Hyperkalemic Periodic Paralysis Research Articles

Allele frequency of muscular genetic disorders in bull-catching (vaquejada) quarter horses

Quarter horses (QH), a prominent athletic breed in Brazil, are affected by muscular genetic disorders such as myosin-heavy chain myopathy (MYHM), polysaccharide storage myopathy (PSSM1), hyperkalemic periodic paralysis (HyPP), and malignant hyperthermia (MH). Bull-catching (vaquejada), primarily involving QH, is a significant equestrian sport in Brazil. Since the allele frequencies (AF) of MYHM, PSSM1, HyPP, and MH in vaquejada QH remain unknown, this study evaluated the AF in 129 QH vaquejada athletes, specifically from the Brazilian Northeast. These variants were exclusively observed in heterozygosity. The MYHM exhibited the highest AF (0.04 ±0.01), followed by PSSM1 (0.01 ±0.01) and the HyPP variant (0.004 ±0.01), while the MH variant was not identified in this study. This study represents the first identification of these variants in vaquejada QH, emphasizing the need to implement measures to prevent the transmission of pathogenic alleles and reduce the occurrence of clinical cases of these genetic diseases.

Muscle MRI in periodic paralysis shows myopathy is common and correlates with intramuscular fat accumulation.

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.

Application of preimplantation genetic diagnosis in 91 equine ICSI embryos

Preimplantation genetic diagnosis (PGD) of in vitro-produced (IVP) equine embryos has been reported in research and clinical settings. In the previous reports, 4-16% biopsied samples failed to yield PCR results of disease-causing genes. There is little information on the feasibility of a second biopsy and refreezing of those PGD-failed frozen IVP equine embryos. In this report, we evaluated biopsy results from 91 IVP equine embryos produced from 2018 to 2022 and tested for hereditary equine regional dermal asthenia (HERDA), glycogen branching enzyme deficiency (GBED) and hyperkalemic periodic paralysis (HYPP) genes. We also examined the pregnancy and foaling rates of twice biopsied-frozen (2BF) embryos by comparing them with fresh or once biopsied-frozen (1BF) embryos. IVP embryos were produced by intracytoplasmic sperm injection and in vitro culture of shipped immature oocytes. Biopsy of embryos was performed as previously reported with minor modifications (Choi et al., Reprod Fertil Dev 2016;28:1382-1389). Biopsies were kept frozen for a maximum of 7 days and shipped to the University of California, Davis for genetic analysis. A total of 15 fresh, 39 1BF and 5 2BF IVP embryos were transferred to recipients at embryo transfer facilities. The non-transferred vitrified embryos, 12 1BF and 1 2BF IVP embryos, were kept frozen accordingto owners’ instructions. Among the 91 IVP biopsies, 7 (8%) failed to yield PCR results and 84 samples were genetically analyzed; 14 (24%) were homozygous for HERDA in 58 samples, 4 (21%) were homozygous for GBED in 19 samples and 0 were homozygous for HYPP in 7 samples. The molecular sexes of 84 samples were 44 males and 40 females. Among the 7 2BF IVP biopsies, 1 failed to yield PCR results and 6 were genetically analyzed; 1 was homozygous for GBED. The molecular sexes of 6 2BF samples were 1 male and 5 females. The pregnancy rates of fresh, 1BF and 2BF IVP embryos were not significantly different among groups (60% (9/15), 64% (25/39) and 80% (4/5), respectively, Fisher's exact test). Of these, 3 pregnancies from 1BF were removed from the foaling rate calculation because of unknown and ongoing pregnancies. The foaling rates of fresh, 1BF and 2BF IVP embryos were not significantly different among groups (47% (7/15), 33% (12/36) and 60% (3/5), respectively, Fisher's exact test). Out of 22 foals analyzed, all matched with molecular genders. In summary, PGD for disease-causing genes can be further improved by a second biopsy and refreezing of frozen IVP equine embryos. In addition, two biopsy-freezing cycles of IVP equine embryos were not detrimental to in vivo embryo development.

Sodium channel protein alpha subunit genomics: building an integrated knowledgebase to translate between family members

The sodium channel alpha proteins consist of ten homologous human proteins (SCN1A, SCN2A, SCN3A, SCN4A, SCN5A, SCN7A, SCN8A, SCN9A, SCN10A, SCN11A), many involved in various human physiological pathways and clinical disorders/syndromes. Many human variants connected to these genes remain uncertain for human disease. To better support the understanding of challenging human variants, we have built an ortholog database of the alpha subunit proteins for the sodium channel. We combined 1,680 vertebrate species sequences of family members, protein modeling, molecular dynamic simulation of lipid embedded protein, screening of human variants (gnomAD, ClinVar, Geno2MP), and analysis of a large number of human RNAseq and single-cell RNA-seq to understand the function of each amino acid in the human proteins and how the amino acids are conserved across family members to contribute to sodium channel functions within diverse cells of human. There are 610 amino acids conserved across the alpha subunit family, representing the most conserved amino acids for each member. These amino acids drive the structural fold, membrane interactions, and channel opening. A cluster of amino acids is conserved between a subset of family members that defines subclusters of alpha subunit proteins. Expression analysis of each member reveals clusters of members co-expressed in various cells, where heart and brain datasets show the specificity of cell types that contribute to genotype-to-phenotype associations of each member. Further, to support variant characterizations, the ortholog alignment data provides a unique ability to discover loss vs. gain of function variants found between members, allowing for known pathogenic variants of one member to aid in the characterization of another member's uncertain variants. For example, a clinical variant of SCN8A linked to seizures was supported as loss-of-function through variants within SCN1A (epilepsy), SCN2A (seizures), SCN4A (Familial hyperkalemic periodic paralysis), and SCN5A (Brugada syndrome). Overall, we show an exciting and promising new tool for ortholog genomic mapping that can support clinical variant insights into physiological outcomes (genotype-to-phenotype relationship), which should be applied to other cellular ion channels and transporters. This research was funded by the Gerber Foundation (to JWP), National Institutes of Health (K01ES025435 to JWP), and Michigan State University. This is the full abstract presented at the American Physiology Summit 2023 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

Canalopatías y mitocondriopatías

Episodes of periodic paralysis are secondary to abnormalities in channel composition and are characterized by generalized muscle weakness with hypotonia and areflexia. They do not affect bulbar or respiratory muscles and there are no cognitive abnormalities. At present, genetic tests are the pillar for diagnosing these syndromes. Determining serum potassium levels during attacks, recognizing triggering factors, clinical or electrical myotonia, the results of electrodiagnostic tests, cardiac arrhythmia, and craniofacial and skeletal characteristics help distinguish various forms of hereditary periodic paralysis. Serum potassium levels may remain within normal range during attacks both in hypokalemic periodic paralysis and hyperkalemic periodic paralysis. Acetazolamide is used in chronic treatment for hypokalemic periodic paralysis, hyperkalemic periodic paralysis, and related syndromes. Mitochondrial anomalies may affect any high-energy organ, including the brain, heart, kidneys, gastrointestinal tract, retina, or muscle.

Protocolo diagnóstico de las parálisis periódicas

Current molecular technology has shown that there are mutations in multiple voltage-dependent ion channels. The most frequent mutations are those which affect sodium channels (hyperkalaemic periodic paralysis, paramyotonia congenita, potassium-aggravated myotonia, etc.), potassium channels (Andersen-Tawil syndrome) and the chlorine channel (congenital myotonia). Even so much work still remains to be done to characterize the symptoms and physiopathology even more thoroughly and thereby establish more effective treatments.

Prevalence of genetically confirmed skeletal muscle channelopathies in the era of next generation sequencing

We provide an up-to-date and accurate minimum point prevalence of genetically defined skeletal muscle channelopathies which is important for understanding the population impact, planning for treatment needs and future clinical trials. Skeletal muscle channelopathies include myotonia congenita (MC), sodium channel myotonia (SCM), paramyotonia congenita (PMC), hyperkalemic periodic paralysis (hyperPP), hypokalemic periodic paralysis (hypoPP) and Andersen- Tawil Syndrome (ATS). Patients referred to the UK national referral centre for skeletal muscle channelopathies and living in UK were included to calculate the minimum point prevalence using the latest data from the Office for National Statistics population estimate. We calculated a minimum point prevalence of all skeletal muscle channelopathies of 1.99/100 000 (95% CI 1.981–1.999). The minimum point prevalence of MC due to CLCN1 variants is 1.13/100 000 (95% CI 1.123–1.137), SCN4A variants which encode for PMC and SCM is 0.35/100 000 (95% CI 0.346 – 0.354) and for periodic paralysis (HyperPP and HypoPP) 0.41/100 000 (95% CI 0.406–0.414). The minimum point prevalence for ATS is 0.1/100 000 (95% CI 0.098–0.102). There has been an overall increase in point prevalence in skeletal muscle channelopathies compared to previous reports, with the biggest increase found to be in MC. This can be attributed to next generation sequencing and advances in clinical, electrophysiological and genetic characterisation of skeletal muscle channelopathies.

Hyperkalemic periodic paralysis associated with a novel missense variant located in the inner pore of Nav1.4

BackgroundHyperkalemic periodic paralysis (HyperPP) is an autosomal dominantly inherited disease characterized by episodic paralytic attacks with hyperkalemia, and is caused by mutations of the SCN4A gene encoding the skeletal muscle type voltage-gated sodium channel Nav1.4. The pathological mechanism of HyperPP was suggested to be associated with gain-of-function changes for Nav1.4 gating, some of which are defects of slow inactivation. Case presentation & MethodsWe identified a HyperPP family consisting of the proband and his mother, who showed a novel heterozygous SCN4A variant, p.V792G, in an inner pore lesion of segment 6 in Domain II of Nav1.4. Clinical and neurophysiological evaluations were conducted for the proband and his mother. We explored the pathogenesis of the variant by whole-cell patch clamp technique using HEK293T cells expressing the mutant Nav1.4 channel. ResultsFunctional analysis of Nav1.4 with the V792G mutation revealed a hyperpolarized shift of voltage-dependent activation and fast inactivation. Moreover, steady-state slow inactivation in V792G was impaired with larger residual currents in comparison with wild-type Nav1.4. ConclusionV792G in SCN4A is a pathogenic variant associated with the HyperPP phenotype and the inner pore lesion of Nav1.4 plays a crucial role in slow inactivation.

Hyperkalemic Periodic Paralysis in Twenty-Two Family Members Over Four Generations: A Rare Case Report.

Hyperkalemic Periodic Paralysis in Twenty-Two Family Members Over Four Generations: A Rare Case Report.

Periodic paralysis due to cumulative effects of rare variants in SCN4A with small functional alterations.

Mutations in the SCN4A gene encoding a voltage-gated sodium channel (Nav1.4) cause hyperkalemic periodic paralysis (HyperPP) and hypokalemic periodic paralysis (HypoPP). Typically, both HyperPP and HypoPP are considered as monogenic disorders caused by a missense mutation with a large functional effect. However, a few cases with atypical periodic paralysis phenotype have been caused by multiple mutations in ion-channel genes expressed in skeletal muscles. In this study we investigated the underlying pathogenic mechanisms in such cases. We clinically assessed two families: proband 1 with HyperPP and proband 2 with atypical periodic paralysis with hypokalemia. Genetic analyses were performed by next-generation sequencing and conventional Sanger sequencing, followed by electrophysiological analyses of the mutant Nav1.4 channels expressed in human embryonic kidney 293T (HEK293T) cells using the whole-cell patch-clamp technique. In proband 1, K880del was identified in the SCN4A gene. In proband 2, K880del and a novel mutation, R1639H, were identified in the same allele of the SCN4A gene. Functional analyses revealed that the K880del in SCN4A has a weak functional effect on hNav1.4, increasing the excitability of the sarcolemma, which could represent a potential pathogenic factor. Although R1639H alone did not reveal functional changes strong enough to be pathogenic, Nav1.4 with both K880del and R1639H showed enhanced activation compared with K880del alone, indicating that R1639H may modify the hNav1.4 channel function. A cumulative effect of variants with small functional alterations may be considered as the underpinning oligogenic pathogenic mechanisms for the unusual phenotype of periodic paralysis.

Prevalence of Genetic Mutations in Horses With Muscle Disease From a Neuromuscular Disease Laboratory

Deleterious genetic variants are an important cause of skeletal muscle disease. Immunohistochemical evaluation of muscle biopsies is standard for the diagnosis of muscle disorders. The prevalence of alleles causing hyperkalemic periodic paralysis (HYPP), malignant hyperthermia (MH), polysaccharide storage myopathy 1 (PSSM1), glycogen branching enzyme deficiency (GBED), myotonia congenita (MC), and myosin heavy chain myopathy (MYHM) in horses with muscle disease is unknown. Archived slides processed for immunohistochemical analysis from 296 horses with muscle disease were reviewed blinded and clinical information obtained. DNA isolated from stored muscle samples from these horses were genotyped for disease variants. Histological findings were classified as myopathic in 192, neurogenic in 41, and normal in 63 horses. A third of the population had alleles that explained disease which constituted 45% of the horses with confirmed histological myopathic process. Four of six muscle disease alleles were identified only in Quarter horse breeds. The allele causing PSSM1 was detected in other breeds, and MC was not detected in these samples. The My allele, associated with susceptibility for MYHM, was the most common (62%) with homozygotes (16/27) presenting a more severe phenotype compared to heterozygotes (6/33). All cases with the MH allele were fatal upon triggering by anesthesia, stress or concurrent myopathy. Both, muscle histological and genetic analyses are essential in the investigation of muscle disease, since 10% of the horses with muscle disease and normal histology had a muscle disease causing genetic variant, and 63% of histologically confirmed muscle with alterations had no known genetic variants.

A dangerous food binge: a case report of hypokalemic periodic paralysis and review of current literature

BackgroundHypokalemic periodic paralysis is a rare neuromuscular genetic disorder due to defect of ion channels and subsequent function impairment. It belongs to a periodic paralyses group including hyperkalemic periodic paralysis (HEKPP), hypokalemic periodic paralysis (HOKPP) and Andersen-Tawil syndrome (ATS). Clinical presentations are mostly characterized by episodes of flaccid generalized weakness with transient hypo- or hyperkalemia.Case presentationA teenage boy presented to Emergency Department (ED) for acute weakness and no story of neurological disease, during the anamnestic interview he revealed that he had a carbohydrates-rich meal the previous evening. Through a focused diagnostic work-up the most frequent and dangerous causes of paralysis were excluded, but low serum potassium concentration and positive family history for periodic paralyses raised the diagnostic suspicion of HOKPP. After the acute management in ED, he was admitted to Pediatric Department where a potassium integration was started and the patient was counselled about avoiding daily life triggers. He was discharged in few days. Unfortunately, he presented again because of a new paralytic attack due to a sugar-rich food binge the previous evening. Again, he was admitted and treated by potassium integration. This time he was strongly made aware of the risks he may face in case of poor adherence to therapy or behavioral rules.Currently, after 15 months, the boy is fine and no new flare-ups are reported.ConclusionHOKPP is a rare disease but symptoms can have a remarkable impact on patients’ quality of life and can interfere with employment and educational opportunities. The treatment aims to minimize the paralysis attacks by restoring normal potassium level in order to reduce muscle excitability but it seems clear that a strong education of the patient about identification and avoidance triggering factors is essential to guarantee a benign clinical course. In our work we discuss the typical clinical presentation of these patients focusing on the key points of the diagnosis and on the challenges of therapeutic management especially in adolescence. A brief discussion of the most recent knowledge regarding this clinical condition follows.

Psychopharmacological Treatments for Mental Disorders in Patients with Neuromuscular Diseases: A Scoping Review.

Mental disorders are observed in neuromuscular diseases, especially now that patients are living longer. Psychiatric symptoms may be severe and psychopharmacological treatments may be required. However, very little is known about pharmacotherapy in these conditions. We aimed to summarize the current knowledge on the use of psychopharmacological treatments for mental disorders in patients living with a neuromuscular disease. A scoping review was performed using the methodology of the Joanna Briggs Institute. Four databases were searched from January 2000 to July 2021. Articles were screened based on titles and abstracts. Full-text papers published in peer-reviewed journals in English were selected. Twenty-six articles met eligibility criteria, all being case reports/series focusing on the psychopharmacological control of psychiatric symptoms for the following conditions: myasthenia gravis (n = 11), Duchenne (n = 5) and Becker (n = 3) muscular dystrophy, mitochondrial disorders (n = 3), glycogen storage disease (n = 1), myotonic dystrophy (n = 1), hyperkalemic periodic paralysis (n = 1), and congenital myasthenic syndrome (n = 1). None of the articles provided details on the decision-making process to choose a specific drug/regimen or on follow-up strategies to monitor safety and efficacy. Larger studies showing real-world data would be required to guide consensus-based recommendations, thus improving current standards of care and, ultimately, the quality of life of patients and their families.

CHANNELOPATHIES AND RELATED DISORDERS: EP.226 Muscle fat fraction, cross-sectional area and contractility in patient with skeletal muscle sodium channel disorders

We present a cross-sectional, observational study that investigates the presence of muscle degeneration in patients with skeletal muscle sodium channel disorders (SCN4A gene mutation). This includes paramyotonia congenita (PMC), hyperkalemic periodic paralysis (HyperPP) and potassium-aggravated myotonia (PAM). Little is known about quantitative fat infiltration and contractility of patients with these disorders. So far, we have studied 13 patients (30 planned), older than 18 years and diagnosed with SCN4A mutations using dynamometry testing and quantitative (Dixon) muscle MRI.

Hypokalemic periodic paralysis: an underestimated autosomal-dominant disease with variable phenotypic presentations

Periodic paralysis (PP) diseases are autosomal dominant disorders due to gene-mutations that manifests with episodic muscle weakness and/or paralysis. Their mutations result in faulty ion-leaks that result in sustained muscle depolarization and inexcitability. The group include; hyperkalemic PP, hypokalemic PP (HypoPP type I & II), normokalemic PP, thyrotoxic PP, Paramyotonia congenita and Andersen-Tawil syndrome. The hypoPP is the most common disorder yet is underestimated in prevalence due to missed diagnosis mimicking hysterical disorders and neurological diseases as well as the hypokalemic syndromes (Bartter, Gitelman and renal tubular acidosis). Moreover, and due to their considerable gene-penetrance, their phenotypic spectrum ranges from infrequent attacks to progressive muscular failure. In this case report we present a patient with missed diagnosis for years and describe the algorithm of his diagnosis and management.
 Keywords: chanellopathies, diagnosis, hypokalemia, periodic paralysis, treatment.

Clinical and genetic spectrum of a Chinese cohort with SCN4A gene mutations

Skeletal muscle sodium channelopathies due to SCN4A gene mutations have a broad clinical spectrum. However, each phenotype has been reported in few cases of Chinese origin. We present detailed phenotype and genotype data from a cohort of 40 cases with SCN4A gene mutations seen in neuromuscular diagnostic service in Huashan hospital, Fudan University. Cases were referred from 6 independent provinces from 2010 to 2018. A questionnaire covering demographics, precipitating factors, episodes of paralysis and myotonia was designed to collect the clinical information. Electrodiagnostic studies and muscle MRI were retrospectively analyzed. The clinical spectrum of patients included: 6 Hyperkalemic periodic paralysis (15%), 18 Hypokalemic periodic paralysis (45%), 7 sodium channel myotonia (17.5%), 4 paramyotonia congenita (10%) and 5 heterozygous asymptomatic mutation carriers (12.5%). Review of clinical information highlights a significant delay to diagnosis (median 15 years), reports of pain and myalgia in the majority of patients, male predominance, circadian rhythm and common precipitating factors. Electrodiagnostic studies revealed subclinical myotonic discharges and a positive long exercise test in asymptomatic carriers. Muscle MRI identified edema and fatty infiltration in gastrocnemius and soleus. A total of 13 reported and 2 novel SCN4A mutations were identified with most variants distributed in the transmembrane helix S4 to S6, with a hotspot mutation p.Arg675Gln accounting for 32.5% (13/40) of the cohort. Our study revealed a higher proportion of periodic paralysis in SCN4A-mutated patients compared with cohorts from England and the Netherlands. It also highlights the importance of electrodiagnostic studies in diagnosis and segregation studies.

Clinical experience with Dichlorphenamide in Refractory Hyperkalemic Periodic Paralysis with SCN4 Gene Mutation. (1203)

Clinical experience with Dichlorphenamide in Refractory Hyperkalemic Periodic Paralysis with SCN4 Gene Mutation. (1203)

The Role of Nutrition and Physical Activity as Trigger Factors of Paralytic Attacks in Primary Periodic Paralysis.

Background:Primary periodic paralysis (PPP) are rare inherited neuromuscular disorders including Hypokalemic periodic paralysis (HypoPP), Hyperkalemic periodic paralysis (HyperPP) and Andersen-Tawil syndrome (ATS) characterised by attacks of weakness or paralysis of skeletal muscles. Limited effective pharmacological treatments are available, and avoidance of lifestyle related triggers seems important.Objective:Our aim was to search and assess the scientific literature for information on trigger factors related to nutrition and physical activity in PPP.Methods:We searched Ovid Medline and Embase database for scientific papers published between January 1, 1990, to January 31, 2020.Results:We did not identify published observation or intervention studies evaluating effect of lifestyle changes on attacks. Current knowledge is based on case-reports, expert opinions, and retrospective case studies with inadequate methods for description of nutrition and physical activity. In HypoPP, high carbohydrate and salt intake, over-eating, alcohol, dehydration, hard physical activity, and rest after exercise are frequently reported triggers. Regarding HyperPP, fasting, intake of potassium, alcohol, cold foods or beverages, physical activity, and rest after exercise are frequently reported triggers. No nutrition related triggers are reported regarding ATS, exercise can however induce ventricular arrhythmias.Conclusions:Our results support that dietary intake and physical activity may play a role in causing paralytic attacks in PPP, although the current scientific evidence is weak. To provide good evidence-based patient care, several lifestyle aspects need to be further assessed and described.

Mortality and morbidity in equine anaesthesia

SummaryEquine peri‐anaesthetic mortality and morbidity are of interest to anaesthetists, practitioners, horse owners and insurance companies. The largest prospective study, ‘The Confidential Enquiry into Perioperative Equine Fatalities’ (CEPEF) was conducted more than 20 years ago. It included over 40,000 horses from multiple centres and reported mortality to be 1.9% that decreased to 0.9% when only elective cases were considered. This is in stark contrast to mortality rates in small animal (dogs: 0.17%, cats: 0.24%) and human anaesthesia (0.04–7/10,000). In spite of developments in understanding the pathophysiology of equine anaesthesia mortality has not decreased in the intervening years. The main contributors to peri‐anaesthetic equine mortality are cardiac arrest, fractures and myopathy or neuropathy. Spinal cord myelopathy and cerebral necrosis are less common. Malignant hyperthermia and hyperkalaemic periodic paralysis are diseases associated with genetic mutations that can be triggered during general anaesthesia and may be fatal if not recognised and treated immediately. Morbidities are reported less frequently, presumably because often they do not cause permanent harm and may resolve within a short period of time. Complications in equine anaesthesia are numerous and include injuries at induction and recovery, damage to the airway associated with orotracheal or nasotracheal intubation, post‐anaesthetic myopathy or neuropathy, regurgitation and aspiration of stomach contents, ocular injuries and complications associated with intravascular cannulation. Hypotension, hypoventilation, hypoxaemia, hypothermia and dysrhythmias may occur both during the maintenance phase of anaesthesia but also in recovery. Airway obstruction during recovery has repeatedly been reported over the years as causing pulmonary oedema, which is often fatal if the airway is not restored extremely quickly. This review summarises the literature on the risk of mortality and morbidity. Information has been gathered from single case reports as well as larger research studies.

Presunta parálisis periódica hipercalémica con miotonía en perros Shi-Tzú y Pastor Alemán

En los humanos, las canalopatías del músculo esquelético son entidades de base genética y de incidencia muy baja. En relación al canal de sodio en particular, las diferentes mutaciones SCN4A pueden dar lugar a diversos fenotipos que van desde la parálisis muscular (parálisis periódica hipercalémica, parálisis periódica hipocalémica) a la hiperexcitabilidad muscular (paramiotonía congénita, miotonías agravadas por potasio), pasando por fenotipos combinados de las dos anteriores. Existe una estrecha interrelación entre la parálisis periódica hipercalémica y las miotonías; ambas características pueden coexistir en el mismo paciente.Este trabajo describe un cuadro clínico que afectó a una camada de 7 cachorros Pastor Alemán y a una camada de 4 cachorros Shi-Tzú, con episodios caracterizados por un fenotipo clínico de parálisis muscular combinado con hiperexcitabilidad muscular.De acuerdo a los hallazgos clínicos (fenomenología clínica, edad de aparición, recurrencia de los episodios, ausencia de signos clínicos entre los episodios) y de laboratorio (hipercalemia), y a los resultados del tratamiento con acetazolamida, el diagnóstico presuntivo fue parálisis periódica hipercalémica con miotonía/paramiotonía por una canalopatía SCN4A.Destacamos la importancia del diagnóstico clínico para estas raras patologías. En ausencia de diagnóstico genético, los métodos de diagnóstico complementario tiene valor limitado debido al carácter funcional de estos trastornos.Proponemos esta comunicación como la primera de este tipo en perros de raza Pastor Alemán y Shi-Tzú. In humans, skeletal muscle channelopathies are genetic disease with very low incidence. Regarding the sodium channel in particular, the different SCN4A mutations can result in various phenotypes ranging from muscle paralysis (hyperkalemic periodic paralysis, hypokalemic periodic paralysis) to muscle hyperexcitability (congenit paramyotonia, myotonias aggravated by potassium), through combined phenotypes of the previous two. There is a close interrelation between hyperkalemic periodic paralysis and myotonias; both characteristics can coexist in the same patient.This work describes a clinical picture affecting a litter of 7 German Shepherd puppies and a litter of 4 Shih-Tzu puppies with episodes characterized by a clinical phenotype of muscular paralysis combined with muscular hyperexcitability.Based on clinical findings (clinical phenomenology, age of onset, episodic recurrence, absense of clinical signs in the period between episodes) and laboratory (hyperkalemia), and the results of treatment with acetazolamide, the presumptive diagnosis was hyperkalemic periodic paralysis with myotonia/paramyotonia due to SCN4A channelopathy.We emphasize the importance of clinical diagnosis for these rare pathologies. In absence of genetic diagnosis, complementary diagnostic methods have limited value due to the functional nature of these disorders.We proposed this description as the first communication of this type in German Shepherd and Shi-Tzu dogs.