A prospective, multicenter, noninterventional study in Taiwan to evaluate the safety and tolerability of lacosamide as adjunctive therapy for epilepsy in clinical practice.

RATIONALE: Lacosamide (LCM) was initially approved in Taiwan in March 2014 for use as adjunctive therapy for focal impaired awareness seizures and secondarily generalized seizures (SGS) in patients with epilepsy ≥16 years of age. The efficacy and tolerability of adjunctive LCM for the treatment of patients with focal seizures have been demonstrated in randomized, placebo-controlled trials. However, the trials do not reflect a flexible dose setting. This study (EP0063) was conducted to assess the safety and tolerability of LCM in real-world clinical practice in Taiwan. Effectiveness of LCM was also assessed as an exploratory objective. METHODS: EP0063 was a multicenter, prospective, noninterventional study with an expected observation period of 12 months ±â€¯60 days. Eligible patients were ≥16 years of age, had focal impaired awareness seizures and/or SGS (in line with approved indication in Taiwan at the time of the study), were taking at least one concomitant antiseizure medication (ASM), and had at least one seizure in the 3 months before baseline. Patients were prescribed LCM by their treating physician in the course of routine clinical practice. The primary safety variable was treatment-emergent adverse events (TEAEs) spontaneously reported to, or observed by, the treating physician. Based on safety data from previous studies of LCM and known side effects of other ASMs, certain TEAEs (including but not limited to cardiac and electrocardiogram, suicidality, and rash related terms) were analyzed separately. Effectiveness variables included Clinical Global Impression of Change (CGIC) and change in 28-day seizure frequency from baseline to 12 months (or final visit), and freedom from focal seizures. RESULTS: A total of 171 patients were treated with LCM, of whom 139 (81.3%) completed the study. The Kaplan-Meier estimated 12-month retention was 82.9%. Patients had a mean (standard deviation [SD], range) age of 38.5 (14.0, 16-77) years, and 96 (56.1%) were male. Patients were taking a mean (SD, range) of 2.8 (1.1, 1-6) ASMs at baseline. Mean (SD, range) duration of LCM treatment was 288.7 (111.9, 2-414) days, and the mean (SD, range) daily dosage of LCM was 205.0 (82.7, 50.0-505.2) mg/day. Overall, 95 (55.6%) patients reported at least one TEAE, most commonly dizziness (33 [19.3%] patients). Drug-related TEAEs were reported in 74 (43.3%) patients, and drug-related TEAEs leading to discontinuation of LCM were reported in 14 (8.2%) patients. Two (1.2%) patients died during LCM treatment, which were considered not related to LCM. Two (1.2%) patients had suicidality-related TEAEs; these TEAEs were considered either not related to LCM or the relationship was not recorded. Rash-related TEAEs were reported in five (2.9%) patients (considered LCM-related in two patients). Based on the CGIC, at 12 months (or final visit), 109 (63.7%) patients were considered to have improved, 54 (31.6%) had no change, and the remaining eight (4.7%) were minimally worse. At 12 months (or final visit), the median percentage change in focal seizure frequency was -50.0. During the first 6 months of the study, 21 (12.3%) patients were free from focal seizures; 37 (21.6%) patients were free from focal seizures in the last 6 months of the study; and 14 (8.2%) were free from focal seizures for the full 12 months of the study. CONCLUSIONS: Results of this prospective, noninterventional study suggest that adjunctive LCM was generally safe and well tolerated in this patient group in real-world practice in Taiwan. Effectiveness was also favorable, with more than 60% of patients considered to be improved by their physician at 12 months (or final visit).

A post hoc analysis of the long-term safety and efficacy of perampanel in Asian patients with epilepsy.

This post hoc analysis assessed the long-term safety, tolerability, and efficacy of perampanel in Asian patients with refractory focal seizures; an additional analysis assessed the effect of perampanel on focal impaired awareness seizures (FIAS) with focal to bilateral tonic-clonic (FBTC) seizures. In this subanalysis, data from Asian patients ≥12 years of age who had focal seizures with FBTC seizures despite taking one to 3 concomitant antiepileptic drugs at baseline, and who had entered either the long-term extension phase of 3 phase-3 perampanel trials (study 307) or the 10-week extension phase of study 335, were analyzed for the effect of perampanel on duration of exposure, safety, and seizure outcomes. Of 874 Asian patients included in the analysis, 205 had previously received placebo during the double-blind phase-3 trials and 669 had previously received perampanel 2-12 mg/day; 313 had FIAS with FBTC seizures at core study baseline. The median duration of exposure to perampanel was 385.0 days, and the retention rate at one year was 62.6%. Overall, during the first 52 weeks of perampanel treatment, 777 patients (88.9%) had treatment-emergent adverse events (TEAEs), most of which were mild to moderate in severity. The most frequent TEAEs were dizziness (47.1%), somnolence (22.3%), and nasopharyngitis (17.4%). During the first 52 weeks of perampanel treatment, median percent change in seizure frequency per 28 days from pre-perampanel baseline for all focal seizures was -28.1%, and -51.7% for FIAS with FBTC seizures. The 50% responder rate relative to pre-perampanel baseline for all focal seizures was 33.8%, and 51.1% for FIAS with FBTC seizures. Long-term treatment with perampanel in Asian patients had safety, tolerability, and efficacy similar to that of the global population in the phase-3 trials and extension study 307. The safety profile and response rate suggest benefit for an Asian population of patients with refractory epilepsy.

Carbamazepine-induced toxic effects and HLA-B*1502 screening in Taiwan.

BACKGROUND: Carbamazepine, an anticonvulsant and a mood-stabilizing drug, is the main cause of the Stevens-Johnson syndrome (SJS) and its related disease, toxic epidermal necrolysis (TEN), in Southeast Asian countries. Carbamazepine-induced SJS-TEN is strongly associated with the HLA-B*1502 allele. We sought to prevent carbamazepine-induced SJS-TEN by using HLA-B*1502 screening to prospectively identify subjects at genetic risk for the condition. METHODS: From 23 hospitals in Taiwan, we recruited 4877 candidate subjects who had not taken carbamazepine. We genotyped DNA purified from the subjects' peripheral blood to determine whether they carried the HLA-B*1502 allele. Those testing positive for HLA-B*1502 (7.7% of the total) were advised not to take carbamazepine and were given an alternative medication or advised to continue taking their prestudy medication; those testing negative (92.3%) were advised to take carbamazepine. We interviewed the subjects by telephone once a week for 2 months to monitor them for symptoms. We used the estimated historical incidence of SJS-TEN as a control. RESULTS: Mild, transient rash developed in 4.3% of subjects; more widespread rash developed in 0.1% of subjects, who were hospitalized. SJS-TEN did not develop in any of the HLA-B*1502-negative subjects receiving carbamazepine. In contrast, the estimated historical incidence of carbamazepine-induced SJS-TEN (0.23%) would translate into approximately 10 cases among study subjects (P<0.001). CONCLUSIONS: The identification of subjects carrying the HLA-B*1502 allele and the avoidance of carbamazepine therapy in these subjects was strongly associated with a decrease in the incidence of carbamazepine-induced SJS-TEN. (Funded by the National Science Council of Taiwan and the Taiwan Drug Relief Foundation.).

Morphological and metabolic asymmetries of the thalamic subregions in temporal lobe epilepsy predict cognitive functions.

Both morphological and metabolic imaging were used to determine how asymmetrical changes of thalamic subregions are involved in cognition in temporal lobe epilepsy (TLE). We retrospectively recruited 24 left-TLE and 15 right-TLE patients. Six thalamic subnuclei were segmented by magnetic resonance imaging, and then co-registered onto Positron emission tomography images. We calculated the asymmetrical indexes of the volumes and normalized standard uptake value ratio (SUVR) of the entire and individual thalamic subnuclei. The SUVR of ipsilateral subnuclei were extensively and prominently decreased compared with the volume loss. The posterior and medial subnuclei had persistently lower SUVR in both TLE cases. Processing speed is the cognitive function most related to the metabolic asymmetry. It negatively correlated with the metabolic asymmetrical indexes of subregions in left-TLE, while positively correlated with the subnuclei volume asymmetrical indexes in right-TLE. Epilepsy duration negatively correlated with the volume asymmetry of most thalamic subregions in left-TLE and the SUVR asymmetry of ventral and intralaminar subnuclei in right-TLE. Preserved metabolic activity of contralateral thalamic subregions is the key to maintain the processing speed in both TLEs. R-TLE had relatively preserved volume of the ipsilateral thalamic volume, while L-TLE had relatively decline of volume and metabolism in posterior subnucleus.

Left Frontotemporal Region Plays a Key Role in Letter Fluency Task-Evoked Activation and Functional Connectivity in Normal Subjects: A Functional Near-Infrared Spectroscopy Study.

Letter fluency task (LFT) is a tool that measures memory, executive function, and language function but lacks a definite cutoff value to define abnormalities. We used the optical signals of functional near-infrared spectroscopy (fNIRS) to study the differences in power and connectivity between the high-functioning and low-functioning participants while performing three successive LFTs, as well as the relationships between the brain network/power and LFT performance. We found that the most differentiating factor between these two groups was network topology rather than activation power. The high-functional group (7 men and 10 women) displayed higher left intra-hemispheric global efficiency, nodal strength, and shorter characteristic path length in the first section. They then demonstrated a higher power over the left Broca's area than the right corresponding area in the latter two sections. The low-LFT group (9 men and 11 women) displayed less left-lateralized connectivity and activation power. LFT performance was only related to the network topology rather than the power values, which was only presented in the low-functioning group in the second section. The direct correlation between power and connectivity primarily existed in the inter-hemispheric network, with the timing relationship also seeming to be present. In conclusion, the high-functioning group presented more prominent left-lateralized intra-hemispheric network connectivity and power activation, particularly in the Broca's area. The low-functioning group seemed to prefer using other networks, like the inter-hemispheric, rather than having a single focus on left intra-hemispheric connectivity. The network topology seemed to better reflect the LFT performance than did the power values.

Sesamin ameliorates oxidative stress and mortality in kainic acid-induced status epilepticus by inhibition of MAPK and COX-2 activation.

BACKGROUND: Kainic acid (KA)-induced status epilepticus (SE) was involved with release of free radicals. Sesamin is a well-known antioxidant from sesame seeds and it scavenges free radicals in several brain injury models. However the neuroprotective mechanism of sesamin to KA-induced seizure has not been studied. METHODS: Rodents (male FVB mice and Sprague-Dawley rats) were fed with sesamin extract (90% of sesamin and 10% sesamolin), 15 mg/kg or 30 mg/kg, for 3 days before KA subcutaneous injection. The effect of sesamin on KA-induced cell injury was also investigated on several cellular pathways including neuronal plasticity (RhoA), neurodegeneration (Caspase-3), and inflammation (COX-2) in PC12 cells and microglial BV-2 cells. RESULTS: Treatment with sesamin extract (30 mg/kg) significantly increased plasma α-tocopherol level 50% and 55.8% from rats without and with KA treatment, respectively. It also decreased malondialdehyde (MDA) from 145% to 117% (p=0.017) and preserved superoxide dismutase from 55% of the vehicle control mice to 81% of sesamin-treated mice, respectively to the normal levels (p=0.013). The treatment significantly decreased the mortality from 22% to 0% in rats. Sesamin was effective to protect PC12 cells and BV-2 cells from KA-injury in a dose-dependent manner. It decreased the release of Ca2+, reactive oxygen species, and MDA from PC12 cells. Western blot analysis revealed that sesamin significantly reduced ERK1/2, p38 mitogen-activated protein kinases, Caspase-3, and COX-2 expression in both cells and RhoA expression in BV-2 cells. Furthermore, Sesamin was able to reduce PGE2 production from both cells under KA-stimulation. CONCLUSIONS: Taken together, it suggests that sesamin could protect KA-induced brain injury through anti-inflammatory and partially antioxidative mechanisms.

Network reorganization during verbal fluency task in fronto-temporal epilepsy: A functional near-infrared spectroscopy study.

This is the first study to use functional near-infrared spectroscopy (fNIRS) to investigate how the lateralization of the epileptogenic zone affects the reconfiguration of task-related network patterns. Eleven left fronto-temporal epilepsy (L-FTE) and 11 right fronto-temporal epilepsy (R-FTE), as well as 22 age- and gender-matched controls, were enrolled. Signals from 52-channel fNIRS were recorded while the subject was undertaking verbal fluency tasks (VFTs), which included categorical (CFT) and letter (LFT) fluency tasks. Three analytic methods were used to study the network topology: network-based analysis, hub identification, and proportional threshold to select the top 20% strongest connections for both graph theory parameters and clinical correlation. Performance of CFT is accomplished primarily using the ventral pathway, and bilateral ventral pathways are augmented in fronto-temporal epilepsy patients by strengthening the inter-hemispheric connections, especially for R-FTE. LFT mainly employed the dorsal pathway, and further prioritized the left dorsal pathway in strengthening intra-hemispheric connections in fronto-temporal epilepsy, especially L-FTE. The top 20% of the strongest connections only present differences in CFT network compared with the controls. R-FTE increased inter-hemispheric network density, while L-FTE decreased inter-hemispheric average characteristic path length. Accumulative seizure burden only affects L-FTE network. Better LFT performance and longer educational years seem to promote left fronto-temporal networks, and decreased the demand from RR intra-hemispheric connectivity in L-FTE. LFT scores in R-FTE are maintained by preserved RR intra-hemispheric networks. However, CFT scores and educational years seem to have no effect on the CFT network topology in both FTE.

Statin effects on post-stroke epilepsy and mortality - Taiwan population-based study.

Objectives: Statins have anti-inflammatory effects on several neurological diseases. However, their effects on post-stroke epilepsy and mortality have not been well studied.Method: This is a retrospective cohort study, based on the one-million random data from National Health Insurance Research Database (NHIRD) of Taiwan. We identified stroke inpatients during 2000-2009. They were grouped into statin users and non-users, and followed up to 2010. Excluded were those with in-hospital mortality, in-hospital seizure(s), epileptic history, antiepileptic drug use before admission, or age under 45. The hazard ratios of statin-associated epilepsy and mortality were analyzed separately.Results: There were 16,711 statin non-users and 2246 users. There was no significant differences between the two groups in terms of epilepsy (13.3 vs. 15.7 per 1000 person-years, p = 0.728) and overall mortality (66.3 vs. 104.6 per 1000 person-years, p = 0.351). Subgroup analysis of male patients showed that statin-users had lower mortality risk compared with non-users (60.2 vs. 113.0 per 1000 person-years, p = 0.032).Conclusion: Statins have a modest but non-significant effect in preventing post-apoplectic epilepsy in Taiwan. Statins decrease post-stroke mortality only in men. Further studies are needed to depict their exact roles in these issues.

Eye of the tiger-like MRI in parkinsonian variant of multiple system atrophy.

Parkinsonian variant of multiple system atrophy (MSA-P) clinically presents as autonomic dysfunction with parkinsonian features. Parkinsonian features include bradykinesia, rigidity, tremor, postural instability and poor levo-dopa response. Neuropathologically, MSA-P is characterized by selective neuronal loss and gliosis mainly affecting the putamen and caudate nucleus, substantia nigra, olivopontocerebellar pathway and intermediolateral cell column of the spinal cord. Therefore, the target of magnetic resonance imaging (MRI) is focused on signal changes or volume reduction on putamen, including putaminal slit, gliosis by diffusion studies and reduction of putaminal volume. There have been no reports describing clinical manifestations of MSA-P with imaging abnormalities over globus pallidus. Here, we describe three patients with typical presentations of MSA-P with autonomic dysfunction and disturbances of axial motor function with minimal appendicular symptoms, including postural instability and gait difficulties. MRI showed symmetrical hyperintensity over the center of globus pallidus surrounded by a mild low-signal rims at T2-weighted image that is similar to that of eye of the tiger sign except for the marked hypointense rims. Dopamine transporter scans showed symmetric reduction of uptake over bilateral basal ganglia. This is the first report concerning these unusual imaging findings in MSA-P patients and we believe there is a subgroup of MSA-P with clinical presentation of axial impairment and symmetrically abnormal signal changes of globus pallidus in MRI.

Alteration of proximal conduction velocity at distal nerve injury in carpal tunnel syndrome: demyelinating versus axonal change.

The objective of this study was to determine the cause of median forearm motor conduction velocity (FMCV) slowing in patients with carpal tunnel syndrome, due to either focal conduction abnormality over wrist or retrograde conduction slowing, and to decide whether the slowing is related to severity of compression or not. Fifty carpal tunnel syndrome patients confirmed by conventional nerve conduction study with abnormal electromyography of the abductor pollicis brevis muscle were group 1, and 100 with normal electromyography, group 2. One hundred volunteers served as controls. In addition to conventional nerve conduction study of median and ulnar nerves, palmar stimulations for median mixed and motor nerves were also performed to calculate wrist-palm mixed nerve conduction time and motor conduction velocity (W-P MCV). For group 1, group 2, and control subjects, respectively, W-P MCV were 19.73+/-7.65 (mean+/-SD), 32.7+/-6.83, and 52.75+/-6.4 m/s, whereas median FMCV were 48.63+/-8.32, 54.42+/-2.11, and 57.86+/-4.24 m/s. There was a significant reduction in the W-P MCV (62.6%, P<0.00001) and a decrease in the median FMCV (15.95%, P<0.00001) in group 1, and 38% reduction in W-P MCV (P<0.00001) and 5.9% decrease in median FMCV (P<0.00001) in group 2 when compared with controls, but ulnar FMCV and sensory nerve conduction study results did not, suggesting the reduction of median W-P MCV is not parallel with that of median FMCV in both patients groups. Furthermore, there is a poor correlation of median FMCV and W-P MCV in patient groups, implying conduction blockage of the large myelinating fibers at the wrist, leaving only slower axons to be measured, is not the likely cause of reduction of FMCV. In addition, the reduction of compound muscle action potential amplitude of abductor pollicis brevis muscle, conduction block at wrist and weak correlation of median FMCV and compound muscle action potential amplitude of abductor pollicis brevis exclusively occurred in group 1. Therefore, the retrograde conduction slowing really occurs among patients with carpal tunnel syndrome-markedly in those with abnormal electromyography and mildly in those with only demyelination. This finding counters conventional wisdom that nerve function changes only in segments distal to injured sites.

Unilateral carotid and vertebral artery dissections and contralateral subarachnoid hemorrhage in a postpartum patient.

Postpartum arterial dissection combined with subarachnoid hemorrhage (SAH) is rare and its mechanism is uncertain. A 32 year-old woman had a delivery by cesarean section 12 days prior to admission to our hospital. From the first day of delivery, she breast-fed her baby, sitting with her head always turned to the right. Each feeding lasted around 2 hours. A bilateral throbbing headache began two days after childbirth, and intermittent numbness of the right face, chest and hand as well as weakness of the right hand developed nine days after giving birth. A physical examination revealed transient mild hypertension and right hemiparesis. Her cholesterol ranged from 204 to 263 mg/dl. Computed tomography, magnetic resonance angiography and duplex ultrasound disclosed left fronto-parietal junction SAH and dissections of the right internal carotid (ICA) and vertebral arteries. Our patient demonstrated (1) that postpartum arterial dissection was not limited to natural delivery, (2) postpartum SAH could occur with dissections of the contralateral extracranial carotid and vertebral arteries, and (3) that turning one's head always to the same side during breast-feeding might be a risk factor for this unusual stroke pattern.

Comparison of sensitivity of transcarpal median motor conduction velocity and conventional conduction techniques in electrodiagnosis of carpal tunnel syndrome.

OBJECTIVE: To compare the sensitivity of median wrist-palm motor conduction velocity (W-P MCV) with those of standard sensory conduction techniques in the electrodiagnosis of carpal tunnel syndrome (CTS). METHODS: This study included 280 consecutively suspected CTS patients (360 hands) referred for evaluation and 150 volunteers who served as controls. We determined and calculated (1) median W-P MCV, (2) median motor distal latencies (DL) and median sensory DL for (3) thumb (D1), (4) index (D2) and (5) ring finger (D4), (6) median wrist-palm sensory conduction velocity (W-P SCV) and sensory conduction time (W-P SCT) for index finger and sensory latency differences between (7) median-radial (M-R) for thumb and (8) median-ulnar (M-U) nerves for ring finger. The normal limits were calculated from the median of normal controls +/-2.5 standard deviations. The sensitivities of each test were determined and compared. RESULTS: Among the 360 hands with suspected CTS, 32 hands (8.9%) had normal electrodiagnostic studies and 328 (91.1%) had at least one abnormal electrodiagnostic study. Among the 328 hands with abnormalities, 234 (65%) had abnormal motor DL and 294 (81.7%) had abnormal W-P MCV. The sensitivity was 80.3% for D1, 72.5% for D2, 76.7% for D4, 86.7% for M-R (specificity, 98.7%), 87.2% for M-U (specificity, 96.7%), 80.8% for sensory W-P SCT and 73.6% for W-P SCV. CONCLUSIONS: W-P MCV is a valuable motor conduction technique for the diagnosis of CTS and it is confirmed again that W-P MCV is equal to or more sensitive than W-P SCV and W-P SCT. Furthermore, the findings of the present study are in agreement with the conventional wisdom that internal comparison of latency differences between median and ulnar or radial nerves is the best method for a diagnosis of patients with suspected CTS. Therefore, we recommend that CTS patients be studied according to the following steps: (1) routine sensory and motor DL, (2) if step 1 is negative, then perform and determine W-P MCV or SCT. This may increase the diagnostic yield of 10%, (3) if step 2 is negative, measure the M-U or MR. These are the final and more sensitive techniques in making a diagnosis with an additional diagnostic yield of 10%. SIGNIFICANCE: We provide the evidence of W-P MCV that could be a standard technique for electrodiagnosis of CTS. Furthermore, we make a reasonable flow chart and recommendation for electrodiagnosis of CTS for electromyographers.

Prognosis of cerebral lipiodol embolism caused by transarterial chemoembolization.

OBJECTIVES: Transarterial chemoembolization (TACE) plays an essential role in the management of unresectable hepatocellular cell carcinoma and other hepatic neoplasms. Cerebral lipiodol embolism (CLE) is a rare complication of TACE and its prognostic factors have not been well studied. The aim of this paper was to elucidate the prognostic factors of CLE based on clinical data obtained from our patients and cases published since 2004. METHODS: We present two patients with CLE, analyze the clinical data, and review all CLE cases published since 2004. A poor outcome was defined as stupor, coma, quadriplegia, or death within 45 days. Patients who had other neurological conditions within 45 days were considered as having a good outcome. RESULTS: The rate of poor outcome was 25.7% (9/35). Compared with the patients with good outcome, those with poor outcome were older (mean age 68.3 ± 7.3 vs. 58.3 ± 10.6 years, p = 0.03), more often female (76.9% vs. male 33.3%, p = 0.02), and more likely chemoembolized via both the right hepatic and right inferior phrenic arteries (44.4 vs. 8.7%, p = 0.02). DISCUSSION: The prognosis of CLE was related to age, gender, and the arteries selected for injection.

General paresis with reversible mesial temporal T2-weighted hyperintensity on magnetic resonance image: a case report.

We report a patient with general paresis, whose magnetic resonance image (MRI) showed a T2 high-intensity lesion in bilateral mesial temporal regions. Serum rapid plasma reagin test showed reactive at 64 dilutions and serum Treponema pallidum haemagglutination test was 1:20480. Cerebrospinal fluid analysis showed: RBC 111/mm3, WBC 8/mm3, Venereal Disease Research Laboratory reactive at 1 dilution and protein 60 mg/dl. His neuropsychiatric symptoms recovered gradually after penicillin treatment two months later. Repeated MRI revealed resolution of the bilateral mesial temporal lesions. We demonstrated the first Taiwanese patient with general paresis whose clinical improvement was associated with the disappearance of the temporal lobe MRI abnormality. The diagnosis of neurosyphilis must be considered when MRI shows mesial temporal lesions. MRI may be used to predict prognosis in patients with general paresis.

Behavior, neurochemistry and histology after intranigral lipopolysaccharide injection.

Inflammation and neuronal degeneration of the substantia nigra (SN) occur in Parkinson's disease (PD). We studied the effects of intranigral lipopolysaccharide (LPS) injection on adult Sprague-Dawley rats. Locomotor activity measurement, neurotransmitter determination and perfusion fixation for immunohistochemistry were done on the 7th day. Bilateral LPS injection increased locomotor activity 2- to 3-fold. In the SN, dopamine (DA) and serotonin (5-HT) decreased but the ratios dihydroxyphenylacetic acid (DOPAC)/DA, homovanillic acid (HVA)/DA and 5-hydroxyindole-acetic acid (5-HIAA)/5-HT increased. In the striatum, DA, DOPAC, HVA, 3-methoxytyramine and epinephrine decreased but HVA/DA and 5-HIAA/5HT ratios increased. Unilateral LPS decreased dopamineric neurons ipsilaterally but increased contralaterally. This study provides the first evidence of behavioral hyperactivity, epinephrine suppression and neuronal plasticity in the LPS model of PD.

Does retrograde axonal atrophy really occur in carpal tunnel syndrome patients with normal forearm conduction velocity?

OBJECTIVE: The cause of decreased median forearm motor conduction velocity (FMCV) in carpal tunnel syndrome (CTS) is best ascribed to retrograde axonal atrophy (RAA); however, the relationships between the occurrence of RAA and electrophysiological or clinical severity remains controversial. We attempt to determine whether RAA really occurs in CTS patients with normal median FMCV and to investigate any relationships between RAA and severity of compression at the wrist. METHODS: Consecutive CTS patients were enrolled and age-matched volunteers served as controls. We performed conventional nerve conduction studies (NCS) and measured median and ulnar distal motor latencies (DML), FMCV, compound muscle action potential (CMAP) amplitudes, distal sensory latencies (DSL), and sensory nerve action potential (SNAP) amplitudes. Furthermore, palmar median stimulation was done to calculate the wrist-palm motor conduction velocity (W-P MCV). Patients included for analysis should have normal FMCV and needle examination. We compared each electrodiagnostic parameters between the patient group and controls. RESULTS: The mean+/-SD of the W-P MCV for patients and controls were 33.26+/-6.74 and 52.14+/-5.85 m/s and those of median FMCV were 55.26+/-3.56 and 57.82+/-3.9 m/s, respectively. There was a significant reduction in the W-P MCV (36.2%, P<0.00001), significant decrease in the median FMCV (4.43%, P<0.00001) and SNAP amplitudes, and an increase of the DML and DSL in the patient group (P<0.00001) compared to the controls; however, there were no differences in median and ulnar CMAP amplitudes, ulnar FMCV and DML between the controls and patients. CONCLUSIONS: RAA and relatively slowed median FMCV do occur in CTS patients with normal median FMCV, regardless of severity of clinical manifestations and electrophysiological abnormalities. SIGNIFICANCE: This article provides new information for research of the electrophysiological changes of the proximal nerve part at distal injury.

Does direct measurement of forearm mixed nerve conduction velocity reflect actual nerve conduction velocity through the carpal tunnel?

OBJECTIVES: The purpose of this study was to determine whether forearm (wrist-elbow) mixed nerve conduction velocity (W-Emix) represents the actual nerve conduction velocity (CV) of nerve fibers passing through the carpal tunnel. BACKGROUND: W-Emix is presumed to reflect the actual forearm CV through the carpal tunnel. However, it has been argued that W-Emix chiefly originates from the nerve fibers passing outside the carpal tunnel. Therefore, the direct measurement of W-Emix cannot be used to assess retrograde axonal atrophy in carpal tunnel syndrome (CTS). SUBJECTS AND METHODS: Thirty patients with clinical signs and symptoms of CTS were recruited and the diagnosis was confirmed with standard electrodiagnosis. Fifty age-matched volunteers served as control. Recording electrodes were placed over the elbow and index finger for mixed nerve and sensory nerve conduction studies, respectively. Stimulation was applied at the palm and wrist for the measurement of mixed nerve wrist-palm CV (W-Pmix), wrist-elbow CV (W-Emix), and elbow-palm CV (E-Pmix). Stimulation was applied at the elbow, wrist, and palm for the measurement of wrist-elbow sensory CV (W-Esen), wrist-palm CV (W-Psen), and elbow-palm CV (E-Psen). Comparisons were made between W-Pmix and W-Psen, W-Emix and W-Esen, and E-Pmix and E-Psen. RESULTS: Correlations between W-Emix and W-Esen, E-Pmix and E-Psen, and W-Pmix and W-Psen were good in the control. In the patient group, there was a strong positive correlation between W-Pmix and W-Psen, and between E-Pmix and E-Psen. However, W-Esen correlated weakly with W-Emix, suggesting that W-Emix chiefly represents the CV of fibers passing outside the carpal tunnel. Therefore, the direct measurement of W-Emix cannot be used to assess retrograde axonal atrophy. Furthermore, the reduction in W-Psen was more marked than the reduction in W-Esen, implying that a conduction block at the wrist is the least likely cause of proximal slowing in CTS. CONCLUSIONS: W-Emix does not reflect the actual CV of the nerve fibers passing through the carpal tunnel. In addition, retrograde axonal atrophy appears to be the primary cause of decreased forearm CV in CTS.

The cause of slowed forearm median conduction velocity in carpal tunnel syndrome: a Palmar stimulation study.

OBJECTIVES: To elucidate the etiopathogenesis of decreased forearm median motor conduction velocity (FMMCV) in carpal tunnel syndrome (CTS), we used segmental stimulation at the palm, wrist and antecubital fossa to determine conduction block at wrist and calculate and compare the segmental median motor conduction velocity (MMCV) to determine the pathogenesis. BACKGROUND: The cause of the decreased FMMCV in CTS remains unclear. Animal models have supported retrograde axonal atrophy as the cause. Some authors believe standard FMMCV, calculated by subtracting the distal latency, may not represent an exact assessment of FMMCV but rather the velocity of small fibers that persist throughout the carpal tunnel. SUBJECTS AND METHODS: Patients with clinical symptoms and signs of CTS which had been confirmed with standard electrodiagnosis, were included. The patients were divided into two groups: one with reduced FMMCV <50m/s (Group I, n=20) and the other with normal FMMCV>50m/s (Group II, n=40). Age-matched volunteers served as controls (n=60). We used palm, wrist and antecubital stimulation, and recorded compound muscle action potential (CMAP) amplitudes at the abductor pollicis brevis (APB) muscle. Based on a ratio of the CMAP amplitudes obtained from wrist and palm stimulation (W/P ratio) and the latency differences, we calculated the W/P ratio and the across wrist MMCV (AWMMCV) and FMMCV and compared and correlated them between two patient groups. RESULTS: There was no difference in median motor and sensory distal latency between Groups I and II. CMAP and sensory nerve action potential amplitudes were reduced in Group I compared with Group II, but the difference was only marginally significant. Four patients had a significant reduction of the W/P ratio in Group I, compared with 7 patients in Group II, which did not reach a significance. Sixteen patients (80%) in Group I demonstrated no conduction block. Furthermore, Group I showed significantly decreased FMMCV when compared with Group II; however, AWMMCV was not significantly reduced in Group I, suggesting that decreased FMMCV does not result from a decrease in AWMMCV. CONCLUSIONS: There was no significant motor conduction block and no correlation of the FMMCV and AWMMCV in CTS patients with a decrease of FMMCV, suggesting retrograde axonal atrophy, and not selective conduction block of the large fibers at the wrist, is the direct cause of decreased FMMCV in CTS.

Forearm mixed nerve conduction velocity: questionable role in the evaluation of retrograde axonal atrophy in carpal tunnel syndrome.

The objective of this study was to determine whether forearm mixed nerve conduction velocity (Fmix) reflects the real conduction velocity of forearm motor nerve (Fmot) and forearm sensory nerve (Fsen) fibers passing through the carpal tunnel. Forearm mixed nerve conduction velocity is presumed to be indicative of the conduction velocity of the median nerve over the forearm. Therefore, Fmix is used widely to assess the causes of slowing forearm conduction velocity in carpal tunnel syndrome. However, some authors claim that Fmix comes chiefly from the undamaged fibers in carpal tunnel syndrome, and thus cannot replace Fmot or Fsen in the evaluation of retrograde axonal atrophy. Patients with clinical symptoms and signs of carpal tunnel syndrome confirmed with standard electrodiagnosis were included. Age-matched volunteers served as control subjects. Conduction velocities across the wrist and over the forearm were measured, including those of the wrist sensory (Wsen), wrist motor (Wmot), and wrist mixed nerves (Wmix); and forearm mixed (Fmix), forearm motor (Fmot), and forearm sensory nerves (Fsen). The authors compared and correlated Wsen, Wmot, and Wmix; and Fmix, Fmot, and Fsen respectively. The mean values of Wsen, Wmot, Wmix, Fmix, Fmot, and Fsen of the control subjects less those of corresponding conduction velocity of carpal tunnel syndrome patients were designated Wsen N, Wmot N, Wmix N, Fmix N, Fmot N, and Fsen N respectively and were compared and correlated again. Wrist motor nerve conduction velocity, Wsen, and Wmix were significantly lower in carpal tunnel syndrome patients, and Fmot and Fsen but not Fmix were reduced significantly when compared with control subjects. Mean wrist sensory nerve conduction velocity, Wmot N, and Wmix N; and Fsen N and Fmot N showed good correlation except for Fmix N, suggesting that Fmix reflects the conduction velocity of undamaged fibers in carpal tunnel syndrome. Forearm mixed nerve conduction velocity cannot replace Fmot or Fsen in the assessment of retrograde axonal atrophy in carpal tunnel syndrome. In the disease state, Fmix possibly represents the conduction velocity of the palmar cutaneous branch.

Temporary cerebellar hypoperfusion with good outcome in cerebellitis.

The relation between clinical outcome and single photon emission tomography (SPECT) results in cerebellitis has not been studied. A 63-year-old man developed cerebellar dysfunction with left emphasis one week after onset of cough. The only abnormality on analysis of cerebrospinal fluid was elevated protein (68 mg/dl). Magnetic resonance imaging was normal on the ninth day of ataxia. SPECT showed unilateral cerebellar hypoperfusion on the 13th day, but was normal on the 20th day. His gait improved a little by discharge on the 28th day and his tandem gait was only slightly unsteady six months later. This is the first evidence that normalization of cerebellar hypoperfusion in adult patients with cerebellitis is related to good outcome. Normalization of cerebellar hypoperfusion can occur in three weeks even when ataxia remains severe.