Indomethacin increases the effect of isosorbide dinitrate on cerebral hemodynamic in migraine patients: pathogenetic and therapeutic implications

Intracerebral vascular reactivity induced by the nitric oxide (NO) donor isosorbide dinitrate (IDN, 5 mg sublingually) is more major and longer-lasting in migraine patients who develop delayed headache in response to the drug. The headache is purportedly due to neuronally-mediated vascular mechanisms. Indomethacin inhibits prostaglandin synthesis, which is involved in NO generation. Indomethacin also decreases cerebral blood flow by constricting precapillary resistance vessels. In the present study, the hemodynamic effects of indomethacin were evaluated in migraine patients and healthy controls by means of transcranial Doppler monitoring. Indomethacin caused a significant decrease in mean flow velocity in the middle cerebral artery. This was an additional effect to the mean velocity decrease induced by IDN. The interactions between the two drugs suggest that their effects on cerebral hemodynamics (and pain) may be of relevance both in understanding the role of NO in migraine pathogenesis and in evaluating symptomatic treatments for migraine attacks.     

Calcium entry blocker: Treatment in acute pain in cluster headache patients

15 chronic cluster headache patients in whom pain was induced by nitroglycerin received acute intravenous treatment with a calcium entry blocker. At the time of peak pain we noted a sudden decrease after the Verapamil injection. The mechanism by which the calcium entry blocker afforded relief is unlikely to have been vasodilatation in patients whose blood vessels had just been dilated by nitroglycerin. A more probable mechanism is blockade of the release of the pain-inducing neurotransmitters. The vasodilatation phase is not a primary factor in the onset of pain.

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Sommario Sono stati studiati 15 soggetti affetti da Cluster cronica inducendo loro la crisi dolorosa con Trinitrina, trattandoli poi con calcio antagonista (Verapamil) per via endovenosa. Al momento dell'apice del dolore, valutato dal paziente con un analogo visivo, la somministrazione di Verapamil endovena, determina una rapida estinzione del dolore. L'azione efficace del Ca-antagonista non può sicuramente essere rapportata alla vasodilatazione poiché la crisi dolorosa insorge già in una fase di vasodilatazione per l'azione della Trinitina. Il meccanismo d'azione più probabile è il blocco del release di neurotrasmettitori inducenti l'attacco doloroso. Si sottolinea che la vasodilatazione non è il fattore primario dell'induzione del dolore.

     

Prediction of outcome from intensive care after gastroenterologic emergency

Prognostic factors determining the outcome from intensive care were studied in 952 patients admitted to 25 Finnish ICUs after gastroenterologic emergency. Logistic regression analysis was used to create predictive models based on the APACHE II–system. The models were constructed by using data from a random two–thirds of the study population and validated in the remaining independent one–third together with the original APACHE II–index. The Acute Physiology Score, age, and a pre–existing liver disease were the three most important determinants of outcome. The inclusion of the TISS score describing the intensity of treatment into a model did not enhance the accuracy of the prediction. Our models were better calibrated than the original APACHE II–equation when tested by the goodness–of–fit –statistics. These statistical models may help the clinicians to predict the outcome for an individual patient by providing them information about the relative impacts of predictive factors or about the probability of death. These probabilities should be interpreted cautiously, taking into acount the limitations of statistical methods. This is especially important when assessing the highrisk patients. Their number in our study was too low for accurate outcome prediction.     

Fear of falling and postural control in Parkinson's disease.

This study investigated the relationship between fear of falling (FOF) and qualitative and quantitative postural control in Parkinson's disease (PD). Fifty-eight nondemented PD patients were studied along with age-matched healthy controls. The degree of FOF was estimated using the Activities-specific Balance Confidence scale. Qualitative postural control was evaluated using a component of the Unified Parkinson Disease Rating Scale. Postural control was quantified, using centre of pressure measures obtained from a force plate, for eight standing balance tests of different challenges. The results showed that FOF was more evident for PD patients when compared with healthy individuals of similar age. Furthermore, FOF was significantly associated with a qualitative estimate of postural control in PD; individuals with PD who had a greater degree of posture impairment reported greater FOF. The results also showed that an estimate of FOF may help to explain quantitative postural instability in PD. FOF, when coupled with a qualitative estimate of postural control, was able to explain a greater amount of variation in quantitative balance performance for five of the eight balance tests. When considered independently, the qualitative measure of postural control, in general, could not well predict quantitative balance performance. The greater degree of FOF and its possible association with altered postural control suggests that FOF should be considered as an important, independent risk factor in the assessment and treatment of postural instability in patients with PD.     

Benign coital headache

We studied the natural history of patients with a diagnosis of benign coital headache who presented to a private neurological clinic between the years 1978 and 1991. Thirty-two patients (24M, 8F) were invited to participate and 26 patients (83%) responded. The period of follow-up ranged from six months to 14 years (median 6 years). Thirteen patients (50%) had recurrent attacks of coital headache epochs separated by intervals of up to 10 years. Eleven of these patients suffered a concomitant primary headache whereas this was present in only one of those patients without recurrent attacks of coital headache (p < 0.001). In all but one patient, who had a transient blurred vision, the headache was not accompanied by nausea, vomiting, visual disturbances, sensory/motor disturbances, or unconsciousness. We concluded that benign coital headache can be clearly distinguished from headaches due to cerebral aneurysm or arteriovenous malformation rupture. The presence of a concomitant primary headache syndrome is a risk-factor for recurrence of coital headache.     

复方速效头痛宁与苯塞啶治疗偏头痛疗效对照研究

目的 观察复方速效头痛宁与苯塞啶治疗偏头痛的临床疗效。方法 将690例偏头痛患者随机分为A、B、C三组。根据患者治疗前后头痛发作次数、头痛程度、头痛持续时间和伴随症状的变化进行疗效评定。结果 A组显效率为46.2％、总有效率82.9％;B组显效率为 45.5％、有效率为 80.0％,;C组显效率 63.6％,,有效率 85.6％;C组显效率明显高于 A、B两组,P<0.01,差异有显著性。结论 复方速效头痛宁是一种安全有效的偏头痛防治药物。     

Cluster headache after orbital exenteration

A 37-year old man developed an ipsilateral headache which fulfilled the criteria for cluster headache after orbital exenteration because of traumatic lesion of the bulb. The headache could be treated successfully by drugs usually applied in the therapy of cluster headache. Six similar cases of cluster headache after orbital exenteration could be identified in the literature suggesting that the eye itself is not necessarily part of the pathogenesis of cluster headache. We hypothesize that orbital exenteration can cause cluster headache by lesions of sympathetic structures. Possibly, these mechanisms are similar to those of sympathetic reflex dystrophy (Sudeck-Leriche syndrome) causing pain of the limbs.     

Brain-derived neurotrophic factor in cerebrospinal fluid of patients with chronic daily headache: relationship with nerve growth factor and glutamate levels

Little has been done to investigate the biochemical basis of chronic daily headache (CDH). Our group has recently demonstrated an increase in the cerebrospinal fluid (CSF) levels of nerve growth factor (NGF) in CDH patients, supporting the involvement of this growth factor in the abnormal processing of head pain in this pathological condition. Other members of the neurotrophin family, especially brain-derived neurotrophic factor (BDNF), have been hypothesized as being involved in the development of chronic head pain in patients affected by CDH, but so far no data are available on this subject. BDNF, NGF and glutamate levels were determined in the CSF of 25 patients affected by CDH with a previous history of migraine. These levels were compared with those of a group of 20 control subjects, for whom the CSF examination and other instrumental investigations excluded diseases of the central and peripheral nervous systems. Significantly higher levels of BDNF, NGF and glutamate were found in CDH patients compared with control subjects (p<0.0001, p<0.0002 and p<0.001, respectively). A significant positive correlation emerged between CSF values of BDNF and those of NGF (r=0.61, p<0.001) and glutamate (r=0.44, p<0.025) in CDH patients. No significant differences were detected in BDNF, NGF and glutamate levels between CDH patients with analgesic overuse and those without. These results support the involvement of BDNF in CDH through the potentiation of glutamatergic transmission involved in the processing of head pain. The significant correlation between BDNF and NGF levels suggests that NGF-mediated up-regulation of BDNF in central sites involved in long-term sensitization plays a key role in persistent head pain in CDH patients. Correspondence to P. Sarchielli     

Platelet-rich plasma serotonin levels in tension-type headache and depression

We measured platelet-rich plasma (PRP) serotonin in patients suffering from tension-type headache, before and after treatment with amitriptyline, comparing them with a healthy control group and patients with untreated depression. We evaluated the severity of headache and depression in each group. PRP serotonin levels were higher in patients with headache than in controls and depressed patients. We observed a fall of PRP serotonin in patients with tension-type headache to similar levels after treatment as the depressed group. This fall was correlated with the improvement of headache but not with depression scales. Our data suggest that the rise of platelet serotonin levels in tension-type headache is related to pain and not depression.     

Pupil responsiveness in cluster headache: A dynamic TV pupillometric evaluation

In this study the variations in pupil diameter induced by different stimuli (dark-light adaptation, light reflex, electric stimulation of the sural nerve) were investigated in episodic (in the active or remission phases) and in chronic cluster headache (CH) patients. Pupil size monitoring was performed with a monocular, infrared TV pupillometer, and sural nerve stimuli were applied after the pain threshold had been measured as the flexion reflex threshold of the biceps femoris muscle (RIII reflex). The results were compared with those obtained in patients with "peripheral" (third neuron) Horner's syndrome and in healthy sex- and age-matched controls. On the symptomatic side we found an impairment of pupil response to light flashes and nociceptive stimuli; similar findings were sometimes evident on the pain-free side, too. These results substantiate previous observations that in cluster headache a dysfunction of the integrative central nervous system pathways also exists intercritically and mostly bilaterally, involving both autonomic regulation and pain perception mechanisms.