Bilateral hearing loss as the initial presentation of reversible Wernicke's encephalopathy with splenial lesion.

BACKGROUND: Wernicke's encephalopathy (WE) is an acute neurological syndrome resulting from thiamine (vitamin B1) deficiency. It has been recognized increasingly in non-alcoholic patients, such as in the condition of malnutrition. Recent literature has shed light on uncommon symptoms and neuroimaging findings. CASE REPORT: We reported a case of a 44-year-old male who initially presented with bilateral hearing loss, and exhibited abnormality in the splenium of the corpus callosum on magnetic resonance imaging (MRI) diffusion-weighted imaging sequence. On the following day the patient developed new symptoms, including unstable walking, double vision and hallucination. The subsequent brain MRI demonstrated lesions involving periaqueductal grey matter and bilateral medial thalamus, indicating the diagnosis of WE. Empirical treatment with intravenous thiamine resulted in complete clinical and radiological resolution. CONCLUSION: To the best of our knowledge, the current case is the first report of WE in literature with uncommon but reversible manifestations. This case warns us to maintain a heightened level of suspicion for WE in malnourished patients with neurological deficits, despite the possibility of atypical presentations encompassing bilateral hearing disturbances and unusual neuroradiological results. Early diagnosis and timely administration of thiamine in WE are likely to lead to a favorable outcome and full recovery.

Chronic lymphocytic inflammation with pontine perivascular enhancement responsive to steroids (CLIPPERS): contemporary advances and current controversies.

Chronic lymphocytic inflammation with pontine perivascular enhancement responsive to steroids (CLIPPERS) is an inflammatory syndrome with characteristic clinical, radiological, and pathological features, and can be effectively treated with corticosteroid-based immunotherapies. The exact pathogenesis of CLIPPERS remains unclear, and specific diagnostic biomarkers are not available. According to the 2017 diagnostic criteria, probable CLIPPERS should be considered in middle-aged patients with subacute onset of pontocerebellar symptoms and typical punctuate and curvilinear gadolinium enhancement lesions ("salt-and-pepper" appearance) located in the hindbrain (especially pons) on magnetic resonance imaging. In addition, CLIPPERS-mimics, such as central nervous system (CNS) lymphoma, and several antibody-associated autoimmune CNS diseases (e.g., myelin oligodendrocyte glycoprotein antibody-associated disease, autoimmune glial fibrillary acidic protein astrocytopathy, and anti-N-methyl-D-aspartate receptor encephalitis), should be extensively excluded. The prerequisite for definite CLIPPERS is the perivascular T-cell-predominant inflammatory infiltration observed on pathological analysis. A biopsy is strongly suggested when clinical/radiological red flags are present. Most patients with CLIPPERS respond well to corticosteroids and have a good prognosis. Long-term low-dose corticosteroid maintenance therapy or corticosteroids coupled with immunosuppressants are recommended to prevent the recurrence of the syndrome. The potential progression of CLIPPERS to lymphoma has been suggested in some cases; therefore, at least 2-year clinical and radiological follow-up is essential. Here, we critically review the recent developments and provided an update on the clinical characteristics, diagnostic criteria, differential diagnoses, and therapeutic management of CLIPPERS. We also discuss the current controversies in this context that can be resolved in future research studies.

Myelin oligodendrocyte glycoprotein antibody and N-methyl-d-aspartate receptor antibody overlapping syndrome: insights from the recent case reports.

The overlapping of two or more types of neural autoantibodies in one patient has increasingly been documented in recent years. The coexistence of myelin oligodendrocyte glycoprotein (MOG) and N-methyl-d-aspartate receptor (NMDAR) antibodies is most common, which leads to a unique condition known as the MOG antibody and NMDAR antibody overlapping syndrome (MNOS). Here, we have reviewed the pathogenesis, clinical manifestations, paraclinical features, and treatment of MNOS. Forty-nine patients with MNOS were included in this study. They were young males with a median onset age of 23 years. No tumors were observed in the patients, and 24 of them reported prodromal symptoms. The most common clinical presentations were psychiatric symptoms (35/49) and seizures (25/49). Abnormalities on magnetic resonance imaging involved the brainstem (11/49), cerebellum (9/49), and parietal lobe (9/49). Most patients mostly responded to immunotherapy and had a good long-term prognosis. However, the overall recurrence rate of MNOS was higher than that of mono antibody-positive diseases. The existence of concurrent NMDAR antibodies should be suspected in patients with MOG antibody-associated disease having psychiatric symptoms, seizures, movement disorders, or autonomic dysfunction. Similarly, serum MOG antibody testing should be performed when patients with anti-NMDAR encephalitis present with atypical clinical manifestations, such as visual impairment and limb weakness, and neuroradiological findings, such as optic nerve, spinal cord, or infratentorial involvement or meningeal enhancement. Early detection of the syndrome and prompt treatment can be beneficial for these patients, and maintenance immunosuppressive therapy is recommended due to the high overall recurrence rate of the syndrome.

Anti-adenylate kinase 5 encephalitis: Clinical characteristics, diagnosis, and management of this rare entity.

The spectrum and understanding of antibody-positive autoimmune encephalitis (AE) have expanded over the past few decades. In 2007, a rare subtype of AE known as anti-adenylate kinase 5 (AK5) encephalitis, was first reported. This disease is more common in elderly males, with limbic encephalitis as the core phenotype (characterized by subacute anterograde amnesia, sometimes with psychiatric symptoms, and rarely with seizures). Brain magnetic resonance imaging typically demonstrated initial temporal lobe T2/fluid-attenuated inversion recovery hyperintensities, and subsequent atrophy. No concomitant tumors have been found yet. AK5 antibody, targeting the intracellular antigen, is a biomarker for a non-paraneoplastic T-cell autoimmunity response, and can be detected in serum and cerebrospinal fluid using tissue-based and cell-based assays. Cytotoxic T-cell-mediating neuronal injury and loss play a pivotal role in the immunopathogenesis of anti-AK5 encephalitis. Patients mostly show poor response to immunotherapy and thus a poor prognosis in the long run. Herein, we review the literature and provide updated knowledge of this less-known entity, focusing on clinical characteristics, paraclinical findings, diagnosis process, and therapeutic approaches.

Myelin oligodendrocyte glycoprotein antibody-associated disease preceding primary central nervous system lymphoma: causality or coincidence?

INTRODUCTION: Primary central nervous system lymphoma (PCNSL) is a rare extranodal lymphomatous malignancy that affects the brain, spinal cord, leptomeninges, or eyes, in the absence of systemic diffusion. Myelin oligodendrocyte glycoprotein (MOG) antibody-associated disease (MOGAD) is a newly identified benign immune-mediated CNS inflammatory disorder with specific anti-MOG antibody seropositivity. These two seemingly unrelated nosological entities both have abundant clinical and radiological manifestations, and whether there is a potential link between them is unclear. CASE REPORT: We describe a 49-year-old man who presented progressive headache, dizziness, and unsteady gait with multifocal scattered T2 hyperintensities with contrast enhancement. The serum anti-MOG antibody test was positive, and a brain biopsy showed inflammatory infiltration. Initially, he was diagnosed with MOGAD and his condition improved after corticosteroid therapy. The patient relapsed with exacerbation of symptoms and neuroimaging showed new mass-forming lesions four months later. A second brain biopsy confirmed PCNSL. DISCUSSION: This is the first report of histologically confirmed successive MOGAD and PCNSL. Our case broadens the phenotypic spectrum of sentinel lesions in PCNSL. Though rare, PCNSL should be considered in patients diagnosed with benign CNS inflammatory disorder and responding well to steroid treatment when their clinical symptoms worsen and the imaging deteriorates. A timely biopsy is critical for accurate diagnosis and appropriate therapy.

Phenotyping the late- and younger-onset neuronal surface antibody-mediated autoimmune encephalitis: a multicenter study.

Neuronal surface antibody-mediated autoimmune encephalitis (NSAE) occurs across a wide age range. However, few studies focused on the onset age and their related characteristics. We aimed to explore the age-dependent profile of NSAE. A total of 134 patients with a definite diagnosis of NSAE were retrospectively enrolled from 3 tertiary hospitals between July 2014 and August 2020. Demographic, clinical, therapeutic, and prognostic data were collected and compared between the late- (≥45) and younger-onset (<45) groups. The results showed that 56 (41.8%) patients were classified as late-onset NSAE, and 78 (58.2%) as younger-onset NSAE. There were more males, especially in the late-onset group (P = 0.036). Prodromal symptoms were more common in the younger-onset group (P = 0.004). Among the onset symptoms, more late-onset patients presented as seizures, while more younger-onset patients presented as psychiatric symptoms. Throughout the disease course, the late-onset patients were more likely to have memory dysfunction (P < 0.001), but less likely to have central hypoventilation (P = 0.045). The late-onset patients also had a significantly lower modified Rankin Scale score on admission (P = 0.042), required intensive care unit (ICU) admission less frequently during hospitalization (P = 0.042) and had a shorter hospital stay (P = 0.014). Our study revealed that the late- and younger-onset NSAE had a distinct spectrum of demographic features, presentations, and prognoses. More attention is needed for the younger-onset patients, given a higher disease severity on admission, more frequent requirement for ICU admission and longer length of stay.

Evaluation of CSF albumin quotient in neuronal surface antibody-associated autoimmune encephalitis.

BACKGROUND AND OBJECTIVES: Disruption of brain barriers is considered to be involved in the pathogenesis of neuronal surface antibody-associated autoimmune encephalitis (NSAE), but few studies have focused on their relationship. We aimed to explore the association between the integrity of brain barriers and clinical and paraclinical characteristics in patients with NSAE. METHODS: This retrospective study consecutively recruited patients with NSAE. The cerebrospinal fluid (CSF) / serum albumin quotient (Qalb) was used to evaluate the function of brain barriers. The data on demographic information, clinical manifestations, magnetic resonance imaging (MRI), CSF findings and prognosis were collected and analyzed. RESULTS: Of the 93 patients included, 33 (35.5%) patients were assigned to the elevated Qalb group and 60 (64.5%) patients to the normal Qalb group. Males and prodromal symptoms were more common in elevated Qalb group (both P < 0.05). The CSF white blood cell, protein, immunoglobulin G and albumin were significantly higher in elevated Qalb group (all P < 0.05). Patients with elevated Qalb were more likely to have brain lesions on MRI (60.6% versus 33.3%, P = 0.011). The modified Rankin Scale (mRS) scores at discharge and at last follow-up were significantly higher in patients with elevated Qalb than those with normal Qalb (both P < 0.05). After univariate and multivariate analyses, Qalb elevation (adjusted odds ratio = 3.96, 95% confidence interval = 1.15-13.59, P = 0.029) was demonstrated as the only independent risk factor for a poor prognosis. DISCUSSION: Males, prodromal symptoms, brain lesions on MRI, CSF pleocytosis, and elevated CSF protein were more common in NSAE patients with increased Qalb. Qalb elevation was an independent prognostic indicator for a poor prognosis in NSAE.

Detecting vulnerable carotid plaque and its component characteristics: Progress in related imaging techniques.

Carotid atherosclerotic plaque rupture and thrombosis are independent risk factors for acute ischemic cerebrovascular disease. Timely identification of vulnerable plaque can help prevent stroke and provide evidence for clinical treatment. Advanced invasive and non-invasive imaging modalities such as computed tomography, magnetic resonance imaging, intravascular ultrasound, optical coherence tomography, and near-infrared spectroscopy can be employed to image and classify carotid atherosclerotic plaques to provide clinically relevant predictors used for patient risk stratification. This study compares existing clinical imaging methods, and the advantages and limitations of different imaging techniques for identifying vulnerable carotid plaque are reviewed to effectively prevent and treat cerebrovascular diseases.

Lymphomatosis cerebri: a rare diffuse leukoencephalopathy you should never miss.

INTRODUCTION: Lymphomatosis cerebri (LC) is a rare variant of primary central nervous system lymphoma that diffusely involves throughout the brain. In recent years, increasingly reported cases have notably broadened the spectrum of clinical and radiological features; however, it remains a great diagnostic challenge. CASE REPORT: We reported an atypical case of LC presented with subacute onset of focal neurological deficits and diffuse T2 hyperintensities without contrast enhancement on magnetic resonance imaging. He was initially considered as inflammatory leukoencephalopathy and received empirical corticosteroids, showing a dramatically clinical response. Three months later, the patient relapsed with deteriorating symptoms and enlarged brain lesions with mass-like enhancement. A diagnosis of LC was finally established according to the radiological and pathological findings. DISCUSSION: Though rare, LC should always be kept as a differential diagnosis of diffuse leukoencephalopathy. Neurologists should be aware of every detailed information about LC to avoid a delay of diagnostic biopsy in clinical practice.

Occurrence of Intracranial Hemorrhage and Associated Risk Factors in Cerebral Autosomal Dominant Arteriopathy With Subcortical Infarcts and Leukoencephalopathy: A Systematic Review and Meta-Analysis.

BACKGROUND AND PURPOSE: Intracranial hemorrhage (ICH) is thought to be a rare but probably underestimated presentation of cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL). We conducted a systematic review and meta-analysis with the aim of comprehensively revealing the occurrence of ICH in patients with CADASIL. METHODS: English-language studies published up to September 30, 2021 were searched for in the MEDLINE (PubMed), Web of Science, and Cochrane Library databases. The design, patient characteristics, occurrence rate of ICH, and associated risk factors were retrieved for each identified relevant study. RESULTS: We enrolled 13 studies in the final meta-analysis, which included 1,310 patients with CADASIL. The probability of ICH occurrence in patients with CADASIL was 10.1% (95% confidence interval [CI]=5.6%-18.0%, I²=85.1%). When stratified by geographic region, the occurrence rate of ICH was much higher in Asians (17.7%; 95% CI=11.0%-28.5%, I²=76.3%) than in Europeans (2.0%; 95% CI=0.4%-10.8%, I²=82.8%). A higher burden of cerebral microbleeds (CMBs) and a history of hypertension were the most commonly recorded risk factors for ICH, which were available for three and two of the included studies, respectively. CONCLUSIONS: Our study suggests that ICH is an important clinical manifestation of CADASIL, especially in Asians. A higher burden of CMBs and the existence of hypertension were found to be associated with a higher probability of ICH occurrence in patients with CADASIL.

Inflammatory markers of hemogram parameters as predictive factors for disease severity in anti-N-methyl-D-aspartate receptor encephalitis.

OBJECTIVE: This study aimed to investigate the utility of inflammatory markers of hemogram parameters as objective indicators of disease severity in anti-N-methyl-D-aspartate receptor (NMDAR) encephalitis. METHODS: A total of 98 patients were retrospectively reviewed. Inflammatory markers of hemogram parameters, including neutrophil-lymphocyte ratio (NLR), monocyte-lymphocyte ratio (MLR), and platelet-lymphocyte ratio, were acquired within 24 h of admission. We then analyzed their utility as predictive factors for disease severity at different time points assessing with the modified Rankin Scale (mRS). RESULTS: There were 49 patients in the mild group (mRS ≤ 2) and 49 patients in the moderate-to-severe (mRS > 2) group at admission. The moderate-to-severe group presented more frequently with psychiatric symptoms and central hypoventilation, as well as a lower lymphocyte count, a higher neutrophil count, a higher NLR and a higher MLR (all p < 0.05) when compared with the mild group. NLR and MLR showed similar positive correlations with mRS scores (r = 0.40, r = 0.40, both p < 0.001). Further multivariate logistic regression analyses indicated that NLR > 4.232 was an independent risk factor for moderate-to-severe status at admission. Meanwhile, NLR and MLR were associated with disease severity at different stages of follow-up but showed no independent predictive value. CONCLUSION: Our findings suggested that NLR was an independent risk factor for moderate-to-severe status in the initial stage of anti-NMDAR encephalitis with a cut-off value of > 4.232.

First-line immunotherapy of neuronal surface antibody-mediated autoimmune encephalitis: Assessment of therapeutic effectiveness and cost-efficiency.

OBJECTIVE: To evaluate the therapeutic effectiveness and cost-efficiency of first-line immunotherapies on neuronal surface antibody-mediated autoimmune encephalitis (AE) based on a real-world observational study in China. METHODS: Our study retrospectively collected the clinical and paraclinical data of patients with definite neuronal surface antibody-mediated AE between July 2014 and July 2020. Regular follow-up was performed after administering standard regimens of first-line immunotherapies, including intravenous methylprednisolone (IVMP) and / or intravenous immunoglobulin (IVIG). Therapeutic effectiveness was reflected by modified Rankin Scale scores. The health resource utilization and direct medical costs were extracted to analyze the cost-efficiency. RESULTS: Among the 78 eligible patients, 48 (61.5%) were males with a median age of 40 years. More than half (56, 71.8%) were treated with combination therapy, with the rest receiving IVMP and IVIG monotherapy (both of 11, 14.1%). Related objective variables, i.e., sex, onset age, disease course, onset symptoms, antibody types, abnormal paraclinical results, disease severity, and the health insurance, showed insignificant differences on the selection of therapy. Each therapy showed similar short-term (4-week) and long-term (1-year) therapeutic effects. Yet the single or combination of IVIG had a slightly better effectiveness but higher cost than the monotherapy of IVMP. CONCLUSION: The combination of IVMP and IVIG was used more frequently than either alone, which may be associated with neurologist's personal experience and patient's wishes. Though with similar therapeutic effectiveness, the use of IVMP alone might be a better choice with a better cost-efficiency.

Kelch-like protein 11 antibody-associated paraneoplastic neurological syndrome: A state-of-the-art review.

The Kelch-like protein 11 antibody-associated paraneoplastic neurological syndrome (KLHL 11-PNS) was first identified in 2019. This novel antibody, targeting the intracellular KLHL 11 antigen, can be detected in serum and cerebrospinal fluid using tissue-based and cell-based assays. It is thought to be a biomarker for a T-cell autoimmunity response. The most likely immunopathogenesis of KLHL 11-PNS appears to be linked to cytotoxic T-cell-mediated neuronal injury and loss. Patients have adult-male predilection, rhombencephalitis (brainstem and / or cerebellar involvement), and a robust oncological correlation with testicular germ cell tumors (predominately seminoma). Brain magnetic resonance imaging demonstrated T2 / fluid-attenuated inversion recovery hyperintensities and atrophy of the temporal lobe, cerebellum, and brainstem. Most patients responded poorly to immunotherapy and oncotherapy and thus had a poor long-term prognosis. We review the literature and provide an update of current knowledge regarding KLHL 11-PNS, including epidemiology, underlying mechanism, clinical presentations, paraclinical and oncological findings, diagnostic workup, and treatment approaches.

Seizures and epilepsy in multiple sclerosis, aquaporin 4 antibody-positive neuromyelitis optica spectrum disorder, and myelin oligodendrocyte glycoprotein antibody-associated disease.

Seizure is one of the manifestations of central nervous system inflammatory demyelinating diseases, which mainly include multiple sclerosis (MS), aquaporin 4 antibody-positive neuromyelitis optica spectrum disorder (AQP4-NMOSD), and myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD). Acute symptomatic seizures secondary to MS/AQP4-NMOSD/MOGAD occur in the acute phase of the diseases, and are more frequent in MOGAD. In contrast, recurrent nonprovoked seizures, mainly attributed to autoimmune-associated epilepsy, occur in the nonacute phase of the diseases. Seizures in MS/AQP4-NMOSD/MOGAD mostly have a focal onset. MS patients with concomitant systemic infections, earlier onset, and greater disease activity are more likely to have seizures, whereas factors such as greater MS severity, the presence of status epilepticus, and cortical damage indicate a greater risk of developing epilepsy. In MOGAD, cerebral cortical encephalitis and acute disseminated encephalomyelitis (ADEM)-like phenotypes (predominately ADEM and multiphasic disseminated encephalomyelitis) indicate a greater seizure risk. Multiple relapses with ADEM-like phenotypes predict epilepsy in pediatrics with MOGAD. Pathophysiologically, acute symptomatic seizures in MS are associated with neuronal hyperexcitability secondary to inflammation and demyelination. Chronic epilepsy in MS is largely due to gliosis, neuronal dysfunction, and synaptic abnormalities. The mainstay of treatment for seizures secondary to MS/AQP4-NMOSD/MOGAD consists of immunotherapy along with antiseizure medications. This critical review discusses the most-updated evidence on epidemiology, clinical correlates, and inflammatory mechanisms underlying seizures and epilepsy in MS/AQP4-NMOSD/MOGAD. Treatment cautions including drug-drug interactions and the impact of treatments on the diseases are outlined. We also highlight pitfalls and challenges in managing such patients and future research perspectives to address unsolved questions.

Case Report: Neuromyelitis Optica Spectrum Disorder With Progressive Elevation of Cerebrospinal Fluid Cell Count and Protein Level Mimicking Infectious Meningomyelitis: A Diagnostic Challenge.

Neuromyelitis optica spectrum disorder (NMOSD) is an autoimmune-mediated idiopathic inflammatory demyelinating disease with a typical clinical presentation of optic neuritis, acute myelitis, and area postrema syndrome. Most NMOSD patients are seropositive for disease-specific and pathogenic aquaporin-4 (AQP4) antibodies, which are key markers for the NMOSD diagnosis. Herein, we report an atypical case of a 41-year-old man who complained of intractable hiccups and vomiting at disease onset, followed by fever, headache, back pain, progressive paresthesia, and weakness of extremities later on. Magnetic resonance imaging revealed longitudinally extensive transverse myelitis. Cerebrospinal fluid analysis showed progressive increases in the white blood cell count and the protein level, which were accompanied by the deterioration of clinical manifestations. The patient was initially suspected of infectious meningomyelitis but was finally diagnosed with NMOSD. This case with distinct cerebrospinal fluid findings broadens the phenotypic spectrum of NMOSD. Furthermore, it also highlights the clinical value of AQP4 antibody test for early definitive diagnosis and proper treatment.