Clinical practice guidelines for the diagnosis and management of Charcot-Marie-Tooth disease.

INTRODUCTION: Charcot-Marie-Tooth disease (CMT) is classified according to neurophysiological and histological findings, the inheritance pattern, and the underlying genetic defect. The objective of these guidelines is to offer recommendations for the diagnosis, prognosis, follow-up, and treatment of this disease in Spain. MATERIAL AND METHODS: These consensus guidelines were developed through collaboration by a multidisciplinary panel encompassing a broad group of experts on the subject, including neurologists, paediatric neurologists, geneticists, physiatrists, and orthopaedic surgeons. RECOMMENDATIONS: The diagnosis of CMT is clinical, with patients usually presenting a common or classical phenotype. Clinical assessment should be followed by an appropriate neurophysiological study; specific recommendations are established for the parameters that should be included. Genetic diagnosis should be approached sequentially; once PMP22 duplication has been ruled out, if appropriate, a next-generation sequencing study should be considered, taking into account the limitations of the available techniques. To date, no pharmacological disease-modifying treatment is available, but symptomatic management, guided by a multidiciplinary team, is important, as is proper rehabilitation and orthopaedic management. The latter should be initiated early to identify and improve the patient's functional deficits, and should include individualised exercise guidelines, orthotic adaptation, and assessment of conservative surgeries such as tendon transfer. The follow-up of patients with CMT is exclusively clinical, and ancillary testing is not necessary in routine clinical practice.

Functional outcomes of patients with NORSE and FIRES treated with immunotherapy: A systematic review.

OBJECTIVE: To determine the frequency of good functional outcomes in patients with NORSE and FIRES treated with immunotherapy. METHODS: We performed a systematic search of the MedLine and EMBASE databases to gather studies including at least 5 patients with NORSE or FIRES and at least one patient treated with immunotherapy, and reporting functional outcomes. Good functional outcome was defined as a modified Rankin Scale (mRS) score ≤ 2 (or an equivalent measure) at the last available follow-up assessment. Only patients with known functional outcomes were included in the analysis. RESULTS: We analyzed 16 studies including a total of 161 patients with NORSE. Six studies were carried out only with FIRES patients (n = 64). Of the 161 patients with NORSE, 141 (87.5%) received immunotherapy. Outcome data were available for 135, 56 of whom (41.4%) achieved good functional outcomes. Twenty-four of the 58 patients with FIRES treated with immunotherapy and for whom outcome data were available achieved good functional outcomes (41.3%). Mortality rates in patients with NORSE and FIRES treated with immunotherapy were 20/121 (16.5%) and 6/58 (10.3%), respectively. By type of immunotherapy, good functional outcomes were achieved in 36/89 patients receiving glucocorticoids (40.4%), 27/71 patients receiving IV immunoglobulins (38%), 11/37 patients treated with plasma exchange (29.7%), 5/17 patients receiving rituximab (29.4%), and 2/13 patients receiving cyclophosphamide (15.3%). CONCLUSION: Despite the lack of randomised clinical trials, immunotherapy is frequently prescribed to patients with NORSE and FIRES. However, rates of functional dependence and mortality remain high in these patients. Second-line therapies achieved lower rates of good outcomes, probably because they were administered to patients with more severe, refractory disease.

Immunomodulation in the acute phase of autoimmune encephalitis.

Autoimmune encephalitides constitute an emerging group of diseases for which the diagnosis and management may be challenging, and are usually associated with antibodies against neuroglial antigens used as biomarkers. In this review, we aimed to clarify the diagnostic approach to patients with encephalitis of suspected autoimmune origin in order to initiate early immunotherapy, and to summarize the evidence of current immunotherapies and alternative options assessed for refractory cases. Currently, the general therapeutic approach consists of steroids, IVIG, and/or plasma exchange as first-line medications, which should be prescribed once a diagnosis of possible autoimmune encephalitis is established. For patients not responding to these treatments, rituximab and cyclophosphamide are used as second-line immunotherapy. Additionally, alternative therapies, chiefly tocilizumab and bortezomib, have been reported to be useful in particularly refractory cases. Although the aforementioned approach with first and second-line immunotherapy is widely accepted, the best therapeutic strategy is still unclear since most available evidence is gathered from retrospective non-controlled studies. Moreover, several predictors of good long-term prognosis have been proposed such as response to first-line therapies, modified Rankin score lesser than 4 at the worst neurologic status, no need for admission in intensive care unit, and early escalation to second-line immunotherapy. Thus, the lack of solid evidence underlines the necessity of future well-conducted trials addressing both the best therapeutic regimen and the outcome predictors, but since autoimmune encephalitides have a relatively low incidence, international collaborations seem imperative to reach a reasonable study population size.

Case fatality of COVID-19 in patients with neurodegenerative dementia. / Análisis de letalidad por COVID-19 en pacientes con demencia neurodegenerativa.

INTRODUCTION: The elderly population is the group most threatened by COVID-19, with the highest mortality rates. This study aims to analyse the case fatality of COVID-19 in a cohort of patients with degenerative dementia. METHODS: We conducted a descriptive case-control study of a sample of patients diagnosed with primary neurodegenerative dementia. RESULTS: Twenty-four of the 88 patients with COVID-19 included in the study died: 10/23 (43.4%) patients diagnosed with dementia and 14/65 (21.5%) controls; this difference was statistically significant. DISCUSSION: Our results suggest that case fatality of COVID-19 is significantly higher among patients with primary degenerative dementia than in other patients with similar mean ages and comorbidities.

Miller-Fisher syndrome after SARS-CoV-2 infection.

INTRODUCTION: On March 11th, 2020, the WHO declared the SARS-Cov-2 pandemic. Syndromes have been detected in relation to COVID-19 such as encephalitis, acute necrotizing hemorrhagic encephalopathy and cerebrovascular complications. There are also cases of peripheral nervous system involvement. METHODS: Our case would be the 3rd patient with MFS associated with COVID-19 as far as we know. RESULTS: We present a 51 years old female diagnosed with MFS two weeks after COVID-19. RTPCR to SARS-CoV-2 was negative but IgG was positive. CONCLUSION: Most of the cases were mild or moderate with typical signs and symptoms. All were treated with IV immunoglobulin with good response in most cases. Despite the short evolution time of the cases surviving the current pandemic, the description of cases of post-infectious neurological syndromes suggests that this is probably not an infrequent complication in the subacute stage of Covid-19 disease.

[Case fatality of COVID-19 in patients with neurodegenerative dementia]. / Análisis de letalidad por COVID-19 en pacientes con demencia neurodegenerativa.

Introduction: The elderly population is the group most threatened by COVID-19, with the highest mortality rates. This study aims to analyse the case fatality of COVID-19 in a cohort of patients with degenerative dementia. Methods: We conducted a descriptive case-control study of a sample of patients diagnosed with primary neurodegenerative dementia. Results: Twenty-four of the 88 patients with COVID-19 included in the study died: 10/23 (43.4%) patients diagnosed with dementia and 14/65 (21.5%) controls; this difference was statistically significant. Discussion: Our results suggest that case fatality of COVID-19 is significantly higher among patients with primary degenerative dementia than in other patients with similar mean ages and comorbidities.