Autoimmune encephalitis during pregnancy: A diagnostic and therapeutic challenge-A systematic review with individual patients' analysis and clinical recommendations.

Several reports have described the autoimmune encephalitis' (AE) possible onset during pregnancy. In this systematic review, we summarize the available data on the diagnostic and therapeutic approach to AE during pregnancy, highlighting the associated maternal and fetal clinical outcomes. A systematic search of the literature was performed. The following databases were used: PubMed, Google Scholar, EMBASE, and CrossRef. The revision was registered on the PROSPERO platform (CRD42022336357). Forty-nine patients were included. AE onset was mainly observed during the first and the second trimester of pregnancy with psychiatric manifestations and seizures as main onset symptoms. CSF analysis showed AE-specific autoantibody positivity in 33 patients (anti-NMDA receptor as the most frequent). EEG generally showed normal findings. MRI revealed pathological findings in less than half of patients. Tumor screening was positive in 14 cases. First-line immunotherapy (single or combined) was generally employed while second line was administered in a minority of patients. Levetiracetam was the most used antiseizure medication. Cesarean section was performed in 18 women. Most of the women had an excellent early outcome after delivery but 22 showed persistent neurological deficits in long-term follow-up. Fetal outcome was positive in 33 cases, whereas 12 cases of fetal death were reported. A logistic regression showed that no variable significantly influenced the odds of good/bad maternal and fetal clinical outcome. Diagnosis and treatment of AE during pregnancy is challenging. The rate of miscarriage in women with AE seems to be higher than the general population. In addition, mothers may show long-term neurological deficits.

Embolic Stroke Following Ingestion of Liquid Nicotine Refill Solution.

The use of e-cigarettes is gaining popularity despite knowing about cardiovascular health risks. Cases of intentional or accidental intoxication following ingestion of the refill solution are also a growing concern. Most of these cases were fatal and related to cardiac arrest and hypoxic brain injury. We report the case of a 54-year-old woman who developed bilateral acute ischemic stroke in the anterior and posterior cerebral circulation following intentional oral intake of e-liquid nicotine refill solution. The diagnostic work-up concluded an etiology of embolic stroke of undetermined source, most likely of cardiac origin. We assume that sympathetic overactivation lead to temporary cardiac arrhythmia and subsequent thrombi formation. Moreover, we discuss several additional pathogenic aspects of oral intake of e-liquid refill solution for the development of central nervous system pathology. This case expands the clinical spectrum of health hazards associated with the introduction of e-cigarettes and raises awareness of the need for preventive measures.

The Manchester Triage System's performance in clinical risk prioritisation of patients presenting with headache in emergency department: A retrospective observational study.

OBJECTIVE: Non-traumatic headache is a frequent reason for visits to the emergency department (ED). We evaluated the performance of the Manchester Triage System (MTS) in prioritising patients presenting to the ED with non-traumatic headache. METHODS: In this single-centre observational retrospective study, we compared the association of MTS priority classification codes with a final diagnosis of a severe neurological condition requiring timely management (ischaemic or haemorrhagic stroke, subarachnoid haemorrhage, cerebral sinus venous thrombosis, central nervous system infection or brain tumour). The study was conducted and reported according to the STROBE statement. The overall prioritisation accuracy of MTS was estimated by the area under the receiver operating characteristic (ROC) curve. The correctness of triage prediction was estimated based on the "very urgent" MTS grouping. An undertriage was defined as a patient with an urgent and severe neurological who received a low priority/urgency MTS code (green/yellow). RESULTS: Over 30 months, 3002 triage evaluations of non-traumatic headache occurred (1.7% of ED visits). Of these, 2.3% (68/3002) were eventually diagnosed with an urgent and severe neurological condition. The MTS had an acceptable prioritisation accuracy, with an area under the ROC curve of 0.734 (95% CI 0.668-0.799). The sensitivity of the MTS for urgent codes (yellow, orange and red) was 79.4% (95% CI 74.5-84.3), with a specificity of 54.1% (95% CI 52.9-55.3). The triage prediction was incorrect in only 6.3% (190/3002) of patients with headache. CONCLUSION: The MTS is a safe and accurate tool for prioritising patients with non-traumatic headache in the ED. However, MTS may need further specific tools for evaluating the more complicated symptoms and for correctly identifying patients with urgent and severe underlying pathologies. RELEVANCE TO CLINICAL PRACTICE: The triage nurse using MTS may need additional tools to improve the assessment of patients with headache, although MTS provides a good safety profile.

Sunlight-induced Painful Skin (Sun Pain): A New Differential Diagnosis in Photodermatology.

Photodermatoses are characterized by the development of skin eruptions following exposure to ultraviolet radiation or visible light. We report here the clinical findings and results of laboratory investigations and phototesting of 6 patients who experience debilitating and excruciating pain after sun exposure ("sun pain") in the absence of any skin eruption. Phototesting with sub-erythemal doses of ultraviolet A radiation triggered localized pain in 4 patients. At follow-up, 3 female patients were found to have developed fibromyalgia, 2 male patients experienced a major depressive disorder, and another male patient had a conversion disorder. One patient also developed allodynia to tactile stimuli and one developed allodynia to thermal and tactile stimuli. Psychiatric conditions should be taken into consideration in patients presenting with excruciating and debilitating pain on exposure to ultraviolet radiation, but with absence of skin eruption. Further research is needed to evaluate whether it represents a type of allodynia triggered by exposure to ultraviolet radiation.

An update on the treatment of Restless Legs Syndrome/Willis-Ekbom Disease: prospects and challenges.

INTRODUCTION: Restless Legs Syndrome/Willis-Ekbom Disease (RLS/WED) is a sleep disorder characterized by an urge to move the legs, frequently associated or triggered by unpleasant sensations in the lower limbs that affects approximately 2.5% of adults. Therapy and management of RLS/WED require long-term interventions, since the typical manifestation of this disorder is chronic. Areas covered: In this review, we provide an update regarding the treatment of RLS/WED with particular attention to future challenges for its management. We reviewed a large variety of treatments studied in clinical trials and supported by the most updated guidelines. Alongside with first-line interventions other pharmacological options including opioids, benzodiazepines, iron therapy, and newly studied drugs are discussed. Furthermore, due to the occurrence of augmentation and worsening of symptoms we also reviewed the development of non-pharmacologic alternatives. Expert commentary: The management of RLS/WED is a challenge because of different long-term issues. Several complications, such as loss of the therapeutic effect of dopaminergic or non-dopaminergic agents and augmentation, are still unsolved concerns. However, the development of new drugs acting on adenosinergic and glutamatergic neurotransmission seems promising. Randomized controlled trials are needed in order to recognize effectiveness of new drugs or non-pharmacological treatment strategies.

Pax3-induced expansion enables the genetic correction of dystrophic satellite cells.

BACKGROUND: Satellite cells (SCs) are indispensable for muscle regeneration and repair; however, due to low frequency in primary muscle and loss of engraftment potential after ex vivo expansion, their use in cell therapy is currently unfeasible. To date, an alternative to this limitation has been the transplantation of SC-derived myogenic progenitor cells (MPCs), although these do not hold the same attractive properties of stem cells, such as self-renewal and long-term regenerative potential. METHODS: We develop a method to expand wild-type and dystrophic fresh isolated satellite cells using transient expression of Pax3. This approach can be combined with genetic correction of dystrophic satellite cells and utilized to promote muscle regeneration when transplanted into dystrophic mice. RESULTS: Here, we show that SCs from wild-type and dystrophic mice can be expanded in culture through transient expression of Pax3, and these expanded activated SCs can regenerate the muscle. We test this approach in a gene therapy model by correcting dystrophic SCs from a mouse lacking dystrophin using a Sleeping Beauty transposon carrying the human µDYSTROPHIN gene. Transplantation of these expanded corrected cells into immune-deficient, dystrophin-deficient mice generated large numbers of dystrophin-expressing myofibers and improved contractile strength. Importantly, in vitro expanded SCs engrafted the SC compartment and could regenerate muscle after secondary injury. CONCLUSION: These results demonstrate that Pax3 is able to promote the ex vivo expansion of SCs while maintaining their stem cell regenerative properties.

Stem cells for skeletal muscle regeneration: therapeutic potential and roadblocks.

Conditions involving muscle wasting, such as muscular dystrophies, cachexia, and sarcopenia, would benefit from approaches that promote skeletal muscle regeneration. Stem cells are particularly attractive because they are able to differentiate into specialized cell types while retaining the ability to self-renew and, thus, provide a long-term response. This review will discuss recent advancements on different types of stem cells that have been attributed to be endowed with muscle regenerative potential. We will discuss the nature of these cells and their advantages and disadvantages in regards to therapy for muscular dystrophies.

Clinical spectrum and evolution of monoclonal gammopathy-associated neuropathy: an observational study.

BACKGROUND: Paraproteinemic neuropathy (PPN) is often under-diagnosed because of its clinical and electrophysiological variability. Progression of neuropathy is considered an alarm bell for possible malignant conversion of underlying monoclonal gammopathy (MG). OBJECTIVE: To report clinical presentation, course, and evolution in a group of patients with PPN in order to identify findings useful for achieving the diagnosis, suspecting progression, and recognizing the underlying hematological conditions. PATIENTS AND METHODS: Thirty-nine patients with PPN underwent clinical examination, electrodiagnostic studies, cerebrospinal fluid analysis, and laboratory tests. These parameters were compared between the different peak groups. RESULTS: IgM MG was found in 51.4%, IgG MG in 33.3%, and IgA MG in 10.3% of our cohort. PPN appeared as mainly sensory, demyelinating, mildly progressive neuropathy, regardless of the type of peak or light chain. However, axonal findings were present in many IgG patients and in part of the IgM patients and a small number of the IgG patients may have presented with motor symptoms at the onset. The IgM patients had a significant tendency toward clinical worsening and IgG subjects had a more elevated rate of malignancy. IgA-related neuropathies were rare, heterogenous, and with a high tendency to evolution and malignancy. CONCLUSIONS: Most of PPN often present a relatively monomorphic clinical picture but they can be clinically heterogenous and must be suspected even if sensory impairment and demyelination are not the dominant features. Tendency to malignancy seems globally elevated and needs intensive follow-up. Diagnostic approach to patients presenting with peripheral neuropathy should always include the typing of monoclonal immunoglobulins in serum and urine. In contrast, patients presenting with MG should be submitted to nerve conduction study/electroneurography and neurological evaluation.

Three-dimensional temporomandibular joint modeling and animation.

The three-dimensional (3D) temporomandibular joint (TMJ) model derives from a study of the cranium by 3D virtual reality and mandibular function animation. The starting point of the project is high-fidelity digital acquisition of a human dry skull. The cooperation between the maxillofacial surgeon and the cartoonist enables the reconstruction of the fibroconnective components of the TMJ that are the keystone for comprehension of the anatomic and functional features of the mandible. The skeletal model is customized with the apposition of the temporomandibular ligament, the articular disk, the retrodiskal tissue, and the medial and the lateral ligament of the disk. The simulation of TMJ movement is the result of the integration of up-to-date data on the biomechanical restrictions. The 3D TMJ model is an easy-to-use application that may be run on a personal computer for the study of the TMJ and its biomechanics.

Screening of EDA1 gene in X-linked anhidrotic ectodermal dysplasia using DHPLC: identification of 14 novel mutations in Italian patients.

Mutations within EDA1 gene, which encodes for the ectodysplasin, cause X-linked anhidrotic ectodermal dysplasia. In this study, 23 Italian patients with anhidrotic ectodermal dysplasia were analyzed for mutations in EDA1 gene. We set up a rapid protocol through denaturing high-performance liquid chromatography, followed by sequencing, that allowed the characterization of 18 mutations, 14 novel and 4 recurrent: 8 missense mutations (p.L51Q, p.H54R, p.R156H twice, p.C332F, p.D316H, p.T378M, and p.A349T), 3 in-frame deletions (p.G82_P84del, p.A179_P191del, and p.L354del), 1 gross deletion (p.G168_G265del, identified through direct sequencing and PCR), 4 altered splicing (c.949-13T > C, c.741 + 1G/T, c.793 + 4A > T, and c.924 + 1G/T), 1 nonsense (p.Y3X), and 1 synonymous mutation (c.741G > A). Moreover, structural analysis of three missense mutations shows that alteration of the electrostatic surface of the protein (p.D316N), the break of intermonomer interactions (p.A349T) and destabilization of the single monomer structure (p.T378M), may irreversibly invalidate the EDA-A1 binding properties. Our data confirm and extend the large spectrum of EDA1 mutations and provide a rapid and efficient molecular protocol for testing EDA1 mutations in EDA patients.

Gene expression analysis in myotonic dystrophy: indications for a common molecular pathogenic pathway in DM1 and DM2.

An RNA gain-of-function of expanded transcripts is the most accredited molecular mechanism for myotonic dystrophy type 1 (DM1) and 2 (DM2). To disclose molecular parallels and divergences in pathogenesis of both disorders, we compared the expression profile of muscle biopsies from DM1 and DM2 patients to controls. DM muscle tissues showed a reduction in the major skeletal muscle chloride channel (CLCN1) and transcription factor Sp1 transcript levels and an abnormal processing of the CLCN1 and insulin receptor (IR) pre-mRNAs. No essential differences were observed in the muscle blind-like gene (MBNL1) and CUG binding protein 1 (CUGBP1) transcript levels as well as in the splicing pattern of the myotubularin-related 1 (MTMR1) gene. Macroarray analysis of 96 neuroscience-related genes revealed a considerable similar expression profile between the DM samples, reflective of a common muscle pathology origin. Using a twofold threshold, we found six misregulated genes important in calcium and potassium metabolism and in mitochondrial functions. Our results indicate that the DM1 and DM2 overlapping clinical phenotypes may derive from a common trans acting mechanism that traps and influences shared genes and proteins. An RNA gain-of-function of expanded transcripts is the most accredited molecular mechanism for myotonic dystrophy type 1 (DM1) and 2 (DM2). To disclose molecular parallels and divergences in pathogenesis of both disorders, we compared the expression profile of muscle biopsies from DM1 and DM2 patients to controls. DM muscle tissues showed a reduction in the major skeletal muscle chloride channel (CLCN1) and transcription factor Sp1 transcript levels and an abnormal processing of the CLCN1 and insulin receptor (IR) pre-mRNAs. No essential differences were observed in the muscle blind-like gene (MBNL1) and CUG binding protein 1 (CUGBP1) transcript levels as well as in the splicing pattern of the myotubularin-related 1 (MTMR1) gene. Macroarray analysis of 96 neuroscience-related genes revealed a considerable similar expression profile between the DM samples, reflective of a common muscle pathology origin. Using a twofold threshold, we found six misregulated genes important in calcium and potassium metabolism and in mitochondrial functions. Our results indicate that the DM1 and DM2 overlapping clinical phenotypes may derive from a common trans acting mechanism that traps and influences shared genes and proteins.