Unilateral perirolandic polymicrogyria with ipsilateral brainstem hypoplasia and compensatory contralateral hyperplasia.

Polymicrogyria (PMG) is a malformation of cortical development that occurs mostly in the perisylvian region bilaterally (60-70%), most often presenting with epilepsy. Unilateral cases are much rarer with hemiparesis being the predominant symptom. We report a case of a 71-year-old man with right perirolandic PMG with ipsilateral hypoplasia and contralateral hyperplasia of the brainstem, with only non-progressive left-sided mild spastic hemiparesis. This imaging pattern is thought to occur due to the normal process of withdrawal of the axons of the corticospinal tract (CST) connected to aberrant cortex, possibly with compensatory contralateral CST hyperplasia. However, the majority of cases is additionally present with epilepsy. We believe it is worthwhile to investigate imaging patterns of PMG with symptoms' correlation, particularly with the help of techniques such as advanced brain imaging to assist in the study of cortical development along with adaptive somatotopic organization of the cerebral cortex in MCD with possible clinical applications.

Clinical pattern and response to treatment of primary stabbing headache: Retrospective case series study from a Portuguese tertiary hospital.

OBJECTIVES: This retrospective case series study aimed to investigate the demographic and clinical patterns of primary stabbing headache (PSH). In addition, we tried to identify subgroups of treatment responses in a neurology outpatient consultation at a Portuguese tertiary hospital. METHODS: Clinical records were retrospectively reviewed and patients meeting the International Classification of Headache Disorders, 3rd edition, criteria for PSH were identified from January 2014 to December 2020. We collected data regarding demographic characteristics, clinical features of the headache, primary headache comorbidities, and information about treatment-related do PSH. RESULTS: Of 1857 patients, 32 (1.7%; mean [SD] age of onset 56 [3.5] years) had the final diagnosis of PSH. Regarding headache characteristics, 20 patients (62.5%) reported episodes of stabbing in fixed locations and 12 (37.5%) in multiple areas; the duration of each attack was between ≤5 s (seven [21.9%]), 5-60 s (20 [62.5%]), and ≥60 s (five [15.6%]). In all, 18 patients (56.3%) had an episodic course (vs. six of 32 [18.8%] an acute course and eight of 32 [25%] a chronic course). In all, 17 patients started medical treatment (53.1%), with total or partial improvement in 10 (58.8%) of them. It was found that patients with pain in fixed locations had a better response to treatment when compared to patients with multiple locations, in a statistically significant way (eight of 11 vs. two of six, p = 0.023). CONCLUSION: In our sample, the mean age of onset of PSH was >50 years and there was a wide range of PSH duration. The duration of each attack (>5 s), the pain in fixed locations, non-daily episodes of the pain in each attack, and the intermittent course of headache were the most prevalent clinical features. Finally, patients with stabbing in localized areas had a better response to treatment.

Cognitive complaints in Parkinson's disease patients: from subjective cognitive complaints to dementia and affective disorders.

Subjective cognitive complaints (SCC) are frequent in elderly populations. PD patients report SCC more often than healthy controls. The association between SCC, objective cognitive impairment and affective symptoms remains controversial. We assessed consecutive PD patients between March 2014 and March 2015. Presence of SCC was defined as a score ≥ 1 in the Non-Motor Symptom Assessment Scale for Parkinson's Disease (NMSS) Domain 5. MoCA was used for cognitive impairment assessment. Pill Questionnaire measured the impact in daily activities. PD with Dementia (PDD) and PD with Mild Cognitive Impairment (PDMCI) were defined as the presence of cognitive impairment with or without impact on daily activities. Anxiety and depression were assessed using the Hospital Anxiety and Depression Scales. Significance was set at p < 0.05. From 134 patients, 128 were included. PDD was diagnosed in 21 (16.4%), PDMCI in 31 (24.2%), and 76 (59.4%) had normal cognition (PDCN). SCC were present in 85% of whole cohort and evenly distributed (p = 0.361), PDD (95.2%), PDMCI (83.9%) and PDCN (82.9%). Severity was significantly different between PDD (20.00 ± 10.81), PDMCI (6.54 ± 5.5) and PDCN (6.97 ± 6.98), p < 0.001. A score ≥ 19 had a specificity of 77.3% and a sensitivity of 78.8% for identifying PDD. In PDCN, SCC severity was found to be related to depression (OR 1.23, CI 95% 1.02-1.47, p = 0.026) more than with MoCA scores (OR: 0.86, CI 95% 0.69-1.05, p = 0.141). SCC are common in PD. Their severity can help distinguish PDD from non-demented PD patients. In PDCN, SCC should alert the clinician for an affective disorder.

Effect of patients' expectations on clinical response to fampridine treatment.

INTRODUCTION: Patient expectation of treatment outcome is one of the primary mechanisms underlying the placebo effect. In multiple sclerosis trials with symptomatic treatments, a robust placebo effect is observed, which might be related to patient expectations. The aim of this study was to evaluate whether patient expectations regarding fampridine treatment influence the clinical response after 4 weeks and 6 months of treatment. MATERIALS AND METHODS: We designed and carried out a prospective study from June 2015 to August 2017. Before treatment, patients completed a questionnaire including a scale evaluating their expectations regarding the treatment. The effect of baseline positive expectancy on the response status after 4 weeks and 6 months of treatment was analyzed through univariable and, when applicable, multivariable analysis. RESULTS: A total of 47 consecutive patients were included in the study. At week 4, 37 (78.7%) patients were classified as responders; a one-point increase in the positive expectancy questionnaire was significantly associated with a fourfold increase in the likelihood of being a responder [OR = 4.020 (95% CI 1.082-14.933); p = 0.038]. At 6 months, 43 patients completed follow-up. The number of responders decreased to 28; at this point, positive expectancy at baseline was no longer associated with response status. CONCLUSION: Baseline positive expectancy regarding fampridine was determinant of the clinical response after 4 weeks of treatment. However, in the long term, fampridine efficacy was not dependent on expectations prior to treatment.

Vascular White Matter Lesions in Young Adults: A Neurology Outpatient Clinic Registry.

INTRODUCTION: Although frequently assumed to be age-related changes, vascular white matter lesions (WML) are sometimes found in young adults. Etiology is usually attributed to sporadic small vessel disease; nevertheless, genetic disorders may also be implicated. We aimed to characterize the population of young adults with vascular WML in Neurology outpatient clinics. METHODS: Neurologists from 12 Portuguese hospitals were invited to include patients aged 18-55 years evaluated in consultation, with vascular WML on MRI, scoring II or III in the Fazekas scale. Central imaging validation was performed by 2 independent, blinded, Neuroradiologists. Demographic and clinical data were collected as well as results of investigations performed. RESULTS: During 2 years, 77 patients were included (mean age 47.7 years). Vascular risk factors were present in 88.3% patients (hypertension in 53.2%) and previous history of stroke in 36.4%. Patients without history of stroke were younger (46.6 ± 7.2 vs. 49.6 ± 3.9 years, p = 0.045) and had fewer vascular risk factors (p < 0.001). They were more frequently females (87.8 vs. 46.4%, p < 0.001), and headache (30.6 vs. 3.6%, p = 0.007), contrary to focal symptoms (16.3 vs. 53.6%, p = 0.001), was the most frequent reason of referral. Etiological investigations performed differed between Neurologists. A genetic disorder was identified in 6 out of 58 patients (CADASIL n = 5; COL4A1 n = 1). CONCLUSION: Young adults with vascular WML evaluated in Neurology outpatient clinics concentrate in the oldest age groups. Vascular risk factors should be screened carefully in this population. Among patients without history of stroke, females largely outweigh males. Diagnostic investigations performed do not follow a standardized protocol.

The Influence of Menopause in Multiple Sclerosis Course: A Longitudinal Cohort Study.

BACKGROUND: Hormonal variations are known to influence the course of multiple sclerosis (MS). OBJECTIVES: We aimed to evaluate the impact of menopause in MS course, including disease activity and disability progression. METHODS: We conducted a retrospective longitudinal cohort study including all women, older than 44, post-menopausal, with a diagnosis of MS at least 1 year before menopause. We evaluated the impact of menopause in MS course comparing clinical and radiologic outcomes within 5 years before and after menopause. We repeated the analysis in subgroups of patients without disease-modifying treatment (DMT) change or co-morbidities diagnosed during the observation period, considering that those factors might also impact MS outcomes. RESULTS: Thirty-seven women, with a mean age at the time of menopause of 49.8 (±4.06) years were included in the analysis. Within 5 years following menopause, we observed a decrease in the annualized relapse rate (0.37 ± 0.35 pre-menopause vs. 0.08 ± 0.18 post-menopause, p < 0.001) compared with the same period before menopause, while the EDSS progression rate remained stable (0.13 ± 0.24 EDSS point/year pre-menopausal vs. 0.13 ± 0.18 post-menopause, p = 0.935). EDSS progression events frequency was similar before and after the menopause (37.8 vs. 48.6%, respectively, p = 0.424). These observations persisted in patients' subgroups without DMT switch or co-morbidities. CONCLUSIONS: Following menopause, we observed a reduction in the relapse rate, but the disability progression continued at a similar rate, compared to the pre-menopausal period. These observations persisted in the subgroup of patients without changes in DMT or co-morbidities diagnosed during the observation period.

Motor and non-motor symptoms in old-age onset Parkinson's disease patients.

Advancing age is a well-known risk factor for Parkinson's disease (PD). With population ageing it is expected that the total number of patients with PD onset at oldage increases. Information on the motor but particularly on non-motor phenotype of this late-onset population is lacking. We recruited 24 patients with PD onset at or over 75 years. Each patient was matched with 1 control patient with PD onset between the ages of 40 and 65 and matched for disease duration. Both groups were assessed with the UPDRS, the Non-motor symptoms scale (NMSS) and other scales to assess non-motor symptoms. Groups were compared with conditional logistic regression analysis. Old-age onset PD was, on average, 80 years at the time of PD onset while middle-age onset were 59. Disease duration was approximately 5 years in both groups. While no difference was observed in the total UPDRS-III scores, old-age onset PD was associated with higher axial symptoms (7.42 vs. 4.63, p = 0.011) and a higher frequency of dementia (7/24 vs. 0/24, p = 0.009). While no difference in the total number of non-motor symptoms was observed (6.79 vs. 6.22, p = 0.310), old-age onset patients had a higher prevalence of gastrointestinal symptoms (20/24 vs. 12/24, p = 0.037). For the same disease duration, older age onset is associated with worse axial motor dysfunction and dementia in PD patients. Beside gastrointestinal symptoms, non-motor symptoms are not associated with age.

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.

Gender-based violence and sexual and reproductive health among low-income youth in three Brazilian cities.

In this article, we investigate how gender-based violence (GBV) affects the sexual and reproductive health of impoverished adolescents and young adults. We analyse data from a 2011 survey of 450 young women and 300 young men aged 15-29, living in poor neighbourhoods of three middle-sized cities in Minas Gerais, Brazil. In this survey we used a closed-ended questionnaire to collect data from 150 women and 100 men in each city. Our main goal was to explore the relationship between GBV and young women's autonomy in relation to their sexuality, using indicators appropriate to Brazil. Our results showed a decreased prevalence of condom use at first intercourse and an increased prevalence of teenage pregnancies among young women who were in a relationship with a controlling and violent partner. Lower condom use was observed mostly among young men who acknowledged being violent and controlling towards a partner and they also were more likely to have made a partner pregnant as teenagers themselves. We conclude that some variables utilized here as indicators of control and violence from a partner and of young women's autonomy can help us to understand how GBV inside relationships affects the reproductive and sexual health of young men and women, and how empowering them can reduce their susceptibility to unwanted pregnancies and HIV and other STI infections.

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.

Headache Phenotypes in Idiopathic Intracranial Hypertension and Its Short-Term Outcomes: A Retrospective Case Series Study.

Background: Idiopathic intracranial hypertension (IIH) presents a complex physiopathology, leading into diverse manifestations, notably variable headache phenotypes. Furthermore, its frequent overlap with migraine complicates the evaluation of treatment benefit for IIH-related headache. Our aim was to investigate if there is any relationship between demographic factors, clinical patterns of headache, treatment response, and headache short-term outcome with the headache phenotype of IIH. Methods: This study was a retrospective analysis of demographic, clinical, and treatment features of patients with idiopathic intracranial hypertension presenting with headache and evaluation of headache outcomes in the first 12 months following treatment. Results: Thirty-two patients were included (median age of onset 29.0 years (interquartile range 25.0 - 38.5), 90% females, median body mass index 32.5 kg/m2; 87.5% (n = 28) with papilledema; median cerebrospinal fluid opening pressure 36.5 cm H2O). Patients presented with migraine (n = 11, 34.4%), tension-type (n = 9, 28.1%), or a not-classifiable headache (n = 12, 37.5%). Regarding treatment and short-term follow-up (12 months), there was a failure of medical treatment in 43.8% (n = 14) and a reduction of headaches (≥ 50%) in 62.5% (n = 20) of the patients. Among headache phenotypes, there were no significant differences regarding demographics, clinical features, clinical patterns, or treatment response at baseline. Also, there were no differences regarding response to treatment or headache outcomes in 1, 3, 6, and 12 months of follow-up. Conclusions: In our study, migraine and unclassifiable types were the most commonly reported headache phenotypes. Headache phenotype does not appear to be an essential factor in allowing clinical distinction, treatment response, or predicting the short-term headache outcome of this intriguing entity.

Diagnosis and referral of patients with AL amyloidosis in Portugal: results from a Delphi panel.

Light chain amyloidosis (AL) is a complex disorder defined by the extracellular deposition of insoluble amyloid fibrils formed by intact or fragmented immunoglobulin light chains, leading to cell dysfunction, rapid organ deterioration, and, ultimately, death. Although the clinical presentation of AL is directly connected to organ involvement, signs and symptoms of AL are frequently nonspecific, misinterpreted, and late recognized. Thus, an early diagnosis combined with effective therapies to cease disease progression and rescue organ function is essential. The aim of this study was to assess the knowledge and characterize the current clinical practice regarding AL diagnosis and referral among Portuguese physicians. A Delphi-like panel (one round only) with a group of national experts from different medical specialties (cardiology, hematology, internal medicine, nephrology, and neurology) was carried out online, in which 30 statements were classified using a 4-point Likert scale. For each statement, the consensus level was set at 70% for "fully agree/disagree" and the majority level was defined as >70% in agreement or disagreement. Although the results suggest the existence of adequate general knowledge of AL amyloidosis, they also disclosed the necessity to raise awareness for this disease. Overall, this Delphi panel revealed a high lack of consensus regarding the diagnosis and early management of patients with AL among different specialties despite the qualified majority obtained in 26 statements. An optimized strategy for AL early diagnosis, transversal to several medical fields, is urgently needed. Moreover, referral centers with access to diagnostic technology and a network of diverse specialties should be established to foster an early diagnosis and better disease approach to boost the possibility of a better outcome for patients with AL.

Multisystemic RFC1-Related Disorder: Expanding the Phenotype Beyond Cerebellar Ataxia, Neuropathy, and Vestibular Areflexia Syndrome.

Background and Objectives: The RFC1 spectrum has become considerably expanded as multisystemic features beyond the triad of cerebellar ataxia, neuropathy, and vestibular areflexia syndrome (CANVAS) have started to be unveiled, although many still require clinical replication. Here, we aimed to clinically characterize a cohort of RFC1-positive patients by addressing both classic and multisystemic features. In a second part of this study, we prospectively assessed small nerve fibers (SNF) and autonomic function in a subset of these RFC1-related patients. Methods: We retrospectively enrolled 67 RFC1-positive patients from multiple neurologic centers in Portugal. All patients underwent full neurologic and vestibular evaluation, as well as neuroimaging and neurophysiologic studies. For SNF and autonomic testing (n = 15), we performed skin biopsies, quantitative sensory testing, sudoscan, sympathetic skin response, heart rate deep breathing, and tilt test. Results: Multisystemic features beyond CANVAS were present in 82% of the patients, mainly chronic cough (66%) and dysautonomia (43%). Other features included motor neuron (MN) affection and motor neuropathy (18%), hyperkinetic movement disorders (16%), sleep apnea (6%), REM and non-REM sleep disorders (5%), and cranial neuropathy (5%). Ten patients reported an inverse association between cough and ataxia severity. A very severe epidermal denervation was found in skin biopsies of all patients. Autonomic dysfunction comprised cardiovascular (67%), cardiovagal (54%), and/or sudomotor (50%) systems. Discussion: The presence of MN involvement, motor neuropathy, small fiber neuropathy, or extrapyramidal signs should not preclude RFC1 testing in cases of sensory neuronopathy. Indeed, the RFC1 spectrum can overlap not only with multiple system atrophy but also with hereditary motor and sensory neuropathy, hereditary sensory and autonomic neuropathy, and feeding dystonia phenotypes. Some clinical-paraclinical dissociations can pose diagnostic challenges, namely large and small fiber neuropathy and sudomotor dysfunction which are usually subclinical.

Influence of age and gender in the sensory nerve fibers excitability.

OBJECTIVES: To assess the influence of age and gender on sensory nerve axonal excitability parameters. METHODS: Thirty-three healthy subjects (21 women) were included, with a mean age of 34.6 (range 21-76). Median sensory nerve excitability measurements (index finger) were performed using the TRONDNF nerve excitability protocol of the QTRAC program. RESULTS: Peak sensory nerve action potential (SNAP) amplitude was significantly higher among women (27.1 vs. 9.2 µV; p = .022), and strength-duration time constant (SDTC) was significantly higher in men (0.7 vs. 0.5; p = .011), not dependent on age. Greater age was negatively correlated with resting I/V slope, not dependent on gender (r = -0.4; p = .024). No other changes in excitability properties with increasing age were found. CONCLUSIONS: Physiological features like as age and gender do not have a relevant impact on sensory nerve excitability measurements, which can have implications regarding pharmacological treatments.

Characterization of a Portuguese family with Charcot-Marie-Tooth disease type 1E due to a novel point mutation in the PMP22 gene.

INTRODUCTION: Point mutations in the Peripheral Myelin Protein 22 (PMP22) gene comprise less than 5% of the Charcot-Marie-Tooth (CMT) type 1 cases, and individualize either the CMT 1E subtype, or Hereditary Neuropathy with Liability to Pressure Palsy. The phenotype of CMT 1E presents with a severe early-onset polyneuropathy associated with deafness, although the clinical spectrum is broad. CASE REPORT: We describe a novel PMP22 gene point mutation (c.84G>T;p.(Trp28Cys)) in three patients of a Portuguese family with variable phenotypes, ranging from asymptomatic to mild complaints of distal limb numbness and gait difficulties, with the age of onset of symptoms ranging from mid-twenties to late-sixties, and no associated disability. In all affected patients, there was evidence of diffuse demyelinating sensorimotor polyneuropathy. Hearing loss does not seem to be associated with this variant, albeit neuropathic pain was reported. CONCLUSIONS: These findings suggest that this particular point mutation in the PMP22 gene is associated with a mild phenotype, further emphasizing that there are still unknown mechanisms (genetic and/or epigenetic) that may play a role in the clinical spectrum of CMT1E patients. Next generation sequencing panels including commonly mutated genes in CMT should be considered in CMT1 cases negative for PMP22 gene duplication.