A síndrome de Isaac é uma doença que afeta os nervos que controlam os músculos (chamados neurônios motores periféricos), e é causada por um ataque do próprio sistema imunológico. Ela se caracteriza por uma atividade constante e involuntária dos músculos, mesmo quando a pessoa está em repouso. Isso leva a sintomas como rigidez muscular, câimbras, tremores musculares finos e contínuos, e dificuldade para os músculos relaxarem depois de se contraírem.
Introdução
O que você precisa saber de cara
A síndrome de Isaac é uma doença que afeta os nervos que controlam os músculos (chamados neurônios motores periféricos), e é causada por um ataque do próprio sistema imunológico. Ela se caracteriza por uma atividade constante e involuntária dos músculos, mesmo quando a pessoa está em repouso. Isso leva a sintomas como rigidez muscular, câimbras, tremores musculares finos e contínuos, e dificuldade para os músculos relaxarem depois de se contraírem.
Escala de raridade
<1/50kMuito rara
1/20kRara
1/10kPouco freq.
1/5kIncomum
1/2k
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Entender a doença
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Sinais e sintomas
O que aparece no corpo e com que frequência cada sintoma acontece
Partes do corpo afetadas
+ 7 sintomas em outras categorias
Características mais comuns
Os sintomas variam de pessoa para pessoa. Abaixo estão as 13 características clínicas mais associadas, ordenadas por frequência.
Linha do tempo da pesquisa
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Genética e causas
O que está alterado no DNA e como passa nas famílias
Nenhum gene associado encontrado
Os dados genéticos desta condição ainda estão sendo catalogados.
Diagnóstico
Os sinais que médicos procuram e os exames que confirmam
Tratamento e manejo
Remédios, cuidados de apoio e o que precisa acompanhar
Onde tratar no SUS
Hospitais de referência no Brasil e o protocolo oficial do SUS (PCDT)
🇧🇷 Atendimento SUS — Síndrome Isaacs
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Pesquisa ativa
Ensaios clínicos abertos e novidades científicas recentes
Pesquisa e ensaios clínicos
Nenhum ensaio clínico registrado para esta condição.
Publicações mais relevantes
Case Report: Dual response to efgartigimod in myasthenia gravis and comorbid autoimmune disorders: a case series.
The coexistence of myasthenia gravis (MG) with other IgG-mediated autoimmune diseases represents a clinically heterogeneous condition, driven by pathogenic autoantibodies. Efgartigimod, a neonatal Fc receptor antagonist, has the ability to clear all IgG subclasses. Here, we report four cases of MG concomitant with IgG-mediated autoimmune diseases, specifically idiopathic inflammatory myopathies (IIM), Isaacs syndrome, autoimmune encephalitis (AE), and IgG4-related disease (IgG4-RD). All of them demonstrated a favorable therapeutic response to efgartigimod, with marked improvement in QMG and MG-ADL scores, along with disease-specific clinical or laboratory manifestations of the overlapping autoimmune conditions. These cases provide preliminary evidence supporting efgartigimod as a promising treatment option for patients with MG complicated by IgG-mediated autoimmune diseases.
Video-Polysomnography in Peripheral Nerve Hyperexcitability: Clues to Morvan Syndrome in Two Patients and Literature Review.
Peripheral nerve hyperexcitability syndromes are characterized by spontaneous motor discharges, fasciculations, and cramps. Morvan syndrome differs from Isaacs syndrome by its central nervous system involvement, autonomic dysfunction, and profound sleep disruption, often presenting as agrypnia excitata. We report two seropositive patients with cramps, fasciculations, insomnia, and autonomic dysfunction but without neuropsychiatric features. Case 1, a 49-year-old man, had LGI1 antibodies and presented with insomnia and autonomic symptoms. Video-polysomnography revealed severe insomnia with absent N3/REM sleep, reduced spindles and K-complexes, and oneiric stupor behaviors. Case 2, a 25-year-old woman, had LGI1 and CASPR2 antibodies, neuropathic pain, and fasciculations. Video-polysomnography demonstrated REM sleep without atonia, rapid N1-to-REM transitions, and microstructural abnormalities of N2 sleep. Tumor screening was negative in both; both improved with immunotherapy. A literature review confirms that video-polysomnography consistently reveals central involvement in Morvan syndrome, characterized by loss of sleep spindles, K-complexes, and pathological REM features, while Isaacs syndrome preserves normal sleep structure. Video-polysomnography is therefore an essential tool to detect subclinical central nervous system dysfunction in Morvan syndrome, especially when neuropsychiatric symptoms are absent, and helps distinguish it from Isaacs syndrome.
Prevalence, clinical profiles, and prognosis of Isaacs syndrome: A nationwide survey study in Japan.
To elucidate current epidemiological, clinical, and immunological profiles, and the treatment of Isaacs syndrome in Japan. We conducted a nationwide survey using established methods. Questionnaires were sent to neurological facilities throughout Japan to identify Isaacs syndrome patients seen between April 2018 and March 2021. The estimated total number of Isaacs syndrome patients was 114 (95 % confidence interval [CI]: 89.63-138.91), and the estimated prevalence was 0.091 per 100,000 population. Detailed clinical data were available for 44 patients. The median age at onset was 40 (range, 17-78 years), and 55 % were female. The median time from symptom onset to diagnosis was 24 months (range, 1-372 months). Electrodiagnostic studies showed evidence of nerve hyperexcitability in 90 % (myokymic discharges in 50 % and stimulus-induced repetitive discharges in 32 %). Of the 28 patients examined in the cell-based assay, 22 % tested positive (11 % for both leucine-rich glioma-inactivated 1 [LGI1] and contactin-associated protein-like 2 [CASPR2] antibodies and 11 % for LGI1 antibodies only). The median modified Rankin Scale (mRS) score was 2 at diagnosis and 1.5 at the last visit. A high mRS score (mRS ≥4) at baseline was an independent risk factor for poor outcomes (mRS ≥3) (Odds ratio, 20.7; 95 % CI, 2.90-209.18; p < 0.001). We elucidated the current epidemiological and clinical characteristics of Isaacs syndrome in Japan. Isaacs syndrome is a rare neuromuscular disorder. Electrophysiologic abnormalities were frequent, and serum antibodies were not detectable in the majority of patients. A high mRS score before treatment was a risk factor for poor outcomes.
Hereditary, non HINT1 related, axonal neuropathy with neuromyotonia.
To date, neuromyotonia in the context of an inherited axonal neuropathy has been linked to autosomal recessive mutations in the histidine triad nucleotide binding protein 1 (HINT1) gene. In this study we describe two unrelated male patients with late-onset, predominantly motor, axonal neuropathy with neuromyotonia, who carried an autosomal dominant c.103G > A mutation in the myelin protein zero (MPZ) gene (NM_000530.8:c.103G > A, p.Asp35Asn), identified by whole-exome sequence analysis (WES). CASE DESCRIPTIONS: The first patient presented progressive leg muscle weakness and stiffness with difficulty in walking, pain and increased creatine kinase levels,during his fifth decade of life. Electrophysiological examination revealed findings of an axonal, length-dependent polyneuropathy with spontaneous activity, mainly neuromyotonia. Over the 20-year disease course since the first reported symptoms, muscle weakness gradually worsened and he is currently unable to walk without assistance. A second male patient, unrelated to the first one, showed similar clinical and electrophysiological features of a length-dependent axonal neuropathy with neuromyotonia. WES detected the same MPZ missensevariant. CONCLUSION: This study suggests a novel entity in the spectrum of Charcot-Marie-Tooth hereditary neuropathies, characterized by autosomal dominant axonal neuropathy with neuromyotonia (AD-NMAN).
Neuromyotonia and CASPR2 Antibodies: Electrophysiological Clues to Disease Pathophysiology.
Contactin-associated protein-like 2 (CASPR2) is a transmembrane protein of the neurexin superfamily, essential for clustering voltage-gated potassium channels, particularly Kv1, at the juxtaparanodal regions of myelinated axons. This precise localisation is essential for maintaining normal axonal excitability and preventing aberrant signal propagation. Autoantibodies targeting CASPR2 have been associated with various neurological syndromes, notably peripheral nerve hyperexcitability (PNH), which presents clinically with neuromyotonia and myokymia. PNH is characterised by distinctive electrophysiological findings, including neuromyotonic discharges, myokymic discharges, and afterdischarges, which provide diagnostic value and insight into underlying pathophysiology. This review explores the mechanisms of anti-CASPR2-associated PNH, focusing on how antibody-mediated disruption of Kv1 channel clustering leads to altered axonal excitability. Current evidence suggests that both the distal and proximal segments of the axon are sites of pathological activity, where impairments in action potential termination and re-entry prevention result in spontaneous, repetitive discharges. While afterdischarges likely originate within the axon, the precise location-whether in the alpha-motoneuron soma or axon-is uncertain. The involvement of spinal inhibitory circuits has also been proposed, though it remains speculative. Understanding the neurophysiological features of anti-CASPR2-associated PNH is essential for improving diagnostic accuracy and guiding treatment strategies. Further research is needed to clarify the mechanisms of CASPR2-related hyperexcitability.
Publicações recentes
Case Report: Dual response to efgartigimod in myasthenia gravis and comorbid autoimmune disorders: a case series.
Video-Polysomnography in Peripheral Nerve Hyperexcitability: Clues to Morvan Syndrome in Two Patients and Literature Review.
A Case of Isaacs Syndrome Developed After Thymectomy for Myasthenia Gravis.
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Prevalence, clinical profiles, and prognosis of Isaacs syndrome: A nationwide survey study in Japan.
📚 EuropePMC110 artigos no totalmostrando 167
Case Report: Dual response to efgartigimod in myasthenia gravis and comorbid autoimmune disorders: a case series.
Frontiers in immunologyVideo-Polysomnography in Peripheral Nerve Hyperexcitability: Clues to Morvan Syndrome in Two Patients and Literature Review.
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Handbook of clinical neurologyTeaching Video NeuroImages: Cold-induced laryngeal pseudomyotonia in Isaacs syndrome.
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European journal of neurologyNeuromyotonia in a horse.
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Internal medicine (Tokyo, Japan)Ocular Neuromyotonia: Case Reports and Literature Review.
Strabismus[Current Perspective on Voltage-gated Potassium Channel Complex Antibody Associated Diseases].
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Clinical neurophysiology : official journal of the International Federation of Clinical NeurophysiologyA rare case of bilateral ocular neuromyotonia.
Canadian journal of ophthalmology. Journal canadien d'ophtalmologieMechanisms of Caspr2 antibodies in autoimmune encephalitis and neuromyotonia.
Annals of neurologyPeripheral Nerve Hyperexcitability Syndromes.
Continuum (Minneapolis, Minn.)Teaching Video NeuroImages: Bilateral abducens ocular neuromyotonia.
NeurologyAgrin-LRP4-MuSK signaling as a therapeutic target for myasthenia gravis and other neuromuscular disorders.
Expert opinion on therapeutic targetsUrinary manifestations in Isaacs's syndrome. Our experience in 8 cases.
Neurourology and urodynamics[A case of stiff-person syndrome due to secondary adrenal insufficiency].
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JAMA neurologyOsteopathic Manipulative Treatment in the Management of Isaacs Syndrome.
The Journal of the American Osteopathic AssociationThe generator site in acquired autoimmune neuromyotonia.
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Brain : a journal of neurologyNeuromyotonia as an unusual neurological complication of primary Sjögren's syndrome: case report and literature review.
Clinical rheumatologyAbducens neuromyotonia: a delayed neuro-ophthalmic complication of cranial radiation.
Canadian journal of ophthalmology. Journal canadien d'ophtalmologieIsaacs' syndrome with overlapping myopathy as the first manifestation of AL amyloidosis.
Journal of neurology[Voltage-Gated Potassium Channel-Complex Antibodies Associated Encephalopathy and Related Diseases].
Brain and nerve = Shinkei kenkyu no shinpoAcquired hemophilia A associated with myasthenia gravis and Isaacs' syndrome.
Journal of the neurological sciencesExtensive Postradiation Ocular and Diffuse Cranial Neuromyotonia Mimicking Myasthenia Gravis.
The neurologistIsaacs' syndrome and Hodgkin lymphoma: a rare association.
Acta neurologica BelgicaCharacterization of a Subtype of Autoimmune Encephalitis With Anti-Contactin-Associated Protein-like 2 Antibodies in the Cerebrospinal Fluid, Prominent Limbic Symptoms, and Seizures.
JAMA neurologyPtosis, Miosis, and Intermittent Esotropia Following Pituitary Adenoma Resection.
JAMA ophthalmologyTeaching NeuroImages: Ocular neuromyotonia: An underrecognized cause of transient diplopia.
NeurologyStructural study of skeletal muscle fibres in healthy and pseudomyotonia affected cattle.
Annals of anatomy = Anatomischer Anzeiger : official organ of the Anatomische GesellschaftIsaacs' syndrome in a patient with dermatomyositis: case report and review of the literature.
International journal of rheumatic diseases[Autoimmune Associated Encephalitis and Dementia].
Brain and nerve = Shinkei kenkyu no shinpoStrabismus Surgery in Patients With Ocular Neuromyotonia: Potential Unmasking of the Condition and Effective Management Tool.
Journal of neuro-ophthalmology : the official journal of the North American Neuro-Ophthalmology SocietyWhen it rains it pours: amyotrophic lateral sclerosis concealed with Isaac's syndrome.
Neurological sciences : official journal of the Italian Neurological Society and of the Italian Society of Clinical NeurophysiologyUse of botulinum toxin type A for the treatment of radiation therapy-induced myokymia and neuromyotonia in a dog.
Journal of the American Veterinary Medical AssociationEndoscopic treatment for esophageal varices complicated by Isaacs' syndrome involving difficulty with conventional sedation.
Clinical journal of gastroenterologyAbducens ocular neuromyotonia as a delayed complication of oropharyngeal carcinoma treated with radiation.
Head & neckCoexistence of ocular neuromyotonia and hemifacial spasm.
NeurologyA Novel Variant in the HINT1 Gene in a Girl with Autosomal Recessive Axonal Neuropathy with Neuromyotonia: Thorough Neurological Examination Gives the Clue.
NeuropediatricsAtypical case of Morvan's syndrome.
Journal of clinical neuroscience : official journal of the Neurosurgical Society of AustralasiaFast-twitch skeletal muscle fiber adaptation to SERCA1 deficiency in a Dutch Improved Red and White calf pseudomyotonia case.
Neuromuscular disorders : NMDThymoma associated with autoimmune diseases: 85 cases and literature review.
Autoimmunity reviews[The Spectrum of Neuromyotonia: Clinics, Therapy and Outcome].
Fortschritte der Neurologie-PsychiatrieA case of neuromyotonia and axonal motor neuropathy: A report of a HINT1 mutation in the United States.
Muscle & nerveOcular Neuromyotonia and Myasthenia Gravis.
Journal of pediatric ophthalmology and strabismusNeuromyotonia with polyneuropathy, prominent psychoorganic syndrome, insomnia, and suicidal behavior without antibodies: a case report.
Journal of medical case reportsImages in clinical medicine. Paraneoplastic neuromyotonia.
The New England journal of medicineAutoimmune channelopathies in paraneoplastic neurological syndromes.
Biochimica et biophysica actaIsaacs syndrome: A review.
Muscle & nerve[A case of Isaacs' syndrome causing various central nervous symptoms successfully treated with high-dose intravenous methylprednisolone therapy].
Rinsho shinkeigaku = Clinical neurologyChildhood onset of acquired neuromyotonia: association with a ganglioneuroma.
Muscle & nerveParaneoplastic nerve hyperexcitability.
Neurological researchAssociações
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Referências e fontes
Bases de dados externas citadas neste artigo
Publicações científicas
Artigos indexados no PubMed ligados a esta doença no grafo RarasNet — título, periódico e PMID direto da fonte, sem intermediação de IA.
- Case Report: Dual response to efgartigimod in myasthenia gravis and comorbid autoimmune disorders: a case series.
- Video-Polysomnography in Peripheral Nerve Hyperexcitability: Clues to Morvan Syndrome in Two Patients and Literature Review.Journal of clinical neurophysiology : official publication of the American Electroencephalographic Society· 2026· PMID 41348524mais citado
- Prevalence, clinical profiles, and prognosis of Isaacs syndrome: A nationwide survey study in Japan.
- Hereditary, non HINT1 related, axonal neuropathy with neuromyotonia.Neurological sciences : official journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology· 2025· PMID 40009145mais citado
- Neuromyotonia and CASPR2 Antibodies: Electrophysiological Clues to Disease Pathophysiology.
- A Case of Isaacs Syndrome Developed After Thymectomy for Myasthenia Gravis.
- A case report of Isaacs' syndrome with treatment-resistant pain responsive to rituximab.
Bases de dados e fontes oficiais
Identificadores e referências canônicas usadas para montar este verbete.
- ORPHA:84142(Orphanet)
- MONDO:0019399(MONDO)
- GARD:6793(GARD (NIH))
- Busca completa no PubMed(PubMed)
- Artigo Wikipedia(Wikipedia)
- Q520797(Wikidata)
Dados compilados pelo RarasNet a partir de fontes abertas (Orphanet, OMIM, MONDO, PubMed/EuropePMC, ClinicalTrials.gov, DATASUS, PCDT/MS). Este conteúdo é informativo e não substitui avaliação médica.
Conteúdo mantido por Agente Raras · Médicos e pesquisadores podem colaborar
