Central motor conduction in motor neuron disease

Central motor conduction time (CMCT) to abductor digiti minimi (ADM) and tibialis anterior (TA) was measured in 21 patients of motor neuron disease (MND). In the upper limb, the motor pathways were inexcitable in 13 and central motor conduction time (CMCT-ADM) was prolonged in 7 sides. In the lower limbs the motor pathways were inexcitable in 10 and CMCT-TA was prolonged in 14 sides. The CMCT abnormalities did not follow a constant pattern but were randomly distributed and were asymmetric in the upper limbs in 7 and lower limbs in 3 patients. Asymmetric and randomly focal abnormalities in central motor conduction in our patients are consistent with asymmetric and focal neuronopathy in MND.     

Oculomotor abnormalities in motor neuron disease

OBJECTIVE: To assess whether giving a leaflet containing norms of self-control to diabetics receiving insulin treatment results in a metabolic improvement. The HbA1c was established prior and subsequent to giving out the leaflet. The written norms contained in the leaflet were highlighted from the wider range of instructions obtained from diabetes education. DESIGN: A longitudinal intervention study with no random allocation. SETTING: Hospital care in a specialised Endocrinology clinic. PATIENTS AND OTHER PARTICIPANTS: 122 types 1 and 2 diabetics, treated with various insulin diets, who had received prior diabetes education and carried out blood self-controls. Cases of meta-diabetic syndrome, serious illnesses and those without apparent hypoglycaemia symptoms were excluded. INTERVENTIONS: Giving out of a leaflet with written norms of self-control. MEASUREMENTS AND MAIN RESULTS: The averages, standard deviations and 95% confidence intervals of the basal HbA1c and of those at four-monthly check-ups were calculated. Basal 8.07 (CI 7.75 - 8.39); 4th month 6.88 (CI 6.74 - 7.17); 8th month 6.59 CI 6.29 - 6.90); 12th month 6.60 (CI 6.23 - 6.94); 16th month 6.06 (CI 5.63 - 6.49); 20th month 5.40 (CI 3.04 - 7.75). Averages were compared by the Student T test and all values had p < 0.005 against the basal. CONCLUSIONS: Following the written norms produced a clear metabolic improvement, represented by the significant fall of HbA1c. Therefore, though without ignoring the overall context of treatment and diabetes education, it is proposed that the relationship of the most practical features of insulin dosing to written norms of self-control should be emphasised.     

The reorganization of motor units in motor neuron disease

We studied 78 patients with motor neuron disease (MND) using concentric needle electromyography. Analysis on weak and maximal effort was performed using our own, fully automated, computer method, EMG-LAB. In addition to the conventional parameters of single motor unit action potentials (MUAPs) and interference pattern, new criteria were applied: the range of the acting motor units and the functional recruitment order. A total of 375 muscles of MND patients and 120 control muscles were investigated. The electromyographic data were analyzed separately in five groups of muscles, classified A, B, C, D, and E according to their clinical condition. Those results allowed us to discern six neurophysiological stages (N(0,1,2,3,4,5)) from the early to the most advanced phase. It has been confirmed that reinnervation in MND is adequate to compensate for the loss of over 50% of motor neurons but it is only a transitory phase in the morbid course. At stages N(O-5), the electrophysiological data reflect structural and functional integrity of the functioning motor units. Evaluation of not only single MUAPs but also of the full range of acting motor units and their recruitment order allowed a deeper look into the underlying pathophysiological mechanisms.     

Geographical epidemiology of residence of patients with motor neuron disease in Lancashire and south Cumbria

OBJECTIVES: To seek objective evidence for geographical clustering of places of residence of patients with motor neuron disease (MND). METHODS: A complete residential history from birth to onset of disease was obtained from a cohort of 130 patients with MND from Lancashire and south Cumbria presenting to the Department of Neurology in Preston between 1 January 1989 and 31 December 1993. These data were compared with population based reference data from the 1991 UK Census. RESULTS: Some areal units showed a greater, others a lesser, number of MND patient residences than expected. The results suggest that the background population incidence of MND is relatively low and that the overall incidence figures previously quoted have been skewed upwards by areas in which the incidence of MND is relatively increased. These findings were further tested by Poisson modelling. The Poisson model provided a poor fit for the data at postcode district and sector levels confirming that patients with MND were significantly more likely to have lived in some areas than others after allowing for variation in population of the different areal units and for variation in duration of residence. CONCLUSIONS: These findings reinforce the results of previous work, much of which has been qualitative rather than quantitative. The results presented here suggest a low background incidence of MND in the context of generally quoted overall incidence figures. This low background incidence is, however, skewed upwards by some areal units with a relatively high incidence, thus achieving overall incidence rates comparable with generally quoted figures. We conclude that there is prima facie evidence of spatial patterns in the distribution of places of residence of patients with MND. Further examination of occupational and environmental factors in the lives of the patients with MND is required to obtain a better understanding of the importance of these findings.     

Proton magnetic resonance spectroscopy of the primary motor cortex in patients with motor neuron disease: subgroup analysis and follow-up measurements

OBJECTIVES: To determine the motor cortex degeneration in patients with amyotrophic lateral sclerosis (ALS) using proton magnetic resonance spectroscopy, and to prove that proton magnetic resonance spectroscopy is suited to monitor the course of disease with follow-up examinations. MATERIALS AND METHODS: We studied 33 patients with ALS whose conditions were diagnosed according to the El Escorial World Federation of Neurology criteria. Nine patients with ALS were followed up for up to 2 years. The control group included 20 healthy volunteers and 4 patients with multifocal motor neuropathy. Proton magnetic resonance spectroscopy determined levels of the brain metabolites N-acetylaspartate (NAA), choline, inositol-containing compounds, glutamate/glutamine, and phosphocreatine. RESULTS: Patients with ALS showed a significant reduction in the NAA-choline (P <.001) and NAA-phosphocreatine (P <.005) metabolite ratios and significantly elevated choline-phosphocreatine (P <.005) ratios compared with controls. Inositol-phosphocreatine ratios were also elevated in case patients, but the increase was less pronounced (P <.05). No differences in glutamate/glutamine-phosphocreatine ratios were detected between case patients and controls. An analysis of subgroups demonstrated less significant differences in NAA-choline metabolite ratios (P<.05), even in patients with pure lower motor neuron syndrome (suspected ALS). No changes in metabolite T1 and T2 relaxation times were observed. Patients with multifocal motor neuropathy showed normal metabolic ratios. Progressive alterations in affected metabolite ratios could be documented in the follow-up examinations. CONCLUSIONS: Spectroscopic changes in the motor cortices of patients with ALS correspond with a reduction in levels of NAA and an elevation in levels of choline and inositol compounds. Since NAA is exclusively expressed in neurons, the observed decrease of NAA reflects neuronal loss or dysfunction. Inositol and choline are associated with plasma membrane metabolism, so the release of these compounds may be related to membrane disorders.     

Neurophysiologic evaluation of lower motor neuron damage in tetraplegia

We quantitatively investigated the extent of damage to motor neurons in tetraplegic subjects. Numbers of motor units in the patients were significantly lower for thenar, wrist extensor, and biceps brachii as compared to controls. Reduction in counts occurred even when M-response amplitudes were normal. Standard electromyography suggested a surprising frequency of lower motor neuron dysfunction below the level of injury. These results confirm previous reports and add data on motor units in the biceps brachii.     

Kinesin and cytoplasmic dynein in spinal spheroids with motor neuron disease

OBJECTIVE: Gene therapy is a promising strategy to modify ischemia-reperfusion injury and rejection after transplantation. We evaluated variables that may affect ex vivo gene transfer to rat lung isografts. METHODS: Left lungs were harvested and perfused via the pulmonary vein with chloramphenicol acetyltransferase complementary deoxyribonucleic acid complexed with cationic liposomes. Several variables were examined: (1) Influence of temperature: In group I (n = 4), grafts were stored for 4 hours at 23 degrees C and transplanted. Chloramphenicol acetyltransferase activity was assessed on postoperative day 2. In groups II and III (n = 4), grafts were stored at 10 degrees and 4 degrees C, respectively. Arterial oxygen tension and inflammatory infiltrate were also determined. (2) Influence of storage time: Grafts were preserved at 10 degrees C for 1, 2, 3, 4 (n = 4), and 10 hours (n = 5). chloramphenicol acetyltransferase activity was assessed on postoperative day 2. (3) Rapidity and duration of transgene expression: Grafts were preserved at 10 degrees C for 1 hour and then transplanted. Chloramphenicol acetyltransferase activity was assessed 2, 4, 6, 12, and 24 hours and 2, 7, 14, 21, and 28 days after implantation. RESULTS: Chloramphenicol acetyltransferase expression was apparently less in lungs transfected at 4 degrees C than in those transfected at 10 degrees and 23 degrees C. Storage for 1 hour at 10 degrees C was sufficient to yield significant expression. Increasing the exposure time to 10 hours did not increase toxicity. There were no differences in arterial oxygen tension between transfected and nontransfected lungs. Chloramphenicol acetyltransferase expression was detected for at least 28 days. CONCLUSION: Ex vivo liposome-mediated transfection of lung isografts can be achieved after a short time of cold storage, with minimal toxicity.     

Amyloid neuropathy simulating lower motor neuron disease

We report a 57-year-old man with progressive symmetric weakness and fasciculation affecting the legs. Electromyography revealed fibrillations and neurogenic motor unit potentials in the leg muscles. Biopsy of a motor branch of the obturator nerve revealed axonal degeneration, loss of myelinated nerve fibers, and amyloidosis with deposits of lambda light chains. At 6-month follow-up, the patient manifested sensory and autonomic symptoms, and lambda light chains were first detected in the serum. In this case, diagnosis of amyloidosis remained elusive until motor nerve biopsy.     

Paraneoplastic motor neuron disease with type 1 Purkinje cell antibodies

Autoimmune serological testing is a useful aid for identifying a paraneoplastic basis for sporadic motor neuron disease. A 67-year-old woman with ovarian carcinoma presented with progressive weakness. Neurological examination was suggestive of motor neuron disease with signs of upper motor neuron disorder. Electromyography revealed severe motor neuronopathy of the upper extremities. Characteristic type 1 Purkinje cell antibodies (anti-Yo antibody) was detected in the serum diluted at 1:61,400.     

Differential features of motor neuron disease mortality in Spain

BACKGROUND: The objective of this study was to describe the temporal and spatial patterns of motor neuron disease (MND) in Spain. METHODS: We studied data where MND was stated as the principal cause of death in official statistics from Spain. Time trends were analysed for age-, sex-specific and age-adjusted rates for the period 1951-1990. Age-adjusted mortality and relative risk, obtained by Poisson regression adjusting for age, were calculated for each province from deaths during the period 1975-1988. Maps were constructed using log transformed rates. Statistical significance of spatial aggregation was assessed using the Ohno et al. test. RESULTS: The 1951-1990 mortality rate, age- and sex-adjusted to the European population, for the population aged > or = 40 years was 1.49 per 100,000; 1.90 and 1.21 for males and females respectively. In general, mortality increased with age. Age-adjusted rates rose until 1960, dropped by 70% during the 1960s and declined slightly over the 1951-1990 period as a whole. From 1970 onwards MND mortality rose evenly, particularly in the 60-69 age group. A North-South gradient was suggested for both sexes with statistically significant clustering in the Northern coastal regions and--for males alone--in the Midwest provinces. CONCLUSIONS: Mortality from MND in Spain displayed a magnitude and recently rising temporal trend similar to that described in several other countries. Specific traits were: a decrease during the 1960s, which has been described for Japan only, as well as spatial heterogeneity and a predominant recent increase among the 60-69 age group. The determinants of these unusual MND mortality patterns are unknown.     

Antibody panels in idiopathic polyneuropathy and motor neuron disease

We prospectively evaluated patients with idiopathic polyneuropathy (PN) and motor neuron disease (MND) with commercial antibody (Ab) panels. Patients with sensorimotor PN received a "sensorimotor neuropathy profile" [3-sulfated glucuronyl paragloboside (SGPG)/myelin-associated glycoprotein (MAG), GM1, asialo-GM1, GD1b, Hu, sulfatide]. Motor neuropathy or MND patients underwent a "motor neuropathy profile" (SGPG/MAG, GM1, asialo-GM1). Seven of 78 patients (9.0%) with sensorimotor PN and 3 of 44 patients (6.8%) with MND had abnormal panels. None of 60 patients with axonal sensory or sensorimotor PN had antisulfatide Ab. Seven of 13 patients (54%) with multifocal motor neuropathy had abnormal panels, with 6 seropositive to GM1. We found abnormal Ab panels in fewer than 10% of patients with idiopathic sensorimotor PN and MND. Moreover, abnormal Ab tests often did not relate to the clinical context. Our data do not support the use of commercial Ab panels in the evaluation of patients with idiopathic PN or MND.     

Arrest of motor neuron disease in wobbler mice cotreated with CNTF and BDNF

Ciliary neurotrophic factor (CNTF) and brain-derived neurotrophic factor (BDNF) each promote the survival and differentiation of developing motor neurons, but do so through distinct cellular signaling pathways. Administration of either factor alone has been shown to slow, but not to arrest, progression of motor neuron dysfunction in wobbler mice, an animal model of motor neuron disease. Because CNTF and BDNF are known to synergize in vitro and in ovo, the efficacy of CNTF and BDNF cotreatment was tested in the same animal mode. Subcutaneous injection of the two factors on alternate days was found to arrest disease progression in wobbler mice for 1 month, as measured by several behavioral, physiological, and histological criteria.     

Association of apolipoprotein E epsilon 4 allele with bulbar-onset motor neuron disease

BACKGROUND: Variants of the apolipoprotein E (APOE) gene influence the age of onset of Alzheimer's disease. APOE may influence the presentation of other neurological diseases. We investigated the relationship between the allelic variants of apolipoprotein E and clinical presentation in motor neuron disease. METHODS: 123 patients with motor neuron disease and 121 controls were studied. Diagnosis, location of onset and date of onset were recorded prospectively. Genotyping was performed blind to clinical information. FINDINGS: Possession of at least one epsilon 4 allele was significantly more common in patients with bulbar onset motor neuron disease (14/33, 42%) than in limb onset patients (20/90, 22%) and controls (26/121, 21%) (chi 2 = 4.93, p = 0.026 and chi 2 = 5.91, p = 0.015, respectively). INTERPRETATION: These results suggest that the apolipoprotein E epsilon 4 allele may influence the pattern of motor neuron loss in motor neuron disease and that it may affect neuronal function in ways unrelated to the deposition of beta-amyloid or accumulation of neurofibrillary tangles.     

Cortical motor neuron activity in the cat during classical conditioning with central stimulation as the CS and the US.

Studied the neuronal basis of associative conditioning in the cat by pairing stimulation of thalamocortical pathways as the CS with antidromic activation of pericruciate pyramidal tract (PT) cells as the UCS in a differential classical conditioning paradigm. For the 18 Ss in Exp I, the target thalamic nuclei for stimulation were nucleus ventralis posterolateralis (VPL) and nucleus ventralis lateralis. For the 10 Ss in Exp II, the target thalamic nuclei were VPL and nucleus cetromedian. Results show that thalamic stimulation was not an effective CS. The response of PT cells to thalamic stimulation did not change as a function of reinforcement with PT stimulation. These results do not support the hypothesis that the simple pairing of any 2 neural events is the essential mechanism underlying associative conditioning changes. Instead, they suggest that the combined activation of specific and nonspecific thalamic nuclei may be important in producing increases in responsiveness of PT neurons. (45 ref) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Opposite motor effects of pallidal stimulation in Parkinson's disease

We studied the effects--on parkinsonian signs, on levodopa-induced dyskinesias, and on levodopa response--of acute experimental high-frequency stimulation of the internal pallidum (GPi) during off-drug and on-drug phases. Thirteen quadripolar electrodes were evaluated in 8 patients with Parkinson's disease (PD). Stimulation of the most ventral contacts, lying at the ventral margin of or just below the GPi, led to pronounced improvement in rigidity and a complete arrest of levodopa-induced dyskinesias. The antiakinetic effect of levodopa was also blocked and the patients became severely akinetic. Stimulation of the most dorsal contacts, lying at the dorsal border of the GPi or inside the external pallidum, usually led to moderate improvement of off-drug akinesia and could also induce dyskinesias in some patients. When using an intermediate contact for chronic stimulation, a good compromise between these opposite effects was usually obtained, mimicking the effect of pallidotomy. We conclude that there are at least two different functional zones within the globus pallidus, at the basis of a different pathophysiology of the cardinal symptoms of PD. The opposite effects may explain the variable results of pallidal surgery reported in the literature and may also largely explain the paradox of PD surgery. A possible anatomical basis for these differential functional effects could be a functional somatotopy within the GPi, with the segregation of the pallidofugal fibers from the outer portion of the GPi, on one hand, forming the ventral ansa lenticularis and from the inner portion of the GPi, on the other hand, forming the dorsal lenticular fasciculus.