Wen-Chuin Hsu

Guillain-Barré syndrome in Taiwan: a clinical study of 167 patients

OBJECTIVE To identify clinical characteristics of various forms of Guillain-Barré syndrome in Taiwan. METHODS The clinical and electrophysiological data of 167 consecutive patients with Guillain-Barré syndrome admitted to Chang Gung Memorial Hospital, a general paediatric and adult hospital in Taiwan, were reviewed. RESULTS Analysis of age distribution disclosed a high incidence (21%) among patients under the age of 10 years. Seasonal preponderance in Spring (March to May) was found. Utilising clinical and electrophysiological data, these 167 patients with Guillain-Barré syndrome were subclassified; 82 (49%) had acute inflammatory demyelinating polyradiculoneuropathy (AIDP), 32 (19%) had Fisher syndrome (FS), and six (4%) had axonal forms of Guillain-Barré syndrome. The remaining 47 (28%) patients were unclassified. Patients with AIDP and FS had many common clinical features, including seasonal distribution, history of preceding illness, sensory abnormalities, cranial nerve involvement except for extraocular motor nerves, and albuminocytological dissociation on examination of CSF. Follow up study on 145 patients disclosed that 127 (87%) recovered satisfactorily, 14 (10%) were persistently disabled, and four (3%) died during admission to hospital. Clinical features associated with poor outcome (persistent disability or death) were requirement for mechanical ventilation, a low mean compound muscle action potential amplitude (⩽ 10% of the lower limit of normal), and age greater than 40 years. CONCLUSION Guillain-Barré syndrome in Taiwan showed a peculiar age and seasonal distribution and a high frequency of FS not seen in other series. Given that patients with AIDP and FS had many common clinical features, AIDP and FS may have similar underlying pathological mechanisms.

Current perception threshold testing in Fabry's disease.

We investigated 16 patients with Fabrys disease (eight hemizygous men and eight heterozygous women) in one family. We used constant current perception threshold (CPT) testing, which evaluated three major sensory nerve fiber populations, to assess subjective complaints of pain and paresthesias. We also examined clinical and biochemical features and compared the values of CPTs and nerve conduction studies (NCS) in detecting the sensory neuropathy. Our results showed that CPT testing at low frequencies (5 and 250 Hz) was significantly more sensitive than at a higher frequency (2 kHz) and NCS in detecting sensory neuropathy in patients with Fabrys disease. However, there was no correlation between CPT testing and clinical symptom scores, duration of disease, creatinine clearance (Ccr) values or α‐galactosidase A (AGA) activities in either hemizygous or heterozygous patients. Hemizygous patients clinically demonstrated more severe symptom scores, poorer renal function, and higher prevalence of hypohidrosis and corpora angiokeratomas than did heterozygous patients, which indicates that detailed clinical examinations can differentiate the clinical status of hemizygous men from heterozygous women. There were no associations between the biochemical levels of serum AGA activity and renal function (Ccr values) or the symptom scores (grading of acroparesthesia), indicating that biochemical parameters do not predict clinical severity.

Influences of Mutuality, Preparedness, and Balance on Caregivers of Patients with Dementia

Background: There is a lack of research exploring the influence of the role implementation process of family caregivers of older people with dementia in Taiwan. Purpose: The purpose of this study was to investigate the predictive ability on positive and negative caregiving outcomes of several role implementation variables, including mutuality, preparedness, and balance between competing needs. Methods: A cross-sectional, correlational study design was used. Data were collected from family caregivers of patients with dementia from neurological clinics at a medical center and at local hospitals through a take-home mail survey. One hundred seventy-six family caregivers of patients with dementia completed the Family Caregiving Inventory. Results: After controlling for age and gender of the family caregiver and the cognitive function of the elderly patients, mutuality was found to associate negatively with role strain and depressive symptoms and positively with rewards and mental health. Higher preparedness was associated with higher caregiving rewards and better mental health. Less balance was associated with more severe depressive symptoms and poorer mental health. Conclusions/Implications for Practice: Greater attention, support, and consultation should be directed at caregivers with low mutuality, less preparedness, and less balance between competing needs. Specifically, family caregivers with low mutuality are at risk of higher role strain and more depressive symptoms. Those in such a category should be identified and should receive intervention as early as possible. Interventions to enhance family caregiver preparedness should be developed to increase caregiving rewards and to improve caregiver mental health.

Elevated haptoglobin level of cerebrospinal fluid in Guillain-Barré syndrome revealed by proteomics analysis

Guillain‐Barré Syndrome (GBS) is a rare autoimmune inflammatory polyneuropathy with a high risk of respiratory failure and unclear pathogenesis. Currently, there are no valid biomarkers for diagnosis of GBS. We used 2‐DE and MS to analyze the protein profiles of five pairs of cerebrospinal fluid (CSF) samples of the GBS patients and the patient controls. Three proteins (orosomucoid, haptoglobin and apolipoprotein A‐IV) were up‐regulated, and two proteins (prostaglandin D2 synthase and transthyretin) were down‐regulated in the CSF of the GBS patients. The CSF haptoglobin level, quantified by enzyme‐linked immunosorbent assay, was significantly higher in the GBS patients (12.44 ± 2.70 μg/mL) compared to the chronic inflammatory demyelinating polyradiculoneuropathy (2.82 ± 0.83 μg/mL), viral meningitis (3.57 ± 0.97 μg/mL) and control patients (1.44 ± 0.35 μg/mL, p<0.05). This study indicated that protein profile analysis using a combination of 2‐DE and MS provides an effective strategy for elucidating the pathogenesis and identifying potential CSF biomarkers for GBS. The raised intrathecal synthesis of haptoglobin specifically only in GBS patients, but not in patients with other neurological diseases examined, provides evidence of central nervous system involvement in GBS, and may be used as a potential diagnostic marker for GBS.

Analyses of haptoglobin level in the cerebrospinal fluid and serum of patients with neuromyelitis optica and multiple sclerosis.

BACKGROUND Neuromyelitis optica (NMO), which was previously considered a variant of multiple sclerosis (MS), is characterized by recurrent optic neuritis and longitudinally extensive spinal cord lesions. It has been shown that the level of haptoglobin in cerebrospinal fluid (CSF) is elevated in NMO. However, it is uncertain whether this change is specific to NMO, or is also seen in MS and other neurological diseases. METHODS We used an enzyme-linked immunosorbent assay (ELISA) to measure the haptoglobin levels in the CSF and serum in 25 NMO, 16 MS, and 15 Alzheimers disease (AD) patients and 22 controls. RESULTS The CSF haptoglobin concentration of the NMO patients (0.309±0.074mg/dl, P<0.001) was significantly higher than that of MS patients (0.081±0.016mg/dl) and AD patients (0.058±0.011mg/dl), and the controls (0.060±0.009mg/dl), whereas the serum haptoglobin and albumin concentrations in the serum and CSF did not differ significantly across groups. NMO patients (0.59±0.15, P=0.001) demonstrated a higher haptoglobin index than MS patients (0.13±0.01), AD patients (0.12±0.03), and the controls (0.17±0.04). Furthermore, the haptoglobin concentration and haptoglobin index in the CSF correlated significantly with the expanded disability scale score (EDSS) in NMO patients. CONCLUSIONS The high CSF haptoglobin concentration in NMO may be explained by increased intrathecal haptoglobin synthesis. The correlation between CSF haptoglobin concentration/haptoglobin index and EDSS highlights the potential of haptoglobin as a biomarker of NMO.

Decreased intrathecal synthesis of prostaglandin D2 synthase in the cerebrospinal fluid of patients with acute inflammatory demyelinating polyneuropathy.

Prostaglandin D(2) synthase (PGDS) is the most abundant brain protein in cerebrospinal fluid (CSF) and is tied closely with inflammatory processes. This study investigated whether CSF PGDS levels in patients with acute inflammatory demyelinating polyneuropathy (AIDP) are altered. The results suggest that PGDS concentration is significantly increased in the CSF of AIDP patients compared with the control patients (p<0.05) due to a blood-CSF barrier dysfunction, whereas the intrathecal synthesis of PGDS, reflected by the CSF PGDS/albumin ratio, is significantly decreased in AIDP compared with the control group (p<0.05). The changes of CSF PGDS/albumin ratio are only observed in AIDP patients, but not in Miller Fisher Syndrome (MFS), chronic inflammatory demyelinating polyradiculoneuropathy (CIDP), or multiple sclerosis (MS) patients.

Analyses of transthyretin concentration in the cerebrospinal fluid of patients with Guillain-Barré syndrome and other neurological disorders.

BACKGROUND Guillain-Barré syndrome (GBS) is an autoimmune inflammatory polyradiculoneuropathy that causes acute areflexic paralysis with a high risk of respiratory failure. Previously, using two-dimensional gel electrophoresis and mass spectrometry, we found that the transthyretin level was altered in the cerebrospinal fluid (CSF) of GBS patients when compared to that in CSF of control patients. METHODS We used enzyme-linked immunosorbent assay (ELISA) to measure the transthyretin levels in the CSF and serum from 22 GBS, 4 Miller-Fisher syndrome (MFS), 9 chronic inflammatory demyelinating polyradiculoneuropathy (CIDP), 22 multiple sclerosis (MS), 10 Alzheimers disease (AD), and 6 viral meningitis (VM) patients, and 18 controls. RESULTS The results show that CSF transthyretin concentration of the GBS patients is significantly higher than that of the control, MS, AD and VM patients (p<0.05), although not significantly different from that of MFS and CIDP patients. CONCLUSION The increased CSF transthyretin level may be explained by barrier dysfunction or decreased CSF flow in the GBS patients along with increased intrathecal synthesis of transthyretin that might be a protective response to nerve damage.

Identification of Gene Networks and Pathways Associated with Guillain-Barré Syndrome

Background The underlying change of gene network expression of Guillain-Barré syndrome (GBS) remains elusive. We sought to identify GBS-associated gene networks and signaling pathways by analyzing the transcriptional profile of leukocytes in the patients with GBS. Methods and Findings Quantitative global gene expression microarray analysis of peripheral blood leukocytes was performed on 7 patients with GBS and 7 healthy controls. Gene expression profiles were compared between patients and controls after standardization. The set of genes that significantly correlated with GBS was further analyzed by Ingenuity Pathways Analyses. 256 genes and 18 gene networks were significantly associated with GBS (fold change ≥2, P<0.05). FOS, PTGS2, HMGB2 and MMP9 are the top four of 246 significantly up-regulated genes. The most significant disease and altered biological function genes associated with GBS were those involved in inflammatory response, infectious disease, and respiratory disease. Cell death, cellular development and cellular movement were the top significant molecular and cellular functions involved in GBS. Hematological system development and function, immune cell trafficking and organismal survival were the most significant GBS-associated function in physiological development and system category. Several hub genes, such as MMP9, PTGS2 and CREB1 were identified in the associated gene networks. Canonical pathway analysis showed that GnRH, corticotrophin-releasing hormone and ERK/MAPK signaling were the most significant pathways in the up-regulated gene set in GBS. Conclusions This study reveals the gene networks and canonical pathways associated with GBS. These data provide not only networks between the genes for understanding the pathogenic properties of GBS but also map significant pathways for the future development of novel therapeutic strategies.

Family caregivers' role implementation at different stages of dementia.

Purpose The purpose of this study was to explore family caregivers’ role-implementation experiences at different stages of dementia. Patients and methods For this cross-sectional, exploratory study, 176 dyads of family caregivers and their community-dwelling elderly relatives with dementia were recruited from the neurological clinics of a medical center in Taiwan. The Family Caregiving Inventory was used to assess family caregivers for caregiving activities, role strain, role preparation, and help from others at different stages of care receivers’ dementia. Results Family caregivers’ caregiving activities were related to patients’ stages of dementia. For patients with mild dementia, caregivers provided more assistance in transportation and housekeeping. In addition to these two activities, family caregivers of patients with moderate dementia provided more assistance with mobility and protection. For patients with severe dementia, family caregivers provided more assistance with personal care, mobility and protection, transportation, and housekeeping. Overall, family caregivers reported having some preparation to provide care; the most difficult caregiving activity was identified as managing behavioral problems. Conclusion This study’s results provide a knowledge base for designing dementia stage-specific interventions in clinical practice and developing community-based, long-term care systems for families of patients with dementia.

Angiotensin‐converting enzyme polymorphisms and risk of spontaneous deep intracranial hemorrhage in Taiwan

Background and purpose:  This study examines whether angiotensin‐converting enzyme (ACE) gene polymorphisms are associated with the risk of spontaneous deep intracerebral hemorrhage (SDICH) in Taiwan using a case–control study.