アイザックス症候群

BACKGROUND: Isaac's syndrome, or neuromyotonia, is a rare autoimmune neuromuscular disorder characterized by continuous muscle fiber activity due to peripheral nerve hyperexcitability. Clinical features include persistent muscle stiffness, cramps, fasciculations, delayed muscle relaxation, and myokymia. These symptoms are often associated with autoantibodies targeting voltage-gated potassium channels (VGKCs) or related proteins such as CASPR2. Conventional treatment typically involves immunosuppressive agents and symptomatic medications, but therapeutic responses can be incomplete or transient. CASE REPORT: We report the case of a 43-year-old woman with a long-standing diagnosis of Isaac's syndrome who experienced limited benefit from prolonged immunosuppressive and symptomatic therapies. The patient presented with disabling motor symptoms, pain, and reduced quality of life. She was treated with major autohemotherapy using an oxygen-ozone (O₂-O₃) protocol. Within two months, notable clinical and electrophysiological improvements were observed, including the resolution of neuromyotonia and significant gains in daily functional abilities. These improvements, assessed via the Barthel Index, remained stable over a three-year follow-up period, indicating sustained autonomy and pain control. The patient also carried MTHFR C677T and A1298C polymorphisms, which may have contributed to the autoimmune disease and influenced treatment response. CONCLUSIONS: This case highlights the potential role of oxygen-ozone therapy as a complementary non-pharmacological approach in refractory autoimmune neuromuscular disorders. The sustained clinical benefit observed suggests that ozone therapy may contribute to immune modulation, redox balance, and restoration of mitochondrial function. Further studies are warranted to evaluate personalized ozone-based protocols in the management of immune-mediated neuromuscular conditions.

Movement disorders associated with neuromuscular diseases are often underrecognized, yet they represent a distinct clinical entity. Abnormalities in areas of the peripheral nervous system, i.e., nerves and muscles, can stem from dysfunction of ion channels and proteins involved in membrane excitability. Hyperexcitability of peripheral motor nerves presents as cramps, stiffness, abnormal posture and gait, as well as changes in motor unit potentials during electromyography studies; hence, it may be classified as a movement problem. Etiologies range from hereditary, immune-mediated, or may be secondary to structural changes. This review focuses on peripheral nervous system and muscle-derived movement disorders associated with autoantibodies. It aims to highlight immune-mediated peripheral nerve hyperexcitability syndromes, stiff-person spectrum disorders, and immune-mediated rippling muscle disease (a movement disorder of muscular origin). It also discusses pathophysiology, diagnosis (particularly immunologic markers), and therapeutics.

Isaacs syndrome (IS) is a rare peripheral nerve hyperexcitability disorder, often associated with an underlying disease. We report a clinical case which appears to be a previously unreported co-occurrence of IS and systemic polyarteritis nodosa, diagnosed in a young woman presenting with subacute back pain, weight loss, fasciculations, diaphoresis, tachycardia, micturition disorder, constipation, cutaneous lesions and mesenteric vasculitis on MRI. The patient achieved clinical remission following treatment with intravenous cyclophosphamide and corticosteroids.

INTRODUCTION: Dopamine D2 receptor antagonists/partial agonists (D2RAs), including the US Food and Drug Administration-approved Tourette syndrome (TS) agents haloperidol, pimozide, and aripiprazole and other antipsychotics with dopamine D2 receptor-modulating properties, are prescribed for TS. This retrospective real-world study compared adverse events (AEs) and health care resource utilization (HCRU) between pediatric patients with TS newly treated versus not treated with D2RAs. METHODS: Data were analyzed retrospectively from an electronic health records database (TriNetX Dataworks-USA Network) containing information for >119 million individuals. Two cohorts aged 6 to 17 years, from 2011-2021, were identified: a D2RA-exposed cohort indexed at first D2RA medication record with TS diagnosis during baseline (18 months before and including index) and a D2RA-nonexposed cohort indexed on a randomly selected TS diagnosis record (2011-2021) with no D2RA record during baseline or follow-up (18 months after index). Monthly D2RA use was estimated, assuming 30-day coverage into the subsequent month; incident AEs and HCRU were evaluated during follow-up using medication records, diagnosis codes, anthropometric measurements, and/or laboratory results. RESULTS: Analyses included 1684 individuals per exact-matched cohort. In the D2RA-exposed cohort, documented D2RA medication records declined by Month 3 (38.8% of patients with a D2RA record) through Month 18 (17.9%). After adjustment for measured demographic and baseline characteristics, the D2RA-exposed cohort had higher recorded odds of incident AEs grouped as mild (e.g., sleep disorder; odds ratio [95% CI], 3.36 [2.68-4.20]), moderate (e.g., QT prolongation; 2.30 [1.65-3.20]), and severe (e.g., tardive dyskinesia; 3.01 [2.18-4.16]; all p <.0001) compared with the D2RA-nonexposed cohort. The D2RA-exposed cohort also had higher rates of all-cause and TS-related HCRU (outpatient, emergency, and inpatient encounters; adjusted incidence rate ratio range, 1.39-4.10; all p <.01). DISCUSSION: Children and adolescents with TS newly treated with a D2RA showed substantial decline in documented D2RA medication records over follow-up and had higher recorded odds of AEs and HCRU rates than did those without D2RA exposure. These findings should be interpreted as associational rather than causal effects and may reflect residual confounding by indication, differential monitoring, and/or greater underlying disease severity/complexity in the treated cohort.

BACKGROUND: Spontaneous muscle twitching observed on clinical examination can be challenging to distinguish between myokymia and fasciculation, particularly in peripheral nerve hyperexcitability syndromes where both phenomena may coexist. Because both fasciculations and myokymia may appear in Isaacs syndrome, ultrasonography alone can be misleading when discharge frequency is low, and correlation with needle EMG is essential for accurate differentiation. CASE PRESENTATION: We report a 53-year-old man with an 11-year history of progressive lower-limb twitching, cramps, and nocturnal muscle pain, in whom superficial muscle contractions were difficult to classify visually. Neuromuscular ultrasound revealed spontaneous contractions in multiple muscles, but their appearance overlapped with isolated fasciculations. Simultaneous needle electromyography and ultrasound of the left vastus medialis demonstrated low-amplitude grouped discharges recurring at intervals of approximately 4-9 s, most frequently 6-8 s, with burst durations of 60-200 ms and amplitudes generally below 200 μV, findings consistent with very low-frequency myokymic discharges. Needle EMG also showed widespread fibrillation potentials, positive sharp waves, and fasciculation potentials. Based on these clinical, electrophysiological, and imaging findings, the patient met the diagnostic criteria for probable Isaacs syndrome. Treatment with intravenous methylprednisolone followed by prednisolone 10 mg/day led to improvement in muscle cramps. CONCLUSION: This case demonstrates that visually similar ultrasonographic muscle contractions may correspond to fundamentally different electrophysiological phenomena on needle EMG, depending on the underlying pathophysiology, such as low-frequency myokymic discharges. Recognition of this distinction may help refine the interpretation of spontaneous muscle activity observed on ultrasonography and avoid oversimplified labeling as fasciculations.