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Cureus Nov 2022Acetazolamide, a carbonic anhydrase inhibitor, is primarily used in the treatment of glaucoma, due to its role in decreasing intraocular pressure by lowering the...
Acetazolamide, a carbonic anhydrase inhibitor, is primarily used in the treatment of glaucoma, due to its role in decreasing intraocular pressure by lowering the production of aqueous humor. Additionally, by lowering cerebrospinal fluid (CSF) production, it is also used in the treatment of raised intracranial pressure. Drug-induced myokymia has rarely been reported, with known triggers being clozapine, gabapentin and flunarizine, and topiramate. Acetazolamide-induced myokymia itself has only been reported once before, to the best of our knowledge, and the exact mechanism behind this occurrence remains unknown. We, therefore, report a rare case of periorbital myokymia induced by the use of acetazolamide in a patient diagnosed with idiopathic intracranial hypertension. The nature of her symptoms was significant, as they caused her considerable distress, and subsided almost immediately upon discontinuation of the drug.
PubMed: 36579233
DOI: 10.7759/cureus.31920 -
Movement Disorders Clinical Practice Dec 2014Autosomal-dominant episodic ataxias (EAs) represent a clinically and genetically heterogeneous group of disorders characterized by recurrent episodes of cerebellar... (Review)
Review
Autosomal-dominant episodic ataxias (EAs) represent a clinically and genetically heterogeneous group of disorders characterized by recurrent episodes of cerebellar ataxia (CA). Ataxia episodes are usually of short duration and often triggered by specific stimuli. There are currently seven classified subtypes of EA. EA types 1 and 2 have the highest prevalence and are therefore the clinically most relevant. Between attacks, EA 1 is associated with myokymia. In EA 2, often an interictal downbeat nystagmus with other cerebellar ocular dysfunctions is present; patients with EA 2 may display slowly progessive ataxia and vermian atrophy. EA 1 and 2 are both channelopathies, affecting the potassium channel gene, , in EA 1 and the PQ calcium channel-encoding gene, , in EA 2. The types EA 3 to 7 are very rare and have to be further elucidated. Here, we review the historical, clinical, and genetic aspects of autosomal-dominant EAs and their current treatment, focusing on EA 1 and 2.
PubMed: 30713867
DOI: 10.1002/mdc3.12075 -
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 -
Frontiers in Cellular Neuroscience 2015Episodic ataxia type 1 (EA1) is a K(+) channelopathy characterized by a broad spectrum of symptoms. Generally, patients may experience constant myokymia and dramatic... (Review)
Review
Episodic ataxia type 1 (EA1) is a K(+) channelopathy characterized by a broad spectrum of symptoms. Generally, patients may experience constant myokymia and dramatic episodes of spastic contractions of the skeletal muscles of the head, arms, and legs with loss of both motor coordination and balance. During attacks additional symptoms may be reported such as vertigo, blurred vision, diplopia, nausea, headache, diaphoresis, clumsiness, stiffening of the body, dysarthric speech, and difficulty in breathing. These episodes may be precipitated by anxiety, emotional stress, fatigue, startle response or sudden postural changes. Epilepsy is overrepresented in EA1. The disease is inherited in an autosomal dominant manner, and genetic analysis of several families has led to the discovery of a number of point mutations in the voltage-dependent K(+) channel gene KCNA1 (Kv1.1), on chromosome 12p13. To date KCNA1 is the only gene known to be associated with EA1. Functional studies have shown that these mutations impair Kv1.1 channel function with variable effects on channel assembly, trafficking and biophysics. Despite the solid evidence obtained on the molecular mechanisms underlying EA1, how these cause dysfunctions within the central and peripheral nervous systems circuitries remains elusive. This review summarizes the main breakthrough findings in EA1, discusses the neurophysiological mechanisms underlying the disease, current therapies, future challenges and opens a window onto the role of Kv1.1 channels in central nervous system (CNS) and peripheral nervous system (PNS) functions.
PubMed: 26347608
DOI: 10.3389/fncel.2015.00317 -
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 -
Clinical Neurology and Neurosurgery Sep 2010Multiple sclerosis (MS) is the most common disabling chronic disease of the central nervous system among young adults. These patients suffer from variety of symptoms... (Review)
Review
Multiple sclerosis (MS) is the most common disabling chronic disease of the central nervous system among young adults. These patients suffer from variety of symptoms that have a profound affect on their working ability, activities of daily living and general quality of life. Treatment of these symptoms is important in order to relief them and improve daily function and quality of life. Many of these symptoms are often resistant to treatment. Botulinum toxin A (BTX) is mainly used for spasticity and bladder dysfunction in MS. It is an effective treatment option for spasticity of the thigh adductor, pes equinus, striatal toe or adductor of the shoulder joint. BTX injections are effective in reducing incontinence episodes and urinary urgency, daytime frequency and nocturia, as well as sustained improvements in quality of life of MS patients with detrusor overreactivity. In addition, BTX is potentially effective in treating pain, trigeminal neuralgia, tremor, neuro-ophthalmologic complications, facial myokymia, gastroparesis, sialorrhea, and hyperhidrosis, however no studies have confirmed its efficacy in MS patients.
Topics: Botulinum Toxins; Dose-Response Relationship, Drug; Humans; Multiple Sclerosis; Muscle Spasticity; Neuromuscular Agents; Pain; Quality of Life; Urinary Bladder, Neurogenic
PubMed: 20615606
DOI: 10.1016/j.clineuro.2010.04.010 -
Clinical Case Reports Jul 2022We describe a patient who presented with fatigue and pulling sensation in his lower limbs. He had continuous muscle contractions over his trunk (myokymia) which pointed...
We describe a patient who presented with fatigue and pulling sensation in his lower limbs. He had continuous muscle contractions over his trunk (myokymia) which pointed towards the diagnosis of Isaacs syndrome which was confirmed by strongly positive CASPR2 antibodies in blood.
PubMed: 35898757
DOI: 10.1002/ccr3.6086 -
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 -
Case Reports in Psychiatry 2016Background. Topiramate (TPM) is a psychotropic drug, which is used mainly as an antiepileptic drug and now over the years is used for a wider range of indications,...
Background. Topiramate (TPM) is a psychotropic drug, which is used mainly as an antiepileptic drug and now over the years is used for a wider range of indications, including migraine prophylaxis and binge eating disorders. Although ocular side effects of Topiramate have been frequently reported, neuroophthalmologic manifestations such as myokymia are rarely reported. Case Presentation. This case report presents a case of a 47-year-old woman who had begun TPM for binge eating problem. She developed unilateral long standing lower eyelid twitching, which progressed to upper eyelid and eyebrow at the same side. The patient was not a smoker or excessive alcohol or caffeine abuser. Increasing the resting time and changing life style made no significant changes in her eyelid twitching. There was no definite evidence by neuroimaging and clinical or laboratory evaluations causing eyelid myokymia. The symptoms resolved with discontinuation of TPM. Conclusion. Although eyelid myokymia is a benign and self-limited condition, it sometimes becomes a source of distress in chronic long standing cases. Physicians should be aware of the neuroophthalmologic side effects of this drug.
PubMed: 27293943
DOI: 10.1155/2016/7901085 -
SN Comprehensive Clinical Medicine 2022The purpose of this study is to report eyelid myokymia in patients recently recovered from COVID-19 disease. A cohort of 15 patients who developed eyelid myokymia during...
The purpose of this study is to report eyelid myokymia in patients recently recovered from COVID-19 disease. A cohort of 15 patients who developed eyelid myokymia during or immediate post-recovery of systemic disease were evaluated. Demographic, clinical characteristics, effect of age, and hospitalization on the disease course were studied. The disease course was evaluated every month for 3 months period. All, except 2, patients had complete resolution of lid myokymia within 3 months of onset. Median [IQR] myokymia recovery time was 42 [31,60] days. Age and duration of hospitalization had a significant linear relationship with myokymia recovery time. Recovery was delayed by 2.64 days with every 1-year increment in age and by 6.19 days with every additional day of hospital stay. Recovery time was independent of severity of systemic disease ( = .055) and gender ( = 0.2). Eyelid myokymia can be a possible manifestation of COVID-19 recovery phase. While myokymia recovers gradually in all these patients, older age and a longer duration of hospitalization are associated with slower recovery.
PubMed: 35036848
DOI: 10.1007/s42399-021-01094-w