Selective serotonin re-uptake inhibitors (SSRIs) for preventing migraine and tension-type headaches.

BACKGROUND: Headache is a common medical problem. In view of recent discoveries about the role of serotonin in pain mechanisms, selective serotonin re-uptake inhibitors (SSRIs) have been evaluated for the prevention of migraine and tension-type headaches (TTH). OBJECTIVES: To evaluate the efficacy and tolerability of SSRIs for preventing migraine and TTH. SEARCH STRATEGY: We searched MEDLINE (1966-2004), EMBASE (1994-2003), the Cochrane Central Register of Controlled Trials (Issue 4, 2003), and reference lists of retrieved articles. Headache Quarterly was hand searched from 1990 to 2003. SELECTION CRITERIA: We included randomised controlled trials comparing SSRIs with any type of control intervention in patients of either sex, over 18 years of age, with migraine or TTH. DATA COLLECTION AND ANALYSIS: Two authors independently extracted data (headache frequency, index, severity, and duration; use of symptomatic/analgesic medication; days off work; quality of life; mood improvement; cost-effectiveness; and adverse events) and assessed the methodological quality of trials. MAIN RESULTS: Thirteen studies utilizing five SSRIs met the inclusion criteria (636 participants). Most of the included studies had methodological and/or reporting shortcomings; follow up rarely extended beyond 3 months. After 2 months SSRIs did not significantly lower headache index scores in patients with migraine when compared to placebo (SMD -0.14; 95% CI -0.57 to 0.30). Patients with chronic TTH treated with an SSRI had a significantly higher analgesic intake of 5 more doses per month when compared to patients treated with a tricyclic antidepressant (WMD 4.98; 95% CI 1.12 to 8.84). Tricyclics also significantly reduced headache duration by 1.26 hours per day (WMD 1.26; 95% CI 0.06 to 2.45) and marginally reduced headache indexes (SMD 0.42; 95% CI 0.00 to 0.85) when compared to SSRIs in patients with chronic TTH. When the data on adverse events were considered without regard to headache diagnostic subgroups, there were no significant differences between SSRIs and placebo for withdrawals due to adverse events (Peto OR 1.02; 95% CI 0.31 to 3.34). For minor adverse events, SSRIs were generally more tolerable than tricyclics (OR 0.34; 95% CI 0.13 to 0.92). However, there were no differences in the number of patients withdrawing due to any reason in the SSRI and tricyclic groups (OR 1.01; 95% CI 0.56 to 1.80). AUTHORS' CONCLUSIONS: Over 2 months of treatment, SSRIs are no more efficacious than placebo in patients with migraine. In patients with chronic TTH, SSRIs are less efficacious than tricyclic antidepressants. In comparison with SSRIs, the burden of adverse events in patients receiving tricyclics was greater. These results are based on short-term trials and may not generalise to longer-term treatment.

[Neurofibromatosis (NF1) and neuroleprosy: immunoreaction against pathologic Schwann-cells. Physiopathogenetic observations]. / Neurofibromatosi (NF1) e neurolebbra: immunoreazione verso cellule di Schwann patologiche. Considerazioni fisiopatogenetiche.

BACKGROUND: We reviewed the literature evaluating the immune reaction in neurofibromatosis (NF1) and neuroleprosy, so as to underline the immunopathegenetic parallelism and the possible therapeutic implications regarding the treatment of these two disorders. In particular we evaluated the systemic modifications and the local fibrotic events that lead to nerve damage in NF1 and complete neuronal destruction as in leprosy. METHODS: With the above aim in mind we studied the histology, histochemistry and immunohistochemistry (Schwann cells and immunoglobulins) of four plexiform neurofibroma, one common neurofibroma and one case of borderline neuroleprosy (BT). RESULTS: Two plexiform neurofibromas showed an evident immune reaction that was antibody mediated with numerous IgG; the remaining neurofibromas represented other stages of disease evolution and disease quiescence and thus showed a scarce immune reaction with a reduced presence of immunoglobulins. All the neurofibromas showed the presence of fibrous bundles. In the case of neuroleprosy (BT), the immune reaction was modest, immunoglobulins were present and fibrotic transformation on neuronal fibers was observed. CONCLUSIONS: Being that pathologic Schwann cell are the site of immune reactions that can become abnormal (at times with autoimmune reactions), clinical as well as biochemical surveillance of leprous neuropathy and NF1 could allow for a timely modification of the abnormal reaction with selective immunomodulators. The inactivation of the mycobacterial RNA polymerase or of the NF1 gene could offer hope for controlling disease activity and disease evolution of the two disorders.

Tumour suppressor genes, immunology and local manifestations of neurofibromatosis phenotypes.

Research on Neurofibromatosis (NF) has been directed at understanding what determines disease quiescence, exacerbation, and the possible malignant evolution. Studies on NF have examined the role of genetic oncosuppression in the evolution of the defence against the non-self. Paraffin fixed specimens of benign and malignant neoplasia, occurring in patients with NF1 and NF2, were tested for the presence of p53: a reliable marker of genetic oncosupression. The wild type variant of p53 is expressed in malignant neoplasia, and is usually not expressed in benign tumors. Contrariwise, an immune reaction it is seen in benign tumors and is practically absent in malignant tumors. Evidence of protein p53 in the various malignant neoplasias studied by our group seems to reflect the up-regulation on the oncosuppresive genetic potential that occurs while there is a lack of immunological defence. In the presence of an immunological defence, the expression p53 is normally not seen e.g. plexiform neurofibromas. The evolution of the various neoplastic types here reported was the same as that reported by current clinical and experimental models: the cell's defective genes are no longer suppressed and after activation the genes undergo initiation, promotion, and the cell sustains inflammatory-immune reactions that lead to fibrosis; what follows is a variable period of apparent quiescence. Severe pathogenic stimuli may act on predisposed cells and deteriorate pre-existing genetic damage, casting the cell into a phase of dysplastic or neoplastic proliferation that overcomes the body's defences. Hope for future therapy lies in the development of drugs that can either mimic the immune system or the proteins encoded by the oncosuppressor genes.

[The clinico-immunological surveillance of neurofibromatosis]. / La sorveglianza clinico-immunologica delle neurofibromatosi.

Considering the more recent physiopathogenetic advancements in neurofibromatosis (NF), we propose to employ novel instrumental and laboratory procedures for the immunological and clinical surveillance of NF. In NF the evolution of the non-self can lead to disease expansion, at times transforming into malignancy. Contemporarily, the resulting immunological reactivity can either lead to the type of fibrosis that one sees in paraneoplastic connective tissue disease or be deficient. Through interdisciplinary biohumoral analyses were carried out contemporarily so as to gain comparative insight into the eventual unfolding of immunological and fibrotic phenomena. The range of the clinical follow-up varied from one to four years with periodic day hospital admissions. We studied ten NF patients that originated from southern Italy and belonged to middle and lower middle class status; we also studied one healthy subject who had the same HLA haplotype as his NF affected twin. We performed biohumoral analyses in clinical stable patients and saw moderate variations in induces useful for monitoring the evolution of this dysplastic-neoplastic condition, e.g. procollagens, interleukin-2, NSE (assayed with radioimmunological methods) and complement these parameters proved to be of use in monitoring the fibrotic evolution of NF. The intent of our work was to complete the earlier studies on NF surveillance, especially during periods of disease evolution and immuno-fibrotic alteration.

Sneddon syndrome: cerebral perfusion studies by Tc99m HM-PAO and SPECT.

Sneddon syndrome is a non-inflammatory, non-atherosclerotic disease involving small and medium-sized arteries of the brain and of the skin. The arteriographic examination is often negative despite progressive impairment of the neurological status. In 3 patients with Sneddon syndrome cerebral perfusion was assessed with single photon emission computerized tomography (SPECT) and technetium99 m-hexamethylpropylenamineoxime (Tc99 HM PAO). A correlation between clinical and SPECT finding was found, with significant focal reduction of regional cerebral blood flow (rCBF) in the two more severely affected patients.

Prognostic relevance of hormonal and kinetic parameters in CNS neoplasms.

With the present study we investigated both the presence of cytoplasmic estrogen (E-Rc) and progesterone (P-Rc) receptor, nuclear E-R (E-Rn) and the percentage of cycling tumor cells with Ki-67 MAB in 32 CNS tumor specimens. The main purpose of our study was to evaluate a possible correlation between the hormonal and kinetic parameters and the clinical and neuroradiological follow-up.

A case of Vogt-Koyanagi-Harada syndrome in a patient affected by Hodgkin's disease.

The Vogt-Koyanagi-Harada (VKH) syndrome, a disease of unknown origin, characterized by inflammation of the uveal tract, retina and meninges, was observed in a patient with Hodgkin's disease (HD) who had been treated with chemotherapy and radiotherapy. Ten years later the patient developed a cluster of neurological symptoms and signs (fever, pain, bilateral hypoacousia, dizziness, uveitis and psychiatric disorder) which were initially interpreted as a relapse of HD. The diagnosis of VKH syndrome was thereafter suspected from the clinical findings, response to therapy and further evolution. During the follow-up (14 months) the patient showed a varying course; hypoacousia remained unaltered while uveitis recurred and only a partial improvement was obtained by immunosuppressive therapy.

[Apropos of a case of cluster headache and a space-occupying lesion in the brain]. / Considerazioni a proposito di un caso di cefalea a grappolo e processo occupante spazio intracerebrale.

Reference is made to a patient with an approximately 20-yr history of cluster headache and crises refractory to medical prophylaxis for 2 years prior to admission. Over the last 30 days, the picture had been complicated by resistance to ergotamine and motor deficiency in the right leg. Neuroradiological investigation revealed a lesion occupying the left parieto-occipital space. This remained undiagnosed. Its aetiology and clinical relations are discussed in the light of other cases of cluster headache associated with a demonstrated organic lesion described in the literature.

Brain-stem haematoma with complete recovery.

A case of CT-diagnosed brain-stem haematoma associated with signs of dorsal medullary involvement is reported. The patient recovered completely within 1 month.

Chronobiological aspects of headache syndromes due to sellar or pituitary pathology.

A chronobiological study was carried out in headache syndromes due to empty sella or to pituitary G.H.- and PRL-secreting adenomas. In the empty sella syndrome only the chrono-organization of G.H. secretion was disturbed, whereas pl. PRL exhibited the usual circadian pattern. The circadian rhythms of pl. G.H. and pl. PRL were abolished in G.H.- and PRL-secreting pituitary tumors, respectively, and were again detectable when patients were cured by selective transsphenoidal adenomectomy. A normal circadian rhythmicity of pl. cortisol was demonstrable in the empty sella syndrome and in pituitary adenomas, both before and after surgery.

Changes of biological rhythms in primary headache syndromes.

The circadian periodicity of some endocrine (PRL, cortisol, GH) and vegetative (oral temperature, blood pressure) functions has been studied in cluster headache, common migraine, atypical facial pain, and "mixed" headache. Changes in several biological rhythms have been found not only in cluster headache (CH) but also in other kinds of headache. Although a great individual variability of rhythometric changes has been observed, particularly in CH, the dysrhythmic condition seems to be more evident in chronic than in episodic CH. The clinical and chronobiological effects of lithium administration and of a short-term sleep deprivation have been studied in CH.

Neuroendocrinological aspects of depression and symptomatological picture.

Cortisol and prolactin circadian rhythms were determined in a group of depressed hospitalized women who were submitted the next day to the dexamethasone suppression test. The depressed were classified as endogenous and non-endogenous according to symptomatological criteria. Some significant differences were found between the two groups when compared to control subjects in cortisol as well as prolactin biorhythms, and the cortisol suppression percentages were significantly lower in the endogenous than in the non-endogenous. This difference is abolished by benzodiazepine treatment.