Restless Legs Syndrome and fatigue in multiple sclerosis: A cross-sectional clinical study.

BACKGROUND: Restless Legs Syndrome is a sleep-related sensorimotor disorder with a higher prevalence in Multiple Sclerosis (MS) patients than in the general population. Our aim was to determine the prevalence of RLS in a group of relapsing-remittent multiple sclerosis (RRMS) patients, and to investigate whether RLS is associated with MS-related disability, sleep quality, mood disorders and fatigue. METHODS: In this retrospective, mono-centric, observational study, 92 RRMS patients were recruited (median age 46.5 years, 68.5% female patients). Data on MS clinical and radiological variables were collected. Patients underwent a subjective evaluation with standardized questionnaires on sleep fatigue and mood, which were evaluated by an expert neurologists specialized in sleep disorders about the occurrence of RLS. RESULTS: Prevalence of RLS in our sample was of 47.8%. Patients with RLS had a significantly higher rate of worse sleep quality and fatigue, compared to non RLS subjects (respectively 56.8% vs. 35.4%, p=0.04 and 54.4% vs 22.7%, p=0.002). Univariate analysis showed that RLS was significantly more frequent in fatigued patients (66.7% vs 38.5% RLS- patients, p=0.009). Multivariate analysis showed that fatigue correlated with MS-related disability (OR 1.556, p=0.011), poor sleep quality (OR 1.192, p 0.036), and mood disorders (OR 1.096, p 0.046). RLS appears to independently increase the risk of fatigue of 50%, without reaching clear statistical significance (OR 1.572, p 0,0079). CONCLUSION: Our study confirms the high prevalence of RLS in patients with multiple sclerosis and highlights the potential impact of RLS on fatigue and its strict interaction with sleep quality.

Alexithymia, impulsiveness, emotion, and eating dyscontrol: similarities and differences between narcolepsy type 1 and type 2.

Non-sleep symptoms, as depression, anxiety and overweight, are often encountered in narcoleptic patients. The purposes of this study are to evaluate mood, impulsiveness, emotion, alexithymia, and eating behavior in patients with narcolepsy type 1 (NT1) and narcolepsy type 2 (NT2) compared to healthy controls and to investigate possible correlations between clinical-demographic data, polysomnographic parameters, and subjective questionnaires. Consecutive patients affected by NT1 and NT2 underwent to Patient Health Questionnaire-9, Generalized Anxiety Disorder-7 Scale, Barratt Impulsivity Scale-11, Difficulties in Emotion Regulation Scale, Toronto Alexithymia Scale, and Eating Disorder Evaluation Questionnaire. Daytime sleepiness was assessed using Epworth sleepiness score. Data were compared with controls. Fourteen NT1, 10 NT2, and 24 healthy subjects were enrolled. Toronto Alexithymia Scale total score was significantly higher in NT1 than NT2. Compared to controls, NT1 patients exhibited significantly higher scores at Patient Health Questionnaire-9 and Difficulties in Emotion Regulation Scale. A positive correlation between hypnagogic hallucinations and Difficulties in emotion regulation was found. NT1 and NT2 share several psycho-emotional aspects, but whereas NT1 patients exhibit more depressive mood and emotion dysregulation compared to controls, alexithymic symptoms are more prominent in NT1 than NT2. Hypnagogic hallucinations, emotion dysregulation, and alexithymia appear to be correlated, supporting the hypothesis of mutual interaction of the above areas in narcolepsy.

Levetiracetam, lamotrigine and carbamazepine: which monotherapy during pregnancy?

OBJECTIVE: Epilepsy treatment during pregnancy is still challenging. The study is aimed at comparing the efficacy and safety of carbamazepine (CBZ), lamotrigine (LTG) and levetiracetam (LEV) monotherapies during pregnancy in women with focal (FE) or generalized (GE) epilepsy. METHODS: A multicentre retrospective study was conducted to evaluate seizures frequency and seizure freedom (SF) rate during 3 months before pregnancy, each trimester of gestation and post-partum period in women on monotherapy with CBZ, LTG and LEV. RESULTS: Fifty-seven pregnancies (45 FE, 12 GE) on monotherapy (29 CBZ, 11 LTG, 17 LEV) were included. A significant reduction of seizure frequency was found in the first trimester of pregnancy as compared with that one before pregnancy (p = 0.004), more evident in GE (p = 0.003) and in LEV group (p = 0.004). The SF rate significantly increased in the first trimester in comparison to that one before pregnancy and persisted in the post-partum period in the whole sample (p < 0.001) and in women on LEV (p = 0.004). Besides, 88.57% of SF women before pregnancy remained unchanged during gestation and the post-partum period. One major heart malformation in CBZ and no major malformations in LTG and LEV groups were found. CONCLUSIONS: A better clinical outcome during pregnancy emerged since the first trimester in comparison to the before-pregnancy period, mostly evident in women with GE and LEV therapy, reinforcing the hypothesis of a protective role of pregnancy versus seizures. SF before pregnancy represents a significant predictive factor of good clinical outcome during gestation and the post-partum period. Compared to CBZ, LTG and LEV showed a better safety profile.

CGRP Inhibitors and Oxidative Stress Biomarkers in Resistant Migraine: A Real-Life Study with Erenumab, Fremanezumab, and Galcanezumab.

Patients with high-frequency resistant migraine and medication-overuse headache are still the main clinical challenge in tertiary headache centers. The approval of targeted antibodies against the calcitonin gene-related peptide (CGRP) and its receptor represents a powerful instrument. In this study, we observed how biological and clinical features of resistant migraineurs responded to erenumab, fremanezumab, or galcanezumab. We found a reduction in advanced oxidation protein products (AOPP) as a biomarker of improved redox state after six months of treatment. We also found that treatment efficacy was precocious and maintained with high individual responder rates. In particular, seven out of ten patients achieved a reduction of 50% from the baseline at three months, which was maintained at six months, while about one out of our patients experienced a 75% reduction in headache frequency from the first month of treatment. The migraine disability assessment (MIDAS) and the associated fatigue, anxiety, and sleep quality also significantly improved. The allodynia symptom dropped from moderate/severe to mild/absent as a sign of central sensitization reduction. Our study confirmed the safety and efficacy of CGRP inhibition in real-life, high-challenging patients. Additional evidence is needed to understand the role of oxidative stress as a migraine biomarker.

Depressive symptoms and difficulties in emotion regulation in adult patients with epilepsy: Association with quality of life and stigma.

OBJECTIVE: The objective of the study was to assess depressive symptoms (DS) and difficulties in emotion regulation (ER) in adult people with epilepsy (PWE) and their correlation with quality of life and stigmatization feelings of patients. MATERIALS AND METHODS: We enrolled consecutively 110 PWE who completed the Beck Depression Inventory-II (BDI-II) questionnaire and, for the first time, the Italian translation of Difficulties in Emotion Regulation Scale (DERS) to evaluate DS and ER. They also fulfilled the Italian version of the Stigma Scale of Epilepsy (SSE), which allowed the quantification of the stigma perception by our cohort of patients and a 3-item Jacoby's Stigma Scale (JSS) and QOLIE-31 (Q31) for the evaluation of stigma and the quality of life. The results of BDI-II and DERS were correlated with clinical details of PWE, as well as the Q31 and SSE scores. Finally, a multiple stepwise regression analysis was applied to identify the main factors affecting DS and ER difficulties in these patients. RESULTS: About 30% of PWE evidenced DS, of which 17.3% showed a BDI-II score higher than 19, suggestive of moderate to severe DS. Several factors related to epilepsy (seizure frequency, number of antiepileptic drugs (AEDs)) as well as ER and quality of life/stigmatization perception resulted significantly correlated with DS. As a new finding, the main factors affecting DS in PWE turned out to be the difficulties in ER and quality of life and stigma perception (as evaluated through Q31 and JSS scores). CONCLUSIONS: Our findings evidenced that DS in PWE are highly prevalent and strongly correlated with ER difficulties that mostly influence DS together with quality of life and stigma perception. Depressive symptoms and emotion dysregulation are linked by a bidirectional relationship and are significantly associated with worse quality of life and higher stigmatization feelings.

Epilepsy-associated stigma from the perspective of people with epilepsy and the community in Italy.

OBJECTIVE: The objective of this study was to assess the stigma related to epilepsy from the perspective of people with epilepsy (PWE) and from the Italian community (Rome and central Italy); moreover, the impact of the perceived stigma on the mood and quality of life of patients was also evaluated. MATERIALS AND METHODS: We consecutively enrolled 100 PWE and 202 nonepileptic subjects (NES). Both PWE and NES completed an Italian version of the Stigma Scale of Epilepsy (SSE), a 24-items questionnaire that has been demonstrated to allow the quantification of the stigma perception by patients and people from the community. Moreover, the PWE fulfilled a 3-item Jacoby's Stigma Scale, the Quality of Life in Epilepsy-31 (QOLIE-31 [Q3])), and Beck Depression Inventory II (BDI-II) questionnaires for the evaluation of the quality of life and depressive symptoms. The results of the SSE were correlated with clinical and demographic details of PWE and NES, as well as the Q31 and BDI-II scores in PWE. RESULTS: The SSE scores were significantly higher in NES with respect to PWE (respectively 47.1 vs 39.5, p < .001). Forty-two percent of PWE reported feeling stigmatized, with 5% reporting feeling highly stigmatized. In PWE, the perceived stigma was not correlated with seizure frequency but was significantly associated with worse quality of life, more severe depressive symptoms, and higher number of AEDs. The multiple regression analysis showed that the quality-of-life overall score and Q31 subscale exploring "social function" are the most significant predictors of stigma. CONCLUSIONS: By using an Italian translation of the SSE questionnaire, even if we cannot consider our sample representative of the whole Italian community our study evidenced higher rates of stigma related to epilepsy in NES than in PWE. The PWE still experience feelings of stigmatization strongly correlated with higher depressive symptoms and worse quality of life that has proven to be the most significant predictor of stigma. Finally, seizure frequency does not affect the perceived stigma, which is instead significantly influenced by antiepileptic therapy.

Long-term efficacy and safety of lacosamide and levetiracetam monotherapy in elderly patients with focal epilepsy: A retrospective study.

OBJECTIVES: Epilepsy management in elderly patients is often complex because of several concomitant comorbidities that may limit the use of some antiepileptic drugs (AEDs). Levetiracetam (LEV) is a second-generation AED widely used in elderly patients with epilepsy while lacosamide (LCM), which has been recently approved in European Union (EU) as monotherapy for the treatment of focal onset seizures, is affected by a scarcity of data in such frail population. This study is aimed at assessing the efficacy and the tolerability of LCM as monotherapy in elderly patients affected by focal onset epilepsy compared with those receiving LEV. METHODS: A retrospective chart review of patients aged ≥65 years suffering from focal onset seizures, with or without secondary generalization on LCM monotherapy or LEV monotherapy, was performed. Data regarding demographic characteristics, seizure type and etiology, LCM and LEV daily dose, number of lifetime AEDs, seizure frequency at baseline and at 12 months of follow-up, and seizure freedom rates were reported. RESULTS: In this observational retrospective study, 22 patients on LCM (10 males, 12 females, mean age: 76.23 ±â€¯7.5) and 24 patients on LEV (10 males, 14 females, mean age: 73.58 ±â€¯6.39) were enrolled. Mean LCM daily dose was 204.51 ±â€¯88.51 mg and mean LEV daily dose was 1281.25 ±â€¯378.15 mg. All patients had comorbidities on chronic treatment. At 12 months of follow-up, mean monthly seizure frequency reduced from 4.23 ±â€¯8.53 to 0.33 ±â€¯0.9 (p < .001) in LCM group and from 2.29 ±â€¯6.11 to 0.2 ±â€¯0.81 (p < .001) in LEV group. Furthermore, 16/22 (72.7%) LCM patients were seizure-free at 12 months of follow-up while seizure freedom was achieved by 17/24 (70.8%) patients in LEV group. DISCUSSION AND CONCLUSION: Epilepsy management in elderly patients is often challenging. In this retrospective real-life study, the efficacy and the tolerability of LCM as monotherapy was favorable even at low doses in older patients and comparable with LEV with a high rate of long-term seizure freedom. Considering the frequent comorbidities and the risk of drug-drug interactions, LCM monotherapy may be a valuable option in elderly patients with focal onset epilepsy because of its favorable pharmacokinetic profile.

Transient epileptic and global amnesia: Real-life differential diagnosis.

OBJECTIVE: Transient epileptic amnesia (TEA) is an underestimated condition in emergency clinical setting, where most of transient amnesic episodes tend to be classified as transient global amnesia (TGA). We designed this study to evaluate the actual frequency of TEA in a real-life scenario and to highlight the features that can help clinicians distinguishing it from TGA. METHODS: We retrospectively collected clinical data of 83 patients who accessed our emergency ward for an abrupt onset of amnesic disorder, initially interpreted as TGA. All patients underwent neurological evaluation, magnetic resonance imaging (MRI) scan, and standard 21-channel scalp electroencephalography (EEG) recording (standard EEG [st-EEG]). Moreover, patients with borderline epileptiform abnormalities on st-EEG or with normal st-EEG but high clinical suspicion for TEA underwent a 16-channel 24-hour ambulatory EEG (24-h EEG). Clinical features, neurophysiological, and neuroimaging data were analyzed and compared in the two groups (TEA and TGA). RESULTS: Diagnosis of TEA, according to Zeman's criteria, was made in 15 patients (18%). From a clinical point of view recurrence (p < .001) and atypical symptoms such as confusion or language disorder (TGA plus manifestations), appear to be key elements in order to discriminate between TEA and TGA (80% of patients with TEA vs 7.8% of patients with TGA; p < .001). In our sample, duration of the episodes did not significantly differ between TGA and TEA, even though it is usually described as shorter for TEA. This result could be related with a prolonged postictal state in these patients. The analysis of st-EEG results evidenced low sensitivity for interictal epileptiform abnormalities (IEAs) detection (52.3%), with not conclusive data in distinguishing TEA from TGA. On the contrary, 24-h EEG showed IEAs in all patients with epilepsy, mostly during sleep, suggesting an essential diagnostic role of long-lasting EEG recording for TEA. Finally, structural abnormalities were more frequent in patients with TEA (26.6%). In the group with TGA, the only imaging alteration found was diffusion weighted imaging (DWI) hippocampal hyperintensity. CONCLUSION: Our findings show that in a real-life clinical scenario, TEA is frequent but often overlooked. However, simple clinical data and widely available neurophysiological examinations can truly help to effectively distinguish TEA from TGA.

Sexual disinhibition and dementia.

To describe inappropriate sexual behaviour (ISB) observed in patients with dementia, we conducted searches using the Cochrane Library, PubMed, and Web of Science to find relevant articles, chapters, and books published from 1950 to 2014. Search terms used included 'hypersexuality', 'inappropriate sexual behaviors', and 'dementia'. Publications found through this indexed search were reviewed for further relevant references. Sexuality is a human's need to express intimacy, but persons with dementia may not know how to appropriately meet their needs for closeness and intimacy due to their decline in cognition. Generally, the interaction among brain, physical, psychological, and environmental factors can create what we call ISB. The most likely change in the sexual behaviour of a person with dementia is indifference. However, ISB in dementia appear to be of two types--intimacy-seeking and disinhibited--that differ in their association with dementia type, dementia severity and, possibly, other concurrent behavioural disorder. Tensions develop from uncertainties regarding which, or when, behaviours are to be considered 'inappropriate' (i.e. improper) or abnormal. While most ISB occur in the moderate to severe stages of Alzheimer's dementia, they may also be seen in early stages of frontotemporal dementia because of the lack of insight and disinhibition. ISB are often better managed by non-pharmacological means, as patients may be less responsive to psychoactive therapies, but non-pharmacological interventions do not always stop the behaviour.

Migraine features in migraineurs with and without anxiety-depression symptoms: a hospital-based study.

BACKGROUND: Migraine, anxiety and depression often coexist. A "neurolimbic" model of migraine has been recently proposed accounting for a dynamic influence of pain, mood and anxiety on the migraine disease. However, very few data exist concerning clinical migraine features in patients reporting anxiety-depression symptoms. OBJECTIVE: Aim of our study was to test differences in clinical migraine features between migraineurs with anxiety-depression symptoms and migraineurs without ones. MATERIALS AND METHODS: We recruited 200 consecutive migraineurs. Other primary headaches comorbidity and migraine prophylaxis were exclusion criteria. Each patient was interviewed following a structured questionnaire including general features about migraine, triggers, allodynia. Anxiety and depression symptoms were evaluated in each patient by two brief self-reported scales: the generalized anxiety disorder 7-item scale (GAD-7) and the Patient Health Questionnaire 9-item scale (PHQ-9). A cut-off of 5 in both the GAD-7 and the PHQ-9 was considered positive for the presence of anxiety-depressive symptoms. RESULTS: One hundred and one patients (51.5%) had anxiety-depression symptoms (GAD-7 and PHQ-9 ≥ 5). They reported a more headaches/month (p = 0.004), higher number of triggers (p < 0.001), and were more allodynic (p = 0.005). In a binary logistic regression model triggers and allodynia made a unique statistical contribution on reporting anxiety-depression symptoms. CONCLUSION: Our results showed that the presence of anxiety-depression symptoms affects migraine clinical presentation. They are associated with enhanced migraine triggers susceptibility, more ictal allodynic symptoms as well as more headaches/month. An altered sensation in migraineurs with anxiety-depression symptoms could be a result of a lower pain threshold and an increased cortical excitability in a broader context of a neurolimbic dysfunction.

Clinical features associated with ictal osmophobia in migraine.

Olfactory hypersensitivity may occur during migraine attacks and has been found to be very specific for this form of headache. Aim of this study was to investigate if migraineurs with ictal osmophobia have particular clinical features comparing to patients without ictal osmophobia. We recruited 200 consecutive migraineurs. Other primary headaches comorbidity and migraine prophylaxis were exclusion criteria. Each patient was interviewed following a structured questionnaire including general features about migraine, depression and anxiety symptoms. Migraine triggers both spontaneously and selecting from a specific list. Allodynia during the migraine attack was measured using the Allodynia symptoms check-list 12 (ASC-12). Eighty four (42 %) patients are non-osmophobic vs. 116 patients (58 %) who are osmophobic. After a logistic regression analysis, pain intensity (OR 1.391; p = 0.008) and anxiety (OR 1.099; p = 0.047) were significantly higher while aura (OR 0.421; p = 0.028) is less frequent in osmophobic migraineurs. We found significant differences in clinical features of osmophobic patients in respect to non-osmophobic ones. Ictal osmophobia seems being related to a broader sensorial hypersensitivity that could lead to a more florid clinical presentation.

Uncommon and/or bizarre features of dementia.

This study aimed at describing uncommon or bizarre symptoms observed in patients suffering from dementia. Medline and Google scholar searches were conducted for relevant articles, chapters, and books published since 1967. Search terms used included uncommon presentation, behavioural and psychological symptoms, dementia, Alzheimer's disease, and fronto-temporal dementia. Publications found through this indexed search were reviewed for further relevant references. The uncommon symptoms are described as case-reports and there are no systematic investigations. Bizarre behaviours arising late in life should be thoroughly investigated as symptoms of dementia.

Delusional misidentification syndromes and dementia: a border zone between neurology and psychiatry.

The delusional misidentification syndromes (DMSs) are psychopathologic phenomena in which a patient consistently misidentifies persons, places, objects, or events. Although often described in relation to psychotic states including schzofrenia, it is, nevertheless, widely considered that these syndromes have an anatomical basis because of their frequent association with organic brain disease; studies have pointed to the presence of identifiable lesions, especially in the right frontal lobe and adjacent regions, in a considerable proportion of patients. The purpose of this article is to examine the phenomenon in people with dementia. We searched the electronic databases for original research and review articles on DMS in patients with dementia using the search terms "Delusional Misidentification Syndrome, Capgras syndrome, Fregoli syndrome, reduplicative paramnesia, and dementia." The DMSs are a frequent problem in dementia. The violence and dangerousness in patients with dementia having these syndromes are well documented, and forensic aspects are highlighted. Pathogenetic viewpoint and management are considered.

A single-center, cross-sectional prevalence study of impulse control disorders in Parkinson disease: association with dopaminergic drugs.

The current study aimed at establishing the prevalence of impulse control disorders (ICDs) in patients with Parkinson disease (PD) and their association with demographic, drug-related, and disease-related characteristics. We performed a single-center cross-sectional study of 805 PD patients. Impulse control disorders were investigated with the Questionnaire for Impulsive Compulsive Disorders in Parkinson's Disease; also comorbid neuropsychiatric complications (dementia, delusions, visual hallucinations) were investigated with clinical interviews and ad hoc instruments (Parkinson Psychosis Questionnaire and Neuropsychiatry Inventory). Impulse control disorders were identified in 65 patients (prevalence, 8.1%), with pathological gambling and hypersexuality the most frequent. Impulse control disorders were present in 57 of 593 cognitively preserved patients (prevalence, 9.6%) and in 8 of 212 demented patients (prevalence, 3.8%). Impulse control disorders were significantly associated with dopamine agonists (odds ratio [OR], 5.50; 95% confidence interval [CI], 2.60-12.46; P < 0.0001) and levodopa (OR, 2.43; 95% CI, 1.06-6.35; P = 0.034). Impulse control disorders frequency was similar for pramipexole and ropinirole (16.6% vs 12.5%; OR, 1.45; 95% CI, 0.79-2.74; P = 0.227). Additional variables associated with ICDs were male sex and younger age. These findings suggested that dopaminergic treatments in PD are associated with increased odds of having an ICD, but also other demographic and clinical variables are associated with ICDs, suggesting the multifactorial nature of the ICD phenomenon in PD.

Affective theory of mind in patients with Parkinson's disease.

AIM: The aim of this study was to assess the hypothesis that patients with Parkinson's disease (PD) may have difficulties in tasks of affective theory of mind (ToM; the inference on others' feelings) especially in moderate/advanced PD stages. Difficulties of cognitive ToM have already been described in several previous studies. METHODS: Affective ToM was assessed with the Reading the Mind in the Eyes task in 35 PD patients and 35 healthy controls. Depression, global cognitive status and executive functioning were also evaluated. Patients were distinguished in early PD and moderate PD according to their scores in the Hoehn and Yahr Staging Scale. RESULTS: PD patients had more difficulties with affective ToM than healthy controls, also controlling for other variables that resulted in association with this ability. Early PD patients outperformed moderate PD patients, but this difference did not reach statistical significance when controlling for other variables. CONCLUSION: These findings confirmed that affective ToM may be impaired in PD, but any conclusion can be made on the effect of disease progression on this ability of social cognition. Therefore, longitudinal studies are needed to investigate this potential effect.

Repetitive and stereotypic phenomena and dementia.

BACKGROUND: Behavioral disturbances of dementia, such as repetitive and stereotypic phenomena, can be distressing to caregivers and may lead to early institutionalization of the patient. OBJECTIVE: The purpose of this article is to examine the phenomenon of repetitive phenomena in patients with dementia. METHODS: We searched the PubMed electronic databases for original research and review articles on repetitive phenomena in patients with dementia using the search terms "repetitive behavior, stereotypic behavior, dementia, Alzheimer's disease, Frontotemporal dementia." RESULTS: Repetitive and stereotypic phenomena are common problems in dementia, which may reflect a disruption of coordinated function within the basal ganglia or corticostriatal structures. CONCLUSIONS: There are no systematic studies concerning repetitive phenomena in patients with dementia, and very little is known about the treatment. Further studies are needed to determine the specific phenomena.