Patterns of symptom development in patients with motor neuron disease

Abstract

Preferred spread of symptoms from one limb to the contralateral limb, and to adjacent sites appears to be a characteristic of MND phenotypes, suggesting that symptom spread is organized, possibly involving axonal connectivity. Non-contiguous symptom development, however, is not uncommon, and may involve other factors.

Genetic Convergence Brings Clarity to the Enigmatic Red Line in ALS

“…In addition, the evolution of symptoms tends to follow several intriguing patterns that may support the proposed mechanism that disease progression is mediated by propagation or spreading of pathology through anatomically connected pathways and/or neighboring regions. For example, the contralateral limb is most frequently affected next in patients with unilateral limb onset, while patients with bulbar onset typically report symptoms in the cervical region as opposed to the more distant lumbosacral region of the spinal cord (Walhout et al, 2018). There also appears to be a preferential direction of disease progression through the spinal cord, with lumbosacral involvement most often following onset in cervical regions (rostrocaudal direction) rather than bulbar region involvement following cervical onset (Figure 1) (Ravits and La Spada, 2009;Walhout et al, 2018).…”

“…For example, the contralateral limb is most frequently affected next in patients with unilateral limb onset, while patients with bulbar onset typically report symptoms in the cervical region as opposed to the more distant lumbosacral region of the spinal cord (Walhout et al, 2018). There also appears to be a preferential direction of disease progression through the spinal cord, with lumbosacral involvement most often following onset in cervical regions (rostrocaudal direction) rather than bulbar region involvement following cervical onset (Figure 1) (Ravits and La Spada, 2009;Walhout et al, 2018). Progression to non-contiguous regions of the body is observed in some patients, but most often with UMN signs, which may reflect the topography of the primary motor cortex (Ravits and La Spada, 2009;Walhout et al, 2018).…”

“…There also appears to be a preferential direction of disease progression through the spinal cord, with lumbosacral involvement most often following onset in cervical regions (rostrocaudal direction) rather than bulbar region involvement following cervical onset (Figure 1) (Ravits and La Spada, 2009;Walhout et al, 2018). Progression to non-contiguous regions of the body is observed in some patients, but most often with UMN signs, which may reflect the topography of the primary motor cortex (Ravits and La Spada, 2009;Walhout et al, 2018). Therefore, although the simultaneous involvement of UMN and LMN systems increases the complexity of tracking disease progression, the combination of rapidly evolving imaging capabilities and recent scientific discoveries will both simplify this process and provide the means to evaluate the relationship with pathological features and genetic factors.…”

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

“…Only three are prospective, 1,2,3 others rely on chart reviews, 4,5,6,7 patient self-administered questionnaire at one time point, 8 or EMG studies. 9 Only four investigators 1,5,7,8 studied the impact and distribution of UMN dysfunction on the pattern and rate of progression of the disease. All these studies, except one 6 were carried out in single centers, and none included patients with frontotemporal dementia (FTD).…”

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

“… 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.…”