Heterogeneity in ALSFRS-R decline and survival: a population-based study in Italy.

Very few studies examined trend over time of the revised Amyotrophic Lateral Sclerosis Functional Rating Scale (ALSFRS-R) and factors influencing it; previous studies, then, included only patients attending tertiary ALS Centres. We studied ALSFRS-R decline, factors influencing this trend and survival in a population-based setting. From 2009 onwards, a prospective registry records all incident ALS cases among residents in Emilia Romagna (population: 4.4 million). For each patient, demographic and clinical details (including ALSFRS-R) are collected by caring physicians at each follow-up. Analysis was performed on 402 incident cases (1279 ALSFRS-R assessments). The average decline of the ALSFRS-R was 0.60 points/month during the first year after diagnosis and 0.34 points/month in the second year. ALSFRS-R decline was heterogeneous among subgroups. Repeated measures mixed model showed that ALSFRS-R score decline was influenced by age at onset (p < 0.01), phenotype (p = 0.01), body mass index (BMI) (p < 0.01), progression rate at diagnosis (ΔFS) (p < 0.01), El Escorial Criteria-Revised (p < 0.01), and FVC% at diagnosis (p < 0.01). Among these factors, at multivariate analysis, only age, site of onset and ΔFS independently influenced survival. In this first population-based study on ALSFRS-R trend, we confirm that ALSFRS-R decline is not homogeneous among ALS patients and during the disease. Factors influencing ALSFRS-R decline may not match with those affecting survival. These disease modifiers should be taken into consideration for trials design and in clinical practice during discussions with patients on prognosis.

Non-alcoholic Wernicke's Encephalopathy mimicking neuromyelitis optica spectrum disorder in a young woman: a case report and literature review.

Wernicke's encephalopathy is an under-recognized life-threatening disease caused by thiamine (vitamin B1) deficiency. It has historically been related to chronic alcoholic intake but other causes of malnutrition, such as invasive gastric surgery and hyperemesis, have been linked to the onset of this illness over the years, often presenting with atypical clinical manifestations.  Herein we report a case of a young obese woman affected by non-alcoholic Wernicke's Encephalopathy following a minimally invasive gastrointestinal surgery. She showed an unusual clinical profile characterized by prominent subacute neuro-ophthalmological involvement which combined to her juvenile age, overweight condition and brain lesions, have made diagnosis challenging due to similarities with Neuromyelitis Optica Spectrum Disorder.   Our case underscores the relevance of prompt diagnosis in order to prevent the development of irreversible neuropathological changes and to avoid the use of a long-term immunosuppressive treatment.

Retroviral microarray-based platform on nanostructured TiO2 for functional genomics and drug discovery.

Living-cell microarrays are powerful tools for functional genomics and drug discovery. However, despite several attempts to improve this technology, it is still a challenge to obtain microarrays of cells efficiently overexpressing or downregulating specific genes to address complex phenotypes. Here, we present a cell-based microarray for phenotype screening on primary and cancer cells based on the localized reverse infection by retroviruses. Viral vectors are immobilized on a nanostructured titanium dioxide (ns-TiO2) film obtained by depositing a supersonic beam of titania clusters on a glass substrate. We validated the retroviral cell array by overexpression of GFP reporter genes in primary and cancer cells, and by RNA interference of p53 in primary cells by analyzing effects in cell growth. We demonstrate that ns-TiO2 retroviral arrays are an enabling tool for the study of gene function of families of genes for complex phenotypes and for the identification of novel drug targets.

Peripheral neuropathy in Wegener's granulomatosis, Churg-Strauss syndrome and microscopic polyangiitis.

OBJECTIVE: To compare the clinical aspects of peripheral neuropathy associated with Wegener's granulomatosis (WG), Churg-Strauss syndrome (CSS) and microscopic polyangiitis (MP). METHODS: Cohort study conducted in a single university hospital. Patients were included when a definite diagnosis of WG, CSS or MP was made according to the current classification criteria in our hospital, between 1999 and 2006. All patients underwent periodically clinical and electrophysiological screening for peripheral neuropathy, assessment of disability, and clinical and laboratory evaluation during a mean follow-up of 38 months. RESULTS: Sixty-four consecutive patients diagnosed with WG (26 patients), CSS (26 patients) and MP (12 patients) were recruited. Peripheral neuropathy occurred in 27/64 patients: six with WG, 15 with CSS and six with MP. Neuropathy occurred earlier in the disease history in CSS and MP compared with WG. Among patients with WG, those who developed peripheral neuropathy during follow-up were older than those without neuropathy both at the time of onset and of diagnosis of vasculitis. Distal symmetric polyneuropathy was present in 11 patients, and single or multiple mononeuropathy in 16. Patients with WG had a less severe form of mononeuritis multiplex than CSS or MPA patients. Disability and pain were greater in patients with mononeuropathy, although one-third of them were painless. Relapses of neuropathy were extremely infrequent. CONCLUSIONS: Peripheral neuropathy in WG occurs less frequently, later in the disease course and in a milder form than in CSS and MP. Single or multiple mononeuropathy associated with these subsets of vasculitis can often be painless.

Biocompatibility of cluster-assembled nanostructured TiO2 with primary and cancer cells.

We have characterized the biocompatibility of nanostructured TiO2 films produced by the deposition of a supersonic beam of TiOx clusters. Physical analysis shows that these films possess, at the nanoscale, a granularity and porosity mimicking those of typical extracellular matrix structures and adsorption properties that could allow surface functionalization with different macromolecules such as DNA, proteins, and peptides. To explore the biocompatibility of this novel nanostructured surface, different cancer and primary cells were analyzed in terms of morphological appearance (by bright field microscopy and immunofluorescence) and growth properties, with the aim to evaluate cluster-assembled TiO2 films as substrates for cell-based and tissue-based applications. Our results strongly suggest that this new biomaterial supports normal growth and adhesion of primary and cancer cells with no need for coating with ECM proteins; we thus propose this new material as an optimal substrate for different applications in cell-based assays, biosensors or microfabricated medical devices.

Bell's palsy-induced blepharospasm relieved by passive eyelid closure and responsive to apomorphine.

OBJECTIVE: We describe the case of a woman with Bell's Palsy-induced blepharospasm (BPIB) of the right eye that appeared simultaneously with a complete left facial nerve palsy. The involuntary spasm was relieved by passive lowering of the upper eyelid on the paretic side. METHODS: The recovery curve of the blink reflex was evaluated on the non-paretic side in baseline conditions, after subcutaneous apomorphine and placebo administration and 8 months later, at recovery from the palsy. RESULTS: We found increased recovery of the test-R2 responses at short interstimulus intervals at baseline, which was normalised by apomorphine but not by placebo. At recovery the blink reflex R2 recovery curve returned to normal. CONCLUSIONS: This report demonstrates for the first time a response of BPIB to a dopamine agonist. SIGNIFICANCE: Our findings are in agreement with an animal model of blepharospasm that suggests a combined role of weakness of the orbicularis oculi muscle and a dysfunction of the dopaminergic system in the pathogenesis of this disorder.

Epidemiology of amyotrophic lateral sclerosis in Emilia Romagna Region (Italy): A population based study.

Our objective was to describe incidence and clinical features of ALS from a prospective population-based study in Emilia Romagna Region (ERR). From 2009 onwards, a prospective registry recorded all incident cases of ALS among residents in the ERR (population, 4.4 million inhabitants), involving 17 neurological departments. For each patient, detailed demographic and clinical information was collected by caring physicians. Results showed that from 1 January 2009 to 31 December 2011, 347 patients received a new diagnosis of ALS with a crude incidence rate of 2.63/100,000/year. There was micro-geographic heterogeneity throughout ERR, with higher incidence rates in the low density population (3.27/100,000) (p < 0.01). ALS patients have been more frequently employed in agriculture than the general ERR population (8.64% vs. 4.6%, p < 0.01). Clinical features were similar to those described in previous population based studies. In conclusion, we report incidence rates similar to those reported by European registries, reflecting good accuracy of our prospective study. We confirmed previous studies reporting higher incidence rates in rural areas and among agricultural workers. Although genetics has been gaining increasing importance in ALS aetiology, some epidemiological data are still unexplained. Identifying geographical areas or populations with high incidence rates can be a starting point for identifying environmental risk factors. Further studies having this specific aim can shed light on these topics.

Outcome and prognostic factors during the course of primary small-vessel vasculitides.

OBJECTIVE: To identify the prognostic factors of relapse and/or death during the course of primary small-vessel vasculitides (PSVV), and to differentiate their prognostic relevance by the type of vasculitis. METHODS: Seventy-five patients were retrospectively followed up after diagnosis: 36 with Wegener's granulomatosis (WG), 23 with Churg-Strauss syndrome (CSS), and 16 with microscopic polyangiitis. Cox regression analysis was used to identify the significant predictors of relapse and death. RESULTS: Gastrointestinal (GI) involvement was associated with an increased risk of relapse, mainly in the patients with CSS, whereas renal disease and perinuclear antineutrophil cytoplasmic antibody positivity were correlated with a lower risk of relapse. Presence of nasal Staphylococcus aureus tended to increase the risk of relapse in CSS [hazard ratio (HR) 4.45, p = 0.087], but to decrease it in WG (HR 0.12, p = 0.066). Older age, renal and hepatic involvement, erythrocyte sedimentation rate >or= 100 mm/h, and serum creatinine level >or= 1.5 mg/dl were all related to higher risk of death in univariate analysis; however, only cerebral (HR 8.52, p = 0.021) and hepatic involvement (HR 4.40, p = 0.028) and serum creatinine level >or= 1.5 mg/dl (HR 5.72, p = 0.044) were independently correlated with an unfavorable prognosis for survival. The risk of death associated with each of these indicators did not depend on the form of PSVV. CONCLUSION: GI involvement increases the risk of relapse in CSS, whereas the prognostic significance of nasal S. aureus in terms of relapse seems to be opposite in patients with CSS and those with WG. Patients with cerebral, hepatic, and renal involvement have the poorest prognosis for survival. Our data do not show that the prognostic relevance of these factors depends on the form of PSVV.

Trigemino-facial inhibitory reflexes in idiopathic hemifacial spasm.

We investigated trigemino-facial excitatory and inhibitory responses in perioral muscles in hemifacial spasm (HFS). We examined 15 patients affected with idiopathic HFS and 8 healthy controls. Five patients had spasms mostly limited to the periocular region and 10 had spasms also involving the perioral muscles. Responses were recorded from the resting orbicularis oculi (OOc), levator labii superioris (LLS) and orbicularis oris (OOr) muscles, after supraorbital (SO) nerve stimulation and during isolated voluntary contraction of LLS muscle. Eight patients showed complete or partial preservation of the late silent period (SP2) in activated LLS muscle. The remaining 7 patients showed absence of SP2. Early and late excitatory responses were variably present in LLS muscle at rest. Patients with HFS clinically restricted to periocular muscles had at least partial preservation of the SP2. In conclusion, in HFS patients inhibitory trigemino-facial reflexes are impaired and excitatory trigemino-facial responses are elicited in perioral muscles. These two phenomena seem to develop independently; the degree of trigemino-facial reflex impairment parallels the extension of involuntary movements to the lower facial muscles.