Showing papers in "Neurological Sciences in 2011"

Resting-state brain networks: literature review and clinical applications

Abstract: This review focuses on resting-state functional connectivity, a functional MRI technique which allows the study of spontaneous brain activity generated under resting conditions. This approach is useful to explore the brain's functional organization and to examine if it is altered in neurological or psychiatric diseases. Resting-state functional connectivity has revealed a number of networks which are consistently found in healthy subjects and represent specific patterns of synchronous activity. In this review, we examine the behavioral, physiological and neurological evidences relevant to this coherent brain activity and, in particular, to each network. The investigation of functional connectivity appears promising from a clinical perspective, considering the amount of evidence regarding the importance of spontaneous activity and that resting-state paradigms are inherently simple to implement. We also discuss some examples of existing clinical applications, such as in Alzheimer's disease, and emerging possibilities such as in pre-operative mapping and disorders of consciousness.

Pretreatment with a novel aquaporin 4 inhibitor, TGN-020, significantly reduces ischemic cerebral edema.

Abstract: We investigated the in vivo effects of a novel aquaporin 4 (AQP4) inhibitor 2-(nicotinamide)-1,3,4-thiadiazole, TGN-020, in a mouse model of focal cerebral ischemia using 7.0-T magnetic resonance imaging (MRI). Pretreatment with TGN-020 significantly reduced brain edema associated with brain ischemia, as reflected by percentage of brain swelling volume (%BSV), 12.1 ± 6.3% in the treated group, compared to (20.8 ± 5.9%) in the control group (p < 0.05), and in the size of cortical infarction as reflected by the percentage of hemispheric lesion volume (%HLV), 20.0 ± 7.6% in the treated group, compared to 30.0 ± 9.1% in the control group (p < 0.05). The study indicated the potential pharmacological use of AQP4 inhibition in reducing brain edema associated with focal ischemia.

Alzheimer and his disease: a brief history

Abstract: More than 100 years ago, Alois Alzheimer first described the clinical and pathological features of an unusual brain disease during the meeting of the Society of Southwest German Psychiatrists in Tubingen: the patient, Auguste Deter, suffered memory loss, disorientation, hallucinations and delusions and died at the age of 55. In 1910, Emil Kraepelin named the condition with the eponym of “Alzheimer’s disease” (AD) that is, now, the most common neurodegenerative disease with more than 25 million cases worldwide and a major medical problem nearing catastrophic levels. The present article discusses Alzheimer’s work in the context of his life and time.

A review on animal models for screening potential anti-stress agents

Abstract: Stress is a state of threatened homeostasis that produces different physiological as well as pathological changes depending on severity, type and duration of stress. The animal models are pivotal for understanding the pathophysiology of stress-induced behavioral alterations and development of effective therapy for its optimal management. A battery of models has been developed to simulate the clinical pain conditions with diverse etiology. An ideal animal model should be able to reproduce each of the aspects of stress response and should be able to mimic the natural progression of the disease. The present review describes the different types of acute and chronic stress models including immersion in cold water with no escape, cold environment isolation, immobilization/restraint-induced stress, cold-water restraint stress, electric foot shock-induced stress, forced swimming-induced stress, food-deprived activity stress, neonatal isolation-induced stress, predatory stress, day–night light change-induced stress, noise-induced stress, model of post-traumatic stress disorder and chronic unpredictable stress models.

Dementia and cognitive impairment in amyotrophic lateral sclerosis: a review.

Abstract: Amyotrophic lateral sclerosis (ALS) is generally considered to be a paradigm of pure motor neuron disorder; nevertheless, the possible occurrence of cognitive impairment up to a frank dementia in patients affected by ALS is recognized. The appraisal of the cognitive impairment in ALS patients is crucial not only to the therapeutic trials of this incurable disease, but also to the planning of care, compliance to interventions, the end-of-life decisions. The cognitive/behavioral changes of ALS patients are consistent with frontotemporal dysfunctions; the overlap of neuropathological features of ALS and frontotemporal lobe degeneration (FTLD) supports, in addition, the putative spectrum of ALS and FTD. In the present review, the pertinent clinical, genetic, neuropathological, neuropsychological and neuroimaging data of the literature are comprehensively and critically discussed. The distinct and overlapping features of ALS and FTD are pointed out, as well as the undisclosed questions deserving additional studies.

Female reproductive steroids and neuronal excitability

Abstract: Oestrogen and progesterone have specific receptors in the central nervous system and are able to regulate neuronal development and plasticity, neuronal excitability, mitochondrial energy production, and neurotransmitter synthesis, release, and transport. On neuronal excitability, estradiol and progesterone seem to have an opposite effect, with estradiol being excitatory and progesterone and its derivative allopregnanolone being inhibitory. Estradiol augments N-methyl-d-aspartate-mediated glutamate receptor activity, while progesterone enhances gamma-aminobutyric acid-mediated chloride conductance. Sex steroid regulation of the balance of neuroexcitatory and neuroinhibitory activities may have a role in modulating clinical susceptibility to different neurological conditions such as migraine, catamenial epilepsy, premenstrual dysphoric disorder, and premenstrual syndrome.

Bone marrow mesenchymal stem cells can be mobilized into peripheral blood by G-CSF in vivo and integrate into traumatically injured cerebral tissue

Abstract: The efficacy of granulocyte colony-stimulating factor (G-CSF) in mobilizing mesenchymal stem cells (MSCs) into peripheral blood (PB) and the ability of PB-MSCs incorporated into injured brain were tested. Colony forming, cell phenotype and differentiation potential of mouse MSCs mobilized by G-CSF (40 μg/kg) were evaluated. Mortality and pathological changes in mice with serious craniocerebral trauma plus G-CSF treatment (40 μg/kg) were investigated. Bone marrow (BM) cells derived from GFP mice were fractionated into MSCs, hematopoietic stem cells (HSCs), and non-MSC/HSCs using magnetic beads and adherent culture. The resultant cell populations were transplanted into injured mice. The in vivo integration and differentiation of the transplanted cells were detected immunocytochemically. The expression of SDF-1 in injured area of brain was tested by Western blot. G-CSF was able to mobilize MSCs into PB (fourfold increase). PB-MSCs possessed similar characteristics as BM-MSCs in terms of colony formation, the expression pattern of CD73, 44, 90, 106, 31 and 45, and multipotential of differentiation. Accumulative total mice mortality was lower in TG group (5/14) than that in T group (7/14). It was MSCs, not HSCs or non-MSC/HSC cells integrated into the damaged cerebral tissue and differentiated into cells expressing neural markers. Increased SDF-1 expression in injured area of brain was confirmed, which could facilitate the homing of MSCs to brain. G-CSF can mobilize MSCs into PB and MSCs in PB can integrate into injured cerebral tissue and transdifferentiated into neural cells and may benefit the repair of trauma.

Free and cued selective reminding test: an Italian normative study

Abstract: The presence of episodic memory impairment is required for the diagnosis of Alzheimer’s dementia by all current diagnostic criteria. The new research criteria proposed by Dubois et al. (Lancet Neurol 6:734–746, 2007) require that the impairment should not improve significantly with cueing, recognition testing nor after the control of effective encoding. This is considered to be the core deficit of “prodromal Alzheimer’s disease”. The Free and Cued Selective Reminding Test (FCSRT) is a memory test that allows in assessing these specific features of memory impairment. Here, we report normative data for an Italian version of the FCSRT. The test is based on the 12 pictorial stimuli, 6 belonging to the living domain, and 6 to the non-living domain. Six scores were derived from the performance of 227 healthy Italian adults, with age, sex and education homogenously distributed across subgroups: immediate free recall (IFR), immediate total recall (ITR), delayed-free recall (DFR), delayed total recall (DTR), Index of Sensitivity of Cueing (ISC), number of intrusions. In multiple regression analyses, age emerged as an influencing factor for both IFR and DFR, with older people obtaining lower scores. Education and gender appear to influence only IFR, with better performance by more educated subjects and females. Adjusted scores were used to determine inferential cutoff scores and to compute equivalent scores.

Ginkgolide B complex efficacy for brief prophylaxis of migraine in school-aged children: an open-label study

Abstract: Primary headaches (migraines and tension-types headaches) are very common in school-aged children. Ginkgolide B, a herbal constituent extract from Ginkgo biloba tree leaves, was considered as a promising pharmacological aid for the treatment of migraine in adult patients because of its modulation of the glutamatergic transmission in the CNS and on antiplatelet activating factor (PAF). The aim of study is to verify the effectiveness and safety of association of Ginkgolide B/Coenzyme Q10/Riboflavin/Magnesium complex for brief prophylaxis in a population of school-aged children with migraine. In our sample after 3 months of treatment with association of Ginkgolide B/CoenzymeQ10/Riboflavin/Magnesium complex, the mean frequency per month of migraine was significantly decreased (9.71 ± 4.33 vs. 4.53 ± 3.96 attacks; p < 0.001). Our findings suggest that in childhood headache management, the use of alternative treatments must be considered not to evoke a placebo effect, but as soft therapy without adverse reactions.

Swedish natalizumab (Tysabri) multiple sclerosis surveillance study.

Abstract: A post-marketing surveillance program was implemented to monitor the safety and open label efficacy of natalizumab since its launch in Sweden August 2006. Patients are registered in the Swedish multiple sclerosis (MS)-registry that has a nationwide coverage using a standardized follow-up that includes EDSS, MSSS, SDMT, MSIS-29, and recording of adverse events (AEs). As of 31 January, 2010, 1,115 patients had been included, of which 363 were treated ≥24 months. Dropout rate was 10%, mainly due to planned pregnancy. Serious AEs were rare, but included three cases of progressive multifocal leukoencephalopathy (PML), none of which had received previous immunosuppressive therapy. All analyzed clinical outcome parameters showed significant improvements compared to baseline for patients exceeding 24 months of treatment. Our results demonstrate good general tolerability and sustained efficacy of natalizumab for patients with severe MS, though the risk of PML remains a concern.

Ear acupuncture in the treatment of migraine attacks: a randomized trial on the efficacy of appropriate versus inappropriate acupoints

Abstract: Ear acupuncture can be a useful mean for controlling migraine pain. It has been shown that a technique called the Needle Contact Test (NCT) can identify the most efficacious ear acupoints for reducing current migraine pain through just a few seconds of needle contact. The majority of the points were located on the antero-internal part of the antitragus (area M) on the same side of pain. The aim of this study was to verify the therapeutic value of area M and to compare it with an area of the ear (representation of the sciatic nerve, area S) which probably does not have a therapeutic effect on migraine attacks. We studied 94 females suffering from migraine without aura, diagnosed according to the ICHD-II criteria, during the attack. They were randomly subdivided into two groups: in group A, tender points located in area M, positive to NCT were inserted; in group B, the unsuitable area (S) was treated. Changes in pain intensity were measured using a VAS scale at various times of the study. During treatment, there was a highly significant trend in the reduction of the VAS value in group A (Anova for repeated measures: p < 0.001), whereas no significance was observed in group B. VAS values were significantly lower in group A than in group B at 10, 30, 60 and 120 min after needle insertion. This study suggests that the therapeutic specificity of auricular points exists and is linked to the somatotopic representation of our body on the ear.

Role of glial cells in neurotoxin-induced animal models of Parkinson’s disease

Abstract: Dopaminergic neurons are selectively vulnerable to oxidative stress and inflammatory attack. The neuronal cell loss in the substantia nigra is associated with a glial response composed markedly of activated microglia and, to a lesser extent, of reactive astrocytes although these glial responses may be the source of neurotrophic factors and can protect against oxidative stress such as reactive oxygen species and reactive nitrogen species. However, the glial response can also mediate a variety of deleterious events related to the production of pro-inflammatory, pro-oxidant reactive species, prostaglandins, cytokines, and so on. In this review, we discuss the possible protective and deleterious effects of glial cells in the neurodegenerative diseases and examine how these factors may contribute to the pathogenesis of Parkinson’s disease. This review suggests that further investigation concerning glial reaction in Parkinson’s disease may lead to disease-modifying therapeutic approaches and may contribute to the pathogenesis of this disease.

Role of TNF-alpha during central sensitization in preclinical studies

Abstract: Tumor necrosis factor-alpha (TNF-α) is a principal mediator in pro-inflammatory processes that involve necrosis, apoptosis and proliferation Experimental and clinical evidence demonstrate that peripheral nerve injury results in activation and morphological changes of microglial cells in the spinal cord These adjustments occur in order to initiate an inflammatory cascade in response to the damage Between the agents involved in this reaction, TNF-α is recognized as a key player in this process as it not only modulates lesion formation, but also because it is suggested to induce nociceptive signals Nowadays, even though the function of TNF-α in inflammation and pain production seems to be generally accepted, diverse sources of literature point to different pathways and outcomes In this review, we systematically searched and reviewed original articles from the past 10 years on animal models of peripheral nervous injury describing TNF-α expression in neural tissue and pain behavior

Cardiovascular safety of aripiprazole and pimozide in young patients with Tourette syndrome

Abstract: The pharmacotherapy for tic management in Tourette syndrome (TS) relies on neuroleptics, which have been associated with electrocardiographic abnormalities, including QTc interval prolongation. This study assessed the cardiovascular safety of the newer antipsychotic aripiprazole in comparison with the neuroleptic pimozide among young patients affected by TS. Fifty patients aged 6–18 years were assigned to either pimozide (n = 25; mean daily dose 4.4 mg/die) or aripiprazole (n = 25; 5.3 mg/die) treatment for up to 24 months. All patients underwent five serial cardiovascular assessments (baseline, 6, 12, 18 and 24 months). The group treated with pimozide showed significant changes in blood pressure (decreased), QT and QTc (both prolonged). The aripiprazole group showed changes from baseline to peak values in blood pressure (increased), whilst modifications in QT and QTc were not statistically significant. At equivalent doses, aripiprazole is characterised by a safer cardiovascular profile than pimozide, being associated with a lower frequency of QTc prolongation.

Efficacy and tolerability of natalizumab in relapsing-remitting multiple sclerosis patients: a post-marketing observational study.

Abstract: To evaluate the efficacy and safety of natalizumab in patients with active relapsing–remitting multiple sclerosis (MS). We included 285 MS patients receiving natalizumab. Clinical, neuroradiological and safety data were registered every 6 months. Neutralizing antibodies (NABs) were tested after 6 months of treatment. After 1 year, the annualized relapse rate decreased to 0.26, with a significant reduction compared to the previous year (2.13). At 24 months the proportion of “relapse free” patients was 78% while that of “MRI free” patients was 69%. Considering clinical and MRI cumulative activity, “disease free” patients were 63% at 24 months. A total of 18 patients showed NABs positivity. We reported 34 cases of treatment interruptions. In conclusion, our data confirm the remarkable efficacy of natalizumab in a group of patients with higher disease activity than that of pivotal studies.

Oxygen cost of treadmill and over-ground walking in mildly disabled persons with multiple sclerosis.

Abstract: Walking impairment is a ubiquitous feature of multiple sclerosis (MS) and the O2 cost of walking might quantify this dysfunction in mild MS. This paper examined the difference in O2 cost of walking between persons with MS who have mild disability and healthy controls and the correlation between the O2 cost of walking and disability. Study 1 included 18 persons with mild MS and 18 controls and indicated that the O2 cost of walking was significantly higher in MS than controls and that disability was significantly associated with the O2 cost of slow, moderate, and fast treadmill walking. Study 2 included 24 persons with mild MS and indicated that disability was significantly correlated with O2 cost of comfortable, fast, and slow over-ground walking. We provide evidence that the O2 cost of walking is an indicator of walking dysfunction in mildly disabled persons with MS and should be considered in clinical research and practice.

Sudden unexpected death in epilepsy (SUDEP): a pilot study on truth telling among Italian epileptologists.

Abstract: Sudden unexpected death in epilepsy (SUDEP) is a syndrome where a person with epilepsy dies suddenly and no other cause of death is found. The question of informing patients and their families about SUDEP remains a problematic issue. The aim of this study is to explore whether Italian physicians interested in epilepsy believe that they should discuss SUDEP with patients and/or their families. A total of 315 questionnaire were distributed, of which 195 (61.9%) were returned. Seventeen respondents (8.76%) discussed SUDEP with all of their patients, 38 (19.59%) with the majority of patients, 120 (61.85%) with very few of their patients and 15 (7.73%) with none of their patients. No statistical differences among groups were found for gender, professional age (≤10 years; ≥11 years≤20 years; ≥21 years≤30 years; ≥31 years) and medical specialty (neurologists vs. others). Open questions offered insights into the physicians’ problem of managing the negative emotions of patients/family and why the physicians decided to give information.

Localization of d -serine and serine racemase in neurons and neuroglias in mouse brain

Abstract: d-Serine is a novel candidate for an intrinsic ligand for the glycine site of N-methyl-d-aspartate (NMDA) receptors in mammalian brain. d-Serine and serine racemase, which produces d-serine from l-serine, have long been presumed to be localized in astrocytes. However, we have reported that d-serine immunoreactivity was observed in neurons in rats. In the present study, the distributions of d-serine and serine racemase were investigated in combination with marker proteins for neurons, astrocytes and oligodendrocytes in mice. Immunoreactivities for d-serine and serine racemase were found in neurons and oligodendrocytes. These results suggest that d-serine can be produced in neurons as well as glias and used as a neurotransmitter, which control the synaptic function of NMDA receptors.

Parkinson's disease in China

Abstract: Paralysis agitans was first documented in 1817 by James Parkinson, and therefore the syndrome was named Parkinson’s disease (PD). In fact, as early as more than 2000 years ago, the clinical manifestations of this disease have been described in Chinese medicine classics, such as the “Huangdi Neijing (Yellow Emperor’s Internal Classic)” and “Zhong Zang Jing (Hua’s Zhong Zang Classic).” In recent years, especially in the past 30 years after reform and opening-up, PD has drawn a lot of attention by Chinese scholars. Although great progress in the studies of PD has been made in recent years, the gap between China and western countries still exists. In this review, we concentrate on the main progress made in epidemic characteristics, etiology, diagnosis and management of PD in China.

Somatic and autonomic small fiber neuropathy induced by bortezomib therapy: an immunofluorescence study

Abstract: Bortezomib is a new chemotherapeutic agent approved for the treatment of relapsed/refractory and newly diagnosed multiple myeloma. One of the major side effects of bortezomib is a peripheral length-dependent sensory axonal neuropathy and, less frequently, a small fiber neuropathy. Autonomic symptoms like postural dizziness, syncope, diarrhoea, ileus, impotence and urinary disturbances have been reported, nevertheless, autonomic neuropathy has never been characterized. We describe by means of immunofluorescence, the involvement of autonomic skin nerve fibers in three patients with small fiber neuropathy induced by bortezomib treatment.

Interictal cortical reorganization in episodic migraine without aura: an event-related fMRI study during parametric trigeminal nociceptive stimulation

Abstract: The aim of our study was to explore the pain processing network in patients with migraine during trigeminal nociceptive stimulation. Sixteen patients with episodic migraine without aura and 16 healthy controls performed functional magnetic resonance imaging during thermal stimuli (at 41, 51 and 53°C). Patients with migraine showed a greater activation in the perigenual part of anterior cingulate cortex at 51°C and less activation in the bilateral somatosensory cortex at 53°C compared to healthy controls. There were no differences in experimental pain perception between groups. Our findings demonstrate a functional reorganization of cerebral areas known to be involved in pain processing in patients with migraine.

Prevalence of bifid median nerve at wrist assessed through ultrasound

Abstract: We performed a prospective study to evaluate the prevalence of bifid median nerve (BMN) and if it has a higher prevalence in carpal tunnel syndrome (CTS) patients than symptom-free subjects. We evaluated by ultrasound (US) 162 median nerves at wrist of 89 consecutive patients with symptoms suggestive of CTS and 104 of 52 consecutive symptom-free subjects. Neurophysiological evaluation confirmed CTS diagnosis. All patients underwent ultrasonographic evaluation of median nerve in the elbow–palm segment through high-frequency probe; BMN was arbitrarily classified as “complete” and “incomplete” on the basis of US results. BMN was observed in 16/104 wrists (15.4%) in control group and in 30/162 (18.5%) wrists in CTS group. Our study showed that BMN is frequent, not always bilateral, more often is “incomplete” and it has similar prevalence in CTS and control group. These findings suggest that BMN is not a risk factor of developing CTS.

Strio-pallido-dentate calcinosis: a diagnostic approach in adult patients.

Abstract: Familial idiopathic bilateral strio-pallido-dentate calcinosis is a rare autosomal dominant disorder characterized by massive symmetric calcification, detectable by CT, into the globus pallidus and striatum, with or without the involvement of the dentate nucleus, thalamus and white matter in the absence of alterations of calcium metabolism. Clinically, it has been associated with movement and/or neuropsychiatric disorders with age at onset typically in the fourth or fifth decade. Other sporadic or familial diseases can be responsible for brain calcifications with a similar anatomic strio-pallidal or strio-pallido-dentate pattern and, a restricted number of them, for neurological symptoms with onset in adulthood. Moreover, physiological age-related basal ganglia calcifications are often incidentally found, although with a far different CT aspect, in elderly patients with movement disorders. Indentifying familial and idiopathic cases may offer the opportunity to study the molecular mechanisms underlying this minerals deposition.

Association between high-sensitivity C-reactive protein and risk of early idiopathic Parkinson's disease.

Abstract: Although neuroinflammation is known to play an important role in the pathogeneses of neurodegenerative diseases, few studies have been conducted on the association between Parkinson’s disease (PD) and high-sensitivity C-reactive protein (hs-CRP), which is the most studied biomarker of systemic inflammation. Therefore, we conducted this study to determine the clinical correlates of hs-CRP levels in early PD patients by comparing findings with those of normal controls. Sixty-three drug-naive patients with early PD and 117 healthy subjects were recruited, and hs-CRP level differences were investigated in these two groups. It was found that hs-CRP levels in the early PD group were higher than those of healthy controls. Furthermore, when compared with normal controls, the odds ratio for PD based on hs-CRP level cut-off of 0.5 was 2.094 (95% CI = 1.017–4.311, P = 0.045). In this study, our findings support the hypothesis that neuroinflammatory reactions play an important role in the pathogenesis of PD.

Non-verbal memory measured by Rey–Osterrieth Complex Figure B: normative data

Abstract: One of the major problems that clinical neuropsychology has had in memory clinics is to apply ecological, easily administrable and sensitive tests that can make the diagnosis of dementia both precocious and reliable. Often the choice of the best neuropsychological test is hard because of a number of variables that can influence a subject’s performance. In this regard, tests originally devised to investigate cognitive functions in healthy adults are not often appropriate to analyze cognitive performance in old subjects with low education because of their intrinsically complex nature. In the present paper, we present normative values for the Rey–Osterrieth Complex Figure B Test (ROCF-B) a simple test that explores constructional praxis and visuospatial memory. We collected normative data of copy, immediate and delayed recall of the ROCF-B in a group of 346 normal Italian subjects above 40 years. A multiple regression analysis was performed to evaluate the potential effect of age, sex, and education on the three tasks administered to the subjects. Age and education had a significant effect on copying, immediate recall, and delayed recall as well as on the rate of forgetting. Correction grids and equivalent scores with cut-off values relative to each task are available. The availability of normative values can make the ROCF-B a valid instrument to assess non-verbal memory in adults and in the elderly for whom the commonly used ROCF-A is too demanding.

Expression of Bcl-2 and Bax after hippocampal ischemia in DHA + EPA treated rats.

Abstract: To determine the impact of ω3 fatty acids on post-ischemic expression of pro- and anti-apoptotic proteins in hippocampus, male rats were received 10 or 100 mg/kg [Docosahexaenoic acid (DHA) + Ecosapentaenoic acid (EPA); gavage; 21 days before ischemia to 2–10 days after ischemia]. Global cerebral ischemia reperfusion (IR) was performed using the four-vessel occlusion model; ischemia 8 min and reperfusion 6, 48 h and 10 days. IR increased Bcl-2 and Bax expression after 48 h (p < 0.05 and p < 0.01 vs. sham) and 10 days (only Bax; p < 0.05), without significant difference with DHA + EPA groups after 6 h. But after 48 h expression of Bcl-2 increased (p < 0.05 vs. IR) and Bax decreased (p < 0.05). At day 10 after ischemia expression of Bax in DHA + EPA acid groups was less than IR (p < 0.05) and in 100 mg/kg DHA + EPA group Bcl-2 expression was more than IR (p < 0.05). These data suggested that long-term gavage with DHA + EPA increase hippocampal neurons survival for days after ischemia, revealed by increased Bcl-2 and decreased Bax expressions.

Recommendations for the management of urinary disorders in multiple sclerosis: a consensus of the Italian Multiple Sclerosis Study Group.

Abstract: Urinary disorders are uncommon in the initial phases of multiple sclerosis, but increase in frequency as the disease progresses, with a negative impact on quality of life. The goal of this study was to propose a protocol for the diagnosis and treatment of urinary disorders in multiple sclerosis, based on data from the scientific literature and the experience of Italian clinical centres. In particular, the following clinical aspects were considered: what to do with patients with asymptomatic multiple sclerosis; what to do with symptomatic patients; how and when to perform a second-level diagnostic evaluation; and how to treat urinary disorders. A diagnostic–therapeutic algorithm is proposed, that can be applied in Italian clinical centres.

The Modified Five-Point Test: normative data for a sample of Italian healthy adults aged 16–60

Abstract: The Five-Point Test is one of the various measures of figural fluency functions that have been developed as nonverbal analogues to word fluency tasks, and used in neuropsychological assessment to evaluate the ability to initiate and sustain mental productivity, and to self-monitor and regulate responding in the visual–spatial domain. The aim of the current study was to collect normative data for a version of the Five-Point Test (M-FPT) administered to a sample of Italian healthy adults aged 16–60 (n = 332). Performance on the M-FPT was scored by computing the cumulative number of unique designs (UDs) performed on a 3-min administration time. Two supplemental scores were also computed: (a) the cumulative strategies (CSs) consisting with the number of UDs incorporated into enumerative or rotational strategies; (b) the error index (ErrI), consisting with the percentage between the number of perseverative or rule-breaking errors and the number of designs overall. Multiple regression analyses revealed a significant effect of age and education, but not gender, for both UDs and CSs. Equivalent scores and cut-off scores were then determined for UDs and CSs. Descriptive statistical analyses and cut-off scores were reported for ErrI. The availability of normative data for the M-FPT will be valuable in clinical settings for assessing of executive dysfunctions on the visual-spatial subdomain of subjects with brain injury. However, in order to increase the usefulness of the test, the upper limits of the age range of the normative sample should be widened. Moreover, further analyses should be required for determining the inter-rater and test–retest reliability for M-FPT performances, and providing evidence of the sensitivity of this measure to brain disturbances generally and to frontal lobe dysfunction specifically.

The effect of natalizumab on cognitive function in patients with relapsing-remitting multiple sclerosis: preliminary results of a 1-year follow-up study.

Abstract: The objective of the study was to assess the natalizumab effect on the course of cognitive impairment in patients with relapsing-remitting multiple sclerosis (MS). Patients with active relapsing-remitting MS (n = 17) were treated with natalizumab for 1 year. The quasi control group included patients (n = 7) with clinically stable MS. Assessment of disease course [expanded disability status scale (EDSS); number of relapses] and neuropsychological impairment [Wisconsin card sorting test (WCST); controlled oral word associations; verbal/non-verbal memory tests; paced auditory serial addition test] was conducted at baseline and after 1 year. Natalizumab-treated patients experienced significantly fewer relapses compared with the previous year (P < 0.05). At 1-year follow-up, EDSS score was unchanged and neuropsychological assessments of memory/executive functions showed a significant improvement in natalizumab-treated patients (all P < 0.05). No changes were observed in the quasi control group. This preliminary study suggests that natalizumab could be effective in ameliorating cognitive functions in patients with active relapsing-remitting MS, over 1-year follow-up.

Therapeutic time window for the neuroprotective effects of NGF when administered after focal cerebral ischemia.

Abstract: In the present study, we evaluated the neuroprotection time window for nerve growth factor (NGF) after ischemia/reperfusion brain injury in rabbits as related to this anti-apoptosis mechanism. Male New Zealand rabbits were subjected to 2 h of middle cerebral artery occlusion (MCAO), followed by 70 h of reperfusion. NGF was administered after injury to evaluate the time window. Neurological deficits, infarct volume, neural cell apoptosis and expressions of caspase-3 and Bcl-2 were measured. Compared to saline-treated control, NGF treatment at 2, 3 and 5 h after MCAO significantly reduced infarct volume, neural cell apoptosis and expression of caspase-3 (P < 0.01), up-regulated the expression of Bcl-2 and improved functional recovery (P < 0.01). However, treatment at latter time points did not produce significant neuroprotection. Neuroprotection treatment with NGF provides an extended time window of up to 5 h after ischemia/reperfusion brain injury, in part by attenuating the apoptosis.