be evaluated without waiting years for the clinical exam to change, if a given drug just stopped lesions from appearing — stability was assumed to ensue (or at least it was when I retired almost exactly 4 presidential elections ago).

Enter Laquinimod [ Proc. Natl. Acad. Sci. vol. 113 pp. E6145 – E6152 ’16 ] which has a much greater beneficial effect on disability progression (e.g. less) than it does on clinical relapse rate (also less) and lesion appearance rate on MRI (also less). So again there is a dissociation between the MRI findings and the patient’s clinical status. Here are references to relevant papers — which I’ve not read —
Comi G, et al.; ALLEGRO Study Group (2012) Placebo-controlled trial of oral laquini- mod for multiple sclerosis. N Engl J Med 366(11):1000–1009.

Filippi M, et al.; ALLEGRO Study Group (2014) Placebo-controlled trial of oral laqui- nimod in multiple sclerosis: MRI evidence of an effect on brain tissue damage. J Neurol Neurosurg Psychiatry 85(8):851–858.

Vollmer TL, et al.; BRAVO Study Group (2014) A randomized placebo-controlled phase III trial of oral laquinimod for multiple sclerosis. J Neurol 261(4):773–783.

It is well known that there are different kinds of lesions in MS (some destroying axons, others just stripping off their myelin). Since I’ve left the field, I don’t know if MRI can distinguish the two types, and whether this was looked at.

The disconcerting thing about this paper, is that we may have given up on drugs which would  clinically help patients (rather than a biological marker) because they didn’t help the MRI ! ! !

Would you be smarter if your mother received different prenatal advice?

Back in the day we worried a lot about the amount of weight a woman gained during pregnancy.  Too much weight gain increased the risk of pregnancy associated hypertension (and worse pre-eclampsia, and even worse eclampsia with fetal and even maternal death).  It also increases the likelihood of pregnancy associated diabetes, with its adverse effects on the fetus.

So when my wife was carrying our two boys, we watched her weight like a hawk (particularly since there was diabetes in her family).  Fellow med students and their wives did the same.

That may have not been so good according to a recent study of birth weight differences between identical twins [ Proc. Natl. Acad. Sci. vol. 109 pp. 11366 – 11371 ’12 ].  To cut to the chase, they found that the bigger twin had a bigger brain and was smarter (by a few IQ points).   It was a big study (139 twin pairs or which 85 were identical — monozygotic if you want to impress your friends).  They only looked at mild levels of weight disparity — the difference in birth weight had to be less than 20% of the weight of the heavier twin.

Greater birth weight resulted in greater  brain volume as shown by magnetic resonance imaging (MRI), mostly due to more cerebral cortex.  Interestingly the cortex wasn’t any thicker in the heavier twin, there was just more of it (the brain was more wrinkled).

Interestingly, the fraternal twins were smarter than the monozygotics by having full scale IQs of 112 vs. 109.  What’s going on? The average IQ should be 100.  However, they excluded twins with IQs under 80, e.g. they only looked at 1.3 standard deviations (which is 15 points) below the mean, while keeping everything above it.   It’s an interesting mathematical problem, which I don’t have time to solve, to integrate the bell curve from 1.3 standard deviations below the mean to all the way above it, and see what the average would be — my guess is that this is why the average IQs are so high.

There is also something called the Flynn effect which you should know about, as long as we’re talking IQ. [ Science vol. 323 p. 989 ’09 ] It was described  nearly 30 years about by  James Flynn of New Zealand.  He noted  that IQ scores rose steadily in the 20th century for children and adults in Western nations.  Using the late 20th century average IQ score of 100, the comparative score for the year 1900 was calculated to 60 — something clearly not true.  Actually the improvements were not in general knowledge or mathematics, but in abstract reasoning.

The conclusions of the PNAS paper seem solid, but behind your back I’ve made several inferential leaps, some of which can be checked fairly easily.  Do bigger babies have bigger brains, and if they do, does this persist throughout life.  Second do people with bigger brains have higher IQs — again the extremes must be cut off — down 2 -3 standard deviations from the average brain size, IQ is way down, and the smaller the brain down here the smaller the IQ.  Similarly with macrocephaly (large brain) — usually there is something wrong.  These are factual matters, whose results are probably in the literature already.

What’s great about the paper is that it controls for heredity, as the genomes of identical twins should be nearly identical — I’m not sure anyone has looked, and given the recent haphazard way our genomes vary between us, it should be.  For details please see https://luysii.wordpress.com/2012/07/31/how-badly-are-thy-genomes-oh-humanity/

The fourth inferential leap, is that bigger birth weight in a twin has to do with better nutrition in utero.  Clearly the bigger twin had more proliferation of cortical precursors resulting in more cerebral cortex.  So maybe your mother should have had a few more fudge cakes and ice creams when she was carrying you.

I don’t know the answer to these questions, but as Mark Twain said :”There is something fascinating about science.  One gets such wholesale returns of conjecture out of such a trifling investment in fact”.