SEZ6L2 Antibody–Associated Cerebellar Ataxia Responsive to Sequential Immunotherapy

ObjectivesSeizure-related 6 homolog like 2 (SEZ6L2) antibody–associated ataxia is an extremely rare disease. Six patients have been reported and none of them improved significantly with immunotherapy. Herein, we present the case of a patient with cerebellar ataxia and SEZ6L2 antibodies who benefited from immunotherapy, which dramatically altered the course of her disease.MethodsWe present a case report of a 73-year-old woman with progressive balance problems. Her condition had rapidly deteriorated in the 2 weeks before the admission to our hospital leading to repeated falls and eventually left her bed-ridden.ResultsShe presented with severe trunk ataxia, bidirectional nystagmus, dysarthric speech, and persistent nausea. With the exception of cerebellar atrophy, extensive imaging studies revealed no pathology. SEZ6L2 antibodies were found in both CSF and serum. Over a period of 9 months, our patient received immunotherapy consisting of steroid pulse therapy, IV immunoglobulin infusions, rituximab, and cyclophosphamide. Consequently, her condition improved markedly, and she was discharged home from the neurologic rehabilitation unit.DiscussionOur case report shows that intense sequential immunotherapy may considerably improve level of functioning in some patients with SEZ6L2 antibody–associated cerebellar ataxia.Classification of EvidenceThis provides Class IV evidence. It is a single observational study without controls.

Acute onset of chronic infl ammatory demyelinating polyneuropathy in combination with COVID-19

Acute onset of chronic infl ammatory demyelinating polyneuropathy (A-CIDP) presents signifi cant diffi culties in differential diagnosis with acute infl ammatory demyelinating polyneuropathy (AIDP). The article presents review of literature about diff erential diagnosis between A-CIDP and AIDP and a clinical case of A-CIDP at 26-year-old man. The disease started after vaccination against infl uenza and an episode of enteritis, the clinical picture matched Guillain–Barré syndrome criteria, according to electromyography data: demyelinating lesion of the left facial nerve, motor and sensory fi bers of the median and ulnar nerves on both sides, demyelinating lesions of motor fi bers of the tibial nerve and peroneal nerve on both sides. Chronic infl ammatory demyelinating polyneuropathy was diagnosed. Lack of eff ect from plasma exchange was the reason for changing the treatment to pulse therapy with prednisolone (with a subsequent transition to a 1 mg/kg dose and further reduction until canceled within 16 weeks). Response to prednisolone — rapid recovery of motor functions, which worsened signifi cantly due to a new coronavirus infection during treatment in the neurology department. Further continuation of prednisolone therapy made it possible to restore motor functions completely, except mild prosopoparesis. At the same time, deep refl exes were absent; no signifi cant EMG dynamics was observed. Considering the eff ect of glucocorticosteroids and lack of positive dynamics on the second electromyography, the patient was diagnosed as A-CIDP.

Case Report: Rehabilitation for Lower Extremity Pain Due to Venous Stasis in a Patient With Multisystem Inflammatory Syndrome in Children

Recently, it was reported that children recovering from coronavirus disease (COVID-19) developed multisystem inflammatory syndrome in children (MIS-C), which causes severe inflammation in multiple organs of the body. Because MIS-C is a new disease, the pathophysiology and prognosis are unknown. Owing to a lack of studies on this subject, we herein provide information on rehabilitation for children with MIS-C. A 12-year-old male patient presented with systemic inflammatory symptoms after approximately 2 months since recovery from COVID-19. He was treated with cyclosporine and steroid pulse therapy after admission to our hospital. His general condition improved significantly within approximately 1 week. Thereafter, his lower legs turned dark purple and he experienced intense pain whenever the lower limbs hung below the heart, such as in the sitting position. The patient was referred to the rehabilitation department, as he had difficulties during standing and walking. Because the symptoms improved with elevation of the lower extremities, we considered that the pain was related to venous stasis. The pain reduced when an elastic bandage was applied for the prevention of venous stasis; therefore, exercise therapy was implemented while the patient wore the elastic bandage. The patient's lower extremity symptoms improved in 10 days. He was discharged after 16 days and could independently perform activities of daily living (ADL). The mechanism underlying the patient's pain could not be determined; however, rehabilitation was effective when combined with compression therapy using an elastic bandage.

The Combination of Nucleotide Analog Therapy and Steroid Pulse Therapy for Acute HBV Infection Effectively Promotes HBV Clearance

Acute hepatitis B virus (HBV) infection occasionally progresses to acute liver failure, often with poor prognosis. The appropriate pharmacological approach is yet to be established. Although nucleotide analogs (NA) and corticosteroids are candidates for the treatment of acute HBV infection, their therapeutic effects, especially their effect on HBV clearance, remain unclear. To clarify effects on the HBV clearance of combination therapy of NA and steroid pulse therapy (SPT) for acute HBV infection, we first analyze the effectiveness of this therapy in patients with HBV infection compared with NA monotherapy (NAM). Of the 57 consecutive patients with acute hepatitis B infection from May 2007 to December 2018, we have included 25 patients for this study, whom we followed up until HBV clearance. According to the administration of NA and SPT, we divided patients into two groups (NAM group and NA + SPT group) and compared their results. Of the 25 patients, 10 received NAM, whereas 15 received NA + SPT. There were no appreciable adverse effects related to SPT. The time required for the clearance of HBsAg (76 (43–116) days vs. 26 (14–51) days, p = 0.0418) and HBV-DNA (NAM group vs. NA + SPT group: 180 (83.5–220) vs. 69 (43–136) days, p = 0.0420) was significantly shorter in the NA + SPT group than in the NAM group. The hazard ratio of NA + SPT for the clearance of HBsAg and HBV-DNA were 0.45 (0.19–1.09) and 0.35 (0.14–0.89), respectively. In conclusion, we showed that NA + SPT promoted HBV elimination. These findings support the use of the NA + SPT combination for acute HBV infection without the concern of persistent HBV infection.

Date of Admission during COVID-19 Pandemic Impacted Patient Outcomes in Addition to the Higher Efficacy of Tocilizumab Plus High-Dose Corticosteroid Therapy Compared to Tocilizumab Alone

Background: The evidence for the efficacy of glucocorticoids combined with tocilizumab (TCZ) in COVID-19 comes from observational studies or subgroup analysis. Our aim was to compare outcomes between hospitalized COVID-19 patients who received high-dose corticosteroid pulse therapy and TCZ and those who received TCZ. Methods: A retrospective single-center study was performed on consecutive hospitalized patients with severe COVID-19 between 1 March and 23 April 2020. Patients treated with either TCZ (400–600 mg, one to two doses) and methylprednisolone pulses (MPD-TCZ group) or TCZ alone were analyzed for the occurrence of a combined endpoint of death and need for invasive mechanical ventilation during admission. The independence of both treatment groups was tested using machine learning classifiers, and relevant variables that were potentially different between the groups were measured through a mean decrease accuracy algorithm. Results: An earlier date of admission was significantly associated with worse outcomes regardless of treatment type. Twenty patients died (27.0%) in the TCZ group, and 33 (44.6%) died or required intubation (n = 74), whereas in the MPD-TCZ group, 15 (11.0%) patients died and 29 (21.3%) patients reached the combined endpoint (n = 136; p = 0.006 and p < 0.001, respectively). Machine learning methodology using a random forest classifier confirmed significant differences between the treatment groups. Conclusions: MPD and TCZ improved outcomes (death and invasive mechanical ventilation) among hospitalized COVID-19 patients, but confounding variables such as the date of admission during the COVID-19 pandemic should be considered in observational studies.

Therapeutic apheresis in the complex pathogenetic therapy of anti-NMDA encephalitis associated with ovarian teratoma at a late stage of the disease

Anti‑NMDA encephalitis is a rare autoimmune disease of the central nervous system caused by the synthesis of autoantibodies to the NR1/NR2 subunits of the NMDA receptor, characterized by the development of acute mental, cognitive, motor, autonomic disorders, epileptic syndrome and central hypoventilation.The article presents a three‑year observation of patient 34 years old with anti‑NMDA ncephalitis associated with late‑ stage ovarian teratoma, accompanied by an increase titer of antibodies to NMDA receptors in serum to 1:640.Based on a detailed analysis of clinical, neurological, neuropsychological (MMSE, MoСA, FAB, 10 words test A.R. Luria) and laboratory‑instrumental characteristics of the disease (titer anti‑NMDA, level of IgG, IgM, IgA, lymphocyte subpopulations, EEG, MRI of the brain, pelvis) suggested a combination scheme of first and second line therapy. The sequential use of two cycles of medium‑volume membrane plasmapheresis (25–30 % of the circulating plasma volume, No. 5 + 5) was carried out in combination with pulse therapy with methylprednisolone 1.0 (No. 4 + 3) and cyclophasphamide 1.0 (No. 2 + 1) on background of persistent ovarian teratoma. Symptom regression was achieved by the end of the first cycle, and full recovery to the initial level of cognitive functions occurred after the second cycle, while maintaining the anti‑NMDA antibody titer to 1:160. After removal of ovarian teratoma, the level of anti‑NMDA decreased in a month to 1:40, and after 7 months it reached normal values (<1:10) against the background of basic pill therapy with methotrexate 12.5 mg/week.Thus, a rational combination and sequence of first and second line therapy and therapeutic apheresis, taking into account the pathogenetic features of each phase of the disease, can quickly achieve complete stable remission in patient with anti‑NMDA encephalitis.

Risk Factors of Oropharyngeal Candidiasis in COVID-19 Patients: A Case-control Study

Background: With the emergence and spread of coronavirus disease 2019 (COVID-19) globally, health care systems have faced the biggest challenge in recent decades. Objectives: The present study aimed to identify risk factors associated with oropharyngeal candidiasis (OPC) in COVID-19 patients. Methods: The total number of confirmed COVID-19 patients was 218 (105 cases with OPC and 113 controls without OPC). The questionnaire used in this study consisted of demographic data, treatment strategy, clinical and laboratory data, and underlying diseases collected from the onset of clinical OPC until the end of hospitalization. Results: Pseudomembranous candidiasis (77/105, 73.3%) was the most prevalent form of OPC in case patients. The majority of the cases (58.1%) and controls (58.4%) were males. Increasing age (P = 0.03) and hospitalization length (P = 0.016) were significantly associated with OPC in COVID-19 patients. Diabetes (P = 0.003), solid tumor (P = 0.019), and hypertension (P = 0.000) were the most common underlying conditions. The use of dentures (P = 0.003) and poor oral hygiene (P = 0.000) were related to OPC in the case group. Therapy with chloroquine (P = 0.012), IVIG (P = 0.001), diuretics (P = 0.000), and corticosteroid pulse therapy (P = 0.000) were significantly associated with developing OPC in case patients. Conclusions: Old age, hospitalization length, poor oral hygiene, corticosteroids use, diabetes, solid tumor, and hypertension may predispose COVID-19 patients to develop OPC.