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Objective: This study examines reading aloud in patients with amyotrophic lateral sclerosis (ALS) and those with frontotemporal dementia (FTD) in order to determine whether differences in patterns of speaking and pausing exist between patients with primary motor vs. primary cognitive-linguistic deficits, and in contrast to healthy controls., Design: 136 participants were included in the study: 33 controls, 85 patients with ALS, and 18 patients with either the behavioural variant of FTD (FTD-BV) or progressive nonfluent aphasia (FTD-PNFA). Participants with ALS were further divided into 4 non-overlapping subgroups--mild, respiratory, bulbar (with oral-motor deficit) and bulbar-respiratory--based on the presence and severity of motor bulbar or respiratory signs. All participants read a passage aloud. Custom-made software was used to perform speech and pause analyses, and this provided measures of speaking and articulatory rates, duration of speech, and number and duration of pauses. These measures were statistically compared in different subgroups of patients., Results: The results revealed clear differences between patient groups and healthy controls on the passage reading task. A speech-based motor function measure (i.e., articulatory rate) was able to distinguish patients with bulbar ALS or FTD-PNFA from those with respiratory ALS or FTD-BV. Distinguishing the disordered groups proved challenging based on the pausing measures., Conclusions and Relevance: This study demonstrated the use of speech measures in the identification of those with an oral-motor deficit, and showed the usefulness of performing a relatively simple reading test to assess speech versus pause behaviors across the ALS-FTD disease continuum. The findings also suggest that motor speech assessment should be performed as part of the diagnostic workup for patients with FTD.

There is increasing evidence of a clinical, neuropathological and genetic overlap between frontotemporal dementia (FTD) and amyotrophic lateral sclerosis (ALS). We conducted a case-control study using a UK dataset to test the hypothesis that polymorphisms in two FTD-related genes (GRN and FT74) are associated with increased susceptibility to ALS. We evaluated the majority of known genetic variability in IFT74 and GRN. The results revealed that the common variations in IFT74 and GRN neither constitute strong ALS risk factors nor modify the age-at-onset. However, the possibility of a modest risk effect remains to be assessed in large datasets.

Repetitive stimulation of the facial nerve is commonly performed in cases of suspected myasthenia gravis (MG) because bulbar weakness is often present, but the most sensitive facial muscle is unknown. We compared the sensitivity of repetitive nerve stimulation (RNS) to the frontalis and nasalis muscles in 244 patients with suspected MG. We found no difference in sensitivity of RNS when recording from these muscles in both ocular and generalized MG. In addition, we confirmed the low sensitivity of RNS for ocular (18%) or generalized (47%) MG. The specificity of facial RNS for both muscles was 100% and, in certain circumstances, may obviate the need for further diagnostic testing.

Chronic inflammatory demyelinating polyneuropathy (CIDP) is an immune mediated neuropathy responding to immunomodulation with IVIG or plasma exchange (PE). We tested the efficacy and safety of selective immunoglobulin removal by Excorim immunoadsorption (IA) in a pilot trial in CIDP patients randomized to monthly IA or IVIG treatments for 6 months. Response rates at 2 and 6 months were greater with IA due to longer disease duration and greater disability at baseline in the patients receiving IVIG. IA appears to be a safe and efficacious therapy for patients with CIDP, but an appropriately powered clinical trial with stratification for disease duration is required.

Objective: Cooling detection threshold testing may be an important quantitative method for assessing polyneuropathy, in that it has traditionally been viewed as a measure of small-fiber involvement. The present study sought to determine the agreement between two common testing devices and to determine whether these are concordant in their association with predictor variables for diabetic sensory polyneuropathy., Research Design and Methods: A total of 83 patients with diabetes (10 patients with type 1 diabetes and 73 patients with type 2 diabetes) and a wide spectrum of diabetic sensory polyneuropathy severity underwent concurrent cooling detection threshold testing using the Medoc and CASE IV instruments. Common predictor variables for diabetic sensory polyneuropathy were measured on the same day., Results: Measurements of cooling detection thresholds by both instruments were highly correlated (Spearman's correlation coefficient 0.81, P < 0.001) and demonstrated a high degree of agreement by the method of Bland and Altman (95% distribution critical values for the difference in cooling detection thresholds, +7.5 and -5.6 degrees C). Cooling detection thresholds by both instruments were strongly correlated with clinical indicators of large-fiber neuropathy but not with the symptoms of small-fiber neuropathy (pain)., Conclusions: These two instruments available for assessment of cooling detection thresholds are interchangeable for research in diabetic sensory polyneuropathy. However, this modality is equivalent to other modalities of quantitative sensory threshold testing in its association with indicators of large-fiber neuropathy and does not seem to provide an advantage for the prediction of small-fiber involvement.

Objective: Low-intensity laser therapy (LILT) has been advocated for treatment of chronic pain disorders. Although the mechanism of pain relief is uncertain, this therapy has been suggested for relief of painful symptoms of diabetic sensorimotor polyneuropathy (DSP). The objective of this study was to determine whether LILT relieves the pain of DSP., Research Design and Methods: We conducted a randomized, double-masked, sham therapy-controlled clinical trial in 50 patients with painful DSP diagnosed with the Toronto Clinical Neuropathy Score. All patients received sham therapy over a 2-week baseline period and were then randomized to receive biweekly sessions of either sham or LILT for 4 weeks. The primary efficacy parameter was the difference in the weekly mean pain scores on a visual analog scale (VAS)., Results: The patients had similar baseline characteristics for pain intensity, HbA(1c), and duration of DSP. Both groups noted a decrease in weekly mean pain scores during sham treatment. After the 4-week intervention, the LILT group had an additional reduction in weekly mean pain scores of -1.0 +/- 0.4 compared with -0.0 +/- 0.4 for the sham group (P = 0.07). LILT had no effect on the Toronto Clinical Neuropathy Score, nerve conduction studies, sympathetic skin response, or quantitative sensory testing., Conclusions: Although an encouraging trend was observed with LILT, the study results do not provide sufficient evidence to recommend this treatment for painful symptoms of DSP.

We have probed the molecular basis of functional effects of ciliary neurotrophic factor (CNTF) and nerve growth factor (NGF) on aspects of the neuronal differentiation of LA-N-2 neuroblastoma cells. The influence of CNTF on the cholinergic phenotype can be accounted for by transcriptional/translational effects without implicating posttranslational mechanisms. Although both NGF receptors are expressed constitutively by LA-N-2 cells, CNTF has a marked stimulatory effect on trkA mRNA and protein. The NGF receptors are functional in serum-free conditions where they mitigate CNTF effects on cell adhesion but do not support process extension. Following priming by CNTF, NGF and CNTF have synergistic influences on process formation but not on choline acetyltransferase-specific activity.