A quantitative measure of handgrip myotonia in non-dystrophic myotonia.

INTRODUCTION: Non-dystrophic myotonia (NDM) is characterized by myotonia without muscle wasting. A standardized quantitative myotonia assessment (QMA) is important for clinical trials. METHODS: Myotonia was assessed in 91 individuals enrolled in a natural history study using a commercially available computerized handgrip myometer and automated software. Average peak force and 90% to 5% relaxation times were compared with historical normal controls studied with identical methods. RESULTS: Thirty subjects had chloride channel mutations, 31 had sodium channel mutations, 6 had DM2 mutations, and 24 had no identified mutation. Chloride channel mutations were associated with prolonged first handgrip relaxation times and warm-up on subsequent handgrips. Sodium channel mutations were associated with prolonged first handgrip relaxation times and paradoxical myotonia or warm-up, depending on underlying mutations. DM2 subjects had normal relaxation times but decreased peak force. Sample size estimates are provided for clinical trial planning. CONCLUSION: QMA is an automated, non-invasive technique for evaluating myotonia in NDM.

Widespread cerebral haemodynamics disturbances occur early in amyotrophic lateral sclerosis.

We wished to longitudinally assess early changes in cerebral perfusion (CP) and its relationship to cognitive impairment (CI) in ALS. Fourteen ALS patients at time of diagnosis and 11 spousal controls, both without CI, were longitudinally assessed to determine a relationship between CP and incidence of CI in early stage disease. Neuropsychological testing and CP measurements were performed in both ALS and control groups at the initial assessment (T0) and two time-periods post initial assessment, T1 and T2, taken on average 6.1 and 17.0 months after initial assessment (T0), respectively. CT perfusion was used to measure cerebral blood flow, blood volume, and mean transit time (MTT) for all cortical lobes, and subcortical grey and white matter. Two of 14 ALS patients progressed to CI. No differences in CP measurements existed at T0 or T1 between the ALS and control groups. At T2, widespread cortical differences in MTT were present between the two groups. The ALS group had significantly increased MTT in all cortical regions, as well as the thalamus, compared with the control group. Our findings suggest early widespread changes in CP occur outside the motor area in the absence of CI in ALS.

Neuropsychological functioning in PLS: a comparison with ALS.

OBJECTIVE: In order to characterize the nature and extent of neuropsychological dysfunction in primary lateral sclerosis (PLS), we studied prospectively cognitive, emotional, and behavioral functioning in PLS, and compared performances to functioning in amyotrophic lateral sclerosis (ALS). METHODS: Eighteen patients with PLS and 13 patients with ALS completed a neuropsychological test battery assessing both cognitive skills and emotional/behavioral functioning. RESULTS: Both PLS and ALS groups scored broadly within normal limits (mean T-scores greater than 40) on all cognitive measures and no significant between-group differences were found with the exception of one variable. However, when examined on a case by case basis, the data revealed considerable heterogeneity amongst patients in both groups. Overall, 39% of PLS patients and 31% of ALS patients were considered cognitively impaired. Ahigher than expected frequency of abnormal scores was noted for several tests of executive function in both groups, and a majority of PLS patients also exhibited abnormal behavioural symptoms. There was no relationship in PLS or ALS groups between cognitive functioning and disease duration, current site of disease, site of onset, functional status, and respiratory variables. Comparison between the PLS and ALS groups indicated virtually no differences in cognitive test scores and overall emotional/behavioural symptoms. CONCLUSIONS: We observed deficits in cognition and behaviour in a significant proportion of PLS patients which were comparable to those observed in ALS cases. Although deficits were not in the range of frontotemporal dementia, both ALS and PLS cases demonstrated deficits most prominently on tests of executive functioning.

Cerebral haemodynamic changes accompanying cognitive impairment in primary lateral sclerosis.

Our objective was to elucidate the relationship between cognitive decline and cerebral haemodynamics in patients with PLS. We examined 18 patients with PLS and contrasted both neuropsychological and cerebral perfusion findings with seven age- and education-matched non-PLS controls. PLS patients were stratified into two groups based on the number of abnormal neuropsychological test scores: 1) cognitively intact PLS patients (PLS; those having zero or one abnormal scores (n =14)), and 2) cognitively-impaired PLS patients (PLSci; those having two or more abnormal test scores (n =4)). There was considerable heterogeneity in level of cognitive functioning with four patients meeting the criteria for cognitive impairment. The findings were highly consistent with a frontotemporal lobar dysfunction. Using CT perfusion to assess cerebral haemodynamics, the PLSci group had increased cerebral blood volume (CBV) and mean transit time (MTT) with reduced cerebral blood flow (CBF). More specifically, MTT was significantly increased (p<0.05) in the PLSci group compared with controls in all regions and affected both grey and white matter, with the exception of the temporal lobe and subcortical parietal white matter. These observations suggest that a subset of PLS patients is subject to cognitive decline and that this process is associated with changes in cerebral haemodynamics.

Differentiation between primary lateral sclerosis and amyotrophic lateral sclerosis: examination of symptoms and signs at disease onset and during follow-up.

BACKGROUND: Motor neuron diseases can affect the upper motor neuron and/or the lower motor neuron. Both amyotrophic lateral sclerosis (ALS) and primary lateral sclerosis (PLS) are motor neuron diseases, and there is much debate as to whether these are 2 separate disorders or simply 2 points on a continuum. OBJECTIVE: To determine which clinical features at onset and during follow-up could help differentiate between PLS and ALS. DESIGN: Retrospective study comparing patients with a diagnosis of PLS or ALS for differences in symptoms or signs at disease onset and during follow-up. SETTING: Tertiary referral center. Patients Six hundred sixty-one patients with ALS and 43 patients with PLS were included in the study. RESULTS: At presentation, stiffness was the only symptom that was significantly different between patients with PLS and patients with ALS (observed in 47% and 4% of patients, respectively; P<.001). During follow-up, limb wasting was rare in patients with PLS (2%, compared with 100% in patients with ALS; P<.001). Disease duration was significantly longer in patients with PLS compared with patients with ALS (mean +/- SD, 11.2 +/- 6.1 vs 3.8 +/- 4.2 years, respectively; P<.001). During the 16 years of follow-up, the mortality rate was significantly lower in patients with PLS compared with patients with ALS (only 33% vs 89%, respectively; P<.001). CONCLUSION: Our findings suggest that a patient presenting with spasticity who does not develop wasting within 3 years most likely has PLS.

Prognosis of amyotrophic lateral sclerosis with respiratory onset.

Respiratory muscle involvement is a recognised, but often late, complication of amyotrophic lateral sclerosis (ALS). The clinical features and prognosis of 21 patients with respiratory onset ALS are reported here. On a retrospective chart review, it was found that 2.7% of patients with ALS presenting to a tertiary care specialty clinic have respiratory symptoms as their first clinical symptom of ALS. Only 14% of these individuals presented acutely and required emergency intubation. The mean survival time of the total group from symptom onset to death or permanent ventilation was 27.0 (14.9) months, which was not significantly different from the survival time in patients with bulbar onset ALS. Non-invasive positive pressure ventilation (NIPPV) significantly improved survival compared with those who did not use NIPPV. This study suggests that ALS with respiratory onset does not necessarily follow a rapidly progressive course.

Preliminary evaluation of the sensitivity to change of DE-STA motor unit number estimation in the upper trapezius muscle in amyotrophic lateral sclerosis.

OBJECTIVE: To compare the sensitivity to change of decomposition-enhanced spike-triggered averaging (DE-STA) motor unit number estimation (MUNE) in the upper trapezius (UT) to that of various clinical outcome measures in subjects with amyotrophic lateral sclerosis (ALS). METHODS: Ten patients with clinically probable or definite ALS were assessed at baseline, 2, 4 and 6months with the following outcome measures: manual muscle testing in five upper extremity muscle groups, scapular elevation and elbow flexion peak force measured with hand-held dynamometry, MUNE, forced vital capacity and the Revised ALS Functional Rating Scale (ALSFRS-R). RESULTS: ALSFRS-R was the only outcome measure for which there was a significant difference between baseline and 6months (p=0.034). ALSFRS-R had the largest standardized response mean (SRM), and was thus the most sensitive to change. MUNE demonstrated a decline over 6months and a moderate SRM (-0.63). CONCLUSIONS: This study has demonstrated a moderate degree of sensitivity to change for DE-STA MUNE as applied to the UT in subjects with ALS. SIGNIFICANCE: In this preliminary study, DE-STA MUNE detected motor unit loss over 6months, with a moderate degree of sensitivity, in the upper trapezius of subjects with ALS.