Enrico Marchioni

Relationship between hallucinations, delusions, and rapid eye movement sleep behavior disorder in Parkinson's disease.

Psychotic symptoms are the main and the most disabling “nonmotor” complications of Parkinsons disease (PD), the pathophysiology of which is poorly recognized. Polysomnographic studies have shown a relationship between visual hallucinations and rapid eye movement (REM) sleep. The objective of this study is to clarify the relationship between psychotic symptoms and REM sleep behavior disorder (RBD) in PD. In a Parkinsons disease outpatient unit, 289 consecutive subjects with idiopathic PD were administered (in the period from January to December 2002) a multiple‐choice questionnaire and structured interview on sleep and mental disorders. RBD was diagnosed in accordance with the minimal diagnostic criteria of the International Classification of Sleep Disorders. Hallucinations and delusional disorders were diagnosed according to the Diagnostic and Statistical Manual of Mental Disorders‐IV criteria. The presence or absence of psychotic symptoms, of RBD, and of daytime sleepiness, as well as motor status, cognitive status, and mood were assessed. Approximately 32% (n = 92) of the subjects presented with psychotic disorders; 30% (n = 86) had experienced hallucinations; 2% (n = 6) had delusions without hallucinations. Sixty‐two (72%) hallucinators reported nocturnal hallucinations. A total of 6.6% (n = 19) of the subjects complained of a delusional disorder. There were 26.6% (n = 77) of subjects who presented with RBD: 28 (36%) with onset before and 49 (63%) with onset after PD diagnosis. The presence of RBD was associated with an increased risk of manifesting hallucinations and delusions (odds ratio [OR], 2.73). Other independent clinical factors found to have an effect on psychotic disorders were cognitive impairment (OR, 3.92), disease duration (OR, 2.46), advanced age (OR, 2.34), and severity of motor symptoms (OR, 2.06). These results suggest that RBD is widely associated with psychosis in PD.

REM sleep behavior disorder, hallucinations, and cognitive impairment in Parkinson's disease

The objective of this study was to evaluate the relationship between REM sleep behavior disorder (RBD), hallucinations, and cognitive impairment in Parkinsons disease (PD). One hundred and ten PD patients, divided into three groups (without RBD or hallucinations; with RBD but no hallucinations; with RBD and hallucinations), were submitted to neuropsychological evaluation. The group without RBD and hallucinations showed normal neuropsychological tests when compared to normal controls. The group with hallucinations was characterized by a more severe cognitive impairment affecting both short‐ and long‐term memory, logical abilities, and frontal functions, while the RBD‐only group presented frontal impairment. The hypothesis that RBD in PD can be considered a risk factor not only of the hallucinations but also of more severe and diffuse cognitive abnormalities needs to be strengthened through a longitudinal evaluation.

Postinfectious inflammatory disorders Subgroups based on prospective follow-up

Background: Acute disseminated encephalomyelitis (ADEM) refers to a monophasic acute multifocal inflammatory CNS disease. However, both relapsing and site-restricted variants, possibly associated with peripheral nervous system (PNS) involvement, are also observed, and a systematic classification is lacking. Objective: To describe a cohort of postinfectious ADEM patients, to propose a classification based on clinical and instrumental features, and to identify subgroups of patients with different prognostic factors. Methods: Inpatients of a Neurologic and Infectious Disease Clinic affected by postinfectious CNS syndrome consecutively admitted over 5 years were studied. Results: Of 75 patients enrolled, 60 fulfilled criteria for ADEM after follow-up lasting from 24 months to 7 years. Based on lesion distribution, patients were classified as encephalitis (20%), myelitis (23.3%), encephalomyelitis (13.3%), encephalomyeloradiculoneuritis (26.7%), and myeloradiculoneuritis (16.7%). Thirty patients (50%) had a favorable outcome. Fifteen patients (25%) showed a relapsing course. Poor outcome was related with older age at onset, female gender, elevated CSF proteins, and spinal cord and PNS involvement. All but two patients received high-dose steroids as first-line treatment, with a positive response in 39 (67%). Ten of 19 nonresponders (53%) benefited from high-dose IV immunoglobulin; 9 of 10 had PNS involvement. The data were not controlled. Conclusions: A high prevalence of “atypical variants” was found in this series, with site-restricted damage or additional peripheral nervous system (PNS) involvement. Prognosis and response to steroids were generally good, except for some patient subgroups. In patients with PNS involvement and steroid failure, a favorable effect of IV immunoglobulin was observed.

Effectiveness of intravenous immunoglobulin treatment in adult patients with steroid-resistant monophasic or recurrent acute disseminated encephalomyelitis

Abstract Randomized Controlled Trials have not jet established the best pharmacological management of Acute Disseminated Encephalomyelitis (ADEM). High dose steroids are usually employed with good results, but in a few cases the clinical outcome is poor. In other patients, particularly those affected by the site restricted ADEM variants (myelitis), the disease shows a recurrent course resembling that of Multiple Sclerosis. We present here five patients, 3 of them affected by classic disseminated encephalomyelitis and 2 by a post infectious myelitis, which showed a good response to intravenous immunoglobulin (IVIg) after steroid treatment failure. In our report high dose steroids administration was substantially uneffective in all but one case, who showed a good response only during the first episode. On the contrary IVIg injection (0,4 gr/kg/day) produced a marked functional improvement in all patients starting within the first five days of drug administration and reaching a maximum within three weeks. One patient experienced a good effect nothwithstanding a steady dysability. In all cases, clinical evidence was supported by MRI controls showing improving posttreatment changes.

ICHD‐II diagnostic criteria for Tolosa–Hunt syndrome in idiopathic inflammatory syndromes of the orbit and/or the cavernous sinus

A bibliographical search was conducted for papers published between 1999 and 2007 to verify the validity of International Classification of Headache Disorders (ICHD)-II criteria for the Tolosa-Hunt syndrome (THS) in terms of (i) the role of magnetic resonance imaging (MRI); (ii) which steroid treatment should be considered as adequate; and (iii) the response to treatment. Of 536 articles, 48, reporting on 62 patients, met the inclusion criteria. MRI was positive in 92.1% of the cases and it normalized after clinical resolution. There was no evidence of which steroid schedule should be considered as adequate; high-dose steroids are likely to be more effective both to induce resolution and to avoid recurrences. Pain subsided within the time limit required by the ICHD-II criteria, but signs did not. We conclude that THS diagnostic criteria can be improved on the basis of currently available data. MRI should play a pivotal role both to diagnose and to follow-up THS.

Patients with psychogenic nonepileptic seizures, alone or epilepsy-associated, share a psychological profile distinct from that of epilepsy patients

Abstract. The aim of this study was twofold: 1 – to identify a psychological profile of patients with psychogenic nonepileptic seizures (PNESs) that is possibly distinct from that of subjects affected by epileptic seizures (ESs) alone; 2 – to detect the possible differences between the clinical features and psychological profile of patients affected by PNESs alone and those of subjects in whom PNESs are associated with epileptic seizures (ES/PNES patients).We assessed the psychological profiles of 2 different groups of subjects. The first group was of 38 patients who had all developed PNESs after epileptic seizures (ES\PNES, group 1). The second group was of 31 patients with PNESs alone (PNES, group 2). We compared the psychological findings of each of these 2 groups with those of 2 control groups, composed of patients who matched groups 1 and 2 for sex, age, and educational level, but who were affected only by ESs (groups 1C and 2C). Finally, we considered possible differences between the ictal symptoms and signs of PNESs occurring in ES/PNES and in PNES patients.Both the ES/PNES group and the PNES group revealed higher percentages of Somatoform Disorders and Cluster B Personality Disorders (DSM-III-R diagnoses) than the ES patients in the control groups. The scores obtained on the Psychophysiological Distress Scale of the Cognitive Behavioural Assessment Battery (CBA) followed the same pattern.Among PNES ictal phenomena, autonomic symptoms and signs were significantly more frequent in the PNES than in the ES/PNES group. The occurrence of PNESs mimicking generalised tonic-clonic ESs (GTC-PNESs) was significantly associated with a low academic level.The results of this study suggest that the patients with PNESs alone and those affected by PNESs and ESs share the same psychological profile, which is different from that of patients with ESs alone. However, some differences between ES/PNES and PNES patients were found in the clinical semiology of their PNESs. Our findings could have implications for the diagnosis and for the treatment of patients with PNESs.

Partial Epileptic Seizures of Different Origin Variably Affect Cardiac Rhythm

Summary: Purpose: The present study was aimed at evaluating electrocardiographic (ECG) changes associated with partial epileptic seizures without seizure activity secondarily generalized.

Neuropsychological assessment in MS: clinical, neurophysiological and neuroradiological relationships.

We assessed cognitive performance and its relationship with clinical and anatomic disease severity in MS with mild to moderate handicap; 34 definite MS and 18 healthy subjects matched for age and education were submitted to a neuropsychological test battery. Both groups were examined for anxiety. MS patients underwent magnetic resonance imaging examination. MS performed worse than controls on all WAIS‐P subtests and had learning, short‐ and long‐term verbal memory impairment. Cognitive deficits were not related to abnormal emotional states, but were found to be associated with attentional process and information‐processing speed impairment. Cognitive impairment did not correlate with severity of physical disability. The most severe memory deficits were found in patients with extensive periventricular damage.

Cytokines and chemokines in cerebrospinal fluid and serum of adult patients with acute disseminated encephalomyelitis.

Cytokines and chemokines contribute to the pathogenesis of acute disseminated encephalomyelitis (ADEM). Using a multiplex immunochemiluminescence ELISA, we measured 8 Th1/Th2 cytokines and 18 chemokines in the cerebrospinal fluid (CSF) and serum of 17 ADEM patients, 14 multiple sclerosis (MS) patients, and 7 healthy controls (HCs). Relative to HCs, ADEM patients had significantly high mean CSF concentrations of chemokines with attractant/activating properties towards neutrophils (CXCL1 and CXCL7), monocytes/T cells (CCL3 and CCL5), Th1 cells (CXCL10), and Th2 cells (CCL1, CCL22, and CCL17). Mean CSF concentrations of CXCL7, CCL1, CCL22, and CCL17 were higher in ADEM than in MS, whereas those of CCL11 were lower in MS than in ADEM and HCs. CSF pleocytosis correlated with CSF concentrations of CXCL1, CXCL10, CCL1, CCL17, and CCL22. Most of the functionally homologous chemokines correlated with each other. CSF Th1/Th2 cytokines were not detectable in most samples. Their mean concentrations did not differ in the three groups, and the same held for serum cytokines and chemokines. Our data suggest that the upregulation of chemokines active on neutrophils and Th2 cells differentiates ADEM from MS inflammation, and that both Th1 and Th2 chemokines might be produced in ADEM. Chemokines upregulated in ADEM could become CSF biomarkers after a posteriori evaluations in unselected case series.

A case of a progressive multifocal leukoencephalopathy patient with four different JC virus transcriptional control region rearrangements in cerebrospinal fluid, blood, serum, and urine

JC virus (JCV) is the etiological agent of progressive multifocal leukoencephalopathy (PML), a fatal demyelinating disease of the central nervous system (CNS). During the acquired immunodeficiency syndrome (AIDS) epidemic, it was the cause of the death in up to 8% of AIDS patients. The genomic organization of JCV and, in particular, the hypervariability of the transcriptional control region (TCR), a regulatory noncoding region, are well known. Given that the TCR plays a central role in the viral replication of JCV, a crucial role in the determination of the neurotropism and in the pathogenic capabilities of the virus is also suspected. Here the authors describe a case of PML that did not respond to highly active antiretroviral therapy (HAART) therapy. There was a simultaneous presence of JCV strains with four different TCR structures in urine, peripheral blood cells, serum, and cerebrospinal fluid (CSF) samples. These data confirmed that the presence of the archetype TCR is restricted to urine, while also suggesting that the degree of the rearrangement varies and increases from the peripheral blood to CSF.