Tetanic Spasms Research Articles

Efficacy of dantrolene sodium in management of tetanus in children.

The effectiveness of dantrolene sodium in controlling tetanic spasms was evaluated in 21 children (aged 4 days-13 years) with tetanus. These dantrolene-treated patients were compared with an historical control group of 26 children previously treated for tetanus by traditional means at the same institution. The groups were comparable in terms of age, other treatments, and severity of disease. All patients received standard treatments for tetanus, including sedatives, antibiotics, and tetanus-immune globulin. Patients in the dantrolene-treated group also received dantrolene, either intravenously (Dantrium Intravenous) or orally, in divided doses totalling 4-6 mg/kg/day. Mortality was 73% (neonates 83%, non-neonates 50%) in the control group, compared with 33% (neonates 50%, non-neonates 0%) in the dantrolene-treated group. Dantrolene did not cause additional respiratory depression when administered alone or in combination with other drugs routinely used to treat tetanus. In this study, the use of dantrolene with traditional conservative therapy significantly reduced mortality from tetanus.

Yohimbine injection in deer

Abstract Extract Sir:— In the 12 months since the completion of the trials reported in this Journal(1) over 3000 doses of yohimbine have been used to reverse xylazine sedation in deer at Invermay and in field trials throughout New Zealand. During this time four deer have suffered transient convulsions characterised by tetanic spasms, paddling of the limbs, inability to stand and rapid nodding of the head. This was accompanied by rapid blinking of the eyelids and grinding of the teeth. These signs abated in 5 to 10 minutes after which time the deer relaxed and regained its ftet in 10 to 20 minutes. In the 30 minutes prior to yohimbine administration these deer had received a single injection of xylazine (0.5 to 1.0 mg/kg) and on one occasion the xylazine was given in conjunction with Img of fentanyl and 8 mg azaperone (0.1 ml Fentaz). On each occasion the intention was to inject yohimbine at the recommended dose rate (1) (0.2 to 0.25 mg/kg) into the jugular vein and the convulsions commenced within five se...

Arginine: An Essential Amino Acid for the Cat

The essentiality of arginine for the near-adult cat was demonstrated in three preliminary and two main experiments. In the pre liminary experiments, changing cats (body weights all in excess of 1.6 kg) from a purified diet containing a complete amino acid mixture (basal) to a similar isonitrogenous diet without arginine ( —Arg) caused rapid loss of body weight ( mean ±SE93.3 ±6.8 g in the first 24 hours ), emesis, and inappetance. In the main experiments the mean ±SE body weight of the cats was 2.6 ±0.4 kg. When eight of these cats were given the —Argdiet after an overnight fast, they all exhibited emesis, had tetanic spasms, and one died. Other symptoms included hypersalivation, depression which in some cases was followed by hyperesthesia, hyperactivity, ataxia, and dyspnea. The plasma of these cats showed hyperammonemia and hyperglycemia indicating that the clinical condition was caused by acute ammonia intoxi cation. The eight cats given the comparable diet with arginine showed no ill effects. Five cats given the basal diet with ornithine replacing arginine on an equimolar basis showed neither an increase in plasma ammonia nor glucose concentrations. Cats given the —Argdiet had extremely low 120 minute post-prandial levels of plasma free arginine (less than one-quarter of the prefceding level ). It was concluded that the cat lacks the ability to synthesize ornithine. The consequence of this metabolic deficiency in the cat is that arginine is an essential nutrient: it provides a unique example of a nutrient so critical that one meal without dietary arginine may result in death. The —Argdiet supported growth in young rats, albeit at a slower rate than rats fed the basal diet. J. Nutr. 108: 1944-1953, 1978. INDEXING

Actions of carbon tetrachloride, hexachlorotethane and the products of their metabolism in sheep on Fasciola hepatica.

1 An invitro preparation of Fasciola hepatica is described which responded to electrical stimulation with tetanic spasms. Both carbon tetrachloride (20-500 nl/ml), and its metabolite chloroform (50-1000nl/ml), produced contractions in the preparation which extinguished the responses to electrical stimulation. It is suggested that the spasmogenic action of carbon tetrachloride and its metabolite may contribute to the fasciolifugal action of the drug. 2 Hexachloroethane, another fasiolifuge, had very little effect in the preparation. However, pentachloroethane and tetrachloroethylene, the main products of the metabolism of hexachloroethane in sheep, were potent spasmogens in preparations of Fasciola hepatica. Pentachloroethane was about twice as potent as carbon tetrachloride. 3 Tetrodotoxin (2mug/ml) did not antagonize the responses of the preparation to electrical stimulation of carbon tetrachloride.

Idiopathic hypomagnesemia with hypocalcemia in an adult

Hypomagnesemia and hypocalcemia were found in a 42-year-old woman with tetanic spasms, which started after a period of starvation in her sixteenth year. Oral magnesium therapy corrected the low serum calcium level. Hypomagnesemia appears to be a consequence of reduced gut absorption. Kinetic studies and hormone measurements do not support theories relating the hypocalcemia observed during magnesium depletion as being solely due to impaired synthesis, impaired secretion of or reversible resistance to parathormone or excess calcitonin secretion.

An inhibitory action of histamine on the guinea-pig ileum.

1. In atropinized, plexus-containing preparations of the longitudinal muscle from the guinea-pig ileum, in which histamine contractions were abolished by mepyramine or diphenhydramine, an inhibitory action of histamine was revealed on the "tetanic spasms" produced by field stimulation.2. The inhibitory action of histamine on the atropine-resistant tetanic spasms, which are due to the excitation of non-cholinergic neurones in Auerbach's plexus (Ambache & Freeman, 1968a, b), was reversible. It is specific for the tetanic spasms, because histamine did not reduce contractions elicited by bradykinin, 5-hydroxytryptamine, prostaglandin E(2), nicotine or dimethylphenylpiperazinium.3. L-Histidinol and 2-mercaptohistamine exerted a considerably weaker inhibitory effect upon the tetanic spasms than histamine. Four other imidazoles tested, L-histidine, murexine, dihydromurexine and imidazolecarboxylcholine, were ineffective; so was the pyrazole ring isomer of histamine, betazole.4. The inhibitory action of histamine persisted after adrenoceptor blockade by phentolamine and pronethalol and after prior reserpinization of the guineapigs.5. The inhibitory action of histamine was also obtained after ganglionic paralysis by hexamethonium or dimethylphenylpiperazinium but was antagonized specifically by nicotine.6. On atropinized preparations of the longitudinal muscle from the guinea-pig descending colon histamine exerted, at most, an insignificant inhibitory effect on the tetanic spasms.

Atropine-resistant longitudinal muscle spasms due to excitation of non-cholinergic neurones in Auerbach's plexus.

1. In accordance with the dual histology of Auerbach's plexus (Dogiel, 1899; Hill, 1927) two types of neurone can be shown to be humorally active in plexus-containing preparations of longitudinal muscle from guinea-pig ileum, taken at measured distances up to 95 cm above the ileocaecal valve, when such preparations are stimulated electrically under different conditions.2. The rapid twitch, lasting 3-8 sec, which is elicited by single shocks of 0.1 or 0.2 msec pulse width, and the effect of 5-15 ng doses of acetylcholine which matched this twitch, were both extinguished equally effectively and completely by atropine sulphate (0.4-1 x 10(-8) g/ml.) or by hyoscine hydrobromide. This twitch-response is therefore caused by an excitation of cholinergic motor neurones of normal susceptibility to atropine. These are believed to be the Dogiel (1899) Type II cells of Auerbach's plexus, as suggested by Hill (1927).3. After extinction of the twitch by the invariably effective atropineblock, a second type of muscle response was revealed by tetanic stimulation with 1 sec trains of 50 pulses of the same voltage and of pulse width preferably 0.2 msec. The tetanic responses consisted of spasms of longer delay and duration (20-60 sec). These spasms could be matched by doses of acetylcholine of the order of 200 ng. However, if the atropine concentration was now raised to 10(-7), or even 10(-6) g/ml., the effect of 200-1000 ng of acetylcholine was abolished, but the tetanic spasms persisted without decrease in amplitude. In other experiments the height of the spasms remained constant as the concentration of atropine sulphate was raised from 10(-8) to 10(-6) g/ml. and was only slightly decreased by 10(-5) g/ml. Hence, these tetanic contractions are not due to a surmounting of the atropine-block by the increased release of acetylcholine following the 50 pulses.4. The tetanic spasms originate from excitation of non-cholinergic neurones, perhaps the associative Dogiel Type I cells of Auerbach's plexus (Hill, 1927), since the spasms were abolished reversibly by tetrodotoxin 2 x 10(-7) g/ml. and were absent from plexus-free, nicotine-insensitive preparations of the longitudinal muscle, both before and after atropinization.5. The tetanic spasms were not reduced by ganglion-block with paralysing doses of nicotine, with (+)-tubocurarine or with hexamethonium.6. The tetanic spasms are not mediated by a release of 5-hydroxytryptamine (5-HT) or of histamine, since they persisted in concentrations of methysergide and mepyramine adequate to block matching doses of histamine or 5-HT, or multiples thereof. Catecholamines were also excluded.7. The tetanic spasms are not mediated by a release of a prostaglandin, because they were not reduced by 0.5-2 x 10(-6) g/ml. of patulin (Ambache, 1957), which blocked the contractions evoked by matching doses of prostaglandins PGE(2) or PGF(2alpha); even after this block, PGE(2) still potentiated subsequent tetanic responses.8. The tetanic spasms were reduced or virtually abolished by strychnine in concentrations which did not depress the twitch.

VERTEBRAL FRACTURES IN WEST AFRICANS SUFFERING FROM TETANUS

1. Radiography of the spines of thirty-three West African patients recently recovered or dead from tetanus revealed vertebral fractures in nineteen. These fractures occurred most frequently in the fourth to eighth thoracic vertebrae. 2. The spines of 111 Nigerians from the same area of West Africa were examined, measurement of the areas and shape of the vertebral bodies carried out, and the proportional incidence of articular shelves and laminar spicules was calculated. 3. The upper mid-thoracic vertebral bodies are relatively long and narrow and have but little greater cross-sectional area than those immediately above them; possessing no neural arch supports to sustain longitudinal compressive forces in flexion, they are at greatest hazard during tetanic spasms. 4. Analyses of these factors and of the clinical features, together with experimental observations drawn from the literature, are used to explain the prevalence of upper mid-thoracic vertebral fractures as a complication of tetanus in West Africans, and in particular the greater degree of compression and higher incidence found in children. 5. Vertebral fracture is not usually an important complication of tetanus; it causes little pain, does not prolong the illness, gives rise to no permanent disability and has no effect on the mortality.

The electroencephalogram and electromyogram in experimental hypocalcemia

The characteristics of the electroencephalographic and electromyographic changes occurring during and after hypocalcemic convulsions were investigated in cats after parathyroidectomy. 1. 1. In the awake intact cat the EEG characteristically exhibited lower voltage and higher frequency potentials with the onset of hypocalcemic convulsions. In some animals no changes in the EEG could be detected. Paroxysmal spikes or spikes and waves were never observed. 2. 2. In six out of seven encéphale isolé preparations there were no changes in the EEG, although severe convulsions involving the entire cat occurred. 3. 3. It is concluded that the arousal reactions observed in the EEG of intact cats were the result, at least in part, of the excitation of peripheral skin and muscle receptors occurring during the tetanic convulsions. 4. 4. Epileptiform seizure patterns occasioned by mechanical damage to the cerebral cortex of two of the hypocalcemic cats were abolished by intravenous injections of calcium gluconate. 5. 5. It is suggested that the epileptiform seizures occurring in chronic hypocalcemia of man are of a different pathophysiological origin from those of acute hypocalcemia, and are possibly a manifestation of degenerative changes in this condition. 6. 6. The convulsions of rachitic hypocalcemic babies are not a single entity. Typical tetanic spasms are the predominant manifestations only in some cases; in others, real cortical seizures occur.

Compression fractures of the thoracic vertebrae in a patient with tetanus.

Tetanus is a disease caused by an anaerobic bacillus, Clostridium tetani, and characterized by stiffness of the jaw and tetanic spasms of the neck and back. The agent causing tetanus is found in soil and in the gastrointestinal tract of man and many animals. It has been isolated occasionally in man from the body surface and oral cavity. Essential to the development of tetanus is the preexistence or fresh deposit of spores in tissues favoring their growth, i. e., traumatized, inflamed, or necrotic tissue. On occasion such conditions prevail without trauma, and in these tetanus may develop without any apparent wound. The case to be presented is in this category. The tetanus bacillus elaborates a toxin affecting the anterior horn cells of the brain stem and cord and the myoneural end-plates. Thus, the chief clinical manifestation is tonic spasticity of various voluntary muscle groups, and the symptoms vary with the

TREATMENT OF TETANUS

THE CONTROL of tetanic muscle spasms and neutralization of the toxin constitute the aims in treatment of tetanus. Firor and his associates1have contributed much to knowledge of the use of antitoxin, but treatment of tetanus is still unsatisfactory and there is a wide disparity in therapeutic regimens employed. It is the purpose of this paper to formulate a plan of treatment based on a review of 82 cases from three Detroit hospitals, including 6 cases in which intocostrin (contains raw crude curare), and d-tubocurarine in wax and oil were used in treatment. Analysis of the entire series is given in table 1. The mortality rate, somewhat higher than reported in other series, is partially explained in table 2, which reveals 36 deaths occurring within forty-eight hours of the time of admission. Nine of the patients died within ten hours, and 1 died in the admitting room. Table 3

CELL CHANGES IN THE CENTRAL NERVOUS SYSTEM UNDER VARIOUS NATURAL AND EXPERIMENTAL CONDITIONS. FIRST PAPER: PARATHYROID TETANY

1. Complete thyroparathyroidectomy was performed on thirteen dogs, with the result that all except one developed typical tetany in some degree within one to fourteen days. The one not showing these symptoms was killed on the twenty‐second day after the operation, to be used as an operated control. The tissue from three normal dogs supplied the necessary control material.2. The symptoms of parathyroid tetany suggest an acute affection of the nervous system, especially of the nerve centres. This fact is strongly supported by microscopic alterations found in the nerve cells, the degree of which corresponds very closely to the acuteness of the attacks. These pictures point to a condition of general toxæmia.3. Not all cells of a single animal or even of a single nerve‐nucleus are affected to the same extent, so that for the same animal various steps in the reaction can be recognised. The alterations cannot be considered as the result of activity alone, but are interpreted as being produced by the same agent or agents which act as stimuli upon the neuromuscular mechanism.4. A careful study of the nerve cells from Nissl preparations has been made, taking representative sections from the spinal cord, medulla oblongata, cerebellum, pons, mid‐brain, thalamus, and cruciate gyrus.5. The nerve cells of dog C, the operated control, are well within the normal. In the remaining twelve animals definite although varying degrees of alterations were found in these elements. In general, one might say that these changes are proportional to the acuteness of the tetanic affection. The milder grades of tetany, although extending over several days, are less drastic in their effects as measured by nerve‐cell reaction than more acute attacks of a few hours' duration.6. Sufficiently graduated stages are represented to warrant an account of the course of the affection. Early in the chromatolytic reaction, as measured by the severity of the symptoms, there is a stage of absolute hyperchromatosis with shrinkage of the cells, after which the amount of stainable material gradually diminishes through fragmentation and dissolution. This begins in the perinuclear region and spreads towards the periphery until a stage is reached in which normal staining Nissl substance can no longer be demonstrated.7. The nucleus, on the other hand, seems to maintain its integrity to a greater extent. Except that it is slightly swollen and clouded, it appears to be normal. Complete degeneration of the cells, with karyorrhexis or karyolysis, was not seen; and in very few cells, if any, did it appear that the alterations were beyond repair had it been possible to restore the normal condition of the animal.8. Shifting of the nucleus toward the periphery, although occasionally seen, occurred no more frequently in the experimental than in the control tissues. Vacuolisation of the cytoplasm commonly accompanied the most acute affection, particularly in the Purkinje cells and granule cells of the cerebrum. This was often associated with perivascular and pericellular œdema.9. The associated hyperpyrexia was roughly proportional to the severity of the tetanic spasms, and followed rather than preceded the latter. This increase in body temperature is sufficient by itself to produce changes in the nerve cells, and undoubtedly exaggerates the condition of general poisoning. But this alone cannot account for the nerve‐cell alterations, since these occur in milder form in animals whose temperature remains about normal.10. This work offers insufficient proof of the conclusion that there is an increase in the number of glia cells, or that the processes can be seen for greater distances from the cell‐bodies. Little importance is attached to these findings of other observers.

THE SELECTIVE ABSORPTION OF POTASSIUM BY ANIMAL CELLS

1. Frog muscles perfused with Ringer solution in which potassium chloride has been replaced by an equivalent amount of rubidium or cesium chloride take up rubidium or cesium and incorporate them into the tissue substance in such form as to be retained during a subsequent perfusion with potassium-free Ringer solution, provided the muscles contract during the first perfusion. Retention of rubidium or cesium by a resting muscle does not occur. 2. Rats on synthetic diets, adequate in all respects except that potassium was replaced by an equivalent amount of rubidium or cesium, died after a period varying from 10 to 17 days with characteristic symptoms including tetanic spasms. Muscle, heart, liver, kidney, spleen, and lung tissues were then found to contain significant amounts of rubidium or cesium. The concentration of these metals in the muscle amounted, in some cases, as shown by a spectroscopic estimation, to about half the concentration of potassium normally found in mammallian muscle. 3. The results are regarded as tending to confirm the theory that the peculiarities in the physiological effects of potassium, including the facility with which it is "selected" by living cells in preference to sodium, are related to the electronic structure of the potassium ion as compared with that of similar ions. The possible relationship of the comparative migration velocity, a function of the electronic structure, to physiological effects is suggested.

Two Cases of Pulmonary Disease with Hemiplegia Developing by Stages. Prof. H. Senator, Berliner Klinische Wochenschrift. Nos. 4, 5, and 6. 1879.

The first case was one of putrid bronchitis, with chronic ulcerating pneumonia. The first paralytic symptom was weakness, with increase of temperature and sweating in the right arm, followed next day by almost complete motor paralysis of this limb. On the third day the arm was convulsed, and subsequently the whole body was seized with tetanic spasms, causing opisthotonism (three attacks). In a few days the inferior branches of the facial became paralysed on the right side. Next the speech was affected, and lastly came motor paralysis of the right leg. The patient, without looking, had no idea in what position his right limbs lay. During this short time rapid atrophy of theright arm had taken place.