Isaacs syndrome: the frontier of neurology, psychiatry, immunology and cancer

Park, Susanna B.; Thurbon, Rick; Kiernan, Matthew C.

doi:10.1136/jnnp-2020-324675

Cited by 14 publications

(20 citation statements)

References 14 publications

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“…Other common manifestations include hyperhidrosis, sialorrhea, piloerection, and abdominal pain. Neuropathic pain is a rare finding in patients with IS [4]. In our case, neuropathic pain was the dominant symptom of IS.…”

Section: Discussionmentioning

confidence: 57%

“…Although the pathophysiology of IS involves the dysfunction of VGKCs by autoantibodies resulting in potassium-ion imbalance that leads to symptoms of muscular hyperexcitability, this case highlights the question of how neuropathic pain can accompany the typical presentation [4]. One possibility is that the potassium-ion imbalance occurring in IS extends to a similar hyperexcitability in sensory neurons.…”

Section: Discussionmentioning

confidence: 99%

“…We believe that these hyperexcitable nerves may also elicit a peripheral neuropathic pain syndrome, as seen in this case. Elevated VGKC antibody titers are observed in PNH disorders, such as IS, Morvan syndrome, limbic encephalitis, and CFS [4]. These autoantibodies have been associated with neoplastic tumors such as thymoma and small-cell carcinoma [3].…”

Section: Discussionmentioning

confidence: 99%

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Isaac Syndrome with Intractable Neuropathic Pain Features: A Case Report

et al. 2022

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Isaac syndrome (IS) is a peripheral nerve hyperexcitability state associated with voltage-gated potassium channel (VGKC) complex antibodies. Major manifestations are muscle twitching, stiffness, hypertrophy, and dysautonomic features such as hyperhidrosis [Ahmed and Simmons. <i>Muscle Nerve</i>. 2015;52(1):5–12]. Neuropathic pain is a rare manifestation. We describe a case of IS characterized by muscle twitching and intractable neuropathic pain. Diagnostic workup included elevated VGKC complex antibodies and EMG/NC that showed neuromyotonic discharges. Neuropathic pain was initially difficult to relieve even after using multiple medications, including opiates, benzodiazepines, anticonvulsants, and intravenous immunoglobulin (IVIg). Moderate pain control was eventually achieved with long-term use of carbamazepine and subcutaneous immunoglobulin (SCIg). Common manifestations of IS are muscle twitching, stiffness hypertrophy, and dysautonomia [Ahmed and Simmons. <i>Muscle Nerve</i>. 2015;52(1):5–12]. Sensory manifestations such as neuropathic pain are rare, but, as illustrated by our patient, can be the most distressing symptom. In our patient, not only was neuropathic pain disabling but it also showed the least response to IVIg. The use of 200 mg of long-acting carbamazepine twice daily with weekly SCIg demonstrated the best response. This case highlights an uncommon but potentially resistant symptom of IS.

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Section: Discussionmentioning

confidence: 57%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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Isaac Syndrome with Intractable Neuropathic Pain Features: A Case Report

et al. 2022

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“…LGI1 antibodies primarily present with CNS symptoms [ 19 ], especially autoimmune encephalitis, which could involve both the limbic and extralimbic systems [ 17 ]. There are 31% of LGI antibody-positive patients who display peripheral nerve system involvement including hyperexcitability and neuropathic pain [ 20 ]. Patients with CASPR2 antibodies could present both CNS and PNS symptoms including neuromyotonia, Morvan syndrome, and limbic or more extensive encephalitis, yet PNS symptoms are more common [ 19 – 21 ] Coexistence of both LGI1 and CASPR2 antibodies in “double positive” individual is not uncommon [ 4 ].…”

Section: Discussionmentioning

confidence: 99%

Isaacs’ syndrome as the initial presentation of malignant thymoma and associated with double-positive voltage-gated potassium channel complex antibodies, a case report

Liao

et al. 2022

BMC Neurol

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Background Isaacs’ syndrome is a peripheral nerve hyperexcitability (PNH) syndrome due to peripheral motor nerve instability. Acquired Isaacs’ syndrome is recognized as a paraneoplastic autoimmune disease with possible pathogenic voltage-gated potassium channel (VGKC) complex antibodies. However, the longitudinal correlation between clinical symptoms, VGKC antibodies level, and drug response is still unclear. Case presentation A 45-year-old man had progressive four limbs soreness, muscle twitching, cramps, and pain 4 months before admission. Electromyography (EMG) studies showed myokymic discharges, neuromyotonia, and an incremental response in the high-rate (50 Hz) repetitive nerve stimulation (RNS) test. Isaacs’ syndrome was diagnosed based on clinical presentations and EMG reports. Serum studies showed positive VGKC complex antibodies, including leucine-rich glioma-inactivated 1 (LGI1) and contactin-associated protein-like 2 (CASPR2) antibodies. The acetylcholine receptor antibody was negative. Whole-body computed tomography (CT) and positron emission tomography revealed a mediastinal tumor with the great vessels encasement, right pleura, and diaphragm seeding. Biopsy confirmed a World Health Organization type B2 thymoma, with Masaoka stage IVa. His symptoms gradually improved and both LGI1 and CASPR2 antibodies titer became undetectable after concurrent chemoradiotherapy (CCRT) and high dose steroid treatment. However, his Isaacs’ syndrome recurred after the steroid was reduced 5 months later. Follow-up chest CT showed probable thymoma progression. LGI1 antibody turned positive again while CASPR2 antibody remained undetectable. Conclusions Our patient demonstrates that Isaacs’ syndrome could be the initial and only neuromuscular manifestation of malignant thymoma. His Isaacs’ syndrome is correlated well with the LGI1 antibody level. With an unresectable thymoma, long-term immunosuppressant therapy may be necessary for the management of Isaacs’ syndrome in addition to CCRT for thymoma.

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“…The EMG shows continuous muscle activity occurring at rest and unaffected by local nerve blockade. A total of 45% to 50% of cases are associated with antibodies that immunoprecipitate voltage-gated potassium channels (VGKCs), [ 9 ] mainly including contactin-associated protein 2 (CASPR2) and leucine-rich glioma inactivated 1 (LGI1). It primarily occurs in patients with immune diseases and tumors, and reported cases of mercury poisoning are rare.…”

Section: Discussionmentioning

confidence: 99%

Mercury poisoning complicated by acquired neuromyotonia syndrome

Ran¹,

Wang²,

Yi³

et al. 2021

Medicine

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Rationale: Acquired neuromyotonia syndrome is a rare form of peripheral nerve hyperexcitability syndrome. It is characterized by spontaneous and continuous muscle contractions. Acquired neuromyotonia syndrome is mainly observed in patients with autoimmune diseases or tumors, but it is a rare neurological clinical manifestation in patients with mercury poisoning. Patient concerns: A 56-year-old woman presented with continuous and involuntary muscle twitching in her legs for 2 months; it was accompanied by a burning sensation in the lower limbs, insomnia, fatigue, and night sweats. These symptoms did not disappear during sleep. Diagnoses: Toxicological blood analysis via atomic fluorescence spectrometry revealed that the level of mercury was 0.07 μmol/L (normal level: <0.05 μmol/L). Her urinary mercury level measured using the cold atomic absorption method was 217.50 μmol/mol creatinine, which was considerably higher than the reference range (0–2.25 μmol/mol creatinine for people not in contact with mercury, 0–20 μmol/mol creatinine following long-term exposure). Upon further testing, a high level of mercury (10,572 mg/kg) was detected in the patient's cream. Accordingly, this patient was diagnosed with mercury poisoning. Interventions: Treatment with 2,3-dimercapto-1-propanesulfonic acid (DMPS) was initiated. Her urinary mercury level decreased to 9.67 μmol/mol creatinine, and her neuromyotonia syndrome and hyponatremia were relieved, with urine protein completely disappearing after 3 months of treatment. Outcomes: After DMPS treatment, the clinical manifestations of the nervous system disappeared and electrolyte parameters returned to normal levels. Lessons: Acquired neuromyotonia syndrome is a rare disorder caused by the hyperexcitability of peripheral nerves, resulting in spontaneous and continuous muscle contraction. Mercury poisoning should be considered in patients with neuromyotonia syndrome. Early detection of mercury poisoning can prevent unnecessary examinations and treatments.

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Isaacs syndrome: the frontier of neurology, psychiatry, immunology and cancer

Cited by 14 publications

References 14 publications

Isaac Syndrome with Intractable Neuropathic Pain Features: A Case Report

Isaac Syndrome with Intractable Neuropathic Pain Features: A Case Report

Isaacs’ syndrome as the initial presentation of malignant thymoma and associated with double-positive voltage-gated potassium channel complex antibodies, a case report

Mercury poisoning complicated by acquired neuromyotonia syndrome

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