Magnetic Resonance Images Implicate That Glymphatic Alterations Mediate Cognitive Dysfunction in Alzheimer Disease.

OBJECTIVE: The glymphatic system cleans amyloid and tau proteins from the brain in animal studies of Alzheimer disease (AD). However, there is no direct evidence showing this in humans. METHODS: Participants (n = 50, 62.6 ± 5.4 years old, 36 women) with AD and normal controls underwent amyloid positron emission tomography (PET), tau PET, structural T1-weighted magnetic resonance imaging, and neuropsychological evaluation. Whole-brain glymphatic activity was measured by diffusion tensor image analysis along the perivascular space (DTI-ALPS). RESULTS: ALPS-indexes showed negative correlations with deposition of amyloid and tau on PET images and positive correlations with cognitive scores even after adjusting for age, sex, years of education, and APOE4 genotype covariates in multiple AD-related brain regions (all p < 0.05). Mediation analysis showed that ALPS-index acted as a significant mediator between regional standardized uptake value ratios of amyloid and tau images and cognitive dysfunction even after correcting for multiple covariates in AD-related brain regions. These regions are responsible for attention, memory, and executive function, which are vulnerable to sleep deprivation. INTERPRETATION: Glymphatic system activity may act as a significant mediator in AD-related cognitive dysfunction even after adjusting for multiple covariates and gray matter volumes. ALPS-index may provide useful disease progression or treatment biomarkers for patients with AD as an indicator of modulation of glymphatic activity. ANN NEUROL 2023;93:164-174.

Safety and efficacy of intracranial vascularized submental lymph node transfer for treating hydrocephalus.

Hydrocephalus is routinely treated with ventriculoperitoneal shunt drainage of cerebrospinal fluid (CSF), a procedure plagued by high morbidity and frequent revisions. Vascularized submental lymph node (VSLN) transplants act as lymphatic pumps to drain interstitial fluid (ISF) from lymphedematous extremities. As the field of neuro-lymphatics comes to fruition, we hypothesize the efficacy of VSLN in the drainage of intracranial CSF-ISF. We report novel placement of VSLN in the temporal subdural space in two patients diagnosed with symptomatic communicating hydrocephalus. At a minimum follow-up of 1 month postoperatively, both experienced radiological and clinical improvements.

Myasthenia gravis and independent risk factors for recurrent infection: a retrospective cohort study.

BACKGROUND: Approximately 10% to 20% of myasthenia gravis (MG) patients have experienced a myasthenic crisis (MC), which contributes to morbidity and mortality. MC triggered by infection is associated with poor outcomes. However, there is a lack of prognostic factors that clinicians can utilize to target interventions for preventing recurrent infection-triggered MC. This study aimed to characterize clinical manifestations, comorbidities, and biochemical profiles associated with recurrent infection-triggered MC in MG patients. METHODS: This retrospective study included 272 MG patients hospitalized with an infection requiring at least 3 days of antibiotics from January 2001 to December 2019. Patients were further stratified into non-recurrent or recurrent infection groups. Clinical features such as gender, age, concomitant diseases, acetylcholine receptor antibodies and biochemical data (including electrolytes and coagulants), muscle strength of pelvic and shoulder girdle, bulbar and respiratory function, management with an endotracheal tube, Foley catheter, or plasmapheresis, duration of hospitalization, and culture pathogens were recorded. RESULTS: The recurrent infection group was significantly older than the non-recurrent group (median age, 58.5 versus 52.0 years). Pneumonia was the most common infection and Klebsiella pneumoniae was the most common pathogen. The presence of concomitant diabetes mellitus, activated partial thromboplastin time prolongation, the duration of hospitalization, and hypomagnesaemia were independently associated with recurrent infection. The presence of deep vein thrombosis, thymic cancer, and electrolyte imbalances i.e., hypokalemia, and hypoalbuminemia were significantly associated with a risk for infection. The influence of endotracheal intubation, anemia, and plasmapheresis during hospitalization were inconsistent. CONCLUSIONS: The independent risk factors for recurrent infections in MG patients identified in this study include the presence of concomitant diabetes mellitus, hypomagnesaemia, activated partial thromboplastin time prolongation, and longer duration of hospitalization, highlighting the need for targeted interventions to prevent recurrent infections in this population. Further research and prospective studies are warranted to validate these findings and refine interventions for optimizing patient care.

Identification of blood metabolic biomarkers associated with diabetic distal symmetric sensorimotor polyneuropathy in patients with type 2 diabetes mellitus.

BACKGROUND: Distal symmetric sensorimotor polyneuropathy (DSPN) is a common neurologic complication of type 2 diabetes mellitus (T2DM), but the underlying mechanisms and changes in serum metabolites remain largely undefined. This study aimed to characterize the plasma metabolite profiles of participants with T2DM using targeted metabolomics analysis and identify potential biomarkers for DSPN. METHODS: A combined liquid chromatography MS/MS and direct flow injection were used to quantify plasma metabolite obtained from 63 participants with T2DM, 81 with DSPN, and 33 nondiabetic control participants. A total of 130 metabolites, including amino acids, biogenic amines, sphingomyelins (SM), phosphatidylcholines, carnitines, and hexose, were analyzed. RESULTS: A total of 16 plasma metabolites and 3 cholesterol-related laboratory parameters were found to have variable importance in the projection score >1.0 and false discovery rate <5.0% between control, T2DM, and DSPN. Among these variables, five serum metabolites, including phenylalanine (AUC = 0.653), alanine (AUC = 0.630), lysine (AUC = 0.622) tryptophan (AUC = 0.620), and SM C16:0 (AUC = 0.630), are potential biomarkers (all p < .05) in distinguishing T2DM with DSPN from those without (AUC = 0.720). CONCLUSIONS: In this cross-sectional study, derangement of several metabolites in the plasma was observed in T2DM with and without DSPN, and these metabolites may be potential biomarkers for predicting DSPN. Longitudinal studies are warranted.

Eplontersen for Hereditary Transthyretin Amyloidosis With Polyneuropathy.

Importance: Transthyretin gene silencing is an emerging treatment strategy for hereditary transthyretin (ATTRv) amyloidosis. Objective: To evaluate eplontersen, an investigational ligand-conjugated antisense oligonucleotide, in ATTRv polyneuropathy. Design, Setting, and Participants: NEURO-TTRansform was an open-label, single-group, phase 3 trial conducted at 40 sites across 15 countries (December 2019-April 2023) in 168 adults with Coutinho stage 1 or 2 ATTRv polyneuropathy, Neuropathy Impairment Score 10-130, and a documented TTR variant. Patients treated with placebo from NEURO-TTR (NCT01737398; March 2013-November 2017), an inotersen trial with similar eligibility criteria and end points, served as a historical placebo ("placebo") group. Interventions: Subcutaneous eplontersen (45 mg every 4 weeks; n = 144); a small reference group received subcutaneous inotersen (300 mg weekly; n = 24); subcutaneous placebo weekly (in NEURO-TTR; n = 60). Main Outcomes and Measures: Primary efficacy end points at week 65/66 were changes from baseline in serum transthyretin concentration, modified Neuropathy Impairment Score +7 (mNIS+7) composite score (scoring range, -22.3 to 346.3; higher scores indicate poorer function), and Norfolk Quality of Life Questionnaire-Diabetic Neuropathy (Norfolk QoL-DN) total score (scoring range, -4 to 136; higher scores indicate poorer quality of life). Analyses of efficacy end points were based on a mixed-effects model with repeated measures adjusted by propensity score weights. Results: Among 144 eplontersen-treated patients (mean age, 53.0 years; 69% male), 136 (94.4%) completed week-66 follow-up; among 60 placebo patients (mean age, 59.5 years; 68% male), 52 (86.7%) completed week-66 follow-up. At week 65, adjusted mean percentage reduction in serum transthyretin was -81.7% with eplontersen and -11.2% with placebo (difference, -70.4% [95% CI, -75.2% to -65.7%]; P < .001). Adjusted mean change from baseline to week 66 was lower (better) with eplontersen vs placebo for mNIS+7 composite score (0.3 vs 25.1; difference, -24.8 [95% CI, -31.0 to -18.6; P < .001) and for Norfolk QoL-DN (-5.5 vs 14.2; difference, -19.7 [95% CI, -25.6 to -13.8]; P < .001). Adverse events by week 66 that led to study drug discontinuation occurred in 6 patients (4%) in the eplontersen group vs 2 (3%) in the placebo group. Through week 66, there were 2 deaths in the eplontersen group consistent with known disease-related sequelae (cardiac arrhythmia; intracerebral hemorrhage); there were no deaths in the placebo group. Conclusions and Relevance: In patients with ATTRv polyneuropathy, the eplontersen treatment group demonstrated changes consistent with significantly lowered serum transthyretin concentration, less neuropathy impairment, and better quality of life compared with a historical placebo. Trial Registration: ClinicalTrials.gov Identifier: NCT04136184; EU Clinical Trials Register: EudraCT 2019-001698-10.

Establishment of a new classification system for chronic inflammatory demyelinating polyneuropathy based on unsupervised machine learning.

INTRODUCTION/AIMS: A model for predicting responsiveness to immunotherapy in patients with chronic inflammatory demyelinating polyneuropathy (CIDP) has not been well established. We aimed to establish a new classifier for CIDP patients based on clinical characteristics, laboratory findings, and electrophysiological features. METHODS: The clinical, laboratory, and electrophysiological features of 172 treatment-naïve patients with CIDP between 2003 and 2019 were analyzed using an unsupervised hierarchical clustering. The identified pivotal features were used to establish simple classifications using a tree-based model. RESULTS: Three clusters were identified: 1, n = 65; 2, n = 70; and 3, n = 37. Patients in Cluster 1 scored lower on the disability assessment score before treatment. More patients in Clusters 2 (90.0%) fulfilled demyelinating criteria than patients in Cluster 1 (30.8%, p < .001). Cluster 3 had more patients with chronic kidney disease (CKD) (27.0%) and hypoalbuminemia (3.40 g/dL) than did Cluster 2 (CKD: 0%, p < .001; hypoalbuminemia: 4.09 g/dL, p < .001). The responsiveness to pulse steroid therapy was higher in Cluster 2 (70.0%) than in Clusters 1 (31.8%; p = .043) and 3 (25.0%; p = .014). A tree-based model with four pivotal features classified patients in our cohort into new clusters with high accuracy (89.5%). DISCUSSION: The established hierarchical clustering with the tree-based model identified key features contributing to differences in disease severity and response to pulse steroid therapy. This classification system could assist clinicians in the selection of treatments and could also help researchers by clustering patients for clinical treatment trials.

The Role of Autophagy and Apoptosis in Neuropathic Pain Formation.

Neuropathic pain indicates pain caused by damage to the somatosensory system and is difficult to manage and treat. A new treatment strategy urgently needs to be developed. Both autophagy and apoptosis are critical adaptive mechanisms when neurons encounter stress or damage. Recent studies have shown that, after nerve damage, both autophagic and apoptotic activities in the injured nerve, dorsal root ganglia, and spinal dorsal horn change over time. Many studies have shown that upregulated autophagic activities may help myelin clearance, promote nerve regeneration, and attenuate pain behavior. On the other hand, there is no direct evidence that the inhibition of apoptotic activities in the injured neurons can attenuate pain behavior. Most studies have only shown that agents can simultaneously attenuate pain behavior and inhibit apoptotic activities in the injured dorsal root ganglia. Autophagy and apoptosis can crosstalk with each other through various proteins and proinflammatory cytokine expressions. Proinflammatory cytokines can promote both autophagic/apoptotic activities and neuropathic pain formation, whereas autophagy can inhibit proinflammatory cytokine activities and further attenuate pain behaviors. Thus, agents that can enhance autophagic activities but suppress apoptotic activities on the injured nerve and dorsal root ganglia can treat neuropathic pain. Here, we summarized the evolving changes in apoptotic and autophagic activities in the injured nerve, dorsal root ganglia, spinal cord, and brain after nerve damage. This review may help in further understanding the treatment strategy for neuropathic pain during nerve injury by modulating apoptotic/autophagic activities and proinflammatory cytokines in the nervous system.

Multidisciplinary approach to Fibromyalgia: What are we learning from updated evidence-based medicine?

Fibromyalgia (FM) is a disease characterized by amplified pain responses; here, hyperalgesia occurs in response to noxious stimuli, and allodynia occurs in response to non-noxious stimuli. The diagnosis of FM is often time consuming because it overlaps with psychosomatic symptoms. Indeed, most cases of FM are combined with other comorbidities, such as rheumatological diseases, mental disorders, or gastrointestinal disorders. The main symptoms of FM, which include pain, fatigue, and sleep disturbance, are poorly discriminatory and, thus, greatly increase the difficulty of diagnosis. The 2017 European League Against Rheumatism treatment guidelines of FM recommend that non-pharmacological therapies based on exercise should first be attempted after a diagnosis of FM. Although drug treatments appear to be effective, evidence supporting the use of this treatment modality is relatively weak. Obtaining a broad understanding of FM can help clinicians formulate individualized treatment to improve patient functions and quality of life. Key words: fibromyalgia, diagnostic criteria, non-pharmacological therapy.

Correlations among disability, anti-AQP4 antibody status and prognosis in the spinal cord involved patients with NMOSD.

BACKGROUND: Neuromyelitis optica spectrum disorder (NMOSD) is a rare neuroinflammatory disorder of the central nervous system that typically involves the optic nerve, the spinal cord and other specific brain regions. In relapse of the disease, factors associated with clinical features and lesion severity are important for clinicians to predict disease-related disability. METHODS: We retrospectively analyzed 22 female patients with NMOSD who had spinal cord lesions. Detailed clinical features, onset symptoms, motor disability, relapse episodes, serum aquaporin-4 (AQP4) and myelin oligodendrocyte glycoprotein (MOG) autoantibodies and MRI characteristics were documented to correlate their associations with the nadir and three-month Expanded Disability Status Scale (EDSS) scores. Patients with three-month EDSS scores below four (< 4) were categorized as the good outcome group, while those with scores of four or more (> 4) were categorized as the poor outcome group. RESULTS: In patients with NMOSD, the mean age was 44.5 ± 12.8 years, and the mean three-month EDSS score was 4.3 ± 1.9. A significantly higher all-limb muscle power score was found in the good EDSS group than in the poor EDSS group (p = 0.01). A tendency toward longer follow-up periods and lower anti-AQP4 antibody levels was found in the good outcome group. Serum anti-AQP4 antibodies were present in 86% of patients with NMOSD, and MOG autoantibodies were found in one anti-AQP4 antibody-negative patient (33.3%). In patients with NMOSD, more than 40% of spinal cord lesions were distributed at the middle cervical and upper thoracic levels. CONCLUSIONS: Our findings suggest that EDSS scores and MRC scores at the nadir had significant associations with three-month EDSS scores. The topographic distributions of the spinal cord lesions might relate to different serum anti-AQP4 antibody status. However, further studies will be needed to corroborate this finding.

Real-world evidence on the safety and effectiveness of fingolimod in patients with multiple sclerosis from Taiwan.

BACKGROUND/PURPOSE: Multiple sclerosis is classified as a rare disease in Taiwan. This study evaluated the safety and effectiveness of fingolimod in patients with relapsing-remitting multiple sclerosis (RRMS) from routine clinical practice in Taiwan. METHODS: In this retrospective, multicentre, observational study, we collected clinical data of patients treated with fingolimod 0.5 mg/day in routine clinical practice between September 2012 and December 2015. Primary outcome was the overall safety of fingolimod; secondary outcome was the annualized relapse rate (ARR). RESULTS: Overall, 62/69 (86.1%) patients were on fingolimod by the end of data collection period. Mean age (±standard deviation [SD]) at inclusion was 37.7 ± 10.10 years; mean duration of MS was 5.4 ± 4.52 years and mean duration of fingolimod exposure was 135.8 patient-years. The most common adverse events (AEs) were bradycardia (21.7%; first-dose related), upper respiratory tract infection, dizziness, and hypoaesthesia (numbness) (11.6% each), followed by urinary tract infection and back pain (7.2% each). Seven patients had liver enzyme-related AEs. Eight patients had absolute lymphocyte counts <0.2 × 103/uL over the study period. One patient developed second degree AV block after first-dosing. Serious AEs were observed in 11 patients (15.9%; mild-to-moderate). No newly developed macular oedema was detected. The ARR was 0.3 ± 0.74 in fingolimod-treated patients and 66.7% of patients were relapse-free. The mean (SD) change from baseline in expanded disability status scale score was -0.30 ± 1.353. CONCLUSION: Fingolimod 0.5 mg/day treatment with an average of 2 years of exposure was associated with a manageable safety profile, and maintained/improved effectiveness in RRMS patients from Taiwan.

Phenotypic expressions of hereditary Transthyretin Ala97Ser related Amyloidosis (ATTR) in Taiwanese.

BACKGROUND: The disease course and early signs specific to ATTR Ala97Ser, the most common endemic mutation in Taiwan, have not been well described. Since new medications can slow down the rate of disease progression, the early diagnosis of this heterogeneous and fatal disease becomes critical. METHODS: We retrospectively reviewed the characteristics of genetically confirmed ATTR Ala97Ser patients at a tertiary referral medical center. RESULTS: Eight patients from 7 different families were enrolled (61.7 ± 5.5 years). Gastrointestinal symptoms, dyspnea or chest tightness, rather than sensory symptoms, were the initial symptoms in two patients (2/7 = 29%). Body weight loss (3/7 = 43%), muscle wasting (4/7 = 57%), or dysphagia (3/7 = 43%) were the consecutive symptoms. Orthostatic symptoms including orthostatic hypotension (7/7 = 100%), dizziness (6/7 = 86%) and syncope (5/7 = 71%) tended to develop in the late phase of the disease. Autonomic dysfunction was conspicuous. Cardiographic findings included a combination of ventricular wall thickening and pericardial effusion (7/7 = 100%), a granular sparkling appearance of the ventricular myocardium (4/7 = 57%), or conduction abnormalities (5/7 = 71%). CONCLUSIONS: This study broadens the recognition of the initial signs and symptoms, including cardiographic findings and longitudinal manifestations in Taiwanese individuals with ATTR Ala97Ser mutation. These manifestations should prompt doctors to perform further studies and make an early diagnosis.

Correction to: Non-alcoholic Wernicke's encephalopathy with cortical involvement and polyneuropathy following gastrectomy.

In the original publication of the article, author name Hong-Shiu Chang was incorrectly written as Hong-Chiu Chang.

Non-alcoholic Wernicke's encephalopathy with cortical involvement and polyneuropathy following gastrectomy.

In this study, we present the clinical manifestations, brain magnetic resonance imaging (MRI) and concurrent polyneuropathies in two patients with non-alcoholic Wernicke's encephalopathy (WE) after gastrojejunostomy (Billroth II) anastomosis procedures. These patients developed sub-acute onset of disorientation and disturbance of consciousness following several weeks of poor intake. Peripheral neuropathy of varying severity was noted before and after the onset of WE. Brain MRI of the patients showed cerebellar vermis and symmetric cortical abnormalities in addition to typical WE changes. Electrophysiological studies demonstrated axonal sensorimotor polyneuropathy. Prompt thiamine supplement therapy was initiated and both patients gradually recovered, however mild amnesia was still noted 6 months later. We reviewed non- alcoholic WE with atypical cortical abnormalities in English language literatures and identified 29 more cases. Eight out of 31 (25.8%) patients died during follow-up. Nine patients with gait disturbance or motor paresis had showed hyporeflexia in neurological examinations. In addition to classic triad, seizure was recorded in seven patients. Dietary deprivation is a risk factor for non-alcoholic WE among elderly patients receiving gastrointestinal surgery. The prognosis is good after thiamine supplement therapy. Recognizing the MRI features and predisposing factors in patients who have undergone gastrectomy can aid in the diagnosis and management.

Deactivation of TBP contributes to SCA17 pathogenesis.

Spinocerebellar ataxia type 17 (SCA17) is an autosomal dominant cerebellar ataxia caused by the expansion of polyglutamine (polyQ) within the TATA box-binding protein (TBP). Previous studies have shown that polyQ-expanded TBP forms neurotoxic aggregates and alters downstream genes. However, how expanded polyQ tracts affect the function of TBP and the link between dysfunctional TBP and SCA17 is not clearly understood. In this study, we generated novel Drosophila models for SCA17 that recapitulate pathological features such as aggregate formation, mobility defects and premature death. In addition to forming neurotoxic aggregates, we determined that polyQ-expanded TBP reduces its own intrinsic DNA-binding and transcription abilities. Dysfunctional TBP also disrupts normal TBP function. Furthermore, heterozygous dTbp amorph mutant flies exhibited SCA17-like phenotypes and flies expressing polyQ-expanded TBP exhibited enhanced retinal degeneration, suggesting that loss of TBP function may contribute to SCA17 pathogenesis. We further determined that the downregulation of TBP activity enhances retinal degeneration in SCA3 and Huntington's disease fly models, indicating that the deactivation of TBP is likely to play a common role in polyQ-induced neurodegeneration.

Porphyric neuropathies in an acute intermittent porphyria family.

The objective of this study was to investigate two patients with porphyric neuropathy in a family with acute intermittent porphyria. Molecular analysis of the porphobilinogen deaminase (PBGD) gene was performed. We analyzed the clinical course of peripheral neuropathy and serial changes in nerve conduction studies (NCS) of the two patients. We also examined the pathological findings of sural nerve biopsy in one patient. Molecular analysis of the PBGD gene revealed a missense mutation (Arg26His) in exon 2 for two patients and their family members. Distal polyneuropathy was noted in the patients with chronic porphyric neuropathy. In the follow-up NCS, recovery was relatively poor in the lower limb in one patient with severe polyneuropathy, and NCS evidence of deterioration was found following frequent hormone-related porphyric attacks in another patient. The sural nerve biopsy showed marked loss of myelinated and unmyelinated fibers in one patient with chronic porphyric neuropathy. In contrast to radial and fibular motor nerves in acute porphyric neuropathy, the sural nerve is vulnerable to involvement in chronic porphyric neuropathy following repeated porphyric attack as seen in the NCS.

Clinical presentation and electrophysiological findings of porphyric neuropathies: a follow-up study.

INTRODUCTION: A case series of acute intermittent porphyria (AIP) is described that focuses on the clinical course of the disease with regard to neurological manifestations of the peripheral nervous system. METHODS: Eight patients were diagnosed with AIP on the basis of characteristic clinical findings, erythrocyte porphobilinogendeaminase activity, neuropathic patterns, serial changes in nerve conduction studies (NCS), and temporal relationship of central nervous system involvement. RESULTS: Six patients diagnosed with AIP<2 months after symptom onset had neuropathy that was predominantly upper extremity, motor, and proximal. NCS recovery rates were slower in the lower than the upper limbs. Two patients diagnosed >2 months after symptom onset had distal sensorimotor polyneuropathy. CONCLUSIONS: The findings from this case series suggest that the peripheral nerves may be differentially and selectively involved in different diagnostic stages of porphyric neuropathy.

Clinical and radiological findings suggesting disorders other than tolosa-hunt syndrome among ophthalmoplegic patients: a retrospective analysis.

OBJECTIVE: To investigate clinical and radiological features of Tolosa-Hunt syndrome (THS) and examine their diagnostic value, and to propose clinical and radiological features that indicate other symptomatic painful ophthalmoplegias (SPOs) in order to distinguish them from THS. BACKGROUND: Clinical presentations of THS are nonspecific and may overlap with many etiologies. Therefore, excluding other SPOs is essential for correct diagnosis. At the present time, the predictive value of the current International Classification of Headache Disorders (ICHD) criteria is not well established, and specific imaging markers that can discriminate SPOs from THS are lacking. METHODS: Patients referred with painful ophthalmoplegia over 12 years were recruited retrospectively and allocated into THS or SPO groups. Typical symptoms (episodic unilateral orbital pain preceding or developing with diplopia) and imaging of THS (inflammatory lesions in the cavernous sinus/orbit by magnetic resonance imaging) were proposed based on ICHD-3 beta criteria and previous literature. Atypical clinical and radiological features suggesting alternative diagnoses were also proposed to predict SPO. Initial presentations and imaging findings were registered and correlated with diagnostic outcomes. The predictive value of clinical and imaging findings was then evaluated. RESULTS: Of the 61 referred cases, 25 were classified as THS and 36 as SPO. Of the SPO cases, 52.8% manifested typical THS symptoms at onset. Patients with SPOs were prone to have atypical symptoms (47.2%) and radiographical findings (82.1%) in comparison to those with THS (4.0% and 4.2%, respectively; both P < .001). Both typical symptoms and imaging findings predicted a diagnosis of THS with high sensitivity (95.8% and 100%, respectively) but low specificity (47.2% and 28.6%, respectively). High sensitivity (82.1%) and specificity (95.8%) were achieved using atypical imaging features to predict SPO. CONCLUSION: A diagnosis of THS based strictly on clinical presentations or imaging results is not completely reliable. Identification of atypical imaging features may have a useful role in discriminating SPOs and thus avoid erroneous diagnoses of THS. Future studies with larger sample sizes are warranted to evaluate their validity in general population.

Wegener's granulomatosis with nervous system involvement: a hospital-based study.

BACKGROUND: The aim of this study was to ascertain the clinical manifestations of granulomatosis with polyangiitis (Wegener's) (GPA) with the involvement of the peripheral nervous system (PNS) and central nervous system (CNS). SUMMARY: All neurologic inpatients in a hospital over a 12-year period were reviewed. Nine patients met both the ACR 1990 traditional format criteria for the classification of GPA and the Chapel Hill nomenclature mandatory criteria for GPA. We focused on the clinical presentation, serological data, biopsy reports, disease activities [as assessed by the Birmingham Vasculitis Activity Score (BVAS)], electrophysiology, and brain images. Nine patients met the diagnostic criteria for GPA. The neurological signs of the initial manifestation of GPA were found in 6/9 (67%) patients. Eight patients had GPA-related CNS involvement, including four patients with chronic hypertrophic pachymeningitis, with either diffuse or focal thickening; three had intracranial hemorrhages and two had orbital mass lesions with optic nerve compression. In addition, six patients showed PNS involvement, including three with asymmetric sensorimotor polyneuropathy, two with symmetric sensorimotor polyneuropathy, and one with bilateral mononeuropathy. Key Messages: Neurological manifestation is not uncommon and can be the first clinical sign of GPA. The involvement of both CNS and PNS raises the possibility of GPA in hospitalized neurologic patients.

Carbamazepine-induced toxic effects and HLA-B*1502 screening in Taiwan.

BACKGROUND: Carbamazepine, an anticonvulsant and a mood-stabilizing drug, is the main cause of the Stevens-Johnson syndrome (SJS) and its related disease, toxic epidermal necrolysis (TEN), in Southeast Asian countries. Carbamazepine-induced SJS-TEN is strongly associated with the HLA-B*1502 allele. We sought to prevent carbamazepine-induced SJS-TEN by using HLA-B*1502 screening to prospectively identify subjects at genetic risk for the condition. METHODS: From 23 hospitals in Taiwan, we recruited 4877 candidate subjects who had not taken carbamazepine. We genotyped DNA purified from the subjects' peripheral blood to determine whether they carried the HLA-B*1502 allele. Those testing positive for HLA-B*1502 (7.7% of the total) were advised not to take carbamazepine and were given an alternative medication or advised to continue taking their prestudy medication; those testing negative (92.3%) were advised to take carbamazepine. We interviewed the subjects by telephone once a week for 2 months to monitor them for symptoms. We used the estimated historical incidence of SJS-TEN as a control. RESULTS: Mild, transient rash developed in 4.3% of subjects; more widespread rash developed in 0.1% of subjects, who were hospitalized. SJS-TEN did not develop in any of the HLA-B*1502-negative subjects receiving carbamazepine. In contrast, the estimated historical incidence of carbamazepine-induced SJS-TEN (0.23%) would translate into approximately 10 cases among study subjects (P<0.001). CONCLUSIONS: The identification of subjects carrying the HLA-B*1502 allele and the avoidance of carbamazepine therapy in these subjects was strongly associated with a decrease in the incidence of carbamazepine-induced SJS-TEN. (Funded by the National Science Council of Taiwan and the Taiwan Drug Relief Foundation.).

Comparison between the cranial magnetic resonance imaging features of neuromyelitis optica spectrum disorder versus multiple sclerosis in Taiwanese patients.

BACKGROUND: Neuromyelitis optica spectrum disorder (NMOSD) and multiple sclerosis (MS) are inflammatory diseases of the central nervous system with different pathogenesis, brain lesion patterns, and treatment strategies. However, it is still difficult to distinguish these two disease entities by neuroimaging studies. Herein, we attempt to differentiate NMOSD from MS by comparing brain lesion patterns on magnetic resonance imaging (MRI). METHODS: The medical records and cranial MRI studies of patients with NMOSD diagnosed according to the 2006 Wingerchuk criteria and the presence of anti-aquaporin 4 (anti-AQP4) antibodies, and patients with MS diagnosed according to the Poser criteria, were retrospectively reviewed. RESULTS: Twenty-five NMOSD and 29 MS patients were recruited. The NMOSD patients became wheelchair dependent earlier than MS patients (log rank test; P = 0.036). Linear ependymal (28% vs. 0%, P = 0.003) and punctate lesions (64% vs. 28%, P = 0.013) were more frequently seen in NMOSD patients. Ten NMOSD patients (40%) had brain lesions that did not meet the Matthews criteria (MS were separated from NMOSD by the presence of at least 1 lesion adjacent to the body of the lateral ventricle and in the inferior temporal lobe; or the presence of a subcortical U-fiber lesion or a Dawson finger-type lesion). The different image patterns of NMOSD didn't correlate with the clinical prognosis. However, NMOSD patients with more (≧10) brain lesions at onset became wheelchair dependence earlier than those with fewer (<10) brain lesions (log rank test; P < 0.001). CONCLUSIONS: The diagnostic sensitivity of NMOSD criteria can be increased to 56% by combining the presence of linear ependymal lesions with unmet the Matthews criteria. The prognoses of NMOSD and MS are different. A specific imaging marker, the linear ependymal lesion, was present in some NMOSD patients. The diagnosis of NMOSD can be improved by following the evolution of this imaging feature when anti-AQP4 antibody test results are not available.