Upper Motor Neuron Dysfunction Research Articles

Clinical features of brain motor control and influence in upper motor neuron dysfunction

Division of Neurosurgery, Center for Neurophysiology and Restorative Neurology, University of California at San Diego School of Medicine, USA Spinal Cord Injury Research and Restorative Neurology, Crawford Research Institute, Shepherd Center, Departments of Neurology and Physiology, Emory University School of nta, G edicine, Atlanta Veterans Administration Medical Center, 2020 Peachtree Rd NW, Atla

Compensatory movement-related recruitment in amyotrophic lateral sclerosis patients with dominant upper motor neuron signs: An EEG source analysis study

Cortical reorganization to simple movement in patients with amyotrophic lateral sclerosis (ALS) has been investigated in neuroimaging studies, reporting recruitment of ipsilateral primary sensorimotor (iSMC) and premotor regions (PMd). In order to investigate the spatiotemporal pattern of such overactivation, EEG source analysis to brisk self-paced finger movements was performed in thirty-two ALS patients, able to initiate their movement as fast as controls and clustered according to their most affected motor neuron (upper or lower). Reduced activity within cortical sources in bilateral SMC and caudal mesial areas was found only in patients subgroup with extensive upper motor neuron (UMN) clinical signs and mild motor weakness (U>L). Its absence in patients with opposite clinical features (L>U) suggest that this reduction might represent a possible marker of UMN impairment, and that the lower motor neuron (LMN) degeneration in L>U patients did not exert a retrograde effect over their cortical motor neurons. An ipsilateral premotor recruitment was observed in U>L patients only and since its extent positively correlated with movement initiation speed and right hand Medical Research Council (MRC) score, it might represent a compensatory recruitment. The latter correlation might suggest that the slight motor weakness in those patients may at least partly depend from a UMN dysfunction that can be compensated by cortical recruitment.

Diffusion Tensor Imaging Evaluation of Corticospinal Tract Hyperintensity in Upper Motor Neuron-Predominant ALS Patients

Amyotrophic lateral sclerosis (ALS) patients with predominant upper motor neuron (UMN) signs occasionally have hyperintensity of corticospinal tract (CST) on T2- and proton-density-(PD-) weighted brain images. Diffusion tensor imaging (DTI) was used to assess whether diffusion parameters along intracranial CST differ in presence or absence of hyperintensity and correspond to UMN dysfunction. DTI brain scans were acquired in 47 UMN-predominant ALS patients with (n = 21) or without (n = 26) CST hyperintensity and in 10 control subjects. Fractional anisotropy (FA), mean diffusivity (MD), axial diffusivity (AD), and radial diffusivity (RD) were measured in four regions of interests (ROIs) along CST. Abnormalities (P < 0.05) were observed in FA, AD, or RD in CST primarily at internal capsule (IC) level in ALS patients, especially those with CST hyperintensity. Clinical measures corresponded well with DTI changes at IC level. The IC abnormalities suggest a prominent axonopathy in UMN-predominant ALS and that tissue changes underlying CST hyperintensity have specific DTI changes, suggestive of unique axonal pathology.

Proton magnetic resonance spectroscopy in patients with early stages of amyotrophic lateral sclerosis

Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disorder primarily affecting upper and lower motor neurons. Due to relative fast progression of the disease, early diagnosis is essential. Proton magnetic resonance spectroscopy ((1)H-MRS) is used for objectivization of upper motor neuron (UMN) lesions. The aim of this study was to assess the use of (1)H-MRS in the early stages of ALS. Eleven patients with clinically definite (n=2), probable (n=7), and probable laboratory-supported (n=2) diagnosis of ALS with disease duration of less than 14 months were studied. Control group consists of 11 sex- and age-matched healthy subjects. All subjects underwent assessment of functional disability using revised ALS Functional Rating Scale (ALSFRS-R) and single-voxel (1)H-MRS examination of both precentral gyri, pons, medulla oblongata, and occipital lobe. Spectra were evaluated with LCModel software. The mean disease duration was 6.5 ± 3.5 months. The median ALSFRS-R was 42. Significant decrease between patient and control groups was found in the NAA/Cre ratio in the left and right precentral gyri (p=0.008, p=0.040). Other metabolite ratios in other areas did not show significant differences. Total ALSFRS-R score weakly positively correlated with NAA/Cre ratio in the left precentral gyrus (p=0.047). (1)H-MRS is sensitive to detect metabolic changes caused by neurodegeneration processes during ALS and can be used for detection of UMN dysfunction. These MRS changes in the early stages of ALS are most prominent in motor cortex.

Sensitivity of electrophysiological tests for upper and lower motor neuron dysfunction in ALS: A six‐month longitudinal study

By following a group of amyotrophic lateral sclerosis (ALS) patients longitudinally using lower motor neuron (LMN) and upper motor neuron (UMN) markers of dysfunction it may be possible to better understand the functional relationships between these motor systems in this disease. We used neurophysiological techniques to follow UMN and LMN dysfunction in a group of 28 patients with ALS, in comparison with the ALS functional rating scale (ALS-FRS) score and the forced vital capacity (FVC). We used motor unit number estimation (MUNE), compound muscle action potential (CMAP) amplitude, and the Neurophysiological Index (NI) to quantify the LMN disorder, and transcranial motor stimulation to study cortical motor threshold, motor-evoked response amplitude, central motor conduction time, and cortical silent period (CSP). The patients were studied shortly after diagnosis and then 6 months later, using both abductor digiti minimi muscles (ADM); ADM strength was initially >MRC 3 (Medical Research Council, UK). The NI and MUNE changed more than any other variable. CSP increased by about 30%, a change more marked than the slight increase observed in the cortical motor threshold (9%). The normal increase of CSP after acute muscle fatigue was preserved during disease progression. The CSP increase correlated with the MUNE rate of decay but not to the NI reduction, perhaps because NI includes F-wave frequency in itscalculation. There was no definite correlation between UMN and LMNdysfunction or progression, but there was a link between CSP and LMN changes in ALS. The CSP may be a useful variable in following UMN dysfunction in clinical practice and in clinical trials.

Clinical Practice of Functional Electrical Stimulation: From “Yesterday” to “Today”

Functional electrical stimulation (FES) is an accepted treatment method for paresis or paralysis after spinal cord and head injury as well as stroke and other neurological upper motor neuron disorders. At the beginning, FES worked like an electrophysiological brace for the correction of drop foot of patients after a stroke. When analyzing early accomplishments, it becomes evident that FES was influenced rather by technological and biomedical engineering development than by contemporary knowledge on neurocontrol of movement in individuals with upper motor neuron paralysis. Nevertheless, with better understanding of pathophysiology of spasticity and neurocontrol of impaired movement, FES advanced from an electrophysiological brace to a treatment modality for the improvement of muscle control, neuroaugmentation of residual movements, and supportive procedure for "spontaneous recovery" of motor control. In the present article we shall illustrate barriers which delayed FES to be applied in clinical practice of neuron rehabilitation from "Yesterday" to "Today." We shall discuss the importance to apply FES early after the onset of neurological conditions to prevent disuse of noninjured portions of the CNS. Moreover, FES can play a significant role in the supporting processes of neuroplasticity in the subacute phase of upper motor neuron dysfunction. Therefore, the electrophysiological brace of "Yesterday" provides "Today" a correction of missing neuromuscular function. At the same time, it is an active external device for the correction of motor deficits interacting with the somatosensory-motor integration. Thus, "Yesterday" and "Today" of the same technological approach can be very different, thanks to a different understanding and assessment of "external" and "internal" components of human motor control.

Magnetic stimulation including the triple‐stimulation technique in amyotrophic lateral sclerosis

To study the relative importance of upper motor neuron (UMN) dysfunction in the weakness of amyotrophic lateral sclerosis (ALS) and to compare the sensitivity of several transcranial magnetic stimulation (TMS) parameters as means of assessing UMN impairment in ALS, we used TMS to evaluate one upper limb of 63 patients. The triple-stimulation technique (TST) and silent period (SP) were found to be the most frequently abnormal parameters (55.6% and 47.6%, respectively), without significant difference in their diagnostic sensitivity. The SP was found to be a useful parameter in patients with suspected or possible ALS. A positive correlation was found between weakness and the TST amplitude ratio, indicating that weakness may partly be caused by UMN dysfunction. Thus, the TST provides a quantitative tool for assessing UMN conduction failure. When used in association with the SP, the TST provides a sensitive diagnostic tool for use on ALS patients.

Failure to Polarize Cortical Motor Neurons in ALS

Early identification, understanding, and measurement of the upper motor neuron (UMN) component of amyotrophic lateral sclerosis (ALS) are problematic. Only in the last decade have physicians attempted to use surrogate markers to detect UMN dysfunction in ALS. Techniques have included transcranial magnetic stimulation, magnetic resonance imaging in a variety of formats, and …

Upper motor neuron involvement in X-linked recessive bulbospinal muscular atrophy

ObjectiveClinicopathological findings of X-linked recessive bulbospinal muscular atrophy (SBMA) are indicative of lower motor neuron and primary sensory neuron involvement. The aim of our study was to investigate the presence of subclinical upper motor neuron (UMN) dysfunction in this disease. MethodsTwo siblings with clinical presentation, routine electrophysiological tests, histopathological features of muscle and nerve biopsies and genetic testing consistent with diagnosis of SBMA underwent transcranial magnetic stimulation (TMS). The analysed parameters were motor evoked potential (MEP) threshold, silent period (SP) and central motor conduction time. Intracortical inhibition with paired pulses from 1 to 6ms interstimulus intervals (ISIs) was evaluated in the older brother. ResultsMEP parameters were significantly altered in limb and cranial muscles and MEP suppression after paired stimulation significantly reduced in the older brother. MEP abnormalities were present in one lower limb, but SP abolished in all limbs, in the younger brother. ConclusionsSubclinical involvement of UMNs may be present in patients affected by SBMA. This finding suggests that the array of neuronal systems whose function may be affected by the pathogenic process of SBMA is larger than it was considered so far. SignificanceTMS is a sensitive diagnostic tool for the identification of UMN dysfunction and should be included in the diagnostic evaluation of patients with SBMA.

Sporadic SCA8 mutation resembling corticobasal degeneration

Spinocerebellar ataxia type 8 (SCA8) is caused by the expansion of CTA/CTG triplet repeats on 13q21. Cases can be familial or sporadic. The clinical findings include cerebellar ataxia with upper motor neuron dysfunction, dysphagia, peripheral sensory disturbances, or cognitive and psychiatric impairments, indicating phenotypic variability in SCA8. We report on a patient with rapidly progressive parkinsonism-plus syndrome resembling corticobasal degeneration and triplet expansions in the SCA8 locus. The relationship between clinical phenotype and triplet expansions in the SCA8 locus requires further study.

Optimising the detection of upper motor neuron function dysfunction in amyotrophic lateral sclerosis?a transcranial magnetic stimulation study

Evidence of upper motor neuron (UMN) dysfunction is essential in making the diagnosis of amyotrophic lateral sclerosis (ALS). Central motor conduction (CMC) abnormalities detected using transcranial magnetic stimulation (TMS) are presumed to reflect UMN dysfunction. CMC is, however, often normal in patients with classical sporadic ALS. The aim of the study was to determine whether the utility of the CMC measure in ALS could be enhanced. We measured CMC to four pairs of muscles (abductor digiti minimi (ADM), biceps, vastus medialis (VM) and abductor hallucis (AH) in 20 controls and 25 ALS patients. The commonest abnormality detected in the ALS patients was an absent MEP, found in 11 patients (44 %) and in 25 of 200 muscles examined. Studying a minimum of three muscles increased the probability of detecting UMN dysfunction. Weakness in the muscle as well as selecting a distal rather than a proximal muscle was significantly associated with an abnormal CMC. Interside differences in CMC were significantly more pronounced in the patient group. In 30% of patients a significant interside difference in AH CMC time was the sole abnormality, suggesting mild UMN dysfunction on the side with the longer CMC.

No correlation between number of MRI‐evident lesions in cerebrum and the soleus stretch reflex in multiple sclerosis patients

The aim of the study was to investigate if the stretch reflex of the soleus muscle was useful in quantifying upper motor neuron lesions. The soleus stretch reflex was recorded in 10 healthy subjects and 20 patients with active relapsing-remitting multiple sclerosis and correlated to the number of MRI lesions in cerebrum and clinical scores (expanded disability status scale and regional functional scoring system). The short latency stretch reflex was elicited by rotating the left ankle joint 4 degrees with a rise time in the interval of 40-640 ms. The amplitude of the stretch was larger in multiple sclerosis patients being 88.5 microV in patients and 12.8 microV in controls, P = 0.007. The sensitivity of the stretch reflex expressed as the slope of the best linear fit was increased in MS patients to 2.6 microVs/degree compared with 0.6 microVs/degree (0.1-2.2) in controls, P = 0.009. There was no correlation between amplitude of the stretch reflex and number of MRI lesions (r = -0.03). In conclusion, the soleus stretch reflex might be useful to quantify spasticity but is not useful in detecting dysfunction of upper motor neurons in MS.

Neonatal loss of motor function in human spina bifida aperta.

In neonates with spina bifida aperta (SBA), leg movements innervated by spinal segments located caudal to the meningomyelocele are transiently present. This study in neonates with SBA aimed to determine whether the presence of leg movements indicates functional integrity of neuronal innervation and whether these leg movements disappear as a result of dysfunction of upper motor neurons (axons originating cranial to the meningomyelocele) and/or of lower motor neurons (located caudal to the meningomyelocele). Leg movements were investigated in neonates with SBA at postnatal day 1 (n = 18) and day 7 (n = 10). Upper and lower motor neuron dysfunction was assessed by neurologic examination (n = 18; disinhibition or inhibition of reflexes, respectively) and by electromyography (n = 12; absence or presence of denervation potentials, respectively). Movements, related to spinal segments caudal to the meningomyelocele, were present in all neonates at postnatal day 1. At day 1, leg movements were associated with signs of both upper (10 of 18) and lower (17 of 18) motor neuron dysfunction caudal to the meningomyelocele. In 7 of 10 neonates restudied after the first postnatal week, leg movements had disappeared. The absence of leg movements coincided with loss of relevant reflexes, which had been present at day 1, indicating progression of lower motor neuron dysfunction. We conclude that the presence of neonatal leg movements does not indicate integrity of functional lower motor neuron innervation by spinal segments caudal to the meningomyelocele. Present observations could explain why fetal surgery at the level of the meningomyelocele does not prevent loss of leg movements.

Electrophysiologic evaluation of upper motor neuron involvement in amyotrophic lateral sclerosis

The demonstration of upper motor neuron (UMN) dysfunction in patients with amyotrophic lateral sclerosis (ALS) with predominantly lower motor neuron (LMN) signs is clinically sometimes difficult. We analyzed the possible role of F and H waves in the diagnosis of UMN dysfunction in 36 patients with different clinical forms of ALS and 20 controls. In both lower limbs we evaluated F-wave persistence and the F/M ratio of tibial nerves, Hmax/Mmax ratio, vibratory and recurrent (paired) inhibition of the H-reflex. The persistence of the F-response was decreased significantly in the LMN group only. The F/M amplitude ratio, vibrated-H/rest-H amplitude ratio and conditioned H/rest H amplitude ratio were significantly increased in patients with predominantly UMN, as well as in those with predominantly LMN signs. H/M amplitude ratios did not differ between the various patient groups. These findings show that ALS patients, including those without clinical evidence of UMN involvement, have a marked disinhibition of anterior horn motor neurons. The simple tests described could support an UMN abnormality when clinical signs are lacking, and help to establish a diagnosis sooner and more accurately.

Quantification of upper motor neuron loss in amyotrophic lateral sclerosis

Objective: To quantitatively estimate upper motor neuron (UMN) loss in ALS. Methods: We used the recently developed triple stimulation technique (TST) to study corticospinal conduction to 86 abductor digiti minimi muscles of 48 ALS patients. This method employs a collision technique to estimate the proportion of motor units activated by a transcranial magnetic stimulus. At the same time, it yields an estimate of lower motor neuron (LMN) integrity. Results: The TST disclosed and quantified central conduction failures attributable to UMN loss in 38 sides of 24 patients (subclinical in 15 sides), whereas conventional motor evoked potentials detected abnormalities in only 18 sides of 12 patients (subclinical in two sides). The increased sensitivity of the TST to detect UMN dysfunction was particularly observed in early cases. Increased central motor conduction times (CMCT) occurred exclusively in sides with conduction failure. In sides with clinical UMN syndromes, the TST response size (but not the CMCT) correlated with the muscle weakness. In sides with clinical LMN syndromes, the size of the peripherally evoked compound muscle action potentials correlated with the muscle weakness. Conclusion: The TST is a sensitive method to detect UMN dysfunction in ALS. It allows a quantitative estimate of the UMN loss, which is related to the functional deficit. Therefore, the TST has a considerable impact on diagnostic certainty in many patients. It will be suited to follow the disease progression and therapeutic trials.

Proton magnetic resonance spectroscopy ( 1 H-MRS) in ALS

Establishing the presence of upper motor neuron (UMN) pathology is essential for an accurate and definite diagnosis of ALS. However, clinical identification of UMN dysfunction can be difficult in early disease or if lower motor neuron signs are prominent. A routine technique such as magnetic resonance imaging is usually normal and non-specific. Proton magnetic resonance spectroscopy (1H-MRS) is a non-invasive neuroimaging technique that has successfully demonstrated evidence of neuronal abnormalities in motor regions of the brain in ALS. This review discusses the advantages and limitations of employing 1H-MRS as an investigative tool in the diagnosis of ALS.

Transcranial magnetic stimulation (TMS): compared sensitivity of different motor response parameters in ALS.

Owing to the low sensitivity of clinical signs in assessing upper motor neuron (UMN) involvement in ALS, there is a need for investigative tools capable of detecting abnormal function of the pyramidal tract. Transcranial magnetic stimulation (TMS) may contribute to the diagnosis by reflecting a UMN dysfunction that is not clinically detectable. Several parameters for the motor responses to TMS can be evaluated with different levels of significance in healthy subjects compared with ALS patients. The central motor conduction time, however, is not sensitive in detecting subclinical UMN defects in individual ALS patients. The amplitude of the motor evoked potential (MEP), expressed as the percentage of the maximum wave, also has a low sensitivity. In some cases, the corticomotor threshold is decreased early in the disease course as a result of corticomotor neuron hyperexcitability induced by glutamate. Later, the threshold increases, indicating a loss of UMN. In our experience, a decreased silent period duration appears to be the most sensitive parameter when using motor TMS in ALS. TMS is also a sensitive technique for investigating the corticobulbar tract, which is difficult to study by other methods. TMS is a widely available, painless and safe technique with a good sensitivity that can visualize both corticospinal and corticobulbar tract abnormalities. The sensitivity can be improved further by taking into account the several MEP parameters, including latency and cortical silent period decreased duration.

Drugs used to treat spasticity.

Spasticity is a common and disabling symptom for many patients with upper motor neuron dysfunction. It results from interruption of inhibitory descending spinal motor pathways, and although the pathophysiology of spasticity is poorly understood, the final common pathway is overactivity of the alpha motor neuron. Therapy for spasticity is symptomatic with the aim of increasing functional capacity and relieving discomfort. Any approach to treatment should be multidisciplinary, including physical therapy, and possibly surgery, as well as pharmacotherapy. It is important that treatment be tailored to the individual patient, and that both patient and care giver have realistic expectations. Pharmacotherapy is generally initiated at low dosages and then gradually increased in an attempt to avoid adverse effects. Optimal therapy is the lowest effective dosage. Baclofen, diazepam, tizanidine and dantrolene are currently approved for use in patients with spasticity. In addition, clonidine (usually as combination therapy), gabapentin and botulinum toxin have shown efficacy, however, more studies are required to confirm their place in therapy. Intrathecal baclofen, via a surgically implanted pump and reservoir, may provide relief in patients with refractory severe spasticity.

Delayed Diffuse Upper Motor Neuron Syndrome after Compressive Thoracic Myelopathy

A 54-year-old man developed progressive spastic paraparesis beginning 2 weeks after a back injury caused by a subacute compressive thoracic myelopathy attributable to a post-traumatic arachnoid cyst. Three to 18 months after surgical decompression of the thoracic arachnoid cyst, the patient developed a diffuse predominantly upper motor neuron syndrome characterized by spastic quadriparesis, pseudobulbar paresis, and pseudobulbar affect. Retrograde corticospinal tract degeneration and upper motor neuron death after spinal cord injury is recognized. This case suggests that focal upper motor neuron injury can occasionally precipitate diffuse upper motor neuron dysfunction.

Tethered Cord Syndrome in Occult Spinal Dysraphism. Timing and Outcome of Surgical Release

Objective To investigate the influence of neurosurgical intervention on the appearance of upper motor neuron (UMN) signs in newborns diagnosed with occult spinal dysraphism and tethered cord (TC) during the first month of life. Methods A prospective study (1990 to 1996) of 22 consecutive newborns with occult spinal dysraphism monitored for the appearance of UMN signs. Untethering was performed when neurologic or urodynamic investigation indicated the presence of UMN dysfunction. Results Of 22 patients, 10 remained free of UMN symptoms during follow-up (mean, 67 ± 22 months). Untethering was performed in 12 of 22 patients because of the presence of UMN symptoms. In 7 of these 12 patients, there was a documented asymptomatic period of 13 ± 11 months before the onset of UMN symptoms. Untethering at a mean age of 18 ± 17 months restored normal neurologic and urinary function in all patients (mean postoperative follow-up, 25 ± 16 months). Of the 12 children, 5 presented with UMN signs at birth. In these children, untethering was performed at a mean age of 9 ± 5 months. In two of these five patients, UMN symptoms did not resolve after surgery, and ongoing conservative bladder treatment was required (mean follow-up, 37 ± 14 months). In none of the 12 operated children did signs of retethering occur. Conclusions A significant number (10/22) of children born with occult spinal dysraphism and TC did not develop UMN symptoms during follow-up; neurosurgical correction after the appearance of an UMN sign restored normal neurologic and urinary function in all children; and untethering in children presenting at birth with UMN symptoms resulted in poorer outcome.