Yumiko Kaseda

Diagnostic significance of tau protein in cerebrospinal fluid from patients with corticobasal degeneration or progressive supranuclear palsy

Distinguishing corticobasal degeneration (CBD) from progressive supranuclear palsy (PSP) is clinically and pathologically difficult, and a useful biological marker to discriminative these two diseases has been a subject of clinical interest. In the present study, we assessed tau protein levels in cerebrospinal fluids by sandwich ELISA to distinguish CBD from PSP. The subjects consisted of 27 cases of CBD, 30 cases of PSP, and 36 healthy controls (CTL). The tau values in CBD were significantly higher than those in PSP (P<0.001) and those in CTL (P<0.001). The assay of CSF tau provided diagnostic sensitivity of 81.5% and specificity of 80.0% between CBD and PSP according to receiver-operating characteristic (ROC) curve analysis. When values were compared separately with respect to stage of the disease, differences in the values for moderate CBD vs. moderate PSP had the greatest significance (P<0.001 sensitivity 92.3%, specificity 100.0%), followed by cases of mild CBD and PSP (P<0.005, sensitivity 100.0%, specificity 87.5%). The values in severe CBD and PSP were not significantly different (P=0.07, sensitivity 100%, specificity 75.0%). Using data obtained from a larger number of disease cases, we confirmed our previous findings that tau protein levels in cerebrospinal fluids in patients with CBD are significantly higher than those in patients with PSP. Because tau protein levels in cerebrospinal fluids are significantly higher in early CBD cases than in early PSP cases, measurement of tau protein levels in cerberospinal fluids may be useful for the differential diagnosis of early CBD from early PSP.

Objective evaluation of fatigue by event-related potentials

The purpose of this study was to assess the relationship between mental fatigue and event-related potentials (ERPs). Six healthy men (mean age: 22 years old) performed a simple calculation for 6 h. Auditory ERPs were recorded before and after the calculating task. The scores of subjective fatigue symptoms were significantly increased, and P300 latency of auditory ERPs was significantly prolonged by the calculating task (P<0.05). We suggest that the recording of ERPs may be useful for the objective evaluation of mental fatigue.

Clinical features of malignant syndrome in Parkinson's disease and related neurological disorders

INTRODUCTION We elucidated the cause and clinical characteristics of malignant syndrome (MS) in patients with Parkinsons disease (PD), early-onset parkinsonism (EOP), and other neurological disorders. MATERIALS AND METHODS Subjects were 260 patients with PD or EOP, and three patients with other neurological disorders associated with MS. We studied clinical symptoms before and after the onset of MS, and evaluated autonomic function particularly before the onset of MS. RESULTS The overall incidence of MS accompanying PD and EOP in our department was eight of 260 patients (3.1%). The incidence of MS in EOP was significantly higher than that in PD. All patients with MS showed comparatively longer duration of illness and advanced stage of PD and EOP. Factors triggering MS included reduced dosage or discontinuation of anti-parkinsonian drugs, reduction of oral intake, dehydration, infectious disease, postoperative state, and treatment with major tranquilizers. Although patients demonstrated marked autonomic symptoms at the onset of MS, in many cases autonomic dysfunction developed before the onset of MS. Even EOP patients, who usually demonstrated milder autonomic dysfunction, showed abnormalities in the correlation between circadian rhythm of blood pressure and pulse rate, and/or abnormal gastric emptying test, suggesting that autonomic dysfunction plays an important role in the cause of MS. Cooling the body, fluid replacement, resumption or increasing the dosage of anti-parkinsonian drugs and administration of dantrolene sodium overcame MS in all cases. CONCLUSION Autonomic dysfunction is related to the cause and clinical features of MS in PD, EOP and some other neurological disorders.

Habituation of event-related potentials in patients with Parkinson's disease

Auditory event-related potential (ERP) was studied in idiopathic Parkinsons disease (PD) using our new procedures. We examined 12 non-demented patients with PD, and 9 age-matched control subjects. Ninety responses induced by rare stimulation were continuously recorded from Fz, Cz, Pz referred to linked earlobe electrode (A1A2), and were divided into nine blocks (one block = 10 responses) for statistical analysis. We assessed the habituation of auditory ERP to detect delicate changes related to the information processing in PD. N100 and P300 latencies were significantly longer in PD than in control subjects (p<0.05). P300 latency gradually increased with progression of recording blocks in both PD and control subjects, whereas N100 latency increased only in PD. Three way analysis of variance for P300 amplitude revealed significant effects of subject group, recording electrode site, and trial block. P300 amplitude was smaller in PD than in control subjects. Significant negative correlation between P300 amplitudes and block numbers were observed at Cz and Pz in PD, and at Fz in the control group. Previous reports as well as present results suggest that prolongation of N100 latency might be related to frontal lobe dysfunction, and abnormality of P300 to dysfunction in both the frontal lobe and hippocampus in PD.

Understanding the Pathophysiology of Alzheimer's Disease and Mild Cognitive Impairment: A Mini Review on fMRI and ERP Studies

The prevalence of Alzheimers disease (AD) is predicted to increase rapidly in the coming decade, highlighting the importance of early detection and intervention in patients with AD and mild cognitive impairment (MCI). Recently, remarkable advances have been made in the application of neuroimaging techniques in investigations of AD and MCI. Among the various neuroimaging techniques, functional magnetic resonance imaging (fMRI) has many potential advantages, noninvasively detecting alterations in brain function that may be present very early in the course of AD and MCI. In this paper, we first review task-related and resting-state fMRI studies on AD and MCI. We then present our recent fMRI studies with additional event-related potential (ERP) experiments during a motion perception task in MCI. Our results indicate that fMRI, especially when combined with ERP recording, can be useful for detecting spatiotemporal functional changes in AD and MCI patients.

Effects of movement on somatosensory N20m fields and high-frequency oscillations.

Somatosensory evoked fields were recorded to determine the effects of movement and attention on high-frequency oscillations during active finger movements of the ipsilateral and contralateral sides in response to electrical stimulation of the median nerve. A whole-scalp neuromagnetometer was used to record somatosensory evoked fields from eight subjects following electric median nerve stimulation at the wrist. The following three sessions were performed: (1) rest, (2) movement of fingers on the ipsilateral in response to stimulation and (3) movement of fingers on the contralateral in response to stimulation. The somatosensory evoked fields with a wide-bandpass (0.1–1000 Hz) were recorded. High-frequency oscillations and N20m were separated by subsequent high-pass (> 300 Hz) and low-pass (< 300 Hz) filtering. The maximum amplitude of high-frequency oscillations decreased during finger movements accompanying a decrease in somatosensory N20m dipole strength. Activation of the motor cortex appeared to suppress both the amplitude of high-frequency oscillations and the N20m dipole strength.

Relevance of in vivo neurophysiological biomarkers for mild cognitive impairment and Alzheimer's disease

Visuospatial dysfunction including defects in motion perception in Alzheimers disease (AD) and mild cognitive impairment (MCI) are clues to search for potential in vivo biomarkers. In this review, we focus on the clinical relevance of non-invasive neurophysiological findings in event-related potentials (ERPs) and functional magnetic resonance imaging (fMRI) to assess visual dysfunction in AD and MCI. We first summarize the current concept of the parallel visual pathways in primates and humans. Next, we outline the results of previous electrophysiological and fMRI studies on visual function in AD and MCI. Finally, we present the recent findings of our systematic ERP and fMRI approach to visual perception in AD and MCI. Our overview strongly indicates that visual impairments in patients with AD and MCI are mainly caused by dysfunction in higher-level parallel visual pathways. In particular, a deficit in ventro-dorsal stream function related to optic flow perception is responsible for the earliest and most prominent visual symptoms in MCI. Therefore, we conclude that ERP and fMRI measurements for visual perception can be used as in vivo biomarkers for early functional brain changes in MCI and AD patients.

Electrophysiological studies in spinocerebellar ataxia type 6 : a statistical approach

In spinocerebellar ataxia type 6 (SCA6), the cerebellum is predominantly affected, but several electrophysiological studies have revealed subclinical disorders other than cerebellar lesions. We conducted statistical analyses by comparing SCA6 patients and age-matched normal controls to assess whether electrophysiological abnormalities are directly associated with SCA6 because late onset of SCA6 may involve senile changes. We performed brain stem auditory evoked potentials (BAEP), visual evoked potentials, somatosensory evoked potentials and nerve conduction studies in 10 SCA6 patients. The BAEP latencies of wave I was prolonged and compound muscle action potentials of peroneal nerve and sensory nerve action potentials of sural nerve reduced in SCA6 patients. Our results suggest an existence of peripheral impairment in the auditory pathway and axonal neuropathy in SCA6.

Subclinical cranial nerve involvement in hereditary motor and sensory neuropathy: a combined conduction study with electrical and magnetic stimulation

OBJECTIVE To evaluate the electrophysiological findings of clinically unaffected cranial nerves (facial, accessory and hypoglossal nerves) in hereditary motor and sensory neuropathy (HMSN). METHODS The conduction times of the facial, accessory, and hypoglossal nerves in 10 patients with HMSN type I (HMSN I), 2 patients with HMSN Type II (HMSN II), and 20 normal controls were determined. The extra- and intracranial segments of the cranial nerves were stimulated electrically and magnetically, respectively. The relationships between the conduction parameters of the cranial nerves and limb nerves were analyzed. RESULTS In patients with HMSN I, the conduction times of the distal and proximal segments were significantly prolonged in all 3 cranial nerves. A positive correlation was found between the conduction parameters of the cranial nerves and the limb nerves. CONCLUSIONS Electrophysiological involvement of the whole segment of the facial, accessory and hypoglossal nerves is common in patients with HMSN I without clinical signs of alterations. The degree of conduction slowing of the facial, accessory, and hypoglossal nerves paralleled that of limb nerves.

Clinical Manifestations of Autosomal Recessive Early-Onset Parkinsonism with Diurnal Fluctuation

Early-onset parkinsonism includes a group of heterogeneous disorders with an onset early in life, which share clinical features with Parkinson’s disease. Among these is autosomal recessive early-onset parkinsonism with diurnal fluctuation (AR-EPDF). In 1973 we7 reported AR-EPDF, struck by the marked diurnal fluctuation of symptoms in a group of patients with early-onset parkinsonism. The disease begins in the second or third decade of age, mostly with familial trait, and presents with dystonias and marked response to antiparkinsonism drugs. Subsequent authors4, 6 have reported similar cases. Diurnal fluctuation, unrelated to drug-induced motor fluctuations, is symptomatic worsening within a few hours of waking and improvement after sleep (sleep benefit). The idea this phenomenon being characteristic of AR-EPDF lead us to compare clinical features of early-onset parkinsonism patients with and without diurnal fluctuation.