RESUMEN
Neuromyotonia is continuous peripheral nerve hyper-excitability manifesting in muscle twitching at rest (myokymia), inducible cramps and impaired muscle relaxation, and characterized by EMG findings of spontaneous single motor unit discharges (with doublet, triplet, or multiplet morphology). The disorder may be genetic, acquired, and often in the acquired cases autoimmune. This chapter focuses on autoimmune acquired causes. Autoimmune associations include mainly contactin-associated protein-like 2 (CASPR2) antibody-associated disease (previously termed as VGKC or voltage-gated potassium channel antibody-associated neuromyotonia) (van Sonderen et al., 2016, p. 2), leucine-rich glioma-inactivated 1 (LGI1) antibody disease, the Guillain-Barré syndrome, NMDAR encephalitis (Varley et al., 2019), and IgLON5 (Gaig et al., 2021) disease. Nonimmune associations include radiation-induced plexopathy. An association with myasthenia gravis and other autoimmune disorders, response to plasma exchange (Newsom-Davis and Mills, 1993) and physiologically induced changes in mice injected with patient-derived immunoglobulins led to the discovery of autoantibodies to juxtaparanodal proteins complexed with potassium channels (Shillito et al., 1995). The target of the antibodies is most commonly the CASPR2 protein. The disorder may be paraneoplastic, and a search for and treatment of an underlying tumor is a necessary step. In cases in which there is evidence for an immune cause, then immune suppression, with an emerging role for B cell-depleting therapies, is associated with a good clinical outcome. In parallel, sodium channel blocking drugs remain effective symptomatic therapies.
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Síndrome de Isaacs , Humanos , Síndrome de Isaacs/terapia , Síndrome de Isaacs/inmunología , Síndrome de Isaacs/diagnóstico , Animales , Autoanticuerpos/inmunología , Proteínas de la Membrana , Proteínas del Tejido NerviosoRESUMEN
OBJECTIVES: Isaac syndrome (IS) is a condition characterized by peripheral nerve hyperexcitability caused by voltage-gated potassium channel (VGKC)-complex antibodies. Muscle twitching, stiffness, hypertrophy, and dysautonomic characteristics, such as hyperhidrosis, are common manifestations. The syndrome can be autoimmune or paraneoplastic, with thymoma being a common cause of paraneoplastic IS. Furthermore, this condition could be handed down from one generation to another. However, there is limited information regarding outcomes, relapses, associated syndromes, associated malignancies (other than thymoma), and treatment options. Despite its rarity, there remains a need for effective management strategies for patients with IS. To address this gap, we conducted a systematic review to summarize the most common and effective treatments of IS in immunomodulatory agents and symptomatic medications, as well as to describe outcomes, relapses, and associated malignancies. Altogether, this review serves to guide clinical practice recommendations for IS and highlight areas for further research. METHODS: We used the Preferred Reporting Items for Systematic Reviews and Meta-Analyses protocol to conduct a systematic review of cases reposted through the PubMed and Google Scholar databases. The terms "Isaac Syndrome" and "Acquired Neuromyotonia" were used. The Joanna Briggs Institute's critical appraisal tool was used to evaluate the quality of the included studies. RESULTS: We identified 61 case reports and 4 case series, comprising a total of 70 patients with IS (mean age at onset: 42.5 ± 18 years, and 69% were males). Fourteen cases reported relapses. Thymoma was the most common malignancy associated with IS, followed by lymphoma. Among various serum antibodies, voltage-gated potassium channel-complex antibodies were the most reported antibodies elevated in IS (reported in 38 patients and elevated in 21 patients [55.2%]), followed by acetylcholine ganglionic receptor antibodies, which were reported in 30% of patients (n = 21) and were elevated in 5 cases. The most common electromyography findings were myokymic discharges (n = 22), followed by fasciculations (n = 21) and neuromyotonia (n = 19). For treatment, combining anticonvulsants such as carbamazepine with immunotherapy therapy showed the best results in controlling the symptoms. Among immunotherapy therapies, the combination of plasma exchange plus intravenous high-dose steroids achieved the best results in the acute treatment of IS ([n = 6], with improvement noted in 83.3% [n = 5] of cases). Among the symptomatic treatments with anticonvulsants, carbamazepine was the most efficacious anticonvulsant in treatment of IS, with an average effective dosing of 480 mg/day (carbamazepine was used in 32.3% of acute treatment strategies [n = 23], with improvement noted in 73.9% [n = 17] of cases). CONCLUSIONS: IS a rare neuromuscular syndrome that tends to affect middle-aged men. These patients should be screened for thymoma and other malignancies such as lymphomas. The management of IS symptoms can be challenging, but based on our review, the combination of multiple immunosuppressives such as IV steroids and plasmapheresis with anticonvulsants such as carbamazepine seems to achieve the best results.
Asunto(s)
Síndrome de Isaacs , Canales de Potasio con Entrada de Voltaje , Timoma , Neoplasias del Timo , Masculino , Persona de Mediana Edad , Humanos , Femenino , Síndrome de Isaacs/diagnóstico , Síndrome de Isaacs/terapia , Timoma/complicaciones , Timoma/terapia , Anticonvulsivantes/uso terapéutico , Neoplasias del Timo/complicaciones , Neoplasias del Timo/diagnóstico , Neoplasias del Timo/terapia , Autoanticuerpos , Carbamazepina , Receptores Colinérgicos , Esteroides , RecurrenciaRESUMEN
PURPOSE OF REVIEW: The current review will cover the clinical presentation, causes, epidemiology, differential diagnoses, workup, and treatment of ocular neuromyotonia (ONM) in detail. RECENT FINDINGS: While ONM largely remains a unilateral eye movement disease affecting adults with a history of sellar radiation, recent case reports highlight an expansion of this presentation to include bilateral, pediatric, and congenital cases. SUMMARY: ONM is a rare but recognizable ocular motility disorder involving sustained contraction of the extraocular muscle, commonly resulting in intermittent diplopia. Diagnosis of ONM relies upon a thorough history and clinical exam, with particular attention to history of radiotherapy and eccentric gaze testing. Treatment with carbamazepine remains first-line therapy, although other membrane stabilizing agents and surgical interventions can be effective.
Asunto(s)
Síndrome de Isaacs , Trastornos de la Motilidad Ocular , Adulto , Carbamazepina/uso terapéutico , Niño , Diplopía/diagnóstico , Diplopía/etiología , Diplopía/terapia , Excipientes/uso terapéutico , Humanos , Síndrome de Isaacs/tratamiento farmacológico , Síndrome de Isaacs/terapia , Trastornos de la Motilidad Ocular/diagnóstico , Trastornos de la Motilidad Ocular/terapia , Músculos Oculomotores/cirugíaRESUMEN
PURPOSE OF REVIEW: Autoimmune neuromyotonia encompasses a group of rare immune-mediated neurological disorders frequently associated with anti-contactin-associated protein-like 2 (CASPR2) antibodies and featuring clinical and electrical signs of peripheral nerve hyperexcitability (PNH). We aim to summarize the current knowledge on immune-mediated neuromyotonia, focusing on clinical presentations, pathophysiology, and management. RECENT FINDINGS: Neuromyotonia is a major feature of several autoimmune neurological syndromes characterized by PNH with or without central neurological system involvement. Experimental and clinical evidence suggest that anti-CASPR2 antibodies are directly pathogenic in autoimmune neuromyotonia patients. SUMMARY: Neuromyotonia, a form of PNH, is a major feature in several syndromes associated with anti-CASPR2 antibodies, including cramp-fasciculation syndrome, Isaacs syndrome, Morvan syndrome, and autoimmune limbic encephalitis. Diagnosis relies on the identification of motor, sensory, and autonomic signs of PNH along with other neurological symptoms, anti-CASPR2 antibody-positivity, and of characteristic electroneuromyographic abnormalities. Paraneoplastic associations with thymoma are possible, especially in Morvan syndrome. Patients usually respond to immune-active treatments, including steroids, intravenous immunoglobulins, plasma exchanges, and rituximab.
Asunto(s)
Enfermedades Autoinmunes , Síndrome de Isaacs , Encefalitis Límbica , Autoanticuerpos , Enfermedades Autoinmunes/terapia , Humanos , Síndrome de Isaacs/diagnóstico , Síndrome de Isaacs/terapiaAsunto(s)
Autoanticuerpos/sangre , Diabetes Mellitus Tipo 1/congénito , Diarrea/sangre , Enfermedades Genéticas Ligadas al Cromosoma X/sangre , Enfermedades del Sistema Inmune/congénito , Síndrome de Isaacs/sangre , Canales de Potasio con Entrada de Voltaje/inmunología , Adolescente , Niño , Diabetes Mellitus Tipo 1/sangre , Diabetes Mellitus Tipo 1/genética , Diabetes Mellitus Tipo 1/inmunología , Diabetes Mellitus Tipo 1/terapia , Diarrea/genética , Diarrea/inmunología , Diarrea/terapia , Factores de Transcripción Forkhead/genética , Enfermedades Genéticas Ligadas al Cromosoma X/genética , Enfermedades Genéticas Ligadas al Cromosoma X/inmunología , Enfermedades Genéticas Ligadas al Cromosoma X/terapia , Trasplante de Células Madre Hematopoyéticas , Humanos , Enfermedades del Sistema Inmune/sangre , Enfermedades del Sistema Inmune/genética , Enfermedades del Sistema Inmune/inmunología , Enfermedades del Sistema Inmune/terapia , Recién Nacido , Síndrome de Isaacs/genética , Síndrome de Isaacs/inmunología , Síndrome de Isaacs/terapia , Masculino , MutaciónRESUMEN
An autoimmune form of Isaacs' syndrome is commonly associated with VGKC complex antibodies and characterized by continuous muscle activity of extremity muscles. Here, we describe a CASPR2 and LGI1 positive patient with neuromyotonia clinically and electrophysiologically isolated to gastrocnemius muscles only. IVIG course and plasma exchange were ineffective, but symptoms significantly improved after a course of high-dose steroids. This case demonstrates that focal hyperexcitability should raise suspicion for autoimmunity. LGI1 antibody can be positive in patients with only peripheral nerve system involvement and if one treatment fails, other should be tried.
Asunto(s)
Péptidos y Proteínas de Señalización Intracelular/inmunología , Síndrome de Isaacs/diagnóstico , Síndrome de Isaacs/inmunología , Proteínas de la Membrana/inmunología , Proteínas del Tejido Nervioso/inmunología , Corticoesteroides/uso terapéutico , Adulto , Autoanticuerpos/sangre , Autoantígenos/inmunología , Femenino , Humanos , Inmunoglobulinas Intravenosas/uso terapéutico , Inmunosupresores/uso terapéutico , Síndrome de Isaacs/terapia , Músculo Esquelético , PlasmaféresisAsunto(s)
Inmunoterapia/métodos , Péptidos y Proteínas de Señalización Intracelular/inmunología , Síndrome de Isaacs/inmunología , Síndrome de Isaacs/terapia , Proteínas de la Membrana/inmunología , Proteínas del Tejido Nervioso/inmunología , Anciano , Autoanticuerpos/inmunología , Autoantígenos/inmunología , Dexametasona/uso terapéutico , Inhibidores Enzimáticos/uso terapéutico , Glucocorticoides/uso terapéutico , Humanos , Masculino , Ácido Micofenólico/uso terapéutico , Plasmaféresis/métodos , gamma-Globinas/uso terapéuticoAsunto(s)
Frío/efectos adversos , Síndrome de Isaacs/diagnóstico , Trastornos de la Voz/etiología , Adulto , Analgésicos no Narcóticos/uso terapéutico , Carbamazepina/uso terapéutico , Electromiografía , Humanos , Inmunoglobulinas Intravenosas/uso terapéutico , Factores Inmunológicos/uso terapéutico , Síndrome de Isaacs/complicaciones , Síndrome de Isaacs/fisiopatología , Síndrome de Isaacs/terapia , Masculino , Dolor/tratamiento farmacológicoRESUMEN
PURPOSE: We report the first case of congenital ocular neuromyotonia (ONM) and the results of strabismus surgery for this patient's co-existing cranial nerve (CN) III palsy. PATIENTS AND METHOD: The patient presented at 18 months with strabismus that had reportedly been present since the time of birth. On exam, she had persistent exotropia (RXT) and hypertropia (RHT) with episodes of esotropia in the right eye that could be evoked by sustained left gaze. A diagnosis of ONM with partial CN III palsy was made. T1-weighted, T2-weighted, and fluid-attenuated inversion recovery magnetic resonance imaging failed to reveal intracranial pathology. RESULTS: Gaze induced intermittent esotropia resolved with carbamazepine. Surgery was performed to improve the patient's RXT and RHT. Post-operatively, the patient's RXT had improved from 12 to 15 prism diopters (∆) at near and 20∆ at a distance to 10∆ RXT at near with no horizontal deviation at distance. Her deviation has remained stable for 13 years, as has her neurological exam and good state of health. CONCLUSION: This case demonstrates that ONM may present congenitally and adds to the body of knowledge regarding surgical outcomes on concurrent CN palsies in these patients.
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Síndrome de Isaacs/congénito , Enfermedades del Nervio Oculomotor/congénito , Estrabismo/congénito , Carbamazepina/uso terapéutico , Movimientos Oculares , Femenino , Humanos , Lactante , Síndrome de Isaacs/diagnóstico , Síndrome de Isaacs/terapia , Músculos Oculomotores/inervación , Enfermedades del Nervio Oculomotor/diagnóstico , Enfermedades del Nervio Oculomotor/cirugía , Procedimientos Quirúrgicos Oftalmológicos , Bloqueadores de los Canales de Sodio/uso terapéutico , Estrabismo/diagnóstico , Estrabismo/terapiaRESUMEN
Acquired neuromyotonia is a form of peripheral nerve hyperexcitability. In adults, pathogenic antibodies that target the extracellular domains of leucine-rich glioma-inactivated protein 1 (LGI1) and contactin-associated protein-like 2 (CASPR2) have been reported. We describe three paediatric patients with acquired neuromyotonia and CASPR2 and LGI1 serum antibodies. They all presented with acute-onset myokymia and pain in the lower limbs; one patient also had muscle weakness. Electromyography was suggestive of peripheral nerve hyperexcitability. Two patients improved without immunotherapy; one treated patient remained immunotherapy-dependent. Although not fatal, acquired paediatric neuromyotonia can be disabling. It is amenable to symptomatic treatment or may undergo spontaneous recovery. More severe cases may require rational immunotherapy. WHAT THIS PAPER ADDS: The symptoms of neuromyotonia may resolve spontaneously or may require sodium channel blockers. Patients with debilitating symptoms who are refractory to symptomatic therapy may require immunotherapy.
NEUROMIOTONÍA ADQUIRIDA EN NIÑOS CON ANTICUERPOS CASPR2 Y LGI1: La neuromiotonía adquirida es una forma de hiperexcitabilidad de los nervios periféricos. En algunos adultos, se han notificado anticuerpos patógenos que se dirigen a los dominios extracelulares de la proteína 1 inactivada por glioma rico en leucina (LGI1) y la proteína 2 asociada a contactina (CASPR2). Describimos tres pacientes pediátricos con neuromiotonía adquirida y anticuerpos séricos CASPR2 y LGI1. Todos presentaban mioquimia de inicio agudo y dolor en las extremidades inferiores; un paciente también tenía debilidad muscular. La electromiografía sugirió hiperexcitabilidad del nervio periférico. Dos pacientes mejoraron sin inmunoterapia; un paciente tratado permaneció dependiente de la inmunoterapia. Aunque no es fatal, la neuromiotonía pediátrica adquirida puede ser incapacitante. Es susceptible de tratamiento sintomático o puede sufrir una recuperación espontánea. Los casos más graves pueden requerir inmunoterapia racional.
NEUROMIOTONIA ADQUIRIDA EM CRIANÇAS COM ANTICORPOS PRCAS2 E GIL1: A neuromiotonia adquirida é uma forma de hiperexcitabilidade nervosa periférica. Em alguns adultos, anticorpos patogênicos que visam os domínios extracelulares da proteína glioma-inativada rica em leucina1 (GIL1) e da proteína contactina-associada 2 (PRCAS2) foram reportados. Descrevemos três pacientes pediátricos com neuromiotonia adquirida e anticorpos séricos PRCAS2 e GIL1 CASPR2. Todos apresentaram miocimia de início agudo e dor nos membros inferiores; um paciente também teve fraqueza muscular. A eletromiografia foi sugestiva de hiperexcitabilidade nervosa periférica. Dois pacientes melhoraram sem imunoterapia; um paciente tratado permaneceu imunoterapia-dependente. Embora não seja fatal, a neuromiotomia pediátrica aguda pode ser incapacitante. É responsiva a tratamento sintomático e pode apresentar recuperação espontânea. Casos mais severaos podem requerer imunoterapia racional.
Asunto(s)
Péptidos y Proteínas de Señalización Intracelular/inmunología , Síndrome de Isaacs/diagnóstico , Síndrome de Isaacs/inmunología , Proteínas de la Membrana/inmunología , Proteínas del Tejido Nervioso/inmunología , Adolescente , Anticuerpos/inmunología , Preescolar , Humanos , Inmunoterapia , Síndrome de Isaacs/terapia , Masculino , Resultado del TratamientoRESUMEN
Isaacs syndrome is a rare peripheral nerve hyperexcitability syndrome. The painful discharges in Isaacs syndrome are abolished by the blockade of the neuromuscular junction but not by peripheral nerve blocks (PNB). However, the efficacy of PNB for intraoperative and postoperative analgesia among those with Isaacs syndrome is unknown. A 41-year-old woman with Isaacs syndrome underwent open reduction and internal fixation of radius fractures. Ultrasound-guided bilateral axillary brachial plexus blocks were performed, followed by general anesthesia. The patient required only a single low dose of rocuronium for intubation and surgery. On emergence from anesthesia, the patient was pain free for 6 hours and did not return to her preoperative pain state for 36 hours. PNB can be an effective means of postoperative pain control for patients with Isaacs syndrome.
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Anestesia General , Bloqueo del Plexo Braquial , Síndrome de Isaacs/terapia , Dolor Postoperatorio/terapia , Adulto , Analgesia , Femenino , HumanosRESUMEN
OBJECTIVE: To investigate the origin of ectopic activity in neuromyotonia (NMT). METHODS: We studied two patients. In addition to routine studies, we tested synchronicity of spontaneous discharges in different motor units in simultaneous recordings made with two needle electrodes in the first dorsal interosseus muscle. Time-locked fasciculations in these double recordings would represent abnormal ectopic activity initiated in a nerve trunk with ephaptic stimulation of a nearby axon. In patient 1, this research protocol was applied once, 15years after regular intravenous immunoglobulin (IvIg) treatment. Patient 2 was investigated before and 1year after IvIg. RESULTS: Both patients improved after IVIg, mirrored by a striking decrease in the amount of spontaneous activity on electromyography. Moreover, our technique did not detect synchronous spontaneous activity (time-locked fasciculations) on the second assessment, although this was predominant before treatment in patient 2. CONCLUSIONS: In NMT, abnormal discharges originate both in distal axonal branches and in more proximal segments. It appears that IvIg is more effective in blocking antibody activity in proximal axonal segments, perhaps related to factors such as blood-nerve barrier, temperature or differing ion channel distributions. SIGNIFICANCE: Treatment effects can shed light on the origin of abnormal activity in NMT.
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Enfermedades Autoinmunes/fisiopatología , Fasciculación , Síndrome de Isaacs/fisiopatología , Músculo Esquelético/inervación , Anciano , Enfermedades Autoinmunes/diagnóstico , Enfermedades Autoinmunes/terapia , Electromiografía , Potenciales Evocados Motores , Humanos , Inmunoglobulinas/administración & dosificación , Inmunoglobulinas/uso terapéutico , Síndrome de Isaacs/diagnóstico , Síndrome de Isaacs/terapia , Masculino , Persona de Mediana Edad , Músculo Esquelético/fisiopatologíaAsunto(s)
Síndrome de Isaacs , Autoanticuerpos/inmunología , Electromiografía , Humanos , Síndrome de Isaacs/diagnóstico , Síndrome de Isaacs/inmunología , Síndrome de Isaacs/fisiopatología , Síndrome de Isaacs/terapia , Canales de Potasio con Entrada de Voltaje/inmunología , Pronóstico , Calidad de VidaRESUMEN
BACKGROUND: Neuromyotonia (NM), Isaacs-Zschoke-Mertens syndrome or continuous muscle fiber activity (CMFA), is a rare condition associated with VGKC-antibodies. Clinically, fasciculations, myokymias, muscle stiffness and a myotonic appearance of movements after contraction are typical findings. In addition, CNS-symptoms vary from moderate fatigue, poor concentration and autonomic symptoms to severe encephalopathy in Morvan's syndrome. In electromyography, spontaneous irregular discharges can be found frequently with typical di-, tri- or multiplet single motor unit discharges. In up to 60â%, serum antibodies against VGKC-complexes can be detected. METHODS: Patients with neuromyotonia were evaluated for clinical symptoms, response to treatment and outcome over a five-year period of follow-up.âFor evaluation, we used video recording of clinical symptoms, electroneurography, electromyography and myosonography as well as immunological tests (VGKC-complex antibody including CASPR2 and IGL1). Furthermore, cerebral fluid and screening for neoplasias were done. Patients with evidence for neuropathy, myopathy or motor neuron disease, even if diagnosed in the follow-up, were excluded. RESULTS: In 3 of 5 patients, neuromyotonia was diagnosed by electromyography and positive VGKC antibodies. In two patients, diagnosis was based on typical clinical symptoms and electromyographical changes. Anticonvulsants (carbamazepine) for symptomatic treatment were moderately effective in four patients; treatment with i.âv. immunoglobulins was highly successful in one patient with high positive VGKC-complex antibody titers. In one patient with low-titer VGKC antibodies, neither anticonvulsants nor i.âv. immunoglobulins nor prednisone was a successful treatment. CONCLUSIONS: Neuromyotonia is a rare, treatable condition. However, due to the high variability of symptoms, response to therapy and outcome, neuromyotonia treatment needs to be highly individualized.
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Síndrome de Isaacs/fisiopatología , Síndrome de Isaacs/terapia , Adulto , Anciano , Anticonvulsivantes/uso terapéutico , Electrodiagnóstico , Femenino , Estudios de Seguimiento , Humanos , Inmunización Pasiva , Síndrome de Isaacs/diagnóstico por imagen , Masculino , Persona de Mediana Edad , Resultado del Tratamiento , UltrasonografíaRESUMEN
Isaacs syndrome is a peripheral nerve hyperexcitability (PNH) syndrome that presents as continuous motor activity. Clinical findings include cramps, fasciculations, and myokymia. Electrodiagnosis plays a key role in diagnosis by demonstrating after-discharges on nerve conduction studies, and fasciculation potentials, myokymic discharges, neuromyotonic discharges, and other types of abnormal spontaneous activity on needle examination. Etiopathogenesis involves the interaction of genetic, autoimmune, and paraneoplastic factors, which requires a broad-ranging evaluation for underlying causes. Initial treatment is symptomatic, but immune therapy is often needed and can be effective. The purpose of this review is to describe the syndrome and its pathogenesis, assist the reader in evaluating patients with suspected Isaacs syndrome and distinguishing it from other disorders of PNH, and suggest an approach to management, including both symptomatic and immunomodulating therapy.
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Manejo de la Enfermedad , Síndrome de Isaacs/diagnóstico , Síndrome de Isaacs/terapia , Diagnóstico Diferencial , Humanos , Síndrome de Isaacs/epidemiología , Síndrome de Isaacs/genéticaRESUMEN
OBJECTIVES: To provide an overview of paraneoplastic nerve hyperexcitability syndromes. METHODS: An extensive review of the literature on nerve hyperexcitability was performed. Particular attention was paid to Isaacs' syndrome and Morvan's syndrome, as well as their relationship to neoplasia. RESULTS: An overview of the history, clinical manifestations (including neurophysiologic findings), pathophysiology, and management is presented. Clinical differences between the exclusively peripheral nervous system involving Isaacs' syndrome and Morvan's syndrome, which also involves the central nervous system (CNS) are detailed. The role of immune-mediated dysfunction of specific components of the voltage-gated potassium channel (VGKC) complex in the pathophysiology of these syndromes is explained. Finally, the limited data on management of these syndromes, including the use of antiepileptic and immunomodulatory therapies are discussed. CONCLUSION: Nerve hyperexcitability syndrome represents a spectrum of neuroimmunologic diseases, which are often paraneoplastic in etiology.
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Síndromes Paraneoplásicos del Sistema Nervioso/fisiopatología , Humanos , Síndrome de Isaacs/patología , Síndrome de Isaacs/fisiopatología , Síndrome de Isaacs/terapia , Síndromes Paraneoplásicos del Sistema Nervioso/patología , Síndromes Paraneoplásicos del Sistema Nervioso/terapia , Canales de Potasio con Entrada de Voltaje/metabolismo , Siringomielia/patología , Siringomielia/fisiopatología , Siringomielia/terapiaRESUMEN
BACKGROUND AND PURPOSE: To conduct a retrospective study to investigate the causes of acquired superior oblique dysfunction, excluding paralysis, in a consecutive series of adult patients and to compare presenting symptoms and clinical findings. METHODS: A retrospective review of all adult patients with superior oblique dysfunction between the ages of 18 and 80 who met the study profile was conducted at Saint Louis University Medical Center between January 2000 and April 2012. The presenting symptoms, clinical findings, and treatment course for each patient was recorded. The study was approved by the Institutional Review Board of our institution. RESULTS: Acquired forms of nonparalytic superior oblique dysfunction were identified in forty-eight patients. These included superior oblique myokymia (twenty-three patients), superior oblique click syndrome or variable Brown syndrome (nine), canine tooth syndrome (five), spontaneous acquired Brown syndrome (four), iatrogenic or traumatic Brown syndrome (four), and ocular neuromyotonia affecting the superior oblique (three). CONCLUSIONS: Several nonparalytic entities were identified that caused superior oblique dysfunction. Clinical findings may be similar despite entirely different mechanisms. Subjective symptoms may be difficult for the patient to describe or for the examiner to elicit on the day of the examination. Specific techniques can be used in eliciting, differentiating, and documenting the conditions. These included trochlear palpation, modified head tilt technique, interpretation of torsion, and Hess charts.
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Síndrome de Isaacs/diagnóstico , Síndrome de Isaacs/etiología , Trastornos de la Motilidad Ocular/diagnóstico , Trastornos de la Motilidad Ocular/etiología , Enfermedades del Nervio Troclear/diagnóstico , Enfermedades del Nervio Troclear/etiología , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Diagnóstico Diferencial , Femenino , Humanos , Síndrome de Isaacs/terapia , Masculino , Persona de Mediana Edad , Trastornos de la Motilidad Ocular/terapia , Ortóptica/métodos , Estudios Retrospectivos , Enfermedades del Nervio Troclear/terapia , Adulto JovenRESUMEN
Isaacs' syndrome is an antibody-mediated potassium channel disorder. Clinical symptoms of Isaacs' syndrome are characterized by muscle cramp, slow relaxation following muscle contraction, and hyperhidrosis. Hyperexcitability of the peripheral nerve cause these symptoms, which are relieved by administration of Na channel blockers and immunotherapy.The target channel proteins are voltage-gated potassium channels (VGKCs). The suppression of voltage-gated outward K(+) current by antibodies induces hyperexcitability of the peripheral nerve. Electrophysiological findings show that antibodies may not directly block the kinetics of VGKCs, but may decrease channel density. From the electrophysiological, pharmacologic and immunologic view points, the site of origin of spontaneous discharges is located principally in the distal portion of the motor nerve."VGKC antibodies" are also detected in Morvan syndrome (severe insomnia with neuromyotonia and various autonomic disorders) and in a form of autoimmune limbic encephalitis. Recent studies indicated that the "VGKC antibodies" are mainly directed toward associated proteins (for example LGI-1, CASPR-2) that complex with VGKCs themselves. The "VGKC antibodies" are now usually known as VGKC-complex antibodies. In general, LGI-1 antibodies are most common in limbic encephalitis with SIADH. CASPR-2 antibodies are present in the majority of patients with Morvan syndrome.
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Autoanticuerpos , Síndrome de Isaacs/inmunología , Canales de Potasio con Entrada de Voltaje/inmunología , Anticonvulsivantes/uso terapéutico , Femenino , Humanos , Péptidos y Proteínas de Señalización Intracelular , Síndrome de Isaacs/diagnóstico , Síndrome de Isaacs/fisiopatología , Síndrome de Isaacs/terapia , Masculino , Proteínas de la Membrana , Proteínas del Tejido Nervioso , Intercambio Plasmático , Proteínas , SiringomieliaAsunto(s)
Autoanticuerpos/inmunología , Síndrome de Isaacs/inmunología , Síndrome de Isaacs/fisiopatología , Canales de Potasio con Entrada de Voltaje/inmunología , Adulto , Autoantígenos/inmunología , Humanos , Inmunosupresores/uso terapéutico , Síndrome de Isaacs/terapia , Masculino , Intercambio PlasmáticoRESUMEN
PURPOSE: Cyclic ocular deviations are relatively uncommon and are seldom seen in adults. We report 3 adult patients with cyclic hypotropia that has clinical characteristics similar to neuromyotonia, suggesting a possible common etiology. METHODS: Three consecutive patients with 48-hour cyclic hypotropia underwent full neuro-ophthalmologic, oculoplastics, and orthoptic evaluations as well as appropriate medical and neurologic studies. Examinations were arranged on consecutive days on multiple visits to document the cyclic pattern. RESULTS: All 3 patients had sustained contraction of a vertically acting extraocular muscle lasting 24 hours and demonstrated characteristics of ocular neuromyotonia. The contraction was absent for the next 24 hours. Two of the patients had thyroid eye disease; the third patient had unilateral ophthalmoparesis and had subsequent frameless robotic radiosurgery for a cavernous sinus schwannoma. Regular cycles lasting 6, 9, or 14 months were documented by all 3 patients. In 2 patients, treatment with carbamazepine and gabapentin effectively reduced or eliminated the cycle. The cyclic deviation in the third patient resolved spontaneously. CONCLUSIONS: On the basis of the response of these patients to membrane-stabilizing medications and the behavior noted as the cycle broke each day, we propose that cyclic vertical strabismus and ocular neuromyotonia may be related conditions with similar underlying physiology.