Phantom limb syndrome: from pathogenesis to treatment. A narrative review.

Phantom Limb Syndrome (PLS) can be defined as the disabling or painful sensation of the presence of a body part that is no longer present after its amputation. Anatomical changes involved in Phantom Limb Syndrome, occurring at peripheral, spinal and brain levels and include the formation of neuromas and scars, dorsal horn sensitization and plasticity, short-term and long-term modifications at molecular and topographical levels. The molecular reorganization processes of Phantom Limb Syndrome include NMDA receptors hyperactivation in the dorsal horn of the spinal column leading to inflammatory mechanisms both at a peripheral and central level. At the brain level, a central role has been recognized for sodium channels, BDNF and adenosine triphosphate receptors. In the paper we discuss current available pharmacological options with a final overview on non-pharmacological options in the pipeline.

Clinical and Immunological Impact of Ocrelizumab Extended Interval Dosing in Multiple Sclerosis: A Single-Center, Real-World Experience.

Ocrelizumab (OCR), an anti-CD20 monoclonal antibody, is approved for treating relapsing remitting (RR) and primary progressive (PP) multiple sclerosis (MS). The standard interval dosing (SID) regimen requires intravenous infusions every six months. Experience of extended dosing due to COVID-19 pandemic-related issues suggests that this strategy may provide comparable efficacy while reducing treatment burden and healthcare costs. This study aimed to evaluate clinical effectiveness, changes in B- and T-cell count, and immunoglobulin dynamics associated with extended interval dosing (EID) of ocrelizumab in a real-world setting. We retrospectively included RRMS or PPMS patients treated with OCR that had already received two OCR cycles and with at least 6 months of follow up after the last infusion. EID was defined as a ≥4 weeks delay compared to SID. Clinical outcomes were occurrence of relapses, MRI activity, 6-months confirmed disability progression (CDP) and their combination (No Evidence of Disease Activity, NEDA-3). We also evaluated changes in CD19+ B cell count, CD4+ and CD8+ T cell count, immunoglobulin titers, and occurrence of hypogammaglobulinemia (hypo-Ig). Frequency tests, multivariate regression models, and survival analysis were applied as appropriate. We analyzed data on 93 subjects (75.3% RRMS) for a total of 389 infusions (272 SID, 117 EID). Clinical and MRI activity, CDP, and NEDA 3 did not significantly differ between EID and SID. EID was associated with lower rates of B-cell depletion. T-cell dynamics and incidence of hypo-Ig were comparable following EID and SID. Hypo-IgG at index infusion was associated with further occurrence of hypo-IgG; male sex and hypo-IgM at index infusion were independently associated with hypo-IgM. In conclusion, OCR EID does not impact MS clinical and radiological outcomes, although it interferes with B-cell dynamics. These findings provide support for a tailored schedule of OCR in MS.

Posterior Reversible Encephalopathy Syndrome: Clinical Differences in Patients with Exclusive Involvement of Posterior Circulation Compared to Anterior or Global Involvement.

INTRODUCTION: Posterior reversible encephalopathy syndrome (PRES) is a clinical-radiologic syndrome not yet fully understood and characterized by transient neurologic symptoms in addition to typical radiological findings. There are only a few articles that describe the clinical differences between patients with PRES that involve carotid and vertebrobasilar circulations. Our study aims to further evaluate the differences between predominantly anterior and posterior circulation PRES. METHODS: We review 54 patients who had received the diagnosis of PRES from 2009 to 2015. The patients were divided into 2 groups: (1) exclusively in posterior zones; and (2) anterior plus posterior zones or exclusively anterior zones. Several clinical characteristics were evaluated, including the following: age, sex, previous diseases, the neurologic manifestations, the highest blood pressure in the first 48 hours of presentation, highest creatinine level during symptoms, and the neuroimaging alterations in brain magnetic resonance imaging. RESULTS: Mean age at diagnosis was 28.5 years old (9 men and 45 women) and mean systolic blood pressure among patients with lesions only in posterior zones was 162.1 mmHg compared to 179.2 mmHg in the anterior circulation. The most common symptoms in the 2 groups were headache and visual disturbances. DISCUSSION: PRES may have several radiological features. A higher blood pressure seems to be 1 of the factors responsible for developing widespread PRES, with involvement of carotid vascular territory. This clinical-radiological difference probably occurs because of the larger number of autonomic receptors in the carotid artery in comparison to the vertebral-basilar system.

Ocular myositis: insights into recurrence and semiological presentation.

Ocular myositis (OM) is a rare clinical entity characterized by idiopathic, nonspecific inflammation of primarily or exclusively extraocular muscles (EOM). Presentation usually encompasses painful diplopia, exacerbated by eye movement. We report two cases of idiopathic OM with unique characteristics. The first presented with pseudo-sixth nerve palsy due to medial nucleus inflammation and the second presented with recurrent OM, subsequently affecting both eyes. Knowledge of different patterns of presentation and recurrence are important to manage this rare inflammatory syndrome.

Blood-brain barrier breakdown in reduced uterine perfusion pressure: a possible model of posterior reversible encephalopathy syndrome.

BACKGROUND: Posterior reversible encephalopathy syndrome (PRES) is a clinical entity characterized by headaches, altered mental status, seizures, and visual disturbances and is associated with white matter vasogenic edema. There are no experimental models to study PRES brain changes. METHODS: Twenty-eight pregnant Wistar rats were divided into 4 groups of 7: (1) pregnant-control; (2) reduced uterine perfusion pressure (RUPP); (3) invasive blood pressure (IBP); and (4) reduced uterine perfusion pressure plus invasive blood pressure (RUPP-IBP). The RUPP and RUPP-IBP groups were submitted to a reduction of uterine perfusion pressure at pregnancy days 13 to 15. The invasive mean arterial pressure of the IBP and RUPP-IBP groups was measured on day 20. The blood-brain barriers (BBBs) of all groups were analyzed using 2% Evans Blue dye on day 21. RESULTS: RUPP rats had higher blood pressures and increased BBB permeability to Evans Blue dye compared with the control animals. Brain staining occurred in 11 of 14 RUPP rats and in none of the control groups (P < .0001). CONCLUSIONS: The physiopathology of PRES remains unclear. Here, we described the use of RUPP rats as a potential model to better comprehend this syndrome.

Risk factors among stroke subtypes in Brazil.

Stroke is a leading cause of mortality and disability in Brazil. Among the risk factors for cerebrovascular disease, some have more influence than others in certain stroke subtypes. Little data are available in the literature on the prevalence of stroke subtypes in Latin America. We analyzed data from 688 patients with acute ischemic stroke (52.3% women; mean age, 65.7 years) who were enrolled in a stroke data bank. Standardized data assessment and stroke subtype classification were used. The most common stroke subtype was large-artery atherosclerosis (n = 223; 32.4%), followed by cardioembolism (n = 195; 28.3%), and microangiopathy (n = 127; 18.5%). Stroke risk factors differ among stroke subtypes. The population of South America is ethnically diverse, and few previous studies have describe the distribution of risk factors among stroke subtypes in this population. In this study, the most important risk factors were hypertension and dyslipidemia.

Data extraction from vintage well sonic log graphs in the ViDEPI project (offshore the Apulia, southern Italy): A multi-useful dataset.

Twelve files have been obtained after the extraction of data from raster PDF images of sonic log graphs. These files data regard exploration wells placed in the Adriatic Sea pertaining the Apulia (Branzino-1, Chiara-1, Cristina-1, Famoso-1, Giove-1, Giove-2, Grazia-1, Grifone-1, Medusa-1, Sabrina-1, Simona-1, and Sparviero-1bis), and the related raster sonic log graphs are free accessible at the ViDEPI Project (www.videpi.com) of the Ministry for the Economic Development of the Italian Government. Two columns A and B of data, i.e., interval transit time Δt [µs/ft] and depth [m], respectively, characterise each file. Hence, 18,396 pairs of Δt-depth values have been obtained. The picking of the data occurred by the use of WebPlotDigitizer© free software. These data are relevant for the interpretation of reflection seismic lines throughout the Adriatic Sea, mainly in the offshore the Apulia. Moreover, the interpretation of those reflection seismic lines located in the adjacent offshore zones, such as the Ionian Sea, can benefit from these data; the values can be important for seismological goals around the Apulia, as well. From these data, Δt-depth diagrams can be originated by the use of software capable of building 2D graphs from values in CSV files (e.g. Matlab©).

Late-Onset MS: Disease Course and Safety-Efficacy of DMTS.

Multiple sclerosis (MS), an inflammatory demyelinating and neurodegenerative disease of the central nervous system, usually begins between the ages of 20 and 49 years, though in rare cases it is diagnosed in childhood and adolescence before the age of 18 years, or at the age of 50 years and later. When the onset of the disease occurs at 50 years or older it is conventionally defined as late onset MS (LOMS). Compared to classical MS, the LOMS is characterized by progressive course, a greater delay in diagnosis and a higher prevalence of motor disability. The older the patients, the greater is the risk of comorbidities that can negatively influence the course of the disease and can limit therapeutic strategies. To date, there is no study focused on the efficacy of Disease Modifying Therapies (DMT) in older patients with MS. The only data available are retrievable from subgroup analysis from phase-3 trials of DMT efficacy. In this work, we discuss how the aging process influences the onset, the clinical course and the therapeutic approach in LOMS.

CNS inflammatory demyelinating events after COVID-19 vaccines: A case series and systematic review.

Background: Vaccinations provided the most effective tool to fight the SARS-CoV-2 pandemic. It is now well established that COVID-19 vaccines are safe for the general population; however, some cases of rare adverse events following immunization have been described, including CNS Inflammatory Demyelinating Events (CIDEs). Although observational studies are showing that these events are rare and vaccines' benefits highly outweigh the risks, collecting and characterizing post-COVID-19 vaccine CIDEs might be relevant to single out potential risk factors and suggest possible underlying mechanisms. Methods: Here we describe six CIDEs, including two acute transverse myelitis (ATM), three multiple sclerosis (MS), and one neuromyelitis optica spectrum disorder (NMOSD), occurring between 8 and 35 days from a COVID-19 vaccine. Moreover, we performed a systematic literature search of post-COVID-19 vaccines CIDEs, including ATM, ADEM, MS, and NMOSD/MOGAD, published worldwide between December 2020 and December 2021, during 1 year of the vaccination campaign. Clinical/MRI and CSF/serum characteristics were extracted from reviewed studies and pooled-analyzed. Results: Forty-nine studies were included in the systematic review, reporting a total amount of 85 CIDEs. Considering our additional six cases, 91 CIDEs were summarized, including 24 ATM, 11 ADEM, 47 MS, and nine NMOSD/MOGAD. Overall, CIDEs occurred after both mRNA (n = 46), adenoviral-vectored (n = 37), and inactivated vaccines (n = 8). Adenoviral-vectored vaccines accounted for the majority of ADEM (55%) and NMOSD/MOGAD (56%), while mRNA vaccines were more frequent in MS new diagnoses (87%) and relapses (56%). Age was heterogeneous (19-88) and the female sex was prevalent. Time from vaccine to symptoms onset was notably variable: ADEM and NMOSD/MOGAD had a longer median time of onset (12.5 and 10 days) compared to ATM and MS (6 and 7 days) and further timing differences were observed between events following different vaccine types, with ATM and MS after mRNA-vaccines occurring earlier than those following adenoviral-vectored ones. Conclusion: Both the prevalence of vaccine types for certain CIDEs and the heterogeneity in time of onset suggest that different mechanisms-with distinct dynamic/kinetic-might underly these events. While epidemiological studies have assessed the safety of COVID-19 vaccines, descriptions and pooled analyses of sporadic cases may still be valuable to gain insights into CIDE's pathophysiology.

Multiple Sclerosis and SARS-CoV-2: Has the Interplay Started?

Current knowledge on Multiple Sclerosis (MS) etiopathogenesis encompasses complex interactions between the host's genetic background and several environmental factors that result in dysimmunity against the central nervous system. An old-aged association exists between MS and viral infections, capable of triggering and sustaining neuroinflammation through direct and indirect mechanisms. The novel Coronavirus, SARS-CoV-2, has a remarkable, and still not fully understood, impact on the immune system: the occurrence and severity of both acute COVID-19 and post-infectious chronic illness (long COVID-19) largely depends on the host's response to the infection, that echoes several aspects of MS pathobiology. Furthermore, other MS-associated viruses, such as the Epstein-Barr Virus (EBV) and Human Endogenous Retroviruses (HERVs), may enhance a mechanistic interplay with the novel Coronavirus, with the potential to interfere in MS natural history. Studies on COVID-19 in people with MS have helped clinicians in adjusting therapeutic strategies during the pandemic; similar efforts are being made for SARS-CoV-2 vaccination campaigns. In this Review, we look over 18 months of SARS-CoV-2 pandemic from the perspective of MS: we dissect neuroinflammatory and demyelinating mechanisms associated with COVID-19, summarize pathophysiological crossroads between MS and SARS-CoV-2 infection, and discuss present evidence on COVID-19 and its vaccination in people with MS.

Vascularization of the uncus - Anatomical study and clinical implications.

BACKGROUND: The objective of this paper was to describe the arterial supply of the uncus and quantify the branches directed to the anteromedial aspect of the human temporal cortex. METHODS: We studied 150 human cerebral hemispheres identifying main afferent arteries supplying the anteromedial temporal cortex with particular attention to the uncus, determining the territory supplied by each artery through either cortical or perforating branches. RESULTS: The uncus was supplied by 419 branches of the anterior choroidal artery (AChA), 210 branches of the internal carotid artery (ICA), 353 branches of the middle cerebral artery (MCA), and 122 branches of the posterior cerebral artery (PCA). The total of supplying vessels was 1104 among the 150 hemispheres studied, which corresponds to 7.36 arteries per uncus. The average of branches per hemisphere was as follows: 2.79 from AChA, 1.40 from ICA, 2.35 from MCA, and 0.81 from PCA. The relative contribution of each artery for the total of specimens studied was as follows: 38% from AChA, 19% from ICA, 32% from the MCA, and 11% from the PCA. We identified cortical anastomoses mostly between the MCA and PCA (27 cases). CONCLUSION: We described and quantified the uncus' vascularization, including anatomical variations. This updated, detailed description of the mesial temporal vascularization is paramount to improve the treatment of neurosurgical conditions.

Posterior reversible encephalopathy syndrome (PRES): Is DWI a prognosis factor?

INTRODUCTION: Posterior reversible encephalopathy syndrome is a clinicoradiologic entity with typical MR imaging showing a white matter vasogenic edema predominantly affecting the occipital and parietal lobes of the brain. The aim of this article is evaluated the importance of DWI as a prognosis factor in patients with PRES. MATERIALS AND METHODS: We reviewed data from 70 patients with PRES (35 with restricted DWI and 35 with no DWI abnormalities), that were admitted to Hospital São Lucas-PUCRS. These two groups were evaluated in age, sex, previous diseases and past medical history, use of medications, the neurologic manifestations, the highest blood pressure during the neurologic presentation and the highest creatinine during the period of observation. RESULTS: Evaluating 70 patients with PRES with a mean age of 25.4 years old (range from 2 to 74 years old; 55 female and 15 male) we identified 35 cases were brain MRI presents with restricted DWI. Restricted DWI was associated with higher mortality in 90 days (14.2% vs 0.0%; p: 0.027). CONCLUSIONS: Few articles present new data that will help clinicians in therapeutic decisions or that modify the knowledge of this syndrome. We suggested that restricted DWI is associated with a worst prognosis in PRES.

Holmes' tremor as a delayed complication of thalamic stroke.

Movement disorders are not commonly associated with stroke. Accordingly, thalamic strokes have rarely been associated with tremor, pseudo-athetosis and dystonic postures. We present a 75-year-old man who developed a disabling tremor 1 year after a posterolateral thalamic stroke. This tremor had low frequency (3-4 Hz), did not disappear on focus and was exacerbated by maintaining a static posture and on target pursuit, which made it very difficult to perform basic functions. MRI demonstrated an old ischemic lesion at the left posterolateral thalamus. Treatment with levodopa led to symptom control. Lesions in the midbrain, cerebellum and thalamus may cause Holmes' tremor. Delayed onset of symptoms is usually seen, sometimes appearing 2 years after the original injury. This may be due to maturation of a complex neuronal network, leading to slow dopaminergic denervation. Further studies are needed to improve our understanding of this unique disconnection syndrome.

Cardioembolic sources in stroke patients in South of Brazil.

Background. Stroke is a leading cause of mortality and disability in Brazil and around the world. Cardioembolism is responsible for nearly 30% of the origins of ischemic stroke. Methods. We analyzed data of 256 patients with cardioembolic ischemic stroke (according to TOAST classification) who were admitted into the Hospital São Lucas-PUCRS from October 2011 to January 2014. The cardioembolic subtype was divided into six subgroups: arrhythmias, valvular heart disease, coronary artery disease, cardiomyopathy, septal abnormalities, and intracardiac injuries. The prevalence of the most important cardiovascular risk factors and medications in use for prevention of systemic embolism by the time of hospital admission was analyzed in each patient. Results. Among 256 patients aged 60.2 +/- 6.9 years, 132 males, arrhythmias were the most common cause of cardioembolism corresponding to 50.7%, followed by valvular heart disease (17.5%) and coronary artery disease (16%). Hypertension (61.7%) and dyslipidemia (43.7%) were the most common risk factors. Less than 50% of patients with arrhythmias were using oral anticoagulants. Conclusions. Identifying the prevalence of cardioembolic stroke sources subgroups has become an increasingly important role since the introduction of new oral anticoagulants. In this study, arrhythmias (especially atrial fibrillation) were the main cause of cardioembolism.

Posterior reversible encephalopathy syndrome: differences between pregnant and non-pregnant patients.

Posterior reversible encephalopathy syndrome (PRES) is a clinical-radiologic entity not yet understood, that presents with transient neurologic symptoms and particular radiological findings. Few papers show the differences between pregnant and non-pregnant patients. We review the cases of 38 women diagnosed with PRES, in order to find significant differences between pregnant (18) and non-pregnant (20) patients. We found differences among the age of patients (25.83 years old in pregnant and 29.31 years old in non pregnant; P=0.001); in the mean of highest systolic blood pressure, that was higher in non-pregnant group (185:162 mmHg; P=0.121); and in creatinine levels that was higher in non-pregnant group (3.47:1.04 mg/dL; P=0.001). To our knowledge, just a few papers analyzed whether PRES syndrome presented in the same way in pregnant and non-pregnant patients. The differences and the possible pathophisiology of this syndrome still remain enigmatic.

Posterior reversible encephalopathy syndrome following a scorpion sting.

Posterior reversible encephalopathy syndrome (PRES) is a clinicoradiologic entity not yet understood, that is present with transient neurologic symptoms and particular radiological findings. The most common imaging pattern in PRES is the presence of edema in the white matter of the posterior portions of both cerebral hemispheres. The cause of PRES is unclear. We report a case of 13-year-old male who was stung by a scorpion and developed a severe headache, visual disturbance, and seizures and had the diagnosis of PRES with a good outcome. Numerous factors can trigger this syndrome, most commonly: acute elevation of blood pressure, abnormal renal function, and immunosuppressive therapy. There are many cases described showing the relationship between PRES and eclampsia, transplantation, neoplasia and chemotherapy treatment, systemic infections, renal disease acute, or chronic. However, this is the first case of PRES following a scorpion sting.

Chronic syphilitic aortic aneurysm complicated with chronic aortic dissection.

BACKGROUND: Historically, tertiary syphilis infection has been the most common cause of thoracic aortic aneurysm, resulting in 5% to 10% of cardiovascular deaths until the era of antibiotics. METHODS: A 49-year-old Caucasian man presented to our institution with progressive dysphagia, weight loss, incomplete bladder emptying, alcohol and tobacco consumption, systemic arterial hypertension, Argyll Robertson pupil, leg paresthesias, and mediastinal widening. He was admitted to investigate clinical alterations. Thoracic computed tomography revealed an aortic aneurysm complicated with chronic aortic dissection from the ascending aorta to the iliac vessels with 2 communicating lumens. Cerebrospinal fluid examination tested positive for neurosyphilis in a venereal disease research laboratory test (titre 1/32). RESULTS: Chronic syphilitic aortic aneurysm complicated with chronic aortic dissection was diagnosed. CONCLUSIONS: This is a unique presentation of a syphilitic infection. Syphilitic aortitis, the hallmark of cardiovascular syphilis, has become rare and is hardly considered by today's clinicians in their differential diagnosis.