Luisa Vinciguerra

Neurotoxicity of Acrylamide in Exposed Workers

Acrylamide (ACR) is a water-soluble chemical used in different industrial and laboratory processes. ACR monomer is neurotoxic in humans and laboratory animals. Subchronic exposure to this chemical causes neuropathies, hands and feet numbness, gait abnormalities, muscle weakness, ataxia, skin and in some cases, cerebellar alterations. ACR neurotoxicity involves mostly the peripheral but also the central nervous system, because of damage to the nerve terminal through membrane fusion mechanisms and tubulovescicular alterations. Nevertheless, the exact action mechanism is not completely elucidated. In this paper we have reviewed the current literature on its neurotoxicity connected to work-related ACR exposure. We have analyzed not only the different pathogenetic hypotheses focusing on possible neuropathological targets, but also the critical behavior of ACR poisoning. In addition we have evaluated the ACR-exposed workers case studies. Despite all the amount of work which have being carried out on this topic more studies are necessary to fully understand the pathogenetic mechanisms, in order to propose suitable therapies.

A Review of Transcranial Magnetic Stimulation in Vascular Dementia

Vascular dementia (VaD) is a clinical syndrome that encompasses a wide spectrum of cognitive disorders caused by cerebrovascular disease. The subcortical ischemic form of VaD is clinically homogeneous and a major cause of cognitive impairment in the elderly. Vascular lesions contribute to cognitive decline in neurodegenerative dementias, and VaD and Alzheimer’s disease often coexist and share clinical features and multiple neurotransmission involvement. These similarities have led several investigators to use transcranial magnetic stimulation (TMS) to enucleate a neurophysiological profile of VaD. TMS studies have identified a pattern of cortical hyperexcitability probably related to the disruption of the integrity of white matter lesions due to cerebrovascular disease. The present review provides a perspective of these TMS techniques by further understanding the role of different neurotransmission pathways and plastic remodeling of neuronal networks in the pathogenesis of VaD.

Excitability of the motor cortex in de novo patients with celiac disease

Introduction Celiac disease (CD) may initially present as a neurological disorder or may be complicated by neurological changes. To date, neurophysiological studies aiming to an objective evaluation of the potential central nervous system involvement in CD are lacking. Objective To assess the profile of cortical excitability to Transcranial Magnetic Stimulation (TMS) in a group of de novo CD patients. Materials and methods Twenty CD patients underwent a screening for cognitive and neuropsychiatric symptoms by means of the Mini Mental State Examination and the Structured Clinical Interview for DSM-IV Axis I Disorders, respectively. Instrumental exams, including electroencephalography and brain computed tomography, were also performed. Cortico-spinal excitability was assessed by means of single and paired-pulse TMS using the first dorsal interosseus muscle of the dominant hand. TMS measures consisted of resting motor threshold, motor evoked potentials, cortical silent period (CSP), intracortical inhibition (ICI) and facilitation (ICF). None of the CD was on gluten-free diet. A group of 20 age-matched healthy controls was used for comparisons. Results CD showed a significantly shorter CSP (78.0 vs 125.0 ms, p<0.025), a reduced ICI (0.3 vs 0.2, p<0.045) and an enhanced ICF (1.1 vs 0.7, p<0.042) compared to controls. A dysthymic disorder was identified in five patients. The effect size between dysthymic and non-dysthymic CD patients indicated a low probability of interference with the CSP (Cohens d -0.414), ICI (-0.278) and ICF (-0.292) measurements. Conclusion A pattern of cortical excitability characterized by “disinhibition” and “hyperfacilitation” was found in CD patients. Immune system dysregulation might play a central role in triggering changes of the motor cortex excitability.

TMS follow-up study in patients with vascular cognitive impairment-no dementia

Vascular cognitive impairment-no dementia (VCI-ND) is a condition at risk for future dementia and should be the target of preventive strategies. Recently, an enhanced intracortical facilitation observed in VCI-ND patients was proposed as a candidate neurophysiological marker of the disease process. The aim of this study was to monitor the excitability of the motor cortex and the functioning of excitatory/inhibitory intracortical circuits in patients with VCI-ND after a follow-up period of approximately 2 years, in order to pick out early markers of disease progression into dementia. Nine patients and 9 age-matched controls were re-evaluated for single and paired pulse TMS measures of cortical excitability, as well as for neuropsycological and functional assessment. Compared to the first evaluation, patients showed a decrease of the median resting motor threshold (rMT). Patients exhibited a significant worsening at Stroop Color-Word Test Interference scores without substantial functional impairment. Our study represents the first evidence of a decrease of rMT in VCI-ND patients during the progression of cognitive impairment. This result might be considered an index of motor cortex plasticity and interpreted as a compensatory mechanism for the loss of motor cortex neurons.

Effect of a Gluten-Free Diet on Cortical Excitability in Adults with Celiac Disease

Introduction An imbalance between excitatory and inhibitory synaptic excitability was observed in de novo patients with celiac disease (CD) in a previous study with Transcranial Magnetic Stimulation (TMS), suggesting a subclinical involvement of GABAergic and glutamatergic neurotransmission in asymptomatic patients. The aim of this investigation was to monitor the eventual changes in the same cohort of patients, evaluated after a period of gluten-free diet. Methods Patients were re-evaluated after a median period of 16 months during which an adequate gluten-free diet was maintained. Clinical, cognitive and neuropsychiatric assessment was repeated, as well as cortical excitability by means of single- and paired-pulse TMS from the first dorsal interosseous muscle of the dominant hand. Results Compared to baseline, patients showed a significant decrease of the median resting motor threshold (from 35% to 33%, p<0.01). The other single-pulse (cortical silent period, motor evoked potentials latency and amplitude, central motor conduction time) and paired-pulse TMS measures (intracortical inhibition and intracortical facilitation) did not change significantly after the follow-up period. Antibodies were still present in 7 subjects. Discussion In patients under a gluten-free diet, a global increase of cortical excitability was observed, suggesting a glutamate-mediated functional reorganization compensating for disease progression. We hypothesize that glutamate receptor activation, probably triggered by CD-related immune system dysregulation, might result in a long-lasting motor cortex hyperexcitability with increased excitatory post-synaptic potentials, probably related to phenomena of long-term plasticity. The impact of the gluten-free diet on subclinical neurological abnormalities needs to be further explored.

Cholinergic circuitry functioning in patients with vascular cognitive impairment – no dementia

BACKGROUND An impairment of central cholinergic activity, as evaluated non-invasively by the short-latency afferent inhibition (SAI) of motor responses evoked by transcranial magnetic stimulation (TMS), was observed in patients with Alzheimers disease (AD) and amnestic Mild Cognitive Impairment. Conversely, the involvement of central cholinergic neurotransmission in vascular dementia (VaD) is still under debate and data on Vascular Cognitive Impairment--No Dementia (VCI-ND) at risk for future VaD are lacking. OBJECTIVE To test for the first time SAI in patients with VCI-ND. METHODS Single-pulse TMS measures of cortical excitability and SAI were evaluated in 25 VCI-ND patients with subcortical ischemic lesions and 20 age-matched healthy controls. Functional status, neuropsychological tests evaluating frontal lobe abilities, and white matter lesions (WMLs) load were assessed. RESULTS A significant difference was found between patients and controls for the mean SAI, although this result did not resist after the Bonferroni correction. In the whole group of patients and controls, SAI showed a correlation with worse scores at the Montreal Cognitive Assessment (r = 0.376, p < 0.01). SAI also positively correlated with the total vascular burden (r = 0.345, p < 0.05) but not with the WML severity. CONCLUSIONS Central cholinergic pathway does not seem to be involved in VCI-ND, and the current results differ from those reported in primary cholinergic forms of dementia, such as AD. SAI might represent a valuable additional tool in the differential diagnosis of the dementing processes and in identifying potential responders to cholinergic agents.

Noninvasive Neuromonitoring: Current Utility in Subarachnoid Hemorrhage, Traumatic Brain Injury, and Stroke

Noninvasive neuromonitoring is increasingly being used to monitor the course of primary brain injury and limit secondary brain damage of patients in the neurocritical care unit. Proposed advantages over invasive neuromonitoring methods include a lower risk of infection and bleeding, no need for surgical installation, mobility and portability of some devices, and safety. The question, however, is whether noninvasive neuromonitoring is practical and trustworthy enough already. We searched the recent literature and reviewed English-language studies on noninvasive neuromonitoring in subarachnoid hemorrhage, traumatic brain injury, and ischemic and hemorrhagic stroke between the years 2010 and 2015. We found 88 studies that were eligible for review including the methods transcranial ultrasound, electroencephalography, evoked potentials, near-infrared spectroscopy, bispectral index, and pupillometry. Noninvasive neuromonitoring cannot yet completely replace invasive methods in most situations, but has great potential being complementarily integrated into multimodality monitoring, for guiding management, and for limiting the use of invasive devices and in-hospital transports for imaging.

Acute isolated trochlear nerve palsy in a patient with cavernous carotid aneurysm and visit-to-visit variability in systolic blood pressure.

Isolated fourth nerve palsy in the elderly is an unusual occurrence due to acquired conditions, being the cavernous carotid aneurysm (CCA) very rarely described (1). An 80-year-old woman experienced sudden onset of double vision when looking downward and to the right, preceded by transient headache. She had visit-to-visit variability (VVV) in systolic blood pressure (SBP). Left hypertropia with positive Bielschowsky test was suggestive of left superior oblique muscle palsy. Neuroimaging showed an intracavernous aneurysm of the left internal carotid artery (ICA) (Fig. 1). Given the size, site, and age-related risk, the aneurysm was not treated. After two-months of blood pressure medications intake, diplopia completely recovered. VVV in SBP may have caused a growth of the CCA (2), leading to a shift of the ICA and a selective compression of the trochlear nerve. Alternatively, an impairment of the intracavernous vascular supply to the nerve via tentorial artery might be hypothesized. A complete diagnostic work-up to detect structural lesions is mandatory in isolated fourth nerve palsy. The identification of VVV in SBP is needed to prevent the growth and rupture of intracranial aneurysms. Giuseppe Lanza, Luisa Vinciguerra, Valentina Puglisi, Salvatore Giuffrida, Pietro Foti, Giuseppe Zelante, Giovanni Pennisi, and Rita Bella*

Can the absence of bilateral posterior communicating artery predispose to artery of Percheron infarction

Artery of Percheron (AOP) is a rare anatomic variant of posterior cerebral circulation consisting in a single arterial trunk that arises by the proximal segment (P1) of one posterior cerebral artery (PCA) and supplies both paramedian thalami and rostral midbrain. We report a case of AOP infarction in a patient with evidence of bilateral posterior communicating artery (PCoA) absence. A 65-year-old man presented to the emergency department 24 h after experiencing drowsiness and gait instability. Neurological examination revealed impaired consciousness, dysarthria, right ptosis, vertical gaze palsy, hypoesthesia, and hemiparesis in the left side. Brain magnetic resonance imaging (MRI) showed asymmetrical infarctions in both paramedian thalami (Fig. 1a) with midbrain involvement (Fig. 1b) and a ‘V’sign (1) in the interpeduncolar fossa (Fig. 1c). Magnetic resonance angiogram (MRA) showed the absence of both PCoAs (Fig. 1d). Thus, we managed patient as an ischemic stroke. AOP infarction is a rare occurrence and often results in a diagnostic challenge for the neurologist. Cardioembolism is the most common identified etiology (2), although an extensive diagnostic workup failed to detect any atherothrombotic or embolic cause in our patient. Based on MRA findings of bilateral PCoA absence, we hypothesize a hemodynamic mechanism as contributing factor for AOP infarction. PCoAs absence is a congenital variant of Willis circle that occurs in 16×6% of the general population (3), and it is known that it becomes symptomatic when associated with internal carotid artery stenosis (4). However, some evidences suggest that PCoA hypoplasia per se predisposes to thalamic lacunar stroke because of the critical role of PCoA in the collateral supply of proximal PCA territory (5). Thus, we suggest that the occurrence of the two anatomic variants might have led to a hemodynamic infarction due to a poor regional collateral flow.

Impaired Cerebral Haemodynamics in Vascular Depression: Insights From Transcranial Doppler Ultrasonography

Introduction: Late-life depression is a well-known risk factor for future dementia. Increasing evidences also show a link between cerebral hypoperfusion and neurodegeneration, although data on Transcranial Doppler ultrasonography (TCD)-derived measures in patients with “Vascular Depression” (VD) are lacking. The aim of this study was to assess and correlate TCD parameters with cognitive function and severity of subcortical ischemic vascular disease in a sample of VD patients. Methods: Seventy six patients (mean age 72.5 ± 5.3 years; 53.9% females) met the DSM-5 diagnostic criteria for unipolar major depression. Mean blood flow velocity (MBFv) and pulsatility index (PI) were recorded from the middle cerebral artery. Quantification of depressive symptoms (17-item Hamilton Depression Rating Scale –HDRS), neuropsychological test evaluating frontal lobe abilities (Stroop Color-Word test interference—Stroop T), and white matter lesions (WMLs) load according to the Fazekas visual score were also assessed. Results: WMLs severity was mild in 20 patients (group I), moderate in 32 (group II), and severe in 24 (group III). The groups were comparable in terms of clinical features, vascular risk factors profile, and HDRS score, whereas Stroop T score was worse in group III. An increased PI and a reduced MBFv were found in VD patients with severe WMLs. According to the regression analysis, a reduced MBFv was independently and significantly associated with depressive symptoms and executive dysfunction, even after adjusting for demographic features and vascular risk factors. Similarly, an independent and significant association was observed between the increase of PI and both Stroop T and WMLs severity. Conclusions: A TCD profile of low perfusion and high vascular resistance in VD patients suggests a diffuse cerebrovascular pathology likely arising from the small vessels and then extending to larger arteries. Hemodynamic dysfunction might play a pathogenic role in the development of cognitive impairment in patients with late-life depression and subcortical ischemic vascular disease. TCD represents a valuable tool in the early detection, assessment, and management of VD patients at risk for dementia.