P132 THE UTILITY OF STATISTICAL MOTOR UNIT NUMBER ESTIMATION IN MOTOR NEUROPATHY
LIU M, CUI L, LI X
Department of Neurology, Peking Union Medical College Hospital, Beijing, China
E-mail address for correspondence: [email protected]
Keywords: motor unit number estimation, demyelination, axonal loss
Introduction: Motor unit number estimation (MUNE) techniques have been applied to the study of muscle denervating disorders to evaluate motor neuron loss. But the features of MUNE in acquired demyelinating neuropathy are not elucidated.
Objective: To compare the features of Statistical motor unit number estimation in amyotrophic lateral sclerosis and acquired demyelinating neuropathy, determine the utility of Statistical MUNE in the differentiating of axonal loss and demyelination.
Methods: 3 groups of subjects including 48 healthy controls, 41 patients with ALS, 25 patients with demyelinating neuropathy (19 patients with acute inflammatory demyelinating polyneuropathy, 2 with chronic inflammatory demyelinating polyneuropathy and 4 with motifocal motor neuropathy) were recruited in 2 years. Statistical motor unit number estimations were performed on the median nerve/ thenar muscle. The features of MUNE, the mean amplitude of surface recorded motor unit potential (SMUP), the maximal amplitude of SMUP and the stimulus response function curves in different groups were compared.
Results: The number weighted-MUNE in ALS, demyelinating neuropathy and healthy controls were 49±20, 109±38, 118±12 respectively, the mean amplitude of SMUP were 121±51µV, 58±33µV, 110±25µV respectively, the maximal amplitude of SMUP were 263±150µV, 107±74µV, 139±36µV respectively, the amplitude of compound muscle action potential were 5.8±2.8mV, 6.5±4.6mV, 13.1±2.8mV respectively. There is significant difference between ALS and healthy controls in MUNE, mean amplitude of SMUP and maximal amplitude of SMUP (p < 0.01). Mean amplitude of SMUP in demyelinating neuropathy was significantly decreased compared to those in healthy controls and ALS, and there is no difference between demyelinating neuropathy and healthy controls in MUNE and maximal amplitude of SMUP. The range of greatest recording window in stimulating-response function curves increased significantly in ALS.
Conclusions: In patients with ALS, there is a significant decrease in MUNE and increase in maximal amplitude of SMUP; while there is a significant decrease in mean amplitude of SMUP in patients with demyelinating neuropathy, which suggest that Statistical MUNE may be a useful non-invasive technique to help differentiate axonal loss and demyelination.
P133 THE UTILITY OF INCHING TECHNIQUE IN DIAGNOSIS OF MOTOR NERVE CONDUCTION BLOCK
LIU M, CUI L, LI X
Department of Neurology, Peking Union Medical College Hospital, Beijing, China
E-mail address for correspondence: [email protected]
Keywords: conduction block, inching technique, diagnosis
Introduction: Both motor nerve conduction block (CB) and abnormal temporal dispersion (TD) are electrophysiological events in motor nerve conduction studies. The presence of abnormal TD may interfere in the diagnosis of CB. Motor nerve conduction block is of great importance in differentiating amyotrophic lateral sclerosis (ALS) from acquired demyelinating neuropathy.
Objective: To assess the utility of inching technique in diagnosis of motor nerve conduction block (CB).
Methods: 3 groups of subjects including 30 healthy controls, 44 patients with ALS, 38 patients with demyelinating neuropathy (14 patients with inflammatory demyelinating polyradiculoneuropathy, 12 with chronic inflammatory demyelinating polyradiculoneuropathy and 12 with multifocal motor neuropathy) were recruited in 4 years. Routine motor nerve conduction studies (long segment) and inching technique (stimulating along the course of the nerve in 2-cm increments from the wrist to axilla) were performed in median nerves and ulnar nerves simultaneously.
Results: In patients with acquired demyelinating neuropathy, 24 long segments of 18 nerves had a reduction in amplitude of 20% to 40%, no CB or probable CB could be diagnosed according to the criteria of AAEM Citation[1], when studied with inching technique, 21 CBs and 18 probable CBs over short segment were detected in 14 nerves, CBs over short segments were detected with inching technique in 5 long segments with abnormal temporal dispersion which had increase in duration more than 60%. In patients with ALS, No CB over short segment was confirmed in 19 nerves which had a reduction in amplitude of 20% to 40%. According to the criteria recommended by AAEM Citation[1], 4 standard segments of 4 patients with ALS met the criteria of CB or probable CB but not confirmed by inching technique. In all the subjects, no CB over short segment was detected in the long segments with a reduction in amplitude of 20% or less.
Conclusions: Inching technique can give more subtle information of the nerve and have additional diagnostic value in motor neuropathy. Because inching technique was performed with 2 cm interval between stimulating sites, these could decrease phase cancellation and temporal dispersion which is length dependent. Inching technique is more sensitive in detecting CB, useful to extract CB from abnormal TD, and helpful to identify the pseudo-CB in ALS. For segments with a reduction in amplitude of 20% or less, inching technique is not recommended.
P134 THE VALUE OF SINGLE FIBER ELECTROMYOGRAPHY IN DIAGNOSIS OF AMYOTROPHIC LATERAL SCLEROSIS
CUI L, LIU M, LI X, CHEN L
Department of Neurology, Peking Union Medical College Hospital, Beijing, China
E-mail address for correspondence: [email protected]
Keywords: Single fiber electromyography, diagnosis, jitter
Introduction: In the EI Escorial revised criteria for the diagnosis of amyotrophic lateral sclerosis (ALS), single fiber electromyography (SFEMG) is not essential.
Objective: To assess the value of SFEMG in differentiating ALS from other neurogenic disorders.
Methods: SFEMG was performed in extensor digitorum communis muscles (EDC) of 165 patients with ALS and 145 patients with other neurogenetic disorders. The parameters of SFEMG included mean jitter, the percentage of jitter >55µs, the percentage of block and fiber density (FD). Grade scale of the Medical Research Council (MRC) in EDC was assessed simultaneously. The patients were divided into four groups according to the MRC scale (MRC > 4 Vs MRC ≤ 4) and different disease (ALS Vs other neurogenetic disorders). The parameters of SFEMG between different groups were compared.
Results: When the strength of EDC was normal (MRC > 4), the mean jitter was (66.1±20.1)µs in ALS and (38.0±9.2)µs in other neurogenic disorders, P50 of the percentage of jitter > 55µs was 55% in ALS and 0 in other neurogenic disorders, P50 of the percentage of block was 6.7% in ALS and 0 in other neurogenic disorders, There were significantly difference in those parameters of SFEMG between the two groups(p < 0.01). When the strength of EDC was abnormal (MRC ≤ 4), the mean jitter was (93.5±31.2)µs in ALS and (52.8±25.9)µs in other neurogenic disorders, P50 of the percentage of jitter > 55µs was 86% in ALS and 20% in other neurogenic disorders, P50 of the percentage of block was 20% in ALS and 0 in other neurogenic disorders, There were significantly difference in those parameters of SFEMG between the two groups (p < 0.01). When SFEMG was performed in EDC with normal muscle strength, the sensitivity and specificity of mean jitter > 55µs for diagnosis of ALS were 70.2% and 92.7%. FD was significantly different between ALS and other neurogenic disorders, but the sensitivity and specificity of FD > 2.0 for diagnosis of ALS were 87.2% and 31.7% respectively.
Conclusions: The mean jitter, the percentage of jitter > 55µs and block are of great importance in differentiating ALS from other neurogenic disorders in the early stage. When SFEMG is studied for early diagnosis of ALS, it is recommended to perform in muscles with normal strength. If jitter increases significantly with block and increased FD in muscles with normal strength, it supports the diagnosis of ALS. If mean jitter and/or FD are within normal limits, it is inconsistent with the diagnosis of ALS and should suggest the presence of other disease.
P135 COMPARISON OF MUNE AND CLINICAL MEASURES IN PATIENTS WITH ALS
NAITO Y, ASAHI M, KUZUHARA S
Mie University, Tsu, Mie, Japan
E-mail address for correspondence: [email protected]
Keywords: MUNE, ALSFRS, CMAP
Background: Motor unit number estimation (MUNE) has been developed to elucidate the pathophysiologic features of axonal loss in ALS. MUNE has been used as endpoint measures in clinical trials for drug studies in ALS. Multiple point stimulation MUNE has good test–retest reliability and can be used on any EMG machine. The advantage of MUNE must be compared to other more familiar metrics such as CMAP, muscle strength and ALSFRS-R.
Objectives: This study aims to evaluate the correlation between neurophysiological measures and clinical functional scales in patients with ALS.
Methods: The subjects of the study included 23 patients with ALS. CMAP and MUNE were recorded from the ADM by stimulating the ulnar nerve. The automated multiple point stimulation method was used for MUNE. MUNE was tested twice by two experienced examiners, and averaged data were adopted as the results. The grip power, ALSFRS and Norris scale were also measured simultaneously to assess the physical functions. In addition to the total scores of ALSFRS (ALSFRS-T) and Norris scale (Norris-T), we applied the sub-scores relating to the hand functions as ALSFRS-H and Norris-H. Both MUNE and CMAP data were compared with the grip power, ALSFRS and Norris scale. Spearman's rank-order correlation coefficient was used for statistical analysis of clinical scales.
Results: MUNE was well correlated with ALSFRS-H (p = 0.723), Norris-T (p = 0.654) and Norris-H (p = 0.846) significantly. The correlation of MUNE with ALSFRS-T (p = 0.350) was not significant. On the other hand, CMAP was correlated significantly with Norris-H (p = 0.812) and ALSFRS-H (p = 0.730). The correlation of CMAP between ALSFRS-T (p = 0.330), and Norris-T (p = 0.613) was not significant. The grip power had linear correlation with MUNE (r = 0.811) and CMAP (r = 0.817) significantly. In some cases at the early stage of ALS, MUNE showed some decline, although both ALSFRS and Norris score were nearly full marks.
Conclusion: MUNE and CMAP were well correlated with the physical functions equally. MUNE was more sensitive than those functional scales at the early stage or pre-clinical stage of ALS, but CMAP was also good as the endpoint measure in the advanced stage.
P136 CONTACT HEAT EVOKED POTENTIALS IN PATIENTS WITH ALS
XU Y, ZHENG J, FAN D, ZHANG J
Department of Neurology, Peking University Third Hospital, Beijing, China
E-mail address for correspondence: [email protected]
Keywords: pain pathway, contact heat evoked potentials
Objectives: Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease involving both upper and lower motor neurons while the sensory system is spared. The purpose of this study is to investigate the characteristics of contact heat evoked potentials (CHEP) in patients with amyotrophic lateral sclerosis (ALS) and evaluate the nociceptive pathway in these patients.
Methods: Sixty cases of definite ALS patients were diagnosed according to the criteria of El Escorial. All patients and sixty healthy controls had pain elicited by a CHEP stimulator with a diameter of 27mm (area 573 mm2) and an accelerated velocity of 70°C/s. Thermal stimuli were sent at 54.5 °C to three body sites: the dorsum of the hand, proximal volar forearm and C7. CHEP was recorded using a Keypoint.net (Medtronic, Skovlunde, Denmark) from midline electrodes (Cz and Pz positions of the standard 10–20 EEG montage. At same time, somaosensory evoked potential (SEP) was performed.
Results: The three mainly described pain evoked potential components were visible at 54.5°C which was a painful level to the subjects. These were Cz/N550, Cz/P750 and Pz/P1000. We measured the peak latency of the main negative components. The waveforms and latencies of CHEP in ALS patients were normal. The latencies were 561.2±28.6 ms at the dorsum of the hand, 540.1±39.2 ms at the proximal volar forearm and 512.7±31.4 ms at C7. There were no significant differences between the ALS patients and the healthy controls in CHEP (t = 4.23, 4.51, 3.74, p > 0.05) or SEP.
Conclusions: CHEP in patients with ALS is normal, which suggests that the nociceptive pathway is intact. This result supports the idea that ALS selectively involves the motor system and that sensory system disturbances are rare.
P137 MODELLING NEUROLOGICAL DECLINE IN ALS PATIENTS
RIDALL P1, PETTITT T2, MCCOMBE P3, HENDERSON R4
1Lancaster University, Lancaster, United Kingdom, 2Queensland University of Technology, Brisbane, Australia, 3Queensland Univesity, Brisbane, Australia, 4Royal Brisbane and Women's Hospital, Brisbane, Australia
E-mail address for correspondence: [email protected]
Keywords: MUNE, Markov death process, Monte Carlo Markov Chain (MCMC)
Background: In order to better understand the mechanisms whereby neurodegenerative diseases such as ALS advance, a number of models have been put forward to describe the declining numbers of surviving motor neurons. The simplest of these models is the'one hit model’. Here the neurons are assumed independent and subject to a fixed risk of a catastrophic biochemical event leading to an exponential decline in the number of surviving neurons.
Objectives: We present in this paper a methodology for evaluating the evidence in favour of the exponential model against a more general model in which the probability of death of a neuron is allowed to vary over the course of the disease.
Methodology: We use a two-stage procedure. The first stage involves the analysis of a surface electromyographical scan carried out on several occasions over a period of time in the course of the disease. The method of Ridall et al. (2006) is used to arrive at an estimate of the number of remaining motor units supplying a given muscle. The method makes use of reversible jump Markov chain Monte Carlo (RJMCMC)(Green 1995), a computationally intensive method in Bayesian inference. The second stage involves the analysis of the RJMCMC output using a hidden stochastic death process. Two models are compared. In the first, the rate parameter is assumed fixed (corresponding to exponential decline), whereas the second allows the rate parameter to evolve over time. The evidence in favour of each of these models is compared by using a Bayes factor.
Results: In eight of the ten ALS subjects studied, we found that the evidence favoured the one hit model, implying that the decline is exponential. For two of the patients the exponential model is inadequate and there is strong evidence suggesting that the rate of decline is not constant.
Discussion: For a majority of the patients studied the decline of surviving motor units can be taken to be exponential and the rate of onset of the disease can be summarised by a credible interval representing the half life of a typical neuron. Such an estimate can be obtained using a programmed electromyographical scan and using software available from the authors. For these patients we can make two conclusions. The first is that the probability of death of a unit does not seem to be related to the number of dying or dead motor units Second, the motor units in question appear to have a similar hazard of death. For two of the patients the exponential model appears inadequate to describe the decline, suggesting that the above conclusions cannot be made.
P138 ISOLATED CONTINUOUS RHYTHMIC LINGUAL MYOCLONUS: UNUSUAL PRESENTATION OF AMYOTROPHIC LATERAL SCLEROSIS
CIVARDI C, COLLINI A, MAZZINI L, TESTA L, MITTINO D, MONACO F, CANTELLO R
Department of Neurology. Università del Piemonte Orientale “A. Avogadro”, Novara, Italy
E-mail address for correspondence: [email protected]
Keywords: Lingual Myoclonus; Bulbar onset.
Introduction: Isolated myoclonus of the tongue is an exceptional entity, poorly documented and understood. Recently we observed a case of isolated continuous rhythmic lingual myoclonus as first symptom of amyotrophic lateral sclerosis (ALS).
Case Description: A 45-year-old woman suddenly manifested a continuous involuntary movement of tongue and dysarthric speech. Neurological examination revealed continuous, rhythmic bilateral symmetric jerks of the tongue that produced a narrowing of its anterior portion, with a slight forward protrusion and without lateral deviation. The movements were continuous, apparently rhythmic, when the tongue was protruded and when it was at rest. No other branchial muscles involvement was observed. At the onset no other neurological signs were manifested. EEG, BAEP SEPs and brain MR were normal. EMG recorded from the bilateral genioglossus muscle showed continuous, low-frequency (1–2 Hz), rhythmic bursts of bilaterally synchronous muscle activity. Six months later she developed a progressive bulbar and motor palsy typical of ALS.
Conclusions: To our knowledge this represents the first report of isolated continuous rhythmic lingual myoclonus as first sign of ALS. Imbalance of excitatory neurotransmission as reported at the pre-clinical phase of bulbar-ALS could explain this rare form of myoclonus.
P139 ALS AND TMS: TRAPEZIUS MUSCLE EVALUATION
COLLINI A, CIVARDI C, MAZZINI L, TESTA L, OGGIONI G, NASUELLI N, MONACO F, CANTELLO R
Department of Neurology. Università del Piemonte Orientale “A. Avogadro”, Novara, Italy
E-mail address for correspondence: [email protected]
Keywords: TMS, Central Motor Conduction Time, Trapezius muscle
Background: Transcranial magnetic stimulation(TMS) is a useful and safe method to test the corticospinal system integrity. In ALS the early detection of the upper motor neuron(UMN) involvement represents an important marker of the disease.
Objectives: We applied TMS in a sample of consecutive ALS.
Methods: We studied 38 ALS patients (23 males; 54±13 yrs; spinal onset, n= 28). Based on the El Escorial criteria we had 18 clinically definite, 17 clinically probable and 3 clinically possible. With a large round coil over the vertex we tested the bilateral trapezius, first dorsal interosseous(FDI) and tibialis anterior(TA) muscles. For all we determined the relaxed threshold, the total, peripheral and central motor conduction time(CMCT). We compared ALS data with a group of 25 normal controls.
Results: Average relaxed threshold was increased in the ALS group(54.0 + 13.5 vs 47.6 + 6.0; p = 0.01). In ALS patients the CMCT was prolonged: in 80% of the cases when based on trapezius recordings; in 66% of the cases when based on TA and in 48% of the cases when based on FDI recordings. Considering all muscles, the CMCT was impaired in 98% of patients. Considering trapezius and TA recordings, the pathological CMCT emerged in 92% of the cases. Although we had only 3 patients with clinically possible ALS, trapezius CMCTs were prolonged in all of them, while were normal for the FDI.
Conclusions: TMS evaluation of the trapezius muscle can represent a promising target of study. It can be expected to be able to distinguish ALS from cervical spondylotic myelopathy, and to detect the early involvement of UMN. The combined evaluation of trapezius and TA muscles appears to increase this probability
P140 ALS AND TMS: CENTRAL SILENT PERIOD
CIVARDI C, COLLINI A, MAZZINI L, TESTA L, OGGIONI G, NASUELLI N, MONACO F, CANTELLO R
Department of Neurology. Università del Piemonte Orientale “A. Avogadro”, Novara, Italy
E-mail address for correspondence: [email protected]
Keywords: TMS; Central silent Period
Background: Suppression of the volitional EMG activity due to a transcranial magnetic stimulus (TMS) is called central silent period (CSP). In amyotrophic lateral sclerosis (ALS) CSP was usually reported reduced in length.
Objectives: To study the CSP in a sample of consecutive ALS.
Methods: We studied 38 ALS patients (23 males; men age 54±13; spinal form = 28). Based on the El Escorial criteria we had 18 clinically definite; 17 clinically probable and 3 clinically possible. TMS was delivered with a large round coil over the vertex; intensity of stimulation was set = 1.5x relaxed threshold. Motor evoked potentials and CSP were recorded bilaterally from the first dorsal interosseous muscle (FDI) while patients performed their maximum effort. For each muscle we recorded at least eight trails. We correlated the CSP duration with clinical variables. We compared data of ALS patients with a group of 25 normal controls.
Results: In patients, the CSP duration was not different as compared with the controls(199.9 ms vs 185.8 ms), while the standard deviation was much higher(±69.7 ms vs ±20.5 ms). A cluster analysis defined three CSP homogeneous groups, termed “short CSP”, mean value = 135 ms, which was the most frequent(42.7%); “normal”(mean value 218 ms; 40.3%), and “long” (mean value 311 ms; 17%). The CSP length was significantly correlated to the Norris score(p = 0.025) and to the Babinski sign(p = 0.047), while did not correlate with the ALS duration.
Conclusions: In our patients, the CSP showed a heterogeneous pattern. The most frequent was represented by a “short” CSP, although “normal” and “long” durations were not so infrequent. CSP length was correlated with ALS clinical severity.
P141 EFFECT OF TRANSCRANIAL DIRECT CURRENT STIMULATION ON THE CORTICAL EXCITABILITY IN PATIENTS WITH ALS
MUNNEKE M, HENGEVELD Y, VAN ELSWIJK G, SIEBNER H, ZWARTS M, STEGEMAN D, SCHELHAAS J
Radboud University Nijmegen Medical Centre, Netherlands
E-mail address for correspondence: [email protected]
Keywords: cortical excitability, transcranial direct current stimulation, transcranial magnetic stimulation
Background: Although the exact aetiology of ALS is unclear, hyper excitability of cortical cells is accepted as a component of the neuronal degeneration in ALS. Cathodal transcranial direct current stimulation (tDCS) is a tool to reduce the cortical excitability. In patients with ALS only one study of tDCS is performed Citation[1]. They used a single protocol where anodal/cathodal tDCS was performed for 7 minutes in ALS patients and healthy controls. They were able to induce a consistent modification of cortical excitability in healthy subjects but not in patients with ALS.
Objectives: To investigate the differences in motor cortex excitability between patients with ALS and healthy controls. To investigate the effects of different tDCS stimulation durations on the motor cortex excitability in patients with ALS compared to healthy controls.
Methods: Cathodal tDCS stimulation in 3 random sessions (7, 11 and 15 minutes), was performed on both 10 healthy controls and 10 patients with ALS. The primary outcome measure was cortical excitability measured by transcranial magnetic stimulation as resting motor threshold (RMT), single-pulse motor evoked potentials (single MEP) at a stimulus intensity producing MEPs with mean amplitudes of 1mV at baseline, intracortical inhibition (ICI) and facilitation (ICF). For the evaluation of the impact of tDCS these TMS indices were measured: before tDCS (pre), 5 and 20 minutes after the tDCS (post 1 and 2).
Results: No significant differences were found in motor cortex excitability between patients with ALS and healthy controls, prior to the tDCS.
Healthy controls showed a significant inhibition of the single MEP amplitudes and an increased RMT after 15 min of tDCS. In the patients, as a group, there was no significant inhibition of the single MEP amplitudes and no significant increase of the RMT after 15 minutes of tDCS. However, of the 10 ALS patients, 6 showed a response of cortical inhibition that resembled those of the healthy controls. The paired pulse results showed an exaggerated, not significant ICF effect in healthy controls, in all sessions. The ICI and ICF were not affected in the ALS patients after tDCS. Repeated measures ANOVA on single MEP 1mV and RMT did reveal a main effect on time, not on group.
Discussion and Conclusion: tDCS is able to induce a duration dependent cortical inhibition in healthy controls. Intriguingly, tDCS induced an exaggerated ICF effect in these healthy subjects. In patients with ALS, the effect of tDCS on cortical inhibition shows much more variation between individuals. For that, we explored the causes of this difference in response to tDCS. Age and disease duration showed no relation with the response to tDCS.
P142 EVALUATION OF CHANGES OF UPPER MOTOR NEURON IN ALS WITH DTI AND TRANSCRANIAL MAGNETIC STIMULATION MOTOR EVOKED POTENTIALS
YAO X, LIANG Y, ZHANG Z, PEI Z, ZENG J
Department of Neurology, The First Affiliated Hospital, SUN Yat-sen University, Guangzhou, China
E-mail address for correspondence: [email protected]
Keywords: UMN, CMCT, FA
Background: Amyotrophic lateral sclerosis (ALS) is selectively characterized by lower motor neuron (LMN) signs of limb and bulbar muscles accompanying with upper motor neuron (UMN) signs. Subclinical LMN involvement is detectable by electromyographic findings of denervation. However, UMN involvement can be evaluated by physiologic and clinical measures without any objective diagnostic criteria.
Objective: To investigate the diffusion tensor imaging (DTI) measures and transcranial magnetic stimulation motor evoked potential (TMS-MEP) changes in ALS and their correlations with clinical features. To assess the value of DTI measures and TMS-MEP in the diagnosis UMN involvement in ALS.
Methods: 35 ALS patients complying with the revised El Escorial criteria and 30 age and sex matched healthy controls were enrolled in the study. We measured central motor conduction times (CMCT) for the bilateral abductor digiti minimi(ADM) and tibialis anterior (TA) muscles by TMS-MEP. At the same time, we investigated 11 patients with ALS from above and 10 healthy controls by DTI and measured fractional anisotropy (FA) within the corticospinal tracts and in the extramotor white matter. Clinical status of each patient was evaluated with the ALS Functional Rating Scale–Revised (ALSFRS-R) and UMN involvements were assessed by Ellis reflex scale.
Results: The abnormalities of the ALS patients measured by TMS-MEP were about 65%. The manifestations were prolonged CMCT and absent MEP, which increased significantly compared with controls. CMCT correlated significantly with Ellis scales and ALSFRS-R. There was a significant decrease of mean FA in all regions of the corticospinal tract in patients with ALS as compared with controls. FA along the corticospinal tract decreased significantly with higher UMN scores.
Conclusions: TMS-MEP could find UMN involvement in the ALS patients, but it is not sensitive for early diagnosis. The changes of CMCT correlated with the degree of UMN involvement. FA reflects functional abnormality of intracranial corticospinal tracts and can be used for objective evaluation of UMN involvement in ALS. Combining CMCT and FA may be a better index for early diagnosis UMN involvement in ALS patients.
P143 A 1H-MRS STUDY OF THE PRECENTRAL GYRUS IN ALS: CORRELATION WITH CLINICAL FINDINGS
WANG H, ZHANG J, FAN D
Department of Neurology, Peking University Third Hospital, Beijing, China
E-mail address for correspondence: [email protected]
Keywords: 1H-MRS, marker, precentral gyrus
Objectives: To explore the significance of 1H-MRS on studying amyotrophic lateral sclerosis (ALS), hoping to find surrogate markers useful for diagnosing ALS, for quantifying the degree of upper motor neuron (UMN) degeneration and for monitoring disease severity and activity.
Methods: Ninety healthy controls, 110 patients with ALS and 24 patients with lower motor neuron syndrome (LMNS) underwent structural MRI and single-voxel 1H-MRS. Measurements of the metabolic ratios NAA/Cr, Cho/Cr and NAA/Cho were compared and correlated with clinical assessments.
Results: The Pearson correlation coefficient was 0.823 for NAA/Cr and 0.712 for Cho/Cr. The 3 metabolic ratios in the precentral gyrus had great ranges in healthy adults, and had no lateral and sexual differences and correlated with aging (Pearson correlation coefficients were −0.220 for NAA/Cr, 0.240 for Cho/Cr and −0.464 for NAA/Cho). When compared with controls, NAA/Cr in total ALS patients and definite ALS patients decreased significantly; NAA/Cr in patients with probable and possible ALS and with LMNS did not change significantly, and Cho/Cr of total ALS patients increased significantly. NAA/Cr in patients with definite ALS was lower than those of patients with probable and possible ALS. No significant differences in metabolite ratios were found within probable ALS, possible ALS and LMNS patients, and the same between the patients with bulbar onset and limb onset between the sides with onset and no onset and between the patients with CST hyperintensity and not. NAA/Cr of patients with definite UMN signs was lower significantly than that of patients with probable UMN signs. We also found the NAA/Cr of corresponding precentral gyrus of more severe clinical manifest was lower statistically than that of the other side. Correlation analyses revealed the following: (1) the 3 metabolite ratios NAA/Cr, Cho/Cr and NAA/Cho all had no correlation with disease duration; (2) NAA/Cr and Cho/Cr were correlated with reflex score, while NAA/Cho were not; (3) NAA/Cr was correlated with ALS-FRS, APPEL total score and all sub-items of APPEL (Pearson correlation coeffetients differed from -0.251 to 0.457).
Conclusions: 1H-MRS was useful to study ALS. The marker NAA/Cr of precentral gyrus might reflect UMN degeneration degree, disease severity and disease progression of ALS patients, while it was not helpful to early diagnosis.
P144 NEUROCHEMICAL ABNORMALITIES IN THE PREFRONTAL CORTEX OF PATIENTS WITH ALS/MND
KALRA S1, CHOI C2, LYNCH M1, WENDY J1, FISHER N1, SERES P1, CAMICIOLI R1
1University of Alberta, Edmonton, Canada, 2University of Texas South Western Medical Center, Dallas, Texas, United States
E-mail address for correspondence: [email protected]
Keywords: magnetic resonance spectroscopy, cognitive impairment
Background: ALS/MND is a heterogeneous disorder and not a pure motor neuron disease. Nearly 50% of patients have some degree of cognitive impairment due to frontotemporal lobar degeneration. A better understanding of the biological basis of cognitive impairment would provide insight into varying pathogenic mechanisms associated with clinical subtypes. Magnetic resonance spectroscopy (MRS) permits in vivo of measurement of metabolites relevant to several aspects of cerebral degeneration, including neuronal and astrocytic density, and neurotransmitter metabolism.
Objectives: To study prefrontal cortex (PFC) neurochemistry and its association with cognitive impairment and disability in ALS.
Methods: High field MRS was performed in the PFC in patients with definite or probable ALS (El Escorial criteria) and controls. Sequences implementing double quantum filtration and spectrally selective refocusing were used to measure the neurotransmitters glutamate and gamma-aminobutyric acid (GABA) as well as their intermediary metabolite glutamine, the neuronal marker N-acetylaspartate (NAA), and the astrocytic marker myo-inositol. Subjects underwent cognitive and behavioural evaluations. Thirteen patients with ALS and 11 healthy controls have been studied to date.
Results: Comparing ALS to control subjects, myo-inositol was increased (6.04±0.9 vs 5.10±0.9, p = 0.03). A reduction in NAA approached statistical significance (9.13±1.6 vs 10.2±1.8, p = 0.09). Glutamate, glutamine, and GABA were unchanged. PFC neurochemicals did not correlate with cognitive measures. However, a correlation was found between glutamate and the ALSFRS-R (r = -0.66, p = 0.02).
Discussion and Conclusions: Cerebral neurochemical abnormalities exist beyond the motor cortex in ALS and correlate with disability. PFC neurochemistry profiling with MRS may provide a biomarker for global impairment in ALS.
P145 BRAIN ENDOPHENOTYPE OF BULBAR AND LIMB ONSET ALS IN DIFFUSION TENSOR IMAGING
PESCHEL T2,3, KAUFMANN J4, HEIL R2,3, BODAMMER N4, DENGLER R2,3, HEINZE HEINZ-JOCHEN4, GROSSKREUTZ J1
1Friedrich-Schiller University, Jena, Germany, 2Medical School Hannover, Hannover, Germany, 3Center for Systems Neuroscience, Hannover, Germany, 4Otto-von-Guericke University, Magdeburg, Germany
E-mail address for correspondence: [email protected]
Keywords: endophenotype, diffusion, diagnosis
Background: In ALS, recent MRI voxel based analyses have found widespread cortical atrophy, and white matter changes along the corticospinal tract (CST) and in frontal and transcallosal projections. It is as yet unclear whether extremity or bulbar onset ALS display different brain endophenotypes.
Objectives: To characterize diffusion alterations in bulbar and limb onset ALS patients brains by whole brain voxel based MRI analyses.
Methods: We examined 17 mildly affected (ALSFRS ∼40) ALS patients and 17 age-matched controls in a GE 1.5 T scanner. Diffusion tensor image sets were generated from 12 planes with eddy current correction. The apparent diffusion coefficient (ADC) and fractional anisotropy (FA) were analyzed in group comparisons and correlated to clinical parameters using SPM software.
Results: All ALS patients showed a significant reduction in FA along the corticospinal tract (CST) compared to controls. ADC images sets, however, were more sensitive in detecting these changes, and showed abnormal diffusion in the white matter extending into frontal regions. In extremity onset ALS only frontal white matter ADC abnormalities were found, whereas in bulbar ALS, the CST and adjacent areas were primarily affected.
Conclusions: This in-vivo neuropatholoy MRI study sheds light on the distribution pattern of diffusion abnormalities of different onset type ALS. It raises the question whether these subtypes are caused by specific degenerative processes.
P146 CORTICAL ACTIVATION IN ALS PATIENTS WITH/WITHOUT BULBAR SIGNS: AN FMRI-STUDY
KOLLEWE K1, KRAMPFL K1, SAMII A2, DENGLER R1, MÜNTE T3, MOHAMMADI B2
1Medical School Hannover, Hannover, Germany, 2International Neuroscience Institute Hannover, Hannover, Germany, 3Otto-von-Guericke-University, Magdeburg, Germany
E-mail address for correspondence: [email protected]
Keywords: fMRI, cortical activation, bulbar signs
Objective: Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disorder of the upper and lower motor neurons with a progressive limbic or bulbar muscular weakness and wasting. Survival of patients with bulbar onset is known to be shorter than of patients with lumbar onset. In this study we investigated the cortical activity during movements of tongue, eyes and extremities with fMRI.
Methods: We studied 18 patients with ALS and 20 healthy controls, using BOLD-fMRI, while they performed an acoustically paced motor task. fMRI data were analyzed with Brain Voyager QX.
Results: Task-related functional activations were identified in motor cortical regions in both patients and healthy controls. There were no differences between the two groups during horizontal eye movements. The movements of tongue in ALS patients caused less activation, especially in subcortical areas, in contrast to healthy controls. However, the motor activity of extremities showed increased cortical activation in the ALS group.
Conclusions: This data demonstrates a different activation mode in ALS patients in contrast to healthy controls. For the first time a different activity pattern between ALS patients and healthy controls during vertical tongue movements could be demonstrated.
P147 IRON DEPOSITS IN ALS AS EVALUATED BY MRI COMBINED WITH FREE RADICAL ASSESSMENT USING EPR PRELIMINARY DATA
STEVIC Z1, BACIC G2, IGNJATOVIC A2, STOSIC-OPINCAL T3, LAVRNIC S3, LAVRNIC D1
1Institute of Neurology, Medical School of Belgrade, 2Faculty of Physical Chemistry, University of Belgrade, 3Center of MRI, Clinical Center of Serbia, Belgrade, Serbia
E-mail address for correspondence: [email protected]
Keywords: amyotrophic lateral sclerosis, magnetic resonance imagining, EPR spectroscopy
Background: It has been suggested that iron-dependent MRI contrast in the brain may provide a new biomarker of the presence and progression of a variety neurodegenerative disorders such as Parkinson's and Alzheimer's disease. The results of the MRI studies were, in one way, different in ALS. Hypointesity of the precentral gray matter (PGGM) in T2W MRI was reported in ALS patients in several studies. Although it was presumed that PGGM were iron deposits, more elaborate MRI techniques are needed. There are not many data available about free radical production capacity of CSF, neither data about the possible role of iron oxidative stress in ALS.
Objectives: The aim of the study was to investigate the MRI sequence as a potential marker for iron and to establish the possible connection between PGGM on MRI in ALS patients and free radical production, by measuring free radical capacity of CSF using EPR spectroscopy.
Methods: Thirty five (24 female and 11 male) newly diagnosed SALS patients aged 56±9 (mean±SD.) (Range 39–74) years with probable or definite ALS according to El Escorial criteria were included in this study. Nine patients had a bulbar onset and 26 patients limb onset of the disease. The mean duration since onset of symptoms, was 14.2± 6.6 months. The ALSFRS-R was performed in all patients before MRI. We used a routine MRI protocol, including FLAIR, but we also added a thin slice T2*W gradient echo technique targeted for detection of iron deposits. The PGGM score was assessed for the presence of hypointensity (graded 0 -3). Samples of CSF represented remains of CSF obtained for routine medical purpose from 20 SALS patients. Control group comprised eleven age- and sex-matched controls. H2O2 was added to induce free radical production and samples were measured with the addition of DEMPRO spin trap using standard EPR spectrometer.
Results: The mean value of ALSFRS-R score was 35±9 points. We found a statistically significant correlation between ALSFRS score and MRI score (r = 0.69). The production of free radicals in the CSF was greatly enhanced in ALS patients reaching 4 times values in comparison to control patients. The correlation between EPR and MRI score was (r = 0.49).
Conclusion: The results of this study showed that the use of T2*W sequence was more efficient than either FLAIR or conventional T2W in detecting iron deposits in precentral gyruses due its sensitivity to iron induced susceptibility artifacts. EPR measurement of free radicals in CSF pointed out to increased total production of free radicals in CSF of ALS patients mostly like through Fenton reaction, which potentially links these findings to iron deposits found in the brain.
P148 MITOCHONDRIAL PERIPHERAL BENZODIAZEPINE RECEPTOR IN AMYOTROPHIC LATERAL SCLEROSIS
PIAZZA S1, CARLESI C1, CHELLI B2, GIACOMELLI C2, VOLPI L1, MANCUSO M1, MARTINI C2, SICILIANO G1
1Department of Neuroscience, Neurology, Pisa, 2Department of Pharmacology, Pisa, Italy
E-mail address for correspondence: [email protected]
Keywords: mitochondria, mitochondrial permeability transition pore, peripheral benzodiazepine receptor
Background: Amyotrophic Lateral Sclerosis (ALS) is a degenerative disease of unknown origin characterized by the progressive loss of motor neurons of the anterior horns in the cortex, bulb and spinal cord. Among the several pathogenetic mechanisms considered in the attempt to explain motor neuron death in ALS, the hypothesis of the occurrence of mitochondrial dysfunction has received considerable interest. Permeabilization of mitochondrial membranes, due to the opening of the mitochondrial permeability transition pore (MPTP), is considered an important step in the apoptotic or necrotic cell death cascade. MPTP is a multiprotein complex in which the peripheral benzodiazepine receptor (PBR) represents a core structural protein. PBR has been recently reported to play an important role in the regulation of MPT and in the control of apoptotic cell death.
Objectives: to evaluate the kinetic binding parameters of the specific PBR ligand, PK 11195, in platelets obtained from patients affected by ALS.
Methods: 16 ALS patients (mean 64.1±2.39 years) and 18 control healthy volunteers (mean, 40.3±3.06 years) were recruited for the study.
Platelets obtained from each ALS patient and healthy volunteer were centrifuged and stored at −80°C. Aliquots of platelet membrane suspensions were incubated with increasing concentrations of [3H] PK 11195, either in the absence (total binding) or in the presence (non-specific binding) of PK 11195. After incubation, the samples were filtered, washed and the radioactivity was counted, using a liquid-phase scintillation counter.
Results: The PBR kinetic binding parameters in platelet membranes from ALS and controls were saturable and with high affinity. Scatchard plots were linear for all analysed subjects, suggesting the presence of a homogeneous population of binding sites. A significant decrease in PBR Bmax values was observed in platelets of ALS patient as compared to controls (p = 0.002), whereas the Kd values did not differ significantly. The relationship between the reduction of platelet PBR Bmax and the disease progression showed a significant correlation (r = 0.62, p < 0.01).
Conclusion: The present data are consistent with an alteration of PBR density in ALS patients. This indicates a possible role of PBR in the pathogenesis of ALS and, at the same time, suggests a perspective use of it as candidate biomarker to trace disease severity and progression.
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