Irish brogue after stroke.

BACKGROUND: We describe a patient who presented a unique variation of the previously described acquired foreign accent syndrome. CASE DESCRIPTION: A 65-year-old women developed an Irish brogue immediately after a deep left hemisphere stroke. The newly accented speech possibly represented a previously learned speech pattern. CONCLUSIONS: Suppressed prosodic speech patterns may reemerge in the setting of brain injury.

Hypothalamic or central obesity is associated with an early rise in plasma insulin concentration.

Insulin levels in a 7-year-old boy with hyperphagia and obesity following an episode of meningoencephalitis were studied sequentially during the course of progressive weight gain. High fasting insulin levels (1183 pmol/L) and strikingly high insulin release in response to glucose (7892 pmol/L) were found within weeks of the onset of the illness. The abnormality in insulin secretion occurred prior to the marked weight gain. Hyperinsulinemia was not accompanied by hypoglycemia. Early hyperinsulinemia may be a primary event in the development of hyperphagia and obesity following hypothalamic injury.

Hypercalcaemia causing declining cognitive function in a head injured patient.

Although hypercalcaemia in young children or adolescents immobilized by fractures or spinal cord injury is well recognized, hypercalcaemia in adult immobilized patients is rare without a pre-existing bone disease. To our knowledge, hypercalcaemia in a head-injured, immobilized patient has not been previously reported. We report here a case where a previously normocalcaemic, immobilized, head-injured adult patient developed cognitive decline secondary to hypercalcaemia five months after injury, when transient interruption of enteral feedings led to mild dehydration. Indices of bone turnover were elevated and parathyroid hormone was appropriately suppressed. Possible predisposing factors in our patient included a severe degree of immobilization and a very high level of athletic activity prior to injury. Careful fluid management and specific monitoring of calcium levels, even several months post-injury, should be performed to avoid the added complications of hypercalcaemia in head-injured patients.

Selective loss of hippocampal granule cells in the mature rat brain after adrenalectomy.

Adrenalectomy of adult male rats resulted in a nearly complete loss of hippocampal granule cells 3 to 4 months after surgery. Nissl and immunocytochemical staining of hippocampal neurons revealed that the granule cell loss was selective; there was no apparent loss of hippocampal pyramidal cells or of gamma-amino butyric acid (GABA)-, somatostatin-, neuropeptide Y-, calcium binding protein-, or parvalbumin-containing hippocampal interneurons. The hippocampal CA1 pyramidal cells of adrenalectomized animals exhibited normal electrophysiological responses to afferent stimulation, whereas responses evoked in the dentate gyrus were severely attenuated. Corticosterone replacement prevented both the adrenalectomy-induced granule cell loss and the attenuated physiological response. Thus, the adrenal glands play a role in maintaining the structural integrity of the normal adult brain.

Neuropeptides and their role in nociception and analgesia.

The authors highlight the potential importance of neuropeptides as clinical tools in the study and treatment of pain. Although many questions remain unanswered, it is encouraging that several clinical and experimental advances have shed new light on the neuropharmacology of nociception and have prompted new hope for more effective treatments of such diverse problems as chronic intractable pain, migraine, and drug dependency. Within the next few years, it is anticipated that further work in this area will lead to better basic and clinical understanding of these important clinical problems.

Neuroendocrine syndromes of the hypothalamus.

These brief reviews of selected neuroendocrine or hypothalamic syndromes reinforce several important concepts. Although the hypothalamus may be relatively inaccessible to the neurologic clinician, it is, paradoxically, the region of the CNS that most closely communicates with virtually all other physiologic systems. This is evident by the fact that hypothalamic dysfunction is frequently associated with "non-neurologic" symptoms such as manifestations of endocrine, gastrointestinal, or gynecologic disease. Traditionally, the hypothalamus has been difficult to study, and progress in understanding hypothalamic disorders has been slow in both neuropathology as well as clinical neurology. Nevertheless, as neurology evolves from a descriptive specialty into one increasingly characterized by therapeutic intervention, the challenge of clinical hypothalamic disease offers many exciting possibilities to the neuropharmacologist, neuroendocrinologist, and all astute bedside clinicians.

Immunofluorescence study of patients with neuropathy and IgM M proteins.

Immunofluorescence histochemistry was used to study the pathogenesis of polyneuropathy in patients with an IgM M protein. Seventeen patients had an M protein that reacted with myelin-associated glycoprotein (MAG), and their serum immunostained myelin sheaths of normal peripheral nerve of humans and certain other species. The staining was specific for the M protein idiotype and was abolished by prior absorption of serum with MAG. The sural nerve biopsy specimens from these 17 patients had pathological features of primary demyelination and deposits of IgM on the myelin sheaths. Sural nerve specimens of 2 patients with an M protein reactive with chondroitin sulfate showed axonal degeneration and diffuse deposits of IgM in the endoneurium. Serum of one of these patients immunostained connective tissue; the staining was specific for the M protein idiotype and was blocked by absorption of the serum with chondroitin sulfate. The antigenic specificity of the IgM M protein in another 9 patients with neuropathy is not known; however, sural nerve specimens obtained from some of the patients showed axonal degeneration and endoneurial deposits of IgM, and the serum IgM immunostained axons in some instances. The findings suggest that IgM M proteins may cause the neuropathy and that more than one autoantigen is involved.

Hypothalamic oxytocin: a cerebrovascular modulator in man?

Immunocytochemical studies in normal rats show an association between oxytocin (OT) neurons and cerebral blood vessels. This is supported by the finding of neurophysin (NP) immunoreactivity in blood vessels and pia-arachnoid tissue of rats with hereditary vasopressin (VP) and VP-NP deficiency. OT and OT-NP fibers were visualized in pia-arachnoid and blood vessels at the base of the brain and, to a lesser extent, over the dorsal surface. OT constricts human basilar artery with a threshold response in the 10(-10) M range, and an ED50 of 4.8 X 10(-9) M. These observations suggest that extrahypothalamic projections of OT neurons may modulate cerebrovascular function.

Extrahypothalamic neurohypophysial peptides in the rat central nervous system.

Vasopressin (VP) and oxytocin (OT) have been identified in a number of extrahypothalamic areas, both by immunohistochemistry and by radioimmunoassay. Because of the incomplete nature of the data available, we have conducted a survey of the VP and OT concentrations in the rat central nervous system. VP and OT were readily detectable in all areas studied. With the exception of the amygdala, OT concentrations were generally 2-4 times those of VP. The physiological function of neurohypophysial hormones in these extrahypothalamic areas is essentially unknown.

The medical treatment of head and neck pain.

Head and neck pain are extremely common and in any year, four of five people will experience a headache. In one out of two the headache will be severe enough to interfere with daily activity. In this article the multiple clinical syndromes of head and neck pain are presented and the current medical therapies reviewed.

Neuropathy and anti-MAG antibodies without detectable serum M-protein.

Anti-MAG IgM antibodies were detected by ELISA in a patient with slowly progressive peripheral neuropathy. Serum IgM content was normal, and no M-protein was detected by serum protein electrophoresis, immunoelectrophoresis, or immunostaining. By immunoblot analysis, the anti-MAG antibodies were IgMk; they reacted with human and bovine MAG but not with mouse MAG. The data suggest that there was an anti-MAG IgM M-protein in concentration too low to be detected by conventional techniques. Tests for anti-MAG antibodies should be done in patients with slowly progressive neuropathy of unknown etiology, even in the absence of detectable serum M-protein.

The luteinizing hormone-releasing hormone pathways in rhesus (Macaca mulatta) and pigtailed (Macaca nemestrina) monkeys: new observations on thick, unembedded sections.

Immunocytochemical procedures on thick, unembedded tissue sections were used to study the localization of LHRH neurons and fibers in the diencephalon and mesencephalon of rhesus and pigtailed macaques. Cell bodies were visualized in large numbers. Much of their dendritic arborization was also filled with reaction product. Cell bodies were present in the preoptic area, the periventricular hypothalamic zone from the level of the anterior hypothalamus to the premammillary nuclei, the infundibular nucleus, supraoptic nucleus, several septal nuclei, the nervus terminalis, and the amygdala. The localization of LHRH cells in several of these areas represents new observations. LHRH axons were observed to innervate the portal vessels in the median eminence, the organum vasculosum of the lamina terminalis, the median eminence, the organum vasculosum of the lamina terminalis, the medial mammillary nuclei, the epithalamus, and the amygdala. These observations are discussed in relationship to the regulation of gonadotropin secretion in the primate.

Postural asymmetry and movement disorder after unilateral microinjection of adrenocorticotropin 1-24 in rat brainstem.

A unilateral microinjection of adrenocorticotropin 1-24 in the rat brainstem in the region of the locus ceruleus resulted in postural asymmetry and movement disorder that resembled human dystonia, the severity and duration (2 to 3 days) being dose-dependent. These results show for the first time that neuropeptides in the brainstem may modulate posture and movement, and they suggest that some forms of movement disorder such as dystonia may be due to a disordered regulation of postural and locomotor mechanisms by adrenocorticotropin 1-24.

Immunocytochemical studies of human peripheral nerve with serum from patients with polyneuropathy and paraproteinemia.

Immunohistochemical binding of IgM paraproteins to nerve was studied using the immunoperoxidase technique with serum from 10 patients with benign plasma cell dyscrasia and neuropathy. We stained the myelin sheaths of peripheral nerves and roots fo five patients who had myelin-absorbable IgM paraproteins. Two patients with IgM paraproteins that did not react with myelin showed predominant staining of axons, while three were completely negative. Serum specimens from normal volunteers and patients with paraproteinemias or ALS were also unreactive. Immunocytochemical methods can detect IgM paraproteins with an affinity for nerve antigens and may assist in the diagnosis and classification of plasma cell dyscrasia associated neuropathy.

Immunocytochemical distribution of corticotropin (ACTH) in monkey brain.

The distribution of adrenocorticotropin (ACTH) in monkey brain was examined by immunoperoxidase immunohistochemistry. An antiserum to ACTH that recognized the C-terminal portion of the molecule was used. Immunoreactive ACTH was visualized as an intraneuronal constituent with a widespread distribution throughout the brain. Reactive cell bodies were seen only in the region of the arcuate nucleus of the hypothalamus. Dense axonal networks were seen in the hypothalamus, mesencephalic gray, and in the region around the anterior commissure. No staining was seen in the cerebral cortex, cerebellum, hippocampus, or striatum. ACTH or fragments of ACTH may function as neurotransmitters or neuromodulators in primate brain.

Neurotensin neurons in the rat hypothalamus: an immunocytochemical study.

Neurotensin was localized in the hypothalamic tissues of adult Sprague-Dawley rats by immunoperoxidase techniques. Visualization of perikarya was greatly enhanced by intraventricular administration of colchicine. Many perikarya containing neurotensin-like immunoreactivity were seen in the medial preoptic area, the periventricular hypothalamus, the parvocellular portion of the paraventricular nucleus, the arcuate nucleus, and the lateral hypothalamus in the perifornical area. There were moderate numbers of cell bodies in the ventral portion of the anterior hypothalamus, the dorsomedial nucleus, and the posterior hypothalamus. No positive cells were seen in the suprachiasmatic, ventromedial, or mammillary nuclei. Reactive fibers were generally distributed in the same regions as cell bodies. Additional dense collections were seen in the lateral part of the zona externa of the median eminence, the pituitary stalk, the posterior mammillary nucleus, and the most lateral portions of the hypothalamus at the medial edge of the crura cerbri. There were smaller numbers of fibers found in the pre-mammillary and posterior hypothalamic nuclei and the posterior pituitary gland. These results indicate that the neurotensin system in the hypothalamus is very extensive and complex, as it is in many other brain regions. Neurons and fibers are found in many hypothalamic areas, including projections to the hypophysial portal system in the median eminence, suggesting that neurotensin may affect neuroendocrine mechanisms at several levels, including the anterior pituitary gland.

Neonatal monosodium glutamate. Effects upon analgesic responsivity and immunocytochemical ACTH/beta-lipotropin.

Neonatal administration of monosodium glutamate (MSG) produces neurotoxic degeneration of the retina and medial-basal hypothalamus, including the arcuate nucleus. Since this hypothalamic area contains the only neuronal cell bodies in brain which contain adrenocorticotrophic hormone (ACTH) and beta-lipotropin (beta-LPH) and beta-endorphin, destruction of these cells by MSG may interfere with pain responses mediated by nerve fibers arising from these perikarya. The present study examined whether MSG-treated rats, as compared to littermate controls, exhibited concomitant changes in the immunocytochemical distribution of ACTH and beta-LPH, and their reactivity to several analgesia-inducing manipulations. Although MSG-treated rats did not differ from control rats in their baseline reactivity to electric shock, they displayed an inability to exhibit analgesia following acute exposure to cold-water swim stress. In addition, MSG-treated rats showed an attenuated analgesic response following morphine administration. However, the analgesia elicited by either abrupt food deprivation, or the glucoprivic stress of 2-deoxy-D-glucose, was unaffected by neonatal MSG treatment. Concomitant with these selective analgesic deficits, MSG-treated rats displayed a marked immunocytochemical reduction in ACTH/beta-LPH perikarya and terminals in brain, but not pituitary. These data indicate that multiple pain-inhibitory systems exist, and that some rely upon an intact medial-basal hypothalamus to produce analgesia.

Triiodothyronine and thyroxine in the serum and thyroid glands of iodine-deficient rats.

Triiodothyronine (T(3)) and thyroxine (T(4)) were measured by immunoassay in the serum and thyroid hydrolysates of control (group A), mildly iodine-deficient (group B), and severely iodine-deficient rats (group C). These results were correlated with changes in thyroidal weight, (131)I uptake and (127)I content as well as with the distribution of (131)I in Pronase digests of the thyroid. There was a progressive increase in thyroid weight and (131)I uptake at 24 h with decrease in iodine intake. The (127)I content of the thyroids of the group B animals was 44% and that of the group C animals 2% of that in group A. The mean labeled monoiodotyrosine/diiodotyrosine (MIT/DIT) and T(3)/T(4) ratios in group A were 0.42+/-0.07 (SD) and 0.12+/-0.01, 0.59+/-0.06 and 0.11+/-0.03 in group B, and 2.0+/-0.3 and 1.8+/-0.9 in the group thyroid digests.Mean serum T(4) concentration in the control rats was 4.2+/-0.6 (SD) mug T(4)/100 ml, 4.5+/-0.3 mug/100 ml in group B animals, and undectectable (<0.5 mu(4)/100 ml) in group C animals. There was no effect of iodine deficiency on serum T(3) concentrations, which were 44+/-9 (Mean+/-SD) ng/100 ml in A animals, 48+/-6 ng/100 ml n B animals, and 43+/-6 ng/100 ml in the C group. Thyroidal digest T(3) and T(4) concentrations were 39 and 400 ng/mg in group A animals and were reduced to 5 and 1% of this, respectively, in group C. The molar ratio of T(3)/T(4) in the thyroid digests of the groups A and B animals was identical to the ratio of labeled T(3)/T(4) and was slightly less (1.0+/-0.9) than the labeled T(3)/T(4) ratio in the group C animals. The mean ratio of labeled T(4) to labeled T(3) in the serum of the severely iodine-deficient animals 24 h after isotope injection was 11+/-1 (SEM). With previously published values, it was possible to correlate the ratio of labeled T(4)/T(3) in the thyroid digest with the labeled T(4)/T(3) ratio in the serum of each iodine-deficient animal. This analysis suggested that the labeled thyroid hormones in the severely iodine-deficient rat were secreted in the ratio in which they are present in the gland. Kinetic analysis of total iodothyronine turnover indicated that two-thirds of the T(3) utilized per day by the iodine-sufficient rat arises from T(4). If the T(4)-T(3) conversion ratio remains the same in iodine deficiency, then the analysis suggests that about 90% of the T(3) arises directly from the thyroid. Therefore, it would appear that absolute T(3) secretion by the thyroid increases severalfold during iodine deficiency. The fact that serum T(3) remains constant and T(4) decreases to extremely low levels, combined with previous observations that iodine-deficient animals appear to be euthyroid, is compatible with the hypothesis that T(4) in the normal rat serves primarily as a precursor of T(3).