Yasuyuki Okuma

Freezing of gait in Parkinson's disease

Freezing of Gait (FOG) is one of the most disabling and least understood symptoms in Parkinson’s disease (PD), and is usually observed in the advanced stage of the disease. FOG can be experienced on turning, in narrow spaces, whilst reaching a destination, and in stressful situations. FOG is commonly observed in the “off” state, but it can also be observed in the “on” state. Dual tasking (cognitive load) aggravates FOG. Visual or auditory cues often resolve FOG. Analysis of gait revealed that the rhythm of stepping suddenly jumps into high frequency (4–5 Hz) in FOG (hastening), and that floor reaction forces are disregulated. Stride-to-stride variability is increased in FOG. Hastening phenomenon was reported not only in PD patients but also in patients with striatal lesions. The basal ganglia and its frontal projections may be one of the essential lesion sites for FOG.A recent study using single-photon emission tomography (SPECT) revealed enhanced lateral premotor cortex (PMC) activity during paradoxical gait in PD, suggesting that PMC can compensate for the impaired function of the medial frontal cortex when cued by visual input. Treatment of FOG includes behavioural, medical, and surgical approaches. Tricks of all kinds (including external cues) are effective therapeutic approaches. If FOG occurs predominantly in the “off” state, dopaminergic therapy can be increased. For “on” freezing or if “on” response is otherwise optimised, the dose of the dopaminergic agent may be manipulated, but it could lead to the deterioration of parkinsonism. Deep brain stimulation of the STN often alleviates FOG in the “off” state.

Disorder in reciprocal innervation upon initiation of voluntary movement in patients with Parkinson's disease

SummaryReciprocal innervation of the soleus motoneurones upon initiation of voluntary ankle dorsiflexion was investigated in eight patients with Parkinsons disease. H-reflex and visually guided step tracking methods were used for testing moto-neurone excitability and for controlling the timing of movement initiation, respectively. While reciprocal inhibition appeared almost simultaneously with the agonist electromyographic (EMG) onset in normal subjects (Kagamihara and Tanaka 1985), facilitation appeared in the majority of patients under the same onset condition. It increased slowly, reaching a maximum at about 100 ms after the EMG onset. It then subsided slowly at around 200–300 ms, and was replaced thereafter by an inhibitory effect. No coactivation of the soleus muscle was detected electromyographically. The facilitation between the EMG onset and the onset of mechanical contraction was attributed to the direct effect of the descending command from the brain, suggesting a certain disorder in controlling the system for reciprocal innervation.

The clinical spectrum of freezing of gait in Parkinson's disease†

Freezing of gait (FOG) is a common and very disabling symptom in Parkinsons disease (PD). It is usually observed in the advanced stage of the disease, although a mild form can be seen in the early stage. Although some studies have suggested that longer duration of dopaminergic treatment is associated with FOG, the disease progression alone may be responsible for the development of FOG. FOG can be experienced on turning, in narrow spaces, while reaching a destination, and in stressful situations. In PD, FOG is strongly associated with motor fluctuation. FOG is commonly observed in the “off” state and is observed less frequently in the “on” state. Dual tasking (cognitive load) aggravates FOG. Visual or auditory cues often resolve FOG. Analysis of gait revealed that the stepping rhythm suddenly jumps into high frequency (4–5 Hz) in FOG (hastening), and that floor reaction forces are disregulated. Since the hastening phenomenon was also reported in patients with lesions in the striatum and/or the frontal lobe, fronto‐basal ganglia projections are considered essential for FOG. Careful observation and gait pattern analysis may lead to a successful management of individual PD patients with FOG.

Prevalence of Abnormal Glucose Metabolism and Insulin Resistance Among Subtypes of Ischemic Stroke in Japanese Patients

Background and Purpose— The purpose was to assess the prevalence of disorders of glucose metabolism and insulin resistance in Japanese ischemic stroke patients with no history of diabetes by performing 75-gram oral glucose tolerance test (OGTT). Methods— We recruited 427 ischemic stroke patients (atherothrombotic infarction, n=220; lacunar infarction, n=125; cardioembolic infarction, n=82). OGTT was used to evaluate disorders of glucose metabolism in stroke patients without previously known diabetes (n=113). We investigated the relationships among the prevalence of abnormal glucose metabolism, ischemic stroke subtypes, and the prevalence of insulin resistance using homeostasis model assessment for insulin resistance and immunoreactive insulin at 120 minutes after glucose loading (IRI120). Results— OGTT identified the presence of disorders of glucose metabolism in 62.8% of ischemic stroke patients without previously known diabetes, including diabetes (24.8%) and impaired glucose tolerance (lone impaired glucose tolerance and impaired fasting glucose plus impaired glucose tolerance, 34.5%). The prevalence of newly diagnosed diabetes and impaired glucose tolerance was the highest in the atherothrombotic infarction group (68.9%). The highest values of homeostasis model assessment for insulin resistance and immunoreactive insulin at 120 minutes after glucose loading were found in atherothrombotic infarction patients with abnormal glucose tolerance. Conclusions— In this study, a significantly large percentage of Japanese patients with ischemic stroke and no history of diabetes were found to have disorders of glucose metabolism by OGTT. Impaired glucose tolerance and insulin resistance could play an important pathogenic role in the development of atherothrombotic infarction.

Excessive daytime sleepiness and sleep episodes in Japanese patients with Parkinson's disease

In Parkinsons disease (PD), sudden unexpected sleep episodes and excessive daytime sleepiness (EDS) while driving and engaging in social activities are important problems. We conducted a multi-center study to clarify the prevalence and contributing factor of EDS and sleep episodes in Japanese patients with PD. We evaluated 188 patients with PD (85 men, 103 women) and 144 age-matched controls for sleepiness. EDS was defined as an Epworth sleepiness scale (ESS) score of >or=10. ESS score was significantly higher (6.6+/-4.2 vs. 5.6+/-3.8) and prevalence of sleep episodes was higher in PD than in controls (6.4% vs. 0.7%). PD patients with EDS were more likely to have sleep episodes (22.5% vs. 2.0%), higher score for disease severity and depressive symptoms, and on higher dose of dopaminergic agents than those without EDS. However, there were no differences in nocturnal disturbances between the two groups. ESS score was not different between patients taking ergot and non-ergot dopamine agonists. Logistic regression analysis demonstrated that mental state, total dose of dopaminergic agents, and ESS score were significant predictors of sleep episodes. ESS score of >or=10 had 75% sensitivity and 82.4% specificity for sleep episodes. These results suggest that sleepiness in PD is dependent on disease itself and dopaminergic treatment rather than nocturnal disturbances.

Characteristics of sleep disturbances in Japanese patients with Parkinson's disease. A study using Parkinson's disease sleep scale

The present multicenter cross‐sectional study was performed using semistructured questionnaires to determine the contributing factors of sleep disturbances in Japanese patients with Parkinsons disease (PD). We used the Parkinsons disease sleep scale (PDSS, Japanese version). All data were obtained by means of interviewed questionnaire and physical examination by neurologists. The study was carried out between April 2005 and December 2005 at eight university hospitals and affiliated facilities in the Kanto area of Japan. A total of 188 (85 men and 103 women) PD patients and 144 controls (64 men and 80 women) were included. Stepwise regression analysis identified complications of treatment, depression, age, and disease duration as significant risk factors of sleep disturbances in PD. Significant differences in total PDSS score were observed between Hoehn & Yahr (H&Y) Stages 1 and 4, between H&Y Stages 2 and 4, and between H&Y stages 3 and 4 (Bonferroni test). The results of this survey suggested that complications due to treatment (dyskinesia, wearing off, on–off), depressive state, and disease stage are significant determinants of sleep disorders in Japanese patients with PD. We speculate that the reduction of neurotransmitters involved in the sleep–wakefulness mechanism and degeneration of neurons progress together in parallel with deterioration of motor function.

Correlation between depressive symptoms and nocturnal disturbances in Japanese patients with Parkinson's disease.

Depression and nocturnal disturbances are frequent in patients with Parkinsons disease (PD). The aim of this study was to determine the correlation between depressive symptoms and nocturnal disturbances in patients with PD in Japan. The subjects of this multi-center cross-sectional study were 188 patients with PD and 144 age-matched controls who were assessed for nocturnal disturbances by the Parkinsons disease sleep scale (PDSS) and for depressive symptoms by Zung Self-Rating Depression Scale (SDS). Depressive symptoms (SDS score of > or =40) were identified in 122 patients (64.9%). The SDS was significantly higher in PD patients than control subjects. The stepwise regression model identified PDSS (p<0.001) and Unified Parkinsons Disease Rating Scale I (mental state) (p=0.002) as significant determinants of SDS. Stepwise regression analysis identified item 15 (daytime sleepiness) (p=0.002), item 13 (early morning tremor) (p=0.008), item 12 (nocturnal dystonia) (p=0.015), and item 3 (sleep maintenance insomnia) (p=0.026) as significant predictors of SDS. Our results indicated that depressive symptoms in PD correlate significantly with nocturnal disturbances, and that daytime sleepiness, dystonia, tremor and sleep fragmentation are the most common nocturnal disturbances in depressed patients with PD.

Segmental zoster paresis of limbs: report of three cases and review of literature.

Objectives:Segmental zoster paresis is a relatively rare complication characterized by focal motor weakness, which may occur in limbs affected by herpes zoster. We demonstrate the clinical characteristics of segmental zoster paresis by reviewing the cases of 138 patients, including 3 of our patients. Case Report and Review Summary:We report 3 patients with zoster paresis of the limbs. Patients 1 and 3 showed motor weakness in the left shoulder and arm after developing a herpetic rash in the left C5–C6 dermatomes. Patient 2 showed weakness in the right thigh and groin after a right L2–L3 herpetic eruption. The electromyograms of all 3 patients showed abnormal spontaneous activity in the affected muscles. Intravenous acyclovir and corticosteroid pulse therapy were added to oral antiviral drugs for patients 1 and 2. All 3 patients recovered favorably. Our review of the literature revealed that antiviral treatment may prevent the occurrence of zoster paresis; however, there is insufficient evidence to show what treatment hastens recovery from zoster paresis. Conclusions:Segmental zoster paresis is still underrecognized by neurologists. Awareness of this disorder is important because it may eliminate unnecessary invasive investigations and lead to appropriate treatment. Further studies on the treatment are necessary.

Sweet's syndrome associated with encephalitis.

The involvement of the central nervous system (CNS) in Sweets syndrome (acute febrile neutrophilic dermatosis) is rare. We report a 47-year-old woman who presented with acute encephalitis and was subsequently diagnosed as having Sweets syndrome. She developed altered consciousness following fever and erythematous skin plaques in the extremities. Cerebrospinal fluid (CSF) examination disclosed neutrophilic pleocytosis without decreased glucose level. Brain magnetic resonance imaging (MRI) showed abnormal signal intensity lesions in the basal ganglia and the hippocampus. Skin biopsy revealed a dense dermal infiltration of neutrophils, which is compatible with Sweets syndrome. Treatment with acyclovir and antibiotics failed, but the subsequent corticosteroid therapy was effective. Awareness of neurological complication in Sweets syndrome may avoid unnecessary empiric therapy for meningoencephalitis and will lead to a successful treatment with corticosteroids.

MRI findings in the mild type of mucopolysaccharidosis II (Hunter's syndrome)

SummaryNeuroradiological findings in a 44-year-old male with the typical mild type of Hunters disease are reported. Cranial MRI revealed patchy areas of increased and decreased signals in T1- and T2-weighted images in the thalamus and the basal ganglia giving rise to a honey comb-like appearance as a whole. The deep white matter showed high signals in the T2-weighted image. To our knowledge, the honey comb-like appearance has never been reported in this disorder. Deposition of mucopolysaccharides and/or glycolipids and increase in fluid content seem to be responsible for these changes.