Encephalopathy as a prognostic factor in adults with acute disseminated encephalomyelitis following COVID-19.

Numerous reports support the possible occurrence of acute disseminated encephalomyelitis (ADEM) following COVID-19. Herein, we report a case of ADEM in a 53-year-old man 2 weeks after SARS-CoV-2 infection. We reviewed the reports of adult cases of ADEM and its variant acute necrotizing hemorrhagic leukoencephalitis (ANHLE) to check for possible prognostic factors and clinical/epidemiological peculiarities. We performed a descriptive analysis of clinical and cerebrospinal fluid data. Ordinal logistic regressions were performed to check the effect of clinical variables and treatments on ADEM/ANHLE outcomes. We also compared ADEM and ANHLE patients. We identified a total of 20 ADEM (9 females, median age 53.5 years) and 23 ANHLE (11 females, median age 55 years). Encephalopathy was present in 80% of ADEM and 91.3% of ANHLE patients. We found that the absence of encephalopathy predicts a better clinical outcome in ADEM (OR 0.027, 95% CI 0.001-0.611, p = 0.023), also when correcting for the other variables (OR 0.032, 95% CI 0.001-0.995, p = 0.05). Conversely, we identified no significant prognostic factor in ANHLE patients. ANHLE patients showed a trend towards a worse clinical outcome (lower proportion of good/complete recovery, 4.5% vs 16.7%) and higher mortality (36.4% vs 11.1%) as compared to ADEM. Compared to pre-pandemic ADEM, we observed a higher median age of people with post-COVID-19 ADEM and ANHLE, a shorter interval between infection and neurological symptoms, and a worse prognosis both in terms of high morbidity and mortality. Despite being affected by the retrospective nature of the study, these observations provide new insights into ADEM/ANHLE following SARS-CoV-2 infection.

Movement disorders in emergency settings: a prospective study.

INTRODUCTION: Acute movement disorders (MD) are etiologically heterogeneous entities. Since studies on the relative frequency of different MD and their underlying diseases are limited, we performed a prospective study to investigate the spectrum of various MD and their causes in patients presenting with acute MD in an emergency room (ER) setting. OBJECTIVE: To describe the spectrum and outcomes of acute MD in a prospective cohort and to guide its management. METHODS: We investigated acute MD in 96 consecutive patients admitted to ERs between 2013 and 2017. Time of disease onset, type of MD according to published criteria, diagnostic workup, and outcome were collected. RESULTS: 73.9% of patients had hyperkinetic MD. Tremor was the most common symptom (19.8%), followed by myoclonus (17.7%), dystonia (15.6%), and chorea (11.4%). Other hyperkinetic MD (9.4%) included were gait disorders (imbalance due to involuntary movement), dyskinesia, akathisia, hemiballism, and oculogyric crisis. Hypokinetic MD included acute parkinsonism (15.6%), off-state (4%), akinesia (3%), and rigidity (3%). Co-occurrence of more than one MD was seen in 19.7% of patients. Time delay to medical consultation was between < 24 h and 28 days. Five etiological groups were recognized: drug-induced (29.2%), functional (19.8%), neurodegenerative diseases (15.6%), structural brain damage (11.5%), others (24.0%, metabolic, inflammatory, infective, undetermined). Outcome was better for neurodegenerative diseases and for drug-induced MD. Functional movement disorders (FMD) showed less favorable outcome. CONCLUSIONS: Acute MD is a distinct cause of ER admission, and a variety of treatable diseases may be the underlying cause of this symptom. Uncertain course is more probable in FMD and in structural brain lesions.

Imaging of the dopamine transporter predicts pattern of disease progression and response to levodopa in patients with schizophrenia and parkinsonism: a 2-year follow-up multicenter study.

Similarly to subjects with degenerative parkinsonism, (123)I-FP-CIT SPECT has been reported either normal or abnormal in patients with drug-induced parkinsonism (DIP), challenging the notion that parkinsonism might be entirely due to post-synaptic D2-receptors blockade by antipsychotic drugs. In a previous multicenter cross-sectional study conducted on a large sample of patients with schizophrenia, we identified 97 patients who developed parkinsonism with a similar bi-modal distribution of DAT-SPECT. In this longitudinal study, we reported clinical and imaging features associated with progression of motor disability over 2-year follow-up in 60 out of those 97 patients with schizophrenia and parkinsonism who underwent (123)I-FP-CIT SPECT at baseline evaluation (normal SPECT=33; abnormal SPECT=27). As second end-point, chronic response to levodopa over a 3-month period was tested in a subgroup of subjects. Motor Unified Parkinson's Disease Rating Scale (UPDRS) at follow-up significantly increased in patients with abnormal SPECT. Specifically, a 6-point worsening was demonstrated in 18.5% of the subjects with abnormal SPECT and in none of the subjects with normal SPECT. Levodopa treatment improved motor UPDRS only in the group with abnormal SPECT. After adjustment for possible confounders, linear regression analysis demonstrated that abnormal SPECT findings at baseline were the only predictor of motor disability progression and of better outcome of levodopa treatment. Our results support the notion that a degenerative disease might underlie parkinsonism in a minority of schizophrenic patients chronically exposed to antipsychotics. Functional imaging of the dopamine transporter can be helpful to select this patient sub-group that might benefit from levodopa therapy.

[¹²³I]FP-CIT single photon emission computed tomography findings in drug-induced Parkinsonism.

Drug-induced parkinsonism (DIP) in patients treated with antipsychotic drugs is considered a form of post-synaptic parkinsonism, caused by D2-receptor blockade. Recent studies, however, carried out on small and heterogeneous patient samples, have shown that DIP may be associated with [(123)I]FP-CIT single photon emission computed tomography (SPECT) abnormalities, which are markers of dopamine nigrostriatal terminal defect. In the present study, outpatients fulfilling the DSM-IV criteria for schizophrenia and treated with antipsychotics for at least 6 months, were enrolled in order to estimate the prevalence of DIP and, among patients with DIP, the prevalence of [(123)I]FP-CIT SPECT abnormalities. Socio-demographic and clinical variables associated with the presence of DIP and SPECT abnormalities were also assessed. DIP was diagnosed in 149 out of 448 patients with schizophrenia (33%). Age, use of long-acting antipsychotics and a positive family history of parkinsonism were the only demographic variables significantly associated with the development of DIP. Neuroimaging abnormalities were found in 41 of 97 patients who agreed to undergo [(123)I]FP-CIT SPECT (42%). Only age differentiated this group of patients from those with normal imaging. These preliminary findings suggest that D2-receptor blockade may coexist with a dopamine nigrostriatal terminal defect, as assessed by [(123)I]FP-CIT SPECT abnormalities, in a relevant proportion of DIP patients. Longitudinal studies should be designed with the aim of improving our understanding of the mechanisms of pre-synaptic abnormalities in DIP patients and identifying specific treatment strategies.

Clinical experiences with levodopa methylester (melevodopa) in patients with Parkinson disease experiencing motor fluctuations: an open-label observational study.

INTRODUCTION: Slow gastric emptying decreasing levodopa (LD) bioavailability contributes to motor fluctuations in Parkinson disease (PD). Melevodopa (LD methylester), ensuring rapid duodenal absorption, has been proposed as rescue therapy for afternoon off periods. OBJECTIVE: To assess daily motor fluctuations by multiple administrations of Sirio (Chiesi Farmaceutici SpA, Parma, Italy) (melevodopa/carbidopa) in PD patients. PATIENTS AND METHODS: In this open-label naturalistic study, 75 PD patients (group A) completely switched standard LD (Sinemet or Madopar) with Sirio at an equivalent dosage (800-1000 mg/d). One hundred nineteen PD patients (group B) partially replaced their standard LD (Sinemet) with Sirio at an equivalent dosage (400-500 mg/d) while continuing Stalevo 100. In both groups, the observational period lasted 6 months. Assessments included an on/off diary, the Unified Parkinson's Disease Rating Scale (motor examination [UPDRS II] and activities of daily living [UPDRS III]), the dyskinesia scale, and an adverse event profile. RESULTS: Group A showed a significant reduction of afternoon off hours at 6 months (P < 0.05). Forty-five patients (69%) reported a subjective early onset of on motor response. Twelve patients (18.5%) reported its shorter duration. The dyskinesia scale score remained unchanged. Ten patients (13.3%) discontinued melevodopa for gastric intolerance. Group B showed at 6 months a significant reduction of total hours of daily off periods (P < 0.05), particularly in the morning (P < 0.01) and afternoon (P < 0.05). Seventy subjects (59%) expressed positive judgment on quickness of onset of on motor response. The dyskinesia scale score was unchanged. No significant adverse events were reported. CONCLUSIONS: Switching PD patients with motor fluctuations to melevodopa, particularly in the presence of entacapone, could optimize critical periods of the day such as the morning delay on and afternoon off periods.