Prognostic factors in epilepsy with eyelid myoclonia (Jeavons syndrome).

PURPOSE: To describe the prognostic factors of drug resistance in 40 patients with epilepsy with eyelid myoclonia or Jeavons syndrome. METHOD: Retrospective analysis from two French tertiary centers. RESULTS: Forty patients were enrolled (31 females and 9 males; mean age at epilepsy onset: 6.2±3.4 years [range: 1-15 years]). Half of the patients (20/40) achieved at least a one-year remission from all seizure types. In the responders, seizure freedom was achieved after a mean 13.85±13.43 years from the onset of epilepsy (range: 1-44). The presence of intellectual disability and an earlier onset of the disease (≤5 years) were the most powerful predictors of poor seizure control (P=0.003 and P=0.005, respectively). When considering the age of onset, patients with early-onset seizures (≤5 years) presented more frequently with intellectual disabilities, psychiatric comorbidities, absences, and a major risk of refractoriness (70% versus 30%, P=0.01) than patients with onset after 5 years. At the last follow-up, 15 patients (37.5%) were taking a single drug, 16 (40%) were taking two, and seven (17.5%) were taking more than two. The most frequent drugs were valproate (23/40, 57.7%), followed by levetiracetam (16/40, 40%), and lamotrigine (14/40, 35%). CONCLUSION: Patients with Jeavons syndrome present a high rate of pharmaco-resistance with the need for long-term treatment. Early onset of epilepsy and the presence of intellectual disability appeared to be the most relevant predictors of poor seizure control, suggesting the use of genetic tests to individualize specific etiologies and perhaps adapt the therapeutic strategy.

Lacosamide in monotherapy in BTRE (brain tumor-related epilepsy): results from an Italian multicenter retrospective study.

PURPOSE: Lacosamide (LCM) is a third-generation anti-seizure medication (ASM) approved for focal onset epilepsy in patients aged ≥ 4.378 Previous studies have reported an efficacy of LCM as add-on treatment in brain tumor-related epilepsy (BTRE). To date, there are no studies in the literature focusing on lacosamide used in monotherapy to treat BTRE. In our retrospective study we investigated efficacy and tolerability of LCM in monotherapy in a multicenter national cohort of primary brain tumor patients. METHODS: We collected from 12 Italian Centers 132 patients with primary brain tumors who were treated with LCM in monotherapy. For each patient we evaluated seizure freedom at 3 and 6 months (primary endpoints), side effects and drop-out rate (secondary endpoints). RESULTS: Overall, LCM led to seizure freedom in 64.4% of patients at 3 months and 55% at 6 months. Patients who used two or more ASMs before LCM had a worse seizure control than patients in monotherapy with LCM as first choice. In 14 patients, we observed seizure control despite tumor progression on magnetic resonance (MRI). Multivariate analysis showed that gross-total resection at diagnosis was significantly associated with higher seizure freedom rate at 6 months. Side effects were mainly mild (grade 1-2 according to CTCAE classification) and drop-out rate was low (1.5%). Main side effects were dizziness and somnolence. CONCLUSIONS: This is the first study showing a good efficacy and tolerability of LCM when used in monotherapy in BTRE. Further prospective studies are needed to confirm these preliminary data, investigating also quality of life and neurocognitive functions.

Insomnia and daytime sleepiness predict 20-year mortality in older male adults: data from a population-based study.

Data regarding the possible relationship of insomnia and EDS with mortality are inconclusive. The aim of this study was to investigate the association between these sleep complaints and the risk of long-term (20 years) all-cause mortality in older adults. Between April 2000 and March 2001, 750 subjects aged 65 years and older, who resided in the seventh district of Udine, were recruited. Data on sociodemographic characteristics, past medical history, and pharmacological treatment were collected. Dementia was diagnosed using a comprehensive neurological and neuroradiological assessment. Older adults were interviewed by neuropsychologists trained in sleep disturbances in order to assess the presence of sleep complaints. Vital status was followed over 20 years until March 2020. Older male adults affected by insomnia and EDS were significantly more likely to die over the follow-up period. Indeed, males reporting poor sleep and daytime somnolence had a 60% and 48% higher chance of dying than subjects who were not affected by these sleep complaints, respectively. The HR was attenuated after adjusting for confounding variables among insomniacs, whereas that of somnolent men strengthened. Differently from men, insomnia and EDS did not have any impact on mortality in older women. In conclusion, older male adults affected by insomnia and EDS had a significant increased risk of mortality, which is independent of cancer, depression, dementia, cardiovascular diseases, and sleeping pill use.

SNCA 3'UTR genetic variants in patients with Parkinson's disease and REM sleep behavior disorder.

REM sleep behavior disorder (RBD) is an early marker of Parkinson's disease (PD); however, it is still unclear which patients with RBD will eventually develop PD. Single nucleotide polymorphisms (SNPs) in the 3'untranslated region (3'UTR) of alpha-synuclein (SNCA) have been associated with PD, but at present, no data is available about RBD. The 3'UTR hosts regulatory regions involved in gene expression control, such as microRNA binding sites. The aim of this study was to determine RBD specific genetic features associated to an increased risk of progression to PD, by sequencing of the SNCA-3'UTR in patients with "idiopathic" RBD (iRBD) and in patients with PD. We recruited 113 consecutive patients with a diagnosis of iRBD (56 patients) or PD (with or without RBD, 57 patients). Sequencing of SNCA-3'UTR was performed on genomic DNA extracted from peripheral blood samples. Bioinformatic analyses were carried out to predict the potential effect of the identified genetic variants on microRNA binding. We found three SNCA-3'UTR SNPs (rs356165, rs3857053, rs1045722) to be more frequent in PD patients than in iRBD patients (p = 0.014, 0.008, and 0.008, respectively). Four new or previously reported but not annotated specific genetic variants (KP876057, KP876056, NM_000345.3:c*860T>A, NM_000345.3:c*2320A>T) have been observed in the RBD population. The in silico approach highlighted that these variants could affect microRNA-mediated gene expression control. Our data show specific SNPs in the SNCA-3'UTR that may bear a risk for RBD to be associated with PD. Moreover, new genetic variants were identified in patients with iRBD.

Amino acid supplementation in l-dopa treated Parkinson's disease patients.

BACKGROUND: The correlation between Parkinson disease and malnutrition is well established, however a protein-restricted diet is usually prescribed because of potentially negative interactions between dietary amino acids and l-dopa pharmacokinetics. This strategy could increase the risk of further nutritional deficits. METHODS: A monocentric, prospective, randomized, double-blind pilot study was performed on two groups of Parkinson-affected, protein-restricted, patients: Intervention (n = 7; amino acid supplementation twice daily) and Placebo (n = 7; placebo supplementation twice daily). At enrolment, after 3- and 6-month supplementation, neurological evaluations (UPDRS III, Hoenh-Yahr scale, l-dopa equivalent dose assessment) were performed and blood sample was collected to define insulin sensitivity (QUICKI index) and oxidative stress (oxidized and reduced glutathione). Repeated measure ANCOVA was applied to define time effect and time × treatment interaction. RESULTS: Participants were comparable at baseline for all assessed parameters. Neurological outcomes and l-dopa requirement were comparable in both group after 6-month of supplementation, without time × treatment interaction. The decrease in insulin sensitivity, as assessed by QUICKI index, observed after 6 months in both groups, was greater in Placebo than in Intervention (time effect p < 0.001; time × treatment interaction p = 0.01). Moreover, despite no changes in total erythrocyte glutathione concentrations, oxidized glutathione levels decreased by 28 ± 17% in the Intervention while increased by 55 ± 38% in Placebo (time effect p = 0.05; time × treatment interaction p = 0.05), after 6-month supplementation. CONCLUSIONS: Amino acid supplementation, assumed with shrewd temporal distribution, did not show detrimental effects on neurological and pharmacological control in protein-restricted Parkinson-affected patients, chronically treated with l-dopa. Furthermore, daily amino acid supplementation partially counteracted insulin resistance development and the loss in antioxidant availability.

The contribution of assessing cognitive impairment in radiologically-isolated syndrome (RIS): a single case report follow-up study.

Radiologically-isolated syndrome (RIS) is a recently-defined entity, described as the incidental discovery of lesions suggestive of multiple sclerosis (MS) on brain magnetic resonance imaging (MRI) scans demonstrating dissemination in space (DIS) without symptom expression and with a normal neurological examination. Recent studies demonstrate that RIS patients present similar features of cognitive impairment as MS patients. We describe a case of a RIS patient in whom investigating cognitive functions was a useful tool for diagnostic and therapeutic decisions.

Rem sleep brady-arrhythmias: an indication to pacemaker implantation?

OBJECTIVES: Important adjustments in the autonomic nervous system occur during sleep. Bradycardia, due to increased vagal tone, and hypotension, caused by reduction of sympathetic activity, may occur during non rapid eye movement (REM) sleep (NREM). Increased sympathetic activity, causing increased heart rate, is conversely a feature of phasic REM sleep. During REM sleep, sinus arrests and atrioventricular (AV) blocks unrelated to apnea or hypopnea have been described. These arrhythmias are very rare and only a few cases have been reported in the literature. PATIENTS/METHODS: Following an ECG performed for other reasons, two patients with no history of sleep complaints nor symptoms of heart failure or heart attack were referred to our center for nocturnal brady-arrhythmias. RESULTS: 24h ECG Holter recorded several episodes of brady-arrhythmia with sinus arrest in the first patients and brady-arrhythmias with complete AV block in the second patient. In both patients, episodes of brady-arrhythmia were prevalent in the second part of the night. Nocturnal polysomnography (PSG) demonstrated that episodes occurred only during REM sleep, particularly during phasic events. Treatment with pacemaker was considered only for the patient with complete AV blocks. CONCLUSIONS: These types of brady-arrhythmias are usually detected accidentally due to their lack of symptoms. It has been suggested that in some patients they may lead to sudden unexpected death. Thus, the identification of predisposing factors is mandatory in order to prevent potentially dangerous arrhythmic events.

Daytime sleepiness is associated with dementia and cognitive decline in older Italian adults: a population-based study.

OBJECTIVE: The occurrence of dementia among the elderly has been associated with several, often not modifiable, risk factors. Recent epidemiological studies focused their interest on a possible association between cognitive decline and sleep, a potentially modifiable risk factor. Due to controversial results and limitations of the previous studies, we decided to reexamine the relationship between disturbed sleep and cognitive impairment in the elderly. METHODS: Seven hundred fifty subjects aged 65years or older were recruited. The Mini-Mental State Examination (MMSE) and the Global Deterioration Scale (GDS) scores were used to evaluate the severity of cognitive decline. Diagnosis of dementia was made by means of the DSM-IV criteria. The older adults were interviewed in order to assess the presence of several sleep complaints (insomnia, snoring and/or witnessed sleep apneas, restlessness and/or leg jerks, sleepwalking and nightmares). Excessive daytime sleepiness was evaluated by means of a validated questionnaire. The principal caregiver of each older adult took part in the interview, providing the information if the subject was unable to answer because of mental impairment. RESULTS: Eighty-six individuals were diagnosed as demented; a large part of them (47.8%), in particular, were recognized as being affected by Alzheimer's disease. The prevalence of each sleep complaint in the older adults was as follows: insomnia 84.7%, snoring and/or witnessed sleep apneas 26.2%, restlessness and/or jerks in the legs 25.7%, sleepwalking 0.5%, nightmares 6.4% and daytime somnolence 30.6%. Among sleep disturbances, excessive daytime sleepiness was independently associated with the presence of dementia in the elderly. In addition, the frequency of excessive daytime sleepiness increased progressively across the different categories of cognitive decline, as measured by means of MMSE and GDS scores. CONCLUSIONS: Insomnia, the most common sleep complaint in our sample, was not associated with the presence of cognitive decline. As opposed to insomnia, excessive daytime sleepiness was significantly related to dementia. Further studies are needed in order to investigate the direction of this association and to evaluate the possible role of daytime somnolence as an early marker of neurodegenerative disease, particularly Alzheimer's disease, in some older adults.

Rhabdomyolysis caused by tocolytic therapy with ritodrine hydrochloride.

We report a case of rhabdomyolysis with severe generalized weakness and muscle pain after administration of ritodrine hydrochloride, in a pregnant patient without history of neuromuscular disease. Laboratory tests showed an increase of blood CK value and myoglobinuria. An electromyography was performed, revealing a typical myogenic pattern and diffuse denervation activity. Muscular biopsy allowed to rule out inflammatory and metabolic myopathy. After delivery, the patient underwent intensive rehabilitation with progressive improvement of her clinical situation, until complete recovery. Three months later, both neurological assessment and CK levels were normal. This case highlights that rhabdomyolysis has to be considered even in patient treated with ritodrine alone and without history of neuromuscular disease. Therefore, muscular symptoms and CK levels should be monitored in women treated with ritodrine for premature labour.

Prevalence of 'poor sleep' among patients with multiple sclerosis: an independent predictor of mental and physical status.

BACKGROUND: Patients with multiple sclerosis (MS) report sleep disturbances more frequently than the general population. Besides specific sleep disturbances, many other conditions could impair nocturnal rest in this population. In addition, information regarding the role of disrupted sleep on quality of life (QoL) in MS patients is lacking. This study was performed to bridge this gap. METHODS: A total of 120 patients with MS were enrolled into the study. Demographic, socioeconomic and clinical characteristics (clinical course and duration of MS, EDSS score, therapeutic information, presence of pain, presence of sexual and/or bladder dysfunction, localization of demyelinating plaques, and presence of anxiety and depression) were collected. The Pittsburgh Sleep Quality Index (PSQI), the Charlson Comorbidity Index (CCI) and the Italian version of the 36-item Short Form (SF-36) were used to assess quality of sleep, comorbidity and QoL, respectively. RESULTS: Nearly half (47.5%) of MS patients were classified as "poor sleepers," having significantly higher EDSS (3.1+/-1.4 vs. 2.3+/-1.4, p=0.009) and CCI scores (0.19+/-0.4 vs. 0.03+/-0.2, p=0.009) than "good sleepers." In addition, pain due to MS was more common among "poor sleepers" (33.3% vs. 17.7%, p=0.05). Scores for each domain of the SF-36, and the mental component summary (MCS) and physical component summary (PCS) scores were significantly lower in poor sleepers than in good sleepers (p<0.001 for each score). Of the different variables associated with MCS, the only independent predictors of mental status were: presence of sexual and/or bladder dysfunction and global PSQI score. The independent predictors for physical status (PCS) were age, EDSS score and global PSQI score. CONCLUSIONS: Poor sleep is common in patients with MS, representing an independent predictor of QoL. Patients with MS who are poor sleepers should receive immediate assessment and treatment, bearing in mind that, in addition to specific sleep disturbances, other clinical conditions (both related and unrelated to MS) can disrupt nocturnal sleep.

Drugs with anticholinergic properties as a risk factor for psychosis in patients affected by Alzheimer's disease.

Emerging evidence suggests that psychosis in persons with Alzheimer's disease (AD) may be linked to the cholinergic deficit associated with the disease. This study sought to evaluate whether anticholinergic (ACH) drugs could be a risk factor for psychosis onset. A total of 230 patients affected with probable AD were recruited. Data on behavioral and psychological symptoms were collected using the Neuropsychiatric Inventory, and diagnosis of psychosis was performed. Patients were divided into those who used ACH drugs and those who used non-ACH drugs. Those using ACH drugs (18.3%) were more likely to have psychosis than those using non-ACH drugs (odds ratio (OR)=2.52; 95% confidence interval (CI), 1.27-5.00); this association remained significant even after adjusting for potential confounding variables (OR=2.13; 95% CI, 1.03-4.43). Our data suggest that patients with AD are frequently treated with ACH drugs and that ACH drug intake should be regarded as a potential risk factor for psychosis.

Restless legs syndrome: diagnosis, epidemiology, classification and consequences.

Restless legs syndrome (RLS) is a sensorimotor disorder characterised by a complaint of an almost irresistible urge to move the legs. RLS is diagnosed clinically by means of the four essential criteria of the International Restless Legs Syndrome Study Group. In doubtful cases, neurophysiological examinations, such as polysomnography and/or a suggested immobilisation test, can be performed to confirm a clinical suspicion of RLS. Several other conditions may present sensorimotor complaints with features similar to RLS; a careful sleep history is required to avoid a misdiagnosis. Three different scales have been validated to assess the severity of RLS. In the general population, RLS prevalence ranges from 0.1% to 11.5%, with a high number of patients affected by a primary form of the sleep disturbance (70%-80%). However, several clinical conditions have been associated with RLS, such as iron deficiency, uraemia, pregnancy and polyneuropathy. Furthermore, recent studies show that RLS may be associated also to type 2 diabetes mellitus and to multiple sclerosis. RLS has a negative impact on sleep, cognitive functions, quality of life and mental status. Higher awareness of RLS among physicians is required; it remains an underdiagnosed clinical condition.

Neurological manifestation of tick-borne encephalitis in North-Eastern Italy.

Tick-borne encephalitis (TBE) is an infectious zoonotic disease, moving from Central Europe to other countries and still rare in Italy. The disease, produced by the European subtype virus, typically takes a biphasic course with neurological disorders of different severity during its second phase. We report the first three TBE cases in Friuli Venezia Giulia (FVG), characterised by extremely variable clinical features. Knowledge of these different presentations will assist physicians in increasing their level of attention to TBE also in this region, where no cases of TBE had been reported in the past, despite the fact that it borders countries with high prevalence of the infection.

Spreading of autoimmunity from central to peripheral myelin: two cases of clinical association between multiple sclerosis and chronic inflammatory demyelinating polyneuropathy.

Demyelinating inflammatory diseases of central and peripheral myelin share similar aetiopathogenesis but rarely occur simultaneously in the same individual. Here we report two clinical cases of temporal association between multiple sclerosis (MS) and chronic inflammatory demyelinating polyneuropathy (CIDP). Our finding supports the hypothesis that clinically manifested central and peripheral demyelinating diseases could result from a common pathogenic event characterised by T-cell autoimmunity spreading from central to peripheral myelin.

Hemifacial spasm due to a tentorial paramedian meningioma: a case report.

Hemifacial spasm (HFS) is a movement disorder characterised by involuntary paroxysmal facial movements that usually involve the orbicularis oculi and then spread to the other facial muscles. A microvascular compression and demyelination of the seventh nerve at its exit from the brain stem is considered to be the main aetiology of HFS. In addition to rare idiopathic (cryptogenetic) cases, others causes of HFS exist: tumours or vascular malformations have been described, of both the ipsilateral and contralateral cerebellopontine angle (CPA). However, space-occupying lesions in locations other than CPA are usually not thought to be responsible for HFS. Here we describe the case of a 45-year-old woman suffering from HFS, who dramatically improved after surgical removal of a tentorial paramedian meningioma.

Greater syntactic impairments in native language in bilingual Parkinsonian patients.

OBJECTIVE: To investigate the presence of syntactic impairments in native language in Parkinson's disease. METHODS: Twelve bilingual patients, with Friulian as their first language (L1) and Italian as their second (L2), with Parkinson's disease and 12 normal controls matched for age, sex, and years of schooling, were studied on three syntactic tasks. RESULTS: Patients with Parkinson's disease showed a greater impairment of L1 than L2. CONCLUSIONS: These findings provide evidence of greater basal ganglia involvement in the acquisition and further processing of grammar in L1 v L2 possibly due to a major involvement of procedural memory in representing L1 grammar.

Sleep disturbances in elderly: a subjective evaluation over 65.

Sleep in elderly people shows progressive changes caused by general aging processes. Several alterations are described in medical literature: changes of sleep/wake rhythm and modifications both in sleep duration and in sleep architecture. The aim of our study was to evaluate sleep disturbances in elderly people, with and without cognitive impairment,through a sleep questionnaire. Our population included 1000 subjects, over 65 years of age, stratified by sex and age. The first 600 interviews were included in this report. All patients underwent a mini mental state examination (MMSE) and a questionnaire concerning excessive daytime sleepiness. In our total sample, we found a high prevalence of excessive daytime sleepiness, insomnia, nighttime awakenings, snoring, restlessness and periodic leg movements during sleep. Patients with cognitive dysfunctions showed less difficulty in falling asleep and fewer nighttime awakenings; they snored less frequently and were the only ones to present enuresis and to fall off the bed. Moreover, patients with cognitive impairment presented excessive daytime sleepiness with variable intensity and frequency. In conclusion, our results indicate significant differences in sleep disorders between healthy subjects and patients cognitively impaired. Besides, our subjective evaluation seems to be a useful method to perform an assessment of sleep disturbances in elderly people.