CSF dynamics of orexin and ß-amyloid42 levels in narcolepsy and Alzheimer's disease patients: A controlled study.

ß-amyloid42 (Aß42) in Alzheimer's disease (AD) and orexin in narcolepsy are considered crucial biomarkers for diagnosis and therapeutic targets, respectively. Recently, orexin and Aß cerebral dynamics have been studied in both pathologies, but how they interact with each other remains further to be known. In this study, we investigated the reliability of using the correlation between orexin and Aß42 CSF levels as a candidate marker to explain the chain of events leading to narcolepsy or AD pathology. In order to test the correlation between these biomarkers, patients diagnosed with AD (n = 76), narcolepsy type 1 (NT1, n = 17), narcolepsy type 2 (NT2, n = 23) and healthy subjects (n = 91) were examined. Patients and healthy subjects underwent lumbar puncture between 8:00 and 10:00 am at the Neurology Unit of the University Hospital of Rome "Tor Vergata". CSF levels of Aß42, total-tau, phosphorylated-tau, and orexin-A were assessed. The results showed that CSF levels of Aß42 were significantly lower (p < 0.001) in AD (332.28 ±â€¯237.36 pg/mL) compared to NT1 (569.88 ±â€¯187.00 pg/mL), NT2 (691.00 ±â€¯292.63 pg/mL) and healthy subjects (943.68 ±â€¯198.12 pg/mL). CSF orexin-A levels were statistically different (p < 0.001) between AD (148.01 ±â€¯29.49 pg/mL), NT1 (45.94 ±â€¯13.63 pg/mL), NT2 (104.92 ±â€¯25.55 pg/mL) and healthy subjects (145.18 ±â€¯27.01 pg/mL). Moderate-severe AD patients (mini mental state examination < 21) showed the highest CSF orexin-A levels, whereas NT1 patients showed the lowest CSF orexin-A levels. Correlation between CSF levels of Aß42 and orexin-A was found only in healthy subjects (r = 0.26; p = 0.01), and not in narcolepsy or AD patients. This lack of correlation in both diseases may be explained by the pathology itself since the correlation between these two biomarkers is evident only in the healthy subjects. This study adds to the present literature by further documenting the interplay between orexinergic neurotransmission and cerebral Aß dynamics, possibly sustained by sleep.

Tau and Amyloid-ß Peptides in Serum of Patients With Parkinson's Disease: Correlations With CSF Levels and Clinical Parameters.

Relevance of blood-based biomarkers is increasing into the neurodegenerative diseases field, but data on Parkinson's disease (PD) remain still scarce. In this study, we used the SiMoA technique to measure serum content of total tau protein and amyloid-ß peptides (Aß-42, Aß-40) in 22 PD patients and ten control subjects. Serum levels of each biomarker were correlated with the respective CSF levels in both the groups; in PD patients, also the correlations between serum biomarkers and main clinical parameters were tested (motor, non-motor, cognitive scores and levodopa equivalent daily dose). Serum biomarkers did not exhibit quantitative differences between patients and controls; however, only PD patients had inter-fluids (serum-CSF) associations in tau and amyloid-ß-42 levels. Moreover, serum content of tau protein was inversely correlated with cognitive performances (MoCA score). These findings, albeit preliminary, indicate that brain-derived peptides may change in parallel in both peripheral blood and CSF of PD patients, eventually even in association with some clinical features. Further studies are now needed to validate the use of blood-based biomarkers in PD.

Perampanel may represent an effective treatment for the prevention of migraine comorbid with epilepsy.

INTRODUCTION: Migraine is a common comorbidity in patients with epilepsy. Considering the proven associations and the common pathophysiological features linking epilepsy and migraine, some anti-seizure medications (ASMs) have been considered as a treatment for both disorders. This study aimed at assessing both the effectiveness of perampanel (PER) on epileptic seizures and migraine attacks in patients with epilepsy and comorbid migraine, as well as the reduction in the monthly mean rate usage of rescue migraine medications. METHODS: This observational, multi-centre study included adult patients with epilepsy and comorbid migraine who started PER to better control epileptic seizures and who were followed up for 12 months. RESULTS: Thirty-one patients were included (mean age 40.13 ±â€¯13.13 years; 67.0% female). At the 12-month follow-up visit, 27 patients were continuing PER concomitantly with 1 (45.2%) or 2 ASMs (54.8%). A significant reduction in epileptic seizures, migraine attacks, and the monthly use of rescue migraine medications between baseline and both 6- and 12-month follow-up visits was documented. CONCLUSION: PER demonstrated good effectiveness in reducing both epileptic seizures and migraine attacks in patients with comorbid epilepsy and migraine. Future studies with possibly larger samples are needed to evaluate the efficacy of PER in migraine other than epilepsy.

Sleep-wake cycle dysregulation in idiopathic REM sleep behaviour disorder.

Alteration of the circadian sleep-wake rhythm has been suggested in patients affected by idiopathic rapid eye movement sleep behaviour disorder. Because actigraphy is the validated instrument to monitor the sleep-wake cycle, the aim of the present study was to investigate the circadian sleep-wake rhythm in patients with idiopathic rapid eye movement sleep behaviour disorder compared with healthy aged controls. Fourteen-day actigraphic recording, a comprehensive sleep interview, and cognitive and behavioural domains were investigated in patients affected by idiopathic rapid eye movement sleep behaviour disorder, and compared with controls similar for age, sex and cognitive performances. Patients with idiopathic rapid eye movement sleep behaviour disorder showed reduced relative amplitude and alteration of both sleep and wake compared with controls. Patients with idiopathic rapid eye movement sleep behaviour disorder also showed subjective sleep and wake complaints, and higher scores at the Beck Depression Inventory, compared with controls. Beck Depression Inventory scores correlated with sleep actigraphic parameters, such as sleep latency, sleep efficiency, time in bed, and relative amplitude. Therefore, the present study showed the dysregulation of the sleep-wake cycle in patients with idiopathic rapid eye movement behaviour disorder. Moreover, depressive symptoms documented in patients with idiopathic rapid eye movement sleep behaviour disorder correlated with the sleep-wake rhythm dysregulation.

Effectiveness of robot-assisted gait training on motor impairments in people with Parkinson's disease: a systematic review and meta-analysis.

The aim of this systematic review and meta-analysis was to evaluate the effectiveness of robot-assisted gait training (RAGT) on motor impairments in people with Parkinson's disease (PD). A computer-based systematic literature search was performed in six databases according to PRISMA guidelines. Randomized controlled trials (RCTs) that assessed the effects of RAGT on motor impairments in people with PD were included. GRADE approach and PEDro scale were used to determine the studies' quality of evidence. Meta-analyses were performed by calculating the weighted mean difference (WMD) at 95% confidence interval. Seven RCTs (PEDro: 5-8) met the inclusion criteria for systematic review and meta-analyses. The meta-analysis showed significant improvement on Unified Parkinson Disease Rating Scale Part III after intervention [WMD=3.292; 95% confidence interval (CI)=1.378-5.207; P=0.000], and after 1-month follow-up (WMD=5.512; 95% CI=2.396-8.629; P=0.001). Stride length (WMD=9.283; 95% CI=7.153-11.414; P=0.00) and gait speed (WMD=0.166; 95% CI=-0.090 to 0.243; P=0.000) showed significant improvements after RAGT. Balance as measured by Berg Balance Scale was improved significantly after intervention (WMD=3.87; 95% CI=0.374-6.735; P=0.029) and at 1-month follow-up (WMD=3.87; 95% CI=1.324-6.413; P=0.002). The pooled analysis did not detect any significant changes regarding stride time, cadence and functional balance scales. GRADE level of evidence ranged between high and low. The RAGT showed better outcomes than conventional interventions on some motor aspects in PD. However, RAGT did not seem superior to control interventions. Further RCTs that examine the effect of RAGT on more specific outcomes and at different medication statuses are required.

Complement system dysregulation in patients affected by Idiopathic Generalized Epilepsy and the effect of antiepileptic treatment.

Complement system dysregulation has been hypothesized as a possible pathogenetic factor triggering epileptogenesis in both animal models and human studies. The aim of the present study is to evaluate the complement system in adult patients affected by idiopathic generalized epilepsy (IGE), either untreated or treated by antiepileptic drugs (AEDs). Thirty-seven IGE patients were compared to a population of 20 matched healthy controls. IGE patients underwent neurological investigation, epilepsy diary, 24-h EEG recording, and blood sample for the assessment of the complement factors C3 and C4, fibrinogen, and C-reactive protein (CRP) serum levels. We excluded patients with clinical and subclinical seizures in the 24h before obtaining the blood sample. We observed decreased C3 and C4 serum levels in IGE patients with respect to controls (p<0.05), and in untreated compared to treated IGE patients (p<0.05). We found significant correlations in the IGE group linking C3 to C4 (R=0.34), CRP (R=0.49), and fibrinogen serum levels (R=0.61). This study proved a significant alteration of the complement system in IGE patients not related to ictal conditions. The hyperactivation of the complement cascade was more significant in untreated than in treated IGE patients. Hence, this study documented the complement factors dysregulation in patients affected by IGE. However, the impact of complement system alteration in the epileptogenetic process needs to be clarified.

The Role of Topiramate in the Management of Cocaine Addiction: a Possible Therapeutic Option.

Topiramate (TPM) is an antiepileptic drug able to play a role in both neurological and psychiatric disorders. TPM facilitates gamma-aminobutyric acid (GABA) transmission and inhibits glutamatergic transmission (i.e. AMPA/kainate receptors). Several studies reported that the modulation of GABAergic and glutamatergic synaptic transmission may reduce cocaine reinforcement. Therefore, TPM could be used in the management of cocaine dependence.

Increase in plasma homocysteine levels induced by drug treatments in neurologic patients.

Homocysteine (Hcy) is a thyol amino acid resulting from de-methylation of methionine, an essential amino acid derived from dietary proteins. It is metabolized through two pathways: re-methylation and transsulfuration, which use as cofactors folate, vitamin B6 and vitamin B12. Hyperhomocysteinemia has been identified as a risk factor for cerebrovascular disease, dementia, impaired cognitive function and depression. Several drugs may interfere with metabolic pathways of Hcy, leading to an alteration of plasma Hcy levels. Lipid-lowering agents, used to reduce the risk of cerebral venous thrombosis or occlusive vascular disease in patients with high levels of plasmatic lipids, can increase plasma Hcy levels. Hyperhomocysteinemia has been also documented in Parkinson disease patients treated with levodopa and in epileptic patients after chronic treatment with antiepileptic drugs. In contrast, vitamins supplementations may be warranted in patients treated with lipid-lowering agents, levodopa and antiepileptic drugs in order to maintain normal plasma Hcy values. In contrast, higher doses of vitamins can induce dysfunctions in central and peripheral nervous system; therefore excessive supplements should be avoided.