Chihiro Akiba

Use of External Lumbar Cerebrospinal Fluid Drainage and Lumboperitoneal Shunts with Strata NSC Valves in Idiopathic Normal Pressure Hydrocephalus: A Single-Center Experience

OBJECTIVE In Japan, idiopathic normal pressure hydrocephalus (iNPH) currently is treated mainly with lumboperitoneal (LP) shunts. Our aim was to evaluate whether LP shunting via the use of Medtronic Strata NSC programmable valves was as effective as ventriculoperitoneal shunting in the treatment of patients with iNPH from the perspectives of safety and symptomatic improvement rate. METHODS The clinical records of 51 iNPH patients (mean age, 75 years; males, 29), who underwent placement of Medtronic Strata NSC LP shunt systems were reviewed retrospectively as a cohort. LP shunting was evaluated with the modified Rankin Scale, the Japan Normal-Pressure Hydrocephalus Grading Scale, the Mini-Mental State Examination, the Frontal Assessment Battery, and the Trail-Making Test A as outcome measures. RESULTS Modified Rankin Scale scores improved from 3.2 to 2.2 (P < 0.01), indicating a 64% response rate 12 months after treatment. Total Japan Normal-Pressure Hydrocephalus Grading Scale scores decreased from 6.5 to 4.0 (P < 0.01), indicating a response rate of 81%. Mini-Mental State Examination scores improved from 22.2 to 25.4 (P < 0.01), Frontal Assessment Battery scores improved from 11.7 to 13.4 (P < 0.05), and Trail-Making Test A scores improved from 122.3 to 112.7 (P = 0.60). During the 12-month follow-up period, complications requiring surgery were observed in 6 cases (11.8%). CONCLUSION LP shunts showed effectiveness rates that were similar to those of ventriculoperitoneal shunts. Despite the relatively high complication rate, LP shunts can be recommended for the treatment of patients with iNPH because of their minimal invasiveness and lack of lethal complications.

Cerebrospinal fluid biomarkers for prognosis of long-term cognitive treatment outcomes in patients with idiopathic normal pressure hydrocephalus

The prognosis of cognitive improvement after cerebrospinal fluid (CSF) shunting in idiopathic normal pressure hydrocephalus (iNPH) remains uncertain, with no reports on CSF biomarkers related to long-term cognitive prognosis. We performed a preliminary study of CSF biomarker protein levels for cognitive outcome prognostication of two-year outcomes after shunt treated iNPH in 36 patients (13 women) with a median age of 75years (IQR 69-78). CSF biomarkers included soluble amyloid precursor proteins (sAPP, sAPPα, sAPPβ), amyloid β (Aβ)1-38, Aβ1-42 and phosphorylated tau (p-tau), lipocalin-type prostaglandin D synthase (L-PGDS)/β-trace, and cystatin C. The results clearly showed that p-tau levels (sensitivity of 71.4%, specificity of 77.8%, cut-off value of 22.0pg/mL), Aβ1-38/Aβ1-42 ratio (77.8%, 81%, 3.58), and the Aβ1-42/p-tau ratio (76%, 72.7%, 14.6) in preoperative CSF have the potential to determine postoperative prognosis. Improved cognition may be associated with the improvement in CSF circulation after LPS, which likely induces cystatin C and L-PGDS and switches synthesis from Aβ1-42 to Aβ1-38.

Lumboperitoneal Shunts for the Treatment of Idiopathic Normal Pressure Hydrocephalus: A Comparison of Small-Lumen Abdominal Catheters to Gravitational Add-On Valves in a Single Center

Abstract BACKGROUND Treating idiopathic normal pressure hydrocephalus (iNPH) with lumboperitoneal shunts (LPSs) may cause cerebrospinal fluid (CSF) overdrainage. OBJECTIVE To investigate whether LPSs, including gravitational “add-on” and programmable pressure valves (PPVs/+GVs), reduce complications and improve outcomes. METHODS We compared PPVs/+small lumen abdominal catheters (SLs) to PPVs/+GVs using different opening pressures for supine and standing positions. We analyzed 115 patients with iNPH in 2 consequent cohorts: 48 patients receiving LPSs with PPVs/+SLs and 67 patients receiving LPSs with PPVs/+GVs. The modified Rankin Scale (mRS), Japan iNPH grading scale, Mini Mental State Examination, Frontal Assessment Battery, and CSF biomarkers were evaluated. RESULTS Comparisons of postoperative clinical factors in 64 patients in the PPV/+SL and PPV/+GV groups using 1:1 propensity score matching revealed differences in the mean (±standard deviation) postoperative mRS (2.65 ± 1.07 vs 2.16 ± 1.02, P = .049) and gait disturbance scores (1.97 ± 1.03 vs 1.39 ± 0.92, P = .011). Thus, outcomes improved in the LPS group with the GV. Serious and nonserious adverse event rates for the PPV/+SL and PPV/+GV groups were 22.9% and 19.4% (P = .647) and 38% and 17.9% (P = .018), respectively, indicating higher rates of subdural collections for the PPV/+SL group. CONCLUSION This is the first study to examine LPS treatment for iNPH using a GV in tandem with a PPV. Our results suggest that the CSF shunt flow volume is restricted in the standing position and maintained in the supine position, thus improving iNPH symptoms. This may reduce intracranial CSF hypotension-related complications.

Decreased Expression of hsa-miR-4274 in Cerebrospinal Fluid of Normal Pressure Hydrocephalus Mimics with Parkinsonian Syndromes

Background: Patients presenting with the classical idiopathic normal pressure hydrocephalus (iNPH) triad often show additional parkinsonian spectrum signs. Accurate differential diagnosis strongly influences the long-term outcome of cerebrospinal fluid (CSF) shunting. Objective: The aim of this study was to find potential CSF microRNA (miRNA) biomarkers for NPH mimics with parkinsonian syndromes that can reliably distinguish them from iNPH patients. Methods: Two cohorts of 81 patients (cohort 1, n = 55; cohort 2, n = 26) with possible iNPH who were treated in two centers between January 2011 and May 2014 were studied. In both cohorts, CSF samples were obtained from patients clinically diagnosed with iNPH (n = 21 and n = 10, respectively), possible iNPH with parkinsonian spectrum (PS) (n = 18, n = 10, respectively), possible iNPH with Alzheimer’s disease (AD) (n = 16), and non-affected elderly individuals (NC) (n = 6). A three-step qRT-PCR analysis of the CSF samples was performed to detect miRNAs that were differentially expressed in the groups. Results: The expression of hsa-miR-4274 in CSF was decreased in both cohorts of PS group patients (cohort 1: p < 0.0001, cohort 2: p < 0.0001), and was able to distinguish PS from iNPH with high accuracy (area under the curve = 0.908). The CSF concentration of hsa-miR-4274 also correlated with the specific binding ratio of ioflupane (123I) dopamine transporter scan (r = –0.494, p = 0.044). By contrast, the level of hsa-miR-4274 was significantly increased in the PS group after CSF diversion. Conclusion: Levels of CSF hsa-miR-4274 can differentiate PS from patients with iNPH, AD, and NC. This may be clinically useful for diagnostic purposes and predicting shunt treatment responses.

Solitary epicranial neurofibroma with NF1-related germline mutation: case report.

A 33-year-old male became aware of a painless soft mass in the left occipital region. His medical and family history were unremarkable for neurofibromatosis type 1 (NF1) or other genetic disorders. Physical examination showed no signs of NF1. Neurological and ophthalmological examinations found no abnormality. Cranial computed tomography showed an isodense mass located subcutaneously with irregular deformities in the adjacent occipital bone. Magnetic resonance (MR) imaging demonstrated that the lesion, 7.5 × 5.5 cm in diameter, was hypointense both on T1- and T2-weighted images and intensely enhanced after gadolinium infusion. The patient requested to remove the large mass. The subcutaneous tumor was well circumscribed, encapsulated, and less vascular, and resected en bloc. The histological diagnosis was neurofibroma without findings of cell atypia, whereas genomic exploration identified abnormal gains in NF1 gene, and resultant absence of neurofibromin, a protein coded on NF1 gene. Solitary neurofibromas in “clinically” non-NF1 patients may originate from the genomic changes in NF1 gene.

Skull Base Chondroid Chordoma: Atypical Case Manifesting as Intratumoral Hemorrhage and Literature Review

ObjectiveChondroid chordoma (CC) is a rare but commonest subtype of chordoma with little reported clinical information. The present study summarizes and updates present knowledge of CC.MethodsLiterature search for demographic data and clinical appearance of cranial CCs except for those entirely confined to the sinonasal region.ResultsA total of 48 English language papers published from 1968–2013 were retrieved describing 132 CCs as skull base tumors. The male-to-female ratio was 1:1. The mean age at diagnosis was 43 years, predisposing to the third to fifth decades of life. The clival (34 %) and spheno-occipital (29 %) regions were the most frequent sites of origin followed by the sellar (12 %) and sphenoid (5 %) regions. Intratumoral calcification and bony erosion were identified as the characteristic neuroimaging findings. Surgical resection by the transcranial, transsphenoidal, transnasal, transpharyngeal, or transpalatal route with or without adjuvant radiotherapy was the main treatment option. The initial treatment outcome was satisfactory in 82 % of cases with considerably better prognosis compared with typical chordomas.ConclusionCC is a distinct entity to be discriminated from the typical type of chordoma. There are no distinguishing features on magnetic resonance imaging between CC and typical chordoma. Intratumoral calcification and concurrent bony erosion on neuroimaging should suggest the possibility of CC. Extensive surgical resection and adjuvant radiotherapy can achieve satisfactory outcome.

Shunt Intervention for Possible Idiopathic Normal Pressure Hydrocephalus Improves Patient Outcomes: A Nationwide Hospital-Based Survey in Japan

Background and Purpose: This study aimed to investigate the efficacy of cerebrospinal fluid shunt intervention for idiopathic normal pressure hydrocephalus (iNPH) using data from a nationwide epidemiological survey in Japan. Methods: We conducted a cross-sectional study using data from a nationwide epidemiological survey performed in Japan. Propensity score matching was used to select 874 patients from 1,423 patients aged ≥60 years, who were diagnosed with iNPH based on clinical guidelines following a hospital visit in 2012. Patients who experienced an improvement of at least 1 modified Rankin Scale (mRS) grade after the intervention were classified as “improved,” while the remaining patients were classified as “non-improved.” In the shunt intervention (n = 437) and non-shunt intervention (n = 437) groups, the differences in mRS grade improvement were analyzed using the Mann-Whitney U-test. Finally, we examined subjects in the shunt intervention group (n = 974) to compare the outcomes and complications of ventriculoperitoneal (VP) shunt (n = 417) with lumboperitoneal (LP) shunt (n = 540). Results: We examined subjects with iNPH to compare the non-shunt intervention group to the shunt intervention group following adjustment for age and mRS grade at baseline by propensity score matching (0.31–0.901). The mRS grade (mean [SD]) was found to improve with non-shunt intervention (2.46 [0.88]) and shunt intervention (1.93 [0.93]) (p < 0.001) in iNPH patients. The mRS outcome score and complications comparison between the VP and LP shunt groups did not show significant difference. Conclusions: In this study, analysis of the efficacy of shunts for possible iNPH conducted in Japan indicated a significant improvement in the mRS grade between baseline and outcome within 1 year, regardless of the surgical technique, and shunt intervention was found to be effective.

Leucine-rich α2-glycoprotein overexpression in the brain contributes to memory impairment

We previously reported increase in leucine-rich α2-glycoprotein (LRG) concentration in cerebrospinal fluid is associated with cognitive decline in humans. To investigate relationship between LRG expression in the brain and memory impairment, we analyzed transgenic mice overexpressing LRG in the brain (LRG-Tg) focusing on hippocampus. Immunostaining and Western blotting revealed age-related increase in LRG expression in hippocampal neurons in 8-, 24-, and 48-week-old controls and LRG-Tg. Y-maze and Morris water maze tests indicated retained spatial memory in 8- and 24-week-old LRG-Tg, while deteriorated in 48-week-old LRG-Tg compared with age-matched controls. Field excitatory postsynaptic potentials declined with age in LRG-Tg compared with controls at 8, 24, and 48 weeks. Paired-pulse ratio decreased with age in LRG-Tg, while increased in controls. As a result, long-term potentiation was retained in 8- and 24-week-old LRG-Tg, whereas diminished in 48-week-old LRG-Tg compared with age-matched controls. Electron microscopy observations revealed fewer synaptic vesicles and junctions in LRG-Tg compared with age-matched controls, which became significant with age. Hippocampal LRG overexpression contributes to synaptic dysfunction, which leads to memory impairment with advance of age.

Epidemiological characteristics of patients with idiopathic normal pressure hydrocephalus in Japan: analysis of the treatment

To clarify the epidemiological and clinical characteristics of idiopathic normal pressure hydrocephalus (iNPH) in Japan, a nationwide epidemiological survey was conducted, focusing on treatment analysis.