Progressive Seizures With Hyperuricosuria Reversed by Allopurinol

Coleman, Mary; Landgrebe, Marilyn; Landgrebe, Albert R.

doi:10.1001/archneur.1974.00490400052005

Cited by 25 publications

(10 citation statements)

References 19 publications

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“…47, 48 Interestingly, allopurinol, a xanthine oxidase inhibitor, was found efficient in reducing symptoms, especially epileptic seizures, in ASD patients displaying high levels of uric acid. 49 However, in our cohort, only 3 out of 10 patients exhibited an abnormal uric acid secretion. It can therefore be postulated that still unknown other MOCOS-associated mechanisms may have a role in the unbalanced stress response observed in ASD OSCs.…”

Section: Discussionmentioning

confidence: 55%

Olfactory stem cells reveal MOCOS as a new player in autism spectrum disorders

et al. 2015

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With an onset under the age of 3 years, autism spectrum disorders (ASDs) are now understood as diseases arising from pre- and/or early postnatal brain developmental anomalies and/or early brain insults. To unveil the molecular mechanisms taking place during the misshaping of the developing brain, we chose to study cells that are representative of the very early stages of ontogenesis, namely stem cells. Here we report on MOlybdenum COfactor Sulfurase (MOCOS), an enzyme involved in purine metabolism, as a newly identified player in ASD. We found in adult nasal olfactory stem cells of 11 adults with ASD that MOCOS is downregulated in most of them when compared with 11 age- and gender-matched control adults without any neuropsychiatric disorders. Genetic approaches using in vivo and in vitro engineered models converge to indicate that altered expression of MOCOS results in neurotransmission and synaptic defects. Furthermore, we found that MOCOS misexpression induces increased oxidative-stress sensitivity. Our results demonstrate that altered MOCOS expression is likely to have an impact on neurodevelopment and neurotransmission, and may explain comorbid conditions, including gastrointestinal disorders. We anticipate our discovery to be a fresh starting point for the study on the roles of MOCOS in brain development and its functional implications in ASD clinical symptoms. Moreover, our study suggests the possible development of new diagnostic tests based on MOCOS expression, and paves the way for drug screening targeting MOCOS and/or the purine metabolism to ultimately develop novel treatments in ASD.

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Section: Discussionmentioning

confidence: 55%

Olfactory stem cells reveal MOCOS as a new player in autism spectrum disorders

et al. 2015

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“…Haig (1892), discussing uric acid as a factor in causation of disease, devoted a chapter to epilepsy and convulsions. The earliest observations with allopurinol suggested that the antiepileptic effects occurred only in patients with hyperuricosuria, suggesting that an alteration in urate metabolism was necessary for the drug response (Coleman et al, 1974). However, enzyme-inducing AEDs reduce serum urate levels (Zagnoni and Sodini, 1986;Zagnoni et al, 1986;Krause et al, 1987;Ring et al, 1991) and, as a consequence, patients Abbreviations as in Tables 1 and 2.…”

Section: Discussionmentioning

confidence: 99%

Allopurinol as Add‐on Therapy in Refractory Epilepsy: A Double‐Blind Placebo‐Controlled Randomized Study Italy, on his retirement.

Zagnoni¹,

Bianchi

Zolo

et al. 1994

Epilepsia

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The antiepileptic effect of allopurinol was assessed in a double-blind, randomized, placebo-controlled, cross-over trial in 84 patients with epileptic seizures refractory to standard antiepileptic drugs (AEDs). During a retrospective baseline period, patients experienced at least four seizures of any type per month. The effects of allopurinol and matching placebo were examined for 4-month periods. Allopurinol dosage was 150 mg daily for children weighing < 20 kg and 300 mg daily for other patients. Efficacy analysis based on the Wilcoxon rank-sum test was conducted for the 80 patients who completed the study. No significant period effect or treatment-period interaction was noted. Allopurinol significantly reduced total seizures (p = 0.005), and secondarily generalized seizures (p = 0.0015). Median seizure reduction for total seizures was 10.5 and 27.9% for secondarily generalized seizures. Subjective preferences by clinicians evaluated blindly significantly favored allopurinol. No significant change occurred in the plasma concentration of concomitant AEDs between treatment periods, but serum urate decreased by 32% during allopurinol treatment. No clinically relevant side effects or changes in routine laboratory clinical chemistry or hematology were ascribed to allopurinol.

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“…Key Words: Epilepsy-Anticonvulsants-Allopurinol-Serotonin-Quinolinic acid-Kynurenine. Coleman et al (1974) first reported use of allopurinol, a xanthine oxdase inhibitor, to treat epilepsy in hyperuricosuria patients. DeMarco and Zagnoni (1986) first reported that allopurinol was effective in patients with intractable epilepsy without hyperuricosuria.…”

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confidence: 99%

Clinical Effects of Allopurinol on Intractable Epilepsy

et al. 1991

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We studied the clinical efficacy of allopurinol as add-on therapy in 31 patients with intractable epilepsy. When administered for a short time, allopurinol was effective in 17 patients (55%); 8 were seizure-free, 8 had 75% decrease in seizure frequency, and 1 had greater than 50% decrease. Allopurinol was most effective in patients with localization-related epilepsy, especially in secondarily generalized tonic-clonic seizures. Allopurinol was not as effective in patients with Lennox syndrome or West syndrome, or in severe myoclonic epilepsy in infants. When allopurinol was administered greater than 1 year, its initial effectiveness continued in 8 of 14 patients who exhibited initial improvement. In 2 of the remaining 6 patients, the initial improvement disappeared during the course of treatment but control was regained by increasing the dosage of allopurinol. Mild side effects were observed in 4 patients (13%): drowsiness in 3 and abdominal pain in 1. Allopurinol may be a useful antiepileptic drug (AED), and a double-blind placebo-controlled trial should be performed.

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Progressive Seizures With Hyperuricosuria Reversed by Allopurinol

Cited by 25 publications

References 19 publications

Olfactory stem cells reveal MOCOS as a new player in autism spectrum disorders

Olfactory stem cells reveal MOCOS as a new player in autism spectrum disorders

Allopurinol as Add‐on Therapy in Refractory Epilepsy: A Double‐Blind Placebo‐Controlled Randomized Study Italy, on his retirement.

Clinical Effects of Allopurinol on Intractable Epilepsy

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