Posterior Reversible Encephalopathy Syndrome Presenting with Atypical Findings: Report of Two Cases

Background. Posterior reversible encephalopathy syndrome (PRES) is characterized by a variable association of symptoms including headache, consciousness impairment, visual disturbances, seizures, and focal neurological signs. Treating the underlying cause usually leads to partial or complete resolution of symptoms within days or weeks. Brain MRI findings include hyperintensities on T2-weighted sequences and their reversibility on follow-up exams. We describe two patients, one with an atypical clinical presentation characterized by a severe and prolonged impairment of consciousness and the other with atypical neuroimaging findings. Case Presentation. The first patient was a 42-year-old woman, with a negative medical history, presenting with seizures, lethargy, and left hemiparesis, 60 hours after uncomplicated delivery. Brain MRI showed an atypical pattern of alterations, with patchy asymmetric distribution in all lobes. Symptoms completely resolved after twelve days. The second patient was a 59-year-old woman with a history of hypertension, presenting with severe impairment of consciousness, vision loss, and seizures. Symptoms partially resolved after three weeks. Conclusion. PRES is characterized by reversible symptoms and radiological findings. Brain MRI usually shows widespread oedema in white matter with typical patterns. The cases we described suggest that PRES may presents with atypical symptoms and radiological manifestations, mimicking other neurological conditions

Gene- and Gender-Related Decrease in Serum BDNF Levels in Alzheimer’s Disease

Brain-derived neurotrophic factor (BDNF) has a protective role in Alzheimer’s disease (AD). Oxidative stress and inflammatory cytokines are potentially implicated in AD risk. In this study, BDNF was detected in serum of AD and mild cognitive impairment (MCI) patients and investigated in association with gene polymorphisms of BDNF (Val66Met and C270T), of some oxidative stress-related genes (FOXO3A, SIRT3, GLO1, and SOD2), and of interleukin-1 family genes (IL-1α, IL-1β, and IL-38). The APOE status and mini-mental state examination (MMSE) score were also evaluated. Serum BDNF was significantly lower in AD (p = 0.029), especially when comparing the female subsets (p = 0.005). Patients with BDNFVal/Val homozygous also had significantly lower circulating BDNF compared with controls (p = 0.010). Moreover, lower BDNF was associated with the presence of the T mutant allele of IL-1α(rs1800587) in AD (p = 0.040). These results were even more significant in the female subsets (BDNFVal/Val, p = 0.001; IL-1α, p = 0.013; males: ns). In conclusion, reduced serum levels of BDNF were found in AD; polymorphisms of the IL-1α and BDNF genes appear to be involved in changes in serum BDNF, particularly in female patients, while no effects of other gene variants affecting oxidative stress have been found. These findings add another step in identifying gender-related susceptibility to AD

Magnetic Resonance-guided Focused Ultrasound thalamotomy for refractory neuropathic pain: a systematic review and critical appraisal of current knowledge

Background: Magnetic Resonance-guided Focused Ultrasound (MRgFUS) is an innovative therapeutical approach for medically refractory tremor. It is currently under investigation for other neurological diseases including refractory neuropathic pain (NP). Objective: The objective of this systematic review is to analyze available evidence about the effectiveness and safety profile of MRgFUS in the treatment of refractory NP. Methods: Eligible studies were identified by searching published studies in PubMed and Scopus databases from inception to December 2022 and by identifying ongoing studies registered on the clinicaltrials.gov website. The study was registered in PROSPERO (ID: CRD42021277154). Results: We found three published observational studies and nine ongoing studies. In published studies, the involved population ranged from 8 to 46 patients with overall 66 patients being included with NP or trigeminal neuralgia. The target lesion was in the posterior part of the central lateral nucleus of the thalamus, bilaterally. Outcomes were assessed at different times through the Visual Analog Scale, showing a variable degree of improvement. Adverse events were rare, mild, and transient (vertigo, paresthesias, and dysesthesias) with intracerebral bleeding being reported as major adverse event in one case only. Among ongoing studies, we found three prospective, randomized, sham-controlled, crossover trials (RCTs) and six observational studies. Inclusion criteria are previous failure of more than three pharmacological treatments and NP duration longer than 6 months. The thalamus is the main proposed target and measured outcomes are accuracy of the procedure and pain relief, with a follow-up period ranging from 1 week to 1 year. Conclusion: This systematic review suggests that, although high-quality studies are lacking, available evidence endorses the effectiveness and safety of MRgFUS in the management of NP. Ongoing RCTs will provide more robust data to understand benefits and risks of the procedure. Registration: PROSPERO (ID: CRD42021277154

Cerebello-Thalamo-Cortical MR Spectroscopy in Patients with Essential Tremor Undergoing MRgFUS Thalamotomy: A Pilot Study

Previous literature studies explored the association between brain neurometabolic changes detected by MR spectroscopy and symptoms in patients with tremor, as well as the outcome after deep brain stimulation (DBS) treatment. The purpose of our study was to evaluate the possible changes in cerebello-thalamo-cortical neurometabolic findings using MR spectroscopy in patients submitted to MRgFUS thalamotomy. For this pilot study, we enrolled 10 ET patients eligible for MRgFUS thalamotomy. All patients were preoperatively submitted to 3T MR spectroscopy. Single-voxel MRS measurements were performed at the level of the thalamus contralateral to the treated side and the ipsilateral cerebellar dentate nucleus. Multivoxel acquisition was used for MRS at the level of the contralateral motor cortex. At the 6-month follow-up after treatment, we found a statistically significant increase in the Cho/Cr ratio at the level of the thalamus, a significant increase of the NAA/Cr ratio at the level of the dentate nucleus and a significant decrease of the NAA/Cho ratio at the level of the motor cortex. We found a significant positive correlation between cortical NAA/Cr and clinical improvement (i.e., tremor reduction) after treatment. A significant negative correlation was found between clinical improvement and thalamic and cerebellar NAA/Cr. Confirming some previous literature observations, our preliminary results revealed neurometabolic changes and suggest a possible prognostic role of the MRS assessment in patients with ET treated by MRgFUS

Levodopa Equivalent Dose of Safinamide: A Multicenter, Longitudinal, Case-Control Study

BackgroundEffects of dopaminergic medications used to treat Parkinson's disease (PD) may be compared with each other by using conversion factors, calculated as Levodopa equivalent dose (LED). However, current LED proposals on MAO-B inhibitors (iMAO-B) safinamide and rasagiline are still based on empirical approaches. ObjectivesTo estimate LED of safinamide 50 and 100 mg. MethodsIn this multicenter, longitudinal, case-control study, we retrospectively reviewed clinical charts of 500 consecutive PD patients with motor complications and treated with (i) safinamide 100 mg (N = 130), safinamide 50 mg (N = 144), or rasagiline 1 mg (N = 97) for 9 +/- 3 months and a control group of patients never treated with any iMAO-B (N = 129). ResultsMajor baseline features (age, sex, disease duration and stage, severity of motor signs and motor complications) were similar among the groups. Patients on rasagiline had lower UPDRS-II scores and Levodopa dose than control subjects. After a mean follow-up of 8.8-to-10.1 months, patients on Safinamide 50 mg and 100 mg had lower UPDRS-III and OFF-related UPDRS-IV scores than control subjects, who in turn had larger increase in total LED than the three iMAO-B groups. After adjusting for age, disease duration, duration of follow-up, baseline values and taking change in UPDRS-III scores into account (sensitivity analysis), safinamide 100 mg corresponded to 125 mg LED, whereas safinamide 50 mg and rasagiline 1 mg equally corresponded to 100 mg LED. ConclusionsWe used a rigorous approach to calculate LED of safinamide 50 and 100 mg. Large prospective pragmatic trials are needed to replicate our findings

The Impact of COVID-19 Quarantine on Patients With Dementia and Family Caregivers: A Nation-Wide Survey

Introduction: Previous studies showed that quarantine for pandemic diseases is associated with several psychological and medical effects. The consequences of quarantine for COVID-19 pandemic in patients with dementia are unknown. We investigated the clinical changes in patients with Alzheimer’s disease and other dementias, and evaluated caregivers’ distress during COVID-19 quarantine. Methods: The study involved 87 Italian Dementia Centers. Patients with Alzheimer’s Disease (AD), Dementia with Lewy Bodies (DLB), Frontotemporal Dementia (FTD), and Vascular Dementia (VD) were eligible for the study. Family caregivers of patients with dementia were interviewed by phone in April 2020, 45 days after quarantine declaration. Main outcomes were patients’ changes in cognitive, behavioral, and motor symptoms. Secondary outcomes were effects on caregivers’ psychological features. Results: 4913 patients (2934 females, 1979 males) fulfilled the inclusion criteria. Caregivers reported a worsening in cognitive functions in 55.1% of patients, mainly in subjects with DLB and AD. Aggravation of behavioral symptoms was observed in 51.9% of patients. In logistic regression analysis, previous physical independence was associated with both cognitive and behavioral worsening (odds ratio 1.85 [95% CI 1.42–2.39], 1.84 [95% CI 1.43–2.38], respectively). On the contrary, pandemic awareness was a protective factor for the worsening of cognitive and behavioral symptoms (odds ratio 0.74 [95% CI 0.65–0.85]; and 0.72 [95% CI 0.63–0.82], respectively). Approximately 25.9% of patients showed the onset of new behavioral symptoms. A worsening in motor function was reported by 36.7% of patients. Finally, caregivers reported a high increase in anxiety, depression, and distress. Conclusion: Our study shows that quarantine for COVID-19 is associated with an acute worsening of clinical symptoms in patients with dementia as well as increase of caregivers’ burden. Our findings emphasize the importance to implement new strategies to mitigate the effects of quarantine in patients with dementia