Iatrogenic cerebral amyloid angiopathy: An illustrative case of a newly introduced disease.

BACKGROUND AND PURPOSE: Iatrogenic cerebral amyloid angiopathy (iCAA) is a specific type of cerebral amyloid angiopathy which is becoming increasingly diagnosed. It has been hypothesized that iCAA might arise as a late consequence of past neurosurgical interventions involving dural patch grafts. Positron emission tomography (PET) scans with amyloid tracers and the assay of beta-amyloid levels in cerebrospinal fluid (CSF) are auxiliary criteria, however, definite diagnosis remains histopathologically determined. METHODS: Case report. RESULTS: We present a 48-year-old patient who suffered multiple lobar cerebral haemorrhages from the age of 47. The patient had undergone surgery for remolval of hemangioblastoma with lyophilized dural graft at the age of 11, in 1987. Brain MRI, amiloid PET and CSF analysis led to a diagnosis of probable iCAA. CONCLUSION: It is necessary to increase the awareness of iCAA, in order to avoid overlooking the potential causal involvement of surgical procedures which took place far back in time. Moreover, the diagnostic relevance of amyloid PET and beta-amyloid levels in CSF must be emphasised.

One-year cognitive follow-up of COVID-19 hospitalized patients.

BACKGROUND AND PURPOSE: Cognitive dysfunction has been observed following recovery from COVID-19. To the best of our knowledge, however, no study has assessed the progression of cognitive impairment after 1 year. The aim was to assess cognitive functioning at 1 year from hospital discharge, and eventual associations with specific clinical variables. METHODS: Seventy-six patients (aged 22-74 years) who had been hospitalized for COVID-19 were recruited. Patients received neuropsychological assessments at 5 (n = 76) and 12 months (n = 53) from hospital discharge. RESULTS: Over half (63.2%) of the patients had deficits in at least one test at 5 months. Compared to the assessment at 5 months, verbal memory, attention and processing speed improved significantly after 1 year (all p < 0.05), whereas visuospatial memory did not (all p > 0.500). The most affected domains after 1 year were processing speed (28.3%) and long-term visuospatial (18.1%) and verbal (15.1%) memory. Lower PaO2 /FiO2 ratios in the acute phase were associated with worse verbal long-term memory (p = 0.029) and visuospatial learning (p = 0.041) at 5 months. Worse visuospatial long-term memory at 5 months was associated with hyposmia (p = 0.020) and dysgeusia (p = 0.037). CONCLUSION: Our study expands the results from previous studies showing that cognitive impairment can still be observed after 1 year. Patients with severe COVID-19 should receive periodic cognitive follow-up evaluations, as cognitive deficits in recovered patients could have social and occupational implications.

Immunotherapy treatment: an issue for metabolic response.

Since the beginning of second decade of last century, when it was introduced in many oncologic scenarios, immunotherapy has become an important tool in the management of a growing number of cancers. Immunotherapy for cancer appears to be useful, improving not only progression free survival but also overall survival, thus achieving the goal that many advanced cancers, previously considered without effective treatment options, have now become successfully treatable. However, considering the relatively recent introduction of these drugs in clinical scenarios and the continuous release of new drugs, there is a lack of large validated clinical experiences and many issues are today debated amongst which the evaluation of the response to immune-therapy. Engaging the host immune system in fighting against cancer is an energy-consuming process, requiring T-cell recruiting; this process, named "pseudo-progression," sometimes produces an increase of both dimensional and metabolic ratio of the lesions, as well as the appearance of "new lesions." This behavior, always considered as undisputed progressive disease when traditional chemotherapy is employed, should be carefully considered in the field of immunotherapy, where the phenomenon of "flare" followed by regression of the disease can occur. In this paper, Authors analyzed the best available evidence in this field, reviewed the most important issues concerning the development of immunotherapy, and addressed evidence and concerns about the evaluation of response when using immunotherapy drugs, in terms of both radiological and nuclear medicine criteria.

18FFlutemetamol-PET Aided Classification of Cerebral Amyloid Angiopathy: A Multicenter Study.

OBJECTIVES: Cerebral amyloid angiopathy (CAA)-related features on neuroimaging often coexist with signs of arteriolosclerosis-small vessel disease on neuroimaging in people with intracranial hemorrhage (ICH). This study aimed at defining the value of amyloid pathology detected by 18Fflutemetamol PET in reclassification and stratification of risk of bleeding in people with mixed CAA-arteriolosclerosis features. METHODS: We included consecutive patients admitted to 2 institutions (2018-2023) with spontaneous symptomatic ICH, subarachnoid hemorrhage (SAH), transient focal neurologic episodes (TFNE), or cognitive impairment and MRI showing CAA hallmarks. All patients underwent brain magnetic resonance imaging (MRI) with susceptibility weighted imaging and 18Fflutemetamol PET imaging and were followed up for at least 1 year. We compared cases with CAA and arteriolosclerosis + CAA features and defined long-term outcomes (composite outcome including death, ICH, ischemic stroke, SAH, TFNE) depending on PET status (CAA/amyloid pathology vs arteriolosclerosis-predominant groups). RESULTS: Among 47 patients, according to PET and MRI imaging, 38 patients were reclassified in the CAA/amyloid pathology group and 9 in the arteriolosclerosis-predominant group, with similar cardiovascular risk factors but a significantly higher lobar microbleed burden for the former group. The CAA/amyloid pathology group had higher rates of composite outcome (43.9 vs 11.1 events per 100 patient-year; p = 0.039) and ICH (36.5 vs 5.6 events per 100 patient-years; p = 0.04) compared with the arteriolosclerosis-predominant group. DISCUSSION: 18FFlutemetamol PET imaging can help in reclassification of mixed arteriolosclerosis + CAA into CAA/amyloid pathology and arteriolosclerosis-predominant, with implications on long-term risk of recurrent events. CLASSIFICATION OF EVIDENCE: This study provides Class IV evidence that 18Fflutemetamol PET can distinguish between CAA + arteriolosclerosis and arteriolosclerosis-predominant pathology.

Brain positron emission tomography (PET) and cognitive abnormalities one year after COVID-19.

Emerging evidence indicates that the etiologic agent responsible for coronavirus disease 2019 (COVID-19), can cause neurological complications. COVID-19 may induce cognitive impairment through multiple mechanisms. The aim of the present study was to describe the possible neuropsychological and metabolic neuroimaging consequences of COVID-19 12 months after patients' hospital discharge. We retrospectively recruited 7 patients (age [mean ± SD] = 56 years ± 12.39, 4 men) who had been hospitalized for COVID-19 with persistent neuropsychological deficits 12 months after hospital discharge. All patients underwent cognitive assessment and brain (18F-FDG) PET/CT, and one also underwent 18F-amyloid PET/CT. Of the seven patients studied, four had normal glucose metabolism in the brain. Three patients showed various brain hypometabolism patterns: (1) unilateral left temporal mesial area hypometabolism; (2) pontine involvement; and (3) bilateral prefrontal area abnormalities with asymmetric parietal impairment. The patient who showed the most widespread glucose hypometabolism in the brain underwent an 18F-amyloid PET/CT to assess the presence of Aß plaques. This examination showed significant Aß deposition in the superior and middle frontal cortex, and in the posterior cingulate cortex extending mildly in the rostral and caudal anterior cingulate areas. Although some other reports have already suggested that brain hypometabolism may be associated with cognitive impairment at shorter intervals from SarsCov-2 infection, our study is the first to assess cognitive functions, brain metabolic activity and in a patient also amyloid PET one year after COVID-19, demonstrating that cerebral effects of COVID-19 can largely outlast the acute phase of the disease and even be followed by amyloid deposition.

[18F]Fluoro-Deoxy-Glucose positron emission tomography to evaluate lymph node involvement in patients with muscle-invasive bladder cancer receiving neoadjuvant pembrolizumab.

BACKGROUND: Data regarding the role of positron emission tomography/computed tomography (PET/CT) to stage lymph nodes in patients receiving neoadjuvant immunotherapy before radical cystectomy are lacking. The aim of this study is to evaluate the role of PET/CT to predict the pathologic lymph node involvement (LNI) in patients with MIBC receiving neoadjuvant pembrolizumab within the PURE-01 trial (NCT02736266). MATERIAL AND METHODS: Three courses of pembrolizumab were administered before radical cystectomy and extended pelvic lymph node dissection in clinical T2-4aN0M0 MIBC based on contrast-enhanced CT scan. LNI was also assessed with PET/CT before and after treatment. PET/CT results were compared with histopathological findings. The ability of baseline and post-therapy PET/CT to evaluate LNI was assessed, and univariate logistic regression analyses were performed. RESULTS: From February 2017 to August 2019, a total of 108 patients and 105 patients had evaluable baseline and post-pembrolizumab scans, respectively. The sensitivity to detect LNI was 27% and 37.5% for pre- and post-pembrolizumab PET/CT, and specificity was 97% and 98%, respectively. In total, 4 of 7 patients (57%) showing baseline FDG-uptake had LNI vs. 11 of 101 (11%) with no baseline uptake. All but 1 of the 7 patients did not respond to pembrolizumab. Both pre- and post-pembrolizumab PET/CT significantly predicted LNI (P = 0.004 and P < 0.001) at univariate analyses. Our results warrant further validation in larger datasets. CONCLUSIONS: PET/CT performance does not justify its use in routine practice for cN0 MIBC. However, our preliminary data revealed opportunities for the use of baseline PET/CT, within clinical trials, to optimally select patients with MIBC who are best suited for neoadjuvant immunotherapy strategies. Validation in larger datasets, as well as a cost analysis, are needed.

Incidence and Clinical Impact of Inflammatory Fluorodeoxyglucose Positron Emission Tomography Uptake After Neoadjuvant Pembrolizumab in Patients with Organ-confined Bladder Cancer Undergoing Radical Cystectomy.

BACKGROUND: Data regarding the incidence and prognostic impact of immune-related imaging changes, assessed by 18[F] fluorodeoxyglucose (FDG) positron emission tomography/computed tomography (PET/CT) scan, in patients receiving immune-checkpoint inhibitors (ICIs) are lacking. We relied on the population of patients enrolled in the PURE-01 study to evaluate such changes. OBJECTIVE: To evaluate the role of PET/CT to visualize the immune-related adverse events (irAEs) following pembrolizumab. DESIGN, SETTING, AND PARTICIPANTS: From February 2017 to August 2019, in 103 patients with nonmetastatic, clinical T2-4aN0M0 bladder cancer, PET/CT scan was performed before and after neoadjuvant pembrolizumab (N = 206 scans), before radical cystectomy. INTERVENTION: PET/CT before and after neoadjuvant pembrolizumab, before radical cystectomy. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: We analyzed the occurrence of irAEs, evaluated according to the Common Terminology Criteria for Adverse Events (CTCAE) version 5.0, against the development of inflammatory FDG uptake described at PET/CT (irAEs + PET/CT). Logistic regression analyses evaluated the association between irAEs + PET/CT and the pathological response to pembrolizumab. Kaplan-Meier curves tested their association with progression-free survival (PFS) after pembrolizumab and radical cystectomy. RESULTS AND LIMITATIONS: Forty patients (39%) developed irAEs + PET/CT in several target organs. The most frequent target organs were the thyroid (N = 18), stomach (N = 14), mediastinal lymph nodes (N = 9), and lung (N = 5). These changes were clinically evident in 18 (45%) and were not associated with the pathological response, neither in terms of complete response (ypT0N0, p = 0.07) nor as downstaging to ypT≤1N0 disease (p = 0.1), although ypT0N0 responses were numerically more frequent in patients with irAEs+ PET/CT (47.5% vs 32%). Furthermore, irAE+ PET/CT events were associated with longer, not statistically significant, 24-mo PFS: 88.3% versus 76.5% (p = 0.5). Our results warrant further validation in larger datasets. CONCLUSIONS: We presented unique surrogate data of PET/CT that could help improve our understanding of nonclinically evident effects of ICI administration, especially in patients at the early disease stage. PATIENT SUMMARY: We evaluated the utility of PET/CT to visualize the occurrence of inflammatory changes after pembrolizumab in patients with localized bladder cancer without metastases. After immunotherapy, 39% of the patients developed 18[F] fluorodeoxyglucose uptake consistent of inflammatory changes. Overall, our data improve our knowledge on the effects induced by immunotherapy, which may have a clinical impact at longer follow-up. Take Home Message ● In the PURE-01 study, T2-4N0M0 muscle-invasive bladder cancer patients were staged with fluorodeoxyglucose (FDG) positron emission tomography/computed tomography (PET/CT) before and after pembrolizumab. ● PET/CT after pembrolizumab revealed inflammatory FDG uptake in 39% of patients, but only 45% of these cases of uptake corresponded to clinically evident adverse events. ● The development of inflammatory uptake was associated with a higher pathological complete response rate and longer progression-free survival, although these differences were not statistically significant.

Impact of low-dose SPECT imaging on normal databases and myocardial perfusion scores.

PURPOSE: We have recently demonstrated that iterative reconstruction algorithms with resolution recovery require the adoption of specific normal databases (NDBs) for perfusion SPECT quantification. This work was aimed at investigating the impact of patient low-dose imaging on NDBs and percent summed rest (SR%) and stress (SS%) scores. METHODS: Assuming that count statistics of shorter acquisition time may simulate that of lower patient dose, three simultaneous scans were acquired (BrightView, Philips) with different acquisition-time/projection: 30, 15 and 8 s (from 100% to 25% of the reference). Fifty-two normal patients with low likelihood of coronary artery disease were enrolled and three homemade NDBs were then generated and compared (Astonish™ algorithm with default parameters): 100%-HM-NDBs, 50%-HM-NDBs and 25%-HM-NDBs. SR% and SS% were subsequently calculated for another group of 38 patients (normal/abnormal = 5/33). SR% and SS% values of 100%-HM-NDBs were compared with those obtained with the NDBs available on the workstation. Moreover, the impact of the study count statistics on perfusion scores was evaluated using the count-specific NDBs. RESULTS: Significantly higher standard-deviation values were found for 25%-HM-NDBs compared to the other HM-NDBs (p < 0.02). Significantly higher SS% were also found for the 100%-HM-NDBs compared to the workstation NDBs (95%CI: 0.15-2.11%). Moreover, a post-hoc test showed significantly lower SR% and SS% for 25%-count statistics compared to 100%-HM-NDBs (p < 0.03). CONCLUSIONS: NDBs and perfusion scores depend significantly on study count-statistics. A 50% reduction in patient dose is ultimately the limit for Astonish™ (with the default parameters) in order to prevent a significant variation in myocardial perfusion quantification.

Impressive Response to Tandem Treatment With [90Y]DOTATOC and [177Lu]DOTATOC in Grade 3 Pancreatic Neuroendocrine Carcinoma.

Peptide receptor radionuclide therapy is an effective, well-tolerated, treatment for well-differentiated neuroendocrine tumors, resulting in a significant survival benefit and improvement of quality of life. Very few data are available on peptide receptor radionuclide therapy effectiveness in grade 3 neuroendocrine carcinomas with high somatostatin receptor expression. We report the case of a 70-year-old woman with metastatic pancreatic grade 3 neuroendocrine carcinoma who underwent 6 cycles of tandem treatment with investigational radiopharmaceuticals Y-DOTATOC and Lu-DOTATOC achieving an impressive response.

Delayed Gastric Emptying in Advanced Parkinson Disease: Correlation With Therapeutic Doses.

INTRODUCTION: Gastrointestinal dysfunction is often described in patients with Parkinson disease (PD), and gastrointestinal symptoms are usually attributed to gastroparesis. The consequent delayed gastric emptying (GE) may be an important pharmacokinetic mechanism underlying some of the response fluctuations that develop after long-term levodopa (L-dopa) therapy.The aim of this prospective study was to assess GE time by a liquid meal scintigraphy, in PD patients, and to correlate them with demographic, clinical, and therapeutic data. METHODS: Scintigraphy with radiolabeled albumin nanocolloids added to acidified orange juice was performed in 51 consecutive PD patients 1 hour after their usual dopaminergic therapy first dose and after a 12-hour fast. Demographic, neurologic, gastrointestinal, and pharmacologic data were collected. RESULTS: Fifty-one patients were divided into 2 groups using the cutoff point obtained in normal subjects (40 minutes): group 1 included 29 patients with GE T½ of 27.60 ± 7.30 minutes (normal), group 2 showed a GE T½ of 84.90 ± 53.80 minutes (delayed). The most striking significant difference between the 2 groups was the dopa-decarboxylase inhibitor mean dose that was significantly higher in the group of patients with delayed GE (201.32 ± 97.26 vs 127.65 ± 79.74; P = 0.005). CONCLUSIONS: The impairment of gastric motility, frequently represented in PD patients, occurs in approximately 42% of patients with motor complications. A mechanism that may explain the GE delay is the effect of L-dopa on dopaminergic receptors in the stomach. Therefore, the dosage of dopa-decarboxylase inhibitor, increasing the L-dopa concentration, may contribute to GE delay and its consequent effect on drug delivery and efficacy.