关键词： child-pugh classification   fatigue   liver cirrhosis   MELD score   MUNE  

摘要： Liver cirrhosis is a global health problem that can be associated with several neurological manifestations. We aimed to assessment of the relation between the severity of the liver cirrhosis and the neurological symptoms, nerve conduction studies (NCS), as well as detecting subclinical neuropathic affection using motor unit number estimation (MUNE) technique. This cross-sectional study was conducted on 56 cirrhotic patients and 61 age- and sex-matched healthy controls. Neurological manifestations, Child-Pugh classification, Model for End-Stage Liver Disease score, NCS and MUNE using a modified spike-triggered averaging technique were studied. Forty-five (80.3%) of the cirrhotic patients had neurological manifestations. Muscle cramps were the most frequently reported manifestation, followed by fatigue and then numbness. NCS abnormality was significantly related to the presence of neurological symptoms (p < 0.001) and not only to peripheral numbness. Only fatigue was significantly related to the lower MUNE values (p < 0.017). Child-Pugh classification progression was significantly related to the presence of fatigue and abnormal NCS results (p < 0.001);no similar relation was detected between the Child-Pugh classification and the MUNE value (p = 0.103). Higher MELD scores were significantly related to NCS abnormalities (p = 0.014) and negatively correlated, although not significantly, with the MUNE values (r = -0.246 and p = 0.067). The progression of liver cirrhosis was related to the presence of neurological manifestations and nerve conduction abnormalities. Nerve conduction abnormalities may be present even in the absence of clinical numbness. A decline in motor unit number could explain the pathophysiology of fatigue in cirrhotic patients.

关键词： Blood biomarkers   Good neurological outcome   Cardiac arrest   Neurofilament light   Prognostication   ERC   ESICM guidelines  

摘要： Purpose The majority of unconscious patients after cardiac arrest (CA) do not fulfill guideline criteria for a likely poor outcome, their prognosis is considered "indeterminate". We compared brain injury markers in blood for prediction of good outcome and for identifying false positive predictions of poor outcome as recommended by guidelines. Methods Retrospective analysis of prospectively collected serum samples at 24, 48 and 72 h post arrest within the Target Temperature Management after out-of-hospital cardiac arrest (TTM)-trial. Clinically available markers neuron-specific enolase (NSE) and S100B, and novel markers neurofilament light chain (NFL), total tau, ubiquitin carboxy-terminal hydrolase L1 (UCH-L1) and glial fibrillary acidic protein (GFAP) were analysed. Normal levels with a priori cutoffs specified by reference laboratories or defined from literature were used to predict good outcome (no to moderate disability, Cerebral Performance Category scale 1-2) at 6 months. Results Seven hundred and seventeen patients were included. Normal NFL, tau and GFAP had the highest sensitivities (97.2-98% of poor outcome patients had abnormal serum levels) and NPV (normal levels predicted good outcome in 87-95% of patients). Normal S100B and NSE predicted good outcome with NPV 76-82.2%. Normal NSE correctly identified 67/190 (35.3%) patients with good outcome among those classified as "indeterminate outcome" by guidelines. Five patients with single pathological prognostic findings despite normal biomarkers had good outcome. Conclusion Low levels of brain injury markers in blood are associated with good neurological outcome after CA. Incorporating biomarkers into neuroprognostication may help prevent premature withdrawal of life-sustaining therapy.

关键词： Antibiotic-associated encephalopathy   Aseptic meningitis   Mental disorders   gamma-Aminobutyric acid   N-methyl-D-aspartate receptor  

摘要： Psychosis is a common and intractable disorder of hospitalization, especially in patients hospitalized in Intensive Care Unit (ICU). Along with the widely use of multiple antibiotics in community-acquired infection and hospital-acquired infection, the occurrence of antibiotic-associated neurological disorders has become more frequently. However, antibiotic neurotoxicity is often overlooked or misinterpreted. In this review, we summarized the neurological disorders caused by antibacterial agent usage and firstly systematically formulated the pathogenesis of antibiotic-associated neurotoxic reactions. Precautions of the complications are critical in preventing serious clinical outcome as the inducement is curable. Regular neurological physical examination, electroencephalogram (EEG) examination, lumbar puncture and therapeutic drug monitoring closely are essential for early diagnosis and differential diagnosis. (C) 2021 Elsevier Ltd. All rights reserved.

关键词： infective endocarditis   Lemierre's syndrome   thrombophlebitis  

摘要： Lemierre's syndrome (LS) is characterized by septic thrombophlebitis of the internal jugular vein with septicemia and metastatic infection following an oropharyngeal infection. LS is rare but can cause infective endocarditis (IE), complicating IE management. We report a case of IE secondary to thrombophlebitis in the left vertebral vein following pharyngitis (LS variant) with distinctively severe manifestations, including metastatic infection and severe neurological impairment with multiple cerebral infarctions. A pedunculated abscess was noted on the left ventricular free wall. Despite the patient's highly impaired consciousness level (i.e., comatose state), we performed early surgery to remove the abscess after excluding LS-related brain complications. Preoperative antibiotics included clindamycin to cover LS-related anaerobic bacteria, and thrombophlebitis required postoperative anticoagulation. By managing LS as well as IE, the infection was controlled, and the neurological status normalized. This report provides insights into the perioperative management of IE secondary to LS.

关键词： Movement disorders   Neurodegenerative diseases   Neurodevelopmental disorders  

关键词： astrocytes   behaviour   calcium signalling   development   IP(3)R2  

摘要： Astrocytes are key players in the regulation of brain development and function. They sense and respond to the surrounding activity by elevating their intracellular calcium (Ca2+) levels. These astrocytic Ca2+ elevations emerge from different sources and display complex spatio-temporal properties. Ca2+ elevations are spatially distributed in global (soma and main processes) and/or focal regions (microdomains). The inositol 1,4,5-trisphosphate receptor type 2 knockout (IP(3)R2 KO) mouse model lacks global Ca2+ elevations in astrocytes, and it has been used by different laboratories. However, the constitutive deletion of IP(3)R2 during development may trigger compensating phenotypes, which could bias the results of experiments using developing or adult mice. To address this issue, we performed a detailed neurodevelopmental evaluation of male and female IP(3)R2 KO mice, during the first 21 days of life, as well as an evaluation of motor function, strength and neurological reflexes in adult mice. Our results show that male and female IP(3)R2 KO mice display a normal acquisition of developmental milestones, as compared with wild-type (WT) mice. We also show that IP(3)R2 KO mice display normal motor coordination, strength and neurological reflexes in adulthood. To exclude a potential compensatory overexpression of other IP(3)Rs, we quantified the relative mRNA levels of all 3 subtypes, in brain tissue. We found that, along with the complete deletion of Itpr2, there is no compensatory expression of Itpr1 or Itrp3. Overall, our results show that the IP(3)R2 KO mouse is a reliable model to study the functional impact of global IP(3)R2-dependent astrocytic Ca2+ elevations.

关键词： Synapse   Cell adhesion molecules   Nectin   Necl   Afadin   Puncta adherentia junction  

摘要： Synapses are interneuronal junctions which form neuronal networks and play roles in a variety of functions, including learning and memory. Two types of junctions, synaptic junctions (SJs) and puncta adherentia junctions (PAJs), have been identified. SJs are found at all excitatory and inhibitory synapses whereas PAJs are found at excitatory synapses, but not inhibitory synapses, and particularly well developed at hippocampal mossy fiber giant excitatory synapses. Both SJs and PAJs are mediated by cell adhesion molecules (CAMs). Major CAMs at SJs are neuroligins-neurexins and Nectin-like molecules (Necls)/CADMs/SynCAMs whereas those at PAJs are nectins and cadherins. In addition to synaptic PAJs, extrasynaptic PAJs have been identified at contact sites between neighboring dendrites near synapses and regulate synapse formation. In addition to SJs and PAJs, a new type of cell adhesion apparatus different from these junctional apparatuses has been identified and named nectin/Necl spots. One nectin spot at contact sites between neighboring dendrites at extrasynaptic regions near synapses regulates synapse formation. Several members of nectins and Necls had been identified as viral receptors before finding their physiological functions as CAMs and evidence is accumulating that many nectins and Necls are related to onset and progression of neurological diseases. We review here nectin and Necls in synapse formation and involvement in neurological diseases.

关键词： CIDP   diagnosis   GRADE   guideline   treatment  

摘要： To revise the 2010 consensus guideline on chronic inflammatory demyelinating polyradiculoneuropathy (CIDP). Seventeen disease experts, a patient representative, and two Cochrane methodologists constructed 12 Population/Intervention/Comparison/Outcome (PICO) questions regarding diagnosis and treatment to guide the literature search. Data were extracted and summarized in GRADE summary of findings (for treatment PICOs) or evidence tables (for diagnostic PICOs). Statements were prepared according to the GRADE Evidence-to-Decision frameworks. Typical CIDP and CIDP variants were distinguished. The previous term "atypical CIDP" was replaced by "CIDP variants" because these are well characterized entities (multifocal, focal, distal, motor, or sensory CIDP). The levels of diagnostic certainty were reduced from three (definite, probable, possible CIDP) to only two (CIDP and possible CIDP), because the diagnostic accuracy of criteria for probable and definite CIDP did not significantly differ. Good Practice Points were formulated for supportive criteria and investigations to be considered to diagnose CIDP. The principal treatment recommendations were: (a) intravenous immunoglobulin (IVIg) or corticosteroids are strongly recommended as initial treatment in typical CIDP and CIDP variants;(b) plasma exchange is strongly recommended if IVIg and corticosteroids are ineffective;(c) IVIg should be considered as first-line treatment in motor CIDP (Good Practice Point);(d) for maintenance treatment, IVIg, subcutaneous immunoglobulin or corticosteroids are recommended;(e) if the maintenance dose of any of these is high, consider either combination treatments or adding an immunosuppressant or immunomodulatory drug (Good Practice Point);and (f) if pain is present, consider drugs against neuropathic pain and multidisciplinary management (Good Practice Point).

关键词： Sturge-weber syndrome   Intellectual disability   Language disorder   Angioma   Epilepsy   Port-wine stain  

摘要： Introduction: This study of children with Sturge-Weber syndrome (SWS) profiled neurological presentations;compared patients with (+) and without (-) port-wine stain (PWS);and determined risk factors for intellectual and language impairments. Methods: A retrospective case note review was conducted at a national centre. Results: This cohort (n = 140, male 72, median follow up 114 months) showed sex parity. Intellectual disability ("ID": IQ < 70) affected half (66), being severe (IQ < 40) in two-fifths (27) with ID. Language disorder (core score<70) affected half (57). Neurological presentations were: status epilepticus 57% (80), hemiplegia 58% (81), headaches 36% (50) and acutely acquired neurological deficits lasting over 24 h 40% (56). One-seventh (20) were PWS(-). This group had: fewer lobes with angioma (p < 0.0001);and less frequent ID (p = 0.002) or language disorder (p = 0.013). Seizure frequency and status epilepticus prevalence did not differ from PWS(+). ID and language disorder were associated with: more lobes with angioma;earlier seizure onset;more frequent status epilepticus and seizure clusters. On multivariable analysis recurrent status epilepticus (p = 0.037) and multi-lobe involvement (p = 0.002) increased the risk of severe intellectual disability. Active epilepsy was associated with language disorder (p = 0.030). Conclusions: This is the largest reported series documenting detailed developmental profiles of children with SWS, including ID and ASD. PWS(+) shows high rates of ID and language disorder. PWS(-) SWS has a more favourable outcome. Cognitive outcome is contingent on number of affected lobes and bilateral involvement. Epilepsy exerts an additional deleterious effect on language and cognition. A high percentage of children have a history of status epilepticus, with evidence that this impacts language and cognitive outcomes. Acutely acquired neurological deficits did not penalise either. Regular structured clinical and developmental assessment