Elevated levels of autoantibodies against DNAJC2 in sera of patients with atherosclerotic diseases.

BACKGROUND: Serum antibody markers have been increasingly identified not only for cancer and autoimmune diseases but also for atherosclerosis-related diseases such as acute ischemic stroke (AIS), acute myocardial infarction (AMI), diabetes mellitus (DM), and chronic kidney disease (CKD). Biomarkers for transient ischemic attack (TIA) and non-ST segment elevation acute coronary syndrome (NSTEACS) are potentially useful for detection of early phase of atherosclerotic changes against AIS and AMI, respectively. METHODS: We utilized serological identification of antigens by recombinant cDNA expression cloning (SEREX) using a human aortic endothelial cell cDNA phage library and sera from patients with TIA or NSTEACS. Serum antibody levels were measured by amplified luminescent proximity homogeneous assay-linked immunosorbent assay (AlphaLISA) using purified recombinant antigens. RESULTS: Screening of sera from patients with TIA identified DnaJ heat shock protein family (Hsp40) member C2 (DNAJC2) as a candidate antigen, which was also isolated by SEREX screening using sera of patients with NSTEACS. The validation cohort revealed significantly higher DNAJC2 antibody (DNAJC2-Ab) levels in the sera of patients with TIA or AIS than those in healthy donors (HDs). Multivariate logistic regression analysis indicated that the predictive odds ratios (OR) of DNAJC2-Ab levels for TIA and AIS were 2.54 (95% confidence interval [CI]: 1.36-4.74, p = 0.0034) and 2.14 (95% CI: 1.39-3.30, p = 0.0005), respectively. Serum DNAJC2-Ab levels were also higher in patients with AMI, DM, and CKD than those in HDs. CONCLUSION: Serum DNAJC2-Ab level may be useful for early detection of atherosclerotic lesions, which lead to AIS and AMI.

Sagittal splitting of the temporalis muscle for encephalo-myo-synangiosis to prevent ischemic complications due to a swollen temporalis muscle without inhibiting collateral developments in patients with moyamoya disease.

OBJECTIVEEncephalo-myo-synangiosis (EMS) is an effective revascularization procedure for the treatment of moyamoya disease (MMD). However, the temporalis muscle used for EMS sometimes swells and causes ischemic complications by compressing the underlying brain. This study aimed to elucidate the effect of sagittal splitting (SS) of the muscle for prevention of ischemic complications and its impact on the postoperative development of collateral vessels.METHODSIn this historical case-control study, we analyzed 60 hemispheres in adult patients with MMD who underwent EMS using the temporalis muscle from December 1998 to November 2017. The muscle was divided anteroposteriorly by coronal splitting, and the anterior, posterior, or both parts of the muscle were used for EMS in 17, 4, and 39 hemispheres, respectively. In cases performed after 2006, the muscle was halved by SS, and the medial half was used for EMS to reduce the muscle volume (n = 47). The degree of postoperative muscle swelling was evaluated by measuring the maximum thickness of the muscle on CT scans obtained 3 to 7 days after surgery. The collateral developments of the anterior deep temporal artery (aDTA), posterior deep temporal artery (pDTA), and middle temporal artery (MTA) were assessed using digital subtraction angiography and MR angiography performed 6 months or more after surgery.RESULTSSS significantly reduced the temporalis muscle thickness from 12.1 ± 5.0 mm to 7.1 ± 3.0 mm (p < 0.01). Neurological deterioration due to the swollen temporalis muscle developed in 4 of the 13 hemispheres without SS (cerebral infarction in 1, reversible neurological deficit in 2, and convulsion in 1) but in none with SS. There were no significant differences in the postoperative collateral developments of the aDTA, pDTA, and MTA between hemispheres with and without SS. The MTA more frequently developed in hemispheres with EMS in which the posterior part of the muscle was used (30/37) than those in which this part was not used (4/16) (p < 0.01).CONCLUSIONSSS of the temporalis muscle might prevent neurological deterioration caused by the swollen temporalis muscle by reducing its volume without inhibiting the development of the collateral vessels.

Cortical Venous Redness Represents Tissue Circulation Status in Patients With Moyamoya Disease.

BACKGROUND AND PURPOSE: Venous oxygen saturation (SO2) is measured in medical fields to assess tissue circulation insufficiency. This study aimed to elucidate the use of a cortical venous redness measurement to evaluate hemodynamic changes during revascularization surgery for patients with moyamoya disease. METHODS: In this retrospective case-series analysis, we first quantitatively measured and correlated SO2 and R intensity of 24-bit color digital red-green-blue pictures of blood samples from 3 volunteers. Subsequently, based on intraoperative digital pictures of 29 patients with moyamoya disease, we measured the R intensities of a cortical vein near the anastomosis site before and after anastomosis. Cerebral blood flow (CBF) at the site was measured using a single-photon emission computed tomography before and 1 to 3 days after surgery. Venous R intensity and CBF were measured twice by 4 raters, and their correlations were examined using generalized linear mixed effect model and linear regression analysis. RESULTS: A strong linear correlation was found between blood R intensity and its SO2 (coefficients, 0.522; 95% confidence interval, 0.364-0.680, using generalized linear mixed effect model). Venous R intensity before the anastomosis was not correlated with preoperative CBF (coefficients, 0.000352; 95% confidence interval, -0.000369 to 0.00107, by generalized linear mixed effect); however, the increases in venous R intensity after anastomosis were correlated with postoperative increases in CBF (R2, 0.367; 95% confidence interval, 0.116-0.618 to 0.548; 95% confidence interval, 0.331-0.764, by linear regression analysis). CONCLUSIONS: Cortical venous redness represented impaired CBF and could be a useful parameter for assessing hemodynamic changes during revascularization surgery.

Cutaneous sympathetic dysfunction in patients with Machado-Joseph disease.

Although the clinical symptoms of Machado-Joseph disease (MJD) vary widely, those involving the autonomic nervous system, such as cutaneous sympathetic dysfunction, have rarely been investigated. In addition, there are no reports on cutaneous vasomotor function in patients with MJD. To determine the effects of MJD on cutaneous sympathetic function, we evaluated cutaneous vasomotor and sudomotor responses in the palms of 15 patients (mean age, 49 ± 15 years; seven men and eight women) who were genetically diagnosed with MJD as well as in the palms of 15 age-matched, healthy controls (mean age, 48 ± 16 years; nine men and six women). Sweat response was absent in 10 (67 %) patients with MJD, and the mean amplitude of sweat response was significantly lower (p<0.0001) in patients with MJD than in healthy controls following mental stress (mental arithmetic) and physiological stimuli. Although vasoconstrictive response was absent in three patients with MJD (20 %), there were no significant differences in the mean amplitude of vasoconstrictive response between patients with MJD and healthy controls. These results indicate that patients with MJD have reduced cutaneous sympathetic response, including severely impaired sudomotor functions and mildly affected vasomotor functions.

Spectral analysis of heart rate variability in patients with Machado-Joseph disease.

OBJECTIVE: Tachycardia is a clinical feature of Machado-Joseph disease (MJD), and it may be attributable to cardiac autonomic dysfunction. We investigated heart rate variability in MJD patients to reveal heart rate dysregulation in MJD. METHODS: Power spectral analysis of successive R-R intervals (300 beats) was performed in 10 genetically diagnosed MJD patients and 10 healthy control subjects to obtain frequency-domain measures, including high- (HF; 0.15-0.4 Hz) and low frequency power (LF; 0.04-0.15 Hz) and the ratio of LF to HF (LF/HF) of heart rate variability. In addition, the coefficient of R-R intervals (CV(R-R)) was calculated as a time-domain measure. RESULTS: HF in the MJD patients (26.2+/-25.3 ms(2)) was lower than that in the controls (82.1+/-82.6 ms(2), p=0.004). LF was also lower in the MJD patients (70.6+/-69.4 ms(2)) than in the controls (106.9+/-81.3 ms(2); p=0.029). There was no significant difference in LF/HF or CV(R-R) between the groups. CONCLUSION: HF, which is modulated by parasympathetic vagal activity, was low in our MJD patients. The reduced parasympathetic activity may be a cause of tachycardia in MJD patients.

Differences in skin sympathetic involvements between two chronic autonomic disorders: multiple system atrophy and pure autonomic failure.

OBJECTIVE: Certain stimuli evoke increased sweat secretion (sympathetic sweat response; SSwR) and reduced skin blood flow (skin vasomotor reflex; SkVR) in the palm/sole. We evaluated SSwR and SkVR in patients with multiple system atrophy (MSA) and pure autonomic failure (PAF). METHODS: SSwR and SkVR on the palm in response to deep inspiration and mental arithmetic were recorded in 11 MSA patients, 11 PAF patients, and 11 healthy controls. In addition, the head-up tilt test was performed, and the coefficient of variation of R-R intervals (CV(R-R)) was obtained. RESULTS: SSwR amplitudes were significantly lower in the MSA and PAF patients than the controls. SkVR amplitudes in the PAF patients were significantly lower than the controls, but preserved in the MSA patients. In head-up tilt tests, all MSA and PAF patients showed orthostatic hypotension, with similar severity. CV(R-R) was low in the MSA and PAF patients, but a significant difference was found only between the PAF and control groups. CONCLUSION: In the MSA patients, SkVR was preserved, but SSwR was diminished. In the PAF patients, both SkVR and SSwR were attenuated. The combination of SkVR and SSwR tests may differentiate MSA and PAF.

Measurements of sweat response and skin vasomotor reflex for assessment of autonomic dysfunction in patients with diabetes.

AIMS: Some physical or arousal stimuli induce a rise in sweat secretion (sympathetic sweat response or SSwR) and a reduction in skin blood flow (skin vasomotor reflex or SkVR) to the palm. We recorded SSwRs and SkVRs in diabetic patients and assessed the usefulness of these parameters for evaluating autonomic dysfunction in diabetes. METHODS: We studied 42 diabetic patients (58+/-12 years) and 42 normal control subjects (59+/-11 years). Focal sweat secretion and skin blood flow were measured on the palm by a sudorometer and a Doppler flowmeter, respectively. SSwRs and SkVRs to deep inspiration, mental arithmetic, and isotonic exercise were recorded. SSwR amplitude was measured from baseline to peak, and SkVR amplitude (reduction rate) was calculated as: (blood flow reduction/basal blood flow)x100%. We also conducted head-up tilt tests and R-R interval variation tests (coefficient of variation of R-R intervals or CV(R-R)). RESULTS: The SSwR or SkVR amplitudes in the diabetic group were significantly lower than those in the control group for any stimulus. CV(R-R) in the diabetic group was significantly less than that in the control group. The diabetic group showed a significantly greater reduction in systolic blood pressure during head-up tilt compared with the control group. In the diabetic group, there were significant correlations in SSwR or SkVR amplitudes versus blood pressure falls during the head-up tilt test, and CV(R-R) values. CONCLUSION: We believe that SSwR and SkVR are useful indexes for the evaluation of autonomic involvement in diabetic patients.

Skin vasodilator response to local heating in multiple system atrophy.

Local heating of nonglabrous skin increases skin blood flow (SkBF) in two phases. The initial peak (P1) is mediated by a sensory-axon reflex and the plateau phase (P2) by local production of substances such as nitric oxide. We evaluated the SkBF response to local heating in 15 multiple system atrophy (MSA) patients with autonomic failure and 12 age-matched healthy controls. The mean ratio of SkBF at P1 to that at baseline (SkBF(P1)/SkBF(base) ratio) in MSA was significantly lower than that in controls (P < 0.01). The mean ratio of SkBF at P2 seemed to be slightly reduced in the MSA patients, compared with controls, although there was no significant difference. The P1 phase is thought to be mediated by a sensory-axon reflex modulated by sympathetic nerve activity. These findings are indicative of the skin sympathetic vasomotor dysfunction in MSA.

Diminished skin vasodilator response to local heating in patients with long-standingsubacute myelo-optico-neuropathy.

BACKGROUND: Local heating of non-glabrous skin increases skin blood flow (SkBF) in two phases: the initial peak (P1) is mediated by sensory axon reflex, and the plateau phase (P2) is thought to be mediated by local production of substances including nitric oxide. We evaluated P1 and P2 responses in subacute myelo-optico-neuropathy (SMON). METHODS: SkBF response to local heating from 32 degrees C (5 min of baseline) to 42 degrees C (at least for 30 min) of the dorsal surface of the hand skin were measured in 7 SMON patients (67.6+/-10.0 years) and 7 normal control volunteers (65.0+/-7.4 years) participated. RESULTS: Mean values of SkBF at P1 (SkBFP1) and SkBF during P2 (SkBFP2) were significantly lower in SMON patients than in controls (p<0.05, p<0.05). Mean SkBFP1/SkBF at baseline (SkBFbase) and SkBFP2/SkBFbase ratios were significantly lower in SMON patients than in controls (p<0.01 and p<0.05, respectively). CONCLUSIONS: The SkBF response to local heating was diminished in SMON patients. This may reflect the involvement of the spinal cord, peripheral sensory nerves, and sympathetic post-ganglionic nerves in SMON.