Optimizing electrical impedance myography of the tongue in amyotrophic lateral sclerosis

Introduction: Electrical impedance myography (EIM) can quantify muscle health at a range of frequencies, including that most commonly employed, 50 kHz . However, disease‐related changes in EIM data suggest the distinction between normal and patient EIM values could be more apparent at frequencies of >50 kHz . We investigated at what other selected frequencies tongue EIM may differentiate healthy individuals and amyotrophic lateral sclerosis (ALS) patients, remain reliable, and correlate with a standard metric of bulbar function. Methods: Tongue EIM phase data from 30 volunteers and 11 ALS patients were analyzed at 6 discrete frequencies from 50 to 500 kHz . Results: Of the frequencies assessed, EIM demonstrated maximal separation and reliability at 100 kHz , where phase value was also significantly correlated with the bulbar subscore on the revised version of the ALS Functional Rating Scale. Conclusions: One hundred kilohertz could serve as an optimal frequency at which to measure EIM phase values of the tongue in ALS. Muscle Nerve 55 : 539–543, 2017     

Needle electromyography of the frontalis muscle in patients with amyotrophic lateral sclerosis

Introduction: We sought to determine which muscles to choose for better assessment of the craniobulbar region in establishing the diagnosis of amyotrophic lateral sclerosis (ALS). Methods: We studied the frontalis muscle in 83 controls and compared it with the tongue, sternocleidomastoid (SCM), and trapezius muscles in 105 definite or probable ALS patients (54 bulbar, 51 nonbulbar). Results: More patients achieved complete relaxation of the frontalis muscle than the tongue or SCM. Motor unit potentials were of longer duration and higher amplitude in ALS patients than in controls (P < 0.05). The frontalis had the same frequency of spontaneous potentials as the tongue, SCM, and trapezius muscles in bulbar ALS patients, but fewer than in the trapezius in nonbulbar patients. Conclusions: Examining the frontalis provides useful information in establishing the diagnosis of ALS by identifying clinically evident or subclinical abnormalities in the craniobulbar region. Muscle Nerve 54 : 1093–1096, 2016     

Electrical impedance myography in the evaluation of the tongue musculature in amyotrophic lateral sclerosis

Introduction: Electrical impedance myography (EIM) quantifies muscle health and is used as a biomarker of muscle abnormalities in neurogenic and myopathic diseases. EIM has yet to be evaluated in the tongue musculature in patients with amyotrophic lateral sclerosis (ALS), who often show clinical bulbar signs. Methods: The lingual musculature of 19 subjects with motor neuron disease and 21 normal participants was assessed using EIM, strength and endurance testing, and clinical assessment. Results: Tongue musculature in the ALS group was characterized by significantly smaller phase (Ph) and greater resistance (R) when compared with the healthy cohort. Ph and tongue endurance were correlated in the ALS group. Conclusions: EIM of tongue musculature could distinguish those with ALS from healthy controls. The demonstrated relationship between tongue function and Ph supports further testing of EIM of the tongue as a potential biomarker in ALS. Muscle Nerve 52: 584–591, 2015     

不同阶段肌萎缩侧索硬化患者肌电图的研究

目的研究不同阶段肌萎缩侧索硬化(ALS)患者的定量肌电图(EMG)表现,寻找早期诊断ALS的敏感电生理指标。方法对60例ALS患者进行定量EMG检查,分析不同阶段运动单位动作电位(MUPs)多相参数、自发电位和大力收缩募集相变化,并与健康对照组进行比较。结果不同阶段ALS EMG表现不同,从最早期阶段到最后阶段可分为N0~N56个连续的电生理阶段。N2期MUPs的时限、波幅、面积、运动单位指数(SI)、多相波数值均较健康对照组显著升高(均P<0·001),N0、N4期MUPs部分多相参数数值明显升高(P<0·05);自发电位在病变的各个阶段均可见到,以N2~N5多见,分别为63·6%、83·0%、91·2%、100%。结论ALS患者早期阶段如出现自发电位,即为下运动神经元受累的特征表现;定量EMG检查中运动单位面积和波幅增大是其显著特点。     

Utility of trapezius EMG for diagnosis of amyotrophic lateral sclerosis

Needle electromyography (EMG) of the tongue is traditionally used as a key to the diagnosis of amyotrophic lateral sclerosis (ALS), although relaxation of the tongue is often difficult to achieve. Recently, frequent abnormalities in the EMGs of the sternocleidomastoid (SCM) and upper trapezius muscles in ALS have been reported. To elucidate the diagnostic utility of these muscles we performed a multicenter prospective study to examine EMGs of the tongue (genioglossus), SCM, and trapezius in 104 ALS or suspected ALS patients. We also examined EMGs of the SCM and trapezius in 32 cervical spondylosis (CS) patients. We mainly evaluated fibrillation potentials/positive sharp waves (Fib/PSWs) and fasciculation potentials. Complete relaxation was achieved in 85% of ALS patients in the trapezius, but in only 6% of patients in the tongue. Fib/PSWs were observed in 8%, 13%, and 45% of ALS patients in the tongue, SCM, and trapezius, respectively, whereas fasciculation potentials were observed in 1%, 7%, and 39%, respectively. Abnormal spontaneous activity of any type was found in 9%, 17%, and 63% of patients, respectively. The high frequency of abnormal spontaneous activity in the trapezius was similar among the different diagnostic categories, and even 72% of clinically suspected ALS (progressive muscular atrophy) patients showed them in their trapezius. We did not observe Fib/PSWs or fasciculation potentials in any of our CS patients, thus these findings have excellent specificity. Tongue EMG added little utility over the clinical sign of tongue atrophy. Abnormal spontaneous activity in the trapezius would be more useful for the early diagnosis of ALS. Muscle Nerve 39: 63–70, 2009     

Immunoglobulin-mediated activity against red blood cells in the saliva of amyotrophic lateral sclerosis (ALS) patients

Immunoglobulin (Ig)-mediated activity in plasma directed towards normal blood type matched red blood cells (RBC) inducing haemolysis in vitro has earlier been demonstrated to be a characteristic feature in ALS-patients. In this study, saliva of ALS-patients, normal and diseased controls was tested with the same in vitro test. An increased degree of haemolysis was induced by the ALS-patient as compared with control samples. The activity thus found in saliva had the same basic characteristics as that earlier described for plasma; it reacted similarly to serial dilution and was retained in salivary Ig. The effect on red blood cells of saliva from patients with bulbar paralysis was larger than that of saliva from ALS-patients lacking bulbar symptoms. It is discussed whether cytotoxic Ig in saliva could be pathophysiologically active in bulbar paralysis by means of passage through the oral mucosa and local action on motor end plates in perioral muscles.     

Motor unit changes in thoracic paraspinal muscles in amyotrophic lateral sclerosis

In 38 amyotrophic lateral sclerosis (ALS) patients and 28 controls, we performed motor unit potential (MUP) analysis in the C‐6 and T‐5 paraspinal and biceps muscles. In ALS cases, we found similar abnormalities in MUPs in paraspinal and limb muscles. Fasciculation potentials (FPs) were more frequent in biceps than in paraspinal muscles, but fibrillation potentials and positive sharp waves (fibs‐sw) were equally frequent in all three muscles. These results confirm the value of paraspinal MUP analysis in the diagnosis of ALS. © 2009 Wiley Periodicals, Inc. Muscle Nerve 39: 83–86, 2009     

Cerebrospinal fluid filtration in amyotrophic lateral sclerosis

By means of a randomized, controlled and open study the authors wanted to find out if cerebrospinal (CSF)-filtration was of substantial benefit to patients with sporadic amyotrophic lateral sclerosis (SALS). Five SALS patients, aged 51-75 years, being treated with riluzole underwent CSF-filtration daily over five days (group A). Five other SALS patients, aged 52-70 years, were treated only with riluzole (group B). Although all five patients in the first group reported a subjective benefit following CSF- filtration, the Norris score, the Frenchay score, the vital capacity, the ulnar nerve F-wave persistence and the peak-ratio of the brachial biceps and anterior tibial muscles did not change significantly after five days of therapy, either in group A or in group B. In conclusion, filtration of 200-250 ml CSF daily, over five days, does not seem to have a substantial therapeutic effect in patients with SALS. Copyright Lippincott Williams & Wilkins     

The onset of amyotrophic lateral sclerosis

Two patients in whom both the neurological examination and electromyography (EMG) were normal prior to the onset of amyotrophic lateral sclerosis (ALS) are reported. In each patient, the onset of ALS some 18 months later was clearly defined clinically and confirmed by subsequent EMG studies. These unique observations show that ALS commences at a defined time, and that there is early generalisation with an initial phase of rapid progression.     

Comparison of corticomotoneuronal EPSPs and macro-MUPs in amyotrophic lateral sclerosis

We correlated the size of the corticomotoneuronal excitatory postsynaptic potential (CM-EPSP) arising in a single spinal motor neuron with the function of the target motor unit as measured by conventional and macro EMG in early amyotrophic lateral sclerosis (ALS). Macro motor unit potentials (macro-MUPs) were recorded from a surface electrode after spike-triggered averaging in the extensor digitorum communis muscle. The size of the CM-EPSP projecting to the same motor unit was measured from changes in the firing probability of single motor units induced by transcranial magnetic stimulation using peristimulus time histograms. In controls, the amplitudes of CM-EPSPs and macro-MUPs correlated inversely, probably reflecting a lower input resistance of larger spinal motoneurons. In ALS the amplitude of macro-MUPs did not correlate with that of CM-EPSPs and one third of normal ALS motor units had a reduced or temporally dispersed CM-EPSP. The findings indicate primary dysfunction of the corticomotoneuronal projection system in ALS that is independent of functional changes of spinal motoneurons. © 1998 John Wiley & Sons, Inc. Muscle Nerve, 21: 18–24, 1998.     

Needle electromyography of the rectus abdominis in patients with amyotrophic lateral sclerosis

We examined the role of needle electromyography (EMG) of the rectus abdominis (RA) in assessing thoracic involvement in amyotrophic lateral sclerosis (ALS). Needle EMG of the RA was performed in 67 patients with sporadic ALS and 110 healthy controls. The presence of abnormal spontaneous activity, configuration of motor unit action potentials (MUAPs), and recruitment pattern of motor unit potentials were examined. In ALS patients, MUAPs in the RA were of prolonged duration, large amplitude, and showed increased prevalence of polyphasic waveforms compared to controls. Significant differences in MUAP parameters, presence of abnormal spontaneous potentials, and interference patterns were noted between ALS patients and controls. Additionally, we found that active denervation was more frequent in the RA of ALS patients with dyspnea than those without dyspnea. Thus, conventional needle EMG of the RA is a valuable electrophysiological method to assess clinical and subclinical involvement of thoracic lower motor neurons in patients with suspected ALS.     

Multimodality evoked potentials in amyotrophic lateral sclerosis

Visual, brainstem auditory and somatosensory evoked potentials to medial nerve stimulation were recorded in 27 patients affected by amyotrophic lateral sclerosis. VEP N75, P100, N140, N75-P100 latencies and P100 amplitude, BAEP I-III, III-V and I-V interpeak-latencies were within normal limits in all ALS patients. Somatosensory evoked potentials were abnormally delayed in 8 patients: in 3 arms because of a delayed N9-N13 latency, in 9 arms because of a delayed N13-N19 latency.     

Diagnostic problems and delay of diagnosis in amyotrophic lateral sclerosis

Objective

Initial symptoms of amyotrophic lateral sclerosis (ALS) mimic several neurological syndromes that may decelerate a correct diagnosis. The aim of our study was to investigate if diagnostic and therapeutic parameters have influence on the time of diagnosis.

Methods

We retrospectively reviewed the medical records of 100 consecutive ALS patients focusing on clinical and diagnostic data, the timing of diagnosis and treatments attributed to the onset of symptoms of ALS.

Results

Among 100 consecutive patients with ALS, 12% underwent surgery due to symptoms retrospectively attributable to ALS. The comparison of duration from first symptoms to correct diagnosis showed a significant difference between operated and non-operated patients. 35% of all ALS patients had bulbar onset symptoms. The mean time from first symptoms to diagnosis was 9 months in this group. In patients without bulbar onset it was 16.4 months which also represents a significant difference. In 44% of patients other diagnoses were considered and medically treated previous to correct diagnosis, but there was no significant delay of diagnosis.

Conclusion

Our study confirms that diagnosis of ALS is still a common clinical problem and shows the need of sensitive and specific diagnostic tests.     

Neuromuscular transmission in amyotrophic lateral sclerosis

The functional and structural characteristics of the neuromuscular junction were studied in anconeus muscle biopsies of 10 patients with amyotrophic lateral sclerosis (ALS). Intracellular recordings revealed decreased amplitudes of miniature endplate potentials (MEPPs). The MEPP frequencies were highly variable in ALS patients but the average MEPP frequency was not different from that of control patients. The mean quantal content of endplate potentials (m), the mean quanta available for immediate release (n), and the mean quantal stores (N) were all decreased. In contrast, the mean probability of quantal release (p) was normal and the mean probability of quantal store release (P) was surprisingly high at the majority of ALS endplates. Histologic evidence of denervation and small or absent nerve terminals were observed in all ALS patients. These functional and structural abnormalities of the neuromuscular junction may explain the fatigability and the electromyographic evidence of impaired neuromuscular transmission often encountered in ALS patients. © 1993 John Wiley & Sons, Inc.     

Telephone follow-up for patients with amyotrophic lateral sclerosis

The relentless evolution of amyotrophic lateral sclerosis (ALS), a severe neurodegenerative disorder of the upper and lower motoneurons, leads to an increasing level of disability. Most patients, during the course of the disease, become unable to attend the tertiary clinical care center and are thus prevented from enrolling in clinical trials or benefiting from specialized care and management. The main objective of this study was to verify whether the ALS functional rating scale (ALSFRS) could be reliably administered by telephone to patients, when unable to attend the ALS clinic, or to their caregivers. ALSFRS is a validated instrument that assesses the functional status and the disease progression in ALS. We first administered the functional rating scale directly in the clinic to 30 patients, with definite or probable ALS, and to their respective caregivers, and found a very high agreement between the two groups for the total score and the majority of the rating items. Next, we showed, in both patients and caregivers, a high degree of correlation between the total score of the ALSFRS measured by telephone and that reported in the clinic. This indicates that ALSFRS is a reliable instrument for monitoring the disease progression in homebound patients, even when the person contacted by telephone is the caregiver. We also performed a telephone clinic, based on an unstructured interview, with 16 ALS patients at an advanced stage of the disease and unable to attend the ALS clinic. On some occasions, the person interviewed was the caregiver. The symptoms most frequently reported were a worsening of muscle strength, swallowing and breathing problems, constipation, and inability to clear lung secretions. Several patients asked for assistive and adaptive equipment. All patients and caregivers found the telephone clinic very useful and considered it a good complement to the management and care programme.     

Emotional responding in amyotrophic lateral sclerosis

Amyotrophic lateral sclerosis (ALS) is a fatal disease, leaving the patient in a partially or completely deafferented state. In an explorative study, we investigated responses to visual socio–emotional stimuli in ALS patients. Pictures from the International Affective Picture System (IAPS) were verbally judged by 12 moderately affected ALS patients with a spinal onset and a slow progression and 18 age–matched controls, and data were compared with psychophysiological responses. Verbal emotional judgments of patients were more positive than ratings of controls. Regarding arousal, patients neutralized extreme pictures, in that they rated calm pictures as more exciting than controls and exciting pictures as more calm. These changes of emotional processing were unrelated to depression or frontal lobe dysfunction. There were no major differences between patients and controls concerning physiological responses to emotional stimuli. We conclude that emotional responses of ALS patients tend to be altered towards positive valence and towards a more balanced arousal state in early stages of the disease. These findings contradict assumptions of a generally negative impact of the disease on the emotional disposition and may indicate compensatory cognitive or neuroplastic changes.     

Brain-computer interfaces for amyotrophic lateral sclerosis

A brain-computer interface (BCI) is a device that detects signals from the brain and transforms them into useful commands. Researchers have developed BCIs that utilize different kinds of brain signals. These different BCI systems have differing characteristics, such as the amount of training required and the degree to which they are or are not invasive. Much of the research on BCIs to date has involved healthy individuals and evaluation of classification algorithms. Some BCIs have been shown to have potential benefit for users with minimal muscular function as a result of amyotrophic lateral sclerosis. However, there are still several challenges that need to be successfully addressed before BCIs can be clinically useful.     

Immune system alterations in amyotrophic lateral sclerosis

Amyotrophic lateral sclerosis is a disease of which the underlying cause and pathogenesis are unknown. Cumulatative data clearly indicates an active participation by the immune system in the disease. An increasingly recognized theory suggests a non‐cell autonomous mechanism, meaning that multiple cells working together are necessary for the pathogenesis of the disease. Observed immune system alterations could indicate an active participation in this mechanism. Damaged motor neurons are able to activate microglia, astrocytes and the complement system, which further can influence each other and contribute to neurodegeneration. Infiltrating peripheral immune cells appears to correlate with disease progression, but their significance and composition is unclear. The deleterious effects of this collaborating system of cells appear to outweigh the protective aspects, and revealing this interplay might give more insight into the disease. Markers from the classical complement pathway are elevated where its initiator C1q appears to derive primarily from motor neurons. Activated microglia and astrocytes are found in close proximity to dying motor neurons. Their activation status and proliferation seemingly increases with disease progression. Infiltrating monocytes, macrophages and T cells are associated with these areas, although with mixed reports regarding T cell composition. This literature review will provide evidence supporting the immune system as an important part of ALS disease mechanism and present a hypothesis to direct the way for further studies.