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Neonatal seizures


Enviado por   •  9 de Noviembre de 2023  •  Apuntes  •  9.867 Palabras (40 Páginas)  •  15 Visitas

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Neonatal seizures


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Pediatr Clin N Am 51 (2004) 961– 978 

 

The presence of neonatal seizures often signals an underlying ominous neurological condition, most commonly hypoxia-ischemia. The other common etiologies of neonatal seizures are stroke, intraventricular hemorrhage or intraparenchymal hemorrhage, meningitis, sepsis, or metabolic disorders. New animal research suggests that neonates may exhibit some neuroprotection from prolonged seizures, but brief, recurrent seizures can result in significant, permanent changes in the central nervous system, an increased risk of epilepsy, and long-term cognitive disabilities.  

 

PATHOPHYSIOLOGY

A seizure is the occurrence of an abnormal synchronous electrical discharge (depolarization) of a group of neurons within the central nervous system. Depolarization is the result of an influx of sodium ions into neuronal cells, whereas repolarization occurs when potassium ions are pumped out of the cell, creating the normal negative electrical potential across the cell membrane. This electrical potential is maintained by a sodium-potassium pump, which requires adenosine tri-phosphate (ATP) as its energy source. Excessive depolarization is generally felt to be the end common pathway by which seizures occur.  

 

Hypoxia ischemia, the most common cause of neonatal seizures, results in a sharp decrease in energy production, causing a failure of the sodium-potassium pump. In addition, hypocalcemia and hypomagnesemia can alter membrane potential, producing sodium influx and depolarization.

 

WHAT ARE THE FEATURES THAT MAKE THE IMMATURE BRAIN MORE VULNERABLE TO SEIZURES?

 

There is a developmental imbalance between maturation of excitatory and inhibitory circuits. GABA-A, (gamma aminobutyric acid), the primary inhibitory neurotransmitter in adults, is actually excitatory in the hippocampal neurons. GABA-A responses are associated with a chloride efflux depolarization and activation of sodium (Na) and calcium (Ca) channels. This depolarization by GABA is potent enough to remove the voltage-dependent magnesium (Mg) block from the N-methyl-D-aspartate (NMDA) channels, producing a concomitant Ca influx into the immature neurons. There is a higher density of NMDA receptors in the hippocampus and neocortical regions of the brain, resulting in enhanced excitatory activity. There are also specific properties of the immature NMDA receptor that make it susceptible to enhanced excitation: prolonged duration of the NMDA action potential; greater sensitivity to glycine (an excitatory neurotransmitter); a reduced ability of magnesium to block the NMDA receptor activity; and diminished ability of the polyamine inhibitory binding sites.

 

The proconvulsant network of the substantia nigra is fully functional early on in brain development; the anticonvulsant network develops later. There is also delayed maturation of other postsynaptic inhibitory systems, including postsynaptic GABA-B, adenosine, and 5-hydroxytryptamine. Presynaptic inhibition, mediated by adenosine, GABA-delta, and other receptors, is fully operational at birth. This implies that inhibition in the neonatal brain predominantly relies on transmitter release. There are differences in membrane potentials in the immature dendrites, with a large input resistance in developing neurons. Prevalence of gap junctions in the immature brain may amplify small imbalances in neuronal activity, resulting in synchronized electrical activity. There is a shorter refractory period/hyperpolarization during the postictal phase in young animals.

 

DO RECURRENT SEIZURES OR PROLONGED SEIZURES CAUSE HARM TO THE IMMATURE BRAIN?

Animal studies document that the consequences of seizures in the immature brain are different from those in the adult brain. Following a single prolonged seizure in the developing rat brain, there is less neuronal cell death, limited mossy fiber sprouting, and fewer cognitive deficits than typically seen in the adult rat. The reasons for this are not fully understood, but may involve developmental differences in glutamate-induced damage at the cellular level, and differences in the intracellular calcium-buffering capabilities in the immature brain.

 

Long-term physiologic and developmental consequences to brief, recurrent seizures in the immature brain, including: (1) permanent reduction in seizure threshold, and (2) significant deficits in learning and memory.  

 


WHAT IS THE MECHANISM OF ACTION FOR THE CHANGES THAT ARE SEEN WITH NEONATAL SEIZURES?  

The most significant biochemical effects of neonatal seizures are the changes in energy metabolism. Within 5 minutes after the onset of a seizure, there are significant changes: (1) decline in ATP; (2) decline in the storage form of ATP, phosphocreatine; (3) substantial increase in adenosine diphosphate(ADP); (4) increase in glycolysis, with concomitant increase in pyruvate and lactate; and (5) significant decline in central nervous system (CNS) glucose concentration.  

 

There are other changes in metabolism that can occur with recurrent seizures, these include significant declines in DNA, RNA, and protein metabolism. There is a significant decline in DNA synthesis during a seizure, as well as impairment of neuronal differentiation and myelination. We know that there is impairment of cerebrovascular autoregulation and increased cerebral blood flow (CBF) with seizures in the newborn. Although this can be seen as a adaptive mechanism to improve substrate delivery (particularly glucose) in a preterm infant or asphyxiated infant, the increase in blood flow could potentially rupture blood vessels in highly vulnerable areas of the brain, such as the germinal matrix in premature infants or the penumbra of an infarction in an asphyxiated infant.

 

There is new and emerging evidence that the neonatal brain is more resistant to cell death than its adult counterpart. Specifically, in the immature rat brain, prolonged seizures result in less neuronal cell loss than in their adult counterparts. The lack of neuronal cell loss may have important ramifications, including abnormal ratio of granule cell:pyramidal cell ratio, differences in synaptogenesis among these cells, and important changes in excitability/seizure threshold. Even though there is less neuronal cell death in neonatal rat models with status epilepticus in comparison with adult rat models, there is still some neuronal cell death. Excitatory amino acids may play a major role as the mechanism of neuronal cell death with prolonged seizures. Prolonged seizures cause excessive release of glutamate and aspartate.

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