people of the world

Periodic Paralysis News Desk

Resources for the Periodic Paralysis Community since 1995

PHYSICIAN'S INFORMATION SHEET

Hyperkalemic Periodic Paralysis

Sodium Channel - a subunit (SCN4A); Gene Map Locus 17q23.1-q25.3;

Ten Mutations or sequence variants identified: T704M; S906T; A1156T; M1360V; A1448C; M1592V, I693T, L6891, I1495F, I1495F, S246L and T323M

Genetic-Clinical correlations:

T704M : Permanent weakness common; 60% of cases

M1592V : Myotonic; Non-Dystrophic; 30% of cases

A1156T & M1360V: Reduced penetrance (unaffected carriers can pass gene to next generation.)

Family history:

Autosomal dominant inheritance (Statistically 50% of an affected person's offspring will inherit). All who inherit the most common genes develop symptoms (complete penetrance) but severity is very variable. There is reduced penetrance with mutations A1156T & M1360V. Age at onset: Infancy to second decade of life.

Clinical signs:

Attacks of weakness, lasting from 10 min to 1 hour, very rarely up to 1-2 days. Some patients experience only a few attacks of weakness in their lifetime, others have attacks of generalized weakness every day.

The term 'hyperkalemic' is misleading since patients are most often normokalemic during attacks. It is the fact that attacks are precipitated by potassium administration that best defines the disorder...Diagnosis is suggested by a modest elevation of serum potassium during attacks in nearly half of patients; however at times the serum K+ is normal or even falls below normal. Serum sodium levels may fall as potassium rises. This results from sodium entry into the muscle. Water also moves into the cell causing further hyperkalemia. Hyperregulation may occur at the end of an attack causing hypokalemia, which may result in a misdiagnosis of hypokalemic PP. Water diuresis, creatinuria, and an increase in CK may also occur at the end of an attack. The so-called hyperkalemic and normokalemic entities of this disease are not separate entities.

Cardiac signs and Emergency Treatment of an Attack

Institute emergency treatment if EKG changes occur or serum K > = 7 mEq/L. EKG change sequence: tall peaked T waves, diminished R waves amplitude, increased QRS or PR intervals and P wave disappearance.

Treatment:

Slow infusion (over 5 min) of 10% calcium gluconate (reduces cardiac sensitivity to hyperkalemia). Sodium bicarbonate i.v. infusion to raise pH (lower H+) thereby lowering K+ via intracellular shift of H+ and K+ ions (H+ and K+ go in same direction). Infusion of 1 mg/kg D50W containing regular insulin 0.5- 1.0 unit/ml (drives K+ into cells).

Appropriate care

For severe hyperkalemia or weakness - inpatient with cardiac monitoring. Mild hyperkalemia or weakness - outpatient with close follow up. Be alert to possible complications: Cardiac arrhythmias, respiratory collapse. May need respiratory support.

Symptoms

Patient's Descriptions of Hyperkalemic Symptoms & Episodes Typically Include:
Weakness or paralytic 'attacks or spells' which may come on very rapidly. Falls may occur in sudden attacks. Rest after activity is a common trigger. Changes in the daily level of activity and periods of inactivity (sleep, sitting through a movie, car or plane trip, especially in cool temperatures) triggers weakness in many patients. Many patients learn to move around to abort episodes. Some patients chew gum constantly to abort episodes. Patients may describe muscle stiffness (myotonia). The stiffness in HyperKPP can be 'worked' or 'walked' off and has been dismissed many times as rheumatism, arthritis, or fibromyalgia. High carbohydrate food (candy bar) or drink (sugar cola, sweet tea, Gator Ade) taken at the first sign of weakness may abort or relieve episodes.

HyperKPP may be accompanied by: Paramyotonia Congenita von Eulenburg. This may mean that the patient's serum potassium is labile during attacks, and paradoxical myotonia may be a prominent feature of attacks. Paradoxical myotonia is myotonia which worsens with activity. Aggressive lowering of potassium may precipitate attacks of paramyotonia.

Diagnosis of HyperKPP:

CMAP amplitude Test: Positive in 80% of HyperKPP patients
This test is easier on patients than provocative tests and is almost specific for periodic paralysis. CMAP amplitude is low in muscle weakened by periodic paralysis and measurable weakness can be induced by exercise. The test is conducted by measuring the CMAP in hypothenar muscle by means of surface electrodes. The test takes approximately 45 minutes and is non-invasive.

Patient must be medication-free, i.e. no K+, K+ wasting diuretics, CAI inhibitors, mexitiline, etc. for 48 hours prior to test.

CMAP amplitude:
Increased immediately after sustained (5 min) maximal contraction
Progressively reduced (by 40%) during rest 20 to 40 min after initial increment
In Normals: Mildly increased CMAP amplitude after exercise

Provocative Testing: Oral K+ load Only if renal, cardiac function and serum K+ are normal (never if arrhythmic). Perform fasting, in am, after exercise 0.05 g/kg KCl in sugar-free liquid over 3 minutes. If negative may give 0.10 to 0.15 g/kg KCl, monitor electrolytes, EKG & strength every 20 minutes. Weakness is typically most noticable after 90 to 180 minutes.

IV glucose loading does not provoke weakness in HyperKPP but K+ loading tests (0.05 to .15 g/kg) will induce weakness. K+ loading tests are potentially hazardous and are contraindicated in patients with renal disease and diabetes. Patients should be screened for Andersen's Syndrome before provocative testing begins. Random serum K+ measurements may suggest the diagnosis, since K+ elevations are frequent during attack-free intervals. EMG evidence of myotonia and finding of vacuoles on muscle biopsy provide supporting data.

Genetic testing for a small number of mutations is available through a number of commercial laboratories. See Genetic Labs

Management and Therapy of HyperKPP

The goals of treatment are relief of acute symptoms and prevention of further attacks. Attacks of HyperKPP are brief and seldom severe enough to require emergency treatment. However, progressive weakness can occur with repeated attacks, so treatment should occur as soon as possible.

Diet

A high-carbohydrate diet, which avoids food rich in potassium, may be recommended. Glucose or other carbohydrates given during an attack may reduce the severity. Patients can be counseled to drink a sweetened beverage at the first sign of an attack.

To Treat Weakness in HyperKPP

K+ sensitive
Hydrochlorothiazide (250 to 1,000 mg/day)
Acetazolamide (125 to 1,000 mg/d)
Dichlorphenamide (50 to 150 mg/day)
Albuterol by inhaler or motor-driven nebulizer

To Treat Myotonia

Antiarrhythmic drugs
Mexiletine 100 to 1,000 mg/day;
Paxil 20 mg day;

To Treat Weakness/Rigidity in Paramyotonia (in PMC):

Mexiletine 100 to 1,000 mg/day
Potassium supplementation as required
Paxil 20 mg daily
Calcium gluconate syrup 15 ml dissolved in sweet tea may serve to abort developing attacks.

Other Considerations

Andersen's Syndrome

Andersen's Syndrome is a distinct periodic paralysis occurring in the setting of either hyper- or hypokalemia, with severe cardiac involvement (LQT) and skeletal abnormalities. Every patient with periodic paralysis must be screened for this potentially lethal condition. Partial manifestations are common and the subtle nature of the cardiac and dysmorphic features may delay diagnosis but clinical recognition of this syndrome is vital given the predisposition for dysrhythmias and sudden death. Cardiac evaluations using serial ECGs with measurements of the QTc interval are essential and should be performed on all patients undergoing workup for periodic paralysis before provocative tests are performed.

Malignant Hyperthermia in Hyperkalemic PP

While the incidence of MH averages 1:50,000 anesthetics, a recent survey of 64 periodic paralysis patients revealed that 10% had experienced MH during surgery. MH has now been proven to be allelic to Periodic Paralysis. All Periodic Paralysis patients are at greatly increased risk to this life-threatening complication of surgery.

REFERENCES:

  1. Barch R, Furman RE: Pathophysiology of myotonia and periodic paralysis. In: Asbury AK, McKhann GM, !McDonald WI, eds. Diseases of the Nervous System, Clinical Neurobiology. 2nd Ed. Philadelphia, W.B. Saunders Co., 1992
  2. Ptacek LJ, Griggs RC: Periodic paralysis. In: Isselbacher KJ, Wilson JD, et al, eds. Harrison's Principles of Internal Medicine. 13th Ed. New York, McGraw Hill, 1994
  3. S Bendahhou; TR Cummins; AF Hahn; et al; A double mutation in families with periodic paralysis defines new aspects of sodium channel slow inactivation. J Clin Invest 106:431-8, 2000
  4. Sterns RH, Narins RG: Disorders of potassium balance. In: Stein JH, ed. Internal Medicine. 4th Ed. Boston, Little Brown & Co, 1994
  5. Hoffman EP: Voltage-gated ion channelopathies: inherited disorders caused by abnormal sodium, chloride, and calcium regulation in skeletal muscle. Annual Review of Medicine 1995;46:431-441
  6. Lehmann-Horn F, Rudel A: Channelopathies: the nondystrophic myotonias and periodic paralyses. Seminars in Pediatric Neurology 1996;3(2):122-139
  7. Brooke M. H.; Disorders of Skeletal Muscle. Neurology in Clinical Practice, Third Edition, Bradley, W.G.; Daroff, R.B.; Fenichel G.M. & Marsden, D.C.: Eds. Boston, MA: Butterworth/Heinemann. 2000
  8. Doyle D. John; Emergency treatment of Hyperkalemia; Critical Care Medicine 1980 8:562-569
  9. Neuromuscular Disease Center, Washington Univ school of Medicine, St. Louis, Mo. 2002
  10. Mendell, Griggs, Ptacek in Harrison's 'Principles of Internal Medicine' 14th ed. 1998, Chap 14
  11. Levitt, L. P.; Rose, L. I.; Dawson, D. M. : Hypokalemic periodic paralysis with arrhythmia. New Eng. J. Med. 286: 253-254, 1972
  12. Sansone, V.; Griggs, R. C.; Meola, G.; Ptacek, L. J.; Barohn, R.; Iannaccone, S.; Bryan, W.;
  13. Baker, N.; Janas, S. J.; Scott, W.; Ririe, D.; Tawil, R. : Andersen's syndrome: a distinct periodic paralysis. Ann. Neurol. 42: 305-312, 1999
  14. Kuntzer T, Flocard F, Vial C, Kohler A, Magistris M; et al: Muscle Nerve 2000 Jul;23(7):1089-94: Exercise test in muscle channelopathies and other muscle disorders.
  15. McManis PG; Lambert EH; Daube JR:The exercise test in periodic paralysis. Muscle Nerve, 1986 Oct, 9:8, 704-10
  16. J. S. Katz, MD; G. I. Wolfe, MD; S. Iannaccone, MD; et al: The Exercise Test in Andersen Syndrome; Archives of Neurology / volume:56 (page: 352)
  17. G.W. Abbott; M.H. Butler; S Bendahhou; et al; MiRP2 forms potassium channels in skeletal muscle with Kv3.4 and is associated with periodic paralysis. Cell 104:217-31, 2001
  18. Kuzmenkin A, Jurkat-Rott K, Lehmann-Horn F, Mitrovic N.; Impaired slow inactivation due to a polymorphism and substitutions of Ser-906 in the II-III loop of the human Nav1.4 channel. Pflugers Arch. 2003 Oct;447(1):71-7. Epub 2003 Jul 26. PMID: 12898257

Where can I get more information?

Please visit our web site at http://www.hkpp.org

Disclaimer

The information on this site is based on current medical knowledge but should never at any time be substituted for the advice and care of a properly qualified medical consultant.