Myoclonus Survey in Periodic Paralysis Patients Part 1

Myoclonus is the sudden, involuntary jerking of a muscle or group of muscles. Myoclonic jerks may occur alone or in sequence, in a pattern or without pattern. They may occur infrequently or many times each minute. Myoclonus sometimes occurs in response to an external event or when a person attempts to move. The twitching cannot be controlled by the person experiencing it.

In its simplest form, myoclonus consists of a muscle twitch followed by relaxation. A hiccup is an example of this type of myoclonus. Another example of myoclonus are the jerks or “sleep starts” that some people experience while drifting off to sleep. These simple forms of myoclonus occur in normal, healthy persons and are no cause for concern. When more widespread, myoclonus may involve persistent, shock-like contractions in a group of muscles. In some cases, myoclonus begins in one region of the body and spreads to muscles in other areas. The brief positive muscle contractions of myoclonus are often accompanied with sudden, unexpected inhibitions of muscle contraction, or lapses of posture. This phenomenon, termed negative myoclonus, makes standing, walking, reaching, or grasping objects very difficult 1.

Numerous members of our listserv report that they experience myoclonus in association with their episodes of periodic paralysis. We have observed a patient, while so thoroughly flaccid that she could not maintain an airway without support, experience random myoclonic jerks so violent as to injure herself striking nearby furniture. The patient jerked as if touched by a high- voltage wire, and immediately fell flaccid again. The myoclonus was repeated at intervals of 20-30 seconds until the paralysis resolved several minutes later. Myoclonus in association with the ion channelopathy forms of periodic paralysis has not been investigated or reported in medical literature as far as we can determine.

The lifetime prevalence of myoclonus, as of January 1, 1990, was estimated at 8.6 cases per 100,000 in the general population, with the prevalence increased with advancing age. Statistically this would be one person in 11,627 2. It is difficult to say what percentage of HKPP Listserv members experience myoclonus, but it appears to be higher than found in the general population.

The Listserv has approximately 175 members, of whom 35 to 50 are active participants, i.e. they post to the list at least once or twice monthly. Many of the active members post on a weekly or even daily basis. No member of the Listserv who is normally inactive responded to the myoclonus survey though some inactive members are known to experience myoclonus. From the group of active participants (say 50 people) 17 reported experiencing myoclonus. This is approximately one individual in three.

Myoclonus has been reported due to metabolic alkalosis with hypokalemia, hypocalcemia and hyponatremia, but the familial forms of periodic paralysis do not cause these acid/base disturbances. 3,4 Ruling out acid/base disturbances should be part of every workup for hypokalemic periodic paralysis. A very low rate of K+ excretion coupled with the absence of a metabolic acid-base disorder suggests Hypokalemic Periodic Paralysis. A high rate of K+ excretion accompanied by either metabolic alkalosis or metabolic acidosis favors a diagnosis other than HypoKPP 4.

Our Survey

We surveyed the members of the HKPP Listserv, asking those who experience myoclonus to answer a number of questions about both their periodic paralysis and the nature of their myoclonus. Seventeen list members who experience myoclonus responded to the survey. Of these 3 were male, and 14 were female. One survey from a female participant was not included because she did not finish the survey. While all but one of these patients have clinical diagnoses, none of the respondents to this study have identified PP mutations. Some are enrolled in genetic research programs, some have undergone limited commercial testing, some have had no genetic testing.

Of the three male respondents one has HypoKPP, one has the hypokalemic variant of ATS2, one has HyerKPP/PMC von Eulenburg. All male respondents had onset of PP symptoms by age of six years; age of onset of myoclonus ranged from nine years (patient with HyperKPP/PMC) to late teens (patient with HypoKPP).

Of the 13 female respondents, age at onset of PP symptoms ranged from infancy to the early 40s. Six have HypoKPP, one has HyperKPP, one has HyperKPP/PMC, one has the hypokalemic form of ATS2 and one is yet undiagnosed for type, but develops weakness with carbohydrate intake. Age at onset of myoclonus in female respondents ranged from 12 to 48 years. In the respondents who have a HypoKPP diagnosis, serum K+ values during PP episodes vary less than reported in genetically identified forms of HypoKPP, with no patient in this group reporting less than a serum K+ level of 3.2 during paralysis. None the less, all but one (female) HypoKPP patient in this group reported experiencing generalized paralysis, with many reporting that facial muscles are affected during episodes. Several reported respiratory weakness during episodes.

Nature of Myoclonus

Twelve (12) respondents have repetitive myoclonus, eight (8) have random myoclonus, ten (10) have both repetitive and random myoclonus. Three (3) have negative myoclonus (abrupt, brief loss of muscle tone). This has resulted in falls and injuries such as striking the head on furniture or pavement.

Triggers for Myoclonus

All respondents reported that weakness was a triggering factor for myoclonus. Other mentioned triggers were: Startle or an adrenal surge, seven (7); Stimulus such as lights or noise, four (4); movement or the intention to move, five (5); cold, three (3); fatigue, three (3) and sleep, two (2).

Timing of Myoclonus

Most respondents experienced myoclonus in association with attacks of periodic paralysis, and most had myoclonus at more than one point during their attacks of PP. One female patient described her myoclonus in conjunction with episodes of periodic paralysis: “I begin to feel arrhythmia, dizziness, difficulty breathing, an inner 'coldness' that nothing can warm. I begin to tremble - like chills. I lose muscle function very quickly. As it goes, I am usually trying to call for help or remember the medical records I will need in ER or hospital. In attempts to continue moving, the jerking begins to get really bad - totally out of control - much like epileptic jerking - but I remain conscious most of the time. “For about 30-40 minutes, I can do nothing to control the jerking. When total paralysis has set in (I can only move my eyes), the jerking finally ceases. After I finally begin to regain a little muscle function, I try to move a little and the jerking begins again. Once it begins again, the only way I can try to control it is not try to move for quite a long time. Each attempt to move or respond to a request to try to move begins the violent jerking again.”

Six (6) patients reported that myoclonus occurs just prior to an attack of PP. Eight (8) reported that myoclonus occurs in the early stages of an attack. Four (4) reported that myoclonus occurs when PP attack is fully established. Eight (8) respondents reported that they have experienced myoclonus at least once when they were otherwise paralyzed. Eight (8) reported that myoclonus occurs when the PP attack is resolving, six (6) reported that myoclonus occurs after the PP attack has ended. Two (2) report that myoclonus occurs outside of PP attacks and two (2) report that myoclonus occurs during sleep. One (1) reports that periods of myoclonus alternate with periods of flaccid paralysis.

Episodes of myoclonus last from a few minutes to hours. Some patients report that clonic twitches persist for up to 48 hours after a PP episode. One female respondent was diagnosed "NormoKPP" after experiencing paralysis during a glucose/insulin challenge. Her potassium level fell from baseline of 4.6 before the test began to 3.7 at the height of her symptoms, with a return of strength after administration of 40 mEq of potassium orally. (Since "Normokalemic" is now used to denote patients who are potassium-sensitive, this patient has been labelled HypoKPP for this survey.) In the discharge summary written after her test the physician noted, "...Various tests to elicit signs of conversion reaction, hysteria, or a subversion on the part of the patient were all negative... More importantly the patient's reflexes were brisk prior to administration of insulin and glucose and became virtually absent in lower extremities during the height of her symptoms. She also exhibited myotonic jerks with attempted elicitation of myotatic reflexes."

Summary and Discussion

Myoclonus in association with the ion channelopathy forms of periodic paralysis has not been investigated or reported in medical literature as far as we can determine. The lifetime prevalence of myoclonus, as of January 1, 1990, was estimated at 8.6 cases per 100,000 in the general population, with the prevalence increased with advancing age. Statistically this would be one person in 11, 627. 2 It is difficult to say what percentage of HKPP Listserv members experience myoclonus, or if this survey represents an accurate cross-section of patients with periodic paralysis, but the incidence of myoclonus reported in these patients with periodic paralysis appears to be higher than found in the general population.

The Listserv has approximately 175 members, of whom 35 to 50 are active participants, i.e. they post to the list at least once or twice monthly. No member of the Listserv who is normally inactive responded to the myoclonus survey though some of them do experience myoclonus. From the group of active participants (say 50 people) 17 reported experiencing myoclonus. This is approximately one individual in three. The question is why? Myoclonus has been reported due to metabolic alkalosis with hypokalemia, hypocalcemia and hyponatremia, but the familial forms of periodic paralysis do not cause significant acid/base disturbances. 3,4 Patients who take a carbonic anhydrase inhibitor may experience mild metabolic acidosis, but the majority of patients on our list who take these drugs do not report myoclonus, and not all of the survey respondents take a carbonic anhydrase inhibitor. Interestingly, all of the respondents to this survey have episodes of paralysis associated with a fall in serum potassium, regardless of diagnosis. Even those with HyperKPP and Paramyotonia Congenita require potassium at times to treat their episodes of PMC.

Patients with the periodic paralyses are more than normally reactive to shifts in serum potassium, is it possible that some patients with PP are also overly sensitive to the small shifts in serum Na+ and Ca+ which occur during PP episodes? Or, does myoclonus within the context of an episode suggest that an additional factor which affects membrane permeability or ion channel function is involved?

Further we must ask if at least some of these patients have been misdiagnosed, and their episodes of paralysis, and the myoclonus, are not a form of hemiplegic or basilar migraine? Fragmentation of specialties and the difficulty accessing care frequently means the need for organized investigation is not met, and as a result patients do not receive appropriate therapy or management. 

A copy of the myoclonus survey we used is included.

1. Myoclonus Fact Sheet; National Institute of Neurological Disorders and Stroke; 

2. Caviness, JN; Alving, LI; Maraganore DM; et al.; The incidence and prevalence of myoclonus in Olmsted County, Minnesota. Mayo Clinic proceedings, 1999, vol. 74, no6, pp. 565-569

3. Simons P; Nadra I; McNally PJ; Metabolic alkalosis and myoclonus. Postgraduate Medical Journal 2003;79:414-415

4. Okada K; Kono N; Kobayashi S; Yamaguchi S; Metabolic alkalosis and myoclonus from antacid ingestion. Intern Med. 1996 Jun;35(6):515-6. 5. Lin SH; Chiu JS; Hsu CW; Chau T; A simple and rapid approach to hypokalemic paralysis. Am J Emerg Med. 2003 Oct;21(6):487-91.

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