Clinical Assessment Scales in Autonomic Nervous System Disorders

The autonomic nervous system plays an important role in maintaining homeostasis mediated by the parasympathetic, sympathetic and enteric systems. Autonomic failure adversely affects body function and may increase morbidity and mortality. Therefore, the scoring systems, such as Ewing’s classification and Composite Autonomic Scoring Scale (CASS), were developed to detect and quantify autonomic deficits, primarily focusing on the cardiovascular reflex system. Autonomic disorders manifest with a myriad of symptoms resulting from the dysfunction of the gastrointestinal, genitourinary, secretomotor, pupillomotor systems as well as cardiovascular system. Several self-report questionnaires, such as Composite Autonomic Symptom Scale (COMPASS), Scale for Outcomes in Parkinson’s disease for Autonomic Symptoms (SCOPA-AUT), Survey of Autonomic Symptom (SAS), were also used to support to detect various signs and symptoms of autonomic dysfunction in clinical settings. In this review, we introduce clinically useful assessment scales in autonomic nervous system disorders.

Clinical Assessment Scales in Autonomic Nervous System Disorders

The autonomic nervous system plays an important role in maintaining homeostasis mediated by the parasympathetic, sympathetic and enteric systems. Autonomic failure adversely affects body function and may increase morbidity and mortality. Therefore, the scoring systems, such as Ewing’s classification and Composite Autonomic Scoring Scale (CASS), were developed to detect and quantify autonomic deficits, primarily focusing on the cardiovascular reflex system. Autonomic disorders manifest with a myriad of symptoms resulting from the dysfunction of the gastrointestinal, genitourinary, secretomotor, pupillomotor systems as well as cardiovascular system. Several self-report questionnaires, such as Composite Autonomic Symptom Scale (COMPASS), Scale for Outcomes in Parkinson’s disease for Autonomic Symptoms (SCOPA-AUT), Survey of Autonomic Symptom (SAS), were also used to support to detect various signs and symptoms of autonomic dysfunction in clinical settings. In this review, we introduce clinically useful assessment scales in autonomic nervous system disorders.

Biphasic Anaphylaxis and Delayed onset Cerebellar Ataxia following a Wasp Sting

Anaphylaxis usually develop immediately after wasp sting, but may develop even after few days later. Neurological complications after stings are uncommon, although several cases have been reported involving central and/or peripheral nervous system. Although wasp sting-induced encephalitis has been rarely reported, all reported cases showed mental change and severe neurological deterioration. Herein, we report an atypical case who showed biphasic anaphylaxis and delayed-onset cerebellar ataxia following a wasp sting, characterized by mild cerebellar ataxia and excellent response to corticosteroids.

‘Sirim’ (Cold) Pain as a Common Symptom in Korean Patients with Clinically Suspected Small-Fiber Neuropathy

BACKGROUND AND PURPOSE: Diagnosing small-fiber neuropathy (SFN) is challenging because there is no gold-standard test and few diagnostic tests. This study investigated the clinical symptom profile and its associations with the results of quantitative sensory testing (QST) and the quantitative sudomotor axon reflex test (QSART) as well as the quality of life (QOL) in patients with clinically suspected SFN. METHODS: This study involved 63 patients with clinically suspected length-dependent SFN. Assessments were performed using QST, QSART, SFN Symptoms Inventory Questionnaire, Neuropathic Pain Symptom Inventory, ‘Sirim’ frequency and ‘Sirim’ (cold) pain severity, and 36-item Short-Form Health Survey. Multiple logistic and linear regression analyses were performed to predict risk factors for QST or QSART abnormalities and QOL, respectively. RESULTS: ‘Sirim’ and ‘Sirim’ pain was the most-common (84%) and the most-severe complaint (mean score of 6.3 on a numerical rating scale ranging from 0 to 10) in patients with clinically suspected SFN. The findings of QST [cold detection threshold (CDT)] and QSART were abnormal in 71% (n=45/57) and 62% (n=39/56) of the patients, respectively. An abnormal CDT was correlated with more-severe stabbing pain (odds ratio=2.23, 95% CI=1.02–4.87, p=0.045). Restless-leg symptoms (β=−7.077) and pressure-evoked pain (β=−5.034) were independent predictors of the physical aspects of QOL. CONCLUSIONS: ‘Sirim’ pain, similar to cold pain, should be considered a major neuropathic pain in SFN. Among pain characteristics, stabbing pain of a spontaneous paroxysmal nature may be more pronounced in the setting of dysfunctional Aδ fibers with functional autonomic C fibers.

Autonomic Dysfunction in Dizziness Clinic / 대한평형의학회지

Orthostatic dizziness is a common type of dizziness. In general, orthostatic dizziness is provoked by standing or tilting, and subsided by supine position. The patient with orthostatic intolerance complains multiple symptoms such as dizziness, palpitation, lightheadness, fatigue and rarely syncope. Common orthostatic intolerance is orthostatic hypotension (classic, initial, transient, and delayed orthostatic hypotension) and postural orthostatic tachycardia syndrome. Transcranial Doppler is a noninvasive technique that provides real-time measurement of cerebral blood flow velocity. It can be useful for understanding the relationship between orthostatic symptoms and cerebral autoregulatory function. The reciprocal causal relationship between vestibular and autonomic dysfunction should always be kept in mind.

Dynamic postural stability in patients with diabetic peripheral neuropathy and relationship to presence of autonomic neuropathy

@#Diabetic neuropathy is a common complication that can negatively influence balance and is a major cause of falls. We evaluated the association between postural sway and diabetic autonomic neuropathy (DAN) among patients with diabetic peripheral neuropathy (DPN). Patients with DPN documented by typical symptoms with abnormal results of nerve conduction study were included and postural stability was assessed using dynamic posturography. Composite autonomic scoring scale (CASS) score was calculated by evaluating sudomotor, cardiovagal, and adrenergic functions. CASS score ≥2 indicated DAN and the severity of DAN was indicated by the CASS scores divided into three subscales of 10-point total CASS: none or mild autonomic failure (0-3), moderate failure (4-6), and severe failure (7-10). A total of 34 patients comprised the DAN group (n=19) and non-DAN group (n=15). Patients with DAN had higher prevalence of diabetic retinopathy(p=0.011), higher urine albumin-creatinine ratio (p = 0.009), and lower HbA1c levels (p<0.001) than those with non-DAN. With regard to dynamic postural instability, the presence (p=0.025) as well as the severity of DAN (p<0.05) was associated with postural instability in the eyes-opencondition. Interestingly, the poorer dynamic postural instability in moderate/severe DAN compared to mild DAN was observed only in medio-lateral direction and this association remained significant after adjusting for age, sex, and glycemic control state (HbA1c). In patients with DAN accompanied by DPN, the dynamic postural instability was affected by visual feedback and medio-lateral directional instability was closely associated with the severity of DAN.

Atorvastatin pretreatment attenuates kainic acid-induced hippocampal neuronal death via regulation of lipocalin-2-associated neuroinflammation

Statins mediate vascular protection and reduce the prevalence of cardiovascular diseases. Recent work indicates that statins have anticonvulsive effects in the brain; however, little is known about the precise mechanism for its protective effect in kainic acid (KA)-induced seizures. Here, we investigated the protective effects of atorvastatin pretreatment on KA-induced neuroinflammation and hippocampal cell death. Mice were treated via intragastric administration of atorvastatin for 7 days, injected with KA, and then sacrificed after 24 h. We observed that atorvastatin pretreatment reduced KA-induced seizure activity, hippocampal cell death, and neuroinflammation. Atorvastatin pretreatment also inhibited KA-induced lipocalin-2 expression in the hippocampus and attenuated KA-induced hippocampal cyclooxygenase-2 expression and glial activation. Moreover, AKT phosphorylation in KA-treated hippocampus was inhibited by atorvastatin pretreatment. These findings suggest that atorvastatin pretreatment may protect hippocampal neurons during seizures by controlling lipocalin-2-associated neuroinflammation.

Clinical Applications of Heart Rate Variability in Neurological Disorders

Heart rate variability (HRV) is a useful marker for predicting mortality and cardiovascular events in cardiac diseases. Various time- and frequency-domain parameters are used for assessing HRV. The time-domain measures include standard deviation of the NN intervals (SDNN), standard deviation of the average NN interval, root mean square of the successive differences SDNN index, NN50 count, and pNN50, while the power spectrum that is used the most widely in frequency-domain analyses is divided into low frequency (LF), high frequency (HF), LF norm, HF norm, and LF/HF. The HF band is modulated by the parasympathetic nervous system, while the LF band is modulated by both the sympathetic and parasympatheticnervous systems. Altered or reduced HRV parameters have been shown to be related to cardiovascular events in patients with various neurological disorders, such as parkinsonian syndromes, dementia, cerebrovascular disorder, and epilepsy. Furthermore, analyses of HRV have attempted to distinguish different diseases and evaluate the degree of disability. This article discusses the clinical use of HRV in the neurological field.

Erratum to: The KMDS-NATION Study: Korean Movement Disorders Society Multicenter Assessment of Non-Motor Symptoms and Quality of Life in Parkinson's Disease NATION Study Group

The original version of this article contained wrong informations of some authors which should be changed.

Effects of age, sex, and body mass index on sudomotor and cardiovagal functions in a healthy Korean population

Background: Hypertension results from an impaired baroreceptor reflex and enhanced sympathetic activity. The prevalence of hypertension differs among ethnicities and is more frequent in South Asians than in Caucasians, suggesting that baseline autonomic nervous system functions and their regulation may also differ among ethnic groups. In most studies, the reference values for clinical autonomic function tests are obtained from heterogeneous ethnic populations, or ethnic factors are not considered in the study design. Obtaining reference data in a homogenous ethnic group and comparing them within various ethnic groups could be helpful to detect ethnic differences in autonomic functions. The aim of this study was to identify normative reference values for standard autonomic reflex measurements in a homogeneous Korean population. Methods: A total of 181 healthy Korean volunteers (age, 20–74 years) underwent standard autonomic function tests: heart rate difference during deep breathing, Valsalva maneuver, and the quantitative sudomotor axon-reflex test. Mean and 5th and 95th percentile values were obtained for each age group. We also analyzed factors (age, sex, and body mass index) that can influence autonomic functions. Results: The heart rate difference during deep breathing and expiratory-inspiratory ratio were higher in males than in females and were inversely related to age. The Valsalva ratio was inversely related to age. Males had higher sweat volumes at all body areas evaluated than those of females, and only forearm sweat volume was significantly different between the age groups. Conclusions: Cardiovagal function was affected by age and sex in Koreans. Sudomotor function was affected by sex, and only forearm sweat volume was affected by age and sex. These results represent preliminary normative clinical autonomic data in a Korean population comprised of a single ethnicity

Toxocara canis-Associated Myelitis with Eosinophilic Pneumonia

The existence of Toxocara canis-specific antibodies has recently been reported in patients with atopic myelitis. Here, we report the case of a 35-year-old male patient admitted with a chief complaint of right lower limb hypoesthesia lasting for a month. The patient was diagnosed with eosinophilic pneumonia 3 months ago, and a spine MRI revealed the presence of myelitis in the cervicothoracic cord. After confirming the presence of hyper-IgE-emia and Toxocara canis antibodies, the patient was treated with steroids and albendazole treatment, which improved his symptoms. To our knowledge, this is the first case of Toxocara canis-associated myelitis with eosinophilic pneumonia.

The KMDS-NATION Study: Korean Movement Disorders Society Multicenter Assessment of Non-Motor Symptoms and Quality of Life in Parkinson's Disease NATION Study Group

BACKGROUND AND PURPOSE: Nonmotor symptoms (NMS) in Parkinson's disease (PD) have multisystem origins with heterogeneous manifestations that develop throughout the course of PD. NMS are increasingly recognized as having a significant impact on the health-related quality of life (HrQoL). We aimed to determine the NMS presentation according to PD status, and the associations of NMS with other clinical variables and the HrQoL of Korean PD patients. METHODS: We surveyed patients in 37 movement-disorders clinics throughout Korea. In total, 323 PD patients were recruited for assessment of disease severity and duration, NMS, HrQoL, and other clinical variables including demographics, cognition, sleep scale, fatigability, and symptoms. RESULTS: In total, 98.1% of enrolled PD subjects suffered from various kinds of NMS. The prevalence of NMS and scores in each NMS domain were significantly higher in the PD group, and the NMS worsened as the disease progressed. Among clinical variables, disease duration and depressive mood showed significant correlations with all NMS domains (p<0.001). NMS status impacted HrQoL in PD (rS=0.329, p<0.01), and the association patterns differed with the disease stage. CONCLUSIONS: The results of our survey suggest that NMS in PD are not simply isolated symptoms of degenerative disease, but rather exert significant influences throughout the disease course. A novel clinical approach focused on NMS to develop tailored management strategies is warranted to improve the HrQoL in PD patients.

Primary Aldosteronism Presenting as Hypokalemia and Rhabdomyolysis / 대한임상신경생리학회지

Primary aldosteronism is one of the most common cause of secondary hypertension and can be accompanied with hypokalemia. Rhabdomyolysis with hypokalemia in primary aldosteronism has been rarely reported. We describe a patient of primary aldosteronism who presented with limb-girdle type weakness.

Usefulness of Extracorporeal Treatment for Combined Intoxication with Controlled-Release Carbamazepine and Topiramate

Controlled-release carbamazepine (CBZ) could be more harmful than the regular form in special situations due to their respective biochemical characteristics. When primary treatment is not effective in acute intoxication, extracorporeal treatment (ECTR) could be an option. We recently applied ECTR to a patient with combined intoxication of topiramate and controlled-release CBZ who deteriorated despite receiving primary treatment. The patient improved after administering ECTR. Early ECTR intervention may be beneficial for the treatment of CBZ intoxication, especially of the controlled-release form.

Age, hypertension, and genetic polymorphisms and their relative associations with white matter hyperintensities in Korean patients with Alzheimer’s disease

Objectives: White matter hyperintensities are known to influence dementia in Alzheimer’s disease. Genetic components are suggested as putative risk factors for vascular pathology and cognitive decline. This study aimed to determine whether there is an association between candidate genetic polymorphisms and the severity of white matter hyperintensities in patients with Alzheimer’s disease. Methods: Seventy-five patients diagnosed with Alzheimer’s disease underwent genetic tests for specific alleles of apolipoprotein E, angiotensin-converting enzyme, and methylenetetrahydrofolate reductase. All patients underwent brain magnetic resonance imaging scans and neuropsychological tests. The severity of white matter hyperintensities was semiquantified using the CREDOS rating scale, and patients were divided into three groups according to their rating. Results:The severity of white matter hyperintensities was related to age and hypertension. However, none of the gene polymorphisms we tested was found to be associated with the severity of white matter hyperintensities. Conclusion:The genetic polymorphisms found in apolipoprotein E, angiotensin-converting enzyme and methylenetetrahydrofolate reductase did not contribute to white matter hyperintensities in Alzheimer’s disease.Only age and hypertension factors were found to be contributory to white matter hyperintensities.

Seizure Induction by Artemisia Annua in an Epilepsy Patient Taking Levetiracetam

Artemisia annua is a wormwood. Because it may induce Cytochrome P450 2C19 enzyme, Artemisia annua may have an influence on antiepileptic drugs which are substrates for the enzyme. This influence may negatively affect seizure control of epilepsy patient. We present a patient whose seizures were induced by Artemisia annua, despite he was taking levetiracetam which is not a substrate for the hepatic enzyme. Therefore there would be another mechanism of seizure induction of Artemisia annua besides hepatic metabolism.

Seizure-induced Cerebral Edema Mimicking Multiple Cerebral Infarction

No abstract available.

Myeloma-associated Amyloidosis Presenting as Orthostatic Intolerance / 대한임상신경생리학회지

Amyloidosis is a systemic disorder associated with clonal plasma cell dyscrasia. Nephrotic syndrome, congestive heart failure, autonomic and peripheral neuropathy is often associated features in amyloidosis. Early diagnosis is most important because of different prognosis by stage. The diagnosis can be delayed since symptoms of amyloidosis may vary or nonspecific. We describe a patient of myeloma-associated amyloidosis, who showed orthostatic intolerance as the first symptom of the disease.

Assessing Methods of Heart Rate Variability / 대한임상신경생리학회지

Heart rate variability is significantly associated with cardiovascular complications in various neurological disorders with cardiac impairment. Measures of spontaneous heart rate variability might be different from provocating tests of heart rate variability such as deep breathing and Valsava maneuver. Methods for analysis are divided into time domain methods and frequency domain methods. There are standard deviation of NN interval, standard deviation of average NN interval, root mean square of the successive differences, NN50, and pNN50 in time domain methods. Frequency domain bands can be divided into very low, low, and high frequency. Each variables are influenced by sympathetic and/or parasympathetic activity.

Prevalence of Anti-Ganglioside Antibodies and Their Clinical Correlates with Guillain-Barre Syndrome in Korea: A Nationwide Multicenter Study

BACKGROUND AND PURPOSE: No previous studies have investigated the relationship between various anti-ganglioside antibodies and the clinical characteristics of Guillain-Barre syndrome (GBS) in Korea. The aim of this study was to determine the prevalence and types of anti-ganglioside antibodies in Korean GBS patients, and to identify their clinical significance. METHODS: Serum was collected from patients during the acute phase of GBS at 20 university-based hospitals in Korea. The clinical and laboratory findings were reviewed and compared with the detected types of anti-ganglioside antibody. RESULTS: Among 119 patients, 60 were positive for immunoglobulin G (IgG) or immunoglobulin M antibodies against any type of ganglioside (50%). The most frequent type was IgG anti-GM1 antibody (47%), followed by IgG anti-GT1a (38%), IgG anti-GD1a (25%), and IgG anti-GQ1b (8%) antibodies. Anti-GM1-antibody positivity was strongly correlated with the presence of preceding gastrointestinal infection, absence of sensory symptoms or signs, and absence of cranial nerve involvement. Patients with anti-GD1a antibody were younger, predominantly male, and had more facial nerve involvement than the antibody-negative group. Anti-GT1a-antibody positivity was more frequently associated with bulbar weakness and was highly associated with ophthalmoplegia when coupled with the coexisting anti-GQ1b antibody. Despite the presence of clinical features of acute motor axonal neuropathy (AMAN), 68% of anti-GM1- or anti-GD1a-antibody-positive cases of GBS were diagnosed with acute inflammatory demyelinating polyradiculoneuropathy (AIDP) by a single electrophysiological study. CONCLUSIONS: Anti-ganglioside antibodies were frequently found in the serum of Korean GBS patients, and each antibody was correlated strongly with the various clinical manifestations. Nevertheless, without an anti-ganglioside antibody assay, in Korea AMAN is frequently misdiagnosed as AIDP by single electrophysiological studies.