Neratinib and Capecitabine for the Treatment of Leptomeningeal Metastases from HER2-Positive Breast Cancer: A Series in the Setting of a Compassionate Program.

BACKGROUND: Leptomeningeal metastasis is a neurological complication from HER2-positive breast cancer with a poor prognosis and limited treatment options. This study has evaluated the activity of neratinib in association with capecitabine in 10 patients with LM from HER2-positive BC after the failure of multiple lines of treatment, including trastuzumab-based therapy, within a compassionate program, and a comparison was made with a historical control group of 10 patients. METHODS: Patients aged ≥ 18 years with histological diagnosis of primary HER2-positive BC, either amplified or mutated, and newly-diagnosed LM were enrolled. Coexistence of BM that has or has not received radiotherapy, as well as prior chemotherapy, hormone therapy, or monoclonal HER2-targeting antibodies or antibody-drug conjugates, were allowed, with the exclusion of lapatinib. RESULTS: Six-months OS was 60% with a median OS of 10 months (95% CI: 2.00-17.0). Three-month intracranial PFS was 60% with a median intracranial PFS of 4.0 months (95% CI: 2.00-6.0). The neurological benefit was observed in 70% of patients with a median duration of neurological response of 6.5 months. The best radiological response was stable disease in 60% of patients. CONCLUSIONS: This small series shows that the combination of neratinib and capecitabine is a safe treatment in LM from heavily pretreated HER2-positive BC with clinical efficacy in some patients and is worth investigating in a larger study.

Impulsivity traits in eyelid myoclonia with absences.

PURPOSE: Eyelid myoclonia with absences (EMA) shares some clinical characteristics with juvenile myoclonic epilepsy (JME), in which impulsivity traits have been described. Aim of the study was to evaluate whether EMA patients could present a peculiar behavioural profile. METHODS: Patients with EMA, JME and healthy controls (HCs) were enrolled. Subjects with intellectual quotient <80 were excluded from the study. All the enrolled subjects underwent the Italian version of the Barratt Impulsiveness Scale (BIS-11) and the three dimensions of impulsivity (motor, attentional-cognitive and nonplanning impulsivity) were considered. RESULTS: Seventeen patients with EMA (12 females [70.6%], age 30.8±10 years), 29 patients with JME (17 females [58.6%], age 29.1±9.7 years) and 31 HCs (15 females [48.4%], age 27.6±5.8 years) were enrolled. Both EMA and JME patients presented a borderline significantly higher BIS total score than HCs (p=0.064). EMA patients presented a significantly higher BIS nonplanning subscore than JME patients and HCs (p=0.001). CONCLUSION: The study showed the presence of peculiar behavioral characteristics in EMA patients, slightly different from patients with JME.

iNPH with parkinsonism: response to lumbar CSF drainage and ventriculoperitoneal shunting.

OBJECTIVES: To evaluate clinical response after external lumbar drainage (ELD) and ventriculoperitoneal shunting (VPS) in a cohort of patients with idiopathic normal pressure hydrocephalus associated with parkinsonism (iNPH-P), considering parkinsonism as clinical primary outcome. METHODS: Patients underwent long-term 72-h intracranial pressure-controlled CSF ELD. Clinical motor response before and after ELD was evaluated using changes in UPDRS-ME as outcome measure. A standardized cognitive assessment was also performed. iNPH-P patients who underwent VPS were clinically followed-up after surgery. RESULTS: Fourteen iNPH-P patients (age: 69.3 ± 11.6 years) were studied. The time of evaluation after ELD removal was 3.5 ± 1.8 days. We observed a significant motor improvement after the drainage in eight (57.1%) patients. Percent clinical motor response was 18.4 ± 6.7%. Twelve (85.7%) patients underwent VPS. Nine patients were examined after surgery at 31.6 ± 7 months. Four (44.4%) patients presented a clinically detectable improvement in motor response after VPS. No significant changes in cognitive performances were detected. CONCLUSIONS: A clinically detectable motor response on parkinsonian signs was observed in a consistent part of iNPH-P patients few days after ELD as well as over two and half years after VPS. Parkinsonism should be considered as outcome measure for the clinical management of patients with iNPH-P.

Phonemic Verbal Fluency and Midbrain Atrophy in Progressive Supranuclear Palsy.

BACKGROUND: The neuropsychological profile of progressive supranuclear palsy (PSP) patients is mainly characterized by executive dysfunction, but the relationship between the latter and midbrain atrophy is still unclear. OBJECTIVE: The aims of the study were to investigate which test evaluating executive functioning is more frequently impaired in PSP patients and to evaluate the relationship between midbrain-based MRI morphometric measures and executive dysfunction. METHODS: PSP patients who had undergone a neuropsychological battery assessing executive functioning with the Frontal Assessment Battery (FAB), the phonemic verbal fluency F-A-S, the Raven's Progressive Colored Matrix, and the Stroop word colors test (time and errors) were enrolled in the study. A group of Parkinson's disease (PD) patients matched by age, sex, education, and global cognitive status was selected. All the enrolled patients also underwent a volumetric T1-3D brain MRI. RESULTS: Thirty-five PSP patients and 35 PD patients were enrolled. Patients with PSP as compared to patients with PD showed a significant greater impairment in verbal fluency (16.0±7.9 and 23.4±8.7 words/180 s; p < 0.001) and a significant lower score at the FAB total score (11.5±3.8 and 13.7±3.4; p = 0.013). Midbrain area was significantly smaller in PSP patients than in PD patients (83.9±20.1 and 134.5±19.9 mm2; p < 0.001). In PSP patients, a significant positive correlation between verbal fluency and the midbrain area (r = 0.421; p = 0.028) was observed. CONCLUSION: Our findings suggest that the phonemic verbal fluency is among the most frequently impaired executive functions in PSP patients and is strongly correlated to midbrain atrophy.

Asymmetry index of Blink Reflex Recovery Cycle differentiates Parkinson's disease from atypical Parkinsonian syndromes.

BACKGROUND: Differential diagnosis between Parkinson's disease (PD) and atypical Parkinsonian syndromes (APS), such as multiple system atrophy (MSA) and progressive supranuclear palsy (PSP), is often difficult because of overlap of common clinical features. We evaluated R2 Blink Reflex Recovery Cycle (R2BRRC) in drug-naive PD patients and in MSA and PSP patients to differentiate early PD from APS. METHODS: We investigated 43 patients: 15 drug-naive PD patients, 16 MSA patients, and 12 PSP patients. R2BRRC was evaluated bilaterally at interstimulus intervals (ISIs) of 100, 150, 200, 300, 400, 500, and 750 ms. An asymmetry index (AI) of R2BRRC for each ISI was computed. RESULTS: R2BRRC of PD patients showed an increased brainstem excitability for less affected side (LAS) stimulation at ISIs of 100, 150, 200 (p < 0.001), and 300 ms (p = 0.03) compared to more affected side (MAS) stimulation, whereas no differences between LAS and MAS stimulation were found in APS. AI of 0.87 at ISI of 100 ms differentiated PD from MSA with a sensitivity of 86.7% and a specificity of 100%, whereas AI of 0.78 at ISI of 100 ms permitted to discriminate PD from PSP with a sensitivity of 86.7% and a specificity of 91.7%. CONCLUSION: AI of R2BRRC may represent a reliable tool in differentiating PD from APS, especially at the early stage of the disease.

Imaginário coletivo de idosos participantes da Rede de Proteção e Defesa da Pessoa Idosa / Collective imaginary of elderly people participating in the Protection and Defense Network of the Elderly Person

Resumo A concepção de Rede de Proteção e Defesa da Pessoa Idosa (RPDI) se destaca como espaço de luta coletiva pelo direito dos idosos, por meio de reuniões sistemáticas destes com profissionais de diferentes instituições e pela articulação para a implantação de políticas públicas. Este estudo, caracterizado como pesquisa qualitativa pautada no método psicanalítico, teve o objetivo de compreender o imaginário coletivo de idosos que participam de encontros organizados pela RPDI sobre o envelhecimento. Os participantes foram convidados para entrevista coletiva, na qual foi utilizado o procedimento de desenhos-estórias com tema como recurso facilitador da comunicação emocional. A análise dos desenhos e narrativas possibilitou reconhecer dois campos de sentido afetivo-emocional denominados "velhice como desamparo" e "velhice como responsabilidade pessoal". Os caminhos que levaram aos campos de sentido apontaram dinâmicas heterogêneas no imaginário coletivo sobre o envelhecimento, além de contradições inerentes ao ser idoso. Apesar do desamparo, da luta contínua e persistente, das fatalidades e da negação da velhice, está também presente a força que a experiência de vida lhes dá e a motivação que encontram na união com seus pares para enfrentar os desafios da vida e lutar por seus direitos.

Abstract The conception of the Protection and Defense Network of the Older Person (RPDI) stands out as a space of collective struggle for the right of the older people, through systematic meetings between them and professionals from different institutions and by articulation for the implantation of public policy. This study, characterized as qualitative research and based on the psychoanalytic method, aimed at understanding the collective imaginary of the older adults, who attend meetings on aging organized by the RPDI. The RPDI participants were invited to a collective interview, in which the Drawing-Story with Theme Procedure was used as a resource for facilitating emotional communication. The analysis of these drawings and narratives made it possible to recognize two affective-emotional meaning fields, named "Old age as helplessness" and "Old age as personal responsibility". The paths that led to the fields of meaning indicated heterogeneous dynamics in the collective imaginary about aging, and contradictions in aging have been identified. Despite the helplessness, continuous and persistent struggle, fatalities, and the denial of old age, there is also the strength that the experience of life gives them and the motivation they find in union with their pairs to face the challenges of life and fight for their rights.

O imaginário coletivo de cuidadores de idosos na saúde pública: um estudo psicanalítico / The collective imaginary of caretakers of the elderly in public health: a psychoanalytic study

A formação de cuidadores de idosos da saúde pública deve ser considerada, atualmente, questão de grande relevância, num pais em que expressiva parcela da população não conta com recursos para enfrentar despesas que surgem a partir do envelhecimento. Esta capacitação deve incluir não apenas conhecimentos específicos em relação a cuidados corporais, mas também preparo de caráter psicológico, que permita a instauração de vinculação suficientemente saudável entre cuidador e idoso. Neste contexto, a presente investigação visa estudar empiricamente o imaginário coletivo de cuidadores de idosos profissionais da saúde pública a respeito da pessoa idosa. Concebida e realizada a partir do uso do método psicanalítico, em todas as suas etapas, esta pesquisa articulou-se ao redor de uma entrevista com cuidadores, durante a qual o Procedimento de Desenhos-Estórias com Tema foi usado como recurso facilitador da comunicação emocional, bem como da consideração de experiências vivenciadas, no cotidiano institucional, em situações formais e informais, junto a idosos, cuidadores e da equipe, constituída por profissionais de várias formações. O conjunto do material emergente permitiu a elaboração de duas narrativas transferenciais, a partir das quais seis campos de sentido afetivo-emocional, ou inconscientes relativos, puderam ser criados/encontrados: cuidar enobrece a alma, cuidado com esse velho!, mas eu sou de confiança!, perdendo a autonomia, empobrecendo a convivência e vontade de viver(?). A condição de idoso frágil gera impactos emocionais e os cuidadores são sensíveis aos delicados aspectos que ligam a dimensão relacional inerente ao cuidado do idoso(AU)

The training of caretakers for the elderly in public health must be considered, nowadays, a matter of great importance, in a country in which a considerable part of the population does not have the means to handle expenses that come with aging. This training must include not only specific knowledge on physical care, but also psychological preparation which allows for the creating of a bond strong and healthy enough between caretaker and elderly citizen. In such context, this investigation aims to study empirically the collective imaginary of professional public health caretakers of the elderly regarding older citizens. Conceived and executed using the psychoanalytic method, in all its steps, this research was organized based on an interview with the caretakers, during which the Drawing-Stories with Theme Procedure was used a facilitating resource for emotional communication, in discussing experiences lived, in the institutional daily happenings, in formal and informal situations, together with the elderly, caretakers and the staff, which is constituted by professionals from several backgrounds. The resulting material allowed for the creation of two transferential narratives, from which six affective-emotional or relative unconscious, fields could be created/derived: care-taking ennobles the soul, take care around that old man/woman!, but I'm trustworthy!, losing autonomy, crippling relationships and will to live(?). The condition of frail elderly citizen impacts emotionally and caretakers are sensitive to the delicate aspects that connect the relationship dimension inherent to taking care of an older person(AU)