Michiharu Nagahama

The effects of combine treatment of memantine and donepezil on Alzheimer's Disease patients and its relationship with cerebral blood flow in the prefrontal area

In this study, we evaluated the effect on cognitive function of memantine, behavioral and psychological symptoms of dementia, and the care burden, in patients with moderate‐to‐severe Alzheimers disease (AD). Furthermore, with near‐infrared spectroscopy (NIRS), we examined the association between effect of memantine and brain blood flow.

Yi-gan san for treatment of charles bonnet syndrome (visual hallucination due to vision loss): an open-label study.

Background:Recent studies indicate that the traditional Japanese herbal medicine yi-gan san (YGS, yokukan-san in Japanese) may be safe and useful for treating behavioral and psychological symptoms in dementia, borderline personality disorder, neuroleptic-induced tardive dyskinesia, and treatment-resistant schizophrenia. Visual hallucinations are common and often distressing consequences of vision loss, particularly in age-related macular degeneration. Charles Bonnet syndrome (CBS) is defined by the triad of complex visual hallucinations, ocular pathology causing visual deterioration, and preserved cognitive status. We aimed at evaluating both the efficacy and safety of YGS in patients with CBS. Methods:Twenty patients diagnosed with CBS were investigated, according to the diagnostic criteria established by Gold and Rabins and Teunisse. Participants were treated in a 4-week open-label study with YGS at an average daily dose of 5.8 ± 2.6 g (2.5-7.5 g). Psychometric instruments used to assess efficacy included the Neuropsychiatric Inventory, hallucination subscale of the Positive and Negative Syndrome Scale, and Clinical Global Impression. No cases of serious adverse events were attributed to the studys drug therapy. Results:A significant decrease in visual hallucination was observed at 2 and 4 weeks in the Neuropsychiatric Inventory, hallucination subscale of the Positive and Negative Syndrome Scale, and Clinical Global Impression scores. Conclusions:Yi-gan san may be an effective and safe therapy to control visual hallucination in patients with CBS and should be further tested in double-blind, placebo-controlled trials. Given the design characteristics of this trial, the present findings should be taken cautiously.

Charles Bonnet syndrome: Successful treatment of visual hallucinations due to vision loss with Yi-gan san

Visual hallucination is a common (10–15% prevalence) and often distressing consequence of vision loss, particularly in age-related macular degeneration (for review see Rovner, 2006). Charles Bonnet syndrome (CBS) is defined by the triad of complex visual hallucinations, ocular pathology causing visual deterioration and preserved cognitive status. The strongest risk factors for CBS are bilateral visual system impairment, declining visual acuity, cerebral damage, cognitive defects, social isolation and sensory deprivation (Menon, 2005). So far, although this condition is frequent, no established treatment for CBS has been stated in the literature. Neuroleptics, particularly atypical ones with high amount of serotonergic activity, have been proven to be effective in single cases (Moja et al., 2005). Yi-gan san (YGS, yokukan-san in Japanese) was developed in 1555 by Xue Kai as a remedy for restlessness and agitation in children (Aizawa et al., 2002). It was reported a fewmild and transient adverse events, including headache, nausea, tiredness, and hypokalemia. Iwasaki et al., (2005) reported that YGS improved BPSD and activities of daily living in a randomized, observer-blind, control trial. Moreover, we reported that YGS therapy is a well-tolerated and effective remedy that improves the symptoms of some psychiatric disorder (Miyaoka et al., 2008a,b,in press). Depending on the traditional Japanese medicine studied, those detailed case observations and clinical trials can offer hints at new treatments for CBS. To our knowledge there have been no prior reports of its efficacy, or the efficacy of YGS in the treatment of CBS.

Simple and rapid detection of HLA-A*31:01 for prediction of carbamazepine-induced hypersensitivity using loop-mediated isothermal amplification method.

BACKGROUND Carbamazepine (CBZ), which is widely used in management of epilepsy or neuropathic pain, causes fatal severe cutaneous adverse reactions (SCARs). CBZ-induced SCARs are known to occur in strong association with human leukocyte antigen (HLA)-A*31:01 in Japanese and European populations. HLA genotyping is currently used to detect human HLA-A*31:01. OBJECTIVE To establish a simple and rapid screening assay specific for HLA-A*31:01, the loop-mediated isothermal amplification (LAMP) method was employed on a sample Japanese population. METHODS A set of LAMP primers targeting exon 2 of HLA-A*31:01 were designed. Thirty-two clinical samples including the representative HLA-A allele in Japan were used to assess the specificity of LAMP primers in the detection of HLA-A*31:01. RESULTS The HLA-A*31:01-specific LAMP assay showed consistency with polymerase chain reaction reverse sequence-specific oligonucleotide probe (PCR-rSSO) and polymerase chain reaction-sequence based typing (PCR-SBT) results. CONCLUSION High sensitivity and specificity of the HLA-A*31:01 LAMP assay was confirmed. Considering its convenience, the assay can be widely used to screen patients at high genetic risk of CBZ-induced SCARs.

Ramelteon as adjunctive therapy for delirium referred to a consultation‐liaison psychiatry service: a retrospective analysis

Delirium is one of the most common and serious mental disorders of attention and cognition, with high morbidity, mortality, and healthcare costs. Although the pathology of delirium remains unclear, delirium is generally treated with antipsychotics, which have occasionally induced serious adverse events. Ramelteon is an agonist of melatonin receptor that is used to treat insomnia. We reported a case series that adjunctive ramelteon with antipsychotics successfully treated delirium (Furuya et al., 2012). We hypothesized that adjunctive ramelteon with antipsychotics would be more effective for delirium than antipsychotics monotherapy.

Gunn rats with glial activation in the hippocampus show prolonged immobility time in the forced swimming test and tail suspension test

Recent studies imply that glial activation plays a role in the pathogenesis of psychiatric disorders, such as schizophrenia and major depression. We previously demonstrated that Gunn rats with hyperbilirubinemia show congenital gliosis and schizophrenia‐like behavior.

Aceruloplasminemia With Psychomotor Excitement and Neurological Sign Was Improved by Minocycline (Case Report)

AbstractAceruloplasminemia is an autosomal recessive disorder of iron metabolism caused by mutations in the ceruloplasmin gene. Its prevalence is 1 in 2,000,000 people in Japan. This is a disorder of neurodegeneration with iron accumulation in the brain revealed by MRI. The iron overload induces oxidative stress and generation of reactive oxygen species, which triggers a cascade of pathological events that lead to neuronal death. Intravenous administration of an iron chelator, deferoxamine has been proposed as a method of inhibiting the accumulation of iron.The patient was a 46-year-old Japanese woman. She was diagnosed at the age of 33 years. Deferoxamine was administrated for 6 months but was discontinued due to adverse effects. On admission at the age of 46, psychomotor excitement was acute in onset. The extrapyramidal symptoms reflected iron deposition in the basal ganglia and substantia nigra in the midbrain. Ataxia and a wide-based gate reflected iron deposition in the dentate nuclei of the cerebellum. An antibiotic, minocycline at 150 mg/day successfully ameliorated the clinical symptoms.Minocycline, a second generation tetracycline, has a direct radical scavenging property due to its chemical structure. It has been reported that minocycline is similar to deferoxamine in its ability to chelate iron. Minocycline is also involved in preventing the upregulation of proinflammatory cytokines. The iron-chelating, antioxidant, and anti-inflammatory effects of minocycline were involved in this case.

Treatment of Paroxysmal Perceptual Alteration in Catatonic Schizophrenia by Switching to Aripiprazole from Risperidone: A Case Report

Paroxysmal perceptual alteration (PPA) is the occurrence of brief and recurrent episodes of perceptual changes. It is mainly caused by the treatment of schizophrenia patients with antipsychotics. However, diagnosis of PPA is not very prevalent among psychiatrists, partly due to underrecognition or misunderstanding that it is a worsening of psychiatric symptoms. If psychiatrists do not understand PPA, they cannot treat it appropriately, and the patients quality of life is impaired. We present a case of PPA in catatonic schizophrenia that was successfully treated by switching to aripiprazole from risperidone. We suggest that the disappearance of PPA in our case was due to both discontinuing risperidone, which completely blocks D2 receptors, and replacing it with aripiprazole, which is characterized as a partial agonist of D2 receptors. Treatment of PPA will improve medication adherence and quality of life. It is important to recognize PPA as a possible side effect of treatment with antipsychotics.