Rita Rinaldi

Paroxysmal periodic motor attacks during sleep: clinical and polygraphic features

Three patients complained of paroxysmal motor attacks during sleep. Videopolygraphic recordings showed that motor activity could be divided into events of increasing behavioural complexity. Simpler motor events often represented the initial fragment of more complex attacks. Clinical features suggested the attacks represented frontal lobe epileptic seizures. The attacks recurred during NREM sleep with a periodic repetition every 20-60 sec. This periodicity could be related to the analogous physiological oscillation during light sleep and the periodicity of K complexes, exerting a facilitating influence upon epileptic mechanisms.

Epidemiology of status epilepticus in a rural area of northern Italy : a 2-year population-based study

We performed a 2‐year population‐based study on status epilepticus (SE) in adults in the rural area of Lugo di Romagna, northern Italy, to verify whether an area of low‐level urbanization has a lower risk of occurrence of SE (as recently suggested), different clinical features and short‐term prognosis than areas of high‐level urbanization. We found crude and age‐ and sex‐adjusted annual incidence rates of SE of 16.5/100 000 and 11.6/100 000, respectively. In patients under 60 years crude incidence was 2.9/100 000 and in the elderly (≥60 years) 38.6/100 000. Acute symptomatic SE accounted for 30% and a cerebrovascular pathology was the most frequently associated etiologic condition (60%). A history of seizures was reported in 41% of patients. The first therapeutic intervention was mainly benzodiazepines (lorazepam 46%; diazepam 33%). The 30‐day case fatality was 7%. We observed that the adult population of an area with a low level of urbanization has the same risk for SE, clinical features and short‐term prognosis as European urban areas. The only contrasting result is the 30‐day case fatality of 7% against the 39% found in the other Italian study (Bologna), despite the similarity of the SE features in these two areas of the same region. We infer that the short‐term prognosis of SE could also be considerably influenced by differences in health service organization (and hence management) possibly due to different levels of urbanization.

Satellite cell characterization from aging human muscle

Abstract Objectives: Satellite cells (SCs) are skeletal muscle progenitor cells located between the basal lamina and the sarcolemma of muscle fibers. They are responsible for muscle growth and repair. In humans, aging results in the depletion of the SC population and in its proliferative activity, but not in its function. It has not yet been determined whether under conditions of massive muscle fiber death in vivo, the regenerative potential of SCs is totally or partially compromised in old muscle. No studies have yet tested whether advanced age is a factor that restrains the response of SCs to muscle denervation in humans; this is also due to difficulties in the isolation and in the culture of SCs from a small human surgery fragment. The aim of this study was to study in depth muscle regeneration analysing the SC ability of SCs to proliferate and differentiate in aging human patients. Methods: In order to study in more detail the molecular mechanism, the proliferative and differentiative ability of aging SCs, we isolated SCs from aging human muscle biopsies and analysed their morphology by transmission electron microscopy and immunocytochemical analysis (antibodies against desmin, N-CAM and M-cadherin) and their capacity to grow and to expand in vitro. Moreover, in order to evaluate gene expression of myogenic regulatory factors Myf5, MyoD and myogenin (Myf4), RT-PCR was performed. Results and discussion: SCs isolated from aging human muscle biopsies and plated into favorable proliferation and differentiation conditions were able to proceed through the myogenic program and actively form myotubes, although taking longer than the young control sample. The RT-PCR analysis together with the ultrastructural SC features showed that the myogenic potential seemed to be compromised during the aging human muscle proliferation in vitro.

Magnetic resonance diagnostic markers in clinically sporadic prion disease: a combined brain magnetic resonance imaging and spectroscopy study

The intra vitam diagnosis of prion disease is challenging and a definite diagnosis still requires neuropathological examination in non-familial cases. Magnetic resonance imaging has gained increasing importance in the diagnosis of prion disease. The aim of this study was to compare the usefulness of different magnetic resonance imaging sequences and proton magnetic resonance spectroscopy in the differential diagnosis of patients with rapidly progressive neurological signs compatible with the clinical diagnosis of sporadic prion disease. Twenty-nine consecutive patients with an initial diagnosis of possible or probable sporadic prion disease, on the basis of clinical and electroencephalography features, were recruited. The magnetic resonance protocol included axial fluid-attenuated inversion recovery-T2- and diffusion-weighted images, and proton magnetic resonance spectroscopy of the thalamus, striatum, cerebellum and occipital cortex. Based on the clinical follow-up, genetic studies and neuropathology, the final diagnosis was of prion disease in 14 patients out of 29. The percentage of correctly diagnosed cases was 86% for diffusion-weighted imaging (hyperintensity in the striatum/cerebral cortex), 86% for thalamic N-acetyl-aspartate to creatine ratio (cutoff ≤1.21), 90% for thalamic N-acetyl-aspartate to myo-inositol (mI) ratio (cutoff ≤1.05) and 86% for cerebral spinal fluid 14-3-3 protein. All the prion disease patients had N-acetyl-aspartate to creatine ratios ≤1.21 (100% sensitivity and 100% negative predictive value) and all the non-prion patients had N-acetyl-aspartate to myo-inositol ratios >1.05 (100% specificity and 100% positive predictive value). Univariate logistic regression analysis showed that the combination of thalamic N-acetyl-aspartate to creatine ratio and diffusion-weighted imaging correctly classified 93% of the patients. The combination of thalamic proton magnetic resonance spectroscopy (10 min acquisition duration) and brain diffusion-weighted imaging (2 min acquisition duration) may increase the diagnostic accuracy of the magnetic resonance scan. Both sequences should be routinely included in the clinical work-up of patients with suspected prion disease.

Transient Hypohidrosis Induced by Topiramate

Summary:  Purpose: Hypohidrosis during topiramate (TPM) treatment was recently reported in children. We describe an adult epilepsy patient who developed inability to sweat as well as heat intolerance while undergoing treatment with TPM.

Multiple Sclerosis with Very Late Onset: Report of Six Cases and Review of the Literature

Multiple sclerosis (MS) usually starts in young adulthood. However, the disease may appear late or very late in life. We report 6 cases with onset after the age of 59 years and review the literature. As in early onset disease, the diagnosis is mainly clinical. Laboratory findings and paraclinical evidence may support the diagnosis of clinical data are not sufficient. In elderly patients clinical history and laboratory data should be thoroughly appraised to exclude conditions more common in old age such as vascular diseases.

Accuracy of ICD-9 codes in identifying ischemic stroke in the General Hospital of Lugo di Romagna (Italy)

Abstract. We assessed the sensitivity and the positive predictive value (PPV) of the ICD-9 codes in identifying ischemic strokes. The study involved the cross-sectional comparison between patients with an ischemic stroke diagnosis made by neurologists and patients with the 434 or 436 discharge codes. Sensitivity of the codes (all diagnostic levels and first level respectively) was 82% and 76%; PPV: 71% and 76%. The annual crude incidence of ischemic stroke was 2.62 per 1000 based on verified strokes and 3.03 per 1000 based on 434 or 436 coded medical records (at all diagnostic levels). Thirty-day case fatality ratio was 22.3% in verified strokes and 36.8% among patients diagnosed with codes 434 or 436 but without stroke (all levels). Our results disclosed inaccuracy in use of the ICD-9 codes in the diagnosis of ischemic stroke in the general hospital of Lugo di Romagna, Ravenna Province, Italy. The misdiagnosis of patients could be influenced by the degree of severity of clinical features. Epidemiological data and cost-analysis forecasts based only on the ICD-9 system must be considered with caution.

Validation of Symptoms Related to Excessive Daytime Sleepiness

The aim of this study was to validate some recurring definitions of excessive daytime sleepiness (EDS) obtained from descriptive epidemiological studies. We devised questions concerning concepts such as ‘tiredness’, ‘resistible sleepiness’, ‘irresistible sleepiness’ and ‘sudden sleep attacks’. The validation was done by comparing the answers with the results of the Multiple Sleep Latency Test (MSLT), considered the gold standard, or criterion measure, for the diagnosis of EDS. The sample study comprised 73 subjects, 57 outpatients referred to our Sleep Center complaining of daytime sleepiness, snoring or sleep apnea and 16 inpatients admitted to our Neurological Institute for causes other than sleep disorders. A moderate correlation (p = –0.38, 95% confidence interval –0.57 to –0.19) was found between ‘irresistible sleepiness’ and mean sleep latency (MSL). The best combinations of sensitivity and specificity in identifying EDS, for 5- and 8-min MSL cutoffs, were observed for the questions concerning ‘sudden sleep attacks’ and ‘irresistible sleepiness’ (areas under the receiver-operating characteristic curves = 66 and 67%, respectively). The subitems exploring the frequency and situations of occurrence of these symptoms improved the validity in identifying EDS. The items regarding ‘tiredness’ and ‘resistible sleepiness’ were not related to the results of the MSLT. In subgroup analysis, irresistible sleepiness failed to identify pathologic MSLT in sleep-disordered breathing subjects. According to previous observations, we suggest that the concept of sleepiness includes various domains heterogeneously related with MSL and that questionnaires must be tailored to the different populations studied.

Impact of treatment on the short-term prognosis of status epilepticus in two population-based cohorts

PurposeEpidemiological surveys on status epilepticus (SE) in adults in two Italian areas (Bologna and Lugo di Romagna) disclosed a major difference in 30-day case fatality (33% versus 7 %). Since suboptimal management was hypothesised in the first site, we compared the quality of treatment in the two cohorts and examined its contribution to prognosis.MethodsThe Bologna and Lugo di Romagna cohorts of adults with incident SE were included. Patients with post-anoxic encephalopathy were excluded. Quality of treatment was independently classified by two experts. Clinical and treatment features were compared in the two sites. The contribution of variables collected to the 30-day case fatality was explored through multivariate logistic analysis in the whole group of patients.ResultsFifty-seven patients were included. No differences were observed between Bologna and Lugo di Romagna either in clinical features or the time of management. The quality of global drug treatment significantly differed in disfavour of Bologna (p = 0.044). Independent predictors of a worse 30-day case fatality in the whole group of patients were the onset of SE in hospital (OR 9.67, p = 0.0095) and the poor global quality of treatment (partially correct versus correct OR 3.59, p = 0.55, and incorrect versus correct OR 21.09, p = 0.0084). By subgroup analysis, the site of onset factor encompasses the aetiologic background of patients.ConclusionIn addition to previously known prognostic factors, epidemiological comparison of mortality rates of SE between different regions must also consider the quality of treatment.

Liver as a Source for Thymidine Phosphorylase Replacement in Mitochondrial Neurogastrointestinal Encephalomyopathy

Mitochondrial neurogastrointestinal encephalomyopathy (MNGIE) is a rare autosomal recessive mitochondrial disease associated with mutations in the nuclear TYMP gene. As a result, the thymidine phosphorylase (TP) enzyme activity is markedly reduced leading to toxic accumulation of thymidine and therefore altered mitochondrial DNA. MNGIE is characterized by severe gastrointestinal dysmotility, neurological impairment, reduced life expectancy and poor quality of life. There are limited therapeutic options for MNGIE. In the attempt to restore TP activity, allogenic hematopoietic stem cell transplantation has been used as cellular source of TP. The results of this approach on ∼20 MNGIE patients showed gastrointestinal and neurological improvement, although the 5-year mortality rate is about 70%. In this study we tested whether the liver may serve as an alternative source of TP. We investigated 11 patients (7M; 35–55 years) who underwent hepatic resection for focal disorders. Margins of normal liver tissue were processed to identify, quantify and localize the TP protein by Western Blot, ELISA, and immunohistochemistry, and to evaluate TYMP mRNA expression by qPCR. Western Blot identified TP in liver with a TP/GAPDH ratio of 0.9±0.5. ELISA estimated TP content as 0.5±0.07 ng/μg of total protein. TP was identified in both nuclei and cytoplasm of hepatocytes and sinusoidal lining cells. Finally, TYMP mRNA was expressed in the liver. Overall, our study demonstrates that the liver is an important source of TP. Orthotopic liver transplantation may be considered as a therapeutic alternative for MNGIE patients.