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Hyperkalemic Periodic Paralysis and Permanent Weakness

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Hyperkalemic Periodic Paralysis and Permanent Weakness Note: This copy is for your personal non-commercial use only. To order presentation-ready copies for distribution to your colleagues or clients, contact us at www.rsna.org/rsnarights. NG I AG M Hyperkalemic Periodic Paralysis and Permanent Weakness: 3-T MR Imaging Depicts Intracellular 23Na Overload—Initial Results1 MUSCULOSKELETAL I MUSCULOSKELETAL n Erick Amarteifio, MD Purpose: To assess whether myoplasmic ionic sodium (Na+) is Armin M. Nagel, PhD increased in muscles of patients with hyperkalemic per- Marc-André Weber, MD, MSc 23 ESEARCH iodic paralysis (HyperPP) with 3-T sodium 23 ( Na) mag- R Karin Jurkat-Rott, PhD netic resonance (MR) imaging and to evaluate the effect Frank Lehmann-Horn, MD, PhD of medical treatment on sodium-induced muscle edema. ORIGINAL Materials and This study received institutional review board approval; Methods: written informed consent was obtained. Proton (hydro- gen 1 [1H]) and 23Na MR of both calves were performed in 12 patients with HyperPP (mean age, 48 years 6 14 [standard deviation]) and 12 healthy volunteers (mean age, 38 years 6 12) before and after provocation (uni- lateral cooling, one calf). 23Na MR included spin-density, T1-weighted, and inversion-recovery (IR) sequences. To- tal sodium concentration and normalized signal intensities (SIs) were evaluated within regions of interest (ROIs). Muscle strength was measured with the British Medical Research Council (MRC) grading scale. Five patients un- derwent follow-up MR after diuretic treatment. Results: During rest, mean myoplasmic Na+ concentration was sig- nificantly higher in HyperPP with permanent weakness (40.7 µmol/g 6 3.9) compared with HyperPP with tran- sient weakness (31.3 µmol/g 6 4.8) (P = .004). Mean SI in 23Na IR MR was significantly higher in HyperPP with per- manent weakness (0.83 6 0.04; median MRC, grade 4; range, 3–5) compared with HyperPP without permanent weakness (0.67 6 0.05; median MRC, grade 5; range, 4–5) (P = .002). Provocation reduced muscle strength in HyperPP (before provocation, median MRC, 5; range, 3–5; after provocation, median MRC, 3; range, 1–4) and increased SI in 23Na IR from 0.75 6 0.09 to 0.86 6 0.10 (P = .004). Spin-density and T1-weighted sequences were less sensitive, particularly to cold-induced Na+ changes. 23Na IR SI remained unchanged in volunteers (0.53 6 0.06 1 From the Department of Diagnostic and Interventional Ra- before and 0.54 6 0.06 after provocation, P = .3). Ther- diology, University Hospital of Heidelberg, Im Neuenheimer apy reduced mean SI in 23Na IR sequence from 0.85 6 Feld 110, D-69120 Heidelberg, Germany (E.A., M.A.W.); 0.04 to 0.64 6 0.11. Department of Medical Physics in Radiology (A.M.N.) and Radiology (E.A., M.A.W.), German Cancer Research Center, 23 + Heidelberg, Germany; and Department of Neurophysiology, Conclusion: Na MR imaging depicts increased myoplasmic Na in + Ulm University, Ulm, Germany (K.J., F.L.). From the 2009 HyperPP with permanent weakness. Na overload may RSNA Annual Meeting. Received May 12, 2011; revision cause muscle degeneration developing with age. 23Na MR requested July 2; final revision received December 16; imaging may have potential to aid monitoring of medical accepted December 29; final version accepted January 6, treatment that reduces this overload. 2012. Address correspondence to E.A. (for MR imaging, e-mail: [email protected]) or F.L. (for q hyperkalemic periodic analysis, e-mail: frank.lehmann- RSNA, 2012 [email protected]). q RSNA, 2012 154 radiology.rsna.org n Radiology: Volume 264: Number 1—July 2012 MUSCULOSKELETAL IMAGING: MR Depiction of 23Na Overload in Hyperkalemic Periodic Paralysis Amarteifio et al yperkalemic periodic paralysis (Hy- in vivo after provocation with specific a weighting toward intracellular sodium perPP) is a dominantly inherited triggers by using sodium 23 (23Na) mag- (20). In an analysis on paramyotonia, an Hmuscle disease characterized by netic resonance (MR) imaging (11). allelic disorder, noninvasive 23Na MR im- attacks of flaccid weakness and interic- Recent studies have shown the poten- aging techniques at 1.5-T for detecting tal myotonia (1). The incidence of Hy- tial of 23Na MR imaging for quantification changes of the Na+ signal in muscular tis- perPP is approximately one per 200 000 of total sodium amount in human muscle sue after provocation were implemented persons, and its penetrance within the (12). A central problem in 23Na MR im- (16). Also, these techniques have been population is high with more than 90% aging is that the signal emitted from mus- successfully refined to aid qualitative vi- (2). HyperPP is a channelopathy caused cle tissue is roughly 50 000 times smaller sualization of changes of the muscular by mutations in the SCN4A gene cod- than the signal received from standard Na+ amount in patients with hypokale- ing for the Nav1.4 muscle sodium chan- proton (hydrogen 1 [1H]) MR imaging mic periodic paralysis in a state of severe nel (3–5). The disease includes both (13). The short T2 relaxation time of permanent weakness (9,20). The studies hyper- and hypoexcitability of muscle 23Na in (muscular) tissue causes a low mentioned above present important find- fibers, frequently in the same patient at signal-to-noise ratio when conventional ings on channelopathies. However, to our different times (6). The flaccid muscle measuring times are used. This is still the knowledge, the researchers in none of weakness (paralysis) is typically triggered case when newer density-adapted three- the published studies noninvasively ana- by ingestion of potassium-rich foods or dimensional radial acquisition techniques lyzed the myoplasmic sodium amount in rest following physical strain (7). Some are used to improve the results (14,15). patients with various types of HyperPP. patients require medication, including A further challenge with any imaging In the current study, IR 23Na MR imaging hydrochlorothiazide (Hct Hexal; Hexal, method is the precise differentiation be- sequences were included to allow for a Holzkirchen, Germany) or acetazolamide tween intra- and extracellular 23Na. With reduction of signal emitted by blood ves- (Diamox; Goldshield Pharmac, Croydon, T1-weighted 23Na MR imaging sequences, sels and muscular edema. The rationale England) (8). a muscular Na+ accumulation in muscular was a better visualization of intracellular The underlying sodium ion (Na+) channelopathies can be visualized (16), sodium content changes that are primar- channel mutations destabilize the in- but a measure of intra- and extracellu- ily responsible for muscle weakness. activated channel state. This results lar Na+ amounts is not provided. Shift Thus, the aim of the current study in a persistent current, which could reagents would enable a clear separation was to assess whether the myoplasmic lead to Na+ accumulation in the mus- between intra- and extracellular Na+, but Na+ in patients with HyperPP with per- cle (9). Until now, Na+ accumulation they cannot be administered to humans manent weakness is increased during has been described in HyperPP fibers because of their toxicity (17). Other tech- rest or after provocation by using 3-T exposed to increased extracellular po- niques do not allow a separate measure- tassium ion (K+) concentration in vitro ment of intra- and extracellular Na+. by using Na+-sensitive microelectrodes The extracellular Na+ concentration (10). Also Na+ accumulation during is about 10 times higher than the intracel- weakness episodes has been described lular Na+ concentration, which allows a Published online before print rough estimation of intracellular sodium 10.1148/radiol.12110980 Content code: content changes by measuring the total Na+ concentration (18). Meanwhile, it is Radiology 2012; 264:154–163 Advances in Knowledge possible to provide a partial suppression Abbreviations: 23 of signal from sodium ions in the extra- HyperPP = hyperkalemic periodic paralysis n The implementation of a Na IR = inversion recovery MR imaging inversion-recovery cellular milieu (eg, cerebrospinal fluid, MRC = British Medical Research Council sequence allowed for a weighting blood) by using an inversion-recovery (IR) 23 ROI = region of interest 23 Na MR imaging sequence (19). Fur- toward intracellular Na with a SI = signal intensity high sensitivity. thermore, results from investigations of STIR = short inversion time inversion recovery patients with muscular channelopathies n With this technique, a markedly indicate that an IR preparation allows for Author contributions: increased intracellular sodium Guarantors of integrity of entire study, E.A., M.A.W.; study concentration of resting skeletal concepts/study design or data acquisition or data analysis/ muscle was detected in patients interpretation, all authors; manuscript drafting or manu- with hyperkalemic periodic script revision for important intellectual content, all authors; approval of final version of submitted manuscript, all paralysis (HyperPP) with perma- Implication for Patient Care authors; literature research, E.A., F.L.; clinical studies, E.A., nent weakness. n Increased myoplasmic sodium A.M.N., M.A.W., F.L.; experimental studies, E.A., A.M.N., n Acetazolamide and hydrochloro- acts as an indicator of perma- K.J., F.L.; statistical analysis, E.A., F.L.; and manuscript thiazide decreased the intracel- nent muscle weakness in editing, all authors lular sodium level and increased HyperPP and precedes fatty Potential conflicts of interest are listed at the muscle strength. muscle degeneration. end of this article. Radiology: Volume 264: Number 1—July 2012 n radiology.rsna.org 155 MUSCULOSKELETAL IMAGING: MR Depiction of 23Na Overload in Hyperkalemic Periodic Paralysis Amarteifio et al 23Na MR imaging. Moreover, the effect 30 times. In five patients, follow-up time (100 msec; flip angle, 90°; voxel of medical treatment was evaluated MR imaging was performed after treat- size, 5 3 5 3 5 mm3; acquisition time, with 23Na MR imaging. ment with acetazolamide or hydrochlo- 8 minutes 20 seconds). rothiazide lasting several weeks.
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