Maria Gabriella Rosso

Friedreich's ataxia: a descriptive epidemiological study in an Italian population

All the cases of Friedreichs ataxia (FA) diagnosed between 1945 through 1984 among residents of a defined area of northwestern Italy were ascertained (N = 59). Cases were diagnosed according to the criteria of the “Quebec Cooperative Study on Friedreichs Ataxia (QCSFA)” with minor modifications. We identified 39 families with 47 probands and 12 secondary cases. Therefore ascertainment probability was 80%. Male to female ratio was 1:1. Pedigrees were compatible with autosomal recessive inheritance. Segregation ratio was 0.28 with both Weinbergs method and the “singles” method (under incomplete ascertainment). Point prevalence ratio was 1.2/100 000 population. Birth incidence rate was 1/36 000 live births. Gene frequency was estimated to be 1/191. The ratio of first‐cousin marriages observed among parents of FA patients (3%) was lower than expected from Dahlbergs formula (8%). This finding is not compatible with the hypothesis of genetic heterogeneity for FA.

Motor neuron disease in the Province of Turin, Italy, 1971-1980

ABSTRACT The incidence and prevalence of motor neuron disease (MND) in the Province of Turin, North‐West Italy, were investigated for the period 1971‐1980. The crude incidence rate of MND was 0.67/100,000/year. The annual incidence rate, age and sex adjusted to the Italian population in 1971 was 0.69 cases per 100,000 inhabitants, 0.94 for men and 0.45 for women, with a male to female incidence ratio of 2.09:1. The prevalence of MND was 2.62/100,000, 3.57 for males and 1.71 for females. The mean age at the time of diagnosis was 55.6 years. Annual incidence rates increased with advancing age. Amyotrophic lateral sclerosis was found to be 4 times more frequent than progressive muscular atrophy (0.53/100,000/year v. 0.14/100,000/year). The distribution of MND was uneven in the Province suggesting a proportional relationship to the distribution of population density. Possible explanations of this finding are discussed.

Disability and quality of life in hereditary ataxias: a self-administered postal questionnaire

A postal questionnaire was sent to 151 patients affected by Friedreichs disease (FD) and other hereditary ataxias (OHA) to study their disability and quality of life. A 79.5% response rate was obtained. A scoring system based on disability in walking, dressing, personal care, eating and speaking was developed and used. Walking was the most impaired activity. The degree of disability was similar between FD and OHA. Institutionalization, frequency of social contacts, work activity, recreational and social activities were influenced by disability.

A Study of Prognostic Factors in Motor Neuron Disease

Latest advances in the study of motor neuron disease (MND) have pointed out some differences in the course of the illness; subgroups of patients with different survival experience have been identified. A review of studies based on survival analysis is reported in Table 1. It shows the 5-year survival variable from 10 to 50%. Few reports have been devoted to an extensive study of prognostic factors in MND[2, 14, 20, 23]. Age and clinical type at diagnosis are generally considered to influence the course of the disease.

Aluminium blunts the proliferative response and increases apoptosis of cultured human cells: putative relationship to alzheimer's disease

Aluminium (Al) has been investigated as a neurotoxic substance. Al ranks among the potential environmental risk factors for Alzheimers disease (AD). Epidemiological studies tested the relationship between Al in drinking water and AD, showing a significant correlation between elevated levels of monomeric Al in water and AD, although data to date remain inconclusive with respect to total Al. The aim of this study was to test whether or not Al exacerbates cellular toxicity mediated by the amyloid β (Aβ) peptide. We evaluated the role of Al in modulating programmed cell death (apoptosis) in human cell cultures. We used the osteosarcoma cell line monolayer (SaOs-2) to demonstrate that treatment of SaOs-2 cultures with the Aβ peptide mid-fragment (25 to 35) at nano M, followed by co-incubation with physiological concentrations of aluminium chloride, which release monomeric Al in solution, led to marked expression of caspase 3, but not caspase 9, key markers of the apoptotic process. The same experimental conditions were shown to blunt significantly the proliferative response of normal human peripheral blood mononuclear cells (PBMC) to phytohemagglutinin (PHA) stimulation. Our observations support the hypothesis that Al significantly impairs certain cellular immune responses, and confirm that Al-mediated cell toxicity may play an important role in AD.

Physiologic modulation of natural killer cell activity as an index of Alzheimer's disease progression

Patients with Alzheimers disease (AD) are characterized by an altered sensitivity to cortisol-mediated modulation of circulating lymphocytes. Longitudinal studies are needed to address the clinical applicability of these abnormalities as prognostic factors. Therefore, we designed a longitudinal study to address the clinical applicability of physiologic modulation of Natural Killer (NK) cell activity as a prognostic factor in AD. NK activity was assessed as baseline measurement and in response to modulation by cortisol at 10-6M. To verify the immunophysiological integrity of the NK cell population, we tested augmentation of NK cytotoxicity by human recombinant interleukin (IL)-2 (100 IU/ml) as control. The response to modulation by cortisol or by IL-2 was significantly greater in patients with AD. Based on change in the Mini-Mental State score at entry and at 18 months, patients with AD could be assigned to a “fast progression” (Δ > 2 points) or to a “slow progression” group (Δ ≤ 2 points). The change in the response of NK cytotoxic activity to cortisol, and the strength of the association of this parameter with circulating activated T cells in time was greater in patients with Fast Progression vs. Slow Progression AD. These results suggest that changes in the response of NK cells to negative (e.g., cortisol) or positive modifiers (e.g., IL-2) follow progression of AD.

Epidemiology of Motor Neuron Disease in Two Italian Provinces

Incidence and prevalence rates of motor neuron disease in two Italian provinces (Asti and Cuneo, Piedmont region) in the period 1971 through 1985 were estimated. The data were omogeneous in the investigated area, but an increasing incidence of the disease during the period studied was found, particularly in older age groups and in females. An increasing trend in mean age of onset of symptoms was also found.

Systemic autonomic involvement in episodic cluster headache: a comparison between active and remission periods

In this study we compared systemic autonomic involvement in episodic cluster headache during active and silent periods. Seventeen patients were studied with sympathetic skin response, lying to standing test, Valsalva manoeuvre, deep breathing test and orthostatic hypotension evaluation. Each of them underwent these tests during active and silent periods. Values were then compared with normal controls. Our data show a parasympathetic, but not sympathetic, involvement. Moreover, this impairment seems to be “chronic”, as it persists beyond the active period.

Neuroendocrine immunity in patients with Alzheimer's disease: toward translational epigenetics.

The emerging domain of epigenetics in molecular medicine finds application for a variety of patient populations. Here, we present fundamental neuroendocrine immune evidence obtained in patients with senile dementia of the Alzheimers type (sDAT), and discuss the implications of these data from the viewpoint of translational epigenetics of Alzheimers disease. We followed 18 subjects with mild sDAT treated with acetylcholinesterase inhibitors, and 10 control subjects matched for age in a repeated measure design every six months for 18 months. We monitored psychosocial profile (Mini-Mental State Examination, Functional Assessment Staging, Independence in Activities of Daily Living, Depression, Profile of Moods States) in parallel to immunophenotypic parameters of T cell subpopulations by flow cytometry. Based on change in the mini-mental state score at entry and at 18 months, patients with sDAT were assigned to a “fast progression” (delta greater than 2 points) or to a “slow progression” group (delta less than or equal to 2 points). The change in circulating activated T cells (CD3+Dr+) with time in patients with sDAT was significantly inversely correlated with the change in time in natural killer (NK) cytotoxic activity to cortisol modulation in these patients, which was greater in patients with fast progression, compared to slow progression sDAT. These data indicate underlying neuroendocrine immune processes during progression of sDAT. Our observations suggest that psychoimmune measures such as those we have monitored in this study provide relevant information about the evolving physiological modulation in patients with sDAT during progression of Alzheimers disease, and point to new or improved translational epigenetic treatment interventions.