COVID-19-associated Guillain-Barré syndrome in the early pandemic experience in Lombardia (Italy).

OBJECTIVE: To estimate the incidence and describe clinical characteristics and outcome of GBS in COVID-19 patients (COVID19-GBS) in one of the most hit regions during the first pandemic wave, Lombardia. METHODS: Adult patients admitted to 20 Neurological Units between 1/3-30/4/2020 with COVID19-GBS were included as part of a multi-center study organized by the Italian society of Hospital Neuroscience (SNO). RESULTS: Thirty-eight COVID19-GBS patients had a mean age of 60.7 years and male frequency of 86.8%. CSF albuminocytological dissociation was detected in 71.4%, and PCR for SARS-CoV-2 was negative in 19 tested patients. Based on neurophysiology, 81.8% of patients had a diagnosis of AIDP, 12.1% of AMSAN, and 6.1% of AMAN. The course was favorable in 76.3% of patients, stable in 10.5%, while 13.2% worsened, of which 3 died. The estimated occurrence rate in Lombardia ranges from 0.5 to 0.05 GBS cases per 1000 COVID-19 infections depending on whether you consider positive cases or estimated seropositive cases. When we compared GBS cases with the pre-pandemic period, we found a reduction of cases from 165 to 135 cases in the 2-month study period in Lombardia. CONCLUSIONS: We detected an increased incidence of GBS in COVID-19 patients which can reflect a higher risk of GBS in COVID-19 patients and a reduction of GBS events during the pandemic period possibly due to a lower spread of more common respiratory infectious diseases determined by an increased use of preventive measures.

Vitamin D, Chronic Migraine, and Extracranial Pain: Is There a Link? Data From an Observational Study.

Several studies focused on the role of vitamin D (vitD) in pain chronification. This study focused on vitD level and pain chronification and extension in headache disorders. Eighty patients with primary headache underwent neurological examination, laboratory exams, including serum calcifediol 25(OH)D, and headache features assessment along with three questionnaires investigating depression, anxiety, and allodynia. The 86.8% of the population had migraine (48% episodic and 52% chronic). The 44.1% of patients had extracranial pain, and 47.6% suffered from allodynia. A vitD deficit, namely a serum 25(OH)D level <20 ng/ml, was detectable in 46.1% of the patients, and it occurred more frequently (p = 0.009) in patients suffering from chronic migraine (CM)-medication overuse migraine (MOH) (62.9%) than in episodic migraine (EM, 25.7%) or tension-type headache (TTH, 11.4%). The occurrence of extracranial pain and allodynia was higher in the CM-MOH than in the EM and in the TTH groups but was not related to the co-occurrence of vitD deficiency (Fisher's exact test p = 0.11 and p = 0.32, respectively). Our findings show that 25(OH)D deficit is also related to chronic headache, probably because of vitD anti-inflammatory and tolerogenic properties, reinforcing the idea of a neuroinflammatory mechanism underpinning migraine chronification.

Posterior reversible encephalopathy syndrome and COVID-19: A series of 6 cases from Lombardy, Italy.

Posterior reversible encephalopathy cases are increasingly being reported in patients affected by COVID-19, but the largest series so far only includes 4 patients. We present a series of 6 patients diagnosed with PRES during COVID-19 hospitalized in 5 Centers in Lombardia, Italy. 5 out of the 6 patients required intensive care assistence and seizures developed at weaning from assisted ventilation. 3 out of 6 patients underwent cerebrospinal fluid analysis which was normal in all cases, with negative PCR for Sars-CoV-2 genome search. PRES occurrence may be less rare than supposed in COVID-19 patients and a high suspicion index is warranted for prompt diagnosis and treatment.

An Example of a Stroke Unit Reshaping in the Context of a Regional Hub and Spoke System in the COVID-19 Era.

During the COVID-19 outbreak, the Neurology and Stroke Unit (SU) of the hospital of Varese had to serve as a cerebrovascular hub, meaning that the referral area for the unit doubled. The number of beds in the SU was increased from 4 to 8. We took advantage of the temporary suspension of the out-patient clinic and reshaped our activity to guarantee the 24/7 availability of recombinant tissue Plasminogen Activator (rtPA) intravenous therapy (IVT) in the SU, and to ensure we were able to admit patients to the SU as soon as they completed endovascular treatment (EVT). In 42 days, 46 stroke patients were admitted to our hospital, and 34.7% of them underwent IVT and/or EVT, which means that we treated 0.38 patients per day; in the baseline period from 2016 to 2018, these same figures had been 23.5% and 0.23, respectively. The mean values of the door-to-first CT/MRI and the door-to-groin puncture, but not of the onset-to-door and the door-to-needle periods were slightly but significantly longer than those observed in the baseline period in 276 patients. On an individual basis, only one patient exceeded the door-to-groin puncture time limit computed from the baseline period by about 10 min. None of the patients had a major complication following the procedures. None of the patients was or became SARS-CoV2 positive. In conclusion, we were able to manage the new hub-and-spoke system safely and without significant delays. The reshaping of the SU was made possible by the significant reduction of out-patient activity. The consequences of this reduction are still unknown but eventually, this emergency will suggest ways to reconsider the management and the allocation of health system resources.

Reversible Encephalopathy Syndrome (PRES) in a COVID-19 patient.

Recently WHO has declared novel coronavirus disease 2019 (COVID-19) outbreak a pandemic. Acute respiratory syndrome seems to be the most common manifestation of COVID-19. Besides pneumonia, it has been demonstrated that SARS-CoV-2 infection affects multiple organs, including brain tissues, causing different neurological manifestations, especially acute cerebrovascular disease (ischemic and hemorrhagic stroke), impaired consciousness and skeletal muscle injury. To our knowledge, among neurological disorders associated with SARS-CoV2 infection, no Posterior Reversible Encephalopathy Syndrome (PRES) has been described yet. Herein, we report a case of a 64-year old woman with COVID19 infection who developed a PRES, and we suggest that it could be explained by the disruption of the blood brain barrier induced by the cerebrovascular endothelial dysfunction caused by SARS-CoV-2.

Does robot-assisted gait training improve ambulation in highly disabled multiple sclerosis people? A pilot randomized control trial.

BACKGROUND: Robotic training is commonly used to assist walking training in patients affected by multiple sclerosis (MS) with non-conclusive results. OBJECTIVE: To compare the effect of robot-assisted gait training (RAGT) with that of conventional walking training (CWT) on gait competencies, global ability, fatigue and spasticity in a group of severely affected patients with MS. METHODS: A pilot, single-blind randomized controlled trial was conducted in 43 severe (Expanded Disability Status Scale (EDSS) score of 6-7.5) and non-autonomous ambulant in-patients with MS. Experimental group performed 12 sessions of RAGT, whereas control group performed the same amount of CWT. Primary outcome measures were gait ability assessed by 2 minutes walking test and Functional Ambulatory Category; secondary outcomes were global ability (modified Barthel Index), global mobility (Rivermead Mobility Index), severity of disease (EDSS) and subjectively perceived fatigue (Fatigue Severity Scale). RESULTS: The number of subjects who achieved a clinical significant improvement was significantly higher in RAGT than in CWT ( p < 0.05 for both primary outcome measures). RAGT also led to an improvement in all the other clinical parameters (global ability: p < 0.001, global mobility: p < 0.001, EDSS: p = 0.014 and fatigue: p = 0.001). CONCLUSIONS: RAGT improved the walking competencies in non-autonomous ambulant patients with MS, with benefits in terms of perceived fatigue.

Chronic pain in multiple sclerosis: is there also fibromyalgia? An observational study.

BACKGROUND: Chronic pain is common in persons with multiple sclerosis (MS), but the co-morbidity of fibromyalgia (FM) has yet to be investigated in MS. Objectives of the study were to evaluate, among the various types of chronic pain, the frequency of FM in MS and its impact on MS patients' health-related quality of life (HRQoL). MATERIAL AND METHODS: 133 MS patients were investigated for the presence and characterization of chronic pain within 1 month of assessment. A rheumatologist assessed the presence FM according to the 1990 ACR diagnostic criteria. Depression, fatigue, and HRQoL were also assessed by means of specific scales. RESULTS: Chronic pain was present in 66.2% of patients (musculoskeletal in 86.3%; neuropathic in 13.7%; absent in 33.8% [called NoP]). Pain was diagnosed with FM (PFM+) in 17.3% of our MS patients, while 48.9% of them had chronic pain not FM type (PFM-); the prevalence of neuropathic pain in these 2 sub-groups was the same. PFM+ patients were prevalently females and had a higher EDSS than NoP. The PFM+ patients had a more pronounced depression than in the NoP group, and scored the worst in both physical and mental QoL. CONCLUSIONS: In our sample of MS patients we found a high prevalence of chronic pain, with those patients displaying a higher disability and a more severe depression. Moreover, FM frequency, significantly higher than that observed in the general population, was detected among the MS patients with chronic pain. FM occurrence was associated with a stronger impact on patients' QoL.

From high- to low-frequency administered interferon-beta for multiple sclerosis: a multicenter study.

OBJECTIVES: To investigate whether clinical and magnetic resonance imaging (MRI) outcomes of patients with multiple sclerosis (MS) who required a reduction of administration frequency of interferon-beta (IFNB) were similar to those of patients who did not. METHODS: We identified three subgroups of patients under treatment for 24 months with subcutaneous (sc) high-frequency IFNB-1a or -1b: those continuing to receive IFNB according to the drug label (recommended frequency group), those reducing the administration frequency of sc IFNB-1a or -1b (reduced frequency group), and those switched to once weekly intramuscular (im) IFNB (switched group). All patients were followed for further 24 months. The occurrence of relapse, MRI activity and disability worsening were considered as outcome measures. RESULTS: We identified 308 patients, 201 in the recommended frequency group, 70 in the reduced frequency group, and 37 in the switched group. Patients in the reduced frequency group had increased risk for relapses (HR = 1.95, p < 0.001) and MRI activity (HR = 1.41, p < 0.001), while patients in the switched group had increased risk for relapses (HR = 1.67, p = 0.012), but not for MRI activity (HR = 1.26, p = 0.08) than those in the recommended frequency group. Predictors for disease activity re-start after the reduction of IFNB administration frequency were younger age, higher pre-IFNB relapse rate, and reducing sc IFNB frequency to twice weekly rather than switching to im IFNB-1a once weekly. CONCLUSION: Our findings discourage the reduction of sc IFNB administration frequency, especially in younger patients with a higher pre-IFNB relapse rate. However, switching to im IFNB-1a may be considered in some selected cases.

Care management of spasticity with botulinum toxin-A in patients with severe acquired brain injury: a 1-year follow-up prospective study.

OBJECTIVE: To evaluate the efficacy and the safety of repeated botulinum toxin type A (BT-A) injections in patients with severe acquired brain injury (ABI) and to gain a better knowledge of possible clinical or demographic characteristics associated with a better rehabilitation outcome. DESIGN: Prospective study with a 1-year follow-up period. SUBJECTS: Twenty-one patients with spasticity due to severe ABI and no further improving with rehabilitation treatment and oral anti-spastic drugs. INTERVENTION: Repeated BT-A injections associated to a rehabilitation programme. MAIN MEASURES: Barthel Index (BI), Modified Ashworth Score (MAS) and VAS score for pain subjective perception were recorded. RESULTS: At the end of the follow-up study, MAS, BI and VAS significantly improved. Despite the number of BT-A injections, a shorter interval between severe ABI onset and first BT-A treatment correlated to a better BI improvement. None of the patients experienced adverse events attributable to BT-A. CONCLUSION: BT-A was effective and safe in the treatment of spasticity in severe ABI patients, with a better functional outcome in those subjects treated earlier after spasticity onset. The lack of correlation between clinical outcome and number of injections suggests, in addition to a direct inhibition at the neuromuscular junction, a more distant BT-A long-term effect.

Enhanced-MRI and ultrasound evaluation of painful shoulder in patients after stroke: a pilot study.

BACKGROUND: Epidemiological and radiological studies have previously been performed to identify the possible causes of hemiplegic shoulder pain (HSP). Many different etiologies have been postulated, though no clear correlations have emerged, and a multifactorial pathogenesis of HSP has been proposed. Recently, two MRI-based studies have described different shoulder findings as possible causes of pain in chronic stroke survivors. PURPOSE: The aim of this study was to describe the structural abnormalities of the painful shoulder in the first months after stroke by ultrasound and enhanced MRI. The secondary aims were to identify possible predisposing factors for HSP and to evaluate its impact on motor recovery. METHODS: One hundred and fifty-three first-time stroke patients, admitted to the Santa Lucia Foundation for rehabilitation, were investigated for HSP. Twenty-five stroke patients with HSP and 16 stroke patients without shoulder pain were included. An ultrasound evaluation and enhanced shoulder MRI were performed for all the patients. RESULTS: Among the shoulder abnormalities detected by both imaging studies, only capsulitis, which was detected by enhanced shoulder MRI in 88% of the HSP patients, was independently associated with pain (p < 0.001) and proven to be predictive of pain intensity as expressed by the VAS score (p < 0.003). HSP correlated with a worse global recovery (p < 0.05) as well as with male sex (p = 0.006), neglect (p = 0.02) and subluxation (p = 0.03), although none of these features were found to be independent predictors of pain. CONCLUSION: Adhesive capsulitis was found to be a possible cause of HSP. However, MRI, which is more expensive than other diagnostic tools, may be considered the gold standard tool for understanding the etiology of HSP.

Hypogonadism in DM1 and its relationship to erectile dysfunction.

Myotonic dystrophy type 1 (DM1) is characterized by both a premature appearance of age-related phenotypes and multiple organ involvement, which affects skeletal and smooth muscle as well as the eye, heart, central nervous system, and endocrine system. Although erectile dysfunction (ED) is a frequent complaint in patients with DM1, it has not been investigated in great depth. Hypogonadism, which is reported to be one of the physical causes of ED in the general population, frequently occurs in DM1. We planned this case-control study to evaluate the relationship between hypogonadism, as defined by the sexual hormone profile (FSH, LH, testosterone (T) and prolactin) and ED, as assessed by means of an internationally validated self-administered questionnaire (IIEF). DM1 patients had significantly increased mean levels of both gonadotropins (FSH and LH) (p < 0.0001) and a reduced mean level of T (p < 0.0001) when compared to controls. Twelve patients were eugonadic (normal LH, T, and FSH), while 18 displayed hormonal evidence of hypogonadism, characterized by tubular failure (increased FSH) in all the subjects and associated with interstitial failure in 14 subjects: seven with primary hypogonadism (increased LH and reduced T) and seven with compensated hypogonadism (increased LH and normal T). Patients with hormonal evidence of interstitial failure had a larger CTG expansion (p = 0.008), longer disease duration (p = 0.013), higher grade of disease (p = 0.004) and lower erectile function score (p = 0.02) than eugonadic patients. Impotence occurred in 13/14 hypogonadic patients with interstitial failure and in 5/12 eugonadic patients (p = 0.017, OR = 18.2).

Short-term brain atrophy changes in relapsing-remitting multiple sclerosis.

The objective of this study was to establish whether the time interval of 3 months is sufficient to detect whole-brain atrophy changes in patients with relapsing-remitting (RR) multiple sclerosis (MS). Another aim was to assess the value of monthly gadolinium (Gd)-enhanced magnetic resonance imaging (MRI) and of different Gd-enhancement patterns as predictors of brain atrophy. Thirty patients with RRMS (mean disease duration 4.9 years, mean age 34.4 years and mean Expanded Disability Status Scale [EDSS] 1.4) were assessed at baseline and monthly for a period of 3 months with clinical and MRI examinations. Calculations of baseline and monthly absolute and percent changes of MRI measures have been obtained using two semiautomated (Buffalo and Trieste) and one automated (SPM99) segmentation method. Changes of brain parenchymal fraction (BPF) were investigated according to Gd-enhancement patterns. Mean absolute and percent changes of BPF did not significantly differ at any time point in the study for any of the three methods. There was slight but not significant decrease of BPF from baseline to month 3: -0.0004 (0.05%), p=0.093 for Trieste; -0.0006 (0.07%), p=0.078 for Buffalo; and -0.0006 (0.08%), p=0.081 for SPM99 method. In ring-enhancement positive patients, there was a significant difference between baseline and month 3 changes of BPF, EDSS, and number of relapses. Over the study period, we did not demonstrate differences between changes of BPF according to the presence of Gd enhancement. Longitudinally, multiple regression analysis demonstrated that the only clinical or MRI parameter that predicted BPF decrease was the mean absolute change of ring-enhancing lesion load (R=0.62, p=0.003). The noteworthy findings of this study are (1) the observation that a significant brain atrophy progression cannot be detected over a 3-month period in RRMS; (2) the demonstration that the ring-enhancement pattern may contribute to more severe brain tissue loss in the short term; and (3) the lack of relationship between the presence and duration of Gd-enhancement activity and brain volume changes in the short term.

Neutralizing antibodies against endogenous interferon in myasthenia gravis patients.

Anti-cytokine antibodies (Abs) play an important role in the regulation of the immune response, both under normal conditions and in several autoimmune and neoplastic disorders. In the present study, we have investigated the occurrence and the clinical significance of natural neutralizing Abs (NAbs) against interferons (IFNs) alpha, beta, and gamma, as detected by bioassay, in 52 patients with myasthenia gravis (MG), and 43 sex- and age-matched healthy individuals. Patients showing titres > or = 1.3 Log t(1/10), confirmed in 2 consecutive samples collected two months apart, were considered positive. NAbs against any of the IFNs were not detected in healthy subjects. Of the 52 MG patients, 11 (21.1%) had NAbs against IFNalpha and three (5.8%) had NAbs against IFNbeta. None of these patients was found to be positive for NAbs against IFNgamma. Of the patients positive for NAbs against IFNalpha, eight (15.4%) had NAbs at titres > or =2 Log t(1/10). A positive association was observed between high titres of NAbs and the presence of thymoma. These data suggest the presence of a generalized activation of the humoral response in MG.