Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C1762617 (weakness)
 37,932 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We studied 13 patients with lipoamide dehydrogenase (LAD) deficiency, originating from seven Ashkenazi Jewish families. Their disease was characterized by recurrent attacks of vomiting, abdominal pain, and encephalopathy accompanied by elevated liver transaminases, prolonged prothrombin time, and occasionally associated with lactic and ketoacidemia or with myoglobinuria. Two patients who presented neonatally suffered from residual neurological damage with attention deficit hyperactive disorder, mild ataxia, motor incoordination, muscle hypotonia, and weakness. Nine patients who presented in early childhood or later suffered from exertional fatigue between decompensation episodes but were otherwise asymptomatic. Two patients died because of intractable metabolic acidosis and multi-organ failure. In all patients LAD activity was reduced to 8 to 21% of the control in muscle or lymphocytes. In four patients LAD protein in muscle was reduced to 20 to 60% of the control. Direct sequencing of the cDNA of the LAD gene showed that 12 of the 14 mutated alleles carried the G229C mutation and two carried an insertion mutation 105insA (Y35X). The patients who presented neonatally and had more severe sequelae were compound heterozygotes for the two mutations; patients who presented in early childhood or later were homozygous for the G229C mutation. Using an allele-specific oligonucleotide hybridization technique, nine heterozygotes for the G229C mutation were identified among 845 anonymous individuals of Ashkenazi Jewish origin disclosing a carrier rate of 1:94. Because of the significant morbidity associated with the disease, screening for the G229C mutation among Ashkenazi Jewish couples should be considered.
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PMID:Molecular basis of lipoamide dehydrogenase deficiency in Ashkenazi Jews. 993 85

This report concerns an autopsy case of amyotrophic lateral sclerosis (ALS) with unusual clinical and neuropathological findings. The patient was a Japanese man without hereditary burden who was 49 years old at the time of death. His clinical manifestation included dysarthria at age 48, followed by dysphagia, atrophy and fasciculation of the tongue, muscle weakness in the four extremities, tremor, rigidity, increased deep tendon reflexes in the upper and lower extremities, and incoordination of the four extremities. He died of respiratory failure 12 months after the disease onset. No respirator administration was performed throughout the clinical course. The neuropathological examination revealed not only degeneration of upper and lower motor neuron systems, including the presence of Bunina bodies and ubiquitin-immunoreactive neuronal inclusions in the lower motor neurons, but also prominent degeneration of the substantia nigra and dentate nucleus with slight neuronal loss in the locus ceruleus and pontine nucleus. To our knowledge, this is the first reported case of sporadic ALS without dementia and respirator support, showing degeneration of the substantia nigra and dentate nucleus. This report may contribute to the resolution of the question concerning the neuropathological heterogeneity of sporadic ALS with respiratory support.
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PMID:Sporadic amyotrophic lateral sclerosis with multiple system degeneration: a report of an autopsy case without respirator administration. 1054 75

A 57-year-old man was admitted to our hospital in November 1997 because of dysarthria, progressive ataxia, generalized weakness, and incoordination in both hands. He had been aware of the dysarthria 6 months earlier. Chest roentgenograms and computed tomographic films disclosed a 5 cm x 6 cm mass in the left S3b. The patient was given a diagnosis of small cell lung cancer (T3N2M0, stage IIIA) associated with paraneoplastic cerebellar degeneration (PCD). Three courses of chemotherapy (carboplatin and etoposide) eliminated the tumor and slightly alleviated the PCD symptoms. In March 1998, electromyograms revealed a fall in the single-stimulated M wave and a waxing phenomenon that had not been observed on admission. Anti-P/Q type voltage gated calcium channel antibody was detected in serum samples obtained on admission and after chemotherapy. These findings confirmed an association with Lambert-Eaton myasthenic syndrome. No relapse of the tumor has been observed 15 months after the last course of chemotherapy.
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PMID:[Small cell lung cancer associated with paraneoplastic cerebellar degeneration and Lambert-Eaton myasthenic syndrome]. 1070 41

Patients with developmental disorders, including adolescents, comprise a large and heterogeneous group of individuals who vary in underlying diagnosis and degree of disability. The largest numbers of patients are those with cerebral palsy and with traumatic brain injury. While these conditions themselves do not directly cause airway or parenchymal lung dysfunction, consequences of neuromuscular dysfunction, especially aspiration and ineffective cough, may lead to lung damage. Poor nutritional status, impairment of airway clearance by muscular weakness or incoordination and poor pulmonary reserve (due to chest wall or spine deformity) increase the risk of significant morbidity and mortality from respiratory infections. Individuals who were premature infants or who had prolonged neonatal courses may also have residual chronic lung disease (bronchopulmonary dysplasia) contributing to their pulmonary problems. This review discusses conditions that have adverse effects on the airway and lung (drooling, feeding problems, gastroesophageal reflux, aspiration, spasticity, scoliosis) and some of the consequences of these insults (disordered airway clearance, pneumonia, sleep apnea). Also discussed are issues important to the prevention or amelioration of respiratory difficulties, including preventive care, the effects of exercise, dental hygiene, and surgical intervention.
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PMID:Respiratory problems in the adolescent with developmental delay. 1106 May 58

There is nothing more discouraging than for a patient to be given a specific diagnosis, then to be told that there is nothing that can be done. Physicians are equally disheartened to see exponential progress being made in the understanding of the pathophysiology of a complex disorder but few direct benefits resulting for their patients. Over the past 5 years, molecular genetic research has completely revolutionized the way in which the progressive cerebellar ataxias are classified and diagnosed, but it has yet to produce effective gene-based, neuroprotective, or neurorestorative therapies. The treatment of cerebellar ataxia remains primarily a neurorehabilitation challenge, employing physical, occupational, speech, and swallowing therapy; adaptive equipment; driver safety training; and nutritional counseling. Modest additional gains are seen with the use of medications that can improve imbalance, incoordination, or dysarthria (amantadine, buspirone, acetazolamide); cerebellar tremor (clonazepam, propranolol); and cerebellar or central vestibular nystagmus (gabapentin, baclofen, clonazepam). Many of the progressive cerebellar syndromes have associated features involving other neurologic systems (eg, spasticity, dystonia or rigidity, resting or rubral tremor, chorea, motor unit weakness or fatigue, autonomic dysfunction, peripheral or posterior column sensory loss, neuropathic pain or cramping, double vision, vision and hearing loss, dementia, and bowel, bladder, and sexual dysfunction), which can impede the treatment of the ataxic symptoms or can worsen with the use of certain drugs. Treatment of the associated features themselves may in turn worsen the ataxia either directly (as side effects of medication) or indirectly (eg, relaxation of lower limb spasticity that was acting as a stabilizer for an ataxic gait). Secondary complications of progressive ataxia can include deconditioning or immobility, weight loss or gain, skin breakdown, recurrent pulmonary and urinary tract infections, aspiration, occult respiratory failure, and obstructive sleep apnea, all of which can be life threatening. Depression in the patient and family members is common. Although no cures exist for most of the causes of cerebellar ataxia and there are as yet no proven ways to protect neurons from premature cell death or to restore neuronal populations that have been lost, symptomatic treatment can greatly improve the quality of life of these patients and prevent complications that could hasten death. Supportive interventions should always be offered-- education about the disease itself, genetic counseling, individual and family counseling, referral to support groups and advocacy groups, and guidance to online resources. Misinformation, fear, depression, hopelessness, isolation, and financial and interpersonal stress can often cause more harm to the patient and caregiver than the ataxia itself.
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PMID:Cerebellar Ataxia. 1109 49

Low literacy is termed 'developmental dyslexia' when reading is significantly behind that expected from the intelligence quotient (IQ) in the presence of other symptoms--incoordination, left-right confusions, poor sequencing--that characterize it as a neurological syndrome. 5-10% of children, particularly boys, are found to be dyslexic. Reading requires the acquisition of good orthographic skills for recognising the visual form of words which allows one to access their meaning directly. It also requires the development of good phonological skills for sounding out unfamiliar words using knowledge of letter sound conversion rules. In the dyslexic brain, temporoparietal language areas on the two sides are symmetrical without the normal left-sided advantage. Also brain 'warts' (ectopias) are found, particularly clustered round the left temporoparietal language areas. The visual magnocellular system is responsible for timing visual events when reading. It therefore signals any visual motion that occurs if unintended movements lead to images moving off the fovea ('retinal slip'). These signals are then used to bring the eyes back on target. Thus, sensitivity to visual motion seems to help determine how well orthographic skill can develop in both good and bad readers. In dyslexics, the development of the visual magnocellular system is impaired: development of the magnocellular layers of the dyslexic lateral geniculate nucleus (LGN) is abnormal; their motion sensitivity is reduced; many dyslexics show unsteady binocular fixation; hence poor visual localization, particularly on the left side (left neglect). Dyslexics' binocular instability and visual perceptual instability, therefore, can cause the letters they are trying to read to appear to move around and cross over each other. Hence, blanking one eye (monocular occlusion) can improve reading. Thus, good magnocellular function is essential for high motion sensitivity and stable binocular fixation, hence proper development of orthographic skills. Many dyslexics also have auditory/phonological problems. Distinguishing letter sounds depends on picking up the changes in sound frequency and amplitude that characterize them. Thus, high frequency (FM) and amplitude modulation (AM) sensitivity helps the development of good phonological skill, and low sensitivity impedes the acquisition of these skills. Thus dyslexics' sensitivity to FM and AM is significantly lower than that of good readers and this explains their problems with phonology. The cerebellum is the head ganglion of magnocellular systems; it contributes to binocular fixation and to inner speech for sounding out words, and it is clearly defective in dyslexics. Thus, there is evidence that most reading problems have a fundamental sensorimotor cause. But why do magnocellular systems fail to develop properly? There is a clear genetic basis for impaired development of magnocells throughout the brain. The best understood linkage is to the region of the Major Histocompatibility Complex (MHC) Class 1 on the short arm of chromosome 6 which helps to control the production of antibodies. The development of magnocells may be impaired by autoantibodies affecting the developing brain. Magnocells also need high amounts of polyunsaturated fatty acids to preserve the membrane flexibility that permits the rapid conformational changes of channel proteins which underlie their transient sensitivity. But the genes that underlie magnocellular weakness would not be so common unless there were compensating advantages to dyslexia. In developmental dyslexics there may be heightened development of parvocellular systems that underlie their holistic, artistic, 'seeing the whole picture' and entrepreneurial talents.
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PMID:The magnocellular theory of developmental dyslexia. 1130 28

Significant potential exists for enhancing physical rehabilitation following neurologic injury through the use of robotic and mechatronic devices (or "rehabilitators"). We review the development of a rehabilitator (the "ARM Guide") to diagnose and treat arm movement impairment following stroke and other brain injuries. As a diagnostic tool, the ARM Guide provides a basis for evaluation of several key motor impairments, including abnormal tone, incoordination, and weakness. As a therapeutic tool, the device provides a means to implement and evaluate active assist therapy for the arm. Initial results with three stroke subjects demonstrate that such therapy can produce quantifiable benefits in the chronic hemiparetic arm. Directions for future research regarding the efficacy and practicality of rehabilitators are discussed.
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PMID:Understanding and treating arm movement impairment after chronic brain injury: progress with the ARM guide. 1132 Oct 1

This study describes the adverse effects of dietary lupines in broiler chickens for which lupine seeds (Lupinus angustifolius) in raw, dehulled, or autoclaved forms were used as a replacement for soybean meal (SBM) in practical diets. Test diets contained 35% SBM (control) or raw (40%), autoclaved (40%), or dehulled (35%) lupine seed meal. All diets were isocaloric (3,230 kcal/kg AME) and isonitrogenous (23% crude protein). Each diet was offered ad libitum to a group of 16 (four replicates with four birds per replicate) day-old male broiler chicks for 21 d. Chemical analysis of lupine seeds showed no detectable levels of mycotoxins, and total alkaloid contents were below 0.01%. Decreased food intake and growth rate were the main signs observed in all birds fed lupine-based diets. These adverse effects were observed during the first week and persisted throughout the trial. Acute signs of toxicity were observed in four chicks fed the diet containing raw lupine seed during the first week of exposure. Initial clinical signs included leg weakness, lack of coordination, and torticollis. In later stages, during Weeks 2 and 3, some birds fed lupine-based diets showed signs of muscle paralysis and skeletal deformity. Postmortem examination did not show gross pathological changes associated with the dietary treatments. Liver microsomal cytochrome P-50 content was higher (P < 0.05) in birds fed the raw lupine-based diet (mean 0.56 pmol/mg protein) in comparison with controls (mean 0.25 pmol/mg protein), which indicated a systemic effect. Based on the present results, it can be stated that high levels of some varieties of sweet lupines in broiler diets may cause significant adverse effects manifested as 1) decreased feed intake and growth rate in most of the birds, and 2) specific signs of acute and chronic toxicity in some individuals.
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PMID:Adverse effects of dietary lupine in broiler chickens. 1137 12

The autosomal dominant (AD) spinocerebellar ataxias (SCAs) and hereditary sensory neuropathies (HSN) are heterogeneous disorders characterized by variable clinical, electrophysiological, and neuropathological profiles. The SCAs are clinically characterized by slowly progressive incoordination of gait often associated with poor coordination of hands, speech, and eyes. Peripheral neuropathy is not a frequent part of the SCA syndrome. In contrast, the HSNs are primarily characterized by progressive sensory loss. There is substantial clinical overlap between the various SCAs and the various HSNs, and they often cannot be differentiated on the basis of clinical or neuro-imaging studies. We have identified a five-generation American family of Irish ancestry with a unique neurological disorder displaying an AD pattern of inheritance. There was variable expressivity and severity of symptoms including sensory loss, ataxia, pyramidal tract signs, and muscle weakness. Nerve conduction studies were consistent with a sensory axonal neuropathy. Muscle biopsy revealed neurogenic atrophy and brain MRI showed mild cerebellar atrophy. To identify the responsible locus we pursued a whole genome linkage analysis. After analyzing 114 markers, linkage to D7S486 was detected with a two point LOD score of 4.79 at theta = 0.00. Evaluation of additional markers in the region provided a maximum LOD score of 6.36 at theta = 0.00 for marker D7S2554. Haplotype analysis delimited an approximately 14-cM region at 7q22-q32 between markers D7S2418 and D7S1804 cosegregating with the disease. Because this disorder does not easily fall into either the SCA or HSN categories, it is designated sensory/motor neuropathy with ataxia (SMNA).
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PMID:Autosomal dominant sensory/motor neuropathy with Ataxia (SMNA): Linkage to chromosome 7q22-q32. 1199 70

Eales' disease is a primary retinal perivasculitis of an undetermined etiology seen predominantly in the Indian subcontinent. However, neurological involvement is rare. We report here a patient of retinal perivasculitis with neurological dysfunction. Our patient is a 39 years male who developed acute diminished vision right eye in March 99, which progressed for four days and remained static. In April 99 he developed acute diminished vision left eye, which progressed to near total blindness in 48 hours. He was undergoing ophthalmic evaluation. Fourty five days later he developed incoordination and weakness left half of body. The examination revealed bilateral retinal perivasculitis with pyramidal signs and left sided cerebellar signs. Investigations revealed an ESR of 40 mm at the end of first hour. His CT head revealed bilateral basal ganglionic infarcts. MRI head revealed enhancing lesions both basal ganglia and right parietal region. Cerebrospinal fluid examination showed xanthochromic fluid with markedly elevated protein and lymphocytic pleocytosis. His workup for connective tissue disorders was negative. He was put on ATT with steroids. Eales' disease is presumed allergy to tuberculoprotein. A trial of ATT with steroids has been tried with varying results. Our patient had bilateral retinal perivasculitis and neurological dysfunction. He had lymphocytic pleocytosis with markedly elevated protein in the CSF.
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PMID:Eales' disease with neurological manifestations. 1563 51


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