Restless leg syndrome as a complication of primary hyperparathyroidism: insights from a retrospective study.

INTRODUCTION: Restless leg syndrome (RLS) is an invalidating neurological disorder with a complex, largely unknown pathophysiology. While RLS is observed in Parkinson's disease and in renal failure, idiopathic cases are common. Limited reports associate RLS with parathyroid hormone (PTH). This study analyzes a cohort of patients with primary hyperparathyroidism (PHPT) and chronic post-surgical hypoparathyroidism (hypo PTH), to investigate RLS prevalence, and associated risk factors. METHODS: Ninety-five patients (54 PHPT, 41 hypo PTH) were consecutively enrolled at the bone metabolism outpatient clinic. The revised IRLSSG diagnostic criteria were used to diagnose RLS, with assessments conducted through face-to-face interviews and neurological examination. When RLS was confirmed, the RLS severity scale was applied. Retrospective records included calcium-phosphate metabolism-related parameters, surgery details, renal lithiasis, fragility fractures, and densitometric features (T-score). RESULTS: RLS was diagnosed in 22.2% PHPT patients, compared to 4.9% of patients with hypo PTH (p = 0.02). Of RLS diagnosed patients, 91.7% had a history of parathyroidectomy, compared to 47.6% of patients without RLS (p = 0.01). Most of the operated patients reported that surgery determined an improvement of symptoms; however, mean score severity of RLS at our evaluation was 15/40, defined as moderate. PTH and calcium levels were not statistically associated to the presence of RLS. CONCLUSION: Our study suggests that PHPT may be one of the etiologies of RLS. Parathyroidectomy alleviates symptoms in the vast majority of the cases but does not remove them.

A new gene for autosomal dominant facial palsy/migraine identified in a family by whole exome sequencing.

BACKGROUND: Facial palsy manifests as unilateral or bilateral weakness and inability to move some of the facial muscles. The aetiology may be different including idiopathic, trauma, infections or brain tumours or it can be associated with chronic neurological diseases. For instance, in recurrent migraine, an increased risk of idiopathic facial palsy (often unilateral) has been observed. Migraine is a neurovascular disorder characterized by mild to severe intensity of headaches, often associated with neuro-ophthalmological symptoms. METHODS: A family is reported where five members were affected by facial palsy associated with other clinical features including migraine, diplopia, facial swelling, eye conjunctivitis following a vertical transmission. Whole exome sequencing was performed in three members (two affected and one healthy) in order to identify potential variants causative of their phenotype. RESULTS: A missense variant c.304G>A was found leading to the p.(Ala102Thr) substitution in the TRPM8 gene, previously related to migraine by genome wide association studies. This variant was classified as deleterious by several predictor tools, and the mutant residue was predicted to alter the protein structure in terms of flexibility and interactions with the surrounding residues. CONCLUSION: These findings suggest that TRPM8 could be a new causative gene further linking migraine and recurrent facial palsy.

Defense style and psychopathology in oncological patients: a preliminary report.

INTRODUCTION: Previous studies shows that 30-40% of oncological and hematological patients report symptoms of distress compatible with a psychiatric disorder. The use of various and mostly unconscious defense mechanisms is implemented to cope with increased suffering after a cancer diagnosis. In this preliminary report, we explored the presence of defense mechanisms and their associations with psychopathological dimensions in a sample of late-stage cancer patients without history of psychiatric disorders. METHODS: We recruited 50 patients (28 females, 18-64 years old) with cancer diagnosis without prior history of any substance use disorder or psychiatric disorders. All participants were given the following self-report questionnaires: the Symptom Checklist 90 (SCL-90) and the 40-item version of the Defense Style Questionnaire (DSQ-40). RESULTS: In our study we demonstrated significant psychiatric distress in a third of our patients (defined as SCL-90 ≥2 points). A Pearson correlation analysis on all patients shows that psychotic defense styles were correlated with hostility, obsessive-compulsive, anxiety, somatization, interpersonal sensitivity, and psychoticism, while neurotic defense styles correlated with somatization. DISCUSSION AND CONCLUSION: Our results are in line with previous findings showing that one third of cancer patients suffers from a psychiatric disorder. Moreover, we found that somatization correlates with both psychotic and neurotic defense mechanism styles. This demonstrates the importance of assessing oncological patients coping mechanisms to achieve best possible treatment.

Melkersson-Rosenthal Syndrome and Migraine: A New Phenotype Associated with SCN1A Variants?

Peripheral facial palsy rarely occurs as part of Melkersson-Rosenthal syndrome (MRS), which is characterized by the classical triad of tongue cheilitis, recurrent episodes of orofacial swelling, and palsy. MRS is a disorder with variable expressivity and clinical as well as genetic heterogeneity; however, the causative gene remains to be identified. Migraine is a common neurological disorder, presenting with or without aura, which may be associated with neurological symptoms. The classical example of monogenic migraine is familial hemiplegic migraine (FHM), which has phenotypic variability in carriers of variants in the same gene or even carriers of the same variant. We present a family in which two sisters displayed recurrent migraines, one of which presented recurrent facial palsy and had clinical diagnosis of MRS. We performed WES and Sanger sequencing for segregation analysis in the available family members. We identified a c.3521C>G missense heterozygous variant in SCN1A carried only by the affected sister. Variants in the SCN1A gene can cause a spectrum of early-onset epileptic encephalopathies, in addition to FHM; therefore, our finding reasonably explains the proband phenotype, in which the main symptom was recurrent facial palsy. This report also adds knowledge to the clinical spectrum of SCN1A alterations and suggests a potential overlap between MRS and FHM.

Subclavian artery revascularization with subclavian-carotid transposition for TEVAR and non-TEVAR patients.

BACKGROUND: Subclavian artery revascularization (SAR) has become an increasingly performed technique in patients undergoing thoracic endovascular aortic aneurysm repair (TEVAR), in order to optimize the proximal landing zone, or in patients with significant atherosclerotic diseases. SAR was usually achieved through carotid-subclavian bypass (CSB) which is daunted by graft and patency-related issues, or through subclavian carotid transposition (SCT) which has recently been reconsidered as a potential solution. Nowadays, multiple endovascular strategies including parallel grafts, chimney graft and branch-fenestrated repair, are available in patients unfit for open SAR. However, there is no consensus on the preferable technique in both TEVAR- and non TEVAR-patients. The purpose of this study was to evaluate our experience with SCT in terms of overall postoperative adverse events and mid-term patency rate. METHODS: We performed a retrospective cohort study, including all patients who underwent SCT between June 2014 and March 2020 at our Division. Preoperative risk factors, symptoms, intraoperative details, postoperative outcomes and follow-up data were collected. RESULTS: A total of 27 patients were included in this study. Indications for SCT included aortic arch debranching for TEVAR for thoracic aortic aneurysm and type B dissection and symptomatic subclavian steal syndrome (SSS). There were no major perioperative adverse events or major neurological complications; five minor adverse events occurred (18.5%) (3 Horner' Syndrome, 1 hematoma requiring reoperation,1 pneumothorax). Peripheral nerve injuries and lymphatic lesions were not recorded. On a mean follow-up of 21±16 months, SCT patency was confirmed in all patients and no deaths occurred. Comparison of baseline and operative characteristics and intraoperative details between groups of patients with or without adverse events did not found differences. CONCLUSIONS: SCT should be considered a feasible, effective and safe technique for SAR, with low perioperative complications and optimal mid-term patency. This surgical technique appears to provide a lower risk of neurological events and mortality, particularly in TEVAR patients, reducing the complications caused by the coverage of the left subclavian artery.

Clinical diagnostic utility of transcranial magnetic stimulation in neurological disorders. Updated report of an IFCN committee.

The review provides a comprehensive update (previous report: Chen R, Cros D, Curra A, Di Lazzaro V, Lefaucheur JP, Magistris MR, et al. The clinical diagnostic utility of transcranial magnetic stimulation: report of an IFCN committee. Clin Neurophysiol 2008;119(3):504-32) on clinical diagnostic utility of transcranial magnetic stimulation (TMS) in neurological diseases. Most TMS measures rely on stimulation of motor cortex and recording of motor evoked potentials. Paired-pulse TMS techniques, incorporating conventional amplitude-based and threshold tracking, have established clinical utility in neurodegenerative, movement, episodic (epilepsy, migraines), chronic pain and functional diseases. Cortical hyperexcitability has emerged as a diagnostic aid in amyotrophic lateral sclerosis. Single-pulse TMS measures are of utility in stroke, and myelopathy even in the absence of radiological changes. Short-latency afferent inhibition, related to central cholinergic transmission, is reduced in Alzheimer's disease. The triple stimulation technique (TST) may enhance diagnostic utility of conventional TMS measures to detect upper motor neuron involvement. The recording of motor evoked potentials can be used to perform functional mapping of the motor cortex or in preoperative assessment of eloquent brain regions before surgical resection of brain tumors. TMS exhibits utility in assessing lumbosacral/cervical nerve root function, especially in demyelinating neuropathies, and may be of utility in localizing the site of facial nerve palsies. TMS measures also have high sensitivity in detecting subclinical corticospinal lesions in multiple sclerosis. Abnormalities in central motor conduction time or TST correlate with motor impairment and disability in MS. Cerebellar stimulation may detect lesions in the cerebellum or cerebello-dentato-thalamo-motor cortical pathways. Combining TMS with electroencephalography, provides a novel method to measure parameters altered in neurological disorders, including cortical excitability, effective connectivity, and response complexity.

Phase-amplitude coupling between low- and high-frequency activities as preoperative biomarker of focal cortical dysplasia subtypes.

OBJECTIVE: To evaluate whether ictal phase-amplitude coupling (PAC) between high-frequency activity and low-frequency activity could be used as a preoperative biomarker of Focal Cortical Dysplasia (FCD) subtypes. We hypothesize that FCD seizures present unique PAC characteristics that may be linked to their specific histopathological features. METHODS: We retrospectively examined 12 children with FCD and refractory epilepsy who underwent successful epilepsy surgery. We identified ictal onsets recorded with stereo-EEG. We estimated the strength of PAC between low-frequencies and high-frequencies for each seizure by means of modulation index. Generalized mixed effect models and receiver operating characteristic (ROC) curve analysis were used to test the association between ictal PAC and FCD subtypes. RESULTS: Ictal PAC was significantly higher in patients with FCD type II compared to type I, only on SOZ-electrodes (p < 0.005). No differences in ictal PAC were found on non-SOZ electrodes. Pre-ictal PAC registered on SOZ electrodes predicted FCD histopathology with a classification accuracy > 0.9 (p < 0.05). CONCLUSIONS: The correlations between histopathology and neurophysiology provide evidence for the contribution of ictal PAC as a preoperative biomarker of FCD subtypes. SIGNIFICANCE: Developed into a proper clinical application, such a technique may help improve clinical management and facilitate the prediction of surgical outcome in patients with FCD undergoing stereo-EEG monitoring.

Asymptomatic carotid stenosis and cognitive impairment.

INTRODUCTION: The aim of this review was to assess the evidence supporting an association between asymptomatic carotid stenosis (ACS) with impaired cognitive function due to chronic cerebral hypoperfusion and/or silent cerebral embolization. EVIDENCE ACQUISITION: PubMed/Medline, Embase and the Cochrane databases were searched up to December 1, 2022 to identify studies focusing on the association between ACS and cognitive function, as well as the mechanisms involved. EVIDENCE SYNTHESIS: A total of 49 studies were identified. The evidence supports an association between ACS and progressive cognitive deterioration. The mechanisms involved in the cognitive decline associated with ACS include cerebral hypoperfusion and silent cerebral embolization. Irrespective of the mechanism involved, severe ACS is associated with a progressive decline in several aspects of cognitive function, including global cognition, memory and executive function. CONCLUSIONS: Patients with ACS are at increased risk of developing a progressive decline in their cognitive function. The evidence from the present systematic review suggests that it may be inappropriate to consider ACS patients developing cognitive dysfunction as "asymptomatic". Besides stroke, myocardial infarction and death rates, future studies should include evaluation of cognitive function as part of their outcomes.

Deep brain stimulation of the dentato-rubro-thalamic tract in a case of Holmes tremor: a constrained spherical deconvolution (CSD)-guided procedure.

Deep brain stimulation (DBS) is an established treatment for movement disorders, including Holmes tremor (HT). HT is a rest and action tremor that occurs as a late symptom of brainstem lesions such as stroke. Unfortunately, it is frequently refractory to medical treatment, hence DBS surgery may be a good option. Due to variable results, the ideal target for DBS in HT still remains to be established, ranging from the thalamus to the globus pallidus internus, to the subthalamic nucleus. Pre-operative imaging also is very challenging, as the complexity of brain fiber architecture may prevent the correct positioning of the directional lead. Herein, we describe the case of a patient affected by a rubral tremor secondary to a brain hemorrhage, who had advanced pre-operative neuroimaging with constrained spherical deconvolution (CSD)-based tractography obtained from diffusion-weighted imaging (DWI) to identify the dentato-rubro-thalamic tract, involved in the pathophysiology of HT. The patient was then addressed to an awake DBS surgery, and with the help of intraoperative microelectrode recordings, a tailored DRTT-targeted procedure was performed. The stimulation determined an almost complete tremor suppression, with no significant side effects at a follow-up of 6 months, paving the way towards new effective techniques for the planning, i.e., CSD-based tractography and the treatment of refractory tremors.

Why do guidelines recommend screening for abdominal aortic aneurysms, but not for asymptomatic carotid stenosis? A plea for a randomized controlled trial.

BACKGROUND: Current guidelines do not recommend screening for asymptomatic carotid artery stenosis (AsxCS). The rationale behind this recommendation is that detection of AsxCS may lead to an unnecessary carotid intervention. In contrast, screening for abdominal aortic aneurysms is strongly recommended. METHODS: A critical analysis of the literature was performed to evaluate the implications of detecting AsxCS. RESULTS: Patients with AsxCS are at high risk for future stroke, myocardial infarction and vascular death. Population-wide screening for AsxCS should not be recommended. Additionally, screening of high-risk individuals for AsxCS with the purpose of identifying candidates for a carotid intervention is inappropriate. Instead, selective screening for AsxCS should be considered and should be viewed as an opportunity to identify individuals at high risk for atherosclerotic cardiovascular disease and future cardiovascular events for the timely initiation of intensive medical therapy and risk factor modification. CONCLUSIONS: Although mass screening should not be recommended, there are several arguments suggesting that selective screening for AsxCS should be considered. The rationale supporting such selective screening is to optimize risk factor control and to initiate intensive medical therapy for prevention of future cardiovascular events, rather than to identify candidates for an intervention.

A pathogenic variant in the FLCN gene presenting with pure dementia: is autophagy at the intersection between neurodegeneration and cancer?

Introduction: Folliculin, encoded by FLCN gene, plays a role in the mTORC1 autophagy cascade and its alterations are responsible for the Birt-Hogg-Dubé (BHD) syndrome, characterized by follicle hamartomas, kidney tumors and pneumothorax. Patient and results: We report a 74-years-old woman diagnosed with dementia and carrying a FLCN alteration in absence of any sign of BHD. She also carried an alteration of MAT1A gene, which is also implicated in the regulation of mTORC1. Discussion: The MAT1A variant could have prevented the development of a FLCN-related oncological phenotype. Conversely, our patient presented with dementia that, to date, has yet to be documented in BHD. Folliculin belongs to the DENN family proteins, which includes C9orf72 whose alteration has been associated to neurodegeneration. The folliculin perturbation could affect the C9orf72 activity and our patient could represent the first human model of a relationship between FLCN and C9orf72 across the path of autophagy.

Markerless Radio Frequency Indoor Monitoring for Telemedicine: Gait Analysis, Indoor Positioning, Fall Detection, Tremor Analysis, Vital Signs and Sleep Monitoring.

Quantitative indoor monitoring, in a low-invasive and accurate way, is still an unmet need in clinical practice. Indoor environments are more challenging than outdoor environments, and are where patients experience difficulty in performing activities of daily living (ADLs). In line with the recent trends of telemedicine, there is an ongoing positive impulse in moving medical assistance and management from hospitals to home settings. Different technologies have been proposed for indoor monitoring over the past decades, with different degrees of invasiveness, complexity, and capabilities in full-body monitoring. The major classes of devices proposed are inertial-based sensors (IMU), vision-based devices, and geomagnetic and radiofrequency (RF) based sensors. In recent years, among all available technologies, there has been an increasing interest in using RF-based technology because it can provide a more accurate and reliable method of tracking patients' movements compared to other methods, such as camera-based systems or wearable sensors. Indeed, RF technology compared to the other two techniques has higher compliance, low energy consumption, does not need to be worn, is less susceptible to noise, is not affected by lighting or other physical obstacles, has a high temporal resolution without a limited angle of view, and fewer privacy issues. The aim of the present narrative review was to describe the potential applications of RF-based indoor monitoring techniques and highlight their differences compared to other monitoring technologies.

Global Neurocognitive and Frontal Functions Analysis and Precision Intrathecal Pressure Measurement to Settle the Diagnostic Dilemma of the Normal Pressure Hydrocephalus: A Preliminary Experience.

INTRODUCTION: Normal-pressure hydrocephalus (NPH) is a common condition associated with a cognitive deterioration and possibly involving up to 9%-14% of all nursing home residents older than 65 years old. The purpose of the present paper is to introduce an inclusive study protocol aimed at increasing the diagnostic precision and follow-up accuracy. METHODS: A total of 28 patients were operated on for NPH in our institution in the period ranging between January 2015 and December 2019. All the patients underwent magnetic resonance imaging of the brain with standard sequences, calculation of the Evans index and corpus callosum angle, and evaluations by means of Montreal Cognitive Assessment (MOCA), Mini-Mental State Examination, and Frontal Assessment Battery (FAB) neuropsychological tests preoperatively and at 1 and 6 months. A preoperative lumbar test infusion (LIT) with fine measurement of the intrathecal pressures at the beginning and at the end of the procedures was performed. RESULTS: MOCA and FAB proved an overall improvement of the neurocognitive conditions at 1 month postoperatively. The mean pressure at the beginning of the LIT, was negatively associated with the neuropsychological outcome variables (Mini-Mental State Examination, FAB, and MOCA) in the 3 different evaluations, with FAB and MOCA at 6 months. We found a strong positive correlation between the Evans index as measured on the first magnetic resonance imaging scan both with the diastolic and systolic pressure at the beginning of the test. CONCLUSIONS: Neuropsychological assessment, combined with LIT with intrathecal pressure managements aids the diagnostic process in patients affected by NPH. It allows standardizing in a rigorous fashion the follow-up evaluation of patients undergoing surgery for a ventriculoperitoneal shunt.

Neurophysiology tools to lower the stroke onset to treatment time during the golden hour: microwaves, bioelectrical impedance and near infrared spectroscopy.

Reperfusion therapy administration timing in acute ischaemic stroke is the main determinant of patients' mortality and long-term disability. Indeed, the first hour from the stroke onset is defined the "golden hour", in which the treatment has the highest efficacy and lowest side effects. Delayed ambulance transport, inappropriate triage and difficulty in accessing CT scans lead to delayed onset to treatment time (OTT) in clinical practice. To date brain CT scan is needed to rule out intracranial haemorrhage, which is a major contraindication to thrombolytic therapy. The availability, dimension and portability make CT suitable mainly for intrahospital use, determining further delays in the therapies administration. This review aims at evaluating portable neurophysiology technologies developed with the scope of speeding up the diagnostic phase of acute stroke and, therefore, the initiation of intravenous thrombolysis. Medline databases were explored for studies concerning near infrared spectroscopy (NIRS), bioelectrical impedance spectroscopy (BIS) and Microwave imaging (MWI) as methods for stroke diagnosis. A total of 1368 articles were found, and 12 of these fit with our criteria and were included in the review. For each technology, the following parameters were evaluated: diagnostic accuracy, ability to differentiate ischaemic and haemorrhagic stroke, diagnosis time from stroke onset, portability and technology readiness level (TRL). All the described methods seem to be able to identify acute stroke even though the number of studies is very limited. Low cost and portability make them potentially usable during ambulance transport, possibly leading to a reduction of stroke OTT along with the related huge benefits in terms of patients outcome and health care costs. In addition, unlike standard imaging techniques, neurophysiological techniques could allow continuous monitoring of patients for timely intrahospital stroke diagnosis.KEY MESSAGESFirst hour from the stroke onset is defined the "golden hour", in which the treatment has the highest efficacy and lowest side effects.The delay for stroke onset to brain imaging time is one of the major reasons why only a minority of patients with acute ischaemic stroke are eligible to reperfusion therapies.Neurophysiology techniques (NIRS, BIS and MWI) could have a potential high impact in reducing the time to treatment in stroke patients.

Decompressive hemicraniectomy in patients with malignant middle cerebral artery infarction: A real-world study.

BACKGROUND: Malignant middle cerebral artery infarction (mMCA) is a devastating disease with rates of fatality as high as 80%. Decompressive hemicraniectomy (DHC) reduces mortality, but many survivors inevitably remain severely disabled. This study aimed to analyze patients with mMCA undergoing DHC or best medical treatment (BMT) baseline characteristics and factors linked to therapeutic choice and determinants of prognosis. METHODS: We recorded clinical and radiological features of patients undergoing BMT or DHC. The two groups were compared for epidemiology, clinical presentation, neuroimaging, and prognosis. Regression analysis was performed to identify predictors of surgical treatment and outcome. RESULTS: One hundred twenty-five patients were included (age 67.41 ± 1.39 yo; 65 M). Patients undergoing DHC (N = 57) were younger (DHC 55.71 ± 1.48 yo vs. BMT 77.22 ± 1.38) and had midline shift (DHC 96.5% (55/57) vs. BMT 35.3% (24/68), a larger volume of the affected hemisphere and reduced ventricles volume as compared to BMT. The chance of surgery depended on age (Exp(B) = 0.871, p < 0.001), clinical status at onset (NIHSS Exp(B) = 0.824, p = 0.030) and volume of the ventricle of the affected hemisphere (Exp(B) = 0.736, p = 0.006). Death rate during admission was significantly lower for DHC (DHC 15% (6/41) vs BMT 71.7% (38/53), Fisher's test = 30.234, p < 0.001). CONCLUSION: Although DHC may cause prolonged hospitalization and long-term disabled patients, it is a lifesaving therapy that should be considered for selected patients with mMCA but perioperative complications and cost-utility should be considered. Patients and families should be correctly counseled about this therapeutic choice and its short- and long-term consequences.

A Rare Neuro-Ophthalmological Condition in a Patient with Lung Adenocarcinoma: The Eight-and-a-Half Syndrome, Case Report and Review of the Literature.

The eight-and-a-half syndrome is a rare neuro-ophthalmological condition caused by a structural lesion in the dorsal portion of the pons, involving critical areas of the brainstem, i.e., medial longitudinal fasciculus (MLF), abducens nucleus, facial genu, and colliculus. It is characterized by internuclear ophthalmoplegia with horizontal gaze palsy and peripheral facial palsy. Although the syndrome is most frequently caused by vascular or demyelinating diseases, several different underlying causes might occur. Herein, we describe a case of the eight-and-a-half syndrome caused by a lung adenocarcinoma metastasis localized in the lower pontine tegmentum. Then, we review the current literature on the underlying causes of the eight-and-a-half syndrome.

Pulsed Electromagnetic Fields: A Novel Attractive Therapeutic Opportunity for Neuroprotection After Acute Cerebral Ischemia.

OBJECTIVES: Acute cerebral ischemia is characterized by several pathological processes evolving during time, which contribute to the final tissue damage. Secondary processes, such as prolonged inflammatory response, impaired mitochondrial function, and oxidative stress, are responsible for the progression of brain injury to the peri-infarct area, called "penumbra." Adenosine has been shown to play a crucial role in regulating the inflammatory cascade following brain ischemia. Pulsed electromagnetic fields (PEMFs) act as modulators of adenosine receptors, increasing the functionality of the endogenous adenosine. In particular, PEMF exposure induces a significant upregulation of A2A and A3 adenosine receptors in different neuronal cell types. Several lines of evidence suggest that PEMF exposure might play a neuroprotective role after ischemic damage. MATERIALS AND METHODS: This review summarizes the current knowledge on the mechanism of action of PEMFs and their biological effects on neuronal damage both in preclinical and clinical studies. RESULTS: PEMFs counteract hypoxia-induced apoptosis and ROS production in neuronal-like cells and exert a strong anti-inflammatory effect on microglial cells. Data from stroke animal models showed that PEMFs exposure is able to reduce the size of the infarct area and decrease the levels of pro-inflammatory mediators. In clinical studies, PEMFs stimulation proved to be safe and well tolerated. Preliminary results on acute ischemic stroke patients showed a dose-dependent reduction in the lesion size. CONCLUSIONS: Altogether, these data demonstrate the efficacy of PEMFs against several mechanisms underlying ischemic damage and suggest that PEMFs might represent a novel noninvasive adjunctive treatment for acute ischemic stroke, providing neuroprotection and reducing functional deficits following ischemia.

Focused Ultrasound (FUS) for Chronic Pain Management: Approved and Potential Applications.

Chronic pain is one of the leading causes of disability and disease burden worldwide, accounting for a prevalence between 6.9% and 10% in the general population. Pharmacotherapy alone results ineffective in about 70-60% of patients in terms of a satisfactory degree of pain relief. Focused ultrasound is a promising tool for chronic pain management, being approved for thalamotomy in chronic neuropathic pain and for bone metastases-related pain treatment. FUS is a noninvasive technique for neuromodulation and for tissue ablation that can be applied to several tissues. Transcranial FUS (tFUS) can lead to opposite biological effects, depending on stimulation parameters: from reversible neural activity facilitation or suppression (low-intensity, low-frequency ultrasound, LILFUS) to irreversible tissue ablation (high-intensity focused ultrasounds, HIFU). HIFU is approved for thalamotomy in neuropathic pain at the central nervous system level and for the treatment of facet joint osteoarthritis at the peripheral level. Potential applications include HIFU at the spinal cord level for selected cases of refractory chronic neuropathic pain, knee osteoarthritis, sacroiliac joint disease, intervertebral disc nucleolysis, phantom limb, and ablation of peripheral nerves. FUS at nonablative dosage, LILFUS, has potential reversible and tissue-selective effects. FUS applications at nonablative doses currently are at a research stage. The main potential applications include targeted drug and gene delivery through the Blood-Brain Barrier, assessment of pain thresholds and study of pain, and reversible peripheral nerve conduction block. The aim of the present review is to describe the approved and potential applications of the focused ultrasound technology in the field of chronic pain management.

ATTRv in Lazio-Italy: A High-Prevalence Region in a Non-Endemic Country.

Hereditary transthyretin amyloidosis (ATTRv, v for variant) prevalence in Italy, a non-endemic region, has been established by ATTRv amyloidosis Italian Registry. However, values of prevalence were extremely heterogeneous, considering different regions. To properly establish the prevalence of the disease in the Lazio region, a survey was sent to university regional hospitals and to main regional hospitals, in order to collect all affected patients regularly followed. We identified 100 ATTRv patients and, considering a Lazio population of 5.8/million, we estimated a ATTRv prevalence of 17.2/million. The ATTRv amyloidosis Italian Registry reported a prevalence of 8.0/million in Lazio, while our survey showed a value of double this. Our survey documented a high-prevalence for a non-endemic country. The increased awareness of the disease among general practitioners and medical specialists is a fundamental step to reduce the diagnostic delay and start an effective treatment of this disease.