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INTRODUCTION

STARTING POINT FOR DISEASE DESCRIPTIONS

 
The Periodic Paralyses

Patrick E. Cochran, Ph.D., C. S. D.
President, Periodic Paralysis Research Library

NOTES:
We have provided links throughout to relevant information from the following Resources:
National Center for Biotechnology Information (NCBI):

Neuromuscular Disease Center (NDC): Washington University, St. Louis, MO USA.

NINDS Periodic Paralyses Information Page: National Institute of Neurological Disorders and Stroke.

Gene Reviews, a service of Gene Clinics: Online publication of expert-authored descriptions for physicians and other healthcare providers.

The National Library of Medicine - Medical Subject Headings (MeSH): The MeSH Descriptor Data links are provided where available. However, it should be pointed out that in some cases, the current MeSH descriptors may be incomplete or inaccurate, based on the most recent information. The PPRL is working with the National Library of Medicine to correct the descriptors for these disorders.

WHAT IS PERIODIC PARALYSIS?

The term Periodic Paralysis describes a collection of disorders now known to be associated with mutations in genes that code for ion channels in the muscle membrane. Ion channels are important in controlling the movement of ions across the cell membrane and in the shift of ions from one cell compartment to another. Mutations in the genes that map the structure of these channels result in the disruption of muscle contraction mechanisms inhibiting the proper function of muscles (Cannon, 2002).

According to Brooke (2000), rather than resulting in permanent malfunction, some mutations produce intermittent symptoms, which is the case in periodic paralysis. It has been suggested that episodic paralysis may be a more accurate description for this class of disorder, to better convey the unpredictable nature of symptom onset, but over 100 years of established convention retains its hold.

The primary forms of periodic paralysis are transmitted by autosomal dominant inheritance. Individuals with autosomal dominant diseases have a 50-50 chance of passing the mutation on to their children.

Genetic diagnostic resources are available for most known variants of periodic paralysis; however, access to genetic testing is still limited primarily to research centers. In the research environment, the diagnostic process can take several months to years to establish confirmation. While positive genetic results can generally be considered dependable, false negatives are still known to occur at a relatively high rate. Many research protocols do not allow the researcher to report the results to the individual patient. As a consequence, for the majority of cases, diagnosis is still dependent on clinical evaluation.

Mutations have now been characterized in four voltage-gated skeletal muscle ion channels —calcium (Ca), sodium (Na), chloride (Cl), and potassium (K). Due to this association with abnormalities in ion channels, the periodic paralyses belong to the class of disorders referred to as channelopathies.

Rüdel, Hanna, and Lehmann-Horn (1999). list the periodic paralyses along with paramyotonia congenita, the non-dystrophic myotonias, and malignant hyperthermia, in this expanding class of primary skeletal muscle disorders (also see Jurkat-Rott K, Lerche H, Lehmann-Horn F., 2002, J Neurol).

GENERAL DESCRIPTION OF SYMPTOMS:

Although Hartwig provided “the first unmistakable account” in 1874 (Adams, Victor & Ropper, 1997), the periodic paralyses remain relatively obscure in our present time. Ruff and Gordon (1986), A. G. Engel (1988), and T. P. Links (1992) list a number of characteristics considered common to this group of disorders.
Common Characteristics Associated with the Periodic Paralyses


  • Attacks may last from minutes to days, and occur sporadically.

  • Weakness can be local or generalized.

  • The deep tendon reflexes become depressed, diminished, or lost in the course of the attacks.

  • The muscle fibers become unresponsive to either direct or indirect electrical stimulation during attacks.

  • The generalized attacks usually begin in proximal muscles and then spread to distal ones.

  • Respiratory and cranial muscles tend to be spared but eventually may also be paralyzed.

  • Rest after exercise tends to provoke weakness of the muscles that had been exercised, but continued mild exercise may abort attacks.

  • Exercise restricted to a single muscle or a small group of muscles can induce weakness of the exercised muscles without a detectable change of the potassium level in systemic circulation.

  • Exposure to cold may provoke weakness in the primary forms of the disease.

  • Complete recovery usually occurs after initial attacks.

  • Permanent weakness and irreversible pathological changes in muscle can develop after repeated attacks.


  • The symptoms listed in the table above are representative of the descriptions used by clinicians for at least the last three decades. As more knowledge is gained about the periodic paralyses, both the molecular and clinical descriptions have taken on new dimensions and our understanding is becoming more complete.

    Please See:

    Muscle weakness or rigidity due to hereditary ion channel diseases. Links TP, van der Hoeven JH.

    Voltage-gated ion channels and hereditary disease. Lehmann-Horn F, Jurkat-Rott K. (an excellent review article).

    THE PRIMARY VARIANTS:

    There are a number of lists provided by authors showing a wide spectrum of disorder variants. Some of the variability between these lists can be attributed to evolving opinions regarding the characterization of diverse clinical presentations and interpretation of non-standardized naming conventions. One of the more inclusive lists is provided by Dr. Alan Pestronk at the NDC. The NDC has an excellent search function by key word, and provides a wealth of information.

    While the periodic paralyses are commonly grouped with the non-dystrophic myotonias, the classic forms of periodic paralysis traditionally include: Hypokalemic Periodic Paralysis, Hyperkalemic Periodic Paralysis, and Normokalemic Periodic Paralysis. Today Normokalemic Periodic Paralysis, now a questionable entity, is rarely listed, and Andersen’s Syndrome (now Andersen-Tawil Syndrome) is more frequently included.

    The traditional naming of the classic forms of Periodic Paralysis based on varying levels of serum potassium, has led to some confusion in understanding these diseases. This confusion is exemplified in the case of the variant described as Normokalemic Periodic Paralysis.

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    Section Last Modified:
    12/29/2009 07:38 PT
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