Fatigue in immune-mediated polyneuropathies
Citation Manager Formats
Make Comment
See Comments

Abstract
Objectives: To determine the prevalence and severity of ongoing fatigue and to investigate the internal consistency, reliability, and validity of the Fatigue Severity Scale (FSS) in patients with immune-mediated polyneuropathies.
Methods: The FSS was assessed in 113 patients who either experienced Guillain-Barré syndrome in the past or currently have a stable, chronic, inflammatory demyelinating polyradiculoneuropathy or a polyneuropathy associated with a monoclonal gammopathy of undetermined significance, and in 113 age- and sex-matched healthy controls. Data on four additional scales (Medical Research Council sumscore, functional grading scale [f-score], INCAT sensory sumscore, medical outcome study 36-items health survey [SF-36]) were obtained in all patients. SF-36 also was assessed in 59 controls.
Results: “Severe” fatigue (FSS scores ≥95th percentile values in controls) was present in 80% of the patients. Fatigue was not significantly related to general strength, sensory deficits, f-score, and duration of symptoms. Severe fatigue was reported in 81% to 86% of patients with normal strength or sensation. Eighty percent of the patients (controls, 12%) reported their fatigue being among the three most disabling symptoms. SF-36 health status scores in the patient group were significantly lower than the obtained values of the controls and partially related to the FSS scores. Good internal consistency, significant reliability, and validity were obtained for the FSS.
Conclusions: Fatigue is a major symptom in patients with immune-mediated polyneuropathies and may persist for years after apparent recovery. The Fatigue Severity Scale seems appropriate for assessing fatigue in these patients because good internal consistency, reliability, and validity were demonstrated.
Guillain-Barré syndrome (GBS) and chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) are immune-mediated diseases of the peripheral nervous system primarily characterized by symmetrical weakness, sensory disturbances, and reduction or loss of myotatic reflexes.1,2 Although the reported outcome percentages differ, approximately three-quarters of the patients with GBS or CIDP experience good physical recovery after adequate therapy.3 However, despite a good clinical improvement, we noticed that many of these patients still are restricted in their daily and social activities, sometimes consistently for many years. Moreover, these patients often address fatigue as the most important cause of their dysfunction. A decrement in their quality of life resulting from fatigue also has been repeatedly claimed.
Fatigue has been briefly addressed as a complaint in a few cases of GBS only.4,5 Because attention is directed primarily toward weakness and sensory disturbances in immune-mediated polyneuropathies, fatigue may have been underrecognized by neurologists and rehabilitation physicians. Currently, no cross-sectional study has compared the presence and severity of fatigue in these patients with healthy controls. Prompted by these considerations, we investigated the presence and severity of fatigue in a cross-sectional group of patients with GBS, CIDP, or a polyneuropathy associated with a monoclonal gammopathy of undetermined significance (MGUSP). It was argued that, on one hand, these illnesses represent parts of a spectrum.3 On the other hand, this choice provided the opportunity to compare fatigue in patients having a more ongoing disease (CIDP and MGUSP) with fatigue of those with a residual clinical condition caused by GBS in the past. In addition, the internal consistency, reliability, and validity of the selected fatigue scale were examined.
Patients and methods.
Participants.
A group of 113 patients with a stable clinical condition (83 GBS, 22 CIDP, 8 MGUSP) were recruited from the Rotterdam immune-mediated polyneuropathy databank and the Dutch GBS study group (table 1). A stable clinical condition was required to obtain the highest reliability for the selected fatigue scale. The selected patients still had residual signs or symptoms resulting from illness, representing a broad range of disability (functional grading score [f-score] of at least 1; see also assessment scales6). None of the patients have been treated with steroids or another immune-suppressive agent in the 6 months before the start of the study. Nine CIDP patients required interval treatment, ranging from weeks to months, with intravenous immunoglobulins. With this therapy, their clinical condition was stable for more than 6 months. The patients with GBS and CIDP met the international criteria for their illness.1,2 The diagnosis of MGUSP was established after excluding all possible underlying causes for the gammopathy and polyneuropathy.7 Six patients with MGUSP had an associated demyelinating polyneuropathy with minor concurrent axonal damage in three. An axonal polyneuropathy was diagnosed in the remaining two patients with MGUSP. Patients were excluded from participation if there was any concomitant disease or use of medication that might cause chronic fatigue. All selected patients declared to have experienced only mild and transient fatigue before their illness.
Basic characteristics of the participants*
Controls, stratified for gender and age, were recruited from hospital personnel, companions (relatives, friends) of patients visiting our outpatient clinic, and volunteers unfamiliar with the study (see table 1). The controls declared themselves to be healthy, free from any chronic medical condition, and were not taking medication that could contribute to fatigue.
Assessment scales.
The Fatigue Severity Scale (FSS), a brief and simple self-assessed questionnaire, was selected and translated into Dutch before its use.8 The FSS is a nine-item questionnaire with answers ranging from 1 (strongly disagree) to 7 (strongly agree) for each inquiry. The mean score of the 9 inquiries ranges from 1 (no signs of fatigue) to 7 (most disabling fatigue). Internal consistency, reliability, validity, and sensitivity of the FSS have been established in patients with systemic lupus erythematosus, MS, and Lyme disease but never in patients with immune-mediated polyneuropathies.8
The Medical Research Council (MRC) sumscore and functional grading scale (f-score) were applied in the patient group to measure the physical condition of the patients at the impairment and disability levels.6 The MRC sumscore ranges from 0 (paralysis) to 60 (normal strength). For each muscle group, a standardized joint/limb position as well as the point at which counter-force is administered was predefined and taken when assessing muscle strength. The f-score of the patients included in this study ranges from 1 (minor neurologic symptoms or signs and able to run) to 4 (bed or chair bound). Good reliability and validity have been demonstrated for these two scales.6
The INCAT sensory sumscore ranges from 0 (normal sensation) to 20 (most severe sensory deficit) and is composed by the summation of the following sensation qualities: pinprick arm grade (range 0 to 4) + vibration arm grade (range 0 to 4) + pinprick leg grade (range 0 to 4) + vibration leg grade (range 0 to 4) + 2-point discrimination grade (range 0 to 4). The vibration examination was performed using the recently validated graduated Rydel-Seiffer tuning fork, and the obtained measures were compared with the reported normative threshold values.9 Pinprick and vibration sense examination took place from distal to proximal, and only the highest extension of dysfunction of the most affected arm and leg was recorded for both qualities. The sites of examination with corresponding grades were defined as followed: normal (grade 0) or disturbed (grade 1) pinprick or vibration sense at the dorsum distal interphalangeal joint of the index finger or hallux; and abnormal sense at the ulnar styloid process or medial malleolus (grade 2), at the medial humerus epicondyle or patella (grade 3), and at acromioclavicular joint or anterior superior iliac spine (grade 4). For the 2-point discrimination quality, a sliding esthesiometer was used where the exact measurable distance in millimeters could be read on the instrument. This instrument was assessed in a “static” manner at the ventral side, distal phalanx of the index finger, and the corresponding grades were arbitrarily chosen (grade 0: ≤4 mm; grade 1: 5 to 9 mm; grade 2: 10 to 14 mm; grade 3: 15 to 19 mm; grade 4: ≥20 mm).
The medical outcomes study 36-item short form health survey (SF-36), a generic health status questionnaire, consists of 36 items assigned to the domains of physical functioning (10 items), role limitations—physical (4), role limitations—emotional (3), social functioning (2), body pain (2), mental health (5), vitality (4), general health perception (5), and change in health which is scored separately.10 The numbers of response categories per item range from two to six. Each domain has a scoring range from 0 to 100. A high score indicates better health or less body pain. The Dutch version we used was developed as a part of the International Quality of Life Assessment Project, which aims to translate, validate, and determine norms for the SF-36 in a range of languages and cultural settings.11
Test procedure.
All participants gave informed consent for the study. Participants were lucid and competent to answer the questionnaires to the best of their ability. All individuals received brief instructions on how to fill in the fatigue and health status forms. These questionnaires were answered in random order. Patients were examined at our outpatient clinic, and all scales were completed at study enrollment. The FSS was mailed 4 to 6 months later to the patients for a second assessment. The patients also were asked to report whether their clinical condition had improved, gotten worse, or remained the same since completing the first questionnaire. Patients whose health had remained the same were included in the FSS test/retest reliability analyses. The FSS was completed once by all healthy controls. SF-36 was self-administered by 59 controls, taking into account the age and sex distribution of the patients. The study took place between March 1997 and August 1998 and was part of a more comprehensive outcome assessment research in patients with immune-mediated polyneuropathies on behalf of the European Inflammatory Neuropathy Cause and Treatment Group.
Statistics.
“Severe” fatigue was arbitrarily defined as a score ≥FSS 95th percentile in healthy individuals. The FSS scores obtained in the patients and in healthy controls were compared using the Mann-Whitney U test and univariate/multivariate quantile regression analyses.12 The median FSS values were compared within the categories (healthy controls, GBS, CIDP, and MGUSP patients) using design variables (0 to 1) representing each category. The design variables were defined in an appropriate manner, making it possible to test (by the likelihood ratio test) the hypothesis that the median fatigue values were equal for the diagnoses of CIDP and MGUSP but unequal to the median fatigue values in GBS patients and healthy controls, separately. Box plots, with the upper and lower adjacent values defined according to Tukey, were applied to visualize some of these observations (also see the legend to figure 1 for explanation of the various components of a box plot).13
Figure 1. Box plots demonstrating the obtained Fatigue Severity Scale (FSS) scores in the healthy controls versus patient group (A) related to diagnosis (B) and sex (C). The patients were more fatigued than the healthy controls (Mann-Whitney U test, whole patient group versus healthy controls: p < 0.0001). All diagnostic categories were more fatigued than the healthy controls (likelihood ratio test combined with quantile regression analysis: p < 0.0001). The GBS patients had a higher median fatigue value compared with the other subgroups and healthy controls (likelihood ratio test combined with quantile regression analysis: p < 0.0001 for the comparisons GBS versus CIDP + MGUSP, and GBS versus healthy controls). Women were more tired in both groups, but this was significant only in the patient group (Mann-Whitney U test; in healthy controls: p = 0.28; in patient group: p = 0.02). HC = healthy controls; HM = healthy males; HF = healthy females; MP = male patients; FP = female patients. The various components of the box plots can be explained as follows. The median (50th percentile) FSS value corresponds to the horizontal line within the box. The box extends from the first quartile (25th percentile = x[25]) to the third quartile (75th percentile = x[75]), the so-called interquartile range (IQR). The vertical lines emerging from the box extend to the upper and lower adjacent values. The upper adjacent value is defined as the largest FSS value less than or equal to x[75] + 1.5 × IQR. The lower adjacent value is defined as the smallest FSS value greater than or equal to x[25] − 1.5 × IQR. Measured FSS values more extreme than the adjacent values are referred to as “outside values” and are individually plotted.13
The mean SF-36 subscale values were compared within the three diagnostic categories and between the whole patient group and healthy controls for each domain. One-way analysis of variance (ANOVA) with corrections according to Bonferroni multiple-comparison tests were applied.
The Cronbach’s alpha coefficient was estimated for the FSS in the patients and healthy participants.14 The test/retest reliability for the recruited FSS values in the polyneuropathy patients was quantified by estimation of the intraclass correlation coefficient using a one-way random effects analysis of variance model. The correlation between the FSS and other scales was analyzed using Spearman rank-correlation test. All analyses were performed using Stata 5.0 for Windows 95 (Stata Statistical Software, Stata Corporation, release 5.0, College Station, TX 1997). A value of p ≤ 0.05 was considered to be statistically significant.
Results.
Characteristics of participants.
The characteristics of all participants are presented in table 1. One hundred thirteen patients and 113 age- and sex-matched healthy individuals were enrolled. The CIDP patients were relatively younger (mean age 45.0 [SD 18.0] years) compared with the GBS (mean age 55.7 [SD 13.6] years) and the MGUSP patients (mean age 66.1 [SD 8.1] years). One hundred seven of the 113 patients (95%) completed the second FSS assessment. One hundred five patients reported a stable clinical condition, whereas two reported an improved clinical condition at the second FSS assessment. These two were excluded from reliability analyses. Two patients died during the interval between the two measures, and another was hospitalized because of myocardial infarction. The remaining three patients did not return the second FSS assessment for various reasons. Fifty-nine healthy volunteers (29 women, 30 men; mean age 53.5 [SD 13.6] years) completed the SF-36 questionnaire.
FSS comparison between patients and controls.
At entry, the median FSS value in the patient group was slightly higher (6.1) (corresponding mean value: 5.6 [SD 1.4]) compared with the median value at the second assessment (5.8) (corresponding mean value: 5.5 [SD 1.4]). Unless otherwise stated, further comparisons were made using only the FSS values obtained at entry. The median FSS value in the patient group was higher compared with the result in healthy individuals (median fatigue value 2.9; corresponding mean value: 2.9 [SD 1.1]) (figure 1A; Mann-Whitney U test: p < 0.0001). By the likelihood ratio test, it was demonstrated that the median FSS values were equal for the CIDP and MGUSP patients but unequal to the median fatigue values in healthy controls and GBS patients. This test also revealed that the GBS patients had a higher median fatigue value (6.2) compared with the other subgroups and healthy controls (CIDP 5.6, MGUSP 5.3, healthy controls 2.9; figure 1B; quantile regression analyses combined with likelihood ratio test; p < 0.0001 for the comparisons GBS versus CIDP + MGUSP, and GBS versus healthy controls).
The FSS 95th percentile in the healthy controls was 5.0. Severe fatigue, arbitrarily defined as a FSS score more than the FSS 95th percentile in the healthy controls, was demonstrated in 90 of 113 patients (80%). Remarkably, of the patients with a completely recovered general strength (MRC sumscore 60) relatively more patients reported a fatigue score that fell within the severe fatigue range (19 of 22, 86%). Severe fatigue also was reported in 17 of the 21 (81%) patients with normal sensation (sensory sumscore 0). Six of the eight patients (75%) with both normal general strength and sensation experienced severe fatigue. Eighty percent of the patients scored 5 or more on the 7-point scale for question 8 (“Fatigue is among my three most disabling symptoms”) compared with 12% (13/113) of the healthy controls.
FSS correlation with clinical parameters.
General strength, as measured by the MRC sumscore, the f-score values, and sensory sumscore, showed no significant association with the FSS values (Spearman rank correlation test: r = 0.07 to 0.13; p ≥ 0.18). Fatigue score was not significantly related to age and duration of symptoms in the patient group. Fatigue in women was consistently higher than in men, but this was significant only in the patient group (figure 1C; Mann-Whitney U test in healthy controls: p = 0.28; in patient group, p = 0.02).
SF-36 evaluation and its association with FSS in patients.
The SF-36 values showed no substantial difference between the three diagnostic categories (GBS, CIDP, and MGUSP) within each domain (ANOVA with Bonferroni tests: all p values ≥ 0.46). A separation was made between the GBS (acute subgroup; n = 83) and the CIDP and MGUSP patients (chronic subgroup; n = 30) based on these results combined with the FSS likelihood ratio test findings (also see FSS Comparison Between Patients and Controls in the Results section). For all SF-36 domains, both subgroups scored notably lower values compared with the scores obtained in healthy controls (figure 2; ANOVA with Bonferroni tests: p < 0.0001 for all domains, except for the dimension “role functioning—emotional” in the chronic subgroup versus controls: p = 0.03).
Figure 2. Short Form-36 (SF-36) health status in patients with immune-mediated polyneuropathies and healthy controls. Both patient subgroups demonstrated a lower score for all SF-36 domains compared with the scores of the healthy controls (p < 0.0001 for all domains, except “role functioning—emotional” in the CIDP/MGUSP patients versus controls: p = 0.03). No statistically significant difference was obtained at all domain levels between the GBS and the CIDP/MGUSP patients (all p values ≥ 0.27). Analyses were performed using ANOVA with corrections according to the Bonferroni multiple-comparison tests.
The correlations between the FSS and SF-36 domains for the two subgroups are presented in table 2. In both subgroups, FSS demonstrated the highest significant inverted association with the domains “general health perception” and “vitality.” Fatigue scores in GBS patients were significantly associated with the socioemotional domains but not with the physical subscales. Conversely, fatigue values in the chronic subgroup were significantly related to the physical (but not the socioemotional) dimensions (table 2, boxes).
Correlations between the FSS and SF-36 health status in patients with immune-mediated polyneuropathies*
Internal consistency, reliability, and validity evaluation of the FSS.
A good internal consistency for the FSS was found at both assessments for the whole patient group (α = 0.93 and 0.95, respectively) and in healthy controls (α = 0.84). The FSS demonstrated good test/retest reliability (R = 0.86) and construct validity when correlated with the SF-36 vitality domain (r = −0.56, p < 0.0001).
Discussion.
The findings in the current study demonstrate that fatigue is a prominent and highly disabling symptom in immune-mediated polyneuropathies. Four of five (80%) patients rated their fatigue as one of the three most disabling symptoms compared with only 12% in the healthy controls. Also, severe fatigue, defined as a score equal to or higher than the FSS 95th percentile in the healthy controls, was present in 80% of the patients. These observations are consistent with reports on fatigue in other chronic conditions such as MS and systemic lupus erythematosus.15-18 The current study also demonstrated a difference with literature findings. The mean FSS score in our patient group was higher than the reported FSS values in various chronic immune-mediated conditions (mean FSS ≤5.1 versus 5.6 in the current study).8,18-21 This was remarkable because approximately two thirds of the population in the study consisted of patients with residual clinical conditions caused by experiencing GBS many years (median 5.2) before the start of this study. Surprisingly, the prevalence of fatigue was the highest among the GBS patients (see figure 1B). Fatigue in these patients was independent of the time that elapsed since the acute phase of the GBS was experienced. Despite a good physical recovery, GBS still can be considered as a long-term event causing a “post-GBS fatigue syndrome” in most patients that may interfere with functionality. Such an “illness-related fatigue syndrome” also was noted in the CIDP and MGUSP patients we investigated.
Variables such as age, duration of the disease, MRC sumscore, f-score, and sensory sumscore were not significantly associated with fatigue. Fatigue was significantly related to gender only in the patient group. Severe fatigue also was highly prevalent in patients with normal general strength or normal sensory modalities. These results clearly emphasize that fatigue should be considered as a serious, relatively independent and highly disabling entity in patients with immune-mediated polyneuropathies, irrespective of clinical variables or course of time.
The SF-36, a generic health status questionnaire, also clearly distinguished the patient group from healthy controls but could not differentiate between the three diagnostic categories (GBS, CIDP, and MGUSP) at all domain levels. The GBS (acute) group and the chronic (CIDP/MGUSP) patients had significantly lower scores compared with the controls at all SF-36 levels (see figure 2). A significantly worse functional status also has been reported by Bernsen et al. using the sickness impact profile health status in 123 patients who had GBS 3 to 6 years previously.22 These authors also conclude that the psychosocial functioning of the patients was seriously affected, even when the patients reached a complete physical recovery or showed only mild residual signs.22 The socioemotional dimensions of the SF-36 applied in the current study are comparable with the psychosocial categories of the sickness impact profile and were fairly associated with fatigue in the GBS patients23 (see table 2). Fatigue presumably attributes to a reduced psychosocial functioning in GBS patients. Contrary to these findings, fatigue was significantly associated with the SF-36 physical dimensions in patients with a “chronic” polyneuropathy. Perhaps these patients are more preoccupied with the potential threat of changes in their physical status, making them prone to relate disabling symptoms such as fatigue to their physical condition.
As a basis for their study, several reports addressing the influence of fatigue on health status in chronic disorders state that engagement in less physical activities and exercises may induce deconditioning, which may explain fatigue leading to decrements in health status.17,24 Conversely, Pitetti et al. report reduction in daily fatigue with improvements in activities of daily living following a supervised training program in a 54-year-old man who had residual deficits for many years after GBS.25 An enhancement in functional capacity also has been reported in chronic relapsing GBS after low-intensity aerobic exercise.26 Less engagement in physical activities also was noted in all patients in the current study compared with healthy controls (see figure 2). However, because fatigue was primarily related to the SF-36 physical domains only in the chronic group and not in the GBS patients, other explanatory factors leading to a reduced health status also should be considered.
Instruments for measuring outcome must be appropriate to the patient group being studied, efficient, easy to administer, and user friendly.27 Good reliability and validity also are necessary.27 In the current study, the FSS was demonstrated to be brief, was easily self-administered with good test/retest reliability, and had significant validity. The internal consistency of the FSS in the patients and healthy controls was higher than the recommended 0.7 score by Nunnally.14 Hence, the applicability of the FSS as an instrument for measuring fatigue is shown in patients with immune-mediated polyneuropathies. The responsiveness to changes in time of the FSS currently is being evaluated in a longitudinal study including patients with recently diagnosed GBS and CIDP with changing clinical course, but already has been established in patients with MS and Lyme disease.8
Some methodologic issues of the current study should be addressed. First, the selected patients had a stable clinical condition, which was necessary for an optimal FSS reliability evaluation. However, a stable clinical condition was based on the subjective report by the patient rather than on the patient’s actual clinical evaluation by an investigator. The latter probably would have resulted in a more accurate judgment of the clinical condition of the patient. Despite this, an acceptable FSS reliability value still was obtained. Second, it is unclear whether patients with changing clinical conditions would be more or less fatigued or whether the associations between FSS and SF-36 subscales would give different outcomes. Third, it also is unsettled whether fatigue still would not be related to the various clinical variables when assessed over time. Fourth, results should be interpreted with some caution because we did not systematically investigate or control for possible pathophysiologic associated factors with fatigue, such as sleep disturbances, depression, and inactivity leading to deconditioning.17-20,24-26,28 Despite these issues, the current observations still buttress our clinical experience that fatigue is a prominent complaint among patients with immune-mediated polyneuropathies.
Appendix
Members of the INCAT Group include: J. Aubry, PhD; N. Baumann, PhD; P. Bouche, MD, PhD; G. Comi, MD, PhD; M.C. Dalakas, MD, PhD; H.P. Hartung, MD, PhD; R.A.C. Hughes, MD, PhD; I. Illa, MD, PhD; M.R.J. Knapp, PhD; J.-M. Léger, MD, PhD; R. Nemni, MD, PhD; E. Nobile-Orazio, MD, PhD; K.V. Toyka, MD, PhD; P. van de Bergh, MD, PhD; F.G.A. van der Meché, MD, PhD; P.A. van Doorn, MD, PhD; H.J. Willison, MD, PhD; and B. Younes-Chennoufi, PhD.
Footnotes
- Received February 5, 1999.
- Accepted June 7, 1999.
References
- ↵
Asbury AK, Cornblath DR. Assessment of current diagnostic criteria for Guillain-Barré syndrome. Ann Neurol 1990;27 (suppl):S21–S24.
- ↵
Ad Hoc Subcommittee of the American Academy of Neurology AIDS Task Force.Research criteria for diagnosis of chronic inflammatory demyelinating polyneuropathy (CIDP). Neurology 1991;41:617–618.
- ↵
- ↵
Wessely S, Powell R. Fatigue syndromes: a comparison of chronic “postviral” fatigue with neuromuscular and affective disorders. J Neurol Neurosurg Psychiatry 1989;52:940–948.
- ↵
- ↵
- ↵
- ↵
- ↵
Martina ISJ, van Koningsveld R, Schmitz PIM, van der Meché FGA, van Doorn PA, for the European Inflammatory Neuropathy Cause and Treatment (INCAT) Group. Measuring vibration threshold with a graduated tuning fork in normal aging and in patients with polyneuropathy. J Neurol Neurosurg Psychiatry 1998;65:743–747.
- ↵
- ↵
- ↵
Gould WW, Rogers WH. Quantile regression as an alternative to robust regression. In: 1994 Proceedings of the statistical computing section. Alexandria, VA: American Statistical Association, 1994.
- ↵
Tukey JW. Exploratory data analysis. Reading, MA:Addison-Wesley Publishing, 1977.
- ↵
Nunnally JC. Psychometric theory. New York:McGraw Hill, 1978.
- ↵
- ↵
Robb-Nicholson LC, Daltroy L, Eaton H, et al. Effects of aerobic conditioning in lupus fatigue: a pilot study. Br J Rheumatol 1989;28:500–505.
- ↵
- ↵
- ↵
- ↵
Bernsen RAJAM, Jacobs HM, de Jager AEJ, van der Meché FGA. Residual health status after Guillain-Barré syndrome. J Neurol Neurosurg Psychiatry 1997;62:637–640.
- ↵
- ↵
- ↵
- ↵
- ↵
Hobart JC, Lamping DL, Thompson AJ. Evaluating neurological outcome measures: the bare essentials. J Neurol Neurosurg Psychiatry 1996;60:127–130.
- ↵
Letters: Rapid online correspondence
REQUIREMENTS
If you are uploading a letter concerning an article:
You must have updated your disclosures within six months: http://submit.neurology.org
Your co-authors must send a completed Publishing Agreement Form to Neurology Staff (not necessary for the lead/corresponding author as the form below will suffice) before you upload your comment.
If you are responding to a comment that was written about an article you originally authored:
You (and co-authors) do not need to fill out forms or check disclosures as author forms are still valid
and apply to letter.
Submission specifications:
- Submissions must be < 200 words with < 5 references. Reference 1 must be the article on which you are commenting.
- Submissions should not have more than 5 authors. (Exception: original author replies can include all original authors of the article)
- Submit only on articles published within 6 months of issue date.
- Do not be redundant. Read any comments already posted on the article prior to submission.
- Submitted comments are subject to editing and editor review prior to posting.
You May Also be Interested in
Hemiplegic Migraine Associated With PRRT2 Variations A Clinical and Genetic Study
Dr. Robert Shapiro and Dr. Amynah Pradhan
Related Articles
- No related articles found.