Hyperconnectivity in Dementia Is Early and Focal and Wanes with Progression.

We investigated in a longitudinal multicenter cohort study functional cortical connectivity changes along the course of frontotemporal dementia (FTD) and Alzheimer's disease (AD) from the prodromal stage of the diseases. Electroencephalography (EEG) was recorded in 18 FTD and 18 AD patients at the prodromal stage of dementia, at dementia onset, and 3 years after dementia onset. Twenty healthy controls (HC) underwent EEG recordings at the same time interval as the patients. Mutual information (MI) analysis measured the strength of functional network connectivity. FTD and AD patients showed greater MI at the prodromal stage of dementia (FTD vs. HC P = 2 × 10-8; AD vs. HC P = 4 × 10-3). Local connectivity was higher in left and right frontal areas of FTD (P = 7 × 10-5 and 0.03) and in left and right posterior areas in AD (P = 3 × 10-5 and 5 × 10-5) versus HC. We showed cortical hyperconnectivity at the prodromal stage of dementia in areas involved in the specific pathological process of FTD (frontal regions) and AD (posterior regions). Hyperconnectivity disappeared during follow-up, thus suggesting that it is an early electrophysiological feature of dementia, potentially useful to identify prodromal FTD and AD.

Cerebral venous thrombosis without thrombocytopenia after a single dose of COVID-19 (Ad26.COV2.S) vaccine injection: a case report.

BACKGROUND: The coronavirus pandemic became the hard challenge for the modern global health system. To date, vaccination is the best strategy against Sars-Cov-2-related illness. About 3 billions of people received at least one of the approved vaccines. The related adverse events were reported during the various experimental phases, but newer and less common side effects are emerging post-marketing. Vaccine-induced thrombocytopenia with thrombosis (VITT) is one of these insidious adverse reactions and it is considered responsible of venous thrombosis, in both the splanchnic and the cerebral circulation. Although its mechanism has been presumably established, resembling that observed in heparin-induced thrombocytopenia, some venous thromboses seem not to recognize this etiology and their pathogenesis remains unknown. Here we described a case of cerebral venous thrombosis after administration of the Ad26.COV2.S, presenting without thrombocytopenia, paving the way for possible novel causes of this vaccine-induced pathological condition. CASE PRESENTATION: A 45-year-old woman came to our observation for bilateral periorbital headache associated with retro-orbital pain started 8 days after administration of COVID vaccine Jannsen. Ophthalmologic exam showing a bilateral papilledema raised the suspicion of intracranial hypertension. Cerebral magnetic resonance imaging revealed signal alteration with T1-positive contrast enhancement in the right temporal and insular lobes suggestive of cerebral venous thrombosis. The absence of thrombocytopenia and platelet factor 4 (PF-4) antibodies led the clinicians to rule out VITT. The patient was treated successfully with warfarin. CONCLUSION: Venous thrombosis occurring after COVID-19 vaccination represents an adverse event of special interest. Patients with thrombosis and thrombocytopenia appear to be affected by a general thrombophilic state, sustained by an autoimmune mechanism, and show a higher mortality. Thrombosis without thrombocytopenia's pathogenesis has not yet been clarified, but laboratory data and good response to vitamin K antagonists help clinicians in the differential diagnosis with VITT. Future research will allow us to discover other possible mechanisms and maybe identify a subgroup of patients with a higher risk of developing this medical complication.

The predictive power of transcranial sonography in movement disorders: a longitudinal cohort study.

Transcranial sonography (TCS) is a noninvasive, easily performed, and commonly available neuroimaging technique useful for the study of brain parenchyma in movement disorders. This tool has been increasingly used in the diagnosis of Parkinson's disease and atypical parkinsonism. The aim of the study was to evaluate the applicability of this technique as supportive tool in the early diagnosis of movement disorders. We performed TCS on 315 individuals which were diagnosed as healthy controls or affected by idiopathic Parkinson's disease, monogenetic subtypes of Parkinson's disease, atypical parkinsonism, and Dementia with Lewy bodies. Five TCS diagnostic patterns were defined on the basis of substantia nigra's and lenticular nuclei's echogenicity. TCS evaluations were performed by two blinded neuro-sonographers. Clinical diagnosis on all individuals was performed at baseline and at 4-year follow-up. The concordance rate between TCS patterns and clinical diagnosis and the specificity of TCS pattern to discriminate each group of individuals were compared at baseline and at follow-up. The concordance rate between TCS patterns and clinical diagnosis of all individuals was 84% at baseline and increased at follow-up (91%) significantly (p = 0.01). The specificity of TCS pattern in the comparison between patients diagnosed as affected by idiopathic Parkinson's disease and atypical parkinsonism showed a significant increase at follow-up (p = 0.03). Our study strongly confirms the role of TCS as a noninvasive and cost-effective tool in early diagnosis of movement disorders.

Cortical network modularity changes along the course of frontotemporal and Alzheimer's dementing diseases.

Cortical network modularity underpins cognitive functions, so we hypothesized its progressive derangement along the course of frontotemporal (FTD) and Alzheimer's (AD) dementing diseases. EEG was recorded in 18 FTD, 18 AD, and 20 healthy controls (HC). In the FTD and AD patients, the EEG recordings were performed at the prodromal stage of dementia, at the onset of dementia, and three years after the onset of dementia. HC underwent three EEG recordings at 2-3-year time interval. Information flows underlying EEG activity recorded at electrode pairs were estimated by means of Mutual Information (MI) analysis. The functional organization of the cortical network was modelled by means of the Graph theory analysis on MI adjacency matrices. Graph theory analysis showed that the main hub of HC (Parietal area) was lost in FTD patients at onset of dementia, substituted by provincial hubs in frontal leads. No changes in global network organization were found in AD. Despite a progressive cognitive impairment during the FTD and AD progression, only the FTD patients showed a derangement in the cortical network modularity, possibly due to dysfunctions in frontal functional connectivity.

Median-to-Ulnar Nerve Communication in Carpal Tunnel Syndrome: An Electrophysiological Study.

The median-to-ulnar communicating branch (MUC) is an asymptomatic variant of the upper limb innervation that can lead to interpretation errors in routine nerve conduction studies. The diagnosis of carpal tunnel syndrome (CTS) or ulnar nerve lesions can be complicated by the presence of MUC. In this study, we describe electrophysiological features of MUC in CTS patients presenting to our clinic. We enrolled MUB cases from consecutive CTS patients referred to our laboratory between the years 2014 and 2019. MUC was present in 53 limbs (36 patients) from the studied population. MUC was bilateral in 53% of patients. MUC type II was the most common subtype (74%), followed by types III and I; more coexisting MUC types were found in the majority of tested limbs. A positive correlation was demonstrated between the severity of CTS and the presence of positive onset, faster CV, or a double component of the compound muscle action potentials. We emphasize the importance of suspecting the presence of MUC in CTS in the presence of a positive onset or a double component in routine motor conduction studies.

Diabetes Mellitus and Amyotrophic Lateral Sclerosis: A Systematic Review.

BACKGROUND: Amyotrophic Lateral Sclerosis (ALS) is a degenerative disorder which affects the motor neurons. Growing evidence suggests that ALS may impact the metabolic system, including the glucose metabolism. Several studies investigated the role of Diabetes Mellitus (DM) as risk and/or prognostic factor. However, a clear correlation between DM and ALS has not been defined. In this review, we focus on the role of DM in ALS, examining the different hypotheses on how perturbations of glucose metabolism may interact with the pathophysiology and the course of ALS. METHODS: We undertook an independent PubMed literature search, using the following search terms: ((ALS) OR (Amyotrophic Lateral Sclerosis) OR (Motor Neuron Disease)) AND ((Diabetes) OR (Glucose Intolerance) OR (Hyperglycemia)). Review and original articles were considered. RESULTS: DM appears not to affect ALS severity, progression, and survival. Contrasting data suggested a protective role of DM on the occurrence of ALS in elderly and an opposite effect in younger subjects. CONCLUSIONS: The actual clinical and pathophysiological correlation between DM and ALS is unclear. Large longitudinal prospective studies are needed. Achieving large sample sizes comparable to those of common complex diseases like DM is a challenge for a rare disease like ALS. Collaborative efforts could overcome this specific issue.

Agitation and Dementia: Prevention and Treatment Strategies in Acute and Chronic Conditions.

Agitation is a behavioral syndrome characterized by increased, often undirected, motor activity, restlessness, aggressiveness, and emotional distress. According to several observations, agitation prevalence ranges from 30 to 50% in Alzheimer's disease, 30% in dementia with Lewy bodies, 40% in frontotemporal dementia, and 40% in vascular dementia (VaD). With an overall prevalence of about 30%, agitation is the third most common neuropsychiatric symptoms (NPS) in dementia, after apathy and depression, and it is even more frequent (80%) in residents of nursing homes. The pathophysiological mechanism underlying agitation is represented by a frontal lobe dysfunction, mostly involving the anterior cingulate cortex (ACC) and the orbitofrontal cortex (OFC), respectively, meaningful in selecting the salient stimuli and subsequent decision-making and behavioral reactions. Furthermore, increased sensitivity to noradrenergic signaling has been observed, possibly due to a frontal lobe up-regulation of adrenergic receptors, as a reaction to the depletion of noradrenergic neurons within the locus coeruleus (LC). Indeed, LC neurons mainly project toward the OFC and ACC. These observations may explain the abnormal reactivity to weak stimuli and the global arousal found in many patients who have dementia. Furthermore, agitation can be precipitated by several factors, e.g., the sunset or low lighted environments as in the sundown syndrome, hospitalization, the admission to nursing residencies, or changes in pharmacological regimens. In recent days, the global pandemic has increased agitation incidence among dementia patients and generated higher distress levels in patients and caregivers. Hence, given the increasing presence of this condition and its related burden on society and the health system, the present point of view aims at providing an extensive guide to facilitate the identification, prevention, and management of acute and chronic agitation in dementia patients.

Atypical radiological presentation of multiple cystic brain metastases from lung cancer simulating neurocysticercosis.

Brain metastases (BMs) are usually characterised by vasogenic oedema and mass effect, but cystic appearance can rarely occur, mimicking parasitosis, such as neurocysticercosis (NCC). A woman in her mid-50s was admitted for dizziness and upper left extremity paresis. Neuroimaging showed multiple cystic lesions consistent with multiple stages of NCC evolution, and empiric albendazole was started, without any clinical improvement. A whole-body CT revealed a pulmonary lesion in the right superior lobe. Pathological analysis from brain specimen demonstrated a clear cell lung carcinoma. The patient gradually worsened and died 4 months after the diagnosis. In conclusion, multiple cystic BMs are an atypical presentation on neuroimaging; in these cases, a meticulous diagnostic workup should be performed, looking for the possible site of malignancy. Even when it is not possible to perform a biopsy from the primitive lesion, as reported in this case, a brain biopsy should be considered.

A Stage-Based Approach to Therapy in Parkinson's Disease.

Parkinson's disease (PD) is a neurodegenerative disorder that features progressive, disabling motor symptoms, such as bradykinesia, rigidity, and resting tremor. Nevertheless, some non-motor symptoms, including depression, REM sleep behavior disorder, and olfactive impairment, are even earlier features of PD. At later stages, apathy, impulse control disorder, neuropsychiatric disturbances, and cognitive impairment can present, and they often become a heavy burden for both patients and caregivers. Indeed, PD increasingly compromises activities of daily life, even though a high variability in clinical presentation can be observed among people affected. Nowadays, symptomatic drugs and non-pharmaceutical treatments represent the best therapeutic options to improve quality of life in PD patients. The aim of the present review is to provide a practical, stage-based guide to pharmacological management of both motor and non-motor symptoms of PD. Furthermore, warning about drug side effects, contraindications, as well as dosage and methods of administration, are highlighted here, to help the physician in yielding the best therapeutic strategies for each symptom and condition in patients with PD.