Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0004134 (ataxia)
 15,886 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The study was conducted to evaluate the effects of xylazine individually (0.05 mg/kg), ketamine individually (2.5 mg/kg), and a combination of xylazine and ketamine (0.05 mg/kg and 2.5 mg/kg) after lumbar epidural administration in water buffalo calves. Fifteen non-descript, male water buffalo calves of 6-8 months of age weighing between 55 and 75 kg were randomly placed in three groups (groups A, B and C). The agents were administered at the first lumbar epidural space. Clinico-physiological parameters, such as analgesia, ataxia, sedation, salivation, heart rate, respiratory rate and rectal temperature were studied. Other haematological and biochemical parameters monitored were haemoglobin, packed cell volume, total leukocyte count, plasma glucose, cortisol, protein albumin, globulin, blood urea nitrogen (BUN), creatinine, alanineamino transferase (ALT), sodium, potassium and chloride. The onset of analgesia (mean +/- SEM) was faster in group C (3.2 +/- 0.20 min) compared with that of group B (4.6 +/- 0.22 min) and group A (34.0 +/- 1.86 min). Analgesia of the thorax, flank, inguinal region, hind limbs, perineum and tail was complete in group C, but mild to moderate in groups A and B. Ataxia was severe in group C and mild in groups A and B. Mild to deep sedation was produced by groups A and C animals. Group B animals failed to produce sedation. Longer duration and greater depth of analgesia was produced in animals of group C. Heart rate, respiratory rate and rectal temperature decreased in groups A and C. The haematological parameters decreased in all the groups. The biochemical parameters like glucose, cortisol, BUN, creatinine, and ALT increased in all the animals. However, total proteins and albumin decreased in the three groups. The plasma electrolytes sodium, potassium and chloride did not show any significant change. The results of this study indicated a possible synergistic analgesic interaction between epidurally administered xylazine and ketamine, without causing any marked systemic effects in water buffalo calves.
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PMID:Xylazine, ketamine and their combination for lumbar epidural analgesia in water buffalo calves (Bubalus bubalis). 1697 Jun 33

Myokymia is characterized by spontaneous, involuntary muscle fiber group contraction visible as vermiform movement of the overlying skin. Myokymia with episodic ataxia is a rare, autosomal dominant trait caused by mutations in KCNA1, encoding a voltage-gated potassium channel. In the present study, we report a family with four members affected with myokymia. Additional clinical features included motor delay initially diagnosed as cerebral palsy, worsening with febrile illness, persistent extensor plantar reflex, and absence of epilepsy or episodic ataxia. Mutation analysis revealed a novel c.676C>A substitution in the potassium channel gene KCNA1, resulting in a T226K nonconservative missense mutation in the Kv1.1 subunit in all affected individuals. Electrophysiological studies of the mutant channel expressed in Xenopus oocytes indicated a loss of function. Co-expression of WT and mutant cRNAs significantly reduced whole-oocyte current compared to expression of WT Kv1.1 alone.
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PMID:Functional analysis of a novel potassium channel (KCNA1) mutation in hereditary myokymia. 1713 96

Eleven dogs diagnosed with refractory idiopathic epilepsy were treated orally with gabapentin for a minimum of three months at an initial dose of 10 mg/kg every eight hours. They were all experiencing episodes of generalised tonic-clonic seizures and had been treated chronically with a combination of phenobarbital and potassium bromide at doses sufficient to reach acceptable therapeutic serum levels without causing significant side effects. In each dog, the number of seizures per week, the average duration of the seizures and the number of days on which seizures occurred were compared for the three months before and after they were treated with gabapentin. A minimum 50 per cent reduction in the number of seizures per week was interpreted as a positive response to gabapentin, and six of the dogs showed a positive response. After the addition of gabapentin, both the number of seizures per week (P= 0.005) and the number of days with any seizures in a one-week period (P=0.03) were significantly reduced. Mild side effects of ataxia and sedation were observed in five of the dogs, but they were not severe enough to warrant the treatment being discontinued during the trial.
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PMID:Treatment with gabapentin of 11 dogs with refractory idiopathic epilepsy. 1718 99

Episodic ataxia type 1 is a paroxysmal neurological disorder characterized by short-lived attacks of recurrent midline cerebellar dysfunction and continuous motor activity. Mutations in KCN1A, the gene encoding Kv1.1, a voltage-gated neuronal potassium channel, are associated with the disorder. Although rare, the syndrome highlights the fundamental features of genetic ion-channel diseases and serves as a useful model for understanding more common paroxysmal disorders, such as epilepsy and migraine. This review examines our current understanding of episodic ataxia type 1, focusing on its clinical and genetic features, pathophysiology, and treatment.
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PMID:Episodic ataxia type 1: a neuronal potassium channelopathy. 1739 36

Episodic ataxia type 2 (EA 2) is a rare neurological disorder of autosomal dominant inheritance resulting from dysfunction of a voltage-gated calcium channel. It manifests with recurrent disabling attacks of imbalance, vertigo, and ataxia, and can be provoked by physical exertion or emotional stress. In the spell-free interval, patients present with central ocular motor dysfunction, mainly downbeat nystagmus. A slow progression of cerebellar signs accompanied by a slight atrophy of midline cerebellar structures is commonly observed during the course of the disease. EA 2 is caused most often by the loss of function mutations of the calcium channel gene CACNA1A, which encodes the Ca(v)2.1 subunit of the P/Q-type calcium channel and is primarily expressed in Purkinje cells. To date, more than 30 mutations have been described. Two effective treatment options have been established for EA 2: acetazolamide (ACTZ), which probably changes the intracellular pH and thereby the transmembraneous potential, and 4-aminopyridine (4-AP), a potassium channel blocker. Approximately 70% of all patients respond to treatment with ACTZ, but the effect is often only transient. In an open trial, 4-AP prevented attacks in five of six patients with EA 2, most likely by increasing the resting activity and excitability of the Purkinje cells. These findings were confirmed by experiments in animal models of EA 2. Many aspects of the pathophysiology (e.g., induction of the attacks) and treatment of EA 2 (e.g., mode of action of ACTZ and 4-AP) still remain unclear and need to be addressed in further animal and clinical studies.
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PMID:Episodic ataxia type 2. 1739 37

In infancy, the autosomal dominant inherited ataxias are severe neurological diseases, due to inherited mutations of ion channels. The main forms are: episodic ataxia type 1 (EA1), episodic ataxia type 2 (EA2), spinocerebellar ataxia type 6 (SCA6). EA1 is due to a mutation in KCNA1, the gene encoding human Kv1.1 on chromosome 12p13, which contributes as a subunit to the formation of potassium channels in motor nerve terminals and in many central nervous system neurones. To date, there are fifteen different mutations, which affect potassium channel's properties and lead to phenotypic variability and to different responses to therapy. EA2 can result from mutations in the CACNA1A gene, encoding calcium channels on chromosome 19p13.1 and widely distributed throughout the central nervous system. To date, associated with EA2, in the CACNA1A gene thirty different mutations have been described, resulting in altered or truncated protein products and, as a consequence, in nonfunctional calcium channels. There is phenotypic variability, also inside the same family, without correlation genotype-phenotype. SCA6 is a progressive neurodegenerative disease due to mutations of the CACNA1A gene. CACNA1A is responsible for both EA2 and SCA6. Nevertheless, the pathogenesis of the two diseases is different: SCA6 is associated with small expansion of a CAGn repeat, while EA2 is due to point mutations. Clinically, SCA6 is characterized by a slowly progressive development and by an inverse correlation between the number of repeats and the severity of the disease.
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PMID:[Spinocerebellar ataxias in infancy: pathogenesis of potassium and calcium channels' diseases, clinical features and therapeutical approach]. 1740 65

Calcium-activated potassium channels modulate calcium signaling cascades and membrane potential in both excitable and non-excitable cells. In this article we will review the physiological properties, the structure activity relationships of the existing peptide and small molecule modulators and the therapeutic importance of the three small-conductance channels KCa2.1-KCa2.3 (a.k.a. SK1-SK3) and the intermediate-conductance channel KCa3.1 (a.k.a. IKCa1). The apamin-sensitive KCa2 channels contribute to the medium afterhyperpolarization and are crucial regulators of neuronal excitability. Based on behavioral studies with apamin and on observations made in several transgenic mouse models, KCa2 channels have been proposed as targets for the treatment of ataxia, epilepsy, memory disorders and possibly schizophrenia and Parkinson's disease. In contrast, KCa3.1 channels are found in lymphocytes, erythrocytes, fibroblasts, proliferating vascular smooth muscle cells, vascular endothelium and intestinal and airway epithelia and are therefore regarded as targets for various diseases involving these tissues. Since two classes of potent and selective small molecule KCa3.1 blocker, triarylmethanes and cyclohexadienes, have been identified, several of these postulates have already been validated in animal models. The triarylmethane ICA-17043 is currently in phase III clinical trials for sickle cell anemia while another triarylmethane, TRAM-34, has been shown to prevent vascular restenosis in rats and experimental autoimmune encephalomyelitis in mice. Experiments showing that a cyclohexadiene KCa3.1 blocker reduces infarct volume in a rat subdural hematoma model further suggest KCa3.1 as a target for the treatment of traumatic and possibly ischemic brain injury. Taken together KCa2 and KCa3.1 channels constitute attractive new targets for several diseases that currently have no effective therapies.
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PMID:Modulators of small- and intermediate-conductance calcium-activated potassium channels and their therapeutic indications. 1758 55

Episodic ataxia type 1 (EA1) is an autosomal-dominant neurological disease caused by point mutations in the potassium channel-encoding gene KCNA1. It is characterized by attacks of ataxia and continuous myokymia. Respiratory muscle involvement has not been previously reported in EA1. We clinically evaluated a family with features of EA1 and paroxysmal shortness of breath. Coding and flanking intronic regions of KCNA1 were sequenced. We identified a novel 3-nucleotide deletion mutation in KCNA1 in the affected individuals. Our findings of a deletion mutation with unusual respiratory muscle involvement expand the genetic and clinical spectrum of EA1.
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PMID:Novel mutation in KCNA1 causes episodic ataxia with paroxysmal dyspnea. 1791 52

During neuronal activity, extracellular potassium concentration ([K+]out) becomes elevated and, if uncorrected, causes neuronal depolarization, hyperexcitability, and seizures. Clearance of K+ from the extracellular space, termed K+ spatial buffering, is considered to be an important function of astrocytes. Results from a number of studies suggest that maintenance of [K+]out by astrocytes is mediated by K+ uptake through the inward-rectifying Kir4.1 channels. To study the role of this channel in astrocyte physiology and neuronal excitability, we generated a conditional knock-out (cKO) of Kir4.1 directed to astrocytes via the human glial fibrillary acidic protein promoter gfa2. Kir4.1 cKO mice die prematurely and display severe ataxia and stress-induced seizures. Electrophysiological recordings revealed severe depolarization of both passive astrocytes and complex glia in Kir4.1 cKO hippocampal slices. Complex cell depolarization appears to be a direct consequence of Kir4.1 removal, whereas passive astrocyte depolarization seems to arise from an indirect developmental process. Furthermore, we observed a significant loss of complex glia, suggestive of a role for Kir4.1 in astrocyte development. Kir4.1 cKO passive astrocytes displayed a marked impairment of both K+ and glutamate uptake. Surprisingly, membrane and action potential properties of CA1 pyramidal neurons, as well as basal synaptic transmission in the CA1 stratum radiatum appeared unaffected, whereas spontaneous neuronal activity was reduced in the Kir4.1 cKO. However, high-frequency stimulation revealed greatly elevated posttetanic potentiation and short-term potentiation in Kir4.1 cKO hippocampus. Our findings implicate a role for glial Kir4.1 channel subunit in the modulation of synaptic strength.
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PMID:Conditional knock-out of Kir4.1 leads to glial membrane depolarization, inhibition of potassium and glutamate uptake, and enhanced short-term synaptic potentiation. 1794 30

Megalencephaly means an increased size or weight of a generally well-formed brain. It is a feature of a heterogeneous group of mostly familial human disorders with prenatal or early childhood onset. Seizures, motor deficits, mental retardation or milder cognitive impairment are sometimes present. This review discusses idiopathic megalencephalies with regard to possible etiology and treatment opportunities. Idiopathic megalencephalies with neurological deficits as well as unilateral megalencephaly are hypothesized to be caused by disturbances of proliferation, survival or migration of neurons in the brain. The current knowledge of postnatal and adult generation of neurons and survival of adult-borne neurons is reviewed. We show an example of how a genetic potassium channel dysfunction causes not only temporal lobe epilepsy, but also postnatal progressive megalencephaly in a mouse model. We also summarize novel data on neuro-protective effects of the antiepileptic drug carbamazepine in the treatment of brain overgrowth. Findings propose that potassium ion channelopathy may underlie disease for a group of infants or young children displaying idiopathic megalencephaly and early onset epilepsy or episodic ataxia type 1. Carbamazepine's remarkable protective effects on the neuronal plasticity in the hyperexcitable state should be further studied, and maybe this drug should be considered more in treatment of temporal lobe epilepsy and megalencephaly.
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PMID:Idiopathic megalencephaly-possible cause and treatment opportunities: from patient to lab. 1824 8


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