A decade with anomic primary progressive aphasia.

Some patients with primary progressive aphasia (PPA) demonstrate only anomia. The lack of longitudinal observations of anomic PPA precluded us from determining whether progressive anomic aphasia was simply an early stage of semantic or logopenic variants, or a relatively independent variant. Herein, we report the 10-year clinical course of a patient with PPA who presented with pure anomic aphasia for 9 years. He is a right-handed man with anomia, who noticed word-finding difficulty at age 73. He was admitted to the hospital at age 77. On admission, the patient showed pure anomic aphasia with preserved other language function. Episodic memory and visuospatial function were preserved. Magnetic resonance imaging (MRI) revealed left temporal lobe atrophy. At 82 years of age, the patient presented with pure anomic aphasia. At 83 years old, he showed mild impairment in word comprehension and semantic memory, in addition to anomia. MRI demonstrated further atrophy in the bilateral anterior temporal lobes, predominantly on the left side. This case suggests the possibility of slowly progressive, late-onset anomic PPA, which could be differentiated from the early stage of semantic or logopenic variants.

The grasp reflex in patients with idiopathic normal pressure hydrocephalus.

OBJECTIVE: To investigate the prevalence and intensity of grasp reflexes and to examine changes in these reflexes after shunt surgery in patients with idiopathic normal pressure hydrocephalus (iNPH). METHODS: We enrolled 147 patients with probable iNPH. A standard procedure was used to determine the presence of grasp reflexes, and the intensity of these reflexes was assessed using a four-category classification. Clinical rating scales and their correlation with grasp reflexes were also evaluated. Grasp reflexes were reassessed in 72 patients 1 year after surgery. RESULTS: We found that approximately 50.3% of patients with iNPH exhibited a positive grasp reflex. Among these patients, 69% exhibited bilateral positivity, while the remaining patients showed unilateral positivity. Furthermore, the intensity of the grasp reflex was significantly correlated with the severity of gait and with cognitive, urinary, motor, and behavioural symptoms. Surgical interventions led to a reduction (41.7%) or maintenance (30.6%) of the reflex intensity in 72.3% of iNPH patients. The changes in reflex intensity showed significant positive correlations with changes in the number of steps of the Timed Up and Go test and Trail Making Test-A scores but not with changes in total scores on the iNPH Grading Scale. CONCLUSION: This retrospective study identified grasp reflexes as a highly prevalent phenomenon in patients with iNPH. These reflexes can assist in evaluating the severity of various symptoms, including cognitive, gait, urinary, motor and emotional symptoms.

Auditory phonological identification impairment in primary progressive aphasia.

OBJECTIVE: To examine the audiological characteristics and neuroanatomical regions associated with auditory phonological identification impairment in primary progressive aphasia (PPA). METHODS: Twenty-seven patients with PPA [13 non-fluent/agrammatic variant PPA (nfvPPA), three logopenic variant PPA (lvPPA), seven semantic variant PPA (svPPA), and four mixed type PPA] were included in the study. Neuropsychological, language, audiological, and neuroradiological examinations were also performed. Auditory function examinations consisted of a pure-tone threshold test, a phonological identification task, and temporal auditory acuity tests, such as click counting or fusion. As an evaluation value of phonological identification ability, we calculated the discrepancy scores, which were the smaller discrepancy (left or right ear) in phonological identification ability scores between measured and expected values from the pure-tone threshold. In the neuroradiological examination, we evaluated the regional cerebral blood flow using 123I-iodoamphetamine single-photon emission computed tomography. RESULTS: Eight of the 27 patients were allocated to the impaired phonological identification group, and four were considered to have significant impairment on further analysis. Two of these patients, one with lvPPA and one with mixed type of lvPPA and nfvPPA, showed apparent phonological identification deficits that could be observed in daily life. The discrepancy scores were not significantly related to the results of neuropsychological, language, or any other auditory examinations, except for the click counting score in the left ear. Voxel-based correlation analyses revealed that regional cerebral blood flow in the bilateral superior temporal gyrus and bilateral primary auditory cortex was significantly and positively correlated with phonological identification ability. CONCLUSIONS: Our results suggest that progressive dysfunction of the bilateral superior temporal gyrus and bilateral primary auditory cortex due to neurodegenerative diseases leads to phonological identification impairment in PPA syndrome.

Buccofacial apraxia in primary progressive aphasia.

Buccofacial apraxia (BFA) is associated with nonfluent/agrammatic variant primary progressive aphasia (nfvPPA) as well as with the severity of apraxia of speech (AOS), a core symptom of nfvPPA. However, an association with agrammatism has not been established. The aim of this study was to examine the association between BFA and agrammatism in nfvPPA and to determine differences in atrophic regions in primary progressive aphasia (PPA) with and without BFA. Seventy-four patients with PPA were recruited, including 34, 15, 10, and 15 patients with nfvPPA, semantic variant PPA, logopenic variant PPA, and unclassified PPA, respectively. All patients underwent language examination and BFA evaluations. Voxel-based morphometry (VBM) was performed to determine whether atrophy of a specific lesion correlated with the presence of BFA. BFA was observed in 20 and 3 patients with nfvPPA and unclassified PPA, respectively. In a comparison of patients with nfvPPA with and without BFA, the BFA group showed significantly worse spontaneous speech and writing in the Western Aphasia Battery. The agrammatism ratio or the ratio of agrammatic errors to the total number of particles was higher in the BFA group; however, the severity of prosodic and phonetic components of AOS did not differ between the two groups. VBM showed that the severity of BFA correlated with atrophy of the opercular and triangular areas of the inferior frontal gyrus to a part of the left middle frontal gyrus. BFA has a different anatomical basis from AOS in patients with nfvPPA and that BFA is characterized by more anterior degeneration compared to that of AOS.

Dyslexia and dysgraphia of primary progressive aphasia in Chinese: A systematic review.

Introduction: Currently, little is known about Chinese-speaking primary progressive aphasia (PPA) patients compared to patients who speak Indo-European languages. We examined the demographics and clinical manifestations, particularly reading and writing characteristics, of Chinese patients with PPA over the last two decades to establish a comprehensive profile and improve diagnosis and care. Methods: We reviewed the demographic features, clinical manifestations, and radiological features of Chinese-speaking PPA patients from 56 articles published since 1994. We then summarized the specific reading and writing errors of Chinese-speaking patients. Results: The average age of onset for Chinese-speaking patients was in their early 60's, and there were slightly more male patients than female patients. The core symptoms and images of Chinese-speaking patients were similar to those of patients who speak Indo-European languages. Reading and writing error patterns differed due to Chinese's distinct tone and orthography. The types of reading errors reported in Chinese-speaking patients with PPA included tonal errors, regularization errors, visually related errors, semantic errors, phonological errors, unrelated errors, and non-response. Among these errors, regularization errors were the most common in semantic variant PPA, and tonal errors were specific to Chinese. Writing errors mainly consisted of non-character errors (stroke, radical/component, visual, pictograph, dyskinetic errors, and spatial errors), phonologically plausible errors, orthographically similar errors, semantic errors, compound word errors, sequence errors, unrelated errors, and non-response. Conclusion: This paper provides the latest comprehensive demographic information and unique presentations on the reading and writing of Chinese-speaking patients with PPA. More detailed studies are needed to address the frequency of errors in reading and writing and their anatomical substrates.

Determination of language areas in patients with epilepsy using the super-selective Wada test.

The Wada test is the gold standard for determining language-dominant hemisphere. However, the precise determination of language areas in each patient requires more invasive methods, such as electrocortical stimulation. Some studies have reported the use of anesthetic injection into selective cerebral arteries to predict postoperative function. To assess the function of the anterior and posterior language areas separately, we developed an advanced test named the "super-selective Wada test" (ssWada). The ssWada procedure is as follows: an endovascular neurosurgeon identifies the arterial branches of the middle cerebral artery (MCA) perfusing the anterior language area of the inferior frontal gyrus and the posterior language area of the posterior part of the superior temporal gyrus using angiography. Behavioral neurologists assess language symptoms before and after propofol administration using a microcatheter tip in the selected arterial branch. From 30 serial patients with epilepsy who underwent ssWada test at Tohoku University Hospital, we retrospectively reviewed patients in whom multiple areas in the bilateral MCA region was examined. Eight cases were identified in this study. All eight cases had been considered for resection of the area overlapping the classical language area. Three of the eight cases were left-dominant, and the within-hemisphere distribution was also considered typical. One case was determined to be left-dominant but atypical in the intra-hemispheric functional distribution. Two cases were right-dominant, and the intra-hemispheric functional distribution was considered a mirror image of the typical pattern. The remaining two cases were considered atypical, not only in terms of bilateral language function, but also in terms of anterior-posterior functional distribution. This case series demonstrates the potential utility of ssWada in revealing separate function of the anterior and posterior language areas. The ssWada allows simulation of local surgical brain resection and detailed investigation of language function, which potentially contributes to planning the resection area. Although indications for ssWada are quite limited, it could play a complementary role to noninvasive testing because it provides information related to resection using a different approach.

Echolalia in patients with primary progressive aphasia.

OBJECTIVE: This study aimed to examine echolalia and its related symptoms and brain lesions in primary progressive aphasia (PPA). METHODS: Forty-five patients with PPA were included: 19 nonfluent/agrammatic variant PPA (nfvPPA), 5 semantic variant PPA, 7 logopenic variant PPA, and 14 unclassified PPA patients. We detected echolalia in unstructured conversations. An evaluation of language function and the presence of parkinsonism, grasp reflex, imitation behaviour, and disinhibition were assessed. We also measured regional cerebral blood flow (rCBF) using single-photon emission computed tomography. RESULTS: Echolalia was observed in 12 nfvPPA and 2 unclassified PPA patients. All patients showed mitigated echolalia. We compared nfvPPA patients with echolalia (echolalia group) to those without echolalia (non-echolalia group). The median age of the echolalia group was significantly lower than that of the non-echolalia group, and the echolalia group showed a significantly worse auditory comprehension performance than the non-echolalia group. In contrast, the performance of repetition tasks was not different between the two groups. The prevalence of imitation behaviour in the echolalia group was significantly higher than that in the non-echolalia group. The rCBFs in the bilateral pre-supplementary motor area and bilateral middle cingulate cortex in the echolalia group were significantly lower than those in the non-echolalia group. CONCLUSIONS: These findings suggest that echolalia is characteristic of nfvPPA patients with impaired comprehension. Reduced inhibition of the medial frontal cortex with release activity of the anterior perisylvian area account for the emergence of echolalia.

Agitation of the syringe and release of silicone oil.

BACKGROUND/OBJECTIVES: To investigate whether agitation promotes the release of silicone oil by different models of syringe used for intravitreal injection. METHODS: This lab study analyzed eight syringe models by light microscopy for the release of silicone oil under agitation (flick), without agitation, and positive controls. Fourier-Transform Infrared Spectroscopy (FTIR) was performed to identify the molecular compounds inside the syringes. RESULTS: A total of 240 syringes were analyzed. The presence of silicone oil droplets was observed in all positive controls. When agitated by flicking, 100% of the samples of the syringes disclosed silicone oil, except the BD Plastipak syringe, which presented 40% of positivity. Without agitation, a smaller percentage of samples with silicone oil was observed. Agitation by flicking had a 265-fold greater chance of presenting oil droplets when compared with the syringes without agitation. There was a statistically significant difference between the three conditions (P < 0.05). Analysis of the tip of the plunger rubber by FTIR indicated the presence of polysiloxane (silicone oil) in all models of syringe. CONCLUSIONS: Agitation of the syringe promotes the release of silicone oil. It is recommended to improve the technique of injection and the manufacture of specific syringes for ophthalmological use.

Release of silicone oil and the off-label use of syringes in ophthalmology.

BACKGROUND/AIMS: To assess silicone oil (SO) release by different brands of syringes used for intravitreal injection under different handling conditions. METHODS: Eight syringes were analysed: from the USA, Terumo 0.5 mL, Becton-Dickinson (BD) Tuberculin 1 mL, BD Luer-lok 1 mL, BD Ultra-Fine 0.3 mL and Exel Insulin 0.3 mL; from Germany, Braun Omnifix-F 1 mL and Braun Injekt-F 1 mL and from Spain, BD Plastipak 1 mL. The impact of air, priming the plunger, agitation by flicking and fluid temperature on SO release were assessed by light microscopy. Fourier transform infrared spectroscopy (FTIR) was performed to identify the molecular compound in each syringe. RESULTS: Five hundred and sixty syringes were analysed. Terumo 0.5 mL and BD Ultra-Fine 0.3 mL released more SO than all others. BD Luer-lok 1 mL, BD Plastipak and Braun Omnifix-F 1 mL released little SO; BD Tuberculin 1 mL, Exel 0.3 mL and Braun Injekt-F 1 mL released the least SO. Priming the syringe and different temperatures did not significantly affect SO release. Agitation by flicking caused a significantly higher proportion of samples to have SO droplets and an increased number of oil droplets. Air had an additive effect on the release of oil in the agitation groups. FTIR identified polysiloxane in all syringes but Injekt-F. CONCLUSION: Syringes commonly used for intravitreal injections frequently release SO droplets, especially when agitated by flicking. To avoid unnecessary ocular risks, syringes should not be agitated before intravitreal injection. It is desirable that syringes be manufactured specifically for ophthalmic use.

Sentence composition ability in two patients with non-fluent/agrammatic variant primary progressive aphasia.

Agrammatism is one of the core clinical features of non-fluent/agrammatic variant primary progressive aphasia, and it has traditionally been considered the hallmark of non-fluent aphasia in Western countries. However, agrammatic speech may remain undetected in Japanese patients because of the agglutinative structure of the language and high flexibility in word order. In the present study, we aimed to analyze agrammatism in the speech production of Japanese patients with aphasia due to neurodegenerative disease using an anagram test generated by our laboratory. Four patients were recruited from the dementia clinic at Tohoku University Hospital between December 2014 and August 2015: two patients with non-fluent/agrammatic variant primary progressive aphasia, one with semantic variant primary progressive aphasia, and one with probable Alzheimer's disease experiencing episodic memory impairment accompanied by transcortical sensory aphasia. All patients underwent thorough neurological and neuropsychological testing before performing a Japanese anagram task based on the Northwestern Anagram Test. Our findings indicated that the two patients with non-fluent/agrammatic variant primary progressive aphasia exhibited poorer performance on the anagram task than the remaining two patients. Therefore, the anagram test used in the present study may aid in detecting output aspects of agrammatism in Japanese patients with aphasia, although future studies are required to develop a standardized version of test.

The Reliabilities of Several Measurement Methods of Cervical Sagittal Alignment in Cases with Cervical Spine Rotation Using X-ray Findings in Cervical Spine Disorders.

INTRODUCTION: Several measurement methods designed to provide an understanding of cervical sagittal alignment have been reported, but few studies have compared the reliabilities of these measurement methods. The purpose of the present study was to investigate the intraexaminer and interexaminer reliabilities of several cervical sagittal alignment measurement methods and of the rotated cervical spine using plain lateral cervical spine X-rays of patients with cervical spine disorders. METHODS: Five different measurement methods (Borden's method; Ishihara index method (Ishihara method); C2-7 Cobb method (C2-7 Cobb); posterior tangent method: absolute rotation angle C2-7 (ARA); and classification of cervical spine alignment (CCSA)) were applied by seven examiners to plain lateral cervical spine X-rays of 20 patients (10 randomly extracted cases from a rotated cervical spine group and 10 from a nonrotated group) with cervical spine disorders. Case 1 and Case 2 intraclass correlation coefficients (ICCs) were used to analyze intraexaminer and interexaminer reliabilities. The necessary number of measurements and the necessary number of examiners were also determined. The target coefficient of correlation was set at ≥0.81 (almost perfect ICC). RESULTS: In both groups, an ICC(1, 1) ≥ 0.81 was obtained with Borden's method, the Ishihara method, C2-7 Cobb, and ARA by all examiners. The necessary number of measurements was 1. With CCSA, a kappa coefficient of at least 0.9 was obtained. In both groups, with Borden's method, the Ishihara method, C2-7 Cobb, and ARA, the ICC(2, 1) was ≥0.9, indicating that the necessary number of examiners was 1. The standard error of measurement (SEM) was lowest with Borden's method, and the Ishihara method and C2-7 Cobb had almost the same values. CONCLUSIONS: Among cervical sagittal alignment measurement methods for cervical spine disorders, regardless of cervical spine rotation, Borden's method, Ishihara method, and C2-7 Cobb offer stronger reliability in terms of the ICC and SEM.

Development of Microelectrode Arrays Using Electroless Plating for CMOS-Based Direct Counting of Bacterial and HeLa Cells.

The development of two new types of high-density, electroless plated microelectrode arrays for CMOS-based high-sensitivity direct bacteria and HeLa cell counting are presented. For emerging high-sensitivity direct pathogen counting, two technical challenges must be addressed. One is the formation of a bacteria-sized microelectrode, and the other is the development of a high-sensitivity and high-speed amperometry circuit. The requirement for microelectrode formation is that the gold microelectrodes are required to be as small as the target cell. By improving a self-aligned electroless plating technique, the dimensions of the microelectrodes on a CMOS sensor chip in this work were successfully reduced to 1.2 µm × 2.05 µm. This is 1/20th of the smallest size reported in the literature. Since a bacteria-sized microelectrode has a severe limitation on the current flow, the amperometry circuit has to have a high sensitivity and high speed with low noise. In this work, a current buffer was inserted to mitigate the potential fluctuation. Three test chips were fabricated using a 0.6- µm CMOS process: two with 1.2 µm × 2.05 µm (1024 × 1024 and 4 × 4) sensor arrays and one with 6- µm square (16 × 16) sensor arrays; and the microelectrodes were formed on them using electroless plating. The uniformity among the 1024 × 1024 electrodes arranged with a pitch of 3.6 µm × 4.45 µm was optically verified. For improving sensitivity, the trenches on each microelectrode were developed and verified optically and electrochemically for the first time. Higher sensitivity can be achieved by introducing a trench structure than by using a conventional microelectrode formed by contact photolithography. Cyclic voltammetry (CV) measurements obtained using the 1.2 µm × 2.05 µm 4 × 4 and 6- µm square 16 × 16 sensor array with electroless-plated microelectrodes successfully demonstrated direct counting of the bacteria-sized microbeads and HeLa cells.