Neuromyelitis optica spectrum disorders may be misdiagnosed as Wernicke's encephalopathy.

PURPOSE: To raise doctors' attention to the differential diagnosis of neuromyelitis optica spectrum disorders (NMOSD) and Wernicke's encephalopathy (WE). PATIENTS AND METHODS: We extensively reviewed the medical records of 136 patients who had visited our hospital since 2008 and were suspected of having central nervous system demyelinating diseases. Four of those patients had somnolence, electrolyte imbalance and brain lesions around the third ventricle and were included in the study. We tested the serum of the four patients for the presence of aquaporin-4 (AQP4) M23 antibody. RESULTS: All the four patients had positive AQP4 antibody in their serum. Two of the patients were misdiagnosed as WE before AQP4 antibody detection occurred. CONCLUSIONS: NMOSD and WE have similar brain lesion locations, histopathological changes and clinical manifestations. It is important to distinguish NMOSD from WE by detecting AQP4 antibody in serum or cerebral spinal fluid. Vitamin B1 should also be administered to the patients who have a history of thiamine deficiency.

Dynamic change in magnetic resonance imaging of patients with neuromyelitis optica.

OBJECTIVE: To analyze changes in magnetic resonance imaging (MRI) of spinal cord lesions in neuromyelitis optica (NMO) and the correlation between segmental length of spinal cord lesions and expanded disability status scale (EDSS) scores. METHODS: Twenty-five patients with confirmed NMO were examined from the Second Affiliated Hospital of Guangzhou Medical University, China. The information collected included their treatment, MRI, laboratory tests, and EDSS scores at different stages. RESULTS: All cases exhibited spinal cord lesions, with 23 (92%) having longitudinally extensive transverse myelitis (extending ≥3 vertebral segments). There was a positive correlation between segmental length of spinal cord lesions and EDSS scores: during the acute phase, r = 0.430 (P = 0.032); during remission, r = 0.605 (P = 0.002). Enlarged spinal cord lesions and swelling were found in 18 cases (72%) during the acute phase, and 4 cases (16%, P = 0.000) after 6 months of treatment. Lesion enhancements were found in 17 cases (68%) during the acute phase, and 8 cases (32%, P = 0.023) after 6 months of treatment. Leptomeningeal enhancement was found in three cases during the acute phase, which disappeared after treatment. Atrophy of spinal cord lesions occurred in two cases. Change in lesions was statistically significant (P = 0.006) after 12 months of treatment. CONCLUSION: Positive correlation was found between segmental length of spinal cord lesions and EDSS scores, which was more significant during remission. After 6 months of regular treatment, restorative changes compared with the acute phase were found by MRI.

No Overlap among Serum GAD65, NMDAR and AQP4 Antibodies in Patients with Neuromyelitis Optica Spectrum Disorders.

OBJECTIVE: To evaluate whether serum glutamic acid decarboxylase (GAD), N-methyl-D-aspartate-receptor (NMDAR), and aquaporin-4 (AQP4) autoantibodies coexist in patients with neuromyelitis optica (NMO)/NMO spectrum disorders (NMOSD). METHODS: Serum samples were collected from 98 patients with NMO/NMOSD. Serum GAD65, NMDAR and AQP4 antibodies were measured using a cell-based assay. RESULTS: A total of 63 patients (64.3%) had myelitis and optic neuritis and satisfied the revised diagnostic criteria for NMO. Longitudinally extensive transverse myelitis was seen on spinal cord magnetic resonance imaging, showing continuous T2-weighted signal abnormalities in at least three vertebral segments in 26 patients (26.5%); 5 patients (5.1%) had recurrent optic neuritis, and 4 patients (4.1%) had brain syndromes with optic neuritis and myelitis. None of the 98 patients had diabetes, stiff-man syndrome, or epilepsy. All 98 patients tested positive for AQP4 antibody. No patients tested positive for GAD65 and NMDAR antibodies. CONCLUSIONS: In the present study, we found no simultaneous presence of serum GAD65, NMDAR and AQP4 antibodies in patients with NMO/NMOSD.

Autoimmune Glial Fibrillary Acidic Protein Astrocytopathy: A Review of the Literature.

Autoimmune glial fibrillary acidic protein (GFAP) astrocytopathy is an autoimmune disease of the nervous system first defined in 2016. GFAP autoantibody, especially IgG that binds to GFAPα, has been reported in the cerebrospinal fluid (CSF) and serum of patients with GFAP astrocytopathy. The positive predictive value of GFAP antibody in the CSF is higher than in the serum. Tissue-based assay (TBA) and cell-based assay (CBA) are both recommended methods for the detection of GFAP antibody. GFAP astrocytopathy is accompanied by neoplasms, but the relationship between virus infection and GFAP astrocytopathy is unclear. GFAP antibody itself does not induce pathological changes; it is only a biomarker for the process of immune inflammation. The pathology of GFAP astrocytopathy in humans is heterogeneous. GFAP astrocytopathy is commonly diagnosed in individuals over 40 years old and most patients have an acute or subacute onset. Clinical manifestations include fever, headache, encephalopathy, involuntary movement, myelitis, and abnormal vision. Lesions involve the subcortical white matter, basal ganglia, hypothalamus, brainstem, cerebellum, and spinal cord. The characteristic MRI feature is brain linear perivascular radial gadolinium enhancement in the white matter perpendicular to the ventricle. Currently, there are no uniform diagnostic criteria or consensus for GFAP astrocytopathy and coexisting neural autoantibodies detected in the same patient make the diagnosis difficult. A standard treatment regimen is yet to be developed. Most GFAP astrocytopathy patients respond well to steroid therapy although some patients are prone to relapse or even die.

Serum PPARγ level and PPARγ gene polymorphism as well as severity and prognosis of brain injury in patients with arteriosclotic cerebral infarction.

The aim of the study was to study the serum peroxisome proliferator-activated receptor gamma (PPARγ) level and PPARγ gene polymorphism as well as the severity and prognosis of brain injury in patients with arteriosclotic cerebral infarction (ACI). A total of 246 ACI patients presenting at the Department of Neurology of Zengcheng District People's Hospital of Guangzhou between April 2009 and July 2015 were selected as the case group, and 382 control subjects were enrolled as the control group. The hepatic and renal functions and homocysteine (Hcy) expression levels were measured. Enzyme-linked immunosorbent assay (ELISA) kit was used to detect the serum PPARγ levels of the ACI patients. Polymerase chain reaction-restriction fragment length polymorphism method was applied to measure the PPARγ gene polymorphism. The proportions of hypertension patients, diabetes patients and smoking people in the case group were significantly higher than those in the control group. The levels of cholesterol and fasting blood glucose in the case group were elevated obviously compared with those in the control group. The levels of indexes related to the hepatic function and renal function in the case group were remarkably higher than those in the control group. The serum PPARγ levels were increased progressively at acute stage. The distribution frequencies of PPARγ genotypes CC, CT and TT in the case group were higher than those in the control group; compared with that in the control group, the proportion of C allele in the case group was raised obviously, while that of T allele was significantly decreased. The serum PPARγ level has a close correlation with the PPARγ gene polymorphism in ACI patients, and PPARγ is also remarkably related to the severity of brain injury; therefore, PPARγ has great significance in the diagnosis and treatment of cerebral infarction.

Cerebral venous sinus thrombosis may be associated with hepatitis B virus infection: a preliminary finding.

OBJECTIVE: To assess the clinical significance of hepatitis B virus (HBV) infection in patients with cerebral venous sinus thrombosis (CVST). METHODS: Twenty-two patients with CVST confirmed by magnetic resonance venography (MRV) or digital subtraction angiography (DSA) and 743 controls with ischemic stroke confirmed by magnetic resonance imaging (MRI) were analyzed retrospectively. RESULTS: Among all researches, HBV surface antigen (HBsAg)-positive rate was high. Six of the 22 (27.3%) confirmed cases had HBsAg. However, HBsAg-positive rate in patients with ischemic stroke was only 45 of the 743 cases (6.1%), closed to the average prevalence in China (∼ 8.6%), but much lower than the positive rate in CVST patients (27.3 vs 6.1%, P  =  0.002). Odd ratio (OR) value between HBsAg-positive CVST patients (27.3%) and HBsAg-positive ischemic stroke patients (6.1%) was 5.78. The OR value between HBsAg-positive CVST patients (27.3%) and average prevalence of HBV infection in China (8.6%) was nearly 3.99. It meant that HBV infection might be a risk factor for CVST. However, there existed no statistically significant difference in HBV surface antibody (HBsAb), HBV e antigen (HBeAg), HBV e antibody (HBeAb), and HBV central antibody (HBcAb)-positive rate. The HBV surface antigen (HBsAg)-positive CVST patients did not show worse liver function. Most of them were inactive HBV carriers. CONCLUSION: Hepatitis B virus infection may be a risk factor for CVST.

Clinical manifestations of neuromyelitis optica in male and female patients.

Neuromyelitis optica (NMO) is a severe, idiopathic, immuno-mediated, inflammatory demyelinating disease of the central nervous system. We examined the clinical features between male and female NMO patients, for which not much data exist. One hundred and eight Chinese Han patients with NMO were analysed retrospectively, all had been detected for the aquaporin-4 (AQP4) antibody using a cell-based assay. Of 108 NMO patients, 92 were female and 16 were male (female/male = 5.75). Ninety-four (87%) were positive for the AQP4 antibody in their serum and/or cerebral spinal fluid. Aquaporin-4 antibody-positive NMO patients had a higher female/male ratio than the negative group (P = 0.001). Female NMO patients had a higher positive rate of the AQP4 antibody than male NMO patients (92.4 vs 56.3%, P = 0.001). All NMO male patients were divided according to their AQP4 antibody status. 77.8% (7/9) of patients in the seropositive group had initial optic neuritis, while only one patient (14.3%, 1/7) in the negative group had optic neuritis (P = 0.041). Limb paraesthesia was reported in only one patient in the negative group (11.1%), but it was reported in all patients in the positive group (100%) (P = 0.001). The mean length of vertebral segments of the spinal cord lesions was 3.6 ± 1.3 in the positive group, while it was 6.6 ± 2.6 in the negative group (P < 0.0001). The involvement of the cervical spinal cord was found in 88.9% (8/9) of the positive members, but only 11.1% in the negative group (P = 0.009). However, the involvement of the thoracic spinal cord was found in 22.2% of patients in the positive group and 85.7% of patients in the negative members (P = 0.041). In conclusion, male NMO is rare and has a low positive rate of AQP4 antibody.

Syndrome of inappropriate antidiuretic hormone secretion in patients with aquaporin-4 antibody.

The objective of this study was to analyze the frequency of syndrome of inappropriate antidiuretic hormone secretion (SIADH) in patients with positive aquaporin-4 (AQP4) antibodies and evaluate the relationship between SIADH and hypothalamic lesions in patients with NMO and NMO spectrum disorder (NMOSD). AQP4 antibodies were tested by an indirect immunofluorescence assay employing HEK-293 cells transfected with recombinant human AQP4. Clinical data of patients were analyzed retrospectively. In total, 192 patients with AQP4 antibodies were certified, of which 41 patients (21.4 %) were included in the present study. Six patients (14.6 %, 6/41) met the criteria of SIADH, of which hyponatremia was mild in one patient, and severe in five. Five patients experienced confusion or decreased consciousness. Four patients were diagnosed with NMO and two were diagnosed with recurrent optic neuritis. Magnetic resonance imaging showed 11 of 41 patients (26.8 %) had hypothalamic lesions. All patients with SIADH had hypothalamic abnormalities. Hyponatremia resolved in all patients after intravenous methylprednisolone and intravenous immunoglobulin therapy. SIADH is not rare in patients with NMO/NMOSD, especially in patients with lesions close to the hypothalamus.

Serum thyroid-stimulating hormone and anti-thyroglobulin antibody are independently associated with lesions in spinal cord in central nervous system demyelinating diseases.

Transverse myelitis (TM) is associated with neuromyelitis optica (NMO) and multiple sclerosis (MS). Early recognition of useful parameters may be helpful to distinguish their difference. This retrospective study analyzed thyroid parameters from 243 serum samples (relapse = 128; remission = 115) of 178 patients with demyelinating diseases (NMO, n = 25; TM, n = 48; MS, n = 105). The relationship between thyroid and clinical parameters was analyzed. Patients with NMO and TM had a higher frequency of abnormal thyroid-stimulating hormone (TSH), anti-thyroglobulin antibodies (TG-Ab), and antithyroid peroxidase antibody (TPO-Ab) than MS patients (p<0.05). The level of TSH and TG-Ab returned to normal levels after administration of high-dose intravenous methylprednisolone (p<0.05). In 96 patients (NMO, n = 19; TM, n = 25; MS, n = 52) without treatment, serum levels of TSH, TG-Ab and TPO-Ab were significantly different between patients with and without myelitis (p<0.01). Patients positive for aquaporin-4 (AQP4) antibodies showed higher abnormalities of TSH (p = 0.001), TG-Ab (p = 0.004) and TPO-Ab (p<0.0001) levels than AQP4 antibodies negative patients. Logistic regression analyses revealed independent relationships between TSH (odds ratio [OR]  = 33.994; p<0.0001), TG-Ab (OR = 7.703; p = 0.017) and myelitis occurrence in 96 patients at the active stage. In 52 MS patients experiencing their first attack, MS patients with myelitis were associated with TSH abnormalities (OR = 42.778; p<0.0001). This study showed increased abnormalities of thyroid parameters in patients with NMO and TM than in MS patients. MS patients with myelitis also had greater TSH abnormality than in MS patients without myelitis. Abnormal TSH and TG-Ab were independently associated with myelitis occurrence in central nervous system demyelinating disorders.

Development of a cell-based assay for the detection of anti-aquaporin 1 antibodies in neuromyelitis optica spectrum disorders.

OBJECTIVE: To develop a cell-based assay (CBA) to detect aquaporin 1 (AQP1) antibodies and determine sensitivity/specificity in patients with neuromyelitis optica (NMO) spectrum disorders. METHODS: A HEK-293T transfected cell model expressing AQP1 was established and detected to be serum AQP1 antibodies. RESULTS: AQP1 antibodies were present in 73/98 (74.5%) AQP4 antibody-positive patients. Some AQP4 antibody-negative patients were also AQP1 antibody-positive. Test sensitivity was 74.5% in 98 AQP4 antibody-positive patients. Test specificity was 79.6% in 67 multiple sclerosis (MS) patients and 31 controls. CONCLUSION: A sensitive and simple CBA was developed to detect serum AQP1 antibodies. AQP1 antibodies were mainly present in NMO and its high-risk syndrome, but also in some MS patients.