Safety and efficacy of dichlorphenamide in patients with periodic paralysis: A systematic review and meta-analysis.

Hypokalaemic periodic paralysis (HPP) is an uncommon disorder characterised by episodic muscle weakness due to reduced serum potassium levels. The condition may result from hereditary channelopathies or secondary causes such as diuretic exposure, gastrointestinal potassium loss or renal tubular acidosis (RTA). RTA can be either proximal or distal; the distal form reflects impaired urinary acid secretion, whereas the proximal variant results from inadequate bicarbonate reabsorption. Both can occur in isolation or in association with systemic or autoimmune diseases. We describe a young woman who presented with recurrent episodes of severe hypokalaemia leading to quadriparesis and respiratory compromise. Further evaluation demonstrated a distal RTA responsible for her electrolyte abnormalities. Detailed clinical assessment, serology and a salivary gland biopsy subsequently confirmed a diagnosis of primary Sjögren syndrome. Recognition of the underlying aetiology is essential because prompt correction of chronic acidosis and potassium depletion can prevent recurrent weakness and long-term metabolic complications.

Background: Hypokalemic paralysis is a reversible yet potentially life-threatening cause of acute flaccid weakness. While primary periodic paralysis is well recognised, secondary forms due to renal tubular dysfunction are often overlooked. Fanconi syndrome, a proximal tubulopathy, is an uncommon autoimmune manifestation of Sjögren’s syndrome, which more typically presents with distal renal tubular acidosis (RTA). Its occurrence in a 19-year-old young female is highly atypical and proximal tubular involvement in Sjögren’s is distinctly rare. Case Summary: We describe a 19-year-old female who presented with acute flaccid quadriparesis and severe hypokalaemia. Laboratory evaluation revealed hypophosphatemia, non-anion gap metabolic acidosis and inappropriately alkaline urine. Urinalysis showed phosphaturia, glucosuria and proteinuria, confirming Fanconi syndrome. Electromyography (EMG) demonstrated a myopathic pattern. Strongly positive Anti-Sjögren’s syndrome-related antigen A (Ro) antibody (anti-SSA/Ro) antibodies and polyclonal hypergammaglobulinemia suggested an autoimmune aetiology consistent with renal-limited Sjögren’s syndrome. Targeted correction of electrolytes, vitamin D deficiency and metabolic acidosis led to rapid and complete recovery. The combination of very young age and isolated proximal tubular dysfunction underscores the diagnostic challenge and highlights the importance of considering renal-limited autoimmune disease even without sicca symptoms. Conclusion: This case illustrates a rare presentation of autoimmune Fanconi syndrome manifesting as hypokalemic paralysis in a young female. Anti-SSA/Ro seropositivity and polyclonal hypergammaglobulinemia, despite absent sicca features, should prompt evaluation for renal-limited Sjögren’s syndrome. Early recognition is crucial, as timely metabolic correction results in complete clinical recovery.

Introduction Hypokalemic Periodic Paralysis (HPP) constitutes a rare subgroup of neuromuscular channelopathies characterized by sudden, reversible episodes of flaccid muscle weakness that coincide with profound hypokalemia (serum potassium <3.5 mmol/L). While the majority of HPP cases are attributed to inherited familial disorders (FPP), secondary forms are recognized, often precipitated by hormonal or metabolic imbalances. The co-occurrence of severe HPP manifesting as the primary acute complication of uncontrolled non-ketoacidotic diabetes is exceptionally uncommon and poses a significant diagnostic and therapeutic challenge, especially when the clinical picture suggests an underlying monogenic etiology, such as Maturity-Onset Diabetes of the Young (MODY). Case Illustration This report presents a detailed account of a 19-year-old female (Nn. R) who presented to the emergency department on November 7, 2025, with acute and complete flaccid paralysis of the lower extremities (Motor Strength 2/2). Initial biochemical analysis revealed life-threatening hypokalemia (Serum K+=1.50 mEq/L) concomitant with severe, non-ketotic hyperglycemia (Glucose 451 mg/dL, Keton 0.1). The presence of QT prolongation on the electrocardiogram (ECG) indicated high cardiac risk and necessitated immediate admission to the Intensive Care Unit (ICU) for aggressive intravenous potassium replacement and continuous cardiac monitoring. Complete motor function was successfully restored following the normalization of potassium levels (K+ = 3.81 mEq/L) over a six-day hospitalization period. Discussion The rapid and complete recovery of muscle strength upon correction of the potassium deficit confirmed the diagnosis of secondary HPP induced by a massive transcellular shift. This shift was triggered by the potent Na+/K+-ATPase activity stimulated by acute metabolic stress (hyperglycemia). Significantly, the patient's presentation—young age, absence of ketoacidosis, and the high efficacy observed upon clinical transition to long-term sulfonylurea (Glikuidone 30 mg) therapy at discharge—strongly suggests an underlying HNF1A- or HNF4A-MODY phenotype. This clinical finding underscores the utility of recognizing atypical diabetic presentations to ensure appropriate, precision-guided long-term care. Conclusion This case emphasizes the necessity of prompt, aggressive, and strategically administered potassium management in severe HPP to avert fatal cardiac events. Furthermore, the report highlights the critical diagnostic pathway required to identify underlying MODY in patients with HPP and atypical diabetic features, ensuring the selection of appropriate therapy (sulfonylureas) to prevent recurrent paralytic episodes.

Hypokalemic periodic paralysis (HypoPP) is a rare but important cause of acute flaccid paralysis that may be easily overlooked during initial evaluation. Timely recognition is essential, as management differs significantly from other neurological or metabolic causes of weakness. We report the case of a 51-year-old male who presented with an acute onset of flaccid quadriparesis. Despite initial treatment, the patient exhibited persistently low serum potassium levels, which did not respond adequately to standard potassium replacement. This unusual biochemical profile, combined with the clinical picture, led to a focused diagnostic approach that confirmed HypoPP. This case highlights the importance of including HypoPP in the differential diagnosis of acute flaccid paralysis, especially in patients with recurrent or persistent hypokalemia. Early identification and appropriate management can significantly alter patient outcomes and are essential to establish appropriate long-term management strategies to prevent recurrent episodes.

Thyrotoxic periodic paralysis is a rare but potentially life-threatening complication of thyrotoxicosis characterised by hypokalaemia-induced flaccid paralysis due to an intracellular potassium shift rather than total body depletion. We report a male in his early 40s of Filipino origin who awoke with acute bilateral lower-limb weakness after he had consumed a large carbohydrate meal and performed strenuous exercise within the preceding 12 hours. Venous blood gas was normal; initial serum potassium was 1.7 mmol/L with phosphate 1.07 mmol/L. The ECG showed sinus tachycardia, first-degree atrioventricular block and prominent U-waves with QTc 388 ms. Urine potassium/creatinine ratio was 1.7 mmol/mmol (expected <2.0 in hypokalaemia), indicating appropriate renal conservation. A point-of-care thyroid panel did not include thyroid-stimulating hormone (TSH); the laboratory TSH was reported later as suppressed (0.001 mIU/L) with elevated FT4/FT3. There was no diuretic, insulin or β-agonist use. The patient received potassium chloride totalling 80 mEq (≤10 mEq/hour peripherally with continuous ECG monitoring) with serum potassium checks every 1-2 hour, and supplementation was stopped once K+ reached 4.0 mmol/L; propranolol 40 mg orally every 8 hours and methimazole 10 mg orally every 8 hours were started. Muscle strength normalised within 24 hours. This case underscores the diagnostic triad of hypokalaemia without an acid-base disorder, appropriate renal K+ conservation and characteristic ECG changes, and highlights pragmatic dosing/monitoring plus the need for definitive control of thyrotoxicosis to prevent recurrence.

Hypokalemic periodic paralysis (hypoPP) is a rare autosomal dominant skeletal muscle ion channelopathy characterized by recurrent episodes of reversible flaccid paralysis with concurrent hypokalemia. Most of the familial hypoPP patients have missense mutations in the CACNA1S gene, which encodes the α-1S subunit of the L-type voltage-dependent calcium channel. A family with four cases of hypoPP is presented. A 67-year-old male patient with symptoms of hypokalemic paralysis was examined neurologically and genetically. His family history revealed some cases with some similar symptoms. CACNA1S gene sequencing analysis was performed in the proband and six of his relatives. The missense mutation Arg528His was identified in heterozygosity with the normal allele in the proband, three of his sons, and two other close relatives. The molecular genetic analysis confirmed the diagnosis of hypoPP in several members of the studied family.

COVID-19 infection and intense physical activity in hypokalemic periodic paralysis

Background: Andersen-Tawil Syndrome (ATS) is an autosomal dominant disorder marked by dysmorphic features, periodic paralysis, and ventricular arrhythmias. While the overall risk of cardiac arrest in ATS patients is low, mutations in the C-terminal region of the KCNJ2 gene are linked to a higher risk of arrhythmias. This study aims to evaluate the significance of mutations in this region compared to others. Methods: We conducted a meta-analysis by reviewing literature on KCNJ2-positive ATS cases and cohort studies from 1994 to 2025. Cases were included if they had a cardiac condition, categorized by the location of the mutation. Numerical variables were presented as mean and standard deviation (SD), and Student’s t-test was used for analysis. Categorical variables were evaluated with chi-square or Fisher’s exact test. Odds ratios (ORs) with 95% confidence intervals (CIs) were calculated for binary comparisons, with a significance level set at p &lt; 0.05. Results: A total of 221 patients with KCNJ2-positive ATS were analyzed, including 85 females. Those with C-terminal mutations had significantly higher odds of presenting with the ATS triad (p &lt; 0.001) and periodic paralysis (p &lt; 0.001). Dysmorphic features such as hypertelorism, micrognathia, and low-set ears were more common in this group. C-terminal mutations were also linked to increased QTc prolongation (p = 0.02) and higher frequencies of non-sustained ventricular tachycardia (nsVT) and sustained ventricular tachycardia (sVT) (52% vs. 50.0% and 12% vs. 9%, respectively). Ventricular fibrillation (VF) affected 18% of the C-terminal group (8% in other locations, p = 0.03). Non-fatal cardiac arrest (NFCA) was slightly more common in the C-terminal group (9% vs. 8%). Sudden cardiac death (SCD) occurred in 7% of patients in the C-terminal group, while none experienced it in the other location group (p = 0.01). Conclusion: Mutations located at the C-terminal of the KCNJ2 gene in ATS are associated with a more severe clinical phenotype, periodic paralysis, QTc prolongation, dysmorphic features, and life-threatening arrhythmias, including ventricular fibrillation and sudden cardiac death.

Hypokalemic paralysis is a rare but potentially life-threatening neuromuscular emergency characterized by the sudden onset of flaccid weakness due to reduced serum potassium. While inherited channelopathies represent primary causes, secondary etiologies-particularly endocrine, renal, and metabolic disorders-are more frequently encountered and require timely recognition to avoid complications. We report four patients presenting with acute flaccid paralysis associated with documented hypokalemia (serum potassium <3.5 mmol/L). The first case involved a pregnant woman with primary hyperaldosteronism due to an adrenal adenoma, managed initially with spironolactone and subsequently cured by adrenalectomy. The second case was a normotensive female diagnosed with distal renal tubular acidosis (dRTA) in the setting of Sjögren's syndrome, treated with potassium citrate and sodium bicarbonate. The third case was a young male with thyrotoxic periodic paralysis (TPP) secondary to Graves' disease, who improved with antithyroid drugs and beta-blockers. The fourth case described a young male with primary hypokalemic periodic paralysis (HPP), presenting with exertion-induced weakness, successfully treated with intravenous potassium supplementation. This case series underscores the diverse etiologies of hypokalemic paralysis, spanning endocrine, renal, autoimmune, and genetic causes. A systematic diagnostic approach, guided by clinical and biochemical evaluation, is essential for timely treatment. Identifying the underlying cause not only ensures effective acute management but also prevents recurrence and reduces the risk of serious complications, including cardiac arrhythmias.

Genetic analysis of a family with skeletal muscle ion channelopathy and hereditary spastic paraplegia type 7 caused by SCN4A and SPG7 double mutations.

BackgroundParesis and paralysis are often alarming symptoms of a stroke or spinal cord injury and are typically associated with neurological disorders. However, several rare conditions, including myopathies and neuropathies, can also cause paralysis. Due to their low incidence, these diseases are often overlooked, resulting in prolonged diagnostic delays and delayed treatment.Case presentationHere, we present the case of a 26-year-old German Caucasian male carpenter who was admitted to the neurological emergency department with acute tetraplegia. On admission, his potassium level was critically low but returned to normal levels after oral potassium supplementation. He was discharged symptom-free with a diagnosis of hypokalaemic paralysis of unclear origin. However, after he experienced a second episode approximately 1.5 years later, we performed genetic analysis and identified an R528H CACNA1S mutation as the underlying cause of hypokalaemic periodic paralysis. Further genealogical testing revealed that his asymptomatic mother and maternal grandmother were the carriers of the mutation. A decade after his initial presentation, the patient continues to manage episodes of muscle weakness effectively with oral potassium supplementation, avoiding hospitalization.ConclusionThis case highlights the importance of considering rare diseases in the differential diagnosis when common causes remain unconfirmed, emphasizing the need for timely genetic testing to facilitate an early precise diagnosis and appropriate management.LEARNING POINTSCACNA1S mutations should be considered in patients with recurrent episodes of muscle weakness or paralysis accompanied by hypokalaemia, especially if there is a family history of similar symptoms.

Disclosure: J.E. Villarreal Del Moral: None. M. Azevedo Jales Brandao: None.Thyrotoxicosis periodic paralysis (TPP) is a rare and potentially lethal complication of hyperthyroidism characterized by muscle paralysis and hypokalemia. We present a case of a Hispanic patient with an unknown history of hyperthyroidism who developed TPP. A 31-year-old healthy male presented to the emergency department with acute generalized weakness and myalgia, unable to move his arms and legs. He reported recurrent episodes of thigh numbness and weakness for twelve months before the current presentation. Physical examination revealed 4/5 strength in distal extremities and proximal weakness in all four limbs, with intact sensation. Laboratory results were significant for severe hypokalemia (2.1 mmol/L), and hypomagnesemia (1.6 mmol/L), with normal kidney function (creatinine 0.44 mg/dL and BUN 15 mg/dL) . Thyroid studies revealed suppressed TSH (<0.01mIU/ml) and elevated T4 (3.6 ng/dL) and T3 (19.5 pg/dL). Thyroid ultrasound showed an enlarged, hypervascular thyroid, and serology confirmed positive thyroid peroxidase and thyroglobulin antibodies, consistent with Graves' disease. The patient did not present any overt hyperthyroid symptoms. He was started on methimazole and potassium and electrolytes were repleted with quick improvement of symptoms. The patient was discharged on methimazole and advised to follow a high-potassium diet. Symptoms of TPP typically range from recurrent, transient episodes of muscle weakness to complete paralysis. Notably, only about 10% of patients report other symptoms of thyrotoxicosis during an event (1). Our case highlights the importance of recognizing thyrotoxicosis periodic paralysis as a rare but serious complication of hyperthyroidism, even in the absence of overt thyrotoxicosis symptoms. The hallmark feature of TPP is hypokalemia, primarily attributed to increased activity of the Na+/K+-ATPase pump. However, increased activity is also observed in other conditions, including thyrotoxicosis, without consistently resulting in hypokalemia (1). In TPP, hypokalemia is associated with impaired outward potassium flux, linked to mutated Kir (inward rectifier potassium) channels (2). Environmental factors such as hyperinsulinemia, alcohol consumption, or strenuous physical activity further inhibit Kir channel function, leading to intracellular potassium sequestration within skeletal muscle cells (2). Thus, the pathophysiology in TPP includes a genetic predisposition, thyrotoxicosis, and environmental influences (3). TPP has traditionally been recognized as a prevalent complication of thyrotoxicosis in Asian populations but has been underdiagnosed in Caucasians. Emerging evidence indicates that TPP is increasingly observed across diverse populations (1), as highlighted by the present case.Presentation: Saturday, July 12, 2025

Abstract Disclosure: J. Arguinchona: None. N. Allen: None. M. Vahidi Rad: None. K. Doshi: None. Background: Thyrotoxic periodic paralysis (TPP) is a distinct disorder characterized by episodic, generalized muscle weakness due to hypokalemia, occurring predominantly in young adult males (20-40 years) with hyperthyroidism, particularly Graves' disease. TPP is common in East Asian populations, affecting approximately 2% of individuals with hyperthyroidism, but is rare in Western populations (0.1-0.2%) and often underrecognized in the United States. Herein, we present three cases of TPP in young Hispanic and Caucasian males with Graves’ disease, underscoring the importance of diagnostic vigilance. Clinical Cases: Case 1: A 21 y.o. Hispanic male presented to endocrine clinic following multiple hospitalizations for severe hypokalemia and myopathy. During admission, labs showed a potassium (K) 1.2 mmol/L (3.6-5.2), undetectable thyroid stimulating hormone (TSH), and free thyroxine (FT4) 2.8 ng/dL (0.9-1.7). K was replaced and Graves’s disease was confirmed by positive TSH receptor antibodies. He was started on methimazole and subsequently underwent radioactive iodine (I-131) therapy. Following development of hypothyroidism, he was placed on levothyroxine replacement, with no further recurrence of paralysis. Case 2: An 18 y.o. Caucasian male with a history of Graves’ disease presented after multiple hospitalizations for hypokalemia and lower extremity weakness. Hospitalization labs showed a suppressed TSH, FT4 2.2 ng/dL, free triiodothyronine (FT3) 7.9 pg/mL (2.3-4.1), and K 2.8 mmol/L. His weakness improved with K replacement. Methimazole was initiated and the patient subsequently opted for total thyroidectomy for definitive therapy. No recurrence of TPP was observed after thyroidectomy. Case 3: A 29 y.o. Hispanic male with Graves’ disease, non-adherent to methimazole was hospitalized due to symptoms of diffuse upper and lower extremity weakness. Labs showed K 1.6 mmol/L, undetectable TSH, and T4 &amp;gt;7.7 ng/dL. Symptoms resolved with K replacement. He was restarted on methimazole as well as atenolol and advised on medical adherence. Unfortunately, he was lost to follow up, and re-hospitalized 7 months later with similar symptoms and labs, again due to nonadherence with thionamide medication. After aggressive K replacement and methimazole resumption, he was discharged with urgent endocrine follow-up for definitive management of Graves’ disease. Conclusion: These cases highlight the under recognition of TPP in non-Asian populations in the United States, leading to delayed diagnosis and recurrent hospitalizations. Clinicians should maintain a high index of suspicion for TPP in young males with hypokalemia, and generalized weakness, particularly in the setting of undiagnosed or untreated hyperthyroidism. Prompt recognition and definitive treatment of hyperthyroidism is critical to preventing recurrent episodes and associated morbidity. Presentation: Saturday, July 12, 2025

Disclosure: S. Abusharar: None. K.S. Manglani: None. W. Kuenstner: None. M.B. Sharma: None.Background: Thyrotoxic periodic paralysis (TPP) is a rare but potentially life-threatening complication of hyperthyroidism, characterized by acute hypokalemia-induced muscle weakness. Sometimes it can be the first presentation of hyperthyroidism. Although it is more commonly reported in Asian populations, early recognition across diverse demographics is essential to prevent severe morbidity.Case Presentation: A 26-year-old previously healthy Hispanic male presented with sudden-onset bilateral lower extremity weakness upon awakening, following a large carbohydrate-rich meal the night prior. He denied sensory deficits, bowel/bladder dysfunction, or preceding gastrointestinal symptoms. Examination revealed tachycardia and hyporeflexia and weakness of lower extremities without sensory impairment. Initial labs showed profound hypokalemia of (K⁺ 1.7 mmol/L; ref 3.5-5.0) and suppressed TSH (<0.008 mIU/L; ref 0.4-4.0), elevated free T4 (2.88 ng/dL; ref 0.8-1.8) and free T3 (7.74 pg/mL; ref 2.3-4.2). TT3 was on the upper border of normal (174.9 ref 60-180.0 ng/dL). EKG demonstrated an accelerated junctional rhythm with prolonged QTc 657 ms (ref >460 ms). Further evaluation revealed positive thyroid-stimulating immunoglobulins, and thyroid ultrasound demonstrated a mildly heterogeneous gland without nodules or hypervascularity, consistent with early Graves' disease. The patient was started on methimazole, propranolol and aggressive potassium repletion with clinical improvement. Discussion: TPP results from a sudden intracellular potassium shift triggered by thyrotoxicosis and potentiated by insulin and adrenergic stimulation. Although rare in non-Asian populations, it must be considered in any patient presenting with painless paralysis and hypokalemia. Management focuses on cautious potassium repletion, beta-adrenergic blockade, and definitive treatment of the underlying thyroid dysfunction. Conclusion: Early recognition of TPP, even in atypical demographics, is critical to prevent potentially fatal complications such as cardiac arrhythmias. Awareness of this condition among diverse populations remains essential.Presentation: Saturday, July 12, 2025

Disclosure: T. Hinshaw: None. H. Woomer: None. A. Haider: None.Background: Thyrotoxic periodic paralysis (TTP) is an acquired painless paralysis characterized by high thyroid hormone levels and hypokalemia. Gitelman syndrome (GS) is an autosomal recessive disorder that causes hypokalemia, hypomagnesemia, and metabolic alkalosis. We present a case of worsening hypokalemia from new onset hyperthyroidism in a patient with well compensated GS. Clinical Case: An 18-year-old white female with history of GS (biallelic mutation of SLC12A3) and recently diagnosed Graves’ disease presented with three-week history of bilateral lower extremity weakness that acutely worsened her ability to ambulate the morning of presentation. On exam, she was unable to move her lower extremities against resistance. She was found to be hypokalemic (K 2.0 mmol/L) with hypomagnesemia (Mg 1.3 mg/dL) despite adherence to home medications of potassium chloride 140mEq total daily and magnesium oxide 2800mg total daily. She was admitted for IV electrolyte replacement. Patient had been admitted two months prior for similar concerns; one month ago, she had been diagnosed with Graves’ disease (TSH <0.0008 ulU/mL, free T4 2.72 ng/dL, and TRAb 22.65 IU/L) and started on methimazole 15mg daily and propranolol 20mg TID. Upon admission, her thyroid levels remained uncontrolled (TSH <0.0008 ulU/mL, free T4 2.32 ng/dL), prompting endocrinology consultation. Given patient had previously been stable on electrolyte replacement for many years, patient’s worsening hypokalemia and lower extremity weakness was likely due to hyperthyroidism. Methimazole was increased to 30mg daily. Two days later, the patient’s lower extremity weakness improved, and patient was able to ambulate independently prior to discharged. Free T4 decreased to 2.17 ng/dL and potassium and magnesium levels were within normal limits. She was continued on new methimazole dose of 30mg daily; no changes to home electrolyte replacement regimen were made. At outpatient follow up one week later, patient’s weakness had not recurred, and electrolyte levels remained within normal limits.Clinical Lesson: The incidence of concurrent thyroid dysfunction in GS is higher than the general population. The exact reason is not defined, however SLC12A3 gene is not associated pathogenesis of thyroid dysfunction. Electrolyte abnormality, including severe magnesium deficiency, is associated with the recurrence of thyroid dysfunction. TTP is thought to cause hypokalemia due to the rapid shift of potassium into cells due to thyroxine-induced activation of Na+/K+-ATPase channels. GS interferes with NaCl reabsorption in the distal convoluted tubule, leading to hypokalemic metabolic acidosis. Despite a previously stable home electrolyte regimen for patient’s GS, her potassium levels became uncontrolled shortly after she was diagnosed with Graves’ disease and did not normalize until treatment of her thyroid disease was optimized.Presentation: Sunday, July 13, 2025

This article describes the clinical approach to rhabdomyolysis and the diagnosis and management of episodic disorders of skeletal muscle including skeletal muscle channelopathies. New gene variants that cause periodic paralysis have been identified. While these are exceedingly rare, they are now included in relevant genetic testing panels. Dantrolene is emerging as an additional option for the treatment of severe muscle stiffness, along with typical sodium channel blockers in sodium channel myotonia. Deep phenotyping in Andersen-Tawil syndrome shows significant heterogeneity with new features such as fasciculations, pain, and fatigue. A normal screening ECG is insufficient to rule out a diagnosis of Andersen-Tawil syndrome. In patients with episodic weakness, Holter monitoring is required to further investigate the possibility of Andersen-Tawil syndrome. Growth/differentiation factor-15 and fibroblast growth factor 21 serve as biomarkers of mitochondrial myopathies and can point to a mitochondrial etiology in patients with rhabdomyolysis. This article also discusses recently identified genetic abnormalities associated with rhabdomyolysis and highlights the current approach for evaluating unprovoked rhabdomyolysis. Episodic disorders of skeletal muscles include skeletal muscle channelopathies and rhabdomyolysis. The genetic variants that underlie both disorders can also cause persistent and progressive muscle weakness. The availability and expanded use of genetic testing allow for the identification of new genes causing periodic paralysis and rhabdomyolysis. Diagnostic approaches are evolving due to easier access to and availability of genetic testing. Advances in diagnostic techniques have highlighted the lag in therapeutics for patients with these rare disorders.

Generation of three iPSC lines from patients with CACNA1S related congenital myopathy.

Recently introduced potassium-39-( 39 K)-MRI provides a noninvasive approach to assess typically high intracellular K + -levels and can be combined with sodium-23-( 23 Na)-MRI. The aim of this study was to evaluate 39 K/ 23 Na muscle ion homeostasis in hypokalemic periodic paralysis (HypoPP), a rare muscular ion channelopathy, using 7 T MRI. Lower legs of patients with HypoPP and healthy controls were prospectively examined between August 2022 and July 2023 (case-control study). Scanning protocol at 3 T included T 1 -weighted, T 2 -weighted STIR sequences, a 6-point-Dixon-type gradient echo and a T2-mapping sequence. 39 K/ 23 Na data were acquired at 7 T using acquisition-weighted Stack-of-Stars sequences. Apparent tissue 39 K/ 23 Na concentrations (aTPC/aTSC) were calculated after correcting for partial-volume and relaxation effects and corrected for proton-density fat-fractions to account for fatty replacement. A 23 Na-inversion-recovery ( 23 Na-IR) sequence served to introduce a stronger intracellular weighting. Differences in central tendency between the HypoPP and control groups and correlations were analyzed. Thirteen HypoPP-participants and 13 controls were included. Extent of fatty replacement/edema-like changes varied highly with the gastrocnemius medialis muscle most affected. The HypoPP group showed significantly increased aTSC in all 7 analyzed muscles and decreased aTPC in 3 specific muscles. Across all muscles, the mean aTSC was higher in the HypoPP group (median: 33.4 vs 22.5 mM, mean ± SD: 34.3 ± 6.8 vs 21.0 ± 4.8 mM, P < 0.001), whereas the mean aTPC was lower (98.7 vs 109.0 mM, 97.9 ± 12.0 vs 108.7 ± 10.4 mM, P = 0.02). The 23 Na-IR signal was strongly correlated with aTSC (r = 0.77, P < 0.001). Combined 39 K/ 23 Na MRI at 7 T demonstrated alterations of sodium and potassium ion homeostasis in HypoPP. These findings could be helpful for a better pathophysiological understanding of HypoPP and may aid in future studies to assess disease extent or monitor treatment efficacy.

Thyrotoxic Periodic Paralysis: Acute Paralysis as the Initial Presentation of Graves’ Disease