A Neuropathological Study on the Brainstem Lesion in Infantile Spasm

Abstract

Purpose: It has been discusscd whether thc supratentorial brain structures or the brainstem may play a inore predominant role in the epileptogcnic mechanism in infantilc spasm. Previously, we reported the frequent occurrence of fibrillary gliosis in the central gray intitter or the midbrain in autopsy cases of infantile spasm. To investigate the involvemcnt or the brainstem lesion in the pathological mechanism o f infantile spasm in more detail, we examined the expressions of iieurotransinitters and calcium‐binding proteins in the brainstein in autopsy cases who suffered from both West and Lcnnox‐Gastaut syndromcs (WL).Method: The WL patients consisted of 4 subjects each of lisscncephaly, age 5–21 years, and a sequela of perinatal hypoxic ischemic cncephalopathy, age 10–24 years. The healthy and disease controls were composcd of 6 subjects without neuromuscular disorders, age 7–24 years, and 6 cases of a seqiiela of perinatal hypoxic ischemic cnccphalopathy, age 6–25 years with neither West nor Lennox‐G/yndrome, respcctively. In these subjects, the expressions of tyrosine hydroxylase (TH), tryptophan hydroxylase (TrH), and parvalhumin (PV), corresponding to functional markers of the catccholaminergic neurons, serotonergic neurons, and brainstem auditory system, individually, wcrc immunohistocheinically determined in serial scctions of the midbrain, pons, and medulla oblongata, using monoclonal antibodies against TH, TrH, and PV. Results: In the healthy controls, TH‐iinmunopositive neurons and ncuronal processes were found in the central gray matter and substnntia nigra in the midbrain, the locus ceruleus and reticular formation in the pons, and the vagal dorsal motor nucleus and lateral tegmentum in the medulla oblongata, while TrH‐immunopositive structures wcrc obscrvcd i n the central gray matter of the midbrain and lateral tegmentumof the medulla oblongata, in addition to the raphc nuclei from the lower midbrain to the upper medulla oblongata. The anti‐PV immunostaining clearly visualized the brainstem auditory system, including the inferior colliculus, lateral lemniscus, superior olivary complex, and vestibular nuclei. The TH‐immunopositive neurons were reduced in the dorsal motor nucleus of the vagal nerve in all of the WL patients, and the central gray matter of the midbrain and/or locus ceruleus in 4 cases of lissencephaly. Furthermore, most of the WL patients showed a mild reduction of the TrH‐immunoreactive neurons in the lateral tcgmentum of the medulla oblongata. In the anti‐parvalbuinin iinmunoslaining, the brainstem auditory system was poorly identificd in the WL patients, especially in cases of lissencephaly. In contrast, the disease controls demonstrated the similar imniorcaclivitie for TH, TrH, and PV with those in the healthy controls. Conclusion: Recently, the surgical specimens have diwloscd the dysplastic changes of the cerebral cortex in patients with West and/or Lennox‐Gastaut syndromcs, and the importance of thcse supratentorial lesions i n the epileptogenesis of inlaiitile spasin has tcndcd to bc stressed. On the onc hand, all night polysomnography and auditory evoked potential have demonstrated the brainstem lesions i n childrer with infantile spasm. It is more likcly that the disturbance of immunoreactivities for TH and PV observed i n our WL autopsy cases can be rclated to the pathogenesis of infantile spasm, becausc the diseasc controls did not show any changes in cither of ininiunostaining against TH, TrH, and PV. Accordingly, it is necessary [or the further delincation of epileptogenic mechanism in infantile spasm to clarify thc interrelationship between the neuropathological and elcctrophysiological brainstem lesions.