Diffusion and structural MRI as potential biomarkers in people with Parkinson's disease and cognitive impairment.

OBJECTIVE: To explore the neuroimage change in Parkinson's disease (PD) patients with cognitive impairments, this study investigated the correlation between plasma biomarkers and morphological brain changes in patients with normal cognition and mild cognitive impairment. The objective was to identify the potential target deposition regions of the plasma biomarkers and to search for the relevant early neuroimaging biomarkers on the basis of different cognitive domains. METHODS: Structural brain MRI and diffusion weighted images were analyzed from 49 eligible PD participants (male/female: 27/22; mean age: 73.4 ± 8.5 years) from a retrospective analysis. Plasma levels of α-synuclein, amyloid beta peptide, and total tau were collected. A comprehensive neuropsychological assessment of the general and specific cognitive domains was performed. Difference between PD patients with normal cognition and impairment was examined. Regression analysis was performed to evaluate the correlation between image-derived index and plasma biomarkers or neuropsychological assessments. RESULTS: Significant correlation was found between plasma Aß-42 level and fractional anisotropy of the middle occipital, angular, and middle temporal gyri of the left brain, as well as plasma T-tau level and the surface area of the isthmus or the average thickness of the posterior part of right cingulate gyrus. Visuospatial and executive function is positively correlated with axial diffusivity in bilateral cingulate gyri. CONCLUSION: In nondemented PD patients, the target regions for plasma deposition might be located in the cingulate, middle occipital, angular, and middle temporal gyri. Changes from multiple brain regions can be correlated to the performance of different cognitive domains. CLINICAL RELEVANCE STATEMENT: Cognitive impairment in Parkinson's disease is primarily linked to biomarkers associated with Alzheimer's disease rather than those related to Parkinson's disease and resembles the frontal variant of Alzheimer's disease, which may guide management strategies for cognitive impairment in Parkinson's disease. KEY POINTS: • Fractional anisotropy, surface area, and thickness in the cingulate, middle occipital, angular, and middle temporal gyri can be significantly correlated with plasma Aß-42 and T-tau level. • Axial diffusivity in the cingulate gyri was correlated with visuospatial and executive function. • The pattern of cognitive impairment in Parkinson's disease can be similar to the frontal variant than typical Alzheimer's disease.

Plasma total tau predicts executive dysfunction in Parkinson's disease.

OBJECTIVES: Cognitive impairment is an important non-motor aspect of Parkinson's disease (PD). Amyloid-ß and tau pathologies are well-established in Alzheimer's disease and commonly coexist with synucleinopathy in PD. However, the levels of these biomarkers in the plasma of patients with PD and their relationship with specific cognition domains remain to be clarified. The current study compared the motor severity and neuropsychological assessment of general and specific cognition, with plasma levels of α-synuclein (α-syn), amyloid-ß 42 (Aß42), and total tau (t-tau) in PD subjects. METHODS: Plasma levels of α-syn, Aß42, and t-tau were measured in 55 participants with PD through immunomagnetic reduction assay. The evaluation of motor severity and comprehensive neuropsychological assessment was performed in all participants. RESULTS: The level of plasma α-syn was negatively correlated with the scores of Unified Parkinson's Disease Rating Scale part III [r = (-.352), p = .008]. The level of plasma t-tau was negatively correlated with the scores of digits recall forwards and digits recall backwards [r = (-.446), p = .001; r = (-.417), p = .002, respectively]. No correlations were found between the levels of α-syn and Aß42 and any neuropsychological tests. CONCLUSIONS: This study concluded a lower level of plasma α-syn was correlated with motor dysfunction in PD patients, and a higher level of plasma t-tau was correlated with lower cognitive performance, especially for attention and executive function. These results propose the possibility of using plasma biomarkers to predict specific cognitive performance in PD subjects.

Do cognitive performance and physical function differ between individuals with motoric cognitive risk syndrome and those with mild cognitive impairment?

BACKGROUND: Motoric cognitive risk syndrome (MCR) is defined by slow gait speed combined with subjective cognitive complaint. MCR is a predementia syndrome, similar to mild cognitive impairment (MCI). However, there is currently no study comparing the differences in cognitive performance and physical function between these two types of cognitive impairment. Thus, the aim of this study is to compare cognitive performance and physical function in individuals with MCR versus MCI. METHODS: A total of 77 participants, free of dementia, were recruited from the neurological outpatient clinic of a medical center in Taiwan. Participants were separated into 2 groups, MCR (n = 33) and MCI (n = 44) groups, based on definition criteria from previous studies. The priority was to assign a diagnosis of MCR first, followed by MCI. Hence, "pure" MCI had no overlap with MCR syndrome. Cognitive performance, including executive function, attention, working memory, episode memory, visuospatial function, and language, were measured. Physical functions such as activities in daily living, the Tinetti Assessment Scale, and the Timed Up and Go test were also measured. RESULTS: Executive function, attention, working memory, episodic memory and language were all significantly lower in the MCR group than the MCI group. Abilities related to physical function, including those measured by the Tinetti Assessment Scale and the Timed Up and Go test, were significantly lower in the MCR group than the MCI group. CONCLUSIONS: We noted that cognitive performance and physical function were lower in MCR individuals than MCI but without MCR syndrome. However, the conclusions were based on the enrollment procedure of participants prioritizes the MCR syndrome. Because of the overlap of MCR and MCI, future studies should use different enrollment strategies to further clarify the status of these two populations.

Gait-Based Machine Learning for Classifying Patients with Different Types of Mild Cognitive Impairment.

Mild cognitive impairment (MCI) may be caused by Alzheimer's disease, Parkinson's disease (PD), cerebrovascular accident, nutritional or metabolic disorders, or mental disorders. It is important to determine the cause and treatment of dementia as early as possible because dementia may appear in remission. Decline in MCI cognitive function may affect a patient's walking performance. Therefore, all participants in this study participated in an experiment using a portable gait analysis system to perform walk, time up and go, and jump tests. The collected gait parameters are used in a machine learning classification model based on a support vector machine (SVM) and principal component analysis (PCA). The aim of the study is to predict different types of MCI patients based on gait information. It is shown that the machine learning classification model can predict different types of MCI patients. Specifically, the PCA-SVM model demonstrated better classification performance with 91.67% accuracy and 0.9714 area under the receiver operating characteristic curve (ROC AUC) using the polynomial kernel function in classifying PD-MCI and non-PD-MCI patients.

Gender Gap and Risk Factors for Poor Stroke Outcomes: A Single Hospital-Based Prospective Cohort Study.

BACKGROUND: This study intended to investigate whether etiological stroke subtypes and their corresponding major risk factors have differential effects on outcomes between genders. PATIENTS AND METHODS: We enrolled 403 consecutive patients with first-ever acute ischemic stroke (170 women, 233 men), from a referral hospital in Taiwan over a 2-year period. Gender differences in demographics, vascular risk factors, access to health care, etiological stroke subtypes, stroke severity, and outcomes were examined. The primary outcome variable of the study was any unfavorable outcome due to acute ischemic stroke, defined as a modified Rankin Scale score of 3 or higher at 90 days after stroke. Multivariable logistic regression models were used to identify predictors of poor outcomes. RESULTS: There were no gender disparities in baseline severity, stroke subtypes, access to health care, and medical comorbidities. Although women had poorer outcomes, female gender was not a predictor of unfavorable outcomes. Important predictors included age of 75years or older (odds ratio [OR] = 2.67; 95% confidence interval [CI], 1.46-4.90), National Institutes of Health Stroke Scale greater than or equal to 8 (OR = 8.38; 95% CI, 4.61-15.2), lack of cohabitation (OR = 2.13; 95% CI, 1.26-3.61), subtypes of cardioembolism (OR = 2.76; 95% CI, 1.29-5.93), and large-artery atherosclerosis (OR = 2.93; 95% CI, 1.47-5.85). In subgroup analyses, the gender-specific independent predictors were cardioembolism (OR = 7.42; 95% CI, 2.21-24.9) or atrial fibrillation (OR = 3.57; 95% CI, 1.31-9.74) in women, and large-artery atherosclerosis (OR = 3.35; 95% CI, 1.30-8.64) or symptomatic large-artery stenosis (OR = 3.42; 95% CI, 1.69-6.96) in men. The differential effects of these predictors according to gender were revealed by interaction tests. CONCLUSION: Atrial fibrillation and symptomatic large-artery stenosis are predictors of poor stroke outcomes in women and men, respectively.

Intrafamilial phenotypic heterogeneity in a Taiwanese family with a MAPT p.R5H mutation: a case report and literature review.

BACKGROUND: Frontotemporal degeneration (FTD) is a clinically and genetically heterogeneous neurodegenerative disorder characterized by deficits in executive function that frequently overlaps with parkinsonism and motor neuron disorders. Several genes have been identified to cause autosomal dominant forms of FTD, including the gene coding for the protein associated with microtubule tau (MAPT). While most reported pathogenic mutations in MAPT occur in exons 9-13, few families have been reported with mutations outside of this region. Herein, we report a first Taiwanese family having the exon 1 p.Arg5His mutation in MAPT with intrafamilial phenotype heterogeneity. CASE PRESENTATION: A 63-year-old man presented with progressive non-fluent speech and impaired memory for 3 years. He then developed apraxia, myoclonus and parkinsonism feature at his right hand. Extensive neurologic and neurocognitive examination lead to a diagnosis of FTD mixed with corticobasal syndrome. Magnetic resonance imaging revealed asymmetric atrophy in the left frontal and temporal lobes and single-photon emission computed tomography indicated decreased metabolism in the same areas as well as the left basal ganglia. The patient's mother had been diagnosed with amyotrophic lateral sclerosis (ALS) at the age of 60 and was deceased 10 years later due to respiratory failure. The patient's younger sister had persistent depressive disorder in her early forties and did not have any prominent cognitive or motor dysfunctions. We performed genetic analysis applying a targeted next generation sequencing (NGS) panel covering MAPT, GRN, VCP, FUS, CHMP2B, and TARDBP on the proband, followed by Sanger sequencing of candidate genes in eight family members. Hexanucleotide repeat expansion of C9Orf72 was determined by repeat-primed PCR. We identified a missense mutation in exon 1 of MAPT gene, c.14G > A (p.R5H), which was previously reported in only two Japanese patients in a literature review. This substitution co-segregated with the disease phenotypes in the family. CONCLUSIONS: This is the first report of the occurrence of the MAPT p.R5H mutation in the Taiwanese population. Our findings extend the current knowledge of phenotypic heterogeneity among family members carrying the MAPT p.R5H mutation.

Relapsing Polychondritis Presenting with Meningoencephalitis and Dementia: Correlation with Neuroimaging and Clinical Features.

PURPOSE: Relapsing polychondritis (RP) is a rare systemic autoimmune disease affecting cartilaginous and non-cartilaginous structures. Neurological involvement is rarer but results in profound disability. Early identification and treatment of underlying RP may promote neurological recovery. CASE REPORT: We illustrated a 53-year-old man diagnosed with dementia. Neuroimaging and cerebrospinal fluid studies disclosed meningoencephalitis. "Prominent ear sign" was evident on diffusion-weight magnetic resonance imaging. After glucocortisone administration, the improvement of clinical manifestations was closely correlated subsequent neuroimaging findings. CONCLUSION: The importance of better understanding of this disease in terms of the prevention of further tissue damage in patients with RP cannot be overemphasized.

Associations between blood-based biomarkers of Alzheimer's disease with cognition in motoric cognitive risk syndrome: A pilot study using plasma Aß42 and total tau.

Background: Motoric cognitive risk (MCR) syndrome is a conceptual construct that combines slow gait speed with subjective cognitive complaints and has been shown to be associated with an increased risk of developing dementia. However, the relationships between the pathology of Alzheimer's disease (AD) and MCR syndrome remain uncertain. Therefore, the purpose of this study was to determine the levels of plasma AD biomarkers (Aß42 and total tau) and their relationships with cognition in individuals with MCR. Materials and methods: This was a cross-sectional pilot study that enrolled 25 individuals with normal cognition (NC), 27 with MCR, and 16 with AD. Plasma Aß42 and total tau (t-tau) levels were measured using immunomagnetic reduction (IMR) assays. A comprehensive neuropsychological assessment was also performed. Results: The levels of plasma t-tau proteins did not differ significantly between the MCR and AD groups, but that of plasma t-tau was significantly increased in the MCR and AD groups, compared to the NC group. Visuospatial performance was significantly lower in the MCR group than in the NC group. The levels of plasma t-tau correlated significantly with the Montreal Cognitive Assessment (MoCA) and Boston naming test scores in the MCR group. Conclusion: In this pilot study, we found significantly increased plasma t-tau proteins in the MCR and AD groups, compared with the NC group. The plasma t-tau levels were also significantly correlated with the cognitive function of older adults with MCR. These results implied that MCR and AD may share similar pathology. However, these findings need further confirmation in longitudinal studies.

Prediction of Cognitive Degeneration in Parkinson's Disease Patients Using a Machine Learning Method.

This study developed a predictive model for cognitive degeneration in patients with Parkinson's disease (PD) using a machine learning method. The clinical data, plasma biomarkers, and neuropsychological test results of patients with PD were collected and utilized as model predictors. Machine learning methods comprising support vector machines (SVMs) and principal component analysis (PCA) were applied to obtain a cognitive classification model. Using 32 comprehensive predictive parameters, the PCA-SVM classifier reached 92.3% accuracy and 0.929 area under the receiver operating characteristic curve (AUC). Furthermore, the accuracy could be increased to 100% and the AUC to 1.0 in a PCA-SVM model using only 13 carefully chosen features.

Corrigendum: Associations between blood-based biomarkers of Alzheimer's disease with cognition in motoric cognitive risk syndrome: A pilot study using plasma Aß42 and total tau.

[This corrects the article DOI: 10.3389/fnagi.2022.981632.].

Factors Associated with Fear of Falling in Individuals with Different Types of Mild Cognitive Impairment.

Mild cognitive impairment (MCI) is considered an intermediate state between normal aging and early dementia. Fear of falling (FOF) could be considered a risk indicator for falls and quality of life in individuals with MCI. Our objective was to explore factors associated with FOF in those with MCI due to Alzheimer's disease (AD-MCI) and mild cognitive impairment in Parkinson's disease (PD-MCI). Seventy-one participants were separated into two groups, AD-MCI (n = 37) and PD-MCI (n = 34), based on the disease diagnosis. FOF was assessed using the Activities-specific Balance Confidence scale. The neuropsychological assessment and gait assessment were also measured. FOF was significantly correlated with global cognitive function, attention and working memory, executive function, Tinetti assessment scale scores, gait speed, and stride length in the AD-MCI group. Moreover, attention and working memory were the most important factors contributing to FOF. In the PD-MCI group, FOF was significantly correlated with gait speed, and time up and go subtask performance. Furthermore, turn-to-walk was the most important factor contributing to FOF. We noted that FOF in different types of MCI was determined by different factors. Therapies that aim to lower FOF in AD-MCI and PD-MCI populations may address attention and working memory and turn-to-walk, respectively.

Mechanism mediating oligomeric Aß clearance by naïve primary microglia.

The accumulation of soluble oligomeric amyloid-ß peptide (oAß) proceeds the formation of senile plaques and contributes to synaptic and memory deficits in Alzheimer's disease (AD). The mechanism of mediating microglial oAß clearance remains unclear and thought to occur via scavenger receptors (SRs) in microglia. SRs respond to their ligands in a subtype-specific manner. Therefore, we sought to identify the specific subtypes of SRs that mediate oAß internalization and proteases that degrade oAß species in naïve primary microglia. The component of oAß species were characterized by western blot analysis, analytical ultracentrifugation analysis, and atomic force microscopy. The oAß species remained soluble in the medium and microglial lysates during incubation at 37 °C. SR-A, but not CD36, mediated oAß internalization in microglia as suggested by the use of subtype-specific neutralizing antibodies and small interfering RNAs (siRNAs). Immunoprecipitation analysis showed that oAß interacted with SR-A on the plasma membrane. After internalization, over 40% of oAß vesicles were trafficked toward lysosomes and degraded by cysteine proteases, including cathepsin B. The inhibitors of proteasome, neprilysin, matrix metalloproteinases, and insulin degrading enzyme failed to protect internalized oAß from degradation. Our study suggests that SR-A and lysosomal cathepsin B are critical in microglial oAß clearance, providing insight into how microglia are involved in the clearance of oAß and their roles in the early stages of AD.

Predicting Cognitive Decline in Parkinson's Disease with Mild Cognitive Impairment: A One-Year Observational Study.

We conducted an observational study to investigate clinical predictors of cognitive decline in patients with mild cognitive impairment (MCI), with a focus on patients with Parkinson's disease (PD) and Alzheimer's disease (AD). The study was performed with detailed neuropsychological testing, a portable device for gait analysis, and a comprehensive geriatric assessment for patients with MCI. Cognitive decline was defined as subjective cognitive impairment with an objective decline in the Mini-Mental State Examination (MMSE) ≥2 points at the one-year follow-up. Participants (n = 74) had a median age of 70 (interquartile range 60-79) years, and 45.9% of them were women. At the end of the study, 17.6% of the patients with MCI had a cognitive decline. Although no differences were observed between groups at the baseline cognitive study, patients with PD-MCI demonstrated more cognitive decline than patients with AD-MCI (28.6% vs. 7.7% p = 0.03). Patients with PD-MCI had more physical disabilities, including scores of instrumental activities of daily living (IADL), Tinetti balance, and gait scores, and some Timed Up and Go components. Initial Clinical Dementia Rating-Sum of Boxes score was a better predictor of future cognitive decline than MMSE in PD-MCI. For predicting the occurrence of cognitive decline in PD-MCI, the prediction accuracy increased from the reduced model (AUC = 0.822, p < 0.001) to the full model (a total of five independent variables, AUC = 0.974, p < 0.001). Given the potentially modifiable predictor, our findings also highlight the importance of identifying sleep quality and the ability to perform IADL.

Dynamic responses of DOC and DIC transport to different flow regimes in a subtropical small mountainous river.

Transport of riverine dissolved carbon (including DOC and DIC) is a crucial process linking terrestrial and aquatic C reservoirs, but has rarely been examined in subtropical small mountainous rivers (SMRs). This study monitored DOC and DIC concentrations on a biweekly basis during non-event flow periods and at 3 h intervals during two typhoon events in three SMRs in southwestern Taiwan between January 2014 and August 2016. Two models, HBV (the Hydrologiska Byråns Vattenbalansavdelning model) and a three-endmember mixing model, were applied to determine the quantities of DOC and DIC transport from different flow paths. The results show that the annual DOC and DIC fluxes were 2.7-4.8 and 48.4-54.3 t C km-2 yr-1, respectively, which were approx. 2 and 20 times higher than the global mean of 1.4 and 2.6 t C km-2 yr-1, respectively. The DIC / DOC ratio was 14.08, which is much higher than the mean of large rivers worldwide (1.86), and indicates the high rates of chemical weathering in this region. The two typhoons contributed 12%-14% of the annual streamflow in only 3 days (about 1.0% of the annual time), whereas 15.0%-23.5% and 9.2%-12.6% of the annual DOC and DIC flux, respectively, suggested that typhoons play a more important role in DOC transport than DIC transport. The end-member mixing model suggested that DOC and DIC export was mainly from surface runoff and deep groundwater, respectively. The unique patterns seen in Taiwan SMRs characterized by high dissolved carbon flux, high DIC / DOC ratio, and large transport by intense storms should be taken into consideration when estimating global carbon budgets.

Quality of Life in Patients with Dementia with Lewy Bodies.

Dementia with Lewy bodies (DLB) is a complex, multisymptom disorder. When making decisions regarding the treatment of DLB, the patient's quality of life (QoL) should always be the main consideration. To our knowledge, this is the first review article focusing on the QoL in DLB patients. We searched the PubMed database using the keywords "quality of life" and "dementia with Lewy bodies." Previously, no specific instrument had been developed for assessing the QoL in DLB patients. Patients with DLB have a decreased QoL compared to patients with Alzheimer's disease, which is reportedly caused by several factors including level of independence in instrumental activities of daily living, whether the patient is living with the caregiver, apathy, delusion, and dysautonomia. The direct effect of visual hallucination, sleep, and movement disorders on the QoL in DLB patients has not been previously studied. The role of cognitive function on the QoL is still controversial. In a randomized controlled study, memantine may improve the QoL in PDD or DLB patients. We concluded that it is important to develop a specific instrument to assess the QoL in DLB patients. Furthermore, there is an urgent need for large clinical trials to identify factors associated with the QoL and how they can be managed.

Risk Factors for the Progression of Mild Cognitive Impairment in Different Types of Neurodegenerative Disorders.

OBJECTIVE: Mild cognitive impairment (MCI) is a transitional state between normal aging and early dementia. It has a heterogeneous etiology and clinical course. This study aimed to examine the factors associated with the progression of MCI in different types of dementia disorders. METHOD: A retrospective, longitudinal, observational study of outpatients with MCI was conducted at a medical center in northern Taiwan. Patient medical records were reviewed, and risk factors were analyzed by multivariate analysis. RESULTS: Among 279 patients with MCI, 163 (58.4%), 68 (24.4%), and 48 (17.2%) were diagnosed with Alzheimer's disease, vascular cognitive impairment, and Lewy body diseases, respectively. During the observation period, 37.2% of patients progressed to dementia. Older age and a higher Clinical Dementia Rating Scale-Sum of Boxes were associated with the risk of progression. Hyperlipidemia was associated with a decreased risk. Converters were more likely to receive an antidementia prescription. CONCLUSION: Our study suggests the importance of comprehensive clinical profiling, risk factor assessment, and detailed drug history evaluations in improving our understanding and management of dementia subtypes.

Scrub typhus-associated acute disseminated encephalomyelitis.

BACKGROUND: Acute disseminated encephalomyelitis (ADEM) is a monophasic demyelinating disease of the central nervous system, typically occurring after infections or vaccinations. To our knowledge, scrub typhus has not been described in association with ADEM. CASE REPORT: A 77-year-old man was admitted with fever, convulsions and an altered level of consciousness. On neurological examination, the patient was stuporous and had nuchal rigidity and left hemiparesis. A generalized tonic-clonic seizure was observed. Serum and cerebrospinal fluid samples were positive for anti-Orientia tsutsugamushi antibody. Despite a 10-day course of parenteral minocycline, his clinical condition deteriorated. Serial cranial magnetic resonance images demonstrated progressively extensive areas of signal hyperintensity on conventional T2-weighted and fluid attenuated inversion recovery sequence images, mainly affecting the periventricular white matter. After administration of intravenous high-dose corticosteroids, the patient had limited improvement. CONCLUSIONS: This is the first identifiable case of ADEM temporally associated with scrub typhus alone.

Risk factors and prevalence rate of restless legs syndrome among pregnant women in Taiwan.

BACKGROUND: The goal of this study was to assess the prevalence and clinical correlates of restless legs syndrome (RLS) among pregnant Taiwanese women. METHODS: We enrolled 461 pregnant women (18-45 years) admitted at Mackay Memorial Hospital for delivery from September 2010 to May 2011. The face-to-face questionnaire used to gather data included assessment of RLS diagnostic criteria, and questions related to RLS. RESULTS: The overall prevalence rate of RLS among the study participants was 10.4%; 2.8% were categorized as having chronic RLS. Participants without RLS reported higher folate and iron supplement consumption than those with RLS. Multivariate analysis revealed significant associations of RLS with anemia and peptic ulcer disease. Participants with transient RLS during pregnancy reported more regular coffee consumption before pregnancy, and better sleep latency, duration, and efficiency, than those with chronic RLS. Overall, 81.2% of RLS sufferers reported sleep disturbances. CONCLUSIONS: Our study revealed highly prevalent but poorly recognized RLS among Taiwanese pregnant women. The identification of predictors such as medical comorbidities, and protectors such as folate and iron supplements, is warranted for obstetric RLS. In most cases, symptoms began during the second or third trimester and resolved within a week after delivery. Restricted coffee consumption before pregnancy is encouraged, but further evidence is needed to support this recommendation.

Classifying Ischemic Stroke, from TOAST to CISS.

Ischemic stroke classification is critical in conducting basic research and clinical practice. A precise analysis of stroke subtypes requires the integration of clinical features, findings from diagnostic tests, and knowledge about potential etiologic factors by competent diagnostic investigators. We performed a literature review of the published stroke classification systems and examined each for its benefits and limitations in the evaluation of the stroke etiology. Two major approaches to etiologic classifications of ischemic stroke are currently being used: the causative and phenotypic subtyping. The most widely used causative system is the Trial of Org 10172 in acute stroke treatment (TOAST) classification. With the advances in modern diagnostic technology, new stroke subclassification systems, such as the causative classification system (CCS) and Chinese ischemic stroke subclassification (CISS) system, have been developed to enhance the accuracy of TOAST. The A-S-C-O (Atherosclerosis, Small-vessel disease, Cardiac source, Other cause) phenotypic classification system makes efforts to identify the most likely etiology but not neglecting the possibility of other potential multiple causes. We conclude that the ideal stroke classification system needs to be valid, easy to use, evidence-based, and incorporate new information as it emerges.

Stroke during pregnancy and puerperium: clinical perspectives.

Stroke is a rare but potentially devastating disease during pregnancy and puerperium. Pregnancy is well recognized as a risk factor for stroke. Accurate and timely identification of stroke is crucial for clinical practice. However, the optimal management of pregnant women with stroke remains a clinical challenge. Thus, identification of risk factors and modification of underlying pathophysiological mechanisms would be of great value for stroke prevention and management. In terms of pharmacological intervention, it is important to determine the safety of a drug for mothers, their fetuses, and nursing infants. Neurologists treat non-pregnant patients without those considerations. Based on the above issues, we have reviewed the current literature and summarized clinically relevant issues for obstetricians and neurologists in treating stroke during pregnancy and puerperium.