Anti-osteoporotic treatments in the era of non-alcoholic fatty liver disease: friend or foe.

Over the last years non-alcoholic fatty liver disease (NAFLD) has grown into the most common chronic liver disease globally, affecting 17-38% of the general population and 50-75% of patients with obesity and/or type 2 diabetes mellitus (T2DM). NAFLD encompasses a spectrum of chronic liver diseases, ranging from simple steatosis (non-alcoholic fatty liver, NAFL) and non-alcoholic steatohepatitis (NASH; or metabolic dysfunction-associated steatohepatitis, MASH) to fibrosis and cirrhosis with liver failure or/and hepatocellular carcinoma. Due to its increasing prevalence and associated morbidity and mortality, the disease-related and broader socioeconomic burden of NAFLD is substantial. Of note, currently there is no globally approved pharmacotherapy for NAFLD. Similar to NAFLD, osteoporosis constitutes also a silent disease, until an osteoporotic fracture occurs, which poses a markedly significant disease and socioeconomic burden. Increasing emerging data have recently highlighted links between NAFLD and osteoporosis, linking the pathogenesis of NAFLD with the process of bone remodeling. However, clinical studies are still limited demonstrating this associative relationship, while more evidence is needed towards discovering potential causative links. Since these two chronic diseases frequently co-exist, there are data suggesting that anti-osteoporosis treatments may affect NAFLD progression by impacting on its pathogenetic mechanisms. In the present review, we present on overview of the current understanding of the liver-bone cross talk and summarize the experimental and clinical evidence correlating NAFLD and osteoporosis, focusing on the possible effects of anti-osteoporotic drugs on NAFLD.

Transorbital sonography in idiopathic intracranial hypertension: Single-center study, systematic review and meta-analysis.

BACKGROUND AND PURPOSE: Transorbital sonography (TOS) provides a noninvasive tool to detect intracranial pressure by assessing optic nerve sheath diameter (ONSD) and optic disc elevation (ODE). The utility of TOS in the diagnosis of idiopathic intracranial hypertension (IIH) has been increasingly recognized. METHODS: A single-center case-control study sought to compare TOS-acquired ONSD and ODE among IIH-cases versus patients with other neurological diseases (controls). Furthermore, a systematic review and meta-analysis was conducted to present pooled mean differences and diagnostic measures of ONSD and ODE between IIH-cases and controls. RESULTS: In the single-center study, consisting of 31 IIH-cases and 34 sex- and age-matched controls, ONSD values were higher among IIH-cases than controls (p<.001), while ODE was more prevalent in cases (65% vs. 15%; p<.001). The receiver-operating characteristic (ROC)-curve analysis revealed that the optimal cutoff value of ONSD for predicting IIH was 5.15 mm, with an area under the curve (AUC) of 0.914 (95% confidence interval [CI]: 0.861-0.967) and sensitivity and specificity values of 85% and 90%, respectively. In a meta-analysis of 14 included studies with 415 IIH-cases, ONSD and ODE values were higher in IIH-cases than controls (mean difference in ONSD 1.20 mm; 95% CI: 0.96-1.44 mm and in ODE 0.3 mm; 95% CI: 0.33-0.67 mm). With regard to ONSD, pooled sensitivity, specificity, and diagnostic odds ratio were calculated at 85.5% (95% CI: 77.9-90.8%), 90.7% (95% CI: 84.6-94.5%), and 57.394 (95% CI: 24.597-133.924), respectively. The AUC in summary ROC-curve analysis was 0.878 (95% CI: 0.858-0.899) with an optimal cutoff point of 5.0 mm. CONCLUSIONS: TOS has a high diagnostic utility for the noninvasive diagnosis of IIH and may deserve wider implementation in everyday clinical practice.

Multiple cerebral microinfarcts: an uncommon presentation of Cerebral Amyloid Angiopathy-related inflammation.

BACKGROUND: Cerebral Amyloid Angiopathy-related inflammation (CAA-ri) is a distinct but rare subset of CAA. The greater availability of high resolution Magnetic Resonance Imaging (MRI) has currently allowed the increasing recognition and diagnosis of this entity, without the risk of a brain biopsy. However, in rare cases with typical clinical characteristics but uncommon neuroimaging findings at presentation, the brain-biopsy is required for an early and reliable diagnosis. CASE DESCRIPTION: A 71-year-old man with arterial hypertension presented due to 1-week history of headache, vomiting, disorientation and impaired consciousness. Brain MRI revealed multiple acute cortical/subcortical microinfarcts, scarce microbleeds, extensive right parietooccipital and left frontotemporal leptomeningeal enhancement. After an extensive diagnostic work-up, excluding infectious, neoplastic and autoimmune etiologies, the patient underwent brain-biopsy. Histology disclosed amyloid deposition in an arteriolar wall and the patient fulfilled diagnostic criteria for probable CAA-ri with supporting pathology. He received intravenous methylprednisolone, followed by oral tapering with steroids showing clinical and radiological improvement with complete resolution of gadolinium enhancement. Follow-up MRI revealed an increase of cerebral microbleeds and the patient fulfilled CAA-ri neuroimaging criteria. CONCLUSIONS: This case highlights the importance of continuous vigilance from clinical neurologists to detect CAA-ri diagnosis and the diagnostic value of brain-biopsy in CAA-ri patients with atypical neuroimaging presentation, such as acute microinfarcts. The early diagnosis and the prompt treatment initiation can improve the prognosis and the evolution of this rare disorder.

Safety of COVID-19 vaccines in multiple sclerosis: A systematic review and meta-analysis.

BACKGROUND: Data are sparse regarding the safety of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccines in patients with multiple sclerosis (MS). OBJECTIVE: To estimate (1) the pooled proportion of MS patients experiencing relapse among vaccine recipients; (2) the rate of transient neurological worsening, adverse events, and serious adverse events; (3) the previous outcomes of interest for different SARS-CoV-2 vaccine types. METHODS: Systematic review and meta-analysis of pharmacovigilance registries and observational studies. RESULTS: Nineteen observational studies comprising 14,755 MS patients who received 23,088 doses of COVID-19 vaccines were included. Mean age was 43.3 years (95% confidence interval (CI): 40-46.6); relapsing-remitting, secondary-progressive, primary-progressive MS and clinically isolated syndrome were diagnosed in 82.6% (95% CI: 73.9-89.8), 12.6% (95% CI: 6.3-20.8), 6.7% (95% CI: 4.2-9.9), and 2.9% (95% CI: 1-5.9) of cases, respectively. The pooled proportion of MS patients experiencing relapse at a mean time interval of 20 days (95% CI: 12-28.2) from vaccination was 1.9% (95% CI: 1.3%-2.6%; I2 = 78%), with the relapse risk being independent of the type of administered SARS-CoV-2-vaccine (p for subgroup differences = 0.7 for messenger RNA (mRNA), inactivated virus, and adenovector-based vaccines). After vaccination, transient neurological worsening was observed in 4.8% (95% CI: 2.3%-8.1%) of patients. Adverse events and serious adverse events were reported in 52.8% (95% CI: 46.7%-58.8%) and 0.1% (95% CI: 0%-0.2%) of vaccinations, respectively. CONCLUSION: COVID-19 vaccination does not appear to increase the risk of relapse and serious adverse events in MS. Weighted against the risks of SARS-CoV-2-related complications and MS exacerbations, these safety data provide compelling pro-vaccination arguments for MS patients.

The Effect of Neuromuscular Electrical Nerve Stimulation in the Management of Post-stroke Spasticity: A Scoping Review.

Stroke is a cerebrovascular disorder characterized by the sudden onset of symptoms and clinical signs caused by either vascular infraction or hemorrhage. One of the main symptoms in the majority of post-stroke patients is spasticity. The main therapeutic options of spasticity in post-stroke patients include pharmacological interventions, rehabilitation techniques, and surgery. This review aims to explore the effectiveness of Neuromuscular Electrical Stimulation (NMES) for post-stroke spastic hemiparetic limb (upper and lower). Thorough research of the PubMed Medline database was performed. Records were limited to clinical studies published between 01/01/2010 and 01/01/2022. The results were screened by the authors in pairs. The search identified 26 records. After screening, nine records met the inclusion-exclusion criteria and were assessed. There were seven studies for spastic upper limbs and two for spastic lower limbs. The approaches investigated the effectiveness of electrical stimulation on post-stroke spastic upper or lower limb. Spasticity was measured through the modified Ashworth scale (MAS) and electromyographic recordings (EMG). In most cases, spasticity was decreased for at least two weeks post-intervention. In conclusion, NMES can be used either solo or in combination with different physical therapy modalities in order to produce optimal results, taking into consideration the specific needs and limitations of each individual patient. Based on the existing literature, as well as the limitations of the included studies, the authors believe that future studies on the subject of NMES in the management of post-stroke spasticity should focus on carefully examining each electrical parameter.

Bilateral non-bifurcating carotid arteries in a patient with recurrent cerebrovascular events.

INTRODUCTION: Among congenital anomalies of the carotid artery circulation, the presence of a non-bifurcating carotid artery is extremely rare. Relevant cases with unilateral non-bifurcating carotid artery have scarcely been described in the literature. After extensive literature review, only one case with asymptomatic bilateral non-bifurcating carotid arteries associated with persistent proatlantal artery was identified. METHODS: We present the case of a 40-year-old man with recurrent cerebrovascular events presenting non-bifurcating carotid arteries bilaterally. RESULTS: A 40-year-old man presented in the emergency department with a transient ischemic attack. Past medical history included prior ischemic stroke of unknown etiology in the distribution of the left middle cerebral artery, untreated hyperlipidemia and tobacco use. Complete work-up in order to identify the underlying mechanism of the patient's recurrent cerebrovascular events was negative, except for the finding of non-bifurcating carotid arteries bilaterally, associated with an extensive intracranial anastomosing arterial network. Long-term antiplatelet therapy and statins were administered as secondary stroke prevention therapy. DISCUSSION: Previous reports suggest that non-bifurcating carotid arteries may be associated with atherosclerotic plaque formation in symptomatic cases due to shear stress, tortuosity or other local factors. However, in the absence of atherosclerosis, the pathogenic association of bilateral non-bifurcating carotid arteries with cerebrovascular events remains questionable, but may be considered when other stroke etiologies are excluded.

Placental Mesenchymal Dysplasia: Ultrasound Characteristics and Diagnostic Pitfalls.

Placental mesenchymal dysplasia (PMD) is a rare, benign developmental anomaly with a reported prevalence of 0.02% (Arizawa and Nakayama, 2002). It is characterized by placentomegaly with multiple cystic lesions of the stem villi and vascular anomalies (Pawoo and Heller, 2014). Early detection of PMD has been described during routine prenatal ultrasound (Vaisbuch et al., 2009). The sonographic characteristics of PMD include increased placental thickness and multiple cystic areas within the placenta with either an absence of blood flow or with low venous Doppler signals (Vaisbuch et al., 2009). The differential diagnosis of multicystic placental lesions with the presence of a live fetus include partial molar pregnancy, multiple hematomas, chorioangioma Beckwith-Wiedemann syndrome and PMD. Chorioangiomas are well circumscribed masses within the placenta and they are characterized by the presence of a single feeding vessel with the same pulse rate as the umbilical cord (Zalel et al., 2002). Invasive prenatal testing is required for the exclusion of partial molar pregnancy and Beckwith-Wiedemann Syndrome (Vaisbuch et al., 2009). Definitive diagnosis of PMD is based on the pathologic examination of the placenta. Histology reveals aneurysm or dilated blood vessels that may be thrombosed. The stem villi are edematous and enlarged with thick-walled vessels, without trophoblastic proliferation (Pawoo and Heller, 2014). This case report highlights the significance of the early detection of PMD, illustrates the pitfalls in differential diagnosis and provides valuable insights regarding PMD management in a clinical setting.

Three new case reports of Arteriovenous malformation-related Amyotrophic Lateral Sclerosis.

Despite recent advances in genetics, in most cases of Amyotrophic Lateral Sclerosis (ALS) no etiological factor can be identified. Cerebral Arteriovenous Malformations (AVMs) have been associated with ALS development in a few studies, but the nature of this connection is unclear. We report here 3 additional cases of young adults, who had undergone repeated embolizations for complex AVMs, and who then developed, after many years, ALS symptoms and signs. In two of these cases Vascular Endothelial Growth Factor (VEGF) levels were found to be extremely high, in contrast to previous reports. Our 3 cases, together with the previously reported ones, suggest that a subgroup of patients with AVMs, with a particular profile of a complex nidus with repeated embolization procedures, are at increased risk of developing ALS. The reason for this association is unclear, but may relate to dysregulation of secreted vascular factors, as suggested by our VEGF results, or more broadly to the neurovascular hypothesis of ALS. Alternatively, a transneuronal type of neurodegeneration may be involved.