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PubMed2000

The current use of botulinum toxin.

Botulinum toxin is the most potent neurotoxin known, and has been in clinical use since the late 1970s. The toxin inhibits the release of acetylcholine from nerve terminals by inhibiting transport of the synaptic vesicles, thus causing functional denervation lasting up to 6 months. Our understanding of the mechanism of action of the toxin and the spectrum of diseases treatable with this agent continues to increase. Efficacy has been demonstrated in hemifacial spasm, dystonia, spasticity, hyperhidrosis and other conditions. Alternative serotypes are used in some centres, generally after the development of immunoresistance to the standard toxin (serotype A), and are likely to be in routine use in the near future. This paper reviews the history, pharmacology and current uses of botulinum toxin.

Animals↗
PubMed2001

[Zinsser-Engman-Cole syndrome (dyskeratosis congenita) with severe sicca syndrome, panuveitis and corneal perforation--a case report].

BACKGROUND: Zinsser-Engman-Cole syndrome (Z.E.C.) is a very rare type of ectodermal dysplasia, inherited in X-linked recessive manner and characterised by poikiloderma, nail dystrophy, lingual leucoplakia, bone marrow hypoplasia, hyperkeratosis and hyperhidrosis of planta and palms, dental anomalies and caries, premature grey hair. PATIENT AND METHODS: We report on a 46-year-old man who presented with occlusion of lacrimal puncta, trichiasis, severe dry eye, recurrent corneal ulceration and perforation, uveitis. HLA typing, flow cytometry of peripheral lymphocytes, bone marrow biopsy, conjunctival biopsy and extensive laboratory evaluation towards autoimmune and infectious diseases were performed. RESULTS: CD4+ T cells fraction was decreased, CD8+ and CD3+ HLA DR+ elevated. The patient was HLA-B27 positive. Laboratory studies revealed increased erythrocyte sedimentation rate and C-reactive protein level, hypochromic and hypoplastic anaemia, negative serum titers of antibodies to Epstein-Barr virus, HIV, HTLV-I, toxoplasma gondii and treponema pallidum, repeated titers to cytomegalovirus, herpes simplex and herpes zoster viruses--IgM negative, IgG positive. Corneal perforation was treated with amniotic membrane transplantation and corneal transplantation. CONCLUSION: The defect in cell-mediated immune mechanisms in Z.E.C. syndrome explains the corneal perforation, sicca syndrome and uveitis, first reported in this syndrome.

Autoimmune Diseases↗
PubMedDate not supplied

[Attempted suicide with L-thyroxine in an adolescent girl].

BACKGROUND: Attempted suicide with l-thyroxine (LT4) is very rare, only being published in some case reports concerning young women. Experiences in the management of LT4 intoxication have already been made because overdosage in infants occurs more often. Guidelines and recommendations depend on the quantity of LT4 that has been ingested. PATIENT: A 17-year-old girl presented to the pediatric emergency department after intentional ingestion of 20 mg of LT4 20 hours prior to admission. Anamnestically she had increased the thyroxine dose rate up to 800 microg per day during the previous 4 months in order to obtain loss of weight. In spite of massive overdosage and extremely high serum thyroxine levels (fT4 794 pg/ml, TSH suppressed) the girls showed low symptoms and a mild clinical course. Because of tachycardia, hyperhidrosis and muscle tremor propranolol was applied. During the following 22 days fT4 levels returned to normal range and the adolescent was remitted to the outpatient clinic of the department of psychiatry. Whereas patients with graves disease and thyreotoxicosis present with severe symptoms our patient showed a mild clinical course in spite of having extremely high fT4 levels. CONCLUSIONS: The reasons are ambiguous. A possible answer could be an adaptation in higher fT4 levels in cause of the reported chronic LT4 overdosage.

Adolescent↗
PubMed1993

Prerequisites, indications, and techniques of video-assisted thoracoscopic surgery.

During the last two years video-assisted operative thoracoscopy has introduced new impetus into thoracic surgery. Today it is viewed as a sparing and safe alternative to thoracotomy for a wide spectrum of indications. The prerequisites, instruments, and operative techniques are discussed. In oncological thoracic surgery it still remains to be verified whether the criteria of radicality are fulfilled by this new technique. Using video-assisted operative thoracoscopy, we have successfully operated on 209 patients with the following indications: recurrent pneumothorax (n = 94), interstitial lung disease (n = 25), coin lesion (n = 20), pleural effusion (n = 17), hyperhidrosis (n = 14), mediastinal tumor or lymphoma (n = 10), thoracic empyema (n = 9), bullous emphysema (n = 8), pleural tumor (n = 5), hematothorax (n = 3), malignant pericardial effusion (n = 3), and chylothorax (n = 1). The advantages of this minimally traumatizing operating technique lie in a better view of the operative site, the objectively measurable reduction in postoperative restriction, less pain, earlier postoperative mobilization, and shorter hospital stay. This operating technique, in addition to being sparing, requires markedly less time than a thoracotomy. The disadvantages are the two-dimensional monitor picture and, especially, the loss of palpation.

Anesthesia, General↗
PubMed1999

[POEMS-Syndrome--unusual manifestation with bilateral Charcot's Joint].

HISTORY AND CLINICAL FINDINGS: A 45-year-old patient with no significant past medical history was admitted 8 weeks after minor foot trauma with injury of the left ankle joint with massive destructive arthropathy. On admission the arch of both feet was flattened and both feet showed massive painless soft tissue swelling. Due to loss of muscle strength elevation of feet and toes was reduced and there was a "stocking-like" loss of sensation of the lower extremity. The gait was ataxic. No other abnormalities were detected besides hepatomegaly and hyperhidrosis. INVESTIGATIONS: Advanced polyneuropathy was confirmed by nerve conduction study. Laboratory tests revealed paraproteinaemia type IgG-lambda. Bone marrow biopsy, bone scan and skeletal survey did not provide additional information. Sonography confirmed hepatosplenomegaly, endocrinological work up showed impaired glucose tolerance and lowered testosterone levels. Based on these findings the diagnosis of POEMS syndrome (polyneuropathy, organomegaly, endocrinopathy, M-protein and skin changes) was established. TREATMENT AND COURSE: Plasma exchange was unsuccessful and due to worsening of the symptoms long term treatment with cyclophosphamide was started. Furthermore the patient received NSAIDs for symptomatic relief and orthopedic shoes. One year after initial presentation the patient continues to walk. CONCLUSION: Usually neurogenic arthropathy is associated with diabetes mellitus, syringomyelia or with infections. Our report illustrates that POEMS syndrome might present with Charcot arthritis.

Ankle Injuries↗
PubMed1995

[The neuroleptic malignant syndrome].

HISTORY AND CLINICAL FINDINGS: A 22-year-old oligophrenic patient had on several occasions over several months been given various neuroleptics (haloperidol, benperidol, levomepromazine) for exacerbations of paranoid schizophrenia. For a few days before hospitalization he had become quiet and withdrawn, but on the day of admission 100 mg chlorprothixene was administered intramuscularly when he had become agitated. At admission he was somnolent, his general condition was disturbed. He had hyperhidrosis and hypersalivation, as well as tachycardia (112/min) with a normal body temperature of 37.8 degrees C. He also exhibited the cogwheel phenomenon of the limbs and neck, as well as tremor of the hands. The differential diagnosis included inflammatory disease of the brain, sinus thrombosis and, especially, malignant neuroleptic syndrome and febrile catatonia. INVESTIGATIONS: The activities of creatine kinase (3840 U/l), GOT (75 U/l) and GPT (88 U/l) were all increased. Serum myoglobin was 77 micrograms/l. CSF contained blood and there was pleocytosis of 50/3 cells. The ECG showed sinus tachycardia. EEG, chest radiogram, computed tomography, magnetic resonance imaging and cerebral angiography showed no abnormalities. Febrile catatonia could not be excluded. TREATMENT AND COURSE: 4 hours after admission the patient began to respond with normal orientation. Shortly afterwards he was able to walk a few steps, i.e. there was no catatonia. But rigor, tremor, hypersalivation and tachycardia persisted and 12 hours later he developed a fever (up to 39.2 degrees C). Blood pressure varied with peak pressures up to 190/110 mm Hg. After 2 days muscle tone had clearly increased so much that voluntary movement was hardly possible. After amantadine administration (200 mg daily) the rigor improved and for the first time body temperature became normal again. There were no signs pointing to psychotic symptoms. CONCLUSION: Neuroleptic malignant syndrome is difficult to distinguish from febrile catatonia and the diagnosis can often only be made through the clinical course.

Adult↗
PubMed1994

[Endoscopic transthoracic sympathectomy in a paraneoplastic Raynaud's syndrome].

Six months after nephrectomy for renal-cell carcinoma and during treatment with interferon-alpha and vinblastin, a 70-year-old patient developed necrotizing Raynaud's phenomenon in both hands (at first: pain, livid skin and hyperhidrosis; later: painful acral ulcers; finally: trophic changes plus almost complete impairment of mobility and fine movements in both hands). These changes persisted even after the end of chemotherapy and despite several months on aspirin, naftidrofuryl, nitrates and glucocorticoids, so that the patient's general health was seriously affected. Because repeated sympathetic blocks were efficacious for brief periods, bilateral transthoracic endoscopic sympathectomy (TES) was performed. The patient became free of pain at once, the acral ulcers healed within a few weeks and he could again use his hands. Until his death from advanced metastases 10 months later the Raynaud's phenomenon did not recur. This case suggests that sympathetic vasoconstriction is apparently involved in the maintenance and progression of malignant neoplasm-associated Raynaud's phenomenon. TES is recommended as a reasonable palliative measure in patients with limited life expectancy, as long as preceding sympathetic blockage has indicated likely success and the procedure is performed under intraoperative monitoring of acral and facial skin temperature.

Aged↗
PubMed2000

Pharmacology of botulinum toxin.

BACKGROUND: Botulinum toxin has a well-defined role among dermatologists for the treatment of facial wrinkling, brow position, and palmar and axillary hyperhidrosis. OBJECTIVE: The purpose of this study is to educate dermatologists on the pharmacology of botulinum toxin. METHODS: A retrospective review of the literature on botulinum toxin from 1962 to the present was conducted. We examined the clinical applications of botulinum toxin, cholinergic neuromuscular transmission, the toxin's structure and molecular actions, drug and disease interactions at the neuromuscular junction, toxin assays, determinants of clinical response, and adverse side effects. RESULTS: Botulinum toxin blocks the release of acetylcholine from the presynaptic terminal of the neuromuscular junction. Several drugs and diseases interfere with the neuromuscular junction and the effects of botulinum toxin. The mouse bioassay, the most sensitive and specific measurement of toxin activity, is the gold standard for botulinum toxin detection and standardization. The major determinants of clinical response to treatment are the toxin preparation, individual patient's anatomy, dose and response relationships, length of toxin storage after reconstitution, and immunogenicity. To minimize potential antibody resistance, one should use the smallest effective dose, utilize treatment intervals of more than 3 months, and avoid booster injections. Uncommon adverse effects include ptosis, ectropion, diplopia, bruising, eyelid drooping, hematoma formation, and temporary headaches. CONCLUSION: Botulinum toxin is a safe and effective treatment. Knowledge of the pharmacologic basis of therapy will be useful for standardizing techniques and achieving consistent therapeutic results in the future.

Acetylcholine↗
PubMed2002

Eccrine angiomatous hamartoma.

Four patients with eccrine angiomatous hamartoma are described. Blue-purple color, enlarging size, location on an extremity, pain, and hypertrichosis were common features and aided differentiation from other vascular anomalies and hamartomas of childhood. None of our patients experienced lesional hyperhidrosis, and simple excision alleviated pain.

Adolescent↗
PubMed2002

Anatomic variations of the T2 nerve root (including the nerve of Kuntz) and their implications for sympathectomy.

OBJECTIVE: The aim of this study was to clarify the anatomic variations of the intrathoracic nerve of Kuntz, and this should help delineate the resection margins during video-assisted thoracic sympathectomy. METHODS: Sixty-six thoracic sympathetic chains of 39 adult Korean cadavers were dissected on both sides of the thorax in 27 cadavers (54 sides) and on one side in 12 cadavers (12 sides). RESULTS: The intrathoracic nerve was observed in 45 (68.2%) sides and was present bilaterally in 48.1% of cadavers. No intrathoracic nerve or ascending ramus communicans arising from the second thoracic nerve was observed in only 5 (7.6%) sides. The diameter of the intrathoracic nerve was 1.25 plus minus 0.55 mm on average. The arising point of the intrathoracic nerve from the second thoracic nerve was 7.3 mm on average from the sympathetic trunk. Presence of the stellate ganglion was noted in 56 (84.8%) sides, and 6 (9.1%) sides showed a single large ganglion formed by the stellate and the second thoracic sympathetic ganglia. The second thoracic sympathetic ganglion was most commonly located (50%) in the second intercostal space. CONCLUSION: The anatomic variations of the intrathoracic nerve of Kuntz and the second thoracic sympathetic ganglion were characterized in human cadavers. It is hoped that this study will help to improve the recurrence of symptoms caused by the intrathoracic nerve in an upper thoracic sympathectomy for hyperhidrosis.

Female↗
PubMed2002

Functional requirement of aquaporin-5 in plasma membranes of sweat glands.

The distribution and function of aquaporins (AQPs) have not previously been defined in sweat glands. In this study, AQP1, AQP3, and AQP5 mRNA were demonstrated in rat paw by reverse transcription (RT)-PCR, but AQP2 and AQP4 were not. AQP1, AQP3, and AQP5 protein were confirmed in these tissues by immunoblotting. AQP1 was identified in capillary endothelial cells by immunohistochemical labeling, but not in sweat glands or epidermis. Abundant AQP3 expression was seen in basal levels of epidermis, but not in sweat glands. AQP2 and AQP4 were not observed in either skin or sweat glands. Immunohistochemical labeling revealed abundant AQP5 in secretory parts of rat and mouse sweat glands, where immunoelectron microscopy demonstrated abundant AQP5 labeling in the apical plasma membrane. AQP5 immunolabeling of human sweat glands yielded a similar pattern. To establish the role of AQP5 in sweat secretion, we tested the response of adult mice to s.c. injection of pilocarpine, as visualized by reaction of secreted amylase with iodine/starch. The number of active sweat glands was dramatically reduced in AQP5-null (-/-) mice compared with heterozygous (+/-) and wild-type (+/+) mice. We conclude that the presence of AQP5 in plasma membranes of sweat glands is essential for secretion, providing potential insight into mechanisms underlying mammalian thermoregulation, tactile sensitivity, and the pathophysiology of hyperhidrosis.

Animals↗
PubMed2004

The assessment of vegetative and functional symptoms in fibromyalgia patients: the tropisetron experience.

Vegetative and functional symptoms are, besides pain and tenderness of tender points, considered as additional information for the diagnosis of fibromyalgia (FM). In clinical trials, vegetative and functional symptoms have been included for selection of patients (e.g. sleep disturbances) and as secondary outcome parameters. Despite the relevance of these symptoms, no validated method is currently available but symptom lists are ad hoc developed by investigators. In this manuscript, data from a published double blind, randomised study are reanalysed which compared oral therapy over 10 days with 5 mg, 10 mg, and 15 mg to placebo in FM patients. This study applied a list of 17 vegetative and functional symptoms, which had to be scored by the patients by use of a 4-point severity scale (0 = none to 3 = severe). Factor analysis of the baseline data from 195 patients suggested to separate 6 sub-scales: Cardiovascular, gastrointestinal, psychiatric (sleep disturbance), nervous, autonomic system, and general disorders. Sleep disturbances, general symptoms (morning stiffness, fatigue) and autonomic symptoms (cold extremities, hyperhidrosis) were most severe in intensity. Analysis of sensitivity for treatment effects made use of differences between placebo and 5 mg tropisetron in changes between baseline and final assessment of the tropisetron trial. While, on the item level, differences in favour of tropisetron could only be demonstrated for sleep disorders, on the sub-scale level, also favourable effects of tropisetron could be shown for cardiovascular and nervous system complaints and, as a tendency, for general symptoms. On the other side, the sub-scale score of gastrointestinal symptoms worsened under tropisetron whilst it improved under placebo which effect was due to side effects of the active treatment. It is concluded that symptom clusters like sub-scales of a list of vegetative and functional symptoms will be more suitable for diagnostic purposes and evaluation of treatment outcome of clinical trials. Further research is urgently required which addresses the development of a FM-specific scale to assess vegetative and functional symptoms.

Fibromyalgia↗
PubMed2003

The role of the sympathetic nervous system in anxiety: Is it possible to relieve anxiety with endoscopic sympathetic block?

The function of the autonomic nervous system is divided so that the parasympathetic system spares central nervous system energy and the sympathetic system makes extra energy available and consumes it. The sympathetic nervous system then prepares our body for emergency and it always functions when our conscious or even unconscious mind notices a need for defence or to provide energy. A surgical procedure, where the upper thoracic sympathetic ganglions are ablated, either with cauterization or clamping with metallic clips, has been used to treat sweating of the hands and facial blushing for decades. Instead of ablating large areas of sympathetic trunk, which can cause severe side-effects such as reflex sweating of the body, the surgical procedure is nowadays carried out in a more precise symptom-mediating level of uppermost thoracic sympathetic ganglia. Blushing, hyperhidrosis of palms and head, and trembling are common in social phobia, and they seem to be provoked by the activation of the sympathetic nervous system. Preliminary studies show that some social phobia patients may benefit from the endoscopic sympathetic block (ESB). If the patient with generalized social phobia has not received help with adequate medication or psychotherapy, the ESB may be a new possible treatment of choice.

Anxiety Disorders↗
PubMed1998

Complications of endoscopic sympathectomy.

Four cases are presented in which complications occurred during or after thoracic endoscopic sympathectomy (TES). In one patient inappropriate TES resulted in disabling hyperhidrosis. In one patient laceration of the subclavian artery required major surgery. In two cases intraoperative cerebral damage occurred. Training in TES is essential.

Adolescent↗
PubMed2004

Does botulinum toxin A make prosthesis use easier for amputees?

Four post-amputation patients (1 with phantom pain, 3 with stump pain) were each treated with 100 IU botulinum toxin A, divided between several trigger points in the distal stump musculature. In 1 female patient (along with a pronounced reduction in phantom pain) hyperhidrosis of the stump ceased completely, probably after diffusion of the drug into the dermal sweat glands, leading to longer and safer use of the prosthesis. Intentional intradermal injection for this issue therefore could be valuable. Another patient was able to use her prosthesis for the whole day again after botulinum toxin A treatment for substantial stump pain, compared with only 4 hours a day before treatment. In 2 male patients, stump pain while wearing the prosthesis subsided to a considerable extent, 1 of the 2 reported an improvement in steadiness of gait. We suggest that stump treatment with botulinum toxin in rehabilitative medicine should be investigated in more detail.

Adult↗
PubMed1998

Effect of acupuncture stimulation of the auricular sympathetic point on evoked sudomotor response.

OBJECTIVES: To investigate whether stimulation of the auricular sympathetic acupuncture point would affect the mean maximum amplitude of evoked sudomotor responses. DESIGN: A placebo-controlled trial. Two types of controls were used: no acupuncture and acupuncture of an alternate "non-sympathetic nervous system" related (i.e., a non-sympathetic, placebo) point. Subjects were included in either the placebo or the test group. Each subject would have one session of acupuncture and one session without acupuncture, the acupuncture was applied in either the first or the second session. Initially, each group was unaware in which of the two sessions they would receive acupuncture (cross-over design). Each individual was unaware of which group they were to participate in. SETTINGS/LOCATION: A quiet, sealed room with a constant temperature, in the research department of the Anglo-European College of Chiropractic. SUBJECTS: Thirty-eight asymptomatic male, white volunteers (18 to 40 years old). INTERVENTIONS: The two groups underwent two electrodermal response (EDR) recording sessions, at an interval of 5 weeks. During each session, they were also presented with eight stimuli, each of which was designed to stimulate the sympathetic nervous system. In each session, subjects either received auricular acupuncture (AA) or did not. OUTCOME MEASURES: The maximum amplitude of the EDR for each stimulus. RESULTS: AA at the non-sympathetic, placebo point significantly increased EDR both with respect to the individual stimuli (p < or = 0.05 to < or = 0.001) and for the pooled data (p = 0.0001). AA to the sympathetic point produced no significant change in EDR for either individual stimuli (p range > or = 0.8 to > or = 0.1) or for the pooled data (p > 0.8). A significant difference was found between the results from placebo and sympathetic point stimulated groups during AA for 2 of the 8 stimuli (p < 0.05), and for the pooled data from all 8 stimuli (p = 0.0006). CONCLUSION: Stimulation of the sympathetic AA point significantly decreased the stimulus-evoked EDR when compared with an AA stimulation to a non-sympathetic (placebo) point. However, it did not significantly alter EDR compared with no treatment. This implies that the increase in response as a result of inserting the needles was negated by placing the electrodes in the AA sympathetic point. Consequently, one might surmise that there may be a specific action of AA in respect to hyperhidrosis resulting from an increase in sympathetic activity.

Acupuncture Points↗
PubMed1997

Obliteration of a posttraumatic spinal cord cyst with solid human embryonic spinal cord grafts: first clinical attempt.

Cystic lesions of the spinal cord (syringomyelia) may occur after spinal cord injury. Posttraumatic syringomyelia may result in a myelopathy causing symptoms of sensory and motor loss, as well as worsening spasticity, pain, hyperhidrosis, and autonomic dysreflexia. Shunting of the cyst cavity along with untethering of the scarred spinal cord is widely accepted as the treatment of choice. However, the long-term stabilization of the progressive myelopathy caused by a posttraumatic cyst is suboptimal because of arachnoidal rescarring, shunt tube blockage, and cyst reexpansion. A new neurosurgical strategy to overcome the complication of cyst reexpansion was designed. Experimental studies have shown the successful use of embryonic spinal cord grafts, including human grafts, to obliterate induced spinal cord cavities in rats. The authors report the first use of solid human embryonic spinal cord grafts to successfully obliterate 6 cm of a large cyst cavity in a patient becoming myelopathic from a posttraumatic cyst. The grafts are well visualized by MRI to the 7-month postoperative follow-up and cyst obliteration is seen in the region where the grafts were placed.

Fetal Tissue Transplantation↗
PubMed1991

Reflex sympathetic dystrophy: the significance of differing plasma catecholamine concentrations in affected and unaffected limbs.

In 26 patients with features of reflex sympathetic dystrophy, venous blood was collected from painful and unaffected limbs. Levels of plasma adrenaline, noradrenaline and its intracellular metabolite, 3,4-dihydroxyphenylethyleneglycol (DHPG), were measured by combined gas chromatography/mass spectrometry. Plasma DHPG was lower on the painful side. Concentration of plasma noradrenaline was also lower on the painful side in patients with widespread allodynia, and in those with hyperhidrosis in the affected hand or foot. These findings do not support the widely held view that autonomic disturbances in reflex sympathetic dystrophy are due to sympathetic overactivity. Rather, they suggest that sweating and changes in peripheral blood flow result from supersensitivity to sympathetic neurotransmitters. After injury, supersensitivity to noradrenaline may also contribute to spontaneous pain and allodynia by disrupting efferent sympathetic modulation of sensation. This would explain why pain and allodynia are relieved by sympathetic blockade, and why noradrenaline rekindles pain in sympathectomized skin.

Adolescent↗