Elderly patients with suspected Charcot-Marie-Tooth disease should be tested for the TTR gene for effective treatments.

BACKGROUND AND AIMS: Some hereditary transthyretin (ATTRv) amyloidosis patients are misdiagnosed as Charcot-Marie-Tooth disease (CMT) at onset. We assess the findings to identify ATTRv amyloidosis among patients with suspected CMT to screen transthyretin gene variants for treatments. METHODS: We assessed clinical, cerebrospinal fluid, and electrophysiological findings by comparing ATTRv amyloidosis patients with suspected CMT (n = 10) and CMT patients (n = 489). RESULTS: The median (interquartile range) age at onset of neurological symptoms was 69 (64.2-70) years in the ATTRv amyloidosis vs 12 (5-37.2) years in CMT group (Mann-Whitney U, p < 0.01). The proportion of patients with initial sensory symptoms was 70% in the ATTRv amyloidosis group vs 7.1% in CMT group (Fisher's exact, p < 0.01). The proportion of patients with histories of suspected chronic inflammatory demyelinating polyneuropathy (CIDP) were 50% in the ATTRv amyloidosis group vs 8.7% in CMT group (Fisher's exact, p < .01). Other measures and outcomes were not different between the two groups. Five of the six patients with ATTRv amyloidosis received treatment and survived. INTERPRETATION: For effective treatments, the transthyretin gene should be screened in patients with suspected CMT with old age at onset of neurological symptoms, initial sensory symptoms, and histories of suspected CIDP.

Increased cerebrospinal fluid adenosine 5'-triphosphate in patients with amyotrophic lateral sclerosis.

BACKGROUND: Extracellular adenosine 5'-triphosphate (ATP) has been suggested to cause neuroinflammation and motor neuron degeneration by activating microglia and astrocytes in amyotrophic lateral sclerosis (ALS). Since we have developed a highly sensitive ATP assay system, we examined cerebrospinal fluid (CSF) ATP levels in patients with ALS whether it can be a useful biomarker in ALS. METHODS: Forty-eight CSF samples from 44 patients with ALS were assayed for ATP with a newly established, highly sensitive assay system using luciferase luminous reaction. CSF samples from patients with idiopathic normal pressure hydrocephalus (iNPH) were assayed as a control. Patients were divided into two groups depending on their disease severity, as evaluated using the Medical Research Council (MRC) sum score. Correlations between the CSF ATP levels and other factors, including clinical data and serum creatinine levels, were evaluated. RESULTS: CSF ATP levels were significantly higher in patients with ALS than in the iNPH (716 ± 411 vs. 3635 ± 5465 pmol/L, p < 0.01). CSF ATP levels were significantly higher in the more severe group than in the iNPH group (6860 ± 8312 vs. 716 ± 411 pmol/L, p < 0.05) and mild group (6860 ± 8312 vs. 2676 ± 3959 pmol/L, p < 0.05) respectively. ALS functional rating scale-revised (ALSFRS-R) (37.9 ± 5.7 vs. 42.4 ± 2.8, p < 0.01) and serum creatinine levels (0.51 ± 0.13 vs. 0.68 ± 0.23 mg/dL, p < 0.05) were significantly lower in the severe group than in the mild group respectively. A negative correlation of CSF ATP levels with MRC sum score was demonstrated in the correlation analysis adjusted for age and sex (r = -0.3, p = 0.08). CONCLUSIONS: Extracellular ATP is particularly increased in the CSF of patients with advanced ALS. CSF ATP levels may be a useful biomarker for evaluating disease severity in patients with ALS.

A Parkinson's disease patient displaying increased neuromelanin-sensitive areas in the substantia nigra after rehabilitation with tDCS: a case report.

Previous studies have reported that transcranial direct current stimulation (tDCS) of the frontal polar area (FPA) ameliorated motor disability in patients with Parkinson's disease (PD). Here we report changes in neuromelanin (NM) imaging of dopaminergic neurons before and after rehabilitation combined with anodal tDCS over the FPA for 2 weeks in a PD patient. After the intervention, the patient showed clinically meaningful improvements while the NM-sensitive area in the SN increased by 18.8%. This case study is the first report of NM imaging of the SN in a PD patient who received tDCS.Abbreviations FPA: front polar area; PD: Parkinson's disease; NM: neuromelanin; DCI: DOPA decarboxylase inhibitor; STEF: simple test for evaluating hand function; TUG: timed up and go test; TMT: trail-making test; SN: substantia nigra; NM-MRI: neuromelanin magnetic resonance imaging; MCID: the minimal clinically important difference; SNpc: substantia nigra pars compacta; VTA: ventral tegmental area; LC: locus coeruleus; PFC: prefrontal cortex; M1: primary motor cortex; MDS: Movement Disorder Society; MIBG: 123I-metaiodobenzylguanidine; SBR: specific binding ratio; SPECT: single-photon emission computed tomography; DAT: dopamine transporter; NIBS: noninvasive brain stimulation; tDCS: transcranial direct current stimulation; MAOB: monoamine oxidase B; DCI: decarboxylase inhibitor; repetitive transcranial magnetic stimulation: rTMS; diffusion tensor imaging: DTI; arterial spin labeling: ASL.

Impact of Pulmonary Valve Regurgitation on Pressure Difference of Pulmonary Valve Stenosis in Patients with Tetralogy of Fallot After Repair.

Pressure difference (PD) is an important parameter in evaluating the degree of stenotic lesion. However, PD is influenced by the blood flow volume passing through the stenosis. In patients with tetralogy of Fallot (TOF), pulmonary valve regurgitation (PR) and pulmonary valve stenosis (vPS) are common post-operative complications. The aim of this study was to evaluate the influence of PR on the PD. First, we examined the relationship between the peak-to-peak PD and the valve orifice area in 7 patients with vPS from their cardiac catheterization data. Second, an estimated PD, i.e., PD assuming no PR, was calculated in 8 patients with TOF with vPS and PR from their valve orifice area using the relational equation in patients with vPS. Moreover, an excess of PD, equating to the difference between the measured and estimated PD, was calculated. Finally, the relationship between the regurgitant fraction (RF) and the excess PD was analyzed. There was a strong relationship between the reciprocal of the valve orifice area and the PD in patients with vPS (r = 0.904, p = 0.0053). The excess PD showed a significant correlation with the RF in patients with TOF (r = 0.889, p = 0.0032). PR of over 25% in RF augmented the PD depending on the regurgitant volume. Severity of vPS could be overestimated in post-operative patients with TOF who had significant PR when their RF was above 25%.

Increased Cerebrospinal Fluid Adenosine 5'-Triphosphate Levels in Patients with Guillain-Barré Syndrome and Chronic Inflammatory Demyelinating Polyneuropathy.

Background: Extracellular adenosine 5'-triphosphate (ATP) acts as a signaling molecule in the peripheral nerves, regulating myelination after nerve injury. The present study examined whether the cerebrospinal fluid (CSF) ATP levels in patients with Guillain-Barré syndrome (GBS) and chronic inflammatory demyelinating polyneuropathy (CIDP) are related to disease severity. Methods: CSF ATP levels in 13 patients with GBS and 18 patients with CIDP were compared with those in a control group of 16 patients with other neurological diseases (ONDs). In patients with CIDP, CSF ATP levels were compared before and after treatment. The correlations between CSF ATP levels and other factors, including clinical data and CSF protein levels, were also evaluated. Results: Median CSF ATP levels were significantly higher in patients with GBS and CIDP than in those with ONDs. When patients with CIDP were classified into two groups depending on their responsiveness to immunotherapy, median CSF ATP levels were significantly higher in good responders than in ONDs. CSF ATP levels tended to decrease after treatment in patients with CIDP. In patients with CIDP, there is a negative correlation between CSF ATP and CSF protein levels. Conclusions: CSF ATP levels were increased in patients with GBS and CIDP. In particular, CSF ATP levels tended to decrease following treatment in patients with CIDP. CSF ATP levels may be useful biomarkers for the diagnosis or monitoring of therapeutic effects in patients with GBS and CIDP.

Identification of double-stranded DNA in the cerebrospinal fluid of patients with acute neuromyelitis optica spectrum disorder.

Neuromyelitis optica spectrum disorder (NMOSD) is an inflammatory disease of the central nervous system (CNS) characterized by severe myelitis and optic neuritis. Double-stranded DNA (dsDNA) is involved in the pathogenesis of various autoimmune diseases, such as systemic lupus erythematosus. However, its role in NMOSD remains unclear. In this study, the concentration of dsDNA in the cerebrospinal fluid (CSF) was quantified in 23 patients with NMOSD and 16 patients with other neurological diseases (ONDs). CSF dsDNA levels in patients with NMOSD (median: 0.03 ng/µL) were significantly higher than those in patients with ONDs (median: 0.01 ng/µl). CSF dsDNA levels showed no significant difference before and after treatment. Elevation of CSF dsDNA levels may suggest its essential role in the augmentation of CNS inflammation in patients with NMOSD.

Serum neurofilament light chain in chronic inflammatory demyelinating polyneuropathy.

OBJECTIVES: Neurofilament light chain (NfL) levels have been suggested as reflecting axonal damage in various inflammatory and neurodegenerative disorders, including acquired peripheral neuropathies. We aimed to investigate if serum NfL (sNfL) levels can be a biomarker of disease activity and treatment response in patients with chronic inflammatory demyelinating polyneuropathy (CIDP). MATERIALS AND METHODS: The sNfL levels of eleven newly diagnosed patients with CIDP were retrospectively assayed and compared with seven healthy volunteers. The levels were assayed before and after intravenous immunoglobulin treatment in patients with CIDP and were also assayed in the remission period. RESULTS: Baseline sNfL levels in patients with CIDP before treatment were significantly higher than those in healthy controls. The levels significantly decreased overtime after one month of treatment and in remission period. There were significant negative correlations between the sNfL levels and the disease duration (the interval between the onset of the disease and the time of sampling), and weak correlations between the sNfL levels and overall neuropathy limitations scale. CONCLUSIONS: sNfL may be a potential biomarker reflecting the disease activity in patients with CIDP.

Cerebrospinal fluid ATP as a potential biomarker in patients with mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke like episodes (MELAS).

Mitochondrial encephalopathy, lactic acidosis, and stroke-like episodes (MELAS) is caused by defective oxidative phosphorylation in the cerebral parenchyma, cerebral blood vessels, and leptomeningeal tissue. Although increased blood and cerebrospinal fluid (CSF) lactate level has been used as a diagnostic biomarker in patients with MELAS, no biomarkers reflecting disease activity exist. Since we have developed a highly sensitive ATP assay system using luciferase luminous reaction, we examined CSF ATP in patients with MELAS and found that it negatively correlates with disease activity and that it reflects the efficacy of the treatment. CSF ATP might be a novel disease monitoring marker for MELAS.

[Case of anosmia which appeared after anaphylactic shock due to intravenous heparin].

A patient developed anaphylactic shock after a heparin dosage during an operation to make inner shunt for chronic renal failure of Alport syndrome. The operation was canceled and the patient was admitted to the ICU with tracheal intubation. He was extubated safely on the fifth postoperative day, but he lost the sense of smell from the day after. Abnormality of the nasal mucosa was not recognized. The smell disorder improved slowly in three or four weeks. Anosmia after anaphylactic shock is very rare, but we should be careful for this complication after anaphylactic shock.

[A case of neurolymphomatosis presented as cauda equine syndrome accompanied with M-proteinemia].

A 63-year-old man developed a syndrome of cauda equine, with the numbness which is a left lower extremity from the left buttocks, weakness of left leg, and a dysfunction of bladder and bowel. Enhanced MRI revealed the enhancement of lower cauda equine, and a nerve conduction test revealed decreased F-wave persistency in the tibial nerve and increased F-wave latency in the peroneal nerve on the both sides. M-proteinemia was admitted and myeloma was suspected. By a biopsy of a vertebral arch, we diagnosed with diffuse large B-cell lymphoma. We treated with dexamethasone and R-CHOP (rituximab, cyclophosphamide, hydroxydaunorubicin, oncovin, prednisone (prednisolone)), then the symptom was improved. In case of caude equine syndrome with M-proteinemia, a possibility of the malignant lymphoma should also be considered.

Effects of Transcranial Direct Current Stimulation (tDCS) Over the Frontal Polar Area on Motor and Executive Functions in Parkinson's Disease; A Pilot Study.

Parkinson's disease (PD) is a neurodegenerative disorder with motor and non-motor symptoms due to degeneration of dopaminergic neurons. The current pharmacological treatments induce complications associated with long-term use. However, current stimulation techniques for PD treatment, such as deep brain stimulation (DBS), are too invasive. In this context, non-invasive brain stimulation including transcranial direct current stimulation (tDCS) may be a safe and effective alternative treatment for PD. We previously reported that anodal tDCS over the frontal polar area (FPA) improved motor functions in heathy subjects. Therefore, in the present study, effects of tDCS over the FPA on motor and cognitive functions of PD patients were analyzed. Nine PD patients (3 men and 6 women) participated in this cross over study with three tDCS protocols; anodal, cathodal or sham tDCS over the FPA. Each tDCS protocol was applied for 1 week (5 times/week). Before and after each protocol, motor and cognitive functions of the patients were assessed using Unified PD Rating Scale [UPDRS (part III: motor examination)], Fugl Meyer Assessment set (FMA), Simple Test for Evaluating hand Function (STEF) and Trail Making Test A (TMT-A). The results indicated that anodal stimulation significantly decreased scores of motor disability in UPDRS-III compared with sham and cathodal stimulation, and significantly increased scores of motor functions in FMA compared with sham stimulation. Furthermore, anodal stimulation significantly decreased time to complete a motor task requiring high dexterity in STEF compared with those requiring low and medium levels of dexterity. In addition, anodal stimulation significantly decreased time to complete the TMT-A task, which requires executive functions, compared with sham stimulation. To the best of our knowledge, this is the first clinical research reporting that tDCS over the FPA successfully improved the motor and non-motor functions in PD patients. These findings suggest that tDCS over the FPA might be a useful alternative for the treatment of PD patients.

Perioperative Elevation in Cell-Free DNA Levels in Patients Undergoing Cardiac Surgery: Possible Contribution of Neutrophil Extracellular Traps to Perioperative Renal Dysfunction.

Background. This study aimed to determine the perioperative change in serum double-strand DNA (dsDNA) as a marker potentially reflecting neutrophil extracellular trap concentration in samples from patients undergoing cardiac surgery and to analyze a relationship between serum dsDNA concentrations and perioperative renal dysfunction. Methods. Serum dsDNA concentrations in samples that were collected during a previously conducted, prospective, multicenter, observational study were measured. Eighty patients undergoing elective cardiac surgery were studied. Serum samples were collected at baseline, immediately after surgery, and the day after surgery (POD-1). Results. Serum dsDNA concentration was significantly increased from baseline (median, 398 ng/mL [interquartile range, 372-475 ng/mL]) to immediately after surgery (median, 540 ng/mL [437-682 ng/mL], p < 0.001), and they were reduced by POD-1 (median, 323 ng/mL [256-436 ng/mL]). The difference in serum creatinine concentration between baseline and POD-1 was correlated with dsDNA concentration on POD-1 (rs = 0.61, p < 0.001). Conclusions. In patients undergoing cardiac surgery, serum dsDNA concentration is elevated postoperatively. Prolonged elevation in dsDNA concentration is correlated with perioperative renal dysfunction. Further large-scale studies are needed to determine the relationship between serum concentration of circulating dsDNA and perioperative renal dysfunction.

Polymyxin B-immobilized fiber column hemoperfusion removes endotoxin throughout a 24-hour treatment period.

PURPOSE: The purpose of this study was to evaluate the extent of endotoxin adsorption by polymyxin B-immobilized fiber column hemoperfusion (PMX) performed for a 24-hour treatment period in patients with septic shock. MATERIALS AND METHODS: Nineteen patients with septic shock were retrospectively studied. The plasma endotoxin concentrations of blood drawn from the radial artery and from the outlet circuit of the PMX column were measured by kinetic turbidimetric limulus assay using an MT-358 Toxinometer (Wako Pure Chemical Industries, Ltd, Osaka, Japan) after 24 hours of PMX treatment. The endotoxin removal rate was defined by the following equation: ([radial artery endotoxin concentration - outlet circuit of PMX column endotoxin concentration]/radial artery endotoxin concentration) × 100%. RESULTS: The patients had a median Acute Physiology and Chronic Health Evaluation II score of 29 at intensive care unit admission and a 28-day mortality of 47%. Before the start of the PMX treatment, the median radial arterial plasma endotoxin concentration was 16.48 pg/mL. After 24 hours of PMX treatment, the median radial plasma endotoxin concentration had decreased to 1.857 pg/mL, and the concentration at the outlet circuit of the PMX column was further decreased to 0.779 pg/mL. The median endotoxin removal rate was 74.4%. CONCLUSION: These findings suggest that 24-hour PMX treatment was effective in removing endotoxin continuously throughout the entire treatment period.

Medication errors in anesthesia: an 8-year retrospective analysis at an urban university hospital.

PURPOSE: The Japanese Society of Anesthesiologists (JSA) has investigated critical events in several fields of anesthesiology. However, the types, frequency, and characteristics of medication errors related to anesthesia have not been investigated. By analyzing incident reports retrospectively, we investigated medication errors that occurred during anesthetic practice over the past 8 years at our institution. METHODS: Incident reports related to medication errors that occurred between May 1999 and March 2007 were analyzed retrospectively using a questionnaire published by the JSA in the "Survey of medication errors related to anesthesia". During these 8 years, 233 incidents were reported, in a total of 27454 anesthesia cases conducted during this period. Of these incidents, 61 (26.2%) were anesthetic drug administration errors. In these 61 incidents, clerical error (e.g., erroneous prescription writing), and pre-error (defined as any incident with the potential to become an error) were excluded from the analysis. Consequently, 13 incidents were excluded and 48 incidents were analyzed. RESULTS: Medication errors due to overdose were the most frequent kind of error (25%), followed by substitution (23%), and omission (21%). Errors due to an incorrect route of administration were rare. The drugs most frequently involved in these errors were antibiotics and muscle relaxants. Most of the patients involved in the incidents were, fortunately, not harmed seriously. The total frequency of medication errors in the survey period was 0.175% (48 incidents in 27 454 total anesthesia cases). CONCLUSION: We found that overdose, substitution, and omission were the main causes of anesthesia-related medication errors in our department.

Delayed emergence from anesthesia resulting from cerebellar hemorrhage during cervical spine surgery.

Cerebellar hemorrhage is an unpredictable complication of spinal surgery. We encountered a case of cerebellar hemorrhage presenting with delayed emergence from anesthesia and hemiplegia after resection of an intradural extramedullar tumor from the cervical spine. Postoperative brain computed tomography revealed hematoma in the cerebellar vermis and right cerebellar hemisphere. The patient made a gradual recovery with conservative treatment. Although the mechanism of cerebellar hemorrhage remains speculative, loss of cerebrospinal fluid may play an important role. Cerebellar hemorrhage must therefore be considered in patients with unexplained neurological deterioration or disturbance on emergence from anesthesia after spinal surgery.