. . Objective: To obtain an objective measure of muscle force in periodic paralysis, we studied ankle dorsiflexion torque during induced paralytic attacks in hyperkalemic and hypokalemic patients. . Subjects, Patients, and Methods: Dorsiflexor torque after peronealnerve stimulation wasrecorded during pro. vocative tests on 5 patients with hypokalemic or hyper- kalemic disorders and on 2 control subjects (1995-2001). Manual strength assessmentwas simultaneously per- formed in a blinded fashion. Standardized provocation procedureswere used. . Results:The loss of torque in hyperkalemic patients roughly paralleledthe lossof clinically detectable strength, whereasin the hypokalemic patients, pronounced torque lossoccurred well before observed clinical effects.No dra- matic changes occurred in the control subjects. Torque H ypokalemic andhyperkalemic periodic paralysis dis- ordersare characterized by intermittent episodes of muscleweakness. I Theseepisodes can be attributedto a primary muscledisorder or can occur secondary to sys- temic disease (eg,chronic potassium imbalance or hyper- thyroidism).The primary disorders can be either sporadic or inherited as an autosomal dominant condition.2'9 Re- cent studies have provided more direct information re- garding the genotype-phenotype associationsin these disorders.1o-16 In addition, a slowly progressive vacuolar myopathy thataccompanies eithercondition may beexac- erbated by frequent paralytic attacks.. Hence,early diag- nosis can facilitate treatmentthat may decrease perma- nent muscledamage. However, the paralytic attacksare frequently brief and occur when the patient is far from a medical center,mak.ing the study of spontaneous attacks From the Department of Neurology (J.W.D., G.J.P.J, Department of - .. ."'~ ~ ~.., ---I ,, ~_. ~. Dh..~;~I~rl.. ID A I \ Anestneslology (l,;.:S., t-'.A.I.), ana uepartment Of t-'nyslology (t-'.A.I.), University of Minnesota School of Medicine, Minneapolis; and De- partment ot Applied PhySiOlOgy, University of Ulm. Ulm. Germany (F.L.-H.). Rnancial support provided by the University of Minnesota Graduate School and the Center for Muscle and Muscle Disorders at the University of Minnesota, Minneapolis. Address reprint requests and correspondence to Paul A. laizzo, PhD, Department of Anesthesiology, University of Minnesota, 420 Dela- ware St SE, Mayo Mail Code 294, Minneapolis, MN 55455 (e-mail: [email protected]). Mayo Clin Proc. 2002;77:232-240 amplitude decreased more than 70% in all patients during the provocation tests;such decreases were associated with alterations induced in serum potassiumconcentrations. . Conclusions: Stimulated torque measurement otTers several advantages in characterizing muscle dysfunction in periodic paralysis: (1) it is independentof patient etTort; (2) it can showa definitely abnormal response early during provocative maneuvers; and (3) characteristics of muscle contraction can be measured that are unobservable during voluntary contraction. Stimulated torque measurements can characterizephenotypic musclefunction in neuromus- cular diseases. Mayo Clin Proc. 2002;77:232-240 CMAP = compound muscle action potential; ECG = electro- cardiogram conduction.9.17'23 @2002Mayo Foundation for Medical Education andResearch~ 232
Transcript
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. Objective: To obtain an objective measure of muscleforce in periodic paralysis, we studied ankle dorsiflexiontorque during induced paralytic attacks in hyperkalemicand hypokalemic patients.
. Subjects, Patients, and Methods: Dorsiflexor torqueafter peroneal nerve stimulation was recorded during pro.vocative tests on 5 patients with hypokalemic or hyper-kalemic disorders and on 2 control subjects (1995-2001).Manual strength assessment was simultaneously per-formed in a blinded fashion. Standardized provocationprocedures were used.
. Results: The loss of torque in hyperkalemic patientsroughly paralleled the loss of clinically detectable strength,whereas in the hypokalemic patients, pronounced torqueloss occurred well before observed clinical effects. No dra-matic changes occurred in the control subjects. Torque
H ypokalemic and hyperkalemic periodic paralysis dis-orders are characterized by intermittent episodes of
muscle weakness. I These episodes can be attributed to a
primary muscle disorder or can occur secondary to sys-temic disease (eg, chronic potassium imbalance or hyper-thyroidism). The primary disorders can be either sporadicor inherited as an autosomal dominant condition.2'9 Re-cent studies have provided more direct information re-garding the genotype-phenotype associations in thesedisorders.1o-16 In addition, a slowly progressive vacuolarmyopathy that accompanies either condition may be exac-erbated by frequent paralytic attacks.. Hence, early diag-nosis can facilitate treatment that may decrease perma-nent muscle damage. However, the paralytic attacks arefrequently brief and occur when the patient is far from amedical center, mak.ing the study of spontaneous attacks
From the Department of Neurology (J.W.D., G.J.P.J, Department of- .. ."'~ ~ ~.., ---I ,, ~_. ~. Dh..~;~I~rl.. ID A I \Anestneslology (l,;.:S., t-'.A.I.), ana uepartment Of t-'nyslology (t-'.A.I.),University of Minnesota School of Medicine, Minneapolis; and De-partment ot Applied PhySiOlOgy, University of Ulm. Ulm. Germany(F.L.-H.).
Rnancial support provided by the University of Minnesota GraduateSchool and the Center for Muscle and Muscle Disorders at theUniversity of Minnesota, Minneapolis.
Address reprint requests and correspondence to Paul A. laizzo, PhD,Department of Anesthesiology, University of Minnesota, 420 Dela-ware St SE, Mayo Mail Code 294, Minneapolis, MN 55455 (e-mail:[email protected]).
Mayo Clin Proc. 2002;77:232-240
amplitude decreased more than 70% in all patients duringthe provocation tests; such decreases were associated withalterations induced in serum potassium concentrations.. Conclusions: Stimulated torque measurement otTersseveral advantages in characterizing muscle dysfunctionin periodic paralysis: (1) it is independent of patient etTort;(2) it can show a definitely abnormal response early duringprovocative maneuvers; and (3) characteristics of musclecontraction can be measured that are unobservable duringvoluntary contraction. Stimulated torque measurementscan characterize phenotypic muscle function in neuromus-cular diseases.
monitor treatment efficacy.24'28 The Medical Research
Council scale commonly used for manual strength mea-
surement is highly nonlinear (with mild to moderately
weak muscles being rated between 4 and 5) and is thus
unreliable for measuring modest changes. Quantitatiye vol-
untary strength assessment with use of a force transducer
substantially increases measurement precision and has
been used frequently to monitor patients in treatment tri-
als.24-3o However, because this approach depends on patient
effort, unreliable results are often obtained if the patient is
in pain or systemically ill.9.26.31 Several investigators have
measured the ankle torque produced by activation of the
dorsiflexor muscles by percutaneous stimulation of the
common peroneal nerve to monitor various neuromuscular
conditions.32-37 Our laboratory has described the further
automation of this approach with online analyses of re-
corded responses.32 The present study was performed to
determine whether such an approach could aid in the phe-
notypic characterization of either hyperkalemic or hy-
pokalemic periodic paralysis.
@ 2002 Mayo Foundation for Medical Education and Research~232
Mayo Clin Proc, March 2002, Vol 77 Muscle Force in Periodic Paralysis 233
SUBJECTS, PATIENTS, AND METHODSThe University of Minnesota Committee on Human Sub-jects approved the investigational protocols used in thisstudy (1.995-2001). All study participants were informed ofthe potential risks of the tests and signed informed consentforms. They all had a physical examination, an electrocar-diogram (ECG), and serologic testing to rule out diabetesand renal, liver, and cardiac disease before enrolling in thestudy. Testing was performed in the early morning on well-rested study participants who had not exercised and hadfasted for 12 hours. Study participants discontinued anymedications that could interfere with paralytic attacks (eg,carbonic anhydrase inhibitors, potassium, diuretics, andsodium channel blockers) 1 week before the test.
Five patients previously diagnosed with periodic paraly-sis participated in the study. The 3 patients withhyperkalemic periodic paralysis came from families pos-sessing the 1704M mutation of the adult skeletal musclesodium channel gene on chromosome 17. One patient withhypokalemic periodic paralysis had an R528H mutation insegment S4 of repeat II of the skeletal muscle L-type Ca2+channel. The mutation in the other hypokalemic patientwas not identified. .
Two control subjects underwent each provocation pro-tocol (potassium loading or depletion) on separate days.They also participated in 4-hour control recording sessionsin which no manipulations of their serum potassium levelswere made but during which their stimulated force wasassessed continually.
Torque MeasurementsChanges in isometric ankle torque after either voluntary
activation or involuntary nerve-stimulated activation of thedorsiflexor muscles were recorded with use of an alumi-num frame device that held the study participant's legsecurely.34 Force was measured by a strain gauge attachedto an aluminum bar that restrained movement of thefootplate.32.34 A preamplifier (Grass Medical Instruments,Quincy, Mass) amplified the output of the strain gauge;output was then digitized and stored on an IBM-compatiblepersonal computer.32 The computer provided online mea-surement of torque magnitude, rise time, and duration. Thefootplate position was rotated for each study participant tostretch the dorsiflexor muscles for maximal force genera-tion. All data acquisition and analysis programs were writtenwith Lab VIEW 2 (National Instruments, Austin, Tex).32
For involuntary contractions, the peroneal nerve wasstimulated supramaximally by surface electrodes with useof 100 to 150 V with O.3-millisecond pulse durations at thefibular head with use of a stimulator (S II, Grass MedicalInstruments).32.34.37 Torque measurements were recordedfor single twitch (after I stimulus), tetanic contraction (af-
ter 4 stimuli delivered at 50 Hz), and maximal voluntarycontraction.
Provocative ManeuversProvocative testing was performed in a hospital room
with emergency equipment and personnel readily available(clinical research center). Serum electrolyte and glucosevalues were available within 5 minutes of blood beingwithdrawn.
For all provocative studies, the patients and controlsubjects had their left legs inserted into the ankle torquemeasuring device and were seated in a chair adjusted tokeep their thighs parallel to the floor. Intravenous catheterswere placed in both of their arms; one was used only toobtain blood samples, while the other was available foradministration of glucose, insulin, or potassium. The ECGswere monitored continually throughout each study, andtraces were printed every 15 minutes. To maintain cutane-ous leg temperatures above 30°C, convective air-warmingcoverlets (model 525, Augustine Medical, Inc, Eden Prai-rie, Minn) were wrapped around their legs and warm air(41°C) was continuously delivered via an air heater-blower unit (Bair Hugger model 500, Augustine Medical,Inc). The surface temperatures of their legs were monitoredwith use of a cutaneous probe (Yellow Springs Instrument,Yellow Springs, Ohio).
Manual strength testing (of right elbow flexion, wristextension, hip flexion, ankle dorsiflexion, and great toedorsiflexion) and single-pulse ankle dorsiflexor twitchtorque measurements (done on the left legs) were per-formed approximately every 15 minutes, while 4-pulsetetanic torque and voluntary torque of the left ankledorsiflexors were alternately measured every 15 minutes.Four-pulse stimulation was occasionally done more fre-quently during periods of rapid loss of strength. Testingcontinued until the serum potassium normalized and thestudy participants were asymptomatic; hence, the length ofthe study periods varied among the study participants.
Potassium DepletionTo test for hypokalemic periodic paralysis, glucose and
insulin were administered to lower serum potassium. Eachstudy participant drank a solution containing 1.5 g/kg ofglucose (maximum, 100 g) over a 3-mi9ute period at theonset of the test. Electrolytes (sodium.-potassium, and bi-carbonate) were measured every 30 minutes for 2 hours. Ifno weakness had developed and no contraindications oc-curred, glucose (3 g/kg, maximum of 200 g, in a solution of2 g/5 mL) was infused intravenously over 1 hour withregular insulin (0.1 U/kg) administered intravenously 15minutes and 45 minutes after the start of the glucose infu-sion. Serum glucose and electrolyte levels were measured
234 Muscle Force in Periodic Paralysis Mayo Clin Proc, March 2002, Vol 77.
Table I. Stimulated Force Measurements During Potassium Loading Protocol
Baseline values Values during potassium loading
Half- Half- TimeForce Force Voluntary Time maximal Force Force Voluntary Time maximal during
Age I-pulse 4-pulse force to peak duration I-pulse 4-pulse force to peak duration protocol(y) (nm) (nm) (nm) (ms) (ms) (nm) (nm) (nm) (ms) (ms) (min)
every 15 minutes for 2 hours after the glucose infusionbegan and then every 30 minutes for the next 2 hours.Because maximal potassium decreases and weakness oc-curred within 3 hours after the initiation of the glucoseinfusion, patients were given a meal containing complexcarbohydrates 2 to 3 hours after completing the glucoseinfusion to help prevent symptomatic hypoglycemia. Thepotassium-lowering protocol was reversed by oral andintravenous potassium chloride administration if (1) potas-sium level decreased below 2.5 mEqlL, (2) marked weak-ness developed indicative of a severe attack, or (3) poten-tially serious ECG changes developed (prominent T wavesor ST-segment depression).
Potassium LoadingTo test for hyperkalemic periodic paralysis, study par-
ticipants drank an unsweetened solution of 0.1 glkg (1.3mEqlkg) of potassium chloride over a period of 2 to 3minutes at the onset of the test. Electrolytes (sodium, potas-sium, chloride, bicarbonate) were measured every 15 min-utes for the first 2 hours, then every 30 minutes for thesubsequent 2 hours. These studies were terminated by aglucose infusion of 50 mL of 50% glucose with 10 U ofregular insulin if urgent treatment was needed because of(1) serum potassium level exceeding 7 mEq/L, (2) pro-found weakness, and/or (3) a serious change in the ECGsignal (ie, bradycardia, atrioventricular block, QRS widen-ing, QRS T-wave fusion).
AnalysesTorque amplitudes and timing parameters wen~ auto-
matically determined via software. Statistical analyses ofthe data were based on analyses of variance and t tests asappropriate. Statistical significance was inferred if P<.O5.
RESULTSEffects of Potassium Manipulation onMeasured Force
Tables I and 2 detail the measured features of stimu-lated torque in control subjects and patients. For patients,the values during the protocol were those at which thetorque amplitude produced by 4-pulse stimulation first de-creased below 75% of baseline; values for I-pulse andvoluntary amplitudes were those that had been determinedimmediately before the chosen 4-pulse response. Pointschosen later in the protocol would have shown a moredramatic amplitude decrease, but the time to peak and half-maximal duration values become less meaningful for suchlower amplitude responses. Values for control subjects inthe tables were chosen at 75 minutes into the protocol toprovide a meaningful comparison for patients; at this time,torques were dramatically affected in the patients.
As seen in Tables I and 2, there was a trend for lowerbaseline torque measurements in hyperkalemic patientscompared with both control subjects and hypokalemic pa-tients. Although this was true for I-pulse, 4-pulse, andvoluntary torque measurements, the difference was notstatistically significant for any of these determinations in-dividually. There was no statistically significant differencein baseline time to peak or half-maximal duration for eitherpatient group compared with control subjects.
For the points during the protocol that are reported inTables I and 2, the 4-pulse stimulated force amplitudes of thepatients showed moderate loss of force, being less than 75% ofbaseline by definition. The data for control subjects showed 4-pulse stimulated force amplitudes that were 89% to 102% ofbaseline amplitude after 75 minutes of both potassium ma-nipulation protocols. Other than amplitude, the only statisti-cally significant change in muscle response at the time of
Mayo Clin Proc, March 2002, Vol" . Muscle Force in Periodic Paralysis 235
Table 2. Stimulated Force Measurements During Potassium Depletion Protocol
Baseline values Values during potassium depletion
Half- Half- TimeForce Force Voluntary Time maximal Force Force Voluntary Time maximal during
Age I-pulse 4-pulse force to peak duration I-pulse 4-pulse force to peak duration protocol(y) (nm) (nm) (nm) (ms) (ms) (nm) (nm) (nm) (ms) (ms) (min)
moderate loss of force was for time to peak: in both hypo-kalemic and hyperkalemic patients, which were shorter than incontrol subjects (t test values .01 and .02, respectively).
Time Course of Torque Changes DuringPotassium Manipulations
Control Subjects.-In the same setting that was usedfor the potassium manipulation protocols, the 2 controlsubjects had torque and strength measured every 15 min-utes for 4 hours. The control subjects remainedasymptom-atic and retained normal strength, as assessed via manualtesting throughout the study. Twitch (single stimuli), 4-pulse (tetanic), and maximal voluntary torque amplitudesvaried by less than 10% in each control subject throughoutthe study (data not shown), with a slight trend towarddecreasing amplitude as the study progressed.
There was no substantial change in the manually as-sessed strength of control subjects at any time during eitherpotassium loading or potassium depletion studies. Torquemeasurements varied little for the first 2 hours of the ex-periment; however, loss of amplitude that was less than25% of baseline did occur in 1 control subject after 2 to 3hours (Figures 1 and 2).
Patients.-All 3 patients with hyperkalemic periodicparalysis experienced a substantial decrease in left ankledorsiflexor torque that preceded or paralleled the decreasein manually assessed strength of every muscle tested (Fig-ure 1). The 2 patients with hypokalemic periodic paralysisshowed a dramatic decrease in ankle dorsiflexor torquethat greatly preceded any recognizable change in strength(Figure 2). The dorsiflexor torque decreased rapidly afterthe onset of the provocation studies in patients with bothconditions, but the peak changes were well delayed in thehypokalemic patients (Figure 3). Additionally, the tempo-ral relationship between the maximal change in serum po-
tassium levels and loss of force differed in the 2 disorders(Figure 3); torque diminution paralleled the decrease andsubsequent increase in potassium in hyperkalemic pa-tients but substantially preceded the changes in hypokale-mic patients.
Systemic Effects of Potassium ManipulationIn the potassium depletion study, the initial ingestion of
glucose was associated with mild to moderate nausea with-out vomiting in all study participants (including the 2 con-trol subjects). Three or 4 hours after intravenous infusion ofglucose and insulin, all study participants became symp-tomatic (diaphoretic, tachycardic, nauseated, presyncopal)in association with transient hypoglycemia. A meal pro-vided 2 to 3 hours after glucose infusion ameliorated butdid not eliminate the symptoms. In 1 patient with hypokale-mic periodic paralysis, an attack of severe weakness wasprecipitated, and potassium was administered orally andintravenously to terminate the study. No study participantsexperienced appreciable ECG changes, and in no studyparticipants did potassium concentration fall below 2.5mEq/L. Weakness was typically maximal within 2 to 3
hours of glucose infusion.In the potassium loading study, nausea without vomit-
ing and a flushed sensation occurred for 15 to 30 minutesafter potassium ingestion. In 1 patient with hyperkalemicperiodic paralysis, the potassium increased to 7 mEq/L;subsequently, the study protocol was terminated by glucoseinfusion. No study participants experienced substantialECG changes. Weakness was typically maximal within I
to 2 hours of potassium ingestion.
DISCUSSIONClinical measurement of strength is a cornerstone of dis-ease management in neuromuscular clinics. An accurate
236 Muscle Force io Periodic Paralysis Mayo Clio Proc, March 2002, Vol 77.
Figure 1. Force during potassium loading in control subjects and 1 patient with hyperkalemic periodic paralysis. Upper graphs representleft ankle dorsiflexor torque after single stimuli (twitch contractions), 4cstimuli at 50 Hz (tetanic contractions, labeled 4-pulse), andmaximal voluntary contraction in 2 control subjects (left) and in 1 patient with hyperkalemic periodic paralysis (right). Middle graphsshow the right ankle dorsiflexor strength assessed manually (Medical Research Council [MRC) scale). Lower graphs illustrate thesimultaneous serum potassium concentration. Note that the 4-pulse and voluntary contractions were alternated every] 5 minutes.
record of variable or progressive weakness can aid in cor-rectly diagnosing a disease or phenotypically characteriz-ing a genetic mutation. In addition, precise measurement ofstrength is often essential for accurate assessment of treat-ment efficacy and development of an appropriate therapeu-tic regimen.
Periodic paralysis is a clinical feature associated withmultiple point mutations of genes encoding either (1) skel-etal muscle tetrodotoxin-sensitive voltage-gated Na+ chan-nels, (2) the skeletal muscle L-type Ca2+ channel,2.S.10,12.13.1S.16.3S
or (3) proteins that regulate potassium channel function.Published methods used to demonstrate periodic paraly-SiSl.9.17.19,21.22 either induce attacks of paralysis in vivo byexercise, potassium manipulation, or drug injection, orthey measure muscle function in vitro.1.17.19 Alternatively,exercise-induced changes in serum potassium levels havebeen reported in hypokalemic and hyperkalemic pa-tients.21 Muscle fiber conduction velocity can be used todistinguish affected from unaffected family members and
can be abnormal even in affected individuals with-out attacks of periodic weakness; however, this test isnonspecific, being abnormal in many myopathic disor-ders.9.22.23 Nevertheless, none of these tests is completelysensitive. Postexercise shifts in serum potassium may bemild, and absolute values may remain within the refer-ence range, making assessment difficult. Manipulation ofserum potassium may induce systemic effects, as in ourcontrol subjects, making elicitation and interpretation ofmild voluntary weakness difficult. The ability to provokean attack by potassium manipulation alone makes thefindings more specific than provocative tests that usemuscle exercise alone because exercise can induce anattack of weakness in both hypokalemic and hyper-kalemic periodic paralysis. Similarly, changes in com-pound muscle action potential (CMAP) measurementscan vary and are well defined for small distal muscles thatmay be least affected in a mild attack. Of note, twitchtension measurements are less sensitive in small distal
Mayo Clio Proc, March 2002, Vol 77 Muscle Force io Periodic Paralysis 237
Figure 2. Force during potassium depletion in control subjects (left) and a patient with hypokalemic periodic paralysis (right). Graphs areorganized as in Figure I. Loss of force assessed with use of the torque measurements preceded weakness noted by the neurologist, who wasunaware of the torque measurements. The initial rise in serum potassium was due to' hemolysis. Note that the 4-pulse and voluntarycontractions were alternated every 15 minutes.
muscles (low signal-to-noise ratios) relative to larger,more severely affected muscles.
In our study, stimulated torque measurements involvedthe tibialis anterior muscle, which is often affected early inan attack of periodic paralysis. The decrease in measuredtorque clearly preceded the decrease in strength as assessedmanually in the hypokalemic patients. Furthermore,changes in simultaneously recorded CMAP amplitudes ofdistal muscles lagged behind changes in ankle dorsiflexiontorque during manipulations of serum potassium (J. W. D.,unpublished data, 2001). CMAP amplitudes measured afterstimulation of either the peroneal.or tibial nerves (measur-ing from extensor digitorum brevis or abductor hallucismuscle, respectively) decreased to 10% of initial values,but these changes could occur several hours after theobserved maximal decreases in ankle torque. For ex-ample, for the data shown in Figure 2, right, at 40 minuteswhen ankle torque was minimal, the peroneal and tibialCMAP amplitudes were 54% and 114% of original val-ues, respectively. Nerve compression may have occurred
during these prolonged investigations, leading to poten-tial alterations in CMAP amplitudes. In subsequent simi-lar studies, torque recordings were performed while con-trol subjects were supine; variations in CMAP amplitudeswere then minimized.
Stimulated. force measurement, being independent ofsubject effort, cannot be affected by the systemic symp-toms that can substantially alter manual strength or volun-tary force measurements. The decreased force observed inour study was not due to repeated stimulation of themuscle because it has been shown previously that inhealthy controls the average peak tetanic torque generatedby the dorsiflexor muscles varies by less than 4% withrepeated ~ting.n In contrast, force amplitudes decreasedby lO%'fo 25% in the control subjects during the study.Even though changes in control subjects were smallcompared with those in patients, they were greater thanthe typical 4% variation. Although observations in con-trol subjects may reflect true change in muscle functionproduced by the potassium manipulations, continued op-
238 Muscle Force in Periodic Paralysis Mayo Clin Proc, March 2002, Vol 77.
Figure 3. Time course of potassium manipulation effect on ankle dorsiflexor torque inall 5 patients. Upper 3 records are from 3 patients with hyperkalemic periodic paralysis(Hyper PP). Lower 2 records are from 2 patients with hypokalemic periodic paralysis(Hypo PP). Shown for comparison are ankle dorsiflexion force amplitudes in tetaniccontraction (torque, 4-pulse stimulation at 50 Hz) and Medical Research Council(MRC) strength assessments of multiple muscle groups (ankle, hip, and wrist) for eachpatient. Vertical dashed lines represent time points at which changes in serum potassiumwere maximaJ.
timization of our study methods (in part by perform-ing tests in supine subjects for better control of limbtemperature and comfort) is desirable to attenuate furtherthe observed decreases in torque in control subjects.In general, the stimulated force procedure was well toler-ated by control subjects and did not interfere with partici-pation in the study; the pain of nerve stimulation wascomparable to that of typical peroneal nerve conductionstudies.
The loss of force in hyperkalemic patients roughly par-alleled the loss of clinically detectable. ~trength. None-theless, stimulated force measurements were valuable inthese patients. to determine that the strength loss wasnot due to diminishing effort in face of systemic adverseeffects from potassium administration. The voluntarystrength loss for hypokalemic patients lagged behind theloss of stimulated force much more dramatically than wasseen in the hyperkalemic patients. This difference in voIun-
Mayo Clin Proc, March 2002, Vol 77 Muscle Force in Periodic Paralysis 239
tary strength is unlikely due to variable effort becausevoluntary responses in humans are generally consideredreliable.29.3o Somehow the cellular pathophysiology of hy-pokalemic periodic paralysis must affect muscle responseto a 4-pulse stimulus more than it affects the longer stimu-lation responsible for voluntary contraction. The moreabrupt onset of weakness and loss of force in hyperkalemicperiodic paralysis may relate to the somewhat lowerbaseline force amplitudes seen in these patients. One canonly speculate why muscle in hypokalemic patients canretain voluntary strength for a longer period, whereasmuscle in hyperkalemic patients loses voluntary strength inparallel with the loss of stimulated force. Likewise, theshortened time to peak measurements at the point of mod-erate weakness for both conditions, with preserved lengthof half-maximal duration, may reflect changes in sarcolem-mal excitability.
Stimulated torque/force assessment is a reproducibleand sensitive method that is valuable in selectively study-ing neuromuscular function in situations in which volun-tary strength is affected by other factors. For instance, itcan measure lower motor neuron function and strength inamyotrophic lateral sclerosis, independent of upper motorneuron disease. We have used this method to monitor theonset and progression of skeletal muscle weakness during aprovoked attack of periodic paralysis, which will help incompletely characterizing the phenotype of each mutationthat can produce periodic weakness. Stimulated skeletalmuscle torque assessment may both substantiate the diag-nosis of a specific form of periodic paralysis in a particularpatient and further clarify the underlying genotype-phimo-type associations in this class of disorders. Furthermore,stimulated force studies allow various physiological forceparameters to be measured (eg, contraction time, peakforce, or time to peak force development), which are unob-servable in voluntary contraction and may be selectivelyaffected in different disease states.32
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