Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0026827 (hypotonia)
 5,860 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We report cystinuria and symptoms of cerebellar atrophy in a 45-year-old man. His parents were first cousins, and many members of his family had stones of urinary tract or gait impairment. Neurological examination disclosed cerebellar signs resembling those of spinocerebellar degeneration. Urinalysis disclosed high cystine, lysine, ornitine and arginine output. Cystine was 1153.8 micro mol/day (normal range, 22-170); lysine, 3443.9 (normal range, 44-1000); ornitine, 283.8 (normal range, 7-40); and arginine, 154.0 (normal range, 9-50). Neurological complications reported to be associated with cystinuria include mental retardation, muscular dystrophy, hypotonia and dwarfism, mongolism, paroxysmal dyskinesia, myopathy, migraine, spastic paraplegia, multiple sclerosis, subacute combined degeneration and cranial polyneuropathy. Cerebellar signs have been reported in only two cases, and to our knowledge, this is the first case of cystinuria with cerebellar atrophy ever reported. Some common metabolic errors may have caused both disorders, although they also may have developed independently.
 ...
PMID:[Cystinuria with symptoms of cerebellar atrophy--a case report]. 189 74

Baclofen, the most effective drug for treating spasticity, is a specific agonist of gamma-aminobutyric acid-B receptors, and is very abundant in the superficial layers of the spinal cord. Given orally, baclofen does not easily penetrate the blood-brain barrier, and is distributed equally to the brain and spinal cord. Direct intrathecal administration was given in order to change the distribution of the drug by preferentially perfusing the spinal cord. Eighteen patients presenting a severe spastic syndrome were treated with chronic intrathecal infusion of baclofen in the lumbar cerebrospinal fluid. After clinical preselection, 38 patients were implanted with a lumbar access port allowing long-term trials in order to determine the efficacy of baclofen therapy and the effective 12-hour dose. The 18 patients selected for chronic administration were implanted with a programmable pump. The pathology in these cases was: multiple sclerosis (6 cases), posttrauma spastic syndrome (eight cases), and (one case each) cerebral palsy, ischemic cerebral lesion, spinal ischemia, and transverse myelitis. The mean follow-up period was 18 months (range 4 to 43 months). The clinical results were evaluated according to muscular hypertony on Ashworth's scale (changed for occurrence of painful spasms) and functional improvement. Results were better for spastic syndrome secondary to traumatic medullary lesion than for demyelinating disease. Hypertonia was improved in all cases as confirmed by the registration of the Hoffman (H) reflex. Painful muscular spasms disappeared in 14 of the 16 affected patients. Significant functional improvement was noted in nine patients and was considerable in three. The risk of side effects secondary to overdose (such as excessive hypotonia or central depression) and the absence of a specific baclofen antagonist stresses the necessity for accurate determination of the efficient dose. After an initial titration period and adjustment of the therapeutic dose, the individual doses were from 21 to 500 micrograms/24 hrs (mean 160 micrograms/24 hrs). This new conservative method is very effective, perfectly reversible, and safe when administered in conditions favorable to its use.
 ...
PMID:Chronic intrathecal baclofen administration for control of severe spasticity. 230 74

We studied the effect of the intrathecal infusion of baclofen, an agonist of gamma-aminobutyric acid, on abnormal muscle tone and spasms associated with spinal spasticity, in a randomized double-blind crossover study. Twenty patients with spinal spasticity caused by multiple sclerosis or spinal-cord injury who had had no response to treatment with oral baclofen received an intrathecal infusion of baclofen or saline for three days. The infusions were administered by means of a programmable pump implanted in the lumbar subarachnoid space. Muscle tone decreased in all 20 patients (mean [+/- SD] Ashworth score for rigidity, from 4.0 +/- 1.0 to 1.2 +/- 0.4; P less than 0.0001), and spasms were decreased in 18 of the 19 patients who had spasms (mean [+/- SD] score for spasm frequency, from 3.3 +/- 1.2 to 0.4 +/- 0.8; P less than 0.0005). Tests for motor function, neurologic examination, and assessments by the patients correctly indicated when baclofen was being infused in all cases. All patients were then entered in an open long-term trial of continuous infusion of intrathecal baclofen. During a mean follow-up period of 19.2 months (range, 10 to 33), muscle tone has been maintained within the normal range (mean Ashworth score, 1.0 +/- 0.1) and spasms have been reduced to a level that does not interfere with activities of daily living (mean spasm score, 0.3 +/- 0.6). No drowsiness or confusion occurred, one pump failed, and two catheters became dislodged and had to be replaced. No infections were observed. Our observations suggest that intrathecal baclofen is an effective long-term treatment for spinal spasticity that has not responded to oral baclofen.
 ...
PMID:Intrathecal baclofen for severe spinal spasticity. 265 24

Functional methionine synthase deficiency is generally characterized by homocystinuria and hypomethioninemia in the absence of methylmalonic aciduria. Patients are divided into two classes, cblE and cblG, on the basis of complementation analysis. Presentation has usually been in the first 2 years of life, but one patient came to medical attention at age 21 years with symptoms initially diagnosed as multiple sclerosis. Common findings among 11 patients (4 with cblE and 7 with cblG) have included megaloblastic anemia (all patients) and various neurological deficits including developmental retardation (10 patients), cerebral atrophy (8 patients), hypotonia (7 patients), EEG abnormalities (6 patients), and nystagmus (5 patients). Hypertonia, seizures, blindness, and ataxia were less frequent. All patients have responded to therapy with cobalamin with resolution of anemia and biochemical abnormalities; neurological deficits resolved more slowly and in some cases incompletely. Hydroxycobalamin has been more effective than cyanocobalamin. Fibroblasts from patients with cblE (5 patients) and cblG (6 patients) all showed decreased intracellular levels of methylcobalamin (MeCbl) and decreased incorporation of label from 5-methyltetrahydrofolate into macromolecules, suggesting decreased activity of the MeCbl-dependent enzyme methionine synthase. Methionine synthase specific activity in extracts of all cblE fibroblasts was normal or near-normal under standard reducing conditions; synthase specific activity in extracts of 5 cblG patients was low but was high in a 6th patient measured in another laboratory. Thus, there is heterogeneity among patients with functional methionine synthase deficiency both in clinical presentation and in the results of biochemical studies of cultured cells.
 ...
PMID:Functional methionine synthase deficiency (cblE and cblG): clinical and biochemical heterogeneity. 268 21

Dantrolene sodium acts primarily by affecting calcium flux across the sarcoplasmic reticulum of skeletal muscle. Recently, dantrolene has been used very successfully in the treatment of several rare hypercatabolic syndromes which have previously been associated with high mortality rates. In malignant hyperthermia, where early diagnosis and treatment usually with intravenous dantrolene in association with other supportive measures (and often subsequent dantrolene therapy) is performed, recovery is seen in virtually 100% of patients. There is a rapid resolution of hyperthermia, dysrhythmias, muscle rigidity, tachycardia, hypercapnia, mottled or cyanotic skin, and metabolic acidosis, and a slower normalisation of myoglobinuria and elevated serum creatine phosphokinase levels. In patients with family history or previous episodes of malignant hyperthermia, prophylactic treatment with dantrolene prior to anaesthesia prevents the syndrome occurring in most cases. Where malignant hyperthermia has developed patients have been successfully treated with further dantrolene therapy. Dantrolene has also been used successfully in the treatment of a few cases of heat stroke and the neuroleptic malignant syndrome--both of which have many similarities to malignant hyperthermia. Dantrolene is well established in the treatment of patients with muscle spasticity where it generally improves at least some of the components of spasticity (i.e. hyper/hypotonia, clonus, muscle cramps and spasms, resistance to stretch and flexor reflexes, articular movement, neurological and motor functions and urinary control). However, in some patients, particularly those with multiple sclerosis, dantrolene may not be effective, and in many cases muscular strength may diminish. Long term dantrolene therapy has been associated with hepatic toxicity and may cause problems in patients treated for disorders of muscle spasticity. Thus, dantrolene offers a unique advance in the therapy available for the treatment of hypercatabolic disorders and is also useful in the treatment of muscle spasticity of various aetiology.
 ...
PMID:Dantrolene. A review of its pharmacodynamic and pharmacokinetic properties and therapeutic use in malignant hyperthermia, the neuroleptic malignant syndrome and an update of its use in muscle spasticity. 352 59

The dorsal (posterior) root ganglion is a relatively neglected part of the nervous system from the clinical point of view. In recent studies on the pathophysiology of experimental allergic encephalomyelitis (EAE), the main animal model of multiple sclerosis, the DRG of the rabbit was shown to be the site of extensive inflammation and demyelination and of focal conduction block in a high proportion of the large diameter afferents. The resulting severe functional peripheral deafferentation accounts for the postural disturbance, hypotonia, ataxia and areflexia in rabbits with EAE. The vulnerability of the DRG is due to a deficient blood-nerve barrier and possibly also to a susceptibility of the branch point of the ganglion neurone to demyelination-induced conduction block. These and other studies in experimental animals suggest that in man the DRG may be a preferential (but neglected) site of focal structural and functional abnormalities in inflammatory and also other neurological diseases.
 ...
PMID:Vulnerability of the dorsal root ganglion in experimental allergic encephalomyelitis. 384 21

This pilot-study should contribute to the question whether Pyrethroid intoxication can be distinguished from other diseases by characteristic clinical symptoms. The results show that the characteristics of the intoxication do not consist in singular symptoms but in combinations and correlations of symptoms, i.e. of central-neurological with peripheral- and autonomic-neurological as well as with characteristic immunological disturbances. Neurological symptoms consist in cerebro-organic disfunctions, locomotory disorders reminiscent of multiple sclerosis or M. Parkinson, and sensory, motoric and vegetative polyneuropathy, leading, for instance, to cardiovascular regulatory disorder like sympathicotonia or, orthostatic hypotonia. Non-neurological symptoms include immunosuppression with consecutive opportunistic infections, like candida albicans, most frequently of the alimentary tract, but also dermal and mucosal swellings, lichen-ruber-like efflorescences, loss of hair, conjunctivitis. Other symptoms are: hypoglycaemic crises inhibition of fertility, disturbances of blood clotting, and most frequently in children, suspected hematopoetic disorders.
 ...
PMID:[A new method for early detection of neurotoxic diseases (exemplified by pyrethroid poisoning)]. 885 Nov 33

This report presents the case of a child with atopic dermatitis, who developed progressive muscular weakness and hypotonia of the four limbs. The cervical spinal cord magnetic resonance imaging revealed a C(4) lesion (T(2)-weighted images); the cerebrospinal fluid findings were normal. Treatment with intravenous immunoglobulins and methylprednisolone obtained rapid clinical improvement, and approximately 1 month later the small C(4) lesion disappeared. Various diagnostic hypotheses are discussed: acute myelitis by infective agents, acute disseminated encephalomyelitis, multiphasic disseminated encephalomyelitis, multiple sclerosis, and isolated postinfective myelitis. Another hypothesis relates to atopic myelitis, a form recently described in the Japanese literature, associated with atopic dermatitis, hyperIgEemia, and high levels of specific immunoglobulin E to Dermatophagoides farinae and Dermatophagoides pteronyssinus. This diagnosis is difficult to confirm without biopsy evidence of eosinophilic inflammation.
 ...
PMID:Acute myelitis in a child: current hypotheses. 1713 14

A male patient diagnosed elsewhere as having multiple sclerosis (MS) was recently referred to our MS centre. Despite the presence of scattered T2-hyperintense MS-like lesions on MRI and cerebrospinal fluid (CSF) oligoclonal bands, his MS diagnosis was unpersuasive. Distal symmetric hypotonia, tendon areflexia and distal muscle weakness were present. A mostly demyelinating sensory polyneuropathy was disclosed at electroneurography. Serum IgM band, free monoclonal light chains and increased anti-myelin-associated glycoprotein IgM were detected. At 18 months later, and after three intravenous Ig treatments, a clinical electroneurographic improvement was evident along with the disappearance of some brain MRI lesions, reduction of serum anti-myelin-associated glycoprotein (MAG) IgM level and of the number of CSF oligoclonal bands. Although the cause/effect relation cannot be proven, we hypothesise that not only peripheral but also central demyelination may be related to the presence of anti-MAG antibodies with central nervous system (CNS) patterns on MRI resembling those seen in MS.
 ...
PMID:A case of anti-myelin-associated glycoprotein polyneuropathy and multiple sclerosis: one disease instead of two? 2168 95

The sortilin-related VPS10 domain-containing receptor 3 (SORCS3) is a type-I receptor transmembrane protein and a member of the vacuolar protein sorting 10 receptor family. Proteins of this family are defined to have a vacuolar protein sorting 10 domain at the N-terminus. They play important roles as a sorting agency within the cells and transport a variety of intracellular proteins between the Golgi apparatus, endosome, lysosome, secretory granules, and plasma membrane. They are also involved in signal transduction. Clinically, they have been implicated in the pathophysiology of multiple sclerosis and Alzheimer's disease. Here, we report details on two brothers deceased at 20 months and 2 years of age, respectively, with a neurological phenotype including infantile spasms, intellectual disability, global developmental delay, microcephaly, hypotonia, spastic quadriplegia, and delayed myelination. Whole exome sequencing and autozygome analysis showed homozygous missense variant in the SORCS3 gene. The pathogenicity is supported by functional studies in the patient mesenchymal stem cells. Patients' cells showed less proliferation capability than normal cells. In addition, making the same mutation in normal cells revealed a viability defect in them. This is the first study on human subjects with a SORCS3 gene defect and supports the important role of SORCS3 in the central nervous system.
 ...
PMID:The SORCS3 gene is mutated in brothers with infantile spasms and intellectual disability. 3058 38


1