A case of hemichorea associated with nonketotic hyperglycaemia: A new magnetic resonance spectroscopy (MRS) finding and possible future implications.

BACKGROUND: Diabetic Striatopathy (DS) is a rare complication of a poor-controlled Diabetes Mellitus consisting of sudden onset of movement disorders. To date, there is still poor knowledge about the pathogenesis. CASE: We describe a 79 year old men affected by sudden onset hemichoreic movements whose cause was a non-ketotic hyperglycaemia diagnosed despite the normal blood glucose levels thanks to brain CT and magnetic resonance imaging. Then, we introduce a new magnetic resonance spectroscopy (MRS) finding never described until today which allowed us to produce a new pathogenetic theory of a phenomenon still without definitive explanations. LITERATURE REVIEW: We performed a review of DS cases using the Medline database and we extracted main data regarding imaging findings. CONCLUSIONS: Thanks to our MRS we show new imaging findings never described until today, with a new pathogenetic explanation, since all the causative hypotheses produced during the past years have never found evidence.

A retrospective multicentric study on the effectiveness of intravenous brivaracetam in seizure clusters: Data from the Italian experience.

OBJECTIVE: Nearly half of people with epilepsy (PWE) are expected to develop seizure clusters (SC), with the subsequent risk of hospitalization. The aim of the present study was to evaluate the use, effectiveness and safety of intravenous (IV) brivaracetam (BRV) in the treatment of SC. METHODS: Retrospective multicentric study of patients with SC (≥ 2 seizures/24 h) who received IV BRV. Data collection occurred from January 2019 to April 2022 in 25 Italian neurology units. Primary efficacy outcome was seizure freedom up to 24 h from BRV administration. We also evaluated the risk of evolution into Status Epilepticus (SE) at 6, 12 and 24 h after treatment initiation. A Cox regression model was used to identify outcome predictors. RESULTS: 97 patients were included (mean age 62 years), 74 (76%) of whom had a history of epilepsy (with drug resistant seizures in 49% of cases). BRV was administered as first line treatment in 16% of the episodes, while it was used as first or second drug after benzodiazepines failure in 49% and 35% of episodes, respectively. On the one hand, 58% patients were seizure free at 24 h after BRV administration and no other rescue medications were used in 75 out of 97 cases (77%) On the other hand, SC evolved into SE in 17% of cases. A higher probability of seizure relapse and/or evolution into SE was observed in patients without a prior history of epilepsy (HR 2.0; 95% CI 1.03 - 4.1) and in case of BRV administration as second/third line drug (HR 3.2; 95% CI 1.1 - 9.7). No severe treatment emergent adverse events were observed. SIGNIFICANCE: In our cohort, IV BRV resulted to be well tolerated for the treatment of SC and it could be considered as a treatment option, particularly in case of in-hospital onset. However, the underlying etiology seems to be the main outcome predictor.

Trends of recanalization therapies and state of art for ischemic stroke treatment in Campania region, Italy.

BACKGROUND: According to the last Italian report by the Ministry of Health in 2018, the estimated number of acute ischemic strokes (AIS) in Campania is 10,000/year, with an expected number of 1390 intravenous thrombolysis (IVT) and 694 mechanical thrombectomies (MT). In 2017, only 1.5% of expected patients received IVT and 0.2% MT. This study analyzed the trend of IVT and MT in 2019-2020 and depicted the state of art of Stroke Care in Campania. METHODS: From the regional health task force, we obtained the hospital discharge forms from all private and public hospitals in Campania; we selected patients with a principal diagnosis of AIS and measured the rate of patients admitted to neurology units and the rate of IVT, MT, and IVT + MT for both 2019 and 2020. RESULTS: In 2019, we observed 4817 admissions for AIS; 2858/4817 (59.3%) patients were admitted to neurology units. Out of 4817 patients, 192 received IVT, 165 MT, and 131 IVT + MT (488 treated patients; 10.1%). In 2020, we observed 4129 admissions for AIS; 2502/4129 (62.7%) patients were admitted to neurology units. Out of 4129 patients, 198 received IVT, 250 MT, and 180 IVT + MT (628 treated patients; 15.2%). These results showed that despite a reduction of AIS admissions in 2020, the relative and absolute rate of recanalization treatments increased. However, the number of patients who were not admitted to neurology units nor received acute treatments remained dramatically high. CONCLUSION: Despite the development of acute treatments, the Campania Stroke Network still needs significative efforts to improve.

Neuropsychological assessment in different King's clinical stages of amyotrophic lateral sclerosis.

Emerging evidence shows that cognitive deficits associated with frontal lobe dysfunction occur from early stages of amyotrophic lateral sclerosis (ALS). We aimed to assess neuropsychological functioning at different stages of ALS to further delineate the occurrence of cognitive impairment alongside the trajectory of ALS as defined by standard assessment procedures. We investigated several cognitive domains in 74 ALS patients classified into four different clinical stages of disease, according to a recently validated staging system for ALS (known as 'King's' system), and evaluated and compared the corresponding cognitive profiles. We found that data derived from global cognitive assessment and several executive (i.e. Frontal Assessment Battery and Trail Making Test B-A) and long-term memory (i.e. memory prose) tests were significantly different among the subsets of ALS patients, showing poorer performances with increasing clinical disability. In conclusion, our preliminary results support the notion that mainly frontotemporal abilities may be impaired during the ALS course and suggest that neuropsychological information could supplement the current clinical staging of patients. However, ALS-specific multi-domain screening instruments, which allow to correct neuropsychological scores for physical disability, should be validated in larger populations worldwide and routinely introduced in clinical practice.

Microstructural changes across different clinical milestones of disease in amyotrophic lateral sclerosis.

Neurodegenerative process in amyotrophic lateral sclerosis (ALS) has been proven to involve several cortical and subcortical brain regions within and beyond motor areas. However, how ALS pathology spreads progressively during disease evolution is still unknown. In this cross-sectional study we investigated 54 ALS patients, divided into 3 subsets according to the clinical stage, and 18 age and sex-matched healthy controls, by using tract-based spatial statistics (TBSS) diffusion tensor imaging (DTI) and voxel-based morphometry (VBM) analyses. We aimed to identify white (WM) and gray matter (GM) patterns of disease distinctive of each clinical stage, corresponding to specific clinical milestones. ALS cases in stage 2A (i.e., at diagnosis) were characterized by GM and WM impairment of left motor and premotor cortices and brainstem at ponto-mesenchephalic junction. ALS patients in clinical stage 2B (with impairment of two functional regions) exhibited decreased fractional anisotropy (FA) (p<0.001, uncorrected) and increased mean (MD) and radial diffusivity (RD) (p<0.001, uncorrected) in the left cerebellar hemisphere and brainstem precerebellar nuclei, as well as in motor areas, while GM atrophy (p<0.001, uncorrected) was detected only in the left inferior frontal gyrus and right cuneus. Finally, ALS patients in stage 3 (with impairment of three functional regions) exhibited decreased FA and increased MD and RD (p<0.05, corrected) within WM underneath bilateral pre and postcentral gyri, corpus callosum midbody, long associative tracts and midbrain, while no significant clusters of GM atrophy were observed. Our findings reinforce the hypothesis that the neurodegenerative process propagates along the axonal pathways and develops beyond motor areas from early stages, involving progressively several frontotemporal regions and their afferents and efferents, while the detection of GM atrophy in earlier stages and its disappearance in later stages may be the result of reactive gliosis.

Functional overlap and divergence between ALS and bvFTD.

Amyotrophic lateral sclerosis (ALS) and behavioral variant frontotemporal dementia (bvFTD) lie on a clinical, pathologic, and genetic continuum. Neuroimaging techniques have proven to be potentially useful to unravel the shared features of these syndromes. Using resting-state functional magnetic resonance imaging (RS-fMRI), we investigated functional connectivity of brain networks in 15 ALS and 15 bvFTD patients in early stages of disease and 15 healthy controls, looking expressly for connectivity pattern divergence or overlap between the 2 disorders. Compared with controls, we found decreased RS-fMRI signals within sensorimotor, right frontoparietal, salience, and executive networks in both patient groups. Within the default mode network (DMN), divergent connectivity patterns were observed, with RS-fMRI signals in the posterior cingulate cortex enhanced in bvFTD patients and suppressed in ALS patients. Our findings confirm that ALS and bvFTD not only broadly share common RS-fMRI connectivity patterns, probably representing different phenotypical expressions of the same neurodegenerative process, but also differ in the DMN, probably reflecting a different stage of neurodegeneration.

An Italian kindred with FALS due to c.149T>C mutation in the SOD1 gene: case report of an affected family member.

We report the first Italian kindred with Familial Amyotrophic Lateral Sclerosis (FALS) due to c.149T>C mutation in the exon 5 of superoxide dismutase-1 (SOD1) gene. The proband was a 49-year-old woman who came to our observation because of an history of progressive limbs weakness and gait impairment. She belonged to a family of 24 affected members. The prevalent phenotype of the affected members was characterized by slowly progressive spinal impairment with proximal distribution of weakness, and bulbar involvement in advanced stages. We briefly reviewed the few previous reports about the same SOD1 mutation and discussed the hypothesis that structural instability of the mutant codon 149 protein may underlie some toxic effects significantly involved in FALS pathogenesis.

Motor and extramotor neurodegeneration in amyotrophic lateral sclerosis: a 3T high angular resolution diffusion imaging (HARDI) study.

In amyotrophic lateral sclerosis (ALS), diffusion weighted magnetic resonance imaging (DW-MRI) has produced mounting evidence of a widespread white matter (WM) damage within motor and extramotor pathways. To provide novel information about the degenerative process in ALS, overcoming some of the limitations imposed by diffusion tensor imaging (DTI), we performed a high angular resolution diffusion imaging (HARDI) analysis of DW-MRI data. Generalized fractional anisotropy (GFA) was evaluated in 19 patients with ALS and 19 matched control subjects, and was correlated with clinical scores of disability, pyramidal impairment by upper motor neuron (UMN) score and frontal dysfunction by the Frontal Systems Behaviour (FrSBe) scale. Results demonstrated that ALS patients showed a significant decrease of GFA in the WM tracts underneath the left and right precentral gyri and the body of the corpus callosum (p < 0.05, corrected), where GFA was significantly related to UMN scores (p < 0.001, uncorrected); and in the left superior longitudinal fasciculus (p < 0.05, corrected), where GFA was significantly related to FrSBe scale scores (p < 0.01, uncorrected). In conclusion, this study revealed a pattern of motor and extramotor frontal diffusivity abnormalities (probably related to behavioural and cognitive dysfunctions) showing a spatial distribution similar to what was previously described in ALS - frontotemporal dementia continuum.

Clinical features and lifestyle of patients with amyotrophic lateral sclerosis in Campania: brief overview of an Italian database.

BACKGROUND: Physical activity and occupational exposures appeared to play a relevant role in pathogenesis of amyotrophic lateral sclerosis (ALS), a neurodegenerative disease of unknown origin. MATERIALS AND METHODS: We aimed to make an overview of the clinical characteristics and lifestyle (occupation and sport) of a population of 395 patients with ALS from Campania, in southern Italy. RESULTS: ALS onset resulted anticipated of about 11 years in industry workers, whilst the more frequent site of onset among farmers was upper limbs. Compared to non-athletes, athletes, particularly soccer players, showed a 7 years anticipation of ALS onset, with higher mortality after 5 years. DISCUSSION AND CONCLUSIONS: We suggest that subjects genetically prone to abnormal response to hypoxia during strenuous physical activity or exposed to neurotoxic agents, such as athletes, farmers or industry workers, might present increased risk to develop ALS. Future case-control and follow-up studies on our population should be implemented to deepen the present results.

Interaction between aging and neurodegeneration in amyotrophic lateral sclerosis.

We assessed the spontaneous blood-oxygen-level-dependent signal fluctuations in the resting-state brain networks of amyotrophic lateral sclerosis patients and their relation to physiologically sensitive and disease modified functional magnetic resonance imaging parameters. Resting-state functional magnetic resonance imaging was performed at 3 Tesla on 20 amyotrophic lateral sclerosis patients with minimal frontal cognitive dysfunction and 20 age- and sex-matched healthy volunteers. Resting-state network maps were extracted with independent component analysis and group-level statistical analyses were performed to detect disease and disease-by-age interaction effects. Whole-brain global and regional atrophy measures were obtained from same-session structural scans. The sensori-motor network showed significant disease effects, with signals suppressed in patients bilaterally in the primary motor cortex. The default-mode network showed a significant disease-by-age interaction in the posterior cingulate cortex, where signals correlated with age positively in patients and negatively in controls. Both disease and disease-by-age interaction effects were detected in the right fronto-parietal network. Although global atrophy did not show significant differences, regions of reduced gray matter volume were detected in patients compared with controls adjacent to regions of reduced functional connectivity. Our results confirm that resting-state functional magnetic resonance imaging signals in the sensori-motor network are suppressed in amyotrophic lateral sclerosis. A similar suppression is evident in the right fronto-parietal network, possibly reflecting the patients' frontal dysfunction and right-lateralized patterns of regional atrophy. The interaction between disease and aging in the default-mode network unravels a possible mechanism of compensation between motor and extramotor systems emerging as a supplementary functional push to help motor disturbances.

Amyotrophic lateral sclerosis and multiple sclerosis overlap: a case report.

The concurrence of amyotrophic lateral sclerosis (ALS) and multiple sclerosis (MS) is extremely rare. We reported the case of a 33-year-old woman with a past history of paresthesias at the right hand, who developed progressive quadriparesis with muscular atrophy of limbs and, finally, bulbar signs and dyspnea. Clinical and neurophysiologic investigations revealed upper and lower motor neuron signs in the bulbar region and extremities, suggesting the diagnosis of ALS. Moreover, magnetic resonance imaging (MRI) and cerebrospinal fluid (CSF) analysis demonstrated 3 periventricular and juxtacortical lesions, hyperintense in T2 and FLAIR sequences, and 3 liquoral immunoglobulin G (IgG) oligoclonal bands, consistent with diagnosis of primary progressive MS (PPMS). This unusual overlap of ALS and MS leads to the discussion of a hypothetical common pathological process of immunological dysfunction in these two disorders, although the role of immune response in ALS remains ambivalent and unclear.