Monitoring cognitive and psychological alterations in COVID-19 patients: A longitudinal neuropsychological study.

BACKGROUND: SARS-COV-2 infection has been associated to long-lasting neuropsychiatric sequelae, including cognitive deficits, that persist after one year. However, longitudinal monitoring has been scarcely performed. Here, in a sample of COVID-19 patients, we monitor cognitive, psychological and quality of life-related profiles up to 22 months from resolution of respiratory disease. METHODS: Out of 657 COVID-19 patients screened at Manzoni Hospital (Lecco, Italy), 22 underwent neuropsychological testing because of subjective cognitive disturbances at 6 months, 16 months, and 22 months. Tests of memory, attention, and executive functions were administered, along with questionnaires for depressive and Post-traumatic stress disorder (PTSD) symptoms, psychological well-being and quality of life. Cross-sectional descriptives, correlational, as well as longitudinal analyses considering COVID19-severity were carried out. A preliminary comparison with a sample of obstructive sleep apneas patients was also performed. RESULTS: Around 50% of COVID-19 patients presented with cognitive deficits at t0. The most affected domain was verbal memory. Pathological scores diminished over time, but a high rate of borderline scores was still observable. Longitudinal analyses highlighted improvements in verbal and non-verbal long term memory, as well as attention, and executive functioning. Depression and PTSD-related symptoms were present in 30% of patients. The latter decreased over time and were associated to attentional-executive performance. CONCLUSIONS: Cognitive dysfunctions in COVID-19 patients may extend over 1 year, yet showing a significant recovery in several cases. Cognitive alterations are accompanied by a significant psychological distress. Many patients displaying borderline scores, especially those at higher risk of dementia, deserve clinical monitoring.

Headache in cerebral venous thrombosis.

Headache has been consistently reported as the most common symptom of cerebral venous thrombosis and as the most frequent presenting feature. It is often the heralding symptom, preceding other manifestations of the disease by days or even weeks. This aspect highlights the importance of recognizing headache due to cerebral venous thrombosis, as early recognition of the disease can lead to a rapid diagnosis with appropriate imaging techniques and as early treatment with heparin can dramatically change the course of the disease and alter the prognosis. Unfortunately, although common, the headache has no specific features, and the clinical presentation of CVT is highly variable, making the correct diagnosis in the emergency setting a challenging task for clinicians, even in the case of highly specialized ones such as neurologists. In this review, we will briefly summarize the epidemiology and physiopathology of CVT, and then we will discuss in more details the causes, features, and course of headache, focusing on its relevance for differential diagnosis and on red flags that should suggest the possibility of CVT as the cause of the headache.

Size, shape and location of lacunar strokes and correlation with risk factors.

OBJECTIVE: We evaluated a prospective cohort of 150 patients under observation in our centre for lacunar strokes. The purpose of this study was to investigate if lacunar stroke of varying size, shape and locations had different risk factors between them and possibly different mechanisms and causes. PATIENTS AND METHODS: 150 patients with a lacunar stroke were included in the present study. Infarcts were classified by size, shape and location. We evaluated the correlation between several risk factors of stroke and the radiological characteristics of the infarcts. RESULTS: Older age was associated with the presence of a basal ganglia lesion (p < 0.001) and with the presence of a smaller lesion (trend to statistical significance, p = 0.07). Patients with infarcts >15 mm had higher NIHSS score at admission (p 0.01). CONCLUSION: The different subtypes of lacunar infarcts have distinct pathogenesis. Further studies, with a larger numbers of patients, are necessary to confirm our data.

Irisin and BDNF serum levels and behavioral disturbances in Alzheimer's disease.

Behavioral dysfunctions (BPSD) represent the most important problem in Alzheimer's dementia (AD) management. We assessed the serum levels of two myokines in AD patients, preliminary investigating, as secondary aim, their role as potential biomarkers for agitation/aggression (AA) and aberrant motor behavior (AMB): irisin, since it is able to modify the motor pattern, and BDNF, since it was transcribed following irisin stimulation. Forty AD patients were recruited and characterized according to the expressed neuropsychiatric syndrome. Myokines were measured by ELISA. Irisin serum levels were slightly elevated in AA+ patients (+ 10.0%; p < 0.05) and correlated with the duration of AA (r = 0.74, p < 0.03). BDNF failed to show such differences. We propose that these selected myokines are not useful as surrogate markers for agitation in AD, but might represent interesting secondary outcomes when testing drugs for those BPSD implying elevated motor activity.

Voluptuary Habits and Risk of Frontotemporal Dementia: A Case Control Retrospective Study.

Alcohol, coffee, and tobacco consumption was assessed on 151 FTD outpatients and 151 matched controls in a multicenter retrospective case-control design. No association was found for smoking and coffee intake. The risk of FTD was decreased by alcohol consumption (adj. OR 0.30, 95% CI 0.14-0.63); risk reduction was significant in current alcohol consumers (adj. OR 0.22, 95% CI 0.10-0.51). The risk of FTD inversely correlated with the duration of exposure (adj. OR 0.88, 95% CI 0.81-0.95, for every 5 years of exposure increase). Retrospective information and the unknown amount of consumed alcohol are limits of the present work.

Genetic Counseling Dilemmas for a Patient with Sporadic Amyotrophic Lateral Sclerosis, Frontotemporal Degeneration & Parkinson's Disease.

Amyotrophic lateral sclerosis (ALS), frontotemporal degeneration and Parkinson's disease may be different expressions of the same neurodegenerative disease. However, association between ALS and parkinsonism-dementia complex (ALS-PDC) has only rarely been reported apart from the cluster detected in Guam. We report a patient presenting with ALS-PDC in whom pathological mutations/expansions were investigated. No other family members were reported to have any symptoms of a neurological condition. Our case demonstrates that ALS-PDC can occur as a sporadic disorder, even though the coexistence of the three clinical features in one patient suggests a single underlying genetic cause. It is known that genetic testing should be preferentially offered to patients with ALS who have affected first or second-degree relatives. However, this case illustrates the importance of genetic counseling for family members of patients with sporadic ALC-PDC in order to provide education on the low recurrence risk. Here, we dicuss the ethical, psychological and practical consequences for patients and their relatives.

Donepezil modulates the endogenous immune response: implications for Alzheimer's disease.

OBJECTIVE: Donepezil (DNPZ) is a drug commonly used for Alzheimer's disease (AD) that may favour a T helper 2 phenotype leading to increased naturally occurring auto-antibodies (NAb) against beta-amyloid (Aß). We hypothesized the involvement of the cholinergic receptors [α7-nicotnic acetylcholine receptor (α7nAChR)] expressed on peripheral blood mononuclear cells (PBMC). METHODS: Fifty patients with mild-to-moderate AD, DNPZ treated (DNPZ+, n = 25) or not (DNPZ-, n = 25), and 25 matched controls were enrolled and PBMC extracted for both in vitro cultures, and real-time polymerase chain reaction and chromatin immunoprecipitation assay. Plasma samples were also obtained for Aß and NAb determination. RESULTS: Donepezil increased in vitro the expression of the transcription factor GATA binding protein 3 (GATA3) through α7nAChR, because prevented by the specific antagonist methyllycaconitine. Ex vivo PBMC α7nAChR mRNA expression was increased in both AD groups, while GATA3 expression was not. A significant increase in the GATA3/interleukin 5 promoter association was found in DNPZ+ patients. Finally, DNPZ+ patients showed both significantly higher plasma levels of anti-Aß NAb with respect to DNPZ- patients and Aß 1-42 with respect to normal controls. CONCLUSIONS: Donepezil might modulate a T helper 2 bias via α7nAChR leading to increased expression of NAb. Further studies on the role of the modulation of the immune response against Aß may pave the way to innovative therapeutic strategies for AD. Copyright © 2016 John Wiley & Sons, Ltd.

Muscle ultrasonography for detecting fasciculations in frontotemporal dementia.

Ultrasound detection of muscle fasciculations was recently proposed for assessing lower motor neuron (LMN) dysfunction in ALS patients. Given the continuum between ALS and frontotemporal degeneration (FTD), the aim of the present study was to evaluate muscle ultrasound (MUS) in FTD both for feasibility and prevalence of fasciculations. Twenty-two FTD patients were examined (five muscles bilaterally: biceps brachii, first dorsalis interosseous, T10 paraspinalis, vastus lateralis, tibialis anterior) with a 7-MHz linear array transducer and a fasciculation score (FS) computed. Twenty-two matched cognitively-intact control subjects and six ALS patients were also included. Results showed that MUS was feasible, reliable and well tolerated in all subjects. Two FTD/MND patients displayed very high FS values, similar to those in ALS patients. The remaining 20 FTD patients displayed a mean FS value significantly higher than the control group with six patients (30%) having FS values out of the range of controls. Disease progression rate correlated with the FS. In conclusion, MUS can be easily applied to FTD patients and represents a non-invasive technique for defining LMN involvement in these patients. LMN dysfunction is a frequent condition in FTD and might identify a subset of patients with a different clinical course.

Dissection of the epiaortic and intracranial arteries.

Dissection of epiaortic vessels is a rare event but can have serious clinical consequences such as ischaemic injury to the brain, cerebellum or, more rarely to the retina and is an important cause of stroke in young adults. The main clinical presentation is headache or neck pain, usually but not always associated with Horner syndrome or other local symptoms, followed by an ischemic event in the carotid or vertebral district. Very rarely, the dissection can extend to the intracranial vessels leading to subarachnoid hemorrhage. The time between the headache and the stroke is variable, ranging from a few seconds to weeks. Suspecting an arterial dissection in cases of unexplained head or neck pain in young patients is than crucial to avoid cerebrovascular events; the clinical suspect must be confirmed by ultrasound examination of the epiaortic vessels as a first screening exam, followed by an appropriate neuroimaging study. Treatment with anticoagulants, although not supported by randomized trials, is generally employed to prevent embolic events. The prognosis of stroke caused by arterial dissection does not differ from that of ischaemic events of other origin; the rate of recurrence is low and most patients have only one event in their live. Clinical research with multicenter recruitment is ongoing to provide more solid evidence on the management and prognosis of arterial dissections.

Alterations in the cerebral venous circulation as a cause of headache.

The alterations of the cerebral venous circulation are a rare but clinically important cause of headache. Although any process involving the cerebral veins or sinuses may cause headache, the most frequent and important are cerebral venous thrombosis and idiopathic intracranial hypertension. The headache of cerebral venous thrombosis does not have specific features and may be isolated; therefore, all patients with headache and risk factors for venous thrombosis should undergo the appropriate neuroradiologic examinations to rule out the diagnosis. In fact, early anticoagulant treatment may dramatically change the clinical outcome. Also idiopathic intracranial hypertension, if untreated, may have serious clinical consequences such as permanent visual loss. The pathogenesis of this disorder has not been clearly established and several possibilities involving the cerebral circulation are discussed.

Cerebral venous thrombosis.

Cerebral venous thrombosis (CVT) was formerly considered a rare disorder, associated with an unfavorable outcome. More recent data based on modern imaging techniques, however, have changed our perception of this disorder. The use of angiography and, especially, MRI have allowed an early diagnosis and have proved that the incidence of CVT is, in fact, higher than previously thought, approximately 3-4 cases per million people per year, and that the majority of patients have a favorable outcome. At present, the most frequent causes are oral contraceptives assumption and pregnancy/puerperium; as a consequence, 75% of patients are females. CVT may cause isolated intracranial hypertension or lead to an ischemic stroke, which does not follow the distribution of an arterial vessel and has a relevant vasogenic edema. Venous strokes often have a hemorrhagic component, ranging from small petechiae to an actual intracerebral hemorrhage; the latter is associated with a worse clinical course. The clinical presentation of CVT is highly variable and includes patients with just a mild headache, others with focal neurological deficits and a few with a dramatic syndrome with coma; seizures are a frequent presenting symptom. The best radiological examination to confirm the suspicion of CVT is MRI of the brain, which can both demonstrate parenchymal lesions and directly show evidence of sinus occlusions. The available evidence suggests that anticoagulants are effective in reducing mortality and dependency in CVT patients; the possible role of systemic or localized thrombolysis is still to be established.

Migraine and hypertension.

Although the possibility of a comorbidity between migraine and hypertension has long been suspected, the epidemiologic evidence is controversial, with studies demonstrating positive, negative or no correlation between the two diseases. A unifying view that takes into account the most recent evidence suggests that there might be a different effect of diastolic and systolic pressure, with the former having a positive and the latter a negative correlation with migraine. In this paper, the methodologic and clinical reasons for the discrepancies in epidemiologic studies are discussed, together with the possible biological mechanisms that might account for the migraine-hypertension correlation. One such mechanisms may be the renin angiotensin system, which is certainly involved in hypertension and has activities in the CNS that may be relevant for migraine pathogenesis. Despite the uncertainty still present in this field, the control of hypertension in migraine patients is an important factor for the success of migraine treatment and to lower cerebrovascular risk.

Migraine and cardiocerebrovascular risk in women.

The interest of the medical community has recently focused on the relationship between gender and cardiocerebrovascular risk. In this paper, we will first review gender differences in cardiocerebrovascular disorders, then we will discuss the existing evidence on the links between migraine and stroke and cardiovascular disease in women, and speculate on the possible physiopathological interpretations of this emerging epidemiological link. In the third part of this work, we will address the issue of the effect of sex hormones on vascular risk, and consider the evidence concerning the safety of oral contraceptives and hormone-replacement therapy. Finally, we will outline the main trends of future research and its possible clinical and therapeutic implications.

Increased plasma glutamate in stroke patients might be linked to altered platelet release and uptake.

Experimental studies have shown the role of excitotoxicity in the pathogenesis of ischemic brain lesions, and glutamate levels have been found to be elevated in CSF and plasma from patients, early after stroke. In this study, we investigated whether platelets could be involved in the mechanism of altered plasma glutamate levels after stroke. Forty four patients, from 6 hours to 9 months after ischemic stroke, 15 age-related healthy controls and 15 controls with stroke risk factors or previous transient ischemic attack were enrolled. Glutamate plasma levels, platelet glutamate release after aggregation and platelet glutamate uptake were assessed. Plasma glutamate levels were increased up to 15 days after the ischemic event in stroke patients, and the levels at day 3 were inversely correlated with the neurologic improvement between day 3 and 15. Ex vivo platelet glutamate release was decreased by 70% in stroke patients, suggesting previous in vivo platelet activation. Moreover, platelet glutamate uptake in these patients was decreased by 75% up to 15 days and was still reduced 90 days after stroke. Our data show a prolonged increase of glutamate in plasma after stroke, which might presumably be linked to altered platelet functions, such as excessive release of the amino acid or impaired uptake.