Chronic Hypoxemia Triggers a Neuropathic Process in Chronic Obstructive Pulmonary Disease:Insight From In Vivo Neurophysiological Assessments

Background@#and PurposePeripheral neuropathies (PNs) are a common but poorly understood complication of chronic obstructive pulmonary disease (COPD). To clarify the initial trigger of a PN in COPD, we investigated the excitability of peripheral nerves in patients with COPD. @*Methods@#The automated nerve excitability test (NET) using the threshold-tracking paradigm was applied to 20 COPD patients. The recording protocol calculated the strength–duration time constant, threshold electrotonus (TE), current–threshold relationship, and recovery cycle (RC). Each NET parameter was compared with two control groups: normal controls group (NC group) and smokers without COPD group (smoker group). @*Results@#In the motor NETs, the change in the threshold in the mid-depolarizing phase of TE (40–60 ms) was smaller in the COPD group (50.7%±1.2%, mean±SEM; n=20) than in the NC group (54.5%±0.7%, n=25; p<0.01), as was the prominence of superexcitability in the RC (-22.6%±1.5% and -26.4%±1.1%, respectively; p=0.04). There were no significant differences in the sensory NETs. Comparisons between the COPD and smoker groups (n=25) also showed no differences in either the motor or sensory NETs. @*Conclusions@#The pattern of excitability in COPD revealed a membrane depolarization attributable to Na+–K+–ATPase failure in the axolemma of distal motor nerves. This finding suggests that chronic hypoxemia and adaptative process can alter axonal excitability and trigger a resultant neuropathic process that is antecedent to PN in COPD.

Pain Control and Sedation in Neuro Intensive Critical Unit

Neurocritical patients who can self-report pain use the 0-10 numerical rating scale (NRS, verbal or visual form). However, critically ill patients whose nervous systems cannot express pain use the behavioral pain scale (BPS) and the critical care pain observation tool (CPOT) behavioral pain assessment tools. These tools reveal pain-related changes in movement, facial expression, posture, and physiological indicators such as heart rate, blood pressure, and respiratory rate. In pain control, it is first essential to reduce unnecessary painkillers through non-drug therapy and maximize the effect of the administered analgesics. For nonneuropathic pain, narcotic analgesics such as fentanyl, hydromorphone, morphine, and remifentanil are administered intravenously. Gabapentin, pregabalin, and carbamazepine are recommended along with narcotic analgesics for neuropathic pain control. In addition, nonnarcotic analgesics for multi-modal analgesia are used to reduce the use of narcotic analgesics or the side effects of narcotic analgesics. In the intensive care unit (ICU), the sedation-agitation scale (SAS) and the Richmond agitation-sedation scale (RASS) are used to determine the depth of sedation to be maintained during shallow or deep sedation, considering the condition of the critically ill patient. When selecting sedatives for critically ill patients, preferentially consider nonbenzodiazepines such as propofol or dexmedetomidine rather than benzodiazepines such as midazolam or lorazepam. In addition, patients use painkillers or sedatives for over a week, and neurological changes or physiological dependence may occur. Therefore, clinicians should evaluate the critically ill patient’s condition, and sedatives and painkillers should be reduced or discontinued.

Clinical Scales for Peripheral Neuropathy - Revision 2021

Outcome measurements are essential to monitor the clinical course or the treatment response of peripheral neuropathy. Even though there are no designated standard scale for peripheral neuropathy currently, several clinical scales were validated to use for outcome measurements based on many researches. Here, we reviewed clinical scales commonly used and fulfilled clinimetric properties in peripheral neuropathy, especially focusing on inflammatory neuropathy (Guillain-Barré syndrome, chronic inflammatory demyelinating polyneuropathy, multifocal motor neuropathy). Each scale was classified according to the International Classification of outcome measure model - the International Classification of Functioning, Disability and Health to achieve a comprehensive concept of clinical scale in peripheral neuropathy.

Clinical Scales for Peripheral Neuropathy - Revision 2021

Outcome measurements are essential to monitor the clinical course or the treatment response of peripheral neuropathy. Even though there are no designated standard scale for peripheral neuropathy currently, several clinical scales were validated to use for outcome measurements based on many researches. Here, we reviewed clinical scales commonly used and fulfilled clinimetric properties in peripheral neuropathy, especially focusing on inflammatory neuropathy (Guillain-Barré syndrome, chronic inflammatory demyelinating polyneuropathy, multifocal motor neuropathy). Each scale was classified according to the International Classification of outcome measure model - the International Classification of Functioning, Disability and Health to achieve a comprehensive concept of clinical scale in peripheral neuropathy.

Polyneuropathy Following Nitrous Oxide Abuse / 대한신경근육질환학회지

Nitrous oxide (N2O), an anesthetic gas, has been abused by some people for entertainment purposes. Recently, N2O (under the name of "Happy Balloon") abuse has become problematic among young people in Korea. N2O intoxication can develop a neuropathy, as well as other systemic disorders, either by inactivating vitamin B12 or by a direct neurotoxic mechanism. Here, we report a case of peripheral neuropathy with possible coexisting myelopathy following N2O abuse.

Pain in Guillain-Barré Syndrome / 대한신경근육질환학회지

Pain in Guillain-Barré syndrome (GBS) is known as a common symptom, experienced by about 72% of patients. Various types of pain are associated with GBS, including paresthesia, dysesthesia, radicular pain, meningism, myalgia and visceral pain. Pain in GBS can vary from mild to severe, often under-recognized and poorly managed. This article reviews the various pains associated with Guillain-Barré syndrome and their management.

Recent Concepts of Guillain-Barré Syndrome

Guillain-Barré syndrome (GBS) is a representative form of post-infectious autoimmune neuropathy with heterogenous manifestations. It was originally considered as an ascending demyelinating polyneuropathy in Western countries. However, the discovery of anti-ganglioside antibodies on the basis of molecular mimicry theory could help us better understand various kinds of focal and regional variants as well as axonal type of GBS those were frequently found from Asian countries. Recent development of new techniques about anti-ganglioside complex antibodies is making more detailed descriptions for specific or unusual clinical manifestations. It has been regarded that GBS has good prognosis if treated properly as early as possible, but it still shows high mortality and morbidity rate with frequent long term neurologic and medical complications. Unfortunately, there are only two options for medical treatment, intravenous immunoglobulin and plasmapheresis, for the last 100 years. Several clinical studies on new immunotherapy targeting complement activating system with background of molecular mimicry using animal model are underway. We hope that these new treatments will be helpful for the future patients.

Pattern of Extraocular Muscle Involvements in Miller Fisher Syndrome

BACKGROUND AND PURPOSE: The most-common initial manifestation of Miller Fisher syndrome (MFS) is diplopia due to acute ophthalmoplegia. However, few studies have focused on ocular motility findings in MFS. This study aimed to determine the pattern of extraocular muscle (EOM) paresis in MFS patients. METHODS: We consecutively recruited MFS patients who presented with ophthalmoplegia between 2010 and 2015. The involved EOMs and the strabismus pattern in the primary position were analyzed. Antecedent infections, other involved cranial nerves, and laboratory findings were also reviewed. We compared the characteristics of the patients according to the severity of ophthalmoplegia between complete ophthalmoplegia (CO) and incomplete ophthalmoplegia (IO). RESULTS: Twenty-five patients (15 males and 10 females) with bilateral ophthalmoplegia were included in the study. The most-involved and last-to-recover EOM was the lateral rectus muscle. CO and IO were observed in 11 and 14 patients, respectively. The patients were aged 59.0±18.4 years (mean±SD) in the CO group and 24.9±7.4 years in the IO group (p<0.01), and comprised 63.6% and 21.4% females, respectively (p=0.049). Elevated cerebrospinal fluid protein was identified in 60.0% of patients with CO and 7.7% of patients with IO (p=0.019) for a mean follow-up time from the initial symptom onset of 3.7 days. CONCLUSIONS: The lateral rectus muscle is the most-involved and last-to-recover EOM in ophthalmoplegia. The CO patients were much older and were more likely to be female and have an elevation of cerebrospinal fluid protein than the IO patients.

A Systematic Literature Review for Evaluating the Clinical Usefulness of the Customized Vestibular Exercise / 대한이비인후과학회지

BACKGROUND AND OBJECTIVES: This study aims to evaluate the usefulness of customized vestibular exercise through literature review. MATERIALS AND METHOD: We searched several literature database such as Ovid-MEDLINE, Ovid-EMBASE, and Cochrane Library etc., with the following inclusion criteria: 1) studies of patients with dizziness and balance disorders, 2) studies in which a customized vestibular exercise was performed, and 3) studies in which one or more of the appropriate medical outcomes have been reported. At the same time, we excluded the following: 1) non-human studies and pre-clinical studies, 2) non-original articles, for example, non-systematic reviews, editorial, letter and opinion pieces, 3) research not published in Korean and English, 4) grey literature (thesis, congress or conference materials, abstract etc.), and 5) case studies. Finally, 10 studies were selected and analyzed. RESULTS: The safety of customized vestibular exercise was reported in three documents which reported no side effects related to the procedure. The effectiveness of customized vestibular exercise was proven by the assessment of symptom change, functional change, and other physiological measures based on a total of 10 randomized clinical trial studies. CONCLUSION: For patients with vestibular dysfunction, a customized vestibular exercise can be a safe and effective technique for improving dizziness and balance function.

Clinical Heterogeneity of Anti-GM2-Ganglioside-Antibody Syndrome

BACKGROUND AND PURPOSE: Antiganglioside antibodies are known to play a pathogenic role in Guillain-Barré syndrome (GBS). Either an immunoglobulin (Ig)G- or IgM-type anti-GM2 antibody is detected in rare cases in GBS patients. However, the specific pathogenic role of these antibodies in GBS has not been reported previously. This study aimed to define and characterize the clinical spectrum of GBS with anti-GM2 positivity. METHODS: We reviewed the database of the Dong-A University Neuroimmunology Team, which has collected sera of GBS and its variants from more than 40 general and university-based hospitals in Korea. Detailed information about the involved patients was often obtained and then corrected by the charge doctor applying additional questionnaires. RESULTS: Four patients with acute monophasic peripheral neuropathy or cranial neuropathy with isolated IgM-type anti-GM2-antibody positivity were recruited. In addition, IgG-type anti-GM2 antibody was solely detected in the sera of another four patients. The IgM-positive group comprised heterogeneous syndromes: two cases of acute motor axonal neuropathy, one of acute inflammatory demyelinating polyneuropathy, and one of isolated facial diplegia. In contrast, all of the cases enrolled in the IgG-positive group manifested with dizziness with or without oculomotor palsy due to cranial neuropathy syndrome. CONCLUSIONS: This study has identified that anti-GM2 antibody can be found in various subtypes of GBS and its variants in rare cases. Compared to the clinical heterogeneity of the IgM-positive group, the IgG-positive group can be characterized by cranial-dominant GBS variants presenting mainly with oculomotor and vestibular dysfunctions.

Renal Cholesterol Embolism during Warfarin Treatment

Cholesterol embolization syndrome (CES) usually occurs after endovascular procedures, it may also occurs after using anticoagulants and thrombolytics. We report a case of 66-year-old man with sudden elevation of creatinine after using warfarin due to cortical infarction. Histologic examinations revealed a cholesterol cleft on the arcuate artery. We concluded it as warfarin induced atheroembolic renal disease. Careful observation of kidneys is necessary in the case of renal abnormalities after using anticoagulation, considering the possibility of cholesterol embolism due to anticoagulant therapy.

Acute Ischemic Stroke in Moyamoya Syndrome Associated with Thyrotoxicosis

BACKGROUND: A few cases of moyamoya syndrome associated with thyrotoxicosis have been reported. However, studies on the association of hyperthyroidism with moyamoya syndrome are insufficient. CASE REPORT: Here we report a case of hyperthyroidism associated with moyamoya syndrome in a 41-year-old woman with aphasia and right side weakness. Brain imaging revealed acute cerebral infarction of left middle cerebral artery territory and occlusion of bilateral distal internal carotid arteries. CONCLUSION: Antithyroid medication stabilized the patient's neurologic deterioration, suggesting that thyrotoxicosis could aggravate acute cerebral infarction caused by moyamoya syndrome.

Miliary Tuberculosis Mimicking Brain Metastasis from Renal Cell Carcinoma

BACKGROUND: Miliary tuberculosis (TB) can cause diagnostic confusion for clinicians because its radiological appearance can resemble that of metastatic cancer. CASE REPORT: Here, we describe the case of a 72-yearold woman with miliary TB mimicking brain metastasis from renal cell carcinoma. The patient visited our clinic because of dysarthria and sluggish speech. A metastatic cancer such as renal cell carcinoma or brain tumor was suspected. However, the patient was diagnosed with miliary TB associated with multiple intracranial tuberculomas and a subsequent paradoxical response to anti-TB therapy. CONCLUSION: Clinicians should be aware that miliary TB can mimic metastatic cancer even in older people, especially in TB-endemic regions.

The Impacts of Influenza Infection and Vaccination on Exacerbation of Myasthenia Gravis

BACKGROUND AND PURPOSE: Upper respiratory infection (URI), including influenza, may exacerbate the symptoms of myasthenia gravis (MG), which is an autoimmune disease that causes muscle weakness. There is also concern that the influenza vaccine may trigger or worsen autoimmune diseases. The objective of this study was to determine the impacts of influenza infection and vaccination on symptom severity in MG patients. METHODS: Patients diagnosed with MG were enrolled from 10 university-affiliated hospitals between March and August 2015. Subjects completed a questionnaire at the first routine follow-up visit after enrolling in the study. The patient history was obtained to determine whether a URI had been experienced during the previous winter, if an influenza vaccination had been administered before the previous winter, and whether their MG symptoms were exacerbated during or following either a URI or vaccination. Influenza-like illness (ILI) was defined and differentiated from the common cold as a fever of ≥38℃ accompanied by a cough and/or a sore throat. RESULTS: Of the 258 enrolled patients [aged 54.1±15.2 years (mean±SD), 112 men, and 185 with generalized MG], 133 (51.6%) had received an influenza vaccination and 121 (46.9%) had experienced a common cold (96 patients) or ILI (25 patients) during the analysis period. MG symptoms were aggravated in 10 (40%) patients after ILI, whereas only 2 (1.5%) experienced aggravation following influenza vaccination. The rate of symptom aggravation was significantly higher in patients experiencing an ILI (10/25, 40%) than in those with the common cold (15/96, 15.6%, p=0.006). CONCLUSIONS: The results of this study suggest that the potential risk of aggravating autoimmune disease is higher for ILI than for influenza vaccination, which further suggests that influenza vaccination can be offered to patients with MG.

Erratum: Diagnostic Performance of Intravascular Ultrasound-Derived Minimal Lumen Area to Predict Functionally Significant Non-Left Main Coronary Artery Disease: a Meta-Analysis

In the article, the weighted overall mean MLA cut-off value has been miscalculated. Tha authors deeply apologize for any inconvenience it may have caused.

Co-occurrence of Guillain-Barré Syndrome and Acute Disseminated Encephalomyelitis with Dual Positive of Anti-GT1a and Anti-GM1 Antibodies

Acute disseminated encephalomyelitis (ADEM) and Guillain-Barré syndrome (GBS) are both rare post-infectious neurological disorders. The co-existence of these conditions has often been reported despite of low incidence. We describe a 20-year-old male, who presented with acute flaccid paralysis and encephalopathy. The patient showed reversible MRI lesions suggesting ADEM. This case showed anti-GT1a IgG and anti-GM1 IgM antibodies positivity. We suggest that certain immunogenicity within central and peripheral nervous system may share a common autoimmune process during the disease course.

Dissociation of Structural and Functional Integrities of the Motor System in Amyotrophic Lateral Sclerosis and Behavioral-Variant Frontotemporal Dementia

BACKGROUND AND PURPOSE: This study investigated the structural and functional changes in the motor system in amyotrophic lateral sclerosis (ALS; n=25) and behavioral-variant fronto-temporal dementia (bvFTD; n=17) relative to healthy controls (n=37). METHODS: Structural changes were examined using a region-of-interest approach, applying voxel-based morphometry for gray-matter changes and diffusion tensor imaging for white-matter changes. Functional changes in the motor system were elucidated using threshold-tracking transcranial magnetic stimulation (TMS) measurements of upper motor-neuron excitability. RESULTS: The structural analyses showed that in ALS there were more white-matter changes in the corticospinal and motor-cortex regions and more gray-matter changes in the cerebellum in comparison to controls. bvFTD showed substantial gray- and white-matter changes across virtually all motor-system regions compared to controls, although the brainstem was affected less than the other regions. Direct comparisons across patient groups showed that the gray- and white-matter motor-system changes inclusive of the motor cortex were greater in bvFTD than in ALS. By contrast, the functional integrity of the motor system was more adversely affected in ALS than in bvFTD, with both patient groups showing increased excitability of upper motor neurons compared to controls. CONCLUSIONS: Cross-correlation of structural and functional data further revealed a neural dissociation of different motor-system regions and tracts covarying with the TMS excitability across both patient groups. The structural and functional motor-system integrities appear to be dissociated between ALS and bvFTD, which represents useful information for the diagnosis of motor-system changes in these two disorders.

Diagnostic Performance of Intravascular Ultrasound-Derived Minimal Lumen Area to Predict Functionally Significant Non-Left Main Coronary Artery Disease: a Meta-Analysis

BACKGROUND AND OBJECTIVES: Intravascular ultrasound (IVUS)-guided percutaneous coronary intervention frequently results in unnecessary stenting due to the low positive predictive value of IVUS-derived minimal lumen area (MLA) for identification of functionally significant coronary stenosis. We appraised the diagnostic accuracy of IVUS-derived MLA compared with the fractional flow reserve (FFR) to assess intermediate coronary stenosis. SUBJECTS AND METHODS: We searched MEDLINE and Cochrane databases for studies using IVUS and FFR methods to establish the best MLA cut-off values to predict significant non-left main coronary artery stenosis. Summary estimates were obtained using a random-effects model. RESULTS: The 17 studies used in our analysis enrolled 3920 patients with 4267 lesions. The weighted overall mean MLA cut-off value was 2.58 mm². The pooled MLA sensitivity that predicted functionally significant coronary stenosis was 0.75 (confidence interval [CI]: 0.72 to 0.77) and the specificity was 0.66 (CI: 0.64 to 0.68). The positive likelihood ratio (LR) was 2.33 (CI: 2.06 to 2.63) and LR (-) was 0.33 (CI: 0.26 to 0.42). The pooled diagnostic odds ratio (DOR) was 7.53 (CI: 5.26 to 10.76) and the area under the summary receiver operating characteristic curve for all the trials was 0.782 with a Q point of 0.720. Meta-regression analysis demonstrated that an FFR cut-off point of 0.75 was associated with a four times higher diagnostic accuracy compared to that of 0.80 (relative DOR: 3.92; 95% CI: 1.25 to 12.34). CONCLUSION: IVUS-derived MLA has limited diagnostic accuracy and needs careful interpretation to correlate with functionally significant non-left main coronary artery stenosis.

Early Electrodiagnostic Features of Upper Extremity Sensory Nerves Can Differentiate Axonal Guillain-Barré Syndrome from Acute Inflammatory Demyelinating Polyneuropathy

BACKGROUND AND PURPOSE: Serial nerve conduction studies (NCSs) are recommended for differentiating axonal and demyelinating Guillain-Barré syndrome (GBS), but this approach is not suitable for early diagnoses. This study was designed to identify possible NCS parameters for differentiating GBS subtypes. METHODS: We retrospectively reviewed the medical records of 70 patients with GBS who underwent NCS within 10 days of symptom onset. Patients with axonal GBS and acute inflammatory demyelinating polyneuropathy (AIDP) were selected based on clinical characteristics and serial NCSs. An antiganglioside antibody study was used to increase the diagnostic certainty. RESULTS: The amplitudes of median and ulnar nerve sensory nerve action potentials (SNAPs) were significantly smaller in the AIDP group than in the axonal-GBS group. Classification and regression-tree analysis revealed that the distal ulnar sensory nerve SNAP amplitude was the best predictor of axonal GBS. CONCLUSIONS: Early upper extremity sensory NCS findings are helpful in differentiating axonal-GBS patients with antiganglioside antibodies from AIDP patients.

Diabetic vagal mononeuropathy manifesting with isolated dysphagia

Vagal mononeuropathy is very rare. Diabetes mellitus is one of the causes of this rare disease condition. Here we report a 44-year-old woman who presented with an idiopathic vagal mononeuropathy and was finally diagnosed with diabetic vagal mononeuropathy. She presented with isolated dysphagia without hoarseness or other symptoms related with vagal dysfunction. Except for diabetes mellitus, no abnormalities were found by routine and specific checkups including brain imaging, gastroscopy, electromyography, and laryngoscopy. Finally, 12 days later, she abruptly developed hoarseness without other cranial nerve dysfunction.We suggest that her neurological symptoms originated from diabetes affecting the vagus nerve in isolation. Clinicians should pay attention to this association, especially when they encounter a patient with diabetes mellitus with sudden idiopathic dysphagia even without problems of vocalization.