Levodopa effect on electromyographic activation patterns of tibialis anterior muscle during walking in Parkinson's disease.

Previous studies have reported that patients with Parkinson's disease (PD) show, in the "off medication" state, a reduced activation of tibialis anterior (TA) in the late swing-early stance phase of the gait cycle. In PD patients the pathophysiological picture may cause differences among the stride cycles. Our aims were to evaluate how frequently TA activity is reduced in the late swing-early stance phase and if there is a relationship between the TA pattern and the clinical picture. Thirty PD patients were studied 2 h after Levodopa administration ("on-med") and 12 h after Levodopa wash-out ("off-med"). They were evaluated by the Unified Parkinson's Disease Rating Scale (UPDRS III) and surface electromyography of TA and gastrocnemius medialis (GM). The root mean square (RMS) of the TA activity in late swing-early stance phase (RMS-A) was normalized as a percent of the RMS of the TA activity in late stance-early swing (RMS-B). RMS-A was reduced in 30% of patients in the "off-med" condition. Within these patients, the percentage of stride cycles with reduced RMS-A, ranged between 28% and 83%. After Levodopa intake, no stride cycle showed reduced RMS-A. Patients with reduced RMS-A had a lower UPDRS III total score in the "on-med" rather than in the "off-med" condition (p=0.02). Our data confirm and extend previous observations indicating that, in "off-med" the function of TA is impaired in those patients clinically more responsive to Levodopa. TA activation is reduced in a relatively high percent of gait cycles in the "off-med" state. Since the variability of TA activation disappears after Levodopa administration, this phenomenon could be the expression of an abnormal dopaminergic drive.

Occurrence and characterization of Pain in immune-mediated neuropathies: a multicentre prospective study.

BACKGROUND: pain is a common symptom of peripheral neuropathies that may severely affect patients' Quality of Life. Pain questionnaires, based on verbal descriptors, are a useful way to investigate it. METHODS: we performed a multicentre study through validated measures to characterize pain in a sample of consecutive patients affected by immune-mediated neuropathies. RESULTS: ninety-three patients were enrolled in 16 Italian centres. Based on the numeric rating scale, almost half of the patients complained of moderate pain and one-third of the patients severe pain. Overall, up to 50% of our patients with immune-mediated neuropathies complained of neuropathic pain. The most common neuropathic symptoms were paraesthesia/dysesthesia and superficial spontaneous pain. Surprisingly, also patients with neuropathies commonly thought to be painless (such as multifocal motor neuropathy) reported discomfort and painful symptoms. CONCLUSIONS: pain questionnaires should be considered in the clinical evaluation of immune-mediated neuropathies, also when evaluating therapy efficacy, because they may provide clinicians with useful information on painful symptoms and patients' quality of life.

Seipin S90L mutation in an Italian family with CMT2/dHMN and pyramidal signs.

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.

A novel HSPB1 mutation in an Italian patient with CMT2/dHMN phenotype.

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.

Epstein-Barr virus antibodies in serum and cerebrospinal fluid from multiple sclerosis, chronic inflammatory demyelinating polyradiculoneuropathy and amyotrophic lateral sclerosis.

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.

"Dropping objects": a potential index of severe carpal tunnel syndrome.

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.

A new clinical scale to grade the impairment of median nerve in carpal tunnel syndrome.

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.

Light chain deposition in peripheral nerve as a cause of mononeuritis multiplex in Waldenström's macroglobulinaemia.

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.

Triple A syndrome: a novel compound heterozygous mutation in the AAAS gene in an Italian patient without adrenal insufficiency.

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 attacks triggered by hyperprolactinemia.

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.

Correlations between peripheral blood mononuclear cell production of BDNF, TNF-alpha, IL-6, IL-10 and cognitive performances in multiple sclerosis patients.

The aim of this study was to investigate the role of Brain Derived Neurotrophic Factor (BDNF) and inflammatory factors in the development of cognitive dysfunctions in Multiple Sclerosis (MS). We correlated peripheral blood mononuclear cell (PBMC) production of BDNF, Tumor Necrosis Factor-alpha (TNF-alpha), Interleukin (IL)-6 and IL-10 with performances on specific neuropsychological tasks in a selected series of MS patients. We studied a sample of 30 patients with relapsing-remitting (RR)MS, segregated by gender and matched for age, education, disease duration, type of immunomodulating therapy, degree of disability and overall cognitive status. We found that low BDNF levels were correlated with increased time of execution on a divided attention and visual scanning task whereas high levels of IL-6 were correlated with low Mini Mental State Examination scores. We did not observe any significant correlations between IL-10, TNF-alpha levels and cognitive performances in our patients. In conclusion our study shows a correlation between low BDNF and high IL-6 production by PBMCs and poorer performances in cognitive tasks in RRMS patients suggesting a possible role of these factors in cognitive impairment in MS.

Natural history of Charcot-Marie-Tooth 2: 2-year follow-up of muscle strength, walking ability and quality of life.

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.

The difficulty in confirming clinical diagnosis of myasthenia gravis in a seronegative patient: a possible neurophysiological approach.

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.

T-bet and pSTAT-1 expression in PBMC from coeliac disease patients: new markers of disease activity.

Coeliac disease (CD) is considered a T cell-mediated autoimmune disease, and up-regulation of T-bet and phosphorylated signal transducers and activators of transcription (pSTAT)1, key transcription factors for the development of T helper type 1 (Th1) cells, has been described in the mucosa of patients with untreated CD. Using transcription factor analysis, we investigated whether T-bet and pSTAT1 expressions are up-regulated in the peripheral blood of CD patients and correlate with disease activity. Using flow cytometry, we analysed T-bet, pSTAT1 and pSTAT3 expression in CD4(+), CD8(+) T cells, CD19(+) B cells and monocytes from peripheral blood of 15 untreated and 15 treated CD patients and 30 controls, and longitudinally in five coeliac patients before and after dietary treatment. We evaluated using enzyme-linked immunosorbent assay (ELISA), interferon (FN)-gamma, interleukin (IL)-17 and IL-10 production by peripheral blood mononuclear cell (PBMC) cultures. T-bet expression in CD4(+), CD8(+) T cells, CD19(+) B cells and monocytes and IFN-gamma production by PBMC was higher in untreated than in treated CD patients and controls. pSTAT1 expression was higher in CD4(+)T cells, B cells and monocytes from untreated than from treated CD patients and controls. pSTAT3 was increased only in monocytes from untreated patients compared with CD-treated patients and controls. The data obtained from the longitudinal evaluation of transcription factors confirmed these results. Flow cytometric analysis of pSTAT1 and T-bet protein expression in peripheral blood mononuclear cells could be useful and sensible markers in the follow-up of CD patients to evaluate disease activity and response to dietary treatment.

Tourettism in multiple sclerosis: a case report.

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.