Menopause in multiple sclerosis: therapeutic considerations

While the onset of multiple sclerosis (MS) typically occurs during the childbearing years, many women living with MS are of perimenopausal age. There is frequent overlap between menopausal and MS-related symptoms and co-morbidities (e.g. sexual dysfunction, mood disorders and bladder function). Furthermore, some MS symptoms may be exacerbated by perimenopausal changes such as hot flashes or sleep disturbance. The MS neurologist may frequently be the first to become aware of these symptoms and to play a role in monitoring and managing them. In this review, we describe immunological and neurologic changes at menopause as they may impact MS. We then review common symptoms, including fatigue, depression, sexual function, pain and insomnia, and provide both behavioral and pharmacological suggestions for their management. Next, we discuss the need for osteoporosis and cancer screening in perimenopausal women with MS. Finally, we highlight important research gaps, including what effect, if any, the menopausal transition may play on MS disease course as well as the potential modulatory role of hormone replacement therapies.     

Dendritic electrogenesis in rat hippocampal CA1 pyramidal neurons: functional aspects of Na+ and Ca2+ currents in apical dendrites

The regenerative properties of CA1 pyramidal neurons were studied through differential polarization with external electrical fields. Recordings were obtained from somata and apical dendrites in the presence of 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX), DL-2-amino-5-phosphonovaleric acid (APV), and bicuculline. S+ fields hyperpolarized the distal apical dendrites and depolarized the rest of the cell, whereas S÷ fields reversed the polarization. During intradendritic recordings, S+ fields evoked either fast spikes or compound spiking. The threshold response consisted of a low-amplitude fast spike and a slow depolarizing potential. At higher field intensities the slow depolarizing potential increased in amplitude, and additional spikes of high amplitude appeared. During intrasomatic recordings, S+ field evoked repetitive firing of fast spikes, whereas S÷ fields evoked a slow depolarizing, potential on top of which high- and low-amplitude spikes were evoked. Tetrodotoxin (TTX) blocked all types of responses in both dendrites and somata. Perfusion with Ca²⁺-free, Co²⁺-containing medium increased the frequency and amplitude of fast spikes evoked by S+ field and substantially reduced the slow depolarizing potential evoked by S÷ fields. Antidromic stimulation revealed that an all-or-none dendritic component was activated in the distal apical dendrites by back-propagating somatic spikes. The dendritic component had an absolute refractory period of about 4 ms and a relative refractory period of 10–12 ms. Ca²⁺-dependent spikes in the dendrites were followed by a long-lasting afterhyperpolarization (AHP) and a decrease in membrane input resistance, during which dendritic excitability was selectively reduced. The data suggest that generation of fast Na⁺ currents and slow Ca²⁺ currents in the distal part of apical dendrites is highly sensitive to the dynamic state of the dendritic membrane. Depending on the mode and frequency of activation these currents can exert a substantial influence on the input-output behavior of the pyramidal neurons. © 1996 Wiley-Liss, Inc.     

Influence of left ventricular mass on coronary artery cross-sectional area

Observations from cardiac catheterization suggest that coronary artery cross-sectional area (CSA) is increased in patients with left ventricular (LV) hypertrophy and is proportional to LV mass. This hypothesis was tested using computer-based quantitative analysis of LV mass and CSA from angiographic images of the left ventricle and proximal coronary arteries from 19 men and 21 women, aged 23 to 78 years (mean 56). Twenty-seven patients had valvular heart disease, 16 of whom had multivalvular involvement; diagnoses included aortic stenosis in 19, aortic regurgitation in 13 and mitral regurgitation in 12. Thirteen patients had normal valvular and ventricular function. All patients had normal coronary arteries. Significant differences between normal patients and those with valvular disease were noted in LV mass (88 +/- 7 vs 165 +/- 12 g/m2, p less than 0.001) and coronary CSA (26 +/- 2 vs 46 +/- 3 mm2, p less than 0.001). Furthermore, a linear relation between LV mass and coronary CSA was noted (r = 0.788, p less than 0.001). Thus, proximal coronary artery CSA is significantly larger in valvular heart disease patients with LV hypertrophy than in those with normal ventricles, and proximal coronary artery area increases in proportion to LV mass in hypertrophied ventricles.     

Ventricular arrhythmias during coronary angiography in patients with angina pectoris or chest pain syndromes

Of 7,915 patients undergoing coronary angiography from 1978 to 1983, 39 (25 men and 14 women with a mean age of 57 years [range 37 to 79]) had sustained ventricular tachycardia (VT) or ventricular fibrillation (VF) during the procedure. Nine patients had atypical chest pain and 30 had typical angina. Fifteen had had a previous myocardial infarction. One patient had a history of VT or VF. Electrocardiograms taken at rest revealed a prolonged QT interval in 14. A normal ejection fraction was found in 79%. Coronary angiography revealed that 10 patients had 3-vessel disease, 15 had 1- or 2-vessel disease and 14 had normal coronary arteries. The VT or VF was seen with injection of contrast medium into the right coronary artery in 24, the left coronary artery in 10 and vein bypass grafts in 5 patients. Of the episodes of VT or VF, 67% occurred after injection of contrast medium into a minimally diseased coronary artery. In patients in whom VT or VF occurred after injection into a minimally diseased coronary artery, the arrhythmia was preceded by bradycardia, usually with pronounced widening of the QRS and QT intervals. This response was significantly different from that in patients in whom VT or VF occurred after injection into a coronary artery with significant stenosis; in these patients, VT or VF was initiated by a single premature ventricular contraction on a T wave. VT or VF was successfully cardioverted in all instances, without further arrhythmias.     

ELECTRON MICROSCOPIC SUB-CLASSIFICATION OF SMALL CELL CARCINOMA OF THE LUNG

An electron microscopic study of 28 small cell carcinomas of the lung is presented. Cytoplasmic secretory granules, characteristic of endocrine cells of the human foetal lung were observed in a variable number of tumor cells. Two groups of tumors could be distinguished based on the morphology of the cytoplasmic secretory granules. Twenty-three tumors showed cells with granules resembling type 1 or P₁ cells of the human fetal lung, and 5 tumors with granules resembling type 3 cells of the human fetal lung. No relationship was found between the light microscopic WHO classification of small cell carcinoma of the lung and the results obtained by electron microscopy. Increased serum calcitonin as well as inappropriate ADH secretion may be correlated with one of the two types of small cell carcinoma, but further investigations are needed.     

No evidence for tumorigenesis of AAV vectors in a large-scale study in mice.

Six hundred ninety-five mice received adeno-associated virus (AAV) vectors, mostly via portal vein injection. At necropsy, the livers were inspected for tumors, and tissue sections were prepared for histology. We observed only one tumor, a lipoma, resulting in a tumor frequency of 0.14%. This tumor contained fewer vector genomes per total DNA than the surrounding liver tissue, as shown by quantitative PCR. In another mouse we found a macroscopically visible nodule containing lymphocytes. Immunohistochemistry revealed cells not of monoclonal origin, and they contained fewer AAV genomes than the surrounding hepatocytes. There were no macroscopic tumors in 226 control mice. Upon microscopic examination, lymphocytic infiltrates were found in 5% of livers of both control and vector-treated mice; no transgene expression was seen in those infiltrates in AAV-injected animals. Compared to an average frequency of spontaneous liver tumors in C57BL/6 mice (0-10%), and given the absence of high levels of vector DNA in the observed tumor, we conclude that AAV vectors do not predispose these target animals to the formation of liver tumors.     

History of Acta Ophthalmologica – the first 50 years

Acta Ophthalmologica appeared as the scientific journal of the Nordic ophthalmological Societies in 1923. The intention was to expose the clinical and experimental developments among the ophthalmological communities of the four Nordic countries: Denmark, Finland, Norway and Sweden. The collaboration within the field of ophthalmology had been attempted with the publication of ‘Nordisk ophthalmologisk Tidsskrift’ in the years 1889–1892. Now, once again, the wish for a tighter Nordic cooperation was explored by enthusiastic ophthalmologists in all four countries. One person stands out as the driving force, K.K.K. Lundsgaard, who in spite of his early death in 1931 was remembered by name on the front page of Acta since 1936 by the Latin phrase ‘A K.K.K. Lundsgaard edi coepta’. The present review recalls details from the early years when the journal found its place in the ophthalmology and creates the background for some reflections on purpose and goals by publishing a scientific journal.