Case report: Asp194Ala variant in MFN2 is associated with ALS-FTD in an Italian family.

Background: MFN2 gene encodes the protein Mitofusin 2, involved in essential mitochondrial functions such as fusion, trafficking, turnover, and cellular interactions. We describe a family carrying a novel MFN2 mutation associated with ALS-frontotemporal dementia (FTD) clinical phenotype in the mother and Charcot-Marie-Tooth disease type 2A (CMT2A) in her son. Case presentation: The mother, a 67-year-old woman, referred to us for a three year-history of mood disturbance and gait impairment, and a more recent hypophonia, dysarthria, dysphagia, and diffuse muscle wasting. Family history was positive for psychiatric disorders and gait disturbances. Brain 18F-FDG PET showed severe hypometabolism in the fronto-temporal brain cortex bilaterally. Electrodiagnostic studies (EDX) showed severe motor axonopathy in the bulbar, cervical and lumbosacral districts. Her 41-year-old son had a history of mood depression and sensory disturbances in the limbs, along with mild muscle wasting, weakness, and reduced reflexes. Nerve conduction studies revealed a moderate sensory-motor polyneuropathy, while brain MRI was normal. Whole exome sequencing of the patients' DNA identified the novel MFN2 (NM_014874.4) variant c.581A>C p.(Asp194Ala). Conclusion: Our findings provide evidence of heterogenous clinical manifestations in family members sharing the same MFN2 molecular defect. Additionally, we present the first documented case of ASL-FTD associated with an MFN2 mutation, thereby expanding the range of MFN-related disorders. Further research involving larger cohorts of patients will be needed to better understand the role of MFN2 as a contributing gene in the development of ALS-FTD.

Attachment styles, identification of feelings and psychiatric symptoms in functional neurological disorders.

OBJECTIVE: The contribution of psychological and psychiatric symptoms in the development of Functional Neurological Disorders (FND) is unclear. We therefore aimed to investigate the role of different attachment styles (AS) and their relationship with psychiatric symptoms in FND patients as compared with both subjects with neurological disorders (ND) and healthy controls (HC); and the possible differences between patients with functional movement disorders (FMD) and with functional seizures. METHODS: In this case-control study, forty-six patients with FND were compared to 34 with ND and 30 HC, by means of an extensive battery to investigate the presence of alexithymia, depression, anxiety, dissociation and to explore their AS using the Revised Experiences in Close Relationships instrument (ECR-R). RESULTS: Patients with FND had higher depression and alexithymia as well as an avoidant pattern on the ECR-R than patients with ND. In the FND group, ECR-R avoidance was an independent predictor of psychiatric symptoms and, altogether, ECR-R avoidance, the somatic-affective component of depression and difficulty identifying feelings were independent predictors of FND. Gender, anxiety and difficulty identifying feelings predicted the presence of functional seizures. CONCLUSION: The avoidant AS may be an important psychological factor influencing the presence of mood disorders and alexithymia. Their co-occurence might drive maladaptive responses underlying the presence of FND. Although we demonstrated a large overlap between FND phenotypes, patients with functional seizures might have higher alexithymia, which in turn could explain a defensive response less anchored to body reactions and physical symptoms.

Comparing postural instability and gait disorder and akinetic-rigid subtyping of Parkinson disease and their stability over time.

BACKGROUND AND PURPOSE: Parkinson disease (PD) patients are classically classified according to two alternative motor subtyping methods: (i) tremor-dominant versus postural instability and gait disorder; (ii) tremor-dominant versus akinetic-rigid. The degree of overlap between the two classification systems at diagnosis of PD and their temporal stability, as well as the correspondence between the two systems, were examined over a follow-up period of 4 years. METHODS: Newly diagnosed, untreated PD patients were classified as tremor-dominant versus postural instability and gait disorder and tremor-dominant versus akinetic-rigid at baseline and after 2 and 4 years. RESULTS: There was a poor overlap between the two classification systems at any time point and baseline subtype status could not predict 4-year subtype membership. In fact, about half of our cohort shifted category during the first 2 years, regardless of the classification scheme adopted. A lower rate of shift was observed from 2- to 4-year follow-up. CONCLUSIONS: The two classical motor subtyping methods of PD poorly overlap, which implies that a patient can be categorized as tremor-dominant in one classification system but not in the other. Moreover, their temporal instability undermines their prognostic value in the early stage of PD.

Psychometric properties of the Italian version of the multifactorial memory questionnaire for adults and the elderly.

Reliable and valid metamemory measures are needed to assess subjective memory complaints that can be distinct from objective memory performance. The Multifactorial Memory Questionnaire (MMQ) evaluates dimensions of subjective memory functioning such as frequency of memory problems (Ability), affect related to memory abilities (Contentment), and strategy use in everyday life (Strategy). To examine the psychometric properties of the Italian version of the MMQ, six hundred Italian healthy individuals (aged 25-91 years) completed MMQ, a questionnaire assessing metacognition (Cognitive Failures Questionnaire, CFQ) and two batteries assessing cognitive global status (Montreal Cognitive Assessment, MoCA; Mini Mental State Examination, MMSE). MMQ was easy to administer, acceptable, and had good test-retest reliability (r for the total MMQ score 0.95), and internal consistency (Cronbach's α for the total MMQ score = 0.83). An exploratory factor analysis provided a four-factor solution: "Ability" (α = 0.99), "Contentment" (α = 0.91), "External Strategies" (α = 0.85) and "Internal Strategies" (α = 0.78) factors. MMQ total score and MMQ-Ability factor score showed good convergent validity when compared to CFQ score (r rho ≥ 0.51), whereas MMQ total score and the four MMQ factors showed good divergent validity when compared to MoCA and MMSE score (r rho ≤ 0.27). Demographic variables significantly influenced MMQ total score and most subscale scores. From the derived linear equations, we computed correction factors for raw scores and percentile distribution of adjusted scores. The Italian version of MMQ is reliable and valid to assess dimensions of metamemory in adult and elderly subjects.

Relationship between apathy and cognitive dysfunctions in de novo untreated Parkinson's disease: a prospective longitudinal study.

BACKGROUND AND PURPOSE: Apathy may be either a symptom of major depression or a behavioral disturbance occurring in concomitance with depression or alone in Parkinson's disease (PD). The aim of the present study was to determine the progression of cognitive impairment in drug-naïve untreated PD patients with or without clinically significant apathy. METHODS: Sixty-two PD patients with a disease duration <2 years and without history of present or past therapy with pro-dopaminergic agents were included and underwent the Apathy Evaluation Scale (S-AES), a clinical interview based on diagnostic criteria for apathy and a comprehensive neuropsychological battery to assess memory, frontal functions and visuospatial functions. Two years after the first assessment, all patients were re-evaluated on the S-AES, a clinical interview and neuropsychological tests. RESULTS: According to the cut-off value of the S-AES and diagnostic criteria for apathy, eight patients experienced apathy at both baseline and follow-up (A+A+), nine patients had apathy only at follow-up (A-A+), 37 patients never experienced apathy (A-A-) and eight patients showed apathy at the baseline only (A+A-). Cognitive performance significantly declined in all four groups. At both baseline and follow-up A+A+ performed worse than A-A- on visuospatial and frontal tests; A-A+ had lower scores than A-A- on the interference task of the Stroop test (IT-ST). Regression analysis showed that poor performance on the IT-ST at baseline was the only independent predictor of onset of apathy at follow-up. CONCLUSIONS: The results indicated a relationship between apathy and dysexecutive syndrome in early PD. Reduced scores on the IT-ST may predict development of apathy in PD patients.