Impact of delaying botulinum toxin treatment in patients with migraine during the COVID-19 pandemic.

BACKGROUND: Due to coronavirus disease 2019 (COVID-19) pandemic response measures, the administration of botulinum toxin (BTX) was delayed for many patients during the first lockdown period in Portugal. OBJECTIVES: To review the impact of postponing BTX treatment on migraine control. METHODS: This was a retrospective, single-center study. Patients with chronic migraine who had done at least three previous BTX cycles and were considered responders were included. The patients were divided into two groups, one that has had their treatment delayed (group P), and one that has not (controls). The Phase III Research Evaluating Migraine Prophylaxis Therapy (PREEMPT) protocol was used. Migraine-related data were obtained at baseline and at three subsequent visits. RESULTS: The present study included two groups, group P (n = 30; 47.0 ± 14.5 years; 27 females, interval baseline -1st visit: 5.5 [4.1-5.8] months) and the control group (n = 6; 57.7 ± 13.2 years; 6 females; interval baseline-1st visit 3.0 [3.0-3.2] months). No difference between the groups was present at baseline. When compared to baseline, the number of days/month with migraine (5 [3-6.2] vs. 8 [6-15] p < 0.001), days using triptans/month (2.5 [0-6] vs. 3 [0-8], p = 0.027) and intensity of pain (7 [5.8-10] vs. 9 [7-10], p = 0.012) were greater in the first visit for group P, while controls did not present a significant variation. The worsening of migraine-related indicators decreased in the following visits; however, even in the third visit, it had not returned to baseline. Correlations were significant between the delayed time to treatment and the increase in days/month with migraines at the first visit after lockdown (r = 0.507; p = 0.004). CONCLUSIONS: There was a deterioration of migraine control after postponed treatments, with a direct correlation between the worsening of symptoms and the number of months that the treatment was delayed.

ANTECEDENTES: Devido às medidas de resposta à pandemia de coronavirus disease 2019 (covid-19), a administração de toxina botulínica (TXB) foi adiada para muitos pacientes durante o primeiro confinamento em Portugal. OBJETIVOS: Avaliar o impacto do adiamento do tratamento com TXB no controle da enxaqueca. MéTODOS: Estudo retrospectivo unicêntrico. Foram incluídos pacientes com enxaqueca crônica com pelo menos três ciclos prévios de TXB e que tenham sido considerados respondedores. Os pacientes foram divididos em dois grupos, sendo um com atraso do tratamento (grupo P) e outro sem atraso (controles). O protocolo Phase III Research Evaluating Migraine Prophylaxis Therapy (PREEMPT) foi utilizado. Dados clínicos relacionados com a enxaqueca foram obtidos na consulta inicial (T0) e nas três consultas subsequentes (T1­3). RESULTADOS: O presente estudo incluiu dois grupos, o grupo P (n = 30; 47,0 ± 14,5 anos; 27 mulheres, intervalo T0-1ª visita: 5,5 [4,1­5,8] meses) e o grupo controle (n = 6; 57,7 ± 13,2 anos; 6 mulheres; intervalo T0­1ª visita 3,0 [3,0­3,2] meses). Os grupos não apresentavam nenhuma diferença no início do estudo. Quando comparado à T0, o número de dias/mês com enxaqueca (5 [3­6,2] vs. 8 [6­15], p < 0,001), dias usando triptanos/mês (2,5 [0­6] vs. 3 [0­8], p = 0,027) e intensidade da dor (7 [5,8­10] vs. 9 [7­10], p = 0,012) foram maiores na primeira visita no grupo P, não apresentando os controles variação significativa. A piora dos indicadores relacionados com a enxaqueca diminuiu nas visitas seguintes; porém, mesmo na terceira visita, ainda não haviam retornado ao basal. As correlações foram significativas entre o atraso do tratamento e o aumento de dias/mês com enxaqueca na primeira consulta após o confinamento (r = 0,507; p = 0,004). CONCLUSãO: Houve piora clínica da enxaqueca após o adiamento do tratamento em correlação direta com a duração do atraso.

Impact of delaying botulinum toxin treatment in patients with migraine during the COVID-19 pandemic / O impacto do atraso no tratamento com toxina botulínica em pacientes com enxaqueca no contexto da pandemia da COVID-19

Abstract Background Due to coronavirus disease 2019 (COVID-19) pandemic response measures, the administration of botulinum toxin (BTX) was delayed for many patients during the first lockdown period in Portugal. Objectives To review the impact of postponing BTX treatment on migraine control. Methods This was a retrospective, single-center study. Patients with chronic migraine who had done at least three previous BTX cycles and were considered responders were included. The patients were divided into two groups, one that has had their treatment delayed (group P), and one that has not (controls). The Phase III Research Evaluating Migraine Prophylaxis Therapy (PREEMPT) protocol was used. Migraine-related data were obtained at baseline and at three subsequent visits. Results The present study included two groups, group P (n = 30; 47.0 ± 14.5 years; 27 females, interval baseline -1st visit: 5.5 [4.1-5.8] months) and the control group (n = 6; 57.7 ± 13.2 years; 6 females; interval baseline-1st visit 3.0 [3.0-3.2] months). No difference between the groups was present at baseline. When compared to baseline, the number of days/month with migraine (5 [3-6.2] vs. 8 [6-15] p < 0.001), days using triptans/month (2.5 [0-6] vs. 3 [0-8], p = 0.027) and intensity of pain (7 [5.8-10] vs. 9 [7-10], p = 0.012) were greater in the first visit for group P, while controls did not present a significant variation. The worsening of migraine-related indicators decreased in the following visits; however, even in the third visit, it had not returned to baseline. Correlations were significant between the delayed time to treatment and the increase in days/month with migraines at the first visit after lockdown (r = 0.507; p = 0.004). Conclusions There was a deterioration of migraine control after postponed treatments, with a direct correlation between the worsening of symptoms and the number of months that the treatment was delayed.

Resumo Antecedentes Devido às medidas de resposta à pandemia de coronavirus disease 2019 (covid-19), a administração de toxina botulínica (TXB) foi adiada para muitos pacientes durante o primeiro confinamento em Portugal. Objetivos Avaliar o impacto do adiamento do tratamento com TXB no controle da enxaqueca. Métodos Estudo retrospectivo unicêntrico. Foram incluídos pacientes com enxaqueca crônica com pelo menos três ciclos prévios de TXB e que tenham sido considerados respondedores. Os pacientes foram divididos em dois grupos, sendo um com atraso do tratamento (grupo P) e outro sem atraso (controles). O protocolo Phase III Research Evaluating Migraine Prophylaxis Therapy (PREEMPT) foi utilizado. Dados clínicos relacionados com a enxaqueca foram obtidos na consulta inicial (T0) e nas três consultas subsequentes (T1-3). Resultados O presente estudo incluiu dois grupos, o grupo P (n = 30; 47,0 ± 14,5 anos; 27 mulheres, intervalo T0-1ª visita: 5,5 [4,1-5,8] meses) e o grupo controle (n = 6; 57,7 ± 13,2 anos; 6 mulheres; intervalo T0-1ª visita 3,0 [3,0-3,2] meses). Os grupos não apresentavam nenhuma diferença no início do estudo. Quando comparado à T0, o número de dias/mês com enxaqueca (5 [3-6,2] vs. 8 [6-15], p < 0,001), dias usando triptanos/mês (2,5 [0-6] vs. 3 [0-8], p = 0,027) e intensidade da dor (7 [5,8-10] vs. 9 [7-10], p = 0,012) foram maiores na primeira visita no grupo P, não apresentando os controles variação significativa. A piora dos indicadores relacionados com a enxaqueca diminuiu nas visitas seguintes; porém, mesmo na terceira visita, ainda não haviam retornado ao basal. As correlações foram significativas entre o atraso do tratamento e o aumento de dias/mês com enxaqueca na primeira consulta após o confinamento (r = 0,507; p = 0,004). Conclusão Houve piora clínica da enxaqueca após o adiamento do tratamento em correlação direta com a duração do atraso.

Posterior Circulation Stroke: Coma (More Than Time) is Brain.

BACKGROUND AND PURPOSE: Contrary to anterior circulation, the legitimacy of endovascular treatment in posterior circulation stroke is still being questioned. Finding reliable prognostic factors and determining how patient selection should be done has become top priority. METHODS: Observational and retrospective study from two Portuguese hospitals, including all consecutive patients with posterior circulation occlusions who underwent thrombectomy between January 1st 2015 and December 31st 2019. RESULTS: Out of a total of 126 patients, the median age was 74 (IQR 61-80) and 39.7% were female. A good clinical outcome (mRS ≤2) was associated with a lower incidence of coma (24,2% vs 66,7%, p < 0,001) and of sudden onset coma (3% vs 18%,=0,04), a lower NIHSS at admission (14 vs 19, p < 0,001), a higher pc-ASPECTS at admission (10 vs 9, p < 0,001) and at 24 h (8 vs 6, p < 0,001) and a higher BATMAN score (7 vs 6, p = 0,017). Differences in the times of symptom-onset-to-recanalization (496 vs 536, p = 0,19) and symptom-onset-to-coma (130 vs 195, p = 0,52) were not remarkable. When excluding NIHSS and pc-ASPECTS at 24 h, coma (p = 0,003; OR=0,22; 95% CI: 0,08-0,59) and the pc-ASPECTS at admission (p = 0,037; OR=1,63; 95% CI: 1,03-2,57) become independent predictors of good outcome. CONCLUSIONS: In strokes from the posterior circulation, coma, more than time, appears to be an important prognostic factor. The BATMAN and the pc-ASPECTS scores were also associated with clinical outcome and coma.

Female preponderance in genetic generalized epilepsies.

INTRODUCTION: Epilepsy is more prevalent in men but Genetic Generalized Epilepsies (GGE) seem to be more common in women. A predominant maternal inheritance has been previously described in GGE. Our objective was to determine sex and inheritance patterns in a GGE population compared to mesial temporal lobe epilepsy with hippocampal sclerosis (MTLEHS). METHODS: We performed a prospective observational study including adult GGE and MTLEHS patients followed up at a tertiary epilepsy center from January 2016 to December 2019. Patients' familial history was obtained by a detailed questionnaire. Clinical and demographic data was retrieved from clinical notes. RESULTS: A cohort of 641 patients, 403 with GGE and 238 with MTLEHS, was analyzed. GGE was more common in women than MTLEHS (58.8% vs 44.5%, OR=1.63, p = 0.004). Compared to MTLEHS patients, more GGE patients had familial history of epilepsy (45.4% vs 25.2%; p<0.001). The GGE group had a higher percentage of female relatives with epilepsy (55% vs 37%; p = 0.006). The prevalence of maternal inheritance was not different between GGE and MTLEHS groups (62.9% vs 57.7%; p = 0.596). Photosensitivity was more common in females than in males (44.7% vs 34.3%, p = 0.036). CONCLUSION: There is a female preponderance in GGE when compared to MTLEHS, as both GGE patients and their affected relatives are more frequently women. The prevalence of maternal inheritance was not higher in GGE than in MTLEHS.

Parkinsonism and iron deposition in two adult patients with L-2-hydroxiglutaric aciduria.

L-2-hydroxiglutaric aciduria (L2HGA) is a rare, childhood-onset, organic aciduria, with characteristic clinical (cerebellar ataxia) and neuroimaging (subcortical leukodystrophy) features. Movement disorders in this condition are usually of hyperkinetic type. Herein is reported the case of two adult siblings with recent L2HGA diagnosis, presenting with dopa-responsive parkinsonism and MRI iron deposition.

Paraneoplastic neurological syndromes with onconeural antibodies: A single center retrospective study.

INTRODUCTION: Paraneoplastic neurological syndromes (PNS) are immune-mediated diseases that occur in patients with tumors and can be associated with onconeural antibodies. Our aim was to describe our cohort of patients with PNS. METHODS: Retrospective analysis of a cohort of patients followed in a Portuguese tertiary center, with autoantibodies against intracellular antigens from our PNS panel, between 2012 and 2017. RESULTS: Among the 882 patients with suspected PNS (1029 samples), 37 (4.2%) had positive and 27 (3.1%) weak positive antibodies. A total of 17 (29.3%) PNS were diagnosed, 5 were classic syndromes. Autoantibodies found were anti-Yo, anti-Hu, anti-titin, anti-Ma2, anti-SOX1, anti-Ri and anti-CV2/CRMP5. They were associated with thymoma, breast, colon, parotid gland and lung (small-cell, neuroendocrine or carcinoid) cancer. Among the 17 PNS patients, no tumor was found in 4 (mean follow-up of 46 months); no patients improved with tumor treatment, while 8 improved with immunotherapy; ten patients (59%) died during follow-up. Twenty (60.6%) patients with positive antibodies and 21 (84.0%) with weak positive were not diagnosed with a PNS. CONCLUSIONS: PNS had highly heterogenous clinical presentations. Response to tumor treatment was overall poor, with an unfavorable prognosis. In our cohort, only 29.3% of the patients with positive antibodies were diagnosed with a PNS.

Spontaneous Intracranial Hypotension Followed by Intracranial Hypertension.

INTRODUCTION: Spontaneous intracranial hypotension is a secondary cause of headache caused by suspected cerebrospinal fluid leaks. It is associated with vascular changes that may predispose to superficial siderosis. When treated with an epidural blood patch, rebound intracranial hypertension may ensue. CASE REPORT: A 55-year-old man presented with orthostatic headaches responsive to rest and hydration. Brain magnetic resonance revealed subdural collections, consistent with intracranial hypotension. Three weeks later, the patient experienced sudden severe holocranial headache and spontaneous subarachnoid hemorrhage was found. This resulted in rebound intracranial hypertension with bilateral papilledema and sixth-nerve palsy, which completely resolved with acetazolamide. DISCUSSION: Spontaneous intracranial hypotension may predispose to subarachnoid hemorrhage through vascular compensatory changes. Blood in subarachnoid space may seal the hidden cerebrospinal fluid leak or trigger an inflammatory reaction, leading to rebound intracranial hypertension, a well-known epidural blood patch complication.

Diagnosis of Aicardi-Goutières Syndrome in Adults: A Case Series.

INTRODUCTION: Aicardi-Goutières syndrome (AGS) is a genetic disease presenting with early-onset encephalopathy, generalized dystonia, spasticity, and cognitive disability. Diagnosis may be difficult in adults, as the clinical course seems static from infancy. METHODS: AGS patients from an adult movement disorders outpatient clinic were retrospectively analyzed. RESULTS: A total of 5 patients and 1 asymptomatic carrier from 3 different families were identified. All had a homozygous c.529G>A,p.A177T mutation in exon 7 of the RNASEH2B gene. Two patients had neonatal-onset AGS, 2 had later onset forms, and 1 was slightly symptomatic. All were diagnosed in adulthood after chilblains, and basal ganglia calcifications were identified on computed tomography scans. DISCUSSION: AGS patients have marked phenotypic variability regarding psychomotor development and morbidity. The present series included 1 asymptomatic carrier and 1 slightly symptomatic patient, both with homozygous RNASEH2B mutations. Chilblains and basal ganglia calcifications identified on computed tomography scan (but not on magnetic resonance imaging) are important clues for late diagnosis.

Cerebral autoregulation is preserved in multiple sclerosis patients.

Multiple sclerosis (MS) is an inflammatory disease that may also be associated with vascular dysfunction. One master component of vascular regulation is cerebral autoregulation (CA). We aimed to investigate the integrity of CA in MS patients and study its relationship with autonomic dysfunction (AD), magnetic-resonance-imaging (MRI) lesion load and hemodynamic parameters. We enrolled 20 relapsing-remitting MS and 20 healthy subjects. CA was assessed by transfer function analysis parameters (coherence, gain and phase), as obtained in the very low, low and high-frequency domains (VLF, LF, HF, respectively). We evaluated the autonomic parameters heart rate variability and spontaneous baroreflex sensitivity (BRS). There were no significant differences in CA parameters between MS and controls (p>0.05). Lesion load was not correlated with any CA parameter. LF gain was positively correlated with BRS in both groups (MS: p=0.017; controls: p=0.025). Brainstem lesion load in MS was associated with higher systolic blood pressure (SBP; p=0.009). Our findings suggest that CA is preserved in our MS cohort. On the other hand, AD in MS patients with brainstem lesions could contribute to the increase of supine SBP. Whether this systemic deregulation could contribute to disease burden remains to be investigated.

Autonomic dysfunction in multiple sclerosis is better detected by heart rate variability and is not correlated with central autonomic network damage.

BACKGROUND: MS-associated autonomic dysfunction (AD) in multiple sclerosis (MS) is poorly understood and the best method for its detection unestablished. We compared classical Ewing battery and newer methods as heart rate variability (HRV) and spontaneous baroreflex sensibility (BRS) to detect AD in MS and related them to central autonomic network (CAN) lesions. METHODS: We enrolled 20 relapsing-remitting MS patients, median age of 36 (interquartile range 32-46) years, disease duration of 5.5 (2.2-6.8) years, Expanded Disability Status Scale (EDSS) score of 1.0 (1.0-1.5) and 20 age- and gender-matched healthy controls. We assessed Ewing battery and spontaneous HRV and BRS. CAN involvement was evaluated by magnetic resonance imaging. RESULTS: HRV showed both parasympathetic and sympathetic significant impairment in MS (p<0.05). From Ewing battery only isometric test was significantly decreased in MS (p=0.006). Disease duration and severity, lesion burden and CAN involvement were not correlated with laboratorial parameters. CONCLUSIONS: Our MS cohort had both sympathetic and parasympathetic dysfunction independently from disease duration, neurological deficits and lesion burden or CAN involvement. HRV analysis maybe more useful than classical Ewing battery to screen AD.

Prevalence of autonomic dysfunction in patients with multiple sclerosis.

BACKGROUND: Autonomic nervous system dysfunction is commonly seen in multiple sclerosis patients and should be explored in the routine evaluation. Composite Autonomic Symptom Score questionnaire was validated as a self-assessment instrument of autonomic symptoms. OBJECTIVES: Determine the frequency of autonomic symptoms in multiple sclerosis patients through a Portuguese version of Composite Autonomic Symptom Score; compare questionnaire results between patients and a control group; assess the feasibility of this questionnaire application in multiple sclerosis Portuguese patients. MATERIAL AND METHODS: This case-control study used a Portuguese translated version of Composite Autonomic Symptom Score to determine the frequency of autonomic symptoms in multiple sclerosis patients. RESULTS: One-hundred and three relapsing-remitting multiple sclerosis patients - median age 41 years, median disease duration 6 years, median EDSS score 1 - and 80 healthy subjects were included. Alterations in autonomic function were reported in 97.1% of the cases, with statistical significance in orthostatic intolerance and gastrointestinal domain scores. Nevertheless, the difference between multiple sclerosis patients (41.7%) without confounding factors that could interfere with autonomic dysfunction (i.e. comorbidities or medications) and controls showed no statistical significance. DISCUSSION: Our results may be related to the short disease duration, young age and lowdisability status of our patients unaffected by confounding factors. The questionnaire was not designed specifically for multiple sclerosis and it may not be as sensible to early autonomic symptoms as to more severe manifestations. CONCLUSIONS: Further studies are needed to achieve more robust results, validate this questionnaire and assess its application in multiple sclerosis patients in Portugal.

Introdução: A disfunção do sistema nervoso autónomo é comum na esclerose múltipla e deveria ser explorada na avaliação de rotina. O questionário Composite Autonomic Symptom Score foi validado como instrumento de auto-avaliação de sintomas autonómicos. Objetivos: Determinar a frequência de sintomas autonómicos em doentes com esclerose múltipla através de uma versão portuguesa do Composite Autonomic Symptom Score; comparar os resultados do questionário entre um grupo de doentes e um grupo controlo; avaliar a viabilidade da aplicação deste questionário em doentes portugueses. Material e Métodos: Neste estudo caso-controlo utilizou-se uma tradução portuguesa do questionário para determinar a frequência de sintomas autonómicos em doentes com esclerose múltipla. Resultados: Incluíram-se 103 doentes com esclerose múltipla surto-remissão ­ idade média 41 anos, mediana de duração da doença 6 anos, EDSS médio 1 - e 80 indivíduos saudáveis. Dos doentes, 97,1% tinham alterações da função autonómica, com significado estatístico nos domínios intolerância ortostática e gastrointestinal. Não encontramos diferenças estatísticas entre doentes (41,7%) sem fatores de confundimento que podiam interferir com a função autonómica (i.e. comorbilidades ou medicações) e o grupo controlo. Discussão: Os resultados obtidos podem estar relacionados com a curta duração de doença, idade jovem e baixo grau de incapacidade dos doentes sem fatores de confundimento. O questionário utilizado não foi desenhado especificamente para a esclerose múltipla e pode não ser tão sensível para sintomas autonómicos mais precoces como para manifestações mais graves da doença. Conclusões: Outros estudos serão necessários para obter resultados mais robustos, validar este questionário e avaliar a sua aplicação nos doentes portugueses.