P35 UTILITY OF A BRIEF SCREENING PROTOCOL TO IDENTIFY COGNITIVE AND BEHAVIORIAL ABNORMALITIES IN ALS PATIENTS
Murphy J, Julian L, Lomen‐Hoerth C
San Francisco, USA
E‐mail address for correspondence: [email protected]
Obejctives: To evaluate the utility of a brief screening battery to be used in ALS clinics for the purpose of identifying patients with cognitive and behavioral abnormalities, issues that significantly affect clinical management and decision‐making regarding long‐term ventilation.
Background: ALS patients were once thought to be cognitively intact with the exception of a small number of patients with frontotemporal dementia (FTD). Substantial evidence now demonstrates that approximately half of ALS patients display a continuum of frontal lobe based cognitive and behavioral abnormalities, with some patients having mild to moderate behavioral problems that do not meet the threshold for FTD (ALS behaviorally impaired, ALSbi), others with cognitive dysfunction (ALS cognitively impaired, ALSci), and a third group that meets full criteria for FTD (ALS‐FTD). Busy, interdisciplinary clinics frequently lack the resources to conduct thorough neuropsychological evaluations.
Methods: Thirty‐two patients who met WFN criteria for the diagnosis of ALS underwent a 20‐minute screening battery consisting of the Abrahams verbal fluency test or FAS fluency test, the Frontal Behavioral Inventory, the Neuropsychiatric Inventory Questionnaire version (NPI‐Q), the CNS‐LS, and the Beck Depression Inventory‐II.
Results: Of 32 patients studied, 20 (63%) scored in the abnormal range on the Frontal Behavioral Inventory, as indicated by a score of above 30. Most frequently endorsed items on the FBI were irritability, inflexibility, apathy, restlessness, and logopenia. Four patients (13%) scored in the abnormal range on the NPI‐Q, most frequently endorsing depression, anxiety, and night‐time behaviors. Eight patients (25%) scored in the impaired range on verbal fluency, as indicated by an impaired score on the FAS or 1.5 SD below the group mean on the Abrahams Verbal Fluency Test. Five of the eight patients scoring abnormally on verbal fluency also scored abnormally on behavioral measures. Depression, pseudobulbar affect, FVC, age, and ALSFRS‐R scores were not statistically correlated with behavioral measures.
Conclusions: This simple screening battery appears to be sensitive in identifying abnormalities in this population. The Frontal Behavioral Inventory is a more sensitive measure of behavioral problems than the NPI‐Q. The traditional FBI cut‐off may, in fact, be overly inclusive, as it identified nearly two‐thirds of the sample as having behavioral problems. The NPI‐Q, in contrast, identified 13% of patients as having moderate severity problems in at least two areas (>12). Verbal fluency deficits were observed in 25% of these patients, which is a rate consistent with the literature. Of these patients with verbal fluency deficits, approximately half had comorbid behavior problems, suggesting that cognitive and behavioral problems among ALS patients are not always co‐occurring. Sound judgment and organizational planning skills are particularly necessary cognitive abilities to make critical decisions in long‐term care for ALS patients (e.g. ventilation, PEG tube). Patients and family members may benefit from a brief assessment to identify potential difficulties in making such decisions. Counselling may also inform family members and patients about how behavioral and personality changes affect family relationships and the patient's ability to comply with treatment recommendations.
P36 THE RELATIONSHIP BETWEEN FRONTAL BEHAVIORIAL AND COGNITIVE CHANGES IN ALS
Mosnik DM1, York M1, Pinto‐Patarroyo GP1, Witgert M2, Brasdshaw M1, Schulz PE1
1Baylor College of Medicine, Houston, TX, USA, 2University of Houston, Houston, TX, USA
E‐mail address for correspondence: [email protected]
Background: It is estimated that 51% of amyotrophic lateral sclerosis (ALS) patients exhibit at least a mild cognitive dysfunction throughout the course of their disease, with 15% of these patients meeting criteria for frontotemporal dementia (FTD) (1). However, the frontal behavioral changes that may be associated with ALS have not been well described. Clinical observation suggests that patients with ALS tend to be particularly ‘nice’, and they also may exhibit behavioral changes similar to those seen in FTD patients including apathy, disinhibition and/or executive dysfunction. These changes can affect patients' daily activities and increase caregiver's burden and distress (2).
Objective: Our objective is to determine the prevalence and patterns of frontal behavioral changes and their relation to cognitive impairment in ALS patients.
Methods: In 225 patients with diagnoses of probable or definite ALS by El Escorial criteria, we administered a comprehensive neuropsychological evaluation and the caregivers completed the Frontal Systems Behavior Scale (FrsBe)(3). The population was divided into three subgroups based on cognitive assessment outcome: cognitively intact, mild cognitive impairment and moderate to severe cognitive impairment. The behavioral areas evaluated by the FrsBe test are: apathy, disinhibition and executive dysfunction. The data were analysed by comparing the FrsBe results in the three groups using an ANOVA test.
Results: Using FrsBe cut‐off scores, behavioral dysfunction was found in 24.4% of ALS patients. Caregivers reported that apathy was the most prevalent frontal behavior symptom (31%), but a high prevalence of executive dysfunction (19.6%) and disinhibition (16.9%) was also reported. ALS patients with greater cognitive impairment exhibited greater behavioral dysfunction.
Conclusions: There is a high prevalence of frontal behavioral symptoms reported in patients with ALS. Caregivers report that apathy is the most prevalent behavioral symptom in patients with ALS, but disinhibition and executive dysfunction are also present. Cognitive impairment and behavioral changes may be two manifestations of the same pathologic process in patients with ALS. Future research should investigate the degree of behavioral change demonstrated in ALS patients following diagnosis.
References
- Ringholz GM, et al. Neurology 2005;65:586–90.
- Hecht MJ, et al. Palliat Med. 2003;17:327–33.
- Grace J, Malloy PF. Professional Manual. 2001.
P37 WHAT IS THE BEST BEDSIDE TEST TO SCREEN FOR COGNITIVE IMPAIRMENT IN ALS?
Woolley‐Levine S, Miller R, Katz J
Forbes Norris ALS Center, San Francisco, CA, USA
E‐mail address for correspondence: [email protected]
Background: The diagnosis of cognitive impairment (CI) in ALS has relied on detailed neuropsychological assessments. This methodology requires several hours and may be impractical where neuropsychologists are not available. Some centers utilize a strategy of screening with a single measure, often letter fluency, and perform detailed testing on patients who fall below a specific cut‐off. It is important to understand how practical this screening strategy is and whether any bedside measure can predict overall CI.
Objectives: To determine how well specific cognitive and behavioral measures predict CI in ALS.
Methods: Neuropsychological assessments were performed on 55 patients at a multidisciplinary ALS center. Patients with major depressive disorders or other neurologic conditions affecting cognition were excluded. Patients completed three to five individual measures and CI was considered present in patients with scores of 1.5 or more standard deviations below the mean on two or more measures. Caregivers completed a behavioral questionnaire (FrSBe). We used logistic regression to determine which measures correlated best with our definition of CI. Then, a classification model using ROC analyses was performed on measures correlating with CI at or below p = 0.10 to determine which test predicts impairment with the fewest errors (greatest diagnostic accuracy) based on a specific cut‐off. Stepwise backwards logistic regression was performed to find combinations of tests that improve the performance of any single measure.
Results: Forty‐nine per cent of patients met criteria for CI. CI did not correlate significantly with demographic or disease‐related variables (age, gender, FVC, ALS‐FRS score, site of onset). Four neuropsychological tests correlated with overall CI by logistic regression (Trail Making Test, (p = 0.004), Letter Fluency (p = 0.029), Design Fluency (p = 0.030) and Digit Span (p = 0.031)). The executive dysfunction subscale of the FrSBe approached significance (p = 0.052). Once the predictors were identified, subsequent analysis using ROC classification showed that Letter Fluency made the fewest errors in predicting CI (accuracy, 77%; specificity, 73%; sensitivity, 80%). The performance was not improved by additional information. The Trail Making Test had the second highest accuracy (accuracy 71%, specificity 89%, sensitivity 50%).
Discussion and conclusions: This is, to our knowledge, the first study to systematically assess the utility of specific bedside neuropsychological measures as a cognitive screen in ALS. Letter fluency is the best measure for predicting CI in ALS according to our model, supporting its role as a screening tool. This simple bedside test improves the prediction over the roughly 50% prior probability at baseline and alerts clinicians to probable cognitive impairment. The Trail Making test may be of value for patients who cannot complete verbal fluency measures.
P38 UTILITY OF THE FRONTAL SYSTEMS BEHAVIOR SCALE (FRSBE) IN THE ASSESSMENT OF NEURO BEHAVIORAL SYMPTOMS IN ALS
Grossman A1, Woolley‐Levine S2, Bradley W1
1University of Miami Miller School of Medicine, Miami, FL, USA, 2Forbes Norris ALS Research Center, San Francisco, CA, USA
E‐mail address for correspondence: [email protected]
Background: The behavioral disturbances involving personal and social conduct that are initial symptoms of frontotemporal dementia (FTD) may not be detected using a traditional neuropsychological test battery. Behavioral screening measures may be more effective in detecting these early symptoms of FTD in patients with ALS.
Objectives: To examine the utility of the Family Rating form of the FrSBe in assessing behavioral changes in patients with ALS.
Methods: Forty‐five patients from the Kessenich Family MDA ALS Center at the University of Miami Miller School of Medicine (n = 20) and the Forbes Norris ALS Research Center in San Francisco (n = 25) participated in this study. Caregivers completed the Family Rating Form of the FrSBe providing ratings of patients' behavioral functioning (i.e. apathy, disinhibition, executive dysfunction) pre‐ and post‐illness onset. Patients received neurological examinations including forced vital capacity testing and the ALS Functional Rating Scale (ALSFRS). All ALS patients were administered verbal fluency measures and Miami patients underwent more comprehensive neuropsychological testing.
Results: Results of paired t‐tests indicated that caregivers reported significant changes in patients' levels of apathy from pre‐ to post‐illness onset (p<0.01, Miami and p<0.001, San Francisco). After ALS onset, 56% of patients had clinically significant ratings on the Apathy scale (T>65 ⩾94th percentile). Clinically significant changes were noted in disinhibition and executive dysfunction, but did not reach significance at both centers. Although behavioral ratings were not associated with most of the disease‐related factors assessed, ALS patients with bulbar onset disease had significantly higher post‐illness Apathy scores than did those with limb onset disease (F = 4.86, p<0.05). The severity of current bulbar symptoms was not associated with post‐illness Apathy scores. Behavioral ratings on the FrSBe were associated with performance on neuropsychological testing. Post‐illness Apathy predicted performance on verbal fluency tests (p<0.03). Additional neuropsychological testing of Miami patients revealed that disinhibition was associated with performance on visual spatial tasks (p<0.001), and executive dysfunction was associated with short delay verbal recall (p<0.05).
Discussion and conclusions: The FrSBe is a useful tool for assessing behavioral change in patients with ALS. It is quickly completed by a caregiver and scored. The behavioral changes observed in this study occurred independently of mood and physical disease parameters, suggesting an underlying, organic neurodegeneration. Caregiver rating scales may provide useful information about cognitive functioning even if patients are physically unable to complete formal neuropsychological testing. Future investigations should compare the FrSBe with other measures of neurobehavioral symptoms such as the Neuropsychiatric Inventory (NPI) and Frontal Behavioural Inventory (FBI).
P39 COGNITIVE SCREENING IN AN ALS CLINIC
Haring K, Statland JM, Wang YX, Herbelin L, Brown E, McVey AL, Holt V, Walsh M, Gronseth G, Burkett D, Burns J, Barohn RJ
University of Kansas Medical Center, Kansas City, KS, USA
E‐mail address for correspondence: [email protected]
Background: Frontotemporal dementia is increasingly being recognized as a component of the disease process affecting patients with amyotrophic lateral sclerosis (ALS). There is still debate about the best methods for screening ALS patients for early signs of cognitive impairment.
Objectives: To compare the results of three, simple cognitive screening tests (Verbal Fluency, Trail Making A, and Trail Making B) in consecutive ALS patients. Outcomes were correlated with ALS phenotype (limb, bulbar, mixed bulbar/limb), markers of disease progression (ALSFRS), and the Beck's Depression Rating Scale.
Methods: Forty‐eight patients (22 females and 26 males) diagnosed with ALS were recruited from our multidisciplinary ALS Clinic. All tests were performed during the routine ALS clinic visit. Abnormal cognitive tests were defined as: Verbal Fluency <12 words in 60 seconds; Trail Making A >40 seconds; and Trail Making B >120 seconds. Failure to perform or complete any test was considered abnormal. Comparisons between different groups were made using Student's t‐test.
Results: Our study group consisted of 21 limb ALS, 15 bulbar ALS, and 12 mixed bulbar/limb ALS. For the total population, the average age was 60.6 (range 32–89), and did not differ significantly across subtype. Overall Verbal Fluency was abnormal in 56.3% of the total population; Trail Making A in 54.2%; and Trail Making B in 39.6%. In patients with bulbar ALS, Verbal Fluency was abnormal in 73.3%, Trail Making A in 66.7% and Trail Making B in 66.7%. In patients with limb ALS, Verbal Fluency was abnormal in 52.4%, Trail Making A in 42.9%, Trail Making B in 23.8%. In mixed bulbar/limb ALS, Verbal Fluency was abnormal in 41.7%, Trail Making A in 58.3%, Trail Making B in 33.3%. Twenty‐nine per cent of the total population had abnormal values on all three tests. By phenotype, 46.7% of bulbar ALS failed all three tests; 19.0% of limb and 25.0% of mixed limb/bulbar ALS. Using the raw scores, there were no significant differences between subtypes on the Trail Making A and Trail Making B, the ALSFRS, or Beck's Depression Scale.
Discussion: All three tests are potentially useful for screening cognitive abnormalities in ALS patients in the clinic. However, in this pilot study, we found that bulbar patients were more likely to have abnormal scores on all three tests than limb or mixed bulbar/limb patients. It is difficult to determine whether abnormal results are secondary to motor weakness or true frontal executive function impairment. In addition, full neuropsychological testing is needed to confirm dementia in patients who fail screening tests. Future studies are needed to determine which screening test is most sensitive for detecting early cognitive impairment in different ALS subtypes.
P40 IS FACE RECOGNITION SELECTIVELY IMPAIRED FOR NEGATIVE EMOTIONS IN AMYOTROPHIC LATERAL SCLEROSIS?
Lulé D, Altintas E, Kassubek J, Ludolph AC
Department of Neurology, Section of Neurophysiology, Ulm, Germany
E‐mail address for correspondence: [email protected]
Background: Extra‐motor structural abnormalities seem to be an epiphenomenon in patients with amyotrophic lateral sclerosis (ALS) with no evidence of cognitive change. This raises questions about how this affects the processing of emotional material. An impact on verbal ratings of socioemotional stimuli (more positive, lower range of arousal) (1) and memory of emotional words (2) has been shown in patients. The aim of the current study was to find out if changes are selective for the quality of emotion (positive vs. negative).
Objectives: Ability to recognize different facial expressions was investigated in ALS patients. Parameters that might influence the emotional experience of a person were measured and correlated to performance in the recognition task.
Methods: Twenty‐one ALS patients with spinal onset, 13 patients with bulbar onset and 11 healthy controls were compared in the performance of the Ekman 60 Faces test in the facial expression of emotion. Influence of functional impairment of the patients, age, depression and intelligence as well as quality of life, personality and coping strategies on recognition task performance were assessed.
Results: ALS patients with spinal onset and bulbar onset showed no significant difference in emotional judgement ratings of different faces. Compared to healthy controls ALS patients presented a significant impairment in the recognition of disgust (p = 0.015) and fear (p = 0.002) in faces. Recognition task performance correlated with functional impairments in the patients (p = 0.02), as well as with age (p = 0.015). IQ had only a low impact on face recognition task performance (p = 0.049).
Discussion and conclusion: ALS patients present significant impairments selectively for the recognition of negative facial expressions of disgust and fear. This is in contrast to other findings where no significant difference was found for the same task (2). Since task performance decreased with functional impairments, the patients in the present study might have been in a more advanced stage of the disease. There has been evidence for impairments in the limbic system in ALS patients. In a previous study a loss of volume in the amygdala in a group of 22 ALS patients (including 11 patients of the present study) had been shown. The function of the amygdala as an early alarm centre of the brain might be the key to the understanding of the differences we found in the task performance of ALS patients compared to healthy controls. Our data might be interpreted tentatively as the failure of the brain of ALS patients to reach the level of attention necessary for the complex information processing of negative facial expressions due to a missing early response of the limbic system.
References
- Lule D, Kurt A, Jurgens R, Kassubek J, et al. Emotional responding in amyotrophic lateral sclerosis. J Neurol. 2005;252:1517–24.
- Papps B, Abrahams S, Wicks P, et al. Changes in memory for emotional material in amyotrophic lateral sclerosis (ALS). Neuropsychologica 2005;43:1107–14.
P41 DEFICIENT LEXICAL ACCESS IN ALS IS ASSOCIATED WITH POOR DIVERGENT PRODUCTION AND SOCIAL INTELLIGENCE
Flaherty‐Craig C, Pinnelli SJ, Eslinger P, Simmons Z
Penn State College of Medicine, Hershey, PA, USA
E‐mail address for correspondence: [email protected]
Background: The occurrence of deficits in pre‐frontal functions in many patients with ALS is now recognized, characterized by behavioral change, as well as diminished capacities for lexical access, abstract reasoning and verbal problem solving (1). Greater characterization of verbal problem solving deficiencies in ALS is of relevance to treatment planning, particularly in the terminal stages. Divergent production is the ability to generate an alternate response set in the process of creative problem solving. Social intelligence includes the ability to comprehend non‐verbal communication as well as cause and effect relationships in the course of social interaction.
Objectives: To determine whether ALS patients with frontal dysfunction have deficiencies in divergent production and social intelligence. To evaluate the relationship between verbally mediated divergent production and social intelligence.
Methods: Word generation, a 3‐minute frontal task of letter fluency, was evaluated in 110 consecutive patients seen in our multidisciplinary clinic.
A subset of seven patients with deficient letter fluency agreed to undergo more extensive evaluation to characterize their capacities for problem solving. Measures administered included Guilford Alternate Uses and Consequences, verbal measures of divergent production, Expression Grouping, a visual measure of interpretation of facial expression and body language, and Cartoon Predictions, a visual measure of cause‐and‐effect in social interactions. Mood was assessed by the Profile of Mood States. Spearman rho correlations evaluated the relationship between letter fluency and Guilford divergent production findings.
Results: Five patients were free of depression, while two acknowledged mild depression. All patients evidenced deficiencies for Consequences, Cartoon Predictions, and Expression Grouping. Five patients evidenced deficiencies for Alternate Uses. Alternate Uses was seen to positively correlate with both letter fluency (r = 0.90, p<0.037) and Expression Grouping (r = 0.836, p<0.019) findings.
Discussion and conclusions: In this pilot study of a cohort of ALS patients selected for deficient letter fluency, frontal executive deficits were also detected for divergent production and social intelligence. Executive functioning change in ALS appears to be characterized by diminished reasoning across a broad spectrum of capacities. An understanding of this in the clinical setting is vital to treatment planning, with greater emphasis needed on support of both patient and caregivers in the process of decision‐making throughout the course of the disease process.
References
- Ringholz G, Appel S, Bradshaw M, et al. Neurology 2005;65:586–90.
P42 AGRAPHIA IN ALS: THE OMISSION OF KANA LETTERS
Satoh M1, Takeda K2, Kuzuhara S3
1Mie St. Cross Hospital, Mie, Japan, 2Japanese Red Cross Medical Center, Tokyo, Japan, 3Mie University School of Medicine, Mie, Japan
E‐mail address for correspondence: [email protected]
Background: It is generally agreed that various cognitive dysfunctions can occur in classical ALS. We have already reported a patient with classical ALS who showed the omission of kana letters (OKL) in writing. Now we have performed neuropsychological investigations including writing for 13 patients with classical ALS.
Objectives: To clarify the frequency and mechanism of the OKL, the symptomatic pattern of ALS which causes the OKL, and the presence of morphological characteristics by neuroimaging studies.
Methods: Subjects were 13 patients with classical ALS (right handed, male 5, female 8, 47∼79 years of age (mean 63 years of age), disease duration <1.5 year, normal respiratory function, independent daily life, characteristic change is absent. We performed physical examinations, the Western Aphasia Battery (WAB) writing test, Raven Progressive Colored Matrices (RPCM), and brain MRI. We also required subjects to write down the names of common animals and tools that were represented by line‐drawn cards.
Results: In writing kana, the OKL was observed in two patients who were intellectually normal. Both patients had bulbar ALS, and revealed disturbance of resolution to ‘mora’, which means sub‐syllabic rhythmic units of kana. In brain MRI, one patient revealed atrophy of bilateral frontal and temporal lobes; the other was normal.
Discussion and conclusions: In writing Japanese kana, three cognitive steps are hypothesized: the first is the resolution to mora. The word is analysed phonologically to a single syllabic unit. The second is phonological extraction. Each verbal sound is applied onto each syllabic unit. In addition, the third is the correspondence between the sound and kana. Each kana is chosen corresponding to each verbal sound. It was supposed that the OKL was caused by the disturbance of mora resolution. Mishima reported that the SPECT of a patient with the OKL in writing kana showed a decrease of regional cerebral blood flow (rCBF) in the bilateral frontal lobes. Ludolph pointed out that, in classical ALS, rCBF of the bilateral frontal lobes was often decreased. Thus, we may say that the OKL might have a relationship with frontal dysfunction. In conclusion, we should notice that, in bulbar type of ALS, some patients revealed the OKL in writing from the early stage of the illness.
P43 OCULAR APRAXIA AND COGNITIVE IMPAIRMENT IN ALS
Katz J, Woolley‐Levine S, Miller R
Forbes Norris ALS Center, San Francisco, CA, USA
E‐mail address for correspondence: [email protected]
Objective: To describe concurrence of ocular motility abnormalities and cognitive impairment in ALS.
Background: A variety of ocular motor abnormalities are reported in ALS. Cognitive impairment also occurs in up to half of patients ranging from mild executive and behavioral dysfunction to FTD. The co‐occurrence of these two phenomena has rarely been articulated.
Design and methods: We performed neuropsychological testing in 52 ALS patients suspected of having cognitive abnormalities and manual ocular motor examinations looking specifically for ocular apraxia (frequent saccadic intrusions and difficulty in disengagement of fixation when initiating voluntary saccades) in more than 200 patients with ALS. Video recordings were obtained to demonstrate the ocular motility difficulty.
Results: Seven patients had ocular apraxia, as defined above. The ocular motility abnormalities were most severe on vertical eye movements but were present on horizontal gaze in each case. The frequency of the saccadic intrusions could be reduced by having the patient point with a finger at the moving target during testing. Six of the seven patients had bulbar onset and one had limb onset but had developed bulbar involvement by the time the ocular motility abnormalities were discovered. Examination suggested that the bulbar weakness was primarily upper motor neuron in nature (slow, non‐fasciculating tongue). All patients were cognitively impaired (defined as scoring at least 1.5 standard deviations below age‐adjusted means on at least two tests in a cognitive battery). They also had profound behavioral impairments, marked primarily by the presence of apathy and executive dysfunction. Scores on the FrSBe for apathy were 4.5 standard deviations above the mean for the general population and were still 2 standard deviations above other patients with ALS who had cognitive impairment but had normal eye movements. As a group these patients had poor outcomes, with four surviving less than 15 months from the first symptom and five surviving less than six months from the time ocular apraxia was initially discovered. We did not find these ocular motor abnormalities in any cognitively‐impaired patients who lacked bulbar involvement or in any non‐demented ALS patients.
Conclusions and relevance: A subset of patients with ALS developed ocular apraxia. This occurs in the setting of a cognitive behavioral syndrome marked by pronounced executive dysfunction, severe apathy, upper motor neuron bulbar dysfunction, and poor outcomes. The characteristic appearance of these gaze abnormalities in patients with cognitive impairment suggests they relate to frontal lobe dysfunction, as opposed to degeneration within the motor cortex. The poor outcome for this syndrome may relate to the combined effects of bulbar dysfunction and cognitive impairment.
P44 THE DISSOCIATION OF DYSARTHRIA FROM COGNITIVE DYSFUNCTION IN ALS
Sterling LE1, Mosnik DM2, Wheaton M2, Appel SH3, Schulz PE2
1The Methodist Hospital, Houston, Texas, USA, 2Baylor College of Medicine, Houston, Texas, USA, 3Methodist Neurological Institute, Houston, Texas, USA
E‐mail address for correspondence: [email protected]
Background: The relationship between dysarthria and the presence of cognitive impairment in ALS patients has come under question. Recent studies have investigated whether cognitive dysfunction was associated with bulbar onset illness. Strong et al. (1) found that patients with bulbar onset disease showed greater impairment in working memory and problem‐solving/cognitive flexibility and that cognitive impairment was progressive over time, but did not find a relationship between motor speech performance and cognition. Ringholz et al. (2) found that patients with cognitive impairment were more likely to have motor programming difficulties, dysarthria, decreased phrase length and difficulty with word finding. However, patients with bulbar onset ALS did not differ from limb onset patients in either level of impairment or pattern of cognitive performance.
Objective: To examine the relationship between cognitive performance and dysarthria in a large sample of ALS patients.
Methods: One hundred and seventy‐five consecutive patients (112 male, 63 female) with a diagnosis of probable or definite ALS (El Escorial criteria) were seen for an initial neurological work‐up to reveal degenerative neurological processes. Subjects completed an extensive battery of neuropsychological measures that assessed multiple areas of cognition. A motor speech examination by a speech‐language pathologist was also completed.
Results: There was a significant effect of gender on cognitive performance across tests of intelligence with males performing better than females irrespective of dysarthria. There was also a significant effect of gender on severity of dysarthria with women being more dysarthric than men (p = 0.003), probably relating to a higher rate of bulbar onset women. There was a significant overall effect of dysarthria severity on only a few cognitive test performances (Stroop test, Verbal Series Attention test, animal fluency). Post hoc analyses indicated this performance difference was in the more severely dysarthric women. There were no other significant effects of dysarthria on cognitive test performances including tests of executive skills, attention or learning and memory.
Conclusions: There does not appear to be a significant relationship between dysarthria severity and cognitive performance. There appears to be a subgroup of female patients with severe dysarthria who exhibit significantly poorer performance on some cognitive tests requiring verbal output. We conclude that dysarthria is unlikely to be related to cognitive dysfunction in patients with ALS.
References
- Strong MJ, Grace MG, Ornge JB, et al. A prospective study of cognitive impairment in ALS. Neurology 1999;53:1665–70.
- Ringholz GH, Appel SH, Bradshaw M, et al. Prevalence and patterns of cognitive impairment in sporadic ALS. Neurology 2005;60:1094–7.
P45 EXECUTIVE FUNCTION DISORDERS AND ALS: IMPLICATIONS FOR INTERVENTION
Sterling LE1, Mosnik DM2, Appel SH3, Schulz PE2
1The Methodist Hospital, Houston, TX, USA, 2Baylor College of Medicine, Houston, TX, USA, 3The Methodist Neurological Institute, Houston, TX, USA
E‐mail address for correspondence: [email protected]
Background: Historically ALS has been viewed as a progressive neurodegenerative disease with a low incidence of cognitive abnormalities. Current literature indicates a significant incidence of cognitive change primarily involving executive functions (1). Executive functions are a set of processes that underlie goal directed behavior (e.g. planning and sequencing). Disorders of executive function are manifested by poor initiation, and difficulties planning and organizing strategies for problem solving. The prevalence of executive function disorders in this population prompted a change in our speech pathology intervention strategies. The typical intervention of providing patients and caregivers with lists of multiple speech and swallowing strategies was determined to be overwhelming. Patients and families frequently acknowledged poor compliance with the strategies. Further probing indicated it was difficult for patients to choose which strategy to use and in which situations. This issue is typical of executive dysfunction. We developed a more practical approach to minimize options and provide two or three focused strategies to patients and their caregivers. Additionally, we saw a need for caregiver education regarding executive dysfunction and its effect on behavior.
Purpose: To determine if a change in the manner of delivery, content of intervention, and specific caregiver training improved compliance with speech pathology management of dysarthria and dysphagia.
Method: Patients and families at a multidisciplinary ALS clinic were provided with two to three focused, individualized goals to manage dysarthria and dysphagia. Patients were informally surveyed at their next clinic to determine compliance with the strategies provided. Additionally, caregivers were educated with verbal and written material regarding executive function disorders and management strategies (e.g. introducing topic shifts in conversation).
Results: Informal survey revealed patient compliance with strategies to be 40%. Anecdotally, caregivers reported that patients used strategies more frequently when they were given cues. Many caregivers also reported they recognized executive function disorders in activities of daily living and were able to apply the management strategies to these settings. This reportedly improved communication and reduced frustrations between patient and caregiver.
Discussion: Although compliance issues remain, patients did utilize speech and swallowing strategies more frequently when specific strategies were targeted for individual patients. More importantly, caregivers had a better understanding of executive function deficits, were able to manage behaviors and to communicate more effectively with the patients. The prevalence of executive dysfunction in this population suggests the need for modification of intervention methods and strategies across the multidisciplinary field to enhance patient compliance.
References
- Ringholz GM, Appel SH, Bradshaw M, et al. Prevalance and patterns of cognitive impairment in sporadic ALS. Neurology 2005; 65:586–90.
P46 TREATMENT OF COGNITIVE IMPAIRMENT IN ALS
Raji A, Winkler G
Centre of Neurology, Hamburg Bergedorf, Hamburg, Germany
E‐mail address for correspondence: [email protected]
Background: Cognitive impairment in ALS is known and is correlated with pathological and morphological findings. Therapeutic approaches have not yet been systematically studied.
Objective: This meta‐analysis evaluates the diagnostic tools and the results concerning the extent and the character of cognitive impairment. The data of a pilot study with rivastigmine in ALS are presented.
Materials and methods: Studies of cognition in ALS published between 1996 and 2006 were acquired and sorted with regard to the design, the prospectivity, control and complexity of the studies, the selection of the control sample, the length of the observation period and the statistical revision.
The newly acquired data from this meta‐analysis were reviewed in terms of possible therapeutic approaches and the therapeutic concepts for cognitive impairment were deduced. Ten consecutive patients with ALS and cognitive impairment were treated with rivastigmine.
Results: The best fit diagnostic tools for the ALS tests seem to be those that cover verbal and executive functions. A scale of depression is essential. This meta‐analysis, which analyses studies with cohorts of about 30 patients with the aid of these tools, shows a highly significant prevalence of cognitive impairment in 30–50% of the patients with ALS. There is a distinct trend towards characterization of cognitive impairment in terms of a frontotemporal dementia. The selection of patients in terms of bulbar and extremity involvement shows unhomogeneous results. There is overall evidence for a stronger development of cognitive impairment in bulbar patients. Cognitive impairment is seen in about 40% of our own patients. The first results of the pilot study suggest a controlled study should be performed.
Discussion and conclusions: The pattern of cognitive impairment suggests a therapeutic approach analogous to that used in frontotemporal dementia. Central cholinesterase inhibitors or alternatively memantine are worth discussing. Our preliminary data suggest a positive effect of rivastigmine in ALS. The considerable extent of cognitive impairment especially in the bulbar form is to be considered clinically relevant. It has yet to be discussed how far the dementia affects the prognosis of ALS through lack of compliance in vital therapy decisions, or vice versa if successful therapy of cognitive impairment improves prognosis and quality of life.
We advise, on the basis of the present data, diagnosis and individual therapy of cognitive impairment. The extent of the coexistent or consecutive depression also has to be diagnostically and therapeutically considered.
Acknowledgement: This study was supported by a grant of the Karberg‐Stiftung, Hamburg
P47 FRONTOTEMPORAL DEMENTIA WITH ALS IN AKITA
Wada C, Kamada S, Obara K, Abe E, Okawa S, Kobayashi M, Sugawara M, Toyoshima I
Akita University School of Medicine, Akita, Japan
E‐mail address for correspondence: [email protected]
Background and objectives: Cognitive impairment in ALS has been reported to vary from 5 to 75% of patients. Recently, reports of ALS with dementia (ALS‐D) have been increasing in the context of frontotemporal dementia (FTD) and Yuasa‐Mitsuyama type‐ALS. We have experienced ALS‐D patients with severe dementia in Akita. Here we describe the clinical features and neuroimaging of the patients.
Methods: Of 75 ALS patients in our database, we chose 10 patients with marked dementia and compared them with 10 ALS patients without dementia (ALS‐C) in terms of age of onset, initial symptom, neurological signs especially muscle stretch reflex, the type of dementia, HDS‐R score, time course, and neuroimaging.
Results: Sixteen (22%) of 75 ALS patients showed severe dementia. The mean age of onset was 63 and 68 years in 10 patients of ALS‐D and 10 with ALS‐C, respectively. The gender ratio was 1:1 in both; the initial symptoms varied (dementia in three patients and weakness in seven patients in ALS‐D); the scores of the HDS‐R test were 10/30 (ALS‐D) and 26/30 points (ALS‐C). Character change, disinhibition, loss of insight, and aphasia (paragraphia, decreasing of speech) were recognized during the course of ALS‐D. The average length of time between onset of weakness and dementia was 16 months. All patients had hyperreflexia and seven patients showed Babinski sign. The duration from onset to death or continuous ventilation in ALS‐D was shorter than in ALS‐C: 23.6±14.6 and 36.2±20.3 months, respectively. On CT or MRI, severe frontotemporal atrophy with rapid progression was remarkable in six patients. SPECT showed the reduction of blood flow even in the early stage of ALS‐D patients without atrophy sign.
Discussion and conclusions: ALS‐D in Akita presented severe dementia and a rapid course of ALS with pyramidal signs, which are atypical both in Yuasa‐Mitsuyama type ALS and FTD with motor neuron disease. Pathological and immunocytochemical investigation is awaited.
P48 COPING STRATEGIES IN A POPULATION OF 50 ALS PATIENTS
Bongioanni P, Tramonti F, Tuccio MC, Cagnacci M, Pepe G, Rossi B
Azienda Ospedaliero‐Universitaria Pisana, Pisa, Italy
E‐mail address for correspondence: [email protected]
Background: Coping has a strong influence on the quality of life of amyotrophic lateral sclerosis (ALS) patients and carers (1), and is one among the most relevant components in the assessment of subject psychological status.
Objectives: In this study, we evaluated twice over time specific ALS patients' coping strategies, in order to observe how coping strategies evolve with patient ageing and increasing physical impairment.
Methods: We used a translation of the MND Coping Scale (2), a questionnaire of 22 items concerning behaviours and attitudes strictly related to six factors representing particular coping strategies: 1) Support; 2) Positive Action; 3) Independence; 4) Avoidance/Venting; 5) Information Seeking; 6) Positive Thought. The scale was submitted twice to 50 ALS patients (19 female, 31 male; mean age at first testing 61.5 years). Second testing took place one year after the first test. Patients were divided into three age groups (Age 1, 29–55 years; Age 2, 56–74 years; Age 3, 75–86 years) and in three classes of illness severity (according to ALS‐Functional Rating Scale (ALS‐FRS): Class 1, 30–40; Class 2, 20–29; Class 3, 0–19).
Results: At first testing, we found significant (p<0.05) differences in Factor 2 between Age 1 and Age 3 groups and between Class 1 and Class 3: older and more impaired patients were less active than others. As far as second testing was concerned, many significant differences emerged between the ALS‐FRS classes: on Factor 2 between Class 2 and Class 3 (p<0.05) and between Class 1 and Class 3 (p<0.001); on Factor 3 between Class 3 and both Class 1 and 2 (p<0.001); on Factor 4 between Class 1 and Class 3 (p<0.05); and on Factor 6 between Class 1 and Class 3 (p<0.05). As might be supposed, increased physical impairment seems to disadvantage adaptive coping strategies, but on the other hand we did not find significant differences by comparing first testing data with those from second testing. Finally, at second testing, male patients appeared to be more independent than females (p<0.05).
Discussion: Understanding the evolution of ALS patient coping strategies can be the first step to optimizing psychological intervention. Without forgetting the unique features of each patient, the identification of common trends in the development of patients' behaviour and attitudes could help us to reinforce those strategies that often tend to weaken along with increasing clinical disability and ageing of patients.
References
- Goldstein LH, Atkins L, Leigh PN. Amyotroph Lateral Scler Other Motor Neuron Disord. 2002;3:123–9.
- Lee JN, et al. Journal of the Neurological Sciences 2001;191:79–85.
P49 EVALUATION OF PSYCHOLOGICAL STATE IN ALS PATIENTS USING THE PROFILE OF MOOD STATES
Kikuchi H1, Tateishi T1, Ishizaka M2, Iwaki M4, Kitayama O3, Kira J1
1Department of Neurology, 2Graduate School of Human Environment Studies, 3Faculty of Human‐Environment Studies, Kyushu University, Fukuoka, Japan, 4The Fukuoka Prefectural Medical Committee for Intractable Disease, Fukuoka Prefectural Government, Fukuoka, Japan
E‐mail address for correspondence: [email protected]
Background: Psychological problems frequently occur in patients with amyotrophic lateral sclerosis (ALS), including depression, anxiety and fatigue. Understanding the psychological status in ALS is important for the comprehensive management of patients. The Profile of Mood States (POMS) is an instrument composed of six mood scales that were developed using clinical populations to analyse mood and anxiety (1). Before now, no psychological evaluation has been reported using the POMS scale in ALS patients.
Objectives: To evaluate the status of mood and anxiety in patients with ALS.
Methods: Thirty patients with ALS in our hospital (15 men and 16 women, average age at examination 59±25 years old, men 58±29 years old, women 60±21 years old, average disease duration 32±72 months) were evaluated. We (neurologists, medical coordinator and clinical psychologist) performed psychological evaluation. Patients were interviewed with a questionnaire to evaluate their mood and anxiety using the Profile of Mood States (POMS), which assesses six subjective subscales rated on a five‐point scale: tension‐anxiety (0–36), depression‐dejection (0–60), anger‐hostility (0–48), fatigue‐inertia (0–28), vigor‐activity (0–32), and confusion‐bewilderment (0–28). Their disease progression was estimated using the ALS Functioning Rating Scale (ALS‐FRS). We performed correlation analysis between POMS score and age, gender, ALS‐FRS and disease duration.
Results: The mean POMS score for all 30 patients was as follows: tension‐anxiety (55.9±21.2), depression‐dejection (62.5±24.9), anger‐hostility (51.5±18.9), fatigue‐inertia (53.3±20.5), vigor‐activity (40.8±20.1), and confusion‐bewilderment (55.2±25.5). Significantly greater frequency of tension‐anxiety (r = 0.40, p = 0.03) and depression‐dejection (r = 0.46, p = 0.01) was seen in younger aged patients, and also significantly greater frequency of anger‐hostility was seen in lower ALS‐FRS score patients and more disabled ALS patients (r = 0.38, p = 0.04). No significant correlation between POMS scores and gender or disease duration was found.
Discussion and conclusions: Younger ALS patients have more tension, anxiety, depression and dejection. On the other hand, disabled ALS patients have more anger and hostility. We should provide mental care especially for both younger and severely disabled ALS patients according to their characteristic mental state.
References
- McNair DM, Lorr M, Droppleman LF. Profile of Mood States. Multi-Health System Inc. 1992
P50 CONCERNS OF JAPANESE CHILDREN OF PEOPLE WITH ALS
Kitamura Y1, Ueda R2
1National Rehabilitation Center, Saitama, Japan, 2Okinawa Prefectural College of Nursing, Okinawa, Japan
E‐mail address for correspondence: [email protected]
Background: Children of people with disabilities are known to have their own concerns because of their unique experiences. The Motor Neurone Disease Association in the UK publishes booklets for children of parents who have motor neuron disease, and Tsuchiya reported Japanese children's burden as caregivers for their parents who live at home with ventilators. The burden of Japanese children of ALS patients is estimated to be higher than that of US and European countries because 10% of ALS patients stay at home with invasive ventilators and require 24 hour a day care, although the total amount of social service is limited.
Purpose: The purpose of this study is to discover the concerns of children of ALS patients at different developmental stages in order to develop a support system for them.
Methods: Semi‐structured interviews were conducted with seven ALS patients with ventilators at home and nine family members. The conversations with the patients were facilitated by the family members using transparent boards and lip reading. The family members included two wives, one elder sister, one nephew and four daughters. The interview was fully recorded with an IC recorder and transcribed to categorize the contents.
Results: 1) The ages of children of ALS patients were from 2 years to the 40s; 2) Concerns of children differed with age – understanding of the disease for school‐aged children, emotional support for adolescents and physical burden for adults; 3) There was no support or service for children of ALS patients except support from family members and home helpers.
Discussion: Children of ALS patients showed common concerns with the children of parents with physical disabilities and siblings of individuals with disabilities. The children of ALS patients require support in the form of information, emotional support and care burden support in a manner appropriate to disease development.