[Show abstract][Hide abstract] ABSTRACT: We report a patient of 68-year-old woman who developed numbness of feet in 2008. Ataxic gait disturbance, truncal ataxia, muscle weakness of lower limbs have gradually appeared and she couldn't walk without assistance in 2013. Her cognitive function declined subacutely in 2014. When she was admitted to our hospital, it was difficult to fully evaluate her neurological symptoms and cognitive function. The tendon reflex were absent and Babinski reflex showed positive in both sides of the lower limbs. Diffusion weighted image of MRI showed high intensity in cerebrocortical area, and variation P102L prion protein gene mutation was detected. We diagnosed her with Gerstmann-Sträussler-Scheinker (GSS) disease. Cerebellar symptom such as ataxic gait occurs as the initial manifestation in 90% of patients with GSS disease. Her initial symptom was numbness of lower limbs and cerebellar symptom gradually appeared during the course of disease. In addition, her cognitive function declined six years after the onset. This case presented atypical clinical course as described above. Consequently, it led to diagnostic delay in GSS disease.
[Show abstract][Hide abstract] ABSTRACT: We report 10 cases with arterial ischemic stroke (AIS) with nephrotic syndrome (NS), and clarified its incidence and clinical characteristics. The patients having albumin less than 3.0g/dl and serum cholesterol greater than 250mg/dl at the same time were retrospectively screened from 11,161cases of stroke. Furthermore, the patients of AIS showing heavy proteinuria were selected. The 10 cases were diagnosed as AIS with NS. Its incidence was 0.09% of all kinds of stroke and 0.12% of AIS. Their subtypes were 6 large-artery atherosclerosis, 3 small-vessel occlusion, and 1 cardioembolism. We carried out a retrospective cohort study to assess the association between NS and atherosclerosis progression in AIS patients. Seven AIS patients with NS due to diabetic nephropathy (cases; NS group) were compared with patients with AIS and diabetes mellitus (DM) without NS (control group). Control group subjects were matched in a 2:1 ratio to cases by age, sex, use of medications for DM, and hemoglobin A1c (HbA1c) level. The NS group had high cerebral artery atherosclerosis scores, especially in the anterior circulation. The NS group demonstrated atherosclerosis of the internal carotid and lower extremity arteries, although there were no statistical differences between the two groups. Study subjects had high serum fibrinogen and D-dimer levels, suggesting that AIS patients with NS have a greater degree of hypercoagulability than AIS patients without NS.
[Show abstract][Hide abstract] ABSTRACT: The number of patients with late-onset myasthenia gravis (MG) among patients ≥50 years has been increasing recently. We encountered three patients who developed elderly-onset MG at a particularly advanced age (≥80 years). All were female and positive for anti-acetylcholine receptor antibodies. About 4 years have passed since MG onset in all three patients and symptoms have been controlled without recurrence using a combination of oral low-dose prednisolone and tacrolimus. As many cases of elderly-onset MG do not require strong immunosuppression, we recommend minimum immunosuppressive treatment to avoid adverse events, particularly in patients at an advanced age of ≥80 years.
[Show abstract][Hide abstract] ABSTRACT: We herein report a case of Human T-lymphotropic virus type-I (HTLV-I)-associated myelopathy with bulbar palsy-type amyotrophic lateral sclerosis-like symptoms. A 52-year-old woman developed dyslalia at approximately 40 years of age, which slowly progressed. She presented with muscular atrophy and increased tendon reflexes of the extremities as well as bulbar palsy, from which motor neuron disease was suspected. Cerebrospinal fluid (CSF) testing revealed no abnormalities except for an elevated neopterin concentration at 143.17 pmol/mL (normal ≤30 pmol/mL). Her serum and CSF anti-HTLV-I antibody titers were also high. Intravenous infusions of methylprednisolone decreased the CSF neopterin concentration to 50.33 pmol/mL. Subsequent oral prednisolone therapy was effective in alleviating the symptoms.
No preview · Article · May 2015 · Internal Medicine
[Show abstract][Hide abstract] ABSTRACT: BackgraoudThere are two formulation of levodopa, levodopa/benserazide 100/25 mg and levodopa/carbidopa 100/10 mg in Japan and a few other countries, which have been generally regarded as interchangeable in Parkinson's disease (PD) treatment.AimWe investigated the pharmacokinetics of levodopa in the two kinds of levodopa/DCI (benserazide or carbidopa) formulation to study their equivalenceMethods
Population pharmacokinetic analysis was conducted using levodopa data from the healthy subject study and, additionally, for 70 plasma concentration data points from PD patients receiving either levodopa/DCI combination in clinical practice.ResultsIn healthy subjects, mean±SD plasma levodopa Cmax and AUC0-3hr (512±139 vs 392±49 μmol•hr/L, P < 0.05) were significantly higher after levodopa/benserazide compared to levodopa/carbidopa. Levodopa Tmax and t1/2 were not significantly different comparing the respective formations. Levodopa pharmacokinetic parameters were the same between the PD patients and healthy subjects except for levodopa apparent clearance which was about two-thirds lower in PD patients compared to healthy subjects for both levodopa/DCI combinations, which may result in higher levodopa AUC in patients with Parkinson's disease than in healthy volunteers.Conclusion
Levodopa pharmacokinetics differ after administration of levodopa/benserazide and levodopa/carbidopa. This information may be useful for adjustment of medication in PD patients especially with motor complications.This article is protected by copyright. All rights reserved.
[Show abstract][Hide abstract] ABSTRACT: A 53-year-old woman was admitted to our hospital because of gait disturbance and paresthesia of the lower extremities. She also had marked deep sense impairment in her lower limbs. Cervical MRI showed a longitudinally extensive spinal cord lesion of the dorsal column at levels C1-T11. The findings of cerebrospinal fluid examination, including the IgG index (0.65), were normal. Serum anti-AQP4 antibody was negative, but anti-amphiphysin antibody was positive. Electrophysiological examinations suggested the presence of lesions in the dorsal column of the spinal cord and dorsal root ganglion (DRG). Enlargement of and fluorodeoxyglucose accumulation in her left parasternal lymph node was observed on contrast-enhanced CT and PET-CT, respectively. The lymph node biopsy was underwent by using thoracoscopy. The metastasis of carcinoma was pathologically confirmed. Although the primary tumor was not detected on PET-CT re-examination, immunostaining of the biopsied lymph node specimen was positive for both the progesterone receptor and estrogen receptor. On the basis of these findings, the patient was diagnosed with paraneoplastic neurological syndrome due to potential breast cancer. The disorder is an immunological subacute sensory neuropathy with a longitudinally extensive spinal cord lesion of the dorsal column and a DRG lesion.
No preview · Article · Aug 2014 · Rinsho shinkeigaku = Clinical neurology
[Show abstract][Hide abstract] ABSTRACT: We report two cases of cerebral venous thrombosis as a complication of nephrotic syndrome. No urine protein or kidney disease was noted in either case. The patients were diagnosed with nephrotic syndrome after admission to our hospital. Case 1: The patient was a 46-year-old man. He experienced headache and vomiting the day after he drank heavily. Contrast brain computed tomography (CT) and magnetic resonance imaging (MRI) revealed a defect in the transverse sinus, straight sinus, and superior sagittal sinus. His blood was hemo-concentrated, and blood test results indicated high D-dimer and fibrinogen levels and decrease of antithrombin III. Case 2: The patient was an 89-year-old woman. After the diarrhea lasted suffering from ischemic colitis, she developed left hemiplegia and headache. Brain CT revealed hematoma in the subcortical region of the right frontal lobe and a high signal in the straight sinus. The superior sagittal sinus showed high-signal intensity on T1-weighted MRI and mild high-signal intensity on T2-weighted MRI. High fibrinogen levels were detected in the blood. Patients with nephrotic syndrome have a thrombotic tendency; both venous thrombosis and arterial thrombosis may occur. In the literature, the number of published cases of cerebral venous thrombosis was 10-fold that of cerebral artery thrombosis as a complication of nephrotic syndrome in individuals aged <20 years. In adults, however, the number of cerebral venous thrombosis was 2-fold that of cerebral artery thrombosis cases were reported. Nephrotic syndrome shows a thrombotic tendency, but cerebral venous thrombosis may develop as a result of another thrombotic factor. Management of life along with the conventional treatment of nephrotic syndrome is important.
[Show abstract][Hide abstract] ABSTRACT: Abstract Acetylcholine is one of the main neurotransmitters. It is involved in autonomic activities of the peripheral organs and forms a part of complicated neural networks in the central nervous system. Anticholinergic drugs are used in the treatment of various diseases, and many drugs have anticholinergic side effects. Thus, estimating the total burden of anticholinergic activity of drugs is important to assess the related adverse effects for patients taking such drugs. Serum anticholinergic activity (SAA) is measured using a competitive radioreceptor binding assay of muscarinic receptors. In addition to this direct measurement, several drug scales like the Anticholinergic Drug Scale (ADS), Anticholinergic Cognitive Burden Scale (ACB), and Anticholinergic Risk Scale (ARS) have been developed to estimate the total anticholinergic burden of drugs. These measurements have been used to demonstrate that certain drugs may be responsible for the cognitive impairment in the elderly or certain groups of patients with neurologic disorders. Clinicians should be aware of the impact of such drugs because central adverse effects are often obscure in these patient groups and are easily overlooked.
No preview · Article · May 2014 · Brain and nerve = Shinkei kenkyū no shinpo
[Show abstract][Hide abstract] ABSTRACT: Pregabalin, a novel agent for treating partial epilepsy and peripheral neuropathic and central pain, was studied for its effect on driving performance in healthy volunteers. Sixteen healthy male volunteers who drove regularly were enrolled in a double-blind, parallel-group, placebo-controlled study assessing the effect of pregabalin on driving performance. Subjects received an oral dose of pregabalin 75 mg or placebo, and a second dose 12 hours later. A driving simulator was used to test simple and complicated braking reaction time, and simple and complicated steering-wheel techniques before the first dose, and 1 hour and 3 hours after the second dose of pregabalin or placebo. The effect of training during the driving test on the driving performance of each group was also evaluated. There were no statistically significant differences in driving performance between the pregabalin and the placebo groups. However, the pregabalin group showed no significant improvement in steering-wheel skills with training, whereas the placebo group showed a significant (P<0.05) improvement with training. In this study using a driving simulator, pregabalin did not impair driving performance but mildly reduced the training effects of driving experiments. Although pregabalin caused sleepiness, it had no severe effect on driving ability after a second dose of 75 mg after the initial introduction of pregabalin.
Full-text · Article · Jan 2014 · International Journal of General Medicine
[Show abstract][Hide abstract] ABSTRACT: In the last 30 years, a lot of drugs to treat neurological disorders have been developed. Now neurology is one of the fields where the medication is the most important factor deciding the prognosis of the treated patients. Neurologists are now required to have precise knowledge of drug metabolisms and interactions on the medication to treat neurological disorders. Insert Packages contain most useful and important information for medications, however, information for the drugs are not enough to prescribe some drugs, and even though in the same drugs, information offered is different especially on drug interactions. Pharmacists and physicians should choose the drugs which offer proper and useful drug information to treat patients. Developments of drugs to treat patients are important as a physician in Japan. It can also contribute to treat patients in the all of the world. The role of neurologists is especially big because the drugs of the brain are rapidly developed than any other fields in medicine.
[Show abstract][Hide abstract] ABSTRACT: Objective:
The concentrations of neopterin and osteopontin in the cerebrospinal fluid (CSF) were measured in patients with HTLV-I-associated myelopathy/tropical spastic paraparesis (HAM/TSP) in order to evaluate their utility as biomarkers for the treatment response.
Seven HAM/TSP patients were treated intravenously with high-dose methylprednisolone (1,000 mg/day) for 3 days. CSF samples were collected before and after the treatment. The neopterin and osteopontin concentrations were determined using high-performance liquid chromatography (HPLC) and an enzyme immunoassay, respectively. The clinical symptoms were evaluated using the Osame Motor Disability Score and the Urinary Disturbance Score.
Four out of the seven patients showed an improvement in motor function with the treatment, and were therefore classed as responders. The pre-treatment CSF neopterin concentration exceeded the upper limit of normal in all seven of the patients, and tended to be higher in treatment responders as compared to non-responders. The CSF neopterin concentration was reduced following treatment in all patients. The mean CSF neopterin concentration significantly (p<0.01) decreased following treatment by almost 60% (from 124.1±79.9 nmol/L to 49.2±29.8 nmol/L). The mean CSF osteopontin concentration was significantly (p<0.01) higher in the HAM/TSP patients in comparison to the 18 HTLV-1-seronegative patients who were designated as controls (9.54±4.53 mg/L vs. 3.72±3.04 mg/L). No significant (p=0.47) reduction of the CSF osteopontin concentration was observed following the intravenous administration of high-dose methylprednisolone.
These results indicate that the CSF neopterin concentration, but not the osteopontin concentration, is a potentially valuable biomarker for monitoring the treatment response in HAM/TSP patients. Furthermore, high pre-treatment CSF neopterin concentrations may be a predictive biomarker for a response to intravenous high-dose methylprednisolone therapy.
No preview · Article · Oct 2013 · Internal Medicine
[Show abstract][Hide abstract] ABSTRACT: Objective:
For patients with Parkinson's disease (PD), driving is challenging due to an impaired motor function and decreased attention capabilities. This study assessed the driving capacity in PD patients by comparing neurological signs.
The driving ability of PD patients was evaluated using a driving simulator (Safety Master NT-932) that tested the reaction time in response to traffic signals and steering wheel errors. We studied the correlations between the total Unified Parkinson's Disease Rating Scale (UPDRS) score, the UPDRS part III score, the subscores of the UPDRS part III score, age, PD disease duration, braking reaction time, steering wheel errors and total scores for driving safety test results. 'On' state regular PD licensed drivers (n=42; mean age: 63 years) in Hoehn and Yahr stages II-III participated after their cognitive status was confirmed using mini-mental state examinations.
The UPDRS scores, the UPDRS part III scores and the postural instability subscores exhibited significant (p<0.05) correlations with the number of steering wheel errors but not with the braking reaction time or the total safety scores of the test results.
The UPDRS is an established evaluation method used to estimate PD signs, although it is not sufficient alone for deciding whether PD patients should be allowed to drive. Our findings suggest that determining the driving ability using a driving simulator might be a useful adjunct to UPDRS scores in the assessment of PD patients who are active drivers. Estimating the driving ability requires complex measurements, including motor performance with perception of stimuli and attention.
No preview · Article · Apr 2013 · Internal Medicine
[Show abstract][Hide abstract] ABSTRACT: Some patients with Parkinson disease improved their symptoms on treatment with nicotine patch or gum. Nicotine has also been studied for its antidyskinetic effect on levodopa-induced dyskinesia. We determined the effects of nicotine on levodopa pharmacokinetics and gastric emptying in healthy subjects and on levodopa transport in Caco-2 monolayers in vitro.
Healthy subjects received transdermal nicotine patch application followed by oral levodopa/benserazide, 100/25 mg, in a fasting state and with enteral nutrition. Levodopa pharmacokinetics was determined, and gastric emptying was evaluated by carbon 13 (C)-labeled acetic acid breath testing. In vitro studies using intestinal Caco-2 cell monolayers evaluated whether the intestinal transport of levodopa was affected by nicotine and its metabolite, cotinine.
Nicotine did not increase mean plasma concentration significantly during fasting or with enteral nutrition, although the extent of levodopa absorption was reduced by 34% to 60% in some individuals and the mean plasma concentration of levodopa was statistically decreased by nicotine in subjects who received enteral nutrition. However, gastric parameters were not significantly affected by nicotine. Nicotine and cotinine at 0.1 μmol/L significantly reduced levodopa uptake by Caco-2 cells (P < 0.01).
We found that nicotine reduced plasma levodopa concentration in some healthy subjects but with no alteration of gastric emptying rate. In vitro, nicotine inhibited levodopa transport by Caco-2 cell monolayers in an α-methyl amino isobutyric acid-independent, 2-amino-norbornanecarboxylic acid-dependent manner. These results suggest that nicotine may inhibit the transport of levodopa by the system L-amino acid transporter.
No preview · Article · Mar 2013 · Clinical neuropharmacology
[Show abstract][Hide abstract] ABSTRACT: Randomized clinical trials have shown that pramipexole has an antidepressant effect in patients with Parkinson's disease. We investigated the comparative efficacy of pramipexole toward dopamine receptor D(2) and D(3) expression in rat brain. Groups of rats were treated subacutely with pramipexole (1 mg/kg), imipramine (10 mg/kg), or bromocriptine (5 mg/kg), with appropriate controls. Using real-time RT-PCR and immunoblotting, dopamine receptor D(2) and D(3) expression was up-regulated in the striatum following pramipexole treatment, while imipramine and bromocriptine had no significant effects. These findings support that pramipexole exerts additional therapeutic benefits such as decreasing depression by increasing dopamine receptor D(3) expression in the striatum.
No preview · Article · Sep 2012 · Journal of Pharmacological Sciences
[Show abstract][Hide abstract] ABSTRACT: The effect of renal impairment on the pharmacokinetics of a single oral dose of memantine (10 mg) was determined in Japanese subjects. Subjects were assigned to four groups based on baseline creatinine clearance (CL(CR)): normal renal function (> 80 mL/min, n = 6), and mild (50 to ≤ 80 mL/min, n = 6), moderate (30 to < 50 mL/min, n = 6), and severe renal impairment (5 to < 30 mL/min, n = 7). Mean memantine maximum plasma concentration (C(max)) was similar in the groups (12.66, 17.25, 15.75, and 15.83 ng/mL, respectively), as was mean time to C(max) (6.2, 5.2, 4.3, and 5.4 h, respectively). However, exposure to memantine determined from mean area under the plasma concentration-time curve was 1.62-, 1.97-, and 2.33-times higher in subjects with mild, moderate, and severe renal impairment, respectively, as compared to controls with normal renal function. Mean memantine plasma elimination half-life increased according to increasing renal impairment (61.15, 83.00, 100.13, and 124.31 h, respectively), while mean cumulative urinary recovery of unchanged memantine in 72 h after dosing decreased according to increasing renal impairment (33.68%, 33.47%, 23.60%, and 16.17%, respectively). These results are the same as those in the previous study on caucasian individuals, when compared per body weight. It is suggested that the dose of memantine should be halved in patients with renal impairment.
[Show abstract][Hide abstract] ABSTRACT: We report a 33-year-old woman with myasthenia gravis (MG) who developed optic neuritis after the treatment of MG for 22 years. At 10 years of age, she was diagnosed with generalized MG (MGFA V) and at 11 years, she underwent thymectomy. She had been treated successfully only with anti-cholinesterase inhibitors for 22 years despite lasting high titer of anti-acetylcholine receptor antibody. She could manage everything in her life and had two children. At 33 years of age, she experienced acute visual loss in her left eye. Laboratory examination showed positive anti-acetylcholine receptor, antinuclear, anti-ssDNA, anti-dsDNA, anti-SS-A, and anti-aquaporin 4 (AQP4) antibodies. Brain MRI showed an enlarged left optic nerve with enhancement by gadolinium. Three courses of steroid pulse therapy did not show any effect on her visual acuity. However, plasma exchange therapy mildly ameliorated her visual acuity. Her MG symptoms were not exacerbated during the course of the optic neuritis. Furthermore blephalopstosis caused by MG has disappeared completely after the treatment with steroid pulse and plasma exchange. This case had 23 years of immunosuppressive treatment free durations with stable condition. The cause of development of optic neuritis would be her predisposed tendency other than thymectomy or treatment with immunosuppressive therapies.