André Caetano

Embolic stroke of unknown source (ESUS) in young patients

The Cryptogenic Stroke International Working Group defined a new subgroup of cryptogenic stroke – embolic stroke of undetermined source (ESUS), based on clinical and imaging findings. Minor cardioembolic and atheroembolic sources were putatively implicated, and it was hypothesized that anticoagulant therapy might be warranted (1). We aimed to assess the role of minor embolic sources in ESUS in young stroke patients by comparing the prevalence of minor embolic sources in patients with ESUS and in patients with stroke of determined origin. Etiology was defined according to the TOAST criteria. ESUS and minor cardioembolic/atheroembolic stroke were defined according to the proposed criteria (1). We studied 100 consecutive ischemic stroke patients (see Table 1) aged between 18 and 55 years admitted in a Neurology department between January 2010 and August 2014 (mean age 46 years, range 22–55; 56% male; mean NIHSS at admission 4). The overall prevalence of minor cardioembolic sources was 53%, and of atheroembolic sources was 32%. Cryptogenic stroke was diagnosed in 51 patients. Among these, 42 patients were ESUS (mean age 45 years, range 26–55; 50% male; mean NIHSS at admission 4). The ESUS group neither have a higher prevalence of minor cardioembolic, 50% (21/42) vs. 50% (27/54), nor a higher prevalence of minor atheroembolic, 38·1% (16/42) vs. 30·8% (15/47), P = 0·641, sources, when compared with all strokes with a determined cause other than cardioembolic and other than large vessel disease, respectively. Although most young patients with cryptogenic stroke fulfill ESUS criteria, minor embolic sources do not seem to be more prevalent in ESUS than in strokes of determined cause; therefore, further explanations should be sought in this group.

Stroke-Like Episodes Heralding a Reversible Encephalopathy: Microbleeds as the Key to the Diagnosis of Cerebral Amyloid Angiopathy–Related Inflammation—A Case Report and Literature Review

BACKGROUND Cerebral amyloid angiopathy (CAA) is a common, often asymptomatic disease. Lobar intracerebral hemorrhage is the most frequent manifestation of CAA. Nevertheless, presentation of CAA with subacute cognitive decline, seizures, or headache with concomitant hyperintensities on T2-weighted magnetic resonance imaging (MRI) sequences and neuropathologic evidence of inflammation has been described. This disorder is known as CAA-related inflammation (CAA-ri). METHODS Description of a stroke-like presentation of CAA-ri and systematic review of case reports and case series of CAA-ri. RESULTS A 75-year-old woman with a history of atrial fibrillation, and a transient episode of aphasia 2 days before, presented in the emergency room with sudden onset aphasia. Brain computed tomography disclosed a left temporal hypodensity. A diagnosis of probable stroke was given. During the following days, there was a progressive clinical deterioration. MRI revealed coalescent edematous white matter lesion, hyperintense on T2-weighted sequences, and multiple lobar microbleeds on T2*-weighted sequences. A diagnosis of CAA-ri was considered, and the patient was started on steroids with clinical and imaging improvement. From our systematic review, microbleeds were present in almost 90% of patients with CAA-ri. CONCLUSIONS Imaging findings associated with CAA-ri allow the early diagnosis and treatment of this potentially reversible disorder. Aside from the most common subacute presentations, CAA-ri can have a stroke-like presentation and be a stroke mimic.

Characterization of motor events in REM sleep behavior disorder

We used video-polysomnography to characterize motor events (ME) in 14 Parkinson’s disease (PD-RBD) and 18 idiopathic (iRBD) REM sleep behavior disorder cases. ME occurred predominantly in the upper limbs and were mostly simple, non-emotional, distal and focal. There were no significant differences in ME features between PD-RBD and iRBD groups. Our data suggests that RBD ME are mostly non violent. Similarity between PD-RBD and iRBD groups suggests that motor dysfunction does not affect ME features.

Association of depressive symptoms with allodynia in patients with migraine: A cross-sectional study.

Aims Migraine and depression have a strong association. We aimed to determine whether this relationship was particularly evident in migraineurs with allodynia. Methods A cross-sectional study was carried out of 98 consecutive patients with episodic migraine presenting for their first evaluation in an outpatient clinic. The participants completed a demographic questionnaire, the Allodynia Symptom Checklist and the Hospital Anxiety and Depression Scale (HADS). Results Among the migraineurs, 75 (77%) reported allodynia. Allodynia was associated with higher median HADS-Anxiety (9 vs. 6, p = 0.038) and HADS-Depression (6 vs. 4, p = 0.014) scores. In a multiple regression model, the HADS-Depression scores were independently associated with allodynia (odds ratio 1.236, 95% confidence interval 1.046–1.461). An increased severity of allodynia correlated with higher depression scores (r = 0.224; p = 0.027). Conclusion Anxious and depressive symptoms are more common in migraineurs with allodynia than in those without allodynia. Further studies are necessary to clarify the relationship between depressive symptoms and allodynia, as well as its therapeutic implications in migraine.

Improving door‐to‐needle times: the effect of positive reinforcement via text message

The benefits of intravenous thrombolysis in stroke treatment are directly related to the time elapsed from symptom onset (1,2). Extending the thrombolytic window to 4·5 h increased the number of eligible patients, but may have led clinicians to forget the urgency of acute stroke, especially regarding patients arriving early to the hospital (3). We aimed to assess the effect of a positive text message sent via mobile phone, on the door-to-needle time (DNT) of a tertiary reference center. During the second semester of 2013, one of two messages was sent daily to the on-call neurology team: a general incentive – ‘1 min is enough to lose 1.900.000 brain cells. Contribute to a better door-to-needle time! Stroke is a medical emergency!’ (4); and a personal incentive – ‘What if your department director gave you a day off for having the best door-to-needle time in your department? Stroke is a medical emergency!’. Comparing with the first half of 2013, the average DNT decreased from 81 (range 30–158, median 67, treated patients n = 14) to 56 (range 27–120, median 46, treated patients n = 21) mins, (twotailed t-test for independent samples, P = 0·02). No significant differences were found regarding onset-to-treatment time (average 167 and 138 mins, respectively), message content, and patient [gender, age, and National Institutes of Health Stroke Scale (NIHSS)] or physician (age, years in neurology and cerebrovascular subspecialization) characteristics. During the first semester of 2014, average DNT remained under 60 mins. The interpretation of results is limited by the small sample and retrospective comparison, but they suggest that this simple strategy might contribute to lowering the DNT. Reinforcing the idea of urgency regarding thrombolysis should be considered as a measure to optimize stroke treatment. Further studies are necessary to understand the need of repeating the message and to assess different strategies aimed at other elements of the in-hospital pathway of thrombolytic therapy.

“Dr Google” will see you now – time trends in online searches on headache

Headaches are a large group of neurological disorders, with a high personal and social burden (1). Evidence on temporal changes in headache prevalence remains conflicting, with some studies reporting an increase while others report relative stability (2). Google Trends is a web-based facility that analyses unbiased samples of Google search queries. It calculates the amount of searches for a given term relative to the total number of searches entered on the Google search engine. Search volume for medical subjects has been pointed out as a valuable epidemiological indicator of disease prevalence over time. There is a high correlation between Google search volume and laboratorysupported epidemiological data of seasonal disorders such as influenza (3). To analyse the evolution of the search for migraine and other headaches, we extracted Google Trends world data since its inception (January 2004) to September 2016. We used migraine and headache as keywords and compared search trends with other high burden neurological disorders. We also included asthma, a non-neurological condition that has a similar prevalence to migraine in children and young adults. The Google Trends algorithm excludes queries made by very few people or the same person over a short period of time. It normalises data against total search volume, scaling results from 0 to 100 (details on support.google.com/trends). The Matlab polyfit function was used to fit the data with a second-degree polynomial (Figure 1). We observed an increase in online headache searches since September 2004. The relative number of online headache searches increased by 158% between January 2004 and January 2016, and a 15% increase was also observed for migraine. During this time period, searches for stroke (6%), multiple sclerosis (MS) (40%) and asthma (28%) decreased. In January 2016, the volume of headache searches was 266% higher than for MS, 141% higher than for stroke and 227% higher than for asthma. Migraine

Cerebral amyloid angiopathy – The modified Boston criteria in clinical practice

BACKGROUND Early identification of patients with cerebral amyloid angiopathy (CAA) is relevant considering the increased risk for cerebral hemorrhage. A new set of diagnostic criteria for CAA was recently proposed, which include the presence of superficial siderosis. We aimed to assess the impact of applying these criteria regarding use of antithrombotic therapy. METHODS Review of consecutive patients admitted to a Neurology Department from 2014 to 2016, with acute parenchymal or subarachnoid hemorrhage and/or atypical transient focal neurological episodes. Patients with a possible or probable CAA according to the original and modified Boston criteria were included. Information was collected regarding presentation, imaging findings and concomitant therapy. RESULTS Among a total of 1436 admitted patients, 52 with acute hemorrhagic lesions or atypical TFNE were screened: 22 met criteria for CAA; 4 were deemed too young; 21 had other causes for hemorrhagic parenchymal lesions; and 5 had uncertain diagnosis. Using the modified Boston criteria, 8 patients fulfilled criteria for probable CAA and 14 for possible CAA. When we applied the original Boston criteria to the same patients, only 7 fulfilled criteria for probable CAA and 8 for possible CAA. Among the additional patients identified with the modified Boston criteria, 4 were using antithrombotic therapy. CONCLUSIONS The use of the modified Boston criteria allowed for the identification of 7 additional patients, more than half of which were taking antithrombotic therapy. Systematic use of these criteria could have an important impact in clinical practice. Raising awareness on the different presentations of CAA among clinicians is of the utmost importance.

Letter to the Editor: Medication-Overuse Headache is Common in Portuguese Migraineurs

Carta ao Editor: A Cefaleia por Uso Excessivo de Medicacao e Comum em Doentes Portugueses com Enxaqueca

A sporadic case of late-onset familial amyloid polyneuropathy with a monoclonal gammopathy

A 77-year-old Portuguese woman reported gradual worsening of burning and numbness in the feet and hands, fatigue, anorexia, weight loss, diarrhoea and decreased visual acuity. She had a medical history of atrial fibrillation and recent episodes of dizziness and blood pressure fluctuations. There was no relevant family history. The diagnostic workup documented a severe axonal sensorimotor peripheral neuropathy, a monoclonal IgG kappa protein on serum, a severe left ventricular hypertrophy on the echocardiogram and probable vitreous deposits of amyloid on ophthalmologic examination. Pain and dysautonomia with an axonal neuropathy and multisystemic involvement raised the possibility of amyloidosis. The presence of a detectable monoclonal protein, older age at disease onset and absence of family history of disease usually suggest immunoglobulin light-chain amyloidosis. However, in this case, both the genetic testing and the biopsy of the salivary glands confirmed transthyretin amyloidosis. In those patients with a monoclonal protein, particularly in sporadic and late-onset cases, the diagnosis of transthyretin amyloidosis can be challenging, mimicking immunoglobulin light-chain amyloidosis.

Neuromyelitis optica spectrum disorder developing 40 years after myasthenia gravis remission

Neuromyelitis optica (NMO) and myasthenia gravis are antibody‐mediated diseases that frequently occur in patients with other autoimmune systemic or organ‐specific diseases. We report the case of a Portuguese woman diagnosed with generalized myasthenia gravis in her mid 20s, and who remained symptom‐free after undergoing thymectomy. Approximately 40 years later, at the age of 74 years, the patient presented with recurrent episodes of longitudinally extensive transverse myelitis within a period of 4 months. The work‐up showed positive antibodies to aquaporin‐4, and a NMO spectrum disorder was diagnosed. Under treatment with high‐dose oral corticosteroids and azathioprine, there were no further relapses. As far as we know, this is one of the longest latency periods reported between the two diagnoses, highlighting that NMO should be kept in mind in any patient with myasthenia gravis developing central nervous system signs and/or loss of visual acuity.