Background and Aims:

The ongoing COVID-19 pandemic is having a huge impact on clinical activity of all hospitals, including the ones involved in training of residents. In addition, neurology residents underwent substantial modifications of their training program. As young section of the Italian Society of Neurology (SIgN), we aimed to evaluate the effects of COVID-19 pandemics on the educational activities of Italian neurology residents from both a clinical and a research point of view.

Methods:

we administered, during May 2020, an online questionnaire of 22 items to all neurology residents attending the 36 Teaching Hospital in Italy.

Results:

We had a response rate of 41% from all the 36 schools. Results showed that almost 30% of the respondents were redistributed to COVID-19 units. Neurology departments underwent substantial modifications of their organization influencing clinical educational activities (Fig.1). Lessons and seminars were rescheduled online and research activities were interrupted or reduced in 59% of the cases and transferred to remote working, when feasible. There was a relevant increase in the use of telemedicine (Fig.2): around 1/3 of residents used telemedicine in case of urgency and around 1/3 for all outpatients. Unfortunately, most of the respondents had never been trained before.

The increase of work shifts, the number of residents recruited in COVID-19-dedicated units and the access to psychological support showed a North to South gradient (Fig.3), following the epidemiology of the pandemic.

Conclusions:

The data obtained from our survey highlight points to address to be prepared for the current recrudescence of COVID-19 pandemic and for possible future emergencies.

Background and Aims:

Neurology residents are facing huge modifications in the routine practice of neurological patient management and profound changes of the neurological residency programs due to COVID 19 pandemic.

As young section of the Italian Society of Neurology, we aimed at investigating the point of view of neurology residents about the future of neurology after COVID-19 pandemic.

Methods:

An online questionnaire was administered to the Italian neurology residents attending all the 36 Teaching Hospital in Italy. The questionnaire was composed by six items: two dealt with the organization of neurological activities, two related to the care of patients, and the last two were on the allocation of economic resources for neurological care.

Results:

254 participated to the survey.

Organization of neurological activity: 86.2% of the participants reported that the COVID-19 pandemic will lead to a general reorganization of neurological activity in the future. 65% of the trainees argued that neurological inpatient spots will decrease in the future, with consequent increase of internist/generic inpatient beds and neurological consultations.

Patient care: 64%of residents forecasted an incrementation of outpatients’ activities with a parallel reduction of ward assistance and hospital services.

Funding availability for neurological diseases: according to 65% ofresidents,The management of neurological diseases and neuroscience research will receive less funding in the future,

Conclusions:

A rethinking of neurologist role should lead to appropriate reprogramming of training needs, to provide professionals able to deal with the whole clinical neurology. Allocations of resources should follow, to guarantee that educational systems are working to meet the healthcare demand.

Background and Aims:

About 10 millions epileptic patients live in sub-Saharan Africa (SSA), the treatment gap is more than 70%. HIV, highly prevalent in SSA is a risk factor for epilepsy and WHO indicated to unify epilepsy and HIV/AIDS treatment at HIV centres. The dramatic lack of neurologists in SSA imposes that many epileptic patients are seen by non-medical health-care providers (NMHCP), hence task-shifting is needed. To show the need of education in epilepsy and the short-term effects of local teaching courses to NMHCP in SSA-Malawi.

Methods:

The Disease Relief through Excellent and Advanced Means (DREAM) health program operates in Malawi since 2005 to prevent and treat HIV/AIDS and related conditions; there it follows 17,280 patients (88% HIV+). In 2021 two 2-full-days teaching courses on epilepsy have been offered by DREAM-volunteer neurologists to 40 NMHCP from both DREAM and governmental HIV/primary care from distinct areas. NMHCP were asked to answer some questions.

Results:

All NMHCP see epileptic patients in their daily practice. No one received education from neurologists; 90% were unsatisfied with their education on epilepsy. All NMHCP used phenobarbitone, out of stock was frequent; other antiepileptic drugs are difficult to get. 43.6% (pre-course) considered epilepsy a brain treatable disorder (100% post-course); 14.7% considered epilepsy more frequent in HIV+ and in children (94.6% post-course).

Conclusions:

Basic knowledge in epilepsy among NMHCP in SSA can be easily improved. Neurologists should increase education and training programs to NMHCP at primary care and HIV centres level to reduce epilepsy treatment gap in SSA.

Background and Aims:

In 2018 we surveyed the use of social media and digital devices among Italian neurologists. In the present study, we evaluated whether major changes had occurred in a short time-frame and indirectly assessed the impact of the Sars-COV-2 virus and the related COronaVIrus Disease 19 (COVID-19) pandemic.

Methods:

Online survey (September 2020 to January 2021) to collect information on attitude toward digital health of members of the Italian Society of Neurology (SIN). The outline of the survey was the same as the prior study.

Results:

One hundred and nine neurologists participated in the survey. Some major changes were found compared to 2018: fewer participants reported using the tablet (23% versus 43%; p<0.001) and Facebook (18% versus 32%; p=0.006) for professional purposes. More participants reported that social media had worsened the doctor-patient relationship, and were against a friendship with their patients in social media. There was a trend towards higher use of WhatsApp (92% versus 82%; p=0.018), and a significant reduction in active involvement in personal websites, blogs, or online forums.

Conclusions:

Dramatic changes in the attitudes towards social media have occurred in Italy in a very short timeframe, probably due to the concurrent pandemic and its impact on daily practice, and the dissemination of online misinformation.

Background and Aims:

The major cause of Parkinson's disease (PD) is thought to be the loss of dopaminergic substantia nigra neurons and the formation of alpha-synuclein-containing Lewy bodies. Although dopamine supplementation is a vital therapy, it is not facile to cross the BBB. 3,4-Dihydroxyphenylalanine (L-DOPA), a dopamine precursor, is one of the main drugs to treat PD since L-DOPA can cross the BBB better than dopamine; however, there are strong demands to develop further effective drugs due to the short half-life and several adverse effects such as dyskinesia. In this study, we studied new drugs based on novel molecular self-assembling at overcoming the drawbacks of L-DOPA and creating safe and effective Parkinson's disease drugs, viz., a nanoparticle consists of poly(diacetyl L-DOPA) was designed, which improved the controlled release of L-DOPA and improved the therapeutic effects, suppressing its adverse effects.

Methods:

A newly designed hydrophilic-hydrophobic block copolymer poly(ethylene glycol)-b-poly (L-DOPA(diacetyl)) forms self-assembling nano-sized particle (Nano^DOPA), which is examined to the effect on Parkinson's disease model mice.

Results:

Nano^DOPA significantly prolonged the retention of L-DOPA in the blood (mouse; n=3) and not only showed recovery in Parkinson's disease mice (n=8) but also reduced Dyskinesia symptoms (n=8).

Conclusions:

Nano^DOPA is anticipated as a new high-performance Parkinson's disease drug.

Background and Aims:

RNA processing protein 40 (RRP40) is an exosome complex involved in processing RNA, of which EXOSC3 forms a non-catalytic subunit. Homozygous mutation in EXOSC3 causes Pontocerebellar hypoplasia-1 (PCH-1), characterised by postnatal psychomotor retardation with spinal motor neuron degeneration. Imaging in PCH-1 shows severe cerebellar and variable pontine atrophy. Here we report an adolescent male with EXOSC3 mutation who presented with spastic paraparesis and nystagmus since childhood with severe vermian atrophy and normal pons suggestive phenotypically Hereditary spastic paraplegia plus syndrome (HSP-Plus).

Methods:

A 19 years old male born of non-consanguinous parentage presented with symptoms of unsteadiness while walking along with slurring of speech since three years of age. Examination showed a high arched palate, low set ears, elbow joint contracture, gaze-evoked nystagmus, spastic dysarthria, upper limb power 3/5, and spasticity of lower limbs with power 4/5 and bilateral extensor plantar.

Results:

The visually evoked potential was prolonged bilaterally. MRI brain showed severe atrophy of vermis with moderate atrophy cerebellar hemispheres without pontine atrophy (Figure). Clinical exome sequencing revealed a homozygous mutation in exon 3 of EXOC3 (variant- c.571G>A).

Conclusions:

This report reveals the variable phenotypic spectrum of EXOSC3 mutation and its analysis to be considered in patients with early-onset spastic paraparesis and nystagmus with cerebellar atrophy in the absence of pontine atrophy and other classical features.

Background and Aims:

Spinocerebellar ataxia type 12 begins with action tremor of hand followed by gait ataxia. The tremor matches with ET and PD in early illness which has shown impairment of DRTT. We aimed to determine the white matter changes in regions of the DRT tract using Diffusion tensor imaging (DTI) in SCA-12 patients.

Methods:

Twenty-six genetically confirmed SCA12 patients and 13 healthy controls were enrolled. Clinical and electrophysiological evaluation of tremors was done in SCA12 patients. DTI was performed on a 3T scanner, with b=800 s/mm² and 32 directions. Fractional anisotropic (FA) values were measured for regions in the DRRT.

Results:

Electrophysiology of tremor showed a synchronous pattern of muscle activation, with an average frequency of 4-5 Hz and varying amplitude in SCA12 patients. DTI in SCA12 patients showed significant reduction in the FA values for the left dentate nucleus (0.30± 0.01in controls versus 0.28 ± 0.04 in SCA12 patients, p=0.0256), left red nucleus (0.11±0.01 in controls versus 0.08 ± 0.02 in SCA12 patients, p=0.007), thalamus (0.10 ± 0.02 in controls, 0.07 ± 0.01in SCA12 patients, p=0.000), and VL nucleus of thalamus (0.39 ± 0.03 in controls, 0.35 ± 0.03 in SCA12 patients, p=0.007). The FTM tremor rating scale and FA value in the red nucleus showed a significant negative correlation (r=-0.5128-, p=0.0074).

Conclusions:

Microstructural white matter changes were found in specific regions (Dentate nucleus, red nucleus, thalamus, and VL nucleus) of DRTT in SCA12 patients. Dysfunction of DRRT may be implicated in the emergence of tremors in SCA12 patients.

Background and Aims:

Hereditary transthyretin amyloidosis (hATTR), a progressive, debilitating, and ultimately fatal disease, causes multisystem dysfunction. We report long-term efficacy and safety for inotersen, an antisense oligonucleotide inhibitor of transthyretin protein production.

Methods:

Patients completing the NEURO-TTR trial (NCT01737398) enrolled in its open-label extension (OLE; NCT02175004). Assessments included modified Neuropathy Impairment Score +7 (mNIS+7), Norfolk Quality of Life–Diabetic Neuropathy questionnaire (Norfolk QOL-DN), and safety monitoring. As of July 28, 2020, efficacy is reported for patients from Europe and North America and safety is reported for all patients.

Results:

Patients who switched from placebo to inotersen in the OLE (n=39) demonstrated slowing of neurologic disease progression compared with natural history (based on placebo projection); mean mNIS+7 and Norfolk QOL-DN scores at OLE baseline/1/2/3 years were 102.7/111.2/113.6/112.3 and 61.2/59.0/63.5/67.7, respectively. Patients receiving inotersen for 51 months (15 months in NEURO-TTR + 36 months in OLE; n=67) continued to show benefit, with mean mNIS+7 and Norfolk QOL-DN scores at OLE baseline/1/2/3 years of 84.3/90.7/98.1/95.1 and 50.3/52.4/53.1/57.2, respectively. Few patients (6/135; 4.4%) had serious treatment-related adverse events; no treatment-related deaths occurred. Under enhanced monitoring, there have been no reports of grade 4 thrombocytopenia or acute glomerulonephritis despite increased duration of exposure. No new safety concerns were identified.

Conclusions:

Extended treatment with inotersen for over 3 years slowed progression of the polyneuropathy associated with hATTR, with neurologic preservation observed in patients who initiated inotersen earlier, highlighting the importance of early treatment. Enhanced monitoring has reduced risks of severe thrombocytopenia and acute glomerulonephritis.