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Introduction: Magnetic resonance-guided focused ultrasound (MRgFUS) thalamotomy of the ventralis intermediate (Vim) nucleus is an "incisionless" treatment for medically refractory essential tremor (ET). We present data on 49 consecutive cases of MRgFUS Vim thalamotomy followed-up for 3 years and review the literature on studies with longer follow-up data., Methods: A retrospective chart review of patients who underwent MRgFUS thalamotomy (January 2018-December 2020) at our institution was performed. Clinical Rating Scale for Tremor (CRST) and Quality of Life in Essential Tremor (QUEST) scores were obtained pre-operatively and at each follow-up with an assessment of side effects. Patients had post-operative magnetic resonance imaging within 24 h and at 1 month to figure out lesion location, size, and extent. The results of studies with follow-up ≥3 years were summarized through a literature review., Results: The CRST total (baseline: 58.6 ± 17.1, 3-year: 40.8 ± 18.0) and subscale scores (A + B, baseline: 23.5 ± 6.3, 3-year: 12.8 ± 7.9; C, baseline: 12.7 ± 4.3, 3-year: 5.8 ± 3.9) and the QUEST score (baseline: 38.0 ± 14.8, 3-year: 18.7 ± 13.3) showed significant improvement that was stable during the 3-year follow-up. Three patients reported tremor recurrence and two were satisfactorily retreated. Side effects were reported by 44% of patients (severe: 4%, mild and transient: 40%). The improvement in tremor and quality of life in our cohort was consistent with the literature., Conclusion: We confirmed the effectiveness and safety of MRgFUS Vim thalamotomy in medically refractory ET up to 3 years., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The author(s) declared that they were an editorial board member of Frontiers, at the time of submission. This had no impact on the peer review process and the final decision., (Copyright © 2024 Tamburin, Paio, Bovi, Bulgarelli, Longhi, Foroni, Mantovani, Polloniato, Tagliamonte, Zivelonghi, Zucchella, Cavedon, Nicolato, Petralia, Sala, Bonetti, Tinazzi, Montemezzi and Ricciardi.)

Aluminum (Al) is a widespread metal in the environment, and is found in fresh or processed foods, household utensils, packaging, and medicines. In addition to its high toxicity, Al can also have estrogenic agonistic effects on target organs. Considering that the Al effects on the prostate are little known, the aim of this study was to evaluate the impact of aluminum chloride (AlCl 3 ) subacute exposure on the morphophysiology of the male ventral prostate and the female prostate of adult gerbils. Furthermore, the glandular restoration capacity in face of the Al insults was evaluated in gerbils that were submitted to 30 days of recovery. Male and female gerbils were orally exposed to AlCl 3 (10 mg/kg) for 30 consecutive days. The animals were euthanized 1 day (Al1D) or 30 days (Al30D) after the end of treatment. Prostates were dissected out and processed for structural, ultrastructural and immunohistochemical analyses. Male ventral prostates and female prostates of the Al1D group showed increased cell proliferation, glandular hyperplasia, increased secretory activity and greater androgen receptor immunoreactivity. In males, Al withdrawal (Al30D) allowed a partial recovery of the prostate, as the glandular secretory activity, and frequency of androgen receptor positive cells were similar to the control group. In females, the recuperation interval (Al30D) was not enough to restore the prostatic morphology, since the gland remained hyperplastic, proliferative, and with greater androgen and estrogen receptor immunoreactivity. These data alert to the importance of avoiding Al exposure, since this metal can have a harmful and prolonged action on the prostate., (© 2021 Wiley Periodicals LLC.)

Anticoagulant treatment as stroke prevention, particularly direct oral anticoagulant (DOAC), may reduce the risk of dementia in patients with atrial fibrillation (AF). We aimed to assess factors influencing cognitive performance after 1-year treatment with DOAC in patients with AF and previous ischemic stroke. We recruited 33 ischemic stroke patients who were discharged from Verona Stroke Unit with diagnosis of AF and prescription of treatment with DOAC. For each cognitive test, we estimated the effect of T0 (first session) variables on T1 (1-year session) cognitive performance using ordinal logistic regression fitted to a 1 point-shift from 4 to 0 on ESs. The effect of T0 clinical variables was presented as odds ratio (OR) with 95% confidence interval (CI) after adjustment for T0 total score of the corresponding cognitive test. Sustained AF (OR: 4.259, 95% CI 1.071-16.942) and ischemic heart disease (OR: 6.654, 95% CI 1.329-33.300) showed a significant effect on T1 MoCA Test; congestive heart failure on T1 RAVLT Immediate recall (OR: 9.128, 95% CI 1.055-78.995), T1 RAVLT Delayed recall (OR: 7.134, 95% CI 1.214-52.760), and T1 Trail Making Test (Part A) (OR: 16.989, 95% CI 1.765-163.565); sustained AF (OR: 5.055, 95% CI 1.224-20.878) and hyperlipidemia (OR: 4.764, 95% CI 1.175-19.310) on T1 Digit span forward Test; ischemic heart disease (aOR: 8.460, 95% CI 1.364-52.471) on T1 Stroop Color and Word Test (time); Dabigatran use (aOR: 0.084, 95% CI 0.013-0.544) on FAB; age ≥ 75 years (aOR: 0.058, 95% CI 0.006-0.563) and hyperlipidemia (aOR: 5.809, 95% CI 1.059-31.870) on T1 Phonemic word fluency Test; female sex (aOR: 6.105, 95% CI 1.146-32.519), hyperlipidemia (aOR: 21.099, 95% CI 2.773-160.564), total Modified Fazekas Scale score > 1 (aOR: 78.530, 95% CI 3.131-1969.512) on Semantic word fluency Test. Sustained AF, ischemic heart disease, congestive heart failure, hyperlipidemia, and female sex were the factors influencing cognitive performance after 1-year treatment with DOAC in patients with AF and previous ischemic stroke. Modified Fazekas Scale score in the first session was the only radiological variable that had a significant effect on cognitive performance.

Pain is a common and disabling non-motor symptom (NMS) of Parkinson's disease (PD), which occurs through the course of the disease, often unrecognized and undertreated. For this study, we evaluated the efficacy and safety of safinamide to reduce pain in PD patients with motor fluctuations. A total of 13 PD patients with pain receiving safinamide (Xadago®, 100 mg/daily) were prospectively evaluated for 12 weeks. The primary outcome measures were changes in the total score of the King's Pain Scale for Parkinson's Disease (KPPS), Brief Pain Inventory (BPI) Intensity and Interference, and the Numeric Rating Scale (NRS). Secondary outcomes were the proportion of pain responders, changes in the Clinical Global Impression of Change (CGI), the Parkinson's disease Quality of Life 39 (PDQ39), the Unified Parkinson's Disease Rating Scale parts III and IV (UPDRS III and IV), and laser-evoked potentials (LEPs). LEPs were used to assess potential changes in the central processing of nociceptive inputs. The safety profile was evaluated based on the occurrence of treatment-emergent side effects and the dropout rate. After 12 weeks of add-on safinamide therapy, a significant improvement was noted in the primary (KPPS, BPI Intensity and interference, and NRS) and the secondary outcomes (UPDRS III, IV, CGI, and PDQ39). No significant changes in LEP complexes were observed. All patients completed the study and no treatment-emergent side effects were reported. Our preliminary findings suggest that safinamide 100 mg/day may be effective for the management of pain in PD patients with motor fluctuations and is safe. Further randomized controlled trials are needed to confirm its efficacy.

Background: There is mutual influence between the liver and thyroid hormone metabolism. Patients with diabetes mellitus (DM) also have an increased prevalence of thyroid disorders (TDs). The objectives of this study were to evaluate the frequency of TD before and after liver transplantation (LT) in a population of patients with DM as a whole and when categorized by sex., Materials and Methods: This was a retrospective study involving interview and medical record analysis of 46 consecutive patients followed at the diabetes mellitus and liver transplantation unit of a tertiary university hospital., Results: Of all patients, 76.1% were men with a median age of 60 years old (interquartile range: 56 to 65 years) and time since LT of 5 years (range, 0.6 to 9 years). Hypertension, hypercholesterolemia, hypertriglyceridemia, alcoholism, and smoking were present in 47.8%, 34.8%, 23.9%, 34.8%, and 30.4% of the patients, respectively. The most frequent immunosuppressant in use was tacrolimus (71.1%). TD was present in 4.3% and 13% before and after LT, respectively (P = .058). In women and men, these frequencies were 9.1% and 18.2% (P = .563), and 2.9% and 11.8% (P = .045), respectively., Conclusions: Frequency of TD was high both before and after LT. After transplantation, prevalence of TD increased in men and differences between males and females almost disappeared. Further studies are needed to assess if screening for TD before and after LT in patients with DM might be beneficial, especially in men., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Background: Over the years, survival after liver transplantation has increased and metabolic complications are becoming more common, contributing to patients' morbidity and mortality. The objectives of this study were to describe a population of patients with hepatic transplantation and diabetes mellitus (DM), evaluate the frequency of metabolic complications, and assess the impact of a multidisciplinary team on DM management., Materials and Methods: This was a retrospective study involving interview and medical record analysis of 46 consecutive patients followed at the diabetes mellitus and liver transplantation unit of a tertiary university hospital, all evaluated by a multidisciplinary team., Results: Of all patients, 76.1% were men, with a median age 60 years old (interquartile range: 56 to 65 years) and liver transplantation time of 5 years (interquartile range: 0.6-9 years). Hypertension, hypercholesterolemia, hypertriglyceridemia, alcoholism, and smoking were present in 47.8%, 34.8%, 23.9%, 34.8%, and 30.4% of the patients, respectively. The most frequent immunosuppressant in use was tacrolimus (71.1%). Regarding nutritional status, 37.9% of patients were classified as overweight according to body mass index, and 41.2% were considered overweight according to the triceps skin fold. The median glycosylated hemoglobin and weight before and after intervention of the multidisciplinary team in all 46 patients were, respectively, 7.6% (5.7% to 8.8%) versus 6.5% (5.7% to 7.7%); P = .022 and 70.5 kg (64.7 to 82.0 kg) versus 71.6 kg (65.0 to 85.0 kg); P = .18., Conclusions: Hypertension and dyslipidemia were common in transplanted patients with DM. Intervention of the multidisciplinary team resulted in a significant improvement in glycosylated hemoglobin without significant weight gain., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Similarly to subjects with degenerative parkinsonism, (123)I-FP-CIT SPECT has been reported either normal or abnormal in patients with drug-induced parkinsonism (DIP), challenging the notion that parkinsonism might be entirely due to post-synaptic D2-receptors blockade by antipsychotic drugs. In a previous multicenter cross-sectional study conducted on a large sample of patients with schizophrenia, we identified 97 patients who developed parkinsonism with a similar bi-modal distribution of DAT-SPECT. In this longitudinal study, we reported clinical and imaging features associated with progression of motor disability over 2-year follow-up in 60 out of those 97 patients with schizophrenia and parkinsonism who underwent (123)I-FP-CIT SPECT at baseline evaluation (normal SPECT=33; abnormal SPECT=27). As second end-point, chronic response to levodopa over a 3-month period was tested in a subgroup of subjects. Motor Unified Parkinson's Disease Rating Scale (UPDRS) at follow-up significantly increased in patients with abnormal SPECT. Specifically, a 6-point worsening was demonstrated in 18.5% of the subjects with abnormal SPECT and in none of the subjects with normal SPECT. Levodopa treatment improved motor UPDRS only in the group with abnormal SPECT. After adjustment for possible confounders, linear regression analysis demonstrated that abnormal SPECT findings at baseline were the only predictor of motor disability progression and of better outcome of levodopa treatment. Our results support the notion that a degenerative disease might underlie parkinsonism in a minority of schizophrenic patients chronically exposed to antipsychotics. Functional imaging of the dopamine transporter can be helpful to select this patient sub-group that might benefit from levodopa therapy., (Copyright © 2013 Elsevier B.V. All rights reserved.)

The pathophysiology of postural abnormalities in patients with Parkinson's disease is poorly understood. In the present study, 13 patients with Pisa syndrome (PS) underwent EMG study of paraspinal lumbar (L2-L4) and thoracic (T8-T10) muscles, and of non-paraspinal muscles. Patients also underwent a whole spine X-ray and an MRI assessment of paraspinal muscles (L1-S1). The EMG evaluation disclosed two main patterns: patients with pattern I (n = 6, hyperactivity of lumbar paraspinals ipsilateral to the trunk leaning side) or pattern II (n = 7: hyperactivity of lumbar paraspinals contralateral to the trunk leaning side. In pattern I, half the patients also had ipsilateral hyperactivity of the thoracic paraspinals, the other half had contralateral thoracic hyperactivity; in pattern II, thoracic paraspinal hyperactivity was contralateral in all patients (like the lumbar paraspinal hyperactivity). Non-paraspinal muscles were hyperactive ipsilaterally in four of six patients with pattern I and in all patients with pattern II. The MRI showed mild muscular atrophy with fatty degeneration in patients with pattern I, whereas in pattern II patients this was greater and prevalent on paraspinal lumbar muscles ipsilateral to the leaning side. The present data support the hypothesis that two main patterns of muscular activation are associated with PS. In both patterns, hyperactivity of contralateral paraspinal muscles is probably compensatory for the trunk leaning.

The Movement Disorder Society-sponsored revision of the Unified Parkinson's Disease Rating Scale (MDS-UPDRS) has been available in English since 2008. As part of this process, the MDS-UPDRS organizing team developed guidelines for development of official non-English translations. We present here the formal process for completing officially approved non-English versions of the MDS-UPDRS and specifically focus on the first of these versions in Italian. The MDS-UPDRS was translated into Italian and tested in 377 native-Italian speaking PD patients. Confirmatory and exploratory factor analyses determined whether the factor structure for the English-language MDS-UPDRS could be confirmed in data collected using the Italian translation. To be designated an 'Official MDS translation,' the Comparative Fit Index (CFI) had to be ≥0.90 relative to the English-language version. For all four parts of the Italian MDS-UPDRS, the CFI, in comparison with the English-language data, was ≥0.94. Exploratory factor analyses revealed some differences between the two datasets, however these differences were considered to be within an acceptable range. The Italian version of the MDS-UPDRS reaches the criterion to be designated as an Official Translation and is now available for use. This protocol will serve as outline for further validation of this in multiple languages.

Isolated paresthesia, or paresthesia not accompanied by sensory and/or motor deficits, is an extremely rare manifestation of a cerebrovascular accident. Lacunar pure sensory stroke (PSS) confined to thalamus is characterized by persistent or transient numbness, tingling, pain, burning, or another unpleasant sensation on one side of the body. However, in this condition a sensory loss to all primary modalities in the contralateral face and body is very often encountered. Also previous reported cases of PSS due to lacunar stroke in regions other than thalamus are characterized by the presence of sensory loss together with positive sensory symptoms, none of them reporting isolated paresthesia as the only clinical feature of PSS. We present a case of isolated paresthesia as only clinical manifestation of a lacunar PSS involving both trigeminal and medial lemniscus in dorsal paramedian pontine region. A PSS manifesting with isolated paresthesias may be secondary not only to a thalamic lacunar stroke, but also to a small ischemic lesion confined to both trigeminal and medial lemniscus in dorsal paramedian pontine region.

Pisa Syndrome is clinically defined as the sustained lateral bending of the trunk worsened by a prolonged sitting position or by walking. Pisa syndrome, also termed lateral trunk flexion (LTF), has been rarely reported in patients affected by Parkinson's disease (PD) and, therefore, the pathophysiology has been poorly investigated. In some cases, the hyperactivity of paravertebral muscles contralateral to the leaning side has been interpreted as a sign of dystonia; however, it is well known that paravertebral muscles flex the trunk ipsilaterally. We systematically explored the pattern of muscular activation underlying the lateral flexion of trunk in 10 PD patients (mean disease duration: 9.2 ± 3.0 years) presenting LTF for 3.6 ± 2.1 years. EMG performed during stance and during left and right lateral trunk flexion showed a continuous ipsilateral muscular hyperactivity in three patients, while in the remaining ones there was no ipsilateral activity during standing and a tonic contraction of paravertebral muscles contralateral to the leaning side. In conclusion, this EMG study investigating the synergies of paravertebral muscles during dynamic conditions detected two different patterns with a typical dystonic activation in only a minority of cases. Possible pathophysiologic mechanisms and treatment approaches are discussed.

Olfactory impairment has been reported in drug-induced parkinsonism (DIP), but the relationship between dopaminergic dysfunction and smell deficits in DIP patients has not been characterized. To this end, we studied 16 DIP patients and 13 patients affected by Parkinson's disease (PD) using the "Sniffin' Sticks" test and [(123)I] FP-CIT SPECT (single-photon emission computed tomography). DIP patients were divided based on normal (n = 9) and abnormal (n = 7) putamen dopamine transporter binding. Nineteen healthy age- and sex-matched subjects served as controls of smell function. Patients with DIP and pathological putamen uptake had abnormal olfactory function. In this group of patients, olfactory TDI scores (odor threshold, discrimination and identification) correlated significantly with putamen uptake values, as observed in PD patients. By contrast, DIP patients with normal putamen uptake showed odor functions-with the exception of the threshold subtest-similar to control subjects. In this group of patients, no significant correlation was observed between olfactory TDI scores and putamen uptake values. The results of our study suggest that the presence of smell deficits in DIP patients might be more associated with dopaminergic loss rather than with a drug-mediated dopamine receptor blockade. These preliminary results might have prognostic and therapeutic implications, as abnormalities in these individuals may be suggestive of an underlying PD-like neurodegenerative process.

We recently found that patients with drug-induced parkinsonism (DIP) may have normal (group I) or abnormal (group II) putamen [(123)I]FP-CIT DAT (dopamine transporter) binding. In this study we reassessed clinical features and DAT binding in 19 of the original 32 patients (10 of group I and 9 of group II) after a 19-39-month follow-up period and tested the effects of chronic levodopa treatment in both cohorts of patients. In group I patients, [(123)I]FP-CIT SPET (single photon emission tomography) was still normal in all patients at follow-up; DAT binding and UPDRS (Unified Parkinson's Disease Rating Scale) motor score values did not differ from baseline. In group II patients, [(123)I]FP-CIT SPET was still abnormal at follow-up; putamen DAT binding was significantly reduced and UPDRS III score higher compared to baseline. Levodopa treatment improved motor symptoms in three out of ten patients of group I and in eight out of nine patients of group II. No adverse psychiatric effects were observed in any of the patients. This study shows that DAT binding imaging may help to identify subjects with DIP secondary to a loss of dopamine nerve terminals in the context of a progressive degenerative parkinsonism. Patients with DIP may benefit from levodopa therapy, particularly when dopamine nerve terminal defects are present, and this should be considered in the therapeutic management of these patients.

The light insensitive maize (Zea mays) mutant elongated mesocotyl1 (elm1) has previously been shown to be deficient in the synthesis of the phytochrome chromophore 3E-phytochromobilin (PPhiB). To identify the Elm1 gene, a maize homolog of the Arabidopsis PPhiB synthase gene AtHY2 was isolated and designated ZmHy2. ZmHy2 encodes a 297-amino acid protein of 34 kD that is 50% identical to AtHY2. ZmHY2 was predicted to be plastid localized and was targeted to chloroplasts following transient expression in tobacco (Nicotiana plumbaginifolia) leaves. Molecular mapping indicated that ZmHy2 is a single copy gene in maize that is genetically linked to the Elm1 locus. Sequence analysis revealed that the ZmHy2 gene of elm1 mutants contains a single G to A transition at the 3' splice junction of intron III resulting in missplicing and premature translational termination. However, flexibility in the splicing machinery allowed a small pool of in-frame ZmHy2 transcripts to accumulate in elm1 plants. In addition, multiple ZmHy2 transcript forms accumulated in both wild-type and elm1 mutant plants. ZmHy2 splice variants were expressed in Escherichia coli and products examined for activity using a coupled apophytochrome assembly assay. Only full-length ZmHY2 (as defined by homology to AtHY2) was found to exhibit PPhiB synthase activity. Thus, the elm1 mutant of maize is deficient in phytochrome response due to a lesion in a gene encoding phytochromobilin synthase that severely compromises the PPhiB pool.