Epidemiology and Clinical Characteristics of Seizures in Patients with Acute Intermittent Porphyria

Bylesjö, Ingemar; Forsgren, Lars; Lithner, Folke; Boman, Kurt

doi:10.1111/j.1528-1157.1996.tb00018.x

Cited by 70 publications

(44 citation statements)

References 38 publications

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“…High levels of ␤4 mRNA expression were detected in the pineal gland and in the medial habenula (17,49). The pineal gland produces melatonin, a hormone with anticonvulsant properties in rodents (9) and humans (7,20,42). Melatonin was shown to interact with nicotinic receptors; it inhibited fast excitatory postsynaptic potentials in guinea pig submucosal neurons by blocking nAChR (2) and also inhibited nicotine-stimulated dopamine release in PC12 cells (50).…”

Section: Discussionmentioning

confidence: 99%

Mice lacking neuronal nicotinic acetylcholine receptor β4-subunit and mice lacking both α5- and β4-subunits are highly resistant to nicotine-induced seizures

Kedmi

Beaudet

Orr-Urtreger

2004

Physiological Genomics

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Kedmi, Merav, Arthur L. Beaudet, and Avi Orr-Urtreger. Mice lacking neuronal nicotinic acetylcholine receptor ␤4-subunit and mice lacking both ␣5-and ␤4-subunits are highly resistant to nicotineinduced seizures. Physiol Genomics 17: 221-229, 2004. First published March 2, 2004 10.1152/physiolgenomics.00202.2003.-Nicotine, the main addictive component of tobacco, evokes a wide range of dose-dependent behaviors in rodents, and when administrated in high doses, it can induce clonic-tonic seizures. Nicotine acts through the nicotinic acetylcholine receptors (nAChRs). Mutations in the human ␣4-and the ␤2-nAChR subunit genes cause autosomal dominant nocturnal frontal lobe epilepsy. Using transgenic mice with mutations in nAChR subunits, it was demonstrated previously that the ␣4-, ␣5-, and ␣7-subunits are involved in nicotine-induced seizures. To examine the possibility that the ␤4-subunit is also involved in this phenotype, we tested mice with homozygous ␤4-subunit deficiency. The ␤4 null mice were remarkably resistant to nicotine-induced seizures compared with wild-type and ␣5 null mice. We also generated mice with double deficiency of both ␣5-and ␤4-nAChR subunits and demonstrated that they were more resistant to nicotine's convulsant effect than either the ␣5 or the ␤4 single mutant mice. In addition, the single ␣5 mutants and the double ␣5␤4-deficient mice exhibited a significantly shorter latency time to seizure than that of the wild-type mice. Our results thus show that ␤4-containing nAChRs have a crucial role in the pathogenesis of nicotine-induced seizures. Furthermore, by comparing multiple mutant mice with single and double subunit deficiency, we suggest that nicotinic receptors containing either ␣5-or ␤4-subunits are involved in nicotine-induced seizures and that receptors containing both subunits are likely to contribute to this phenomena as well. However, the ␣5-subunit, but not the ␤4-subunit, regulates the rate of response to high doses of nicotine.neuronal nicotinic acetylcholine receptor ␣5-and ␤4-subunits; knockout mice NICOTINE ACTS THROUGH THE nicotinic acetylcholine receptors (nAChRs) and can be toxic in high doses in mice, inducing tremors, seizures, and even death (41). The nAChRs are allosteric membrane proteins that belong to a large family of ligand-gated ion channels. Each receptor is composed of a combination of five subunits. To date, 12 neuronal subunits (␣2-␣10 and ␤2-␤4) have been identified (reviewed in Ref. 29). They are widely distributed in the central and peripheral nervous systems and are also expressed in nonneuronal cells (11,14,23,30,37).In humans, nAChRs are associated with a number of pathological conditions, including epilepsy (reviewed in Ref. 35). Mutations in the ␣4-and ␤2-subunit genes were associated with familial cases of autosomal dominant nocturnal frontal lobe epilepsy (15, 45, 52-54). In addition, genetic linkage was found between juvenile myoclonic epilepsy and the chromosomal region encompassing the ␣7-subunit gene (18).In mice, a genetic linkage was shown betw...

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Section: Discussionmentioning

confidence: 99%

Mice lacking neuronal nicotinic acetylcholine receptor β4-subunit and mice lacking both α5- and β4-subunits are highly resistant to nicotine-induced seizures

Kedmi

Beaudet

Orr-Urtreger

2004

Physiological Genomics

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“…During the seizure episode, the patient may be given benzodiazepines, which in low doses are said to be safe in AIP. 5 Except for gabapentin and vigabatrin, almost all other antiepileptic drugs can exacerbate porphyric crisis. 6 In our case, seizures were due to SIADH which was managed with benzodiazepines.…”

Section: Discussionmentioning

confidence: 99%

An elusive case of acute abdomen

Aggarwal

Dwivedi

Akulwar

2011

Medical Journal Armed Forces India

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“…The neurological complications of AIP are cranial neuropathy, peripheral neuropathy, autonomic neuropathy and generalized convulsions [5,6]. Peripheral neuropathy is caused by segmental demyelination or axonal degeneration with secondary loss of myelin.…”

Section: Discussionmentioning

confidence: 99%

Diagnostic Dilemmas in Acute Intermittent Porphyria

Vembu¹,

Shubaili²,

Girsh

2002

Med Princ Pract

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Objective: To present the importance of early diagnosis of acute intermittent porphyria (AIP) in patients with atypical presentation and discuss the diagnostic problems encountered in this case. Clinical Presentation: A 15-year-old girl presented with upper respiratory tract infection, fever, seizures and abdominal pain. An initial diagnosis of encephalitis was made. She received antiviral drugs and anticonvulsants. Two weeks later, she developed progressive flaccid quadriplegia and facial weakness. She also developed respiratory paralysis and was intubated. Cytoalbuminous dissociation was seen in the cerebrospinal fluid. A diagnosis of severe Guillain-Barré syndrome was made. Intervention: The patient received a course of intravenous immunoglobulins which did not result in any clinical improvement. Plasmapheresis, started after 12 weeks, led to partial improvement. The patient continued to have attacks of seizures, abdominal pain and vomitting with severe quadriparesis. A repeat screening test for urine porphyrins was positive, and AIP was confirmed by specific porphobilinogen deaminase in the blood. The patient was treated with large doses of intravenous glucose, followed by injections of hematin. The patient improved remarkably. She was extubated, discharged from Intensive Care Unit and started on a rehabilitation program. Conclusion: This patient was initially diagnosed erroneously with a negative screening test for AIP and consequently treated inappropriately. The proper diagnosis was made after repeating the screening test followed by specific tests of porphobilinogen deaminase.

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Epidemiology and Clinical Characteristics of Seizures in Patients with Acute Intermittent Porphyria

Cited by 70 publications

References 38 publications

Mice lacking neuronal nicotinic acetylcholine receptor β4-subunit and mice lacking both α5- and β4-subunits are highly resistant to nicotine-induced seizures

Mice lacking neuronal nicotinic acetylcholine receptor β4-subunit and mice lacking both α5- and β4-subunits are highly resistant to nicotine-induced seizures

An elusive case of acute abdomen

Diagnostic Dilemmas in Acute Intermittent Porphyria

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