Validation of the DYALS (dysphagia in amyotrophic lateral sclerosis) questionnaire for the evaluation of dysphagia in ALS patients.

BACKGROUND: Dysphagia is a common symptom during the trajectory of ALS, and it can significantly impact on the quality of life and prognosis of patients. Nowadays, no specific tool for the screening of dysphagia in ALS is validated, and the approach is heterogeneous across the Italian centres. OBJECTIVE: To validate the DYALS (dysphagia in amyotrophic lateral sclerosis) questionnaire, adapting the DYMUS (dysphagia in multiple sclerosis) questionnaire, for the assessment of dysphagia in ALS patients, in order to uniform the evaluations across the Italian ALS network. METHODS: We included 197 patients diagnosed with ALS following the El Escorial criteria, in sixteen Italian ALS centres between 1st December 2019 and 1st July 2020. For each patient, we collected clinical and demographic data and obtained ALSFRS-r score, ALSAQ-5 score, DYMUS score, and EAT-10 score. RESULTS: Across the 197 patients, the ratio M/F was 113/84, and the median age was 64 years (IQR 56-72.5). Bulbar patients were 20%, and spinal patients 80%. The median ALSFRSr total score of patients was 35 (IQR 28-39). DYALS score was statistically higher in bulbar ALS than in spinal ALS (median = 6, IQR 4.5-9 vs median = 1, IQR 0-5, z = 6.253, p < 0.0001). DYALS questionnaire showed a high internal consistency (Cronbach's alpha = 0.88). There was a statistically significant correlation between DYALS and EAT-10 (rho = 0.90, p < 0.0001). CONCLUSIONS: DYALS scale is reliable, manageable, and easily usable for the screening of dysphagia in ALS. It can be shared with all the Italian ALS centres in order to collect uniform data for therapeutic strategies and clinical trials.

Neurologic manifestations in 1760 COVID-19 patients admitted to Papa Giovanni XXIII Hospital, Bergamo, Italy.

OBJECTIVES: Evidences from either small series or spontaneous reporting are accumulating that SARS-CoV-2 involves the Nervous Systems. The aim of this study is to provide an extensive overview on the major neurological complications in a large cohort of COVID-19 patients. METHODS: Retrospective, observational analysis on all COVID-19 patients admitted from February 23rd to April 30th, 2020 to ASST Papa Giovanni XXIII, Bergamo, Italy for whom a neurological consultation/neurophysiological assessment/neuroradiologic investigation was requested. Each identified neurologic complication was then classified into main neurologic categories. RESULTS: Of 1760 COVID-19 patients, 137 presented neurologic manifestations that manifested after COVID-19 symptoms in 98 pts and was the presenting symptom in 39. Neurological manifestations were classified as: (a) cerebrovascular disease [53 pts (38.7%)] including 37 ischemic and 11 haemorrhagic strokes, 4 transient ischemic attacks, 1 cerebral venous thrombosis; (b) peripheral nervous system diseases [31 (22.6%)] including 17 Guillain-Barrè syndromes; (c) altered mental status [49 (35.8%)] including one necrotizing encephalitis and 2 cases with RT-PCR detection of SARS-Cov-2 RNA in CSF; (d) miscellaneous disorders, among whom 2 patients with myelopathy associated with Ab anti-SARS-CoV-2 in CSF. Patients with peripheral nervous system involvement had more frequently severe ARDS compared to patients with cerebrovascular disease (87.1% vs 42%; difference = 45.1% 95% CI 42.0-48.2; χ2= 14.306; p < 0.0002) and with altered mental status (87.1% vs 55.6%; difference = 31.5% 95% CI 27.5-37.5%; χ2= 7.055; p < 0.01). CONCLUSION: This study confirms that involvement of nervous system is common in SARS-CoV-2 infection and offers clinicians useful information for prevention and prompt identification in order to set the adequate therapeutic strategies.

The Italian multicenter experience with edaravone in amyotrophic lateral sclerosis.

OBJECTIVES: The aim of the study is to analyze the ALS disease progression and respiratory function of Italian patients treated with edaravone (EVN), as well as the adherence to, and the effects of, the therapy. METHODS: We performed an observational study of patients treated with EVN from May 2017 to May 2019, in 39 Italian ALS Centers. Taking into account ALS patients with at least 12 months of EVN treatment, we compared the decline of ALSFRS-R and FVC with a group of matched historical controls from the Pooled Resource Open-Access ALS Clinical Trials (PRO-ACT) database, using both descriptive and survival analysis approaches. RESULTS: A total of 331 ALS Italian patients treated with EVN and 290 matched historical controls were recruited in this study. No significant differences on disease progression or respiratory function were found comparing the two cohorts in both descriptive and survival analyses. The EVN treatment was overall well tolerated. CONCLUSIONS: The study showed that EVN treatment was well tolerated. No significant differences were reported in ALS patients treated and not treated with EVN, in terms of both disease progression and respiratory function. These findings prove that further studies are required to better clarify whether EVN could be considered an effective treatment for ALS disease.

Posterior reversible encephalopathy and Guillain-Barré syndrome: which came first, the chicken or the egg? A review of literature.

Posterior reversible encephalopathy (PRES) is a rare occurrence in patients with Guillain-Barré syndrome (GBS) with only nine adult cases reported to date. We conducted a review of the literature and compared previous cases with a novel case admitted to our clinic. In light of the timing of the symptoms, it is assumable that arterial hypertension can develop acutely during a phase of GBS-related autonomic dysfunction and subsequently precipitates PRES. According to this, dysautonomia caused by GBS could precede motor weakness; thus, PRES in the absence of any strong alternative etiology may suggest an underlying GBS.

Persistent Interictal Musical Hallucination in a Patient With Mesial Temporal Sclerosis-Related Epilepsy: First Case Report and Etiopathological Hypothesis.

Musical hallucination is a disorder of complex sound processing of instrumental music, songs, choirs, chants, etc. The underlying pathologies include moderate to severe acquired hearing loss (the auditory equivalent of Charles Bonnet syndrome), psychiatric illnesses (depression, schizophrenia), drug intoxication (benzodiazepines, salicylate, pentoxifylline, propranolol), traumatic lesions along the acoustic pathways, and epilepsy. The hallucinations are most likely to begin late in life; 70% of patients are women. Musical hallucination has no known specific therapy. Treating the underlying cause is the most effective approach; neuroleptic and antidepressant medications have only rarely succeeded.Musical hallucination in epilepsy typically presents as simple partial seizures originating in the lateral temporal cortex. To our knowledge, no formal report of musical hallucination in the interictal state has been published before. In contrast, other interictal psychotic features are a relatively common complication, especially in patients with long-standing drug-resistant epilepsy.We describe a 62-year-old woman with a long history of mesial temporal lobe epilepsy whose musical hallucination was solely interictal. We speculate on the possible link between temporal epilepsy and her hallucination. We hypothesize that, as a result of her epileptic activity-induced damage, an imbalance developed between the excitatory and inhibitory projections connecting the mesial temporal cortex to the other auditory structures. These structures may have generated hyperactivity in the lateral temporal cortex through a "release" mechanism that eventually resulted in musical hallucination.

Erythroblastaemia in natalizumab-treated patients with multiple sclerosis.

BACKGROUND: Natalizumab is a monoclonal antibody that significantly reduces the occurrence of relapses in relapse-remitting multiple sclerosis (RRMS) patients. Early papers on the clinical use of natalizumab in RRMS patients reported erythroblastemia as occasional and transient. OBJECTIVES: to determine the prevalence and absolute count of erythroblasts (nucleated red blood cells, NRBCs) in peripheral blood of RRMS patients in different treatment groups and healthy controls from the same geographic area using the same equipment for laboratory analysis. METHODS: We retrospectively evaluated the samples of 203 consecutive RRMS patients including 26 subjects on natalizumab, 17 on fingolimod, 72 on interferon, 41 on glatiramer acetate, 47 treatment-naïve and 240 healthy controls from the same geographic area. Blood samples were processed using an XN-9000-Hematology Analyzer and subsequent microscopic verification. In the natalizumab-treated patients we performed an additional analysis in order to detect the expression of CD34+ cells in peripheral blood, as confirmation of a bone marrow mobilization. RESULTS: The prevalence of patients with NRBCs positivity was significantly higher in natalizumab-treated patients (92%) compared with the other treatment groups and healthy controls (0%) (p<0.0005). The median absolute NRBCs count was significantly higher in natalizumab-treated patients (median 0.020, p<0.0005) than in the other treatment groups and healthy controls. Natalizumab-treated patients also had higher levels of white blood cells than all other groups and lower haemoglobin levels than healthy subjects (p<0.01), but no morphologic alterations were evident at a subsequent review of red blood cells, platelets and white blood cells. CD34+ cells levels were consistent with mobilization of haematopoietic stem cells from the bone marrow (median 8 cells/µL, IQR 5-12). CONCLUSIONS: We confirm erythroblastaemia as a frequent finding of natalizumab treatment in RRMS patients. More extended knowledge and adequate long-term observation of this phenomenon are essential to better understand any pathological implication.

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.

Understanding delusion in dementia: a review.

Alzheimer's disease and other dementia are associated with cognitive and functional impairment, as well as neuropsychiatric sequelae, including psychotic features. Research has largely concentrated on the study of cognitive decline, but the associated behavioral and neuropsychiatric symptoms are of equal importance in the clinical profile of the disease. Delusions are common, disabling and persistent in the course of dementia. The purpose of the present review was to examine the phenomenon of delusion in people with dementia. We searched the electronic databases for original research and review articles using the search terms "delusion, dementia, Alzheimer's disease, frontotemporal dementia, vascular dementia and Lewy body disease". Various types of explanations have been proposed regarding the etiology of delusional belief in dementia, and cerebral correlates are considered. Pharmacological and non-pharmacological treatments are analyzed.

Glatiramer acetate-induced hepatitis in a young female patient with multiple sclerosis.

We report the first Italian case of glatiramer acetate-related acute hepatotoxicity. A 25-years-old woman suffering from multiple sclerosis presented acute hepatitis after eight months of treatment. Neither infective, nor autoimmune markers were detected. Liver biopsy histology was consistent with drug-induced acute injury. Liver function tests became normal after eight weeks of treatment discontinuation. This report points out the importance of monitoring liver function during the first year of treatment with glatiramer acetate.

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.

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.

How aware are migraineurs of their triggers?

BACKGROUND: Broad discrepancies in the number of migraine triggers have been reported in several studies. Migraineurs do not seem to recognize easily headache triggers in clinical practice. OBJECTIVE: To evaluate how aware migraineurs are about their headache triggers. MATERIALS AND METHODS: We recruited 120 consecutive migraineurs. Each patient was first asked to report spontaneously any migraine trigger. Subsequently, the patient selected from a list of commonly known triggers. RESULTS: Ninety-seven patients (72.5%) spontaneously reported at least 1 migraine trigger, and 120 patients (100%) reported at least 1 migraine trigger selecting from a specific list of precipitants. The mean number of spontaneously identified triggers was 1.5 (±1.5), and the total number of triggers identified was 7.20 (±3.9). CONCLUSIONS: A relevant discrepancy between the number of spontaneously recognized triggers and the total number of triggers was found. This may suggest that migraineurs display poor awareness about headache triggers.

Triggers in allodynic and non-allodynic migraineurs. A clinic setting study.

BACKGROUND: Allodynia is considered a phenomenon of central sensitization that may lead to migraine transformation, lowering the attack threshold. Migraine triggers are factors that may induce headache attacks in susceptible individuals. We hypothesize that because allodynia decreases the migraine-attack threshold, allodynic migraineurs are more susceptible to triggers than the non-allodynic ones. OBJECTIVE: To determine if the number of headache triggers differs between migraineurs with no/mild allodynia and those with moderate/severe allodynia. MATERIALS AND METHODS: We recruited 120 consecutive migraineurs. Other primary headache comorbidity and migraine prophylaxis were exclusion criteria. Each patient was interviewed according a structured questionnaire including general features about migraine, depression, and anxiety symptoms. Patients reported any migraine trigger both spontaneously and by selecting from a specific list. Allodynia during the migraine attack was measured using the Allodynia Symptoms Check-List 12 (ASC-12): a cut-off of ASC-12 score of >2 defined allodynic patients; 3-5 score indicated mild allodynia; a 6-8 score moderate allodynia; and score of >8 severe allodynia. RESULTS: The total number of identified triggers was significantly and positively related to allodynia measured with ASC-12 (ρ(s) 0.33; P < .001). In a logistic regression model, allodynia independently influenced the risk to have a higher number of triggers. Moderate/severe allodynic patients had an odds ratio of 2.8 to report a number of triggers >7 in respect to non-/mild allodynic ones. CONCLUSIONS: Migraineurs with moderate/severe allodynia had more triggers than those with no/mild allodynia. It is unknown if those with moderate/severe allodynia are more susceptible to triggers, or repetitive stimulation of the trigeminal system by triggers resulted in moderate/severe allodynia.

Sociopathic behavior and dementia.

The maintenance of appropriate social behavior is a very complex process with many contributing factors. Social and moral judgments rely on the proper functioning of neural circuits concerned with complex cognitive and emotional processes. Damage to these systems may lead to distinct social behavior abnormalities. When patients present with dysmoral behavior for the first time, as a change from a prior pervasive pattern of behavior, clinicians need to consider a possible, causative brain disorder. The aim is to explore sociopathy as a manifestation of dementia. We searched electronic databases and key journals for original research and review articles on sociopathy in demented patients using the search terms "sociopathy, acquired sociopathy, sociopathic behavior, dementia, and personality". In conclusion, dementia onset may be heralded by changes in personality including alteration in social interpersonal behavior, personal regulation, and empathy. The sociopathy of dementia differs from antisocial/psychopathic personality disorders.

Dangerous passion: Othello syndrome and dementia.

Jealousy is a complex emotion that most people have experienced at some time in life; pathological jealousy refers primarily to an irrational state. Othello syndrome is a psychotic disorder characterized by delusion of infidelity or jealousy; it often occurs in the context of medical, psychiatric or neurological disorders. At least 30% of cases in the literature show a neurological basis for their delusion of infidelity, although its biological basis is not fully understood. The purpose of this paper is to examine the phenomenon of pathological jealousy in people with dementia. We searched the electronic databases for original research and review articles on Othello syndrome in demented patients using the search terms 'Othello syndrome, morbid jealousy, pathological jealousy, delusional disorders, dementia'. Convictions about the partner's infidelities may form the content of psychopathological phenomena, such as delusions. Delusional jealousy is a frequent problem in dementia. Coexistent delusions and hallucinations are frequent. The violence in demented patients suffering from this syndrome is well documented and forensic aspects are highlighted. There are no systematic researches about the clinical characteristics of Othello syndrome in persons suffering from dementia, but only case reports and it is not possible to differentiate or compare differences of delusional jealousy across the various type of dementia or distinguish the syndrome in demented patients from the syndrome in other psychiatric disorders. Frontal lobe dysfunction may be called into question in delineating the cause of the delusional jealousy seen in Othello syndrome.

Peri-ictal prolonged atrial fibrillation after generalized seizures: description of a case and etiopathological considerations.

Cardiac rhythm changes are not uncommon in connection with seizures and should be considered and recognized given their potentially harmful consequences including Sudden Unexpected Death in Epilepsy (SUDEP). The most well known are ictal tachycardia and bradycardia. However, other potentially dangerous peri-ictal arrhythmias have been reported. Brief atrial fibrillation episodes, never longer than 2 min, have rarely been described in connection with seizures. We report the case of a patient who presented with two generalized tonic-clonic seizures associated with prolonged atrial fibrillation. Extensive non-invasive cardiac investigations failed to disclose cardiac abnormalities, and after proper antiepileptic drug treatment the patient had neither further seizures nor cardiac events in an 18-month follow-up. Our case, to our knowledge, is the first report of prolonged (more than 1 h) peri-ictal atrial fibrillation.

Diogenes syndrome in patients suffering from dementia.

Diogenes syndrome (DS) is a behavioral disorder of the elderly. Symptoms include living in extreme squalor, a neglected physical state, and unhygienic conditions. This is accompanied by a self-imposed isolation, the refusal of external help, and a tendency to accumulate unusual objects. To explore the phenomenon of DS in dementia we searched for the terms: "Diogenes syndrome, self-neglect, dementia. " It has long been understood that individuals with dementia often become shut-ins, living in squalor, in the Eastern Baltimore study, dementia was present in 15% of the elderly cases with moderate and severe social breakdown syndrome; twice as many as in the general population of the same age group. Researchers have underlined the frequent presence of DS (36%) in frontotemporal dementia (FTD): different neuropsychological modifications in FTD may contribute to symptoms of DS. The initial treatment should be a behavioral program, but there is not sufficient information regarding pharmacological treatment of the syndrome.

El síndrome de Diógenes (SD) es un trastorno de la conducta de los ancianos. Los síntomas incluyen: vivir en la miseria extrema, un abandono del estado físico y condiciones antihigiénicas. Esto se acompaña de un aislamiento autoimpuesto, el rechazo a la ayuda externa y una tendencia a acumular objetos extraños. Para explorar el fenómeno del SD en la demencia se buscaron los términos: "síndrome de Diógenes, autoabandono, demencia". Desde hace tiempo se sabe que las personas con demencia con frecuencia llegan a estar confinados, viviendo en la miseria. En el estudio Eastern Baltimore la demencía se encontró en el 15% de los ancianos con un síndrome de desintegración social moderado o grave; el doble que en el mismo grupo etario de la poblacíon general. Los investigadores han destacado la presencia frecuente de SD (36%) en la demencia fronto-temporal (DFT) y diversas modificaciones neuropsicológicas de ésta pueden contribuir a los síntomas del SD. El tratamiento inicial debe ser un programa conductual, pero no hay suficiente informatión relacionada con el tratamiento farmacologico del síndrome.

Le syndrome de Diogène (SD) est un trouble comportemental des personnes âgées. Les symptômes consistent en des conditions d'hygiène déplorables, un aspect physique négligé et l'absence de soins corporels. Le tout accompagné d'un isolement auto-imposé, du refus d'aide externe et d'une tendance à accumuler des objets inhabituels. Pour explorer le phénomène du SD dans la démence, nous avons recherché les termes: « syndrome de Diogène, laisser-aller, démence ¼. On a longtemps cru que les individus déments ne sortaient plus de chez eux et vivaient dans des conditions d'hygiène déplorables. Dans l'étude de Baltimore Est, la démence était présente chez 15 % des personnes les plus âgées atteintes d'un syndrome de trouble social modéré à sévère ; deux fois plus que dans la population générale d'un même groupe d'âge. Des chercheurs ont souligné la présence fréquente de SD (36 %) dans la démence frontotemporale (DFT): différentes modifications neuropsychologiques dans la DFT peuvent contribuer aux symptômes du SD. Le traitement initial devrait être un programme comportemental, mais les informations sur le traitement pharmacologique du syndrome ne sont pas suffisantes.