Thursday, October 1, 2015

Sleep Murder..... A Sleep Entry For the Month of Halloween

A very disconcerted patient of mine sent me the above clipping. She has Parkinson's Disease and REM Behavior Disorder (RBD) as a part of her symptoms overall. And now this sweet, older woman is terrified that she is going to "sleepwalk strangle" her grandchildren when she babysits. When she babysits her grandchildren overnight, she has come up with an ingenious solution and wants my approval: She plans to lock herself in her master bedroom at night, and her husband of 50+ years will sleep in the guestroom outside the locked room in case the grandchildren needed something in the middle of the night. She has asked my approval of the overall plan's logistics and on the specific sliding bolt lock she has found at Home Depot and whether she will open this lock in her sleep (versus an alternative combination lock-bolt system she found). 

I felt very bad for her situation, or her perspective, rather. 
I was trying to imagine this future situation where "scary" grandma locks herself in her room at night as though she were a werewolf or some other Wes Craven creature of the night. Definitely something more frightening than my grandmother's pantry of eternal cookies. 

First of all, parasomnia is the term for abnormal sleep behavior in all its forms (other than things like epileptic events and movement disorders, etc... which aren't really called behaviors). We are referring to complex motor events resembling what someone might do while awake. Parasomnia literally means "next-to-sleep," like paranormal means "next-to-normal" or in this case, behavior outside of normal sleep behavior, or in the latter, something happening outside of the normal. Parasomnia come in two broad flavors: NREM and REM parasomnias. Either you do this during non-dreaming sleep (NREM sleep), or while you're dreaming (REM sleep--Rapid Eye Movement).

The actual prevalence of all parasomnic behavior happening sometime over a lifetime (ALL SPECTRUM AND FORMS OF BEHAVIOR, from soft mumbling to eating a stick of butter or driving a car) is quite variable, as high as 67% of the population in some studies, so it's relatively common. Actual lifetime sleep walking behavior is as high as 22% and at any given time affects 1.7% of the population, which is heavily skewed toward kids who make up a majority of these walkers. More complex behavior like eating in one's sleep (4.5%) and sexual behavior (7%) is relatively rare and more likely in the adult population. 

For self-injurious behavior, the current prevalence in the population is only 0.9% and injuring someone else is only 0.4%.  And of all self-injurious behaviors and injuries to someone else, almost 99.99% of reported incidents involved accidental quick punching out/thrusting out/kicking out/falling off the side of bed/tripping on something in one's sleep, or other such simple, abrupt, relatively non-complex behaviors. AND, these latter, injurious-type behaviors are more common in person's with co-morbid psychiatric disorders such as active depression, anxiety, PTSD, etc. which skews the probability this direction. 

So I reassured the patient that probability is in her favor, since her grossest probability of even attempting the type of aggressive behavior she is concerned about is 4 x 10 to the negative 4th power in logarithmic terms, and there is lots of wiggle room for poor math which would push the probability to even lesser degrees. Even if we use this number, she still would have to attempt this behavior without the child waking up and waking her in the process; have to negotiate her house without accidental self-injurious behavior in the process such as tripping or bumping herself awake; not wake her likely curious husband while getting up; and assume that she will have a directed effort again the children as opposed the man with whom she's had 50+ years of marital arguments with. And... we are treating her with medication, since parasomnias are treatable, so she would have to fail this too. 

No, I think they are quite safe. But I still thought you might find this interesting all the same.

Thursday, May 8, 2014

Do Statins (anti-cholesterol medications) Cause Nerve Damage or Muscle Damage?

A patient of mine brought this in and I thought it should be shared because I field questions about it all the time.

 The summary of the question/answer article above is essentially: 
My primary care doctor put me on a statin medication. My cholesterol improved but was replaced with "peripheral neuropathy" in my fingers & toes to the point that I had difficulty gripping things. The primary doctor and one of my fellow neurologists reportedly found no cause, and told the patient suck it up (but hopefully in a more eloquent manner). The patient stuck to their guns, and with their doc's blessing, tried a few weeks off the statin with rapid improvement of the numbness.

Peripheral neuropathy is not a specific term. It literally means, "pathology of the nerve," or "nerve-something-wrong-with." You can imagine that coming to your doctor with that complaint is inherently ambiguous, even if your concern is specifically troublesome. 

The hard part is that "peripheral neuropathy" causes in people of an age advanced enough to start statin medications (as opposed to, say, an 8 year old with neuropathy), is a very long list. I started counting truly unique potential causes in one of my neuropathy textbooks here in my office (yes, I have multiple 300+ page textbooks dedicated to neuropathy alone), and stopped when I hit over 101 causes, because I kept wanting to read about some of the more esoteric causes and the digressions were eating into my other work responsibilities.

So, because a statin-relationship to neuropathy is actually rare, and the other common and not-so-common causes as a group much more likely, it is relatively easily to miss this tree among the forest of other potential causes. 

But to expand the statin concern:

Statins currently include simvastatin, atorvastatin, pravastatin, fluvastatin, lovastatin, pitavastatin, and rosuvastatin, commonly known respectively as Zocor, Lipitor, Pravachol, Lescol, Mevacor, Livalo, and Crestor, with the bold ones most commonly seen by me in my patients.

They ALL inhibit an enzyme Beta-hydroxy-Beta-methylglutaryl-CoA reductase which is essential in the formation of cholesterol. It is already well established that they can cause myalgias (muscle pain & tenderness) and myopathy (actual muscle breakdown & weakness), and this is one of the reasons someone would be switched from one of these to another. Sometimes multiple ones have to be tried before a "good" one is found that both lowers one's cholesterol and doesn't cause significant myalgias or myopathy.

More controversial, however, is the potential claim of toxicity to the actual nerves. Some studies show a definitive effect in people and many studies do not. And the question is whether it is direct or indirect. For instance, we know that eating lead paint or being exposed to frostbite causes DIRECT damage to nerves. But with statins, we know that some/many people have some slight increase in their triglycerides, and we know that other people with unusually high triglyceride levels can have damage to their nerves from that... so is the cause in some people indirectly through the slight bump in triglycerides? Who knows--no one for sure yet.

If you undergo a nerve conduction study (NCS) to characterize the neuropathy, the type of neuropathy is usually an axonal sensorimotor neuropathy (which, by the way, also includes such common causes as thyroid disease, B vitamin deficiencies, other medications, diabetes, too much alcohol, HIV, kidney disease... lots of stuff essentially). 

Just to make things harder, the onset of neuropathy if actually due to the statin medication, can start 1 to 7 years AFTER starting and continuing the medication, so think of what other things can enter someone's life over that period of time. BUT the good news is that it should resolve or improve dramatically and relatively quickly after you stop the medication.

So what does all this mean? It means that IF you get a neuropathy, and IF it is the specific kind which RARELY CAN be associated with statin use, then if you aren't in desperate need of uninterrupted statin therapy because you've had a heart attack or stroke or are teetering on the cusp of one, then, WITH YOUR PRIMARY DOCTOR'S BLESSING, you could try to come off the statin for 2 to 3 weeks, to see if things improve before wading into the deeper waters of more exotic workup of causes.

Tuesday, May 6, 2014

Migraineurs have a different intracranial vascularity than people who don't get migraines.

This study, while interesting, told neurologists something already known, or at least strongly suspected by most. It does support, however, our thoughts that there is a significant vascular cause behind migraines, and especially some of the asymmetry associated with them. We knew it was true at the microscopic and less-microscopic level, but this little study supported the suspicion at even the larger-vessel suspicion as well.

What is the Circle of Willis? Below is a picture of it by itself and what it looks like perched on the underbelly of the brain. In summary, you have four main arteries coming from the heart to supply the brain. The two in front are the carotid arteries and the two in back are the vertebral arteries. The Circle of Willis is essentially the anatomy of how these "trunks" branch into the various recesses of the brain.

In this picture, the Internal carotid artery on one side is labeled, and the Vertebral arteries are NOT labeled but you can see them at the very bottom, joining together as an upside down "V" to make the labeled Basilar artery.

Now, this study was unique in that it looked at these larger vessels for differences in anatomy between different types of migraine patients. As I was saying before, what neurologists have always known however is that that the tiny branches everywhere from a tenth of mm in size (smaller than this period:  .  ) to a mm in size (about the width of this n)-- that these billions of blood vessels that imbue every nook & cranny of your brain are also different by design in some manner, and more likely to show some damage at a greater frequency than other people just like you who don't have migraines. There is something different about a migraineur's brain vasculature. That being said, there are numerous studies (especially in the psychology and psychiatric journals) showing that there is no long-term negative cognitive changes (thinking problems) associated with these small vascular changes, and many non-migraineurs ALSO have this same thing to some degree or another but for other reasons.

Anyway, if you have migraines and you have an MRI showing something like "non-specific T2 changes," or "subtle white matter changes consistent with small vessel disease," or the like, you should know it is a relatively common finding, is a relatively underwhelming finding, not associated with any changes in thinking, and that this below is often what it looks like:

The two white spots toward the front on your left (perhaps a subtle third spot just above can also be seen)

Sunday, March 30, 2014

Melatonin for High Altitute Sleep.... What can we down here learn from it?

This was presented at the 27th annual meeting of the Associated Professional Sleep Societies LLC (June 4, 2013), as an abstract, also published as an online supplement in the journal SLEEP.

The official title of the abstract was
“Melatonin as a countermeasure to the effects of high altitude on sleep and cognition on North America’s highest peak,”

The study only involved 13 people (climbers). 2 were women.
Average age: 34
The were climbing at14,200 feet on North America's highest peak, Denali, in Alaska.
Keep in mind that 140 MILLION people live among 8,000 feet and many ski resorts in the contiguous United States have people skiing precariously on them greater than 10,000 feet.

They each were given melatonin or placebo on 2 consecutive nights. Neither they nor the person who gave them the pill at that time knew which night they were getting the melatonin versus the placebo, so they couldn't "predict" how well they should sleep or perform the next day on a test.
They took the medication 1.5 hours before bed.
They wore a wireless sleep monitoring device (polysomnogram) to help judge how much they slept.

The amount of time they slept was judged, as well as how they performed on the Stroop test the next day.... as a hopeful, indirect sign they actually got more sleep and would therefore have better cognitive acuity as a result.
-On average they fell asleep in 20 minutes (with melatonin) versus 44 minutes with placebo. They also had less wake after sleep onset time.
-The next day they also performed better on the Stroop test, which is a mark of reaction time, judging how fast one can correctly name a series of colors who's name (in word form) is different than the color you are to name. There are other variations on this test as well.


Things I believe you should take away from this study:
-Melatonin should be taken not just before bed (as many people are tempted to do) but at least 1.5 hours before bed.
-Melatonin helps with sleep solidarity and time to sleep onset, and does so without being a prescription, without as many side effects of the prescription sleep aids, and without the reliance & habituation which can come from regular prescription sleep aid use.

Things this study doesn't tell you:
-What dose will work for you personally
-Melatonin works best if you take it EVERY night at the SAME TIME before bed as part of regular pre-sleep ritual. Melatonin does not work like Ambien/Sonata/Lunesta, etc. Melatonin encourages the orchestra of sleep, but by itself cannot force sleep.You really need to use it regularly for some period of time to see a more robust positive & sustained effect.
-Whether other supplements could be just as effective or was it specific to melatonin's affect on a specific location within the brain or because of its affects on the circadian rhythm

Problems with the study: 
-It might lead someone to believe, erroneously, that the medication could or should work one night at a time, when melatonin is NOT designed to be a "rescue" medication.
-The wireless sleep study hardware/software could only offer a limited assessment. It was not as good as in-lab study, and it may be missing some key information.
-These were fit 34 year-olds... We don't know what type of implication the medication would have for older or younger people...
                       ...or people who snore or have apnea (Could melatonin make it worse by having them sleep more deeply and not protect their airway?)
-Small study: 13 people. How well can we extrapolate to a large population from that?
-We don't know what happens with longer use.

Saturday, January 11, 2014

High Blood Sugar a Risk for Dementia? Yes. Oxidative Stress Ripping Us Apart From the Inside.

I thought this was an insightful little summary (below) of a New England Journal of Medicine study. It followed a large number of patients which give the results more "weight" than if the study had followed fewer individuals. They followed blood sugar levels at the moment taken and also glycated hemoglobin (HgA1c) which is a measure of how "sugary" your blood has been over the past month or more at least. The number of patients studied were about half men and half women.
-None had actual diabetes (because we already know diabetes has so many unfortunate outcomes if untreated). This study was meant to follow patients who sugars are trending high, but not high enough to have an actual disease name attached to it.
-None had dementia or Mild Cognitive Impairment  (MCI--a dementia precursor sometimes) at the start of the study.
-Average patient starting age: 76
-They were all followed for about 7 years.

What they essentially found was that IF YOUR SUGAR TRENDED HIGH, YOU HAD A 54% HIGHER CHANCE OF DEVELOPING DEMENTIA than the other person your age over that course of time who had a lower blood sugar trend.

To be honest, this really isn't news in general. To the medical community, we have known for decades, and every decade brings hundreds more articles that support the truth in subtle and profound ways, that too much sugar in our blood causes oxidative stress and premature aging (damage we just can't repair) of cells throughout the entire body.

When I mention "glucose (sugar)-related oxidative stress," almost all my patients give me a blank look. That's okay. It's actually very straightforward at its core: 
We need oxygen to help literally burn energy, in this case, sugar. When we use oxygen however, we make something called free radicals, which is a fancy name for atoms of molecules that are kind of unstable because an electron orbiting around it has been ripped off in the metabolic fire... and the atom doesn't like that instability, so it will literally rip an electron from anything around it to get one back and be stable again. Unfortunately, when this happens in the human body, our biological cell's inner workings take the damage which can just lead to inefficiencies in their function or can throw enough of a kink in the cell's machinations that the cell dies off.And yes, we have been designed with defenses against this, each of our trillions of trillions of cells producing enzymes to take this hit for us, and antioxidant substance we are all aware of such as Vitamin E are happy to donate electrons as well. The problem is when sugar is in greater abundance than we can handle. WE are aware, but our body ISN'T AWARE of itself in the same way. It doesn't know to stop burning up sugar for fuel because there is too much. So it keeps on burning that sugar, putting it forms that can be stored against a future lack of food or perhaps a long stretch of exertion... and making free radicals in the process that it assumes are going to be handled by other enzymes somewhere down the line. 

To me, it's something I'll be thinking about as I eat that extra jumbo-cookie I don't need; picturing it breaking down, and then it's free-radical oxygen byproducts literally ripping at the fabric of nerve cells in my brain, and the fragile little blood vessels that supply them.

Monday, January 6, 2014

Memantine (Namenda) for Lewy Body Dementia

Thing you should know #1: Memantine, also known by its trade name Namenda, works by blocking a receptor called NMDA (stands for N-methyl-D-aspartate). It is thought that in dementia, like Alzheimer's, over-excitation of this receptor (usually by a specific chemical glutamate which is the most important excitatory chemical in the human brain)--over-excitation of this receptor can actually lead to cell death and be a part of the process that causes dementia (neurodegeneration) to progress further. Blocking this receptor is supposed to selectively block the excitatory pathway while allowing the normal day-to-day functions of the cell to continue unabated. And the initial studies on dementia & this medication were really only done with the Alzheimer's kind of dementia.

Thing you should know #2: Namenda is only FDA approved for moderate to severe Alzheimer's disease.

Thing you should know #3: If we in the medical world waited for the FDA to catch up by approval to all that is being treated in certain ways in Medicine, we would push back the way Medicine is practiced 40 years... at least.

Thing you should know #4: There are many types of dementia. You hear about Alzheimer's all the time because it is the most common form of one category of dementia and because the media really highlights this form of dementia. But.... B12 deficiency can cause a dementia; thyroid dysfunction and depression and Obstructive Sleep Apnea can mimic dementia; large strokes or many smaller strokes can cause dementia ....on and on. And of the specific category of dementias known as NEURODEGENERATIVE DEMENTIAS, Alzheimer's is just one of them among others like Lewy Body Dementia, Frontotemporal Dementia, Semantic Dementia, Non-fluent Aphasia Dementia.....and so-on.

So, this quick article summary essentially suggests what many neurologists have already been recommending: We should be using this medication that decreases over-excitation leading to brain cell death in dementia, more broadly that just in Alzheimer's type. And, although this study summary above doesn't mention it, we should also be using the classic medication used for Alzheimer's, Aricept (donepezil) more broadly as well among the other dementias.

This study from August 2010 The Lancet Neurology, showed that over 24 weeks (half a year) of the study's duration, the patients had statistically significant improvements (over placebo), actual improvements, in overall cognition and in behavioral measures as well (since many patients understandably have behavioral issues when aspects of the brain lose their path, but other conflicting aspects remain fully capable).

In this study, complete data was a available for 159 patients, which is a pretty robust number.

But, to me, it really just confirms that we shouldn't be waiting to place our loved ones on medications, such as this, until studies are built to prove what should work based on our neurologic understanding and what we see in clinical practice.... as long as the treatment does not break our fundamental oath of "Do no harm." That being said, even that truth has shades of grey. I'm perfectly comfortable given someone a touch of stomach-nausea (harm) if I think I can delay some memory problems/behavioral problems just a bit longer, especially if that means you/your family can stay in your/their home a few months or years longer before having to transition to expense home nursing or to a nursing home.

Monday, October 7, 2013

More Salt Equals More Multiple Sclerosis

This was a recent abstract (not formally published yet) which I found interesting. It was only a small study but showed a NEGATIVE TREND between increased salt intake and increased Multiple Sclerosis manifestations, both in terms of clinical events, like MS exacerbations, and in terms of new lesions on the MRI. Yikes.
The magic number was more than 4.8 grams a day. Once that number was reached, MS event relapse rates were 4 times higher than those who had less than 2 grams a day. Obviously, what to say about the in-between range is a grey area.

That being said the causal relationship is harder to prove. In other words, HOW this would be true is harder to determine and therefore the fundamental truth that salt itself is responsible also has to be further questioned. Other possibilities: Maybe people with worse, more aggressive MS are hungrier for more salt for some reason.

Theories on how salt would cause this are unclear. Many argue that salt causes and increased inflammatory condition in the human body or increased oxidative stress indirectly in the human body. It also may increase the permeability of the blood brain barrier which keeps the brain "locked off" from the body. This increased permeability would make it easier for the person to mistakenly "accidentally remember" that the myelin around the brain and spinal cord neurons is not part of you (of course, it is) and attack it again, inappropriately.

Interestingly a Big Mac alone contains almost 1gram. 
A cup of broccoli (29mg), a cup of grapes, a pre-made-pre-cooked chicken cordon blue (490 mg), an Oikos greek Yogurt (100mg) and a cup of milk chocolate Blue Bell ice cream (100mg).... is still only 719 mg of sodium.

I have included the full reader-friendly article below, and put a bold on my favorite part:

COPENHAGEN -- Sodium intake was positively correlated with risk of increased disease activity in patients with multiple sclerosis, according to a small study reported here.
Each gram of estimated daily sodium intake above the average in a 52-patient sample was associated with an increase of 3.65 in MRI lesion counts, said Mauricio Farez, MD, PhD, of Buenos Aires.
Also, patients with estimated salt intake classified as high -- more than 4.8 g daily -- showed relapse rates that were 3.95 times greater (95% CI 1.39-11.21) than those with intakes less than 2 g/day, he told attendees at the European Committee for Treatment and Research in Multiple Sclerosis annual meeting.
Farez emphasized repeatedly that the findings did not prove that high salt intake caused the increased disease activity. He acknowledged that, if there is a causal relationship, it possibly could go in the reverse direction -- that patients with highly active MS may increase their salt intake as a result. But he said he did not view that as very likely.
The study in a total of 122 patients with relapsing-remitting MS grew out of previous research connecting salt intake with vitamin D levels and body mass index, he said. Numerous studies have indicated an association between vitamin D status and MS risk.
He and colleagues initially recruited 70 patients for a first phase of the observational study. They underwent a baseline MRI scan in November 2010, followed by MRI scans and analysis of urinary sodium excretion as a means of estimating sodium intake 1 year later. Finally, in November 2013, relapse rates for the preceding 2 years were calculated.
During this first phase, the MRI analyses included "combined unique activity" counts -- the total of new T2 lesions and new gadolinium-enhancing T1 lesions since the baseline scan.
A second group of 52 patients was examined in June 2013 with MRI scans and urinary sodium testing to provide replication data for the association between sodium intake and MRI lesion activity. Because this group had only a single scan and no follow-up, Farez and colleagues could only calculate T2 lesion loads, not the combined unique activity lesion counts nor relapse rates.
Farez acknowledged that an important limitation of the study was that it did not measure urinary sodium excretion with 24-hour urine collections, which he said were impractical since they require participants to carry a large container to capture all their urine for a whole day and night.
Instead, his team relied on spot urine collections and a published formula to estimate daily sodium excretion and, from that, daily sodium intake.
He reported that, in the first group of patients, not only those with high sodium intake (more than 4.8 g/day) but also those with "average" consumption showed increased risk of relapse. Participants with estimated daily intake of 2.0 to 4.8 g/day had relapse rates that were 2.75 times that of the low-intake group (95% CI 1.30-5.81).
Comparing both the average- and high-intake groups, the trend was significant at P=0.001, he reported.
Also in the first group, combined unique activity lesion counts were approximately three times greater in both the average- and high-intake groups compared with the low-intake group (P not reported), Farez said.
And, T2 lesion counts were similar in the first cohort's low- and average-intake groups at an average of about 6, but they reached a mean of approximately 14 in the high-intake group (P<0.05).

In the replication set of 52 patients, similar results were seen, Farez said. He and his colleagues calculated that each increment in intake of 1 g above the cohort average was associated with 3.65-lesion increase in T2 count (SD 0.77, P<0.001).

He did not specify the cohort average, but he said that the national average in Argentina has been measured at nearly 5 g/day, well above the U.S. mean of 3.4 g/day.

The World Health Organization has recommended a maximum daily intake of 2 g/day. In the U.S., several government agencies have jointly called for a maximum of 1.5 g/day-- but earlier this year, the Institute of Medicine complained that the scientific evidence did not a support such a low figure, instead backing an older standard of 2.3 g/day.

Farez and colleagues also measured serum sodium but found no relationship between it and clinical or MRI activity. It was also not significantly associated with estimated sodium intake, with an R2 value of just 0.0082.
Asked by the session moderator what a causal mechanism might be, Farez said previous studies had suggested that high salt levels can promote increased inflammatory activity throughout the body. Also, he said, it may increase permeability in the blood-brain barrier, which could contribute to inflammation in the central nervous system.
Whatever such a mechanism may be, he said, "it does not seem to occur in peripheral blood."