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.     

Central motor conduction evaluation in glycogenosis type III

We report a 20-year-old man affected by glycogenosis type III with distal muscle weakness, more severe in distal leg muscles. The electromyogram showed myopathic features. Nerve conduction studies and central motor conduction after magnetic stimulation of the brain were normal. Our results suggest that there is no involvement of central motor pathways in this disease.     

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.     

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.     

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.     

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.     

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.     

Root stimulation studies in the evaluation of patients with motor neuron disease

Nerve root stimulation may be employed in patients with motor neuron disease (MND) to rule out motor neuropathy with conduction block. The diagnostic utility of these studies is unknown, in part because the range of amplitude changes across nerve root segments in patients with active neuronal degeneration has not been well studied. We reviewed root stimulation studies in 32 patients (59 nerves) with MND and found segmental amplitude reduction from 0 to 45%, a range similar to values reported for normal subjects; there was no suggestion of conduction block based on our usual criteria.     

Postradiation motor neuron syndrome

We report an unusual case of selective lower motor neuron syndrome (MNS) complicating whole neuraxis radiation therapy. Only three well-documented similar cases have been found in a thorough review of the literature. The syndrome has a stereotyped time course and is self-limited. We discuss here possible pathogenetic mechanisms and their relationship to motor neuron disease.     

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.     

Kinesin mutations cause motor neuron disease phenotypes by disrupting fast axonal transport in Drosophila

Previous work has shown that mutation of the gene that encodes the microtubule motor subunit kinesin heavy chain (Khc) in Drosophila inhibits neuronal sodium channel activity, action potentials and neurotransmitter secretion. These physiological defects cause progressive distal paralysis in larvae. To identify the cellular defects that cause these phenotypes, larval nerves were studied by light and electron microscopy. The axons of Khc mutants develop dramatic focal swellings along their lengths. The swellings are packed with fast axonal transport cargoes including vesicles, synaptic membrane proteins, mitochondria and prelysosomal organelles, but not with slow axonal transport cargoes such as cytoskeletal elements. Khc mutations also impair the development of larval motor axon terminals, causing dystrophic morphology and marked reductions in synaptic bouton numbers. These observations suggest that as the concentration of maternally provided wild-type KHC decreases, axonal organelles transported by kinesin periodically stall. This causes organelle jams that disrupt retrograde as well as anterograde fast axonal transport, leading to defective action potentials, dystrophic terminals, reduced transmitter secretion and progressive distal paralysis. These phenotypes parallel the pathologies of some vertebrate motor neuron diseases, including some forms of amyotrophic lateral sclerosis (ALS), and suggest that impaired fast axonal transport is a key element in these diseases.     

Lead toxicosis in 2 horses: similarity to equine degenerative lower motor neuron disease

Endoscopical measurement of gastric mucosal blood flow seems to provide substantial advantages for noninvasive and repetitive scrutiny, especially in small animals. We employed a quartz probe 0.5 mm in diameter which was inserted into the gastric lumen through the forceps channel (0.8 mm in diameter) of the endoscope. Gastric mucosal blood flow determined with this probe in combination with laser Doppler velocimetry were sufficiently consistent and reproducible in the corpus as long as the tissue-to-probe distance was positioned in gentle contact with the gastric mucosa perpendicularly. Topical application of endothelin-1 produced a significant long-lasting decline in gastric mucosal blood flow, although laparotomy per se resulted in a slight decrease of the blood flow. Endoscopic measurement of gastric mucosal blood flow seems simple and reproducible with high potential for chronic studies.     

Ultrastructural study of the synapses of central chromatolytic anterior horn cells in motor neuron disease

This report deals with an ultrastructural investigation of the synapses on the somata of central chromatolytic anterior horn neurons of seven patients with amyotrophic lateral sclerosis (ALS) and four patients with lower motor neuron disease (LMND) who had no upper motor neuron or corticospinal tract involvement. Specimens from 24 age-matched individuals who died of non-neurological diseases served as controls. We examined a total of 171 anterior horn neurons with central chromatolysis (51 from ALS, 42 from LMND and 78 from controls), and 174 normal-appearing anterior horn neurons as controls. The cross-sectional area, the number of synapses, and the length of active zone were significantly reduced in the chromatolytic neurons of both patients and controls as compared with normal-appearing neurons of the controls (p < 0.0001). However, regarding chromatolytic neurons, no significant differences were seen in the number of synapses, length of each individual synapse, and length of its active zone between patients and controls and also in the frequency of presynaptic alterations on the somata. There was no overall difference between ALS and LMND patients in any of these parameters. Our findings suggest that the flow of electrophysiological information from afferent fibers to the somata may be greatly impaired in central chromatolytic neurons of both control individuals and patients with motor neuron disease (MND), and that the observed synaptic alterations may reflect pathological events resulting from anterior horn neuron degeneration. It may represent a compensatory mechanism of the synapses for diminished synaptic function that synapses were relatively well preserved on the somata of central chromatolytic neurons of the MND patients as compared with those of the chromatolytic neurons of the controls despite of markedly reduced cross-sectional area in the former. It also suggests that the pathomechanism involved in central chromatolysis differs between normal individuals and patients with MND.