Pain in the Periodic Paralyses
Pain Often Overlooked
Pain is an often overlooked component of the periodic paralyses. Patients who report muscle pain in association with their episodes are too often told that the periodic paralyses are not painful despite many authoritative reports to the contrary. In fact the pain which accompanies the periodic paralyses is described in some of the literature as prominent or constant.
Cases Cited From the Literature:
- "Parathesias and muscle pain are frequent during attacks." 1
- "During episodes weak muscles may ache." 2
- "Parathesias and myalgias may be prominent ... ." 3
- " ... in total paralysis the patients had such muscular tenderness that they required help to change positions in order to mitigate the tenderness. Two patients also had considerably tender muscles, even without being totally paralyzed, and often this tenderness would persist for up to three days after the attack. ... One man was told by his doctor that his muscle pain and morning stiffness and weakness were due to rheumatism. The same explanation had been given to two female patients."4
The following references are all from the same extensive study:
- "Some patients complained of muscle pain in the recovery phase and the day after a paralytic attack ... "
- Nine patients, all older than 40 years who suffered from permanent muscle weakness (PMW) ... "were complaining of pain and stiffness of the muscles, especially in the lower back and upper legs. The severity of this pain sometimes fluctuated with cold and stress but was present almost continuously ... "
- "Patient 2 ... suffered from paralytic attacks since the age of 17 ... PMW started when he was 57. He was wheel-chair bound from the age of 67. When he was 75 his legs were amputated due to ischemic pain and necrosis due to vascular insufficiency." (Note: report included results of biopsies performed on amputated limbs and after death at age 79. Both reveal widespread total or subtotal replacement of muscle tissue with fat in a typical Hypokalemic PP pattern, which report states may or may not have been complicated by vascular insufficiency).
- A 44-year-old woman was evaluated after five years on Diamox, " ... she was evaluated clinically because of progressive muscle weakness and muscle pain. No other diagnosis was made but CT scanning showed progressive myopathy."5
- "An otherwise healthy 33-year-old woman had experienced fatigue and muscle pain which curtailed her activities by the end of the day, since her thirteenth year. Her symptoms were exacerbated by her menses and had steadily increased over the years."6
- "This 64-year-old woman had been healthy until the age of 60 years, when she first experienced stiffness and muscle pain ... .on cold days and after sitting. " 6 • " ... these patients ... all complained of lack of strength in general and stiffness and pain ... all patients performed the tests more easily during (double-blind) acetazolomide (less tired, less pain, less trembling of used muscle groups)." 7
- "Sensory symptoms, including paresthesias, heaviness, and muscle pain often precede the attack. Muscle tenderness may be present until full recovery from the episode has occurred. Clinical features of hyperkalemic periodic paralysis ... included ... the association with muscle pain and sensory symptoms ... 8
- "Symptoms would begin with an aching, cramping pain in his legs, which was sometimes associated with a tingling sensation in both legs and hands. ... Weakness and aching would be most prominent in his legs and less so in the arms ... (During CMAP testing) The patient complained of generalized muscle aching ... After 5 hours the CMAP had returned to 80% of prechallenge value and there was still mild generalized muscle aching and weakness and considerable weakness in the small hand muscles and the anterior compartment muscles." 8
- "Residual aching and weakness persisted for several days during these episodes. (After testing) Subjective recovery of full muscle strength and disappearance of aching sensation took 2-3 days. After treatment cooling was experienced as less painful." 8
- "Immediately after exercise pain occurred in both thighs, along with slight weakness. These complaints persisted for 4-5 minutes only. About 40 minutes after potassium ingestion, minor stiffness and weakness occurred. Within 20 minutes the patient could no longer raise his arms and legs." 9
- "A 43-year-old woman presented at the age of 38 with joint pains and muscle stiffness. Tender points were found fulfilling ACR criteria (1) for fibromyalgia ... Muscle pains increased after exercise. Her 10-year-old son had similar symptoms and one paralytic attack. Muscle pain and fatigue increasing with age were found by history in three close relatives." 10
- Muscle pain associated with episodes have been reported in Hypokalemic calcium channel mutations R528H and R1239H and the sodium channel mutation R672G. In R528H and R1239H the muscle pain preceded attacks, in R672G the pain followed the attacks. 11
In an attempt to determine how many patients with periodic paralysis experience pain we have conducted surveys among 42 randomly selected patients with periodic paralysis. Patients were asked the following questions:
- What is your age?
- At what age did you begin having episodes?
- What type of Periodic Paralysis do you have?
- Do you have pain associated with your Periodic Paralysis?
- Has your pain level increased over time?
- Do you take medication for your Periodic Paralysis pain on a daily basis?
- What medication/s do you take?
- Do you take medication for other pain? If so what?
Age range of surveyed patients was from 6-84 years. Shortest length of time with symptoms was one year. Longest reported length of time was 71 years. All patients were receiving appropriate therapy for their type of PP, i.e. Diamox, Daranide, Dyrenium, potassium supplementation, Thiazide diuretics, Mexetil, Albuterol, etc.
Of the 42 patients surveyed, 36 (86%) reported pain associated with their periodic paralysis. Pain might precede, accompany or follow episodes, depending on the patient. All but two patients who reported pain reported that their pain levels had increased over time. Older patients believe this is in response to lengthening of episodes as they age. Dr. Links' extensive Dutch studies seem to indicate that pain is an indication of ongoing muscle destruction. Length of time since onset of symptoms seemed to bear little relation to severity of pain, as some of the patients who reported the most severe pain had been affected the shortest period of time.
Of the patients surveyed:
- Two (2) were Hyperkalemic who reported associated pain
- Seven (7) were Hyperkalemic with Paramyotonia Congenita (PMC) of which five (5) reported pain
- Thirty two (32) were Hypokalemic, of which twenty eight (28) reported pain
- One (1) was Thyrotoxic Hypokalemic, and reported pain.
- Of the patients surveyed only ten (23%) took pain medication on a regular basis for pain arising from other sources, including migraine, simple headache, osteoporosis, fibromyalgia.
- Three (3) patients had pre-existing or co-existing neck/spinal trauma which created severe pain. Oddly enough, the medications prescribed for this pain did not necessarily relieve the muscle pain associated with episodes of PP. Episodic pain may require the occasional use of additional analgesia of a different type.
- Many patients report that pain interferes with quality of sleep. One (1) Hypokalemic patient who has considerable myopathy reported that a low dose of Elavil (15 mg daily one hour prior to bedtime) improved sleep quality and reduced pain levels and stiffness without daytime sedation or weakness. Medications reported included: Ibuprofin, Percocet, Darvocet, Darvon, Tylenol 2, Norco 10/375, Motrin, Flexeril, Tylox, Loratab 7.5, Codeine, Oxycodone, MS- Contin, Vicodin, Soma, Elavil, vicaprofen and zanaflex.
- About half of the patients required some pain medication on a daily basis. Most reported keeping intake to a minimum, preferring to 'tough out' minor pain, or using alternative methods to counteract it, like moist heat, meditation, analgesic creams, massage etc. Only one patient reported taking more than the prescribed amounts of pain medications on a regular basis, and this overusage was attributed to severe pain arising from another source. Another patient reported occasionally using a larger than prescribed dosage of pain medication.
- On the whole patients reported that their physicians monitored their usage of pain medications closely (some reported being required to sign 'contracts' to obtain prescriptions) and abuse did not appear to be a problem. A much larger problem is denial of appropriate treatment to patients who are experiencing significant daily pain.
- Chronic pain can have a devastating impact on quality of life, especially if it keeps patients from maintaining daily activities which serve to conserve muscle strength. Patients and physicians need to work together to design pain-management strategies which enable the patient to lead as active and productive a life as possible. Based on current knowledge this includes carefully selected and monitored analgesics. While it is true some patients with periodic paralysis are sensitive to medications such reactions do not preclude the use of pain relief, only make it important to tailor the drug and dosage to the patient.
1. Riggs, Jack E; Review of the Periodic Paralysis; Clinical Neuropharmacology 1989
2. Swash, Michael; Martin S Schwartz; Neuromuscular Diseases; A Practical Approach to Dianosis and Management, 1988
3. Engel, AG; Hypokalemic and Hyperkalemic Periodic Paralysis In: Scientific Approaches to Clinical Neurology 1977
4. Johnsen, Torsten; Familial Periodic Paralysis with Hypokalaemia, Danish Medical Bulletin, 1981
5. Links, Thera; Familial Hypokalemic Periodic Paralysis, 1992
6. Links, T et al; Permanent Muscle Weakness in Familial Hypokalemic Periodic Paralysis, Brain 1990
7. Link, T et al; Improvement of Muscle Strength in Familial Hypokalemic Periodic Paralysis with Acetazolomide; Journal of Neurology, Neurosurgery and Psychiatry 1988
8. Streib E.W; Paramyotonia Congenita: Successful treatment with Tocainide. Muscle and Nerve 1987
9. Ricker, K; et al; Different Effectiveness of tocainide and hydroclorothiazide in paramyotonia congentia with hyperkalemic episodic paralysis; Neurology 1983
10. Gotze FR, et al; Fibromyalgia in Hyperkalemic Periodic Paralysis; Scand J Rheumatol 1998
11. Stermbern, D; Maisonobe, T; Jurkat-Rott, K; et al; Hypokalemic periodic paralysis type 2 caused by mutations at codon 672 in the muscle sodium channel gene SCN4A: Brain (2001), 124, 1091-1099