Timothy C. Hain, MD. Page last modified: March 25, 2013
Movie of Palatal Myoclonus (5 meg) (Examiner is holding a camera pointing towards back of throat of patient with PM). This individual was largely normal, other than having OPM.
Another movie of palate in oculopalatal myoclonus (14 meg). This individual has a degenerative nervous system disorder.
Movie of pendular nystagmus in oculopalatal myoclonus (7 meg).
Movie of X-ray of pharynx in oculopalatal myoclonus (11 meg). Contributed by Dr. Dario Yacovino.
Also see a more OPM cases here.
Palatal myoclonus (PM) is characterized by rhythmic involuntary jerky movements of the soft palate of the throat, and also sometimes other muscles related to the throat. When associated with eye movements, as is not unusual, it is called "oculopalatal myoclonus", or OPM. A clicking sound is commonly heard. The frequency of the jerking is ordinarily 1-2 hz. PM is exceptional among movement disorders because of persistence during sleep and frequently lack of modulation by voluntary influences. This likely results from it's mechanism which is not mediated via the basal ganglia but rather is driven by a low-level oscillator in the brainstem.
The youngest reported case is 18 months, and the oldest, 91 years old. Unsteadiness and tremor is common in persons with OPM.
Example case (Click here for many other cases.):A 72 year old woman came to medical attention when she developed inward turning of her left eye. An MRI scan was obtained which documented a vascular malformation in her pons. An operation was attempted, following which she developed near complete paralysis of horizontal eye movements. Balance was poor and one eye began to "bob". On an examination done one year later, there was a constant pendular (sinusoidal) nystagmus of one eye, severe unsteadiness, and a one cycle/second up and downward movement of the soft palate (palatal myoclonus), accompanied by contractions of muscles in the throat. The combination of the "bobbing" ocular nystagmus and palatal myoclonus, defines a case of OPM. The cause is presumably related to interruption of the central tegmental tract (see below).
The triangle of Guillain-Mollaret -- Source: http://www.mni.mcgill.ca/neuroimage/
Another schematic of the triangle of Guillain-Mollaret -- source: http://www.neurology.org/cgi/content/full/71/4/301/F119. This view is a coronal view mainly showing the brainstem.
How to find the inferior olivary nucleus on the MRI.
|Location of Inferior olive, image adapted from Deluca et al, J Neurol Neurosurg Psychiatry 2007;78:832-835||MRI (flair) of posterior fossa of patient with oculopalatal myoclonus. Notice the white spot in the medulla.|
There are two forms of PM. Ordinary PM is caused by a lesion in the triangle of Guillain-Mollaret (1933). Guillain and Mollaret were French neurologists, and perhaps this is why much of the literature is from French authors. At any rate, this triangle (see figure above) is found in the brainstem -- and it is composed of the inferior olivary nucleus in the medulla of the brainstem, the central tegmental tract which connects the inferior olive to the red nucleus in the midbrain, the inferior cerebellar peduncle which connects the inferior olive to the cerebellum, the superior cerebellar peduncle which connects the red nucleus to the contralateral dentate (or dental) nucleus of the cerebellum. The red nucleus and inferior olive are generally thought to be "outboard" cerebellar nuclei, while the dentate nucleus is within the substance of the cerebellum. The superior olive is not involved in PM, but rather has to do with sound processing.
|Another patient with OPM, post severe cerebellar stroke. There are many areas of cerebellar damage, but this damage in the deep cerebellar nuclei area (i.e. dentate portion of GM triangle) is probably the origin of his OPM. He had no nystagmu, just palatal myoclonus.||Patient with ataxia, OPM and orthostatic hypotension of uncertain etiology. This flair images shows increased signal in the IO area.|
It is felt that the inferior olive enlarges and develops rhythmic discharges of between 0.5 to 3 hz, when it is denervated by ipsilateral brainstem disease or contralateral cerebellar disease, and is responsible for the palatal myoclonus. The inferior olive is provided with a massive inhibitory (GABA) projection from the cerebellar nuclei. This differs from most other cerebellar output which is excitatory. Olivary neurons are extensively coupled by gap junctions, which may account for their tendency to oscillate when inhibition is released (Mugnaini and Nelson, 1989).
The lesion in the triangle of Guillain Mollaret may be caused by a variety of structural disorders . Considering all PM, both ordinary and essential, the breakdown by percentage is stroke (40%), tumor (7%), trauma (8%), MS(8%), encephalitis (2%), and degenerative disease (2%) (percentages taken from Deuschel, 1990). There frequently is an asymptomatic period of roughly a year between the advent of a structural lesion such as a stroke, and appearance of the PM. Ordinary PM has an age peak of 50-60.
Essential PM is the phenotype of PM, without an obvious lesion (usually on MR imaging) in the triangle of Guillain Mollaret. Roughly 27% of all PM is essential. Essential PM may be more variable than PM, and sometimes can be stopped by intention of the patient, modified by neck position, or eliminated on mouth opening. The cause of essential PM is unclear. Essential PM has an age peak of 30-40. The eyes are rarely involved in essential PM (the author has seen a very subtle case).
It seems likely to us that OPM and essential PM are structurally different conditions, one which is due to a pattern generator in the brainstem, and the other which is due to peripheral irritibility in a sensory feedback loop involving the palate. Essential PM could, in some instances, be "functional" or simulated.
Vertical pendular nystagmus associated with oculopalatal myoclonus syndome. Recording method: infrared video. Click here to see the movie of this segment.
(c) 2003-5 Timothy C. Hain, M.D. All rights reserved
When the eyes are involved (25%) there is a pendular nystagmus (see above) which can be horizontal, vertical or rotatory. To see a 1-meg movie, click here. The nystagmus may respond to valproic acid (Lefkowitz and Harpold, 1985). It has also been reported to be successfully treated with INH (200 mg BID to QID, with pyridoxine) combined with converging prisms. We have never attempted this as we are dubious that giving patients sedating medications or ocular appliances could possibly help the nystagmus that is being driven by a brainstem oscillator.
When the limbs are involved (about 10%), there is commonly a pendular tremor time locked to palatal movements.
Symptomatic and essential palatal myoclonus were extensively reviewed in an article by Deuschel and others, 1990.
Ordinarily the diagnosis is not difficult at all, and mainly depends on the examiner looking at the palate. If one sees the palate oscillation, then the options are very limited -- mainly OPM and a functional syndrome (i.e. simulated) in which the person is simulating PM by voluntarily elevating their palate. It also seems possible that the palatal reflexes are just more irritable in certain people.
Usually, the distinction is made by associated findings. If the eyes move with the palate -- OPM must be real and not simulated. In fact, in our practice, usually we see the eyes move, and then we look at the palate, knowing it must be moving too.
If the MRI is abnormal -- generally with a lesion in the triangle of GM, - - it should be the "non-essential" variant of OPM.
If the timing is irregular -- could be simulated. If it goes away in sleep --it should not be the central OPM. The LACK of eye movements is not a good way to determine if simulated or real. Sometimes there is an ambiguity between "essential" PM, mainly meaning PM with a normal MRI, and "simulated" PM.
Palatal myoclonus is a clinical diagnosis and the differential diagnosis with respect to cause is very limited. In our experience, about half of patients have had a stroke.
Whipple's disease is associated with an oculomasticatory myorhythmia. In these cases the eyes have a pendular vergence oscillation accompanying paralysis of vertical gaze, and there are contractions of the masticatory muscles. The vergence nystagmus differentiates this disorder from PM. Intestinal biopsy establishes the diagnosis in Whipples.
Hashimoto's encephalitus has been reported to cause PM (Erickson et al, 2002), but like Whipples disease, this is exceedingly rare.
Gluten sensitivity has been associated with a few cases of PM (Kheder et al, 2012; Finelli et al, 1980). As PM and gluten sensitivity (10%) are both common conditions, we suspect that this is just a chance occurence and does not imply causality. According to Finelli et al (1980), a gluten free diet is rarely successful in persons with neurologic complications. On the other hand, as the causual connection between gluten sensitivity and cerebellar degeneration is tenuous at best, and because OPM to our knowledge is due to neural loss and thus is not likely to be eliminated by any drug treatment, we do not think that one should embark on aggressive and possibly dangerous treatments such as immunosuppressants.
It seems plausible that encephalitus syndromes such as West Nile virus might cause OPM, and where an encephalitus is endemic, testing for this also seems reasonable although not necessary as there are generally no treatment changes to anticipate.
We have never encountered a case of OPM in paraneoplastic cerebellar degeneration, and we do not routinely use blood tests to check for a remote cancer. Of course, if patients are deteriorating and losing weight, as well as are a smoker, this line of inquiry becomes more reasonable.
Alexander's disease is an obscure and rare degenerative neurological disease, usually fatal, sometimes inherited, that most commonly affects infants and young children, but it can also occur in adults. It resembles multiple sclerosis, and is often associated with palatal myoclonus (Deprez et al, 1999; Schwankhauss et al, 1995). Namekawa et al (2002) reported that a mutation in the GFAP -- glial fibrillary acid protein -- gene was found on autopsy in two cases, and according to Johnson, other cases have been found to have the same mutation (Johnson and Brenner, 2003). A single case report suggested that an antibiotic, ceftriaxone given for 20 months intravenously, was effective (Sechi et al, 2013). It is difficult to understand why an antibiotic would reverse the consequences of a mutant glial fibrillary protein and also too soon to know if this treatment will work in others.
Tests that we recommend in all persons with palatal myoclonus:
No other laboratory testing is routine in PM, but there are some investigational possibilities.
We have recently developed the ability to record sound in the external ear using an ear microphone. As periodic clicking is common in OPM, an "ear-mike" recording could point towards OPM.
Nemni et al (1994), suggested that anti-glutamic acid decarboxylase antibodies ("anti-GAD") should be obtained in cases of essential PM. This test is available as a "send-out" test, to be collected in a gold top. Anti-GAD is also often positive in diabetes, and in a rare neurological condition, the so-called "stiff person syndrome". Anti-GAD has also been reported in several patients with cerebellar ataxia (Abele et al, 1999). Our experience is that there are lots of people with anti-GAD, so the specificity (i.e. usefulness) of this test is almost nil.
As PM has been reported in Hashimoto's encephalitis, anti-microsomal antibodies as well as anti-TPO and anti-thyroglobulin antibodies may also be considered. Again, our experience has been that these antibodies are commonly positive in many people without PM, and like the situation with anti-GAD, the chances of a false positive type error are enormous.
Similarly, we think that checking for anti-gliaden antibodies and paraneoplastic antibodies is very unlikely to be productive, not needed routinely, but might be entertained in someone who has associated symptoms -- i.e. GI disturbance for gluten, and significant weight loss or other signs of a cancer for the case of the paraneoplastic antibodies.
In patients with symptomatic palatal myoclonus, generally no treatment works. In reported papers, about 20% of treatments have been successful, but some indicate that no treatment works. There are sporadic reports however of successful treatment with the following medications:
As a summary of the author's judgement about these things, for the central version of PM, drugs worth trying are baclofen, gabapentin, memantine and clonapin, as they all have a reasonable chance of working and relatively few side effects. If one wants to exhaust all possibilities, the others on the list may be worth considering with considerable caution. We are dubious that any medication other than those useful for neuralgia (some of the anticonvulstants) will be useful in the peripheral form of PM (i.e. essential PM). Of course, if the PM is being simulated, medication is not going to do much good.
Although anticholinergics such as trihexyphenidil (Artane) have been reported useful in acquired pendular nystagmus (Jabbari et al. 1983; Jabbari et al. 1987), we have had no success. Neither did Leigh et al (1991). Problems include lack of efficacy and severe side effects.
Seizure medications -- as a general comment, one would expect these medications might possibly work in the "peripheral" type of PM (without nystagmus), where their mechanism would be similar to a medication used for neuralgia. For the central type of PM (with nystagmus), GABA agonists might be useful.
Memantine, a recently available drug in the USA, has been reported useful in 9 patients with pendular nystagmus due to MS (Starck, Albrecht et al. 1997). We have not found it helpful in a single patient trial on a vertical pendular nystagmus associated with palatal myoclonus.
Cannibis has been reported useful in suppressing pendular nystagmus in multiple sclerosis. (Schon, Hart et al. 1999; Dell'Osso 2000). We have not heard of any reports of its good or bad effect in OPM.
Surgical treatment has been attempted to alleviate ear clicks.
A newer method of treatment that seems logical to us is the use of Botulinum toxin to paralyze the tensor veli palatini (Bryce and Morrison, 1998; Varney et al, 1996). We have had success with this treatment for palatal motion in our clinic setting in Chicago. It does nothing for the nystagmus however and it also is a temporary (4 month) fix. In persons who respond to Botox, after several relapses, some authors have gone on to use of destructive procedures (e.g. Aydin et al, 2006).
Mondria et al reported successful treatment with a "simple dental device" (2007). While interesting, we are dubious that this method of treatment is generally useful.
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