Subacute motor neuron hyperexcitability with mercury poisoning: a case series and literature review.

Motor neuron hyperexcitability (MNH) indicates a disorder characterized by an ectopic motor nerve discharge on electromyogram (EMG). Here, we present a series of three cases of subacute MNH with mercury poisoning. The first case showed hyperhidrosis, insomnia, generalied myokymia, cramps, tremor, weight loss, and myokymic and neuromyotonic discharges, followed by encephalopathy with confusion, hallucinations, and memory decrease. The second case was similar to the former but without encephalopathic features. The third case showed widespread fasciculation, fatigue, insomnia, weight loss, and autonomic dysfunction, including constipation, micturition difficulty, and impotence, with multiple fibrillation, unstable fasciculation, widened motor neuron potential, and an incremental response at high-rate stimulation in repetitive nerve stimulation. Based on the symptoms, the three cases were diagnosed as Morvan's syndrome, Isaacs' syndrome, and Lambert-Eaton myasthenic syndrome with ALS-like syndrome, respectively. Mercury poisoning in the three cases was confirmed by analysis of blood and urine samples. All cases recovered several months after chelation therapy and were in good condition at follow-up. Very few cases of MNH linked with mercury exposure have been reported in the literature. The mechanism of mercury-induced MNH may be associated with ion channel dysfunction.

Chinese talismans as a source of lead exposure.

We describe a case of lead exposure after prolonged intake of ashes from burnt Chinese talismans. A 41-year-old woman presented with elevated blood lead level during screening for treatable causes of progressive weakness in her four limbs, clinically compatible with motor neuron disease. The source of lead exposure was confirmed to be Chinese talismans obtained from a religious practitioner in China. The patient was instructed to burn the Chinese talismans to ashes, and ingest the ashes dissolved in water, daily for about 1 month. Analysis of the Chinese talismans revealed a lead concentration of 17 342 µg/g (ppm).

Fishing for causes and cures of motor neuron disorders.

Motor neuron disorders (MNDs) are a clinically heterogeneous group of neurological diseases characterized by progressive degeneration of motor neurons, and share some common pathological pathways. Despite remarkable advances in our understanding of these diseases, no curative treatment for MNDs exists. To better understand the pathogenesis of MNDs and to help develop new treatments, the establishment of animal models that can be studied efficiently and thoroughly is paramount. The zebrafish (Danio rerio) is increasingly becoming a valuable model for studying human diseases and in screening for potential therapeutics. In this Review, we highlight recent progress in using zebrafish to study the pathology of the most common MNDs: spinal muscular atrophy (SMA), amyotrophic lateral sclerosis (ALS) and hereditary spastic paraplegia (HSP). These studies indicate the power of zebrafish as a model to study the consequences of disease-related genes, because zebrafish homologues of human genes have conserved functions with respect to the aetiology of MNDs. Zebrafish also complement other animal models for the study of pathological mechanisms of MNDs and are particularly advantageous for the screening of compounds with therapeutic potential. We present an overview of their potential usefulness in MND drug discovery, which is just beginning and holds much promise for future therapeutic development.

Role of glutamate and nitric oxide in onset of motor neuron degeneration in neurolathyrism.

Neurolathyrism is associated with a complex pattern of alterations in the glutamatergic system of the cortical motor region of brain. It is a neurological disorder consorted with excessive consumption of Lathyrus sativus (Grass pea), comprising large amounts of the neurotoxin, ß-N-oxalyl-L-α,ß-diaminopropionic acid (ODAP). ODAP being a potent agonist of ionotropic glutamate receptors enhances their activity and also blocks the astrocytic glutamate/cystine transporters, abutting the neurons. This leads to the sustained increase in the concentration of Glutamate in the synapse which triggers excitotoxicity. L. sativus also contains high levels of arginine and homoarginine which are natural substrates of nitric oxide production, when NO levels increases, it forms peroxynitrite radicals which cause irreparable damage to mitochondria and cellular macromolecules leading to motor neuron degeneration. This review brings together all the molecular events reported so far, emphasizing on the possible role of glutamate and nitric oxide mediated cell death.

Clinical spectrum of neurosyphilis in North East India.

BACKGROUND: Symptomatic neurosyphilis (NS) can have varied syndromic presentations: Meningitis, meningovascular and parenchymatous involvement. AIMS: To evaluate the different types of clinical syndrome of NS in a tertiary care hospital. MATERIAL AND METHODS: This was a study of clinical profile of 16 patients with NS, seen in between August 2008 and December 2010. RESULTS: There were 13 male and 3 female patients in the age group of 23-48 years. The clinical syndromes included: Neuropsychiatric syndromes (10), myelopathy (5), and posterior circulation stroke (1). Neuropsychiatric symptoms were dementia, behavioral abnormalities, chronic psychosis, and myelopathy syndromes included acute transverse myelitis (ATM), chronic myelopathy, and syphilitic amyotrophy. Thirteen patients had positive venereal disease research laboratory test (VDRL) and/or high Treponema pallidum hemagglutination titer in blood. Cerebrospinal fluid was positive for VDRL in 14 patients, raised protein was seen in 13 patients and lymphocytic pleocytosis was seen in 10 patients. Human immunodeficiency virus serology was negative in all the patients. Fourteen patients fulfilled the criteria of definitive NS and two of presumptive NS. All the patients except one received injection Procaine penicillin for 14 days. The patient with myelitis received a course of steroid, and one patient with associated hypothyroidism received thyroid supplement in addition to penicillin. On follow-up, dementia of short duration and ischemic stroke improved significantly and clinical status remained the same for ATM; others with mild symptoms improved with residual deficit. CONCLUSION: Syphilis can affect any part of the neuraxis. A high index of clinical suspicion is required to diagnose NS and institute the treatment early, particularly in patients with promiscuous sexual behavior.

Conservative treatment with hyperbaric oxygen therapy for cervical spondylotic amyotrophy.

STUDY DESIGN: Small case series of patients with cervical spondylotic amyotrophy (CSA) managed by conservative treatment with hyperbaric oxygen (HBO) therapy. OBJECTIVE: To study the effects of conservative treatment with HBO therapy of CSA patients. SETTING: Department of Orthopaedic Surgery, Imakiire General Hospital, Kagoshima, Japan. METHODS: This study included 10 patients with CSA who underwent rehabilitation, including cervical traction and muscle exercise, for some period of time but did not respond well to it, and were then managed by additional HBO therapy for rehabilitation. Information was obtained on the duration of symptoms and strength of the most atrophic muscle, intramedullary high-signal-intensity changes on T2-weighted magnetic resonance imaging, presence of 'snake-eyes' appearance and the number of stenotic canal levels. RESULTS: The mean duration of symptoms before HBO treatment was 3.1 months. The axial T2-weighted magnetic resonance images of all 10 patients showed a 'snake-eyes' appearance. The mean number of stenotic canal levels was 0.3. There was marked improvement on manual muscle testing from a mean of 1.9 pretreatment to a mean of 4.4 at the last follow-up after HBO therapy. The outcomes of all 10 patients, whose results were classified as excellent or good, were considered clinically satisfactory. CONCLUSION: To our knowledge, conservative treatment with HBO therapy for CSA patients has not previously been described. It appears that HBO therapy might improve ischemic injury of the anterior horns in CSA patients with short duration of symptoms.

Modulation of motoneuronal firing behavior after spinal cord injury using intraspinal microstimulation current pulses: a modeling study.

We simulated the effects of delivering focal electrical stimuli to the central nervous system to modulate the firing rate of neurons and alleviate motor disorders. Application of these stimuli to the spinal cord to reduce the increased excitability of motoneurons and resulting spasticity after spinal cord injury (SCI) was examined by means of a morphologically detailed computer model of a spinal motoneuron. High-frequency sinusoidal and rectangular pulses as well as biphasic charge-balanced and charge-imbalanced pulses were examined. Our results suggest that suprathreshold high-frequency sinusoidal or rectangular current pulses could inactivate the Na+ channels in the soma and initial segment, and block action potentials from propagating through the axon. Subthreshold biphasic charge-imbalanced pulses reduced the motoneuronal firing rate significantly (up to approximately 25% reduction). The reduction in firing rate was achieved through stimulation-induced hyperpolarization generated in the first node of Ranvier. Because of their low net DC current, these pulses could be tolerated safely by the tissue. To deliver charge-imbalanced pulses with the lowest net DC current and induce the largest reduction in motoneuronal firing rate, we studied the effect of various charge-imbalanced pulse parameters. Short pulse durations were found to induce the largest reduction in firing rate for the same net DC level. Subthreshold high-frequency sinusoidal and rectangular current pulses and low-frequency biphasic charge-balanced pulses, on the other hand, were ineffective in reducing the motoneuronal firing rate. In conclusion, the proposed electrical stimulation paradigms could provide potential rehabilitation interventions for suppressing the excitability of neurons to reduce the severity of motor disorders after injury to the central nervous system.

Ependymoma of the spinal cord presenting in a chiropractic practice: 2 case studies.

OBJECTIVE: The purpose of this study is to discuss the cases of 2 patients with previously undiagnosed primary spinal cord tumors presenting in a private chiropractic clinical setting. An overview of treatment and outcome for an ependymoma at T12-L1 and L1-L2 is discussed. CLINICAL FEATURES: One patient was a 46-year-old Hispanic woman with 3 to 4 years of intermittent backache that usually resolved with conservative care but failed to do so during an acute episode. Lower motor neuron signs, including bowel and bladder dysfunction, were revealed upon clinical assessment. The second patient, a 38-year-old white man under routine treatment, had no lower motor neuron signs or symptoms. INTERVENTION AND OUTCOME: Both patients were referred, one to a local hospital emergency department and the other directly to a neurosurgeon. Both underwent surgery. Upon returning home, the first patient received follow-up treatment primarily consisting of radiation therapy. Follow-up telephone interviews (3, 6, 12, 24, and 40 months) revealed the patient doing well. The second case did not require radiation therapy and was doing well at 4, 10, 12, and 18 months; the patient returned for unrelated treatment 1 year after the surgery. CONCLUSION: These cases show that with a careful history and patient examination, enough clinical data may be gathered to make an accurate health care determination under various conditions. It also illustrates the importance of interprofessional cooperation for various disciplines of health care providers regardless of training or specialty.

Evaluation of the risk of motor neuron disease in horses fed a diet low in vitamin E and high in copper and iron.

OBJECTIVE: To determine whether equine motor neuron disease (EMND) could be induced in adult horses fed a diet low in vitamin E and high in copper and iron. ANIMALS: 59 healthy adult horses. PROCEDURE: Horses in the experimental group (n = 8) were confined to a dirt lot and fed a concentrate low in vitamin E and high in iron and copper in addition to free-choice grass hay that had been stored for 1 year. Control horses (n = 51) were fed a concentrate containing National Research Council-recommended amounts of copper, iron, and vitamin E. The hay fed to control horses was the same as that fed to experimental horses, but it had not been subjected to prolonged storage. Control horses had seasonal access to pasture, whereas experimental horses had no access to pasture. Horses that developed clinical signs of EMND were euthanatized along with an age-matched control horse to determine differences in hepatic concentrations of vitamin E, vitamin A, copper, iron, and selenium. RESULTS: 4 experimental horses developed clinical signs of EMND. Plasma concentrations of vitamin E decreased in all 8 experimental horses. There were no significant changes in plasma concentrations of vitamin A, selenium, and copper or serum concentrations of ferritin. There were no significant differences in those analytes between experimental horses with EMND and experimental horses that did not develop EMND. No control horses developed EMND. CONCLUSIONS AND CLINICAL RELEVANCE: Results suggest that lack of access to pasture, dietary deficiency of vitamin E, or excessive dietary copper are likely risk factors for EMND.

Muscle biopsies show that FES of denervated muscles reverses human muscle degeneration from permanent spinal motoneuron lesion.

This paper presents biopsy analyses in support of the clinical evidence of muscle recovery induced by a new system of life-long functional-electrical-stimulation (FES) training in permanent spinal-motoneuron-denervated human muscle. Not earlier than 1 year after subjects experienced complete conus cauda lesion, their thigh muscles were electrically stimulated at home for several years with large skin surface electrodes and an expressly designed stimulator that delivered much longer impulses than those presently available for clinical use. The poor excitability of long-term denervated muscles was first improved by several months of twitch-contraction training. Then, the muscles were tetanically stimulated against progressively increased loads. Needle biopsies of vastus lateralis from long-term denervated subjects showed severe myofiber atrophy or lipodystrophy beginning 2 years after spinal cord injury (SCI). Muscle biopsies from a group of 3.6- to 13.5-year denervated subjects, who underwent 2.4 to 9.3 years of FES, show that this progressive training almost reverted long-term muscle atrophy/degeneration.

Cassava cyanogens and free amino acids in raw and cooked leaves.

Cassava leaves (Manihot esculenta Crantz) constitute the main daily source of protein as supplement to the major staple food, the processed cassava roots in remote rural areas of Africa. Konzo, an upper motoneurone disease with permanent spastic paralysis of both legs, has been reported among populations consuming this unbalanced diet. In commercial pounded cassava leaves residual cyanogens and the presence of inherent potentially toxic non-protein amino acids were analysed to check their safety. The initial total cyanogens before cooking ranged from 35.9+/-0.4 to 107.5+/-0.8 mg HCN (hydrogen cyanide) equivalent kg(-1) dry weight. After cooking, the residual cyanogens were significantly reduced (P<0.05) ranging from 0.30+/-0.04 to 1.9+/-0.2 mg HCN equivalent kg(-1) dry weight, and were below the recommended FAO/WHO safe limit set at 10 mg HCN equivalent kg(-1) dry weight. The total free amino acids and trigonelline (N-methyl-nicotinic acid) detected varied from 10.8 g kg(-1) dry weight to 38.2 g kg(-1) dry weight in the raw and from 7.4 g kg(-1) dry weight to 25.6 g kg(-1) dry weight in the cooked cassava leaves. The non-protein amino acids gamma-amino butyric acid (GABA) and alpha-amino butyric acid (alpha-ABA) were detected. No known potentially toxic non-protein amino acid was found. In konzo-affected areas, cassava leaves with inadequate preparation and cooking can be a non-negligible source of dietary exposure to cyanogens apart from the cassava roots that are suggested to be involved in the aetiology of konzo.

[Neurological syndromes linked with the intake of plants and fungi containing a toxic component (I). Neurotoxic syndromes caused by the ingestion of plants, seeds and fruits]. / Síndromes neurológicos asociados con el consumo de plantas y hongos con componente tóxico (I). Síndromes neurotóxicos por ingesta de plantas, semillas y frutos.

INTRODUCTION: A wide range of plants, seeds and fruits used for nutritional and medicinal purposes can give rise to neurotoxic symptoms. DEVELOPMENT: We review the neurological pathology associated with the acute or chronic consumption of plants, seeds and fruits in human beings and in animals. Of the plants that can trigger acute neurotoxic syndromes in humans, some of the most notable include Mandragora officinalis, Datura stramonium, Conium maculatum (hemlock), Coriaria myrtifolia (redoul), Ricinus communis, Gloriosa superba, Catharanthus roseus, Karwinskia humboldtiana and Podophyllum pelatum. We also survey different neurological syndromes linked with the ingestion of vegetable foodstuffs that are rich in cyanogenic glycosides, Jamaican vomiting sickness caused by Blighia sapida, Parkinson dementia ALS of Guam island and exposition to Cycas circinalis, Guadeloupean parkinsonism and exposition to Annonaceae, konzo caused by ingestion of wild manioc and neurolathyrism from ingestion of Lathyrus sativus, the last two being models of motor neurone disease. Locoism is a chronic disease that develops in livestock feeding on plants belonging to Astragalus and Oxytropis sp., Sida carpinifolia and Ipomea carnea, which are rich in swainsonine, a toxin that inhibits the enzyme alpha mannosidase and induces a cerebellar syndrome. CONCLUSIONS: The ingestion of neurotoxic seeds, fruits and plants included in the diet and acute poisoning by certain plants can give rise to different neurological syndromes, some of which are irreversible.

Konzo outbreak, in the south-west of the Democratic Republic of Congo, 1996.

In August 1996, cases of poliomyelitis were reported in Kahemba zone, in the south-west of the Democratic Republic (DR) of Congo. The diagnosis was reviewed and charged to Konzo, a spastic paraparesis attributed to food cyanide intoxication. In order to describe the phenomena, a community-based survey took place and found 237 people affected. The highest prevalence was found in the most isolated part of the zone. The patients suffered from an isolated non-progressive spastic paraparesis of abrupt onset. Children and women were the most affected groups, especially women after childbirth. Most of the patients developed the disease after 1990 with 101 cases in 1996. Cassava processing was the same over time and in all the villages. The study did not fully explain the increased number of cases in 1996 but suggested that complementary investigations regarding micronutrient intakes, especially vitamin A, would be necessary.

Chronic poisoning by hydrogen cyanide in cassava and its prevention in Africa and Latin America.

Africa produces more than 30 million tons of cassava on about 5 million hectares (6 tons per hectare). Approximately 80% of the root production and 70% of the harvested area are from Western Africa. Recent reports suggest that the ingestion of poorly processed cassava roots is associated with the incidence of an ataxic neuropathy (konzo) in African countries. When cassava-based diets are not supplemented with good sources of protein and iodine, goiter and rickets are also prevalent. In certain countries of Africa where the rate of ataxic neuropathy is high, the incidence of thyroid disorders is also high. Persons consuming poorly processed cassava in large quantities are susceptible to neuropathologies caused by cyanide. Cyanide detoxification in the body is impaired by protein deficiency. When properly processed, the root of cassava is safe and cheap as a major dietary energy source for humans and domestic animals; however, a cassava-based diet will lack sufficient protein and will be particularly deficient for the growth and development of children unless it is supplemented by protein from animal, including fish, or legume sources. Cassava leaves, if they are appropriately cooked, can be a useful source of some nutrients.

Concentrations of trace minerals in the spinal cord of horses with equine motor neuron disease.

OBJECTIVE: To compare concentrations of trace minerals in the spinal cord of horses with equine motor neuron disease (EMND) with those of horses without neurologic disease (control horses). ANIMALS: 24 horses with EMND and 22 control horses. PROCEDURE: Spinal cord trace mineral concentrations in horses with EMND and control horses were analyzed by use of inductively coupled plasma atomic emission spectroscopy (calcium, phosphorus, sodium, potassium, magnesium, copper, iron, manganese, nickel, zinc, aluminum, cobalt, and chromium), atomic absorption spectrophotometry (lead and cadmium), flameless atomic absorption (mercury), and fluorometry (selenium). RESULTS: Copper concentration was significantly higher in the spinal cord of horses with EMND, compared with control horses; spinal cord concentrations of all other trace minerals were similar between groups. CONCLUSION AND CLINICAL RELEVANCE: Among spinal cord trace minerals investigated in the study, only copper concentrations were significantly different between horses with EMND and horses without neurologic disease, which suggests that copper may be involved in the pathogenesis of EMND. An hypothesis of oxidative injury in this disease is supported by the finding of increased copper concentrations in the spinal cord and by low vitamin E concentrations reported by other researchers.

Intrinsic, management, and nutritional factors associated with equine motor neuron disease.

OBJECTIVE: To identify intrinsic, management, nutritional, and environmental risk factors associated with equine motor neuron disease (EMND) and to determine whether epidemiologic evidence supports oxidative stress as a risk factor for developing EMND. DESIGN: Case-control study. ANIMALS: 87 horses with EMND and 259 control horses. PROCEDURE: Information concerning each horse's history of exposure to multiple environmental factors prior to developing EMND was obtained by means of a questionnaire or personal interview. Exposure histories of horses with EMND and control horses were compared, and the association of each risk factor with EMND was evaluated, using logistic regression analysis. RESULTS: Factors significantly associated with risk of developing EMND included age, breed of horse, duration of residence at the farm, not vaccinating against rabies, and certain feeding practices. Horses that were exercised on green pasture or in grass paddocks were less likely to develop EMND, compared with horses that were exercised in dirt pad-docks. Feeding complete pelleted feed as the only source of concentrate or combined with sweet feed was associated with a significant increase in the risk of EMND. Supplementary feeding of vitamin and mineral mixtures not formulated to provide vitamin E or selenium was associated with increased risk of EMND. Horses with a history of cribbing or coprophagia were also at higher risk of developing EMND. CLINICAL IMPLICATIONS: Several husbandry practices and intrinsic characteristics of horses appear to modify the risk of EMND. The relationship of specific nutritional factors to EMND supports the hypothesis that a deficiency of vitamin E contributes to the disease.

Mesh-glove. 1. A method for whole-hand electrical stimulation in upper motor neuron dysfunction.

A newly devised method for electrical stimulation via a wired mesh-glove is described. The stimulation paradigm is novel in that a whole hand is the target of stimulation. Specific standardized stimulation modalities are reviewed. The protocol for mesh-glove stimulation for patients with and without volitional movements, but increased muscle tone is outlined. A sequenced program based on restoration of motor functions is described. The mesh-glove stimulation is well suited for home use. On the basis of our experience working with 40 patients after stroke, head and spinal cord injuries, we concluded that this procedure is beneficial and safe.

Equine motor neuron disease: findings in 28 horses and proposal of a pathophysiological mechanism for the disease.

Over a three and one-half year period, 28 adult horses were diagnosed with equine motor neuron disease (EMND). The most commonly identified environmental risk factors for a horse having EMND were absence of grazing for more than a year and provision of poor quality hay. Quarter Horses were 5.4 times more at risk than other breeds but this was thought to be an epiphenomenon related to the frequency of Quarter Horses at boarding stables. Weight loss, excessive recumbency and/or trembling were the first signs noted. Other clinical diagnostic signs included: constant shifting of the weight in the rear limbs, abnormally low head carriage and muscle fasciculations. Excellent to ravenous appetites were present in all cases and marked coprophagia in some cases. Abnormally high serum concentration of muscle-derived enzymes was the only consistent serum chemistry abnormality found. Abnormal glucose absorption, increased cerebrospinal fluid total protein and intrathecal production of IgG were identified in a number of cases. Euthanasia was performed on 5 horses within 4 days of hospital admission, because of inability to stand or respiratory distress, and on 18 horses after the diagnosis had been completed. Five affected horses were maintained for observational purposes for periods of 9 months to over 2 years after the onset of clinical signs. They were given access to pasture and 2 were given supplemental vitamin E as the only therapy. Marked clinical improvement occurred in the 4 more acutely affected horses. Pathological findings, preference of type 1 muscle fibre atrophy and lipopigment accumulation within the capillary endothelium of the spinal cord of all cases, supported the hypothesis of EMND being an oxidative disease.(ABSTRACT TRUNCATED AT 250 WORDS)