Spreading in ALS: The relative impact of upper and lower motor neuron involvement

Gromicho, Marta; Figueiral, Manuel; Uysal, Hilmi; Großkreutz, Julian; Kuźma‐Kozakiewicz, Magdalena; Pinto, Susana; Petri, Susanne; Madeira, Sara C.; Swash, Michael; Carvalho, Mamede de

doi:10.1002/acn3.51098

Cited by 41 publications

(35 citation statements)

References 24 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…ALS is characterized by focal and regional susceptibility in pathophysiologic mechanism, which implies that the region adjacent to onset site is apt to be prior involved [ 12 ]. In a recent study, Gromicho et al found that contiguous spreading was the leading progression pattern in ALS and regional progression of LMN degeneration was most likely contiguous [ 13 ]. The 3rd to 5th segments of cervical spinal cord, which innervate diaphragm, are tightly adjoined to medulla oblongata, and LMNs in the two regions may be concurrently impaired in ALS.…”

Section: Discussionmentioning

confidence: 99%

Disease duration of progression is helpful in identifying isolated bulbar palsy of amyotrophic lateral sclerosis

et al. 2021

View full text Add to dashboard Cite

Background Compared with typical bulbar onset amyotrophic lateral sclerosis (ALS), isolated bulbar palsy (IBP), an often under-understood variant of ALS, is characterized by symptoms confined to bulbar region for extended periods and relative preservation of limb and ventilation function. To find a cutoff value of disease duration that can distinguish IBP from typical bulbar onset ALS well, the association of survival with disease progression in bulbar onset ALS patients was analyzed. Methods Clinical data of bulbar onset ALS patients were collected from January 2009 to December 2013. The duration from bulbar onset to first significant limb involvement was analyzed by a cutoff point analysis with maximally selected log-rank statistics and dichotomized to categorize patient outcomes. The patients were divided into two groups, the IBP and typical bulbar onset ALS groups, according to the cutoff value. Clinical features were compared. Results 115 bulbar onset ALS patients were recruited, and the duration from bulbar onset to first significant limb involvement was associated with survival (P < 0.001). The cutoff duration was 20 months. 19 patients were identified as IBP and 96 patients as typical bulbar onset ALS using 20 months as the cutoff duration. Female was more common, limb weakness was less frequent and pure upper motor neuron (UMN) bulbar signs were more frequent in the IBP group than in the typical bulbar onset ALS group (P = 0.047; P = 0.004; P = 0.031). The median survival time of the IBP group was significantly longer than that of the typical bulbar onset ALS group (64 months and 26 months, respectively; P < 0.001). Conclusions A cutoff duration of 20 months from bulbar onset to first significant limb involvement may be used to specifically distinguish IBP from typical bulbar onset ALS. IBP was characterized by female predominance, relative preservation of limb function, more pure UMN bulbar signs and a relatively benign prognosis.

show abstract

Section: Discussionmentioning

confidence: 99%

Disease duration of progression is helpful in identifying isolated bulbar palsy of amyotrophic lateral sclerosis

et al. 2021

View full text Add to dashboard Cite

show abstract

“…ALS is known to show a high heterogeneity of symptom worsening and patterns of spread throughout the affected regions [ 33 , 34 ]. Thus, nonreflective postponements of consultations, that were impromptu demanded by many patients in March 2020, could cause significant harm or delay supportive therapies.…”

Section: Discussionmentioning

confidence: 99%

Triage of Amyotrophic Lateral Sclerosis Patients during the COVID-19 Pandemic: An Application of the D50 Model

Steinbach

Prell

Gaur

et al. 2020

JCM

Self Cite

View full text Add to dashboard Cite

Amyotrophic lateral sclerosis (ALS) is a progressive neuromuscular disease, the management of which requires the continuous provision of multidisciplinary therapies. Owing to the novel coronavirus disease (COVID-19) pandemic, regular contact with ALS patients at our center was severely restricted and patient care was at risk by delay of supportive therapies. We established a triage system based on the D50 disease progression model and were thus able to identify a prospective cohort with high disease aggressiveness (D50 < 30). Thirty-seven patients with highly aggressive disease were actively offered follow-up, either via telephone or on-site, depending on their disease-specific needs and abilities. We describe here the procedures, obstacles, and results of these prescient efforts during the restrictions caused by COVID-19 in the period between March and June 2020. In conclusion, four patients with highly aggressive disease were initiated with non-invasive ventilation and two received a gastrostomy. We could show that a comparable amount of advanced care was induced in a retrospective cohort within a similar time period one year prior to the COVID-19 outbreak. Our workflow to identify high-risk patients via D50 model metrics can be easily implemented and integrated within existing centers. It helped to maintain a high quality of advanced care planning for our ALS patients.

show abstract

“… 4 , 6 , 17 , 18 However, a non-contiguous pattern of progression in clinical manifestations in ALS was also reported in previous studies; and the difference has been attributed to variable onset subtypes of ALS. 19 , 20 In a study with a large cohort, ALS patients with bulbar UMN or LMN onset showed progression more frequently to the upper limbs than to the lower limbs and to the lower limbs more frequently than to the thoracic region, 5 although there are no sensitive clinical or functional signs of thoracic region involvement. In the present study on patients with BO-ALS, a large proportion of patients showed a contiguous progression and the highest involvement was in the bulbar region and the lowest in the lower limbs innervated by the lumbosacral segment in clinical investigation, suggesting a descending pattern from the rostral to the caudal regions along the anatomical structure from the brainstem to the spinal cord in the majority of patients.…”

Section: Discussionmentioning

confidence: 99%

“… 1 The region of onset and speed of progression in ALS are highly variable, with a spreading pattern to adjacent anatomical sites (contiguous anatomical propagation) being more likely than non-contiguous symptom development (skipping pattern). 2 – 4 In particular, ALS with bulbar-onset (BO-ALS), constituting up to 25% of the ALS population, 5 is featured by initial symptoms of bulbar involvement such as dysarthria or dysphagia; and progresses more rapidly with poorer prognosis than ALS with limb-onset. 5 , 6 Thus, a full recognition of BO-ALS is indispensable in clinical practice.…”

Section: Introductionmentioning

confidence: 99%

“…[2][3][4] In particular, ALS with bulbar-onset (BO-ALS), constituting up to 25% of the ALS population, 5 is featured by initial symptoms of bulbar involvement such as dysarthria or dysphagia; and progresses more rapidly with poorer prognosis than ALS with limbonset. 5,6 Thus, a full recognition of BO-ALS is indispensable in clinical practice.…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

The rostral to caudal gradient of clinical and electrophysiological features in sporadic amyotrophic lateral sclerosis with bulbar-onset

Liao

Huang

Lai³

et al. 2020

J Int Med Res

View full text Add to dashboard Cite

Objective Amyotrophic lateral sclerosis (ALS) with bulbar-onset (BO-ALS) tends to propagate to the adjacent anatomical regions symptomatically. However, the spreading pattern of clinical and electrophysiological features is not well documented. Methods This retrospective study enrolled consecutive patients with sporadic BO-ALS. The clinical progression and electrophysiological data by electromyography examination were retrospectively analysed based on information from the medical records. Results The study enrolled 57 patients: 43 presented with contiguous (37 of 57) or non-contiguous (6 of 57) progression clinically; and 14 patients did not present with symptomatic propagation to other spinal segments. Lower motor neuron dysfunction was more frequently involved in the bulbar and cervical segments and less in the thoracic and lumbosacral segments. As a result, a small proportion of patients had intact thoracic paraspinal or leg muscles or both by electromyography examination. Furthermore, the patients with diagnostic latency ≤6 months showed a significantly lower incidence of neurogenic changes in the lumbosacral spinal cord compared with those with diagnostic latency > 6 months. Conclusion This current study demonstrated a relative rostral–caudal descending gradient of lower motor neuron dysfunction in patients with BO-ALS. These results suggest that follow-up EMG might be necessary for a proportion of patients.

show abstract

Spreading in ALS: The relative impact of upper and lower motor neuron involvement

Cited by 41 publications

References 24 publications

Disease duration of progression is helpful in identifying isolated bulbar palsy of amyotrophic lateral sclerosis

Disease duration of progression is helpful in identifying isolated bulbar palsy of amyotrophic lateral sclerosis

Triage of Amyotrophic Lateral Sclerosis Patients during the COVID-19 Pandemic: An Application of the D50 Model

The rostral to caudal gradient of clinical and electrophysiological features in sporadic amyotrophic lateral sclerosis with bulbar-onset

Contact Info

Product

Resources

About