Hypokalemic periodic paralysis presenting as asymmetric focal flaccid paralysis: A case report and literature review.

Patients with the most common form of hypokalemic periodic paralysis (HypoKPP) exhibit symmetrical limb weakness. However, few patients present with asymmetric limb weakness. Here, we describe a unique case of HypoKPP presenting as asymmetric focal flaccid paralysis. In addition, a literature review is performed to provide a perspective for clinical management of similar cases. We present a detailed characterization of this rare type of HypoKPP. The initial presentation was right hand weakness, which progressed to bilateral lower limb weakness. Neurological examination showed that the affected muscles were uniquely confined to specific nerve innervation, i.e., right distal median nerve-innervated muscle, right deep peroneal nerve-innervated muscle and left side. The patient's serum level of potassium was lower than normal; the decline of long exercise test (LET) was higher than normal range; neurophysiological assessment revealed low amplitude compound muscle action potential (CMAP) during attack, the CMAP and patient's weakness rapidly returned to normal level after potassium supplementation. Therefore, HypoKPP can be formally diagnosed based on neurological examination, medical history, timely neural electrophysiological examinations and measurement of blood potassium level.

The long exercise test as a functional marker of periodic paralysis.

AIMS: The aim of this study was to evaluate the sensitivity of the long exercise test (LET) in the diagnosis of periodic paralysis (PP) and assess correlations with clinical phenotypes and genotypes. METHODS: From an unselected cohort of 335 patients who had an LET we analyzed 67 patients with genetic confirmation of PP and/or a positive LET. RESULTS: 32/45 patients with genetically confirmed PP had a significant decrement after exercise (sensitivity of 71%). Performing the short exercise test before the LET in the same hand confounded results in four patients. Sensitivity was highest in patients with frequent (daily or weekly) attacks (8/8, 100%), intermediate with up to monthly attacks (15/21, 71%) and lowest in those with rare attacks (9/16, 56%) (p = .035, Mann-Whitney U-test). Patients with a positive LET without confirmed PP mutation comprised those with typical PP phenotype and a group with atypical features. DISCUSSION: In our cohort, the LET is strongly correlated with the frequency of paralytic attacks suggesting a role as a functional marker. A negative test in the context of frequent attacks makes a diagnosis of PP unlikely but it does not rule out the condition in less severely affected patients.

Clinical and neurophysiological variability in Andersen-Tawil syndrome.

INTRODUCTION: Andersen-Tawil syndrome (ATS) is characterized by a triad of periodic paralysis, ventricular arrhythmias, and dysmorphism. However, patients often lack one or more of these features. METHODS: Clinical and neurophysiological features were reviewed of five members in two families with heterozygous mutations in KCNJ2 (R218Q and R67W). RESULTS: Only one patient had all features of the triad of ATS. One patient had low-set ears, and the others had minor anomalies. Bidirectional ventricular tachycardias were seen in two patients. Two patients (R67W) never had episodes of paralysis. The long exercise test was abnormal in three patients with episodes of paralysis, but normal in two without paralytic episodes. DISCUSSION: ATS patients without skeletal muscle symptoms can have normal neurophysiological examinations. They can show variability in phenotype or the severity of arrhythmias. Such variability among patients who share the same gene mutations may result in underdiagnosis of ATS.

Long Exercise Test in Periodic Paralysis: A Bayesian Analysis.

INTRODUCTION: The long exercise test (LET) is used to assess the diagnosis of periodic paralysis (PP), but LET methodology and normal "cutoff" values vary. METHODS: To determine optimal LET methodology and cutoffs, we reviewed LET data (abductor digiti minimi motor response amplitude, area) from 55 patients with PP (32 genetically definite) and 125 controls. Receiver operating characteristic curves were constructed, and area under the curve (AUC) was calculated to compare (1) peak-to-nadir versus baseline-to-nadir methodologies and (2) amplitude versus area decrements. Using bayesian principles, we calculated optimal cutoff decrements that achieved 95% posttest probability of PP for various pretest probabilities (PreTPs). RESULTS: AUC was highest for peak-to-nadir methodology and equal for amplitude and area decrements. For PreTP ≤ 50%, optimal decrement cutoffs (peak-to-nadir) were > 40% (amplitude) or > 50% (area). DISCUSSION: For confirmation of PP, our data endorse the diagnostic utility of peak-to-nadir LET methodology using 40% amplitude or 50% area decrement cutoffs for PreTP ≤50%. Muscle Nerve 59:47-54, 2019.

The study of exercise tests in paroxysmal kinesigenic dyskinesia.

OBJECTIVE: To unravel if there was muscular ion channel dysfunction in paroxysmal kinesigenic dyskinesia (PKD) patients using the exercises tests (ET). METHODS: Sixty PKD patients including 28 PRRT2 mutations carriers were enrolled in this study, as well as 19 hypokalaemic periodic paralysis (HypoPP) patients as the positive controls and 45 healthy subjects as the negative controls. ET including long exercise test (LET) and short exercise test (SET) was performed in the corresponding subjects. RESULTS: In the LET, both the overall PKD patients and HypoPP patients had greater CMAP amplitude and area increments during exercise than healthy controls. At most 25% of PKD patients were identified from the normality with greater amplitude increment than the area. On the contrary, 50% of HypoPP patients were differentiated with greater area increment than the amplitude. More percentage of PRRT2- patients than PRRT2+ patients had abnormal average amplitude increment. Unexpectedly, five PKD patients had abnormal maximum CMAP amplitude decrements after exercise in the LET, and one had abnormal maximum immediate amplitude decrement in the SET. CONCLUSIONS: Distinct ET manifestations were found in PKD patients compared to normal controls and HypoPP patients. SIGNIFICANCE: Abnormal muscle membrane excitability might be involved in the mechanisms responsible for PKD.

The role of electrodiagnosis with long exercise test in mcardle disease.

INTRODUCTION: In this study we evaluated the role of an electrodiagnostic provocative test (long exercise test) in McArdle disease. METHODS: Twenty-five McArdle patients and 2 control groups underwent an electrodiagnostic protocol with long exercise test (LET), consisting of recording the compound muscle action potential (CMAP) before and after 5 minutes of isometric contraction. RESULTS: The LET disclosed a postexercise decrease in CMAP amplitude in 23 of 25 McArdle patients. The immediate and long-lasting decrease differentiated McArdle patients from controls. Patients with a normal LET demonstrated milder symptoms and/or residual myophosphorylase activity. DISCUSSION: The LET is a sensitive, safe, and noninvasive provocative test that may guide clinicians toward molecular analysis of the myophosphorylase gene. The abnormalities observed on LET point toward complex biochemical mechanisms determined by the absence of myophosphorylase, beyond simple glycolytic blockade (ionic pump dysfunction, sarcolemmal inexcitability). The normal LET in patients with milder symptoms indicates a relationship of the LET with clinical severity, thus identifying it as a potential outcome measure. Muscle Nerve, 2018.

Clinical features and long exercise test in Chinese patients with Andersen-Tawil syndrome.

INTRODUCTION: Andersen-Tawil syndrome (ATS) is a rare multisystem channelopathy characterized by periodic paralysis, ventricular arrhythmias, and developmental dysmorphology. There are few reports concerning ATS in the Chinese population. We analyzed clinical features and evaluated the long exercise test as a tool for diagnosis of periodic paralysis in ATS. METHODS: Direct sequencing of KCNJ2 was performed in 12 subjects from mainland China with suspected ATS. Clinical features, therapeutic responses, and long exercise tests (LET) were retrospectively analyzed. RESULTS: Twelve patients were genetically confirmed to have ATS. A small mandible and clinodactyly were demonstrated in all patients. Premature ventricular contractions were the most prevalent form of cardiac arrhythmia. The LET revealed an early amplitude decrement. CONCLUSIONS: Chinese ATS patients shared some common clinical features with reported subjects in other countries. An early amplitude decrement in LET may be useful for diagnosis of ATS. Muscle Nerve 54: 1059-1063, 2016.