Makio Takahashi

Idiopathic normal pressure hydrocephalus has a different cerebrospinal fluid biomarker profile from Alzheimer's disease.

The diagnosis of idiopathic normal pressure hydrocephalus (iNPH) is sometimes complicated by concomitant Alzheimers disease (AD) pathology. The purpose of the present study is to identify an iNPH-specific cerebrospinal fluid (CSF) biomarker dynamics and to assess its ability to differentiate iNPH from AD. Total tau (t-tau), tau phosphorylated at threonine 181 (p-tau), amyloid-β (Aβ) 42 and 40, and leucine-rich α-2-glycoprotein (LRG) were measured in 93 consecutive CSF samples consisting of 55 iNPH (46 tap test responders), 20 AD, 11 corticobasal syndrome, and 7 spinocerebeller disease. Levels of t-tau and p-tau were significantly decreased in iNPH patients especially in tap test responders compared to AD. Correlation was observed between Mini-Mental State Examination scores and Aβ42 in AD (R = 0.44) and mildly in iNPH (R = 0.28). Although Aβ42/40 ratio showed no significant difference between iNPH and AD (p = 0.08), the levels of Aβ40 and Aβ42 correlated positively with each other in iNPH (R = 0.73) but much less in AD (R = 0.26), suggesting that they have discrete amyloid clearance and pathology. LRG levels did not differ between the two. Thus, our study shows that although CSF biomarkers of iNPH patients can be affected by concomitant tau and/or amyloid pathology, CSF t-tau and p-tau are highly useful for differentiation of iNPH and AD.

N-cadherin enhances APP dimerization at the extracellular domain and modulates Aβ production

J. Neurochem. (2011) 119, 354–363.

α-synuclein BAC transgenic mice as a model for Parkinson's disease manifested decreased anxiety-like behavior and hyperlocomotion.

α-Synuclein (α-syn), the main component of Lewy bodies, was identified as a genetic risk factor for idiopathic Parkinsons disease (PD). As a model for PD, we generated human α-syn bacterial artificial chromosome transgenic mice (BAC tg mice) harboring the entire human α-syn gene and its gene expression regulatory regions. The α-syn BAC tg mice manifested decreased anxiety-like behaviors which may reflect non-motor symptoms of early PD, and they exhibited increased SERT expression that may be responsible for decreased anxiety-like behaviors. Our α-syn BAC tg mice could be a valuable tool to evaluate α-syn gene dosage effects in vivo.

Magnetic Resonance Imaging of Primary Spinal Intramedullary Lymphoma

The authors report 2 cases of primary spinal intramedullary lymphoma and review all previously reported magnetic resonance imaging findings on this disease. The most common finding was a solid and homogeneously enhanced mass that was hyperintense on T2‐weighted images, without associated syringomyelia. In a few cases, swelling of the spinal cord was minimal.

Cerebrospinal Fluid Rhinorrhea and Subsequent Bacterial Meningitis due to an Atypical Clival Fracture

Cases of cerebrospinal fluid (CSF) rhinorrhea due to clival fracture are rare. We present a case of bacterial meningitis with CSF rhinorrhea after a clival fracture. Heavily T2-weighted images showed a bone flap in the thinned clivus and fluid collection in the sphenoid sinus. CSF rhinorrhea developed at 1 month after mild trauma. The fracture may have been caused by the trauma and/or by the pressure gradient between the intracranial CSF space and the sphenoid sinus. A detailed history to identify trauma and an examination to detect bone defects in the skull base are necessary when patients present with bacterial meningitis and persistent rhinorrhea.

Antidepressants for Depression, Apathy, and Gait Instability in Parkinson's Disease: A Multicenter Randomized Study

Objective Depression, apathy, and gait instability are cardinal symptoms in patients with Parkinson’s disease (PD). Selective serotonin reuptake inhibitors (SSRIs) and serotonin and norepinephrine reuptake inhibitors (SNRIs) are used for treating the psychiatric symptoms of PD. This is the first prospective randomized study to compare the efficacy of an SNRI (duloxetine) with SSRIs (paroxetine, escitalopram) in improving depressive symptoms and apathy (primary) and freezing of gait (FOG; secondary) in patients with PD. Methods In this prospective, multicenter, open-label, randomized study, Japanese PD patients with a Quick Inventory of Depressive Symptomatology-Japanese (QIDS-J) score ≥6 were randomly assigned to receive an SSRI (27 enrolled, 25 analyzed) or duloxetine (28 enrolled, 27 analyzed) and were assessed at 6 and 10 weeks. Results The mean change (SD) in the QIDS J [SSRI -2.4 (3.6), p=0.015; SNRI -2.3 (3.9), p=0.029] and FOG-Questionnaire [SSRI -2.9 (4.2), p=0.012; SNRI -3.4 (4.7), p=0.010] scores (from baseline) at 10 weeks was statistically significant, while the mean change in the Apathy Scale scores was not [SSRI -2.7 (5.4), p=0.054; SNRI -1.5 (3.7), p=0.109]. No significant differences were observed between the SSRI and SNRI groups. The treatments were well-tolerated; however, gastrointestinal events were more common with SSRIs. Two SNRI-treated patients reported an exacerbation of tremor. Conclusion SSRIs and SNRIs improve the depressive symptoms and FOG in PD patients with mild to severe depressive symptoms. However, their effectiveness in treating apathy remains to be elucidated.

Longitudinally Extensive Transverse Myelitis and Optic Neuropathy Associated with Syphilitic Meningomyelitis and Human Immunodeficiency Virus Infection: A Case Report and Review of the Literature

The incidence of co-infection with Treponema pallidum and human immunodeficiency virus (HIV) is increasing in developing and developed countries. The neurological complications of both infections occasionally occur simultaneously during a clinical course. We herein report the case of an HIV carrier with syphilitic meningomyelitis and subclinical optic neuropathy. The patient presumably had latent syphilis and slowly developed longitudinally extensive transverse myelitis (LETM). A cerebrospinal fluid examination confirmed the diagnosis of active neurosyphilis based on an elevated T. pallidum hemagglutination assay index. A change in the patients immune status, possibly due to HIV, might have converted the syphilis from latent to active, leading to LETM of the spinal cord.