关键词： Paraneoplastic neurological syndrome   Lymphoma   Encephalomyelitis   Rapidly progressive cerebellar syndrome  

摘要： Background Paraneoplastic neurological syndromes (PNS) associated with lymphoma are rare diseases that usually have different peculiar features when compared to PNS associated with solid neoplasms. Methods We retrospectively identified patients with NHL-associated PNS. Clinical and demographic data are reported. Results We report two cases of NHL-associated PNS: a 72-years old female that presented with rapidly progressive cerebellar syndrome (RCPS) and a 65-years old male that presented with encephalomyelitis (confusion, sensory neuropathy, lower motor neuron involvement). Both PNS were associated with a NHL, small lymphocytic lymphoma and nodal marginal zone lymphoma respectively, and onconeural antibodies tested negative. All patients received first-line immunotherapy with absent or minimal benefit and died of intercurrent infection before cancer or immunosuppressive treatment. Discussion RCPS and encephalomyelitis rarely present in association with NHL. In our cases, those syndromes took place in the setting of non-aggressive advanced hematological disorders, had an unfavorable prognosis with minimal benefit from immunotherapy, and were seronegative for onconeural antibodies. Our patients fulfilled the criteria for "definite PNS" in the 2004 PNS criteria, but they would be classified as "probable", in the new 2021 PNS criteria. The newest criteria rely on onconeural antibodies testing and on the evidence of antigen expression in cancer cells, features that are usually absent in NHL-associated PNS. New antibodies are being discovered but are still not available to promptly test yet. Conclusion NHL-associated PNS are rare and bear unfavorable prognosis. The diagnosis should not be overlooked even in seronegative patients.

关键词： Neurologic adverse events   Immune checkpoint inhibitors   Neurological complications   Encephalitis   Myositis  

摘要： As the use of cancer immunotherapy with immune checkpoint inhibitors (ICIs) is expanding rapidly for the treatment of many tumor types, it is crucial that both neurologists and oncologists become familiar with the diagnosis and treatment of neurological immune-related adverse events (n-irAEs). These are rare complications, developing in their severe forms in only 1-3% of the patients, but are highly relevant due to their mortality and morbidity burden. The diagnosis of n-irAEs is-however-challenging, as many alternative diagnoses need to be considered in the complex scenario of a patient with advanced cancer developing neurological problems. A tailored diagnostic approach is advisable according to the presentation, clinical history, and known specificities of n-irAEs. Several patterns characterized by distinct clinical, immunological, and prognostic characteristics are beginning to emerge. For example, myasthenia gravis is more likely to develop after anti-programmed cell death protein 1 (PD-1) or anti-programmed cell death ligand 1 (PD-L1) treatment, while meningitis appears more frequently after anti-cytotoxic T lymphocyte antigen-4 (CTLA-4) therapy. Also, peripheral neuropathy and Guillain-Barre syndrome seem to be more common in patients with an underlying melanoma. Central nervous system disorders (CNS) are less frequent and are more often associated with lung cancer, and some of them (especially those with limbic encephalitis and positive onconeural antibodies) have a poor prognosis. Herein, we provide an update of the recent advances in the diagnosis and treatment of neurological toxicities related to ICI use, focusing on the exclusion of alternative diagnoses, diagnostic specificities, and treatment of n-irAEs.

关键词： N6-methyladenosine (m6A)   Neurological diseases   Epigenetic modifications   Alzheimer's disease   Parkinson's disease  

摘要： N6-methyladenosine (m6A) is a dynamic reversible methylation modification of the adenosine N6 position and is the most common chemical epigenetic modification among mRNA post-transcriptional modifications, including methylation, demethylation, and recognition. Post-transcriptional modification involves multiple protein molecules, including METTL3, METTL14, WTAP, KIAA1429, ALKBH5, YTHDF1/2/3, and YTHDC1/2. m6A-related proteins are expressed in almost all cells. However, the abnormal expression of m6A-related proteins may occur in the nervous system, thereby affecting neuritogenesis, brain volume, learning and memory, memory formation and consolidation, etc., and is implicated in the development of diseases, such as Parkinson's disease, Alzheimer's disease, multiple sclerosis, depression, epilepsy, and brain tumors. This review focuses on the functions of m6A in the development of central nervous system diseases, thus contributing to a deeper understanding of disease pathogenesis and providing potential clinical therapeutic targets for neurological diseases.

关键词： 22q11   2 deletion syndrome   DiGeorge syndrome   Epilepsy   Movement disorders   Parkinson's disease  

摘要： 22q11.2 deletion syndrome is the most common microdeletion syndrome. This article reviews the different neurological manifestations of 22q11.2 deletion syndrome. The syndrome is associated with neurological disorders such as epilepsy and movement disorders. Patients with 22q11.2 DS have an increased incidence of provoked and unprovoked seizures. Provoked seizures include, amongst others, seizures due to hypocalcemia, surgery, perioperative hypoxia, antipsychotic medication, and fever. Both focal seizures, myoclonus and generalized tonic-clonic seizures occur in 22q11.2 DS. Generalized epilepsy occurs more often than in the background population. Furthermore, 22q11.2 DS is associated with a significantly increased risk of developing Parkinson's disease, and an increased incidence of dystonia has also been suggested. Abnormal neuroradiological findings - amongst them polymicrogyria - are common in 22q11.2.2 DS and reviewed in the article. The risk of psychiatric disorders, in particular schizophrenia, is increased in 22q11.2 DS.

摘要： Cutaneous infection by Balamuthia mandrillaris is a rare condition that is sometimes complicated by life-threatening CNS involvement. It often evades timely diagnosis due to its rarity and non-specific clinical manifestations. Patients can be either immunocompetent or immunocompromised. It is probably transmitted via inhalation or inoculation through broken skin, and then spreads to the brain and other organs through haematogenous spread. It is important for clinicians to be aware of this disease because rapid diagnosis and subsequent therapy has, in some cases, been associated with survival. In this Grand Round, we report the case of a 7-year-old boy who presented with large, chronic plaques on his face. Several biopsies showed non-specific granulomatous inflammation. The patient deteriorated rapidly and died within 1 month of displaying abnormal symptoms in the CNS. Immunohistochemical staining of skin tissue identified B mandrillaris as the infectious agent. The diagnosis was confirmed with PCR, which detected B mandrillaris DNA in formalin-fixed skin tissue sections. B mandrillaris infection should be considered in the differential diagnosis of patients with chronic granulomatous lesions. We also reviewed the epidemiology, B mandrillaris in nature and in the laboratory, clinical manifestations, histopathology, diagnosis, and treatment of infection.

关键词： Systemic lupus erythematosus   meningitis   radiculitis   spinal magnetic resonance imaging   corticosteroids  

摘要： Background Neurological complications of systemic lupus erythematosus (SLE) are wide and may rarely involve the peripheral nervous system. However, no case of meningoradiculitis has been well-detailed. Methods We report a patient with lupus-associated meningoradiculitis. Results A 57-year-old woman had SLE without neurological involvement, treated with hydroxychloroquine, methotrexate, and prednisone for 10 years. Six months after the drug discontinuation for SLE, she acutely developed gait instability, paresthesia, and neuropathic pain of the four limbs. The neurological examination and nerve conduction studies were consistent with radiculopathies. Cerebrospinal fluid (CSF) analysis showed lymphocytic meningitis. The spinal magnetic resonance imaging (MRI) revealed thickening and an enhancement of the lumbosacral roots consistent with meningoradiculitis. The extensive investigations did not argue for a differential diagnosis of SLE. The patient dramatically improved upon corticosteroids. At the last follow-up, the patient still reported mild paresthesia but the clinical examination, the CSF, and the spinal MRI were normal. Conclusion This well-detailed case of meningoradiculitis broadens the spectrum of neurological complications in SLE. Early recognition of such complications might lead to efficient immunotherapy.

关键词： CIDP   diagnosis   GRADE   guideline   treatment  

关键词： gait   walking   wearable sensors   reliability   neurology   inertial measurement units  

摘要： Evaluating gait is part of every neurological movement disorder assessment. Generally, the physician assesses the patient based on their experience, but nowadays inertial measurement units (IMUs) are also often integrated in the assessment. Instrumented gait analysis has a longstanding tradition and temporal parameters are used to compare patient groups or trace disease progression over time. However, the day-to-day variability needs to be considered especially in specific patient cohorts. The aim of the study was to examine day-to-day variability of temporal gait parameters of two experimental conditions in a cohort of neurogeriatric patients using data extracted from a lower back-worn IMU. We recruited 49 participants (24 women (age: 78 years +/- 6 years, BMI = 25.1 kg/m(2) and 25 men (age: 77 years +/- 6 years, BMI = 26.5 kg/m(2))) from the neurogeriatric ward. Two gait distances (4 m and 20 m) were performed during the first session and repeated the following day. To evaluate reliability, the Intraclass Correlation Coefficient (ICC2,k) and minimal detectable change (MDC) were calculated for the number of steps, step time, stride time, stance time, swing time, double limb support time, double limb support time variability, stride time variability and stride time asymmetry. The temporal gait parameters showed poor to moderate reliability with mean ICC and mean MDC95% values of 0.57 +/- 0.18 and 52% +/- 53%, respectively. Overall, only four out of the nine computed temporal gait parameters showed high relative reliability and good absolute reliability values. The reliability increased with walking distance. When only investigating steady-state walking during the 20 m walking condition, the relative and absolute reliability improved again. The most reliable parameters were swing time, stride time, step time and stance time. Study results demonstrate that reliability is an important factor to consider when working with IMU derived gait parameters in specific patient

关键词： Digital therapeutics   Exergames   Neurological disorders   Rehabilitation   Validation studies  

摘要： Digital therapeutics (DTx) is a section of digital health defined by the DTx Alliance as "delivering evidence-based therapeutic interventions to patients that are driven by software to prevent, manage, or treat a medical disorder or disease. They are used independently or in concert with medications, devices, or other therapies to optimize patient care and health outcomes". Chronic disabling diseases could greatly benefit from DTx. In this narrative review, we provide an overview of DTx in the care of patients with neurological dysfunctions.

关键词： Animal model   cerebral blood flow   embolic MCAO   laser speckle   thrombolytic therapy  

摘要： The embolic middle cerebral artery occlusion (eMCAO) model mimics ischemic stroke due to large vessel occlusion in humans and is amenable to thrombolytic therapy with rtPA. However, two major obstacles, the difficulty of the eMCAO surgery and unpredictable occurrence of clot autolysis, had impeded its application in mice. In this study, we modified catheters to produce suitable fibrin-rich embolus and optimized the eMCAO model using cerebral blood flow (CBF) monitored by both laser Doppler flowmetry (LDF) and 2D laser speckle contrast imaging (LSCI) to confirm occlusion of MCA. The results showed that longer embolus resulted in higher mortality. There was a compensatory increase in MCA territory perfusion after eMCAO associated with decreased infarct volume;however, this was only partly dependent on recanalization as clot autolysis was only observed in similar to 30% of mice. Cortical CBF monitoring with LSCI showed that the size of peri-core area at 3 h displayed the best correlation with infarct volume that is attributed to compensatory collateral blood flow. The peri-core area best predicted functional outcome after eMCAO. In summary, we developed a reliable eMCAO mouse model that better mimics embolic ischemic stroke in humans, which will increase the potential for successful translation of stroke neuroprotective therapies.