Innervation of footpads of normal and mutant mice lacking sweat glands

Footpads of normal adult mice are innervated by sympathetic and sensory fibers. The sympathetic fibers associated with sweat glands contain acetylcholinesterase and immunoreactivity for vasoactive intestinal peptide. Although catecholamine histofluorescence is absent, the gland innervation exhibits immunoreactivity for tyrosine hydroxylase. A distinct population of sympathetic fibers, which possess catecholamines and neuropeptide Y as well as tyrosinehydroxylase immunoreactivity, innervates blood vessels. Sensory fibers containing immunoreactivity for substance P and calcitonin gene-related peptide course beneath the epidermis and some form endings in it. Treatment of neonatal mice with the adrenergic neurotoxin, 6-hydroxydopamine, results in loss of sympathetic innervation of sweat glands and blood vessels, permits growth of sensory axons into sweat glands, but does not alter the peptidergic sensory innervation of the dermis and epidermis. Three mouse mutations, Tabby (Ta), crinkled (cr), and downless (dl), disrupt the interactions between the mesenchyme and epidermis that are required for normal development of specific epidermal derivatives, including sweat glands. The sympathetic innervation of blood vessels and sensory innervation of footpad skin of the three mutant mice that lack sweat glands is indistinguishable from normal. The sympathetic fibers that normally innervate sweat glands, however, are not present. These results indicate that in the absence of their normal target, the sympathetic fibers that innervate sweat glands are lacking. Furthermore, they suggest that, although sensory fibers may sprout into sympathetic targets in the footpad, the domains occupied by sensory fibers are not normally accessible to sympathetic axons. © 1994 Wiley-Liss, Inc.     

Absent innervation of skin and sweat glands in congenital insensitivity to pain with anhidrosis.

OBJECTIVES: A case of a 10-year-old girl with congenital insensitivity to pain with anhidrosis (CIPA) is reported. METHODS AND RESULTS: Parents referred several hyperpyretic episodes without sweating occurring since birth, and insensitivity to pain, noticed when the child was 2 years old. Her body had many bruises and scars, bone fractures and signs of self-mutilation. Neurological examination was normal except for insensitivity to pain. Her IQ was 52. Electrical and tactile sensory nerve conduction velocities were normal. The patient was unable to detect thermal stimuli. Histamine injection evoked a wheal but not a flare; pilocarpine by iontophoresis did not induce sweat. Microneurography showed neural activity from A-beta sensory fibers while nociceptive and skin sympathetic C fiber nerve activity was absent. No small myelinated fibers and very rare unmyelinated fibers were found in the sural nerve. Immunohistochemistry showed a lack of nerve fibers in the epidermis and only few hypotrophic and uninnervated sweat glands in the dermis. CONCLUSIONS: The lack of innervation of the skin (C and A-delta fibers) appears to be the morphological basis of insensitivity to pain and anhidrosis, and is consistent with the loss of unmyelinated and small myelinated fibers in the sural nerve biopsy.     

Neurodegeneration in sweat glands and skin of aged rats

In order to compare age-associated neurodegenerative changes in peripheral nerves of laboratory mammals and humans, we have investigated the density and pattern of different nerve populations innervating sweat glands of ageing rats and compared our results with a previous study of the innervation of human sweat glands. We have also studied age-changes in subepidermal afferent nerves that may be involved in reflex activation of sweat glands. Total nerve density, measured by immunohistochemical staining for the general neuronal marker, protein gene product (PGP9.5) and image analysis, showed a significant decline around secretory coils of sweat glands of old compared to young rats. Marked reductions of acetylcholinesterase (AChE) histochemical staining and of vasoactive intestinal polypeptide (VIP)- and calcitonin gene-related peptide (CGRP)-like immunoreactivity were observed in nerves around sweat glands. In the sub-epidermis, PGP- and CGRP-like immunoreactive nerves were significantly reduced in old rats. The age-related changes in sweat gland innervation of old rats were comparable to those reported in elderly human subjects suggesting that these tissues may provide a suitable model for experimental studies of neuronal ageing.     

Case of Horner's syndrome associated with ophthalmic herpes zoster]

We reported a 74-year-old man with right Horner's syndrome associated with ophthalmic herpes zoster. He presented acute onset of pain, swelling, vesicular cutaneous eruption around the right eyelid. A diagnosis of herpes zoster ophthalmicus was made and he was started on acyclovir 750 mg/day. Seven days later he manifested right abduction deficit On admission nine days later, the right eyelid became ptotic and the right pupil was smaller than the left There was gradual improvement over the next 10 days in ptosis and miosis, and over the next 3 weeks in the right abduction deficit. As the sympathetic nerve runs with the carotid artery, it partially joins the sixth nerve within the cavernous sinus. We have identified a patient in whom herpes zoster ophthalmicus has resulted in a syndrome involving the sympathetic nerves, the sixth nerve, and the first division of the fifth cranial nerve. As the Horner's syndrome was transient, we might miss the symptom in the early stage, so we should carefully examine the patients.     

Effect of age on collateral reinnervation of sweat glands in the mouse

This study demonstrates that the number of sweat glands (SGs) innervated by individual peripheral nerves in the mouse hind paw decreases with aging but the ability for reinnervation by collateral sprouting is maintained throughout life. In one experiment, the saphenous, peroneal and tibial nerves were cut and tied, denervating all SGs of the hind paw except those receiving axons from the intact sural nerve. In another, the saphenous was the only nerve left intact. The initial number of SGs supplied only by the single intact nerve was significantly higher in young adult than older mice. The capacity of the sural and saphenous nerves to collaterally reinnervate the denervated SGs was followed by serial testing for the return of sensitivity to pilocarpine stimulation. Collaterally reinnervated SGs appeared during the second and third weeks postoperation adjacent to already active SGs, thereby increasing the total sweat area of the intact nerve, and its SG number about 3, 2 and 5 times for the sural, and 8, 2 and 2 times for saphenous nerve, in young, adult and old animals respectively. Reinnervation was slightly faster and the degree of extension greater in young than adult mice, and the degree of extension was decreased in older mice. These observations suggest that the number of sudomotor axons in the peripheral nerve, as well as their capacity for collateral reinnervation, is reduced with aging.     

A magnetoencephalographic study of patients with Panayiotopoulos syndrome

Summary:  Purpose: Panayiotopoulos syndrome (PS) is a newly identified type of benign childhood epilepsy characterized by ictal vomiting and eye deviation. It is usually accompanied by occipital spike discharges; however, its classification as an early-onset benign childhood occipital epilepsy is controversial. To characterize this condition further, we examined the localization of equivalent current dipoles (ECDs) of spike discharges by magnetoencephalography (MEG) in patients with PS.
Methods: We studied 13 patients with a mean age at time of examination of 5 years (range, 3–14 years). MEG was measured by using a whole-head 204-channel neuromagnetometer with simultaneous EEG recordings. The estimated locations of ECDs of each peak of the spike discharges were overlaid on magnetic resonance images of the brain.
Results: Eleven (84.6%) patients showed clustered ECDs in the areas alongside the parietooccipital sulcus (eight of 13; 61.5%) and/or the calcarine sulcus (four of 13; 30.8%). Despite Fp-O synchronization of the spike discharges in the scalp EEG of five patients, no frontal locations of ECDs were found. All five (38.5%) boys with sylvian seizures, who also showed clustered ECDs in rolandic areas, had an earlier age at onset and higher seizure frequency than did other patients. ECD orientations were regular in all but one patient, who showed irregular and dispersed ECDs alongside bilateral calcarine sulci.
Conclusions: Our results demonstrate localized cortical hyperexcitability in the areas alongside major cortical sulci in PS and indicate that PS is closely related to benign childhood epilepsy with centrotemporal spikes.     

An adult case of congenital Horner's syndrome with heterochromia iridis--with special reference to alteration of Horner's sign associated with development

It is well known that when the Horner's syndrome is congenital, a defect in pigmentation of the iris is usual; all or part of the iris remains light brown. We reported an adult case of congenital Horner's syndrome with remission and relapse of unilateral ptosis. A 25-year-old man was admitted to our hospital for ophthalmologic surgical treatment of right ptosis. According to the patient's mother, the patient was delivered with the aid of forceps at birth, and the right ptosis was observed during the first few days of his life. At 2 to 3 years of age, his parents noted lighter color of the right eye. The right ptosis was gradually improved as he grew older. However, he developed right ptosis again with left meralgia paresthesia since eighteen age. At age 25 years, he was noted to have right ptosis, right miosis (the left pupil measured 4.5 mm in diameter and the right 3.0 mm), right heterochromia iridis with pigmented iris nevi, and left meralgia paresthesia . Laboratory data of urine, blood and CSF as well as radiological studies of chest X-ray, skull X-ray, spine X-ray, brain MRI and spinal cord MRI showed unremarkable. Sweating test was intact, pharmacologic test to Horner's syndrome with 5% cocaine and 1.25% 1-epinephrine indicated that the damage was pointed to the post ganglionic sympathetic neuron. Ten patients with congenital Horner's syndrome reported in Japan since 1953 were reviewed including our case. Ten of eleven were male and Horner's sign was recorded on the left eye in 8 cases.(ABSTRACT TRUNCATED AT 250 WORDS)     

The diagnosis of Horner's syndrome. Use and limitations of the cocaine test

We prospectively studied the value of the cocaine test in the diagnosis of Horner's syndrome, by performing the test in 20 control subjects and in 20 patients with a provisional diagnosis of Horner's syndrome. Photographic testing of the darkness reflex of the pupil was used as an independent criterion of oculosympathetic dysfunction, and confirmed the diagnosis in 12 of the 20 patients. A mydriatic response to cocaine that was at least 1.0 mm less than in the unaffected eye occurred only with Horner's syndrome (7 patients). On the other hand, if the difference is smaller than 1.0 mm the chance that the patient does not have Horner's syndrome is only around 60%. There was no relationship between the magnitude of the response to cocaine and the site of the lesion in the sympathetic system.     

Reinnervation of sweat glands in the rat hind paw following peripheral nerve injury

Electrophysiological experiments have been carried out to investigate the time course and extent of sweat gland reinnervation in the rat hind paw. The first evidence of functional reinnervation after nerve transection was obtained at 12 weeks, when the extent of innervation was 20% of that measured in control animals. By 20 weeks, reinnervation had reached almost 50% of control values but then there was no further improvement up to 52 weeks. These results are comparable to those for skin reinnervation by polymodal nociceptor afferents.     

Reinnervation of sweat glands in the mouse: axonal regeneration versus collateral sprouting

The capacity of sudomotor axons to reinnervate sweat glands by regeneration after freezing was compared with their capacity to reinnervate by the mechanism of collateral sprouting. Two groups of mice were prepared in the same manner, with a single exception. All nerves to the hind paw were cut and tied to prevent regrowth. The exception, the lateral plantar nerve, was left intact in one group and frozen at the ankle in the other group. Reinnervation of sweat glands in the paw was charted frequently for 10 weeks using a silastic mold method. We found that sudomotor axons regenerating from the frozen nerve functionally reinnervated sweat glands of the paw sooner, beginning at 15 days postoperation, and at a higher rate than reinnervation from the collateral branching intact nerve, that began at about 25 days. Full recovery occurred by 41 days in most animals of both groups. We also found that stimulation of sweating by pilocarpine activated more sweat glands during the reinnervation period than stimulation by heating the mice, suggesting that the newly regenerating sudomotor axons have a high threshold.     

A device to measure secretion of individual sweat glands for diagnosis of peripheral neuropathy

There is a need for quantitative, precise assessment of small fiber peripheral nerve function. We tested a customized camera device and protocol designed to quantify secretions of individual sweat glands (SGs). Testing was performed on 178 healthy controls and 20 neuropathy subjects. Sweating was stimulated on a 2.25 cm² skin area by iontophoresis of pilocarpine. The camera imaged sweat from 50 to 400 sweat ducts. We calculated secretion rate of individual SGs, total sweat volume, and number of secreting SGs at four body sites. Neuropathy subjects were tested at the two distal sites to demonstrate the device's capability to detect abnormal sudomotor function. Normal ranges were calculated for each body site. Neuropathy subjects had lower sweat rates per SG, lower total sweat, and lower SG density. The normal values decreased with advancing age, were lower in females, and differed between body sites. There was good agreement with repeat testing. The device provides reliable, precise quantitative measures of sweat secretion from single SGs for characterization of sudomotor nerve function in healthy control subjects and in subjects with known peripheral neuropathy. The test combines the capabilities of existing tests of sudomotor function while providing additional capabilities.     

Development and treatment of anorexia nervosa in patients with Turner syndrome. A case study

summary We describe the case of a girl with Turner syndrome who has also developed anorexia nervosa. According to the available literature, patients with Turner syndrome do not have an increased risk of developing anorexia nervosa. However, if such comorbidity should occur, as it did in our case, then some aspects of treatment will have to be adjusted.     

Incidence of post-thrombotic syndrome in patients with previous pulmonary embolism. A retrospective cohort study

There is little information available about the true incidence of post-thrombotic syndrome (PTS) after pulmonary embolism (PE). The aim of this study was to investigate the incidence of PTS in patients with previous pulmonary embolism without concomitant ultrasonographically-detectable deep vein thrombosis (DVT). A retrospective cohort study was conducted at a single tertiary care centre, Cosenza, Italy. Forty-seven consecutive patients with proved PE without DVT within the previous 2 to 6 years, 45 patients with previous DVT in the same years, and 45 patients with diseases unrelated to venous thromboembolism (VTE) underwent a blind assessment for PTS using a clinical score. Two of 47 (4.2%, 95%CI: 0.01-9.9) patients with PE, 2 of 45 (4.4%, 95%CI: 0.01-10.4) patients with diseases unrelated to VTE, and 23 of 45 (53.3%, 95%CI: 38.7-67.9) patients with DVT showed signs and symptoms of PTS. The difference between the first two groups was not statistically significant (p = 0.7). In conclusion, the incidence of PTS after pulmonary embolism without DVT is low, and no different from that of patients without previous VTE.     

Small adrenal glands in chronic fatigue syndrome: a preliminary computer tomography study.

No inclusive or satisfactory biomedical explanation for chronic fatigue syndrome (CFS) has as yet been forwarded. Recent research suggests that a dysregulated hypothalamic-pituitary-adrenal axis (HPA) may be contributory, and in particular that there may be diminished forward drive and adrenal under-stimulation. In this preliminary study we wished to examine a cohort of CFS patients in whom evidence for such hypofunctioning was found. Our aim was to establish whether these patients had altered adrenal gland size. Patients were recruited from a fatigue clinic. Those who fulfilled the Centre for Disease Control and Prevention (CDC) criteria underwent a 1 microgram adrenocorticotropin (ACTH) stimulation test, a test of adrenal gland functioning. Eight subjects (five females, three males) with a subnormal response to this test underwent a computer tomography (CT) adrenal gland assessment. Measurements were compared with those from a group of 55 healthy subjects. The right and left adrenal gland bodies were reduced by over 50% in the CFS subjects indicative of significant adrenal atrophy in a group of CFS patients with abnormal endocrine parameters. This is the first study to use imaging methods to measure adrenal gland size in CFS. It is a limitation of this study that a selected CFS sample was employed. A future larger study would optimally employ an unselected cohort of CFS patients. This study has implications not only for the elucidation of CFS pathophysiology, but also for possible therapeutic strategies.