Upper Motor Neuron Dysfunction Research Articles

A neurophysiological approach to mirror movements in amyotrophic lateral sclerosis

ObjectiveTo investigate mirror activity in amyotrophic lateral sclerosis (ALS) patients, using a simple paradigm of signal quantification. MethodsPatients were asked to perform a brief isometric maximum contraction of the abductor digiti minimi (ADM) or tibialis anterior (TA) on one side, while relaxing the contralateral side of the body. Both sides were investigated. Signals were stored and analyzed offline, for quantification of electromyographic signal. Clinical signs of upper motor neuron (UMN) dysfunction, transcranial magnetic stimulation (TMS) for the upper (UL) and lower limbs (LL), the ADM ipsilateral cortical silent period (iSP) and the Edinburgh Cognitive and Behavioral ALS Screen (ECAS) cognitive scale were also investigated. Results42 ALS patients were included. In the 4 investigated muscles the amount of mirror activity was significantly higher than in the matched healthy group. The amount of mirror activity was similar between sides, but significantly higher in UL and LL with abnormal TMS results for ADM (p = 0.005) and TA (p = 0.002), as well as in UL with abnormal iSP values (p = 0.009). No association was found between mirror activity and clinical signs of UMN involvement. ConclusionsMirror activity is a common phenomenon in ALS. Mirror activity intensity corresponds to the severity of UMN dysfunction, as measured by TMS, and probably derives from the abnormal transcallosal inhibition as mirrored by iSP abnormality. SignificanceMirror activity is increased in ALS and is associated with abnormal transcallosal inhibition and UMN dysfunction.

Phosphorylated tau in plasma could be a biomarker of lower motor neuron impairment in amyotrophic lateral sclerosis.

Plasma levels of phosphorylated tau (P-tau181) have been recently reported to be increased in amyotrophic lateral sclerosis (ALS) and associated with lower motor neuron (LMN) impairment. We quantified plasma P-tau181 (pP-tau181) in a cohort of 29 deeply phenotyped ALS patients using the new fully automated Lumipulse assay and analysed phenotype-biomarker correlations. pP-tau181 levels correlated positively with a clinical LMN score (r = 0.3803) and negatively, albeit not significantly, with a composite index of muscle strength (r =  - 0.3416; p = 0.0811), but not with Penn Upper Motor Neuron (UMN) Score. Accordingly, pP-tau181 correlated with electromyographic indices of spinal active and chronic denervation (r = 0.4507 and r = 0.3864, respectively) but not with transcranial magnetic stimulation parameters of UMN dysfunction. pP-tau181 levels did not correlate with those in the cerebrospinal fluid (CSF), serum NFL, serum GFAP, CSF/serum albumin ratio, or estimated glomerular filtration rate, but correlated with plasma creatine kinase levels (r = 0.4661). Finally, while not being associated with neuropsychological phenotype, pP-tau181 correlated negatively with pH (r =  - 0.5632) and positively with partial pressure of carbon dioxide (PaCO2; r = 0.7092), bicarbonate (sHCO3-; r = 0.6667) and base excess (r = 0.6611) on arterial blood gas analysis. pP-tau181 has potential as ALS biomarker and could be associated with LMN impairment. Its raised levels might reflect pathophysiological processes (tau hyperphosphorylation and/or release) occurring in the axons of LMNs distantly from the CNS and the CSF. pP-tau181 could also be associated with respiratory dysfunction.

Characterization of white matter alterations using diffusion kurtosis imaging in patients with amyotrophic lateral sclerosis.

To evaluate the degeneration of the corticospinal tract (CST) and corpus callosum (CC) in patients with motor neuron disease and upper motor neuron (UMN) dysfunction using diffusion kurtosis imaging (DKI). Twenty-seven patients and 33 healthy controls underwent magnetic resonance imaging along with clinical and neuropsychological testing. Tractography of diffusion tensor images was performed to extract tracts of the bilateral CST and CC. Group mean differences both across the entire averaged tract and along each tract were assessed, including correlations between diffusion metrics and clinical measures. Tract-based spatial statistics (TBSS) was performed to evaluate the spatial distribution of whole-brain microstructural abnormalities in patients. In comparison to controls, patients had significantly higher mean and radial diffusivity and lower fractional anisotropy (FA), kurtosis anisotropy, mean kurtosis (MK), and radial kurtosis (RK) in the CST and CC (p<.017). Along-the-tract analysis revealed changes concentrated in the posterior limb of the internal capsule, corona radiata, and primary motor cortex (false-discovery rate p<.05). FA of the left CST correlated with disease progression rate, whereas MK of the bilateral CST correlated with UMN burden (p<.01). TBSS results corroborated along-tract analysis findings and additionally revealed reduced RK and MK in the fornix, where diffusion tensor imaging (DTI) changes were absent. DKI abnormalities in the CST and CC are present in patients with UMN dysfunction, potentially revealing complementary information to DTI regarding the pathology and microstructural alterations occurring in such patients. DKI shows promise as a potential in vivo biomarker for cerebral degeneration in amyotrophic lateral sclerosis.

Quantitative Brain MRI Metrics Distinguish Four Different ALS Phenotypes: A Machine Learning Based Study.

Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease whose diagnosis depends on the presence of combined lower motor neuron (LMN) and upper motor neuron (UMN) degeneration. LMN degeneration assessment is aided by electromyography, whereas no equivalent exists to assess UMN dysfunction. Magnetic resonance imaging (MRI) is primarily used to exclude conditions that mimic ALS. We have identified four different clinical/radiological phenotypes of ALS patients. We hypothesize that these ALS phenotypes arise from distinct pathologic processes that result in unique MRI signatures. To our knowledge, no machine learning (ML)-based data analyses have been performed to stratify different ALS phenotypes using MRI measures. During routine clinical evaluation, we obtained T1-, T2-, PD-weighted, diffusion tensor (DT) brain MRI of 15 neurological controls and 91 ALS patients (UMN-predominant ALS with corticospinal tract CST) hyperintensity, n = 21; UMN-predominant ALS without CST hyperintensity, n = 26; classic ALS, n = 23; and ALS patients with frontotemporal dementia, n = 21). From these images, we obtained 101 white matter (WM) attributes (including DT measures, graph theory measures from DT and fractal dimension (FD) measures using T1-weighted), 10 grey matter (GM) attributes (including FD based measures from T1-weighted), and 10 non-imaging attributes (2 demographic and 8 clinical measures of ALS). We employed classification and regression tree, Random Forest (RF) and also artificial neural network for the classifications. RF algorithm provided the best accuracy (70-94%) in classifying four different phenotypes of ALS patients. WM metrics played a dominant role in classifying different phenotypes when compared to GM or clinical measures. Although WM measures from both right and left hemispheres need to be considered to identify ALS phenotypes, they appear to be differentially affected by the degenerative process. Longitudinal studies can confirm and extend our findings.

The cutaneous silent period as a measure of upper motor neuron dysfunction in amyotrophic lateral sclerosis

ObjectivesWe investigated the cutaneous silent period (CutSP) as a measure of upper motor neuron (UMN) dysfunction in amyotrophic lateral sclerosis. MethodsThe onset latency, duration, and amount of EMG suppression of the CutSP were compared with clinical UMN signs in 24 patients with amyotrophic lateral sclerosis (ALS). UMN signs were quantified using a clinical index and transcranial magnetic stimulation (TMS). Central motor conduction time (CMCT), cortical motor threshold and motor evoked potential amplitudes were assessed as measures of UMN dysfunction. CutSP was studied in abductor digit minimi (ADM) and tibialis anterior (TA) EMG recordings following stimulation of the 5th finger and sural nerves respectively. Non-parametric tests and binomial logistic regression were applied to evaluate the data. ResultsCutSP onset latency was increased in ALS patients, compared to healthy controls, both for ADM and TA muscles. In limbs with clinical UMN signs or abnormal TMS findings, the CutSP onset latency was particularly increased. There was a significant positive correlation between CutSP onset latency and the UMN score in both upper and lower limbs. In TA muscles there was also a negative correlation between CutSP onset latency and EMG suppression. The logistic regression model based on CutSP parameters correctly classified more than 70% of the cases regarding the presence of clinical signs of UMN lesion, in both upper and lower limbs. The results were not significant for TMS. ConclusionWe conclude that upper limb CutSP changes associates with UMN lesion in ALS. This neurophysiological measurement merits further investigation in ALS.

Characterising ALS disease progression according to El Escorial and Gold Coast criteria

BackgroundThe Gold Coast criteria (GCC) have been proposed as a means of selecting patients for amyotrophic lateral sclerosis (ALS) clinical trials. We aimed to characterise disease progression according to the...

Electrodiagnostic findings in facial onset sensory motor neuronopathy (FOSMN)

ObjectiveTo determine the electrodiagnostic characteristics of facial onset sensory and motor neuronopathy (FOSMN). MethodsElectrophysiological data from 10 FOSMN patients in Newcastle-upon-Tyne and Sydney were reviewed. Relevant literature was reviewed. ResultsFindings on standard electrophysiological assessment were in broad agreement with those published: blink reflexes were abnormal in all but one patient; sensory nerve action potentials were reduced but compound muscle action potentials preserved; mixed acute and chronic neurogenic change was identified on needle electromyography in bulbar and cervico-thoracic muscles in approximately 50% of patients.Upper limb somatosensory evoked potential (SEP) central conduction times were increased (n = 4) and progressed on repeat testing (n = 3). Upper motor neuron dysfunction was revealed by several measures [ipsilateral motor evoked potentials (MEPs) (n = 1); reduced short interval intra-cortical inhibition on threshold-tracking transcranial magnetic stimulation (n = 2); absent beta-band intermuscular coherence (n = 3)]. ConclusionsElectrodiagnostic investigation of FOSMN should include blink reflex testing, SEPs and tests of upper motor neuron function. The combination of progressive lower motor neuron disease and upper motor neuron disease on neurophysiological investigation provides further support for the contention that FOSMN is a rare variant of motor neurone disease. SignificanceThese findings will aid the neurologist and neurophysiologist in making a confident diagnosis of FOSMN, thus expediting appropriate care.

Assessing the upper motor neuron in amyotrophic lateral sclerosis using the triple stimulation technique: A multicenter prospective study

ObjectiveTo evaluate the relevance of transcranial magnetic stimulation (TMS) using triple stimulation technique (TST) to assess corticospinal function in amyotrophic lateral sclerosis (ALS) in a large-scale multicenter study. MethodsSix ALS centers performed TST and conventional TMS in upper limbs in 98 ALS patients during their first visit to the center. Clinical evaluation of patients included the revised ALS Functional Rating Scale (ALSFRS-R) and upper motor neuron (UMN) score. ResultsTST amplitude ratio was decreased in 62% of patients whereas conventional TMS amplitude ratio was decreased in 25% of patients and central motor conduction time was increased in 16% of patients. TST amplitude ratio was correlated with ALSFRS-R and UMN score. TST amplitude ratio results were not different between the centers. ConclusionsTST is a TMS technique applicable in daily clinical practice in ALS centers for the detection of UMN dysfunction, more sensitive than conventional TMS and related to the clinical condition of the patients. SignificanceThis multicenter study shows that TST can be a routine clinical tool to evaluate UMN dysfunction at the diagnostic assessment of ALS patients.

SY3.2. Neurophysiological biomarkers in ALS

Amyotrophic lateral sclerosis (ALS) is a rapidly progressive neurodegenerative disorder of the motor neurons, characterized by upper motor neuron (UMN) and lower motor neuron (LMN) dysfunction. There have been significant technological advances in the development of neurophysiological biomarkers of UMN and LMN dysfunction in ALS. In this presentation, I will discuss the major advances in development of neurophysiological biomarkers in ALS, critiquing their potential in diagnosis and prognosis of ALS, as well as utility in monitoring treatment effects. The threshold tracking transcranial magnetic stimulation (TMS) technique has established cortical hyperexcitability as an early and specific biomarker of UMN dysfunction in ALS and associated with neurodegeneration. In addition to establishing cortical hyperexcitability as a pathophysiological mechanism, threshold tracking TMS has enabled an earlier diagnosis of ALS and provided a means of monitoring effects of therapeutic agents. Biomarkers of LMN dysfunction, including motor unit number estimation, the neurophysiological and split hand index, electrical impedance myography and axonal excitability techniques, all of which have exhibited utility in monitoring disease progression and contributing to diagnosis. In addition to enhancing ALS diagnosis, the development of novel neurophysiological biomarkers has implications for clinical trials research and drug development, enabling the assessment of biological efficacy of agents in early stages of drug development.

Corticospinal Tract and Related Grey Matter Morphometric Shape Analysis in ALS Phenotypes: A Fractal Dimension Study

A pathological hallmark of amyotrophic lateral sclerosis (ALS) is corticospinal tract (CST) degeneration resulting in upper motor neuron (UMN) dysfunction. No quantitative test is available to easily assess UMN pathways. Brain neuroimaging in ALS promises to potentially change this through identifying biomarkers of UMN dysfunction that may accelerate diagnosis and track disease progression. Fractal dimension (FD) has successfully been used to quantify brain grey matter (GM) and white matter (WM) shape complexity in various neurological disorders. Therefore, we investigated CST and whole brain GM and WM morphometric changes using FD analyses in ALS patients with different phenotypes. We hypothesized that FD would detect differences between ALS patients and neurologic controls and even between the ALS subgroups. Neuroimaging was performed in neurologic controls (n = 14), and ALS patients (n = 75). ALS patients were assigned into four groups based on their clinical or radiographic phenotypes. FD values were estimated for brain WM and GM structures. Patients with ALS and frontotemporal dementia (ALS-FTD) showed significantly higher CST FD values and lower primary motor and sensory cortex GM FD values compared to other ALS groups. No other group of ALS patients revealed significant FD value changes when compared to neurologic controls or with other ALS patient groups. These findings support a more severe disease process in ALS-FTD patients compared to other ALS patient groups. FD value measures may be a sensitive index to evaluate GM and WM (including CST) degeneration in ALS patients.

Upper Motor Neuron Signs in the Cervical Region of Patients With Flail Arm Syndrome.

Objective: We investigated upper motor neuron (UMN) signs in the cervical region in a Chinese clinic-based cohort of patients with flail arm syndrome (FAS) by clinical examination and neurophysiological tests such as triple stimulation technique (TST) and pectoralis tendon reflex testing.Methods: A total of 130 consecutive FAS patients from Peking University Third Hospital underwent physical examination and neurophysiological tests at baseline and 3 months, 6 months, 9 months, and 12 months later. Pyramidal signs, pectoralis tendon reflex and TST results were evaluated to estimate the function of cervical spinal UMNs.Results: At the first visit, weakness of the bilateral proximal upper limbs was found in 99 patients, while weakness of a single proximal upper limb was found in 31 patients. There were 49 patients with tendon hyperreflexia, 42 patients with tendon hyporeflexia and 39 patients with tendon areflexia. All except 4 of the patients had brisk pectoralis tendon reflex. The UMN score of the cervical region was 1.7 ± 0.4, and the lower motor neuron score of that region was 3.5 ± 0.3. The TSTtest/TSTcontrol amplitude ratio was 65.7 ± 7.5%. The latency of quantitative detection of the pectoralis tendon reflex was 7.7 ± 1.2 ms. In the follow-up study, the UMN score and the TSTtest/TSTcontrol amplitude ratio decreased, while the lower motor neuron score increased, and the latency of quantitative detection of the pectoralis tendon reflex remained steady.Conclusion: Although the signs of cervical spinal UMN dysfunction in patients with FAS were often concealed by muscle atrophy in the progression of the disease, TST and pectoralis tendon reflex could reveal it.

The NEALS primary lateral sclerosis registry

Background and objective Primary lateral sclerosis (PLS) is a neurodegenerative disease characterized by progressive upper motor neuron dysfunction. Because PLS patients represent only 1 to 4% of patients with adult motor neuron diseases, there is limited information about the disease’s natural history. The objective of this study was to establish a large multicenter retrospective longitudinal registry of PLS patients seen at Northeast ALS Consortium (NEALS) sites to better characterize the natural progression of PLS. Methods: Clinical characteristics, electrophysiological findings, laboratory values, disease-related symptoms, and medications for symptom management were collected from PLS patients seen between 2000 and 2015. Results: The NEALS registry included data from 250 PLS patients. Median follow-up time was 3 years. The mean rate of functional decline measured by ALSFRS-R total score was −1.6 points/year (SE:0.24, n = 124); the mean annual decline in vital capacity was −3%/year (SE:0.55, n = 126). During the observational period, 18 patients died, 17 patients had a feeding tube placed and 7 required permanent assistive ventilation. Conclusions: The NEALS PLS Registry represents the largest available aggregation of longitudinal clinical data from PLS patients and provides a description of expected natural disease progression. Data from the registry will be available to the PLS community and can be leveraged to plan future clinical trials in this rare disease.

Electrodiagnosis of Amyotrophic Lateral Sclerosis: A Review of Existing Guidelines.

Amyotrophic lateral sclerosis (ALS) is characterized by degeneration of upper motor neurons in the motor cortex and lower motor neurons (LMN) in the brainstem and spinal cord, resulting in a progressive functional impairment. Neurophysiology is a diagnostic tool to detect dysfunction of upper motor neurons and LMN, even when the changes are subclinical. Electromyography is the standard neurophysiological investigation to detect LMN changes, which is essential to exclude mimicking disorders and attain early diagnosis. Recently, Awaji criteria was proposed to support ALS diagnosis, in these criteria fasciculation potentials associated with neurogenic motor unit potentials represents a sufficient marker of LMN involvement, in each muscle. Many studies have confirmed that Awaji criteria are more sensitive, permitting earlier diagnosis without loss of specificity when compared with the revised El Escorial criteria. Fasciculations are easily detected by ultrasound; increasingly, this technique has been used to diagnose ALS, combined with electromyography. This combination can increase diagnostic accuracy. Many techniques for estimating the number of motor units have been proposed, they are useful to quantify LMN loss. Electrical impedance myography is an emerging technique with great potential to monitor ALS progression. Neurophysiological investigation of upper motor neuron dysfunction is difficult in ALS, detecting decreased cortical inhibition by threshold tracking cortical magnetic stimulation is a promising method, which needs to be validated in different centers.

Spreading in ALS: The relative impact of upper and lower motor neuron involvement.

ObjectiveTo investigate disease spread in amyotrophic lateral sclerosis (ALS), and determine the influence of lower (LMN) and upper motor neuron (UMN) involvement.MethodsWe assessed disease spread in ALS in 1376 consecutively studied patients, from five European centers, applying an agreed proforma to assess LMN and UMN signs. We defined the pattern of disease onset and progression from predominant UMN or lower motor neuron (LMN) dysfunction in bulbar, upper limbs, lower limbs, and thoracic regions Non‐linear regression analysis was applied to fit the data to a model that described the relation between two random variables, graphically represented by an inverse exponential curve. We analyzed the probability, rate of spread, and both combined (area under the curve).ResultsWe found that progression was more likely and quicker to or from the region of onset to close spinal regions. When the disease had a limb onset, bulbar motor neurons were more resistant. Furthermore, in the same time frame more patients progressed from bulbar to lower limbs than vice‐versa, whether predominantly UMN or LMN involvement. Patients with initial thoracic involvement had a higher probability for rapid change. The presence of predominant UMN signs was associated with a faster caudal progression.InterpretationContiguous progression was leading pattern, and predominant UMN involvement is important in shortening the time for cranial‐caudal spread. Our results can best be fitted to a model of independent LMN and UMN degeneration, with regional progression of LMN degeneration mostly by contiguity. UMN lesion causes an acceleration of rostral‐caudal LMN loss.

Central motor conduction time reveals upper motor neuron involvement masked by lower motor neuron impairment in a significant portion of patients with amyotrophic lateral sclerosis

ObjectiveWe retrospectively investigated the utility of the central motor conduction time (CMCT) in detecting upper motor neuron (UMN) involvements in patients with amyotrophic lateral sclerosis (ALS). MethodsFifty-two ALS patients and 12 disease control patients participated in this study. Surface electromyograms were recorded from the first dorsal interosseous (FDI) and tibialis anterior (TA) muscles. We stimulated the motor cortex, brainstem, and spinal nerve using transcranial magnetic stimulation (TMS) in order to measure the cortical, brainstem, and spinal latencies. We divided the ALS patients into 2 subgroups (with UMN impairment vs. without UMN impairment) and calculated the rates of abnormal CMCT prolongation judged by their comparison with the normal ranges obtained by the measurement in the control patients. ResultsThe CMCTs in the FDI and TA were abnormally prolonged in over 40% of the ALS patients with UMN impairment and in nearly 30% of those without UMN impairment. ConclusionsCMCT shows UMN dysfunction in ALS patients without clinical UMN impairment. SignificanceTMS still has diagnostic utility in a significant portion of ALS patients.

P66-S Corticospinal function in poliomyelitis survivors

Background Poliomyelitis survivors (PS) become candidates to post-polio syndrome (PPS) in their later lives. The mechanism of PPS has been suggested to be multifactorial involving cortical, spinal and peripheral mechanisThe aim of this study was to evaluate TMS parameters in PS and to compare them with those of amyotrophic lateral sclerosis (ALS) patients and controls. Material and methods Single and paired TMS, contralateral and ipsilateral silent period (SP) and triple stimulation technique (TST) were performed by recording from abductor digiti minimi (ADM) and abductor pollicis brevis (APB) muscles of 18 PS, 31 ALS patients and 21 controls. The results were compared with mixed ANOVA and nonparametric independent tests. Results No significant difference was present for within and between subject factors except those for the different interstimuli intervals. Resting motor threshold and MEP/M% in ADM, MEP amplitudes and latencies and TST% in both ADM and APB were significantly different. In posthoc analyses, MEP latencies were higher and TST% were lower in both ADM and APB in ALS group (20.7 ± 4.2 ms, 22.4 ± 5.0 ms, 83.1 ± 42.2, 72.3 ± 29.9) as compared to PS (18.3 ± 1.0 ms, 19.2 ± 2.0 ms, 101.6 ± 15.9, 98.1 ± 14.9), MEP/M% in ADM were lower in PS group (56.0 ± 13.4) as compared to controls (85.2 ± 23.9). SPs, TST, MEP amplitudes and latencies and MEP/M amplitudes did not show any significant difference between ADM and APB in both patient groups. Conclusions Our results revealed upper motor neuron dysfunction in ALS compared to PS and may provide limited evidence about presence of an abnormal cortical drive to mostly uninvolved upper extremity muscles in PS.

Neurophysiological biomarkers in amyotrophic lateral sclerosis.

Amyotrophic lateral sclerosis (ALS) is a rapidly progressive neurodegenerative disorder of the motor neurons, characterized by upper motor neuron (UMN) and lower motor neuron (LMN) dysfunction. There have been significant technological advances in the development of neurophysiological biomarkers of UMN and LMN dysfunction in ALS. In this review, we discuss major advances in development of neurophysiological biomarkers in ALS, critiquing their potential in diagnosis and prognosis of ALS, as well as utility in monitoring treatment effects. The threshold tracking transcranial magnetic stimulation (TMS) technique has established cortical hyperexcitability as an early and specific biomarker of UMN dysfunction in ALS, and associated with neurodegeneration. In addition to establishing cortical hyperexcitability as a pathophysiological mechanism, threshold tracking TMS has enabled an earlier diagnosis of ALS and provided a means of monitoring effects of therapeutic agents. Biomarkers of LMN dysfunction, including motor unit number estimation, the neurophysiological index, electrical impedance myography and axonal excitability techniques, have all exhibited utility in monitoring disease progression. In addition to enhancing ALS diagnosis, the development of novel neurophysiological biomarkers has implications for clinical trials research and drug development, enabling the assessment of biological efficacy of agents in early stages of drug development.

Coordination and timing deficits in speech and swallowing in autosomal recessive spastic ataxia of Charlevoix–Saguenay (ARSACS)

Autosomal recessive spastic ataxia of Charlevoix-Saguenay (ARSACS) is a rare early onset neurodegenerative disease that typically results in ataxia, upper motor neuron dysfunction and sensorimotor peripheral neuropathy. Dysarthria and dysphagia are anecdotally described as key features of ARSACS but the nature, severity and impact of these deficits in ARSACS are not known. A comprehensive quantitative and qualitative characterization of speech and swallowing function will support diagnostics, provide insights into the underlying pathology, and guide day-to-day clinical management. 11 consecutive non-Quebec ARSACS patients were recruited, and compared to healthy participants from several published and unpublished cohorts. A comprehensive behavioural assessment including objective acoustic analysis and expert perceptual ratings of motor speech, the Clinical Assessment of Dysphagia in Neurodegeneration (CADN), videofluoroscopy and standardized tests of dysarthria and swallowing related quality of life was conducted. Speech in this ARSACS cohort is characterized by pitch breaks, prosodic deficits including reduced rate and prolonged intervals, and articulatory deficits. The swallowing profile was characterized by delayed initiation of the swallowing reflex and late epiglottic closure. Four out of ten patients were observed aspirating thin liquids on videofluoroscopy. Patients report that they regularly cough or choke on thin liquids and solids during mealtimes. Swallowing and speech-related quality of life was worse than healthy controls on all domains except sleep. The dysphagia and dysarthria profile of this ARSACS cohort reflects impaired coordination and timing. Dysphagia contributes to a significant impairment in functional quality of life in ARSACS, and appears to manifest distinctly from other ARSACS dysfunctions such as ataxia or spasticity.

Title: Quantifying the change of spasticity after intrathecal baclofen administration: A descriptive retrospective analysis

ObjectivesExploratory research quantifying the change of spasticity among patients who underwent baclofen intrathecal drug delivery system (IDDS) implantation.Patients and Methods: 88 patients with a baclofen IDDS were identified. Patient characteristics, spasticity scores pre/post intrathecal baclofen test dose, and IDDS perioperative implantation records were collected. The primary outcome was to quantify the extent to which there was a change in Modified Ashworth Scores (MAS) pre/post-intrathecal baclofen test dose administration. Secondary outcomes included the prevalence of perioperative IDDS implantation complications. ResultsThe mean age at IDDS implant was 44.2 years (range, 19–71), and 62.5% were male. 45.5% had spasticity of spinal cord origin, 9% of cerebral origin, and 45.5% of other upper motor neuron dysfunction. Reduction of MAS in the spinal cord origin group was 2.6 (mean, 3.5 to 0.9), cerebral origin group was 2.9 (mean, 3.3 to 0.4), and other origin group was 2.5 (mean, 3.6 to 1.1). In all patients, post dural puncture headache was the most commonly reported complication at 22.7%. ConclusionThis report offers novel findings documenting a quantifiable change of at least two points on the MAS before and after intrathecal baclofen test dose as statistically significant and could prove to be useful information to enhance the decision making process to proceed with intrathecal baclofen beyond assessment of functional abilities.

S17-4. Nerve and muscle ultrasound assessment in ALS

In the diagnosis and assessment of amyotrophic lateral sclerosis (ALS), the roles of nerve and muscle ultrasound vary widely. Nerve ultrasound has revealed that cross-sectional area (CSA) was decreased in the median and ulnar nerves and the nerve roots in ALS. In addition, a longitudinal study demonstrated the possibility that ulnar nerve CSA could be a useful biomarker to monitor disease progression in ALS. Muscle ultrasound is useful for detecting widespread fasciculations in the diagnosis of ALS. Ultrasound technique is suitable for assessing the distribution and frequency of fasciculations non-invasively. Furthermore, muscle ultrasound is also used to measure the thickness of the diaphragm and bulbar muscles. Decreased thickness of the diaphragm indicates pulmonary dysfunction, and decreased the thickness of the tongue suggests swallowing dysfunction. Interestingly, the thickness change of the bulbar muscle during swallowing relates to the severity of upper motor neuron dysfunction. Although modern MRI technique also has progressed and is increasingly being used as a nerve and muscle imaging tool, nerve and muscle ultrasound can be disseminated widely due to its convenience and non-invasiveness and will enable neurologist/neurophysiologists to diagnose and to assess ALS more accurately coupled with an electromyography machine.