Truncal dystonia with isolated middle cerebral artery ischemia: A case report of revascularization therapy for dystonia.

Background: Dystonia is a rare movement disorder with some cases being difficult to treat. Although dystonia can occur as a symptom of moyamoya disease, few studies have reported truncal dystonia occurring with middle cerebral artery (MCA) stenosis. Here, we report a case of truncal dystonia with MCA occlusion. Case Description: The patient was a 48-year-old female clerical worker who lived alone. An abnormal cervical posture initially appeared 7 years before (right flexion). Symptoms improved with medication and botulinum toxin injection. Five years before this report, her symptoms worsened, so the dose of oral medication was increased and botulinum treatment was performed, but the symptoms did not improve. The patient showed decreased cerebral blood flow (CBF) in the cortical areas but not in the basal ganglia. We performed superficial temporal artery-MCA bypass surgery because we believed that the dystonia was due to right MCA stenosis. The patient's symptoms improved immediately after surgery, except for her mild cervical backbend. Seven months after the surgery, the patient's involuntary movements showed further improvement, and symptoms have not worsened even after 2 years. Conclusion: Revascularization therapy improved CBF and truncal dystonia and could be a viable treatment option for dystonia with ischemia in the MCA region. Extensive cerebral ischemia can result in cortical inhibition loss or over-adapted cerebral plasticity and cause dystonia. Revascularization therapy may be useful for patients with dystonia and decreased CBF in the MCA region.

Morphological analyses of nephrin expression in progressive glomerulonephropathy of common marmosets.

In this study, we focused on nephrin, one of the key molecules within the slit diaphragm of podocytes, as although there have been reports on its expression in humans and rats, their presence in common marmosets has not been reported. We investigated nephrin expression and changes in glomeruli, depending on the development of spontaneous progressive glomerulonephropathy in common marmosets. Nineteen common marmosets at two to ten years of age were evaluated. The kidney was examined by microscopy with hematoxylin and eosin and immunohistochemical staining for nephrin. The lesions were classified into three grades according to a renal lesion grading system reported previously. The nephrin-positive area was measured by morphometric analysis, and the nephrin-positive ratio was calculated. Nephrin expression was observed along the glomerular capillary loop in a continuous linear pattern in renal lesion grades 0 to 2 and either discontinuous linear or coarse granular pattern in grade 3. Nephrin expression tended to decrease significantly depending on the grade of renal lesions. Alteration in nephrin expression has been suggested to play an important role in the progression of renal lesions.

Prognostic impact of multiple fragmented QRS on cardiac events in idiopathic dilated cardiomyopathy.

AIMS: To evaluate the prognostic impact of fragmented QRS (fQRS) on idiopathic dilated cardiomyopathy (DCM). METHODS AND RESULTS: We conducted a prospective observational study of 290 consecutive patients with DCM (left ventricular ejection fraction ≤ 40%) and narrow QRS who underwent cardiac magnetic resonance. We defined fQRS as the presence of various RSR' patterns in ≥2 contiguous leads representing the anterior (V1-V5), inferior (II, III, and aVF), or lateral (I, aVL, and V6) myocardial segments. Multiple fQRS was defined as the presence of fQRS in ≥2 myocardial segments. Patients were divided into three groups: no fQRS, single fQRS, or multiple fQRS. The primary endpoint was a composite of hard cardiac events consisting of heart failure death, sudden cardiac death (SCD), or aborted SCD. The secondary endpoints were all-cause death and arrhythmic event. During a median follow-up of 3.8 years (interquartile range, 1.8-6.2), 31 (11%) patients experienced hard cardiac events. Kaplan-Meier analysis showed that the rates of hard cardiac events and all-cause death were similar in the single-fQRS and no-fQRS groups and higher in the multiple-fQRS group (P = 0.004 and P = 0.017, respectively). Multivariable Cox regression identified that multiple fQRS is a significant predictor of hard cardiac events (hazard ratio, 2.23; 95% confidence interval, 1.07-4.62; P = 0.032). The multiple-fQRS group had the highest prevalence of a diffuse late gadolinium enhancement pattern (no fQRS, 21%; single fQRS, 22%; multiple fQRS, 39%; P < 0.001). CONCLUSION: Multiple fQRS, but not single fQRS, is associated with future hard cardiac events in patients with DCM.

A spontaneous middle ear adenocarcinoma characterized by abundant eosinophilic matrix in a young male Crl:CD(SD) rat.

A mass was detected in the right tympanic cavity of a 15-week-old male Crl:CD(SD) rat. Histological examination revealed papillary or tubular proliferations of epithelial cells including ciliated cells that produce mucus and have an abundant eosinophilic matrix. The malignancy of this tumor was revealed by its destructive proliferation, cellular polymorphism, and high proliferative activity. The tumor was diagnosed as a middle ear adenocarcinoma due to its location and histological characteristics. This is the first report of a middle ear adenocarcinoma in rats and the first middle ear tumor accompanied by eosinophilic matrix observed in either humans or animals. The eosinophilic matrix was positive for periodic acid-Schiff and periodic acid-silver methenamine stains and for laminin and collagen Type IV, immunohistochemically, but negative for Congo red, which suggested that this matrix was a basement membrane substance.

Prognosis and Clinical Characteristics of Dilated Cardiomyopathy With Family History via Pedigree Analysis.

BACKGROUND: The clinical characteristics and prognostic outcomes of dilated cardiomyopathy (DCM) with a familial history (FHx) via pedigree analysis are unclear.Methods and Results:We conducted a prospective observational study of 514 consecutive Japanese patients with DCM. FHx was defined as the presence of DCM in ≥1 family member within 2-degrees relative based on pedigree analysis. The primary endpoint was a composite of major cardiac events (sudden cardiac death and pump failure death). The prevalence of FHx was 7.4% (n=38). During a median follow-up of 3.6 years, 77 (15%) patients experienced a major cardiac event. Multivariable Cox regression analysis identified FHx as independently associated with major cardiac events (hazard ratio [HR] 4.32; 95% confidence interval [CI], 2.04-9.19; P<0.001) compared with conventional risk factors such as age, QRS duration, and left ventricular volume. In the propensity score-matched cohort (n=38 each), the FHx group had a significantly higher incidence of major cardiac events (HR, 4.48; 95% CI, 1.25-16.13; P=0.022). In addition, the FHx group had a higher prevalence of a diffuse late gadolinium enhancement (LGE) pattern than the no-FHx group (32% vs. 17%, P=0.022). CONCLUSIONS: DCM patients with FHx had a worse prognosis, which was associated with a higher prevalence of a diffuse LGE pattern, than patients without FHx.

Immunohistochemical Characteristics of Thymomas and Hyperplastic Lesions in Wistar Hannover Rats.

Previously, we investigated the higher incidence of hyperplastic lesions and thymomas and histopathological resemblance of cortex-medullary structures between thymomas and normal thymuses in Wistar Hannover (WH) rats. Thymomas had pale-staining cell foci (PA) similar to medulla but without lymphocytes. Here, we focused on the differences in cytokeratin (CK) expression in the thymic epithelia of the cortex and medulla and compared the structures of thymomas and normal thymuses. Thymomas, hyperplastic lesions, and normal thymuses obtained from background studies of WH rats were stained with antibodies against CK14, CK18, and CD20. In normal thymuses, the epithelial cells were positive for CK14 in the medulla and subcapsular area and for CK18 in the cortex, B-cells were positive for CD20 in the medulla. In thymomas, the epithelial cells were positive for CK14 in the medullary differentiation (MD) areas and for CK18 in the cortex-like lymphocyte rich and PA, and B-cells were positive for CD20 in the MD areas.

CT-pathologic correlation of non-calcified atherosclerotic arterial plaques: a study using carotid endarterectomy specimens.

OBJECTIVE: Pathologic features of atherosclerotic plaques on CT are not established. We compared CT values among pathologically confirmed plaque constituents and evaluated their ability to distinguish plaque constituents. METHODS: 50 histopathological images of carotid endarterectomy samples from 10 males and 2 females (age 54-74 years, average 65.9 years) were examined. We compared pre-operative CT [pre-contrast (CT-P), early post-contrast phase (CT-E), delayed post-contrast phase (CT-D)] of lipid-rich necrotic core (NC) and fibrous tissue (F) plaque components with pathological images. The ability of features to differentiate plaque components using several discrimination techniques were compared. RESULTS: CT values of NC and F were 36 ± 13, 45 ± 11 (mean ± standard deviation, Hounsfield unit, HU), 41 ± 17, 69 ± 18, and 44 ± 16, 70 ± 13 in CT-P (p < 0.01), CT-E (p < 0.0001), and CT-D (p < 0.0001), respectively. The threshold, sensitivity, and accuracy for distinguishing NC from F were 44 HU, 74%, and 68%; 55 HU, 85%, and 85%; and 63 HU, 92%, and 84% in CTP, CT-E, and CT-D, respectively. CT-P had lower accuracy than CT-E and CT-D (both p < 0.05), but CT-E and CT-D were similar. CT-E and CT-D yielded 90 and 91% sensitivity and accuracy, respectively in linear discrimination analysis. CONCLUSION: In both pre- and post-contrast CT, CT values were lower in NC than F. Although values overlapped, using two-phase post-contrast CTs improved discrimination ability. ADVANCES IN KNOWLEDGE: Our findings may help to establish computer-aided diagnosis of vulnerable atherosclerotic plaques in future.

Supplemental study on 2', 3'-Cyclic Nucleotide 3'-Phosphodiesterase (CNPase) activity in developing rat spinal cord lesions induced by hexachlorophene and cuprizone.

In a previous study, we showed that 2', 3'-Cyclic Nucleotide 3'-Phosphodiesterase (CNPase) expression is induced in different temporal patterns in the cerebrum, cerebellum and medulla oblongata of hexachlorophene (HCP) and cuprizone (CPZ) treated rats. Here, we additionally examined the histopathological changes and CNPase expression in the spinal cord to clarify the reproducibility of different temporal patterns of CNPase expression in the spinal cord showing low degree or lack of spongy changes. Spongy changes were observed in HCP-treated rats, but not in CPZ-treated rats. Immunohistochemistry showed that intense expression of CNPase was not induced following HCP or CPZ treatment. Our data reveal that expression intensity of CNPase may be dependent on the degree of HCP- and CPZ-induced damage of the myelin sheath.

Small Hyperintensities in the Area of the Perforating Arteries in Patients with Seizure.

BACKGROUND/AIM: We previously observed spotty hyperintense lesions in the region of the perforating arteries on peri-ictal diffusion-weighted imaging (DWI); however, no report has formally described these findings. The aim of this study was to investigate focal intensities on peri-ictal DWI, and to evaluate the clinical significance of these lesions. METHODS: We conducted a retrospective review of 677 consecutive patients with seizure who completed peri-ictal DWI within 24 h after seizure onset. Patients were grouped according to the presence or absence of diffusion hyperintense lesions (DHLs) in the region of the perforating arteries. We compared clinical and imaging characteristics between these 2 groups. RESULTS: Among 677 patients, 23 patients (3.4%) had DHLs. Analyses of apparent diffusion coefficient values and fluid attenuated inversion recovery images suggested that DHLs were acute or subacute ischemic lesions that had appeared prior to seizure onset. Patients with DHLs were more likely to be older in age, have atrial fibrillation, and coronary artery disease, and have more severe deep white matter hyperintensity or leukoaraiosis compared to patients without DHLs. CONCLUSION: DHLs detected on peri-ictal DWI may represent incidental acute cerebral microinfarcts in the aging brain, especially in patients with small vessel disease.

Mortality and Sudden Cardiac Death Risk Stratification Using the Noninvasive Combination of Wide QRS Duration and Late Gadolinium Enhancement in Idiopathic Dilated Cardiomyopathy.

BACKGROUND: The aim of this study was to investigate whether the combination of QRS duration ≥120 ms (wide QRS duration [wQRS]) and late gadolinium enhancement (LGE) is a precise prognostic indicator for dilated cardiomyopathy. METHODS AND RESULTS: We investigated the association between the combination of LGE plus wQRS and the primary end point (all-cause death) and a composite of sudden cardiac death (SCD) or aborted SCD in 531 patients with dilated cardiomyopathy. We also analyzed the association between the combination of LGE and wQRS and these end points among patients with a class I indication for implantable cardioverter defibrillator implantation. We divided study patients into 3 groups according to LGE status and QRS duration: 2 negative indices (LGE negative and narrow QRS), 1 positive index (LGE positive or wQRS), or 2 positive indices (LGE positive and wQRS), and followed them for 3.8 years. Multivariable Cox regression analysis identified 2 positive indices as a significant predictor of all-cause death (hazard ratio, 4.29 [1.19-15.47]; P=0.026). Among 317 patients with a class I indication for implantable cardioverter defibrillator, the 5-year event rate of SCD or aborted SCD was the lowest in the 2 negative indices group (1.4%). With propensity score-matching cohorts, the 2 negative indices group had a significantly lower event rate of SCD or aborted SCD than the other 2 groups (hazard ratio, 0.12 [0.01-0.97]; P=0.046). CONCLUSIONS: The combination of LGE and wQRS provides additional prognostic stratification compared with LGE status alone and might improve the appropriate use of implantable cardioverter defibrillator therapy in patients with dilated cardiomyopathy.

Relationship Between Immunoglobulin Deposition and Early Lesions of Progressive Glomerulonephropathy in Young Common Marmosets.

The authors previously investigated progressive glomerulonephropathy in 2- to 11-year-old common marmosets and characterized age-related changes of the renal glomeruli and development of tubulointerstitial lesions. In this study, immunoglobulin deposition and ultrastructural changes of the glomeruli were investigated in 5 young marmosets from 6 months to 3 years of age with pre-onset or early glomerulonephropathy. In all animals, the foot processes of podocytes were effaced, and IgM was deposited into the glomeruli. In glomeruli without glomerular basement membrane (GBM) alteration, IgM was the only immunoglobulin type deposited in the glomeruli. In cases with more advanced lesions of reticulation and thickening of GBM, IgA and IgG deposits were also observed. Therefore, the authors conclude that IgM may be the primary or earliest immunoglobulin deposited in this nephropathy, whereas IgA and IgG deposition may be connected to the progression of the glomerular lesions. IgM deposition and foot process effacement of podocytes occur early in the life of affected marmosets.

Silent ischemic lesion laterality in asymptomatic internal carotid artery stenosis relates to reduced cerebral vasoreactivity.

BACKGROUND: We investigated the relationship between silent ischemic lesions, defined as hyperintense lesions on T2-weighted magnetic resonance imaging scans of brain white matter and cerebral hemodynamics (baseline cerebral blood flow and cerebral vasoreactivity). METHODS: Between January 2007 and December 2012, 61 patients with asymptomatic internal carotid artery stenosis were evaluated for asymptomatic silent ischemic lesions, acute infarction, and cerebral hemodynamics. Patients were divided into 2 groups based on silent ischemic lesion distribution; the Symmetry group (n = 34) included patients who showed symmetrical distribution of lesions (or had no lesions), and the Asymmetry group (n = 27) included patients with a greater number of lesions in the ipsilateral than that in the contralateral hemisphere. The Asymmetry group was further divided into Internal (n = 15) and External (n = 12) types. RESULTS: Two External-type patients (17%) showed spotty asymptomatic acute infarction in the ipsilateral hemisphere. There were no significant differences in patient characteristics, histopathological findings, vascular risk factors, or cerebral blood flow values between the groups. The mean cerebral vasoreactivity value in the ipsilateral hemisphere for the Internal type was 13.0 ± 15.2% (range: -11.4% to 41.6%), which was significantly lower than values of the contralateral hemisphere (36.7 ± 20.8%; range: 3.9% to 75.7%; P <.01) and ipsilateral hemispheres of the other groups (P <.01). CONCLUSIONS: The finding that increased ipsilateral asymmetrical silent ischemic lesions correlated with cerebral vasoreactivity reduction may help predict the risk of cerebral infarction in patients with asymptomatic internal carotid artery stenosis.

Lymphocytic adrenal medullitis and lymphocytic thyroiditis in a laboratory beagle dog.

Lymphocytic adrenal medullitis characterized by inflammation and atrophy in the medulla of the bilateral adrenal glands was observed in an 18-month-old male laboratory beagle dog. It might be that the present lymphocytic adrenal medullitis is an autoimmune-mediated disease as the histological characteristics are consistent with an autoimmune pathogenesis. However, the actual cause remains unclear as the existence of serum autoantibodies against the adrenal medulla could not be confirmed. Although this dog also contracted lymphocytic thyroiditis along with serum thyroglobulin autoantibodies, indicating that the thyroiditis occurred with an autoimmune basis; the relation between the adrenal medullitis and thyroiditis is unknown.

Histopathological and immunohistochemical characterization of spontaneous pituitary tumors in dwarfs derived from Wistar Hannover GALAS rats.

Histopathological and immunohistochemical characteristics of spontaneous pituitary adenomas found in dwarfs derived from Wistar Hanover GALAS are being described for the first time. The adenomas were seen in 5 males aged 48 weeks or older and in 11 females aged 34 weeks or older. Immunohistochemically, 13 cases without post-mortem changes could be evaluated; 4 Thyroid stimulating hormone (TSH)-containing adenomas, 2 TSH- and prolactin (PRL)-containing adenomas, 1 PRL-containing adenoma and 6 all-negative adenomas that did not react to any of the examined anti-hormone antibodies. The most common type were TSH-containing pituitary adenomas (a total of 6 cases; 46%) which occurred exclusively in females; the tumors consisted mainly of basophilic or amphophilic cells with bizarre nuclei and neoplastic cells and were positive for TSH in varying degrees. The TSH-containing pituitary adenomas, a characteristic of this mutant rat, could be induced by genetically-controlled hypothyroidism in dwarf rats, with higher sensitivity to possible disturbance of the pituitary-thyroid axis in females.

Late gadolinium enhancement in cardiac amyloidosis: attributable both to interstitial amyloid deposition and subendocardial fibrosis caused by ischemia.

Gadolinium contrast agents used for late gadolinium enhancement (LGE) distribute in the extracellular space. Global diffuse myocardial LGE pronounced in the subendocardial layers is common in cardiac amyloidosis. However, the pathophysiological basis of these findings has not been sufficiently explained. A 64-year-old man was admitted to our hospital with leg edema and nocturnal dyspnea. Bence Jones protein was positive in the urine, and an endomyocardial and skin biopsy showed light-chain (AL) amyloidosis. He died of ventricular fibrillation 3 months later. 9 days before death, the patient was examined by cardiac magnetic resonance (CMR) imaging on a 3-T system. We acquired LGE data at 2, 5, 10, and 20 min after the injection of gadolinium contrast agents, with a fixed inversion time of 350 ms. Myocardial LGE developed sequentially. The myocardium was diffusely enhanced at 2 min, except for the subendocardium, but LGE had extended to almost the entire left ventricle at 5 min and predominantly localized to the subendocardial region at 10 and 20 min. An autopsy revealed massive and diffused amyloid deposits in perimyocytes throughout the myocardium. Old and recent ischemic findings, such as replacement fibrosis and coagulative myocyte necrosis, were evident in the subendocardium. In the intramural coronary arteries, mild amyloid deposits were present within the subepicardial to the mid layer of the left ventricle, but no stenotic lesions were evident. However, capillaries were obstructed by amyloid deposits in the subendocardium. In conclusion, the late phase of dynamic LGE (at 10 and 20 min) visualized in the subendocardium corresponded to the interstitial amyloid deposition and subendocardial fibrosis caused by ischemia in our patient.

Morphometric analysis of progressive changes in hereditary cerebellar cortical degenerative disease (abiotrophy) in rabbits caused by abnormal synaptogenesis.

We previously investigated rabbit hereditary cerebellar cortical degenerative disease, called cerebellar cortical abiotrophy in the veterinary field, and determined that the pathogenesis of this disease is the result of failed synaptogenesis between parallel fibers and Purkinje cells. In this study, longitudinal changes in the development and atrophy of the cerebellum of rabbits with hereditary abiotrophy after birth were morphometrically examined (postnatal day [PD] 15 and 42) using image analysis. Although development of the cerebellum in rabbits with abiotrophy was observed from PD 15 to PD 42, the growth rate of the cerebellum was less than that in normal rabbits. In rabbits with abiotrophy, the number of granular cells undergoing apoptosis was significantly higher at PD 15 and dramatically decreased at PD 42. The number of granular cells did not increase from PD 15 to 42. The synaptogenesis peak at PD 15 occurred when the largest number of apoptotic granular cells in rabbits with abiotrophy was observed. Although 26% to 36% of parallel fiber terminals formed synaptic junctions with Purkinje cell spines, the remainder did not at PD 15 and 42. The rate of failure of synaptogenesis in the present study might be specific to this case of abiotrophy. Morphometric analysis revealed detailed changes in development and atrophy in animals with postnatal cerebellar disease occurring soon after birth.

Spontaneous and bilateral necrosis of the femoral head in a young experimental beagle dog.

This report describes the pathological characterizations of a rare case of necrosis of the femoral head that was spontaneous, bilateral, avascular and nontraumatic. A 14-month-old beagle dog was presented with pain in the hind limbs. At necropsy, the articular surface in the bilateral femoral head was markedly irregular. There were no gross abnormalities other than in the hip joints. Microscopically, a wide range of trabecular bone necrosis localized in the subchondral area was observed in both femoral heads. In the right femoral head, fibrosis and proliferative vessels were noted in the subchondral area. The articular cartilage was thickened irregularly, but there was no evidence of cartilage necrosis. The bone marrow adjacent to the affected area showed severe depression. In the metaphysis, atrophic bone marrow, but not bone necrosis, was observed. This was a rare case of spontaneous necrosis of the femoral head in an experimental beagle dog.

Arrhythmogenic right ventricular cardiomyopathy coincided with the cardiac fibrosis in the inner muscle layer of the left ventricular wall in a boxer dog.

A 7-year-old female boxer dog died suddenly without any clinical signs. It was suspected that the dog had arrhythmogenic right ventricular cardiomyopathy (ARVC) due to ventricular premature complexes and ventricular tachycardia at 3 years of age. The final diagnosis of ARVC was confirmed by histological characteristics, such as loss of cardiocytes and fibrofatty replacement, occurring in the right and left ventricular walls. In the cardiocytes, non-lipid vacuoles were observed. Cardiac fibrosis and intimal thickening of the small arteries occurred without fatty replacement in the inner muscle layer including the papillary muscles of the left ventricular wall. This paper describes the pathomorphological details of an ARVC case with coincidental cardiac fibrosis in the inner muscle layer of the left ventricular wall.

Erratum to: Preoperative brain magnetic resonance imaging and postoperative delirium after off-pump coronary artery bypass grafting: a prospective cohort study.

Erratum to: Can J Anesth/J Can Anesth DOI 10.1007/s12630-015-0327-x. In the published version, the first name of the third author is incorrect and should read Naoaki Yamada as given in this erratum. The publisher apologizes most sincerely for this error.

Prognostic impact of blood pressure response plus gadolinium enhancement in dilated cardiomyopathy.

OBJECTIVE: Late gadolinium enhancement (LGE) is not necessarily ideal for detecting diffuse myocardial fibrosis in idiopathic dilated cardiomyopathy (DCM). Since systolic blood pressure response (SBPR) during exercise has been proposed to reflect cardiac pump reserve in patients with heart failure, we wished to determine whether LGE plus SBPR is a better prognostic factor in patients with DCM. METHODS: LGE and cardiopulmonary exercise testing results in consecutive 207 patients with DCM were examined. Patients were divided into four groups according to the presence or absence of LGE and the SBPR cut-off value of +40 mm Hg according to receiver operating characteristic curve analysis: LGE-positive+SBPR <40 mm Hg (n=65), LGE-positive+SBPR ≥40 mm Hg (n=40), LGE-negative+SBPR <40 mm Hg (n=33) and LGE-negative+SBPR ≥40 mm Hg (n=69). The composite end point was cardiac death, cardiac transplantation, LV assist device implantation, life-threatening arrhythmia or heart failure. RESULTS: Forty-two (20%) patients developed the composite end point, with rates of 35%, 20%, 21% and 6% in patients with LGE-positive+SBPR <40 mm Hg, LGE-positive+SBPR ≥40 mm Hg, LGE-negative+SBPR <40 mm Hg and LGE-negative+SBPR ≥40 mm Hg status, respectively. Multivariable Cox regression analysis identified LGE-positive and SBPR <40 mm Hg as a significant independent predictor of cardiac events (HR 2.08, 95% CI 1.06 to 4.11, p=0.034). Of note, there was no significant difference in the cardiac event-free survival rate between the LGE-positive+SBPR ≥40 mm Hg and LGE-negative+SBPR <40 mm Hg groups (p=0.736). CONCLUSIONS: The combination of LGE and SBPR provides more clinically relevant information for assessing the risk of cardiac events in patients with DCM than LGE status alone.