Salvatore Lo Fermo

Epilepsy and Multiple Sclerosis in Sicily: A Population‐based Study

Summary:  Purpose: To evaluate the association between epilepsy and multiple sclerosis (MS), we analyzed the incidence of epilepsy in a population‐based incidence cohort of MS in Catania, Sicily.

Outcome of psychiatric symptoms presenting at onset of multiple sclerosis: a retrospective study

Psychiatric disturbances may occur at the onset of multiple sclerosis. However, information on their outcome is lacking. Our objective was to document the characteristics of psychiatric symptoms at presentation of multiple sclerosis and to define the long-term evolution of psychiatric disturbances in these patients. Based on a clinical record analysis of patients with defined multiple sclerosis diagnosis and coming under the care of a university multiple sclerosis centre within the period 1997—2007, patients with both psychiatric and neurological symptoms at presentation were identified. Clinical data at onset and at last follow-up were considered. Among 682 evaluated patients, psychiatric disturbances were associated with multiple sclerosis onset in 16 cases (2.3%). Most patients (56%) presented with a mood disorder with clinical characteristics of a major depressive-like episode, five (32%) had psychotic symptoms. Initial psychiatric disturbances improved later than neurological symptoms, or never fully recovered, regardless of the concomitant use of psychotropic medications. In most of the subjects psychiatric disturbances tended to remain over the follow-up period and at last visit, after a mean follow-up of 7.6 years (±2.3), 14 subjects (87%) had a supplementary diagnosis of psychiatric illness. Psychiatric symptoms at onset of multiple sclerosis may be indicators of possible maintenance of psychiatric morbidity in a sizeable proportion of patients.

Increasing frequency of multiple sclerosis in Catania, Sicily: a 30-year survey

Background and Objective: The objective of this study was to determine the prevalence and incidence of multiple sclerosis (MS) and its temporal profiles from 1975 to 2005 in the city of Catania. Methods: The incidence of MS from 1975 to 31 December 1999 had been previously investigated by the same group. The frequency of MS in the community of Catania from 1 January 2000 to 31 December 2004 was studied in a population of 313,110 inhabitants (2001 census). All patients who satisfied Poser’s criteria were considered as prevalent and incident cases. Results: Three hundred and ninety-eight patients with MS who had experienced the clinical onset of the disease before 31 December 2004 were found in a population of 313,110 inhabitants. The prevalence rate was 127.1/100,000 [95% confidence interval (CI) 115.1–140.4]. From 2000 to 2004, 108 patients with MS had clinical onset of the disease. The mean annual incidence was 7.0/100,000 (95% CI 5.7–13.7) and was higher in women (8.4/100,000; 95% CI 6.4–10.5) than in men (5.3/100,000; 95% CI 3.7–7.2). The mean length of time between the date of clinical onset and the date of the diagnosis was 1.4 ± 1.7 years. During the last 30 years the incidence of MS in this population increased from 1.3/100,000 during the first quinquennium (1975–9) to 7.0/100,000 during 2000–4. Conclusions: Incidence rates have further increased in this population, suggesting that the risk of MS is still increasing.

Multiple Sclerosis and CCSVI: A Population-Based Case Control Study

Background Chronic cerebrospinal venous insufficiency (CCSVI) has been associated to multiple sclerosis (MS). Objective To evaluate the possible association between CCSVI and MS, using a population-based control design. Methods A random cohort of 148 incident MS patients were enrolled in the study. We have also studied 20 patients with clinically isolated syndrome (CIS), 40 patients with other neurological diseases (OND), and 172 healthy controls. Transcranial (TCC) and Echo Color Doppler (ECD) were carried out in 380 subjects. A subject was considered CCSVI positive if ≥2 venous hemodynamic criteria were fulfilled. Results CCSVI was present in 28 (18.9%) of the MS patients, in 2 (10%) of CIS patients, in 11 (6.4%) of the controls, and in 2 (5%) of the OND patients. A significant association between MS and CCSVI was found with an odds ratio of 3.41 (95% confidence interval 1.63–7.13; p = 0.001). CCSVI was significantly more frequent among MS subjects with a disease duration longer than 144 months (26.1% versus 12.6% of patients with duration shorter than 144 months; p = 0.03) and among patients with secondary progressive (SP) and primary progressive (PP) forms (30.2% and 29.4, respectively) than in patients with relapsing remitting (RR) MS (14.3%). A stronger association was found considering SP and PP forms (age adjusted OR = 4.7; 95% CI 1.83–12.0, p = 0.001); the association was weaker with the RR patients (age adjusted OR = 2.58; 95%CI 1.12–5.92; p = 0.02) or not significant in CIS group (age adjusted OR = 2.04; 95%CI 0.40–10.3; p = 0.4). Conclusions A higher frequency of CCSVI has been found in MS patients; it was more evident in patients with advanced MS, suggesting that CCSVI could be related to MS disability.

Lights and Shadows of Cyclophosphamide in the Treatment of Multiple Sclerosis

Cyclophosphamide (cy) is an alkylating agent used to treat malignancies and immune-mediated inflammatory nonmalignant processes. It has been used as a treatment in cases of worsening multiple sclerosis (MS). Cy is currently used for patients whose disease is not controlled by beta-interferon or glatiramer acetate as well as those with rapidly worsening MS. The most commonly used regimens involve outpatient IV pulse therapy given with or without corticosteroids every 4 to 8 weeks. Side effects include nausea, headache, alopecia, pain, male and women infertility, bladder toxicity, and risk of malignancy. Previous studies suggest that cy is effective in patients in the earlier stages of disease, where inflammation predominates over degenerative processes. Given that early inflammatory events appear to correlate with later disability, a major question is whether strong anti-inflammatory drugs, such as cy, will have an impact on later degenerative changes if given early in the disease to halt inflammation.

Life-Threatening Constipation Induced by Intrathecal Baclofen Therapy

drugs (4 azathioprine, 2 methotrexate, 1 interferon beta-1b, 8 gabapentin, 2 pregabalin, 2 phenobarbital, 2 paroxetine, 1 citalopram, 1 venlafaxine, 7 furosemide, 4 heparin, 1 risperidone and 1 olanzapine). Fifteen patients did not receive any concomitant medication. ITB was administered with a mean effective daily dose of 251.3 8 11 g (range 90–580 g). Adverse events of ITB were monitored by evaluating patients’ monthly records and constipation was defined as Dear Sir, Intrathecal baclofen (ITB) delivery is a therapeutic option for patients with severe spasticity not responding to common oral medications, such as baclofen, dantrolene or tizanidine. At common doses, ITB is usually tolerated by patients [1] . Unfortunately, higher doses could be necessary to treat many cases of spasticity, thus enhancing the frequency of side effects [2–4] . Concerning gastrointestinal function, ITB could affect peristalsis, which could be severely slowed down to paralytic ileus. Nevertheless, constipation has previously been reported as an infrequent ITB-induced adverse effect, ranging from 3 to 10% of treated patients [2–4] . Here we report that, in our series of patients treated with ITB, constipation was a frequent and serious side effect, leading to death in 1 case. Thirty-eight patients (26 men and 12 women; age 48.7 8 15.4 years, mean 8 SD) were implanted for continuous ITB infusion from August 2002 to July 2006. They had severe spasticity due to different neurological diseases. Thirty-six patients out of 38 (95%) were affected by spinal cord diseases (myelitis, n = 19; multiple sclerosis, n = 13; traumatic injury, n = 4). The remaining 2 patients suffered from spasticity due to anoxic encephalopathy. All patients had previously been treated with oral baclofen, dantrolene, or tizanidine at their optimal doses, without relevant clinical benefit. Twenty-three out of 38 patients (61%) were on treatment with other Received: June 27, 2007 Accepted: October 9, 2007 Published online: June 14, 2008

Sporadic motor neuron disease in a familial novel SOD1 mutation: Incomplete penetrance or chance association?

Abstract Cu/Zn superoxide dismutase (SOD1) gene mutations have been reported in familial and sporadic amyotrophic lateral sclerosis (ALS). We report a novel G61R SOD1 mutation in a patient with a distinct phenotype including prominent lower motor neuron dysfunction, proximal weakness and atrophy with asymmetrical onset in the thigh and buttock and relentless clinical course. The G61R mutation segregated in three unaffected relatives including the 80-year-old mother and two of the probands siblings. Potential mechanisms include an autosomal dominant condition with reduced penetrance or a chance association.

Effectiveness and safety of Rituximab in demyelinating diseases spectrum: an Italian experience

BACKGROUND Rituximab (RTX), a monoclonal antibody targeting the CD20+ B lymphocytes, deserves major attention as therapeutic option in the treatment of demyelinating disorders of the central nervous system (DDCNS). We reported our clinical experience with the use of RTX in terms of efficacy and safety in persons suffering from DDCNS. METHODS An Italian single-center observational analysis of patients who underwent RTX treatment between 2011 and 2017 was performed at MS center of Catania, Italy. No evidence of disease activity (NEDA) was applied to evaluate the response to RTX. CD19+ and CD20+ counts were collected along therapy. RTX-related adverse events were recorded. RESULTS Eleven patients with MS, four with NMOSD and two with NMO were enrolled. Out of them, 4/17 were naïve to previous treatments. According to NEDA status, 11/17 got NEDA3 status at the follow-up. Six patients had relapses (two had a single relapse and four had multiple relapses). One patient with primary progressive MS and one with relapsing remitting MS stopped RTX, the last one for severe lymphopenia. CONCLUSIONS RTX showed efficacy to impact DDCNS worsening with an acceptable safety profile.

Wernicke encephalopathy and systemic sclerosis: rare association of rare conditions

Wernicke encephalopathy (WE) is an acute neurological syndrome due to thiamine (vitamin B1) deficiency. The cardinal signs are ophthalmoplegia, ataxia, and disorientation. Predisposing conditions for thiamine deficiency are gastroenteric diseases and surgery, hyperemesis gravidarum, and starvation. However, the most common cause of thiamine deficiency throughout the world is alcoholism. Herein, we report the case of a patient affected by systemic sclerosis (SS) who developed WE. The association between SS and WE has never been reported; however, SS should be considered as a clinical condition affecting the correct absorption of thiamine when history, clinical presentation, and neuroradiological features lead to the diagnosis of WE. The knowledge of such association is helpful to the clinicians to allow an adequate therapy and recovery. The patient was a 67-year-old woman with a past history of SS. She was not a drinker and previous episodes of upper respiratory or gastrointestinal infections were not reported. The patient complained of nausea and vomit and progressive weakness in her extremities for 1 month. A week before admission to our clinic she experienced an acute onset of diplopia, spatial and temporal disorientation, and personality changes with impulsivity and irritability. Physical examination revealed calcinosis cutis, sclerodactyly, telangiectasia, Raynaud’s phenomenon, and esophageal dysmotility (Video). Neurological examination disclosed complete bilateral external ophthalmoplegia, distal-dominant weakness in the four limbs, dysmetria at finger–nose, and heel to shin tests and hypo-elicitable deep tendon reflex of lower limbs (Video). Nerve conduction study revealed a sensory axonal polyneuropathy. Gastrointestinal endoscopy showed dilated esophageal tract and gastrectasia with the absence of propulsive waves and consequent gastric fluid stasis (Fig. 1). Whole body Computed Tomography (CT) scan excluded other causes of gastrointestinal symptomatology. T2-fluid-attenuated inversion recovery (FLAIR) magnetic resonance (MR) depicted hyperintense bilateral and symmetrical lesions involving the periaqueductal region and extending superiorly to the thalami and the mammillary bodies, and inferiorly to the floor of the fourth ventricle, the cerebellar vermis, and the medulla (Fig. 2, left). Hyperintensity areas were also detected in the splenium of the corpus callosum. On the basis of history, clinical presentation and characteristic findings on neuroimaging, a diagnosis of WE was established. Therefore, the patient was treated with intravenous thiamine 100 mg per day and she recovered from ophthalmoplegia and from the disturbance of consciousness in few days. Brain MR scan was repeated 7 days after starting medical therapy, showing the disappearance of the hyperintensity areas (Fig. 2, right) with the exception of the lesions at the splenium of the corpus callosum. WE is a neurological disorder resulting from thiamine deficiency, presenting with a clinical triad of ocular signs, altered consciousness and ataxia. These features are simultaneously present in only 10 % of cases [1]. Ocular abnormalities occur in 29 % of patients approximately, and Electronic supplementary material The online version of this article (doi:10.1007/s10072-016-2704-9) contains supplementary material, which is available to authorized users.