Illness Cognitions in ALS: New Insights Into Clinical Management of Behavioural Symptoms.

Timely management of frontotemporal dysfunction associated with amyotrophic lateral sclerosis (ALS) has important prognostic and therapeutic implications. However, there remains a paucity of research on best practise recommendations to guide the development of interventions for cognitive and behavioural symptoms as part of ALS care. Accordingly, a focus on illness perceptions may provide a preliminary framework for managing cognitive and behavioural symptoms. The aim of the present study was to explore the nature of illness perceptions among ALS patients with cognitive and behavioural symptoms. A total of 39 patients were recruited from a specialised ALS clinic. Factor analysis showed three independent and clinically interpretable factors corresponding to "cognitive and emotion related ALS perceptions," "cognitive- specific ALS perceptions" and "ALS coherence". Of these factors, greater perceived cognitive and emotional impacts of ALS were associated with an approximate 4-fold increased risk of behavioural changes (p < 0.05). Greater perceived cognitive and emotional impacts of ALS was also associated with more rapid disease progression (p < 0.001). As such, timely provision of intervention addressing perceptions about the impact of ALS on functioning as well as associated emotional distress may optimise clinical management of cognitive and behavioural symptoms of ALS.

Apathy is associated with parietal cortical-subcortical dysfunction in ALS.

Apathy is the core behavioural feature of frontotemporal dysfunction in amyotrophic lateral sclerosis (ALS). Initiation and emotional manifestations of apathy significantly affect patients and carers, particularly in terms of quality of life. As such, the primary aim of the present study was to investigate the prevalence and neural correlates of initiation, and emotional subtypes of apathy in ALS. A total of 109 participants were recruited from a specialised, tertiary referral ALS/FTD clinic. Overall rates of apathy, including cognitive, initiation and emotion subtypes as assessed by the Dimensional Apathy Scale (DAS), were examined and correlated with brain volumes, including voxel-based morphometry on high resolution MRI. Clinically significant apathy ranged between 49% (patient-rated DAS) and 64% (carer-rated DAS), with the most common apathy subtypes being initiation (84-96%) and emotional (74-75%) apathy. The results of the two-way repeated measures ANOVA revealed significant differences across the DAS executive, emotional and initiation subscales (p = .0001). Multivariate analysis using a logistic regression model showed that only initiation; (odds ratio = 3.08, p = .004) and emotional (odds ratio = 2.40, p = .008) apathy were predictive of clinically significant apathy, controlling for education and depression. Increased initiation apathy correlated with reduced grey matter within bilateral superior frontal gyrus and increased emotional apathy correlated with reduced grey matter in prefrontal cortices and right anterior cingulate, previously implicated in apathy. Additional correlations were identified including the angular gyrus (or the temporo-parietal junction), important in reward valuation and subsequent goal-directed behaviour. Taken together, results from the present series highlight the frequency and multi-dimensionality of apathy in ALS. The pathophysiological mechanisms of apathy in ALS may be critically underpinned by neurodegeneration across a distributed brain network, with key roles in task initiation, emotion, reward processing and subsequent goal-directed behaviour.

Problem-focused coping underlying lower caregiver burden in ALS-FTD: implications for caregiver intervention.

Objective: Amyotrophic lateral sclerosis (ALS) is a multisystem neurodegenerative disorder which includes cognitive and behavioral symptoms akin to frontotemporal dementia (FTD). Despite the necessity of caregiver intervention to assist with the management of cognitive and behavioral symptoms, there has been a lack of research on the topic. A focus on caregiver coping may offer a promising foundation to guide the development of interventions as part of ALS care. Accordingly, the aim of the present study was to examine the relationships between caregiver coping, psychological morbidity and burden of care in the context of ALS cognitive and behavioral symptoms. Methods: Fifty-five patient-caregiver dyads were recruited from specialized ALS and FTD clinics. Specific coping strategies were examined using the COPE Inventory/Brief COPE and psychological morbidity and burden were assessed using the Depression, Anxiety, and Stress Scale-21 and Zarit Burden Interview. The relationship between coping, psychological morbidity and burden of care were analyzed using univariate and multivariate methods. Results: High-burden caregivers were more likely to be caring for patients with a diagnosis of ALS-FTD (p =.0001). Caregivers used problem-focused strategies (particularly planning) more frequently (M = 71.4, SD = 15.3) compared to emotion-focused (M = 60.8, SD = 12.3) and dysfunctional coping strategies (M = 42.2, SD = 8.6). A diagnosis of ALS-FTD (p=.0001) and problem-focused strategies (p=.024) emerged as significant predictors of caregiver burden. Caregiver anxiety, depression and stress were not predictive of caregiver burden (p=.151). Conclusions: Timely provision of caregiver support optimizing problem-focused coping strategies as part of multidisciplinary ALS care, particularly for caregivers of ALS-FTD patients may mitigate caregiver burden.

Motor neurone disease.

Motor neurone disease (MND) patients exhibit poor gait, balance, and postural control, all of which significantly increases their risk of falling. Falls are frequent in the MND population, and are associated with an increased burden of disease. The complex interplay of both motor and extramotor manifestations in this disease contributes to the heterogeneous and multifactorial causes of such dysfunction. This review highlights the pathophysiologic influence of motor degeneration in gait disturbance, but also the additional influence on postural instability from other inputs such as cognitive impairment, autonomic dysregulation, cerebellar dysfunction, sensory impairment, and extrapyramidal involvement. In various combinations, these impairments are responsible for reduced gait speed and alteration in gait cycle, as well as structurally more variable and disorganized gait patterns. Based on these features, this chapter will also provide disease-specific interventions to assess, manage, and prevent falls in the MND cohort.

The burden of apathy for caregivers of patients with amyotrophic lateral sclerosis.

OBJECTIVES: Apathy is the most common behavioral symptom of amyotrophic lateral sclerosis (ALS). Despite its known impact on caregiver wellbeing, apathy is typically considered a unitary construct making assessment and targeting treatment problematic. The aim of this study was to explore the relationship between caregiver burden and the behavioral, cognitive, and emotional symptoms of apathy in ALS. METHODS: Fifty-one ALS patient-caregiver dyads from an ALS/frontotemporal dementia Clinic were assessed with the Apathy Evaluation Scale which measured the cognitive, behavioral, emotional, and nonspecific symptoms of apathy as well as the Zarit Burden Interview, a measure of perceived burden among caregivers of cognitively impaired older adults. The relationship between apathy and caregiver burden were analyzed using univariate and multivariate methods. RESULTS: Apathy was identified in 18% of ALS patients. Greater behavioral (p = 0.011) and nonspecific (p = 0.010) symptoms of apathy exhibited by patients were reported by caregivers with higher levels of burden compared to caregivers with lower levels of burden. Of the cognitive, behavioral, emotional, and nonspecific symptoms of apathy, only the behavioral symptoms explained a significant amount of variance in caregiver burden (p = 0.031). CONCLUSIONS: Apathy, specifically the behavioral symptoms of apathy was associated with higher burden of care among ALS caregivers, highlighting the importance of multidimensional assessment of apathy and provision of behavior management support as part of ALS care.

Primary lateral sclerosis and the amyotrophic lateral sclerosis-frontotemporal dementia spectrum.

AIM: To investigate whether primary lateral sclerosis (PLS) represents part of the amyotrophic lateral sclerosis-frontotemporal dementia (ALS-FTD) spectrum of diseases. METHODS: Comprehensive assessment was taken on 21 patients with PLS and results were compared to patients diagnosed with pure motor ALS (n = 27) and ALS-FTD (n = 12). Clinical features, Addenbrooke's Cognitive Examination (ACE) scores, Motor Neuron Disease Behaviour (Mind-B) scores, motor disability on the ALS functional rating scale (ALSFRS) and survival times were documented. Motor cortex excitability was evaluated using transcranial magnetic stimulation (TMS). RESULTS: Global cognition was impaired in PLS (mean total ACE score 82.5 ± 13.6), similar to ALS-FTD (mean total ACE score 76.3 ± 7.7, p > 0.05) while behavioural impairments were not prominent. TMS revealed that resting motor threshold (RMT) was significantly higher in PLS (75.5 ± 6.2) compared ALS-FTD (50.1 ± 7.2, p < 0.001) and ALS (62.3 ± 12.6, p = 0.046). Average short-interval intracortical inhibition (SICI) was similar in all three patient groups. The mean survival time was longest in PLS (217.4 ± 22.4 months) and shortest in ALS-FTD (38.5 ± 4.5 months, p = 0.002). Bulbar onset disease (ß = - 0.45, p = 0.007) and RMT (ß = 0.54, p = 0.001) were independent predictors of global cognition while motor scores (ß = 0.47, p = 0.036) and SICI (ß = 0.58, p = 0.006) were significantly associated with ALSFRS. CONCLUSION: The cognitive profile in PLS resembles ALS-FTD, without prominent behavioural disturbances. A higher RMT in PLS than ALS and ALS-FTD is consistent with differential cortical motor neuronal abnormalities and more severe involvement of corticospinal axons while SICI, indicative of inhibitory interneuronal dysfunction was comparable with ALS and ALS-FTD. Overall, while these findings support the notion that PLS lies on the ALS-FTD spectrum, the mechanisms underlying slow disease progression are likely to be distinct in PLS.

Amyotrophic lateral sclerosis.

Amyotrophic lateral sclerosis (ALS) is an idiopathic, fatal neurodegenerative disease of the human motor system. In this Seminar, we summarise current concepts about the origin of the disease, what predisposes patients to develop the disorder, and discuss why all cases of ALS are not the same. In the 150 years since Charcot originally described ALS, painfully slow progress has been made towards answering these questions. We focus on what is known about ALS and where research is heading-from the small steps of extending longevity, improving therapies, undertaking clinical trials, and compiling population registries to the overarching goals of establishing the measures that guard against onset and finding the triggers for this neurodegenerative disorder.

How common are behavioural changes in amyotrophic lateral sclerosis?

Our objectives were to assess the frequency of behavioural changes in patients with amyotrophic lateral sclerosis (ALS) and to compare the clinical profile of ALS patients with those with behavioural variant frontotemporal dementia (bvFTD). Ninety-two patients with ALS and their carers participated in a postal survey. ALS patients completed self-report measures of motor function and mood. Eighty-one carers of ALS patients and 25 carers of bvFTD patients completed the revised version of the Cambridge Behavioural Inventory (CBI-R). Results showed that reduced motivation was reported in more than 80% of the ALS cases, with almost 41% of them having moderate-severe apathy. Depression was present in 30% of ALS patients and did not contribute significantly to the presence of behavioural symptoms. Bulbar and limb onset ALS patients did not differ. Abnormal behaviour and stereotypical and motor behaviours were present to a moderate-severe degree in around 20%, and 11% reached the criteria for FTD. The rate of behavioural symptoms was significantly higher in the bvFTD group than ALS in all behavioural domains (p <0.001). In conclusion, apathy was the most prominent feature in ALS patients. A substantial proportion of ALS patients manifested behavioural changes of the type seen in FTD, with 11% fulfilling the criteria for FTD.