Autochthonous Cryptococcus gattii genotype VGIIb infection in a Japanese patient with anti-granulocyte-macrophage colony-stimulating factor antibodies.

A 31-year-old Japanese man presented with cerebral and pulmonary cryptococcosis. Cryptococcus gattii (C. gattii) genotype VGIIb was detected in the patient's sputum and cerebrospinal fluid specimens. The serum levels of anti-granulocyte-macrophage colony-stimulating factor (GM-CSF) antibodies were elevated in this patient, which has been associated with pulmonary alveolar proteinosis and is considered a risk factor for C. gattii infection. After undergoing >12 months of antifungal treatments, the patient showed improvements in symptoms and findings on brain and lung imaging. Several Japanese patients who develop C. gattii infection have also been reported; however, most of these patients have been infected outside Japan, as C. gattii infection is rare in Japan. Only one patient with C. gattii genotype VGIIb infection has been reported in Japan, and it is believed that this patient contracted the infection in China. In the present case, our patient has never been outside Japan, indicating that the infection originated in Japan. Our findings suggest that C. gattii might be spreading in Japan. Therefore, patients with positive serum anti-GM-CSF antibodies should be thoroughly monitored for C. gattii infection, even those living in Japan.

Sweating on the palm and sole: physiological and clinical relevance.

In mammals, sweating is a multifunctional response that aids in locomotion, thermal regulation, self-protection, and communication of psychological state. Humans possess three types of sweat glands (apocrine, eccrine, and apoeccrine) that are differentially distributed on the body surface and make unique contributions to these distinct functions of the sweating response. In humans, eccrine glands, which are widely distributed on hairy skin, play an important role in thermoregulation. They are also found on the glabrous skin of the palm and sole, where they are not usually activated by heat, but rather by deep respiration, mental stress, and local tactile stimulation. Sweating on the palm and sole, so-called "emotional sweating", acts to prevent slippage while grasping or performing a delicate task using the fingertips. Although the central pathways of emotional sweating are not yet elucidated in detail, it is thought that the amygdala, cingulate cortex, and medulla participate via efferent fibers that descend through the spinal cord and connect to preganglionic sympathetic neurons in the nucleus intermediolateralis. The limbic system, including the amygdala and cingulate cortex, is critical for emotional processing and many cognitive functions. Thus, measurement of sweat output on the palm or sole is useful for evaluating sympathetic function and limbic activity in autonomic and psychiatric disorders.

Skin sympathetic function in complex regional pain syndrome type 1.

PURPOSE: Cutaneous sympathetic pathophysiology in complex regional pain syndrome type 1 (CRPS-1) is not yet completely understood. To evaluate cutaneous sympathetic dysfunction in CRPS-1, we evaluated sympathetic sweat response (SSwR) and skin vasomotor reflex (SkVR) in CRPS-1 patients. METHODS: We studied 10 CRPS-1 patients (age 41 ± 13 years; 5 females and 5 males; disease duration 20 ± 22 months) and 10 healthy subjects (age 44 ± 13 years; 3 females and 7 males). SkVRs and SSwRs to several sympathetic activating procedures were recorded on the palms of the CRPS-1 patients (affected side) and controls (right side). RESULTS: There were no significant differences in the baselines of sweat output and skin blood flow between the CRPS-1 and control groups. SSwR and SkVR amplitudes were significantly lower in the CRPS-1 group than in the control group. There was no significant correlation between disease duration and SSwR or SkVR amplitudes among the patients. CONCLUSIONS: The reduced SSwRs and SkVRs in the affected limb of our CRPS-1 patients may reflect underlying damage to the sympathetic postganglionic fibres.

Sporadic Late-onset Nemaline Myopathy Associated with Sjögren's Syndrome.

We report the case of a 46-year-old female patient who developed a subacute progression of axial and proximal muscle weakness. Laboratory findings revealed mildly elevated serum creatine kinase levels. No monoclonal gammopathy was detected. A muscle biopsy revealed that she had nemaline myopathy. Serological tests and a lip biopsy revealed Sjögren's syndrome (SjS). We diagnosed her as having sporadic late-onset nemaline myopathy without monoclonal gammopathy of undetermined significance associated with SjS. Her symptoms improved after methylprednisolone pulse therapy followed by intravenous immunoglobulin therapy. A good response to immunotherapy demonstrates the necessity of making a correct diagnosis, for which a muscle biopsy is required.

Autonomic dysfunction in parkinsonian disorders: assessment and pathophysiology.

Parkinson's disease (PD) is a progressive neurodegenerative disorder characterised by motor dysfunction (parkinsonism) and several non-motor features. Dysautonomia is a significant non-motor feature as well as a neuropsychiatric symptom. Autonomic dysfunction can occur even in the early stages of PD, often preceding the onset of the classic motor symptoms of PD. The patterns of autonomic features in PD are different from other parkinsonian disorders. Detection of autonomic dysfunction may therefore be helpful in diagnosing PD in the early or pre-motor stages, and/or in differentiating it from other parkinsonian disorders, such as multiple system atrophy and progressive supuranuclear palsy. The aim of this review is to describe aspects of autonomic dysfunction, including symptoms, assessment and pathophysiology, resulting from autonomic impairment in PD and other parkinsonian syndromes.

Abnormal gastric myoelectrical activity in postural tachycardia syndrome.

OBJECTIVE: Postural tachycardia syndrome (PoTS) is an important cause of orthostatic intolerance resulting from cardiovascular autonomic dysfunction. In addition to postural symptoms, PoTS patients may have allied features, including gastrointestinal (GI) symptoms, which have not yet been thoroughly investigated. We evaluated gastric myoelectrical activity in PoTS patients. METHODS: Using cutaneous electrogastrography (EGG), we recorded gastric myoelectrical activity before and after standard liquid meal ingestion in 15 PoTS patients (age 27 ± 4 years); including 7 with and 8 without GI symptoms, and in 11 healthy individuals (age 23 ± 7 years). We performed spectral analysis of EGG recordings to obtain the dominant frequency of gastric pacemaker rhythm (DF), instability coefficient of DF (ICDF), and low (LFR%), normal (NFR%), and high (HFR%) range power percentages of the total power. RESULTS: Instability coefficient of DF, an index of variability of gastric pacemaker rhythm, was significantly elevated both pre- and post-prandially (30-45 min after the meal) in the PoTS group (8.8 ± 6, 10.0 ± 8 %) compared with controls (4.0 ± 3, 4.0 ± 3 %; both p < 0.05). Patients with GI symptoms had significantly higher post-prandial ICDF (15.0 ± 5 %) than those without GI symptoms (5.6 ± 4 %; p < 0.05). There were no significant differences in DF, LFR%, NFR% and HFR% before and after the meal between the PoTS and control groups, or between PoTS patients with and without GI symptoms. INTERPRETATION: Our study revealed increased variability of gastric pacemaker rhythm in PoTS, and these findings might be related to pathophysiology of functional GI symptoms in PoTS.

[Medication for Neurogenic Orthostatic Hypotension].

Orthostatic hypotension is a phenomenon characterized by reduction in blood pressure secondary to the inability to adapt to changes in blood volume distribution (pooling of blood in the lower extremities) observed when standing from a seated or supine position. Orthostatic hypotension is classified into neurogenic and non-neurogenic types. Neurogenic orthostatic hypotension due to autonomic failure may occur in most neurological diseases and is a major concern encountered in daily practice. In this review, I present an overview of the pathophysiology and diagnosis of neurogenic orthostatic hypotension and describe the therapeutic strategies and characteristics of drugs used for this condition.

Reactivity of observers' facial skin blood flow depending on others' facial expressions and blushing.

Facial skin blood flow (SkBF) has attracted attention as an autonomic indicator because it influences facial colour, which informs others of emotional states, and facial temperature related to social anxiety. Previous studies have examined the facial SkBF in people experiencing emotions; however, facial SkBF changes in the observers of emotions are poorly understood. Our study clarified facial SkBF changes related to observing others' emotions by comparing the changes with other physiological indices. Thirty healthy participants (24 females; mean age: 22.17) observed six types of facial expressions (neutral, angry, and embarrassed expressions with and without facial blushing) and rated the emotional intensity of the other person. We measured their facial SkBF, finger SkBF, and cardiac RR interval as they made their observations. Facial SkBF generally decreased in relation to observing emotional faces (angry and embarrassed faces) and significantly decreased for angry expressions with blushing. None of the participants noticed blushing of facial stimuli. For the RR interval and finger SkBF, there was no variation depending on the observed facial expressions, although there was a general increase related to observation. These results indicated that facial SkBF is sensitive and reactive to emotional faces-especially angry faces with blushing- compared with other autonomic indices. The facial SkBF changes were not related to either RR interval changes or the intensity rating, suggesting that facial SkBF changes may be caused by vasoconstriction and have potential functions for our emotions. The decrease in facial SkBF may have a role in calming observers by preventing them from adopting the same emotional state as a person with intense anger. These findings clarify daily facial SkBF fluctuations and their relationship with our emotional processing in interpersonal situations.

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.

Electrogastrography for diagnosis of early-stage Parkinson's disease.

INTRODUCTION: Patients with Parkinson's disease (PD) often present with gastric symptoms. Electrogastrography (EGG) can noninvasively assess gastric electric activity and may be useful for early PD diagnosis. The present study aimed to compare the efficacy of EGG in early PD diagnosis with those of 123I-metaiodobenzylguanidine (MIBG) myocardial scintigraphy and odor stick identification test -Japanese version (OSIT-J). METHODS: Thirty-seven untreated PD patients (mean age ± SD, 66 ± 8years; disease duration < 3 years) and 20 healthy control subjects (68 ± 6.9 years) were recruited. EGG and OSIT-J were performed in both groups, and MIBG scintigraphy in the PD group. EGG parameters were assessed in the preprandial and early and late postprandial segments using power spectrum analysis. RESULTS: Irregular EGG waves were observed in PD patients. The preprandial instability coefficient of dominant frequency (ICDF), an index of EGG irregularity, in PD patients (9.5% [6.3%]) was higher than that in controls (3.9% [3.9%], p = 0.00005). The OSIT-J score was also lower in PD patients (4.6 [3.3]) than in controls (7.7 [3.3], p = 0.006). In receiver operating characteristics analyses, the areas under the curves of preprandial ICDF and OSIT-J were 0.83 and 0.72, respectively. The sensitivities of preprandial ICDF and MIBG (delayed-phase) scintigraphy were 73% and 70%, respectively. CONCLUSIONS: Early and untreated PD patients showed irregular EGG waves and high ICDF. EGG showed better accuracy than the olfactory test for early PD diagnosis and similar sensitivity to MIBG scintigraphy.

Clear cell injury associated with reduced expression of carbonic anhydrase II in eccrine glands consistently occurs in patients with acquired idiopathic generalized anhidrosis.

Acquired idiopathic generalized anhidrosis (AIGA) is characterized by anhidrosis/hypohidrosis without other autonomic and neurological dysfunctions. It has been believed that AIGA patients usually present no significant morphological alterations in the secretory portion of eccrine glands consisting of clear, dark and myoepithelial cells. However, we have recently revealed morphological damage of eccrine glands in AIGA patients by immunohistochemistry. Moreover, inhibitory side-effects against carbonic anhydrase II (CA II) by the antiepileptic reagent topiramate have been reported to cause heat intolerance mimicking AIGA. To determine the precise morphological changes and CA II expression in eccrine glands of AIGA patients, electron microscopic observation and immunohistochemistry were applied to skin of both anhidrotic (non-sweating) and normohidrotic (sweating-preserved) sites, taken from each patient clinically diagnosed with AIGA. We found consistent clear cell injury in eccrine glands in anhidrotic skin samples of AIGA patients. Electron micrographs demonstrated edematous, swollen and destructive damage in clear cells of eccrine glands from non-sweating areas of almost all AIGA patients. Immunohistochemically, clear cells showed reduced CA II expression that was heterogeneously distributed in non-sweating skin. Some areas showed almost complete loss of CA II expression in spite of preserved dark cells, and others showed mild or moderate loss of it. Selective destruction of clear cells resulting in heterogenous atrophy in AIGA patients may be important to elucidate its etiology.

Neuropsychiatric Symptoms in Parkinson's Disease After Subthalamic Nucleus Deep Brain Stimulation.

Background: Indications for subthalamic nucleus deep brain stimulation (STN-DBS) surgery are determined basically by preoperative motor function; however, postoperative quality of life (QOL) is not necessarily associated with improvements in motor symptoms, suggesting that neuropsychiatric symptoms might be related to QOL after surgery in patients with Parkinson's disease. Objectives: We aimed to examine temporal changes in neuropsychiatric symptoms and their associations with QOL after STN-DBS. Materials and Methods: We prospectively enrolled a total of 61 patients with Parkinson's disease (mean age = 65.3 ± 0.9 years, mean disease duration = 11.9 ± 0.4 years). Motor function, cognitive function, and neuropsychiatric symptoms were evaluated before and after DBS surgery. Postoperative evaluation was performed at 3 months, 1 year, and 3 years after surgery. Results: Of the 61 participants, 54 completed postoperative clinical evaluation after 3 months, 47 after 1 year, and 23 after 3 years. Frontal lobe functions, depression, and verbal fluency significantly worsened 3 years after STN-DBS. Non-motor symptoms such as impulsivity and the Unified PD Rating Scale (UPDRS) part I score were associated with QOL after STN-DBS. Conclusions: Frontal lobe functions, depression, and verbal fluency significantly worsened 3 years after STN-DBS. The UPDRS part I score and higher impulsivity might be associated with QOL after STN-DBS.

Decline in drawing ability and cerebral perfusion in Parkinson's disease patients after subthalamic nucleus deep brain stimulation surgery.

BACKGROUND: Subthalamic nucleus deep brain stimulation (STN DBS) is an established therapy for alleviating motor symptoms in advanced Parkinson's disease (PD) patients; however, a postoperative decline in cognitive and speech function has become problematic although its mechanism remains unclear. The aim of the present study was to elucidate the properties of language and drawing ability and cerebral perfusion in PD patients after bilateral STN DBS surgery. METHODS: Western aphasia battery, including drawing as a subcategory, and perfusion (N-isopropyl-p-[123I] iodoamphetamine) SPECT scan was conducted in 21 consecutive PD patients, before, and three to six months after, bilateral STN DBS surgery while on stimulation. Perfusion images were compared with those of 17 age- and gender-matched healthy volunteers. In the parametric image analysis, the statistical peak threshold was set at P < 0.001 uncorrected with a cluster threshold set at P < 0.05 uncorrected. RESULTS: Although motor symptoms were improved and general cognition was preserved in the patient group, 11 patients (52.4%) showed a decline in the drawing subcategory after surgery, which showed a reduction in Frontal Assessment Battery score in this group of patients. Statistical parametric analysis of the brain perfusion images showed a decrease of cerebral blood flow in the prefrontal and cingulate cortex after surgery. Patients whose drawing ability declined showed decreased perfusion in the middle cingulate cortex comparing before and after surgery. CONCLUSION: Present results show that some PD patients show a decline in drawing ability after bilateral STN DBS which may attributable by dysfunction in the cingulate network.

Gastric myoelectrical differences between Parkinson's disease and multiple system atrophy.

The electrogastrogram (EGG) was recorded for 24 hours in 17 Parkinson's disease (PD) patients, 17 multiple system atrophy (MSA) patients, and 8 healthy control subjects to elucidate the differences in the EGG findings between the two diseases. Eight EGG segments (3 preprandial, 3 postprandial, and 2 sleep segments) were selected from the total recording for spectral analysis, from which we obtained the dominant frequency (DF), instability coefficient of DF (ICDF), and low (LFR%), normal (NFR%), and high (HFR%) range power percentages of the total power. PD patients showed irregular slow waves, high HFR%, and high ICDF, whereas MSA patients showed regular slow waves and low ICDF. Although DF and NFR% increased after meal in controls, postprandial increases in DF and NFR% were less significant in both patient groups compared to the controls. The PD patients presented gastric dysrhythmias indicating gastric pacemaker disturbances. The MSA patients showed regular slow waves with low variability of the slow wave rhythm (low ICDF), which might have resulted from the involvement of gastric autonomic nerve function.

Altered heart rate control in response to postural change in patients with Machado-Joseph disease (SCA3).

To assess heart rate (HR) regulation in Machado-Joseph disease (MJD), we evaluated HR variability at rest and the initial HR response to standing suddenly in 13 MJD patients and 26 normal control subjects. A head-up tilt (HUT) test involving the monitoring of blood pressure, HR, and cerebral oxy/deoxyhemoglobin concentration was also performed in each participant. There was no significant difference in HR variability at rest between the two groups, but the transient HR rise just after standing suddenly in the MJD group was significantly less than that in the control group (p < 0.01). The HUT test, where each participant was gradually tilted upward, induced a significantly greater HR increase in the MJD group compared with the controls (p < 0.01), while there were no significant differences in the blood pressure and cerebral oxygenation changes between the two groups. In our MJD study, the transient HR rise just after standing suddenly was diminished, and HR markedly increased during sustained orthostatic stress.

The severity of motor dysfunctions and urinary dysfunction is not correlated in multiple system atrophy.

OBJECTIVE: Although it is well known that patients with multiple system atrophy (MSA) cerebellar dominant type (MSA-C) show severe autonomic dysfunction, the relationship between autonomic and motor dysfunction remains uncertain. Previously we reported that severe urinary voiding dysfunction is useful in differential diagnosis of MSA and other diseases. Herein, we aimed to clarify the relationship between the severity of motor dysfunctions and urinary dysfunction. METHOD: This study is a retrospective review of 46 patients with MSA-C diagnosed according to Gilman's second consensus criteria. The severity of motor dysfunctions was evaluated using International Cooperative Ataxia Rating Scale (ICARS). Urinary voiding dysfunction was evaluated by measuring post-void residual (PVR). The mean duration of motor unit potentials in external anal sphincter muscles on electromyography, which represents the severity of neurodegeneration in Onuf's nucleus, was also examined. RESULTS: The mean age of patients was 63.8 ±â€¯8.2 years and mean disease duration was 3.0 ±â€¯1.9 years. The mean ICARS score was 40.1 ±â€¯14.7. The mean PVR was 119.1 ±â€¯102 ml and the mean duration of motor unit potentials (MUPs) in anal sphincter electromyography was 9.2 ±â€¯2.2 ms. The correlation coefficient between ICARS and PVR was 0.093 (p = .539), and between ICARS and mean duration of MUPs was 0.105 (p = .811). A significant positive correlation (r = 0.296, p = .005) was noted between PVR and the mean duration of MUP. CONCLUSION: Motor and urinary dysfunctions were not correlated in MSA-C.

Sympathetic sweat responses and skin vasomotor reflexes in carpal tunnel syndrome.

OBJECTIVE: To investigate cutaneous sympathetic functions in carpal tunnel syndrome (CTS) using sympathetic sweat responses (SSwRs) and skin vasomotor reflexes (SVmRs). METHODS: In 29 hands (20 patients) with idiopathic CTS, SSwRs were recorded with a sudorometer from the thenar eminence, and SVmRs were used to measure cutaneous blood flow using a Doppler flowmeter placed on the index finger tip. Normal data were obtained from 15 volunteers of similar age. RESULTS: SSwRs or SVmRs were abnormal in 23 (80%) hands; SSwRs were absent in 38%, whereas SVmRs were abnormally decreased in 59%. Autonomic symptoms were present in 18 (62%) hands; finger edema (38%) and dry hand (35%) were frequent symptoms. Autonomic symptoms, and abnormal SSwRs and SVmRs did not correlate with results of nerve conduction studies. CONCLUSIONS: Skin sudomotor or vasomotor sympathetic function is frequently impaired in CTS. Susceptibility to compression ischemia may be different in sympathetic unmyelinated and large myelinated fibers.

Urinary symptoms are correlated with quality of life after deep brain stimulation in Parkinson's disease.

AIMS: Deep brain stimulation (DBS) is known to dramatically improve motor complications in patients with Parkinson's disease (PD), but its effect on urinary symptoms and health-related quality of life (HRQOL) remains unknown. We aimed to examine the relationship between urinary symptoms and HRQOL in patients with PD who underwent DBS. METHODS: The International Prostate Symptom Score (IPSS) and overactive bladder symptom score (OABSS) were determined to evaluate urinary symptoms in patients with PD who underwent DBS. Postoperative evaluations were performed at 3 months, 1 year, and 3 years postoperatively. We also performed a urodynamic study (UDS) in 13 patients with PD preoperatively and postoperatively. A follow-up UDS was performed 2.0 ± 0.5 years postoperatively. RESULTS: The preoperative urinary symptoms questionnaire was completed by 28 patients, of whom 14 completed the postoperative urinary symptoms questionnaire after 3 months, 18 after 1 year, and 10 after 3 years. The mean OABSS and IPSS did not change significantly at any follow-up periods postoperatively. When assessing the relationship between urinary symptoms and HRQOL and motor functions, the OABSS and IPSS showed significant positive correlations with HRQOL at 3 months postoperatively. The OABSS and IPSS showed significant positive correlations with activities of daily living (ADL) during the off-phase at 3 years postoperatively. All urodynamic parameters remained unchanged postoperatively. CONCLUSIONS: Deep brain stimulation did not significantly affect urinary dysfunctions in patients with PD. Urinary symptoms might partially contribute to HRQOL at 3 months postoperatively and ADL during the off-phase at 3 years postoperatively.

The raphe magnus/pallidus regulates sweat secretion and skin vasodilation of the cat forepaw pad: a preliminary electrical stimulation study.

In the human palm/sole, mental or physical stimuli induce an increase in sweat secretion and a decrease in skin blood flow (SkBF). However, the central pathways of these responses remain unclear. We measured sweat secretion and SkBF in the cat footpad by electrically stimulating the raphe. Stimulation of the rostral raphe magnus/pallidus elicited a reduction in SkBF without affecting sweat secretion. Stimulation of the mid to caudal raphe magnus/pallidus elicited an increase in both sweat secretion and SkBF. The raphe magnus/pallidus may play a crucial role in skin vasomotor and sudomotor responses in the cat footpad.

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.