A case of aphemia following non-dominant sub-insular stroke: unveiling the Foix-Chavany-Marie phenomenon.

Aphemia refers to the clinical syndrome of inability to orally produce speech with intact comprehension and written expression. Aphemia has been primarily reported in dominant frontal lobe strokes resulting in apraxia of speech (AoS), and in Foix-Chavany-Marie (FCM) syndrome where bilateral opercular or sub-opercular lesions result in anarthria due to deafferentation of brainstem nuclei supplying the oro-facio-lingual and pharyngeal musculature. Aphemia is not reported in non-dominant sub-insular strokes. Here, we present a case of aphemia following non-dominant sub-insular stroke in a patient who had previously recovered from a homologous dominant sub-insular stroke without any apparent residual deficits. We discuss the accepted definitions, theories and controversies in the use of the terminology - aphemia, apraxia of speech (AoS), anarthria related to FCM syndrome, a concomitant pathology - unilateral upper motor neuron (UUMN) dysarthria, and their neuro-anatomical bases. We also highlight the importance of attributing localization value to sequential homologous lesions of the brain that can unveil symptoms due to a "loss of compensation phenomenon" that we propose be termed as "FCM phenomenon." These pathological mechanisms may alone or in certain combinations contribute to the clinical syndrome of aphemia included in the diagnostic approach proposed here. The distinction between these mechanisms requires serial careful neurological examination and detailed speech evaluation including in the recovery phase.

Practice guideline recommendations summary: Disease-modifying therapies for adults with multiple sclerosis: Report of the Guideline Development, Dissemination, and Implementation Subcommittee of the American Academy of Neurology.

OBJECTIVE: To develop recommendations for disease-modifying therapy (DMT) for multiple sclerosis (MS). METHODS: A multidisciplinary panel developed DMT recommendations, integrating findings from a systematic review; followed an Institute of Medicine-compliant process to ensure transparency and patient engagement; and developed modified Delphi consensus-based recommendations concerning starting, switching, and stopping DMTs pertinent to people with relapsing-remitting MS, secondary progressive MS, primary progressive MS, and clinically isolated syndromes of demyelination. Recommendations were supported by structured rationales, integrating evidence from one or more sources: systematic review, related evidence (evidence not from the systematic review), principles of care, and inference from evidence. RESULTS: Thirty recommendations were developed: 17 on starting DMTs, including recommendations on who should start them; 10 on switching DMTs if breakthrough disease develops; and 3 on stopping DMTs. Recommendations encompassed patient engagement strategies and individualization of treatment, including adherence monitoring and disease comorbidity assessment. The panel also discussed DMT risks, including counseling about progressive multifocal leukoencephalopathy risk in people with MS using natalizumab, fingolimod, rituximab, ocrelizumab, and dimethyl fumarate; and made suggestions for future research to evaluate relative merits of early treatment with higher potency DMTs vs standard stepped-care protocols, DMT comparative effectiveness, optimal switching strategies, long-term effects of DMT use, definitions of highly active MS, and effects of treatment on patient-specified priority outcomes. This guideline reflects the complexity of decision-making for starting, switching, or stopping MS DMTs. The field of MS treatment is rapidly changing; the Academy of Neurology development process includes planning for future updates.

Comprehensive systematic review summary: Disease-modifying therapies for adults with multiple sclerosis: Report of the Guideline Development, Dissemination, and Implementation Subcommittee of the American Academy of Neurology.

OBJECTIVE: To review evidence on starting, switching, and stopping disease-modifying therapies (DMTs) for multiple sclerosis (MS) in clinically isolated syndrome (CIS), relapsing-remitting MS (RRMS), and progressive MS forms. METHODS: Relevant, peer-reviewed research articles, systematic reviews, and abstracts were identified (MEDLINE, CENTRAL, EMBASE searched from inception to November 2016). Studies were rated using the therapeutic classification scheme. Prior published Cochrane reviews were also used. RESULTS: Twenty Cochrane reviews and an additional 73 full-text articles were selected for data extraction through an updated systematic review (completed November 2016). For people with RRMS, many DMTs are superior to placebo (annualized relapses rates [ARRs], new disease activity [new MRI T2 lesion burden], and in-study disease progression) (see summary and full text publications). For people with RRMS who experienced a relapse on interferon-ß (IFN-ß) or glatiramer acetate, alemtuzumab is more effective than IFN-ß-1a 44 µg subcutaneous 3 times per week in reducing the ARR. For people with primary progressive MS, ocrelizumab is probably more effective than placebo (in-study disease progression). DMTs for MS have varying adverse effects. In people with CIS, glatiramer acetate and IFN-ß-1a subcutaneous 3 times per week are more effective than placebo in decreasing risk of conversion to MS. Cladribine, immunoglobulins, IFN-ß-1a 30 µg intramuscular weekly, IFN-ß-1b subcutaneous alternate day, and teriflunomide are probably more effective than placebo in decreasing risk of conversion to MS. Suggestions for future research include studies considering comparative effectiveness, usefulness of high-efficacy treatment vs stepped-care protocols, and research into predictive biomarkers.