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Studies on second-generation antipsychotics (SGA) augmentation treatment for older adults with major depressive disorder (MDD) remain limited. We aimed to investigate the effectiveness of SGA augmentation for overall and older patients with MDD inpatient history by assessing the change in 1-year hospitalization before and after SGA augmentation using the latest National Health Insurance Research Database (NHIRD) in Taiwan.The samples were MDD patients (ICD-9 CM code: 296.2 and 296.3) who had psychiatric inpatient history. A total of 2602 MDD patients including 430 elderly subjects (age ≥ 60 years) who received SGA augmentation for 8 weeks between January 1998 and December 2012 were included in this 1-year mirror-image study. Outcome measures included number and length of psychiatric and all-cause hospitalizations.After 8-week continuous SGA augmentation in the study subjects, the total number and days of psychiatric hospitalizations among overall patients reduced by 33.57% (p.0001) and 18.24% (p.0001), respectively; the total number and days of psychiatric hospitalizations among older patients (age ≥ 60) reduced by 44.52% (p.0001) and 27.95% (p.0001), respectively. Similarly, the total number and days of all-cause hospitalizations were significantly reduced.MDD patients without inpatient history were not included due to data limitation; hence, the results may not be generalized to all patients.The results support that SGA may be effective in reducing psychiatric and all-cause hospitalization among overall and elderly MDD patients. More studies focusing on the safety of SGA among older MDD patients is warranted.

Background and aims Renal dysfunction is a potent risk factor for cardiovascular diseases, including stroke. This study aimed to evaluate the impact of admission estimated glomerular filtration rate (eGFR) levels on short-term (1-month) and long-term (1-year) mortality in patients with acute ischemic stroke. Methods From the Taiwan Stroke Registry data, we classified ischemic stroke patients, identified from April 2006 to December 2015, into 5 groups by eGFR at admission: ≥ 90, 60–89, 30–59, 15–29, and Results Among 52,732 ischemic stroke patients, 1480 died within one month. The 1-month mortality rate was over 5-fold greater in patients with eGFR Conclusions After acute ischemic stroke, patients with reduced eGFR are at elevated risks of short-term and long-term deaths in a graded relationship.

We investigated the impact of serum cholesterol levels on 30-day mortality after ischemic stroke in dialysis patients.From the Taiwan Stroke Registry data, we identified 46,770 ischemic stroke cases, including 1101 dialysis patients and 45,669 nondialysis patients from 2006 to 2013.Overall, the 30-day mortality was 1.46-fold greater in the dialysis group than in the nondialysis group (1.75 versus 1.20 per 1000 person-days). The mortality rates were 1.64, .62, 2.82, and 2.23 per 1000 person-days in dialysis patients with serum total cholesterol levels of 120 mg/dL, 120-159 mg/dL, 160-199 mg/dL, and ≥200 mg/dL, respectively. Compared to dialysis patients with serum total cholesterol levels of 120-159 mg/dL, the corresponding adjusted hazard ratios of mortality were 4.20 (95% confidence interval [CI] = 1.01-17.4), 8.06 (95% CI = 2.02-32.2), and 6.89 (95% CI = 1.59-29.8) for those with cholesterol levels of 120 mg/dL, 160-199 mg/dL, and ≥200 mg/dL, respectively.Dialysis patients with serum total cholesterol levels of ≥160 mg/dL or 120 mg/dL on admission are at an elevated hazard of 30-day mortality after ischemic stroke.

With a worldwide high disease burden, medication overuse headache (MOH) is an endemic and disabling neurological disorder. Because of the limitations of previous study designs, there are still debates and questions regarding the disease’s nature and treatment strategy. This review will discuss the following concepts; (1) recent progress in association between medication overuse (MO) and MOH; (2) the burden, risk factors and comorbidities of MOH; (3) evidence of treatment in patients with MOH. The causal relationship between MO and MOH has not been identified. Currently, the treatment policy is still mainly based on small clinical observations, some with highly specified patients. In addition to withdrawal and preventive treatment, some studies have provided evidence for nonpharmacological treatments. Well-designed studies for specific treatment strategies with enough statistical power are warranted to make more relevant, better clinical decisions.

Background and purpose Physical activity is associated with a reduced incidence of first-time stroke. However, few studies have examined the effect of pre-stroke physical activity on post-stroke complications and clinical outcomes. Methods A total of 39 835 cases of stroke registered in the nationwide stroke registry system of Taiwan between 2006 and 2009 were analyzed according to five levels of severity as determined by National Institutes of Health Stroke Scale score upon hospital admission. Pre-stroke physical activity was defined in the Taiwan Stroke Registry as dedicated leisure-time physical activity for at least 30 min/day for 3 days/week for more than 6 months. A Cox model was used to compare complications and outcomes between active and inactive groups. Results The active and inactive groups were similar in age distribution and stroke type distribution, but the active group had better National Institutes of Health Stroke Scale scores upon admission. The active group also had significantly fewer post-stroke complications. Active patients had lower hospital mortality and better functional outcomes upon discharge as per the modified Rankin Scale. Improved functional status in the active group was significant at 1, 3 and 6 months post-stroke. Conclusion Dedicated leisure-time physical activity for at least 30 min/day, at least three times per week for more than 6 months was associated with decreased stroke severity, fewer post-stroke complications, lower mortality and better outcomes.

Background N -methyl-D-aspartate receptor (NMDAR)-mediated neurotransmission is vital for learning and memory. Hypofunction of NMDAR has been reported to play a role in the pathophysiology of Alzheimer disease (AD), particularly in the early phase. Enhancing NMDAR activation might be a novel treatment approach. One of the methods to enhance NMDAR activity is to raise the levels of NMDA coagonists by blocking their metabolism. This study examined the efficacy and safety of sodium benzoate, a D-amino acid oxidase inhibitor, for the treatment of amnestic mild cognitive impairment and mild AD. Methods We conducted a randomized, double-blind, placebo-controlled trial in four major medical centers in Taiwan. Sixty patients with amnestic mild cognitive impairment or mild AD were treated with 250–750 mg/day of sodium benzoate or placebo for 24 weeks. Alzheimer's Disease Assessment Scale-cognitive subscale (the primary outcome) and global function (assessed by Clinician Interview Based Impression of Change plus Caregiver Input) were measured every 8 weeks. Additional cognition composite was measured at baseline and endpoint. Results Sodium benzoate produced a better improvement than placebo in Alzheimer's Disease Assessment Scale-cognitive subscale ( p = .0021, .0116, and .0031 at week 16, week 24, and endpoint, respectively), additional cognition composite ( p = .007 at endpoint) and Clinician Interview Based Impression of Change plus Caregiver Input ( p = .015, .016, and .012 at week 16, week 24, and endpoint, respectively). Sodium benzoate was well-tolerated without evident side-effects. Conclusions Sodium benzoate substantially improved cognitive and overall functions in patients with early-phase AD. The preliminary results show promise for D-amino acid oxidase inhibition as a novel approach for early dementing processes.

Background and Purpose— The study aimed to assess whether onset headache is an ominous sign in patients with first-ever ischemic stroke. Methods— A large population of ischemic stroke patients was obtained from the Taiwan Stroke Registry. Stroke subtypes were classified by the Trial of ORG 10172 in Acute Stroke Treatment (TOAST) criteria. On the basis of the International Classification of Headache Disorders, second version, onset headache was defined as a new headache that developed at the onset of ischemic stroke. Clinical features and impact on stroke outcomes, including in-hospital stroke in evolution, changes in National Institutes of Health Stroke Scale on discharge, and Barthel index and modified Rankin scale ≤6 months after stroke were compared between those with and without onset headache. Results— Among 11 523 patients with first-ever ischemic stroke, 848 had onset headache (7.4%). Patients with specific cause, large-artery atherosclerosis, or cardioembolism were more likely to have onset headache. Patients with onset headache were younger, predominantly female, and more likely to have posterior circulation ischemic lesions. Compared with patients without onset headache, those with onset headache had a lower frequency of stroke in evolution (4.5% versus 6.7%; adjusted relative risk, 0.64; 95% confidence interval, 0.52–0.79), greater improvement in National Institutes of Health Stroke Scale score on discharge (0.08 versus −0.20; P =0.02), higher mean Barthel index scores (86.5±20.0 versus 83.9±23.3; adjusted difference, 1.43; 95% confidence interval, 0.28–2.89), and a lower frequency of modified Rankin scale higher than 2 (27.6% versus 31.5%; adjusted relative risk, 0.85; 95% confidence interval, 0.72–0.95) at 1-month follow-up. There was also a trend for better functional outcome in 3- and 6-month follow-ups. Conclusions— By adopting standard classification criteria, this large-scale study demonstrated that onset headache was associated with modest but significantly better outcomes after ischemic stroke.

The relationship between cholesterol level and hemorrhagic stroke is inconclusive. We hypothesized that low cholesterol levels may have association with intracerebral hemorrhage (ICH) severity at admission and 3-month outcomes. This study used data obtained from a multi-center stroke registry program in Taiwan. We categorized acute spontaneous ICH patients, based on their baseline levels of total cholesterol (TC) measured at admission, into 3 groups with 200 mg/dL of TC. We evaluated risk of having initial stroke severity, with National Institutes of Health Stroke Scale (NIHSS) >15 and unfavorable outcomes (modified Rankin Scale [mRS] score >2, 3-month mortality) after ICH by the TC group. A total of 2444 ICH patients (mean age 62.5±14.2 years; 64.2% men) were included in this study and 854 (34.9%) of them had baseline TC 15), with an adjusted odds ratio [aOR] of 1.80; 95% confidence interval [CI], 1.41-2.30), and 3-month mRS >2 (aOR, 1.41; 95% CI, 1.11-1.78) using patients with TC >200 mg/dL as reference. Those with TC >160 mg/dL and body mass index (BMI)

Background and purpose Previous studies on the clinical and pathological manifestations of Parkinson’s disease dementia (PDD) have reported findings more similar to dementia with Lewy bodies (DLB) than to Alzheimer’s disease (AD). The aim of this study was to investigate the neuropsychiatric symptoms of PDD compared to DLB and AD. Methods We conducted a retrospective case-control study on 125 newly diagnosed consecutive PDD patients and age- and dementia stage-matched controls with either DLB (N = 250) or AD (N = 500) who visited the same hospital over the same period. For each case and control, neuropsychiatric symptoms were assessed using the Neuropsychiatric Inventory (NPI). Results Overall, 513 (58.6%) patients were female and 362 (41.4%) were male. Comparisons of clinical data revealed that the PDD group, similar to the AD group, had a lower NPI total score, NPI caregiver burden score, and rate of antipsychotic use (all p < 0.001) than the DLB group. One or more psychiatric symptoms were reported in 95.2% of the PDD, 99.2% of the DLB, and 96.8% of the AD patients. The PDD group had lower subscores in the items of delusions, hallucinations, agitation, anxiety, irritation, aberrant motor behavior compared to the DLB group. Severe neuropsychiatric symptoms among all dementia patients were associated with younger age, more advanced stage, and a diagnosis of DLB. Conclusion Neuropsychiatric symptoms in PDD were more like those in AD than in DLB. Severe neuropsychiatric symptoms in degenerative dementia were associated with younger age, more advanced stage of dementia, and a diagnosis of DLB.

Background: Depression is a common behavioral and psychological symptom of Alzheimer's disease (AD). The aims of the present study were to determine the rate of depression in Taiwanese patients with AD using the National Institutes of Mental Health Provisional Criteria for Depression in AD (NIMH-dAD criteria) and to investigate the association of depression with other behavioral and psychological symptoms.Methods: A consecutive series of 302 AD patients registered in a dementia clinic were investigated in this study. All patients met the criteria of the National Institute of Neurological Disorders and Stroke–Alzheimer's Disease and Related Disorders Association for probable AD. The rates of depression were determined according to the criteria of the fourth edition of the Diagnostic and Statistical Manual of Mental Disorders for major depression (DSM-IV), the International Classification of Diseases-9-Clinical Modification (ICD-9-CM) for neurotic depression, the depression subscale of the Neuropsychiatric Inventory (NPI), and the NIMH-dAD criteria. Depression severity was assessed using the 17-item Hamilton Depression Rating Scale. The rates of depression determined by the NIMH-dAD criteria were compared with the rates derived from each of the other instruments. Other behavioral and psychological symptoms were assessed using NPI. A behavioral neurologist or a geriatric psychiatrist interviewed all the patients.Results: Using the NIMH-dAD criteria, it was found that 90 (29.8%) of the AD patients had depression, and all depressive symptoms in NIMH-dAD were significantly higher among depressed patients. Among other depression instruments, the frequency of depression was lowest using the DSM-IV major depression criteria (9.3%) and highest with the NPI depression subscale (54%). Behavioral and psychological symptoms determined with NPI were significantly higher among depressed patients in all domains except euphoria.Conclusions: This is the first study of depression in Taiwanese patients with AD using the NIMH-dAD criteria. Our findings suggest that comorbid depression is high in Taiwanese patients with AD. It is clinically important to note the high frequency of most behavioral and psychological symptoms among depressed AD patients.

Objective Several genetic variants have been found to increase the risk of restless legs syndrome (RLS). The aim of the present study was to determine if these genetic variants were also associated with the comorbidity of RLS and migraine in patients. Methods Thirteen single-nucleotide polymorphisms (SNPs) at six RLS risk loci ( MEIS1, BTBD9, MAP2K5, PTPRD, TOX3, and an intergenic region on chromosome 2p14) were genotyped in 211 migraine patients with RLS and 781 migraine patients without RLS. Association analyses were performed for the overall cohort, as well as for the subgroups of patients who experienced migraines with and without aura and episodic migraines (EMs) vs. chronic migraines (CMs). In order to verify which genetic markers were potentially related to the incidence of RLS in migraine patients, multivariate regression analyses were also performed. Results Among the six tested loci, only MEIS1 was significantly associated with RLS. The most significant SNP of MEIS1, rs2300478, increased the risk of RLS by 1.42-fold in the overall cohort ( p = 0.0047). In the subgroup analyses, MEIS1 augmented the risk of RLS only in the patients who experienced EMs (odds ratio (OR) = 1.99, p = 0.0004) and not those experiencing CMs. Multivariate regression analyses further showed that rs2300478 in MEIS1 (OR = 1.39, p = 0.018), a CM diagnosis (OR = 1.52, p = 0.022), and depression (OR = 1.86, p = 0.005) were independent predictors of RLS in migraine. Conclusions MEIS1 variants were associated with an increased risk of RLS in migraine patients. It is possible that an imbalance in iron homeostasis and the dopaminergic system may represent a link between RLS incidence and migraines.

Objectives: Morning headache has been considered as an accompanying symptom of obstructive sleep apnoea syndrome (OSAS). However the frequency, characteristics, predictors and impacts of morning headache in habitual snorers are not well defined. Methods: We studied consecutive patients with habitual snoring in a sleep laboratory using polysomnography. All patients were interviewed by a physician regarding the presence or absence of morning headache, migraine and insomnia. Each patient completed the Short Form-36 health survey (SF-36) and the Hospital Anxiety and Depression Scale (HADS). Morning headache was defined as headache on awakening ≥1 day/week for ≥6 months. Results: Of the 268 participants with habitual snoring, 63 (23.5%) had morning headache and 184 (69%) had OSAS. Patients with morning headache reported lower scores in all eight domains of the SF-36 than those without (difference: 10.6 to 29.7 points, all p ≤ 0.005). The independent predictors of morning headache were migraine (adjusted odds ratio (AOR) 6.3), insomnia (AOR 4.2), psychological distress (HADS ≥ 8) (AOR 3.9) and OSAS (AOR 2.6). Morning headache in 12 patients (19%) fulfilled the criteria for migraine attacks. Conclusions: Morning headache was common in habitual snorers and associated with a pervasive impairment of health-related quality of life. Migrainous features were not uncommon. Not only OSAS, but migraine, insomnia and psychological distress were also important predictors for morning headache, even in snoring patients.

Objective Migraine is comorbid with restless legs syndrome (RLS). However, the temporal association between these two episodic disorders remains elusive. The current study investigated the temporal relationship between migraine and RLS attacks. Methods Migraine patients with RLS were recruited from a headache clinic. Patients with symptomatic RLS, RLS mimics, daily headaches, or daily RLS attacks were excluded. The patients recorded their headaches and RLS attacks for two weeks in a diary. The severity of each headache or RLS attack was rated on a four-point (0−3) Likert scale. Logit-normal, random-effects models were employed to estimate the odds ratios (ORs) for the temporal association between migraine and RLS attacks. Results Thirty migraine patients with RLS (28 F/2 M, mean age 35.5 ± 9.0 years) completed the study. On the basis of 420 daily diary records, migraine attacks were associated with subsequent RLS attacks occurring on the same and next nights (OR = 6.94, 95% confidence interval (CI) = 4.39–11.0 and OR = 3.00, CI = 1.92–4.68; both p Conclusions Our study results showed a bidirectional triggering association between migraine and RLS attacks. The association was stronger and lasted longer for migraine triggering subsequent RLS than that for vice versa.

Background Discharge disposition planning is vital for poststroke patients. We investigated clinical factors associated with discharging patients to nursing homes, using the Taiwan Stroke Registry data collected from 39 major hospitals. Methods We randomly assigned 21,575 stroke inpatients registered from 2006 to 2008 into derivation and validation groups at a 3-to-1 ratio. We used the derivation group to develop a prediction model by measuring cumulative risk scores associated with potential predictors: age, sex, hypertension, diabetes mellitus, heart diseases, stroke history, snoring, main caregivers, stroke types, and National Institutes of Health Stroke Scale (NIHSS). Probability of nursing home care and odds ratio (OR) of nursing home care relative to home care by cumulative risk scores were measured for the prediction. The area under the receiver operating characteristic curve (AUROC) was used to assess the model discrimination against the validation group. Results Except for hypertension, all remaining potential predictors were significant independent predictors associated with stroke patient disposition to nursing home care after discharge from hospitals. The risk sharply increased with age and NIHSS. Patients with a cumulative risk score of 15 or more had an OR of 86.4 for the nursing home disposition. The AUROC plots showed similar areas under curves for the derivation group (.86, 95% confidence interval [CI], .85-.87) and for the validation group (.84, 95% CI, .83-.86). Conclusions The cumulative risk score is an easy-to-estimate tool for preparing stroke patients and their family for disposition on discharge.

Ophthalmoplegic migraine (OM) is a rare headache disorder, which usually starts in childhood but sometimes first appears in adulthood. The typical clinical presentation is migraine-like headache accompanied or followed by transient extraocular muscle paresis, mostly involving the oculomotor nerve but sometimes the abducens or trochlear nerves. Ophthalmoplegia recovers spontaneously within weeks. OM was initially classified as a migraine variant in the International Classification of Headache Disorders, 1st edition (ICHD-1) (1). In 1992, Mark et al. (2) described the first OM patient with reversible gadolinium enhancement of the oculomotor nerve on magnetic resonance imaging (MRI). Thereafter, several case reports followed. Because of the self-limiting clinical characteristics, the disease was suspected to be related to recurrent demyelinating neuropathy. In 2004, the International Headache Society (IHS) Classification Committee moved this headache disorder to the group of ‘cranial neuralgias’ in the International Classification of Headache Disorders, 2nd edition (ICHD-2) (3); nonetheless, the terminology of ‘ophthalmoplegic migraine’ remained in use (Table 1). In this issue of Cephalalgia, Akimoto et al. (4) report on a 54-year-old man, who experienced attacks of OM for more than 45 years. The MRI examination in the acute phase showed an enhanced nodular lesion in the root exit zone (REZ) of the left oculomotor nerve. Because the clinical symptoms were progressive, a biopsy was performed. Intriguingly, the biopsy did not show inflammatory cell infiltration or demyelination but neuromuscular hamartoma. This finding obviously does not support a prior belief that the MRI findings imply demyelination as the underlying cause for OM. Even though enhancement of the cisternal portion of the oculomotor nerve is the most common MRI finding for OM, it is not specific. Certain causes can present similar pictures, such as trauma, inflammation, demyelination, small vessel ischemia, tumor (schwannoma, lymphoma, hemangioma and carcinomatous meningitis), postviral syndrome and systemic lupus erythematosus.

The Treatment Guideline Subcommittee of the Taiwan Headache Society evaluated both the acute and the preventive treatments for cluster headache now being used in Taiwan, based on the principles of evidence- based medicine. We assessed the quality of clinical trials and levels of evidence, and referred to other treatment guidelines proposed by other countries. Throughout several panel discussions, we merged opinions from the subcommittee members and proposed a consensus on the major roles, recommended levels, clinical efficacy, adverse events and cautions of clinical practice regarding acute and preventive treatments of cluster headache. The majority of Taiwanese patients have episodic cluster headaches, because chronic clusters are very rare. Cluster headache is characterized by severe and excruciating pain which develops within a short time and is associated with ipsilateral autonomic symptoms. Therefore, emergency treatment for a cluster headache attack is extremely important. Within the group of acute medications currently available in Taiwan, the subcommittee determined that high-flow oxygen inhalation has the best evidence of effectiveness, followed by intranasal triptans. Both are recommended as first-line medical treatments for acute attacks. Oral triptans were determined to be second-line medications. For transitional prophylaxis, oral corticosteroids are recommended as the first-line medication, and ergotamine as the second-line choice. As for maintenance prophylaxis, verapamil has the best evidence and is recommended as the first-line medication. Lithium, melatonin, valproic acid, topiramate and gabapentin are suggested as the second-line preventive medications. Surgical interventions, including occipital nerve stimulation, deep brain stimulation, radiofrequency block of the sphenopalatine ganglion, percutaneous radiofrequency rhizotomy and trigeminal nerve section, are invasive and their long-term efficacy and adverse events are still not clear in Taiwanese patients; therefore, they are not recommended currently by the subcommittee. The transitional and maintenance prophylactic medications can be used together to attain treatment efficacy. Once the maintenance prophylaxis achieves efficacy, the transitional prophylactic medications can be tapered gradually. We suggest the corticosteroids be used within two weeks, if possible. The duration of maintenance treatment depends on the individual patient's clinical condition, and the medications can be tapered off when the cluster period is over.

Background An association between restless legs syndrome and migraine has been reported recently. The clinical correlates and impact of comorbidity of restless legs syndrome (RLS) are not fully described in patients with migraine. Objectives To investigate the frequency of RLS among different primary headache disorders, and its impact and clinical correlates in migraine patients. Methods Consecutive patients with migraine, tension-type headache (TTH) and cluster headache (CH) were recruited in a headache clinic. Each patient completed the Migraine Disability Assessment (MIDAS) questionnaire, Hospital Anxiety and Depression Scale (HADS), Pittsburgh Sleep Quality Index (PSQI) and International RLS Study Group (IRLSSG) Rating Scale. RLS was diagnosed using the IRLSSG criteria. Results A total of 1041 patients (migraine 772, TTH 218, CH 51) completed the study. The frequencies of RLS in patients with migraine (11.4%) was higher than in those with TTH (4.6%) or CH (2.0%) (p=0.002). In migraine patients, comorbidity with RLS was associated with higher frequencies of photophobia, phonophobia, exacerbation due to physical activities, vertigo, dizziness, tinnitus and neck pain, and higher mean scores of MIDAS and HADS. Migraine patients with RLS had a poorer sleep quality (Pittsburgh Sleep Quality Index score 11.1±4.1 vs 8.9±4.0, p Conclusion An association between migraine and RLS among different primary headache disorders is demonstrated. Comorbid RLS in migraine patients worsened sleep quality. A shared underlying mechanism may account for the correlates between migraine features and comorbid RLS.

To identify the possible anatomic sites and risk factors for the development of confusion or delirium in patients with posterior cerebral arterial (PCA) infarction.Twenty-nine patients aged 34-86 years with PCA infarction were divided into two groups: one with and the other without perturbed mentation. The clinical and laboratory data, including neuroimages, were retrospectively reviewed. Student-t, chi-square and Fisher's exact tests were performed for data analysis.Confusion or delirium tended to develop in the left (10/13) or bilateral (5/5) PCA infarction as compared to the right PCA infarction (3/15) (P0.05) and medial occipital-temporal gyri involvement was crucial for its development (P0.05). The results were also noted in the patients with first-ever stroke. Diabetes mellitus was the sole biochemical factor to be associated with confusion or delirium (P0.01).The involvement of the medial occipito-temporal gyri, especially on the left side was the pivotal factor for the development of confusion or delirium in patients with PCA infarction. Higher prevalence of diabetes mellitus was also observed in the group with mental perturbation.