Sandro Iannaccone

Pharmacologic treatment of emotional lability

Emotional lability may be a part of the syndrome of pseudobulbar palsy. Here we report our experience with fluvoxamine, a selective serotonin reuptake inhibitor, used to treat 10 patients with emotional incontinence. Over a 7-month period, we studied and treated 10 consecutive patients (mean age, 61 +/- 8 years) attending our department: four had amyotrophic lateral sclerosis (progressive bulbar palsy form), four had clinically definite multiple sclerosis, and two had had strokes. They were given a single evening dose (100 mg) of fluvoxamine. All 10 patients had > 30 affective outbursts daily. It was observed that in 2 to 6 days, all the patients improved, the number of emotional outbursts dropping to none to five per day. This result suggests that the serotoninergic system may be implicated in emotional lability. The short latency of improvement we observed in our patients suggests that the mechanism of fluvoxamine for treating emotional lability differs from its mechanism for treating affective disorders.

Dominant LMNA mutations can cause combined muscular dystrophy and peripheral neuropathy

The coexistence of neurogenic and myogenic features in scapuloperoneal syndrome is rarely ascribed to a single gene. Defects in the nuclear envelope protein lamin A/C, encoded by the LMNA gene, have been shown to be associated with a variety of disorders affecting mainly the muscular and adipose tissues and, more recently, with autosomal recessive Charcot–Marie–Tooth type 2 neuropathy. This report is about a patient presenting features of myopathy and neuropathy due to a dominant LMNA mutation, suggesting that the peripheral nerve might be affected in primary LMNA myopathy. Our observations further support the marked intrafamilial and interfamilial phenotypic heterogeneity associated with lamin A/C defects.

Emotional empathy in amyotrophic lateral sclerosis: a behavioural and voxel-based morphometry study

Abstract Amyotrophic lateral sclerosis (ALS) is a multisystem condition, in which executive and/or behavioural symptoms can occur. Deficits of social cognition, including defective cognitive and emotional empathy, have been recently reported in ALS subjects. The neurostructural correlates of these disorders in ALS are still unknown. The aims of this study were to evaluate two components of empathy in non-demented ALS subjects, and to associate performance with regional grey-matter density using voxel-based morphometry (VBM). Twenty non-demented sporadic probable or definite ALS patients and 56 matched healthy controls (HC) participated in a non-verbal task requiring the attribution of emotional versus cognitive states to identify the correct ending of comic strips, compared with a control condition requiring identifying causal relationships devoid of social components. A subgroup of 14 ALS and 20 HC joined the VBM study. Results demonstrated that, compared with controls, ALS patients showed defective emotional empathy attribution, related with reduced grey-matter density in the anterior cingulate cortex and right inferior frontal gyrus. Our study provided evidence of a specific impairment of emotional empathy in ALS patients, reflecting neural damage in a limbic prefrontal network involved in emotional processing. Social cognition disorders may represent a marker of cognitive dysfunction in ALS.

Pompholyx (vesicular eczema) after IV immunoglobulin therapy for neurologic disease

High-dose IV immunoglobulin (Ig) therapy has been used to treat various neurologic diseases and is generally considered safe. However, minor side effects occur in 10% of patients during therapy, such as headache, myalgia, chest discomfort, and fever.1 Some major effects are severe anaphylactic reactions in patients with IgA deficiency, and renal tubular necrosis occurs in patients with kidney disease or poorly hydrated patients. Skin reaction to IVIg therapy was reported recently as rare, along with minor side effects such as urticaria, pruritus, and petechiae of the extremities, which is variable in degree of involvement and body extension of dermatologic lesions.1-4 Recently, Sorensen et al.5 reported the presence of eczema as an adverse effect in patients affected by MS submitted to IVIg therapy at high doses (11 of 26 …

The Effects of a Comprehensive Rehabilitation Program of Alzheimer’s Disease in a Hospital Setting

Introduction. The evidence for the clinical effectiveness of cognitive rehabilitation in patients with Alzheimer’s Disease (AD) is debated. Therefore it is important to collect more evidence about the outcome of non-pharmacological therapy of dementia. Material and Methods. We report data concerning the rehabilitation of 50 patients with probable AD admitted during a 17-month period in a specialized unit. Participants were affected by dementia ranging from mild to severe. The patients were treated with the Reality Orientation Therapy (ROT), integrated, when needed, with individualised cognitive approaches. The results concern: the cognitive status, evaluated by means of the Mini Mental State Examination (MMSE), the functional status, evaluated with the Activity of Daily Living (ADL) scale, the assessment of psychological and behavioural disorders measured with the Neuropsychiatry Inventory (NPI). The cognitive, functional, and psychopathological assessments were administered at admission and discharge. Results. The mean MMSE scores at admission and discharge were respectively 16.06 and 17.54 (Wilcoxon Ranks Test: p = 0.005). Mean ADL scores were 4.86 at admission and 5.02 at discharge (p = 0.011). Mean NPI scores were respectively 21.46 and 12.26 (p = < 0.001). Conclusions. This survey of the 17-month experience suggests that a comprehensive treatment program may have beneficial effects on cognitive, functional, and in particular neuropsychiatric outcomes. The results should be verified with a randomised clinical trial.

Microstructural white matter correlates of emotion recognition impairment in Amyotrophic Lateral Sclerosis

Amyotrophic Lateral Sclerosis (ALS) is associated in about half of the cases with behavioral and cognitive disorders, including impairments in socio-emotional processing, considered as key-features for the diagnosis of the behavioral variant of frontotemporal dementia (bv-FTD). The neurostructural bases of emotional deficits in ALS, however, still remain largely unexplored. Here we aim to assess emotion recognition in non-demented sporadic ALS patients compared with healthy controls, and to explore for the first time its microstructural white-matter correlates. Twenty-two subjects with either probable or definite diagnosis of ALS and 55 age-, gender-, and education-matched healthy controls were recruited in the study. All participants performed the Ekman 60-Faces Test, assessing the recognition of six basic emotions (i.e., anger, disgust, fear, sadness, surprise and happiness). A subgroup of subjects, comprising 19 patients and 20 healthy controls, also underwent a Diffusion Tensor Imaging scanning. Behavioral analysis highlighted a significant decline of emotion recognition skills in patients compared to controls, particularly affecting the identification of negative emotions. Moreover, the Diffusion Tensor Imaging analyses revealed a correlation between this impairment and the alteration of white-matter integrity along the right inferior longitudinal fasciculus and inferior fronto-occipital fasciculus. Our findings indicate the presence of an early emotion recognition deficit in non-demented sporadic ALS patients, associated with microstructural changes in ventral associative bundles connecting occipital, temporo-limbic and orbitofrontal regions in the right hemisphere. These changes may represent a frontotemporal-limbic microstructural marker of socio-emotional impairment in ALS.

Intrahemispheric and interhemispheric structural network abnormalities in PLS and ALS

Using diffusion tensor (DT) magnetic resonance imaging (MRI), damage to brain intrahemispheric and interhemispheric connections was assessed in 26 sporadic primary lateral sclerosis (PLS) patients compared with 28 sporadic amyotrophic lateral sclerosis (ALS) patients with similar disability and 35 healthy controls. DT MRI diagnostic accuracy in distinguishing the two motor neuron disease (MND) variants was tested. PLS and ALS patients showed a distributed pattern of abnormalities of the motor system, including the corticospinal tracts and corpus callosum (CC). PLS versus ALS patients showed a more severe damage to the motor CC fibers and subcortical white matter (WM) underlying the primary motor cortices. Both patient groups showed an extra‐motor damage, which was more severe in PLS. This did not appear to be driven by longer disease duration in PLS. In PLS patients, damage to the CC mid‐body correlated with the severity of upper motor neuron clinical burden. CC fractional anisotropy values had the highest accuracy in distinguishing PLS from controls and ALS. PLS and ALS share an overlapped pattern of WM abnormalities. This underscores that PLS, despite its distinct clinical phenotype and long survival, still lies within the wider MND spectrum. Whether CC diffusivity may be a novel marker to increase confidence in an early diagnostic separation of PLS from ALS still needs to be investigated. Hum Brain Mapp 35:1710–1722, 2014.

Structural brain correlates of cognitive and behavioral impairment in MND

To assess the structural correlates of cognitive and behavioral impairment in motor neuron diseases (MND) using multimodal MRI.

The cognitive and behavioural profile of Amyotrophic Lateral Sclerosis: Application of the consensus criteria

Objective: The study aims to assess the spectrum of cognitive and behavioural disorders in patients affected by Amyotrophic Lateral Sclerosis (ALS) according to the recent consensus criteria [9]. The study also intends to assess the impact of physical disability on cognitive and behavioural abnormalities. Methods: Detailed neurological, neuropsychological and neurobehavioral evaluations were administered to 23 ALS patients, 11 Lower Motor Neuron Disease (LMND) patients and 39 healthy controls. Strong et al.’s criteria [9] were applied to diagnose the presence of cognitive/behavioural impairment. Clinical and neuropsychological scores were used for group comparisons and correlation analyses. Results: In comparison with LMND and controls, a subgroup of ALS patients (∼30%) manifested executive dysfunction, which was severe enough to classify them as cognitively impaired. Action naming difficulties and short-term memory deficits were also observed. Aspontaneity, disorganization and mental rigidity reached clinical relevance in 20% of ALS patients. A small percentage of ALS patients (13%) also had comorbid dementia. The cognitive or behavioural status was not related to the clinical features of ALS. Conclusion: The use of consensus criteria for cognitive and behavioural impairment and the comparison with the LMND group proved useful in defining the spectrum of non-motor manifestations of ALS.

Cross-validation of biomarkers for the early differential diagnosis and prognosis of dementia in a clinical setting

PurposeThe aim of this study was to evaluate the supportive role of molecular and structural biomarkers (CSF protein levels, FDG PET and MRI) in the early differential diagnosis of dementia in a large sample of patients with neurodegenerative dementia, and in determining the risk of disease progression in subjects with mild cognitive impairment (MCI).MethodsWe evaluated the supportive role of CSF Aβ42, t-Tau, p-Tau levels, conventional brain MRI and visual assessment of FDG PET SPM t-maps in the early diagnosis of dementia and the evaluation of MCI progression.ResultsDiagnosis based on molecular biomarkers showed the best fit with the final diagnosis at a long follow-up. FDG PET SPM t-maps had the highest diagnostic accuracy in Alzheimer’s disease and in the differential diagnosis of non-Alzheimer’s disease dementias. The p-tau/Aβ42 ratio was the only CSF biomarker providing a significant classification rate for Alzheimer’s disease. An Alzheimer’s disease-positive metabolic pattern as shown by FDG PET SPM in MCI was the best predictor of conversion to Alzheimer’s disease.ConclusionIn this clinical setting, FDG PET SPM t-maps and the p-tau/Aβ42 ratio improved clinical diagnostic accuracy, supporting the importance of these biomarkers in the emerging diagnostic criteria for Alzheimer’s disease dementia. FDG PET using SPM t-maps had the highest predictive value by identifying hypometabolic patterns in different neurodegenerative dementias and normal brain metabolism in MCI, confirming its additional crucial exclusionary role.