Responses of masseter muscles to transcranial magnetic stimulation in patients with amyotrophic lateral sclerosis

We recorded motor responses evoked by transcranial magnetic stimulation (TMS) in the masseter muscles of 30 patients with amyotrophic lateral sclerosis (ALS), 10 patients with cervical spondylotic myelopathy (CSM) and 22 age-matched normal controls. Responses to direct activation of the trigeminal motor root (R-MEPs) were normal both in ALS and CSM patients. Responses to activation of cortico-bulbar descending fibers (C-MEPs) were absent or delayed in 19 ALS patients (63.3%). Abnormalities of masseter C-MEPs were more frequent than abnormalities of limb MEPs and could be observed both in patients with (77.8%) and without (41.7%) clinical bulbar signs. Masseter C-MEPs were normal in all CSM patients. Recording masseter responses to TMS can reveal the frequent impairment of cortico-bulbar projections in ALS and can be useful in the differential diagnosis of spinal cord compression disorders mimicking ALS because of combination of upper and lower motor neuron signs.     

Transcranial magnetic stimulation in patients with cervical spondylotic myelopathy: Clinical and radiological correlations

Motor evoked potentials (MEPs) were studied in 28 patients with cervical spondylotic myelopathy. MEPs after cortical stimulation were abnormal in 27 patients, the responses in the leg muscles being affected the most often. Clinically asymptomatic motor lesions were detected in 7 patients (25%). The central motor conduction time (CMCT) for the abductor digiti minimi muscles correlated significantly with the clinical disability, whereas the radiological findings did not correlate with the clinical and neurophysiological parameters. In 9 patients MEPs were also recorded in the biceps muscles. The 7 patients with an abnormal CMCT for the biceps muscles had the most severe stenosis at the C-4–C-5 level or higher. The 2 patients with normal MEPs of the biceps muscles both had a stenosis at the C-5–C-6 level. The results of this study suggest that MEPs are useful for detecting spinal cord dysfunction and for localizing the level of the lesion. Some recommendations regarding the possible use of MEPs in the clinical evaluation of patients with cervical spondylotic myelopathy are given. © 1994 John Wiley & Sons, Inc.     

胸锁乳突肌肌电图在鉴别肌萎缩侧索硬化与颈椎病性脊髓病的研究

对106例肌萎缩侧索硬化(ALS)与颈椎病性脊髓病(CSM),及两病鉴别困难者进行胸锁乳突肌、肢体肌及舌肌EMG检查。结果ALS组胸锁乳突肌神经源性损害的异常率高于三肢体肌、舌肌;CSM组胸锁乳突肌无1例异常。表明该肌神经源性损害能明显提高ALS亚临床的阳性率,有助于ALS的早期诊断及ALS与CSM两病的鉴别。     

Somatosensory evoked potentials after multisegmental upper limb stimulation in diagnosis of cervical spondylotic myelopathy.

Radial, median, and ulnar nerve somatosensory evoked potentials (SEPs) were recorded, with non-cephalic reference montage, in 38 patients with clinical signs of cervical myelopathy and MRI evidence of spondylotic compression of the cervical cord. Upper limb SEPs are useful in spondylotic myelopathy because SEPs were abnormal in all patients for at least one of the stimulated nerves and SEP abnormalities were bilateral in all patients but one. Reduction of the amplitude of the N13 potential indicating a segmental dysfunction of the cervical cord was the most frequent abnormality; it occurred in 93.4%, 84.2%, and 64.5% of radial, median, and ulnar nerve SEPs respectively. A second finding was that the P14 far-field potential was more sensitive than the cortical N20 potential to slowing of conduction in the dorsal column fibres. The high percentage of N13 abnormalities in the radial and median rather than in the ulnar nerve SEPs correlated well with the radiological compression level, mainly involving the C5-C6 vertebral segments. Therefore the recording of the N13 response is a reliable diagnostic tool in patients with cervical spondylotic myelopathy and P14 abnormalities, though less frequent, can be useful in assessing subclinical dorsal column dysfunction.     

Abnormal excitability of the corticospinal pathway in patients with amyotrophic lateral sclerosis: a single motor unit study using transcranial magnetic stimulation

The pathophysiology of corticospinal tract degeneration in amyotrophic lateral sclerosis (ALS) was investigated by studying the effect of transcranial magnetic stimulation on discharge characteristics of single motor units during voluntary activation. The motor units were recorded from the first dorsal interosseus muscles of 12 patients with ALS, 14 healthy subjects, 12 patients with upper motor neuron lesions and 9 with pure lower motor neuron diseases. More than 100 magnetic stimuli were delivered over the scalp during minimal muscle contraction. The occurrence of motor unit discharges was plotted in a peristimulus time histogram. An increase in discharge probability at latencies of 20–30 msec, that represents monosynaptic activation (primary peak) was found in normal units. Motor units from ALS patients with short disease durations had significantly increased discharge probabilities in the primary peak (P < 0.01). Motor units from 4 ALS patients with upper motor neuron signs showed double primary peaks: an initial synchronized peak followed by a dispersed peak. The latter was ascribed to a slow corticospinal pathway, which remains undetected or is functionally insignificant in healthy subjects. We conclude that the excitabilities of the surviving corticospinal tract pathways are abnormally increased in ALS, especially in the early stage.     

Progressive upper limb monoparesis: a form of primary lateral sclerosis? Two cases with metabolic brain imaging and transcranial magnetic stimulation

Two patients presenting an isolated, slowly-progressive clumsiness affecting one upper limb are described. Clinical evidence, regional cerebral blood flow and transcranial magnetic motor stimulation suggested that this condition resulted from a selective unilateral degeneration of the corticospinal tract. Such progressive hemiparesis may possibly be considered as a rare form of primary lateral sclerosis.     

Impaired sensorimotor integration in cervical dystonia: a study using transcranial magnetic stimulation and muscle vibration.

The authors studied the effects of sensorimotor integration (corticocortical inhibition and facilitation during muscle vibration [MV]) in dystonic patients. Eleven patients with cervical dystonia and 11 age-matched healthy control subjects were enrolled in the study. They were examined using transcranial magnetic stimulation (TMS) and tonic proprioceptive input (MV). Paired-pulse transcranial magnetic stimulation was done at interstimulus intervals of 3 msec (intracortical inhibition) and 13 msec, the intensity of the conditioning stimulus was 70% of the motor threshold, and the test stimulus was 120%. Motor evoked potentials were recorded from the vibrated extensor carpi radialis muscle and its antagonist, the flexor carpi radialis. Duration of MV trains (80 Hz; amplitude, 0.5 mm) was 4 seconds. The authors found differences between patients and healthy control subjects during MV only. Intracortical inhibition was pronounced significantly only in control subjects, whereas intracortical facilitation was significant in patients only (P < 0.05). Furthermore, the significant reduction of motor evoked potentials at 13-msec interstimulus intervals, which can be found in healthy subjects frequently, was observed in one dystonia patient only. The results of the current study suggest that sensorimotor integration is impaired in cervical dystonia, probably by an altered control of proprioceptive (vibratory) input.     

Amyotrophic lateral sclerosis with ophthalmoplegia. A clinicopathologic study.

Ophthalmoplegia is rarely observed in patients with amyotrophic lateral sclerosis (ALS). We describe a patient with ALS in whom ophthalmoplegia, initially appearing midway in her course, progressed to total paralysis of extraocular movements by the time of death. In addition to the usual postmortem findings of ALS in the brain stem and spinal cord, there was extensive neuronal loss and gliosis involving the caudal portions of the dorsal and intermediate components of the oculomotor nuclei, the caudal part of the trochlear nuclei, and the abducens nuclei. This represents the first detailed report of the findings in the nuclei of cranial nerves III, IV, and VI in a patient with ALS and ophthalmoplegia.     

Amyotrophic lateral sclerosis mimic syndromes: a population-based study

BACKGROUND: The Irish ALS Register is a population-based register of the epidemiological characteristics of amyotrophic lateral sclerosis (ALS) in the republic of Ireland. OBJECTIVE: To describe the clinical and demographic details of those patients included in the Irish ALS Register who were incorrectly diagnosed as having ALS (patients who were ultimately rediagnosed as having an "ALS mimic syndrome"). METHODS: The medical records of each patient referred to the register are routinely reviewed and, where possible, patients are examined by our group during their illness. RESULTS: Between January 1, 1993, and December 31, 1997, 32 patients (representing 7.3% of 437 referrals) were rediagnosed as having a condition other than ALS. The median age at onset for these 32 patients was 56.0 years (range, 19.5-85.8 years) for men and 53.5 years (range, 39.5-70.4 years) for women. Twenty-nine patients (91%) presented with symptoms referable to the limbs, and the remainder presented with symptoms involving the bulbar musculature. Multifocal motor neuropathy was the most common condition mistaken for ALS, accounting for 7 cases (22%), followed closely by Kennedy disease (4 cases [13%]). Factors leading to diagnostic revision included evolution of atypical symptoms, results of specific investigations, and failure of symptoms to progress. Twenty-seven (84%) of the patients with an ALS mimic syndrome fulfilled the El Escorial criteria for either "suspected" or "possible" ALS, 4 (13%) met the criteria for probable ALS, and 1 (3%) had definite ALS. CONCLUSIONS: The application of the El Escorial diagnostic criteria may facilitate early recognition of non-ALS cases. Misdiagnosis of ALS remains a common clinical problem despite the increased availability of investigations and a greater awareness among neurologists of potential diagnostic pitfalls.     

Investigation of paroxysmal dystonia in a patient with multiple sclerosis: a transcranial magnetic stimulation study.

OBJECTIVE: To study the pathogenesis of paroxysmal dystonia affecting the right body side in a patient with a demyelinating lesion in the descending motor pathways, also involving the basal ganglia. METHODS: Single-pulse transcranial magnetic stimulation (TMS) was applied to study motor evoked potentials (MEPs) and the following silent periods (SPs) in the first dorsal interosseous muscle (FDI) of both sides and in the right extensor carpi radialis muscle (ECR) during voluntary contractions performed outside the dystonic attacks. During the dystonic paroxysms, single-pulse TMS was used to investigate the time course of MEPs and SPs in both FDI and ECR of the right side. Furthermore, paired-pulse TMS was applied at rest to investigate short-interval intracortical inhibition (SICI) and intracortical facilitation (ICF) in both FDI muscles. RESULTS: At rest SICI and ICF were normal in both motor cortices. During voluntary contraction the MEP was smaller and the SP was longer in the affected FDI than in the contralateral. During the paroxysms, the MEPs and SPs were suppressed in comparison with the responses elicited during voluntary contraction. CONCLUSIONS: These results fit well with the theory of ephaptic excitement of corticospinal axons for the pathogenesis of paroxysmal dystonia due to a demyelinating lesion. SIGNIFICANCE: Identification of the mechanisms underlying paroxysmal dystonia in demyelinating disorders extends our knowledge on the pathophysiology of dystonia.     

The contribution of magnetic stimulation of the motor cortex to the diagnosis of cervical spondylotic myelopathy. Correlation of central motor conduction to distal and proximal upper limb muscles with clinical and MRI findings.

Magnetic stimulation of the motor cortex and cervical spine was performed on 24 patients with cervical spondylotic myelopathy documented by MRI. Compound motor action potentials (CMAPs) were recorded from the biceps and thenar muscles to study the central motor pathways of two different myotomes, C5-C6 and C8-D1. Central motor conduction was abnormal in all 24 patients for thenar muscles and in 5 patients for biceps brachii. In patients with a single compression level, central motor conduction abnormalities were confined to the myotomes caudal to the site of compression documented by MRI, in both proximal and distal upper limb muscles in the patients with upper spondylotic compression, and in distal muscles only in the patients with lower compression. In the patients with multilevel compression, central motor conduction time was abnormal for thenar muscles and always normal for the biceps muscle, but its mean value was significantly greater than in the control subjects, suggesting a slight involvement of central motor pathways for proximal upper limb muscles and major damage of the lower cervical segments. Owing to their high degree of sensitivity, central motor conduction studies may be of considerable value in the functional assessment of central motor pathways in cervical spondylotic myelopathy.     

脊髓型颈椎病病人经颅磁电刺激运动诱发电位的对比研究

目的探讨磁电刺激运动诱发电位（ＭＥＰ）在脊髓型颈椎病（ＣＳＭ）的应用价值，并对其临床相关性进行分析。方法采用经颅磁、电刺激对３０例脊髓型颈椎病病人以及年龄性别等相配匹的３０名健康成人分别于外展小指肌、肱二头肌及下肢展短肌表面进行ＭＥＰ的检测。结果全部病人的ＭＥＰ都出现异常，表现为潜伏期、中枢传导时间（ＣＭＣＴ）延长，时限增宽，波辐降低或不能引出。磁刺激ＭＥＰ的ＣＭＣＴ和皮层刺激潜伏期与脊髓型颈椎病临床日本整形外科协会（ＪＯＡ）评分间有密切相关性，能较好地反映ＣＳＭ病人的病情。结论ＭＥＰ在检测ＣＳＭ病人运动功能方面具有定量评价作用。与电刺激相比，磁刺激ＭＥＰ能更好地反映ＣＳＭ病人的病情。     

Amyotrophic lateral sclerosis with marked neurological asymmetry: clinicopathological study

We attempted to correlate the marked neurological asymmetry observed in two amyotrophic lateral sclerosis patients with their histopathological lesions. Patient 1, a 52-year-old man, developed dysarthria and dysphagia, followed by muscle weakness in the left arm and then of the left leg. Patient 2, a 44-year-old man, developed muscle weakness in the left hand, left leg, tongue with left-sided predominance, right hand and right leg in that order of progression. Both patients exhibited moderate to marked left-sided predominant involvement of the lower motor neuron system, accompanied by retained or hyperactive deep tendon reflexes on the left side in the early stage of their illness. Most of the asymmetry in the lower motor neuron system involvement persisted until the death of the patients. Histopathological examinations, including semiquantitative analysis, revealed that both patients exhibited left-sided predominant degeneration of the lower motor neuron system at those spinal cord levels where the neurological asymmetry was of a moderate to marked degree. In addition left-sided predominant degeneration of the lateral corticospinal tracts was seen in both patients and right-sided predominant involvement of Betz cells in the leg area of the motor cortex of patient 1. This pattern of both the neurological and histopathological asymmetry suggested the probable existence of an intimate somatotopically related linkage between the upper motor neuron system degeneration and lower motor neuron system degeneration in both patients.     

Amyotrophic lateral sclerosis and sports: a case–control study

An increased incidence of amyotrophic lateral sclerosis (ALS) amongst soccer players in Italy has recently been reported. A case-control study (300 cases and 300 matched controls) was conducted to explore the association between ALS and physical/sports activities, with specific reference to trauma-related risk. Neither the practice of competitive sports nor sports-related traumas were found to be associated with an increased risk of ALS. The practice of physical activities or sports is not per se a risk factor for ALS. Our results exclude sports-related microtraumas as etiopathogenic factors in the natural history of ALS.     

Cervical spondylotic myelopathy: a cooperative study.

A series of 521 cases of CSM in 22 clinics in Spain and Portugal were studied. The severity of the clinical picture, both before and after the operations, was graded following a six point scale (a modification of Nurick's). The operations the patients underwent were classified into eight types and their results expressed by using the same scale. Some improvement has been attained in all grades of myelopathy with all types of operations, but better results, especially in advanced cases, have been obtained when surgical fixation of the spine, as well as laminectomy, has been carried out.     

Motor cortex excitability and fatigue in multiple sclerosis: a transcranial magnetic stimulation study

We investigated electrophysiological correlates of fatigue in patients with multiple sclerosis (MS). Transcranial magnetic stimulation (TMS) was used to explore motor excitability in three groups of subjects: MS patients with fatigue (MS-F), MS patients without fatigue (MS-NF) and healthy control subjects. All participants had to perform a fatiguing hand-grip exercise. TMS was performed prior to and after the exercise. Prior to the motor task, MS-F patients had less inhibition in the primary motor cortex compared to both other groups. Postexercise, intracortical inhibition was still reduced in the MS-F patients compared to the MS-NF patients. In MS-F patients the postexercise time interval for normalization of the motor threshold was correlated with the fatigue severity. We conclude that MS patients with fatigue have an impairment of inhibitory circuits in their primary motor cortex. The results also indicate that fatigue severity is associated with an exercise-induced reduction of membrane excitability.     

Motor-evoked potentials from multiple target muscles in multiple sclerosis and cervical myelopathy

Motor-evoked potentials (MEP) from abductor digiti minimi (ADM), biceps brachii (BB) and tibialis anterior (TA) muscle were analysed in 101 patients with multiple sclerosis (MS) and in 72 patients with compressive cervical myelopathy (CM). In definite MS the results were abnormal in 82% and in probable or possible MS in 64% of patients. In CM results were abnormal in 56% when the compression site was at the C4/C5 interspace or higher (CM_C1-C4-), and in 100% when the compression fell between the C5 and C7 level (CM_C5-C7). The pattern of normal responses from BB with abnormal responses from ADM was found in 37% of patients with CM_C5-C7, in 10% of patients with MS (p = 0.01) and in 19% of patients with CM_C1-C4+. Abnormal MEP from both ADM and BB were significantly more frequent in MS than in CM (p = 0.002). Although “specific patterns” of MEP abnormality could be significantly correlated with patient groups and anatomical compression sites, they cannot be taken as a reliable diagnostic clue in the individual case. In particular, abnormal responses from BB were frequently also found in CM_C5-C7. These discrepancies cannot be explained on the basis of a localized mechanical mechanism and raise the question of the pathogenesis in CM.