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Reduced mobility during sleep characterizes a variety of movement disorders and neuromuscular diseases. Facioscapulohumeral muscular dystrophy (FSHD) is the third most common form of muscular dystrophy in the general population, and people with FSHD have poor sleep quality. The aims of the present study were to evaluate nocturnal motor activity in patients with FSHD by means of videopolysomnography and to verify whether activity was associated with modifications in sleep structure.

No abstract available

Charcot-Marie-Tooth (CMT) disease is the most frequent inherited neuropathy, no therapies are available at the moment but clinical trials are ongoing. For that reason it is very important to know the natural history of the disease. We report the results of the natural history of clinical features and quality of life (QoL) in patients with CMT2. Twenty patients were enrolled. At recruitment and at follow-up (2 years), all patients underwent neurological evaluation, QoL and disability assessments. The study-end evaluation took place 20-28 months after the baseline evaluation. During the 2-year follow-up period, CMT2 patients showed a mild reduction of strength of distal muscles of upper limbs and proximal muscles of lower limbs, a worsening sensory function and a mild increase in walking disability. However, there was no relevant worsening of QoL, except for a mild deterioration of one mental health domain.

GM2 gangliosidosis type Sandhoff is caused by a defect of beta-hexosaminidase, an enzyme involved in the catabolism of gangliosides. It has been proposed that substrate reduction therapy using N-butyl-deoxynojirimycin (miglustat) may delay neurological progression, at least in late-onset forms of GM2 gangliosidosis. We report the results of a 3-year treatment with miglustat (100 mg t.i.d) in a patient with chronic Sandhoff disease manifesting with an atypical, spinal muscular atrophy phenotype. The follow-up included serial neurological examinations, blood tests, abdominal ultrasound, and neurophysiologic, cognitive, brain, and muscle MRI studies. We document some minor effects on neurological progression in chronic Sandhoff disease by miglustat treatment, confirming the necessity of phase II therapeutic trials including early-stage patients in order to assess its putative efficacy in chronic Sandhoff disease.

Facioscapulohumeral muscular dystrophy (FSHD) is the third most frequent form of muscular dystrophy. Heart rate variability (HRV) analysis is a means of evaluating the activity of the autonomic nervous system. The aim of this study was to evaluate HRV in FSHD patients. Fifty-five consecutive FSHD patients were enrolled (31 men, age 26-72 years). Muscular impairment was measured using a clinical severity scale (CSS). Patients were compared with a control group of 55 healthy subjects, matched for age and sex. HRV was analyzed in the time domain and in the frequency domain. Patients showed increased spectral power of the low-frequency band. Spectral power of the high-frequency band was inversely correlated with CSS score. FSHD is associated with a slight increase in sympathetic output and with a decrease in parasympathetic output. These modifications become more evident with the progression of the disease and could increase the risk of arrhythmias and other cardiovascular events

Heterozygous mutations in the Berardinelli-Seip congenital lipodystrophy (BSCL2) gene have been associated with different clinical phenotypes including Silver syndrome/spastic paraplegia 17, distal hereditary motor neuropathy type V, and Charcot-Marie-Tooth disease type 2 (CMT2) with predominant hand involvement. We studied an Italian family with a CMT2 phenotype with pyramidal signs that had subclinical sensory involvement on sural nerve biopsy. Direct sequencing analysis of the BSCL2 gene in the three affected siblings revealed an S90L mutation. This report confirms the variability of clinical phenotypes associated with a BSCL2 Ser90Leu mutation and describes the first Italian family with this mutation.

Mutations in the gene encoding 27-kDa small heat-shock protein B1 (HSPB1) have been reported in association with Charcot-Marie-Tooth disease type 2F or dHMN type II. We describe an Italian patient with wasting and weakness of distal muscles, involving primarily and mostly the lower limbs and later the upper limbs, in which a novel mutation of HSPB1, T180I, was detected. Electrophysiological evaluation disclosed a pure motor axonal neuropathy. Sural nerve biopsy showed a mild reduction of myelinated fibre density. All these findings suggested a CMT2/dHMN phenotype.

We describe a patient with painful neuropathy associated with an abnormal anti-MAG titer in which predominant involvement of intra-epidermal nerve fiber was documented. Electrophysiological studies revealed low-borderline amplitude of sensory and compound motor action potentials registering from lower limbs and normal conduction velocity. Sural nerve biopsy disclosed only a slight loss of myelinated fiber. Skin biopsy performed at the proximal thigh and at the distal leg was consistent with a non-length-dependent small fiber neuropathy. It is likely that in this case anti-MAG antibodies played a role in the pathogenesis of small fiber neuropathy.

No abstract

Elevated anti-Epstein-Barr virus (EBV) antibody levels are present in serum of Multiple sclerosis (MS) patients but literature lacks of studies comparing anti-EBV antibody levels between MS and other neurological diseases. We evaluate anti-VCA IgG and IgM, anti-EBNA1 IgG, anti-Cytomegalovirus IgG and IgM titres in serum and cerebrospinal fluid (CSF) of 267 MS, 50 Chronic Inflammatory Demyelinating Polyradiculoneuropathy (CIDP) and 88 Amyotrophic Lateral Sclerosis (ALS) patients. We found increased titres of anti-EBV-IgG in serum and CSF of MS subjects as compared to CIDP and ALS patients thus providing additional evidence for a possible involvement of EBV in MS.

Patients affected by carpal tunnel syndrome (CTS) often report finding themselves "dropping objects". This symptom is perceived as a severe and frustrating problem. We investigated the occurrence of "dropping objects" in a sample of 532 patients affected by CTS, studied with a multidimensional protocol (clinical, neurophysiological, and patient-oriented). To ensure that the definition of "dropping objects" was index of abnormality, we evaluated a control group interviewing 200 subjects. In order to evaluate if "dropping objects" was an index of more severe CTS impairment, we compared the severity measures between the patients with and without this condition. Severity of CTS multidimensionally assessed was significantly greater in patients with a history of dropped objects than those without. Moreover, "dropping objects" was more frequent in females, older patients, and in those patients with more functional impairment. The occurrence of "dropping objects" in CTS patients seems to be an index of CTS severity.

Objective: In carpal tunnel syndrome (CTS) distribution of paresthesias is related to the degree of the nerve impairment. To improve the clinical ability in detecting the damage severity, we have introduced the criteria distribution of paresthesias in a previous clinical scale: the historical-objective scale (Hi- Ob). Methods: We evaluated 100 consecutive patients (40 bilateral CTS) to validate a five stages clinical scale: the Historical-objective-distribution based scale (Hi-Ob-Db). We compared the Hi-Ob-Db with a validated neurophysiological classification and with the Boston Carpal Tunnel Questionnaire (BCTQ). The BCTQ evaluates two domains, one assessing symptoms (SYMPT = patient-oriented symptom), and the other analysing functional status (FUNCT = patient-oriented function). Results: The positive correlation between the Hi-Ob-Db and neurophysiological findings (p < 0.001, r:0.79) was stronger than correlation between the Hi-Ob and the neurophysiological classification (p < 0.001, r:0.74). A linear correlation between the Hi-Ob-Db and the patient-oriented scores was observed, respectively FUNCT (p < 0.003, r:0.38) and SYMPT (p < 0.002, r:0.30). Conclusions: The Hi-Ob-Db is a clinical scale which correlates with the neurophysiological impairment of the median nerve and with patient-oriented findings in patients with CTS. Significance: The new scale may be useful in routine examination and for scientific purposes.

Waldenström's macroglobulinaemia is a form of monoclonal IgM gammopathy associated with a rare B-cell lympho-plasmacytic lymphoma, characterized by the involvement of bone marrow, lymph nodes and spleen. Neurological complications involving peripheral nerves are common and different pathogenic mechanisms have been reported. We describe a patient with severe multineuropathy associated with Waldenström's macroglobulinaemia. Nerve biopsy revealed copious light chain deposition which subverted the normal architecture of the endoneurium and epineurium resulting in massive fascicular hyalinosis and epineural arteries disruption, respectively. This report confirms that massive immunoglobulin deposition is one of the several mechanisms of nerve damage in IgM-related neuropathy. Since their recognition has important therapeutical consequences, nerve biopsy is an essential diagnostic tool in patients with an unusual clinical presentation of IgM-related neuropathies. Copyright © 2010 Elsevier B.V. All rights reserved.

Allgrove syndrome (or triple A syndrome) is a rare autosomal recessive disorder characterized by alacrima, achalasia, ACTH-resistant adrenal insufficiency and autonomic/neurological abnormalities. It is caused by mutations in the AAAS gene, located on chromosome 12q13. We describe a 42-year-old patient who presented with neuropathy and was found to have alacrima, achalasia, mild autonomic dysfunction with significant central and peripheral nervous system involvement. She was later diagnosed with oligosymptomatic triple A syndrome. Sequencing of the AAAS gene identified two heterozygous mutations within exon 14 and its donor splice site (p.L430F-c.1288C>T and c.1331+1G>T), one of which is novel. Allgrove syndrome should be suspected in patients with neurological impairment associated with two or more of the main symptoms (alacrima, achalasia or adrenal insufficiency).

Multiple sclerosis (MS) is a T-cell autoimmune disease of the central nervous system (CNS). Predominance of women in autoimmune diseases suggests that sex hormones may play a role in disease susceptibility. A possible role for prolactin, a neuroendocrine peptide with powerful immunomodulatory properties, is suggested in MS. We describe the case of a 32-year-old man affected by relapsing-remitting MS who experienced the first MS clinical event during the development of a prolactin-secreting adenoma and the only two MS relapses during adenoma recurrence. Prolactin may have facilitated the inflammatory process and triggered MS clinical attacks, suggesting a role of prolactin in immunomodulation and therefore in autoimmune disease course

The term Tourettism refers to Tourette Syndrome (TS)-like symptoms which appear secondary to a variety of both acquired and congenital neurological and neuropsychiatric disorders or following an exposure to several drugs. The association between Tourettism and Multiple Sclerosis (MS) is very rare. Only two cases of patients affected by MS who also showed a simple phonic tic and complex vocal tics respectively have been reported. The case here described reports of a 30 year-old woman affected by secondary-progressive MS who developed, 7 years after the onset of the disease, TS-like symptoms which were responsive to quetiapine. At that time her brain MRI, when compared with the previous scan, showed an increased lesion burden and an increased atrophy in the regions around Sylvian fissures. Considering recent findings on TS, the increased atrophy in these strategic brain regions could be responsible for the tics onset in our patient. At the same time, the diffuse involvement of the white matter and the progressive brain atrophy which we observed could have impaired the cortico-striato-thalamo-cortical circuits consistently implicated in the pathogenesis of TS. In conclusion, we can hypothesize that in our case Tourettism and MS could be considered causal related more than coincidentally associated.

In seronegative myasthenia gravis repetitive nerve stimulation and single-fibre EMG have a crucial diagnostic value but they may be negative, particularly in repetitive nerve stimulation studies. We report the case of a 43-year-old patient with generalized seronegative myasthenia gravis with negative 3 Hz repetitive nerve stimulation at Erb's point and voluntary single-fibre EMG in the orbicularis oculi. We also performed 6 and 12 Hz repetitive nerve stimulation at Erb and stimulated single-fibre EMG in the extensor digitorum communis and our findings were pathological. Our data suggest that, for individual patients with an atypical picture characterised by dissociation between a severe clinical pattern and no definite neurophysiological findings on conventional tests, repetitive nerve stimulation with a stimulation rate higher than 3 Hz and/or stimulated single-fibre EMG with an increasing stimulation rate may be helpful.

Multiple sclerosis (MS) is a chronic inflammatory demyelinating disease of the central nervous system and a defect in the regulatory T-cell subset seems to be involved in the pathogenesis of the disease. Foxp3 is a transcription factor that is selectively expressed in CD4+ CD25+ regulatory T cells and is required for their development and function. T-bet is a key transcription factor for the development of T helper 1 (Th1) cells. We found that both the percentage of circulating CD4+ CD25+ Foxp3+ cells and Foxp3 expression were lower in relapsing-remitting (RR) MS patients during relapses than during remission. Otherwise, the percentage of CD4+ T-bet+ T cells and T-bet expression in CD4+ T cells were higher in relapsing than in remitting RRMS patients. CD4+ CD25+ T cells both from relapsing and from remitting RRMS patients showed significantly less capacity than corresponding cells from healthy subjects to suppress autologous CD4+ CD25(-) T-cell proliferation, despite a similar Foxp3 expression level. CD4+ CD25+ T cells from healthy subjects and patients in remission clearly reduced T-bet mean fluorescence intensity (MFI) in CD4+ CD25(-) T cells up to a ratio of 1:10, whereas CD4+ CD25+ T cells from patients in relapse were able to reduce T-bet expression only at a high ratio. Our data indicate that the increased number of regulatory T (T-reg) cells and the increased Foxp3 expression in circulating CD4+ CD25+ T cells may contribute to the maintenance of tolerance in the remission phase of MS. Moreover, the inhibitory capacity of CD4+ CD25+ T cells seems to be impaired in relapsing patients under inflammatory conditions, as shown by the high levels of T-bet expression in CD4+ T cells.

We describe a patient with a familial form of amyotrophic lateral sclerosis (ALS) in which a heterozygous G>A exchange at position 1087 in the SOD1 gene was detected. This mutation results in an amino acid substitution of aspartate for glycine at position 93 (G93D). The patient had a five-year history of fasciculations in all four limbs, with no clear evidence of muscular atrophy or weakness at last follow-up. However, electrophysiological examination revealed lower and upper motor neuron involvement. His mother and a cousin had died of ALS after prolonged disease. This report shows that G93D may cause a form of ALS with slow progression, long-lasting paucisymptomatic phase and both lower and upper motor neuron involvement.

No abstract

Despite the relatively frequent involvement of the basal ganglia and subthalamic nucleus by multiple sclerosis (MS) plaques, movement disorders (MD), other than tremor secondary to cerebellar or brainstem lesions, are uncommon clinical manifestations of MS. MD were present in 12 of 733 patients with MS (1.6%): three patients had parkinsonism, two blepharospasm, five hemifacial spasm, one hemidystonia, and one tourettism. MD in patients with MS are often secondary to demyelinating disease. Also in cases without response to steroid treatment and demyelinating lesions in critical regions, it is not possible to exclude that MD and MS are causally related.

The Italian CMT study group performed a multicentre, multidimensional, longitudinal 2-year follow-up study using validated measurements of neurological impairment, disability and quality of life. The aim of the study was to evaluate the natural history of clinical features, disability and QoL in patients with CMT1A. On clinical examination, CMT1A patients showed a significant reduction in muscle strength and sensory function during the 2-year follow-up period. However, there was no worsening of QoL or disability, nor was depression observed. The discrepancy between the evolution of clinical features and the evolution of QoL and disability may be due to the development of compensatory strategies that help patients cope with the slow progression of the disease. Our observations provide information which may be useful when designing clinical trials in CMT.

PRIMARY OBJECTIVE: To evaluate the effects of rehabilitation on disability and quality of life (QoL) in patients with chronic stroke. Research design: This is an observational, prospective and multidimensional study. METHODS AND PROCEDURES: Sixty-six consecutive inpatients were enrolled. A rehabilitation programme of 2 months consisting of six exercise periods per week was performed. An impairment of cognitive function was the exclusion criteria for patient enrolment. MAIN OUTCOMES AND RESULTS: European Stroke Scale, Barthel Index, Modified Rankin Scale, Deambulation Index and SF-36 were performed both before and after rehabilitation. A short-term follow-up (2 months after discharge) was performed by phone administration of SF-36. Significant improvement in clinical and disability measurements was observed after rehabilitation. For QoL, a significant improvement was observed both in physical function and in social function immediately after rehabilitation. At follow-up the social function improvement was maintained, while physical function improvement was lost. CONCLUSIONS: The data show that rehabilitation in patients with chronic stroke lessens disability and improves physical and social function and that repeated cycles of treatment are needed to maintain the level of improvement reached.

OBJECTIVE: To assess which are the clinical examination tests that are more related to quality of life (QoL), depression, and disability in CMT patients. DESIGN: Large prospective multicenter study through the use of validated clinical, disability, and QoL measurements. Correlations between clinical pattern and disability/QoL and depression were studied. SETTING: Departments of Neurology. PATIENTS AND PARTICIPANTS: 211 CMT patients (60% females, mean age 42.5 years). INTERVENTIONS: None. MEASUREMENTS AND RESULTS: Sensory function was related to both mental and physical aspects of patient's QoL. Ability to walk on toes and heels was related to physical aspects of QoL/disability but also to bodily pain. Strength of forearm/hand intrinsic muscles was related to disability and physical aspects of QoL. CONCLUSIONS: Some clinical tests may be better outcome measures than others because they are related to aspects of life highly relevant to the patients. This information may be useful in clinical practice and in clinical trials to infer the patient's QoL.

In pregnant women affected by multiple sclerosis (MS) we observed increased percentages of CD4(+)CD25(+)Foxp3(+) T regulatory cells at the 1st and the 2nd trimester of gestation that was associated with a decreased T-bet expression in CD4(+) T cells. In women showing clinical relapse and/or new lesions at MRI after delivery we found, a higher expression of T-bet, pSTAT1 and pSTAT3 in CD4(+), CD8(+) T cells and CD14(+) cells, associated with an increase of IFNgamma and IL17 production by PBMC at the 3rd trimester of gestation and after delivery. Our data suggest that the expansion of circulating CD4(+)CD25(+)Foxp3(+) regulatory T cells and the lower expression of T-bet in CD4(+) T cells may account for the decreased MS activity during pregnancy. The expression of T-bet, pSTAT1 and pSTAT3 in peripheral blood CD4(+) and CD8(+) T cells and monocytes could be useful to identify MS patients who will develop a relapse after delivery.

Multiple sclerosis (MS) and celiac disease (CD) are considered to be T-cell-mediated autoimmune diseases. We describe a woman affected by a relapsing-remitting demyelinating disease of the central nervous system and occult CD (MS-CD), who showed during neurologic exacerbations a strong increased expression of T-bet, the key transcription factor for the development of Th1 cells, in circulating T, B cells and monocytes. Conversely, no difference of T-bet expression was observed in B cells from relapsing-remitting MS patients, either in relapse or in remission, and in controls. In the MS-CD patient, the interaction between MS- and CD-related inflammatory processes may result in an amplification of Th1 immune response

Several conditions have been reported to mimic motor neuron disease (MND) and misdiagnosis remains a common clinical problem. Peripheral neuropathy is a classic feature of many vasculitic syndromes and in some patients it may be the only manifestation of vasculitis. We report a case of ANCA-related vasculitic neuropathy where the clinical presentation was suggestive of MND. A 42-year-old woman was admitted to our centre to confirm a diagnosis of MND made elsewhere. Clinical examination revealed postural tremor at the right hand, mild tongue atrophy with diffuse fasciculations and brisk tendon reflexes without other muscular weakness or atrophies. Electromyography demonstrated denervation in tongue and in the first dorsal interosseous of right hand ; motor evoked potentials disclosed normal central motor conduction time. Laboratory studies revealed only a mild increase of p-ANCA. A muscle biopsy showed a small inflammatory infiltrate around a vessel. The patient started high dosage of oral steroids. After one year of follow-up the patient suspended oral steroids, postural tremor of the right hand disappeared and tongue fasciculations were reduced. Vasculitis may mimic a MND, particularly in the absence of sensory involvement. Caution should be exercised in the clinical diagnosis of MND. Muscle biopsy is indicated in patient with atypical MND especially in those with an exclusive involvement of lower motor neuron.

The Italian CMT study group performed a multicentre, multidimensional, longitudinal 2-year follow-up study using validated measurements of neurological impairment, disability and quality of life. The aim of the study was to evaluate the natural history of clinical features, disability and QoL in patients with CMT1A. On clinical examination, CMT1A patients showed a significant reduction in muscle strength and sensory function during the 2-year follow-up period. However, there was no worsening of QoL or disability, nor was depression observed. The discrepancy between the evolution of clinical features and the evolution of QoL and disability may be due to the development of compensatory strategies that help patients cope with the slow progression of the disease. Our observations provide information which may be useful when designing clinical trials in CMT.

BACKGROUND: Amyotrophic lateral sclerosis (ALS) affects people of all ages, but whether the wide range of age at onset is due to distinct diseases or merely reflects phenotypic variability of the same disorder is still unknown. The purpose of this study is to describe clinical and prognostic features of young-adult ALS, with onset before age 40 years, and to compare them with features of the common adult-onset type. METHODS: We analyzed clinical features and long-term follow-up of 57 young-adult ALS patients, with disease onset between 20 and 40 years, and compared them with 450 patients affected by adult-onset ALS. RESULTS: We found that the majority of young-adult patients showed a predominant upper motor neuron (p-UMN) ALS, characterized by marked spastic paraparesis, with lower motor neuron signs confined to the upper limbs. The proportion of patients with p-UMN ALS phenotype was 59.6% in the young-adult patients and 17.4% in the adult-onset form (p < 0.0001). Young-adult ALS with p-UMN phenotype had longer survival than did the classic phenotype: median survival was 74 months (range 10-226, 95% CI 60.61-87.38) in the former and 56 months (range 6-106, 95% CI 48.65-63.34) in the latter (p = 0.03). In the young-adult patients, a marked male excess was observed in the p-UMN ALS group (5.8:1), whereas the ratio of men to women was 1.1:1 in the classic phenotype (p = 0.01). CONCLUSIONS: Our findings show that young-adult amyotrophic lateral sclerosis with the predominant upper motor neuron phenotype represents a distinctive clinical variant characterized by a unique clinical pattern, longer survival, and male prevalence.

Sialorrhea is frequent and invalidating in patients with amyotrophic lateral sclerosis (ALS) or Parkinson's disease (PD). Botulinum toxin (BTX) emerged as an alternative to traditional treatments. We evaluated efficacy and tolerability of ultrasound-guided BTX-B injections in parotids and submandibular glands in 18 patients with ALS or PD. At 1 week, both objective (cotton rolls weight) and subjective evaluations (dedicated clinical scales) documented sialorrhea reduction (p<0.01). ALS patients reported shorter benefit duration (p<0.001) and higher prevalence of viscous saliva (seven vs one patients), possibly due to different pattern of autonomic involvement. BTX-B seems efficacious in reducing sialorrhea in ALS and PD but the risk-benefit ratio might differ between these two conditions. This might have implications for clinical practice.

In the presence of sensitive symptoms along the lumbar-sacral dermatomeric region, it is easy to suspect a lumbar-sacral radiculopathy, it being a very common disease. Clinical evaluation, neurophysiology and magnetic resonance imaging are common tools in diagnosing lumbosacral radiculopathy. Nevertheless, sometimes tumour may mimic radiculopathy. With the improvement of ultrasound, most peripheral nerves may be virtually identified. We describe two patients where tumour of sural nerve and tibial nerve mimicked S1 radiculopathy. We diagnosed the tumours only through a comprehensive nerve assessment combining clinical evaluation, US and neurophysiology. The association of neurophysiological and imaging US assessments, possibly in the same session, may avoid misdiagnosis.

Electrodiagnostic studies, including electromyograpy (EMG) and nerve conduction studies (NCS), are objective methods for the diagnosis (and classification) of nerve involvement. In an EMG laboratory, diagnosis is usually based on clinical findings and neurophysiological evaluation. Clinical evaluation allows to assess which nerve is involved, the presence of motor and sensitive deficits, the onset and other useful information. All these findings are useful to perform a finalized neurophysiogical pathway. EMG assessment provides evidence of myelin impairment, neuroapraxic block, axonal involvement and other useful information. Moreover, EMG evaluation usually shows the level of the lesion but does not provide spatial information about anatomy of the nerve and its surroundings which might be important for the aetiology. Recently, detail resolution has been increasingly used to aid diagnosing compression and entrapment neuropathies. Advances in ultrasound (US) technology have made it possible to gain higher spatial resolution and even depict nerves with excellent visual quality. The importance of US technique in focal nerve involvement is that we can see, from an anatomic point of view, the nerve along its course. Some of the advantages of US is that it is a non-invasive, low-cost and easily available technique which allows a dynamic examination. We conducted many neurophysiological studies on nerve entrapments and more generally in nerve lesions. Because of the complementary perspectives provided by US and EMG, we acquired an US instrument and we started to add the US assessment simultaneously to EMG evaluation in the same session. In literature, Several case reports were reported in which it is underlined the complementarity of US and EMG in diagnosing nerve involvement. To our knowledge, no systematic evaluation of the usefulness of the combination of these tools was performed. We performed a prospective study to evaluate the usefulness of combination of EMG and US

We identified a novel c.1556A>G transition in exon 12 of the HEXB gene associated with chronic Sandhoff's disease, changing a conserved aspartic acid to glycine at position 494 of the Hex beta-subunit; moreover, RT-PCR showed aberrant exon 12 skipping, causing a frame-shift and premature stop codon, consequent to the disruption of an exonic splicing enhancer motif by the mutation. These data suggest that the c.1556 A>G transition would affect both HEXB mRNA processing and biochemical properties of the beta-subunit.

Comment on Motor assessment of upper extremity function and its relation with fatigue, cognitive function and quality of life in multiple sclerosis patients. [J Neurol Sci. 2006]

Genome-wide gene expression profiling of skeletal muscle from Duchenne muscular dystrophy (DMD) patients has been used to describe muscle tissue alterations in DMD children older than 5 years. By studying the expression profile of 19 patients younger than 2 years, we describe with high resolution the gene expression signature that characterizes DMD muscle during the initial or "presymptomatic" phase of the disease. We show that in the first 2 years of the disease, DMD muscle is already set to express a distinctive gene expression pattern considerably different from the one expressed by normal, age-matched muscle. This "dystrophic" molecular signature is characterized by a coordinate induction of genes involved in the inflammatory response, extracellular matrix (ECM) remodeling and muscle regeneration, and the reduced transcription of those involved in energy metabolism. Despite the lower degree of muscle dysfunction experienced, our younger patients showed abnormal expression of most of the genes reported as differentially expressed in more advanced stages of the disease. By analyzing our patients as a time series, we provide evidence that some genes, including members of three pathways involved in morphogenetic signaling-Wnt, Notch, and BMP-are progressively induced or repressed in the natural history of DMD.

Objective: To assess the effectiveness of the conservative therapy in carpal tunnel syndrome. Data Sources: A computer-aided search of MEDLINE and the Cochrane Collaboration was conducted for randomized controlled trials (RCTs) from January 1985 to May 2006. Review methods: RCTs were included if: 1) the patients, with clinically and electrophysiologically confirmed carpal tunnel syndrome, had not previously undergone surgical release, 2) the efficacy of one or more conservative treatment options was evaluated, 3) the study was designed as a randomised controlled trial. Two reviewers independently selected the studies and performed data extraction using a standardized form. In order to assess the methodological quality, the criteria list of the Cochrane Back Review Group for systematic reviews was applied. The different treatment methods were grouped (local injections, oral therapies, physical therapies, therapeutic exercises and splints). Results: Thirty-three RCTs were included in the review. The studies were analysed to determine the strength of the available evidence for the efficacy of the treatment. Our review shows that: 1) locally injected steroids produce a significant but temporary improvement, 2) Vitamin B6 is ineffective, 3) steroids are better than NSAIDs and diuretics, but they can produce side effects, 4) ultrasounds are effective while laser therapy shows contrasting results, 5) exercise therapy is not effective, 6) splints are effective, especially if used full-time. Conclusion: There is a: 1) strong evidence (level 1) on efficacy of local and oral steroids; 2) moderate evidence (level 2) that Vitamin B6 is ineffective and splints are effective and 3) limited or conflicting evidence (level 3) that NSAIDs, diuretics, Yoga, laser and ultrasound are effective whereas exercise therapy and Botulinum toxin B injection are ineffective.

High dose glucocorticoid (GC) treatment has been demonstrated to have a short-term beneficial effect on functional recovery in relapsing multiple sclerosis (MS) patients but the exact mechanism of action of GCs in MS is unclear. We found that high dose intravenous GCs strongly reduced T-bet and pSTAT1 expression in CD4+, CD8+, CD14+ circulating cells in RRMS patients in relapse. pSTAT1and T-bet reduction was associated with the decline of IFNgamma production by PBMCs. A significant increase of AV-positive CD4+ and CD8+ T cells was detectable after GC treatment without any variation in the percentage of annexin V-positive monocytes. By in vitro analysis, patients during relapse, either before or after GC treatment, exhibited a lower proportion of apoptotic lymphocytes than remitting patients and controls. Our study suggests that GCs can modulate T-bet and STAT1 expression and that IFNgamma signalling inhibition contributes to anti-inflammatory action of GCs in the treatment of relapses of MS patients

BACKGROUND: Either botulinum toxins (BoNTs) A and B have been used for improving drooling in different neurological conditions. METHODS: Consecutive patients affected by Amyotrophic Lateral Sclerosis (ALS) or Parkinson's Disease (PD) accompanied by severe drooling were randomized to receive botulinum neurotoxin type A (BoNT-A) or B (BoNT-B) injections into the salivary glands. Following the first treatment, when sialorrhea returned to baseline (at least three months after the first injection), subjects were re-treated with the other serotype. Ultrasound-guided injections into parotid and submandibular glands were bilaterally performed: total doses were 250 U BoNT-A (Dysport) and 2500 U BoNT-B (Neurobloc). Objective (cotton roll weight) and subjective (ad hoc clinical scales) evaluations were performed at baseline, after 1 and 4 weeks, and every 4 weeks until drooling returned to baseline. RESULTS: Twenty-seven patients (15 ALS and 12 PD) were enrolled, fourteen completed the study. BoNT-A and BoNT-B treatments gave both subjective and objective improvements in all patients. The latency was significantly shorter after BoNT-B treatments (3.2 ± 3.7 days) compared to BoNT-A (6.6 ± 4.1 days; P = 0.002). The mean benefit duration was similar at 75 and 90 days for BoNT-A and BoNT-B, respectively (P = NS). The only toxin-related side effect was a change to saliva thickness. CONCLUSIONS: Either 250 U Dysport or 2500 U Neurobloc have similar effectiveness and safety in controlling sialorrhea. BoNT-B has a shorter latency and comparable duration. Cost analysis, considering the doses used in this study protocol favored BoNT-B treatment.

Multiple sclerosis (MS) is a chronic inflammatory demyelinating disease of the central nervous system, and it is considered to be a T helper 1 (Th1) cell-mediated autoimmune disease. T-bet has been identified as a key transcription factor for the development of Th1 cells and the induction of interferon (IFN)-gamma production. T-bet is induced during T-cell activation by the IFN-gamma signal transducer and activator of transcription (STAT)-1 signalling pathway. In this study we found an up-regulation of T-bet and pSTAT1 in peripheral blood CD4+ and CD8+ T cells and monocytes from relapsing-remitting MS patients in relapse compared with patients in remission and with healthy subjects. The increased expression of pSTAT1 strongly correlated with T-bet expression in CD4+ and CD8+ cells and monocytes from patients in relapse and was associated with an increased production of IFN-gamma by peripheral blood mononuclear cells (PBMCs). pSTAT3 was also up-regulated in CD4+ and CD8+ cells and monocytes from patients in relapse and was associated with an increased production of interleukin (IL)-10 but not of IL-6. pSTAT1, pSTAT3, and T-bet expression strongly correlated with Gd-DTPA-enhanced lesions on brain and spinal cord magnetic resonance imaging. Our data show for the first time that there is an up-regulation of type 1 immunity-correlated transcription factors such as STAT1 and T-bet in peripheral blood subpopulations of MS patients in the active phase of disease. The evaluation of T-bet and pSTAT1 expression in peripheral blood CD4+, CD8+ T cells and monocytes could be used as a marker of disease activity in relapsing-remitting MS.

no abstract available

OBJECTIVE: Mitoxantrone is an antineoplastic agent also used for the treatment of multiple sclerosis (MS). However, despite its efficacy, few data are available on its mechanism of action. The current study was designed to evaluate the short-term (1 month) and long-term (12 months) in vivo effects of mitoxantrone on pro- and anti-inflammatory cytokine production by the peripheral blood mononuclear cells (PBMC) of secondary progressive MS patients. METHODS: Eighteen patients with secondary progressive MS underwent mitoxantrone therapy (at a dose of 12 mg/m(2) once every 3 months) over a 1-year period. Blood samples were obtained at baseline, after 1 month and after 12 months of treatment. The production of cytokines in the PBMC was measured by enzyme-linked immunosorbent assay. RESULTS: There were no significant effects of mitoxantrone on proinflammatory cytokines [interleukin (IL) 6 and IL-12p40] and anti-inflammatory cytokines (IL-10 and transforming growth factor-beta) in our patients. Patients who showed no signs of therapeutic response were characterized by a higher basal PBMC production of IL-6 compared with that of the responding patients (p < 0.05) and mitoxantrone reduced this production after 12 months of treatment (p < 0.05). In the responding patients, IL-10 was significantly increased by mitoxantrone after 12 months of treatment (p < 0.05). CONCLUSION: These findings provide additional information useful in the selection of the patient population suitable for mitoxantrone treatment and suggest that most probably the therapeutic action of mitoxantrone in MS is not entirely mediated by its immunosuppressant effects.

no abstract available

No studies have assessed which variables determine deterioration of Quality of Life (QoL) and disability in Charcot-Marie-Tooth disease (CMT). The aim of our study was to assess which are the variables that influence QoL and disability in patients with CMT. We performed a large prospective multicenter (six centers see affiliations) multidimensional study by using validated clinical, disability, and quality of life measurements. Multivariate analysis was performed using QoL as dependent variables and duration of symptoms, age, gender and CMT type, depression and disability measurements as independent variables. Two hundred eleven patients were enrolled (60% women, mean age 42.5 years). QoL was highly significantly deteriorated with respect to the Italian normative sample. The physical aspect of QoL was mainly related to disability (but it does not increase with age probably for an adaptation between expectation and reality). The mental QoL is influenced by depression (hence we have to consider this aspect approaching CMT patients). Moreover we observed that women refer more severe symptoms than men and that some CMT subtypes are related to higher and others to lower bodily pain. Multiperspective assessment of CMT showed new aspects of CMT we have to deal with: differences between men and women, presence of pain and depression.

The purposes of this study were: (1) to evaluate the relationship between disability and Quality of Life (QoL) in stroke outpatients undergoing rehabilitation and (2) to determine whether and how demographic and social features of the patient, duration of disease and concomitant diseases influence the disability and QoL of the stroke outpatients. We performed a prospective study using several conventional disability measurements (Barthel Index, Functional Independence Measure, Modified Rankin Scale and Deambulation Index) and a validated patient-oriented measurement of QoL (SF-36). Sixty-eight outpatients were evaluated consecutively. As expected, all disability measurements were related to Physical Function: patients with higher disability, according to the physician's perspective, complained of higher deterioration of physical performance. Unexpectedly, patients with higher disability from the physician's point of view perceive that they were not able to do some daily activities not only because of physical problems but also because of emotional problems, and complained of higher deterioration of mental health. Multivariate analysis showed that higher disability is associated with higher age, depression and lower educational level. Physical Composite Score appeared to be deteriorated in patients with lower educational level who lived with family; on the contrary, Mental Composite Score appeared deteriorated in patients with higher educational level who lived alone. The current study provides interesting data about the relationship, not always expected, between disability and QoL for stroke patients and about the influence of patients' characteristics on disability and QoL. Our results showed that in a rehabilitation programme we should consider not only disability assessment but also QoL, which is more relevant for the patient.