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Romanian Journal of Ophthalmology 2024Several ocular adverse effects have been attributed to Topiramate, a sulfonamide derivative. It can cause problems in the eye such as choroidal effusion syndrome, acute...
UNLABELLED
Several ocular adverse effects have been attributed to Topiramate, a sulfonamide derivative. It can cause problems in the eye such as choroidal effusion syndrome, acute angle closure glaucoma, myopic shift, visual field defects, and Myokymia. If not identified early, it can be vision-threatening. It is commonly used for migraine prophylaxis, partial onset, and generalized tonic-clonic seizures. It has also been prescribed for bipolar disorder and alcoholism. The risk of adverse reactions with this drug is 3%. The prognosis is favorable if it is discontinued early and prompt therapy is initiated.
OBJECTIVE
This article reported a case series of topiramate-induced ocular complications.
MATERIALS AND METHODS
The patients presented with high intraocular pressure and blurred vision following a topiramate prescription for headache.
CONCLUSION
Timely recognition and intervention can prevent potential visual loss in such cases.
Topics: Humans; Topiramate; Glaucoma, Angle-Closure; Myopia
PubMed: 38617722
DOI: 10.22336/rjo.2024.14 -
Journal of Veterinary Internal Medicine 2023KCNJ10 and CAPN1 variants cause "spinocerebellar" ataxia in dogs, but their association with generalized myokymia and neuromyotonia remains unclear.
BACKGROUND
KCNJ10 and CAPN1 variants cause "spinocerebellar" ataxia in dogs, but their association with generalized myokymia and neuromyotonia remains unclear.
OBJECTIVE
To investigate the association between KCNJ10 and CAPN1 and myokymia or neuromyotonia, with or without concurrent spinocerebellar ataxia.
ANIMALS
Thirty-three client-owned dogs with spinocerebellar ataxia, myokymia neuromytonia, or a combination of these signs.
METHODS
Genetic analysis of a cohort of dogs clinically diagnosed with spinocerebellar ataxia, myokymia or neuromyotonia. KCNJ10 c.627C>G and CAPN1 c.344G>A variants and the coding sequence of KCNA1, KCNA2, KCNA6, KCNJ10 and HINT1 were sequenced using DNA extracted from blood samples.
RESULTS
Twenty-four Jack Russell terriers, 1 Jack Russell terrier cross, 1 Dachshund and 1 mixed breed with spinocerebellar ataxia were biallelic (homozygous) for the KCNJ10 c.627C>G variant. Twenty-one of those dogs had myokymia, neuromyotonia, or both. One Parson Russell terrier with spinocerebellar ataxia alone was biallelic for the CAPN1 c.344G>A variant. Neither variant was found in 1 Jack Russell terrier with ataxia alone, nor in 3 Jack Russell terriers and 1 Yorkshire terrier with myokymia and neuromyotonia alone. No other causal variants were found in the coding sequence of the investigated candidate genes in these latter 5 dogs.
CONCLUSION
The KCNJ10 c.627C>G variant, or rarely the CAPN1 c.344G>A variant, was confirmed to be the causal variant of spinocerebellar ataxia. We also report the presence of the KCNJ10 c.627C>G variant in the Dachshund breed. In dogs with myokymia and neuromyotonia alone the reported gene variants were not found. Other genetic or immune-mediated causes should be investigated to explain the clinical signs of these cases.
Topics: Humans; Dogs; Animals; Myokymia; Isaacs Syndrome; Spinocerebellar Ataxias; Ataxia; Breeding; Nerve Tissue Proteins; Kv1.6 Potassium Channel; Dog Diseases
PubMed: 37905444
DOI: 10.1111/jvim.16892 -
Medicines (Basel, Switzerland) Sep 2023Gabapentin (GBP)-induced movement disorders (MDs) are under-recognized adverse drug reactions. They are commonly not discussed with patients, and their sudden occurrence... (Review)
Review
BACKGROUND
Gabapentin (GBP)-induced movement disorders (MDs) are under-recognized adverse drug reactions. They are commonly not discussed with patients, and their sudden occurrence can lead to misdiagnosis. This literature review aims to evaluate the clinical-epidemiological profile, pathological mechanisms, and management of GBP-associated MD.
METHODS
Two reviewers identified and assessed relevant reports in six databases without language restriction between 1990 and 2023.
RESULTS
A total of 99 reports of 204 individuals who developed a MD associated with GBP were identified. The MDs encountered were 135 myoclonus, 22 dyskinesias, 7 dystonia, 3 akathisia, 3 stutterings, 1 myokymia, and 1 parkinsonism. The mean and median ages were 54.54 (SD: 17.79) and 57 years (age range: 10-89), respectively. Subjects were predominantly male (53.57%). The mean and median doses of GBP when the MD occurred were 1324.66 (SD: 1117.66) and 1033 mg/daily (GBP dose range: 100-9600), respectively. The mean time from GBP-onset to GBP-associated MD was 4.58 weeks (SD: 8.08). The mean recovery time after MD treatment was 4.17 days (SD: 4.87). The MD management involved GBP discontinuation. A total of 82.5% of the individuals had a full recovery in the follow-up period.
CONCLUSIONS
Myoclonus (GRADE A) and dyskinesia (GRADE C) were the most common movement disorders associated with GBP.
PubMed: 37755242
DOI: 10.3390/medicines10090052 -
Proceedings of the National Academy of... Aug 2023Loss-of-function mutations in the (Kv1.1) gene cause episodic ataxia type 1 (EA1), a neurological disease characterized by cerebellar dysfunction, ataxic attacks,...
Loss-of-function mutations in the (Kv1.1) gene cause episodic ataxia type 1 (EA1), a neurological disease characterized by cerebellar dysfunction, ataxic attacks, persistent myokymia with painful cramps in skeletal muscles, and epilepsy. Precision medicine for EA1 treatment is currently unfeasible, as no drug that can enhance the activity of Kv1.1-containing channels and offset the functional defects caused by mutations has been clinically approved. Here, we uncovered that niflumic acid (NFA), a currently prescribed analgesic and anti-inflammatory drug with an excellent safety profile in the clinic, potentiates the activity of Kv1.1 channels. NFA increased Kv1.1 current amplitudes by enhancing the channel open probability, causing a hyperpolarizing shift in the voltage dependence of both channel opening and gating charge movement, slowing the OFF-gating current decay. NFA exerted similar actions on both homomeric Kv1.2 and heteromeric Kv1.1/Kv1.2 channels, which are formed in most brain structures. We show that through its potentiating action, NFA mitigated the EA1 mutation-induced functional defects in Kv1.1 and restored cerebellar synaptic transmission, Purkinje cell availability, and precision of firing. In addition, NFA ameliorated the motor performance of a mouse model of EA1 and restored the neuromuscular transmission and climbing ability in (Kv1.1) mutant flies (). By virtue of its multiple actions, NFA has strong potential as an efficacious single-molecule-based therapeutic agent for EA1 and serves as a valuable model for drug discovery.
Topics: Animals; Mice; Myokymia; Drosophila melanogaster; Ataxia; Drosophila; Kv1.2 Potassium Channel
PubMed: 37487086
DOI: 10.1073/pnas.2207978120 -
Cells May 2023Dominantly inherited missense mutations of the gene, which encodes the K1.1 potassium channel subunit, cause Episodic Ataxia type 1 (EA1). Although the cerebellar...
Dominantly inherited missense mutations of the gene, which encodes the K1.1 potassium channel subunit, cause Episodic Ataxia type 1 (EA1). Although the cerebellar incoordination is thought to arise from abnormal Purkinje cell output, the underlying functional deficit remains unclear. Here we examine synaptic and non-synaptic inhibition of Purkinje cells by cerebellar basket cells in an adult mouse model of EA1. The synaptic function of basket cell terminals was unaffected, despite their intense enrichment for K1.1-containing channels. In turn, the phase response curve quantifying the influence of basket cell input on Purkine cell output was maintained. However, ultra-fast non-synaptic ephaptic coupling, which occurs in the cerebellar 'pinceau' formation surrounding the axon initial segment of Purkinje cells, was profoundly reduced in EA1 mice in comparison with their wild type littermates. The altered temporal profile of basket cell inhibition of Purkinje cells underlines the importance of Kv1.1 channels for this form of signalling, and may contribute to the clinical phenotype of EA1.
Topics: Purkinje Cells; Neural Inhibition; Animals; Mice; Disease Models, Animal; Kv1.1 Potassium Channel; Synapses; Cell Communication; Synaptic Transmission; Ataxia; Myokymia; Evoked Potentials; Mice, Inbred C57BL; Male; Female
PubMed: 37408217
DOI: 10.3390/cells12101382 -
International Journal of Molecular... May 2023The gene encodes Kv1.1 voltage-gated potassium channel α subunits, which are crucial for maintaining healthy neuronal firing and preventing hyperexcitability.... (Review)
Review
The gene encodes Kv1.1 voltage-gated potassium channel α subunits, which are crucial for maintaining healthy neuronal firing and preventing hyperexcitability. Mutations in the gene can cause several neurological diseases and symptoms, such as episodic ataxia type 1 (EA1) and epilepsy, which may occur alone or in combination, making it challenging to establish simple genotype-phenotype correlations. Previous analyses of human variants have shown that epilepsy-linked mutations tend to cluster in regions critical for the channel's pore, whereas EA1-associated mutations are evenly distributed across the length of the protein. In this review, we examine 17 recently discovered pathogenic or likely pathogenic variants to gain new insights into the molecular genetic basis of channelopathy. We provide the first systematic breakdown of disease rates for variants in different protein domains, uncovering potential location biases that influence genotype-phenotype correlations. Our examination of the new mutations strengthens the proposed link between the pore region and epilepsy and reveals new connections between epilepsy-related variants, genetic modifiers, and respiratory dysfunction. Additionally, the new variants include the first two gain-of-function mutations ever discovered for , the first frameshift mutation, and the first mutations located in the cytoplasmic N-terminal domain, broadening the functional and molecular scope of channelopathy. Moreover, the recently identified variants highlight emerging links between and musculoskeletal abnormalities and nystagmus, conditions not typically associated with . These findings improve our understanding of channelopathy and promise to enhance personalized diagnosis and treatment for individuals with -linked disorders.
Topics: Humans; Channelopathies; Ataxia; Myokymia; Mutation; Epilepsy; Kv1.1 Potassium Channel
PubMed: 37240170
DOI: 10.3390/ijms24108826 -
Toxicon: X Jun 2023A 2-year-old female Dachshund had a witnessed timber rattlesnake envenomation. Although rattlesnake envenomations are a common, potentially life-threatening event in...
A 2-year-old female Dachshund had a witnessed timber rattlesnake envenomation. Although rattlesnake envenomations are a common, potentially life-threatening event in companion animals, timber rattlesnake envenomations in the dog are rarely reported. This dog described in this case report had significant hematologic and neurologic clinical derangements consistent with Types A and B rattlesnake venom and a suspected hypersensitivity reaction to the venom. This patient was treated aggressively with antivenom and fully recovered without any persistent neurologic signs at follow-up.
PubMed: 37168094
DOI: 10.1016/j.toxcx.2023.100156 -
Cureus Mar 2023Lumbosacral plexopathy (LSP) encompasses a group of disorders affecting post-ganglionic fibers derived from the L1-S4 roots. The differential diagnosis is challenging...
Lumbosacral plexopathy (LSP) encompasses a group of disorders affecting post-ganglionic fibers derived from the L1-S4 roots. The differential diagnosis is challenging and includes other neuropathies of medullary, radicular, or peripheral origin. Defining the etiology is equally crucial, as LSP management relies on its cause. A thorough clinical history should address potential neoplastic disease (new-onset, progression, or relapse), diabetes mellitus, lumbar or pelvic trauma, and previous exposure to radiation. This is the case of a 78-year-old male, with a history of prostatic adenocarcinoma, treated with image-guided radiation therapy and hormone therapy five years before, with no evidence of relapse on follow-up. The patient presented with bilateral weakness, numbness, and paresthesia of lower limbs, gradually progressing over a three-month period, and followed by an acute worsening with inability to stand or walk. He also referred to distal mild edema, episodic hematuria, and urinary incontinence. Physical examination revealed paraparesis affecting proximal and distal leg muscles, along with bilateral hypoesthesia, impaired deep tendon reflexes, and proprioception below knee level. Pelvic, dorsal, and lumbosacral MRI excluded neoplastic lesions but identified somatic fracture of L5 without medullary or conus medullaris compromise. These findings did not explain the clinical picture. Further neurophysiologic studies characterized sensory-motor deficits as post-ganglionic, with specific spontaneous discharges of the muscle fibers, known as myokymia. These findings were consistent with radiation-induced LSP and were supported by MRI. Radiation-induced cystitis was also documented in pelvic MRI and urethral cystoscopy. This case highlights the clinical picture and differential diagnosis of radiation-induced LSP. Despite more typical symptoms and course, a neoplastic origin should always be carefully investigated and excluded. Radiation protocol should be carefully accessed, and its complications should not be overlooked, as they might cause severe morbidity.
PubMed: 37123691
DOI: 10.7759/cureus.36842