Denervation findings on EMG in amyotrophic lateral sclerosis and correlation with prognostic milestones: Data from a retrospective study.

OBJECTIVE: To verify whether the finding of denervation activity on EMG at the time of diagnosis has a prognostic value in amyotrophic lateral sclerosis (ALS). METHODS: We retrospectively studied all the patients discharged with a diagnosis of ALS between January 2009 and January 2017. 92 patients met the inclusion criteria. We mainly verified three prognostic targets:All EMG examinations were reviewed and a denervation score (DS) was calculated. The association of DS with clinical milestones was analysed, adjusting for disease duration, age , sex, and clinical phenotype. RESULTS: We found a significant association between bulbar DS and time to NIV/tracheostomy (HR: 3.34, 95% CI: 1.49 to 7.48, p = 0.002) and with survival (HR 3.633, 95% CI 1.681-7.848, p = 0.001), regardless of the clinical phenotype. Furthermore, we found a significant influence of a general DS on survival (HR: 2.62, 95% CI 1.335-5.160, p = 0.005). CONCLUSION: EMG assessment could be of value not just for ALS diagnosis but also for its intrinsic prognostic value. SIGNIFICANCE: EMG could provide additional information about the rate of progression of ALS as early as the diagnosis is made.

Chronic cerebrospinal venous insufficiency in patients with multiple sclerosis.

BACKGROUND: The extracranial venous outflow routes in clinically defined multiple sclerosis (CDMS) have not previously been investigated. METHODS: Sixty-five patients affected by CDMS, and 235 controls composed, respectively, of healthy subjects, healthy subjects older than CDMS patients, patients affected by other neurological diseases and older controls not affected by neurological diseases but scheduled for venography (HAV-C) blindly underwent a combined transcranial and extracranial colour-Doppler high-resolution examination (TCCS-ECD) aimed at detecting at least two of five parameters of anomalous venous outflow. According to the TCCS-ECD screening, patients and HAV-C further underwent selective venography of the azygous and jugular venous system with venous pressure measurement. RESULTS: CDMS and TCCS-ECD venous outflow anomalies were dramatically associated (OR 43, 95% CI 29 to 65, p<0.0001). Subsequently, venography demonstrated in CDMS, and not in controls, the presence of multiple severe extracranial stenosis, affecting the principal cerebrospinal venous segments; this provides a picture of chronic cerebrospinal venous insufficiency (CCSVI) with four different patterns of distribution of stenosis and substitute circle. Moreover, relapsing-remitting and secondary progressive courses were associated with CCSVI patterns significantly different from those of primary progressive (p<0.0001). Finally, the pressure gradient measured across the venous stenosies was slightly but significantly higher. CONCLUSION: CDMS is strongly associated with CCSVI, a scenario that has not previously been described, characterised by abnormal venous haemodynamics determined by extracranial multiple venous strictures of unknown origin. The location of venous obstructions plays a key role in determining the clinical course of the disease.

The severity of chronic cerebrospinal venous insufficiency in patients with multiple sclerosis is related to altered cerebrospinal fluid dynamics.

Chronic cerebrospinal venous insufficiency (CCSVI) is a vascular picture that shows a strong association with multiple sclerosis (MS). The aim of this study was to investigate the relationship between a Doppler cerebral venous hemodynamic insufficiency severity score (VHISS) and cerebrospinal fluid (CSF) flow dynamics in 16 patients presenting with CCSVI and relapsing-remitting MS (CCSVI-MS) and in eight healthy controls (HCs). The two groups (patients and controls) were evaluated using validated echo-Doppler and advanced 3T-MRI CSF flow measures. Compared with the HCs, the CCSVI-MS patients showed a significantly lower net CSF flow (p=0.027) which was highly associated with the VHISS (r=0.8280, r2=0.6855; p=0.0001). This study demonstrates that venous outflow disturbances in the form of CCSVI significantly impact on CSF pathophysiology in patients with MS.

Value of MR venography for detection of internal jugular vein anomalies in multiple sclerosis: a pilot longitudinal study.

BACKGROUND AND PURPOSE: CCSVI was recently described in patients with MS. CCSVI is diagnosed noninvasively by Doppler sonography and invasively by catheter venography. We assessed the role of conventional MRV for the detection of IJV anomalies in patients with MS diagnosed with CCSVI and in healthy controls who underwent MRV and Doppler sonography examinations during 6 months. MATERIALS AND METHODS: Ten patients with MS underwent TOF, TRICKS, Doppler sonography, and catheter venography at baseline. They were treated at baseline with percutaneous angioplasty and re-evaluated 6 months' posttreatment with MRV and Doppler sonography. In addition, 6 healthy controls underwent a baseline and a 6-month follow-up evaluation by Doppler sonography and MRV. RESULTS: At baseline, the sensitivity, specificity, PPV, and NPV of Doppler sonography for detecting IJV abnormalities relative to catheter venography in patients with MS were calculated, respectively, at 82%, 100%, 99%, and 95%. The figures were 99%, 33%, 33%, 99% for TOF and 99%, 39%, 35%, and 99% for TRICKS. Venous anomalies included the annulus, septum, membrane, and malformed valve. No agreement was found between TOF and catheter venography in 70% of patients with MS and between TRICKS and catheter venography in 60% of patients with MS. At follow-up, 50% of the patients with MS presented with abnormalities on Doppler sonography but only 30% were diagnosed with restenosis. CONCLUSIONS: Conventional MRV has limited value for assessing IJV anomalies for both diagnostic and posttreatment purposes.

The reproducibility of colour Doppler in chronic cerebrospinal venous insufficiency associated with multiple sclerosis.

AIM: Chronic cerebrospinal venous insufficiency (CCSVI) is a syndrome described in multiple sclerosis (MS) patients, characterized by stenosis of the main extracranial veins with hampered cerebral venous outflow. In the original description echo-colour Doppler demonstrated to be an ideal non invasive tool for screening CCSVI patients, but the reproducibility was not assessed. Aim of this study is to assess the variability coefficient between trained and in not trained echo-colour Doppler operators. METHODS: Thirty-six (36) subjects, matched for age and gender, were subset in 3 groups (group A, 12 healthy controls, HC; group B, 12 multiple sclerosis patients, MS; group C, 12 patients with other neurological disease, OND) underwent echo-colour Doppler screening for CCSVI according to an original protocol previously described. The inter observer variability rate was assessed by comparing respectively trained vs not trained operators, and trained vs trained operators, by using the same echo-colour Doppler equipment. In addition, by scanning 15 subjects after one month from the first session, intra observer coefficient was also assessed in trained operator. RESULTS: The inter observer variability rate between trained and not trained echo-colour Doppler operators, were not completely satisfactory (K coefficient 0.47 95% CI 0.27-0.68). To the contrary the inter observer agreement between trained operators was much more reliable (K coefficient 0.80 95% CI 0.59-1.01). Finally, the intra observer variability rate in trained operators was 0.93, (95% CI 0.80-1.06) confirming a highly satisfactory agreement. CONCLUSION: Echo-colour Doppler is a powerful, non-invasive and reproducible tool for screening CCSVI-MS but it needs special training.

Hemodynamic patterns of chronic cerebrospinal venous insufficiency in multiple sclerosis. Correlation with symptoms at onset and clinical course.

AIM: Chronic cerebrospinal venous insufficiency (CCSVI) is associated with multiple sclerosis (MS). CCSVI is detected by transcranial and extracranial color-Doppler high-resolution examination (TCCS-ECD) and venography that permit to identify five types of venous malformations and four major (A-D) hemodynamic patterns of anomalous extracranial-extravertebral venous outflow. We investigated possible correlation between such hemodynamic patterns and both the symptoms at onset and clinical course in patients with MS and CCSVI. METHODS: TCCS-ECD, selective venography and clinical records of 65 patients affected by definite MS and CCSVI were reviewed. RESULTS: The four hemodynamic patterns of CCSVI were unevenly (P<0.0001) distributed with respect to the types of clinical presentation and course. In particular the Type A or B patterns were common in patients with onset of optic neuritis, but rare in patients presenting with spinal cord symptoms who typically showed a type D pattern. As well, the type A or type B hemodynamic were more common in patients with relapsing remitting course than in patients with secondary progressive course and rare in patients with primary progressive course. The C hemodynamic pattern was not observed in patients with primary progressive course who showed a remarkable prevalence of the type D pattern. CONCLUSION: The distribution of venous malformations and the resulting hemodynamic pattern show correlation with symptoms at onset and clinical course in patients with MS and CCSVI.

Use of neck magnetic resonance venography, Doppler sonography and selective venography for diagnosis of chronic cerebrospinal venous insufficiency: a pilot study in multiple sclerosis patients and healthy controls.

AIM: Chronic cerebrospinal venous insufficiency (CCSVI) is a vascular condition characterized by anomalies of primary veins outside the skull that restrict normal outflow of blood from the brain. CCSVI was recently described as highly prevalent in patients with multiple sclerosis (MS), and can be non-invasively diagnosed by Doppler sonography (DS) and invasively by selective venography (SV). The aim of this paper was to investigate the value of neck magnetic resonance venography (MRV) for the diagnosis of CCSVI compared to DS and SV in patients with MS and in healthy controls (HC). METHODS: Ten MS patients and 7 HC underwent DS, 2D-Time-Of-Flight venography (TOF) and 3D-Time Resolved Imaging of Contrast Kinetics angiography (TRICKS). MS patients also underwent SV. The internal jugular veins (IJVs) and the vertebral veins (VVs) were assessed by both MRV sequences, and the findings were validated against SV and DS. SV has been considered the diagnostic gold standard for MS patients. RESULTS: All MS patients and none of the HC presented CCSVI, according to the DS criteria. This was confirmed by SV. For CCSVI diagnosis, DS showed sensitivity, specificity, accuracy, PPV and NPV of 100%, whereas the figures were 40%, 85%, 58%, 80% and 50% for 3D-TRICKS, and 30%, 85%, 52%, 75% and 46% for 2D-TOF in the IJVs. In MS patients, compared to SV, DS showed sensitivity, specificity, accuracy, PPV and NPV of 100%, 75%, 95%, 94% and 100%, whereas the figures were 31%, 100%, 45%, 100% and 26% for 3D-TRICKS and 25%, 100%, 40%, 100% and 25% for 2D-TOF in the IJVs. CONCLUSION: The use of MRV for diagnosis of CCSVI in MS patients has limited value, and the findings should be interpreted with caution and confirmed by other imaging techniques such as DS and SV.

CSF dynamics and brain volume in multiple sclerosis are associated with extracranial venous flow anomalies: a pilot study.

AIM: We previously reported unexpectedly robust associations between vascular haemodynamic (VH) anomalies in the principal extracranial cerebral veins, causing chronic cerebrospinal venous insufficiency (CCSVI), and multiple sclerosis (MS). Aim of this study was to investigate the relationship between the VH changes and MRI measures of MS disease severity in a cross sectional survey. METHODS: The number of anomalous VH criteria were measured using an echo-color Doppler, whereas CSF flow, atrophy and lesion measures were obtained from quantitative magnetic resonance imaging (MRI) analysis in sixteen consecutive relapsing-remitting MS patients, (mean age: 36.1+/-SD 7.3 years, disease duration: 7.5+/-1.9 years and median EDSS: 2.5) and in 8 healthy controls (HC) with similar age and sex distributions. RESULTS: All 16 MS patients investigated and none of the HCs met the VH criteria for CCSVI (P<0.0001). MS patients showed significantly lower net CSF flow compared to the HC (P=0.038) that was associated with number of anomalous VH criteria present (r=0.79, P<0.001). Moreover, increases in the number of anomalous VH criteria present were negatively associated with lower whole brain volume (Spearman R=-0.5, P=0.05). CONCLUSION: VH changes occur more frequently in MS patients than controls. Altered VH is associated with abnormal CSF flow dynamics and decreased brain volume.

Chronic cerebrospinal venous insufficiency and iron deposition on susceptibility-weighted imaging in patients with multiple sclerosis: a pilot case-control study.

AIM: Chronic cerebrospinal venous insufficiency (CCSVI) is a vascular phenomenon recently described in multiple sclerosis (MS) that is characterized by stenoses affecting the main extracranial venous outflow pathways and by a high rate of cerebral venous reflux that may lead to increased iron deposition in the brain. Aim of this study was to investigate the relationship between CCSVI and iron deposition in the brain of MS patients by correlating venous hemodynamic (VH) parameters and iron concentration in deep-gray matter structures and lesions, as measured by susceptibility-weighted imaging (SWI), and to preliminarily define the relationship between iron measures and clinical and other magnetic resonance imaging (MRI) outcomes. METHODS: Sixteen (16) consecutive relapsing-remitting MS patients and 8 age- and sex-matched healthy controls (HC) were scanned on a GE 3T scanner, using SWI. RESULTS: All 16 MS patients fulfilled the diagnosis of CCSVI (median VH=4), compared to none of the HC. In MS patients, the higher iron concentration in the pulvinar nucleus of the thalamus, thalamus, globus pallidus, and hippocampus was related to a higher number of VH criteria (P<0.05). There was also a significant association between a higher number of VH criteria and higher iron concentration of overlapping T2 (r=-0.64, P=0.007) and T1 (r=-0.56, P=0.023) phase lesions. Iron concentration measures were related to longer disease duration and increased disability as measured by EDSS and MSFC, and to increased MRI lesion burden and decreased brain volume. CONCLUSION: The findings from this pilot study suggest that CCSVI may be an important mechanism related to iron deposition in the brain parenchyma of MS patients. In turn, iron deposition, as measured by SWI, is a modest-to-strong predictor of disability progression, lesion volume accumulation and atrophy development in patients with MS.

Amyloidoma Involving the Orbit, Meckel's Cave and Infratemporal Fossa: 3T MRI Findings.

Amyloidoma is a rare lesion characterized by tissue deposition of an abnormal fibrillary protein (amyloid). It is the focal and localized counterpart of systemic amyloidosis, where the deposition of amyloid diffusely involves several organs. The few literature reports of intracranial amyloidomas include lesions involving the pituitary gland, orbit, cerebral hemispheres, temporal bone, cerebellopontine angle and jugular foramen. We describe the case of a 27-year-old woman presenting with painless slowly progressive proptosis of the right eye. The patient underwent a contrast-enhanced CT study of the head, followed by 3T MRI which disclosed a homogeneous mass in the right Meckel's cave and cavernous sinus, extending through an enlarged foramen ovale to the infratemporal fossa. The right optic nerve and ocular muscles were enlarged and infiltrated along with the retrobulbar fat by contrast-enhancing tissue. Thin contrast-enhanced MRI scans through the area of interest showed the mass to extend posterior to the gasserian ganglion, involving the cerebellopontine angle cistern, where the intracisternal parts of the III, V, and VI nerves bilaterally appeared enlarged and showed perineural enhancement. The lesion closely mimicked a malignant tumor with perineural tumor infiltration, so we performed fine needle biopsy of the portion of the lesion near the right foramen ovale under fluoroscopic guidance. Histopathology revealed that the lesion was an amyloidoma. Further clinical and blood examinations, serum chemistry, followed by biopsy of the periumbilical fat showed no signs of systemic amyloidosis or an underlying inflammatory or neoplastic disorder. No further treatment was instituted, follow-up MRI six months later showed no enlargement of the mass.

Evolutive study of relapsing-remitting multiple sclerosis with cervical proton magnetic resonance spectroscopy. A case report.

We used quantitative proton magnetic resonance spectroscopy ((1)H-MRS) to evaluate mean relative concentrations ratios for NAA, Cr, Cho and mI during the study of cervical spinal cord plaques in a relapsing-remitting multiple sclerosis (RRMS). A cervical spine MR exam was repeated five times on the following days for two months starting from the onset of a relapse phase, using a 3T whole-body system, with the voxel placed along the demyelinazation lesion. The quantification results were compared with the healthy metabolites content. Quantitative cervical spectroscopy is a reliable tool and can offer important metabolic information as already used on the brain to evaluate the severity, progression and pathogenesis of multiple sclerosis.

Neuropathy in multiple myeloma treated with thalidomide: a prospective study.

BACKGROUND: Thalidomide is effective as a first-line therapy for the treatment of multiple myeloma (MM), but its use is limited by peripheral neurotoxicity. OBJECTIVE: To study the occurrence of both myeloma-related neuropathy and thalidomide-induced neuropathy in 31 patients with newly diagnosed MM. METHODS: Clinical and electrophysiologic examinations were performed in 31 patients with newly diagnosed MM before and after 4 months of therapy with thalidomide (200 mg/day, total dose: 21 g) aimed at debulking MM, before autologous transplantation. After transplantation, the patients took thalidomide, 200 mg/day for another 3 months (total dose over three months: 18 g) and then underwent a final clinical and electrophysiologic checkup. RESULTS: At baseline, four patients presented a mild sensorimotor peripheral neuropathy related to MM, which tended to worsen slightly during treatment with thalidomide. At the end of treatment, 83% of the patients had clinical and electrophysiologic evidence of a mild sensory rather than motor, axonal, length-dependent polyneuropathy, whereas 100% of the patients showed improvement to the basic pathology (>or=partial response). CONCLUSIONS: Peripheral neuropathy, sometimes subclinical, and mild in our patients, is a common, early side effect of thalidomide therapy. The high doses (21 g) used in all patients for a relatively short time (4 months) rule out any correlations between neuropathy, total dose, and duration of treatment.

Detection by in situ hybridization of hepatitis C virus positive and negative RNA strands using digoxigenin-labeled cRNA probes in human liver cells.

In situ hybridization was performed using cRNA probes on human liver biopsies to localize both positive and negative RNA strands of hepatitis C virus. From the 5' non-coding region of the viral genome, 210 bp, were amplified by reverse transcriptase-polymerase chain reaction and cloned in a plasmid. Probes were produced by in vitro transcription, and labeled using digoxigenin-11-UTP. Positive HCV-RNA strands were detected in all 20 of the patients analyzed, whereas negative strands were detected in only nine patients, as confirmed using computerized image analysis. Both probes labeled the cytoplasm of hepatocytes with a perinuclear intensification. Few of the mononuclear cells infiltrating the portal connective space contained positive HCV-RNA strands only. Stacks of dilated endoplasmic reticulum cisternae were observed by electron microscopy and their relationship with the infection was discussed. This study confirmed that non-radioactive in situ hybridization represents a useful tool to analyze the localization and replication of hepatitis C virus in liver tissue.