Periodic Paralysis and the EMG (CMAP)

Hello All,

A member of our PPN Support, Education and Advocacy Group asked for information about EMG’s, also known as CMAP’s. These tests are often used to diagnose or rule out Periodic Paralysis. Unfortunately, the results of these may or may not diagnose Periodic Paralysis depending on several factors: if it is done correctly, the type of Periodic Paralysis an individual has, whether they have had an episode recently, whether they are presently in an paralytic episode and more.

The procedure can be painful and uncomfortable for some individuals, but not unbearable. If it is done properly, it can diagnose only a few forms of Periodic Paralysis. A NEGATIVE TEST RESULT WILL NOT MEAN THAT YOU DO NOT HAVE PERIODIC PARALYSIS. Research indicates that some individuals who have been genetically diagnosed have negative results on the test or varying results on sequential testing.

A decrease of more than 40% (of the amplitude) is considered enough to diagnose PP. Any more than that is complicating to explain. If someone has not had an episode of paralysis in the three weeks before the test, it would be expected to be normal. The forms which may be detected using EMG (CMAP) testing are calcium and sodium channelopathies and thyrotoxic periodic paralysis.

So, for a diagnosis to be made from the results of an EMG/CMAP many things need to be considered. The following is more specific information and links compiled, which explain all of the difficult to understand specifics. Some forms of PP can easily be detected and others cannot and that depends on many factors and that also includes if the testing is done correctly. So, a negative result does not mean that some one does not have PP, just that it was not able to be detected.

For Hypokalemic Periodic Paralysis:

"Diagnosis can be achieved through a specialized form of electromyographic (EMG) testing called the long exercise test. This test measures the amplitude of a nerve response (called the Compound Muscle Action Potential or CMAP) for 40 to 50 minutes following a few minutes of exercise. In affected patients, there is a progressive fall in the amplitude of the potential.....Standard EMG testing cannot diagnose a patient unless they are in a full blown attack at the time of testing."

http://en.wikipedia.org/wiki/Hypokalemic_periodic_paralysis

Info on all forms:

"Electromyogram (EMG). Muscle electrophysiologic testing must be performed during an interictal period. Protocols for implementation [Fournier et al 2004] and interpretation [Tan et al 2011] have been published. EMG testing includes: 

Assessment for myotonic discharges. 

Repeated short exercise tests. 

A long exercise test (the principal discriminating test for primary periodic paralysis).

The diagnosis of primary hypokalemic periodic paralysis relies on:

The absence of myotonic discharges Note: One family with combined heat-induced myotonia and cold-induced hypokalemic periodic paralysis has been described [Sugiura et al 2000].
The presence of a progressive and marked decrease in the amplitude of compound motor action potentials (CMAP) during a long exercise test [McManis et al 1986].

During an attack, EMG findings are not specific; EMG demonstrates a reduced number of motor units and possibly myopathic abnormalities.

Between attacks, EMG may exhibit myopathic abnormalities in individuals with fixed myopathy.

Specific exercise tests can assist with the diagnosis of periodic paralyses and nondystrophic myotonias [Fournier et al 2004]:

Short exercise test (SET). SET consists of recording evoked compound muscle action potential (CMAP) every ten seconds over one minute after a short effort (5-12 seconds) [Streib 1987].

Long exercise test (LET). LET consists of recording evoked CMAP over 30-45 minutes, every one to two minutes and then every five minutes, after a long effort (2-5 minutes, with brief 3- to 4-second rest periods every 15-45 seconds) [McManis et al 1986].
Five patterns (I-V) of abnormal responses to SET and/or LET in periodic paralyses and nondystrophic myotonias have been described [Fournier et al 2004]. Genetically defined periodic paralyses specifically result in: Pattern IV (no or rare myotonic discharges, increase of CMAP on  SET, immediate increase and late marked decrease in LET), more commonly seen in the hyperkalemic type OR Pattern V (no myotonic discharges, normal response to SET, no immediate increase but late marked decrease in LET), more commonly seen in the hypokalemic type.

A false negative normal pattern may be noted in some individuals who have a disease-causing mutation, especially in asymptomatic individuals or those who have not recently had a paralytic attack [Tengan et al 2004].

A decrease of at least 30% in CMAP amplitude and surface on LET is diagnostic for HOKPP. A decrease of less than 30% and greater than 20% is less specific and may indicate a different diagnosis. This decrease corresponds to pattern IV (with initial increment) and pattern V."

http://www.ncbi.nlm.nih.gov/books/NBK1338/#!po=11.0169

"During an episode of weakness, the compound motor action potential (CMAP) may be reduced, and rarely, absent on motor nerve conduction studies; insertional activity is reduced, fibrillation potentials and positive sharp waves are seen and there is an increased proportion of polyphasic motor unit potentials on needle examination (Engel et al., 1965). Surface and invasive EMG studies document reduced muscle fibre conduction velocity (Links and van der Hoeven, 2000). Interictal clinical electrophysiological testing (Table 2) is helpful in the diagnosis of PP. Changes in CMAP after exercise may correlate with exercise-induced symptoms (McManis et al., 1986) and channel mutation (Fournier et al., 2004). Myotonia on EMG needle examination occurs in ∼75% of individuals with HyperPP and in all patients with PMC; EMG myotonia does not occur in HypoPP. Electrodiagnostic studies at room temperature and after cooling the extremity may be more sensitive for HyperPP and PMC. The long exercise protocol also may detect a delayed decrement in ATS patients (Katz et al., 1999)." (more information at the following link)

http://brain.oxfordjournals.org/content/129/1/8

"EMG: In between attacks, there may be fibrillation
and complex repetitive discharges, increased by
cold and decreased by exercise (in hypokalaemic
periodic paralysis). During attacks, EMG will show
electrical silence, in both hyper- and hypokalaemic
periodic paralysis."

http://medind.nic.in/jac/t02/i4/jact02i4p374.pdf

One more about all forms.....

Electrodiagnostic testing is helpful in guiding genetic testing and in distinguishing between PP and other forms of weakness. Some patients with hyperkalemic PP show an initial increment during the
short exercise protocol.14 However, the short exercise test does not have significant diagnostic value in PP as most patients show no abnormalities.14 The LET is more useful in these patients. Some patients with hyperkalemic PP exhibit electrical myotonia; this finding is not described in hypokalemic PP.11,14

Long exercise test

LET is also typically performed stimulating the ulnar nerve at the wrist and recording the ADM motor responses. Supramaximal ADM responses are recorded at baseline, throughout 5 minutes of exercise, and then more than 45 to 60 minutes following exercise; investigators vary on the frequency of recordings following exercise.14,16,19 for 5 minutes with periodic, short-rest periods every 15 seconds. CMAPs are recorded after each minute of exercise. Some investigators then record postexercise CMAPs every minute for 5 minutes followed by every 5 minute CMAPs for 40 to 45 minutes.14 Others recommend postexercise CMAPs every 1 to 2 minutes for 30 to 45 minutes.19  In the initial version of the LET, decrements in amplitude and area were measured from the maximal CMAP obtained during or immediately after exercise.19,20 Subsequent investigators have measured decrement from the baseline 45 minutes.14  Others recommend postexercise CMAPs every 1 to 2 minutes for 30 to 45 minutes.19 In the initial version of the LET, decrements in amplitude and area were measured from the maximal CMAP obtained during or immediately after exercise.19,20 Subsequent investigators have measured decrement from the baseline demonstrated to have a sensitivity of 80% to 100%, which improved to 100% if CMAP area was examined alone.16 Normal controls typically show a small increment in amplitude and area (10%) following exercise and a subsequent decrement of 15% in amplitude and area compared with maximal-exercise CMAP (never more than 30%).19,20 

An abnormal decrease is defined as 40.9% for amplitude and 48% for area (2 SDs).19,20 When recorded after each minute of exercise. Some investigators then record postexercise CMAPs every minute for 5 minutes followed by every 5 minute CMAPs for 40 to 45 minutes.14 Others recommend postexercise CMAPs every 1 to 2 minutes for 30 to 45 minutes.19 In the initial version of the LET, decrements in amplitude and area were measured from the maximal CMAP obtained during or immediately after exercise.19,20 Subsequent investigators have measured decrement from the baseline CMAP obtained before exercise.14 One study shows the methods to be similar, although use of the preexercise baseline may be less sensitive in hyperkalemic PP.16 Among the small cohorts studied, the LET has a sensitivity of 80% to 90% in both hypokalemic PP and hyperkalemic PP.12,14,19,20 In one series of ATS, the LET was demonstrated to have a sensitivity of 80% to 100%, which improved to 100% if CMAP area was examined alone.16
           

Normal controls typically show a small increment in amplitude and area (10%) following exercise and a subsequent decrement of 15% in amplitude and area compared with maximal-exercise CMAP (never more than 30%).19,20 An abnormal decrease is defined as 40.9% for amplitude and 48% for area (2 SDs).19,20 When measured from preexercise baseline, an abnormal decrement in CMAP amplitude is defined as greater than 20% of baseline.14
        

Two typical LET patterns are observed in PP, which may help to distinguish between calcium and sodium channel mutations.14 Patients with a sodium channel mutation often exhibit Fournier pattern IV (Fig. 3) manifest by an increment in CMAP amplitude/area with exercise followed by a decrement in amplitude/area 40% to 80% of baseline (dependent on method); maximal decrement is observed between 30 and 45 minutes postexercise.14,16,20 Fournier pattern V manifest by a maximal decrement in area/amplitude after 20 to 40 minutes is more typical of calcium channel-related PP;
this decrement may or may not be preceded by an initial increment in CMAP amplitude/area.14,16,20 However, there is some cross over between pattern IV and V in hyperkalemic and hypokalemic PP, which may be explained by the proportion of hypokalemic PP patients who have an SCN4A mutation.14 Pattern V is most typical
in ATS.16

https://depts.washington.edu/neurolog/images/emg-resources/Myotonic_Disorders.pdf

Added July 19, 2016

This is about normal EMG's and info from article about Electrodiagnostic Evaluation of Myopathies with comment that, "EDS studies may be normal in selected muscle diseases"... in which the author includes endocrine myopathies. Important to note that MDA refers to PP as 'endocrine metabolic myopathy' in their  2011 Quest Magazine.

Electrodiagnostic Evaluation of Myopathies Sabrina Paganoni, MD, PhDa, *, Anthony Amato, MDb

"EDX studies may be normal in selected muscle diseases (certain endocrine, metabolic, congenital, and mitochondrial myopathies). Thus, in the appropriate clinical context, normal EDX studies do not necessarily rule out the presence of a myopathy. EDX studies are most useful to diagnose a myopathy when further data are needed to exclude alternative diagnoses, confirm the presence of a muscle disease, and narrow down the differential. "

http://www.myositis.org/storage/documents/General_Research/diagnosis_of_myopathies.pdf

Added 06/19/2017

From Maureen......regarding EMG /CMAP...important information....

The following resource with statement about electrophysiological abnormalities would be valuable to save in file for EMG and PP. This article also mentions symptoms/features of PP regarding cranial nerve involvement that some PP articles/textbook info denies being part of PP, so this misleads/misinforms doctors.

Such as that cranial nerves not involved. Or the reliability of EMG to diagnose. That if 'negative/normal' not have have PP.

This article mentions CMAP being normal when not in episode or if EMG had been abnormal during episode, as K+ improved, then CMAP normal. So that may explain why we may have 'normal' EMG when typically being tested for 'scheduled' test when we're not in episode. But when EMG is 'normal' then often PP dx is 'denied'. (WE NEED TO KNOW THIS KIND OF INFO AND RESOURCES TO ADVOCATE FOR OURSELVES).
https://www.ncbi.nlm.nih.gov/

Ann Indian Acad Neurol. 2014 Jan-Mar; 17(1): 100–102.
doi: 10.4103/0972-2327.128566
PMCID: PMC3992744
Reversible electrophysiological abnormalities in hypokalemic paralysis: Case report of two cases
C. M. Sharma, Kunal Nath, and Jigar Parekh
Author information ► Article notes ► Copyright and License information ►

"She also had cranial nerve involvement in form of bilateral facial weakness, neck flexor weakness, and dysphagia. "

"Reversible electrophysiological abnormalities of sensory nerve function have been reported earlier.[2] A prospective study in 10 patients with HPP revealed a pattern of reduced sensory action potentials during paralytic attacks, which normalized with correction of serum potassium."

........................................

EMG (CMAP) reduced during quad HypoKPP episode. NC abnormalities improved with HypoKPP correction.

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3992744/

 "Reversible electrophysiological abnormalities of sensory nerve function have been reported earlier.[2] A prospective study in 10 patients with HPP revealed a pattern of reduced sensory action potentials during paralytic attacks, which normalized with correction of serum potassium."

Until later...