Botulinum toxin treatment improves dysphagia in patients with oculopharyngeal muscular dystrophy and sporadic inclusion body myositis.

OBJECTIVE: Dysphagia can be troublesome in sporadic inclusion body myositis (sIBM) and oculopharyngeal muscular dystrophy (OPMD), but no established treatment exists. Cricopharyngeal muscle botulinum toxin injection has at case level been reported to be effective. We evaluated safety and efficacy of botulinum toxin injections in the cricopharyngeal muscle in patients with dysphagia due to sIBM or OPMD. METHODS: Participants were included from our outpatient clinic. Cricopharyngeal constriction was confirmed by laryngoscopy. After EMG confirmation of needle placement in the cricopharyngeal muscle, botulinum toxin A was injected in awake patients. An individualized dose of 5-10 units of botulinum toxin A was applied initially and titrated up a maximum of 3 times. Outcome measures were change in dysphagia questionnaire, timed cold-water swallow test and subjective dysphagia status (worse, unchanged, improved). Due to the need for individualized dosing and a limited number of available patients, an uncontrolled, un-blinded design was used. RESULTS: Thirteen patients, 3 with OPMD, received at least 1 injection. In the dysphagia questionnaire, all but 2 subjects, none with subjective worsening, improved (p < 0.001). Subjectively, seven felt an improvement, 4 no change and 2 a worsening. No overall change was seen the timed cold-water swallow test. No serious adverse events were observed. CONCLUSION: Botulinum toxin injection of the cricopharyngeal muscle in patients with OPMD and sIBM had a beneficial effect on dysphagia in most of the treated patients. Two of 13 patients experienced a temporary worsening not reflected in dysphagia score. Limitations are the un-blinded and un-randomized design and subjective assessments methods. PROSPECTIVE TRIAL REGISTRATION: EudraCT-number: 2014-002210-23.

Repeated treatments of drooling with botulinum toxin B in neurology.

OBJECTIVES: To investigate efficacy, saliva flow, and composition in repeated BoNT-B treatments of drooling. MATERIALS AND METHODS: Seventeen neurological patients (median 66 years), referred for treatment of drooling participated in this observational study. Median total doses of 4000 units botulinum toxin type B (BoNT-B, Neurobloc(®)) were injected with at least 3 months intervals into parotid and submandibular glands using ultrasound guidance. Measures of drooling and saliva collection for analysis were obtained before treatment, and 6, 12, and eventually 18 weeks after. RESULTS: Number of treatment series in each patient was 1-7. Compared to baseline, saliva flow rate and drooling were reduced 30-70% 6 weeks after treatment in the first series, while sodium, chloride, and total protein increased 20-80% (t-tests; P < 0.05). After 12 weeks, drooling was still significantly reduced, saliva flow tended to be, and saliva composition was back to baseline. Frequent side effects were viscous saliva and dry mouth. Due to fading effect in eight patients, individual decisions were taken to change from BoNT-B to BoNT-A. Similarly, the outcome was significantly reduced over time in six patients completing five subsequent BoNT-B treatment series (ANOVA; P < 0.05). CONCLUSION: In the first series, BoNT-B treatment resulted in marked reduction of drooling and saliva flow rate with some relapse after 12 weeks. The viscous saliva was ascribed to increased total protein content and compensatory mechanisms related to ß-adrenergic receptor-specific actions. With patients needing long-term treatment, it should be noted that the efficacy of repeated BoNT-B may fade with time.

Prednisolone reduces nitric oxide-induced migraine.

BACKGROUND AND PURPOSE: Glyceryl trinitrate (GTN) induces delayed migraine attacks in migraine patients. The purpose of this study was to investigate whether pre-treatment with prednisolon could decrease this effect of GTN. METHODS: In this double-blind, randomized and placebo-controlled, crossover study 15 migraineurs with migraine without aura were pre-treated with 150 mg of prednisolone or placebo followed by a 20-min infusion of GTN (0.5 ug/kg/min). One hour after the GTN-infusion, the participants were sent home, but continued to rate headache and possible associated symptoms by filling out a headache diary every hour for 12 h. There were two equal primary efficacy end-points: frequency of delayed migraine and intensity of delayed headache. RESULTS: Nine patients experienced a GTN headache fulfilling the diagnostic criteria for migraine without aura on the placebo day compared with four patients on the prednisolone day (P = 0.14). Prednisolone pre-treatment did not alter the summed or peak immediate headache responses to GTN significantly (P = 0.08, P = 0.07), whereas the peak headache scores during the following 12 h were significantly lower after prednisolone pre-treatment (median peak score = 1, range 0-8) compared with placebo (median = 4, range 0-8) (P < 0.01). There was no difference between the two treatment days in the effect of GTN on blood flow velocity of the middle cerebral artery (a decrease) or on the dilation of the superficial temporal artery or the radial artery. CONCLUSION: Pre-treatment with prednisolone did not reduce the immediate GTN-induced headache, did not inhibit the frequency of delayed headache but significantly decreased the intensity of delayed GTN-induced headache. These findings suggest that GTN causes induction of inflammatory mediators, and that this is the mechanism of delayed GTN-induced migraine. They also support a role of inflammatory mediators in spontaneous migraine attacks.

Delayed migraine-like headache in healthy volunteers after a combination of acetazolamide and glyceryl trinitrate.

Glyceryl trinitrate (GTN) is a pro-drug dissociating nitric oxide throughout the body. It dilates cephalic arteries without increasing cerebral blood flow (CBF). GTN induces headache in healthy volunteers and migraine attacks in migraineurs. Acetazolamide (Az) increases CBF but does not dilate cerebral arteries. The hypothesis tested here was that Az, by dilating cerebral arterioles but not arteries and thereby decreasing pulsatile stretching of the wall of the large arteries and their perivascular sensory nerves, would reduce or prevent the GTN-induced headache We tested this hypothesis in 14 healthy volunteers. In a randomized, double-blind, cross-over study, they were pretreated with Az or placebo followed on both study days by a GTN infusion of 0.5 microg kg(-1) min(-1) for 20 min. Headache was scored on a verbal rating scale and a headache diary was kept for 12 h. Mean blood velocity of the middle cerebral artery was measured (transcranial Doppler). Our hypothesis was disproved, as Az did not decrease GTN-induced headache. Unexpectedly but interestingly, GTN combined with Az induced more delayed headache than GTN alone. Furthermore, a migraine-like headache was observed in three volunteers, who did not develop migraine after GTN alone. The fact that a suitable pharmacological intervention may trigger migraine in individuals with no prior migraine may suggest that the ability to develop migraine without aura is a quantitative genetic trait.

Steam activation of chars produced from oat hulls and corn stover.

Oat hulls and corn stover were used to produce chars at approximately 500 degrees C. The carbon concentrations of oat hull char and corn stover chars produced were 72.3 and 68.0 wt.%, respectively. Both activation burn-off and Brunauer-Emmett-Teller (BET) surface area appear to exhibit a linear relationship with respect to activation time of oat hulls. As to corn stover activated carbons, there is no linear relationship between activation time and BET surface area. However, activation burn-off of and activation time appear to relate in a linear manner for the activated carbons produced from corn stover chars. Oat hull is better than corn stover as a raw material for the production of activated carbon.

Glyceryl trinitrate induced headache in migraineurs - relation to attack frequency.

Glyceryl trinitrate, a prodrug of nitric oxide, induces a mild to moderate headache in healthy subjects, whilst migraineurs develop a more severe headache, resembling spontaneous migraine attacks. In order to investigate whether this increased nitric oxide sensitivity depends upon the frequency of spontaneously occurring migraine attacks, intravenous infusion of glyceryl trinitrate (0.5 microg/kg/min) was given to 15 migraine patients with rare attacks (/=12 attacks/year) and 14 healthy subjects served as controls. No significant difference between the migraine groups for any of several parameters was detected, although the trend was always towards more headaches in frequent migraineurs. Both migraineurs with frequent and rare attacks experienced a headache that was significantly more severe, longer lasting, and fulfilled the diagnostic criteria for migraine without aura more often, compared to the healthy subjects (P = 0.0001). Conclusively, supersensitivity to glyceryl trinitrate in migraineurs seems to be related to a basic - probably genetically determined - pathophysiological mechanism involving nitric oxide, and not to the environmental influences, which to a large extent determine the expression of migraine.

Glyceryl trinitrate induces attacks of migraine without aura in sufferers of migraine with aura.

Migraine with aura and migraine without aura have the same pain phase, thus indicating that migraine with aura and migraine without aura share a common pathway of nociception. In recent years, increasing evidence has suggested that the messenger molecule nitric oxide (NO) is involved in pain mechanisms of migraine without aura. In order to clarify whether the same is true for migraine with aura, in the present study we examined the headache response to intravenous infusion of glyceryl trinitrate (GTN) (0.5 microg/kg/min for 20 min) in 12 sufferers of migraine with aura. The specific aim was to elucidate whether an aura and/or an attack of migraine without aura could be induced. Fourteen healthy subjects served as controls. Aura symptoms were not elicited in any subject. Headache was more severe in migraineurs than in the controls during and immediately after GTN infusion (p=0.037) as well as during the following 11 h (p = 0.008). In the controls, the GTN-induced headache gradually disappeared, whereas in migraineurs peak headache intensity occurred at a mean time of 240 min post-infusion. At this time the induced headache in 6 of 12 migraineurs fulfilled the diagnostic criteria for migraine without aura of the International Headache Society. The results therefore suggest that NO is involved in the pain mechanisms of migraine with aura. Since cortical spreading depression has been shown to liberate NO in animals, this finding may help our understanding of the coupling between cortical spreading depression and headache in migraine with aura.

No relation between cephalic venous dilatation and pain in migraine.

Evidence for the involvement of the cranial arterial system in migraine is plentiful, but it is unclear whether the cranial venous system may be involved in the mechanism of migraine pain. Venules are the preferentially involved vessels in the neurogenic inflammation animal model of migraine. The cranial and cerebral veins and sinuses are pain sensitive and receive sensory innervation from the trigeminal nerve. If the veins are involved in migraine pathogenesis, a venous dilatation would presumably be painful. The effect of a short lasting cranial venous dilatation, induced by applying pressure on the internal jugular veins (Queckenstedt's manoeuvre), was therefore compared with a placebo procedure, consisting of an equal pressure applied on to the lateral aspect of the neck. In each procedure pressure was applied for 10 seconds. The study used a single blind, randomised, cross over design, and 20 patients with an acute attack of migraine without aura participated. After each procedure, headache intensity was rated on a standardised five point scale. After Queckenstedt's manoeuvre 40% of the patients reported no change in headache intensity, 25% a worsening, and 35% an improvement of their headache. No significant difference between the headache intensity ratings during Queckenstedt's manoeuvre and the placebo manoeuvre was found (p=0.22). The findings make it unlikely that the cephalic venous system is of major importance in migraine pain mechanisms and, therefore, also less likely that neurogenic inflammation plays a significant part in humans during attacks of migraine without aura.

311C90 (Zolmitriptan), a novel centrally and peripheral acting oral 5-hydroxytryptamine-1D agonist: a comparison of its absorption during a migraine attack and in a migraine-free period.

The oral absorption of a 10-mg oral dose of the novel 5-hydroxytryptamine (5HT1D) agonist, 311C90, was compared during a moderate or severe migraine headache and in a migraine-free period in an open, two-period study. The safety and efficacy of 311C90 in acute migraine were also assessed. Twenty patients attended the clinics during a moderate or severe migraine attack and 18 patients returned for a second dose in a migraine-free period. 311C90 was less rapidly absorbed during a migraine attack compared to the migraine-free period, consistent with gastric stasis during a migraine attach. The median area under the curve (AUC) was 15.7 ng/mlh lower during a migraine (median AUC: 18.4 ng/ml.h, range: 0-60.8 ng/ml.h) compared to the migraine-free period (median AUC: 33.4 ng/ml.h, range 9.4-79.5 ng/ml.h) (95% confidence interval: 6.9, 25.3) and the time to reach maximum plasma concentration was delayed (n = 18). Eleven out of 20 patients experienced a significant improvement in migraine headache intensity at 2 h post-dose. Plasma 311C90 concentrations were generally higher in those patients who responded to treatment with 311C90 in the plasma, but there was one patient with no quantifiable 311C90 in the plasma whose headache improved. Minor adverse experiences were reported in 11 out of 20 patients during a migraine attack and in 11 out of 18 patients outside an attack. They occurred shortly following drug administration and were of short duration, but their occurrence did not appear to be related to plasma 311C90 concentration. There were no clinically significant changes in blood pressure or 12-lead ECG during the assessment period.

[Myotonic dystrophy]. / Dystrophia myotonica.

Myotonic dystrophy (MD) is illustrated by a characteristic case report. MD is a dominantly inherited multi-organic disease with complete penetrance, but with highly variable expression illustrated by the near relatives of this patient. The disease usually follows a slow, progressive course. The cardinal symptoms are myotonia, muscle atrophia, cataract and a characteristic facial appearance. Cardial arrhythmias, endocrine and mental changes also occur. The liability to arrhythmias and the weakened respiratory muscles of the patients which lead to ventilatory insufficiency makes anesthesia and surgical operation risky. The diagnosis, which is made by electromyography, is easy in typical cases, but suspicion that the disease is present is seldom raised in very mild cases if there is no recognition of familial cases. Meticulous examination of near relatives of severe cases is therefore essential to take advantage of the possibilities of prenatal diagnosis recently made possible through developments in DNA technology.