Longitudinal changes of early motor and cognitive symptoms in progressive supranuclear palsy: the OxQUIP study.

BACKGROUND: Progressive supranuclear palsy (PSP) is a rare neurodegenerative condition characterised by a range of motor and cognitive symptoms. Very little is known about the longitudinal change in these symptoms over time. Moreover, the effectiveness of clinical scales to detect early changes in PSP is still a matter of debate. OBJECTIVE: We aimed to determine longitudinal changes in PSP features using multiple closely spaced follow-up time points over a period of 2 years. Methods 28 healthy control and 28 PSP participants, with average time since onset of symptoms of 1.9 years, were prospectively studied every 3 months for up to 24 months. Changes from baseline scores were calculated at each follow-up time point using multiple clinical scales to identify longitudinal progression of motor and cognitive symptoms. RESULTS: The Montreal Cognitive Assessment, but not the Mini-Mental State Examination, detected cognitive decline at baseline. Both scales revealed poor longitudinal sensitivity to clinical change in global cognitive symptoms. Conversely, the Movement Disorders Society Unified Parkinson's disease Rating Scale - part III and the PSP Rating Scale (PSPRS) reliably detected motor decline less than 2 years after disease onset. The 'Gait/Midline' PSPRS subscore consistently declined over time, with the earliest change being observed 6 months after baseline assessment. CONCLUSION: While better cognitive screening tools are still needed to monitor cognitive decline in PSP, motor decline is consistently captured by clinical rating scales. These results support the inclusion of multiple follow-up time points in longitudinal studies in the early stages of PSP.

Can SARS-CoV-2 Infection Lead to Neurodegeneration and Parkinson's Disease?

The SARS-CoV-2 pandemic has affected the daily life of the worldwide population since 2020. Links between the newly discovered viral infection and the pathogenesis of neurodegenerative diseases have been investigated in different studies. This review aims to summarize the literature concerning COVID-19 and Parkinson's disease (PD) to give an overview on the interface between viral infection and neurodegeneration with regard to this current topic. We will highlight SARS-CoV-2 neurotropism, neuropathology and the suspected pathophysiological links between the infection and neurodegeneration as well as the psychosocial impact of the pandemic on patients with PD. Some evidence discussed in this review suggests that the SARS-CoV-2 pandemic might be followed by a higher incidence of neurodegenerative diseases in the future. However, the data generated so far are not sufficient to confirm that COVID-19 can trigger or accelerate neurodegenerative diseases.

Neurological symptoms and complications in predominantly hospitalized COVID-19 patients: Results of the European multinational Lean European Open Survey on SARS-Infected Patients (LEOSS).

BACKGROUND AND PURPOSE: During acute coronavirus disease 2019 (COVID-19) infection, neurological signs, symptoms and complications occur. We aimed to assess their clinical relevance by evaluating real-world data from a multinational registry. METHODS: We analyzed COVID-19 patients from 127 centers, diagnosed between January 2020 and February 2021, and registered in the European multinational LEOSS (Lean European Open Survey on SARS-Infected Patients) registry. The effects of prior neurological diseases and the effect of neurological symptoms on outcome were studied using multivariate logistic regression. RESULTS: A total of 6537 COVID-19 patients (97.7% PCR-confirmed) were analyzed, of whom 92.1% were hospitalized and 14.7% died. Commonly, excessive tiredness (28.0%), headache (18.5%), nausea/emesis (16.6%), muscular weakness (17.0%), impaired sense of smell (9.0%) and taste (12.8%), and delirium (6.7%) were reported. In patients with a complicated or critical disease course (53%) the most frequent neurological complications were ischemic stroke (1.0%) and intracerebral bleeding (ICB; 2.2%). ICB peaked in the critical disease phase (5%) and was associated with the administration of anticoagulation and extracorporeal membrane oxygenation (ECMO). Excessive tiredness (odds ratio [OR] 1.42, 95% confidence interval [CI] 1.20-1.68) and prior neurodegenerative diseases (OR 1.32, 95% CI 1.07-1.63) were associated with an increased risk of an unfavorable outcome. Prior cerebrovascular and neuroimmunological diseases were not associated with an unfavorable short-term outcome of COVID-19. CONCLUSION: Our data on mostly hospitalized COVID-19 patients show that excessive tiredness or prior neurodegenerative disease at first presentation increase the risk of an unfavorable short-term outcome. ICB in critical COVID-19 was associated with therapeutic interventions, such as anticoagulation and ECMO, and thus may be an indirect complication of a life-threatening systemic viral infection.

Prothrombotic immune thrombocytopenia after COVID-19 vaccination.

We report 5 cases of prothrombotic immune thrombocytopenia after exposure to the ChAdOx1 vaccine (AZD1222, Vaxzevria) against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Patients presented 5 to 11 days after first vaccination. The spectrum of clinical manifestations included cerebral venous sinus thrombosis, splanchnic vein thrombosis, arterial cerebral thromboembolism, and thrombotic microangiopathy. All patients had thrombocytopenia and markedly elevated D-dimer. Autoantibodies against platelet factor 4 (PF4) were detected in all patients, although they had never been exposed to heparin. Immunoglobulin from patient sera bound to healthy donor platelets in an AZD1222-dependent manner, suppressed by heparin. Aggregation of healthy donor platelets by patient sera was demonstrated in the presence of buffer or AZD1222 and was also suppressed by heparin. Anticoagulation alone or in combination with eculizumab or intravenous immunoglobulin (IVIG) resolved the pathology in 3 patients. Two patients had thromboembolic events despite anticoagulation at a time when platelets were increasing after IVIG. In summary, an unexpected autoimmune prothrombotic disorder is described after vaccination with AZD1222. It is characterized by thrombocytopenia and anti-PF4 antibodies binding to platelets in AZD1222-dependent manner. Initial clinical experience suggests a risk of unusual and severe thromboembolic events.

Postinfectious Onset of Myasthenia Gravis in a COVID-19 Patient.

Objective: We report the case of a young woman with postinfectious onset of myasthenia gravis after COVID-19 with mild respiratory symptoms and anosmia/ageusia 1 month before admission to our neurological department. Methods: Patient data were derived from medical records of Hannover Medical School, Germany. Written informed consent was obtained from the patient. Results: The 21-year-old female patient presented with subacute, vertically shifted double vision evoked by right sided partial oculomotor paresis and ptosis. About 4 weeks earlier she had suffered from mild respiratory symptoms, aching limbs and head without fever, accompanied by anosmia/ageusia. During the persistence of the latter symptoms for around 10 days the patient had already noticed "tired eyes" and fluctuating double vision. Clinical assessment including a positive test with edrophonium chloride and increased acetylcholine receptor antibodies related the ocular manifestation etiologically to myasthenia gravis. Antibodies (IgA/IgG) against SARS-CoV-2 using three different serological tests (Abbott, DiaSorin, Euroimmun) were detected in serum suggesting this specific coronavirus as previously infectious agent in our patient. The myasthenic syndrome was treated successfully with intravenous immunoglobulins and oral pyridostigmine. Conclusion: This is the first case presentation of postinfectious myasthenia gravis as neurological complication in a COVID-19 patient.