Are ALS patients effective after cervical spine surgery?

  Amyotrophic lateral sclerosis (ALS) is a progressive developmental degenerative disease involving the upper and lower motor nervous system. Patients often start with weakness and atrophy of the small muscles of the hands, which gradually progress to the extremities, ball and respiratory muscles. Patients most often die of respiratory failure. The clinical manifestations of ALS are mainly lower motor unit symptoms such as weakness, atrophy and fasciculations of the limbs and upper motor unit symptoms such as spastic gait, hyperreflexia and pathological signs. Since ALS has no specific laboratory features, the diagnosis is based on clinical symptoms and signs. In addition, because the disease is rare and other diseases need to be excluded, the early misdiagnosis rate can be as high as 40% and can be easily misdiagnosed as spinal cervical spondylosis (CSM), multifocal motor neuropathy, etc.  In the early stages of ALS, the disease can be more similar to CSM: 1) the average age of onset of ALS is 55.7 years, which is similar to that of CSM, and the incidence of CSM is high and more common clinically; 2) CSM can also present with increased muscle tone in the lower extremities such as weakness, atrophy and gait instability in the upper extremities, and although typical CSM can have sensory symptoms such as radicular pain and sphincter disorders, there are 3) CSM can also show extensive neurogenic damage in the limbs during electrophysiological examination. 4) Most patients with CSM have a long disease duration, but the disease can progress acutely over a period of time, which makes it difficult to differentiate between the two. There is no effective treatment for ALS, and the decision to operate for CSM generally depends on the following points: 1) whether the patient’s symptoms and signs are consistent with the severity of the imaging damage; 2) whether the patient’s lesions are progressive; 3) whether conventional conservative treatment (drugs, physiotherapy, traction, etc.) is ineffective. ) are ineffective. In general, it is still debated whether surgery is ultimately beneficial, because a proportion of patients with CSM tend to spontaneously resolve after progressive progression and do not require surgical treatment, and because some studies have shown that surgery does not result in an improvement in neurological function scores at 3 years, but only in some degree of symptomatic relief. Therefore, the surgical approach and timing of CSM must be chosen carefully, especially for patients with no sensory impairment and more severe muscle atrophy and fasciculations, and other diseases such as ALS and MS need to be fully excluded before making a decision. Currently, orthopedic surgeons are conscious of the need to perform electromyography and nerve conduction velocity in CSM patients with atypical clinical symptoms in order to identify them, but there are still questions about whether to perform surgery in patients with early ALS or in patients with co-morbid CSM and ALS. Previous studies have often suggested that surgical treatment can aggravate ALS patients and cause a rapid deterioration of their symptoms. However, recent studies have shown that surgery early in the course of ALS does not reduce survival time compared to typical ALS, although the disease continues to progress. In this paper, we will retrospectively analyze typical ALS patients in our hospital and will compare the epidemiological characteristics, disease progression, and survival outcomes of patients who underwent cervical spine surgery after the onset of ALS with those of typical ALS patients, so as to objectively evaluate the impact of cervical spine surgery on disease progression and prognosis of ALS.  Subjects and methods I. I. Study population and grouping: Retrospective analysis of 329 outpatients and inpatients with ALS at our hospital from January 2000 to January 2007, all of whom met the criteria for confirmed or proposed ALS according to the modified El Escorial diagnostic criteria, and each patient recorded medical history, epidemiology, cervical spine MRI findings and surgical history and modified ALS functional class scale score ( ALSFRS-R), etc. There were 19 patients who underwent cervical spine surgery after the onset of ALS, hereinafter referred to as the operated group, and 92 consecutive patients who had not undergone surgery from September 2003 to September 2005, hereinafter referred to as the non-operated ALS group. For this group, in addition to baseline documentation, we conducted face-to-face or telephone follow-up visits every three months until June 2007, when death or tracheotomy or mechanically ventilated assisted breathing was considered an endpoint event. Patients were considered as truncated data if they were missed, died unanticipated and survived beyond the observation time.  The ALSFRS-R replaced the original respiratory function score, which was only one item, and increased it to 12 points for three items. The total score is 48 points for 12 items. Thus, the ALSFRS-R includes four major components: 1) ball function, 2) upper extremity function, 3) lower extremity function, and 4) respiratory function.  In estimating the patient’s progression at diagnosis (△FS1), we invoked the concept of linear rate of change proposed by Amonc, which means that a certain observation recorded at diagnosis is assumed to be the result after a uniform change from the onset to the time point of recording, and the slope of the linear decline is calculated and called the linear rate of change estimate. For example, the linear rate of change estimate of ALSFRS-R △FS = (48- ALSFRS-R at diagnosis)/time from onset to diagnosis. This method is now widely used internationally. The rate of progression of the patient’s disease after diagnosis (△FS2) we took one year as the boundary, △FS2= (ALSFRS-R at diagnosis – ALSFRS-R one year after diagnosis)/12 months, if the patient’s observation time was less than 12 months, the last observation value and the corresponding observation time were used instead.  III. Statistical methods: Count data were expressed as rate (%) using chi-square test; measurement data were expressed as mean ± standard deviation (X ± s), and those conforming to normal distribution were analyzed by ANOVA and t-test, respectively, and those with non-normal distribution were subjected to Mann-Whitney U test of non-parametric test; median survival time was calculated by KaplanCMeier, and log-rank analysis of each single The median survival time was calculated by KaplanCMeier, and the relationship between each single factor variable and survival time was analyzed by log-rank. Cox risk proportional model was used to analyze the effect of multiple variables on survival time and to select statistically significant predictors of survival time. All data were calculated by the SPSS 10.0 for Windows package.  Results I: Clinical data: Surgical group: Among 329 typical ALS patients, cervical spine MRI showed cervical disc herniation, calcification of the posterior longitudinal ligament and other deformation of the dural sac spinal cord with different degrees of compression, accounting for 47.4% of the total number of patients, of which 19 patients (5.78% of the total number) underwent cervical spine surgery (surgical group). The age of onset ranged from 45 to 76 years, with a mean of (55.11±8.92) years; the duration of the disease ranged from 4 to 49 months, with a mean of (22.84±11.25) months. The time from onset to surgery ranged from 1 to 30 months, with a mean of (11.47±7.15) months, and the time from onset to diagnosis ranged from 12 to 36 months, with a mean of (23±6.51) months. Neurological function scores at diagnosis ranged from 27 to 43, with a mean of (35.26±5.01). The disease started in the upper extremity in 13 cases (68.42%), in the lower extremity in 5 cases (26.32%), and in both the upper and lower extremities in 1 case (5.2%). None of the patients developed symptoms in the ball region, but the ball region was involved in 12 cases (63.16%) at the time of diagnosis. There were 5 patients who underwent surgery for unilateral hand weakness and atrophy, 2 patients who underwent surgery for upper limb lifting weakness and atrophy, 3 patients who underwent surgery for both proximal and distal upper limb muscle involvement, 1 patient who underwent surgery for lower limb weakness and easy to fall, 5 patients who underwent surgery for lateral weakness and atrophy, 5 patients who underwent surgery for limb weakness and atrophy, 4 patients with pain or sensory disturbance, and 1 patient One patient had a history of cervical spine trauma. The condition of all patients progressed after surgery, among which 7 patients (36.84%) had significant progression of symptoms after surgery, 6 patients (31.58%) had no significant change in symptoms after surgery, and 6 patients (31.58%) had mild relief of symptoms after surgery, which continued to worsen after a period of time.  The clinical data of the non-operated group are compared with those of the operated group in Table 1. It can be seen that there was no significant difference in the age at onset, gender composition, and neurological function score of the two groups compared at the time of diagnosis (P > 0.05). However, the time from onset to diagnosis was significantly longer in the operated group than in the non-operated group (P < 0.001). And the proportion of ball symptoms at the time of diagnosis was significantly greater in the non-operated group (P < 0.05).  Comparison of clinical data between the cervical spine surgery group and the non-operated group in patients with confirmed and proposed ALS The surgical group non-operated group value Gender (male/female Age of onset (years Proportion of diagnosed ball involvement Time to confirmed diagnosis (months 0.05). See table for comparison of survival outcomes: by June 2007, 19 patients in the operated group were followed up, 10 had endpoint events, 1 was lost to follow-up, and 8 survived, for a total of 9 truncated data, with a mortality rate of 52.63% and a median survival time of 54 months (95% confidence interval of 49-59 months). In the non-surgical group, 92 patients were followed up, 61 had endpoint events, 4 were lost to follow-up, 27 survived, 31 had a total truncated data, the mortality rate was 66.3%, and the median survival time was 45.71 months (95% confidence interval 30-52 months), with no significant difference between the two (P=0.127).  Comparison of the rate of progression before and after diagnosis between the surgical and non-surgical groups group number of cases mean median value value △ surgical group non-surgical group △ surgical group non-surgical group Discussion The differentiation between the two and CSM has been discussed extensively in the previous literature. The difference between the two is mainly made by detailed and continuous neurological examination and electromyography of the sternocleidomastoid muscle. In fact, due to the more aggressive progression of ALS, the disease regression can often be self-evident if there is a long enough observation period. Therefore, it is necessary to analyze patients for follow-up and survival time observation.  From a cross-sectional survey of confirmed and proposed ALS patients at our hospital, we found that nearly half of the ALS patients had cervical spine MRI showing varying degrees of cervical spine pathology, which is consistent with the data reported by Yamada et al. in Japan. This shows the high prevalence of cervical degenerative changes in this age group, but also indicates that the widespread use of MRI has increased the detection rate in this group of patients, which has increased the misdiagnosis rate to some extent. Among them, 19 patients underwent cervical spine surgery, accounting for 5.78% of the total number, which is consistent with the internationally reported 4-9%. In this group of patients, the clinical manifestations were diverse, but unlike the 47 ALS patients who underwent surgery mostly for foot drop reported by Yoshor, our patients underwent surgery mostly for weakness and atrophy of the upper extremities, and a small number of patients underwent surgery for gait instability and poor ambulation. All patients progressed after surgery, but 6 patients (31.58%) showed some improvement in their symptoms after surgery. These 6 patients included all 4 patients with sensory numbness or pain, and we considered these patients as possible co-morbidities of ALS and CSM.  By comparing the epidemiological data with typical ALS at the time of diagnosis, we found that the age at onset, gender composition, and neurological function scores of patients in the surgical group at the time of diagnosis were not significantly different from those in the non-surgical group. However, the time from onset to diagnosis in the surgical group ranged from 12 to 36 months, with a mean of (23 ± 6.51) months, which was significantly longer than that in the non-operated group. And the proportion of ball symptoms at the time of diagnosis was significantly less in the unoperated group. This is not difficult to understand because the patients underwent cervical spine surgery from 1 to 30 months after the onset of the disease, with a mean of (11.47±7.15) months, when none of the patients had obvious bulbar symptoms, and then the diagnosis of ALS gradually became clearer after the progression of the disease partially affecting the bulb. Therefore, the difficulty of early differential diagnosis prolongs the diagnosis time of patients, and cervical spine surgery delays the diagnosis time of patients to some extent.  By comparing the estimated rate of disease progression before diagnosis (△FS1) and the rate of disease progression 1 year after diagnosis (△FS2) in the operated and non-operated groups, the difference was significant in the former and not significant in the latter. This indicates that patients in the pre-diagnosis surgery group tended to progress at a slower rate than typical ALS, while the rate of progression was approximately the same for both after diagnosis. We saw that △FS1 was mainly determined by the time of diagnosis and the neurological function score at diagnosis, and the neurological function scores at diagnosis were approximately the same in both groups; therefore, the patients in the surgery group had a relatively slower rate of progression. In contrast, the rate of progression was the same for both after diagnosis, indicating that although the patients continued to progress after surgery, the rate of progression was not accelerated compared to typical ALS. Comparing the survival time of the two, it was found that the survival time of the operated group was slightly longer, but the difference was not significant compared with the non-operated group. This indicates that although all patients had progressive disease after cervical spine surgery early in the onset of ALS, it did not significantly shorten the survival time or aggravate the progression of the patients. The reasons for this may be as follows: 1) the patients who underwent surgery for ALS had late involvement of the bulb, which is an epidemiologically important factor affecting survival time, and therefore the survival time of these patients was relatively long; 2) the surgery resulted in mild remission of symptoms in about one-third of the patients, and this group of patients may have co-morbidity of ALS and CSM, and the surgery partially improved The surgery partially improved the quality of survival of the patients.  In summary, we need to look at the issue of early cervical spine surgery in ALS patients in a dialectical manner. First, performing cervical spine surgery is a misdiagnostic treatment for early pure ALS patients, causing artificial trauma and unnecessary costs to the patient, as well as prolonging the diagnosis and possibly delaying the entry of ALS patients into early clinical trials, which should be objectively avoided. However, through retrospective analysis, we did not find that surgery caused significant acceleration of disease progression and shortening of survival time in patients. Moreover, for patients with co-morbidities of ALS and CSM, surgery can lead to a certain degree of improvement in their clinical symptoms; therefore, surgical treatment is not absolutely contraindicated and should be combined with the patient’s requirements for quality of survival and the rate of progression of ALS by neurologists, The decision should be made after a comprehensive evaluation by the neurologist, orthopedic surgeon and all aspects of the patient.  Conclusion: About half of the typical ALS patients had cervical spine lesions and 5.78% of them underwent cervical spine surgery. The age, gender, and neurological function scores of patients in the operated group at the time of diagnosis were not significantly different from those in the non-operated group. Surgery did not significantly accelerate the progression of ALS and shorten survival time compared to the non-operated group, but it may delay the diagnosis and treatment opportunities of patients, increase their pain and cost, and should be avoided. Surgery should be performed with caution in patients with co-morbidities of ALS and CSM.