Associations between non-motor symptoms and patient characteristics in Parkinson's disease: a multicenter cross-sectional study.

Objective: Parkinson's disease (PD) is characterized by various non-motor symptoms (NMS), such as constipation, olfactory disturbance, sleep disturbance, mental disorders, and motor symptoms. This study aimed to investigate factors associated with NMS in patients with PD. Methods: Symptoms of PD were evaluated using the Movement Disorder Society Unified Parkinson's Disease Rating Scale (MDS-UPDRS), Parts I-IV. NMS was assessed using the MDS-UPDRS Part I (self-assessment of NMS) and rapid eye movement sleep behavior disorder (RBD) questionnaires. Patients were categorized by age into <70 years and ≥ 70 years (older adults) groups, according to disease duration into early-stage and advanced-stage groups with a cut-off value of 5 years for motor symptoms, and by sex into male and female groups. Results: A total of 431 patients with PD (202 males and 229 females) with a mean age of 67.7 years, a mean disease duration of 6.4 years, and a mean Part I total score of 9.9 participated in this study. The Part I total score was significantly positively correlated (p < 0.01) with disease duration and Part II, III, and IV scores. For Part I sub-item scores, the older group had significantly higher scores for cognitive impairment, hallucinations, sleep problems, urinary problems, and constipation than the <70 years group, whereas the advanced-stage group had significantly higher scores for hallucinations, sleep problems, daytime sleepiness, pain, urinary problems, and constipation (p < 0.05) than the early-stage group. Anxiety was higher in female patients than in male patients, whereas daytime sleepiness, urinary problems, and RBD were higher in male patients than in female patients (p < 0.05). Factors affecting Part I included disease duration, Part II total scores, Part IV total scores, and RBD. Conclusion: According to the self-questionnaire assessment, NMS was highly severe in older adult patients, those with longer illness duration, subjective and objective motor function impairments, and RBD. Sex-based differences were also observed.

Four Cases of Suspected Levetiracetam-Induced Asymptomatic Rhabdomyolysis.

Rhabdomyolysis is a known side effect of levetiracetam. In general, a patient with rhabdomyolysis complains of muscle pain and swelling. Herein, we report four cases of asymptomatic levetiracetam-induced rhabdomyolysis. In all the four cases, the seizures resolved after more than five days. The patients received continuous fluid replacement from the time they were admitted to our hospital. However, serum creatine kinase (CK) levels continued to rise without symptoms consistent with rhabdomyolysis. The serum CK level improved rapidly when levetiracetam was replaced with lacosamide. Because levetiracetam occasionally causes asymptomatic rhabdomyolysis, routine blood tests should be performed after its initiation.

Measurement of individual external doses of Tokyo Electric Power Company Holdings employees working in Fukushima Prefecture and the relationship between individual external doses and air dose rates in areas including difficult-to-return zones.

Since the Fukushima Daiichi Nuclear Power Station accident, evacuation orders have been lifted except for the difficult-to-return zones (DRZs). Within the DRZs, there has been designated a special zone for reconstruction and revitalisation (SZRR). Decontamination of the SZRR has been promoted so that evacuation orders may be lifted. Previous studies measured individual external doses in the evacuation order-lifted zones (ELZs) and other living areas where the annual additional individual external dose was overall less than approximately 5 mSv y-1. However, there have been few reports about the measurement of individual external doses in a SZRR or outside of an SZRR (O-SZRR). In SZRRs and O-SZRRs, Tokyo Electric Power Company Holdings employees work mainly outdoors. Therefore, the employees' individual external doses and air dose rates were measured in these zones from March 2020 through January 2021. Our key results were:The median (minimum to maximum) individual external doses at outdoor locations were 0.16µSv h-1(0.05-0.63µSv h-1), 0.57µSv h-1(0.15-3.92µSv h-1), and 1.36µSv h-1(0.14-11.91µSv h-1) for the ELZ, SZRR, and O-SZRR, respectively.The conversion coefficients for the air dose rate measured by airborne monitoring to individual external dose were 0.23, 0.38, and 0.50 for the ELZ, SZRR, and O-SZRR, respectively. The conversion coefficients were below 0.6, which was used in the national government model for estimating external exposure dose from air dose rate. In addition, the conversion coefficients for the SZRR and O-SZRR in air dose rates of less than 1.5µSv h-1differed from those obtained for the entire measurement range of this study.The conversion coefficient from air dose rate at a height of 1 m above ground level to individual external dose was researched across a broader and higher range of air dose rates than in the previous study (0.24-20.89µSv h-1). The conversion coefficient is confirmed to be 0.7, similar to previous studies.

Prolonged central motor conduction time and pyramidal tract degeneration in amyotrophic lateral sclerosis.

Electrophysiological methods to detect the degeneration of the upper motor neuron system have not been fully established in patients with amyotrophic lateral sclerosis (ALS). This may be partly because the parallel demonstration of electrophysiology and a corresponding pathological abnormality is insufficient, and because a substantial number of patients with ALS do not exhibit upper motor neuron degeneration. Recently, we encountered 2 patients with ALS who had been examined for abnormal central motor conduction time (CMCT) using transcranial magnetic stimulation within a 20-day period prior to their death. Autopsy revealed that 1 patient had marked pyramidal degeneration with prolonged CMCT; in contrast, the other patient had no obvious pyramidal degeneration and showed normal CMCT. Both the patients with contrasting clinicopathological differences contributed to the identification that the prolongation of CMCT was possibly linked to the degeneration of the corticospinal tract. This report indicates that CMCT is useful for predicting the severity of upper motor neuron degeneration in patients with ALS.

Unilateral pallidothalamic tractotomy at Forel's field H1 for cervical dystonia.

BACKGROUND: Neurosurgical ablation of Forel's field H1 for cervical dystonia, which is currently abandoned, was formerly used in the 1960s-1970s. Regardless of the lack of neuroimaging modalities and objective evaluation scales, the reported efficacy was significant. Although recent studies have reappraised the ablation of the pallidothalamic tract at Forel's field H1 for Parkinson's disease, the efficacy for cervical dystonia has not been investigated well. METHODS: Data of 35 patients with cervical dystonia who underwent unilateral pallidothalamic tractotomy at Forel's field H1 were retrospectively analyzed. The Toronto Western Spasmodic Torticollis Rating Scale (TWSTRS) scores, the neck score of the Burke-Fahn-Marsden Dystonia Rating Scale (BFMDRS), and adverse events were evaluated preoperatively and at the last available follow-up period. RESULTS: The mean clinical follow-up period was 13.9 ± 6.5 months. The mean TWSTRS total scores were 34.3 ± 14.0 preoperatively and 18.4 ± 16.5 at the last available follow-up period (46.4% improvement, p < 0.0001). The BFMDRS neck score also improved significantly from 6.2 ± 2.9 preoperatively to 2.8 ± 2.8 at the last available follow-up period (55.0% improvement on the neck score, p < 0.0001). Reduced hand dexterity in seven patients, hypophonia in five patients, dysarthria in four patients, and executive dysfunction in one patient were confirmed as adverse events at the last available follow-up evaluation. One patient had postoperative hemorrhage. CONCLUSION: The current study confirmed significant improvement in TWSTRS total scores and BFMDRS neck scores at the 13.9-month follow-up after unilateral pallidothalamic tractotomy. The pallidothalamic tract in Forel's field H1 is expected to be an alternative treatment target for cervical dystonia.

[MRI arterial spin labeling is useful for diagnosing recovery from nonconvulsive status epilepticus with sustained periodic discharges].

A 75-year-old man with a history of temporal lobe epilepsy (treated with levetiracetam) was transferred to our hospital because of loss of consciousness. At admission, he was drowsy and exhibited myoclonus on the left side of face. We established a diagnosis of status epilepticus and started treatment with levetiracetam, fosphenytoin, and midazolam. FLAIR and DWI showed hyperintensity in the right cerebral cortex. Electroencephalography (EEG) showed lateralized periodic discharges (LPDs) at the right hemisphere, indicative of non-convulsive status epilepticus (NCSE). He regained consciousness after treatment with anti-epileptic drugs but showed persistent LPDs in EEG. MRI arterial spin labeling (ASL) showed normal perfusion in the right hemisphere; therefore, he was deemed to have recovered from status epilepticus and transferred to the rehabilitation hospital. MRI ASL is useful for diagnosing recovery from NCSE irrespective of sustained periodic discharges on EEG.

Association between Excessive Daytime Sleepiness and the Cholinergic Ascending Reticular System in Parkinson's Disease.

BACKGROUND: Excessive daytime sleepiness (EDS) in Parkinson's disease (PD) may occur because of dysfunction on the brain areas in controlling wakefulness; however, the pathophysiology of EDS in PD has not been completely clarified. The Pb component of a middle-latency auditory evoked response (MLR) is generated from the cholinergic ascending reticular activating system (ARAS) projecting to the auditory cortex via the thalamus. We examined the association between EDS and the Pb component in patients with PD. METHODS: Participants were 38 patients with nondemented PD and 18 age-matched controls. EDS was evaluated using the Japanese version of the Epworth Sleepiness Scale (JESS). PD patients were classified into the high sleepiness (HS) group and the low sleepiness (LS) group by the score of JESS. MLRs were recorded from the scalp with each earlobe as a reference under presentation of 1-Hz and 65- to 90-dB click sounds. RESULTS: There was no difference in age, duration, and motor function between the HS PD and the LS PD groups. Peak latencies of Pb were not different between PD group and controls; however, Pb amplitudes were significantly increased in the HS PD group compared with the LS PD group and controls. CONCLUSION: One of the mechanisms of EDS in PD was suggested to be dysregulation of cholinergic neurons from the ARAS projecting to cortical cholinergic neurons.

Magnetic Resonance-Guided Focused Ultrasound Thalamotomy for Focal Hand Dystonia: A Pilot Study.

BACKGROUND: The efficacy of magnetic resonance-guided focused ultrasound (MRgFUS) thalamotomy for the treatment of focal hand dystonia (FHD) is not well known. OBJECTIVE: We aimed to prospectively investigate the efficacy of MRgFUS thalamotomy for the treatment of FHD. METHODS: We performed MRgFUS thalamotomy of the ventro-oral (Vo) nucleus in 10 patients with FHD. We evaluated the scores of the Writer's Cramp Rating Scale (WCRS, 0-30; higher scores indicating greater severity), Tubiana Musician's Dystonia Scale (TMDS, 0-5; lower scores indicating greater severity), and Arm Dystonia Disability Scale (ADDS, 0%-100%; lower scores indicating greater disability) at baseline and 3 and 12 months post-treatment. RESULTS: WCRS, TMDS, and ADDS scores significantly improved from 6.3 ± 2.7, 1.4 ± 0.5, and 58.7% ± 14.3% at baseline to 1.6 ± 3.1 (P = 0.011), 5.0 ± 0 (P = 0.0001), and 81.6% ± 22.9% (P = 0.0229) at 12 months, respectively. There was one prolonged case of dysarthria at 12 months. CONCLUSION: We show that MRgFUS Vo-thalamotomy significantly improved FHD. © 2021 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

Diagnostic Utility of Polymerase Chain Reaction for Paraffin-embedded Sinus Specimens for Rhinocerebral Mucormycosis Complicated by Internal Carotid Artery Thrombosis and Cerebral Infarction.

We herein report a 73-year-old man who experienced cerebral infarction caused by infection with a Mucromycocetes species. A delay in anti-fungal treatment might result in a lethal clinical outcome. We were unable to establish an accurate diagnosis based on histological findings and cerebrospinal fluid culture. Therefore, we performed polymerase chain reaction (PCR) using paraffin-embedded specimens, and based on the findings, successfully started administering anti-fungal treatment. We suggest that PCR using sinus specimens be applied when mucormycosis is suspected as an etiology of cerebral infarction and a confirmative diagnosis cannot be established based on the results of pathological examinations or cerebrospinal fluid culture.

Associations between probable REM sleep behavior disorder, olfactory disturbance, and clinical symptoms in Parkinson's disease: A multicenter cross-sectional study.

BACKGROUND: Rapid eye movement sleep behavior disorder (RBD) and olfactory dysfunction are useful for early diagnosis of Parkinson's disease (PD). RBD and severe olfactory dysfunction are also regarded as risk factors for cognitive impairment in PD. This study aimed to assess the associations between RBD, olfactory function, and clinical symptoms in patients with PD. METHODS: The participants were 404 patients with non-demented PD. Probable RBD (pRBD) was determined using the Japanese version of the RBD screening questionnaire (RBDSQ-J) and the RBD Single-Question Screen (RBD1Q). Olfactory function was evaluated using the odor identification test for Japanese. Clinical symptoms were evaluated using the Movement Disorder Society Revision of the Unified PD Rating Scale (MDS-UPDRS) parts I-IV. RESULTS: In total, 134 (33.2%) patients indicated a history of pRBD as determined by the RBD1Q and 136 (33.7%) by the RBDSQ-J based on a cutoff value of 6 points. Moreover, 101 patients were diagnosed as pRBD by both questionnaires, 35 by the RBDSQ-J only, and 33 by the RBD1Q only. The MDS-UPDRS parts I-III scores were significantly higher and disease duration significantly longer in the pRBD group. pRBD was significantly associated with male gender and the MDS-UPDRS part I score. The olfactory identification function was significantly reduced in the pRBD group. CONCLUSIONS: About 33% of the patients with PD had pRBD based on the questionnaires, and both motor and non-motor functions were significantly decreased in these patients. These results suggest that more extensive degeneration occurred in patients with non-demented PD with RBD.

Unilateral pallidothalamic tractotomy for akinetic-rigid Parkinson's disease: a prospective open-label study.

OBJECTIVE: Neurosurgical ablation is an effective treatment for medically refractory motor symptoms of Parkinson's disease (PD). A limited number of studies have reported the effect of ablation of the pallidothalamic tract for PD. In this study, the authors evaluated the safety and efficacy of unilateral pallidothalamic tractotomy for akinetic-rigid (AR)-PD. METHODS: Fourteen AR-PD patients, who were enrolled in this prospective open-label study, underwent unilateral pallidothalamic tractotomy. The Movement Disorder Society-Unified Parkinson's Disease Rating Scale (MDS-UPDRS) Part III and Part IV (dyskinesia and dystonia) scores and levodopa equivalent daily dose (LEDD) were evaluated at baseline and at 3 and 12 months postoperatively. RESULTS: Of the 14 patients enrolled in the study, 4 were lost to follow-up and 10 were analyzed. The total MDS-UPDRS Part III score significantly improved from 45 ± 4.6 at baseline to 32.9 ± 4.8 at 12 months postoperatively (p = 0.005). Contralateral side rigidity and bradykinesia significantly improved from 4.4 ± 0.5 and 10.4 ± 1.5 at baseline to 1.7 ± 0.4 (p = 0.005) and 5.2 ± 1.4 (p = 0.011) at 12 months, respectively. While posture significantly improved with a 20% reduction in scores (p = 0.038), no significant improvement was found in gait (p = 0.066). Dyskinesia and dystonia were improved with a 79.2% (p = 0.0012) and 91.7% (p = 0.041) reduction in scores, respectively. No significant change was found in the LEDD. Hypophonia was noted in 2 patients, eyelid apraxia was noted in 1 patient, and a reduced response to levodopa, which resulted in an increase in the daily dose of levodopa, was noted in 3 patients. No serious permanent neurological deficits were observed. CONCLUSIONS: Unilateral pallidothalamic tractotomy improved contralateral side rigidity and bradykinesia, dyskinesia, and dystonia in patients with AR-PD. Clinical trial registration no.: UMIN000031138 (umin.ac.jp).

Periventricular White Matter Lesions Influence Gait Functions in Parkinson's Disease.

OBJECTIVE: We quantitatively evaluated the gait of Parkinson's disease (PD) patients over a 10-m course during normal walking and during dual-task walking while performing a calculation task, and clarified which parts of white matter lesions (WML) influence gait in PD patients. METHODS: Gait parameters, including walking speed, gait cycle, stride length, and left-right instability, were measured in 64 PD patients and 20 controls who walked 10 m with normal gait and as they were performing a calculation task. WML on magnetic resonance imaging (MRI) of PD patients were scored according to Scheltens' criteria, and associations with gait parameters were investigated. RESULTS: Compared to controls, the PD group showed decreased walking speed and narrowed stride (p < 0.05), and the stride length and step time coefficient of variation changed significantly during the calculation task (p < 0.001). Frontal lobe functions correlated positively with walking speed and stride during the calculation task in patients with PD (p < 0.05). The total score for periventricular hyperintensity (PVH) on MRI correlated with walking speed and stride (p < 0.01). Multiple regression analysis revealed significant correlations between walking speed and frontal cap of PVH, and between stride and occipital cap (p < 0.05). CONCLUSION: Gait of PD patients deteriorated not only due to motor dysfunction but also due to mental burden in association with frontal lobe function and periventricular lesions of cerebral white matter.

Association Between Cerebral Small Vessel Disease and Central Motor Conduction Time in Patients with Vascular Risk.

BACKGROUND AND PURPOSE: Cerebral small vessel disease (CSVD) is related to motor function disturbance. It includes several types: lacunar infarction, white matter hyperintensity, cerebral microbleeds (CMBs), and enlarged perivascular spaces (EPVS). Transcranial magnetic stimulation (TMS) has been successfully used to evaluate the function of the pyramidal tract. Central motor conduction time (CMCT) is one of the indicators of pyramidal tract dysfunction in motor evoked potential (MEP). The aim of this study was to investigate the association between each type of CSVD and CMCT. METHODS: We enrolled 350 patients with vascular risk factors or a history of cerebrovascular events, who showed signs of CSVD in magnetic resonance imaging in the prospective registry. Among them, 138 patients agreed to the evaluation of MEP. CMCT, resting motor threshold (RMT), and silent period are indicators of the function of motor pathways in MEP. A total of 276 hemispheres were divided into 45 symptomatic hemispheres with a history of pyramidal tract dysfunction and 231 without it. Correlation between each type of CSVD and CMCT were examined in total, symptomatic, and asymptomatic hemispheres. RESULTS: The mean age was 70.5 ± 10.3 (mean ± SD) years, and 89 (65%) were men. In the symptomatic hemisphere, CMCT and RMT were significantly higher than in the asymptomatic hemisphere. In the symptomatic hemisphere, significant association was observed between the number of EPVS in the white matter and CMCT (R2 = 0.201, p < .01). CONCLUSIONS: In the symptomatic hemispheres, CMCT was associated with the number of EPVS in the white matter. The EPVS in the white matter may be involved in the motor disturbance due to CSVD.

Efficacy of istradefylline for gait disorders with freezing of gait in Parkinson's disease: A single-arm, open-label, prospective, multicenter study.

Background: Gait disorders are common in Parkinson's disease patients who respond poorly to dopaminergic treatment. Blockade of adenosine A2A receptors is expected to improve gait disorders. Istradefylline is a first-in-class selective adenosine A2A receptor antagonist with benefits for motor complications associated with Parkinson's disease. Research design and methods: This multicenter, open-label, single-group, prospective interventional study evaluated changes in total gait-related scores of the Part II/III Movement Disorder Society-Unified Parkinson's Disease Rating Scale (MDS-UPDRS) and Freezing of Gait Questionnaire (FOG-Q) in 31 Parkinson's disease patients treated with istradefylline. Gait analysis by portable gait rhythmogram was performed. Results: MDS-UPDRS Part III gait-related total scores significantly decreased at Weeks 4-12 from baseline with significant improvements in gait, freezing of gait, and postural stability. Significant decreases in MDS-UPDRS Part II total scores and individual item scores at Week 12 indicated improved daily living activities. At Week 12, there were significant improvements in FOG-Q, new FOG-Q, and overall movement per 48 h measured by portable gait rhythmogram. Adverse events occurred in 7/31 patients. Conclusions: Istradefylline improved gait disorders in Parkinson's disease patients complicated with freezing of gait, improving their quality of life. No unexpected adverse drug reactions were identified. Trial registration: UMIN-CTR (UMIN000020288).

p.N345K mutation in TARDBP in a patient with familial amyotrophic lateral sclerosis: An autopsy case.

We report the neuropathology of a patient with a family history of amyotrophic lateral sclerosis (ALS) and a p.N345K mutation in the transactivation response DNA-binding protein 43 kDa (TDP-43) gene (TARDBP). A 62-year-old man had bulbar palsy with progressive weakness in the extremities. Neurological examination revealed evident upper motor neuron signs and lower motor neuron involvement corroborated by needle electromyography. The patient was diagnosed as having probable ALS according to the revised El Escorial diagnostic criteria and was eventually diagnosed with familial ALS. At 65 years of age, respiratory failure became critical, and artificial ventilation was initiated. At 70 years of age, the patient died from a urinary tract infection. Histopathological investigation showed Bunina bodies in the remaining motor neurons and anterolateral funicular myelin pallor in the spinal cord. TDP-43-positive cytoplasmic inclusions were quite rare in the spinal cord motor neurons, being predominantly present in the glial cells (especially astrocytes) of the spinal cord anterior horn. Although the reason for the preferential vulnerability of spinal glial cells to TARDBP mutations remains unclear, our findings indicate that TARDBP p.N345K mutation could have an influence on the topography of TDP-43 aggregation.

Ischemic Stroke due to Virologically-Confirmed Varicella Zoster Virus Vasculopathy: A Case Series.

BACKGROUND: Limited data are available regarding the characteristics and prognosis of patients with stroke due to varicella zoster virus (VZV) vasculopathy. METHODS: We studied 4 patients (2 men and 2 women; age, 38-63 years) from a single center who developed acute ischemic stroke due to VZV vasculopathy. The virological diagnosis was confirmed by detecting VZV DNA and/or the IgG antibody to VZV in the cerebrospinal fluid. RESULTS: Three patients were taking immunosuppressive agents, including prednisolone and/or methotrexate, at baseline. Each patient had a characteristic skin rash prior to stroke, with the interval from rash to stroke onset ranging from 13 to 122 days. Two patients experienced antecedent cranial nerve palsies; one had the third, seventh, ninth, and 10th nerve palsies and the other had the fourth nerve palsy before stroke. Cerebral infarctions were located in the anterior circulation lesion (n = 1), in the posterior circulation lesion (n = 2), and in both lesions (n = 1). Intracranial arterial stenosis was only identified in one patient on magnetic resonance angiography. A high plasma d-dimer level was detected in 1 patient, whereas high ß-thromboglobulin and platelet factor 4 levels were detected in 2 patients. As a result of combined therapies with acyclovir, steroid, and antithrombotic agents, neurological symptoms markedly improved in 3 patients, whereas 1 patient was left with moderate hemiplegia. CONCLUSIONS: Cranial nerve palsies may be prodromal symptoms of VZV-associated stroke. Increased levels of thrombotic markers may support the use of antithrombotic agents, although the benefit of combined treatment should be determined through larger studies.

Long-term Monitoring Gait Analysis Using a Wearable Device in Daily Lives of Patients with Parkinson's Disease: The Efficacy of Selegiline Hydrochloride for Gait Disturbance.

OBJECTIVE: The aim of this study was to assess quantitatively the gait disorders in the daily lives of patients with Parkinson's disease (PD) using with a newly developed portable gait rhythmogram (PGR), which has a trunk-mounted acceleration sensor and automatic gait-detection algorithm. METHODS: Using the PGR, we recorded the daily walking profiles of 14 PD patients before and after the addition or increase in dose of an MAO-B inhibitor (selegiline, average dose: 4.0 mg/day) as part of their medicine regimen, and evaluated their gait using the unified Parkinson's disease rating scale (UPDRS) and scores from a freezing of gait (FOG) questionnaire. RESULTS: Before treatment with selegiline, the overall movements per 24 h was decreased below 0.41 m/s2 (mean - 1.5 SD) in eight patients. The mean gait acceleration was decreased below 1.94 m/s2 (mean - 2 SD) in 10 patients. The slope of the linear regression line was increased to 1.6 (mean + 1.5 SD) in eight patients. The cadence was increased to 124 steps/min (mean + 1.5 SD) in four patients. Based on continuous PGR recordings in the daily lives of the patients for 24 h, the addition or increase in dose of selegiline increased the amplitudes of gait accelerations in 4 of 10 patients (40.0%), widened the range of gait accelerations in 5 of 8 patients (62.5%), diminished the cadence in 4 of 4 patients (100%), and diminished the fluctuations in gait throughout the day in 12 of 14 patients (85.7%). The UPDRS III and FOG scores significantly improved after the addition or increase in dose of selegiline (p < 0.005, p < 0.01, respectively). However, changes in gait-related scores of UPDRS were not detected in six patients. CONCLUSION: Improvements in the gait fluctuations of PD patients after the addition or increase in dose of selegiline were detected using the PGR in the daily lives of the patients for 24 h. The PGR had a higher sensitivity for detecting the improvements than UPDRS scores.

Brain Natriuretic Peptide Is a Powerful Predictor of Outcome in Stroke Patients with Atrial Fibrillation
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BACKGROUND: Since stroke patients with nonvalvular atrial fibrillation (NVAF) have poor outcomes in general, the prediction of outcomes following discharge is of utmost concern for these patients. We previously reported that brain natriuretic peptide (BNP) levels were significantly higher in NVAF patients with larger infarcts, higher modified Rankin Scale (mRS) score, and higher CHADS2 score. In the present study, we evaluated an array of variables, including BNP, in order to determine significant predictors for functional outcome in patients with NVAF after acute ischemic stroke (AIS). METHODS: A total of 615 consecutive patients with AIS within 48 h of symptom onset, admitted to our hospital between April 2010 and October 2015, were retrospectively searched. Among these patients, we enrolled consecutive patients with NVAF. We evaluated the mRS score 3 months after onset of stroke and investigated associations between mRS score and the following clinical and echocardiographic variables. Categorical variables included male sex, current smoking, alcohol intake, hypertension, diabetes mellitus, dyslipidemia, coronary artery disease, peripheral artery disease, use of antiplatelet drugs, anticoagulants, or tissue plasminogen activator (tPA), and infarct size. Continuous variables included age, systolic blood pressure (SBP), diastolic blood pressure, hemoglobin, creatinine, D-dimer, brain natriuretic peptide (BNP), left atrial diameter, left ventricular ejection fraction (EF), and early mitral inflow velocity/diastolic mitral annular velocity (E/e'). We also analyzed the association of prestroke CHADS2, CHA2DS2-VASc, and R2CHADS2 scores, and National Institutes of Health Stroke Scale (NIHSS) score on admission with mRS score 3 months after the onset of stroke. Patients were classified into 2 groups according to mRS score: an mRS score ≤2 was defined as good outcome, an mRS score ≥3 was defined as poor outcome. To clarify the correlations between categorical or continuous variables and mRS score, uni- and multivariate logistic regression models using the stepwise variable selection method were applied. RESULTS: Among 157 patients with NVAF after AIS, 63.7% were male and the mean age was 75.9 years. In univariate regression analysis, poor outcome (mRS score ≥3) was associated with use of tPA, infarct size, age, SBP, BNP, EF, and NIHSS score. In multivariate regression analysis, BNP levels (odds ratio [OR] 6.40; 95% confidence interval [CI] 1.26-32.43; p = 0.0235) and NIHSS score (OR 2.87; 95% CI 1.84-4.47; p < 0.001) were significantly associated with poor outcome (mRS score ≥3) after adjusting for use of tPA, infarct size, age, BNP, EF, and NIHSS score. CONCLUSIONS: Apart from NIHSS score, BNP was a very useful predictor for long-term outcomes of patients with NVAF after AIS.
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