Yoshimi Matsuo

Effect of coenzyme Q10 in patients with mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke-like episodes (MELAS): Evaluation by noninvasive tissue oximetry

We evaluated the effect of coenzyme Q10 supplementation to two patients with mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke-like episodes (MELAS) by using noninvasive tissue oximetry with near-infrared spectra of hemoglobin from the quadriceps muscle during bicycle ergometer exercise. Patients showed distinct oxygen consumption patterns reflecting the defect in oxidative phosphorylation and the impairment in oxygen utilization during exercise. Based on the oxygen consumption pattern, we considered one patient as having severe mitochondrial disorder and another patient as having mild one. After coenzyme Q10 supplementation, the oxygen consumption pattern of the patient with the severe form shifted to the mild one, while that of the patient with mild form remained unchanged. The shift of the pattern to the mild form correlated well with reduction of the sum of the serum lactate and pyruvate content during exercise. Noninvasive tissue oximetry may be useful to evaluate the effect of coenzyme Q10 supplementation to patients with mitochondrial encephalomyopathy including MELAS.

Classifying lower limb dynamics in Parkinson’s disease

To classify lower limb dynamics in patients with Parkinsons disease (PD), we conducted a clinical study by using pedaling exercise.Twenty-seven patients with idiopathic PD were included in this study. We measured rotational velocities of pedals during pedaling movements with a newly developed ergometer. The velocity waveforms exhibited different characteristics among patients, which could be categorized into four different clusters. In cluster 1, the amplitude on each side was constant and the relative phase was locked at 180 degrees. The pattern was the same as seen in normal subjects. In cluster 2, the amplitude on each side was constant, but the relative phase was locked at 90 degrees. In cluster 3, the amplitude on each side was modulated, and the relative phase drifted monotonously from 0 to 360 degrees during pedaling cycles. In cluster 4, the amplitude on each side was synchronously and irregularly modulated, and the relative phase fluctuated with intermittent spike-like decrement. In order to evaluate, the correlation between pattern and severity of PD, we divided 13 patients, who underwent measurement of pedaling patterns more than three times, into three groups, and found that the abnormal coordination pattern correlated with the presence of freezing phenomenon in patients with PD. Our clinical analysis may contribute in analyzing and classifying the dynamics of PD.

A coupled oscillator model of disordered interlimb coordination in patients with Parkinson's disease

Abstract. Coordination between the left and right limbs during cyclic movements, which can be characterized by the amplitude of each limbs oscillatory movement and relative phase, is impaired in patients with Parkinsons disease (PD). A pedaling exercise on an ergometer in a recent clinical study revealed several types of coordination disorder in PD patients. These include an irregular and burst-like amplitude modulation with intermittent changes in its relative phase, a typical sign of chaotic behavior in nonlinear dynamical systems. This clinical observation leads us to hypothesize that emergence of the rhythmic motor behaviors might be concerned with nonlinearity of an underlying dynamical system. In order to gain insight into this hypothesis, we consider a simple hard-wired central pattern generator model consisting of two identical oscillators connected by reciprocal inhibition. In the model, each oscillator acts as a neural half-center controlling movement of a single limb, either left or right, and receives a control input modeling a flow of descending signals from higher motor centers. When these two control inputs are tonic-constant and identical, the model has left-right symmetry and basically exhibits ordered coordination with an alternating periodic oscillation. We show that, depending on the intensities of these two control inputs and on the difference between them that introduces asymmetry into the model, the model can reproduce several behaviors observed in the clinical study. Bifurcation analysis of the model clarifies two possible mechanisms for the generation of disordered coordination in the model: one is the spontaneous symmetry-breaking bifurcation in the model with the left-right symmetry. The other is related to the degree of asymmetry reflecting the difference between the two control inputs. Finally, clinical implications by the models dynamics are briefly discussed.

Measurement of tissue oxygen consumption in patients with mitochondrial myopathy by noninvasive tissue oximetry

We measured oxygen consumption in the exercising lower limb by using noninvasive tissue oximetry with the near-infrared spectra of hemoglobin in the quadriceps muscle during bicycle ergometer exercise in four normal controls and three patients with chronic progressive external ophthalmoplegia(CPEO) as well as one patient with mitochondrial myopathy, encephalopathy, lactic acidosis, and strokelike episodes (MELAS). Normal controls showed constant oxygenation during exercise and a rapid recovery after exercise. However, all four patients with mitochondrial myopathy showed abnormal oxygenation during exercise and a slow recovery afterward. The results reflected the defect in oxidative phosphorylation and the impairment in oxygen utilization in those patients. The distinctive patterns of imbalance between oxygen delivery and utilization correlated well with the severity of mitochondrial myopathy as judged by the sum of the serum lactate and pyruvate content during exercise. Noninvasive tissue oximetry may be useful to measure the severity of myopathy and exercise intolerance in patients with mitochondrial myopathy.

Classification of dynamics of a model of motor coordination and comparison with Parkinson's disease data

In our recent reports motor coordination of human lower limbs has been investigated during pedaling a special kind of ergometer which allows its left and right pedals to rotate independently. In particular, relative phase between left and right rotational-velocity waveforms of the pedals and their amplitude modulation have been analyzed for patients with Parkinsons disease (PD). Several patients showed peculiar interlimb coordination different from the regular anti-phase pattern of normal subjects. We have reported that these disordered patterns could be classified into four groups. Moreover, it has been demonstrated that a mathematical model could reproduce most of the disordered patterns. Such a model includes a schematization of the central pattern generator with two identical half-centers mutually coupled and two tonic control signals from higher motor centers, each of which inputs to one of the half-centers. Depending on the intensities of the tonic signals and on the differences between them, the model could generate a range of dynamics comparable to the clinically observed disordered patterns. In this paper, we explore the dynamics of the model by varying the intensities of the tonic signals in the model. Using the same method used for classifying the clinical data, the dynamics of the model are classified into several groups. The classified groups for the simulated data are compared with those for the clinical data to look at qualitative correspondence. Our systematic exploration of the models dynamics in a wide range of the parameter space has revealed global organization of the bifurcations including Hopf bifurcations and cascades of period-doubling bifurcations among others, suggesting that the bifurcations, induced by instability of stable dynamics of the human motor control system, are responsible for the emergence of the disordered coordination in PD patients.

Influence of thoracoabdominal movement on pulmonary function in patients with Parkinson's disease: comparison with healthy subjects.

Patients with Parkinsons disease (PD) may develop pulmonary dysfunction, but the pathogenesis remains unclear. We investigated a correlation between thoracoab dominal movements and pulmonary function in seven patients with PD and 14 healthy controls. We measured vital capacity (VC) and forced vital capacity (FVC) using an autospirometer, and measured chest and abdominal movements using a respiraory in ductance plethysmography by fixing transducers on the rib cage and umbilicus. Pa tients with PD had significantly decreased % VC (90.3 ± 17.1 vs 105.8 ± 13.9%), chest movement (271.3 ± 79.6 vs. 375.2 ± 126.7% VT) and abdominal movement (217.6 ± 93.5 vs. 247.4 ± 100.2% VT) with 100% VT being an average volume of chest and abdomen at rest during measurement of VC. Patients with PD also had sig nificantly decreased % FVC (74.4 ± 20.6 vs. 97.6 ± 14.1%), chest movement (246.2 ± 115.2 vs. 344.5 ± 126.4% VT) and abdominal movement (160.3 ± 105.6 vs 207.6 ± 104.7% VT) with 100% VT being an average volume of chest and abdomen at rest during forced maximal inspiration. Based on the results, we conclude that a reduction of % VC in patients with PD correlated with chest movements, while a reduction of % FVC correlated with ab dominal movement in patients with PD.

Soleus H‐reflex inhibition during gait initiation in Parkinson's disease

The soleus H‐reflex excitability during gait initiation was investigated in Parkinsons disease. Eleven patients participated in this study. Patients stepped forward as soon as the start signal flashed. Soleus H‐reflex was evoked from the trailing leg 100, 300, or 600 msec after the start signal. The electromyographic activity in the soleus muscle immediately before evoking the H‐reflex and the ankle joint motion were recorded. The soleus H‐reflex was inhibited 300 msec after the start signal. The amount of the soleus H‐reflex inhibition was inversely correlated with the Hoehn and Yahr stage; Items 14, 29, and 31 of the Unified Parkinsons Disease Rating Scale; and the delay of the onset of the ankle dorsiflexion from the start signal. In contrast, the amount of electromyographic activity immediately before evoking the H‐reflex was not significantly correlated with those measures but was significantly correlated with Item 22 of the Unified Parkinsons Disease Rating Scale. Those findings indicate that the amount of soleus H‐reflex inhibition during gait initiation depends on the severity of the disease. Abnormality of descending command may be related to the severity‐dependent H‐reflex inhibition.

Intralimb and Interlimb Incoordination: Comparative Study between Patients with Parkinsonism and with Cerebellar Ataxia

Dysfunction of limb coordination may be divided into two categories; intra and inter-limb incoordination. To make clear differential character in these two limb incoordination, we measured 13 patients mainly with cerebellar ataxia and 27 patients mainly with parkinsonism during pedaling of an ergometer with left and right pedals that can be rotated independently. As a result, interlimb incoordination was predominantly observed in patients with parkinsonism, while patients with cerebellar ataxia showed relatively preserved interlimb coordination but intralimb incoordination. We concluded that impairment of intralimb coordination was a character in patients with cerebellar ataxia, while impairment of interlimb coordination was a character in patients with parkinsonism.

Skin hemodynamics during change from supine to lateral position.

&NA; The purpose of this study was to identify the skin hemodynantics during the position change from supine to lateral in patients with neurodegenerative diseases. The participants were 19 patients with neurodegenerative diseases and 12 healthy volunteers. The alteration in the total concentration of oxyhemoglobin and deoxyhemoglobin, indicative of change in blood volume, was measured in the skin of the left flank by using a protable noninvasive tissue oxygen monitor by nearinfrared spectroscopy. The positions were changed from the left and right lateral with a return to the supine between each procedure. In healthy volunteers, total hemoglobin concentration (skin blood volume) increased when the position changed from supine to left lateral and decreased when changed from supine to right lateral. The decreased skin blood volume gradually recovered after a change from the supine to the right lateral position in healthy volunteers. However, it did not recover in three sporadic olivopontocerebellar atrophy (OPCA) patients with marked autonomic dysfunction and one Parkinsonian patient with severe orthostatic hypotension. Our study identified that the intracutaneous blood was changing dynamically during the position change from supine to lateral and was regulated by autonomic nerve function.

Respiratory training for patients with myotonic dystrophy

Myotonic dystrophy (MD) is a dominantly inherited disease.1 The genetic abnormality has been localized to chromosome 19q13.3, where expanded CTG repeat is found in the 3′ untranslated region encoding the putative serine-threonine protein kinase.2 MD is known to cause motor impairment, also affecting respiration. Although chronic respiratory failure in MD is a frequent and potentially life-threatening complication,1,3,4 no effective treatment is available. In this study, we evaluated the effect of respiratory training for patients with MD using an inspiratory resistant device. Patients. Ten patients with MD (six men, four women) who underwent respiratory training in our hospital in 1996 and 1997 were included in this study. The diagnosis in each patient was established based on the criteria of the Working Group on the Molecular Defect in MD, where the diagnosis can be clinically established if both weakness and myotonia are present in distal parts of the upper or lower extremities.5 We also confirmed the presence of …