AFG3L2 Biallelic Mutation: Clinical Heterogeneity in Two Italian Patients.

AFG3-like matrix AAA peptidase subunit 2 gene (AFG3L2, OMIM * 604,581) biallelic mutations lead to autosomal recessive spastic ataxia-5 SPAX5, OMIM # 614,487), a rare hereditary form of ataxia. The clinical spectrum includes early-onset cerebellar ataxia, spasticity, and progressive myoclonic epilepsy (PME). In Italy, the epidemiology of the disease is probably underestimated. The advent of next generation sequencing (NGS) technologies has speeded up the diagnosis of hereditary diseases and increased the percentage of diagnosis of rare disorders, such as the rare hereditary ataxia groups. Here, we describe two patients from two different villages in the province of Ferrara, who manifested a different clinical ataxia-plus history, although carrying the same biallelic mutation in AFG3L2 (p.Met625Ile) identified through NGS analysis.

The Sexual Dimorphism in Cerebrospinal Fluid Protein Content Does Not Affect Intrathecal IgG Synthesis in Multiple Sclerosis.

(1) Background: Multiple sclerosis (MS) is a chronic inflammatory demyelinating disease of the central nervous system (CNS) that mainly affects young adults and females more than males. The detection of intrathecal IgG synthesis (IIS) on cerebrospinal fluid (CSF) analysis supports the diagnosis of MS. A sexual dimorphism has recently been described in CSF protein content. (2) Methods: Clinical and laboratory data from 340 MS patients (F = 231, M = 99) and 89 people with clinically isolated syndrome (CIS) (F = 57, M = 32) were retrospectively analyzed to assess the presence of variables affected by sex and age. (3) Results: In MS, the albumin quotient (QAlb), reflecting the blood-CSF barrier (BCSFB) function, was higher in males (5.6 vs. 4.34) and correlated to age with a constant difference between sexes (F = 41.71). In CIS patients, QAlb increased with age only in males (r = 0.3567). Age was positively correlated to disease duration and severity in MS (r = 0.3502, r = 0.2986, respectively). No differences emerged for quantitative and qualitative IIS determinations. (4) Discussion: Although the main difference between males and females concerns the function of BCSFB assessed by QAlb, this sexual dimorphism does not affect the determination of the IIS evaluated both by quantitative and qualitative methods.

Sex-Related Differences in Cerebrospinal Fluid Plasma-Derived Proteins of Neurological Patients.

BACKGROUND AND AIMS: Cerebrospinal fluid (CSF) protein content presents a sexual dimorphism in humans. We investigated sex-related differences in CSF IgG levels and in the quantification of intrathecal IgG synthesis (IIS). METHODS: CSF, serum albumin and IgG were measured in 1519 neurological patients and both linear and hyperbolic formulas were used for the quantification of IIS. CSF-restricted oligoclonal IgG bands (OCBs) were used as "gold standard". RESULTS: The linear IgG Index showed a weak agreement with OCBs in males and females (k = 0.559, k = 0.587, respectively), while the hyperbolic Reiber's formulas had a moderate agreement with OCBs in females (k = 0.635) and a weak agreement in males (k = 0.565). Higher CSF albumin and IgG levels were found in men than in women in the whole population and in subjects without IIS after adjusting for age and for serum concentrations of albumin and IgG, respectively (Quade statistics, p < 0.000001). CSF and serum albumin and IgG levels positively correlated to age in both sexes. CSF total protein content did not correlate with CSF leukocyte numbers but was higher in patients with marked pleocytosis. CONCLUSIONS: In neurological patients, men have higher levels of CSF serum-derived proteins, such as albumin and IgG.

Attentional avoidance of emotions in functional movement disorders.

OBJECTIVE: Emotional difficulties are common in functional movement disorders (FMD), yet their contribution to the disease remains unclear. We explored the potential role of emotional difficulties as risk and maintaining factors of FMD by looking at the effect of emotions on attention. METHOD: The dot-probe task was used to investigate attentional biases induced by emotional faces in 25 patients with FMD and 25 healthy controls (HC). A pair of faces, one emotional (happy, angry, sad) and the other neutral, was displayed on a monitor to either the left or the right side of a central fixation cross. The face disappeared and a dot was flashed in place of one of the faces. Participants had to indicate the location of the dot. All participants completed the Toronto Alexithymia Scale. Psychological assessment of 23 patients also involved the Short Form Health Survey, the Hamilton Anxiety and the Hamilton Depression Rating Scales. RESULTS: A general attentional bias away from emotional faces was noted for the FMD group compared to the HC. A more fine-tuned analysis revealed an attentional bias specifically away from sad faces for the FMD. CONCLUSION: Our findings suggest a specific effect of emotions on attention in FMD that likely involves avoidance of sadness. Since this was not related to alexithymia or mood, we excluded these factors in explaining the results. Attentional bias away from sad faces correlated with general health, suggesting that avoidance of sadness might contribute to the perception of a better general health status in FMD.