Miastenia gravis en la infancia: una serie de tres casos / Myasthenia gravis in infancy: a series of three cases

La miastenia gravis es una enfermedad neuromuscular crónica debida a deficiencia de transmisión nerviosa en la unión neuromuscular, de origen generalmente autoinmune en el adulto, que se caracteriza por grados variables de debilidad de los músculos esqueléticos del cuerpo, que aumenta durante los períodos de actividad y disminuye después de períodos de descanso. Sin embargo en la infancia cobran especial relevancia los síndromes miasténicos congénitos, que encuentran su origen en mutaciones de genes que codifican proteínas que juegan papeles clave en el mantenimiento de la transmisión neuromuscular, teniendo edad de inicio, distribución de debilidad y respuesta a tratamiento variables. Se presentan tres casos con el objetivo de describir el comportamiento clínico de la enfermedad y la utilidad de estudios complementarios ya que es de suma importancia su precoz identificación y tratamiento. Palabras claves: Miastenia gravis, test de estimulación repetitiva, ptosis palpebral, unión neuromuscular, pares craneanos

Myasthenia gravis is a chronic neuromuscular disease due to deficiency of nerve transmission in the neuromuscular junction, usually of an autoimmune origin in the adult, which is characterized by varying degrees of weakness of the skeletal muscles of the body, which increases during periods of activity and decreases after periods of rest. In childhood, however, congenital myasthenic syndromes, which find their origin in mutations of genes that encode proteins that play key roles in maintaining neuromuscular transmission, which may have a varying age of onset, distribution of weakness and response to treatment, are particularly relevant. Three cases are presented with the aim of describing the clinical presentation and course of the disease and the usefulness of complementary studies, since its early diagnosis and treatment is of paramount importance.Keywords: Myasthenia gravis, repetitive stimulation test, palpebral ptosis, neuromuscular junction, cranial pairs.

Inhibition or enhancement of kindling evolution by antiepileptics.

The influence of antiepileptics on the evolution of rat amygdaloid kindling was studied. Under placebo conditions clonic convulsions and a spike-wave EEG pattern developed. Diazepam, clonazepam, clobazam and phenobarbital were most effective in suppressing the evolution of kindling; the effects of valproate sodium, ethosuximide and acetazolamide were somewhat less pronounced in this respect. Carbamazepine, oxcarbazepine and phenytoin, on the other hand, enhanced kindling development, i.e. the increase in duration of after-discharge was faster than in the placebo group. The results indicate that under the above experimental conditions drugs with no anti-absence component can be distinguished from those with an anti-absence component. The mechanism of action underlying the observed effects is not yet known; the hypothesis that under special conditions protective inhibitory neuronal activity can develop to absence type seizures is proposed.

Pharmacological and neurochemical aspects of kindling.

Rats implanted with amygdaloid stimulating and cortical recording electrodes were kindled by daily low-intensity electrical stimulation. In one experiment amino acid concentrations were measured in amygdala, cortex and hippocampus at behavioural stages 1, 2 and 4 (Racine). Control groups consisted of unstimulated rats. Only alanine showed a significant enhancement of concentration in the kindled rats (stage 4 of Racine). In a second experiment, a group of rats was treated daily with 10mg/kg p.o. of diazepam. Diazepam significantly inhibited kindling and no changes in amino acid concentrations were observed in this group. Increased alanine levels are seen after various seizure types; since pentetrazole, isoniazid and beta-vinyllactic acid seizures were associated with alanine level increases only after and never before seizure occurrence, it is suggested that the alanine increases are a consequence rather than a cause of convulsions. In 3H-flunitrazepam binding studies, no change in affinity or receptor number could be demonstrated during kindling.

The specific protective effect of diazepam and valproate against isoniazid-induced seizures is not correlated with increased GABA levels.

Amino acid concentrations were measured in the cortex, cerebellum and hippocampus of the mouse brain before and during seizures induced by isoniazid (250 mg/kg i.p.), an inhibitor of L-glutamate-1-decarboxylase (EC 4.1.1.15: GAD). Valproate sodium and diazepam dose-dependently delay the onset of convulsive fits caused by isoniazid. However, neither diazepam nor valproate prevented the decrease in GABA concentrations produced by isoniazid alone. Also, these antiepileptic drugs did not modify the rate of GABA depletion elicited by isoniazid. These results, observed in four different brain structures, strengthen those first obtained with beta-vinyllactic acid, another inhibitor of GAD.

The biological activity of d- and l-baclofen (Lioresal).

Racemic d,l-baclofen and l-baclofen depressed the patellar, flexor, linguo-mandibular (0.1--30 mg/kg i.v.) and the H-reflex (1--3 mg/kg i.v.) in a dose-dependent fashion. Racemic and l-baclofen partly antagonized electroshock-induced convulsions in mice (30--60 mg/kg p.o.) and depressed the firing rate of nigral cells when applied iontophoretically. d,l-Baclofen and l-baclofen (0.1--3.0 mg/kg i.v.) moderately reduced the blood pressure in cats. Dextrorotatory baclofen, at identical doses was inactive in all these tests. It is concluded that the biological activity of baclofen resides with the l-enantiomer.