Masa-aki Higuchi

ATP-binding cassette transporter G4 is highly expressed in microglia in Alzheimer's brain.

Apolipoprotein E epsilon4 is an independent risk factor for Alzheimers disease (AD) and is the main constituent of high-density lipoprotein (HDL) as a source of cholesterol in the brain. ATP-binding cassette transporter G4 (ABCG4) is one of the membrane cholesterol transporter which is implicated in HDL-mediated cholesterol efflux, but its precise localization and function in the brain has been unclear. In AD brain, ABCG4 protein was highly expressed in microglial cell that was closely located to senile plaques, whereas in non-neurological cases positive cells were not seen in cortical and nigral tissues. As well as the ABCG4 protein, ABCG4 mRNA signal was detected in microglial cell closely located to senile plaque of AD brain by in situ hybridization histochemistry. These results suggest that upregulated ABCG4 in microglia may accelerate the lipidation of apoE and HDL in the AD brain. This is the first report to show that ABCG4 is highly expressed in microglia on AD brain.

Predictors of the emergence of apathy after bilateral stimulation of the subthalamic nucleus in patients with Parkinson's disease.

Subthalamic nucleus deep brain stimulation (STN‐DBS) is a valid therapeutic tool that ameliorates motor symptoms in patients with Parkinsons disease (PD). However, apathy is one of the neuropsychiatric complications that may occur after STN‐DBS surgery, and this may adversely influence the quality of life of patients despite significant motor improvement.

Effects of subthalamic nucleus deep brain stimulation on the swallowing function of patients with Parkinson's disease

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Anti-cholinergics for axial symptoms in Parkinson's disease after subthalamic stimulation

– see front matter 2012 Elsevier Ltd. http://dx.doi.org/10.1016/j.parkreldis.2012.10.023 Subthalamic nucleus deep brain stimulation (STN-DBS) has become a widely accepted surgical treatment for patients with Parkinson’s disease (PD) associated with medically intractable motor symptoms. However, there have been few quantitative study reports examining swallowing function in patients who have undergone STN-DBS. The present study aimed to investigate a possible relationship between swallowing function and the Unified Parkinson’s Disease Rating Scale (UPDRS) part III (which rates motor function) scores and compare the swallowing function of patients between DBS ON and OFF states using videofluoroscopy (VF). A total of 18 patients (8 males, 10 females; mean age, 66.6 6.2 years; range, 50–76 years; average illness duration,11.6 5.7 years; range, 3–28 years) with advanced PD and clinical swallowing problems who had bilateral DBS electrodes placed in the STN at the Department of Neurology of Fukuoka University Hospital were included. Patients were assessed according to item 7 of the UPDRS part II for swallowing. Their scores were as follows: 1 (rare choking; n 1⁄4 5), 2 (occasional choking; n 1⁄4 5), and 3 (require soft food; n 1⁄4 8). Informed consent was obtained from all participants, and the study was approved by the ethics committee of Fukuoka University Hospital. UPDRS part III and VF findings between the preoperative and DBS ON states with continued medication were compared for 10 of the 18 patients (2 males, 8 females; mean age, 65.9 7.9 years; range, 50–76 years; average illness duration, 8.9 3.5 years; range, 3–15 years). VF examinations were performed 1 week before STNDBS and after 6 months of stimulation. The UPDRS part III motor subscale parameters were assessed by certified neurologists. We evaluated 18 patients to quantitatively compare swallowing function between DBS ON and OFF states after 6 months of STNDBS. VF examination in the DBS OFF state was performed at least 10 min after switching off STN stimulation. In the preliminary study, 5 mL of jelly was used as the test food. In the main study, 5 mL of jelly, honey-thickened water, nectar-

Dysgeusia in a Patient with Guillain-Barré Syndrome Associated with Acute Hepatitis E: A Case Report and Literature Review

OBJECTIVE We studied the effect of anti-cholinergic therapy on axial symptoms that show a tendency to worsen over time after deep brain stimulation of the subthalamic nucleus (STN-DBS) in patients with Parkinsons disease (PD). PATIENTS AND METHODS We conducted a prospective study of 20 consecutive patients treated with the anti-cholinergic agent trihexyphenidyl after bilateral STN-DBS and assessed the effect of anti-cholinergic therapy on parkinsonism 1 month after its initiation using the Unified Parkinsons Disease Rating Scale (UPDRS). RESULTS After a mean post-operative follow-up period of 22.3 months, the scores of axial symptoms on UPDRS part II (ADL score) and part III (motor score) deteriorated by 87% and 54% (baseline), respectively, compared with the pre-operative scores (P < 0.001 for both comparisons). After adding trihexyphenidyl to dopaminergic medication with stimulation, the scores of axial symptoms on UPDRS part II and part III improved from baseline by 33% and 39%, respectively (P < 0.001 for both comparisons). CONCLUSIONS Our findings demonstrated that the anti-cholinergic agent trihexyphenidyl shows positive effect for a patient population developing deterioration of axial symptoms after STN-DBS. The results in the present study may provide insights into the mechanism of emergence or progression of axial symptoms in patients with PD after STN-DBS.

Changes in Motor-Related Cortical Activity Following Deep Brain Stimulation for Parkinson’s Disease Detected by Functional Near Infrared Spectroscopy: A Pilot Study

Guillain-Barré syndrome (GBS) is usually triggered by viral or bacterial infection. In addition, it was recently reported that infection with hepatitis E virus (HEV) also causes GBS. A 49-year-old man presented with acute-onset paralysis in all extremities and dysgeusia during an episode of acute hepatitis. Serological tests showed the presence of anti-HEV IgM antibodies and HEV-RNA in the serum. As an electrophysiological examination showed acute demyelinating polyradiculoneuropathy, the patient was diagnosed as HEV-associated GBS. Following the initiation of treatment with intravenous immunoglobulin, his paralysis and dysgeusia rapidly improved. This case suggests that HEV-associated GBS may rarely be complicated by dysgeusia.

Impulse control disorders and punding in Perry syndrome

It remains unclear how deep brain stimulation (DBS) modulates the global neuronal network involving cortical activity. We aimed to evaluate changes in cortical activity in six (two men; four women) patients with Parkinson’s disease (PD) who underwent unilateral globus pallidus interna (GPI) DBS surgery using a multi-channel near infrared spectroscopy (NIRS) system. As five of the patients were right-handed, DBS was performed on the left in these five cases. The mean age was 66.8 ± 4.0 years. The unified Parkinson’s disease rating scale (UPDRS) motor scores were evaluated at baseline and 1- and 6-month follow-up. Task-related NIRS experiments applying the block design were performed at baseline and 1-month follow-up. The mean of the total UPDRS motor score was 48.5 ± 11.1 in the off-medication state preoperatively. Postoperatively, total UPDRS motor scores improved to 26.8 ± 16.6 (p < 0.05) and 22.2 ± 8.6 (p < 0.05) at 1- and 6-month follow-up, respectively. A task-related NIRS experiment showed a postoperative increase in the cortical activity of the prefrontal cortex comparable to the preoperative state. To our knowledge, this is the first study to use a multi-channel NIRS system for PD patients treated with DBS. In this pilot study, we showed changes in motor-associated cortical activities following DBS surgery. Therapeutic DBS was concluded to have promoted the underlying neuronal network remodeling.

Impact of an Interdisciplinary Deep Brain Stimulation Screening Model on Post-Surgical Complications in Essential Tremor Patients.

Impulse control disorders (ICDs) are psychiatric conditions characterized by poor impulse control such as pathological gambling, hypersexuality, compulsive shopping, compulsive eating, explosive aggressive behavior, reckless driving, and reckless generosity [1,2]. Punding is defined as a complex prolonged, purposeless, and repetitive behavior. It has been increasingly recognized that ICDs and punding are more prevalent in patients with Parkinsons disease (PD) compared with a normal population [1], most likely due to dopaminergic therapy such as levodopa plus pramipexole and ropinirole [3]. Perry syndrome is a rare autosomal dominant neurodegenerative disorder caused by DCTN1 mutations. Parkinsonism is one of the most characteristic features of patients with Perry syndrome, along with apathy/depression, unexpected weight loss, and central hypoventilation [4]. Parkinsonism that occurs in patients with Perry syndrome generally responds well to high dose of dopaminergic therapy; however, to date, neither ICDs nor punding have been reported in patients with Perry syndrome. Herein, we describe two Japanese patients with Perry syndrome who developed ICDs and punding after initiation of dopaminergic therapy. Both patients were from the same family pedigree whomwe previously reported (Fig. 1A).

Interdisciplinary Parkinson’s Disease Deep Brain Stimulation Screening and the Relationship to Unintended Hospitalizations and Quality of Life

Objective To investigate the relationship of our interdisciplinary screening process on post-operative unintended hospitalizations and quality of life. Background There are currently no standardized criteria for selection of appropriate Deep Brain Stimulation candidates and little hard data exists to support the use of any singular method. Methods An Essential Tremor cohort was selected from our institutional Deep Brain Stimulation database. The interdisciplinary model utilized seven specialties who pre-operatively screened all potential Deep Brain Stimulation candidates. Concerns for surgery raised by each specialty were documented and classified as none, minor, or major. Charts were reviewed to identify unintended hospitalizations and quality of life measurements at 1 year post-surgery. Results Eighty-six percent (44/51) of the potential screened candidates were approved for Deep Brain Stimulation. Eight (18%) patients had an unintended hospitalization during the follow-up period. Patients with minor or major concerns raised by any specialty service had significantly more unintended hospitalizations when compared to patients without concerns (75% vs. 25%, p < 0.005). The rate of hospitalization revealed a direct relationship to the “level of concern”; ranging from 100% if major concerns, 42% if minor concerns, and 7% if no concerns raised, p = 0.001. Quality of life scores significantly worsened in patients with unintended hospitalizations at 6 (p = 0.046) and 12 months (p = 0.027) when compared to baseline scores. No significant differences in tremor scores between unintended and non-unintended hospitalizations were observed. Conclusions The number and level of concerns raised during interdisciplinary Deep Brain Stimulation screenings were significantly related to unintended hospitalizations and to a reduced quality of life. The interdisciplinary evaluation may help to stratify risk for these complications. However, data should be interpreted with caution due to the limitations of our study. Further prospective comparative and larger studies are required to confirm our results.

Utility of the Japanese version of the 9-item Wearing-off Questionnaire

Objective To investigate the impact of pre-operative deep brain stimulation (DBS) interdisciplinary assessments on post-operative hospitalizations and quality of life (QoL). Background DBS has been utilized successfully in Parkinson’s disease (PD) for the treatment of tremor, rigidity, bradykinesia, off time, and motor fluctuations. Although DBS is becoming a more common management approach there are no standardized criteria for selection of DBS candidates, and sparse data exist to guide the use of interdisciplinary evaluations for DBS screening. We reviewed the outcomes of the use of an interdisciplinary model which utilized seven specialties to pre-operatively evaluate potential DBS candidates. Methods The University of Florida (UF) INFORM database was queried for PD patients who had DBS implantations performed at UF between January 2011 and February 2013. Records were reviewed to identify unintended hospitalizations, falls, and infections. Minor and major concerns or reservations from each specialty were previously documented and quantified. Clinical outcomes were assessed through the use of the Parkinson disease quality of life questionnaire (PDQ-39), and the Unified Parkinson’s Disease Rating Score (UPDRS) Part III. Results A total of 164 cases were evaluated for possible DBS candidacy. There were 133 subjects who were approved for DBS surgery (81%) following interdisciplinary screening. There were 28 cases (21%) who experienced an unintended hospitalization within the first 12 months following the DBS operation. The patients identified during interdisciplinary evaluation with major or minor concerns from any specialty service had more unintended hospitalizations (93%) when compared to those without concerns (7%). When the preoperative “concern” shifted from “major” to “minor” to “no concerns,” the rate of hospitalization decreased from 89% to 33% to 3%. A strong relationship was uncovered between worsened PDQ-39 at 12 months and increased hospitalization. Conclusions Unintended hospitalizations and worsened QOL scores correlated with the number and severity of concerns raised by interdisciplinary DBS evaluations. The data suggest that detailed screenings by interdisciplinary teams may be useful for more than just patient selection. These evaluations may help to stratify risk for post-operative hospitalization and QoL outcomes.