Yu Kono

The Beneficial Effect of Donepezil on Visual Hallucinations in Three Patients with Parkinson's Disease

Visual hallucinations (VHs) are common psychiatric symptoms in patients with long-standing Parkinsons disease (PD). Treatment with neuroleptics or withdrawal of anti-PD drugs may improve VHs but will worsen motor dysfunctions. The authors report on 3 patients with long-standing PD who were treated with the cholinesterase inhibitor donepezil for the treatment of VHs. Each received a daily dose of 5 mg of donepezil, after reducing or discontinuing anti-PD medications had failed to relieve the VHs. In 2 patients (patient 1, 2), donepezil decreased VHs without worsening motor dysfunctions. In addition, the cognitive status of patient 2 improved. In patient 3, donepezil also resolved VHs, but delusions developed during treatment. After discontinuing donepezil, delusions disappeared and VHs reappeared. Donepezil may ameliorate visual hallucinations in PD patients, but controlled, double-blind trials are necessary to further clarify the effect of this drug on VHs in PD. (J Geriatr Psychiatry Neurol 2003; 16:184-188).

Preserved myocardial [123I] metaiodobenzylguanidine uptake in autosomal recessive juvenile parkinsonism : first case report

A decrease in myocardial uptake of iodine‐123–labeled metaiodobenzylguanidine (123I‐MIBG) has been reported in idiopathic Parkinsons disease (PD) using 123I‐MIBG myocardial scintigraphy. However, the patient with autosomal recessive juvenile parkinsonism (AR‐JP), caused by the parkin gene, presented here showed normal 123I‐MIBG myocardial uptake, suggesting that AR‐JP is a distinct disease entity from PD. Although the clinical features of AR‐JP are sometimes quite similar to those of late‐onset idiopathic PD, 123I‐MIBG myocardial scintigraphy may be a powerful tool to differentiate PD from other parkinsonian syndromes, including AR‐JP.

Facilitation of spontaneous glycine release by anoxia potentiates NMDA receptor current in the hypoglossal motor neurons of the rat

Deficiency in energy supply, such as occurs during hypoxia, anoxia, metabolic stress and mitochondrial failure, strongly affects the excitability of central neurons. Such lowered energy supply evokes various changes in spontaneous synaptic input to the hippocampal and cortical neurons. However, how this energy deprivation affects synaptic input to motor neurons, which are also vulnerable to energy deprivation, has never been addressed. Here we report for the first time the effect of metabolic stress on synaptic input to motor neurons by recording postsynaptic currents in the hypoglossal nucleus. Chemical anoxia with NaCN (1 mm) and anoxia with 95% N2 induced a persistent inward current and a marked and robust increase in action potential‐independent synaptic input. This increase was abolished by strychnine, but not by picrotoxin, CNQX or MK‐801, indicating glycine release facilitation. Blockade of voltage‐dependent Ca2+ channels and extracellular Ca2+ deprivation strongly attenuated this facilitation. The amplitude of inward currents evoked by local application of NMDA to the motor neurons in the presence of strychnine was significantly increased during NaCN application. A saturating concentration of d‐serine occluded this potentiation, suggesting that released glycine activated the glycine‐binding sites of NMDA receptors. By contrast, neurons in the dorsal motor nucleus of the vagus showed no detectable change in synaptic input in response to NaCN. These data suggest that increase in synaptically released glycine in response to metabolic stress may play an exacerbating role in NMDA receptor‐mediated excitotoxicity in motor neurons.

Olfactory function combined with morphology distinguishes Parkinson's disease

OBJECTIVE This study aimed to examine whether the volume of the olfactory bulbs and tracts (OB & T) on magnetic resonance imaging (MRI) is useful for differentiating Parkinsons disease (PD) from PD-related disorders. METHODS The study group comprised 13 patients with PD, 11 with multiple system atrophy (MSA), five with progressive supranuclear palsy, and five with corticobasal degeneration (PSP/CBD). All patients were evaluated using the odor stick identification test for Japanese (OSIT-J), (123)I-meta-iodobenzylguanidine (MIBG) scintigraphy, and brain MRI. OB & T areas on 1-mm-thick coronal images were measured and summed for volumes. We examined relationships between olfactory function and volume, and cardiovascular dysautonomia. We defined the cut-off values for OSIT-J score or MIBG uptake and OB & T volume to discriminate PD from PD-related disorders and calculated the proportional rate of PD in four categorized groups. RESULTS OB & T volume was smaller in PD than in MSA or PSP/CBD (p < 0.05 each). The cut-off for detecting PD patients was OSIT-J score <8, heart/mediastinum ratio <1.6, and OB & T volume <270 mm(3). In the group with OSIT-J score <8 and OB & T volume <270 mm(3), the proportion of PD patients among all patients with PD-related disorders was 91%. The rate of probable PD gradually increased as OSIT-J score and OB & T volume decreased (p < 0.001). CONCLUSIONS Although preliminary, these data obtained from a combined morphological and functional evaluation of OB or cardiovascular dysautonomia could be useful for further differential of PD and other PD-related disorders.

Stroke patients with cerebral microbleeds on MRI scans have arteriolosclerosis as well as systemic atherosclerosis.

Cerebral microbleeds (CMBs) are recognized as a manifestation of arteriolosclerosis in cerebral small vessels. However, little is known regarding whether stroke patients with CMBs often have systemic atherosclerosis. The aim of the present study was to elucidate this issue using the cardio–ankle vascular index (CAVI), a new index of systemic atherosclerosis, in acute ischemic stroke patients. We prospectively studied 105 patients (71 males, median age=70.0 years) with acute ischemic stroke. All of the patients were examined using T2*-weighted gradient echo magnetic resonance imaging (MRI) to look for and assess the CMBs and using fluid-attenuated inversion recovery to evaluate white matter hyperintensity (WMH). We assigned the patients into CMB and non-CMB groups and compared the clinical characteristics of these groups. The factors associated with CMBs were investigated using multivariate logistic regression analysis. T2*-weighted gradient echo MRI revealed CMBs in 47 patients (44.8%) and no CMBs in 58 patients (55.2%). The CAVI was significantly higher in the CMBs group (10.5 vs. 8.6, P<0.001). In the multivariate logistic regression analysis, CAVI per one point increase (odds ratio (OR), 1.50; 95% confidence interval (CI), 1.12–2.00; P=0.006), advanced WMH (OR, 4.78; 95% CI, 1.55–14.74; P=0.006) and impaired kidney function (OR, 3.31; 95% CI, 1.16–9.81; P=0.031) were independent factors associated with the presence of CMBs. A high CAVI was independently associated with CMBs in patients with acute ischemic stroke. Our results indicated that ischemic stroke patients with CMBs may have cerebral arteriolosclerosis as well as systemic atherosclerosis.

Relationship between Vertebral Artery Hypoplasia and Posterior Circulation Ischemia.

PURPOSE Vertebral artery hypoplasia (VAH) is a common congenital anatomical variation. In previous reports, it was unclear whether VAH was an independent risk factor for posterior circulation ischemia. The purpose of this study was to evaluate the impact of VAH on posterior circulation ischemia. METHODS Subjects were patients with acute ischemic stroke who underwent brain magnetic resonance imaging (MRI) and carotid ultrasonography. Diagnostic criteria for VAH were as follows: (1) Vertebral artery (VA) diameter less than 2.5 mm; (2) VA diameter less than 3.0 mm and a difference in length equal to or greater than 1:1.7; (3) VA diameter less than 3.0 mm, peak systolic velocity less than 40 cm/second, and resistance index value greater than .75. The patients were categorized by the location of the ischemic stroke on MRI as follows: lesion in posterior circulation (P group), lesion in anterior circulation (A group), and multiple lesions in both the anterior and posterior circulations (AP group). RESULTS We evaluated 129 consecutive patients. VAH was seen in 39, and VA occlusion was found in 15. The prevalence of VAH in the P group (44.4%) was significantly higher than that in the A + AP group (24.7%, P = .034). Multivariate regression analysis showed that large-artery atherosclerosis (odds ratio, 6.3; 95% confidence interval [CI], 1.3-30.1), posterior circulation ischemia (odds ratio, 12.0; 95% CI, 2.8-51.2), and VAH (odds ratio, 4.2; 95% CI, 1.2-15.0) were independent factors related to VA occlusion. CONCLUSION VAH was an independent factor related to VA occlusion. Therefore, VAH likely plays a role in posterior circulation ischemia.

Characteristics of Cerebral Microbleeds in Patients with Fabry Disease

BACKGROUND AND PURPOSE Fabry disease (FD) is an X-linked lysosomal storage disorder frequently associated with the central nervous system manifestations. Although white matter hyperintensity (WMH) on MRI has been previously reported, little is known about cerebral microbleeds (CMBs) in patients with FD. Our aim is to investigate the clinical characteristics of CMBs in patients with FD. METHODS All patients with FD were diagnosed by enzyme activity and/or gene analysis at Jikei University Hospital. We retrospectively enrolled consecutive patients with FD who underwent MRI study, including fluid-attenuated inversion recovery and susceptibility-weighted imaging, between July 2008 and September 2013. After categorizing the patients into CMB-positive and CMB-negative groups, we compared the clinical characteristics between the 2 groups. RESULTS We enrolled 54 patients (males, 24; median age 39 years, interquartile range; 29-50 years). The CMB-positive group included 16 (30%) patients. The number of males was significantly higher in the CMB-positive group than in the CMB-negative group (75% versus 32%, P = .003). The prevalence rates of chronic kidney disease (CKD) (estimated glomerular filtration rate < 60 mL/min/1.73 m(2)) and WMH were higher in the CMB-positive group than in the CMB-negative group (CKD: 44% versus 13%, P = .013; WMH: 88% versus 58%, P = .035). No significant differences in the number of vascular risk factors were observed between the 2 groups. CONCLUSIONS The distinct characteristics of FD patients with CMBs were male sex, presence of CKD, and WMH. These factors may play an important role in the mechanism of hemorrhagic stroke in FD.

Diffusion-weighted imaging of encephalopathy related to idiopathic hypereosinophilic syndrome.

Encephalopathy related to idiopathic hypereosinophilic syndrome (HES encephalopathy) is a rare (but well-documented) syndrome. Magnetic resonance imaging (MRI) findings of HES encephalopathy, particularly diffusion-weighted images (DWI) findings, have not been reported. We report a case of HES encephalopathy in a 79-year-old male presenting with a focal neurological deficit and cognitive function disorders. Eosinophil number was >20,000/mm(3). Initial DWI revealed multiple high-signal lesions that were clearer than on T2-weighted images. After corticosteroid therapy, symptoms improved and MRI-identified lesions decreased. This is the first report demonstrating DWI findings of HES encephalopathy. We suggest that lesions identified on MRI may be related to a combination of demyelination, inflammation and/or even small-vessel infarction due to local intimal lesions and clotting, secondary to eosinophilic toxicity. Investigation using DWI should therefore be done in patients with HES encephalopathy even if T2-weighted images are normal.

Transcranial Color Flow Imaging Can Evaluate the Severity of Periventricular Hyperintensity

BACKGROUND The goal of this study was to investigate the relationship between white matter lesions on magnetic resonance imaging and flow parameters in the middle cerebral artery (MCA) measured by transcranial color flow imaging. METHODS Patients with acute ischemic stroke or transient ischemic attack were included. The relationship between severities of periventricular hyperintensity (PVH) and ultrasonographic parameters in the MCA was investigated. The frequency of PVH was calculated for different categories according to the presence or absence of 2 considerable parameters according to the value of area under the receiver operating characteristic curve. RESULTS MCA flow was successfully measured in 203 temporal windows among 124 patients. After determining the cutoff value of end-diastolic velocity (EDV) and pulsatility index (PI) for the presence of PVH, 4 different categories were established: Category A, EDV more than 40 cm/second and PI less than .7; Category B, EDV more than 40 cm/second and PI more than .7; Category C, EDV less than 40 cm/second and PI less than .7; and Category D, EDV less than 40 cm/second and PI more than .7. The prevalence of PVH gradually increased along with category (P < .01). CONCLUSIONS The evaluation of MCA parameters using the combination of PI and EDV may be useful for the prediction of PVH.

Stiffness Parameter β of Cardioembolism Measured by Carotid Ultrasound Was Lower Than Other Stroke Subtypes

BACKGROUND We estimated the stiffness parameter β (β value), which is useful in the assessment of premature atherosclerosis, among patients with different subtypes of cerebral infarction (CI; eg, small-vessel occlusion, large-artery atherosclerosis, cardioembolism, and other determined and undetermined etiologies) to determine the clinical utility of the β value in classification of stroke patients into CI subtypes. METHODS Carotid ultrasonography (ALOKA ProSound SSD-alpha10) was performed in 31 CI patients and 38 control subjects, and the β value of the bilateral common carotid artery at 2.0 cm proximal to the bifurcation was measured using the echo-tracking method. The relationship between β value and age was examined, and the β value was compared among the different CI subtypes. RESULTS Positive β value correlated with age in control subjects (R=.69, P<.001) but not in CI patients (R=-.01, P=.996). There was no significant difference in the β value when comparing control patients and patients with cardioembolic stroke (P=.106), but the β value were lower in patients with cardioembolic stroke than in patients with noncardioembolic stroke (eg, small-vessel occlusion, large-artery atherosclerosis, and others, P=.009). CONCLUSIONS The β value was lower in patients with cardioembolic stroke than in patients with noncardioembolic stroke. The β value may be useful for estimating the risk of different stroke subtypes.