Cognitive impairment in motor neuron disease with bulbar onset

Motor neuron disease (MND) is a neurodegenerative disorder which leads to progressive muscle weakness including respiratory muscle decline. The introduction of non-invasive ventilation (NIV) has been shown to improve quality of life, survival and slow the rate of pulmonary function decline. A retrospective chart analysis of patients who attended the MND clinic from 2014 to 2019 at a tertiary-referral, academic, teaching hospital was carried out to evaluate if NIV and greater compliance with NIV was associated with improved survival. 111 patients were included. The mean age at diagnosis was 63.8 years and 61.3% were males. 66.7% of our cohort used NIV and of this 66.7%, 44.1% were compliant. There was a significantly longer survival in those who used NIV ( p = 0.002) and in those who used NIV optimally ( p = 0.02) when both groups were compared to those who did not use NIV. In the bulbar MND group those who were compliant with NIV survived longer than who those who did not use NIV ( p = 0.001). We found a significantly longer survival with the use of NIV, the use of NIV optimally and with use of NIV in those with bulbar onset MND compared to those who did not use NIV.

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042 Respiratory function and cognitive profile in motor neuron disease

Journal of Neurology Neurosurgery & Psychiatry ◽

10.1136/jnnp-2019-anzan.38 ◽

2019 ◽

Vol 90 (e7) ◽

pp. A14.2-A14

Author(s):

William Huynh ◽

Lara E Sharplin ◽

Jashelle Caga ◽

Elizabeth Highton-Williamson ◽

Matthew C Kiernan

Keyword(s):

Cognitive Impairment ◽

Cognitive Function ◽

Motor Neuron ◽

Motor Neuron Disease ◽

Respiratory Function ◽

Normal Function ◽

Cognitive Testing ◽

Respiratory Compromise ◽

Respiratory Dysfunction ◽

Non Invasive Ventilation

IntroductionMotor neuron disease (MND) is increasingly recognised as a multisystems disorder with 30–50% of patients having mild to moderate cognitive impairment. Mechanisms of cognitive dysfunction in MND are multifactorial but chronic hypoxia secondary to respiratory dysfunction may contribute to cognitive decline in patients.ObjectivesThe current study aimed to identify the relationship between respiratory function in MND patients and the presence and degree of cognitive impairment.MethodsMND patients were prospectively recruited from a multidisciplinary MND clinic. Patients meeting the criteria for frontotemporal dementia were excluded. Baseline clinical assessments including respiratory function as assessed by spirometry were recorded with FVC ≤ 75% considered to have reduced respiratory function. Cognitive testing was performed utilising the Addenbrooke’s Cognitive Examination (ACE).ResultsFrom a cohort of 100 MND patients 48% were categorised as having impaired respiratory function whilst 52% had normal function. Compared to the group with normal respiratory function (ACE: 86.83±1.5), patients with respiratory dysfunction had significantly reduced cognitive function (ACE: 90.68±0.89, P=0.025). Subscores demonstrated significant differences between the groups with respect to domains in memory, attention with a trend observed in fluency. There was a significant correlation between FVC and ACE scores as well as between FVC and memory and fluency subscores (P<0.01).ConclusionMND patients with respiratory compromise were more likely to develop reduced cognitive function. In addition to improving physical function, it remains plausible that non-invasive ventilation may alter the progression of cognitive impairment in MND patients, thereby potentially improving their overall quality of life and carer burden.

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Cognitive impairment in motor neuron disease

Acta Neurologica Scandinavica ◽

10.1111/j.1600-0404.1985.tb03231.x ◽

2009 ◽

Vol 71 (6) ◽

pp. 480-484 ◽

Cited By ~ 76

Author(s):

R. Gallassi ◽

P. Montagna ◽

C. Ciardulli ◽

S. Lorusso ◽

V. Mussuto ◽

...

Keyword(s):

Cognitive Impairment ◽

Motor Neuron ◽

Motor Neuron Disease

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PATH47 Slow saccades in bulbar-onset motor neuron disease

Journal of Neurology Neurosurgery & Psychiatry ◽

10.1136/jnnp.2010.226340.15 ◽

2010 ◽

Vol 81 (11) ◽

pp. e20-e20 ◽

Cited By ~ 1

Author(s):

C. Donaghy

Keyword(s):

Motor Neuron ◽

Motor Neuron Disease ◽

Bulbar Onset ◽

Slow Saccades

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Apolipoprotein E ɛ4 in bulbar-onset motor neuron disease

The Lancet ◽

10.1016/s0140-6736(05)64502-3 ◽

1996 ◽

Vol 348 (9023) ◽

pp. 334-335 ◽

Cited By ~ 25

Author(s):

R Glenn Smith ◽

Lanny J Haverkamp ◽

Susan Case ◽

Vicki Appel ◽

Stanley H Appel

Keyword(s):

Apolipoprotein E ◽

Motor Neuron ◽

Motor Neuron Disease ◽

Bulbar Onset

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021 Clinical implications of cortical dysfunction in motor neuron disease: a combined structural and functional approach

Journal of Neurology Neurosurgery & Psychiatry ◽

10.1136/jnnp-2018-anzan.21 ◽

2018 ◽

Vol 89 (6) ◽

pp. A9.3-A10

Author(s):

Thanuja Dharmadasa ◽

Neil G Simon ◽

Chenyu Wang ◽

Steve Vucic ◽

Matthew C Kiernan

Keyword(s):

Motor Cortex ◽

Motor Neuron ◽

Motor Neuron Disease ◽

Disease Progression ◽

Diffusion Tensor ◽

Statistical Parametric Mapping ◽

Functional Approach ◽

Cerebral White Matter ◽

Bulbar Onset ◽

Cortical Dysfunction

IntroductionMotor neuron disease (MND) is characterised by progressive failure of upper (UMN) and lower motor neurons (LMN). UMN dysfunction remains difficult to detect clinically, and the influence of cortical change on disease progression and prognosis remains unclarified. This study quantitatively assessed cortical dysfunction in vivo using a novel combined structural and functional approach.MethodsForty-one newly diagnosed MND patients and 30 controls prospectively underwent 3T diffusion tensor magnetic resonance imaging (DTI) to assess cerebral white matter structural integrity. DTI measures including apparent diffusion coefficient (ADC) and functional anisotropy (FA) were analysed using statistical parametric mapping. Threshold tracking transcranial magnetic stimulation (TT-TMS) studies were additionally performed across all four limbs to concurrently assess the functional integrity of the motor cortex. All patients underwent detailed clinical and cognitive assessment.ResultsCortical abnormalities were prominent, with FA significantly reduced (p<0.01) and ADC enhanced (p<0.03) along the primary motor tracts in all MND patients, suggestive of primary axonal degeneration. These changes correlated with clinical function and disease duration. TT-TMS revealed evidence of cortical hyper-excitability over the motor cortex corresponding with clinical site-of-onset (p<0.05). Structural (FA) and functional (cortical hyper-excitability) changes correlated across all extremities. Patients without clinical UMN signs also showed evidence of UMN dysfunction, identifying subclinical change. Subgroup analysis identified the greatest changes in bulbar-onset patients (p<0.03).ConclusionThis multimodal technique identified UMN dysfunction in patients prior to clinically detectable change, which may contribute to earlier diagnosis. More significant cortical involvement in bulbar-onset patients aligns with their poorer survival, highlighting the cortically driven determination of clinical progression and prognosis. Further clinical translation of such patterns may therefore lend insight into pathophysiological disease mechanisms and may influence stratification for clinical trials. Overall, this can serve as a robust biomarker for earlier diagnosis, disease progression and prognosis.

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

Neurology ◽

10.1212/wnl.0000000000012774 ◽

2021 ◽

pp. 10.1212/WNL.0000000000012774

Author(s):

Barbara Poletti ◽

Federica Solca ◽

Laura Carelli ◽

Alberto Diena ◽

Eleonora Colombo ◽

...

Keyword(s):

Cognitive Impairment ◽

Motor Neuron ◽

Eye Movement ◽

Cognitive Behavioral ◽

Cognitively Impaired ◽

Clinical Markers ◽

Behavioral Alterations ◽

Neuropsychological Battery ◽

Bulbar Onset ◽

Als Patients

Objective:Although oculomotor abnormalities (OMAs) are not usually considered prominent features of amyotrophic lateral sclerosis (ALS), they may represent potential clinical markers of neurodegeneration, especially when investigated together with cognitive and behavioral alterations. The aim of our study was to identify patterns of clinically evident OMAs in ALS patients and to correlate such findings with cognitive-behavioral data.Methods: three consecutive, inpatient cohorts of Italian ALS patients and controls were retrospectively evaluated to assess the frequency of OMAs and cognitive-behavioral alterations. The ALS population was divided in a discovery and a replication cohort. Controls included a cohort of cognitively impaired individuals and of patients with Alzheimer’s disease (AD). Subjects underwent bedside eye movement evaluation to determine the presence and pattern of OMAs. Cognitive assessment was performed using a standard neuropsychological battery (discovery ALS cohort, and AD cohort), and the Italian Edinburgh Cognitive and Behavioural ALS Screen – ECAS (replication ALS cohort).Results:We recruited 864 ALS (635 discovery, 229 replication), 798 cognitively unimpaired, and 171 AD subjects. OMAs were detected in 10.5% of our ALS cohort vs 1.6% of cognitively unimpaired controls (p=1.2x10-14) and 11.4% of AD patients (p=ns). The most frequent deficits were smooth pursuit and saccadic abnormalities. OMAs frequency was higher in patients with bulbar onset, prominent upper motor neuron signs, and advanced disease stages. Cognitive dysfunction was significantly more frequent in patients with OMAs in both ALS cohorts (p=1.1x10-25). Furthermore, OMAs significantly correlated with the severity of cognitive impairment and with pathological scores at the ECAS ALS-specific domains. Lastly, OMAs could be observed in 35.0% of cognitively impaired ALS vs 11.4% of AD patients (p=6.4x10-7), suggesting a possible involvement of frontal oculomotor areas in ALS.Discussion:ALS patients showed a range of clinically evident OMAs, and these alterations were significantly correlated with cognitive, but not behavioral, changes. OMAs may be a marker of neurodegeneration and bedside assessment represents a rapid, highly specific tool for detecting cognitive impairment in ALS.

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