Treatment of cognitive impairment in multiple sclerosis: position paper

Cognitive impairment in multiple sclerosis (MS) is common, debilitating and burdensome. Key evidence from trials was reviewed to enable recommendations to be made to guide clinical practice and research. Behavioural and pharmacological interventions on cognition reported in published studies were reviewed. Most studies evaluating behavioural treatment for impairment in learning and memory, deficits of attention and executive function have demonstrated some improvement. Controlled studies in relapsing remitting MS indicate interferon (IFN) β-1b and IFN β-1a were associated with modest cognitive improvement. The effects of symptomatic therapies such as modafinil and donepezil are inconsistent. Most studies yielding positive findings have significant methodological difficulties limiting the confidence in making any broad treatment recommendations. There are no published reports of glatiramer acetate, natalizumab and fingolimod being effective in improving cognition in controlled trials. The effects of disease modifying therapies in other forms of MS and clinically isolated syndrome have not yielded positive results. Data linking behavioural therapy, symptomatic treatment or disease modifying treatment, to either reducing cognitive decline or improving impaired cognition are limited and inconsistent. The treatment and prevention of cognitive impairment needs to remain a key research focus, identifying new interventions and improving clinical trial methodology.     

Parry Romberg Syndrome associated with chronic facial pain

Parry Romberg Syndrome (PRS) is a rare condition of unknown cause and pathophysiology. It is characterized by progressive facial hemiatrophy, and neurological abnormalities are found in 20% of cases. We describe a 50-year-old woman with PRS and severe neurological involvement (lateralised epileptic seizure activity and facial pain refractory to medication). Pain intensity and frequency was reduced and control of epileptic crises was improved using levetiracetam as an additional therapy. In previous published cases associated with facial pain, the most frequent diagnoses were migraine and trigeminal neuralgia. Our findings suggest that in this patient PRS-related persistent pain has peculiar features possibly attributed to the underlying musculoskeletal abnormalities.     

Palliative embolization for metastases of the spine

Background

To present palliative selective and superselective arterial embolization with N-butyl-cyanoacrylate for cancer patients with spinal metastases.

Materials and methods

We studied the files of 164 cancer patients (94 men and 70 women; mean age 57.6 years; range 35–81 years) treated from March 2003 to March 2013 with 178 selective arterial embolization procedures for metastases of the spine from variable primary cancers. We evaluated the technical success of the embolization procedure with post-procedural angiography, the clinical effect in pain relief, need for analgesics and tumor size reduction, and the embolization-related complications.

Results

Post-embolization angiography showed complete occlusion of the pathological feeding vessels in all procedures. Pain score and need for analgesics reduced by 50 % in 159 patients (97 %); no response was achieved in five patients with metastases of the sacrum. The mean duration of pain relief was 9.2 months (range 1–12 months). Metastatic tumor size reduced from a mean of 5.5 cm (range 3.5–7.5 cm) pre-embolization to a mean of 4.5 cm (range 3–5 cm) at the 6-month follow-up; the difference was not statistically significant. Ninety-three patients (56.7 %) experienced embolization-related complications the most common being post-embolization syndrome (80 patients, 48.8 %) followed by leg paresthesias (ten patients, 6 %), and rupture of a lumbar artery (one patient, 0.6 %).

Conclusion

Selective arterial embolization with N-butyl-cyanoacrylate should be considered for pain palliation of patients with metastases of the spine. However, pain relief is temporary, and complications, although minor may occur.

     

BOLD fMRI integration into radiosurgery treatment planning of cerebral vascular malformations

Functional magnetic resonance imaging (fMRI) is used to distinguish areas of the brain responsible for different tasks and functions. It is possible, for example, by using fMRI images, to identify particular regions in the brain which can be considered as "functional organs at risk" (fOARs), i.e., regions which would cause significant patient morbidity if compromised. The aim of this study is to propose and validate a method to exploit functional information for the identification of fOARs in CyberKnife (Accuray, Inc., Sunnyvale, CA) radiosurgery treatment planning; in particular, given the high spatial accuracy offered by the CyberKnife system, local nonrigid registration is used to reach accurate image matching. Five patients affected by arteriovenous malformations (AVMs) and scheduled to undergo radiosurgery were scanned prior to treatment using computed tomography (CT), three-dimensional (3D) rotational angiography (3DRA), T2 weighted and blood oxygenation level dependent echo planar imaging MRI. Tasks were chosen on the basis of lesion location by considering those areas which could be potentially close to treatment targets. Functional data were superimposed on 3DRA and CT used for treatment planning. The procedure for the localization of fMRI areas was validated by direct cortical stimulation on 38 AVM and tumor patients undergoing conventional surgery. Treatment plans studied with and without considering fOARs were significantly different, in particular with respect to both maximum dose and dose volume histograms; consideration of the fOARs allowed quality indices of treatment plans to remain almost constant or to improve in four out of five cases compared to plans with no consideration of fOARs. In conclusion, the presented method provides an accurate tool for the integration of functional information into AVM radiosurgery, which might help to minimize undesirable side effects and to make radiosurgery less invasive.     

Intracellular and extracellular tumor pH measurement in a series of patients with oral cancer

Reversed pH gradient is an intrinsic feature of tumor phenotype resulting from an upregulation of glycolysis. This is crucial for tumor cell proliferation, invasion, metastasis, drug resistance, and apoptosis. Comprehension of mechanisms of pH regulation in tumors is of paramount importance for therapeutic implications. This is a preliminary report of a larger prospective study dedicated to the measurements of neutral or slightly alkaline pH/extracellular pH (pHi/pHe) in human patients affected by tumors of the head and neck. During surgery, four specimens were obtained from six patients with cancer: two from the tumor site and two from contralateral areas or sane areas near the tumor. pHe and pHi were measured and compared within normal and neoplastic tissues. Our data indicate that human spontaneous tumors show similar reversed gradients as observed in previous analysis on animal tumor models and cell lines.     

Prognostic Factors Associated with Clinical and Economic Outcomes of Appendectomies in Children: A Multilevel Analysis in a National Retrospective Cohort Study

World Journal of Surgery - Acute appendicitis is the most common acute surgical abdominal pathology in children, and it has a large impact on morbidity and the costs incurred by health care...