Tag Archives: square wave jerks

Eye doctors keeping their eyes open

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Yesterday’s post about training general neurologists to recognize PSP early in the course elicited a reader comment about one patient whose first symptom of PSP was dry eyes.  The diagnosis of PSP remained elusive through multiple years and multiple doctors.  So, a word about that symptom seems in order.

Dry eyes are common in the general population, usually as a result of insufficient tear production, but in PSP the problem is too little blinking – about 20 percent of the normal frequency for age.  This causes inflammation of the conjunctiva (the very thin, transparent layer covering the cornea, the sclera and the inside of the eyelid) and a sensation of dryness or itchiness.  Part of the eye’s reaction is to increase the production of the watery component of tears, but that doesn’t help the loss of the oily component, which comes from a different set of glands. 

Often, the eyes’ reactions also include a reflexive increase in blinking when awake.  This is helpful, but during sleep the lids may remain open because of the basic eyelid dysfunction of PSP.  The resulting drying during the night creates more inflammation than can resolve over a waking day’s-worth of increased blinking.

An ophthalmologist or optometrist evaluating someone for dry eyes may fail to evaluate the blink rate.  Or, if the person has reflexively compensated by increasing the blink rate, the doctor may interpret that as only the normal reaction to inflammation of the conjunctiva. 

So, how can an eye doctor start to suspect early-stage PSP in someone with dry eyes?  Examine the movements of the eyes themselves!  The earliest ocular motor abnormalities of PSP (and here I’m mainly referring to PSP-Richardson’s syndrome, which comprises about half of all PSP) are slow saccades, the “round the houses sign” and square-wave jerks.  None of these require special equipment – just a little book knowledge, a few teaching videos and some practice.  Actual limitation of downward, voluntary eye movement – the “palsy” in the name — arrives a year or two later.  Here’s what those three early signs look like:

  1. Slow saccades: A saccade is simply an eye movement, and in PSP they’re slow enough for the doctor to see them in progress, while a normal saccade is too fast – the doctor only sees the starting and ending positions.  In PSP, the slowness is first and worst in the downward direction.
  2. The “round the houses sign” is where an attempt to move the eyes downward takes a curved path, as if trying to avoid a direct downward movement.  Probably a more sensitive way to elicit this sign is to ask the patient to perform a diagonal saccade, say from upper right to lower left.  The eyes will first move mostly horizontally and then, once the patient’s visual system realizes that the target isn’t being reached, will force the eyes to move downward to compensate.
  3. Square wave jerks are pairs of short, involuntary horizontal eye movements performed by both eyes together up to 20 times per minute.  The eyes first go to the right or left (seemingly randomly) and after a very brief pause, return to the starting point.  They’re especially pronounced when staring at an illuminated target in an otherwise dark room.  They occur in most people with PSP but also in a minority of those with other Parkinsonian disorders and even in a few healthy elderly people. 

So, an ophthalmologist or optometrist seeing a patient with dry eyes should look for these things and if even one of them is present, refer the patient to a neurologist (preferably a movement disorders sub-specialist) to investigate further for PSP.  

I don’t need to remind this readership of the advantages of earlier diagnosis of PSP, even if a cure isn’t yet at hand, but I’ll do so anyway: Access to disease-specific counseling and information; ability to plan one’s financial and living arrangements; avoidance of useless, risky and expensive diagnostic tests and treatments; access to PSP clinical trial enrollment; and the intangible benefit of just knowing what you’re dealing with.

Squares and jerks

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The fourth of the five PSP-related research papers to land in PubMed on a single day this week is from Ulm, Germany.   It compared PSP with ALS with regard “small involuntary fixation saccades” or SIFSs.  Here’s what that means and why it’s important: (Red alert: serious, nerdy neuroscience is coming.)

When we stare at a small visual target, we all have small, fast, irregular, eye movements away from the target.  Each is rapidly corrected by an equal and opposite movement and their size ranges from 0.01 degrees to 2 degrees.  (The normal full range of voluntary eye movement in each of the four directions is about 50 degrees.)  In PSP, these SIFSs become larger and more frequent in the horizontal plane (i.e., left and right), ranging up to 3 degrees and occurring up to twice per second.  The largest of these are called “square wave jerks.” They are so common in PSP, even in the earliest stages, that a neurologist finding signs of PSP but no square wave jerks must strongly consider some other diagnosis.  As you’d imagine, SWJs degrade vision by making it difficult to aim the most sensitive, central part of the retina at a target.

Square wave jerks and milder forms of SIFSs also occur in amyotrophic lateral sclerosis (ALS or Lou Gehrig disease).  ALS and PSP both include frontal cognitive loss and affect overall body movement, especially speech and swallowing, have frontal cognitive loss and have a similarly rapid course, but are otherwise not at all similar.  In ALS, the average age of onset is 10 years younger; the cognitive loss is a late occurrence; it affects the spinal cord worst; and the protein aggregating in the cells is TDP-43 rather than tau.  As eye movement are controlled, in part by the frontal lobes, it seems reasonable that the frontal damage is the source of SWJs in both diseases. 

Now, Drs. Wolfgang Becker, Anna Behler, Olga Vintonyak and Jan Kassubek have compared people with PSP and ALS with regard to the details of their SIFSs, including their square wave jerks.  In addition to making some new observations about SIFSs in general, they found that in ALS, the size and frequency of SIFSs are correlated, while such a relationship is absent in PSP. 

The researchers explain this result by suggesting that the basal ganglia, where the substantia nigra, globus pallidus and subthalamic nucleus are the first three nuclei affected in PSP, are the most likely source of SWJs in that disease, while in ALS, the SWJs probably arise from damage to the frontal cortex.  They suggest that in PSP, the amplitude and frequency of the SWJs are regulated by different sites in the basal ganglia, explaining their observed lack of correlation.  More work will be needed to confirm that suspicion, but some support comes from the observation in this paper that the severity of vertical eye movement loss, the cardinal feature of PSP, correlates closely with the amplitude of the (horizontal!) square wave jerks.

Why should anyone care?  First of all, a general point: One never knows when a “basic science” observation may lead to broader insights that could allow treatments to be developed.  More specifically, finding that a feature of PSP arises from multiple parts of the basal ganglia reduces the appeal of targeting just one allegedly critical or rate-limiting area of basal ganglia damage with a preventative or restorative treatment.  Such approaches have been proposed using injection of viral vectors to deliver gene therapy or growth factors.  Non-invasive targeting of the basal ganglia has been proposed using focused ultrasound.  This new paper suggests that a more general approach reaching the whole brain, or at least all the basal ganglia, might work better.