アイザックス症候群

BACKGROUND: U.S. Veterans experience a high burden of COVID-19; characterizing immune responses associated with COVID-19 outcomes could help improve treatment. Changes in peripheral blood cytokines over time may predict both acute outcomes and long COVID symptoms. METHODS: Cytokine concentrations were quantified from peripheral blood collected 0-7 days (early) and 14-42 days (post-acute) after enrollment from SARS-CoV-2 positive participants in the EPIC3 study, a prospective, longitudinal cohort following U.S. Veterans. Responses were correlated with Veterans Affairs Severity Index for COVID-19 criteria and chronic symptoms with the modified Medical Research Council Dyspnea scale, Patient-Reported Outcomes Measurement Information System (PROMIS) Cognitive function, and PROMIS Fatigue scores 3 months after enrollment (60-135 days). Trends in cytokine concentration with COVID-19 severity were assessed. Odds of COVID-19 severity and long-term symptoms were estimated with logistic regression adjusted for sex, age, and morbidity. Longitudinal changes in cytokine concentration were examined for participants sampled during both time periods, by severity and long-term symptom group. RESULTS: Early HGF, IL-18, IL-1RA, IP-10, and VEGF-A and post-acute MIP-1α and VEGF-A concentrations trended positively with increasing COVID-19 severity (q-values < 0.05, Jonckheere-Terpstra trend test). Increases in EGF, MIP-1β, and RANTES concentration and decreases in MIP-1α concentration over time were associated with mild rather than moderate or severe disease. Increases in MIP-1β and RANTES concentration and decreases in Eotaxin concentration over time were associated with the absence of long-term symptoms. CONCLUSIONS: Worse COVID-19 severity by 30 days was associated with higher early and post-acute period cytokine concentrations. Participants with long-term symptoms did not see resolution of cytokine responses over time.

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.