Electroencephalographic findings in urea-cycle disorders

Verma, Narayan P.; Hart, Zwi H.; Kooi, Kenneth A.

doi:10.1016/0013-4694(84)90168-8

Cited by 14 publications

(8 citation statements)

References 21 publications

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“…Previous reports have documented EEG changes in patients with OTCD, with multifocal independent spike and sharp wave discharges being the most common finding, although a nonspecific pattern consistent with a diffuse encephalopathy is more commonly observed (Batshaw 1984;Bourrier et al 1988;Brunquell et al 1999;Brusilow 1985;Engel and Buist 1985). In addition, EEG abnormalities have been reported in infants with OTCD in the absence of clinical seizures (Bogdanovic et al 2000;Brunquell et al 1999;Engel and Buist 1985;Verma et al 1984) and may be used to explain differential responses to intervention and outcome when the clinical examination appears similar. EEG patterns that fail to respond, either in amplitude or frequency, to noxious, auditory, or visual stimuli predict a poor prognosis for meaningful neurological recovery, whereas similar patterns with preserved reproducible reactivity imply the potential for some recovery and should be compared with recordings repeated several days later.…”

Section: Cognitive Outcome Of Urea Cycle Disordersmentioning

confidence: 97%

“…In addition, EEG abnormalities have been reported in infants with OTCD in the absence of clinical seizures (Bogdanovic et al 2000;Brunquell et al 1999;Engel and Buist 1985;Verma et al 1984) and may be used to explain differential responses to intervention and outcome when the clinical examination appears similar. EEG patterns that fail to respond, either in amplitude or frequency, to noxious, auditory, or visual stimuli predict a poor prognosis for meaningful neurological recovery, whereas similar patterns with preserved reproducible reactivity imply the potential for some recovery and should be compared with recordings repeated several days laFter.…”

Section: Cognitive Outcome Of Urea Cycle Disordersmentioning

confidence: 99%

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Neurological implications of urea cycle disorders

Gropman

Summar

Leonard³

2007

J of Inher Metab Disea

191

152

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SummaryThe urea cycle disorders constitute a group of rare congenital disorders caused by a deficiency of the enzymes or transport proteins required to remove ammonia from the body. Via a series of biochemical steps, nitrogen, the waste product of protein metabolism, is removed from the blood and converted into urea. A consequence of these disorders is hyperammonaemia, resulting in central nervous system dysfunction with mental status changes, brain oedema, seizures, coma, and potentially death. Both acute and chronic hyperammonaemia result in alterations of neurotransmitter systems. In acute hyperammonaemia, activation of the NMDA receptor leads to excitotoxic cell death, changes in energy metabolism and alterations in protein expression of the astrocyte that affect volume regulation and contribute to oedema. Neuropathological evaluation demonstrates alterations in the astrocyte morphology. Imaging studies, in particular 1 H MRS, can reveal markers of impaired metabolism such as elevations of glutamine and reduction of myoinositol. In contrast, chronic hyperammonaemia leads to adaptive responses in the NMDA receptor and impairments in the glutamate-nitric oxide-cGMP pathway, leading to alterations in cognition and learning. Therapy of acute hyperammonaemia has relied on ammonia-lowering agents but in recent years there has been considerable interest in neuroprotective strategies. Recent studies have suggested restoration of learning abilities by pharmacological manipulation of brain cGMP with phosphodiesterase inhibitors. Thus, both strategies are intriguing areas for potential investigation in human urea cycle disorders.

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Section: Cognitive Outcome Of Urea Cycle Disordersmentioning

confidence: 97%

Section: Cognitive Outcome Of Urea Cycle Disordersmentioning

confidence: 99%

Neurological implications of urea cycle disorders

Gropman

Summar

Leonard³

2007

J of Inher Metab Disea

191

152

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“…Epilepsy, observed in 40% of patients, presents with tonic clonic, clonic or myoclonic seizures . Electroencephalography can be abnormal even in nonsymptomatic patients, displaying an aspecific pattern . Hyperammonaemia‐related neonatal seizures can be subclinical but are not predictive of developing an epilepsy later in life …”

Section: Biochemical Presentation/ Diagnosismentioning

confidence: 99%

“…39 Electroencephalography can be abnormal even in nonsymptomatic patients, displaying an aspecific pattern. 39,40 Hyperammonaemiarelated neonatal seizures can be subclinical 41 but are not predictive of developing an epilepsy later in life. 39 F I G U R E 1 Argininosuccinate lyase and related metabolic pathways.…”

Section: Systemic Diseasementioning

confidence: 99%

Argininosuccinic aciduria: Recent pathophysiological insights and therapeutic prospects

Baruteau

Dı́ez-Fernández

Lerner³

et al. 2019

J of Inher Metab Disea

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The first patients affected by argininosuccinic aciduria (ASA) were reported 60 years ago. The clinical presentation was initially described as similar to other urea cycle defects, but increasing evidence has shown overtime an atypical systemic phenotype with a paradoxical observation, that is, a higher rate of neurological complications contrasting with a lower rate of hyperammonaemic episodes. The disappointing long-term clinical outcomes of many of the patients have challenged the current standard of care and therapeutic strategy, which aims to normalize plasma ammonia and arginine levels. Interrogations have raised about the benefit of newborn screening or liver transplantation on the neurological phenotype. Over the last decade, novel discoveries enabled by the generation of new transgenic argininosuccinate lyase (ASL)-deficient mouse models have been achieved, such as, a better understanding of ASL and its close interaction with nitric oxide metabolism, ASL physiological role outside the liver, and the pathophysiological role of oxidative/nitrosative stress or excessive arginine treatment. Here, we present a collaborative review, which highlights these recent discoveries and novel emerging concepts about ASL role in human physiology, ASA clinical phenotype and geographic prevalence, limits of current standard of care and newborn screening, pathophysiology of the disease, and emerging novel therapies. We propose recommendations for monitoring of ASA patients. Ongoing research aims to better understand the underlying pathogenic mechanisms of the systemic disease to design novel therapies.Carmen Diez-Fernandez and Shaul Lerner contributed equally to this study.

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“…While there is a paucity of investigation of the incidence/prevalence of seizures in UCD, one early study evaluated 11 EEG tracings of 4 infants, irrespective of clinical seizure status [69]. This small study identified epileptiform EEG alterations and hypothesized that they may be a characteristic manifestation of UCD.…”

Section: Seizures In Ucdmentioning

confidence: 99%

Emerging Knowledge From Noninvasive Imaging Studies: Is Ammonia Control Enough?

Gropman¹

2020

Cellular Metabolism and Related Disorders

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Multiple lines of research suggest that ammonia is harmful to the brain if the levels remain elevated for extended periods of time. Several decades ago, there was no testing or standard of care to monitor the effect of hyperammonemia (HA) on neurological function in urea cycle disorders (UCD), and the timing of HA encephalopathy is still not clear. Magnetic resonance imaging (MRI) was not done routinely, if at all, so it was not known what changes were occurring in the brain, during and after recovery from HA. Decades ago, a diagnosis of a UCD meant severe disability and early death. Earlier diagnosis, improved management, and nitrogen scavenger therapy have improved the lives and life span of patients with UCD. However, many patients suffer from learning difficulties under the umbrella "executive function" which comprises neurologically based skills involving mental control and self-regulation. The general agreement of the core elements of executive functions includes inhibition, working memory, and cognitive flexibility and is necessary in development of skills in reasoning, fluid intelligence, problem-solving, and planning. Our research focuses on the use of noninvasive neuroimaging coupled with neuropsychological testing to understand the complex relationship between ammonia, glutamine, cognitive function, seizures, and specifically impact on development of working memory.

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Electroencephalographic findings in urea-cycle disorders

Cited by 14 publications

References 21 publications

Neurological implications of urea cycle disorders

Neurological implications of urea cycle disorders

Argininosuccinic aciduria: Recent pathophysiological insights and therapeutic prospects

Emerging Knowledge From Noninvasive Imaging Studies: Is Ammonia Control Enough?

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