Chiara Piccininni

Long-term outcome of subthalamic nucleus DBS in Parkinson's disease: from the advanced phase towards the late stage of the disease?

BACKGROUND Deep Brain Stimulation of the Subthalamic Nucleus (STN-DBS) is an effective treatment for Parkinsons disease (PD), but only few studies investigated its long-term efficacy. Furthermore, little is known about the role of PD-subtype on STN-DBS long-term outcome. OBJECTIVE To report the results of a long-term follow-up (mean 11 years, range 10-13) on 26 patients bilaterally implanted in two centres. METHODS Patients were assessed preoperatively and 1, 5 and 11 years after the implant by the Unified Parkinsons Disease Rating Scale (UPDRS) and a battery of neuropsychological tests. Stimulation parameters, drugs dosages, non-motor symptoms and adverse events were also recorded. RESULTS At 11 years, stimulation significantly improved the motor symptoms by 35.8%, as compared to the preoperative off-state. Motor complications were well controlled, with a 84.6% improvement of dyskinesias and a 65.8% improvement of motor fluctuations. Despite this, the UPDRS-II-on score worsened by 88.5%, mainly for the worsening of poorly levodopa-responsive symptoms. More than 70% of the patients performed in the normal range in most of the neuropsychological tests, despite the development of dementia in 22.7%. Age at disease onset, axial subscore in off-condition and presence of REM behaviour disorder at baseline were found to be associated with a higher risk of developing disability over time. CONCLUSIONS Our study confirms the long-term safety and efficacy of STN-DBS in PD. Nevertheless, the functionality of patients worsens over time, mainly for the onset and progression of levodopa-resistant and non-motor symptoms. The role of PD-subtype seems to be relevant in the long-term outcome.

Selective impairment of action-verb naming and comprehension in progressive supranuclear palsy

Some previous studies in brain-damaged patients suggested that neural systems in the left temporal lobe might be crucial in the production and comprehension of nouns, while analogous systems in posterior frontal cortical areas might be involved in the production and comprehension of verbs. We assessed performance on neuropsychological tasks of production and comprehension of nouns and action-verbs in 10 patients with progressive supranuclear palsy (PSP) and in 10 age-matched healthy controls. PSP patients also underwent measurements of regional cerebral blood flow by means of single photon emission computed tomography (SPECT), using 99mTc-Ethyl Cysteinate Dimer. In all PSP patients, SPECT showed a significant hypoperfusion in the inferior frontal gyrus (IFG). PSP patients performed significantly worse than controls on all lexical-semantic tasks, except for the auditory lexical decision task on nouns. Within PSP patients, however, a significantly lower performance was observed on action-verbs as compared to nouns on various lexical-semantic tasks (oral and written confrontation naming, auditory and visual single-word comprehension). Analysis of individual performance revealed heterogeneous patterns of neuropsychological impairment in different PSP patients. Despite some difficulty in drawing clear-cut conclusions about the locus of functional damage, we hypothesise that in most of our PSP patients such selective impairment in the production and in the comprehension of action-verbs could be due to semantic deficits affecting the conceptual category of actions. These findings are consistent with the hypothesis that in PSP a dysfunction of neural systems in posterior frontal cortical areas (mainly involving the IFG) critical for processing the conceptual category of actions might result in a selective impairment of production and comprehension of action-verbs.

The Multiple Features Target Cancellation (MFTC): an attentional visual conjunction search test. Normative values for the Italian population

Several studies, showing that attention disorders during encoding reduce later memory performance, have stressed the critical role of attention for the formation of durable memory traces. Accordingly, some studies suggest that attentive disturbances, together with declarative memory defects, can constitute the earliest cognitive disorders in Alzheimer’s disease. Therefore, the analysis of these disorders can contribute to identify different forms of dementia and to detect demented patients characterized by a faster cognitive decline. In this study, we report the normative data (gathered in a large Italian population) of a short test that assess the ability to detect stimuli characterized by a conjunction of features: the ‘Multiple Features Targets Cancellation’ task (MFTC). Our sample of 465 subjects was composed by urban and rural people. Multiple linear regression analyses revealed significant relation of false alarms with age and educational level, and of time of execution with age, educational level and gender. Regression analyses on accuracy scores did not show any significant correlation with demographics variables. Based on non-parametric techniques, cutoff scores were obtained on the corrected scores of the patients, and equivalent scores were derived for each measure. The MFTC task represents a useful tool that explores attentional disorders (and in particular conjunction search disturbances) and that could be helpful both in discriminating different forms of dementia and to detect mild cognitive impairment patients at risk of conversion to dementia.

Frontotemporal dementia, Parkinsonism and lower motor neuron involvement in a patient with C9ORF72 expansion

It has been recently reported that a large proportion of patients with familial and sporadic amyotrophic lateral sclerosis (ALS) and/or frontotemporal dementia (FTD) carries the hexanucleotide (GGGGCC) repeat expansion in the first intron of C9ORF72. We describe a patient with a complex phenotype characterized by behavioural variant of FTD, Parkinsonism and ALS with predominant lower motor neuron involvement in which the C9ORF72 expansion was detected.

Presentation and Validation of the Multiple Sclerosis Depression Rating Scale: A Test Specifically Devised to Investigate Affective Disorders in Multiple Sclerosis Patients

Accurate diagnosis of depression in patients affected by MS is important, as it may be a cause of reduced quality of life and increased suicide risk. We present a new scale, the Multiple Sclerosis Depression Rating Scale (MSDRS), and assess its diagnostic accuracy in comparison to the Beck Depression Inventory (BDI). A total of 94 MS participants were classified as non-depressed (N = 44) or affected by mood disorder associated to MS with depressive manifestations (MSD-MDDM; N = 37) or with a major depression-like episode (MSD-MDL; N = 13). Each participant underwent a psychiatric interview, MSDRS, and BDI; diagnostic accuracy was evaluated using area under the ROC curve (AROC). The diagnostic accuracy of MSDRS and BDI was comparable when diagnosing both MSD-MDDM and MSD-MDL (AROC respectively 0.8998 and 0.8659); the MSDRS showed higher accuracy for the diagnosis of MSD-MDL (AROC respectively 0.9278 and 0.8314; p = .038). The MSDRS may be a reliable tool for the diagnosis of depression in MS.

Recognition disorders for famous faces and voices: a review of the literature and normative data of a new test battery

Several anatomo-clinical investigations have shown that familiar face recognition disorders not due to high level perceptual defects are often observed in patients with lesions of the right anterior temporal lobe (ATL). The meaning of these findings is, however, controversial, because some authors claim that these patients show pure instances of modality-specific ‘associative prosopagnosia’, whereas other authors maintain that in these patients voice recognition is also impaired and that these patients have a ‘multimodal person recognition disorder’. To solve the problem of the nature of famous faces recognition disorders in patients affected by right ATL lesions, it is therefore very important to verify with formal tests if these patients are or are not able to recognize others by voice, but a direct comparison between the two modalities is hindered by the fact that voice recognition is more difficult than face recognition. To circumvent this difficulty, we constructed a test battery in which subjects were requested to recognize the same persons (well-known at the national level) through their faces and voices, evaluating familiarity and identification processes. The present paper describes the ‘Famous People Recognition Battery’ and reports the normative data necessary to clarify the nature of person recognition disorders observed in patients affected by right ATL lesions.

Cognitive and Behavioral Determinants of Psychotic Symptoms in Alzheimer's Disease

Aims: To investigate the relationship between psychotic symptoms and cognitive impairment in Alzheimers disease (AD). Methods: A total of 108 subjects affected by AD were subdivided into subjects without delusions (ND), subjects with paranoid delusions (PD), subjects with delusional misidentifications (DM), subjects with both DM and PD (DM+PD), subjects with visual hallucinations (v-HALL), and subjects without visual hallucinations (N-HALL). Results: PD and ND subjects performed similarly on neuropsychological tests, while DM patients performed significantly worse than PD and ND patients. v-HALL patients performed worse than N-HALL patients on memory, visuospatial, and executive functions. As for behavioral features, DM and v-HALL subjects reported higher scores on the abnormal motor behavior subscale of the neuropsychiatric inventory (NPI); PD subjects reported higher scores on the disinhibition subscale of the NPI. The severity of PD was predicted by the severity of disinhibition (B = 0.514; p = 0.016) but not by neuropsychological performances. The severity of DM was predicted by age (B = 0.099; p = 0.048) and MMSE (B = -0.233; p = 0.001). The severity of v-HALL was predicted by age (B = 0.052; p = 0.037) and scores on an immediate visual memory task (B = -0.135; p = 0.007). Conclusions: The occurrence of PD may require the relative sparing of cognitive functions and be favored by frontal lobe dysfunction, while DM is associated with the overall level of cognitive impairment. Finally, v-HALL are associated with the impairment of visuospatial abilities.

Standardization, Clinical Validation, and Typicality Norms of a New Test Assessing Semantic Verbal Fluency

OBJECTIVE Semantic verbal fluency (SVF) tests are widely used in clinical neuropsychology. We propose the standardization and clinical validation of a new SVF test based on the production of names of birds and articles of furniture (Birds and Articles of Furniture test-BAF). METHODS A sample of 268 subjects aged 40 years or more underwent the test. The clinical validation was conducted on subjects affected by amnesic Mild Cognitive Impairment (aMCI; N = 106), mild (N = 178), and moderate (N = 114) Alzheimers disease (AD). RESULTS The BAF total score was influenced by both age and education, whereas the single scores obtained on BAF were also influenced by gender. The percentage of subjects with pathological score on BAF increased from aMCI (19%) to mild (45.5%) and moderate (71.1%) AD, and receiver operating characteristic curves analysis showed that the BAF may be highly reliable in distinguishing aMCI and AD patients from healthy subjects. We also provide typicality norms for birds and articles of furniture that could be useful in the assessment of qualitative features of words produced in semantic fluency tests. CONCLUSIONS The BAF test could be a valid and reliable tool in both clinical practice and research on subjects affected by cognitive impairment.

Usefulness of an Integrated Analysis of Different Memory Tasks to Predict the Progression from Mild Cognitive Impairment to Alzheimer's Disease: The Episodic Memory Score (EMS)

Taking into the account both the severity and the consistency of performances obtained on memory tests by patients with amnestic mild cognitive impairment (aMCI) could improve the power to predict their progression to Alzheimers disease. For this purpose, we constructed the Episodic Memory Score (EMS), which is obtained by subdividing in tertiles performances obtained at baseline in verbal (RAVLT) and visual episodic memory (Rey-Osterrieth Figure-delayed recall) and giving a score ranging from 1 (worst result) to 3 (best result) to results falling within each tertile. The EMS was computed for each patient by summing the tertile score obtained on each memory task, so that the total score ranged from 4 (worst performance) to 12 (best performance). The aMCI sample consisted of 198 subjects who completed the two-year follow-up, at the end of which 55 subjects had converted to dementia. The mean EMS score obtained by aMCI converters was significantly lower than that of aMCI-stable patients. In detecting conversion to dementia, the comparison between EMS and individual memory scores obtained at baseline was made by computing ROC curves, and estimating the respective area under the curve (AUC). The EMS had a larger AUC than the individual memory scores. At baseline aMCI converters performed worse than non-converters not only on memory tasks, but also on executive functions tasks. However, in a multiple variables logistic regression analysis in which all scores showing statistically significant differences between aMCI-converters and aMCI-stable were entered, the EMS was the only reliable predictor of progression from aMCI to dementia.

Cognitive and Behavioural Changes After Deep Brain Stimulation of the Subthalamic Nucleus in Parkinson's Disease

In patients with Parkinson’s disease, cognitive impairment is common, may be detectable in early disease stages, even in young patients, and may progress to overt dementia. In addition, a variety of psychiatric and behavioural symptoms may occur in Parkinsonian patients, including depression, apathy, anxiety, visual hallucinations, sleep disorders, impulse control disorders, punding and the dopamine dysregulation syndrome. The cognitive and behavioural symptoms observed in these patients may be part of the non-motor symptoms of Parkinson’s disease, which can appear in various phases of the disease course.