Fluency in multiple sclerosis: which measure is best?

Tests of verbal fluency provide brief and sensitive measures of the deficits in rapidly retrieving overlearned information common in multiple sclerosis (MS). Production of words that begin with the letters F, A, and S is the verbal fluency measure most often used with patients who are fluent in English. However, because of frequency of words beginning with certain letters varies from one language to another, it is unlikely that any fixed set of letters will be appropriate for multicenter trials that involve patients who are fluent in different languages. A possible alternative involves using semantic fluency categories that contain such a large number of exemplars that no fluent speaker of any language could exhaust the category in the allotted response time. To examine the potential usefulness of semantic fluency measures, 203 MS patients and 87 healthy controls generated words that begin with F, A, or S or were exemplars of the categories animals and parts of the body. Receiver operating characteristic (ROC) curve analyses indicated that sensitivities and specificities for the three fluency measures in discriminating patients from controls were quite similar, especially if patients with global cognitive impairment were excluded.     

Endovascular treatment of trigeminal neuralgia caused by arteriovenous malformation: is surgery really necessary?

A case is presented with secondary trigeminal neuralgia (TN) caused by an arteriovenous malformation (AVM) of the cerebellopontine cistern, which was detected by radiological work-up for planned microvascular decompression. An AVM surrounding the trigeminal nerve was demonstrated on thin-slice heavily T (2)-weighted 3D-sequence on magnetic resonance imaging (MRI) and confirmed by angiography. The first therapeutic step was endovascular embolization with complete obliteration of the AVM and cessation of pain. Nevertheless surgical excision was performed in order to remove compressive vessels and to prevent a recurrence of pain.     

What role for genetics in the prediction of multiple sclerosis?

For most of us, the foundations of our understanding of genetics were laid by considering Mendelian diseases in which familial recurrence risks are high, and mutant alleles are both necessary and sufficient. One consequence of this deterministic teaching is that our conceptualization of genetics tends to be dominated by the notion that the genetic aspects of disease are caused by rare alleles exerting large effects. Unfortunately, the preconceptions that flow from this training are frequently erroneous and misleading in the context of common traits, where familial recurrence risks are modest, and for the most part the relevant alleles are neither rare, necessary, nor sufficient. For these common traits, the genetic architecture is far more complex, with susceptibility rather than causality resulting from the combined effects of many alleles, each exerting only a modest effect on risk. None of these alleles is sufficient to cause disease on its own, and none is essential for the development of disease. Furthermore, most are carried by large sections of the population, the vast majority of which does not develop the disease. One consequence of our innate belief in the Mendelian paradigm is that we have an inherent expectation that knowledge about the genetic basis for a disease should allow genetic testing and thereby accurate risk prediction. There is an inevitable feeling that the same should be true in complex disease, but is it? ANN NEUROL 2010;67:3–10     

What is the best adjuvant treatment for very young patients with medulloblastoma?

The standard treatment for medulloblastoma is surgery followed by adjuvant chemotherapy and external beam radiotherapy to the craniospinal axis and posterior fossa. However, in very young children, craniospinal irradiation has a more significant detrimental effect in terms of neurocognitive function and growth. This article reviews the different strategies used for very young patients with medulloblastoma.     

How effective is intravenous immunoglobulin for the treatment of relapsing-remitting multiple sclerosis?

Intravenous immunoglobulin (IVIg) has been extensively used to treat humoral immunodeficiency states and various immune-mediated conditions. Several studies indicate that the benefits of IVIg with respect to relapses and MRI lesion activity compare favorably with those of interferon beta and glatiramer acetate in relapsing-remitting multiple sclerosis (RRMS) or clinically isolated syndromes. Fazekas et al. recently reported the results of a multinational, randomized, double-blind, placebo-controlled phase II trial of a new preparation of IVIg in 127 participants with RRMS. No significant benefit was demonstrated for IVIg compared with placebo for the primary end point (proportion of relapse-free participants), the main secondary end point (cumulative number of unique newly active brain MRI lesions), or a number of clinical and MRI tertiary end points. Neither the previous positive studies nor the negative results reported by Fazekas et al. can be considered to be definitive, and the utility of IVIg in RRMS remains uncertain at present.     

What do we know about the role of IncRNAs in multiple sclerosis?

Multiple sclerosis is a chronic,inflammatory and degenerative disease of the central nervous system of unknown aetiology although well-defined evidence supports...     

Differential diagnosis of multiple sclerosis,is Moyamoya in?

Background and purposeThe pleomorphic presentation of multiple sclerosis underscores the importance of the differential diagnosis with several other pathologies, namely cerebral vascular disease.Summary of caseA 37-year-old woman without any previous relevant pathology presented 3 years ago with two episodes of motor deficit. The first on the right upper extremity with improvement following rehabilitation and a second with left hemiparesis also with improvement in less than a week. After routine etiological investigation and with a brain MRI suggestive of multiple sclerosis the patient initiated β-interferon remaining symptom free.Present day examination revealed bilateral loss of hand dexterity, decreased paleasthesia on the inferior limbs and hyperactive reflexes on the left with a left Babinski response.MRI of the brain showed multiple bilateral T2 lesions in the periventricular white matter. Significantly, there was no infra-tentorial or corpus callosum involvement. There was also no associated restricted diffusion. CSF analysis was normal.Based on this findings and with positive familiar history for Moyamoya the patient underwent a four-vessel angiogram that demonstrated bilateral ICA occlusion with formation of distal collateral circulation through extra-cranial and posterior circulation, consistent with Moyamoya disease.ConclusionMoyamoya disease should be considered in multiple sclerosis differential especially with atypical imaging findings on MRI. Also, the improvement experienced with imunomodulatory treatment highlights the need to better understand the pathophysiology of Moyamoya disease.     

Gabapentin but not vigabatrin is effective in the treatment of acquired nystagmus in multiple sclerosis: how valid is the GABAergic hypothesis?

Acquired nystagmus occurs frequently in patients with multiple sclerosis and is often the cause of illusory motion of the environment (oscillopsia), and blurring of vision. Based primarily on the beneficial effect of gabapentin on acquired pendular nystagmus (APN), a GABAergic mechanism in controlling nystagmus has been hypothesised. If increasing GABA concentrations in the CNS are critical for the treatment of nystagmus, then a selective GABAergic drug should be highly successful. However, as gabapentin is not a selective GABAergic agent, vigabatrin, a "pure" GABAergic medication, and gabapentin, were compared in a single blind cross over trial in eight patients with definite multiple sclerosis.Patients were randomly assigned to begin with gabapentin (1200 mg daily) or vigabatrin (2000 mg daily). Neuro-ophthalmological and electro-oculographic (EOG) evaluations were performed four and three times, respectively. Treatment efficacy was based on improving visual acuity and EOG indices (amplitude or frequency of nystagmus, or both) by at least 50% of pretreatment values. Three out of eight patients dropped out due to adverse effects.In the remaining five patients gabapentin improved symptomatic pendular or gaze evoked jerk nystagmus in four. Three patients decided to continue gabapentin therapy. Importantly, vigabatrin proved useful in only one out of five patients, suggesting that gabapentin effectiveness may be related to additional non-GABAergic mechanisms of action. Interaction with cerebral glutamate transmission by inhibition of NMDA receptor might be an alternative hypothesis for the therapeutic action of gabapentin.     

Does a placebo-effect exist in clinical trials on multiple sclerosis? Review of the literature

To verify whether the outcome in placebo-treated MS patients actually corresponds to that expected on the basis of the natural history and pretrial evolution of the disease, we here review the results of clinical trials conducted according to a placebo-controlled, randomized design, regardless of the experimental therapy used.The frequency of relapse in remitting-relapsing patients decreases during follow-up, and disability in progressive cases increases more slowly than before enrollment. These data should be borne in mind when evaluating the impact of experimental drugs on the natural course of the disease.

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Sommario Sono stati rivisti i trials clinici condotti in pazienti affetti da SM secondo un disegno randomizzato e controllato con placebo, per verificare se i pazienti trattati con placebo evolvono meno rapidamente rispetto alla storia naturale e all'andamento pretrial. La maggioranza degli studi suggerisce che la frequenza di riaccensioni e l'accumulo di disabilità è inferiore rispetto alle condizioni pre-arruolamento. Questi dati vanno considerati nella valutazione dell'impatto di farmaci sperimentali sul decorso naturale della malattia.

     

Frequency and severity of headache is worsened by Interferon-β therapy in patients with multiple sclerosis

Patti F, Nicoletti A, Pappalardo A, Castiglione A, Lo Fermo S, Messina S, D’Amico E, Cimino V, Zappia M. Frequency and severity of headache is worsened by Interferon‐β therapy in patients with multiple sclerosis.
Acta Neurol Scand: 2012: 125: 91–95.
© 2011 John Wiley & Sons A/S. Background – The relationship between multiple sclerosis (MS) and headache (HA) is not well known. It was reported that interferon‐beta (IFNβ) could induce or worsen HA. Objective – To evaluate the impact of IFNβ treatment on HA and the relationship between HA and the various commercial preparations of IFNβ in mildly disabled patients with MS. Methods – A specific questionnaire was administered to 357 relapsing‐remitting MS patients. Characteristics of HAs were considered, including the temporal relationships with IFNβ administration. Results – One hundred and seventeen patients were treated with weekly intramuscular injections of interferon IFNβ‐1a (Avonex^®), 84 with subcutaneous injections of IFNβ‐1b (Betaferon^®) every other day, 48 and 108 with three times weekly subcutaneous injections of IFNβ‐1a (Rebif^®) 22 mcg or IFNβ‐1a (Rebif^®) 44 mcg, respectively. Three hundred and fourteen patients were affected by HA, and among them, 219 patients suffered of pre‐existing HA. In this latter group, 121 subjects (55%) noted a worsening of their HA after starting IFNβ therapy; this was more frequently reported by patients treated with Avonex^® and Rebif^® 44. Ninety‐five patients experienced new HA. Conclusion – IFNβ treatment could worsen HA in patients with pre‐existing HA or cause the appearance of new HA. Among different IFNβ preparations, Rebif^® 44 and Avonex^® seemed to be more cephalalgic than the other drugs.