Kangding Liu

Acute Necrotizing Encephalopathy: An Underrecognized Clinicoradiologic Disorder

Acute necrotizing encephalopathy (ANE) is a rare but distinctive type of acute encephalopathy with global distribution. Occurrence of ANE is usually preceded by a virus-associated febrile illness and ensued by rapid deterioration. However, the causal relationship between viral infections and ANE and the exact pathogenesis of ANE remain unclear; both environmental and host factors might be involved. Most cases of ANE are sporadic and nonrecurrent, namely, isolated or sporadic ANE; however, few cases are recurrent and with familial episodes. The recurrent and familial forms of ANE were found to be incompletely autosomal-dominant. Further the missense mutations in the gene encoding the nuclear pore protein Ran Binding Protein 2 (RANBP2) were identified. Although the clinical course and the prognosis of ANE are diverse, the hallmark of neuroradiologic manifestation of ANE is multifocal symmetric brain lesions which are demonstrated by computed tomography (CT) or magnetic resonance imaging (MRI). The treatment of ANE is still under investigation. We summarize the up-to-date knowledge on ANE, with emphasis on prompt diagnosis and better treatment of this rare but fatal disease.

Distinct Clinical Characteristics of Pediatric Guillain-Barré Syndrome: A Comparative Study between Children and Adults in Northeast China

Objective Clinical characteristics of pediatric Guillain-Barré syndrome (GBS) have been extensively studied whereas scarcely been compared with those of adult GBS. Herein we compared the clinical features of GBS between pediatric and adult patients. Methods We retrospectively collected the clinical data of 750 patients with GBS (541 adults and 209 children), and compared the clinical characteristics between children and adults. Results Pain was a more frequent complaint in children (17.2% vs 9.6%, p < 0.01), who were also found with shorter interval from disease onset to nadir (6.3d vs 7.3d, p < 0.01) and higher incidence of bulbar dysfunction (22.0% vs 14.8%, p < 0.05). The disease severity in children was comparable with adults. In addition, a higher incidence of pediatric GBS was found in summer, especially in July and August (both p < 0.01). However, the incidence of antecedent infections of different seasons in adult and pediatric patients was comparable (p > 0.05). The clinical features of acute motor axonal neuropathy (AMAN) and acute inflammatory demyelinating polyneuropathy (AIDP) in children were overall comparable with adult ones (p > 0.05). Similar to adults, bulbar dysfunction (odds ratio [OR]: 4.621, 95% confidence interval [CI]: 1.240–17.218, p < 0.05) and lower nadir Medical Research Council (MRC) sum score (OR: 0.897, 95% CI: 0.855–0.941, p < 0.01) were also risk factors for mechanical ventilation in children. However, distinct from adult ones, autonomic dysfunction was significantly higher in mechanically ventilated childhood GBS (39.1% vs 8.8%, p < 0.01), which also served as a predictor for mechanical ventilation in pediatric GBS (OR: 70.415, 95% CI: 9.265–535.158, p < 0.01). As to the efficacy of intravenous immunoglobulin, insignificant difference was identified between children and adults. Conclusion The clinical features of pediatric GBS differ from those of adults. Autonomic dysfunction is an independent risk factor for mechanical ventilation in pediatric patients.

Are Th17 cells and their cytokines a therapeutic target in Guillain–Barré syndrome?

Introduction: Guillain–Barré syndrome (GBS) is an immune-mediated inflammatory disorder of the peripheral nervous system (PNS). Experimental autoimmune neuritis (EAN) is a useful animal model for studying GBS. Currently, GBS remains a life-threatening disorder and more effective therapeutic strategies are in urgent need. Areas covered: Accumulating evidence has revealed that T helper (Th) 17 cells and their cytokines are pathogenic in GBS/EAN. Drugs attenuated clinical signs of GBS/EAN, in part, by decreasing Th17 cells or IL-17A. Th17 cells and their cytokines might be potential therapeutic targets. Approaches targeting Th17 cells or their cytokines are in development in treating Th17 cells-involved disorders. In this review, we summarize the up-to-date knowledge on roles of Th17 cells and their cytokines in GBS/EAN, as well potential approaches targeting Th17 cells and their cytokines as clinical applications. Expert opinion: As Th17 cells produce different sets of pro-inflammatory cytokines and Th17-related cytokines are not exclusively produced by Th17 cells, targeting Th17 cell development may be superior to blocking a single Th17 cytokine to treat Th17 cells-involved disorders. Considering the essential role of retinoic acid-related orphan receptor γT (RORγT) and IL-23 in Th17 cell development, RORγT inhibitors or IL-23 antagonists may provide better clinical efficacy in treating GBS/EAN.

Guillain–Barré syndrome and encephalitis/encephalopathy associated with acute severe hepatitis E infection

Dear Editor, We read the case report by Chen and colleagues [1] with great interest. They diagnosed acute severe hepatitis E virus (HEV) infection associated Guillain–Barré syndrome (GBS) and encephalitis/encephalopathy in a 64-year-old male based on clinical manifestations, laboratory investigations, and electrophysiological findings [1]. However, resembling diseases like critical illness polyneuropathy (CIP) and/or critical illness myopathy (CIM) could not seemingly be ruled out as per their presented information. CIP and CIM, which may occur in isolation or concomitantly, are common complications of patients with severe illnesses, especially for those with acute respiratory response syndrome, sepsis, systemic inflammatory response syndrome and multiple organ failure who are admitted to the intensive care units [2]. The manifestations of CIP/CIM including symmetric and flaccid weakness of the limbs resemble those of GBS [3]. GBS is clinically characterized by albumino-cytologic dissociation in the cerebrospinal fluid (CSF) which contributes to the differential diagnosis between GBS and CIP/CIM. However, other factors that may result in the increased level of proteins in CSF remain yet to be taken into consideration, such as intracranial infection [2]. Moreover, serum creatine kinase level, electrophysiology investigations, anti-ganglioside antibody test and nerve/muscle biopsy may provide discriminative information between GBS and CIP/CIM [2, 3]. In this case, the acute severe HEV infection responsible for his jaundice and tender hepatomegaly was confirmed by the positivity for anti-HEV immunoglobulin (Ig) M in the serum. It has been reported that patients with HEV infection could be complicated with several neurological disorders, among which the first and dominant clinical picture is peripheral nerve involvement with incompletely clear mechanisms [4]. The CSF profile in the case characterized by the increased level of proteins alongside with pleocytosis served as supporting evidence for GBS. Nevertheless, it is noteworthy that the mild high signals in bilateral hippocampus revealed by brain magnetic resonance imaging might contribute to the increased protein in CSF as well. An increase of CSF proteins is frequently seen in encephalitis or encephalopathy. The positivity of anti-GM2 IgM antibodies, which is more frequent in GBS secondary to cytomegalovirus (CMV) infection, has actually been found not only in non-GBS patients with acute CMV infection [5], but also in many other disorders, including chronic motor neuropathy, amyotrophic lateral sclerosislike disorder following ganglioside therapy and chronic demyelinating neuropathy with sensory ataxia [6]. In summary, although the electrophysiology examination revealed decreased conduction velocity suggestive of demyelinating changes in the peripheral nerves, the diagnosis of GBS should be cautious without excluding resembling diseases; muscle and nerve biopsy might be most helpful for differentiation.

Comparison of two contrast agents for right-to-left shunt diagnosis with contrast-enhanced transcranial Doppler.

We compared two contrast agents, agitated saline and agitated saline with blood, with respect to their efficacy in the diagnosis of right-to-left shunt with contrast-enhanced transcranial Doppler. Three hundred thirty Chinese patients underwent examinations with one of four different methods in random order: (i) 9 mL agitated saline solution with 1 mL air without the Valsalva maneuver (ASwoVM); (ii) 9 mL agitated saline solution with 1 mL air with the Valsalva maneuver (ASwVM); (iii) 9 mL agitated saline solution, 1 mL air and a drop of the patients blood without the Valsalva maneuver (ASbwoVM); and (iv) 9 mL agitated saline solution, 1 mL air and a drop of the patients blood, with the Valsalva maneuver (ASbwVM). Rates of detection were 11.5%, 17.9%, 16.7% and 23.6% for the ASwoVM, ASwVM, ASbwoVM, and ASbwVM examinations, respectively. The embolus track numbers for these examinations were 4.0 ± 1.83, 11.5 ± 6.2, 10.5 ± 4.9 and 33.7 ± 14.9, respectively. There were significant differences between the four groups (all comparisons, p < 0.001). For contrast-enhanced transcranial Doppler examinations, the agitated saline/blood agent yielded better rates of diagnosis of right to-left shunt than did the agitated saline alone.

Microembolic Signals Detected with Transcranial Doppler Sonography Differ between Symptomatic and Asymptomatic Middle Cerebral Artery Stenoses in Northeast China

Although microembolus monitoring has been widely used for ischemic cerebrovascular disease, the clinical significance of microembolic signal (MES) in asymptomatic middle cerebral artery (MCA) stenosis remains unclear. We aim to investigate the frequency of MES and the value of MES in predicting ischemic stroke secondary to asymptomatic MCA stenosis. From June 2011 to December 2012, microembolus monitoring was performed in 83 asymptomatic and 126 symptomatic subjects. By comparing the demographics and risk factors between the symptomatic and asymptomatic subjects, we found that the ratio of male sexuality and smoking history differed (101/126 vs 43/83, and 88/126 vs 38/83, respectively, p<0.01). The frequency of MES was significantly higher in the symptomatic group than in the asymptomatic group (49/126 vs 2/108, p<0.01). Specifically, the frequency of MES in the symptomatic and asymptomatic groups with mild stenosis, moderate stenosis, severe stenosis and occlusion groups was 4/18 (22.22%) vs 0/30 (0), 13/31 (41.94%) vs 1/28 (3.57%), 30/62 (48.39%) vs 1/39 (2.56%), 2/15 (13.33%) vs 0/11 (0), respectively. Except for the occlusive group, the frequency of MES is correlated with stenosis degree and symptom. Two patients in the asymptomatic group were found positive for MES, and the MES number was 1 for both. During the one-year follow-up, neither of them developed ischemic stroke. In conclusion, MES detected with TCD differs between symptomatic and asymptomatic MCA stenoses. Due to the low frequency, the value of MES as a predictor of subsequent ischemic stroke in patients with asymptomatic MCA stenosis might be limited.

Reversible splenial lesion syndrome associated with lobar pneumonia: Case report and review of literature.

Background:Reversible splenial lesion syndrome (RESLES) is a rare clinico-radiological disorder with unclear pathophysiology. Clinically, RESLES is defined as reversible isolated splenial lesions in the corpus callosum, which can be readily identified by magnetic resonance imaging (MRI) and usually resolve completely over a period of time. RESLES could be typically triggered by infection, antiepileptic drugs (AEDs), poisoning, etc. More factors are increasingly recognized. Methods and results:We reported herein an 18-year-old female patient with lobar pneumonia who developed mental abnormalities during hospitalization. An isolated splenial lesion in the corpus callosum was found by head MRI and the lesion disappeared 15 days later. Based on her clinical manifestations and radiological findings, she was diagnosed with lobar pneumonia associated RESLES. We further summarize the up-to-date knowledge about the etiology, possible pathogenesis, clinical manifestations, radiological features, treatment, and prognosis of RESLES. Conclusion:This report contributes to the clinical understanding of RESLES which may present with mental abnormalities after infection. The characteristic imaging of reversible isolated splenial lesions in the corpus callosum was confirmed in this report. The clinical manifestations and lesions on MRI could disappear naturally after 1 month without special treatment.

Short-Term Prognosis of Mechanically Ventilated Patients With Guillain–Barré Syndrome Is Worsened by Corticosteroids as an Add-On Therapy

AbstractIntravenous immunoglobulin (IVIg) has been proven most effective in treating Guillain–Barré syndrome (GBS). Corticosteroids as an add-on therapy have been prescribed in severe GBS cases. However, the efficacy of intravenous corticosteroids combined with IVIg in dealing with severe GBS remains unclear. We explored the therapeutic effects of different therapeutic regimens on the short-term prognosis of GBS patients, especially the severe cases.We retrospectively analyzed the clinical data of 527 adult patients with GBS who were prescribed to different treatments from 2003 to 2014. The therapeutic effect of a treatment was evaluated by the improvement of Hughes Functional Grading Scale (HFGS) and Medical Research Council (MRC) sum score.With comparable incidence of infectious complications (P > 0.05), more mechanically ventilated patients were found improvement after IVIg treatment than combination IVIg with intravenous corticosteroids (MRC: 97% vs. 72.4%, P < 0.05; HFGS: 97% vs. 72.4%, P < 0.05). As to bedridden patients without mechanical ventilation, incidence of infectious complications (P > 0.05) and ratio of patients who were improved after IVIg were insignificantly different from the combination therapy (MRC: 89.6% vs. 86.5%; HFGS: 69.6% vs. 61.5%; both P > 0.05), even if the intravenous corticosteroids were initiated within 7 days after onset (P > 0.05). In addition, supportive treatment was sufficient for patients who were able to walk with help (HFGS = 3) and mildly affected (HFGS < 3) when compared with IVIg and intravenous corticosteroids.IVIg is sufficient to GBS patients who are unable to walk (HFGS > 3), while corticosteroids are detrimental for short-term prognosis in mechanically ventilated patients when used in combination with IVIg. Further prospective and randomized studies are warranted to validate this finding.

Roles of macrophage migration inhibitory factor in Guillain-Barré syndrome and experimental autoimmune neuritis: beneficial or harmful?

ABSTRACT Introduction: Macrophage migration inhibitory factor (MIF) plays an important role in the pathogenesis of Guillain-Barré syndrome (GBS) and its animal model experimental autoimmune neuritis (EAN), which may offer an opportunity for the development of the novel therapeutic strategies for GBS. Areas covered: ‘macrophage migration inhibitory factor’ and ‘Guillain-Barré syndrome’ were used as keywords to search for related publications on Pub-Med, National Center for Biotechnology Information (NCBI), USA. MIF is involved in the etiology of various inflammatory and autoimmune disorders. However, the roles of MIF in GBS and EAN have not been summarized in the publications we identified. Therefore, in this review, we described and analyzed the major roles of MIF in GBS/EAN. Primarily, this molecule aggravates the inflammatory responses in this disorder. However, multiple studies indicated a protective role of MIF in GBS. The potential of MIF as a therapeutic target in GBS has been recently demonstrated in experimental and clinical studies, although clinical trials have been unavailable to date. Expert opinion: MIF plays a critical role in the initiation and progression of GBS and EAN, and it may represent a potential therapeutic target for GBS.

The clinical characteristics and short-term prognosis in elderly patients with Guillain–Barré syndrome

Abstract To investigate the clinical characteristics and short-term prognosis of elderly patients with Guillain–Barré syndrome (GBS). We retrospectively analyzed the clinical data of adult GBS. According to the age, the enrolled subjects were divided into 2 groups, that is, patients ≥60 years (elderly group) and those aged 18 to 59 years (nonelderly group). The clinical characteristics and short-term prognosis of the patients in the 2 groups were compared. In total, 535 patients were enrolled. There were 67 patients fell into the elderly group with a mean age of 69 years old; while 468 patients fell into the nonelderly group with a mean age of 39 years old. We found that the elderly patients had significantly lower incidence of antecedent infections (49.3% vs 66.2%, P < 0.01). The time from onset to admission (5 vs 4 days, P < 0.05) and time from onset to nadir (7 vs 6 days, P < 0.05) were significantly longer in the elderly patients. It was noteworthy that more elderly patients were found with lymphocytopenia (55.4% vs 37.3%, P < 0.01), hyponatremia (25.0% vs 10.2%, P < 0.01), hypoalbuminemia (9.0% vs 2.6%, P < 0.05), and hyperglycemia (34.3% vs 15.2%, P < 0.01). Importantly, the elderly patients had longer duration of hospitalization (17 vs 14 days, P < 0.05), higher incidence of pneumonia (29.9% vs 18.8%, P < 0.05), and poorer short-term prognosis (58.2% vs 42.7%, P < 0.05). In patients with severe GBS, no significant differences were observed in disease severity, treatment modality, incidence of pneumonia, and duration of hospitalization between the 2 groups. However, more patients in the elderly group showed poor short-term prognosis (84.1% vs 63.8%, P < 0.01). Further, old age (≥60 years) (OR = 2.906, 95% CI: 1.174–7.194, P < 0.05) and lower Medical Research Council (MRC) score at nadir (OR = 0.948, 95% CI: 0.927–0.969, P < 0.01) were risk factors for poor short-term prognosis in severe GBS patients. The clinical characteristics and short-term prognosis of elderly patients with GBS are distinct from nonelderly adults. Old age (≥60 years) and lower nadir MRC score serve as predictor for poor short-term prognosis in severe GBS patients.