Lower Motor Neuron Syndrome Research Articles

TENDON REFLEX AND STRATEGIES FOR QUANTIFICATION, WITH NOVEL METHODS INCORPORATING WIRELESS ACCELEROMETER REFLEX QUANTIFICATION DEVICES, A PERSPECTIVE REVIEW

The deep tendon reflex is a fundamental aspect of a neurological examination. The two major parameters of the tendon reflex are response and latency, which are presently evaluated qualitatively during a neurological examination. The reflex loop is capable of providing insight into the status and therapy response of both upper and lower motor neuron syndromes. Attempts have been made to ascertain reflex response and latency; however, these systems are relatively complex, resource intensive, with issues of consistent and reliable accuracy. The solution presented is a wireless quantified reflex device using tandem three-dimensional (3D) wireless accelerometers to obtain response based on acceleration waveform amplitude and latency derived from temporal acceleration waveform disparity. Three specific aims have been established for the proposed wireless quantified reflex device:(1) Demonstrate the wireless quantified reflex device is reliably capable of ascertaining quantified reflex response and latency using a quantified input.(2) Evaluate the precision of the device using an artificial reflex system.(3) Conduct a longitudinal study respective of subjects with healthy patellar tendon reflexes, using the wireless quantified reflex evaluation device to obtain quantified reflex response and latency.Aim 1 has led to a steady evolution of the wireless quantified reflex device from a singular 2D wireless accelerometer capable of measuring reflex response to a tandem 3D wireless accelerometer capable of reliably measuring reflex response and latency. The hypothesis for aim 1 is that a reflex quantification device can be established for reliably measuring reflex response and latency for the patellar tendon reflex, comprised of an integrated system of wireless 3D MEMS accelerometers. Aim 2 further emphasized the reliability of the wireless quantified reflex device by evaluating an artificial reflex system. The hypothesis for aim 2 is that the wireless quantified reflex device can obtain reliable reflex parameters (response and latency) from an artificial reflex device. Aim 3 synthesizes the findings relevant to aim 1 and 2, while applying the wireless accelerometer reflex quantification device to a longitudinal study of healthy patellar tendon reflexes. The hypothesis for aim 3 is that during a longitudinal evaluation of the deep tendon reflex the parameters for reflex response and latency can be measured with a considerable degree of accuracy, reliability, and reproducibility. Enclosed is a detailed description of a wireless quantified reflex device with research findings and potential utility of the system, inclusive of a comprehensive description of tendon reflexes, prior reflex quantification systems, and correlated applications.

Do A‐waves help predict intravenous immunoglobulin response in multifocal motor neuropathy without block?

Are there electrophysiological findings that predict response to intravenous immunoglobulin (IVIg) in patients with lower motor neuron (LMN) syndromes without multifocal conduction block (MCB)? We enrolled 9 patients with LMN syndromes without MCB to receive 18 weeks of IVIg therapy. Response was measured at weeks 2 and 18 using the Appel Amyotrophic Lateral Sclerosis (AALS) score (includes grip and pincer strength measures), ALS Functional Rating Scale (ALSFRS), and electrophysiological measures, including motor unit estimates (MUNEs). No change occurred in AALS or ALSFRS scores posttreatment. Grip/pincer strength increased in 7 patients (P = 0.028) after initial treatment (responders); 2 showed no improvement (non-responders). No electrophysiological measure changed after treatment in either group but MUNEs trended higher (P = 0.055). "Abnormal A-waves" (complex, repetitive biphasic, or present in multiple nerves) occurred in pretreatment studies more often in responders (P = 0.028). "Abnormal A-waves" may signal IVIg-responsive LMN syndromes even if conduction block is absent.

CSF glial markers correlate with survival in amyotrophic lateral sclerosis

In neurodegenerative diseases such as amyotrophic lateral sclerosis (ALS), CSF biomarkers are increasingly studied to evaluate their relevance for differential diagnosis, disease progression, and understanding of pathophysiologic processes. To identify a biomarker profile of neuronal and glial CSF proteins to discriminate ALS from other motor neuron diseases (MND) and to assess whether baseline levels of CSF measures in ALS are associated with the course of the disease. A total of 122 consecutive subjects with MND were included in this cross-sectional study (ALS, n = 75; lower motor neuron syndrome, n = 39; upper motor neuron diseases, n = 8). Clinical follow-up included 76 patients. We determined baseline levels of protein tau and astroglial S100beta in CSF and microglial sCD14 in CSF and serum in relation to diagnosis, duration of disease, and survival. CSF tau was significantly elevated in ALS and upper motor neuron diseases as compared to lower motor neuron diseases and controls. CSF S100beta levels were significantly lower in lower motor neuron diseases as compared to other MND. CSF concentrations of S100beta and sCD14 correlated with the survival time in patients with ALS. In motor neuron diseases, CSF tau elevation indicates the degeneration of upper motor neurons, while S100 beta and sCD14 may indicate the activation of CNS glial cells. Because S100beta and sCD14 concentrations correlate with survival in amyotrophic lateral sclerosis (ALS), we suppose that the combination of both markers may be useful to obtain prognostic information in patients with ALS.

Predicting Response to Intravenous Immunoglobulin in Lower Motor Neuron Syndromes

Objective: In patients presenting with purely lower motor neuron (LMN) syndromes, the distinction between motor neuropathy and an anterior horn cell disorders may be difficult to appreciate initially. As such, the selection of patients for treatment with intravenous immunoglobulin (IVIg) is often a clinical dilemma, particularly as IVIg is an expensive, limited resource, ideally reserved for treatable patients. Consequently, the present study was undertaken to identify clinical and neurophysiological features that may predict a response to IVIg in patients presenting with pure LMN syndromes.

Sensory-Motor Cortical Rorganization in Lower Motor Neuron Syndrome

Sensory-Motor Cortical Rorganization in Lower Motor Neuron Syndrome

MOTOR NEURON DISEASE FEATURES IN A PATIENT WITH NEUROBORRELIOSIS AND A CERVICAL ANTERIOR HORN LESION

A variety of neurological syndromes has been described in neuroborreliosis: cranial nerve palsies, radiculopathy, axonal neuropathy, stroke, parkinsonism, transverse myelitis, supranuclear palsy, Guillain- Barré syndrome, … We report a case of neuroborreliosis with cervical myelitis presenting clinically as a lower motor neuron syndrome of the upper and lower limbs with proximal and distal pareses and atrophies as well as bulbar dysarthria and dysphagia. During the course of the disease the patient developed the clinical picture of a meningoencephalitis. After initiating ceftriaxone treatment the patient showed a complete recovery.In endemic regions for Lyme disease, in all neurological syndromes neuroborreliosis has to be excluded.

Flail arm-like syndrome associated with HIV-1 infection

During the last 20 years at least 23 cases of motor neuron disease have been reported in HIV-1 seropositive patients. In this report we describe the clinical picture of a young man with HIV-1 clade C infection and flail arm-like syndrome, who we were able to follow-up for a long period. We investigated and prospectively monitored a 34-year-old man with features of flail arm syndrome, who developed the weakness and wasting 1 year after being diagnosed with HIV-1 infection after a routine blood test. He presented in 2003 with progressive, symmetrical wasting and weakness of the proximal muscles of the upper limb of 2 years' duration. He had severe wasting and weakness of the shoulder and arm muscles. There were no pyramidal signs. He has been on HAART for the last 4 years and the weakness or wasting has not worsened. At the last follow-up in July 2007, the patient had the same neurological deficit and no other symptoms or signs of HIV-1 infection. MRI of the spinal cord in 2007 showed characteristic T2 hyperintense signals in the central part of the spinal cord, corresponding to the central gray matter. Thus, our patient had HIV-1 clade C infection associated with a ‘flail arm–like syndrome.’ The causal relationship between HIV-1 infection and amyotrophic lateral sclerosis (ALS)-like syndrome is still uncertain. The syndrome usually manifests as a lower motor neuron syndrome, as was seen in our young patient. It is known that treatment with antiretroviral therapy (ART) stabilizes/improves the condition. In our patient the weakness and atrophy remained stable over a period of 3.5 years after commencing HAART regimen.

Factors affecting neurological outcome in traumatic conus medullaris and cauda equina injuries

The purpose of this review was to describe the relevant factors that influence neurological outcomes in patients who sustain traumatic conus medullaris injuries (CMIs) and cauda equina injuries (CEIs). Despite the propensity for spinal trauma to affect the thoracolumbar spine, few studies have adequately characterized the outcomes of CMIs and CEIs. Typically the level of neural axis injury is inferred from the spinal level of injury or the presenting neurological picture because no study from the spinal literature has specifically evaluated the location of the conus medullaris with respect to the level of greatest canal compromise. Furthermore, the conus medullaris is known to have a small but important variable location based on the spinal level. Patients with a CMI will typically present with variable lowerextremity weakness, absent lower-limb reflexes, and saddle anesthesia. The development of a mixed upper motor neuron and lower motor neuron syndrome may occur in patients with CMIs, whereas a CEI is a pure lower motor neuron injury. Many treatment options exist and should be individualized. Posterior decompression and stabilization offers at least equivalent neurological outcomes as nonoperative or anterior approaches and has the additional benefits of surgeon familiarity, shorter hospital stays, earlier rehabilitation, and ease of nursing care. Overall, CEIs and CMIs have similar outcomes, which include ambulatory motor function and a variable persistence of bowel, bladder, and potentially sexual dysfunctions.

Nose and Eyebrow Reconstruction Following Electrical Injury

Electrical injuries occur world wide and constitute 5 to 10% of all occupational fatalities.1 Factors that determine the type and extent of electrical injuries include voltage and current flow.1,2 Neurologic complications secondary to electrical injury can manifest themselves either early or late including delayed peripheral neuropathy; lower motor neuron syndrome.3 Patients with head wounds seem to be most at risk for development of cataracts.4 We describe a 24 year old male with a history of electrical burns to the face and neck causing full thickness and underlying soft tissue loss of the left eyebrow, left frontal area, most of the nose and posterior neck. The patient was surgically reconstructed in several stages: 1) Nasal reconstruction was accomplished using an anterior neck tubed flap for the columella, bilateral nasolabial flaps with rib cartilage as an intervening structure for the septum and a scalp forehead flap to substitute the skin of entire nose, and eye brow reconstruction. 2) Forehead reconstruction was carried with use of a tissue expander.

The history of progressive muscular atrophy

Since its first description more than a century ago, there has been much debate about the diagnostic entity progressive muscular atrophy (PMA). Initially, PMA included all forms of progressive amyotrophy. With the identification of several myogenic and neurogenic diseases and the recognition of amyotrophic lateral sclerosis (ALS), PMA was deemed to disappear as a nosologic entity at the end of the 19th century. In the last century, various other lower motor neuron syndromes were distinguished which may previously have been designated as cases of PMA. In contrast, several observations provided evidence that PMA can be linked both clinically and pathologically to ALS. Therefore, PMA should be considered as a syndromal subtype within a clinical spectrum of motor neuron diseases.

Multimodal Evoked Potentials of Kennedy's Disease

Kennedy's disease (KD) is an X-linked recessive polyglutamine disease. Traditionally, it is a lower motor neuron syndrome with additional features such as gynecomastia and tremor. Sensory symptoms are minimal if ever present. We used multimodal evoked potential (EPs) tests to study the distribution of the involvement of the disease. Visual, brainstem auditory, somatosensory and motor EPs were studied in six KD patients. All of them had typical presentations and had been proved genetically. Abnormal findings were noted as follows: prolonged peak latencies of visual EPs, increased hearing threshold level, inconsistent brainstem auditory EPs, decreased amplitudes of cortical potentials of somatosensory EPs, and increased motor threshold to transcranial magnetic stimulation. Our multimodal EP studies showed that KD involved multiple levels of the nervous system. It implies the widespread effects of the mutant androgen receptors.

Muscle Nogo‐a expression is a prognostic marker in lower motor neuron syndromes

A proportion of patients with pure lower motor neuron syndrome (LMNS) progress to amyotrophic lateral sclerosis (ALS). Early detection of this progression is impossible, which delays the patient's access to treatment. Muscle expression of Nogo-A is a new candidate marker of ALS. We tested whether detection of Nogo-A in a muscle biopsy from patients with LMNS predicts progression to ALS. Thirty-three patients who had undergone a muscle biopsy during the diagnostic workup of spinal LMNS were observed for 12 months. Nogo-A expression was measured by Western blot in muscle biopsy samples and compared with the final diagnosis. Nogo-A expression was detected in 17 patients and was absent in 16 patients. The detection of Nogo-A in muscle biopsy samples from LMNS patients correctly identified patients who further progressed to ALS with 91% accuracy, 94% sensitivity, and 88% specificity. In patients who later developed typical ALS, Nogo-A may be detected as early as 3 months after the onset of symptoms. Nogo-A test is able to identify ALS early in the course of the disease when diagnosis is difficult, requiring further progression. Use of the test in clinical practice may shorten the delay before introduction of neuroprotective drugs or inclusion in clinical trials.

F wave study in amyotrophic lateral sclerosis: Assessment of balance between upper and lower motor neuron involvement

Objective We sought to record significant F wave variable changes in ALS patients having no advanced disease. Furthermore, an interpretation of these F wave abnormalities in the context of upper (UMN) and lower motor neuron (LMN) dysfunction was attempted. Methods Standard motor and sensory conduction study was performed to the ulnar nerves of 23 patients with ALS (13 males and 10 females with mean age 67.2±5.3 years), having a clinically predominant LMN syndrome. A series of 40 electrical stimuli were also delivered to both their ulnar nerves in order to obtain F waves. The following F wave variables were estimated: F persistence, F wave latency, amplitude, duration and F chronodispersion. Twenty-three, age-and gender-matched healthy volunteers served as controls. Results Both the distal and proximal ulnar a-CMAPs ( P=0.001) and the MCV ( P=0.014) values were significantly decreased in patients, than the controls. The sensory conduction study was normal. The ulnar F wave persistence in the ALS patients was significantly lower than that of the controls ( P=0.0007). The mean ( P=0.0001), minimal ( P=0.0001) and maximal ( P=0.0001) F wave latencies were significantly prolonged, the F wave amplitudes ( P=0.0001) were significantly higher and the F wave chronodispersion ( P=0.014) was significantly increased in the patients than the controls. Conclusions Significant F wave abnormalities occur in patients with ALS, even those patients having no advanced disease. Increased F wave amplitudes combined with low persistence is a pattern consistent with ALS. Significance Our results show that patients with ALS having predominantly LMN involvement also have electrophysiological UMN dysfunction.

The Drew family of Walworth: one century from the first evaluation until the final diagnosis, Machado-Joseph disease

Autosomal dominant spinocerebellar ataxia (SCA) is an heterogeneous group of neurodegenerative diseases involving cerebellum and its connections. Several forms have already been described, and it seems the most common form of SCA observed among the many series of families described worldwide is SCA3 (Machado-Joseph disease). SCA3 is characterized by a marked phenotypic expression with a wide spectrum of clinical findings including cerebellar ataxia, pyramidal and extrapyramidal (e.g. dystonia, parkinsonism), lower motor neuron syndrome and peripheral neuropathy. The Drew family of Walworth, England, has several affected members seen and described by famous neurologists including Gowers, Stewart, Collier, Kinnier-Wilson, Turner, Worster-Drought, Ferguson, Critchley, and Anita Harding from 1895 to our days. In fact, the final genetic diagnosis of this family, 100 years after its initial description, turned out to be SCA3. In this paper, we describe the full of twists and turns historical trajectory from the initial clinical description to the final genetic diagnosis.

Plasmapheresis in immunologically mediated polyneuropathies.

One of the most common uses of therapeutic plasmapheresis is for the treatment of immunologically mediated polyneuropathies. This paper discusses the use of plasmapheresis in Guillain-Barré syndrome, chronic inflammatory demyelinating polyneuropathy, polyneuropathies associated with paraproteins, lower motor neuron syndromes, and polyneuropathies associated with HIV. As the pathogenesis of immunologically mediated polyneuropathies becomes better understood, newer therapies for these syndromes will evolve: however, therapeutic plasmapheresis is likely to continue to play a central role in the treatment of many of these diseases.

A Case Of Paraneoplastic Neuropathy (PN) And Anti‐Glycolipid Antibodies (GLA)

Subacute sensory neuronopathy (SSN) is most commonly seen in association with small cell carcinoma of the lung (SCLC), however lower motor neuron syndrome with or without upper motor neuron involvement may occur. Anti‐neuronal antibodies, called “anti‐Hu”, can be frequently demonstrated. Other antibodies that react with the carbohydrate epitope of ganglioside GM1, associated with primary motor PN, are not frequent. We describe a 73‐year‐old man with subacute onset of paraesthesiae starting in his finger and toes and spreading proximally. A few months later he developed generalized muscle weakness and was admitted to another hospital. On examination he was unable to write, as well as to stand or walk without support. Tendon reflexes were absent. He had no cranial nerve involvement and had no complain of pain. Pinprick, vibration and four limb positions were impaired distally. CSF study revealed increased protein (90 mg/dl) and lymphocytes (14/mm3). SCLC was identified in paratracheal lymphnodes and treated with chemotherapy (Carboplatinum and Etopoxide) and mediastinum irradiation (36 Gray). No clinical improvement was observed after i.v. immunoglobulins (400 mg/kg/day for 5 days). He was wheelchair‐bound and unable to feed himself or to recognize the four limb position when he was admitted in the Neurological Department, University of Verona. Eye movements and winking were markedly reduced. Median (48.6 m/s) and ulnar (46 m/s) nerve study revealed slow conductions. ESP were undetectable. SSEP could not be evoked from the four limbs. Cyclophosphamide (250 mg/day for 5 days), monthly plasma exchange associated with prednisone for six months, and Azatioprine were used. Ambigous low titre of antibodies against neuronal nuclei was identified but anti‐Hu antibodies were not detected. The serum antibody titres against glycolipids (GM1, GM2, GM3, GQ1b, GD1a, GD1b, sulfatides) were elevated (>1:720) and had no substantial change at the bimonthly controls in the last 36 months. As negative control case for GLa, we used the Hu‐negative serum from a patient who had electrophysiologically confirmed selective sensory involvement associated with SCLC and long survival (29 months). We hypothesized that the neurological course with prominent motor deficit is probably related to serum anti‐GL antibody specificities. The presence of ganglioside mimicry in the SCLC (Fuentes et al., Lung Cancer, 1997) appears to be determinant for the induction of anti‐GLa. However the anti‐neural immune‐response may be related to host factors.

Anti-GM 2 IgM antibody-induced complement-mediated cytotoxicity in patients with dysimmune neuropathies

Anti-GM 2 IgM antibodies have been reported in some patients with dysimmune neuropathy or lower motor neuron syndrome. To determine whether these antibodies can induce complement-dependent cytolysis we performed a cytotoxicity assay on neuroblastoma cells with sera from seven patients with demyelinating dysimmune neuropathies and high titers of anti-GM 2 IgM. As controls we used sera from seven patients with other anti-neural reactivities, six with the same neuropathies but no anti-GM 2 or other anti-neural reactivity and from eight normal subjects. Of the seven positive sera tested, six induced complement-mediated cytotoxicity, while none of the controls had any relevant effect on neuroblastoma cells. Preincubation of positive sera with purified GM 2 removed cytotoxic activity. Affinity purified anti-GM 2 IgM had the same cytotoxic effect of whole serum while serum or complement alone did not have any effect. In four anti-GM 2-positive patients the percentage of cell lysis correlated with anti-GM 2 titers and with IgM staining of neuroblastoma cells while in two the cytotoxic effect was higher than expected from antibody titers. Complement-mediated cell lysis induced by anti-GM 2 IgM antibodies may be a possible mechanism of neural damage in patients with dysimmune neuropathy and high titers of anti-GM 2 IgM antibodies.

Are there immunologically treatable motor neuron diseases?

Several studies have addressed the issue of a possible immunological involvement in the pathogenesis of amyotrophic lateral sclerosis (ALS) or motor neuron disease (MND), particularly when the disease was associated with cancer, lymphoma or other monoclonal gammopathies or with the presence of serum antibodies to neural antigens. The hypothesis of the existence of immunologically treatable MND was reinforced by the occasional report of MND patients responding to immune or cytostatic therapies and by the identification among those with a purely lower motor neuron syndrome (LMNS) of a motor neuropathy, presently known as multifocal motor neuropathy (MMN), which almost invariably responded to immune therapies. These observations have led to several attempts to treat patients with MND or LMNS, either idiopathic or associated with the above mentioned conditions, with a number of immune or cytostatic therapies. The aim of this review is to verify whether the available data provide enough evidence to support the concept of dysimmune MND and to justify the use in these patients of potentially harmful immune cytostatic therapies.

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.

Motor neuron disease: usefulness of transcranial magnetic stimulation in improving the diagnosis

Clinical upper motor neuron (UMN) involvement is sometimes difficult to detect in motor neuron disease (MND). For this reason we performed transcranial magnetic stimulation (TMS) to find out whether this technique may be useful in revealing signs of pyramidal tract impairment. Fifty-five MND patients, clinically divided into 22 amyotrophic lateral sclerosis (ALS), 18 ALS with probable UMN signs (ALS-PUMNS), 10 pure lower motor neuron syndrome (LMNS), and 5 progressive bulbar palsy (PBP), underwent standard TMS, recording from abductor digiti minimi and flexor allucis muscles. Prolongation of cortical motor evoked potential (MEP) latency and central conduction time (CCT) and absent MEP were considered as pathologic. ALS-PUMNS and LMNS patients were clinically reclassified after 1 year. TMS was abnormal in 95.4% of ALS, 72.2% of ALS-PUMNS, 50% of LMNS and 20% of PBP. Correlations between TMS parameters and both clinical signs of UMN involvement and disease severity were highly significant. TMS showed a high sensitivity, but lacked specificity. After 1 year, 11 patients among the ALS-PUMNS group were clinically reclassified as definite ALS: all of them had shown TMS abnormalities at the first examination. In conclusion, TMS provides important diagnostic information for an early prediction of ALS in those MND patients presenting with clinically equivocal UMN impairment.