Association of Clinically Evident Eye Movement Abnormalities With Motor and Cognitive Features in Patients With Motor Neuron Disorders

Poletti, Barbara; Solca, Federica; Carelli, Laura; Diena, A.; Colombo, Eleonora; Torre, Silvia; Maranzano, Alessio; Greco, Lucia Catherine; Cozza, Federica; Ferrucci, Roberta; Girotti, F.; Verde, Federico; Morelli, Claudia; Lunetta, Christian; Silani, Vincenzo; Ticozzi, Nicola

doi:10.1212/wnl.0000000000012774

Cited by 17 publications

(27 citation statements)

References 36 publications

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“…As to patients primarily diagnosed with FTD, such findings are unsurprising: indeed, it is unlikely that, in the presence of such a cortical pathology, UMNs are less involved than LMNs ( McKenna et al, 2021 ). Conversely, as to primarily MND patients, these results align with recent evidence on extra-motor cortical burden being greater when UMNs are involved ( Poletti et al, 2021 ; Sbrollini et al, 2021 ; Aiello et al, 2022 ; Maranzano et al, 2022 ).…”

Section: Discussionsupporting

confidence: 86%

Primary progressive aphasia and motor neuron disease: A review

Aiello

Feroldi

Luca

et al. 2022

Front. Aging Neurosci.

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BackgroundThis study aims at reviewing, within the framework of motor neuron disease-frontotemporal degeneration (MND-FTD)-spectrum disorders, evidence on the co-occurrence between primary progressive aphasia (PPA) and MND in order to profile such a complex at pathological, genetic and clinical levels.MethodsThis review was pre-registered (osf.io/ds8m4) and performed in accordance with the 2020 PRISMA guidelines. Case reports/series and group studies were included if addressing (1) progressive non-fluent aphasia (PNFA) or semantic dementia (SD) with MND or (2) MND patients with co-morbid PNFA/SD.ResultsOut of 546 initial records, 56 studies were included. As to case reports/series (N = 35), which included 61 PPA-MND patients, the following findings yielded: (1) PNFA is more frequent than SD in PPA-MND; (2) in PPA-MND, the most prevalent motor phenotypes are amyotrophic lateral sclerosis and predominant-upper MND, with bulbar involvement being ubiquitous; (3) extrapyramidal features are moderately frequent in PPA-MND; (4) PPA-MND patients usually display frontotemporal, left-greater-than-right involvement; (5) TDP-43-B is the typical pathological substrate of PPA-MND; (6) TBK1 mutations represent the most frequent genetic risk factors for PPA-MND.As to group studies, including 121 patients, proportional meta-analytic procedures revealed that: (1) the lifetime prevalence of MND in PPA is 6%; (2) PPA occurs in 19% of patients with co-morbid MND and FTD; (3) MND is more frequent in PNFA (10%) than in SD patients (3%).DiscussionInsights herewith delivered into the clinical, neuropathological and genetic features of PPA-MND patients prompt further investigations aimed at improving clinical practice within the MND-FTD spectrum.

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Section: Discussionsupporting

confidence: 86%

Primary progressive aphasia and motor neuron disease: A review

Aiello

Feroldi

Luca

et al. 2022

Front. Aging Neurosci.

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“…Furthermore, albeit regarding a small number of patients and without reaching the threshold of statistical significance, our data suggest an additional link between sGFAP increase and non‐classical phenotypic manifestations of ALS, namely eye movement abnormalities. Notably, these latter have been recently shown by our group to be in turn associated with cognitive impairment itself 27 . Similarly to the neuropsychological aspect, also in this case it may be hypothesized that astrocytes are involved in neurodegeneration occurring in brain areas other than the main targets of ALS pathology, namely the frontal and supplementary eye fields of the cerebral cortex.…”

Section: Discussionmentioning

confidence: 76%

“…Notably, these latter have been recently shown by our group to be in turn associated with cognitive impairment itself. 27 Similarly to the neuropsychological aspect, also in this case it may be hypothesized that astrocytes are involved in neurodegeneration occurring in brain areas other than the main targets of ALS pathology, namely the frontal and supplementary eye fields of the cerebral cortex. Finally, the correlation with polysomnographic indices suggests a possible specific connection between astrocyte pathology and degeneration of MNs controlling respiratory muscles.…”

Section: Discussionmentioning

confidence: 99%

Serum levels of glial fibrillary acidic protein in patients with amyotrophic lateral sclerosis

Verde

Milone

Maranzano

et al. 2022

Ann Clin Transl Neurol

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Objective To compare serum levels of the astrocyte biomarker glial fibrillary acidic protein (GFAP) in patients with amyotrophic lateral sclerosis (ALS) and neurologically healthy controls and to analyze the relations between serum GFAP (sGFAP) and phenotype in ALS. Methods We studied 114 ALS patients and 38 controls. sGFAP was quantified with single molecule array (Simoa) technology. Results In both ALS patients and controls, sGFAP moderately correlated with age. ALS patients had higher sGFAP levels compared to controls, but this yielded a weak discriminative performance (AUC = 0.6198). In ALS, sGFAP was not associated with most of the motor phenotypic features, including site of onset, functional status, disease progression rate, disease stage, and indices of upper (UMN) and lower motor neuron (LMN) impairment. However, sGFAP negatively correlated with cognitive scores regarding ALS‐nonspecific functions, particularly memory ( r = −0.2082) and tended to be higher in ALS patients with eye movement abnormalities ( p = 0.0628). sGFAP also correlated with polysomnographic indices of oxygen desaturation (ODI; r = 0.2639) and apnea‐hypopnea (AHI; r = 0.2858). In a multivariate analysis, sGFAP was negatively associated with survival (HR = 1.005). Relevantly, we found a negative correlation between sGFAP and estimated glomerular filtration rate (eGFR; r = −0.3500). Interpretation Our work provides neurochemical evidence of astrocyte involvement in ALS pathophysiology and particularly in the development of extra‐motor manifestations (namely, cognitive – memory – impairment) and respiratory dysfunction. The negative correlation between sGFAP and eGFR has practical relevance and should not be disregarded in future investigations.

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“…The evaluation of ocular movements included examinations of slow pursuit movement and ocular saccade speed with the vertical and horizontal gaze. Vertical ophthalmoplegia and slow saccade (slow eye movement) were the most common abnormalities [37,38]. Total quadriplegia indicated a failure to demonstrate visible muscle movements of the limbs.…”

Section: Assessmentmentioning

confidence: 99%

Body Weight Gain Is Associated with the Disease Stage in Advanced Amyotrophic Lateral Sclerosis with Invasive Ventilation

et al. 2022

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We investigated the incidence of weight gain and its related factors in patients with amyotrophic lateral sclerosis (ALS) who underwent tracheostomy and invasive ventilation (TIV). Seventy-eight patients with ALS and TIV were enrolled and followed up prospectively. We clarified the clinical profiles of patients with increased weight following TIV and examined chronological variations in their body mass index (BMI), energy intake, and serum albumin levels. Post follow-up, we determined their disease stage according to their communication impairment (stage I to V) and investigated factors associated with BMI increase following TIV. Patients with a post-TIV BMI increase ≥1.86 kg/m2 demonstrated a higher incidence of ophthalmoplegia (76.2%), total quadriplegia (61.9%), severe communication impairment (stage V; 33.3%), and hypoalbuminemia than those with a BMI increase <1.86 kg/m2. Patients with stage V communication impairment exhibited a larger and faster BMI decrease before TIV (mean −4.2 kg/m2 and −2.5 kg/m2/year, respectively); a larger BMI increase (mean +4.6 kg/m2) following TIV, despite lower energy intake; and lower albumin levels post follow-up than those with lower-stage communication impairment. Multilevel linear regression analysis demonstrated an independent association between communication impairment stages (stage V) and a post-TIV BMI increase (p = 0.030). Weight gain and hypoalbuminemia during TIV in patients with ALS were associated with the disease stage and may be attributable to the neurodegenerative processes that are peculiar to ALS.

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Association of Clinically Evident Eye Movement Abnormalities With Motor and Cognitive Features in Patients With Motor Neuron Disorders

Cited by 17 publications

References 36 publications

Primary progressive aphasia and motor neuron disease: A review

Primary progressive aphasia and motor neuron disease: A review

Serum levels of glial fibrillary acidic protein in patients with amyotrophic lateral sclerosis

Body Weight Gain Is Associated with the Disease Stage in Advanced Amyotrophic Lateral Sclerosis with Invasive Ventilation

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