Proximal Motor Research Articles

Histopathological and electrophysiological indices of rotenone-evoked dopaminergic toxicity: Neuroprotective effects of acetyl-l-carnitine

Exposure to the natural pesticide, rotenone, a potent mitochondrial toxin, leads to degeneration in striatal nerve terminals and nigral neurons. Rotenone-induced behavioral, neurochemical and neuropathological changes in rats mimic those observed in Parkinson’s disease (PD). Here, protective effects of acetyl-l-carnitine (ALC) in the brain dopaminergic toxicity after a prolonged exposure to rotenone were evaluated using electrophysiological and immunolabeling methods. Adult, male Sprague–Dawley rats were injected i.p. with rotenone alone (1mg/kg) or rotenone with ALC (either 10 or 100mg/kg; ALC10 or ALC100, respectively) once daily on days 1, 3, 5, 8, 10, 12, 15, 17, 19, 22, 24, 26, 29, 31, 33 and 37. Control rats received either 100mg/kg ALC or vehicle (30% Solutol HS 15 in 0.9% saline) injections. Animals were weighed on injection days and monitored daily. Motor nerve conduction velocity (MCV) was assessed within two days after treatment using compound muscle action potentials (CMAP) detected from the tail muscle through surface receiver electrodes installed around the distal part of the tail. Rats were perfused immediately after testing with 4% paraformaldehyde and immunohistochemical analysis of dopamine transporter (DAT), tyrosine hydroxylase (TH), glial fibrillary acidic protein (GFAP), and microglial CD11b marker was performed in the caudate-putamen (CPu) and the substantia nigra pars compacta (SNc) in order to estimate dopaminergic neuronal and transporter damage. Additionally, effects of ALC on preventing microglial or astrocytic hypertrophy were also evaluated. In rats exposed to rotenone and rotenone/ACL10, a significant increases in both proximal (S1) and distal (S2) motor latency and a decrease in MCV were detected in tail nerves (p<0.05). The conduction parameters in rats co-treated with rotenone/ACL100 were not different from control. It was found that 100mg/kg ALC prevented loss of TH and a decline of DAT level in the midbrain and also prevented the activation of both microglia and astroglia after rotenone treatment. Data indicate neuroprotective effects of ALC in rotenone-evoked dopaminergic neurotoxicity.

Usefulness of cervical root magnetic stimulation in assessing proximal motor nerve conduction

Objectives: To evaluate the reliability and utility of cervical root magnetic stimulation in exploring proximal motor conduction. Methods: In 20 patients with demyelinating polyneuropathy (DPN), 20 patients with amyotrophic lateral sclerosis (ALS) and 25 healthy subjects, evoked compound muscle action potentials (CMAPs) were recorded from abductor digiti minimi muscle in response to electrical stimulation up to Erb’s point and magnetic stimulation up to the cervical roots. Results: In all healthy and ALS subjects, magnetic root stimulation confirmed the absence of conduction abnormalities, including those in whom supramaximal responses at Erb’s point were not achieved. In the DPN group, conduction block and/or temporal dispersion was revealed by magnetic root stimulation in 9 out of 20 patients (45%), 3 more than those detected at Erb’s point. Conclusions: Cervical root stimulation allowed clear distinction between motor neuronopathy and DPN. It is recommended as part of the routine evaluation of patients suspected of having DPN, especially when distal nerve studies are inconclusive.

The usefulness of proximal radial motor conduction in acute compressive radial neuropathy (P3.183)

The usefulness of proximal radial motor conduction in acute compressive radial neuropathy (P3.183)

Tu1434 Duodenal Acid Perfusion in Healthy Volunteers Alters Proximal Gastric Motor Function Resulting in Impaired Gastric Accommodation and Reduced Food Intake

G A A b st ra ct s overlapping (PD and ED) had the lowest scores in the 5 components of PAGI-QOL (P <0.01) (Figure). Conclusions: The prevalence of dyspeptic symptoms in our country is similar to that reported in the literature and is more common in women. Having dyspeptic symptoms significantly affects the quality of life. Although the subgroup ED is the most common, the coexistence of PD and ED is associated with a sign.

The usefulness of proximal radial motor conduction in acute compressive radial neuropathy.

Background and PurposeThe objective of this study was to determine diagnostic and prognostic values of proximal radial motor conduction in acute compressive radial neuropathy.MethodsThirty-nine consecutive cases of acute compressive radial neuropathy with radial conduction studies-including stimulation at Erb's point-performed within 14 days from clinical onset were reviewed. The radial conduction data of 39 control subjects were used as reference data.ResultsThirty-one men and eight women (age, 45.2±12.7 years, mean±SD) were enrolled. All 33 patients in whom clinical follow-up data were available experienced complete recovery, with a recovery time of 46.8±34.3 days. Partial conduction block was found frequently (17 patients) on radial conduction studies. The decrease in the compound muscle action potential area between the arm and Erb's point was an independent predictor for recovery time.ConclusionsProximal radial motor conduction appears to be a useful method for the early detection and prediction of prognosis of acute compressive radial neuropathy.

Motor Function and Respiratory Capacity in Patients with Late-Onset Pompe Disease

Introduction: The relationship between skeletal muscle strength and respiratory dysfunction in Pompe disease has not been examined by quantitative methods. We investigated correlations among lower extremity proximal muscle strength, respiratory function, and motor performance. Methods: Concentric strength of the knee extensor and flexor muscles was measured with a dynamometer, and pulmonary function was evaluated using spirometry in 7 adult patients. The 6-minute walk test and the 4-step stair-climb test were used for assessing aerobic endurance and anaerobic power, respectively. Results: Anaerobic motor performance correlated with strength of both thigh muscles. Respiratory function did not correlate with either muscle strength or motor function performance. Conclusions: Respiratory and lower extremity proximal muscles could be affected differentially by the disease in individual patients. Motor performance is influenced by thigh muscle strength and is less dependent of respiratory capacity in our cohort of ambulatory patients. Muscle Nerve 49:603–606, 2014

The Effect of Body Weight Support Treadmill Training on Gait Recovery, Proximal Lower Limb Motor Pattern, and Balance in Patients with Subacute Stroke.

Objective. Gait performance is an indicator of mobility impairment after stroke. This study evaluated changes in balance, lower extremity motor function, and spatiotemporal gait parameters after receiving body weight supported treadmill training (BWSTT) and conventional overground walking training (CT) in patients with subacute stroke using 3D motion analysis. Setting. Inpatient department of rehabilitation medicine at a university-affiliated hospital. Participants. 24 subjects with unilateral hemiplegia in the subacute stage were randomized to the BWSTT (n = 12) and CT (n = 12) groups. Parameters were compared between the two groups. Data from twelve age matched healthy subjects were recorded as reference. Interventions. Patients received gait training with BWSTT or CT for an average of 30 minutes/day, 5 days/week, for 3 weeks. Main Outcome Measures. Balance was measured by the Brunel balance assessment. Lower extremity motor function was evaluated by the Fugl-Meyer assessment scale. Kinematic data were collected and analyzed using a gait capture system before and after the interventions. Results. Both groups improved on balance and lower extremity motor function measures (P < 0.05), with no significant difference between the two groups after intervention. However, kinematic data were significantly improved (P < 0.05) after BWSTT but not after CT. Maximum hip extension and flexion angles were significantly improved (P < 0.05) for the BWSTT group during the stance and swing phases compared to baseline. Conclusion. In subacute patients with stroke, BWSTT can lead to improved gait quality when compared with conventional gait training. Both methods can improve balance and motor function.

Plenary conference: Keys to successful physical activity during childhood

Plenary conference: Keys to successful physical activity during childhood

Examining motor network disturbances in patients with frontal lobe epilepsy using fMRI

Frontal lobe epilepsy (FLE) is a seizure disorder that commonly associated with functional motor deficits. While the source of these deficits is unknown, it is postulated that repeated seizure activity within the frontal lobe may impact the proximal motor network. To examine this hypothesis, motor networks were compared between participants with right FLE, left FLE, and controls using two methods. The first was a task-based fMRI study of brain activation during simple and complex motor tasks, and the second was a resting-state fMRI study of motor network connectivity. Both studies revealed motor network disturbances in participants with FLE, disturbances that were more pronounced in participants with higher seizure burden factors. These results demonstrate that motor networks are altered in patients with FLE, providing a possible underlying cause behind functional motor deficits in these patients.

Diagnosis value of abnormal distribution of electrophysiological parameters in Guillaln-Barre syndrome

Objective To investigate diagnosis value of abnormal distribution of electrophysiological parameters in Guillain-Barre syndrome. Methods 40 cases of Guillain-Barre syndrome were chosen as an object of study, all patients electrophysiological examination. Record limbs on both sides, upper and lower extremities and proximal and distal motor nerve distal latency （ DML）, motor conduction velocity （ MCV ）, compound muscle action potential （CMAP） and sensory conduction velocity（SCV） were recorded. Results F wave latency mildly abnormal, moderately abnormal and severe abnormalities were 18.3 % ,6.2 % and 5.3 %, totaling 29.8 %, F-wave occurrence rate mildly abnormal,moderately abnormal and severe abnormalities were 9.3 % 9.8% and 15.6% ,totaling 66.9%. Abnormal sensory conduction velocity was 57.5% ,motor conduction velocity anomaly was 75.7%, there was a statistically significant difference between the two groups （x^2 = 5.34, P 〈 0. 05 ）. bilateral tibial nerve tests showed mild, moderate and severe in patients with H-reflex abnormality rates were 78.0% ,80.9% and 100.0% ,among the three comparison （ Uc = 1.47 ,P 〉 0.05 ）. 3 proximal and distal motor nerve severe damage rates were 48.3 percent and 74.5 percent, the difference was statistically Significant （ x^2= 9.86, P 〈 0. 05 ）. Severe upper limb proximal nerve damage was 51.4%, significantly lower than 71.6% of the distal upper extremity, lower extremity proximal nerve severe damage to 44.2 % , significantly lower than the 81.6% of distal lower extremity between them were statistical difference （x^2 = 8.86,12.43, all P 〈 0.05 ）. Conclusion Electrophysiological parameters detection Guillain-Barre syndrome has a high value, which can be accurate response in patients with neurological damage. Key words: Guillain-Barre syndrome ; Nerve conduction; Physiology; Nerve

Rasch Analysis of the Motor Function Measure in Patients With Congenital Muscle Dystrophy and Congenital Myopathy

ObjectivesTo monitor treatment effects in patients with congenital myopathies and congenital muscular dystrophies, valid outcome measures are necessary. The Motor Function Measure (MFM) was examined for robustness, and changes are proposed for better adequacy. DesignObservational study based on data previously collected from several cohorts. SettingNineteen departments of physical medicine or neuromuscular consultation in France, Belgium, and the United States. ParticipantsPatients (N=289) aged 5 to 77 years. InterventionsNone. Main Outcome MeasuresA Rasch analysis examined the robustness of the MFM across the disease spectrum. The 3 domains of the scale (standing position and transfers, axial and proximal motor function, and distal motor function) were independently examined with a partial credit model. ResultsThe original 32-item MFM did not sufficiently fit the Rasch model expectations in either of its domains. Switching from a 4- to a 3-category response scale in 18 items restored response order in 16. Various additional checks suggested the removal of 7 items. The resulting Rasch-scaled Motor Function Measure with 25 items for congenital disorders of the muscle (Rs-MFM25CDM) demonstrated a good fit to the Rasch model. Domain 1 was well targeted to the whole severity spectrum—close mean locations for items and persons (0 vs 0.316)—whereas domains 2 and 3 were better targeted to severe cases. The reliability coefficients of the Rs-MFM25CDM suggested sufficient ability for each summed score to distinguish between patient groups (0.9, 0.8, and 0.7 for domains 1, 2, and 3, respectively). A sufficient agreement was found between results of the Rasch analysis and physical therapists' opinions. ConclusionsThe Rs-MFM25CDM can be considered a clinically relevant linear scale in each of its 3 domains and may be soon reliably used for assessment in congenital disorders of the muscle.

Electrical stimulation of lumbar spinal nerve roots in dogs.

The aim of this study was to test the applicability of electrical stimulation of lumbar spinal nerve roots and obtain normative electrical root stimulation (ERS) data for L7 nerve root and sciatic nerve in dogs. For that purpose ERS and sciatic nerve stimulations were performed consecutively, in totally 40 healthy dogs. ERS was applied in the L7/S1 intervertebral space via monopolar needle electrodes. Muscle responses were recorded from the gastrocnemius muscles on the left and right hind limbs. Sciatic nerve stimulation was performed at the greater trochanter level on the left hind limb, with records obtained from the left gastrocnemius muscle. Mean root latencies of the left and right side were 5.22 ± 0.49 ms and 5.29 ± 0.53 ms, respectively. There was no significant difference in root latency between the right and left sides. The mean terminal latency was 3.82 ± 0.46 ms. The proximal motor nerve conduction velocity of the sciatic nerve was 63.15 ± 3.43 m/s. The results of this study show that ERS provides objective data about the integrity of lumbar spinal nerve roots by evaluating the entire population of motor fibres and total length of the motor axon in dogs. ERS can be considered a useful diagnostic method for confirmation of diagnoses of lumbosacral diseases.

English Cross-Cultural Translation and Validation of the Neuromuscular Score: A System for Motor Function Classification in Patients With Neuromuscular Diseases

ObjectiveTo develop and validate an English version of the Neuromuscular (NM)-Score, a classification for patients with NM diseases in each of the 3 motor function domains: D1, standing and transfers; D2, axial and proximal motor function; and D3, distal motor function. DesignValidation survey. SettingPatients seen at a medical research center between June and September 2013. ParticipantsConsecutive patients (N=42) aged 5 to 19 years with a confirmed or suspected diagnosis of congenital muscular dystrophy. InterventionsNot applicable. Main Outcome MeasuresAn English version of the NM-Score was developed by a 9-person expert panel that assessed its content validity and semantic equivalence. Its concurrent validity was tested against criterion standards (Brooke Scale, Motor Function Measure [MFM], activity limitations for patients with upper and/or lower limb impairments [ACTIVLIM], Jebsen Test, and myometry measurements). Informant agreement between patient/caregiver (P/C)-reported and medical doctor (MD)-reported NM scores was measured by weighted kappa. ResultsSignificant correlation coefficients were found between NM scores and criterion standards. The highest correlations were found between NM-score D1 and MFM score D1 (ρ=−.944, P<.0001), ACTIVLIM (ρ=−.895, P<.0001), and hip abduction strength by myometry (ρ=−.811, P<.0001). Informant agreement between P/C-reported and MD-reported NM scores was high for D1 (κ=.801; 95% confidence interval [CI], .701–.914) but moderate for D2 (κ=.592; 95% CI, .412–.773) and D3 (κ=.485; 95% CI, .290–.680). Correlation coefficients between the NM scores and the criterion standards did not significantly differ between P/C-reported and MD-reported NM scores. ConclusionsPatients and physicians completed the English NM-Score easily and accurately. The English version is a reliable and valid instrument that can be used in clinical practice and research to describe the functional abilities of patients with NM diseases.

Motor function and respiratory capacity in patients with late-onset pompe disease

The relationship between skeletal muscle strength and respiratory dysfunction in Pompe disease has not been examined by quantitative methods. We investigated correlations among lower extremity proximal muscle strength, respiratory function, and motor performance. Concentric strength of the knee extensor and flexor muscles was measured with a dynamometer, and pulmonary function was evaluated using spirometry in 7 adult patients. The 6-minute walk test and the 4-step stair-climb test were used for assessing aerobic endurance and anaerobic power, respectively. Anaerobic motor performance correlated with strength of both thigh muscles. Respiratory function did not correlate with either muscle strength or motor function performance. Respiratory and lower extremity proximal muscles could be affected differentially by the disease in individual patients. Motor performance is influenced by thigh muscle strength and is less dependent of respiratory capacity in our cohort of ambulatory patients.

Wrist rehabilitation in chronic stroke patients by means of adaptive, progressive robot-aided therapy

Despite distal arm impairment after brain injury is an extremely disabling consequence of neurological damage, most studies on robotic therapy are mainly focused on recovery of proximal upper limb motor functions, routing the major efforts in rehabilitation to shoulder and elbow joints. In the present study we developed a novel therapeutic protocol aimed at restoring wrist functionality in chronic stroke patients. A haptic three DoFs (degrees of freedom) robot has been used to quantify motor impairment and assist wrist and forearm articular movements: flexion/extension (FE), abduction/adduction (AA), pronation/supination (PS). This preliminary study involved nine stroke patients, from a mild to severe level of impairment. Therapy consisted in ten 1-hour sessions over a period of five weeks. The novelty of the approach was the adaptive control scheme which trained wrist movements with slow oscillatory patterns of small amplitude and progressively increasing bias, in order to maximize the recovery of the active range of motion. The primary outcome was a change in the active RoM (range of motion) for each DoF and a change of motor function, as measured by the Fugl-Meyer assessment of arm physical performance after stroke (FMA). The secondary outcome was the score on the Wolf Motor Function Test (WOLF). The FMA score reported a significant improvement (average of 9.33±1.89 points), revealing a reduction of the upper extremity motor impairment over the sessions; moreover, a detailed component analysis of the score hinted at some degree of motor recovery transfer from the distal, trained parts of the arm to the proximal untrained parts. WOLF showed an improvement of 8.31±2.77 points, highlighting an increase in functional capability for the whole arm. The active RoM displayed a remarkable improvement. Moreover, a three-months follow up assessment reported long lasting benefits in both distal and proximal arm functionalities. The experimental results of th- s preliminary clinical study provide enough empirical evidence for introducing the novel progressive, adaptive, gentle robotic assistance of wrist movements in the clinical practice, consolidating the evaluation of its efficacy by means of a controlled clinical trial.

Influence of limb temperature on cutaneous silent periods

ObjectiveThe cutaneous silent period (CSP) is a spinal inhibitory reflex mediated by small-diameter afferents (A-delta fibers) and large-diameter efferents (alpha motoneurons). The effect of limb temperature on CSPs has so far not been assessed. MethodsIn 27 healthy volunteers (11 males; age 22–58years) we recorded median nerve motor and sensory action potentials, median nerve F-wave and CSPs induced by noxious digit II stimulation in thenar muscles in a baseline condition at room temperature, and after randomly submersing the forearm in 42°C warm or 15°C cold water for 20min each. ResultsIn cold limbs, distal and proximal motor and sensory latencies as well as F-wave latencies were prolonged. Motor and sensory nerve conduction velocities were reduced. Compound motor and sensory nerve action potential amplitudes did not differ significantly from baseline. CSP onset and end latencies were more delayed than distal and proximal median nerve motor and sensory latencies, whereas CSP duration was not affected. In warm limbs, opposite but smaller changes were seen in nerve conduction studies and CSPs. ConclusionThe observed CSP shift “en bloc” towards longer latencies without affecting CSP duration during limb cooling concurs with slower conduction velocity in both afferent and efferent fibers. Disparate conduction slowing in afferents and efferents, however, suggests that nociceptive EMG suppression is mediated by fibers of different size in the afferent than in the efferent arm, indirectly supporting the contribution of A-delta fibers as the main afferent input. SignificanceLimb temperature should be taken into account when testing CSPs in the clinical setting, as different limb temperatures affect CSP latencies more than large-diameter fiber conduction function.

Decreased Gait and Function in Duchenne Muscular Dystrophy

Duchenne muscular dystrophy (DMD) is a genetic disorder linked to chromosome Xp21, due to absence of dystrophin production. It is clinically characterized by progressive muscle weakness, fatigue, and development of joint contractures that compromise general motor functionality, mainly the gait. Objective: To characterize the motor function and decrease gait in children with DMD using the Portuguese version of the Motor Function Measure scale (MFM-P). Methods: A review of medical records including chronological age and scores from MFM-P of children with a DMD who attended at the Neuromuscular Diseases Clinic at Campinas State University (UNICAMP), Brazil was performed in this study. A total of 36 medical records of male patients with confirmed clinical diagnosis of DMD, ambulatory or not, regardless of age; excluding those with other associated diseases or other types of muscular dystrophies were selected. Data were analyzed using Kolmogorov-Smirnov and Spearman correlation statistical tests. Results: Analysis of all data collected showed that 75% of our sample had D1 scores lower than 41.02%. There was a linear relationship between the scores of D2 and D3, but no association between D2 and D1 scores was noted. D1 score was between 40% and 80% in those patients presenting D2 scores between 80% and 100%. In all cases patients with low total score presented a greater risk for loss of gait and their functionality. Conclusion: The standing posture and the postural transfers were the worst activities observed in children with DMD, with positive correlation between proximal and distal motor function. Even with high scores according MFM-P in proximal function, the children showed strong predictors for loss of gait.

SPG15: a cause of juvenile atypical levodopa responsive parkinsonism

Autosomal recessive hereditary spastic paraplegias with thin corpus callosum (AR HSP-TCC) are rare and complex neurodegenerative disorders characterized by a genetic heterogeneity of which several genes (SPG11 and SPG15, SPG21, SPG47) or loci (SPG32, SPG46) have been identified. In SPG15, additional features have been described [1]: mental retardation, motor neuropathy, dysarthria and pigmentary maculopathy and recently, in a single family with a new homozygous mutation, parkinsonism [2]. In order to further confirm that SPG15 should be considered in the diagnosis of juvenile atypical parkinsonism, we describe another patient affected with SPG15, including juvenileonset levodopa-responsive parkinsonism. A female of Portuguese origin with consanguinity was 17 years old when referred to our center following 12 months of gait difficulties. The patient’s history included mild dysarthria and scholarly delay. Clinical examination demonstrated spastic paraplegia with bilateral extensor plantar reflexes and mild proximal motor deficit in the lower limbs. Vertical saccades were slightly hypometric. By age 19, a left upper limb rest tremor had developed as well as moderate bilateral akinesia, hypertonia, and hypomimia (video). An acute levodopa challenge (250 mg) led to a 60 % improvement of United Parkinson disease rating scale motor score (UPDRSIII) devoted to upper limbs (items 20–25, from 8/24 to 3/24). Rest tremor disappearance was sustained with a levodopa daily dose of M. Anheim and C. Tranchant contributed equally to the work and should be considered as co-last authors.

Gemcitabine-induced myopathy

BackgroundThere have been few studies on muscle injury caused by cytotoxic agents used in cancer. In particular, only four cases of muscle manifestations have been reported in patients who received gemcitabine as single chemotherapy without adjuvant radiotherapy. In only one of these observations gemcitabine was considered to be the causative agent. MethodsWe report the case of a patient without comorbidity treated with gemcitabine monotherapy for 2 months for pancreatic adenocarcinoma, who developed a proximal motor deficiency of the lower limbs and myolysis (creatinine kinase 1858IU/L) associated with an erythema of both thighs. ResultsMuscle MRI revealed the presence of edema on both the quadriceps muscles. A muscle biopsy showed post-necrotic regeneration and significant vascular proliferation. Only three small inflammatory infiltrates were observed, while expression of the major histocompatibility complex class I in muscle fibers was normal. There was no recurrence of cancer, anti-TIF-1γ antibodies tested negative, and discontinuation of gemcitabine, without further treatment, resulted in complete disappearance of symptoms. ConclusionsThe present observation suggests that gemcitabine monotherapy without adjuvant radiotherapy can cause myopathy through vascular lesions, a mechanism which also underlies the more common side effects of this treatment. These findings have obvious therapeutic implications.

Cervical root stimulation in anti‐myelin associated glycoprotein) neuropathy

AbstractWe report a heretofore undescribed use of cervical root stimulation (CRS) in the evaluation of a patient with anti‐myelin‐associated glycoprotein (MAG) neuropathy. A 62‐year‐old man developed progressive difficulty walking. His neurological examination was significant for an unsteady gait and mild weakness. Laboratory tests showed elevated anti‐MAG antibody. CRS showed proximal partial motor conduction block (CB) of the right radial nerve and bilateral ulnar nerves. CRS may be useful in the diagnosis of anti‐MAG neuropathy when the demyelinating process predominantly affects the proximal nerve segments of the upper extremities.