To better help clinicians diagnose and treat periodic paralysis, Neurology Times asked Jacob Levitt, MD, FAAD, to share his insights and expertise in this two-part series.
Dr Levitt is the President and Medical Director to the Periodic Paralysis Association. His interest in PPP is not just a professional one, as he was diagnosed at 13 years old with primary hypokalemic periodic paralysis. Currently, he is the Vice Chairman of the Department of Dermatology at Mount Sinai Medical Center, NY.
In this installment, Dr Levitt explores the importance of developing a comprehensive treatment approach. In the next article, Dr Levitt shares insights on patient education and partnering with patients to achieve best outcomes and quality of life.
Neurology Times: What are the issues in diagnosing PPP that may impact the development of an appropriate and comprehensive treatment plan?
Dr Levitt: Treatment for periodic paralysis first rests on the appropriate diagnosis, which may be straight forward or elusive. Often patients are treated empirically on a presumed diagnosis and, if the therapy works, clinicians stick with that plan.
The three disorders that comprise periodic paralysis are hypokalemic periodic paralysis (hypoPP), hyperkalemic periodic paralysis (hyperPP) (which can occur with or without paramyotonia congenita), and Andersen-Tawil Syndrome (ATS). Related diseases of ion channels that are often discussed and sometimes misdiagnosed as periodic paralysis (and vice versa) include potassium-aggravated myotonia, myotonia congenita, and episodic ataxia, among others.
Obtaining an accurate diagnosis entails obtaining a serum potassium level during an attack. High values suggest hyperPP and low values suggest hypoPP, but normal values do not rule out the diagnosis.
Genetic testing is a simple next step. Currently, Invitae, sponsored by Strongbridge Biopharma, provides genetic testing as a free service. Short or long exercise EMG (modified McManis protocol) is helpful. Similar episodes in family members is supportive of the diagnosis. It also is important to rule out hyperthyroidism in cases of hypoPP.
Most importantly, however, is patient history. Triggers of rest after exercise, cold or illness can suggest hypoPP or hyperPP. Improvement with oral potassium suggests hypoPP, and improvement with high carbohydrate substances suggests hyperPP. Triggers of high carbohydrate meals or high salt foods suggest hypoPP. Andersen-Tawil Syndrome is another variant of periodic paralysis, usually hypoPP, associated with skeletal deformities (eg, clinodactyly, mandibular hypoplasia, low set ears, etc) and long QT syndrome.
The nature of attacks themselves may cause diagnostic confusion. Classically, attacks of hypokalemic periodic paralysis are described as weakness or flaccid paralysis with areflexia. However, some patients with mutation-negative periodic paralysis have weakness associated with myoclonus or jerking and what looks like seizure activity. These patients may respond well to potassium, but they are not labeled as having periodic paralysis since they do not fit in a neat diagnostic box.
NT: What are the considerations for addressing acute attacks? Are there specific strategies that have proved to be effective?
Dr Levitt: Treating periodic paralysis outside of a hospital setting must take into account three factors: medical therapy of acute attacks, medical therapy to prevent attacks, and behavioral modification (both physical and dietary).
For acute attacks of hypoPP, therapy includes one of a variety of potassium ion preparations. In the acute attack, most patients benefit from relatively high doses of aqueous potassium. For example, 60mEq K+ is a reasonable first dose in 250mL to 500mL water. If the attack does not resolve in approximately 15 minutes, another 20 mEq to 60 mEq may be given. Under-dosing potassium in fear of causing fatal hyperkalemia is a common therapeutic error. Fatal hyperkalemia rarely, if ever, happens at the potassium dose levels that are required to abort an attack. Allowing patients leeway to experiment with dosages is important. Therefore, providing larger quantities of monthly prescriptions for potassium packets or tablets can be life-saving.
Unfortunately, this may become expensive for patients. A single packet of potassium chloride 20mEq costs $7 out of pocket, and insurers often limit the amount to be dispensed. Furthermore, arbitrary stop alerts on electronic medical record prescribing protocols often prevent the appropriate amounts of potassium to be dispensed.