topiramate and Hyperventilation

Pitt-Hopkins syndrome (PTHS) is a neurodevelopmental disorder caused by mutations in TCF4. Seizures have been found to vary among patients with PTHS. We report the case of a PTHS patient with a novel missense mutation in the gene TCF4, presenting with two types of early epileptic encephalopathy.. The patient was a Japanese boy. His first seizure was reported at 17 days of age, with twitching of the left eyelid and tonic-clonic seizures on either side of his body. An ictal electroencephalogram (EEG) showed epileptic discharges arising independently from both hemispheres, occasionally resembling migrating partial seizures of infancy (MPSI) that migrated from one side to the other. Brain magnetic resonance imaging revealed agenesis of the corpus callosum. His facial characteristics included a distinctive upper lip and thickened helices. His seizures were refractory, and psychomotor development was severely delayed. At the age of 10 months, he developed West syndrome with spasms and hypsarrhythmia. After being prescribed topiramate (TPM), his seizures and EEG abnormalities dramatically improved. Also, psychomotor development progressed. Whole-exome sequencing revealed a novel de novo missense mutation in exon 18 (NM_001083962.2:c.1718A > T, p.(Asn573Ile)), corresponding to the basic region of the basic helix-loop-helix domain, which may be a causative gene for epileptic encephalopathy.. To our knowledge, this is the first report of a patient with PTHS treated with TPM, who presented with both MPSI as well as West syndrome. This may help provide new insights regarding the phenotypes caused by mutations in TCF4.

Topics: Anticonvulsants; Facies; Humans; Hyperventilation; Infant; Intellectual Disability; Male; Mutation, Missense; Spasms, Infantile; Topiramate; Transcription Factor 4

Topics: Acidosis; Alkalosis, Respiratory; Bicarbonates; Brain; Carbon Dioxide; Carbonic Anhydrase Inhibitors; Causality; Fructose; Humans; Hyperventilation; Partial Pressure; Topiramate

To report a case of hyperventilation caused by topiramate therapy and propose a pathophysiologic mechanism for this disorder.. A 52-year-old woman with refractory seizure disorder was admitted to the burn care unit with burns over 10% of her body. Her seizure medications, unchanged and well tolerated for several months, included carbamazepine 1200 mg, lamotrigine 500 mg, phenobarbital 80 mg, and topiramate 150 mg per day. During hospitalization, despite a relatively normal arterial pH, the woman developed persistent hyperventilation, with respiratory rates up to 50 breaths/min. Alkalinization did not reduce the hyperventilation. Thoracic contrast-enhanced computed tomographic scan ruled out pulmonary embolism and persistent pneumonia. Salicylate and biguanide screening were negative; results of repeated thyroid and liver function tests were normal. Cerebral magnetic resonance imaging excluded a cerebral pathology. After cerebrospinal fluid (CSF) analysis showed acidosis (pH 7.14), topiramate was withdrawn and the patient's general condition rapidly improved. Forty-eight hours later, the CSF pH had increased to 7.26. The woman was discharged from the burn care unit on the 42nd hospital day.. Hyperchloremic normal anion gap metabolic acidosis, which can lead to hyperventilation, has been reported as an adverse effect of topiramate treatment. However, our patient had respiratory alkalosis. Concurrent etiologies of peripheral hyperventilation were excluded, leaving central neurogenic hyperventilation as the remaining etiology. Such central neurogenic hyperventilation associated with topiramate has previously been reported in intensive care. Our case report demonstrates CSF acidosis. Withdrawing topiramate reduced both CSF acidosis and hyperventilation. The mechanism of topiramate-induced CSF acidosis remains unclear. According to the Naranjo probability scale, the relationship of hyperventilation to administration of topiramate in our patient was probable.. Normal doses of topiramate may provoke central neurogenic hyperventilation, as a result of CSF acidosis. The acid-base status of critically ill patients receiving topiramate should be monitored carefully.

Topics: Acidosis; Anticonvulsants; Drug Therapy, Combination; Female; Fructose; Humans; Hyperventilation; Middle Aged; Seizures; Topiramate

Two children who presented with symptomatic metabolic acidosis after being put on topiramate (TPM) are reported. The first patient was an 11-year-old male with refractory complex partial epilepsy who was put on TPM for 13 months. He developed hyperventilation 1 week after increasing the dose to 300 mg/day. Arterial blood gas revealed hyperchloraemic metabolic acidosis with partial respiratory compensation: pH 7.36, PCO2 27.2 mmHg, bicarbonate 14.9 mEq/L, base excess -8.9 mmol/L. Hyperventilation and acidosis resolved after administration of sodium bicarbonate and reduction of the dose of TPM. The second patient was a female who developed increasing irritability at age 16 months and 21 months, each time associated with introduction of TPM and resolved promptly upon withdrawal of the drug. Venous blood gas taken during the second episode revealed pH 7.34, PCO2 37.4 mmHg, bicarbonate 20.4 mEq/L, base excess -4.2 mmol/L. The predominant mechanism of TPM-induced hyperventilation involves inhibition of carbonic anhydrase at the proximal renal tubule, resulting in impaired proximal bicarbonate reabsorption. The occurrence of hyperpnoea or mental status change in any patient who is on TPM should prompt an urgent blood gas sampling, with correction of the acid-base disturbances accordingly.

Topics: Acidosis; Anticonvulsants; Bicarbonates; Blood Gas Analysis; Child; Dose-Response Relationship, Drug; Epilepsy; Female; Fructose; Humans; Hyperventilation; Infant; Male; Topiramate

Topiramate is a recently released antiepileptic agent used in the treatment of patients with refractory seizure disorders. In addition to its antiepileptogenic activities, it results in inhibition of carbonic anhydrase isoenzymes II and IV, which are present in the central nervous system. A 15-year-old female who presented with hyperpnea and primary respiratory alkalosis is reported. Other possible etiologies of the central hyperventilation syndrome were excluded. The problem resolved within 24 hours after discontinuing topiramate.

Topics: Adolescent; Anticonvulsants; Bicarbonates; Chlorides; Epilepsy; Female; Fructose; Humans; Hyperventilation; Sodium; Topiramate