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Introduction: Before the COVID-19 pandemic, research had shown high (and variable) prevalences of the use of Complementary and/or Alternative Medicine (CAM; eg., 70%), in adults and children, dependent, neverthless, on the type of practice. Objective: To characterize adults’ experience with conventional and non-conventional health (self-)care practices during the COVID-19 pandemic in Portugal. Method: After obtaining the necessary authorizations, between 1/10-27/11/2021, a total of 104 adults living in Portugal answered to a Google Forms questionnaire on health (self-)care practices. Results: As for the last time the participants performed any health (self-)care practice: - 47,6% evaluated the results they obtained as good and 14.3% as very good; - 59.5% were satisfied with that practice; - 27.1% considered it a non-conventional practice and 20% were not sure. In terms of health (self-)care practices: 65.2% reported using conventional and non-conventional practices. Among those who have ever used any non-conventional practice: - 50% did it using a professional and 33.9% by themselves and using a professional; - 48.4% use it rarely; - 17.9% started using it more frequently since the start of the COVID-19 pandemic; - 93.8% had never done it against the recommendation of a (conventional) health professional. Since the beginning of the pandemic: 11.2% had at least one appointment with a non-conventional health professional; and 4.1% had more appointments with non-conventional health professionals than with conventional health professionals. Regarding negative experiences with non-conventional practices, 89.7% never had any. Conclusions: Since: (a) participants were mostly satisfied with their last health (self-)care practice/its results, predominantly a conventional practice, even though the majority use both types of practices; (b) when using non-conventional practices, only a minority use it by themselves and the majority with some frequency; (c) its (generally rational) use did not increase considerably with the pandemic; and (d) few negative experiences were reported, these preliminary results are not alarming. Nevertheless, they do suggest a need to increase health care professionals’, non-conventional users’ and non-users’ knowledge about these practices to ensure patients’ safety.

"Research has shown the frequent use of complementary and alternative medicine (CAM), its potentialities and risks. Aim: To characterize adults’ knowledge and practices of CAM in order to identify the need to develop lifelong learning programs. After obtaining the necessary authorizations, between 1/10-5/12/2021, 115 adults living in Portugal, mostly women with a higher education degree, working full-time, with a monthly income perceived as medium, answered a Google Forms questionnaire on health (self-)care practices (HsCP). Most considered their health as good (44.3%), being satisfied with it (53%). The majority: took some care of their health (60.5%; 28.1% a lot); had no physical (56.1%) or psychological (78.3%) health problem diagnosed by a conventional health care professional. Regarding the extent to which the participants had knowledge of non-conventional health (self-)care practices (NCHsCP), most (39.5%) knew little about it (10.5% had no knowledge). The majority: had already looked for information about NCHsCP (55.8%), was interested in having (more) knowledge about it (77.2%), and had someone close to them who used and/or was using some non-conventional practice - NCP (57%). Only 14.2% had done training in some NCP and 5.3% considered it impossible to reconcile conventional and NCHsCP. The majority (65.8%) stated that knowledge about NCP is important to them as (future) health professionals (not applicable to 26.3%). As for the last time participants performed any HsCP, 30.2% considered it a NCP (19.8% were not sure). In terms of HsCP, 66.7% reported using conventional and NCP. Among those who have ever used any NCP: 47.1% did it with a professional and 34.3% by themselves and with a professional; 45.8% use it rarely; 93.2% had never done it against the recommendation of a (conventional) health professional. Among those regularly (at least once a year) accompanied by one or more conventional health care professionals, 54% had never talked about NCP. Regarding negative experiences with NCP, 89.8% never had any. The minor children of 13.9% had done some NCP (not applicable to 60.2%). Among the health care professionals, 80.2% had no course during their training mentioning NCP; in their professional experience, 64.2% had knowledge of situations in which conventional and NCP were used simultaneously; in the context of their professional activity: 51.9% had recommended, and 40.7% had referred someone to NCP. Even though these preliminary results are not worrying, they suggest adults living in Portugal would greatly benefit from lifelong learning programs focusing on the potentialities and risks of CAM."

Rapidly progressive cognitive impairment is a diagnostic criterion in Creutzfeldt-Jakob disease (CJD), but the diagnosis is usually reached when an analysis of cognitive aspects is no longer possible.This study aims to delineate the cognitive phenotypes preceding severe dementia in CJD compared to secondary metabolic encephalopathies (SME) with rapid cognitive impairment.Patients with rapidly progressive neurological symptoms underwent neuropsychological evaluation, analysis of cerebrospinal fluid (CSF) and codon 129 polymorphism of the prion protein gene (PRNP), magnetic resonance imaging (MRI), and single positron emission computed tomography (Thirty-one patients were diagnosed with CJD (n = 17) or SME; 77 cases of CJD were extracted from the literature. In patients with CJD, verbal initiative, lexical search, long-term memory, attention, and abstract reasoning were the most frequently impaired abilities. Cognitive profiles were mainly related to dysfunction in fronto-temporal areas. Furthermore, they were consistent with areas of hypoperfusion detected byIn CJD, clinical and neuropsychological analyses outline a salient cognitive phenotype suggestive of fronto-temporal dysfunction preceding severe dementia. This phenotype is different from that observed in other rapidly progressive encephalopathies.

Behavioral variant frontotemporal dementia (bvFTD) and theory of mind (ToM) have common neuroanatomical aspects. This pilot study analyzed the qualitative features of ToM relatively to the site of prefrontal atrophy, aiming to identify a neurobehavioral pattern of bvFTD. Fourteen bvFTD patients were compared with 14 healthy subjects with similar age, years of schooling, gender distribution, and social background. The faux pas task (FPT) measured the recognition and comprehension of faux pas (FP) and awareness of the factual details on 20 stories. Magnetic resonance assessed prefrontal atrophy. The bvFTD patients were significantly impaired in FP recognition and comprehension and in attribution of non-existent FP. Qualitative analysis revealed five types of errors: misidentification of characters, misidentification of emotions, excessive cohesiveness to the factual context, delusional interpretations, and non-responses. The FPT recognition and comprehension scores were unrelated to story factual details or other neuropsychological performance. Conversely, the FP comprehension scores related to disease duration, the delusional errors to disease duration and prefrontal orbital atrophy, and the cohesiveness errors to age and prefrontal dorsolateral atrophy. In bvFTD, ToM is characterized by misinterpretation of mental states and concrete thinking, which is related to disease severity and distinct areas of prefrontal atrophy. This neurobehavioral pattern may be a marker for bvFDT.

Purpose The patients with neurological disorders often report a different quality of life (QoL), which is in part explained by clinical–pathological or psychosocial variables. This study evaluated spirituality in patients with chronic brain pathologies, aiming to clarify its specificity and position to a multidimensional model of QoL. Methods A hundred and ninety-nine adult patients with epilepsy (E) (n = 88), mild cognitive impairment (MCI) (n = 32), ischemic vascular disorders (n = 29), tumors (n = 28), or multiple sclerosis (MS) (n = 22), and 66 healthy subjects were assessed using the World Health Organization Quality of Life (WHOQoL) 100, Spiritual, Religious and Personal Beliefs (SRPB), Beck Depression Inventory (BDI), and State–Trait Anxiety Inventory (STAI) for the QoL, spirituality, depression, and anxiety. The Multiple Ability Self-Report Questionnaire (MASQ) and neuropsychological tests evaluated the cognitive functions. Results Factor analysis of the SRPB, STAI, and BDI scores yielded four factors: Personal Meaning, Inner Freedom, Awe and Openness, and Mood. Quality of life and spirituality were very similar between the patient groups. In comparison with the controls, all of the patients showed worse QoL, spirituality, mood, and lexical-memory abilities, and the patients with MCI and brain vascular disorders (BVD) also revealed worse cognitive impairments. Trait anxiety, self-rated health, age, and the SRPB Inner independence and Hope and optimism facets predicted the patients' WHOQoL 100 total score; the spiritual, affective, and socioeconomic variables predicted many QoL domains, but diagnosis only affected the Physical domain. Anxiety, self-rated health, Hope and optimism, and Personal beliefs predicted the controls' WHOQoL 100 total score. Conclusions Spirituality, as marked by the meaning of self, inner independence, and transcendence, is distinct from mood. It cooperates, together with the affective states, to determine the QoL of the patients with chronic brain pathologies whereas diagnosis has a limited impact. These findings support a multidimensional cross-disease model for the QoL in neurological disorders.

To compare neuropsychological function in juvenile myoclonic epilepsy (JME) and frontal lobe epilepsy (FLE) since frontal circuitry is involved in both conditions. By drawing on previously theory-guided hypotheses and findings, a particular emphasis is placed on the way different cognitive-pathophysiological mechanisms act upon to produce frontal dysfunction in JME (frontal-executive and attention-related problems: vigilance, reaction times, processing speed, and response inhibition) and in FLE (reflecting the coproduct of the functional deficit zone), respectively.A total of 16 patients with JME, 34 patients with FLE, and 48 normal controls, all matched for age and education, were administered a comprehensive battery of tests to assess frontal-executive functions, as well as attention, memory, and learning domains. Participants did not take medications other than antiepileptics or have a psychiatric history.Patients with FLE overall showed worse neuropsychological performance compared to both JME and HCs. With respect to JME, patients with FLE did significantly worse in measures of verbal and nonverbal executive function, short-term-, and long-term- auditory-verbal memory and learning, immediate and delayed episodic recall, visual attention and motor function, visuo-motor coordination and psychomotor speed, speed of visual information processing, and vocabulary. Patients with JME performed significantly worse compared to FLE only in associative semantic processing, while the former outperformed all groups in vocabulary, visuomotor coordination, and psychomotor speed.We suggest that selective impairments of visual- and mostly auditory-speed of information processing, vigilance, and response inhibition may represent a salient neuropsychological feature in JME. These findings suggest the existence of an aberrantly working executive-attention system, secondary to pathological reticulo-thalamo-cortical dynamics. Contrariwise, cortically (frontal and extra-frontal) and subcortically induced malfunction in FLE is determined by the functional deficit zone i.e., the ensemble of cortical and subcortical areas that are functionally abnormal between seizures.

Objectives In an integrated model of social cognition (SC), the theory of mind (ToM), the recognition of behavior in social situations (RBSS), empathy, and sensitivity to moral and conventional rules (SMCR) cooperate in generating mental representations of the interpersonal relationships. The aim of this study was to extend our knowledge of the SC of temporal lobe epilepsy (TLE) patients by characterizing its various aspects and predictors. Materials and methods Fifty adult patients with TLE and 50 healthy controls were assessed using ToM, RBSS and SMCR neuropsychological tests, the Empathy Questionnaire, and the psychopathology Symptoms Check List 90R (SCL90-R). Results Patients and controls were similar in terms of occupation, income level, age, sex, marital status and the number of family members. Multivariate analysis of variance with demographic variables as the covariates showed that they were similar in SMCR and empathy. The patients, conversely, had lower ToM and RBSS scores, and higher scores on the SCL90-R psychoticism, depression, paranoid ideation, obsessive-compulsive, somatization and anxiety scales. Impaired RBSS was predicted by psychopathological symptoms, income level, schooling and the duration of epilepsy; ToM related to TLE laterality, seizure frequency and epilepsy duration. Conclusions In adult patients with TLE, SC is simultaneously partially impaired and partially preserved, and the fact this is associated with clinical, demographic and psychological variables suggests that SC depends on the integrity of the temporal lobe and the interconnected brain regions, as well as psychosocial stimuli. This approach may contribute to clarify the neurobehavioural phenotype of TLE.

Objective Previous studies of frontal lobe epilepsy (FLE) have documented different impairments of theory of mind (ToM), while the study of frontal lobe (FL) lesion without seizures has produced inconsistent results. Given the role played by the FLs in ToM, we evaluated this and other functions in patients with FLE with and without FL lesions. The main objective was to clarify the salience of ToM impairment in the cognitive pattern of FLE and its capacity to discriminate these patients from healthy subjects. The effects of FL lesions on ToM were also explored. Methods Seventy-five adult patients with FLE (40 cases with FL lesions) were compared with 42 healthy controls. The Faux Pas Task (FPT) and other neuropsychological tests were utilized to assess ToM, reasoning, language, memory, praxis, attention, and executive abilities. Results The patients obtained lower z scores for the FPT than for other tests. The ToM, Executive, and Verbal factors discriminated patients from healthy subjects. The patients with or without FL lesion showed significant impairments in recognizing and understanding others' epistemic and affective mental states, but adequate capacity to exclude inexistent mental states was retained. In comparison with controls, the patients with FL lesions obtained lower scores for lexical, memory, praxis, attention, and executive functions, whereas those without lesion only showed attention and initiative deficits. Schooling was the major predictor of ToM, whereas the capacity to exclude inexistent mental states was related to seizure onset age and epilepsy duration. Other cognitive functions were related to schooling, age, or FLE laterality. Significance Impaired understanding of real mental states is a specific, salient, and discriminating cognitive aspect of FLE. Poor education is a risk factor for ToM deficit, whereas the clinical variables and FL lesions have no impact. These results suggest that impaired ToM may be a marker of FLE neurobehavioral phenotype.

People with epilepsy often suffer psychiatric symptoms or exhibit maladaptive personality characteristics which can impact them more than seizures. This case illustrates a selective association of a Theory of Mind dysfunction, including an impaired comparison of reality and others' behavior, with an obsessive-compulsive personality disorder in a patient with left temporal lobe epilepsy and crossed cognitive functions. The patient revealed visual memory deficits and impaired interpretation of other people's behavior, mental rigidity, and a tendency to formulate inflexible judgements. Moreover, she shows impairment in understanding and sharing the emotional states of others in reference to herself (Empathic Quotient); her social relations are limited to her parents. Patients with right temporal lobe epilepsy frequently report persistent and rigid actions and thoughts, and this can have substantial psychological and social consequences for everyday life. We suggest that this could be a case of crossed cognitive functions, in particular ToM, and crossed psychobehavioral functions linked to right-hemisphere damage.

Objective In patients with brain lesion, awareness of cognitive deficits is an important aspect of disease awareness. Glioblastoma (GBM) and anaplastic astrocytoma (AA) can cause cognitive deficits, but, to date, awareness of these deficits has not been documented. This study aimed to test cognitive awareness in these patients after the end of treatment. Methods Fifty patients with GBM or AA were assessed using the Multiple Ability Self-Report Questionnaire (MASQ), State-Trait Anxiety Inventory (STAI), Self Rating Depression Scale (SRDS), and memory, attention, mental speed, abstract reasoning, and flexibility neuropsychological tests. Cognitive awareness was calculated as the concordance between the composite score of neuropsychological performance (PEC) and the total MASQ score. The controls were 48 healthy subjects. Analysis of variance and regression analysis compared subject groups and explored variables predicting perceived abilities. Results Patients with GBM or AA showed similar attention, memory, and executive deficits compared with controls. Cognitive awareness was fair/full in 64% of patients. In the entire patients group, the worst MASQ scores were associated with neuropsychological deficits, anxiety, depression, and glioma location in the right hemisphere . In patients with fair/full awareness, MASQ scores were related to affective status and neuropsychological performance, whereas, in those with scarce/no awareness, they were related only to affective status. Conclusions After treatment, many patients with GBM or AA are aware of their cognitive deficits. Anxiety, depression, and right hemisphere tumour exacerbate the perceived difficulties. This neurocognitive approach expands the behavioural phenotypes of high-grade gliomas and may have therapeutic implications over the course of the disease.

Summary Objective Because temporal lobe epilepsy (TLE) can impair theory of mind (ToM), we examined the effects of anterior temporal lobectomy (ATL) by comparing the preoperative to postoperative ToM course with that of other cognitive functions characteristically impaired in TLE. Methods Eighty-five patients with left (n = 39) or right (n = 46) drug-resistant TLE and an age at epilepsy onset of >12 (n = 54) or ≤12 years (n = 31) were evaluated before and 1 year after surgery; 40 healthy controls were assessed at baseline. The participants' recognition and comprehension of faux pas (FPs) or correct rejection of nonexistent FPs was assessed using the Faux Pas task; and their language, memory, and planning were, respectively, assessed using the Boston Naming, Short Story, and Tower of London tests. Results Baseline ToM was impaired in the patients with left or right TLE in comparison with the controls, and significantly influenced by education and age at seizure onset, with more severe deficits being observed in those with less education and an age at onset of ≤12 years. After ATL, their recognition and comprehension of FPs was unchanged, whereas the rejection of nonexistent FPs improved in the patients with early seizure onset. Education, preoperative ToM, postoperative executive function, and fluid intelligence and the number of antiepileptic drugs predicted postoperative ToM. Postoperative naming and episodic memory were associated with ATL laterality and education, and planning was associated with age at seizure onset and chronological age. Significance After ATL, the components of ToM may be unchanged or slightly improved depending on cognitive reserve and age at seizure onset, thus suggesting that ATL does not further aggravate the deficits caused by TLE. Moreover, the course of ToM is distinct from that of other cognitive functions. These findings expand the spectrum of the cognitive phenotypes associated with TLE and ATL, and offer potential elements for individual prognoses.

Purpose This study was aimed to evaluate the impact of frontal (FLE) and temporal lobe epilepsy (TLE) on graphic creativity. Methods A hundred and six patients with FLE (n = 32) or TLE (n = 74) and 38 healthy subjects underwent a design fluency (DF) test constituted by a free and a fixed condition. For each condition, the number of correct designs, as an index of creativity, and unacceptable nonperseveration or perseveration designs were calculated. The participants also underwent a comprehensive neuropsychological battery. Results The number of novel correct designs significantly differed between the groups: patients with FLE produced fewer designs than patients with TLE and controls, while epilepsy laterality had no effect. Patients with FLE also produced more unacceptable nonperseveration designs than controls, with no between-group differences in the perseverations. The number of novel designs was predicted by the type of epilepsy, whereas word fluency, comprehension, attention, set shifting, visual matching, and constructive praxis had no influence. This score was a sensitive marker of FLE discriminating FLE cognitive pattern from the pattern of TLE and healthy condition. Conclusions Left or right FLE, but not TLE, can impair graphic creativity. This finding and that DF was unrelated to other cognitive abilities suggest that creativity is a specific domain, sensitive to epilepsy-related frontal lobe dysfunctions. This behavioral approach including test accuracy may have implications in defining FLE cognitive phenotype.

Purpose Structural brain imaging has revealed that damage to different brain regions may impair theory of mind (ToM) while functional imaging has shown that distributed neural circuits are activated by ToM and empathy. However, the coherence of the electroencephalogram (EEG) frequencies in a definite time span may change during these processes, indicating different neurophysiological correlates. This study evaluated the changes of EEG coherence during ToM tasks in comparison with Empathy, Physical causality, and baseline conditions, aiming to determine the neurophysiological correlates of ToM. Methods Sixteen healthy adults underwent a visual activation paradigm using 30 comic strips concerning ToM, Empathy, or Physical causality during EEG recording. The interhemispheric coherence was estimated using a bivariate autoregressive (AR) parametric model. The coherence spectra were analyzed in the alpha, beta, and gamma frequency EEG bands. Results Coherence analysis taking all of the responses showed that in the gamma band, in comparison with the Empathy, Physical causality, and baseline conditions, ToM was associated with significantly higher peaks between the frontal and parietal areas in the right hemisphere and, in comparison with the Physical causality and baseline conditions, in the left hemisphere. Analysis taking the correct responses confirmed these results. Conclusions In healthy adults, ToM processes are associated with immediate specific changes of brain connectivity, as expressed by high cortical coherence within the right frontal and parietal areas. These previously unexplored aspects indicate an online involvement of the right hemisphere networks in normal ToM. In patients with epilepsy, the study of EEG coherence during specific tasks may help determine the neural dysfunctions associated with impaired ToM. This article is part of the Special Issue “Epilepsy and social cognition across the lifespan”.

Alzheimer’s disease (AD) can impair language, but active music therapy (AMT) and memantine (M) can improve communication. This study aimed to clarify whether adding AMT to M may improve language in comparison with drugs alone in patients with moderate AD on stable therapy with acetylcholinesterase inhibitors (AchEI). Forty-five AD patients treated with stable dose of AchEI were randomized to receive AMT plus M 20 mg/day or M 20 mg/day for 24 weeks. The Severe Impairment Battery-Language (SIB-l), SIB, Mini Mental State Examination, Neuropsychiatric Inventory (NPI), Lubben Social Network Scale, Activities of Daily Living, and Instrumental Activities of Daily Living scores at baseline and 12 and 24 weeks assessed language (primary variable) and overall cognitive, psycho-behavior, social, and functional aspects (secondary variables). The SIB-l showed a stabilization of the baseline condition in both groups, in the absence of between-group differences. The NPI depression and appetite scores significantly improved in the M-AMT group. Moreover, significantly less patients in the M-AMT group than those in the M group showed worsening of the NPI total score. Daily activities, social relationships, and overall cognitive performance did not deteriorate. In patients with moderate AD, AMT added to pharmacotherapy has no further benefits for language in comparison with pharmacotherapy alone. However, this integrated treatment can improve the psycho-behavioral profile.

Recent studies have shown that frontal and temporal lobe epilepsy, the most common forms of focal epilepsy, may impair theory of mind (ToM) by impacting on key zones of ToM's underlying neural network. Clinical research has characterized the severity and specificity of ToM impairments, as well as model methods of assessment, thereby extending the potential of ToM to expand the scope of the neuropsychology of epilepsy. Theory of mind deficits have been linked to self-rating and coping styles, suggesting a role for ToM in awareness and subjective well-being. The study of ToM in epilepsy is important not only for advancing understanding of its underlying neural network but also for clinical care. A task for the future is to identify patients with and without impaired ToM and the subsequent associations with personality complications and vulnerability to psychiatric comorbidities. Knowledge of the type and direction of the relationship between ToM, personality, and behavior might contribute to characterizing the neurobehavioral consequences of specific epilepsy syndromes as well as planning nonpharmacological treatments for alleviating psychobehavioral distress and social maladjustment.

To investigate the cerebral glucose metabolism in subjects with X-linked adrenoleukodystrophy (X-ALD) by using brain [(18)F]-fluorodeoxyglucose PET (FDG-PET).Cross-sectional study in which 12 adults with various forms of X-ALD underwent clinical evaluation and brain MRI, followed by brain FDG-PET, neuropsychological assessment, and personality and psychopathology evaluation using the Symptom Checkist-90-Revised (SCL-90-R) and the Millon Clinical Multiaxial Inventory-III (MCMI-III).When compared to healthy control subjects (n = 27) by using Statistical Parametric Mapping 8 software, the patients with X-ALD-with or without brain MRI changes-showed a pattern of increased glucose metabolism in frontal lobes and reduced glucose metabolism in cerebellum and temporal lobe areas. On single case analysis by Scenium software, we found a similar pattern, with significant (p0.02) correlation between the degree of hypermetabolism in the frontal lobes of each patient and the corresponding X-ALD clinical scores. With respect to personality, we found that patients with X-ALD usually present with an obsessive-compulsive personality disorder on the MCMI-III, with significant (p0.05) correlation between glucose uptake in ventral striatum and severity of score on the obsessive-compulsive subscale.We examined cerebral glucose metabolism using FDG-PET in a cohort of patients with X-ALD and provided definite evidence that in X-ALD the analysis of brain glucose metabolism reveals abnormalities independent from morphologic and signal changes detected by MRI and related to clinical severity. Brain FDG-PET may be a useful neuroimaging technique for the characterization of X-ALD and possibly other leukodystrophies.

Objective: To identify the genetic cause of a familial form of late-onset action myoclonus in 2 unrelated patients. Both probands had 2 siblings displaying a similar disorder. Extensive laboratory examinations, including biochemical assessment for urine sialic acid in the 2 probands, were negative. Methods: Exome sequencing was performed in the probands using an Illumina platform. Segregation analysis of putative mutations was performed in all family members by standard Sanger sequencing protocols. Results: NEU1 mutations were detected in 3 siblings of each family with prominent cortical myoclonus presenting in the third decade of life and having a mild and slowly progressive course. They did not have macular cherry-red spot and their urinary sialic acid excretion was within normal values. Genetic analysis demonstrated a homozygous mutation in family 1 (c.200G>T, p.S67I) and 2 compound heterozygous mutations in family 2 (c.679G>A, p.G227R; c.913C>T, p.R305C). Conclusions: Our observation indicates that sialidosis should be suspected and the NEU1 gene analyzed in patients with isolated action myoclonus presenting in adulthood in the absence of other typical clinical and laboratory findings.

This study analyzed the subjective facets of quality of life (QoL) and their relation to the type of brain tumor (BT) and phase of disease. Two hundred and ninety-one patients with pinealoblastoma, medulloblastoma, low-grade glioma, anaplastic astrocytoma, or glioblastoma were evaluated. With respect to 110 healthy controls, patients in the phases of radiotherapy/chemotherapy, stable disease, or tumor recurrence were significantly more anxious and depressed compared with patients in the early postoperative period. All patients were impaired in mental flexibility and memory, with preservation of abstract reasoning. The Functional Living Index-Cancer (FLIC), previously validated in cancer and BT patients, yielded six subjective factors (disease perception, affective well-being, role and leisure, personal base, nausea, sharing). None of the FLIC factors were predicted by tumor type, which only related to the physical and cognitive performances and mood scores. Affective well-being, role and leisure, and sharing were predicted by the phase of disease. Personal base, including self-perception and confidence, was independent on tumor progression and treatment. To conclude, QoL encompasses different subjective aspects, which vary in relation to the phase of disease and clinical burden. However, some person-related facets appear independent on tumor progression and treatment, indicating individual resources. Knowing this may guide tailored interventions supporting QoL.

Summary Objectives This study describes the effects of active music therapy (AMT) on cognition and behaviour in chronic vascular encephalopathy. Design A single case study investigated different cognitive and psycho-behavioural changes after AMT. Setting An adult patient with memory, attention, and verbal fluency deficits associated with Vascular Cognitive Impairment-No Dementia (VCI-ND) was treated. Intervention A four-months AMT course was based on creative and interactive music playing. Sixteen sessions were conducted simultaneously to the pharmacological therapy. Main outcomes measures Cognitive performances, mood, interpersonal interactions, and perceived abilities were assessed using standardized neuropsychological and psycho-behavioural measurements. Results At baseline, the patient reported a tendency to feel tense, nervous, and angry and difficulties in memory and visuospatial performances, frequently accompanied by attention drops. The social network was a habitual component of the patient's life, but not a source of sharing of personal experiences, safety or comfort. Neuropsychological tests showed deficits in object and figure naming, verbal fluency, short and long-term verbal memory, short-term spatial memory, selective attention, and visuomotor coordination. After AMT, the cognitive profile significantly improved in attention, visuomotor coordination, and verbal and spatial memory. Such positive changes were confirmed at the three-months follow-up. An increase of the interpersonal interactions and consistent reduction of anxiety were also observed. Conclusions In selected patients with VCI-ND, a well-structured AMT intervention added to standard therapy may contribute in determining a stable improvement of cognitive and psycho-behavioural aspects. Controlled studies are needed to confirm these promising results.

Purpose Unlike temporal lobe lesions, temporal lobe epilepsy (TLE) has no definite effects on visuospatial functions. This retrospective study evaluated these functions in patients with TLE, aiming to clarify their relationships to TLE laterality and magnetic resonance imaging (MRI)-detected brain lesions. Methods The Raven Colored Progressive Matrices (RCPM), Attentive Matrices (AM), Trail Making Test A (TMTA), Street Completion Test (SCT), Rey Complex Figure Copying (RCFC) and Delayed Reproduction (RCFDR), and Corsi Blocks Span (CBS) and Supraspan Learning (CBSSL) were used to assess different visuospatial functions in 198 patients with TLE and 90 healthy subjects. Results In 169 patients (83 left), MRI revealed focal temporal lobe lesions [unilateral mesial temporal lobe sclerosis (MTLS) in 88 cases]. The patients with left or right TLE obtained normal scores on the RCPM, AM, TMTA, SCT, and RCFC, but their scores were significantly low on the CBS, CBSSL, and RCFDR. The patients with MTLS obtained lower scores in comparison with the controls and the patients without lesions, whereas those with other lesions obtained low scores only on the CBSSL and those without lesions performed normally. Conclusions Temporal lobe epilepsy does not affect nonmemory visuospatial functions but significantly impairs visuosopatial memory and learning. This pattern is independent of TLE laterality, in keeping with a modality-specific memory model. On the contrary, the type of temporal lobe lesion is relevant to the severity of impairment.

Purpose Impaired theory of mind (ToM) is a neurobehavioral phenotype of epilepsy. Given that the age transitions affect cognitive development and decline, it is important to refine ToM across the lifespan. This study evaluated ToM in healthy subjects, taking into account education, gender, and other functions, aiming to clarify its specificity and relationships to major demographic and cognitive domains. Methods A hundred and seventy subjects from ages 16 to 81 years (68 men) who received five to 17 years of schooling were evaluated using a Faux Pas Task (FPT) that is solved at the end of childhood and is highly sensitive to brain damage and tests for language, memory, praxis, visual perception, initiative, attention, shifting, and planning. Factor analysis, analysis of variance, and correlation and regression analyses were used to assess the data. Results The analysis yielded six factors: Beliefs, Delusions, and Facts, which express the understanding of mental states and contextual details; Matching-Learning, Executive, and Working Memory. On this basis, six composite scores (CSs) were computed. Age and schooling showed significant effects on the Matching-Learning, Executive, and Working Memory CSs. The FPT raw scores and CSs were unrelated to age or schooling, while females showed better performance than males. The Beliefs CS and FPT scores were predicted by the Executive, Working Memory, Delusions, and Facts CSs and gender. Conclusions Theory of mind is a specific cognitive domain independent of age and formal education, but related to gender. Working memory, executive functions, and reality examination support some ToM processes. These findings may provide reference points against which impairment can be assessed. This article is part of the Special Issue "Epilepsy and social cognition across the lifespan"

In recent years, clinical and neuropsychological assessment of patients with epilepsy has dedicated increasing attention to social cognition (SC), which is relevant to interpersonal relations, psychological well-being, and autonomy. The components of SC are supported by distinct but interlinked brain regions that may be affected by focal and generalized epilepsy. This special issue sought to describe some of the societal, clinical, and pathophysiological correlates of SC in patients with epilepsy and healthy subjects, highlighting some of the questions key to clinical care and research. This article is part of the Special Issue "Epilepsy and social cognition across the lifespan".

Cognitive estimation, an ability to attribute measurements to concrete things, is relevant to adaptive behavior. This study evaluated cognitive estimation in patients with temporal lobe epilepsy (TLE) with the goal of verifying its relationship to temporal lobe damage and age of seizure onset. One hundred and eight patients with drug-resistant TLE and 51 healthy controls were evaluated using the Cognitive Estimation Task (CET), which requires simple and complex estimations providing the Total and Bizarreness scores. Different tests assessed reasoning, attention, executive, visuospatial, and lexical-semantic abilities. Patients with right TLE had earlier age of seizure onset than patients with left TLE and lower education than controls. Compared with controls, both patient groups obtained worse CET Total and Bizarreness scores, but only patients with right TLE were significantly impaired. Patients with seizure onset before age 12 showed worse scores than patients with later seizure onset irrespective of the side of TLE. The CET Total and Bizarreness scores were predicted by age of seizure onset and semantic fluency; the Bizarreness score also related to education, chronological age, and visual attention. Results highlight the complexity of the cognitive pattern associated with TLE. Cognitive estimation deficit primarily reflects early age of seizure onset and semantic difficulties. An involvement of visual mental operations mediated by the right hemisphere may accentuate the deficit, while cognitive reserve may play a protective role.

In patients with temporal lobe epilepsy (TLE), assessment of language lateralization is important as anterior temporal lobectomy may lead to language impairments. Despite the widespread use of fMRI, evidence of its usefulness in predicting postsurgical language performance is scant. We investigated whether preoperative functional lateralization is related to the preoperative language performance, peri-ictal aphasia, and can predict language outcome one year post-surgery. We studied a total of 72 TLE patients (42 left, 30 right), by using three fMRI tasks: Naming, Verb Generation and Fluency. Functional lateralization indices were analyzed with neuropsychological scores and presence of peri-ictal aphasia. The key findings are:1)Both left and right TLE patients show decreased left lateralization compared to controls.2)Lateralization correlates with language performance before surgery. In left TLE, decreased left lateralization correlates with better fluency performance. In right TLE, increased left lateralization during the Naming task correlates with better naming.3)Left lateralization correlates with peri-ictal aphasia in left TLE patients.4)Lateralization correlates with language performance after surgery. In a subgroup of left TLE who underwent surgery (17 left), decreased left lateralization is predictive of better naming performance at 6 and 12 months after surgery. The present study highlights the clinical relevance of fMRI language lateralization in TLE, especially to predict language outcome one year post-surgery. We also underline the importance of using fMRI tasks eliciting frontal and anterior temporal activations, when studying left and right TLE patients., Highlights • We used preoperative fMRI to predict language performance in 72 TLE patients. • Language lateralization is clinically important for left and right TLE patients. • Lateralization correlates with language performance before surgery. • Left lateralization correlates with peri-ictal aphasia in left TLE. • Left lateralization predicts language performance 1 year after surgery in left TLE.

The cerebellum is recognized as an affect and cognition modulator, besides the traditional role of movement coordinator [1]. Bidirectional connections exist between the cerebellum and cortical structures involved in the regulation of different cognitive and emotional processes [1–3]. Stoodley and Schmahmann [3] supported a functional dichotomy of the cerebellum: the anterior portion would control the sensory-motor system, while the posterior portion would control the cognitive–affective functions. Schmahmann and Sherman [4] defined the ‘‘cerebellar cognitive affective syndrome’’ (CCAS) as a pattern of deficits in language, visuospatial abilities, executive functioning and affective regulation. The affective component includes changes in personality, lack of inhibitory regulation, inappropriate behaviour, altered mood regulation, blunting of affect, obsessive–compulsive tendencies, and psychotic thinking [4]. These symptoms may be secondary to an impairment of social cognition, the capacity to construct mental representations of social relations and to flexibly use them in the social environment. Social cognition comprehends theory of mind (ToM), one’s perspective taking, empathy, the appreciation of behavior appropriateness, and the understanding of conventional and moral rules, resulting an important prerequisite to successful behavior [5]. ToM, the reading of others’ mental states (beliefs, intentions, desires), allows distinguishing mental states that have a basis in reality from lies, metaphors, persuasion, or delusion [6]. Indeed, in psychiatric patients, some psycho-behavioural symptoms were related to ToM deficit [6]. Functional imaging and clinico-pathological studies indicated that a widely distributed neuronal system underlies ToM, especially the anterior paracingulate cortex, superior temporal sulci, temporal poles, and the dorsolateral and ventromedial prefrontal cortex [7–11]. A study of autism and abnormalities of the cerebellar hemispheres, vermis, and lobules, suggested an involvement of the cerebellum [12]. The cerebellum is linked, through different neural pathways, to the associative and paralimbic cortex that are linked to the regulation of the emotions and social behaviour [4]. Research on connectivity also evidenced that bi-directional pathways link the left lateral cerebellum and the right posterior superior temporal sulcus, supporting a role for the cerebellum in a wide range of social cognitive functions [13]. Few clinical studies addressed the relationship between the cerebellum and ToM, reporting conflicting results: ToM impairment in the absence of emotion attribution and appreciation of social situation deficits in patients with cerebellar siderosis or atrophy [12, 14, 15] or normal ToM functions in patients with cerebellar stroke [16]. Given the differences in the patient samples and ToM tasks, these results are scarcely comparable, preventing general conclusions. Within this research framework, it is interesting to evaluate the case of a right-handed, 65-year-old patient with 8-year education, who was admitted to hospital due to progressive gait and limb ataxia and dysarthria. Neurologic symptoms began at age 63, with progressive walking A. Parente, V. Manfredi, and A. Tarallo have contributed equally to this work.

This study estimated cognitive awareness and the predictors of self-rating in patients with epilepsy (PWE). The Multiple Ability Self-Report Questionnaire (MASQ), State–Trait Anxiety Inventory, and Beck Depression Inventory were used for self-evaluation. Neuropsychological assessment yielded five single-domain scores (Long-Term Memory, Mental Speed, Working Memory, Set Shifting, and Visuospatial Matching) and a total composite score. Awareness was computed as the concordance between the neuropsychological and MASQ scores. In 37 patients with full awareness, self-ratings were predicted by Long-Term Memory, Working Memory, and Mental Speed. In 58 patients with incomplete or no awareness, self-ratings related to depression and seizure frequency. Compared with overestimation, underestimation was associated with higher test scores, better education, and younger age. Brain lesion and the type of epilepsy showed no effect. Therefore, PWE may appear unaware of their cognitive abilities due to negative affect and clinical burden. Understanding patients' awareness of their cognitive deficits can help clarify the clinical pattern provoked by epilepsy, as well as patients' compliance with treatment for seizures or cognitive difficulties.

This controlled randomized single-blind study evaluated the effects of cognitive training (CT), compared to active music therapy (AMT) and neuroeducation (NE), on initiative in patients with mild to moderate Alzheimer’s disease (AD). Secondarily, we explored the effects of CT on episodic memory, mood, and social relationships. Thirty-nine AD patients were randomly assigned to CT, AMT, or NE. Each treatment lasted 3 months. Before, at the end, and 3 months after treatment, neuropsychological tests and self-rated scales assessed initiative, episodic memory, depression, anxiety, and social relationships. At the end of the CT, initiative significantly improved, whereas, at the end of AMT and NE, it was unchanged. Episodic memory showed no changes at the end of CT or AMT and a worsening after NE. The rates of the patients with clinically significant improvement of initiative were greater after CT (about 62%) than after AMT (about 8%) or NE (none). At the 3-month follow-up, initiative and episodic memory declined in all patients. Mood and social relationships improved in the three groups, with greater changes after AMT or NE. In patients with mild to moderate AD, CT can improve initiative and stabilize memory, while the non-cognitive treatments can ameliorate the psychosocial aspects. The combining of CT and non-cognitive treatments may have useful clinical implications.

Magnetic resonance imaging-positive temporal lobe atrophy with temporo-polar grey/white matter abnormalities (usually called 'blurring') has been frequently reported in patients with temporal lobe epilepsy associated with hippocampal sclerosis. The poor distinction of grey and white matter has been attributed to various causes, including developmental cortical abnormalities, gliosis, myelin alterations, a non-specific increase in temporal lobe water content and metabolic/perfusion alterations. However, there is still no consensus regarding the genesis of these abnormalities and no histopathological proof for a structural nature of magnetic resonance imaging changes. The aim of this study was to investigate the pathological substrate of temporo-polar blurring using different methodological approaches and evaluate the possible clinical significance of the abnormalities. The study involved 32 consecutive patients with medically intractable temporal lobe epilepsy and hippocampal sclerosis who underwent surgery after a comprehensive electroclinical and imaging evaluation. They were divided into two groups on the basis of the presence/absence of temporo-polar blurring. Surgical specimens were examined neuropathologically, and selected samples from both groups underwent high-field 7 T magnetic resonance imaging and ultrastructural studies. At the clinical level, the two groups were significantly different in terms of age at epilepsy onset (earlier in the patients with blurring) and epilepsy duration (longer in the patients with blurring). Blurring was also associated with lower neuropsychological test scores, with a significant relationship to abstract reasoning. On 7 T magnetic resonance image examination, the borders between the grey and white matter were clear in all of the samples, but only those with blurring showed a dishomogeneous signal in the white matter, with patchy areas of hyperintensity mainly in the depth of the white matter. Sections from the patients with blurring that were processed for myelin staining revealed dishomogeneous staining of the white matter, which was confirmed by analyses of the corresponding semi-thin sections. Ultrastructural examinations revealed the presence of axonal degeneration and a significant reduction in the number of axons in the patients with blurring; there were no vascular alterations in either group. These data obtained using different methodological approaches provide robust evidence that temporo-polar blurring is caused by the degeneration of fibre bundles and suggest slowly evolving chronic degeneration with the redistribution of the remaining fibres. The article also discusses the correlations between the morphological findings and clinical data.

Study of brain tumors (BT) has revealed the importance of cognitive and behavioral assessment to clinical care and prognosis. This paper overviews recent literature, focusing on the main points of interest and current methods, providing recommendations for advancing research. Histological aspects, disease progression, treatment-related neurotoxicity, and co-morbidities determine the cognitive patterns of BT. Mental slowing with prominent executive and memory compromise usually mark the advanced phases of disease, whereas normal cognitive performance or subtle behavioral symptoms characterize the early disease course, irrespective of tumor location. Neurocognitive assessment may indicate brain damage in otherwise neurologically normal patients, explain pathological behavior, and provide reliable measures of outcome, contributing to improving the management of patients. Scarce attention has been devoted to social cognitive deficits which are expected to impair autonomy and relationships. Interest in non-pharmacological treatment of cognitive impairment is a growing area although methodological difficulties persist. Homogeneous patient populations, longitudinal study designs including baseline evaluations, and measurement of the lowest and highest levels of cognitive performance seem indispensable to advancing the study of the cognitive and behavioral changes provoked by BT. Future investigations are also expected to clarify the clinical significance of such changes, their effect on quality of life, and the efficacy of specific rehabilitation treatments.

Summary Purpose: Theory of mind (ToM) is an important prerequisite to social behavior. This study evaluated ToM in patients with temporal (TLE) or frontal lobe epilepsy (FLE) aiming to determine the cognitive aspects, severity, and pathophysiologic mechanisms of ToM impairment in focal epilepsy. Methods: One hundred thirty-eight patients with TLE (n = 109) or FLE (n = 29) and 69 healthy subjects underwent the Faux Pas task (FPT), which evaluates the recognition and comprehension of others’ mental states, and neuropsychological tests for other cognitive functions. Key Findings: Factor analysis of all test scores yielded two ToM factors (Recognizing faux pas, FP; Excluding nonexistent FP) distinct from the Control, Language, Matching, and Praxis factors. With respect to healthy subjects, both TLE and FLE patients showed correct exclusion of nonexistent FPs but significantly lower recognition and comprehension of real FPs. FLE patients were also impaired with respect to TLE patients. In the whole patient group, schooling and group membership predicted ToM impairment. In FLE patients, the comprehension of mental states was predicted by disease duration, whereas TLE patients’ comprehension of affects and intentions was associated with early age of seizure onset and medial temporal lobe sclerosis (MTLS). Significance: Focal epilepsy impairs advanced ToM abilities. FLE may affect online performances owing to long-lasting dysfunctions of the prefrontal areas. MTLS may provoke selective ToM deficits due to medial temporal damage, prefrontal dysfunctions, or early interference with cognitive development. Future studies are needed to determine the implications of ToM impairment on behavior and quality of life.

We report the case of a 23-year-old Italian female harboring the rare m.3291T>C mutation in the MT-TL1 gene, that encodes the mitochondrial transfer RNA for leucine 1 (UUA/G). MT-TL1 mutations usually cause the MELAS (mitochondrial encephalomyopathy, lactic acidosis and stroke-like episodes) syndrome. Our patient, however, suffered from a non-syndromic mitochondrial disorder (MID), clinically characterized by progressive cognitive and behavioral decline, and hearing loss; brain MRI disclosed diffuse supratentorial and infratentorial atrophy; EKG revealed a Wolff-Parkinson-White syndrome; combined neuroleptic and antidepressant treatment markedly improved her behavioral symptoms. This case expands the clinical spectrum of non-syndromic MIDs, and further confirms that no obvious genotype-phenotype correlation exists for the m.3291T>C DNA mutation; indeed, this mutation has been previously reported in a Japanese child, who suffered from MELAS, and in an Italian child, who presented an apparently isolated mild myopathy. Moreover, it supports the hypothesis that at least in MT-TL1-related MIDs, dementia may be caused by a progressive neurodegenerative process, rather than by injury accumulation due to stroke-like episodes. Finally, our case suggests that common neuroleptic and antidepressant drugs may be clinically efficacious in the management of psychiatric symptoms associated with MIDs.

Neuropsychology plays a vital role in the treatment of epilepsy, providing information on the effects of seizures on higher cortical functions through the measurement of behavioral abilities and disabilities. This is accomplished through the design, administration and interpretation of neuropsychological tests, including those used in functional neuroimaging or cortical mapping and in intracarotid anesthetic procedures. The objective of this paper is to define and summarize in some detail the role and methods of neuropsychologists in specialized epilepsy centers. Included are information and recommendations regarding basic ingredients of a thorough neuropsychological assessment in the epilepsy setting, as well as suggestions for an abbreviated alternative exam when needed, with emphasis on functions associated with specific brain regions. The paper is intended for novice and experienced neuropsychologists to enable them to develop or evaluate their current practices, and also for other clinicians, who seek a better understanding of the methodology underlying the neuropsychological input to their work.

This study investigated the neuropsychological hallmarks of posterior cortical atrophy (PCA). Seventeen patients with PCA, 17 patients with probable Alzheimer's disease (PAD), and 17 healthy age-matched subjects underwent neuropsychological testing for abstract reasoning, visuospatial abilities, memory, language, executive functions, praxes, and attention. The PCA patients were significantly more impaired in visual perception, spatial memory, visual attention, and visuospatial reasoning compared to the PAD patients who were relatively more impaired in episodic memory. In the PCA group, no test score correlated with disease duration or age of clinical onset, whereas, in the PAD group, several scores correlated with disease duration. Compared to the healthy subjects, both patient groups showed multiple cognitive deficits. Thus, PCA is characterised by distinctive visuospatial deficits that reflect the distribution of brain damage and contrast with the memory impairment of PAD patients. Specific neuropsychological tests may contribute to early identification of cortical dementia for diagnostic and research purposes.

This study determined the neuropsychological pattern of Unverricht-Lundborg disease (ULD) and its relationship to disease-related variables. Twenty-one ULD patients were evaluated using neuropsychological tests for abstract reasoning, attention, planning, set-shifting, theory of mind, visual perception, visuomotor coordination, ideomotor, orofacial and constructive praxis, language, learning, and memory. The control groups consisted of 21 healthy subjects and 21 patients with cryptogenic temporal lobe epilepsy (TLE). Multivariate analysis of variance showed that, in comparison with both control groups, the ULD patients showed significantly impaired abstract reasoning, attention, planning, word fluency, constructive praxis, and visuospatial memory and learning. Factor analysis of the test scores obtained by the ULD and TLE groups identified four factors (processing and execution, praxis, memory, theory of mind), and separate ANOVAs using epilepsy-related and demographic variables as covariates showed that the ULD patients had significantly impaired processing and execution. Correlation and regression analyses showed that processing and execution was significantly associated with diagnosis, disease duration and education, and logistic regression analyses indicated that it significantly predicted a diagnosis of ULD. To conclude, ULD is characterised by impaired processing and execution functions. This impairment is a strong independent predictor of ULD and may contribute to the characterisation of the diagnosis.

β-Amyloid precursor protein (APP) mutations cause familial Alzheimer's disease with nearly complete penetrance. We found an APP mutation [alanine-673→valine-673 (A673V)] that causes disease only in the homozygous state, whereas heterozygous carriers were unaffected, consistent with a recessive Mendelian trait of inheritance. The A673V mutation affected APP processing, resulting in enhanced β-amyloid (Aβ) production and formation of amyloid fibrils in vitro. Co-incubation of mutated and wild-type peptides conferred instability on Aβ aggregates and inhibited amyloidogenesis and neurotoxicity. The highly amyloidogenic effect of the A673V mutation in the homozygous state and its anti-amyloidogenic effect in the heterozygous state account for the autosomal recessive pattern of inheritance and have implications for genetic screening and the potential treatment of Alzheimer's disease.

The case of a 64-year-old woman affected by slowly progressive visual agnosia is reported aiming to describe specific cognitive-brain relationships. Longitudinal clinical and neuropsychological assessment, combined with magnetic resonance imaging (MRI), spectroscopy, and positron emission tomography (PET) were used. Sequential neuropsychological evaluations performed during a period of 9 years since disease onset showed the appearance of apperceptive and associative visual agnosia, alexia without agraphia, agraphia, finger agnosia, and prosopoagnosia, but excluded dementia. MRI showed moderate diffuse cortical atrophy, with predominant atrophy in the left posterior cortical areas (temporal, parietal, and lateral occipital cortical gyri). 18FDG-PET showed marked bilateral posterior cortical hypometabolism; proton magnetic resonance spectroscopic imaging disclosed severe focal N-acetyl-aspartate depletion in the left temporoparietal and lateral occipital cortical areas. In conclusion, selective metabolic alterations and neuronal loss in the left temporoparietooccipital cortex may determine progressive visual agnosia in the absence of dementia.

Objective To describe a new dementia phenotype of Gerstmann-Straussler-Scheinker disease (GSS) in a previously unreported Italian family. Design Longitudinal clinical and neuropsychological assessment, combined with magnetic resonance imaging (MRI), single positron emission tomography (SPECT) and molecular genetic studies. Setting Neuropsychology Laboratory, and Division of Neuropathology and Neurology, “C. Besta” National Neurological Institute. Patients and participants Three members of the family. Measurements and results. Standardised neuropsychological tests were used to determine cognitive patterns. The proband had a history of primary dementia characterised by loss of initiative, planning, behaviour control, awareness, language and memory; the two relatives suffered from progressive ataxia. MRI of the demented patient revealed brain atrophy with a hyperintense signal in the frontal cortex; SPECT revealed decreased perfusion in the left temporal and parietal cortex and left thalamus. The two ataxic patients showed cerebellar atrophy with no signs of altered perfusion. Analysis of the PRNP gene showed a proline/leucine substitution at codon 102 in all three patients, associated with methionine/valine heterozygosity at the polymorphic codon 129. Conclusions Primary dementia with prominent frontotemporal signs is a new phenotypical expression of P102L-related GSS that coexists in the same family with the ataxic form of the disease. This remarkable variability suggests that still unidentified genetic or acquired factors may modulate the manifestations of GSS. Genetic examination of the PRNP should be included in the diagnostic work-up of patients with poorly classifiable dementia.