Potentially Unsafe Herb-drug Interactions Between a Commercial Product of Noni Juice and Phenytoin- A Case Report.

PURPOSE: To report the unsafe herb-drug interactions between a commercial product of noni juice and phenytoin in a human case. CASE REPORT: A 49-year-old-male has been treated with phenytoin for epilepsy for more than ten years. In spite of his medication adherence, persistent sub-therapeutic phenytoin levels, which were sometimes from low to undetectable, with the result of having poor seizure control were noted as the noni fruit juice was co-administered daily. The possible mechanism is speculated to be due to noni juiceinduced cytochrome P-450 2C9 metabolism of phenytoin. Owing to many beneficial effects of noni juice, the patient was unwilling to accept our advice to quit taking it. Clobazam treatment was added, and with gradually reducing the amount of juice drunk over six months, the patient's epilepsy has been well controlled. Now only auras along with sometimes minor partial seizures occur, but no major attack has been reported for more than one year. CONCLUSION: Phenytoin had been commonly used for seizure control worldwide and nearly half of patients with epilepsy had received complementary and alternative medicine in Taiwan. Thus, this report is significantly important for clinicians to be aware of the interaction between antiepileptic drugs and some herbs like noni juice. Moreover, as far as we know, this is a rare human case that is reported to disclose this unfavorable herb-drug interaction.

Association between MIF gene polymorphisms and carotid artery atherosclerosis.

Atherosclerosis is a chronic inflammatory disorder. Macrophage migration inhibitory factor (MIF) is a potent cytokine that plays an important role in the regulation of immune responses. Polymorphisms including five- to eight-repeat CATT variants ((CATT)(5-8)) and G-173C in the promoter region of the MIF gene are associated with altered levels of MIF gene transcription. The purpose of the study is to investigate the relationship between promoter polymorphisms of the MIF gene and the severity of carotid artery atherosclerosis (CAA). The severity of CAA was assessed in 593 individuals with a history of ischemic stroke by using sonographic examination, and the MIF promoter polymorphisms of these individuals were genotyped. The carriage of (CATT)7 (compared to genotypes composed of (CATT)5, (CATT)6, or both), carriage of C allele (compared to GG), and carriage of the haplotype (CATT)7-C (compared to genotypes composed of (CATT)5-G, (CATT)6-G, or both) were significantly associated with an increase in the severity of CAA. We conclude that polymorphisms in the MIF gene promoter are associated with CAA severity in ischemic stroke patients. These genetic variants may serve as markers for individual susceptibility to CAA.

Sleep quality and daytime sleepiness in patients with epilepsy.

PURPOSE: Poor sleep quality and excessive daytime sleepiness (EDS) are common complaints of patients with epilepsy (PWE). This study aimed to evaluate possible predisposing factors for EDS and subjective sleep quality in PWE. METHODS: One hundred and seventeen PWE were enrolled and 30 healthy volunteers were recruited as controls. EDS was evaluated by the Epworth Sleepiness Scale (ESS) while the Pittsburg Sleep Quality Index (PSQI) was designed to evaluate overall sleep quality. Clinical baseline data and possible risk factors for sleep disturbances were included in the statistical analysis. RESULTS: Twenty percent of PWE (23/117) and 7% of healthy controls (2/30) had excessive daytime sleepiness (p = 0.007). PWE had significantly higher PSQI total scores (6.5 ± 3.8 vs. 3.7 ± 2.9), sleep latency (1.2 ± 0.8 vs. 0.6 ± 0.7) and sleep efficiency (0.8 ± 1.0 vs. 0.0 ± 0.2) scores than the controls (all p < 0.001). A significantly higher prevalence of poor sleep quality was found in the partial seizure, non-seizure-free, and polytherapy groups (all p < 0.05). Multivariate analysis showed that poor seizure control was the strongest independent risk factor for poor sleep quality (OR = 2.43, 95% CI = 1.15-5.15, p = 0.02). CONCLUSION: EDS and poor sleep quality are common in PWE and are closely related to partial epilepsy, poor seizure control, and polytherapy. These relationships must be addressed in order to provide the best management of sleep disturbance in such patients.

Kennedy disease mimics amyotrophic lateral sclerosis: a case report.

Kennedy disease (KD) is an X-linked inherited motor neuron disease that is often accompanied by androgen insensitivity. Its estimated incidence in the US is approximately 1 case in 40,000 men. KD has also been reported in individuals of different racial backgrounds, especially in Japanese but the prevalence rate in Taiwan has not been fully investigated. Here we report a case of KD definitely diagnosed by abnormal expansion of a polymorphic tandem cytosine-adenine-guanine (CAG) triplet repeat in the first exon of the androgen receptor gene. The direct genotyping from polymerase chain reaction product is subsequently performed utilizing capillary electrophoresis. The patient's neurological conditions mimic amyotrophic lateral sclerosis (ALS). Since these two diseases have different etiologies and prognosis, it reminds us the necessity to rule out KD in face with a suspected male case of ALS.

Right anterior cingulate cortex infarction and transient speech aspontaneity.

BACKGROUND: According to recent functional studies, the medial frontal lobe of the dominant hemisphere plays a role in both word generation and speech initiation. To our knowledge, speech arrest with intact facial expression secondary to the right anterior cingulate cortex (ACC) lesion has not been previously reported. OBJECTIVE: To report 2 cases of speech initiation difficulties associated with a stroke of the right anterior cingulate gyrus with magnetic resonance imaging with tractography results. DESIGN: Two case reports. SETTING: Inpatient neurology clinic at a university medical center. Patients Two women who had acute and transient speech initiation problems. RESULTS: Speech evaluation revealed pure speech initiation difficulties with intact facial praxis and expression. In the patient who could be tested, writing ability was preserved. In addition to acute right ACC infarction, the magnetic resonance imaging also revealed anterior corpus callosum and/or posterior corpus callosum involvement. Tractography in patient 2 revealed fibers from the right ACC that would cross to the contralateral side. Reduced fiber numbers connecting the right supplementary motor area with the ACC were also observed, which differed from the left ACC tractography. CONCLUSIONS: To our knowledge, this is the first case series of right ACC stroke with transient speech initiation problems. Because of the rare findings of the tractography, we suggest that in some patients, speech initiation required the participation of the right ACC in addition to the language network of the left hemisphere.

The role of oxalate in star fruit neurotoxicity of five-sixths nephrectomized rats.

To investigate the role of oxalate in star fruit neurotoxicity, rats were given star fruit or oxalate after a sham operation or modified five-sixths nephrectomy; namely, star fruit (SC) or oxalate (OxC) for sham-operated rats and star fruit (SNx), calcium gluconate treated star fruit juice (SCaNx), or oxalate (OxNx) for nephrectomized rats. After feedings, none of the rats in SC, OxC, and SCaNx groups developed movement disorders or died, while all rats in SNx group and OxNx group presented movement disorders and two rats in SNx group and four rats in OxNx group died within minute to hour after development of myoclonic jerk and/or tonic-clonic convulsion. The plasma oxalate levels rose significantly only in the SNx group and OxNx group that also presented clusters of generalized spike-waves in the electroencephalographic recordings. In conclusion, oxalate may play a key role in star fruit neurotoxicity in nephrectomized rats and probably in uremic patients.

The relation between plasma homocysteine level and cardiovascular risk factors in cerebral ischemia.

PURPOSE: Hyperhomocysteinemia (HHcy) is associated with a higher risk of cerebral ischemia and other vascular thrombosis. Homocysteine is greatly influenced by a broad spectrum of physiological and pathological conditions but the confounding factor for HHcy is unknown in our population, especially in normocreatininemic individuals. It is our aim in this study to elucidate the relation between homocysteine and cardiovascular risk factors, and also describe the distribution of plasma homocysteine level in cerebral ischemia patients with normal serum creatinine level. METHODS: A retrospective study was conducted to understand the frequency of HHcy in cerebral ischemia patients, and the confounding cardiovascular risk factors in HHcy. Patients were classified into two groups by their plasma homocysteine levels; group I patients were those whose level was > or = 12 microM/L whereas group II < 12 microM/L. RESULTS: A total of 218 patients were enrolled. Their plasma homocysteine level ranged from 3.57 to 46.37 microM/L (mean: 10.01 +/- 5.03 microM/L). Group I included 45 patients whereas group II 173 patients. The frequency of hypertension, diabetes mellitus and cardiac disease, as well as age, aminotransferases, total cholesterol, triglyceride, albumin, hematocrit, hemoglobin and leucocyte count did not differ between group I and II patients, except serum creatinine level was higher in group I patients (p < 0.01). Serum creatinine level correlated directly to and was an independent predictor for the plasma homocysteine level. CONCLUSIONS: HHcy is common in our cerebral ischemia patients. Since renal function is a determinant for HHcy even in normocreatininemic patients, as a cardiovascular risk factor which detriments the renal function, it should be regularly monitored as HHcy is amenable for treatment.

Ictal paralysis with tonic eye gazing mimicking a pontine infarction.

PURPOSE: Concomitant positive and negative motor phenomena in a single seizure have not been reported before. METHOD: We used an extensive history review, neurological examination, EEG, MRI and SPECT study to demonstrate a rare combination of motor presentations as an ictal phenomenon. RESULT: A 64-year-old male was brought to the emergency room with dizziness, progressive drowsiness and left hemiparesis. A spontaneous eye deviation to the left side with nystagmus was observed. A right pontine lesion was tentatively diagnosed. However, a focal motor seizure of the patient's left face and limbs occurred 3.5h later. A brain MRI revealed a high signal in the right amygdala, hippocampus and thalamus, instead of the pons. An EEG showed periodic epileptic discharges in the right posterior temporal parietal region. Regional hyperperfusion was found by brain SPECT. The level of consciousness improved dramatically after adequate phenytoin treatment. CONCLUSION: A posterior temporal-parietal seizure can present with a prolonged ictal paralysis, a positive ocular nystagmoid deviation and an altered level of consciousness. The EEG is essential for a correct diagnosis, especially with a negative or an unexplainable MRI study. The SPECT has an additional role for the differential diagnosis.

Neurologic and non-neurologic predictors of mortality in ischemic stroke patients admitted to the intensive care unit.

BACKGROUND/PURPOSE: Patients with severe strokes may have different associated medical comorbidities from those with mild strokes. This study evaluated the neurologic and non-neurologic medical predictors of mortality in patients with severe cerebral infarction in the acute stage. METHODS: Patients admitted to a neurologic intensive care unit (ICU) due to cerebral infarction were included. Neurologic and non-neurologic predictors for in-unit mortality were determined by logistic regression analyses. Two models using (A) neurologic factors and (B) combined neurologic and non-neurologic factors as mortality predictors were developed. The performance of the models in predicting overall, neurologic and non-neurologic mortalities was compared by areas under the receiver-operating characteristic curves (AUC) of the derived regressive equations. RESULTS: Of 231 patients with cerebral infarction admitted to the ICU, 34 (14.7%) died during ICU stay. Conscious state and acute physiologic abnormalities were significant predictors of mortality. The length of ICU stay in patients with non-neurologic mortality was longer than in those with neurologic mortality (p = 0.044). The AUC of Model B was larger than that of Model A in predicting overall (0.768 +/- 0.045 vs. 0.863 +/- 0.033, p = 0.005) and non-neurologic mortalities (0.570 +/- 0.073 vs. 0.707 +/- 0.074, p = 0.009), while there was no difference in predicting death from neurologic causes (0.858 +/- 0.044 vs. 0.880 +/- 0.032, p = 0.217). CONCLUSION: Impaired consciousness and acute physiologic abnormalities are independent predictors of mortality for severe ischemic stroke during the acute stage. Neurologic factors predict early mortality from intrinsic cerebral dysfunction, while non-neurologic factors, especially the associated physiologic abnormalities, predict late mortality from medical complications.

Vigabatrin-attributable visual field defects in patients with intractable partial epilepsy.

INTRODUCTION: Vigabatrin (VGB) is implicated to cause visual field defects. We estimated the prevalence, described the characteristics and investigated the risk factors of VGB-attributable visual field defects. METHODS: Patients with intractable partial epilepsy under VGB add-on treatment received static perimetric examinations. Visual field charts were reviewed and interpreted using a three-grade system. Clinical features and therapeutic courses were analyzed for possible risk factors. RESULTS: Visual field defects in at least one eye were detected in 27 (79%) of 34 patients. In the subgroup of 27 patients with both eyes reliably tested, 16 (59%) had bilateral defect, among whom seven were severely involved and showed nasally dominant, crescent or concentric defect. Five patients had unilateral visual field defects. Four out of the 27 affected patients reported blurred vision. No statistically significant differences were noted between patients with and without visual field defects in terms of gender, age, duration or etiology of the epilepsy, and duration, maximum daily dose, or cumulative dose of VGB. CONCLUSIONS: There was a high prevalence of VGB-attributable visual field defects. No risk factors could be identified. Routine initial and regular follow-up of visual field examination, especially that focusing within a range of central fixation to 60 degrees, should be performed in patients on VGB.

Botulinum toxin type A treatment for Parkinsonian patients with moderate to severe sialorrhea.

PURPOSE: To investigate the effect of botulinum toxin type A (BTX-A; Botox) in reducing saliva in patients with Parkinsonism. METHODS: Fifteen patients with clinical diagnosis of idiopathic Parkinson's disease, dementia with Lewy bodies, or multiple system atrophy were enrolled in this open clinical trial. A total of 40-unit dose of Botox was injected into the bilateral parotid and submandibular glands. Objective measuring of saliva production with dental rods, subjective Drooling Score, personal impression of clinical improvement, and the duration of response were used for the global assessment of sialorrhea after BTX-A treatment. RESULTS: All patients showed objective reduction in saliva production following BTX-A treatment and the mean production was reduced at a significant level. The severity of sialorrhea assessed by Drooling Score was 5.87 +/- 0.92 (range: 5-8) and 3.60 +/- 1.18 (range: 2-6) respectively (p<0.001) before and after BTX-A injection. The mean duration of BTX-A response extended for 16.3 +/- 5.7 weeks (range: 5-24). No severe adverse effect nor worsening of existing dysphagia was observed in all Parkinsonian patients. CONCLUSIONS: Parkinsonian drooling may undermine patient's health and daily activity. BTX-A local injection is a safe and effective measure in counteracting sialorrhea, even in patients associated with moderate dysphagia.

Neurobehavioral changes in Taiwanese lead-exposed workers.

OBJECTIVE: The dysfunction of the central nervous system (CNS) caused by lead exposure was evaluated. METHODS: Workers who have been exposed to lead for at least 3 years and have been informed of having elevated blood lead levels (BLLs) were recruited. According to their current BLLs, 33 and 28 males were assigned to the medium (40-80 microg/dL) and low (<40 microg/dL) BLLs groups, respectively. Sixty-two nonexposed healthy men served as the control group. Their neurobehaviors were examined by a computerized evaluation system. RESULTS: Significantly impaired neurobehavioral functions were shown in the medium BLLs group, which included slow performance of psychomotor tasks, impaired processing of visual-spatial information, reduced memory and learning functions, low performance accuracy, slow execution of responses, and poor attentional control. CONCLUSIONS: Subtle CNS dysfunction could be detected from lead-exposed workers who have no obvious neurologic and cognitive deficits.

The impact of SARS on epilepsy: the experience of drug withdrawal in epileptic patients.

BACKGROUND: During the 2003 severe acute respiratory syndrome (SARS) outbreak, many patients avoided hospital visit because of fear of infection. Antiepileptic drug (AED) withdrawal is a risk factor for seizure recurrence. Therefore, seizure control during the SARS outbreak is a good model for examining the impact of drug withdrawal in seizure control. METHODS: All seizures experienced by each patient before, during, and after the SARS outbreak periods were registered in each patient's seizure diary. The patients were divided into four groups according to the presence of drug withdrawal as well as seizure attack. In each group, seizures occurring during three different periods were compared. Risk factors for seizure recurrence were also examined. RESULTS: Of 227 cases, 49 stopped taking medication during the outbreak. Among them, 28 suffered seizure attacks during AED withdrawal. Four cases developed cluster attacks and two cases had status epilepticus after AED withdrawal. AED withdrawal produced a significant increase in seizure frequency. The major risk factors for withdrawal seizures were symptomatic etiologies, polytherapy and non-seizure free before AED withdrawal. CONCLUSIONS: The SARS outbreak adversely affected seizure control because of AED withdrawal. Patients with polytherapy, non-seizure free and symptomatic etiologies were more susceptible to recurrence of seizures after AED withdrawal.

Fatal meningoencephalitis caused by disseminated strongyloidiasis.

A middle-aged aboriginal man with a history of alcoholism and gastrectomy was diagnosed as having bacterial meningoencephalitis based on the typical clinical manifestations, laboratory findings, and treatment responses. During the recovery stage, he developed consciousness disturbance, seizures, severe diarrhea, and respiratory failure that led us to search for other possibility of the diagnosis. The eosinophilia and repeated stool examinations helped us to make the diagnosis of disseminated strongyloidiasis. In this patient the initial bacterial meningitis was followed by S. stercoralis hyperinfection. Despite treatment with strong antimicrobial agents, the patient died. This case could serve as a reminder to physicians to be alert for strongyloidiasis superimposed on bacterial meningitis.

Serial changes in platelet activation in patients after ischemic stroke: role of pharmacodynamic modulation.

BACKGROUND AND PURPOSE: Enhanced platelet activity has previously been reported in the acute phase after ischemic stroke. We tested the hypothesis that activated platelets (expressed by CD62p) are substantially increased in the acute stage after a stroke and decrease thereafter, and that antiplatelet therapies can suppress CD62p expression. METHODS: We serially examined platelet CD62p expression using flow cytometry after acute ischemic stroke in 87 consecutive patients. The CD62p expression was also evaluated in 20 healthy volunteers and 33 at-risk control subjects. RESULTS: CD62p expression was significantly higher in the acute phase after ischemic stroke than in normal and at-risk control subjects (both P<0.0001). CD62p expression decreased to a significantly lower level on day 21, and to a substantially lower level on day 90. CD62p expression was not significantly suppressed by warfarin. However, CD62p expression was significantly suppressed by aspirin treatment (P=0.024) and more substantially suppressed by clopidogrel (P<0.0001) on day 90. Furthermore, only clopidogrel treatment (P=0.0016) was significantly independently associated with decreased CD62p expression on day 90. CONCLUSIONS: Platelet activation was significantly increased in acute ischemic stroke and substantially decreased thereafter. The lesser long-term pharmacodynamic potency of aspirin relative to clopidogrel raises the prospect of the need for more effective antiplatelet agents or a synergistic combination therapy for stroke prevention in the future.

Risk factors of oxcarbazepine-induced hyponatremia in patients with epilepsy.

OBJECTIVES: To determine the risk factors for hyponatremia in patients with epilepsy treated with oxcarbazepine (OXC). METHODS: Seventy-three adult patients with epilepsy aged older than 17 years who received OXC therapy were enrolled in this study. Patients who had hyponatremia due to any etiology before OXC therapy and patients receiving OXC therapy for nonepileptic disorders were excluded from this study. The baseline level of serum sodium of the patients was measured before the OXC therapy. During OXC therapy, serum sodium levels were measured at least once per 3 months. RESULTS: The frequency of hyponatremia (Na+, ≤ 134 mEq/L) was 24.7% (n = 18) in patients with OXC therapy, and 8.2% (n = 6) of the patients had severe hyponatremia (Na+, ≤ 128 mEq/L). The degree of decline in serum sodium concentration was significantly negatively correlated with the dosage of OXC. An increase of 1 mg in the dosage of OXC increased the risk of hyponatremia by 0.2%. Moreover, increasing the number of combination antiepileptic drugs increased the risk of hyponatremia. CONCLUSIONS: Higher dosages of OXC and the number of combination antiepileptic drugs may increase the risk of OXC-induced hyponatremia in patients with epilepsy. Most patients are asymptomatic, but if symptoms of hyponatremia, such as headache, general malaise, gait disturbance, and somnolence, are suspected, the serum sodium level should be measured; it may be necessary to decrease the OXC dose or to discontinue the drug.

Association of plasma homocysteine concentration with cerebral white matter hyperintensity on magnetic resonance images in stroke patients.

BACKGROUND: Homocysteine (Hcy) has been recognized as a risk factor for atherosclerosis. White matter hyperintensity (WMH) on MRI has been regarded as a hallmark for cerebral small vascular disease. The study is to investigate the relationship between plasma Hcy level and WMH on a hospital-based cohort of Taiwanese stroke patients. METHODS AND RESULTS: A total of 352 consecutive stroke patients (64.7+/-11.2 years) were included. Severity of WMH was semi-quantitatively evaluated with a scoring system. The top WMH score tertile was defined as severe white matter change (sv-WMH). Associations between Hcy tertile levels and sv-WMH were examined, adjusting for demographics and atherosclerosis risk factors. Subjects in the top Hcy tertile (>10.25 micromol/L) had higher WMH scores and prevalence of sv-WMH than those in the middle and in the bottom tertile. The adjusted odds ratio of having sv-WMH was 2.04 (95% confidence interval 1.20-3.47, p=0.008) for the top Hcy level tertile than for the lower two tertiles combined. CONCLUSION: Hcy is a risk factor for cerebral white matter lesion in stroke patients. Even mild hyperhomocysteinemia can significantly increase severity of cerebral microangiopathy.

Cerebellar hemorrhage provoked by combined use of nattokinase and aspirin in a patient with cerebral microbleeds.

Nattokinase is used as a health-promoting medicine for preventing thrombosis due to its fibrinolytic activity. Cerebral microbleed is remnant of blood extravasations from the damaged vessels related to cerebral microangiopathies. We report a patient, having used aspirin for secondary stroke prevention, who had an acute cerebellar hemorrhage after taking nattokinase 400 mg daily for 7 consecutive days. In addition to the hemorrhagic lesion, multiple microbleeds were demonstrated on brain MR images. We suggest that nattokinase may increase risk of intracerebral hemorrhage in patients who have bleeding-prone cerebral microangiopathy and are receiving other antithrombotic agent at the same time.

Time course of platelet activation and von Willebrand factor in patients with non-valvular atrial fibrillation after ischemic stroke.

BACKGROUND: The present study investigated serial changes in platelet activation (expressed by CD62p) and von Willebrand factor (VWF), and the correlation between increased CD62p expression, VWF and brain infarct volume (BIV: measured by magnetic resonance imaging), and prognostic determinants in non-valvular atrial fibrillation (NVAF) patients after acute ischemic stroke (IS). METHODS AND RESULTS: CD62p expression and plasma VWF concentrations were serially measured (<48 h, on days 7, 21 and 90) using flow cytometry and enzyme-linked immunosorbent assay, respectively after acute IS in 61 NVAF patients. CD62p expression and VWF concentrations were also examined in 50 NVAF-risk control and 30 healthy individuals. The VWF concentration had no significant changes at 4 intervals among the patients and did not differ among 3 groups at acute stroke phase. CD62p expression was significantly higher in the acute phase after IS than in both control groups (both p<0.0001). However, CD62p expression declined to a significantly lower level on day 7 and to a substantially lower level thereafter (p<0.0001). CD62p expression did not differ on day 90 in the 3 groups (both p>0.5). Linear regression analysis showed that BIV and modified Rankin scale score (>3) were independently associated with increased CD62p expression (<48 h) (both p<0.01). Furthermore, the Cox proportional hazards model showed that BIV was the only independent predictor of intermediate-term (8.8+/-4.4 months) combined recurrent stroke and death. CONCLUSIONS: The CD62p expression, which reflected increased BIV, was significantly increased in NVAF patients in acute-phase IS and substantially declined thereafter. The BIV was predictive of unfavorable intermediate-term clinical outcomes.

Magnetic resonance imaging and single-photon emission computed tomography changes in hypoglycemia-induced chorea.

We present two case studies, one of generalized chorea and one of hemichorea, both after severe hypoglycemia episodes. Both cases showed hyperperfusion in their SPECT scans. The MRI and SPECT findings serve as clues regarding the role of basal ganglion dysfunction associated with chorea.