Neurophysiology of the pelvic floor in clinical practice: a systematic literature review.

Neurophysiological testing of the pelvic floor is recognized as an essential tool to identify pathophysiological mechanisms of pelvic floor disorders, support clinical diagnosis, and aid in therapeutic decisions. Nevertheless, the diagnostic value of these tests in specific neurological diseases of the pelvic floor is not completely clarified. Seeking to fill this gap, the members of the Neurophysiology of the Pelvic Floor Study Group of the Italian Clinical Neurophysiology Society performed a systematic review of the literature to gather available evidence for and against the utility of neurophysiological tests. Our findings confirm the utility of some tests in specific clinical conditions [e.g. concentric needle electromyography, evaluation of sacral reflexes and of pudendal somatosensory evoked potentials (pSEPs) in cauda equina and conus medullaris lesions, and evaluation of pSEPs and perineal sympathetic skin response in spinal cord lesions], and support their use in clinical practice. Other tests, particularly those not currently supported by high-level evidence, when employed in individual patients, should be evaluated in the overall clinical context, or otherwise used for research purposes.

Sarcoidosis and multiple sclerosis: systemic toxicity associated with the use of interferon-beta therapy.

Sarcoidosis is a multi-systemic inflammatory disease of unknown origin characterized by the presence of noncaseating epitheloid cell granulomas in multiple organs. Diagnosis is made on the basis of a compatible clinical-radiological scenario and the histological demonstration of the typical granulomas in the affected tissues. Interferons are immuno-modulators that have been used in a wide range of diseases, including hepatitis C virus infection, multiple sclerosis, and multiple myeloma and other types of tumours, including leukemia, lymphomas, Kaposi's sarcoma, and melanoma. Interferon-alpha-induced sarcoidosis has been reported repeatedly and there are two reports in the literature of cases of pulmonary sarcoidosis treated with interferon-1b therapy: one for advanced renal cell carcinoma and the other for multiple myeloma. A 35-year-old man on chronic immune-modulant Interferon-1b-based therapy for multiple sclerosis presented to the Neurology Unit with mild dyspnoea, dry cough, and transient pain to right upper abdomen. Lungs, spleen, liver, and almost all lymphnode stations of abdomen and mediastinum were clearly involved on ultrasound examination, chest X-ray, and computed tomography. A transbronchial biopsy showed non-caseating granuloma on histopathologic evaluation of the lungs. To the best of our knowledge, this is the first report of a chronic multisystemic sarcoidosis that was associated with interferon-beta treatment.

Effect of the disclosure of MS diagnosis on anxiety, mood and quality of life of patients: a prospective study.

BACKGROUND: In the light of the new diagnostic criteria for multiple sclerosis (MS) and currently available early treatment, this study aimed to explore whether, and to what extent, disclosure of the diagnosis of MS or clinically isolated syndrome (CIS) affects patients' anxiety, mood and quality of life (QoL). METHODS: Eligible participants were all patients referred for the first time to the Neurological Unit who had manifested symptoms suggestive of MS for no more than 6 months. All patients were evaluated for (i) QoL (SEIQoL and MS-QoL54), (ii) Anxiety (STAI) and Depression (CMDI) on study inclusion (T0), 30 days after diagnosis disclosure (T30), and after 1 (T1y) and 2 (T2y) years' follow-up. RESULTS: Two hundred and twenty-nine patients were enrolled; 93 of these were unaware of their diagnosis. Patients who already knew their diagnosis (100 with CIS and 22 with MS) were excluded from the main analyses and used to perform control analyses. At the end of the screening, an MS diagnosis was disclosed to 18 of the 93 patients, whereas a CIS diagnosis was disclosed to 62 patients (12 patients received a diagnosis other than MS or CIS). Thirty days after diagnosis disclosure, irrespective of the diagnosis disclosed, both QoL and Anxiety and Depression were significantly rated as better compared to the start of screening, (p(s) < 0.03), and this improvement remained stable over the two annual follow-ups. However, as suggested by a significant 'Time' × 'Diagnosis' interaction with regard to both QoL and Anxiety and Depression (p(s) < 0.02), the effect of the disclosure in the short term differed depending on CIS or MS diagnosis. Specifically, on MSQoL, which is a health-related QoL scale, we found a statically significant improvement, immediately after the diagnosis disclosure, in both the MS and CIS groups (p(s) < 0.01). Differently, on SEIQoL, which is a non health-related QoL measure, and on the anxiety scale, we observed a statistically significant improvement only in the group which received a MS diagnosis (p(s) < 0.03). CONCLUSIONS: This first prospective study provides objective data showing that early disclosure of MS diagnosis improves both the patient's QoL and psychological well-being. In addition, the results seem to suggest that CIS disclosure does not lead to the same favourable effects.

Autologous haematopoietic stem cell transplantation with an intermediate intensity conditioning regimen in multiple sclerosis: the Italian multi-centre experience.

BACKGROUND: Over recent years numerous patients with severe forms of multiple sclerosis (MS) refractory to conventional therapies have been treated with intense immunosuppression followed by autologous haematopoietic stem cell transplantation (AHSCT). The clinical outcome and the toxicity of AHSCT can be diverse, depending on the various types of conditioning protocols and on the disease phase. OBJECTIVES: To report the Italian experience on all the consecutive patients with MS treated with AHSCT with an intermediate intensity conditioning regimen, named BEAM/ATG, in the period from 1996 to 2008. METHODS: Clinical and magnetic resonance imaging outcomes of 74 patients were collected after a median follow-up period of 48.3 (range = 0.8-126) months. RESULTS: Two patients (2.7%) died from transplant-related causes. After 5 years, 66% of patients remained stable or improved. Among patients with a follow-up longer than 1 year, eight out of 25 subjects with a relapsing-remitting course (31%) had a 6-12 months confirmed Expanded Disability Status Scale improvement > 1 point after AHSCT as compared with one out of 36 (3%) patients with a secondary progressive disease course (p = 0.009). Among the 18 cases with a follow-up longer than 7 years, eight (44%) remained stable or had a sustained improvement while 10 (56%), after an initial period of stabilization or improvement with median duration of 3.5 years, showed a slow disability progression. CONCLUSIONS: This study shows that AHSCT with a BEAM/ATG conditioning regimen has a sustained effect in suppressing disease progression in aggressive MS cases unresponsive to conventional therapies. It can also cause a sustained clinical improvement, especially if treated subjects are still in the relapsing-remitting phase of the disease.

Psychiatric disorders and depression in multiple sclerosis outpatients: impact of disability and interferon beta therapy.

Associations between psychopathology and gender, duration of MS, disability and therapy with beta-interferons were studied in multiple sclerosis (MS) outpatients. A controlled descriptive epidemiological study was carried out in two Italian outpatient MS centres on 50 outpatients with clinically definite relapsing-remitting MS presenting for regular follow-up and 50 healthy controls matched for sex, age and educational level. Subjects were assessed with the Structured Clinical Interview for DSM-IV (SCID I), the Beck Depression Inventory (BDI) and the State Trait Anxiety Inventory (STAI). MS patients reported a higher prevalence of psychiatric disorders (odds ratio 3.17), with 46% (n=23) suffering from major depressive disorder. The risk of suffering from any non-mood psychiatric disorder was also higher in MS patients than in controls (odds ratio 2.67). Risk factors for depression were female sex and severity of disability, but not therapy with interferon beta or longer duration of illness. Disability level, but not therapy with beta-interferons, is a risk factor for depression in MS outpatients. Regular screening for depression in this population is appropriate.

Juvenile Leigh syndrome with protracted course presenting as chronic sensory motor neuropathy, ataxia, deafness and retinitis pigmentosa: a clinicopathological report.

We herein describe a male patient who died at 37 years of age, after having suffered from a slowly progressive syndrome of chronic sensory motor neuropathy, deafness, retinitis pigmentosa and ataxia. The neuropathological study showed symmetric areas of necrosis and demyelination affecting the cerebellum and brainstem. The type of lesion was consistent with the characteristics of Leigh Syndrome. On the basis of the histology of the lesions, we believe that they appeared only a few months before the death of the patient. We underline the atypical clinical picture and suggest that, in certain cases, brain MRI may not be a reliable diagnostic tool.

X-linked bulbar and spinal muscular atrophy, or Kennedy disease: clinical, neurophysiological, neuropathological, neuropsychological and molecular study of a large family.

We report the clinical, neurophysiological, neuropsychological, neuropathological and molecular findings in a large family with X-linked bulbar and spinal muscular atrophy (X-BSMA). Molecular study, performed in 28 family members, showed an increase in the number of CAG repeats in 6 affected males (including 2 presymptomatic patients), and in 10 females, of whom 5 were obligate carriers. All symptomatic patients showed, besides the typical manifestation of X-BSMA, neurophysiological signs of sensory nerve involvement, and abnormal findings in neuropsychological tests. Sural nerve biopsy, performed in two patients, was consistent with axonal atrophy and slow-rate degeneration, with secondary demyelination. Neurophysiological alterations were also present in 6 out of 8 carriers, consisting of neurogenic EMG changes in 3 cases and abnormal sensory action potentials (SAP) and reduced conduction velocity of the sural nerve in 3 cases. Abnormalities of at last two neuropsychological tests were found in 6 out of 8 carriers. Alterations of the sensory nerves in X-BSMA patients have been previously reported in some cases; however, we demonstrate for the first time sensory nerve involvement also in carriers. Evidence of central nervous system involvement, with neuropsychological impairment in all symptomatic patients and in some carriers, is another feature of this family, not previously reported in X-BSMA. In spite of the variable phenotypic features, the number of CAG repeats ranged from 40 to 44 in the affected patients, indicating that phenotypic expression was not related to the size of the mutation, but was probably age-related.

Neurological complications of herpes zoster.

We report 31 cases of herpes zoster (HZ) with neurological complications: 14 with cranial nerve deficits, 1 with cranial nerve deficit associated with segmental motor disorder, 3 with segmental motor deficits, 2 with meningoencephalitis, 2 with meningoencephalitis associated with cranial neuropathy or myelitis, 2 with meningitis, 2 with hemiplegia contralateral to the ophthalmic HZ. 1 with hemiplegia and motor deficit and finally 1 with hemiplegia and a cranial neuropathy. Smoking was the putative risk factor in 53% of our patients together with diabetes, which has already been mentioned in the literature. We frequently observed more than one complication in succession (19.3%) that could not easily be related to the cutaneous distribution. Acyclovir had no demonstrable positive effects on neurological complication in our patients.

Kennedy disease in an Italian kindred.

An X-linked adult-onset neurogenic muscular atrophy, chiefly proximal, with late involvement of the distal musculature and medulla oblongata was present in 4 members of a single kindred. Associated in all patients were gynecomastia, impotence and essential tremor. Frederickson type IV hyperlipemia was present in 1 patient. Hormonal stimulation tests in 2 patients elicited a borderline low testicular response in the younger of the 2 and a pathological response in the older patient. On the evidence of these and previously reported cases, Kennedy disease would appear to be characterized by an X-linked proximal neurogenic amyotrophy of adult onset and by a testicular endocrine deficit.