The role of puberty and adolescence in the pathobiology of pediatric multiple sclerosis

Abstract Multiple sclerosis (MS) is increasingly recognized in the paediatric age. In a smaller, but well-established, proportion of paediatric MS patients [20% of total paediatric MS cases: 0.2% to 0.7% of the total MS patients] the onset of disease is before 10 years of age [pre-pubescent (childhood) MS]; in the majority [80%] of paediatric MS patients, however [1.7% to 5.6% of the total MS population], the onset of disease is between 10 and 18 years [post-pubertal (juvenile) MS]. Notably, while pre-pubertal MS occurs almost equally in both genders (female/male ratio = 0.9:1; reverting to 0.4–0.6/1 in pre-school MS children) the female/male ratio rises to 2.2/3:1 in the post-pubertal age. Interestingly, precocious puberty has been associated to: (a) a higher risk of developing MS; and (b) a more severe disease course. In addition to that, males are more susceptible to MS (and manifest more neurodegeneration) than females the latter being however more inflammatory than males; pregnancy however reduces MS relapses. All the above findings led to the suggestion of an underlying female sex hormonal involvement in the pathophysiology of MS vs. a protective role of male sex hormones. Epigenetic perspectives indicate that the interplay between genetic background, environmental triggers and neuroendocrine changes, typically occurring around the time of adolescence, could all play a combined role in initiating and/or promoting MS with onset in the paediatric age including many of the most frequent disease-associated risk factors (e.g., overweight/obesity, low vitamin D levels, reduced sunlight exposure, Epstein-Barr virus infection). According to this proposed complex multifactorial model, susceptibility to MS may be thus acquired during pre-pubertal age and children have probably to wait until the adolescence to manifest their first clinical signs/symptoms

Risk factors for cognitive impairment in subjects with Behçet's disease

In the present study we evaluated the prevalence and risk factors for cognitive impairment in subjects with Behçet's Disease (BD). The following risk factors were studied: age, education, disease duration, activity of disease, prednisone dosage, and anxiety and depression levels. Twenty-six BD out-patients without overt neurological involvement and 26 sex-matched controls completed a comprehensive neuropsychological battery. Compared to controls, BD subjects were significantly impaired on tasks evaluating long-term verbal and nonverbal memory, and visuospatial skills. Cognitive impairment was evident in 46.1% of BD patients compared with none of control subjects (p<.0001), with memory representing the cognitive domain most affected. Both high disease activity (OR 1.3, 95% CI 1.0-1.5, p <.04) and prednisone dosages (OR 1.3, 95% CI 1.0-1.7, p <.03) were associated with cognitive impairment in BD after adjustment for demographics. Cognitive impairment is frequent in BD subjects without overt neurological involvement, and involves mainly memory functions. It is more common in patients with active disease and in those receiving prednisone

Migraine without aura as a possible sign of covert neurological involvement in Behçet's disease: A case-control study

In the present study we evaluate the prevalence of headache and the frequency of different primary headaches in patients with Bebçet's Disease (BD) without neurological involvement. Furthermore, we investigate the relationship between headache with other clinical, and behavioural variables. Twenty-seven BD patients and 27 control subjects underwent a validated semi-structured questionnaire based on the International Headache Society criteria. Levels of anxiety and depression, disease activity, and current medication were collected. Headache occurred in about 90% of BD patients. There was no difference in the prevalence of the different headache syndromes between BD patients and controls. Only migraine without aura (MwA) was significantly more frequent in BD patients than controls (44.4% vs 11.1% respectively, p.013). No relationship was found between MwA and clinical, and behavioural variables. Among headache syndromes, MwA showed the highest frequency in BD. A vascular or neuronal brainstem subclinical dysfunction could justify this association. A careful interview for migraine might be included in the diagnostic work-up of BD

Five-year longitudinal study of juvenile migraine headaches

To evaluate the prevalence and the evolution over 5-year of juvenile migraine headaches. Sixty-four subjects selected in our 1989 epidemiological survey were included in the study. The criteria of the International Headache Society were used both in 1989 and 1994. Thirty-two out of 64 subjects (50%) had MWAO, 18 (28.1%) had MD and 14 (21.9%) had headache not classifiable (HnC). MWOA persists in 56.2%, becomes MD and HnC in 9.4% and 3.1% of cases respectively, changes to episodic tension-type headache (ETTH) in 12.5%, and remits in 18.8%. MD persists in 11.1%, becomes MWOA and HnC in 27.8% and 5.5% of cases respectively, changes to ETTH in 11.1, and remits in 44.5%. HnC persists in 14.3%, becomes MD and MWOA in 21.4% and 14.3% of cases respectively, changes to ETTH in 14.3%, and remits in 35.7%. Our data confirm that MWOA and MD with juvenile onset change their characteristics over time having basically a favourable prognosis