Epidemiology of ataxia and hereditary spastic paraplegia in Spain: A cross-sectional study.

INTRODUCTION: Ataxia and hereditary spastic paraplegia are rare neurodegenerative syndromes. We aimed to determine the prevalence of these disorders in Spain in 2019. PATIENTS AND METHODS: We conducted a cross-sectional, multicentre, retrospective, descriptive study of patients with ataxia and hereditary spastic paraplegia in Spain between March 2018 and December 2019. RESULTS: We gathered data from a total of 1933 patients from 11 autonomous communities, provided by 47 neurologists or geneticists. Mean (SD) age in our sample was 53.64 (20.51) years; 938 patients were men (48.5%) and 995 were women (51.5%). The genetic defect was unidentified in 920 patients (47.6%). A total of 1371 patients (70.9%) had ataxia and 562 (29.1%) had hereditary spastic paraplegia. Prevalence rates for ataxia and hereditary spastic paraplegia were estimated at 5.48 and 2.24 cases per 100 000 population, respectively. The most frequent type of dominant ataxia in our sample was SCA3, and the most frequent recessive ataxia was Friedreich ataxia. The most frequent type of dominant hereditary spastic paraplegia in our sample was SPG4, and the most frequent recessive type was SPG7. CONCLUSIONS: In our sample, the estimated prevalence of ataxia and hereditary spastic paraplegia was 7.73 cases per 100 000 population. This rate is similar to those reported for other countries. Genetic diagnosis was not available in 47.6% of cases. Despite these limitations, our study provides useful data for estimating the necessary healthcare resources for these patients, raising awareness of these diseases, determining the most frequent causal mutations for local screening programmes, and promoting the development of clinical trials.

Epidemiology of ataxia and hereditary spastic paraplegia in Spain: a cross-sectional study. / Mapa epidemiológico transversal de las ataxias y paraparesias espásticas hereditarias en España.

INTRODUCTION: Ataxia and hereditary spastic paraplegia are rare neurodegenerative syndromes. We aimed to determine the prevalence of these disorders in Spain in 2019. PATIENTS AND METHODS: We conducted a cross-sectional, multicentre, retrospective, descriptive study of patients with ataxia and hereditary spastic paraplegia in Spain between March 2018 and December 2019. RESULTS: We gathered data from a total of 1.809 patients from 11 autonomous communities, provided by 47 neurologists or geneticists. Mean (SD) age in our sample was 53.64 (20.51) years; 920 patients were men (50.8%) and 889 were women (49.2%). The genetic defect was unidentified in 920 patients (47.6%). A total of 1371 patients (70.9%) had ataxia and 562 (29.1%) had hereditary spastic paraplegia. Prevalence rates for ataxia and hereditary spastic paraplegia were estimated at 5.48 and 2.24 cases per 100 000 population, respectively. The most frequent type of dominant ataxia in our sample was SCA3, and the most frequent recessive ataxia was Friedreich ataxia. The most frequent type of dominant hereditary spastic paraplegia in our sample was SPG4, and the most frequent recessive type was SPG7. CONCLUSIONS: In our sample, the estimated prevalence of ataxia and hereditary spastic paraplegia was 7.73 cases per 100 000 population. This rate is similar to those reported for other countries. Genetic diagnosis was not available in 47.6% of cases. Despite these limitations, our study provides useful data for estimating the necessary healthcare resources for these patients, raising awareness of these diseases, determining the most frequent causal mutations for local screening programmes, and promoting the development of clinical trials.

Work capacity and oxygen uptake abnormalities in hyperthyroidism.

AIM: The aim of our study was to evaluate the haemodynamic and the respiratory response to exercise in patients with hyperthyroidism before and 30 days after normalized thyroid hormones levels. These findings were compared with those of 10 control patients. METHODS: Thirty patients (23 women, aged 34.3 +/- 12 years) with untreated hyperthyroidism were studied. Twenty-four patients were treated with methimazole, 13 of which were also treated with propranolol. Six patients underwent surgery. A symptom-limited cardiopulmonary exercise test and an echocardiography were performed in all patients. RESULTS: At rest patients with hyperthyroidism showed at echocardiography an increased cardiac index (P = 0.006 vs euthyroid, P = 0.007 vs normal) and a higher ejection fraction (P = 0.008 vs euthyroid, P = 0.007 vs normal). The duration of the exercise was lower in hyperthyroid patients (P = 0.006 vs euthyroid; P = 0.0068 vs normal). Anaerobic threshold was reached at 49.6% of peak VO2 during hyperthyroidism, at 60.8% during euthyroidism (P = 0.01) and at 62% in normal (P = 0.01). Work rate was lower in patients with hyperthyroidism at anaerobic threshold (P = 0.01 vs euthyroid, P = 0.03 vs normal) and at maximal work (P = 0.001 vs euthyroid, P = 0.01 vs normal). Patients in hyperthyroidism showed a lower increment of heart rate between rest and anaerobic threshold (P = 0.021 vs euthyroid, P < 0.0001 vs normal) and a lower VO2 at anaerobic threshold (P = 0.03 vs euthyroid; P = 0.04 vs normal). Oxygen pulse at anaerobic threshold was significantly reduced in hyperthyroidism (P = 0.04 vs euthyroid, P = 0.005 vs normal). CONCLUSIONS: The mean result is that after only 30 days of appropriate antithyroid treatment there was an appreciable improvement of exertion capacity.

Left ventricular performance and autonomic dysfunction in patients with long-term insulin-dependent diabetes mellitus.

Cardiac autonomic neuropathy (CAN) is a very frequent complication of insulin-dependent mellitus type 1, affecting the sympathetic or parasympathetic sections or both. The different impairment in the two sections might modify left ventricular function early. To evaluate this relationship, we studied 61 patients (mean age 39.6 +/- 7 years) with type 1 diabetes for more than 10 years, without coronary artery disease (CAD); negative ergometric stress test) and without other pathologies that could interfere with ventricular function. All patients underwent MONO-, 2-dimensional and Doppler echocardiographic examination and radionuclide angiography with 99Tc (RNA). According to the outcome of the Ewing tests, patients were divided into two groups: group A with two or more tests altered (26 patients with CAN) and group B with one or no tests altered (35 patients without CAN). No significant differences between the two groups were found in the systolic function parameters with either technique. In contrast, a pattern of abnormal relaxation was found for the diastolic function parameters: in group A a decrease in E-wave velocity and its time-velocity integral and an increase in A-wave and its time-velocity integral were detected with echocardiography. Moreover, RNA showed a reduced peak filling rate and an increased isovolumic relaxation time. When compared with normal values, an abnormal diastolic filling, defined as two independent echocardiography plus one RNA variable impairment, was found in 15 patients (57.6%) in group A and in only 4 patients (11.4%) in group B (P < 0.001). Our findings suggest an early involvement of diastolic function in patients with CAN.

[ST elevation during ergometric test: correlation with coronary angiography]. / Sopraslivellamento del tratto ST durante test ergometrico: correlazione con l'angiografia coronarica.

BACKGROUND: ST elevation during ergometric stress test (EST) is relatively rare. Its prevalence depends upon the tested population but occurs more frequently in patients who have had myocardial infarction or variant angina. This phenomenon is very rare in patients with typical exertional angina and its pathogenesis is still unclear. MATERIAL AND METHODS: We studied a group of 75 consecutive patients with exertional angina who underwent EST and coronary angiography. A symptom limited EST was performed in the upright position on a cycloergometer with load increases of 25 watts every 3 minutes and 12 leads were monitored during all test. Coronary angiography was performed according to Judkins technique. From these patients, according to Froelicher's criteria, a group of 49 patients (age 32-68, mean 51.6 years), without myocardial infarction and/or left ventricular asynergy, was selected. RESULTS: All patients had a coronary artery disease (16 patients with 3 vessels, 11 patients with 2 vessels and 22 patients with 1 vessel disease). The EST was positive for ST depression in 31 patients (63.3%) and for ST elevation in 5 patients (10.1%), while 13 patients (26.6%) had a non diagnostic EST. The ST elevation occurs in V1-V2 and it was associated in all cases with a stenosis in the left anterior descending (LAD) artery. Therefore we divided the 19 patients with LAD stenosis into two subgroups: subgroups A (9 patients, mean age 49.6 years) with LAD stenosis > or = 90% and subgroups B with LAD stenosis between 70% and 90%. ST elevation occurs in 5 patients (55.5%) of subgroup A and in no patient of the subgroup B. Moreover, in the subgroup A ST elevation seems to be related to the anatomic localization of the stenosis: in fact it appears in 83.3% of patients with LAD stenosis located before the onset of the first diagonal branch. CONCLUSIONS: From these data it can be desumed that ST elevation in V1-V2 that occurs in patients with exertional angina and without myocardial infarction or variant angina is strongly predictive of a very important LAD stenosis.

[Effect of cilazapril therapy on diastolic filling and left ventricular hypertrophy in patients with arterial hypertension]. / Effetti del trattamento con cilazapril sul riempimento diastolico e sulla ipertrofia ventricolare sinistra in pazienti con ipertensione arteriosa.

BACKGROUND: Of the main aspects of hypertension, left ventricular hypertrophy and appearance of cardiac dysfunction seem to be the most common and to produce an early and severe cardiac deterioration. Even in the presence of normal systolic function diastolic filling abnormalities are described. The efficacy of many antihypertensive drugs to decrease blood pressure and to reduce left ventricular hypertrophy has already been demonstrated. Cilazapril is a new ACE-inhibitor that in previous studies showed a very important antihypertensive effect. To assess its capacity, in long-term treatment, to reduce left ventricular hypertrophy we performed a prospective study on patients with mild hypertension. MATERIAL AND METHODS: Nineteen patients (aged 48 +/- 15 years) with mild hypertension (mean arterial pressure automatically recorded for 24 hours with blood pressure ambulatorial monitoring) were treated with cilazapril (5 mg/day) for 1 year. Doppler echocardiography was performed: at the beginning, after 6 months and after one year of therapy. The following parameters were evaluated: interventricular septal and posterior wall thickness, LV end-diastolic diameter, LV mass index, early (E) and late (A) diastolic filling flow velocities and the ratio E/A. RESULTS: A significant decrease was observed in mean arterial pressure (from 130 +/- 14 mmHg at beginning to 102 +/- 11 mmHg at six months of therapy and to 103 +/- 9 mmHg at one year of therapy). A significant reduction in LV hypertrophy and an improved diastolic filling pattern of the left ventricle was shown after six months of therapy with cilazapril; this improvement still remained after 1 year of therapy. CONCLUSIONS: In this study antihypertensive efficacy of cilazapril has been confirmed. Moreover, in long treatment, cilazapril has been useful to reduce left ventricular hypertrophy and to improve diastolic filling without significant side effects.

[Systemic effects of intravenous dipyridamole in patients of various age groups]. / Effetti sistemici del dipiridamolo endovena in soggetti di diverse classi di età.

Aim of this study was to assess the role of age-related vascular response in the onset of i.v. dipyridamole effects. The results of 129 patients who underwent a dipyridamole infusion were reviewed. The patients were divided into three according to age: 47 patients of less than 50 years (group I), 54 patients aged between 50 and 60 years (group II) and 28 patients of more than 60 years (group III). For each group heart frequency (HF) and systolic blood pressure (SBP) were considered in basal conditions, at the end of infusion and at the minimum value of SBP (SBP min); moreover the time in reaching SBP min was considered (time to SBP min). At the end of the infusion no significant changes in SBP were observed in all groups while the SBP min value reached from group III were significantly lower than basal (142.6 +/- 20.4 mmHg, p less than 0.02). The HF, without significant differences among the three groups in basal conditions, increased significantly at the end of infusion only in group I and II, with a more significant increase in group I at the time of SBP min with respect to groups II and III. The group 3 showed moreover, a significant longer time to SBP min (286 +/- 208 sec) respect to the group I and II (145 +/- 130 and 160 +/- 177 sec respectively) (p less than 0.02). From these data it can resume that age could be a factor to determine hemodynamic response to intravenous dipyridamole.

Haemodynamic effects of indenolol at rest and after a submaximal workload in essential hypertension.

The effect of indenolol on heart rate and blood pressure at rest and after submaximal workload has been studied in 19 patients with established essential hypertension. A stepwise increase from moderate to submaximal exercise was chosen to mimic challenges normally occurring in daily life. After 4 weeks of once a day indenolol therapy a significant, gradual reduction in the following cardiovascular parameters was observed: heart rate at rest fell by 20%, 30% after exercise and 31% after recovery; systolic blood pressure showed a fall of 15% at rest, 19% after workload and 14% after recovery; the reduction in diastolic blood pressure was 15% at rest, 11% after exercise and 12% after recovery. The rate-pressure product was decreased by 32% at rest, 43% after exercise and 42% after recovery. It is concluded that the most important pharmacological effect of indenolol is the significant decrease in myocardial oxygen demand. In patients with essential hypertension indenolol not only produces a definite antihypertensive effect, but it also increases workload tolerance and decreases subjective symptoms during physical activity. Compliance was good and no severe side effects were observed.

Hornet building orientation in a vertically rotating centrifuge.

Hornets build combs that are clearly oriented toward the center of gravity and they compensate for any change made in the direction of their cells, provided the gravitational vector remains unchanged. Under natural conditions the first few cells are built by the queen in the spring, following the hibernation period, and building is then continued by the workers. Recently several reports have been published concerning the fact that groups of hornets (V. orientalis workers) may build in the absence of the queen and that such combs resemble those built by the queen. In previous investigations on building orientation, hornets placed in artificial breeding boxes (ABBs) on a horizontal centrifuge were subjected to constant centrifugal and gravitational forces, the resultant of which ranged between 1-1.5 g. Under these conditions young hornets (1-2 days of age) built combs in the direction of the resultant force, while the direction of building by adult hornets (3-7 days of age) was dependent on the presence or absence of a straight roof. Adults placed in the ABBs of rectangular shape built combs the orientation of which was determined by the Earth's gravity alone (perpendicular to the roof) whereas those in spherical ABBs with a convex roof built combs in the direction of the resultant gravitational and centrifugal forces, much the same as combs built by the young hornets. We were, however, also interested in studying the building orientation of hornets placed under conditions of changing resultant forces. The present paper describes comb building by hornets under the alternating gravitational forces of a vertical centrifuge.