[Methemoglobinemia]. / Méthémoglobinémie.

Methemoglobinemia (MetHb) refers to the state of oxidation of the iron ion "ferrous" (Fe2+) to iron "ferric" (Fe3+) within the heme molecule that makes up hemoglobin (Hb). This state is physiological if its level remains controlled. The ferrous state of the heme molecule occurs in the event of significant oxidative stress. The pathophysiology of MetHb involves NADH, NADPH and glucose cycle enzymes such as cytochrome-b5-reductase. MetHb can be acquired or more rarely, congenital. Acquired causes include drug-induced effects such as topical anesthetics, or toxic effects such as nitrites. Primary causes are linked to enzyme deficiencies or constitutional Hb abnormalities. Excessively high MetHb causes symptoms of varying intensity, depending on the level of MetHb and associated comorbidities. Clinical signs are dominated by cyanosis, indicative of tissue hypoxia, which can be complicated by severe metabolic disorders leading to death. Diagnosis can be complex, as the resulting biological abnormalities may go undetected. Treatment is mainly based on identifying the etiology and restoring the heme molecule to its physiological state. Methylene blue is the main antidote in cases of elevated MetHb, but precautions must be taken in its use, and its physico-chemical effects must be understood. We provide an update on methemoglobinemia, summarizing its pathophysiology and clinical presentations, complementary tests and therapeutic principles.

Abducens internuclear neurons and their role in conjugate horizontal gaze.

Experimental evidence suggests that brain stem lesions producing paralysis of lateral gaze and dissociation of conjugate horizontal eye movements have certain common features. Both of these disturbances involve abducens internuclear neurons (Abd IN) or their projections. Attempts were made to determine the course and terminal distribution of Abd IN in the monkey by autoradiographic techniques. Tritiated amino acids injected in the abducens nucleus (Abd N) labeled: (1) root fibers ipsilaterally, and (2) fibers that ascended in medial parts of the contralateral medial longitudinal fasciculus (MLF). In the opposite oculomotor complex (OMC) silver grains were profuse over the ventral nucleus (VN, medial rectus muscle) and patchy over caudal parts of the dorsal nucleus (DN, inferior rectus muscle). Labeling of cells in the reticular formation nucleus to Abd N resulted in transport ipsilaterally, outside the MLF, to the rostral interstitial nucleus of the MLF (RiMLF), a cell group considered to be concerned with vertical eye movements. Bilateral labeling of Abd N and cells of the nucleus prepositus (NPP) resulted in bilateral: (1) transport of isotope via root fibers and the MLF, and (2) selective distribution of silver grains in the OMC. Bilateral silver grain distribution in the OMC suggested profuse terminations in VN, patchy terminations in DN and vertical, linear terminations in caudal parts of the medial nucleus (MN, superior rectus muscle). Comparisons with more discrete unilateral labeling of cells in Abd N suggested that cells of the NPP project selectively to terminations in MN, and may be related to upward eye movements. Two conclusions were drawn: (1) The paresis of ocular adduction which occurs in both anterior internuclear ophthalmophlegia and in paralysis of lateral gaze results from involvement of Abd IN or their ascending projections, and (2) the NPP appears to project selectively to parts of MN of the OMC, a cell group said to provide crossed innervation for the superior rectus muscle.

Transport of radioactivity from primary auditory neurons beyond the cochlear nuclei.

Transneuronal degeneration in secondary brainstem auditory nuclei has been described following cochlear lesions, and Marchi studies have revealed degeneration in the trapezoid body after such lesions. These findings support the view of some early neuroanatomists that primary auditory afferents project beyond the cochlear nuclei. Silver impregnation studies of degenerating cochlear afferents have failed to support this claim, leaving the question unresolved. Using [3H] amino acids auditory projections in the monkey were traced autoradiographically from labeled ganglion cells: (1) in all portions of the spiral ganglion, (2) in apical and middle turns of the cochlea and (3) primarily in the basal turn of the cochlea. Labeling of the entire spiral ganglion resulted in profuse transport of isotope to parts of all cochlear nuclei [anteroventral (AVCN), posteroventral (PVCN), and dorsal (DCN) cochlear nuclei]. Labeled axons entering the trapezoid body (TB) projected ipsilaterally to: (1) the lateral trapezoid nuclei (LTN), (2) the lateral superior olivary nucleus (LSO), (3) the dorsal dendritic zone of the medial superior olivary nucleus (MSO), and (4) the pericollicular or cortical nucleus of the inferior colliculus (IC). Auditory fibers crossing the midline in the TB projected contralaterally to: (1) the medial trapezoid nucleus (MTN), (2) the ventral dendritic zone of the MSO, (3) the ventral nucleus of the lateral lemniscus (VNLL), and (4) the central nucleus of the inferior colliculus (CNIC). Selective labeling of cells in the apical and middle ganglionic turns ofthe cochlea resulted in a similar pattern of centripetal transport. Selective [3H] uptake primarily by ganglion cells in the basal turn of the cochlea resulted in: (1) labeling of restricted parts of all cochlear nuclei, and (2) a considerable reduction of isotope transported beyond the cochlear nuclei. Labeled fibers in the TB were distributed sparsely in the ipsilateral LTN, LSO and dorsal dendritic zone of the MSO. Fibers in the TB were not labeled contralaterally in these animals. Interpretation of these data considers the possibility of transneuronal isotope transport. The pattern of isotope transported beyond the cochlear nuclei does not correspond to the secondary projections of any individual cochlear nucleus, although it bears some resemblance to that of the AVCN. The current study suggests that some primary auditory afferents project beyond the cochlear nuclei.

Brain stem afferents to the fastigial nucleus in the cat demonstrated by transport of horseradish peroxidase.

Although retrograde and anterograde degeneration studies have provided important information concerning brain stem afferents to the fastigal nucleus (FN), these data may be incomplete and should be confirmed by axonal transport methods. Attempts were made to inject horseradish peroxidase (HRP) unilaterally into the FN in a series of adult cats. Animals were perfused with dextran and a fixative solution of paraformaldehyde and glutaraldehyde in 0.1 M phospate buffer. Representative sections were treated by the Graham and Karnovsky ('66) method. Selective HRP injections in one FN resulted in retrograde transport of the marker to Purkinje cells of the ipsilateral vermis and distinctive appendages of the contralateral medial accessory olivary (MAO) nucleus (nucleus beta and the dorso-medial cell column). Retrograde transport of the label was found bilaterally in cells of the medial (MVN) and inferior (IVN) vestibular nuclei, in cell group x and in the nucleus prepositus (PP). Labeled vestibular neurons, most numerous in MVN, were identified in dorsal, caudal and lateral regions, with a slight ipsilateral preponderance. Only a few neurons in caudal, dorsal and lateral regions of the IVN were labeled and none of these included cells of group f. Labeled cells in the caudal third of PP were greatest ipsilaterally. Rostral and caudal injections of FN labeled smaller numbers of cells in MVN, IVN, cell group x and PP. HRP injections of FN and portions of lobules VIII and IX resulted in bilateral retrograde labeling of larger numbers of cells in MVN, IVN and cell group x, and ipsilateral labeling of cells in group y and the interstitial nucleus of the vestibular nerve. Injections of HRP into basal folia of lobules V and VI resulted in retrograde transport of the marker to cells of the medial and dorsal accessory olivary nuclei contralaterally, and to cells of the ipsilateral accessory cuneate nucleus. Transport of label injected into portions of the pyramis was detected in parts of the contralateral MAO and bilaterally in parts of the pontine and reticulotegmental nuclei. This study suggests that the principal afferents of the fastigial nucleus arise from: (1) Purkinje cells of the ipsilateral vermis, (2) restricted portions of the contralateral MAO (nucleus beta and dorsomedial cell column), (3) portions of the MVN and IVN (bilaterally) and (4) caudal parts of the PP. Secondary vestibular inputs to the fastigial nucleus probably are relayed mainly by Purkinje cells in the cerebellar cortex.