Nabiximols and botulinum toxin injections for patients with multiple sclerosis: efficacy on spasticity and spasms in a single-centre experience.

BACKGROUND: Spasticity is a common and disabling symptom in patients with multiple sclerosis (PwMS): as highlighted by many epidemiological studies, it is often a severe and not well treated. Despite the availability of evidence-based spasticity management guidelines, there is still great variability in everyday therapeutic approach, especially for the most complex cases. METHODS: In our single-centre study, we retrospectively evaluated PwMS-treated nabiximols and botulinum toxin injections (BTI) from July 2015 to April 2019. Clinical and demographic data were collected. The severity of spasticity and spasms was recorded by modified Ashworth Scale (mAS) and Penn Spasm Frequency Scale (PSFS) at baseline and after 1 month of treatment. RESULTS: We evaluated 64 treatments for MS-related spasticity: 28 patients were treated with BTI and 36 patients with nabiximols. We found that both BTI and nabiximols are effective in reducing mAS (nabiximols, BTI: p < 0.001), PSFS frequency (nabiximols: p = 0.001, BTI: p = 0.008) and intensity (nabiximols: p = 0.001, BTI p = 0.016). No differences were found when directly comparing the efficacy of the two treatments, except for a statistical trend favouring BTI on spasms intensity (p = 0.091). Eleven patients were treated with both BTI and nabiximols, and only four patients continued both treatments. All dropouts were due to inefficacy of at least one of the two therapies. CONCLUSIONS: Our single-centre experience highlights that both BTI and nabiximols are effective in treating multiple sclerosis-related spasticity; however, BTI treatment may be more effective on spasms intensity. Combined nabiximols and BTI treatment could represent a therapeutic option for severe spasticity.

Action observation improves sit-to-walk in patients with Parkinson's disease and freezing of gait. Biomechanical analysis of performance.

INTRODUCTION: Freezing of gait (FoG) is one of the most disabling gait disorders in Parkinson's disease (PD), reflecting motor and cognitive impairments, mainly related to dopamine deficiency. Recent studies investigating kinematic and kinetic factors affecting gait in these patients showed a postural instability characterized by disturbed weight-shifting, inappropriate anticipatory postural adjustment, worse reactive postural control, and a difficulty executing complex motor tasks (i.e. sit-to-walk). These symptoms are difficult to alleviate and not very responsive to Levodopa. For this reason, additional therapeutic actions based on specific therapeutic protocols may help patients with their daily lives. We conducted a randomized control trial aimed to test if two clinical protocols for PD patients with FoG were effective to improve postural control. METHODS: Rehabilitation protocols, conceived to improve gait, were based on learning motor exercises with the Action Observation plus Sonification (AOS) technique, or by the use of external sensory cues. We collected biomechanical data (Center of Mass COM, Center of Pressure COP, and moving timings), using the sit-to-walk task as a measure of motor and gait performance. RESULTS: Kinetic and kinematic data showed that when treatment effects consolidate, patients treated with AOS protocol are more efficient in merging subsequent motor tasks (sit-to-stand and gait initiation), and diminished the total moving time and the area of the COP positions. CONCLUSION: We demonstrated for the first time that PD patients with FoG treated with an AOS protocol aimed at relearning appropriate gait patterns increased balance control and re-acquired more efficient postural control.

Novel quantitative approach for crossed cerebellar diaschisis detection in acute ischemic stroke using CT perfusion.

PURPOSE: Crossed cerebellar diaschisis (CCD) is a common finding in hyper-acute ischemic stroke, related to supratentorial dysfunction of the contralateral hemisphere. Several studies investigated a possible relationship between CCD and clinical outcomes but still no evidence emerged. We proposed a novel quantitative whole cerebellum analysis using CT perfusion (CTP) imaging to investigate the relationship between CCD and stroke severity, hypoperfused volume and outcome measures. METHODS: 55 patients with supratentorial ischemic stroke who underwent CTP evaluation within 4.5 h since symptom onset were enrolled. CCD was evaluated by CTP image-processing and by calculating the mean transit time (MTT)-map asymmetry index in the whole cerebellum. MTT asymmetry correlation with ischemic volume and clinical outcomes was investigated. RESULTS: MTT asymmetry was found in most of the included patients and significantly correlated with NIH Stroke Scale (NIHSS) score at baseline and CTP ischemic volume. MTT asymmetry was significantly correlated with hemorrhagic transformation, NIHSS and modified Rankin Scale (mRS) score on discharge in treated patients. CONCLUSIONS: CCD was detectable by CTP in acute supratentorial ischemic stroke by processing the whole cerebellum volume. CCD perfusion asymmetry was significantly correlated with neurological and perfusion deficit on admission as well as with clinical outcomes in treated patients.

Brain oscillatory activity and CT perfusion in hyper-acute ischemic stroke.

OBJECTIVES: The combined use of perfusion neuroimaging and brain oscillatory activity may provide a better clinical picture of neurovascular coupling of the injured area in ischemic stroke. The aim is to assess stroke-related topographic electroencephalography (EEG) changes during the earliest phase of ischemic stroke and to compare them with hypoperfusion identified by computer tomography perfusion (CTP). PATIENTS AND METHODS: The study included 15 patients with ischemic stroke, who underwent both CTP and EEG recording within 4.5 h. Topographic representation of power for each band was calculated and compared with hypoperfusion areas estimated by CTP maps. RESULTS: Predominance of slow delta frequencies was found in all patients. The main finding is the agreement between slow rhythms hemispheric prevalence on EEG maps and cerebral hypoperfusion area identified using CTP. CONCLUSION: The results of this preliminary study show that the combined use of EEG and CTP, as highly available techniques, in acute ischemic stroke may be helpful in clinical practice and provide information about functional and metabolic aspects of brain involvement. The joint use of these methodologies may give a better clinical insight of the functionality of injured area in the hyperacute phase.

Epilepsia partialis continua following a Western variant tick-borne encephalitis.

Epilepsia partialis continua (EPC) is a rare entity, first described in 1894 by Kozevnikov, as a variant of simple focal motor status epilepticus. EPC is most frequently characterized by motor symptoms, but as recently described, non-motor manifestations may occur, such as somatosensory symptoms or aura continua. EPC in adults has been attributed to various etiologies: infectious, vascular, neoplastic, and metabolic. According to the recent definition, we reported a case of EPC with behavioral symptoms, following a tick-borne encephalitis (TBE) contracted in an endemic area (North Eastern Italy). Patient's symptom was a poorly localized "whole body sensation", which is reported as a condition occurring only in frontal lobe epilepsy. Patient's EEG showed a left frontal predominance of epileptiform discharges. Literature highlighted the importance of the Far-eastern TBE variant as a cause of EPC, since no Western variant TBE cases are reported. In contrast to what was claimed so far, our case demonstrates that not only the Far-eastern TBE variant, but also Western variant TBE is a cause of EPC. Prognosis of EPC depends largely on the underlying etiology, and it is frequently drug-resistant. Our patient was treated with intravenous levetiracetam, with a subsequent clinical recovery and a disappearance of epileptiform discharges. The rapid clinic and electroencephalographic response to levetiracetam confirm that it can be a promising therapeutic option for treatment of EPC.

Wake-up stroke and CT perfusion: effectiveness and safety of reperfusion therapy.

OBJECTIVE: Ischemic stroke is a neuroemergency condition highly treatable with thrombolysis and thrombectomy. Recently, observational studies have brought insights into clinical and imaging characteristics of wake-up stroke, which interested up to 25% of ischemic stroke patients. In clinical practice, wake-up strokes are usually not considered for reperfusion therapy. The aim of this study was to investigate the use CT perfusion imaging in patients with wake-up stroke and to assess the effect of neuroimaging information provided by CT perfusion maps on the efficacy and safety of thrombolysis and thrombectomy. PATIENTS AND METHOD: We studied 22 wake-up stroke (WUS) patients (13F/9M mean age) who underwent reperfusion therapy after the eligibility assessed by the CT perfusion imaging (< 50% core-to-penumbra ratio and negative CT perfusion). RESULTS: Mean National Institutes of Health Stroke Scale (NIHSS) was 8.1 ± 4.9 at admission while 3.3 ± 5.1 at discharge, significantly different from admission (p < 0.001). As many as ten patients had mRS lower than 3 at discharge. Intracranial hemorrhage occurred in five patients and caused symptoms worsening only in two patients (decrease of NIHSS score of 4 points) of which one patient died. CONCLUSION: The main finding of this study is that wake-up stroke with adequate selection by CT perfusion may benefit reperfusion treatment.

Ischemic Volume and Neurological Deficit: Correlation of Computed Tomography Perfusion with the National Institutes of Health Stroke Scale Score in Acute Ischemic Stroke.

BACKGROUND: The National Institutes of Health Stroke Scale (NIHSS) is the most adopted stroke patients' evaluation tool in emergency settings to assess the severity of stroke and to determine the patients' eligibility for specific treatments. Computed tomography perfusion (CTP) is crucial to identify salvageable tissue that can benefit from the reperfusion treatment. The aim of this study is to identify the relation between the NIHSS scores and the hypoperfused volumes evaluated by CTP in patients with hyperacute ischemic stroke. METHODS: This retrospective study was conducted on 105 patients with ischemic stroke who underwent NIHSS assessment and CTP in the hyperacute phase. Hypoperfused volume was evaluated by CTP maps processed with semi-automatic algorithm. An analysis was conducted to determine the degree of correlation between the NIHSS scores and the ischemic lesion volumes and to investigate the relation between the anterior and the posterior circulation strokes, as well as between the right and the left hemispheric strokes. RESULTS: A significant correlation was found between ischemic volume and NIHSS score at baseline (r = .82; P < .0001) in the entire cohort. A high NIHSS-volume correlation was identified in the anterior circulation stroke (r = .76; P < .0001); whereas, it was nonsignificant in the posterior circulation stroke. NIHSS score and volume correlated for the left and the right hemispheric strokes (r = .83 and .81; P < .0001), showing a slightly higher slope in the left. CONCLUSION: This study showed a strong correlation between the baseline NIHSS score and the ischemic volume estimated by CTP. We confirmed that NIHSS is a reliable predictor of perfusion deficits in acute ischemic stroke. CTP allows fast imaging assessment in the hyperacute phase. The results highlight the importance of these diagnostic tools in the assessment of stroke severity and in acute decision-making.

Role of comorbidities and in-hospital complications in short-term status epilepticus outcome.

OBJECTIVE: pre-morbid patient conditions and hospitalization complications possibly play a role in status epilepticus short-term outcome, although evidence is incomplete and non-conclusive. The study's aim was to define whether comorbidities and in-hospital complications arising after status epilepticus affect its prognosis. METHODS: A retrospective single center study was carried out. All selected patients were adults presenting an EEG-proven status epilepticus episode between 2003 and 2014. Medical charts were comprehensively reviewed. In-hospital mortality and length of hospital stay represented study outcomes. RESULTS: One hundred seventy-three subjects met the inclusion criteria. Seventy-one cases (41%) developed infections and 59 (34%) non-infectious complications. Median hospital stay was 16days and overall in-hospital mortality was 44%. Multivariate analysis revealed the association between in-hospital mortality and the following comorbidities: history of diabetes mellitus (Odds ratio=7.89, p=0.002) and evidence of extracranial malignancy (Odds ratio=10.28, p=0.009). Complications were not associated to death after multivariate statistics, which instead displayed systemic inflammatory response syndrome significance (Odds ratio=12.90, p<0.001). Infections and non-infectious complications were associated with longer hospital stay (p=0.025 and p=0.01 respectively). CONCLUSIONS: status epilepticus management is a multifaceted problem. RESULTS: suggest that some pre-morbid patient conditions and in-hospital adverse events play an unfavorable prognostic role. This preliminary information may help clinicians optimize preventive and therapeutic strategies to guarantee patients the best chances of survival.

Predictors of functional disability at hospital discharge after status epilepticus.

OBJECTIVE: Although status epilepticus is a common neurological emergency, literature about its short term functional disability is scarce and often difficult to interpret. The aim of the present study was to identify possible predictive factors of functional disability in a well-selected cohort of EEG-confirmed status epilepticus patients. METHODS: We carried out a retrospective evaluation of clinical and radiologic parameters potentially affecting status epilepticus-related disability in a cohort of adult patients admitted to our institution between 2003 and 2013. Functional decline was defined as a ≥ 1 increase in the modified Rankin scale from preadmission to discharge. RESULTS: Seventy-nine patients fulfilled inclusion criteria (46% male). Median age was 69 years. History of epilepsy was present in 49% of patients. Deterioration occurred in 46 subjects (58%). Multivariate analysis revealed the following negative predicting factors for disability: normal neuroimaging (OR = 0.031) and presence of status epilepticus on hospital admission (OR = 0.127). SIGNIFICANCE: Patients without evident brain lesions are at low risk of functional deterioration development. SE on admission portends a good prognosis as well, probably because it is more promptly treated and it develops in subjects with less systemic complications compared to those in hospital.