C54 NEUROPHYSIOLOGICAL TESTING: STEPS TOWARDS EARLIER DIAGNOSIS
BURKE D1,2
1University of Sydney, Sydney, Australia, 2Royal Prince Albert Hospital, Sydney, Australia
Email address for correspondence: [email protected]
Keywords: EMG, spinal reflex hyperexcitability, cortical involvement
A focus on diagnostic methods for MND has assumed greater importance as attention has shifted to the need for early diagnosis so that therapies have a chance to arrest disease progress before the degenerative process has become too advanced. Traditionally neurophysiological testing has been used to confirm clinically detectable abnormalities and to exclude alternative diagnoses, but in the current era they are of greatest value when they reveal abnormalities that are not apparent clinically. The “Awaji” criteria assign importance to EMG abnormalities, and represent a major advance because subsequent studies have shown that their use leads to earlier detection or identification of MND/ALS. A minor complication is that upper motor neurone (UMN) lesions such as stroke are associated with lower motor neuron (LMN) abnormalities, but this can be readily recognised and excluded. The Awaji criteria focus on the LMN. Degeneration of the upper motor neuron may be as or more important in many patients with MND syndromes. Three approaches can be used to identify UMN dysfunction: the first involves the demonstration that the spinal reflex arc is intact, perhaps even hyperactive, in a patient with LMN abnormalities involving the test muscle. Here the H reflex can be recorded in normal subjects from most limb muscles during a voluntary contraction of that muscle. Its presence indicates an intact reflex arc, and its presence in certain muscles at rest (for example, tibialis anterior and thenar muscles) indicates that there is hyperreflexia. The second approach involves demonstrating that reflex activation of a paretic muscle is greater than can be achieved in a maximal voluntary contraction of that muscle, again for a muscle that has EMG evidence of LMN abnormalities. For example, with a paretic tibialis anterior greater activation of tibialis anterior by noxious mechanical stimulation of the sole of the foot or in the H reflex than can be achieved voluntarily indicates a loss of the descending voluntary drive on the spinal motor neuron pool. The third approach involves demonstrating cortical hyperexcitability using transcranial magnetic stimulation (specifically, decreased “short-interval intracortical inhibition” in a paired-pulse paradigm). This testing can reveal abnormalities that precede the development of symptoms and signs in patients with familial ALS and, on the other hand, the absence of such abnormalities in Motor Neuron Diseases without corticospinal involvement (such as Kennedy's disease).
C55 CORTICAL HYPEREXCITABILITY APPEARS INTRINSIC TO ALS
VUCIC S1,2, CHEAH B2, KIERNAN M2
1Sydney Medical School Westmead, University of Sydney, Sydney, NSW, Australia, 2Neuroscience Reserach Australia, University of New South Wales, Sydney, NSW, Australia
Email address for correspondence: [email protected]
Keywords: cortical hyperexcitability, cortical plasticity, neurodegeneration
Background: The pathophysiological mechanisms underlying the development of amyotrophic lateral sclerosis (ALS) remain to be fully elucidated. Cortical hyperexcitability appears to be an important mechanism given that cortical hyperexcitability appears to be an early feature of sporadic ALS, linked to peripheral neurodegeneration, and that it precedes the development of familial ALS. It has been argued, however, that these changes in cortical excitability represent plasticity of the motor cortex in response to peripheral neurodegeneration.
Objective: Consequently, the aim of the present study was to determine whether cortical hyperexcitability is intrinsic process to ALS, or whether it simply represents cortical plastic changes.
Methods: Utilising the paired-pulse threshold tracking transcranial magnetic stimulation (TTTMS) technique, cortical excitability was prospectively assessed in a cohort of 156 consecutive patients with neuromuscular symptoms (104 ALS and 52 lower motor neuron syndrome, non-ALS syndrome, NALS). Results were compared to 62 healthy controls. The motor cortex was assessed using a 90 mm circular coil, with the motor evoked potential recorded over the abductor pollicis brevis (APB).
Results: The CMAP amplitude (ALS 5.6 ± 0.4 mV; NALS 7.8 ± 0.4 mV; controls 10.2 ± 0.4 mV, P < 0.0001) and neurophysiological index (ALS 0.6 ± 0.1; NALS 1.4 ± 0.1; controls 2.5 ± 0.1, P < 0.0001) were significantly reduced in ALS and NALS syndrome patients when compared to controls, indicating a comparable degree of peripheral disease burden in ALS and NALS syndrome patients. Cortical excitability studies disclosed a significant reduction in short interval intracortical inhibition (SICI) in ALS patients (2.4 ± 0.9%) when compared to NALS syndrome patients (8.7 ± 0.8%) and healthy controls (10.6 ± 0.8%, F = 23.3, P < 0.0001). Sub-group analysis revealed that although SICI reduction was a uniform finding in ALS, it was greater in ALS patients with less severe disease (SICI ALS CMAP > 4.5 mV 0.1 ± 1.3%; ALS CMAP < 4.5 mV 3.7 ± 1.5%, P < 0.05), thereby reaffirming that SICI reduction occurs as an early feature in ALS. In addition, intracortical facilitation (ALS -2.2 ± 0.7%; NALS -0.6 ± 0.6%; controls -0.4 ± 0.8%, P < 0.05) and MEP amplitude (ALS 38.5 ± 2.7%; NALS 30.9 ± 2.6%; controls 24.9 ± 1.8%, F = 9.6, P < 0.0001) were significantly increased in ALS patients when compared to NALS syndrome patients and controls. Of further relevance, cortical silent period duration was reduced in ALS (180.9 ± 4.4 ms) when compared to NALS syndrome patients (210.0 ± 4.0 ms) and controls (210.3 ± 3.3 ms, F = 12.7, P < 0.0001).
Discussion and conclusions: The findings in the present study would seem to indicate that cortical hyperexcitability is a process intrinsic to ALS, clearly distinguishing ALS from the mimic disorders. In addition to suggesting that the threshold tracking TMS technique may prove useful as a diagnostic investigation for ALS, the present study would seem to argue against the notion that changes in cortical excitability simply represent cortical plasticity in ALS.
C56 MOTOR UNIT RECRUITMENT IN ALS AND OTHER UMN LESIONS
DE CARVALHO M1,2, TURKMAN A1,3, SWASH M1,4
1Neuromuscular Unit, Instituto de Medicina Molecular, Institute of Physiology, Faculty of Medicine, Lisbon, Portugal, 2Department of Neurosciences, Hospital de Santa Maria, Lisbon, Portugal, 3Centro de Estatística e Aplicações, Faculty of Sciences, University of Lisbon, Lisbon, Portugal, 4Departments of Neurology and Neuroscience, Royal London Hospital, Queen Mary University of London, London, UK
Email address for correspondence: [email protected]
Keywords: lower motor neuron, motor unit recruitment
Introduction: Motor unit potential (MUP) recruitment order and firing rate on volition depend on several different physiological factors, involving lower motor neuron (LMN) and upper motor neuron (UMN) interactions. The Henneman principle dictates early recruitment of type I motor units, but recruitment order is not studied during routine MUP analysis. Frequency variation among different MUPs is observed in routine EMG investigation.
Methods: We investigated potential MUP recruitment order and inter-MUP recruitment rate variation (coefficient of variation; CV) in controls and patients affected by different LMN and UMN disorders. Tibialis anterior muscle with preserved strength (normal walk on heels) was the only muscle investigated. We included 42 controls, 37 patients with ALS, 14 with progressive muscle atrophy (PMA), 37 with polyneuropathy, 23 with primary lateral sclerosis (PLS), and 14 with other thoracic/cervical spinal cord lesions (UMN lesion). MUPs were analysed as recorded from a minimum of 60 seconds steady, unquantified, mild muscular contraction, which usually activated 2 to 5 motor units. The same MUP was observed in at least 10 consecutive firings before analysis. Amplitude, area and duration of each MUP, order of recruitment and firing rate were assessed.
Results: In PMA, ALS and neuropathy larger MUP amplitudes, areas and durations were recorded, as expected, compared with the other groups. Correlation analysis did not reveal any specific abnormality of recruitment order in the different patient groups. The coefficient of variation for recruitment rate, applying the Bennett approach, as modified by Shafner and Sullivan, showed that no significant difference between subjects for PLS UMN lesion, but the other groups showed heterogeneity among individual subjects. However, the mean firing rate was similar in the different groups.
Discussion: Our data confirms reduced variation in MUP recruitment with UMN lesion. The limits of this abnormality need further evaluation, but we suggest that MUP recruitment could be useful as a tool to identify functional UMN impairment in the assessment of patients with ALS.
C57 MOTOR UNIT NUMBER INDEX (MUNIX) VERSUS MOTOR UNIT NUMBER ESTIMATION (MUNE): A DIRECT COMPARISON IN A LONGITUDINAL STUDY OF ALS PATIENTS
BOEKESTEIN WA1 ,2, MUNNEKE MAM1, SCHELHAAS HJ1, STEGEMAN DF1, ZWARTS MJ1, VAN DIJK JP1
1Donders Institute for Brain, Cognition and Behavior, Radboud University Nijmegen Medical Centre, Department of Neurology/Clinical Neurophysiology, Nijmegen, The Netherlands, 2Medical Spectrum Twente, Department of Neurology, Enschede, The Netherlands
Email address for correspondence: [email protected]
Keywords: motor unit number index, motor unit number estimation
Background: Motor unit number index (MUNIX) is a surface EMG method that provides an index for the number of motor units and for motor unit size. MUNIX has a theoretical advantage over measuring the CMAP as MUNIX is not masked by reinnervation and it has the advantage over other motor unit number estimation (MUNE) methods as it is easier and quicker to perform. However, as MUNIX is an index and a gold standard is lacking, it is unknown how it is related to the actual number of motor units.
Objectives: To evaluate how MUNIX is related to the number of motor units as estimated by high-density surface EMG MUNE (HD-MUNE) and to determine the potential of MUNIX for monitoring disease progression in patients with ALS.
Methods: Both MUNIX and HD-MUNE of the thenar muscles were determined in 18 ALS patients and 24 healthy controls. Patients were measured at baseline, within two weeks (to assess reproducibility), and after 4 and 8 months. ALSFRS was scored and muscle strength tests were performed.
Results: HD-MUNE showed a slightly better reproducibility than MUNIX. There was a significant relation between MUNE and MUNIX in ALS patients but not in healthy controls. At baseline, MUNIX and MUNE were significantly lower in ALS patients than in healthy controls. Longitudinally, after 8 months, both MUNE and MUNIX of the ALS patients decreased significantly more as compared to MRC, ALSFRS and CMAP. There was no significant difference between the decline in MUNIX and HD-MUNE after 4 and 8 months.
Discussion and conclusion: In patients, MUNIX is related to the number of motor units as estimated by HD-MUNE and can be used to monitor disease progression in ALS. As MUNIX is much easier to perform as compared to HD-MUNE a multi-muscle approach seems feasible and can potentially further increase the sensitivity of the technique.
C58 RELATIONSHIP BETWEEN CLINICO-ELECTROPHYSIOLOGICAL DYSFUNCTION AND CERVICAL CORD 1H-MAGNETIC RESONANCE SPECTROSCOPY IN AMYOTROPHIC LATERAL SCLEROSIS
IKEDA K, YOSHII Y, MURATA K, NAGATA R, HIRAYAMA T, KANO O, KAWABE K, IWASAKI Y
Toho University Omori Medical Center, Tokyo, Japan
Email address for correspondence: [email protected]
Keywords: spinal cord magnetic resonance spectroscopy, clinico-electrophysiology, progression marker
Background: Amyotrophic lateral sclerosis (ALS) is a fatal disease characterized by upper and lower motor neuron degeneration. Previous studies of brain 1H-magnetic resonance spectroscopy (MRS) revealed neuronal and axonal damage of the motor cortex, the corticospinal tract and the extra-motor cortex in ALS patients. Little is known about spinal cord 1H-MRS in ALS patients.
Objectives: The present study aimed to examine whether neurological dysfunction and electrophysiological findings are related to metabolic changes on spinal cord 1H-MRS in ALS patients.
Methods: Fifteen patients (8 men and 7 women) with definite or probable ALS fulfilled the El Escorial revised criteria, and 15 age-matched control subjects (8 men and 7 women) underwent cervical cord 1H-MRS. A volume of interest with three dimensions of approximately 6.0 × 8.0 × 40.0 mm (19.2 mL) was located along the main axis of the 1st to the 3rd segment of the cervical (C1-3) cord on T2-weighted images. Four signal amplitudes of N-acetyl-aspartate (NAA), choline-containing compounds (Cho), creatine plus phosphocreatine (Cr) and myo-Inositol (m-Ins) were measured. ALS functional rating scale (FRS) and forced vital capacity (FVC) were assessed every month. Electromyography was performed at the same period of C1-3 cord 1H-MRS.
Results: NAA/Cr was decreased significantly (p < 0.05) and m-Ins/Cr was increased significantly (p < 0.05) in ALS patients compared to control subjects. NAA/m-Ins was correlated inversely with decline rates of monthly FRS and FVC. NAA/m-Ins was also linked inversely to electromyographic profiles of the motor nerve degeneration, including ongoing denervation and reduced amplitudes of compound muscle action potential in the upper limb muscles. NAA/Cr and m-Ins/Cr were preserved in two patients who had severe degree of bulbar palsy and mild degree of weakness and atrophy in the four limb muscles.
Discussion and conclusions: Neuronal degeneration, axonal loss and demyelination occur in ALS patients, leading to changes of several metabolites. Only one recent study of cervical cord 1H-MRS has suggested reduction of NAA/Cr and NAA/m-Ins in ALS patients at 40% and 38%, respectively. NAA/m-Ins and NAA/Cho are linked to FVC. No significant relationship existed between those ratios and FRS (1). The present study indicated a significant decrease of NAA/Cr and a significant increase of m-Ins/Cr in ALS patients compared to controls. The inverse relationship was found between the NAA/m-Ins, FRS, FVC, and axonal damage in the upper limb muscles on electromyography. Otherwise, cervical cord 1H-MRS did not reflect damage of the bulbar neurons. Thus, cervical cord 1H-MRS could have benefits as a predictive marker for progression of limb and respiratory motor dysfunction in ALS patients. Further serial studies of cervical cord 1H-MRS are needed to elucidate how the metabolic changes are associated with clinico-electrophysiological deterioration in ALS patients.
Reference
- Carew JD, Nair G, Pineda Alnoso N, et al. Amyotrophic Lateral Sclerosis, 2011;May 12(3):185–91.