Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0013421 (dystonia)
 8,418 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Increasing numbers of patients are being recognized with neurological abnormalities associated with the immunochemical changes of plasma cell disease. To illustrate the wide spectrum of clinical disorders that can be found, I discuss in detail 5 patients: 2 with neuropathy, 3 with amyotrophic lateral sclerosis (ALS), all of whom had serum monoclonal paraproteinemia. In addition, I report in tabular form 6 patients with paraproteinemia and the following clinical presentations: 1) systemic lupus with polyneuropathy and severe cerebritis, 2) myasthenia gravis with thymoma, 3) polymyositis, 4) polymyositis, arthritis and Grave's disease, 5) relapsing polyneuritis (one of the original patients diagnosed by Austin) and 6) ALS, dystonia and parkinsonism. Major improvements in clinical condition occurred sometimes, but not always, coincident with reductions in the levels of the paraprotein using prednisone, cyclophosphamide, chlorambucil and plasma exchange treatments even in some of the patients who had the clinical appearance of ALS. Patients with neuromuscular diseases should be routinely screened with serum immunoelectrophoresis for monoclonal gammopathy. If a monoclonal gammopathy is found and if the disease is serious, then those patients should be treated as if they had an autoimmune disorder.
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PMID:Neuropathy and motor neuron syndromes associated with plasma cell disease. 647 86

Dystonia and chorea are uncommon accompaniments, but sometimes the presenting features of certain acquired systemic disorders that presumably alter basal ganglia function. Hypoxia-ischaemia may injure the basal ganglia through hypoperfusion of subcortical vascular watershed regions and by altering striatal neurotransmitter systems. Toxins interfere with striatal mitochondrial function, resulting in cellular hypoxia. Infections may affect the basal ganglia by causing vasculitic ischaemia, through the development of antibodies to basal ganglia epitopes, by direct invasion of the basal ganglia by the organism, or through cytotoxins causing neuronal injury. Autoimmune disorders alter striatal function by causing a vasculopathy, by direct reaction of antibodies with basal ganglia epitopes, or by stimulating the generation of a cytotoxic or inflammatory reaction. Endocrine and electrolyte abnormalities influence neurotransmitter balance or affect ion channel function and signalling in the basal ganglia. In general, the production of chorea involves dysfunction of the indirect pathway from the caudate and putamen to the internal globus pallidus, whereas dystonia is generated by dysfunction of the direct pathway. The time of the onset of the movement disorder relative to the primary disease process, and course vary with the age of the patient and the underlying pathology. Treatment of dystonia or chorea associated with a systemic medical disorder must initially consider the systemic disorder.
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PMID:Dystonia and chorea in acquired systemic disorders. 977 63

Rasmussen's encephalitis is a rare autoimmune disorder characterized by intractable epilepsy and progressive hemispheric dysfunction. The disorder usually affects children, although cases have been reported with symptom onset in late adolescence or adulthood. Myoclonus is common in Rasmussen patients, usually occurring as part of epilepsia partialis continua (EPC); however, other hyperkinetic movements are rare. This report documents a 19-year-old woman with Rasmussen's encephalitis whose clinical presentation was dominated by foot dystonia, arm athetosis, and EPC. Intravenous immunoglobulin improved both hyperkinetic movements and EPC, but benefit was transient. The clinical significance and implications of these findings are discussed.
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PMID:Dystonia, athetosis, and epilepsia partialis continua in a patient with late-onset Rasmussen's encephalitis. 1211 88

Group A Streptococcus can induce autoimmune disease in humans with particular involvement of the heart, joints, and brain. The spectrum of post-streptococcal disease of the central nervous system (CNS) has been widened recently and includes movement disorders (chorea, tics, dystonia, and Parkinsonism), psychiatric disorders (particularly emotional disorders), and associated sleep disorders. Neuroimaging and pathological studies indicate that the most vulnerable brain region is the basal ganglia. The immunopathogenesis of the disease is incompletely defined, and although there is some support for autoantibody-mediated disease, several conflicting studies cast doubt on the autoantibody hypothesis. It has been speculated that post-streptococcal autoimmunity has a role in common neuropsychiatric disease but the evidence is conflicting and routine screening of patients with Tourette syndrome and obsessive-compulsive disorder for post-streptococcal autoimmune abnormalities is not be recommended at present. However, post-streptococcal disorders of the CNS remain a useful model of neuropsychiatric disease, which may improve our understanding of abnormal movements and behaviours in children.
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PMID:Post-streptococcal autoimmune disorders of the central nervous system. 1622 45

We report a patient with adolescent-onset, Rasmussen's encephalitis, presenting with intractable focal seizures, mild hemiparesis, cognitive impairment, dystonia, and severe hemiballism. His father had Behcet's disease, considered to be an autoimmune disorder. Recent reports have directly implicated the role of cytotoxic T lymphocytes in the pathogenesis of both Rasmussen's encephalitis and Behcet's disease. The occurrence of Behcet's disease and Rasmussen's encephalitis in the same family suggests involvement of common genetic factors such as HLA haplotypes in both autoimmune disorders. It is possible that members of this family are genetically susceptible to developing autoimmune conditions that have been precipitated by separate environmental triggers.
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PMID:Rasmussen's encephalitis and Behcet's disease: autoimmune disorders in first degree relatives. 1901 75

Antiphospholipid syndrome (APS) is an autoimmune disorder characterized by recurrent thrombotic events and/or pregnancy morbidity that may be isolated (Primary APS) or associated with other diseases, mainly of autoimmune origin (Secondary APS). A variety of neurological symptoms may occur in association with the disease, including movement disorders. We report on a 79 year old woman with an unremarkable past medical history who progressively developed psychomotor agitation and insomnia through a period of four months, followed by an acute onset complex hyperkinetic syndrome with chorea, focal left foot dystonia, oral dyskinesias and severe speech impairment. Brain MRI showed multiple subcortical lesions without basal ganglia involvement, and a large cortical lesion in the left posterior temporal lobe that appeared to be ischemic. These findings along with a strongly elevated titer of anticardiolipin (aCL) and anti-beta(2) glycoprotein-I antibodies and positive Lupus Anticoagulant (LAC) suggested a diagnosis of Antiphospholipid Syndrome, confirmed 14 weeks later as a Primary syndrome. The autoimmune mechanisms possibly responsible for the patient's clinical picture are discussed. This case underlines the importance of taking into account APS as a cause of unusual movement disorders even in elderly patients without evidence of previous thrombotic events.
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PMID:Complex movement disorders in primary antiphospholipid syndrome: a case report. 1934 15

Autoantibodies to the extracellular domain of neuronal proteins cause different neurological conditions with movement disorders as a prominent feature. We reviewed the literature of autoantibody-mediated and autoantibody-associated diseases focusing on anti-N-methyl-D-aspartate receptor (NMDAR) encephalitis, autoimmune basal ganglia encephalitis, Sydenham chorea, and the rare syndrome of progressive encephalomyelitis with rigidity and myoclonus. NMDAR encephalitis is a diffuse encephalitis with psychiatric and cognitive features associated with autoantibodies against the NR1 subunit of the NMDAR. The movement disorder phenotype is diverse and often generalized in young children. Although orofacial dyskinesia was the initial movement phenotype, chorea, dystonia, catatonia, and stereotypical movements are now described. The stereotypical movements can be bizarre and include cycling movements and compulsive self-injurious behavior. Autoimmune basal ganglia encephalitis is an inflammatory encephalitis localizing to the basal ganglia that is sometimes associated with serum antibodies against dopamine-2 receptor. Although psychiatric features are common, the dominant problem is a movement disorder, with dystonia-parkinsonism being characteristic. Sydenham chorea is the prototypic poststreptococcal autoimmune neuropsychiatric disorder and several autoantibodies may be involved in disease generation. The syndrome is characterized by a pure chorea, although hypotonia, dysarthria, and emotional lability are common. Progressive encephalomyelitis with rigidity and myoclonus is a rare autoimmune disorder causing rigidity, stimulus sensitive spasms, and myoclonus of nonepileptic origin and is associated with autoantibodies of multiple types including those against the glycine receptor. These disorders are important to recognize and diagnose, as immune therapy can shorten disease duration and improve outcome.
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PMID:Autoantibody-associated movement disorders. 2420 56

Multiple sclerosis (MS) is an autoimmune demyelinating disease of the central nervous system that rarely presents with movement disorder symptoms upon primary manifestation. We report the case of a 45-year-old patient with no history of any medical condition who presented to our clinic with left-sided torticollis. Interestingly, MRI scan of the brain revealed multiple periventricular T2 hyperintense lesions. Analysis of cerebrospinal fluid (CSF) showed that cell numbers and protein concentration were normal, while oligoclonal IgG synthesis was suggestive of chronic intrathecal inflammation. Therefore, clinically isolated syndrome (CIS) was diagnosed as a primary manifestation of relapsing-remitting MS. In the MRI scans, one lesion was found to be localized to the right cerebral peduncle, thus providing a potential link between torticollis and the autoimmune disorder. Furthermore, the symptoms were completely resolved with corticosteroid treatment alone. This is to our knowledge the first description of an MS case in which the sole primary manifestation was torticollis that could be completely resolved with corticosteroid treatment. We therefore suggest performing a cerebral MRI scan with particular focus on demyelinating lesions in patients with focal dystonia, since there is an increasing number of reports describing MS as a potential cause of secondary dystonia. Notably, early corticosteroid therapy might resolve symptoms.
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PMID:Corticosteroid-responsive torticollis as a presenting symptom of multiple sclerosis. 2461 67

Movement disorders (MDs) are common in patients with autoimmune disorders affecting the central and peripheral nervous system. They may be observed in autoimmune disorders triggered by an infectious agent, such as streptococcus in Sydenham's chorea, or in basal ganglia encephalitis with antibodies against the dopamine-D2 receptors. In these patients chorea or dystonia are usually the most prominent hyperkinetic MDs. MDs are also observed in patients with diffuse or limbic encephalitis with antibodies directed against neuronal cell-surface antigens. Anti-NMDA receptor encephalitis is one of the most common and may present with a variety of MDs, including: chorea, stereotypies, dystonia and myorhythmia. The recognition of other abnormal motor phenomena such as "faciobrachial dystonic seizures" and neuromyotonia, observed in patients with LGI1 and Caspr-2 antibodies, is important because they may herald the onset of overt limbic encephalitis. Autoimmunity directed against the intracellular enzyme glutamic acid decarboxylase usually presents with MDs, most commonly stiff-person syndrome or cerebellar ataxia. Chorea may be observed in rheumatologic disorders such as systemic lupus erythematosus or antiphospholipid syndrome. Disorders with uncertain autoimmune mechanisms such as Hashimoto's encephalitis and idiopathic opsoclonus-myoclonus syndrome commonly present with tremor, myoclonus and ataxia. A rapid diagnosis of an autoimmune disorder, which typically presents with subacute onset, is critical as early therapeutic intervention improves long-term prognosis and may be life-saving. Treatment usually involves some form of immunotherapy and symptomatic therapy of the abnormal movements with dopamine depleters, dopamine receptor antagonists, or GABAergic drugs. Detection and removal of an underlying tumor is essential for optimal outcome.
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PMID:Autoimmune and paraneoplastic movement disorders: An update. 2940 2

Autoimmune encephalitides, with an estimated incidence of 1.5 per million population per year, although described only 15 years ago, have already had a remarkable impact in neurology and paved the field to autoimmune neuropsychiatry. Many patients traditionally presented with aberrant behavior, especially of acute or subacute onset, and treated with anti-psychotic therapies, turn out to have a CNS autoimmune disease with pathogenic autoantibodies against synaptic antigens responding to immunotherapies. The review describes the clinical spectrum of these disorders, and the pathogenetic role of key autoantibodies directed against: a) cell surface synaptic antigens and receptors, including NMDAR, GABAa, GABAb, AMPA and glycine receptors; b) channels such as AQP4 water-permeable channel or voltage-gated potassium channels; c) proteins that stabilize voltage-gated potassium channel complex into the membrane, like the LGI1 and CASPR2; and d) enzymes that catalyze the formation of neurotransmitters such as Glutamic Acid Decarboxylase (GAD). These antibodies, effectively target excitatory or inhibitory synapses in the limbic system, basal ganglia or brainstem altering synaptic function and resulting in uncontrolled neurological excitability disorder clinically manifested with psychosis, agitation, behavioral alterations, depression, sleep disturbances, seizure-like phenomena, movement disorders such as ataxia, chorea and dystonia, memory changes or coma. Some of the identified triggering factors include: viruses, especially herpes simplex, accounting for the majority of relapses occurring after viral encephalitis, which respond to immunotherapy rather than antiviral agents; tumors especially teratoma, SCLC and thymomas; and biological cancer therapies (immune-check-point inhibitors). As anti-synaptic antibodies persist after viral infections or tumor removal, augmentation of autoreactive B cells which release autoantigens to draining lymph nodes, molecular mimicry and infection-induced bystander immune activation products play a role in autoimmunization process or perpetuating autoimmune neuroinflammation. The review stresses the importance of early detection, clinical recognition, proper antibody testing and early therapy initiation as these disorders, regardless of a known or not trigger, are potentially treatable responding to systemic immunotherapy with intravenous steroids, IVIg, rituximab or even bortezomid.
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PMID:The immunobiology of autoimmune encephalitides. 3161 Nov 42


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