Primary hypokalemic periodic paralysis (HypoPP) is a skeletal muscle channelopathy most commonly caused by pathogenic variants in the calcium channel gene, CACNA1S. HypoPP can present with attacks of paralysis and/or permanent muscle weakness. Previous studies have shown that patients with HypoPP can have impaired quality of life (QoL). In this cross-sectional study, we aimed to describe the QoL in patients with HypoPP caused by pathogenic variants in CACNA1S using The Individualized Neuromuscular Quality of Life (INQoL) questionnaire, a validated tool to measure the QoL of patients with neuromuscular diseases (higher score, worse QoL). We showed that muscle weakness and fatigue were the symptoms with the greatest impact on participants\' lives and that \"activities\", in the life domain of the INQoL, was most affected by HypoPP. Furthermore, we showed that the total INQoL score increased with age. Low QoL was primarily driven by progressive permanent muscle weakness and not attacks of paralysis, although half of the participants reported that attacks of paralysis challenged their daily life. The results suggest that special attention should be given to muscle weakness and fatigue in patients with HypoPP.

Primary hypokalaemic periodic paralysis during pregnancy has been rarely reported. Four pregnant women with the acute onset of flaccid paralysis presented between January 2018 and December 2021. Focussed history and physical examination helped an appropriate radiological and laboratory investigation plan to be made. All women recovered within 4-7 days of potassium supplementation. Supplemental potassium continued until delivery. A pain management plan with continuous epidural infusion helped in avoiding stress-induced hypokalaemia. None of the women developed an episode of muscle weakness during the intervening period. In conclusion, a focussed history and targeted laboratory investigation are needed to diagnose primary hypokalaemic periodic paralysis. Early administration of oral or intravenous potassium is crucial in improving fetomaternal outcomes.

Thyrotoxic periodic paralysis (TPP) is a rare complication of hyperthyroidism characterized by typical muscular symptoms, ranging from paresis to complete paralysis, commonly associated with low potassium blood levels (<3 mmol/l). It is more commonly reported in adult Asian individuals and can lead to life-threatening situations. Therefore, early clinical diagnosis and targeted therapy are of crucial importance. In this article, we report the case of a 17-year-old adolescent with a Vietnamese background and known Graves\' disease who was admitted with typical TPP-related symptoms but no hypokalemia. After treatment with an antithyroid medication and oral potassium supplementation, no new episode of TPP was observed. Using next-generation sequencing, a genetic analysis of TPP-related ion channel genes (KCNJ2, KCNJ18, KCNE3, SCN4A, and CACNA1S) found no known/likely pathogenic variants or variants of unknown significance. To the best of our knowledge, this is only the second reported case of quite normokalemic TPP in the pediatric population. Prompt diagnosis of TPP is essential to prevent harmful complications. Supplementation with potassium appears to be successful alongside non-selective beta-blockers. Normalization of thyroid function should be pursued to prevent new attacks, which is considered the best preventive measure.

UNASSIGNED: CACNA1S related congenital myopathy is an emerging recently described entity. In this report we describe 2 sisters with mutations in the CACNA1S gene and the novel phenotype of congenital myopathy and infantile onset episodic weakness.
UNASSIGNED: Both sisters had neonatal onset hypotonia, muscle weakness, and delayed walking. Episodic weakness started in infancy and continued thereafter, provoked mostly by cold exposure. Muscle imaging revealed fat replacement of gluteus maximus muscles. Next generation sequencing found the missense p.Cys944Tyr variant and the novel splicing variant c.3526-2A>G in CACNA1S. Minigene assay revealed the splicing variant caused skipping of exon 28 from the transcript, potentially affecting protein folding and/or voltage dependent activation.
UNASSIGNED: This novel phenotype supports the notion that there are age related differences in the clinical expression of CACNA1S gene mutations. This expands our understanding of mutations located in regions of the CACNA1S outside the highly conserved S4 segment, where most mutations thus far have been identified.

The aim of this study was to establish whether bumetanide can abort an acute attack of weakness in patients with HypoPP. This was a randomised, double-blind, cross-over, placebo-controlled phase II clinical trial. Focal attack of weakness was induced by isometric exercise of ADM followed by rest (McManis protocol). Participants had two study visits and received either placebo or 2 mg bumetanide at attack onset (defined as 40 % decrement in the abductor digiti minimi CMAP amplitude from peak). CMAP measurements assessed attack severity and duration. Nine participants completed both visits. CMAP percentage of peak amplitudes in the bumetanide (40.6 %) versus placebo (34.9 %) group at 1hr following treatment did not differ significantly (estimated effect difference 5.9 % (95 % CI: (-5.7 %; 17.5 %), p = 0.27, primary outcome). CMAP amplitudes assessed by the area under the curve for early (0-2hr post-treatment) and late (2-4 h post-treatment) efficacy were not statistically different between bumetanide and placebo (early effect estimate 0.043, p = 0.3; late effect estimate 0.085, p = 0.1). Two participants recovered from the attack following bumetanide intake; none recovered following placebo. Bumetanide was well tolerated but not efficacious to rescue a focal attack in an immobilised hand in the majority of patients, although data supports further studies of this agent.

UNASSIGNED: Diagnosis of rare even can be missed due to less familiarity with the disorder.In patients with muscle weakness, infectious causes are prioritized.Electrolyte profile not only identifies the problem, but also prevents unnecessary workup.
UNASSIGNED: In underdeveloped countries, diagnosis of rare disorders is usually delayed due to less familiarity of the clinicians to such disorders. As a result, infectious and inflammatory causes for an ailment are prioritized as compared to non-infectious etiologies. Hypokalemic periodic paralysis (PP) is a rare disorder, characterized by episodic muscle weakness that can rarely be associated with life-threatening cardiac arrhythmia. A teenage Afghan boy presented to the emergency department with an acute flaccid paralysis, that started 1 h after intense exercise The weakness involved both, the upper and lower extremities. Laboratory investigations, led to the impression of hypokalemic PP, precipitated by intense exercise. Accordingly, intravenous potassium chloride infusion diluted with normal saline led to the complete resolution of paralysis as well as correction of electrocardiographic changes. The list of differential diagnosis for flaccid muscle paralysis is wide, which generally requires a extensive investigations, but in hypokalemic PP, a cardinal electrolytes profile can lead towards early diagnosis. High degree of clinical suspicion with appropriate history taking and physical examination helps with the immediate identification and management of this disorder.

UNASSIGNED: Disorders of consciousness (DOC) are neurocognitive disorders related to sharp fluctuations of attention and consciousness, while DOC is characterized by significant interindividual differences, rapid development, and a higher lethal rate.
UNASSIGNED: A 53-year-old female patient underwent general anesthesia with tracheal intubation in otoendoscopic tympanoplasty. The patient suddenly appeared moderate DOC after tracheal tube removal with K+ 3.6 (3.5-5.3 mmol/L). Based on the ancillary testing and routine laboratory workup, the possible causes of DOC, such as general anesthesia drugs and cardio cerebral events, were temporarily excluded. DOC was reversed by intravenous administration of KCl 1 g, with K+ 3.78 mmol/L. On one day after surgery, the patient occurred suddenly DOC again after intravenous guttae of 5% glucose 1000 ml, K+ 3.87 mmol/L, possibly because of her recurrent hypokalemic paralysis (HP) of past medical history. The patient\'s consciousness gradually improved after effective KCl supplementation therapy.
UNASSIGNED: DOC caused by periodic paralysis (PP) has not been reported, we speculate that hypoactive DOC is closely correlated with normokalemic periodic paralysis (NormoPP) in this case.

Muscle channelopathies encompass a wide range of mainly episodic conditions that are characterized by muscle stiffness and weakness. The myotonic conditions, characterized predominantly by stiffness, include myotonia congenita, paramyotonia congenita, and sodium channel myotonia. The periodic paralysis conditions include hypokalemic periodic paralysis, hyperkalemic periodic paralysis, and Andersen-Tawil syndrome. Clinical history is key, and diagnosis is confirmed by next-generation genetic sequencing of a panel of known genes but can also be supplemented by neurophysiology studies and MRI. As genetic testing expands, so have the spectrum of phenotypes seen including pediatric presentations and congenital myopathies. Management of these conditions requires a multidisciplinary approach with extra support needed when patients require anesthetics or when pregnant. Patients with Andersen-Tawil syndrome will also need cardiac input. Diagnosis is important as symptomatic treatment is available for all of these conditions but need to be tailored to the gene and variant of the patient.

The periodic paralyses are muscle channelopathies: hypokalemic periodic paralysis (CACNA1S and SCN4A variants), hyperkalemic periodic paralysis (SCN4A variants), and Andersen-Tawil syndrome (KCNJ2). Both episodic weakness and disabling fixed weakness can occur. Little literature exists on magnetic resonance imaging (MRI) in muscle channelopathies. We undertake muscle MRI across all subsets of periodic paralysis and correlate with clinical features.
A total of 45 participants and eight healthy controls were enrolled and underwent T1-weighted and short-tau-inversion-recovery (STIR) MRI imaging of leg muscles. Muscles were scored using the modified Mercuri Scale.
A total of 17 patients had CACNA1S variants, 16 SCN4A, and 12 KCNJ2. Thirty-one (69%) had weakness, and 9 (20%) required a gait-aid/wheelchair. A total of 78% of patients had intramuscular fat accumulation on MRI. Patients with SCN4A variants were most severely affected. In SCN4A, the anterior thigh and posterior calf were more affected, in contrast to the posterior thigh and posterior calf in KCNJ2. We identified a pattern of peri-tendinous STIR hyperintensity in nine patients. There were moderate correlations between Mercuri, STIR scores, and age. Intramuscular fat accumulation was seen in seven patients with no fixed weakness.
We demonstrate a significant burden of disease in patients with periodic paralyses. MRI intramuscular fat accumulation may be helpful in detecting early muscle involvement, particularly in those without fixed weakness. Longitudinal studies are needed to assess the role of muscle MRI in quantifying disease progression over time and as a potential biomarker in clinical trials.

The field of pediatric skeletal muscle channelopathies has seen major new advances in terms of a wider understanding of clinical presentations and new phenotypes. Skeletal muscle channelopathies cause significant disability and even death in some of the newly described phenotypes. Despite this, there are virtually no data on the epidemiology and longitudinal natural history of these conditions or randomized controlled trial evidence of efficacy or tolerability of any treatment in children, and thus best practice care recommendations do not exist. Clinical history, and to a lesser extent examination, is key to eliciting symptoms and signs that indicate a differential diagnosis of muscle channelopathy. Normal routine investigations should not deter one from the diagnosis. Specialist neurophysiologic investigations have an additional role, but their availability should not delay genetic testing. New phenotypes are increasingly likely to be identified by next-generation sequencing panels. Many treatments or interventions for symptomatic patients are available, with anecdotal data to support their benefit, but we lack trial data on efficacy, safety, or superiority. This lack of trial data in turn can lead to hesitancy in prescribing among doctors or in accepting medication by parents. Holistic management addressing work, education, activity, and additional symptoms of pain and fatigue provides significant benefit. Preventable morbidity and sometimes mortality occurs if the diagnosis and therefore treatment is delayed. Advances in genetic sequencing technology and greater access to testing may help to refine recently identified phenotypes, including histology, as more cases are described. Randomized controlled treatment trials are required to inform best practice care recommendations. A holistic approach to management is essential and should not be overlooked. Good quality data on prevalence, health burden, and optimal treatment are urgently needed.