Showing papers in "Journal of Neurology in 2020"
TL;DR: SARS-CoV-2 RNA detected in a cerebrospinal fluid specimen of a patient with COVID-19 have provided direct evidence to support the theory of neurotropic involvement of SARS- CooperVirus, however, the underlying neurotropics mechanisms are yet to be established.
Abstract: Coronavirus disease 2019 (COVID-19), a disease caused by the novel betacoronavirus (SARS-CoV-2), has become a global pandemic threat. The potential involvement of COVID-19 in central nervous system (CNS) has attracted considerable attention due to neurological manifestations presented throughout the disease process. In addition, SARS-CoV-2 is structurally similar to SARS-CoV, and both bind to the angiotensin-converting enzyme 2 (ACE2) receptor to enter human cells. Thus, cells expressing ACE2, such as neurons and glial cells may act as targets and are thus vulnerable to SARS-CoV-2 infection. Here, we have reviewed the neurological characteristics of COVID-19 and summarized possible mechanisms of SARS-CoV-2 invasion of the CNS. COVID-19 patients have presented with a number of different neurological symptoms such as headache, dizziness, hyposmia, and hypogeusia during the course of illness. It has also been reported recently that some cases of COVID-19 have presented with concurrent acute cerebrovascular disease (acute ischemic stroke, cerebral venous sinus thrombosis, cerebral hemorrhage, subarachnoid hemorrhage), meningitis/encephalitis, acute necrotizing hemorrhagic encephalopathy, and acute Guillain-Barre syndrome. Furthermore, SARS-CoV-2 RNA detected in a cerebrospinal fluid specimen of a patient with COVID-19 have provided direct evidence to support the theory of neurotropic involvement of SARS-CoV-2. However, the underlying neurotropic mechanisms of SARS-CoV-2 are yet to be established. SARS-CoV-2 may affect CNS through two direct mechanisms (hematogenous dissemination or neuronal retrograde dissemination) or via indirect routes. The underlying mechanisms require further elucidation in the future.
276 citations
TL;DR: Both ischemic and hemorrhagic stroke can complicate the course of COVI-19 infection, and stroke developed mostly in patients with severe pneumonia and multiorgan failure, liver enzymes and LDH were markedly increased in all cases, and the outcome was poor.
Abstract: Italy is one of the most affected countries by the coronavirus disease 2019 (COVID-19). The responsible pathogen is named severe acute respiratory syndrome coronavirus (SARS-CoV-2). The clinical spectrum ranges from asymptomatic infection to severe pneumonia, leading to intensive care unit admission. Evidence of cerebrovascular complications associated with SARS-CoV-2 is limited. We herein report six patients who developed acute stroke during COVID-19 infection. A retrospective case series of patients diagnosed with COVID-19 using reverse-transcriptase polymerase chain reaction (RT-PCR) on nasopharyngeal swabs, who developed clinical and neuroimaging evidence of acute stroke during SARS-CoV-2 infection. Six patients were identified (5 men); median age was 69 years (range 57–82). Stroke subtypes were ischemic (4, 67%) and hemorrhagic (2, 33%). All patients but one had pre-existing vascular risk factors. One patient developed encephalopathy prior to stroke, characterized by focal seizures and behavioral abnormalities. COVID-19-related pneumonia was severe (i.e., requiring critical care support) in 5/6 cases (83%). Liver enzyme alteration and lactate dehydrogenase (LDH) elevation were registered in all cases. Four patients (67%) manifested acute kidney failure prior to stroke. Four patients (67%) had abnormal coagulation tests. The outcome was poor in the majority of the patients: five died (83%) and the remaining one (17%) remained severely neurologically affected (mRS: 4). Both ischemic and hemorrhagic stroke can complicate the course of COVI-19 infection. In our series, stroke developed mostly in patients with severe pneumonia and multiorgan failure, liver enzymes and LDH were markedly increased in all cases, and the outcome was poor.
199 citations
TL;DR: As more patients reach the weeks after initial infection with COVID-19, acute disseminated encephalomyelitis should be considered a potentially treatable cause of profound encephalopathy or multifocal neurological deficits.
Abstract: A 51-year-old woman with COVID-19 infection developed coma and an impaired oculocephalic response to one side. MRI of the brain demonstrated acute multifocal demyelinating lesions, and CSF testing did not identify a direct cerebral infection. High-dose steroids followed by a course of IVIG was administered, and the patient regained consciousness over the course of several weeks. As more patients reach the weeks after initial infection with COVID-19, acute disseminated encephalomyelitis should be considered a potentially treatable cause of profound encephalopathy or multifocal neurological deficits.
179 citations
TL;DR: A 70-year-old-woman was referred to the emergency department (ED) on Mar-28 complaining of asthenia, hands and feet paresthesia and gait difficulties progressing within 1 day, and neurophysiologic findings were consistent with a diagnosis of GBS following a clinically resolved paucisymptomatic COVID-19.
Abstract: The coronavirus disease-2019 (COVID-19) pandemic originated in Wuhan (China) on December 2019. So far, more than 1,500,000 cases have been confirmed worldwide (> 150,000 cases in Italy) [1]. Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection is a systemic disorder typically presenting with fever, fatigue and prevalent respiratory disturbances (dry cough, dyspnea, chest pain, interstitial pneumonia) [2], although neurological manifestations are increasingly reported [3]. Guillain-Barré syndrome (GBS) is an acute/subacute immune-mediated polyradiculoneuropathy characterized by varying degrees of limbs or cranial-nerves weakness, loss of deep tendon reflexes, sensory and dysautonomic symptoms due to peripheral nerves and roots demyelination and/or axonal damage [4]. According to a recent review about twothird of all GBS are preceded by upper respiratory infection or enteritis [4]. Here we describe a case of GBS following a clinically resolved paucisymptomatic COVID-19. A 70-year-old-woman was referred to our emergency department (ED) on Mar-28 complaining of asthenia, hands and feet paresthesia and gait difficulties progressing within 1 day. On Mar-4 she had developed fever (body temperature—BT = 38.5 °C) and dry cough. A day later she had been tested positive for SARS-CoV-2-RNA on RT-PCR with a nasopharyngeal swab. Symptoms of COVID-19 had resolved in a few days. The epidemiological survey had revealed a previous hospital visit to an inpatient in an area with high incidence for COVID-19 (Piacenza, Italy) on Feb28, 29. At the ED admission BT was 36.5 °C, oxygen saturation was 98% on room air. Arterial blood gas analysis showed pO2 = 76 mmHg with normal p/f ratio (= 363). Hematological investigations revealed slightly increased white blood cells (10.41 × 109/L, normal = 4–10 × 109/L) with 8.15 × 109/L neutrophils (normal = 2–8 × 109/L) and lymphocytes in the normal range. D-dimer, creatine phosphokinase, blood glucose, hepatic and renal function were normal, as well as c-reactive protein, erythrocyte sedimentation rate, folate and vitamin B12 blood levels. A chest high-resolution computed tomography revealed some small “ground glass” areas in both lungs. A repeated nasopharyngeal swab for SARS-CoV-2-RNA was negative. Mycoplasma Pneumoniae and Cytomegalovirus (CMV) serology (IgM and IgG), Legionella Pneumophila and Streptococcus Pneumoniae urinary tests were unrevealing. The neurological examination disclosed moderate (Medical Research Council grade 4/5) symmetric distal upper and lower limbs weakness, loss of deep tendon reflexes, preserved light touch and pinprick sensation. On Mar-31 a lumbar puncture was performed. The cerebrospinal fluid (CSF) analysis revealed slight albumino-cytological dissociation (CSF proteins = 48 mg/dL, normal = 0–40 mg/dL, white blood cells = 1 × 106/L, normal = 0–8 × 106/L). Microbiologic testing on CSF was negative (including herpes simplex virus, varicella zoster virus, Epstein-Bar virus, CMV, HIV-1, Borrelia Burgdorferi IgM and IgG). Neurophysiologic findings were consistent with a diagnosis of GBS (Table 1), according to current criteria [5]. A trial with 400 mg/die intravenous immunoglobulin (IVIg) for 5 days was started. On Apr-1 the patient was intubated and mechanical ventilation was applied, because of respiratory failure due to the worsening of muscle weakness. * Matteo Foschi mattfos89@gmail.com
171 citations
TL;DR: It is suggested that the diagnosis of idiopathic facial palsy is based on exclusion and is most often made based on five factors including anatomical structure, viral infection, ischemia, inflammation, and cold stimulation responsivity.
Abstract: Bell's palsy is the most common condition involving a rapid and unilateral onset of peripheral paresis/paralysis of the seventh cranial nerve. It affects 11.5-53.3 per 100,000 individuals a year across different populations. Bell's palsy is a health issue causing concern and has an extremely negative effect on both patients and their families. Therefore, diagnosis and prompt cause determination are key for early treatment. However, the etiology of Bell's palsy is unclear, and this affects its treatment. Thus, it is critical to determine the causes of Bell's palsy so that targeted treatment approaches can be developed and employed. This article reviews the literature on the diagnosis of Bell's palsy and examines possible etiologies of the disorder. It also suggests that the diagnosis of idiopathic facial palsy is based on exclusion and is most often made based on five factors including anatomical structure, viral infection, ischemia, inflammation, and cold stimulation responsivity.
133 citations
TL;DR: Lab, electrophysiological, radiological, and pathological evidence supported neurologic involvement of COVID-19, suggesting neurological involvement is an important aspect of the disease.
Abstract: Coronavirus disease 2019 (COVID-19) has become a global pandemic, affecting millions of people. However, clinical research on its neurological manifestations is thus far limited. In this study, we aimed to systematically collect and investigate the clinical manifestations and evidence of neurological involvement in COVID-19. Three medical (Medline, Embase, and Scopus) and two preprints (BioRxiv and MedRxiv) databases were systematically searched for all published articles on neurological involvement in COVID-19 since the outbreak. All included studies were systematically reviewed, and selected clinical data were collected for meta-analysis via random-effects. A total of 41 articles were eligible and included in this review, showing a wide spectrum of neurological manifestations in COVID-19. The meta-analysis for unspecific neurological symptoms revealed that the most common manifestations were fatigue (33.2% [23.1–43.3]), anorexia (30.0% [23.2–36.9]), dyspnea/shortness of breath (26.9% [19.2–34.6]), and malaise (26.7% [13.3–40.1]). The common specific neurological symptoms included olfactory (35.7–85.6%) and gustatory (33.3–88.8%) disorders, especially in mild cases. Guillain–Barre syndrome and acute inflammation of the brain, spinal cord, and meninges were repeatedly reported after COVID-19. Laboratory, electrophysiological, radiological, and pathological evidence supported neurologic involvement of COVID-19. Neurological manifestations are various and prevalent in COVID-19. Emerging clinical evidence suggests neurological involvement is an important aspect of the disease. The underlying mechanisms can include both direct invasion and maladaptive inflammatory responses. More studies should be conducted to explore the role of neurological manifestations in COVID-19 progression and to verify their underlying mechanisms.
117 citations
TL;DR: Lab findings revealed elevated C-reactive protein but normal white blood cell count, and initial treatment with aciclovir and ceftriaxone intravenously was discontinued on day 8 after negative CSF results for respective infective agents.
Abstract: A 60-year-old patient was first admitted to our hospital with typical respiratory symptoms of COVID-19 infection without neurological symptoms. The polymerase chain reaction (PCR) test of the throat swab was positive for SARS-CoV2. A chest x-ray showed mild bilateral ground-glass opacification. Laboratory findings revealed elevated C-reactive protein but normal white blood cell count. The patient’s previous medical history was unremarkable other than hypertension (treated with ramipril and felodipine), mild fatty liver, and ureterolithiasis. Patients and family history revealed no signs of neurological disorders and he received no vaccination in the months before. He recovered rapidly from COVID-19 pneumonia and was discharged home 5 days later without any symptoms. Three days after discharge, he developed bladder dysfunction and progressive weakness of the lower limbs. He was unable to micturate or walk unaided. On re-admission two days later, clinical examination revealed hypesthesia below the Th9 level and a moderate spastic paraparesis. Babinski’s sign was positive bilaterally. Cognition and cranial nerves were unaffected. General lab results were unremarkable including a nearly normalized c-reactive protein. A repeated throat swab showed a negative SARS-CoV2 PCR. Magnetic resonance imaging (MRI) of the spine revealed T2 signal hyperintensity of the thoracic spinal cord at Th9 level suggestive of acute transverse myelitis rather than multiple sclerosis [3] (Fig. 1a). Brain MRI showed no inflammatory changes. Cerebrospinal fluid (CSF) analysis was abnormal with lymphocytic pleocytosis (16/μl) and elevated protein level (793 mg/l). SARS-CoV2-PCR in the CSF and oligoclonal bands were negative. Further work-up was unremarkable including PCR for herpes simplex virus, varicella-zoster virus, antibodies against human herpesvirus 6, Epstein-Barr virus, and Hepatitis E, antineuronal antibody panel, Aquaporin-4, and myelin oligodendrocyte glycoprotein antibodies. Follow-up MRI on day 6 further showed a patchy hyperintensity of the thoracic myelon at Th9-10 and at Th3-5 level (Fig. 1d), suggestive of transverse myelitis. Repeated CSF analysis showed a slight increase in CSF lymphopleocytosis (27/μl) and protein levels (1177 mg/l). Repeated SARSCoV2-PCR in the CSF was negative. There was no specific intrathecal synthesis of Anti-SARS-CoV IgG. Initial treatment with aciclovir and ceftriaxone intravenously was discontinued on day 8 after negative CSF results for respective infective agents. The patients’ clinical status slightly improved 3 days after admission. Because of persisting symptoms and after negative workup for active infection, methylprednisolone was started on day 7 at a dose of 100 mg/d. During the further course, the patient improved rapidly. Follow-up CSF on day 12 showed normalization of cell count (3/μl) and regressing protein levels (734 mg/l), no Maike Munz and Swen Weßendorf authors contributed equally.
115 citations
TL;DR: Evidence linking GM changes with PD is reviewed, highlighting mechanisms supportive of pathological α-synuclein spread and intestinal inflammation in PD and roles of GM modulating therapies including probiotics and faecal microbiota transplantation are discussed.
Abstract: Recently, there has been a surge in awareness of the gastrointestinal microbiome (GM) and its role in health and disease. Of particular note is an association between the GM and Parkinson's disease (PD) and the realisation that the GM can act via a complex bidirectional communication between the gut and the brain. Compelling evidence suggests that a shift in GM composition may play an important role in the pathogenesis of PD by facilitating the characteristic ascending neurodegenerative spread of α-synuclein aggregates from the enteric nervous system to the brain. Here, we review evidence linking GM changes with PD, highlighting mechanisms supportive of pathological α-synuclein spread and intestinal inflammation in PD. We summarise existing patterns and correlations seen in clinical studies of the GM in PD, together with the impacts of non-motor symptoms, medications, lifestyle, diet and ageing on the GM. Roles of GM modulating therapies including probiotics and faecal microbiota transplantation are discussed. Encouragingly, alterations in the GM have repeatedly been observed in PD, supporting a biological link and highlighting it as a potential therapeutic target.
109 citations
TL;DR: A case of a patient with mild respiratory symptoms and neurological manifestations compatible with clinically isolated syndrome is reported, suggesting a possible association of SARS-COV-2 infection with neurological symptoms of demyelinating disease, even in the absence of relevant upper respiratory tract infection signs.
Abstract: The association between coronaviruses and central nervous system (CNS) demyelinating lesions has been previously shown. However, no case has been described of an association between the novel coronavirus (SARS-COV-2) and CNS demyelinating disease so far. SARS-COV-2 was previously detected in cerebrospinal fluid (CSF) sample of a patient with encephalitis. However, the virus identity was not confirmed by deep sequencing of SARS-COV-2 detected in the CSF. Here, we report a case of a patient with mild respiratory symptoms and neurological manifestations compatible with clinically isolated syndrome. The viral genome of SARS-COV-2 was detected and sequenced in CSF with 99.74-100% similarity between the patient virus and worldwide sequences. This report suggests a possible association of SARS-COV-2 infection with neurological symptoms of demyelinating disease, even in the absence of relevant upper respiratory tract infection signs.
104 citations
TL;DR: With the aggravation of population aging and the rapid growth of economy, developing regions following the development pattern of the developed regions may suffer rising ALS prevalence and incidence which may increase their disease burden as well.
Abstract: Amyotrophic lateral sclerosis (ALS) is a global disease, which adversely affects the life quality of patients and significantly increases the burden of families and society. We aimed to assess the changing incidence, prevalence of ALS around the world. We searched Medline, Embase, Web of Science, and Cochrane library to identify articles published until September 9, 2018. Each included study was independently reviewed for methodological quality by two reviewers. We used a random-effects model to summarize individual studies and assessed heterogeneity (I2) with the χ2 test on Cochrane’s Q statistic. We identified 124 studies that were eligible for final inclusion, including 110 studies of incidence and 58 studies of prevalence. The overall crude worldwide ALS prevalence and incidence were 4.42 (95% CI 3.92–4.96) per 1,00,000 population and 1.59 (95% CI 1.39–1.81) per 1,00,000 person-years, respectively. ALS prevalence and incidence increased by age until the age of 70–79. Since 1957, incidence has been significantly rising year by year, and this upward trend was weakened after standardization. The longest survival time were in Asia (ranging from 3.74 years in South Asia to 9.23 years in West Asia). With the aggravation of population aging and the rapid growth of economy, developing regions following the development pattern of the developed regions may suffer rising ALS prevalence and incidence which may increase their disease burden as well. These data highlight the need for research into underlying mechanism and innovations in health-care systems.
101 citations
TL;DR: The review shows that although more and more papers are reporting neurological manifestations associated with COVID-19; however, many items remain unclear and this uncertainty calls for a global action that requires close coordination and open-data sharing between hospitals, academic institutions and the fast establishment of harmonised research priorities and research consortia to face the NeuroCO VID-19 complications.
Abstract: While the epidemic of Coronavirus disease 2019 (COVID-19) continues to spread globally, more and more evidences are collected about the presence of neurological manifestations and symptoms associated with it. A systematic review has been performed of papers published until 5 April 2020. 29 papers related to neurological manifestations associated with COVID-19 were examined. The results show presence of central and peripheral nervous system manifestations related to coronavirus. Neurological manifestations, or NeuroCOVID, are part of the COVID-19 clinical picture, but questions remain regarding the frequency and severity of CNS symptoms, the mechanism of action underlying neurological symptoms, and the relationship of symptoms with the course and severity of COVID-19. Further clinical, epidemiological, and basic science research is urgently needed to understand and address neurological sequalae of COVID-19. Concomitant risk factors or determinants (e.g. demographic factors, comorbidities, or available biomarkers) that may predispose a person with COVID-19 to neurological manifestations also need to be identified. The review shows that although more and more papers are reporting neurological manifestations associated with COVID-19; however, many items remain unclear and this uncertainty calls for a global action that requires close coordination and open-data sharing between hospitals, academic institutions and the fast establishment of harmonised research priorities and research consortia to face the NeuroCOVID-19 complications.
TL;DR: A clinical syndrome of acute muscle weakness, myalgia, and muscle swelling combined with a CK cut-off value of > 1000 IU/L/ or CK’s upper limit of normal (ULN) for the standard definition of a mild RML is recommended.
Abstract: Rhabdomyolysis (RML) is an interdisciplinary condition due to muscle cell injury followed by the release of cell components into circulation. Etiology of RML has a broad range; a serious complication is acute kidney injury (AKI). Despite its high relevance, there is no established formal definition for RML. A systematic review, focusing on RML definition, providing a recommendation for clinicians. Systematic literature research in PubMed and Embase (1968-07/2018). The database research presented 8136 articles in PubMed and 2151 in Embase. After screening, 614 papers were retained for statistical analysis. A retrospective study was the most used design (44%). A definition of RML was stated in 231 studies (37.6%), including a precise creatine kinase level (CK) cut-off most frequently (67.1%). In 53/231 (22.9%) studies the CK cut-off was > 5 × upper limit of normal (ULN), and in 64/231 (27.7%) studies > 1000 IU/L. Further components of definitions were elevated CK without specific thresholds, and clinical symptoms. Exclusion criteria referring to the definition of RML were established in 113 studies, including myocardial, renal, cerebral and neuromuscular characteristics. At present, we recommend a clinical syndrome of acute muscle weakness, myalgia, and muscle swelling combined with a CK cut-off value of > 1000 IU/L/ or CK > 5 × ULN for the standard definition of a mild RML. Additionally measured myoglobinuria and AKI indicate a severe type of RML. Exclusion criteria as well as the chronological sequence need to be considered for a conclusive RML definition.
TL;DR: A systematic literature search using multiple combinations of keywords from PubMed and Ovid Medline databases was able to identify 82 cases of COVID-19 with neurological complications, which are not rare but should be cautious not to overlook other neurological diagnoses that can mimic CO VID-19 during the pandemic.
Abstract: In December 2019, unexplained cases of pneumonia emerged in Wuhan, China, which were found to be secondary to the novel coronavirus SARS-CoV-2. On March 11, 2020, the WHO declared the Coronavirus Disease 2019 (COVID-2019) outbreak, a pandemic. To clarify the neurological complications of SARS-CoV-2 infection including the potential mechanisms and therapeutic options. We conducted a systematic literature search from December 01, 2019 to May 14, 2020 using multiple combinations of keywords from PubMed and Ovid Medline databases according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. We included articles with cases of COVID-19 where neurological involvement was evident. We were able to identify 82 cases of COVID-19 with neurological complications. The mean age was 62.3 years. 37.8% of the patients were women (n = 31). 48.8% of the patients (n = 40) had cerebrovascular insults, 28% (n = 23) had neuromuscular disorders, and 23% of the patients (n = 19) had encephalitis or encephalopathy. Neurological manifestations of COVID-19 are not rare, especially large vessel stroke, Guillain–Barre syndrome, and meningoencephalitis. Moving forward, further studies are needed to clarify the prevalence of the neurological complications of SARS-CoV-2 infection, investigate their biological backgrounds, and test treatment options. Physicians should be cautious not to overlook other neurological diagnoses that can mimic COVID-19 during the pandemic.
TL;DR: This first population-based incidence study of paraneoplastic neurological syndromes found an incidence of PNS that approximates 1/100,000 person-years and a prevalence of 4/ 100,000, probably due to increased awareness and improved detection techniques.
Abstract: The epidemiology of paraneoplastic neurological syndromes (PNS) remains to be defined. We present here the first population-based incidence study and report the clinical spectrum and antibody profile of PNS in a large area in Northeastern Italy. We performed a 9-year (2009–2017) population-based epidemiological study of PNS in the provinces of Udine, Pordenone and Gorizia, in the Friuli-Venezia Giulia region (983,190 people as of January 1, 2017). PNS diagnosis and subgroups were defined by the 2004 diagnostic criteria. Age- and sex-adjusted incidence rates were calculated. We identified 89 patients with a diagnosis of definite PNS. Median age was 68 years (range 26–90), 52% were female. The incidence of PNS was 0.89/100,000 person-years. PNS incidence rates increased over time from 0.62/100,000 person-years (2009–2011), 0.81/100,000 person-years (2012–2014) to 1.22/100,000 person-years (2015–2017). The prevalence of PNS was 4.37 per 100,000. Most common PNS were limbic encephalitis (31%), cerebellar degeneration (28%) and encephalomyelitis (20%). Among antibody (Ab)-positive cases, most frequent specificities included: Yo (30%), Hu (26%), and Ma2 (22%), while the most frequent associated tumors were lung (17%) and breast cancer (16%), followed by lymphoma (12%). PNS developed in 1 in every 334 cancers in our region. Statistically significant associations were observed between cancer type and Ab-specificity (P < 0.001), and between neurological syndrome and Ab-specificity (P < 0.001). This first population-based study found an incidence of PNS that approximates 1/100,000 person-years and a prevalence of 4/100,000. Moreover, the incidence of PNS is increasing over time, probably due to increased awareness and improved detection techniques.
TL;DR: Metronidazole-induced encephalopathy should be considered in patients presenting with neurological symptoms in relation to newly initiated or prolonged metronidrazole treatment, and MRI changes are highly characteristic and specific.
Abstract: Metronidazole, a commonly used antibiotic drug, can cause adverse effects in the central nervous system termed metronidazole-induced encephalopathy, leading to diagnostic challenges. The condition is rare and a detailed description of its phenotype is lacking. In this systematic review we investigated the clinical features of metronidazole-induced encephalopathy to promote recognition and elaborate the description. We performed a systematic literature search using PubMed.gov and hand searched the reference lists of included articles and other publications of interest. We included case series and single reports describing individual patients developing symptoms from the central nervous system in relation to metronidazole treatment. Data were extracted and analyzed descriptively. We identified 779 publications of which 112 papers comprising 136 patients were included. Typical findings were dysarthria, gait instability, limb dyscoordination and altered mental status. Frequently, patients concomitantly presented with metronidazole-induced polyneuropathy. Liver disease was the most common pre-existing condition. MRI showed a characteristic pattern of reversible symmetrical hyperintense lesions on T2/FLAIR of the dentate nuclei in 90% of patients. Most patients improved significantly after discontinuation of metronidazole. Poor outcome was associated with severe comorbidity. Metronidazole-induced encephalopathy should be considered in patients presenting with neurological symptoms in relation to newly initiated or prolonged metronidazole treatment. MRI changes are highly characteristic and specific. Patients with liver disease are at increased risk. Prognosis is good if recognized early.
TL;DR: Serum neurofilament light chain (sNfL) has recently been considered as a specific biomarker to quantitate neuroaxonal damage in several disorders of the peripheral and central nervous system and might also serve as a sensitive screening and follow-up marker for neuronal injury in COVID-19 patients.
Abstract: Even though the coronavirus disease 2019 (COVID-19) affects primarily the respiratory system some reports describe nervous system involvement as well [1–3]. Headache and anosmia have been frequently described as neurological symptoms of mild-to-moderate COVID-19 but a direct impact of COVID-19 on neuronal integrity has not been clarified yet [4]. Therefore, a neuronal biomarker would be extremely useful to elucidate neuro-axonal injury during an infection with Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) and in the post-infection follow-up period. Serum neurofilament light chain (sNfL) has recently been considered as a specific biomarker to quantitate neuroaxonal damage in several disorders of the peripheral and central nervous system [5]. Hence, sNfL might also serve as a sensitive screening and follow-up marker for neuronal injury in COVID-19 patients. We conducted a prospective cohort study in 100 healthcare workers (84 females, 16 males) following a COVID-19 outbreak in a major German children’s and women’s hospital [6]. The Ethics Committee of the University of Regensburg approved the study (file-number: 20-1767-101), and written informed consent was obtained from all study participants. They were categorized according to their SARS-CoV-2 infection status, n = 28 tested positive, n = 72 negative in PCR-based viral RNA amplification from nasopharyngeal swabs (Xpert© Xpress SARS-CoV-2, Cepheid) [5]. To preserve anonymity of study participants, age was assessed in three categories (18–35 years n = 33, 36–50 years n = 37 and 51–65 years n = 30) [7]. sNfL concentrations were measured using the single molecule array (Simoa) NF-light® kit on the HD-X Analyzer (Quanterix, Lexington, MA) [5]. First, descriptive statistics were calculated. Then, a multivariable linear regression model was fitted with sNfL as dependent variable and with sex, age and COVID-19 status as independent variables. All COVID-19 patients had mild-to-moderate symptoms and recovered after 1–3 weeks and showed no or only minor neurological symptoms, including anosmia and headache. First, sNfL measurement was done in COVID-19 patients 23 days (median, IQR 21–26) after onset of disease. sNfL levels for COVID-19 patients and for controls, stratified for age group, are depicted in Fig. 1. Median and interquartile range for COVID-19 patients were 4.5 pg/ml [IQR 3.7–5.7] for the age group 18–35 years, 9.6 [6.5–11.3] for the age group 36–50 years, and 11.6 [8.4–18.3] for the age group 51–65 years, respectively. sNFL levels for controls were 4.4 [3.5–5.5] for the youngest group, 6.8 [5.6–8.8] for the group 36–50 years, and 9.6 [8.2–11.2] for the oldest group (Table 1). Since sNFL levels are highly dependent on age [8] the association between COVID-19 status and sNFL was determined using a multivariable linear regression model with COVID-19 status, age and sex as independent variables. This analysis revealed that COVID-19 status was significantly associated with sNfL (b = 1.87; p = 0.005) when controlling for age and sex (Table 2). In COVID-19 patients with two sNfL measurements (n = 16, time span between Jens Kuhle and Sven Wellmann these authors contributed equally to this work.
TL;DR: A case of a 64-year old woman with COVID19 infection who developed Posterior Reversible Encephalopathy Syndrome is reported, and it is suggested that it could be explained by the disruption of the blood brain barrier induced by the cerebrovascular endothelial dysfunction caused by SARS-CoV-2.
Abstract: Recently WHO has declared novel coronavirus disease 2019 (COVID-19) outbreak a pandemic. Acute respiratory syndrome seems to be the most common manifestation of COVID-19. Besides pneumonia, it has been demonstrated that SARS-CoV-2 infection affects multiple organs, including brain tissues, causing different neurological manifestations, especially acute cerebrovascular disease (ischemic and hemorrhagic stroke), impaired consciousness and skeletal muscle injury. To our knowledge, among neurological disorders associated with SARS-CoV2 infection, no Posterior Reversible Encephalopathy Syndrome (PRES) has been described yet. Herein, we report a case of a 64-year old woman with COVID19 infection who developed a PRES, and we suggest that it could be explained by the disruption of the blood brain barrier induced by the cerebrovascular endothelial dysfunction caused by SARS-CoV-2.
TL;DR: Understanding the risk of infection in MS patients remains important, especially with regard to decisions concerning therapeutic management, and three studies highlight the general increased risk of infections in PwMS and those of specific treatments.
Abstract: Global healthcare systems are rapidly having to change and adapt in the face of the COVID-19 pandemic. At a more individual level, neurologists are being faced with complex decisions regarding the risk of infection in specific patient groups, and in particular those receiving immunosuppressant or immunomodulatory therapy. One such important patient group is those individuals with multiple sclerosis (MS) receiving disease-modifying therapies (DMTs). It has previously been established that people with MS (PwMS) have an increased risk of infections compared with the general population. These infections can lead to significant morbidity and may also contribute to relapses and a worsening of neurological symptoms. First-generation DMTs such as interferon-beta (IFN-β) or glatiramer acetate (GA) are not thought to be associated with a significantly increased risk of infection, although more efficacious second generation DMTs have demonstrated a higher risk profile. However, the majority of these observations are derived from clinical trials of MS DMTs which, because of restricted inclusion criteria and short-term follow-up, may underestimate the overall risk. Real-world experience with longer term follow-up in representative patient groups may be necessary to achieve a more accurate picture, although these data are currently limited. In the context of the evolving COVID-19 pandemic, it has become particularly important to understand these risks to make informed decisions regarding treatment and to be able to communicate this information effectively to patients. In all cases any increased risk of infection and associated morbidity will need to be carefully balanced against risks of stopping treatment and rebound disease activity. From an historical perspective, it is also interesting to note that the coronavirus family has been previously investigated for a potential association with MS, and more recently has been utilised to make a mouse model of the disease (coronavirus-induced encephalomyelitis). We should also not assume that effects of COVID-19 infection, and in particular the rarer but more serious secondary hyperinflammation syndrome, should necessarily be worsened in PwMS on DMTs and they may even be protective; inhaled treatment with interferon-beta as well as Fingolimod are currently under investigation as a potential treatment for COVID-19 infection. Nevertheless, understanding the risk of infection in MS patients remains important, especially with regard to decisions concerning therapeutic management. In this month’s journal club, we consider three papers relevant to the risk of infection in patients with MS. These studies highlight the general increased risk of infections in PwMS and those of specific treatments. Although data from many DMTs are considered in these studies, there are some—notably alemtuzumab and ocrelizumab that are not currently captured by these predominantly registry-based studies. In the meantime, many national neurology associations as well as MS charitable bodies have issued guidance with regard to the use of all DMTs in light of the current pandemic and are a useful practical resource for neurologists to review.
TL;DR: All DMTs were superior to placebo in reducing the relapse rate during the 2 years of follow-up and all drugs were significantly more effective than were placebos.
Abstract: Multiple sclerosis (MS) is an autoimmune, demyelinating disease of the central nervous system. The treatment of MS has always been a focus of neurological research. To date, the US Food and Drug Administration has approved 15 medications for modifying the course of multiple sclerosis. In this study, we examined the effects of disease-modifying therapies (DMTs) on clinical outcomes. We did a systematic review and network meta-analysis based on randomized controlled trials (RCTs) comparing DMTs in patients with relapsing–remitting multiple sclerosis (RRMS). We searched the Cochrane Central Register of Controlled Trials, MEDLINE, Embase, ClinicalTrials.gov and the World Health Organization International Clinical Trials Registry Platform for RCTs published up to Oct 31, 2018. The primary outcome was efficacy (relapse rate over 24 months) and acceptability (treatment discontinuation due to adverse events over 24 months). We identified 23 suitable trials encompassing 14,096 participants. During the 2 years of follow-up, all drugs were significantly more effective than were placebos. The risk ratios with 95% credible intervals were as follows: alemtuzumab, 0.49 (0.40, 0.59); ocrelizumab, 0.49 (0.40, 0.61); mitoxantrone, 0.47 (0.27, 0.80); natalizumab, 0.51 (0.43, 0.61); fingolimod, 0.57 (0.50, 0.65); peginterferon beta-1a, 0.63 (0.52, 0.77); dimethyl fumarate, 0.65 (0.56, 0.74); teriflunomide 14 mg, 0.78 (0.66, 0.92); glatiramer acetate, 0.80 (0.72, 0.89); IFN β-1a (Rebif), 0.81 (0.72, 0.90); IFN β-1b (Betaseron), 0.81 (0.72, 0.91); teriflunomide 7 mg, 0.83 (0.71, 0.98); and IFN β-1a (Avonex). 0.87 (0.77, 0.99). Risk ratios compared with placebo for discontinuation due to adverse events ranged from 1.12 for the best drug (fingolimod) to 0.10 for the worst drug (mitoxantrone); from 0.24 (alemtuzumab) to 0.89 (IFNβ-1b [Betaseron]) for sustained (3-month) disability progression; and from 0.85 (natalizumab) to 1.25 (teriflunomide 14 mg) for the number of participants with serious adverse events. All DMTs were superior to placebo in reducing the relapse rate during the 2 years of follow-up. As to the comparison between drugs, alemtuzumab, ocrelizumab, natalizumab and fingolimod had a relatively higher response and lower dropout rates than did the other DMTs.
TL;DR: Command-following, intelligible verbalization, and intentional communication are not associated with different levels of functional disability, and the MCS + syndrome can be diagnosed based on the presence of any one of these language-related behaviors.
Abstract: We investigated the relationship between three language-dependent behaviors (i.e., command-following, intelligible verbalization, and intentional communication) and the functional status of patients with disorders of consciousness (DoC). We hypothesized that patients in minimally conscious state (MCS) who retain behavioral evidence of preserved language function would have similar levels of functional disability, while patients who lack these behaviors would demonstrate significantly greater disability. We reasoned that these results could then be used to establish empirically-based diagnostic criteria for MCS+. In this retrospective cohort study we included rehabilitation inpatients diagnosed with DoC following severe-acquired brain injury (MCS = 57; vegetative state/unresponsive wakefulness syndrome [VS/UWS] = 63); women: 46; mean age: 47 ± 19 years; traumatic etiology: 68; time post-injury: 40 ± 23 days). We compared the scores of the Disability Rating Scale score (DRS) at time of transition from VS/UWS to MCS or from MCS– to MCS+, and at discharge between groups. Level of disability on the DRS was similar in patients with any combination of the three language-related behaviors. MCS patients with no behavioral evidence of language function (i.e., MCS–) were more functionally impaired than patients with MCS+ at time of transition and at discharge. Command-following, intelligible verbalization, and intentional communication are not associated with different levels of functional disability. Thus, the MCS+ syndrome can be diagnosed based on the presence of any one of these language-related behaviors. Patients in MCS+ may evidence less functional disability compared to those in MCS who fail to demonstrate language function (i.e., MCS–).
TL;DR: Clinical trials that target genetic forms of Parkinson’s disease, i.e., GBA -associated and LRRK2 -associated PD, are reviewed, finding six ongoing studies which explicitely recruit GBA-PD patients, and two studies which recruit LRRk2 -PD patients.
Abstract: In recent years, numerous clinical trials for disease modification in Parkinson’s disease (PD) have failed, possibly because of a “one-size-fits all” approach. Alternatively, a precision medicine approach, which customises treatments based on patients’ individual genotype, may help reach disease modification. Here, we review clinical trials that target genetic forms of PD, i.e., GBA-associated and LRRK2-associated PD. In summary, six ongoing studies which explicitely recruit GBA-PD patients, and two studies which recruit LRRK2-PD patients, were identified. Available data on mechanisms of action, study design, and challenges of therapeutic trials are discussed.
TL;DR: Although rare, anti-paranodal antibodies are clinically valuable, because they are associated with specific phenotypes and therapeutic response, and intravenous immunoglobulins were ineffective in most seropositive patients.
Abstract: IgG4 antibodies against neurofascin (Nfasc155 and Nfasc140/186), contactin (CNTN1) and contactin-associated protein (Caspr1) are described in specific subtypes of chronic inflammatory demyelinating polyradiculoneuropathy (CIDP). Our objective was to assess, in a real-life practice, the incidence, the clinical features and the response to treatment of these forms of CIDP. 1500 sera of patients suspected of having CIDP from France, Belgium and Switzerland were prospectively tested using a flow cytometry technique. The characteristics of patients with antibodies against the node of Ranvier were compared to 100 seronegative CIDP from our department. IgG4 antibodies against Nfasc155, CNTN1, and Caspr1 were, respectively, detected in 15 (prevalence 1%), 10 (0.7%) and 2 (0.2%) sera. Antibodies specific of the Nfasc140/186 were not detected. All subjects with antibodies against the node of Ranvier fulfilled diagnostic criteria for CIDP. CIDP with anti-Nfasc155 were younger, had more sensory ataxia and postural tremor than seronegative CIDP. CIDP with anti-CNTN1 had more frequent subacute onset and facial paralysis, commoner renal involvement with membranous glomerulonephritis and greater disability, than seronegative CIDP. CIDP with anti-Caspr1 had more frequent respiratory failure and cranial nerve involvement but not more neuropathic pain than seronegative CIDP. Intravenous immunoglobulins were ineffective in most seropositive patients. Rituximab produced dramatic improvement in disability and decreased antibodies titres in 13 seropositive patients (8 with anti-Nfasc155 and 5 with anti-CNTN1 antibodies). Although rare, anti-paranodal antibodies are clinically valuable, because they are associated with specific phenotypes and therapeutic response.
TL;DR: The aim of this review is to discuss strategies for the management of FND by focusing on the diagnostic discussion and general principles, as well as specific treatment strategies for various FND symptoms, highlighting the role of the neurologist and proposing a structure for an interdisciplinary FND service.
Abstract: Functional neurological disorder (FND) is a common cause of persistent and disabling neurological symptoms. These symptoms are varied and include abnormal control of movement, episodes of altered awareness resembling epileptic seizures and abnormal sensation and are often comorbid with chronic pain, fatigue and cognitive symptoms. There is increasing evidence for the role of neurologists in both the assessment and management of FND. The aim of this review is to discuss strategies for the management of FND by focusing on the diagnostic discussion and general principles, as well as specific treatment strategies for various FND symptoms, highlighting the role of the neurologist and proposing a structure for an interdisciplinary FND service.
TL;DR: In this paper, the potential of serum NfL (sNfL) as a diagnostic tool between frontotemporal lobar degeneration (FTLD) spectrum disorders and late-onset primary psychiatric disorders (PPD) was evaluated.
Abstract: Due to the significant clinical overlap between frontotemporal lobar degeneration (FTLD) spectrum disorders and late-onset primary psychiatric disorders (PPD), diagnostic biomarkers reflecting the different underlying pathophysiologies are urgently needed. Thus far, elevated cerebrospinal fluid (CSF) levels of neurofilament light chain (NfL) have been reported in various neurological conditions. Furthermore, recent advancements in ultrasensitive analytical methods (e.g., single molecule array, Simoa) have enabled sensitive and less invasive NfL detection also from blood samples. In this study, we evaluated the potential of serum NfL (sNfL) as a diagnostic tool between FTLD and PPD. We analyzed sNfL levels with Simoa from 125 participants including patients from FTLD (n = 91) and PPD (n = 34) spectra. Our results show that sNfL levels are higher in the FTLD group compared to the PPD group as well as in separate clinical subtypes of FTLD compared to different psychiatric manifestations (i.e., mood or psychotic disorders). At single-subject level, discrimination between FTLD and PPD was possible with 80% sensitivity and 85% specificity (AUC = 0.850, 95% CI 0.776–0.923), and between behavioral variant frontotemporal dementia (bvFTD) and PPD with 79% sensitivity and 85% specificity (AUC = 0.830, 95% CI 0.732–0.908). These findings highlight the potential of sNfL as a discriminating biomarker for FTLD over PPD in patients with wide-ranging behavioral, psychiatric and cognitive symptoms.
Walton Centre1, Boston Children's Hospital2, John Radcliffe Hospital3, University College London4, Erasmus University Rotterdam5, Heidelberg University6, Ruhr University Bochum7, University of Göttingen8, Technische Universität München9, Charité10, University of Düsseldorf11, University of California, San Francisco12, University of Basel13, Autonomous University of Barcelona14, University of Florence15, Odense University Hospital16, Istanbul University17, Koç University18, Istanbul Bilim University19, Nitte University20, Thailand Ministry of Public Health21, Hospital Pulau Pinang22, Sun Yat-sen University23, Tohoku Pharmaceutical University24, Fukushima Medical University25, University of Sydney26, Townsville Hospital27, Griffith University28, Universidade Federal de Minas Gerais29, Pontifícia Universidade Católica do Rio Grande do Sul30, Mayo Clinic31, University of Texas Southwestern Medical Center32, Harvard University33, Anschutz Medical Campus34, New York University35, University of Pennsylvania36, University of British Columbia37, University of Liverpool38, Guy's and St Thomas' NHS Foundation Trust39, King's College London40, Cleveland Clinic41
TL;DR: A survey of the current global clinical practice of clinicians treating myelin oligodendrocyte glycoprotein antibody associated disorders (MOGAD) is presented in this paper.
Abstract: Introduction: While monophasic and relapsing forms of myelin oligodendrocyte glycoprotein antibody associated disorders (MOGAD) are increasingly diagnosed world-wide, consensus on management is yet to be developed. Objective: To survey the current global clinical practice of clinicians treating MOGAD. Method: Neurologists worldwide with expertise in treating MOGAD participated in an online survey (February–April 2019). Results: Fifty-two responses were received (response rate 60.5%) from 86 invited experts, comprising adult (78.8%, 41/52) and paediatric (21.2%, 11/52) neurologists in 22 countries. All treat acute attacks with high dose corticosteroids. If recovery is incomplete, 71.2% (37/52) proceed next to plasma exchange (PE). 45.5% (5/11) of paediatric neurologists use IV immunoglobulin (IVIg) in preference to PE. Following an acute attack, 55.8% (29/52) of respondents typically continue corticosteroids for ≥ 3 months; though less commonly when treating children. After an index event, 60% (31/51) usually start steroid-sparing maintenance therapy (MT); after ≥ 2 attacks 92.3% (48/52) would start MT. Repeat MOG antibody status is used by 52.9% (27/51) to help decide on MT initiation. Commonly used first line MTs in adults are azathioprine (30.8%, 16/52), mycophenolate mofetil (25.0%, 13/52) and rituximab (17.3%, 9/52). In children, IVIg is the preferred first line MT (54.5%; 6/11). Treatment response is monitored by MRI (53.8%; 28/52), optical coherence tomography (23.1%; 12/52) and MOG antibody titres (36.5%; 19/52). Regardless of monitoring results, 25.0% (13/52) would not stop MT. Conclusion: Current treatment of MOGAD is highly variable, indicating a need for consensus-based treatment guidelines, while awaiting definitive clinical trials.
TL;DR: The most consistent findings are those showing a progressive cortical atrophy accumulation in caudate, putamen, temporal/hippocampal, frontal and parietal areas in de novo PD cases and in the early/middle phase of the disease, with the achievement of a plateau in the later stage.
Abstract: The current review summarizes the current knowledge on longitudinal cortical and subcortical grey and white matter MRI findings assessed using T1-weighted and one-tensor diffusion-weighted MRI in Parkinson’s disease (PD) patients. Results were reviewed according to disease duration, disease severity and cognitive impairment. The most consistent findings are those showing a progressive cortical atrophy accumulation in caudate, putamen, temporal/hippocampal, frontal and parietal areas in de novo PD cases and in the early/middle phase of the disease, with the achievement of a plateau in the later stage. Analyzing results according to the patient cognitive status, only a few studies used longitudinal MRI metrics to predict mild cognitive impairment or dementia conversion in PD patients, suggesting that atrophy of the hippocampus, fronto-temporal areas, caudate, thalamus and accumbens might play a role in this process. Stratifying patients according to disease severity, findings appear partially controversial, although showing a progressive atrophy of basal ganglia over 1 year of follow up and a widespread cortical thinning over 3–6 years in mild to moderate PD patients. Finally, microstructural damage of the main motor and associative WM tracts seems to be present, and rapidly progress, even in the early phase of PD. The utility of structural MRI metrics as biomarkers of PD progression and their role in improving the accuracy of disease progression prediction is still debated.
TL;DR: The case of a 74-year-old women admitted to the authors' hospital for impaired gait after SARS-Cov2 infection is presented, considered a Miller–Fisher-like syndrome, and it is considered that the neurological symptoms overlapped with the respiratory symptoms; so, maybe they were unattended in her prior admission.
Abstract: Severe acute respiratory syndrome coronavirus 2 (SARSCoV-2) pandemic shows that novel coronavirus mainly impairs respiratory system, but day by day, new non-respiratory symptoms are reported, neurological symptoms included. We present the case of a patient admitted to our hospital for impaired gait after SARS-Cov2 infection. A 74-year-old women, with prior history of hypertension and follicular lymphoma treated from 2014 to 2015, was admitted to our province’s reference hospital in March, for bilateral pneumonia due to coronavirus infection confirmed by swab SARs-CoV2 test. Respiratory symptoms started 10 days before admission. She received hydroxychloroquine and lopinavir/ritonavir, the latter shortly due to gastric intolerance, being discharged 9 days after admission, with two negative swab SARS-CoV-2 tests. Five days after her discharge, she came to our hospital complaining of progressive gait impairment. The interval between first signs of SARS-CoV-2 symptoms and the neurological symptoms was about 12–15 days. Neurological examination showed neither oculomotor nor pupillary reflex impairment, highlighting a lower limbs areflexia with patent gait ataxia, without strength and any sensitivity impairment. Faced with suspicion of neurological pathology related to SARS-CoV-2 prior infection, cranial MRI was performed which showed non-pathological alterations. An electromyography showing slight F-wave delay in upper limbs was done. Ordinary laboratory results showed normality in blood white cell account. Cerebrospinal fluid (CSF) analysis showed an increased protein level (110 mg/ dl, normal 15–45 mg/dl) with less than 5 white cells, 100% lymphocytes. With Guillain– Barré syndrome-like suspicion, she was admitted for intravenous immunoglobulins treatment. She also complained about blurred vision, being assessed by ophthalmology without noticeable alterations, and performing visual-evoked potentials, without findings. She received 20 g of immunoglobulins daily, during 5 days. Antiganglioside antibodies, including anti GD1b, were negative. CSF SARS-CoV-2 PCR was also negative. The day 6, she was discharged. A new neurological exploration was done the 12th day after her first visit to clinics. An improvement in gait was observed, and also, lower limb reflexes were slightly present. A new EMG was done, but it remained unchanged. Guillain–Barré syndrome related to SARS-CoV2 has being reported in at least five cases [1, 2]. Also, Guillain–Barré syndrome related to others coronavirus has been reported [3]. Instead of a proper Guillain–Barré syndrome, we considered our patient a Miller–Fisher-like syndrome, due to her marked ataxia and lower limbs areflexia, probably an acute ataxic neuropathy. Even though no ophthalmoparesis was observed, we consider that the neurological symptoms overlapped with the respiratory symptoms; so, maybe they were unattended in her prior admission. The interval of 12–15 days between time of first respiratory symptoms and time of neurological symptoms onset is similar to other Miller–Fisher and other Guillain–Barré syndromes associated with other viral infections [4]. Even though Guillain–Barré syndrome has been previously reported associated with SARS-CoV-2 infection, and recently, another case of Miller–Fisher related with SARSCoV-2 infection was reported [5], it seems to be an uncommon complication. Though we have done 2 EMG separated in time, we could not demonstrate peripheral demyelination nor axonal damage. Also, we did not find GD1-b antibodies. But the response to immunoglobulins was typical as it is observed in other Miller–Fisher syndromes. Future reports should clarify this observational relationship.
TL;DR: The patients continued teriflunomide therapy and had self-limiting infection, without relapse of their MS, and these observations have implications for the management of MS in the setting of the COVID-19 pandemic.
Abstract: The outbreak of a severe acute respiratory syndrome caused by a novel coronavirus (COVID-19), has raised health concerns for patients with multiple sclerosis (MS) who are commonly on long-term immunotherapies. Managing MS during the pandemic remains challenging with little published experience and no evidence-based guidelines. We present five teriflunomide-treated patients with MS who subsequently developed active COVID-19 infection. The patients continued teriflunomide therapy and had self-limiting infection, without relapse of their MS. These observations have implications for the management of MS in the setting of the COVID-19 pandemic.
TL;DR: Background: COVID-19 (Corona-Virus Disease 2019) in Italy and the measures adopted to contain its diffusion had a strong impact on people's quality of life and
Abstract: Background: COVID-19 (Corona-Virus Disease 2019) in Italy and the measures adopted to contain its diffusion had a strong impact on people's quality of life and
TL;DR: Most patients have autoimmune or limbic encephalitis and corresponding abnormalities on neuroimaging and suggests a role for thymoma screening in CASPR2-related diseases.
Abstract: Contactin-associated protein-like 2 (CASPR2) autoantibody disease has a variable clinical phenotype. We present a case report and performed a systematic review of the literature to summarize: (1) the clinical phenotype of patients with CASPR2 antibodies, (2) the findings in neurological investigations, and (3) the associated neuroimaging findings. A chart review was performed for the case report. A systematic review of the medical literature was performed from first available to June 13, 2018. Abstracts were screened, and full-text peer-reviewed publications for novel patients with CASPR2 positivity in serum or cerebrospinal fluid (CSF) were included. Selected publications were reviewed, and relevant information was collated. Data were analyzed to determine overall frequency for demographic information, clinical presentations, and investigation findings. Our patient was a previously healthy 61-year-old male with both serum and CSF CASPR2 antibodies who presented with limbic encephalitis and refractory epilepsy. He was successfully treated with immunosuppression. For our systematic review, we identified 667 patients from 106 studies. Sixty-nine percent were male. Median age was 54 years (IQR 39–65.5). Median disease duration was 12 months (IQR 5.6–20). Reported overall clinical syndromes were: autoimmune encephalitis [69/134 (51.5%)], limbic encephalitis [106/274 (38.7%)], peripheral nerve hyperexcitability [72/191 (37.7%)], Morvan syndrome [57/251 (22.7%)], and cerebellar syndrome [24/163 (14.7%)]. Patients had positive serum [642/642 (100%)] and CSF [87/173 (50.3%)] CASPR2 antibodies. MRI was reported as abnormal in 159/299 patients (53.1%), and the most common abnormalities were encephalitis or T2 hyperintensities in the medial temporal lobes, or hippocampal atrophy, mesial temporal sclerosis, or hippocampal sclerosis. FDG-PET was abnormal in 30/35 patients (85.7%), and the most common abnormality was temporomesial hypometabolism. The most commonly associated condition was myasthenia gravis (38 cases). Thymoma occurred in 76/348 patients (21.8%). Non-thymoma malignancies were uncommon [42/397 (10.6%)]. Most patients have autoimmune or limbic encephalitis and corresponding abnormalities on neuroimaging. Other presentations include peripheral nerve hyperexcitability or Morvan syndromes, cerebellar syndromes, behavioral and cognitive changes, and more rarely movement disorders. The most commonly associated malignancy was thymoma and suggests a role for thymoma screening in CASPR2-related diseases.