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Background Cerebellar ataxias comprise sporadic and genetic etiologies. Ataxia may also be a presenting feature in hereditary spastic paraplegias (HSPs).

Background Autoimmune encephalitis (AIE) is a group of inflammatory diseases characterized by the presence of antibodies against neuronal and glial antigens, leading to subacute psychiatric symptoms, memory complaints, and movement disorders. The patients are predominantly young, and delays in treatment are associated with worse prognosis.

Background Percussion is an important part of the neurological examination and reflex hammers are necessary to obtain it properly. Objective We aimed to review the historical aspects of the main reflex hammers and to define the favorite one of Brazilian neurologists. Methods We searched original and review articles about historical aspects of the reflex hammers in Scielo and Pubmed and conducted an online survey to investigate the favorite reflex hammer of Brazilian neurologists. Results In the first part, we describe the major milestones in the creation of the reflex hammers. Following, we exhibit the results of the online survey: Babinski-Rabiner was the most voted. Conclusions The origins of the reflex hammers goes back long before their creation, from a basic clinical examination method: percussion. Since the description of deep tendon reflexes and the creation of percussion hammers, much has been improved in this technique. Among all the hammers surveyed, the Babinski-Rabiner was the chosen one by a significant portion of Brazilian neurologists.

BackgroundThe frequency of antibodies in autoimmune encephalitis (AIE) may vary in different populations, however, data from developing countries are lacking. To describe the clinical profile of AIE in Brazil, and to evaluate seasonality and predictors of AIE in adult and pediatric patients.MethodsWe evaluated patients with possible AIE from 17 centers of the Brazilian Autoimmune Encephalitis Network (BrAIN) between 2018 and 2022. CSF and serum were tested with TBAs and CBAs. Data on clinical presentation, complementary investigation, and treatment were compiled. Seasonality and predictors of AIE in adult and pediatric populations were analyzed.ResultsOf the 564 patients, 145 (25.7%) were confirmed as seropositive, 69 (12.23%) were seronegative according to Graus, and 58% received immunotherapy. The median delay to diagnosis confirmation was 5.97 ± 10.3 months. No seasonality variation was observed after 55 months of enrolment. The following antibodies were found: anti-NMDAR (n=79, 54%), anti-MOG (n=14, 9%), anti-LGI1(n=12, 8%), anti-GAD (n=11, 7%), anti-GlyR (n=7, 4%), anti-Caspr2 (n=6, 4%), anti-AMPAR (n=4, 2%), anti-GABA-BR (n=4, 2%), anti-GABA-AR (n=2, 1%), anti-IgLON5 (n=1, 1%), and others (n=5, 3%). Predictors of seropositive AIE in the pediatric population (n=42) were decreased level of consciousness (p=0.04), and chorea (p=0.002). Among adults (n=103), predictors of seropositive AIE were movement disorders (p=0.0001), seizures (p=0.0001), autonomic instability (p=0.026), and memory impairment (p=0.001).ConclusionMost common antibodies in Brazilian patients are anti-NMDAR, followed by anti-MOG and anti-LGI1. Only 26% of the possible AIE patients harbor antibodies, and 12% were seronegative AIE. Patients had a 6-month delay in diagnosis and no seasonality was found. Findings highlight the barriers to treating AIE in developing countries and indicate an opportunity for cost-effect analysis. In this scenario, some clinical manifestations help predict seropositive AIE such as decreased level of consciousness, chorea, and dystonia among children, and movement disorders and memory impairment among adults.

Abstract The present study aimed to characterize clinical and molecular data of a large cohort of subjects with childhood-onset hereditary spastic paraplegias (HSPs). A multicenter historical cohort was performed at five centers in Brazil, in which probands and affected relatives' data from consecutive families with childhood-onset HSP (onset

ABSTRACT For patients with autoimmune diseases, the risks and benefits of immunosuppressive or immunomodulatory treatment are a matter of continual concern. Knowledge of the follow-up routine for each drug is crucial, in order to attain better outcomes and avoid new disease activity or occurrence of adverse effects. To achieve control of autoimmune diseases, immunosuppressive and immunomodulatory drugs act on different pathways of the immune response. Knowledge of the mechanisms of action of these drugs and their recommended doses, adverse reactions and risks of infection and malignancy is essential for safe treatment. Each drug has a specific safety profile, and management should be adapted for different circumstances during the treatment. Primary prophylaxis for opportunistic infections and vaccination are indispensable steps during the treatment plan, given that these prevent potential severe infectious complications. General neurologists frequently prescribe immunosuppressive and immunomodulatory drugs, and awareness of the characteristics of each drug is crucial for treatment success. Implementation of a routine before, during and after use of these drugs avoids treatment-related complications and enables superior disease control.

Autoinflammatory disorders encompass a wide range of conditions with systemic and neurological symptoms, which can be acquired or inherited. These diseases are characterized by an abnormal response of the innate immune system, leading to an excessive inflammatory reaction. On the other hand, autoimmune diseases result from dysregulation of the adaptive immune response. Disease flares are characterized by systemic inflammation affecting the skin, muscles, joints, serosa, and eyes, accompanied by unexplained fever and elevated acute phase reactants. Autoinflammatory syndromes can present with various neurological manifestations, such as aseptic meningitis, meningoencephalitis, sensorineural hearing loss, and others. Early recognition of these manifestations by general neurologists can have a significant impact on the prognosis of patients. Timely and targeted therapy can prevent long-term disability by reducing chronic inflammation. This review provides an overview of recently reported neuroinflammatory phenotypes, with a specific focus on genetic factors, clinical manifestations, and treatment options. General neurologists should have a good understanding of these important diseases.

ABSTRACT Since the late 19th century, when several inherited neurological disorders were described, the close relationship between Neurology and heredity were well documented by several authors in a pre-genetic era. The term Neurogenetics came to integrate two large sciences and clinical practices: Neurology and Genetics. Neurogenetics is the emerging field that studies the correlation between genetic code and the development and function of the nervous system, including behavioral traits, personality and neurological diseases. In this historical note, a timeline shows the main events and contributors since the first reports of neurogenetic diseases until the current days. In the recent years, neurologists are experiencing much broader use of new genetic diagnosis techniques in clinical practice. Thus, new challenges are arising in diagnostic approach, ethical considerations, and therapeutic options. This article aims to summarize the main historical hallmarks of Neurogenetics, from the pre-DNA era to the present, and the future directions of the field.

Abstract Background: Spinocerebellar ataxia type 3 (SCA3) is the most common autosomal dominant spinocerebellar ataxia worldwide. Almost all patients with SCA3 exhibit nystagmus and/or saccades impairment. Objective: To investigate the presence of nystagmus as an early neurological manifestation, before ataxia, in some patients with SCA3 in the first six months of the disease. Methods: We evaluated a series of 155 patients with clinically and molecularly proven SCA3 between 2013 and 2020. Data regarding sex, age, age at onset, disease duration, CAG repeat expansion length, first symptom, presence of ataxia, scores on SARA and ICARS scales, and presence and characteristics of nystagmus were collected. Results: We identified seven patients with symptomatic SCA3 who presented with isolated nystagmus. In these seven individuals the age at onset ranged from 24 to 57 years, and disease duration from four to six months. Conclusions: Our study showed that nystagmus may be the first neurological sign in SCA3. This clinical observation reinforces the idea that the neurodegenerative process in SCA3 patients may start in vestibular system connections or in flocculonodular lobe. This study adds relevant information about pre-symptomatic features in SCA3 that may work as basis for a better understanding of brain degeneration and for future therapeutic clinical trials.

ABSTRACT Importance: Hypertrophic pachymeningitis (HP) is a non-usual manifestation of rheumatologic, infectious, and neoplastic diseases. Etiological diagnosis is a challenge, but when made promptly it creates a window of opportunity for treatment, with the possibility of a total reversal of symptoms. Observations: HP is an inflammatory process of the dura mater that can occur as a manifestation of sarcoidosis, granulomatosis with polyangiitis, and IgG4-related disease. The HP case evaluation is extensive and includes central nervous system imaging, cerebrospinal fluid analysis, serology, rheumatologic tests, and systemic survey for other manifestations sites. After systemic investigation, meningeal biopsy might be necessary. Etiology guides HP treatment, and autoimmune disorders are treated with corticosteroids alone or associated with an immunosuppressor. Conclusion: HP is a manifestation of several diseases, and a precise etiological diagnosis is crucial because of the difference among treatments. An extensive investigation of patients with HP helps early diagnosis and correct treatment.

ABSTRACT The treatment of Parkinson's disease (PD) is challenging, especially since it is considered highly individualized. The Brazilian Academy of Neurology has recognized the need to disseminate knowledge about the management of PD treatment, adapting the best evidence to the Brazilian reality. Thus, the main published treatment guidelines were reviewed based on the recommendations of group from the Movement Disorders Scientific Department of the Brazilian Academy of Neurology.

ABSTRACT Cerebellar ataxias comprise a heterogeneous group of diseases characterized by motor and non-motor symptoms, which can be acquired, degenerative, or have a genetic cause, such as spinocerebellar ataxias (SCA). Usually, the genetic and neurodegenerative forms of cerebellar ataxias present a progressive and inevitable worsening of the clinical picture so that rehabilitation treatment is fundamental. Rehabilitation treatment includes physical therapy, respiratory therapy, speech, voice and swallowing therapy, occupational therapy, and new technologies, such as the use of exergames. The current treatment of patients with cerebellar ataxias, especially neurodegenerative forms, genetic or not, should include these different forms of rehabilitation, with the main objective of improving the quality of life of patients.

Anti Ma 2 encephalitis is an autoimmune encephalitis, usually paraneoplastic, characterized by isolated or combined limbic, diencephalic, or brainstem dysfunction. Limbic encephalitis (LE) is the most common manifestation. Anti-Ma2 LE can also be manifested as a pure psychiatric disturbance associated or not with hypokinesia. Other patients exhibit excessive daytime sleepiness, vertical ophthalmoparesis, or both associated with LE, due to diencephalic and/or upper brainstem involvement. These cases are challenging and demand extensive work-up for differential diagnosis.

Background: Huntington's disease (HD) is a progressive disorder characterized by motor, cognitive and psychiatric features. Cerebellar ataxia is classically considered as uncommon in HD clinical spectrum.Objective: To determine the prevalence of cerebellar ataxia in patients with HD, both in the early and in the late stages of HD.Methods: Seventy-two individuals considered eligible were assessed by two trained doctors, applying the Scale for Assessment and Rating of Ataxia (SARA) and Brief Ataxia Rating Scale (BARS) for ataxia, the Unified Huntington's Disease Rating Scale (UHDRS) and also, Barthel Index (BI), in order to evaluate functional capacity.Results: Fifty-one patients (70.8%) presented with clinical ataxia at the time of examination (mean time of disease was 9.1 years). Six (8.33%) patients presented with cerebellar ataxia as first symptom. When stratified according to time of disease, a decline in the presence of chorea (p = 0.032) and an increase in cognitive deficit (p = 0.023) were observed in the patients as the disease progressed. The presence of ataxia was associated with longer duration of illness and severity of illness (UHDRS) (p < 0.0001), and shorter Barthel (less functionality) (p = 0.001).Conclusions: Cerebellar involvement may play an important role in natural history of brain degeneration in HD. The presence of cerebellar ataxia in HD is relevant and it may occur even in early stages, and should be included as part of the motor features of the disease.

SPG11 mutations are the major cause of autosomal recessive Hereditary Spastic Paraplegia. The disease has a wide phenotypic variability indicating many regions of the nervous system besides the corticospinal tract are affected. Despite this, anatomical and phenotypic characterization is restricted. In the present study, we investigate the anatomical abnormalities related to SPG11 mutations and how they relate to clinical and cognitive measures. Moreover, we aim to depict how the disease course influences the regions affected, unraveling different susceptibility of specific neuronal populations. We performed clinical and paraclinical studies encompassing neuropsychological, neuroimaging, and neurophysiological tools in a cohort of twenty-five patients and age matched controls. We assessed cortical thickness (FreeSurfer software), deep grey matter volumes (T1-MultiAtlas tool), white matter microstructural damage (DTI-MultiAtlas) and spinal cord morphometry (Spineseg software) on a 3 T MRI scan. Mean age and disease duration were 29 and 13.2 years respectively. Sixty-four percent of the patients were wheelchair bound while 84% were demented. We were able to unfold a diffuse pattern of white matter integrity loss as well as basal ganglia and spinal cord atrophy. Such findings contrasted with a restricted pattern of cortical thinning (motor, limbic and parietal cortices). Electromyography revealed motor neuronopathy affecting 96% of the probands. Correlations with disease duration pointed towards a progressive degeneration of multiple grey matter structures and spinal cord, but not of the white matter. SPG11-related hereditary spastic paraplegia is characterized by selective neuronal vulnerability, in which a precocious and widespread white matter involvement is later followed by a restricted but clearly progressive grey matter degeneration. Keywords: Complicated hereditary spastic paraplegia, SPG11, Motor neuron disorder, Thinning of the corpus callosum, White matter, Grey matter, Spinal cord

ABSTRACT Hereditary ataxias (HA) represents an extensive group of clinically and genetically heterogeneous neurodegenerative diseases, characterized by progressive ataxia combined with extra-cerebellar and multi-systemic involvements, including peripheral neuropathy, pyramidal signs, movement disorders, seizures, and cognitive dysfunction. There is no effective treatment for HA, and management remains supportive and symptomatic. In this review, we will focus on the symptomatic treatment of the main autosomal recessive ataxias, autosomal dominant ataxias, X-linked cerebellar ataxias and mitochondrial ataxias. We describe management for different clinical symptoms, mechanism-based approaches, rehabilitation therapy, disease modifying therapy, future clinical trials and perspectives, genetic counseling and preimplantation genetic diagnosis.

ABSTRACT Non-traumatic myelopathies represent a heterogeneous group of neurological conditions. Few studies report clinical and epidemiological profiles regarding the experience of referral services. Objective To describe clinical characteristics of a non-traumatic myelopathy cohort. Method Epidemiological, clinical, and radiological variables from 166 charts of patients assisted between 2001 and 2012 were compiled. Results The most prevalent diagnosis was subacute combined degeneration (11.4%), followed by cervical spondylotic myelopathy (9.6%), demyelinating disease (9%), tropical spastic paraparesis (8.4%) and hereditary spastic paraparesis (8.4%). Up to 20% of the patients presented non-traumatic myelopathy of undetermined etiology, despite the broad clinical, neuroimaging and laboratorial investigations. Conclusion Regardless an extensive evaluation, many patients with non-traumatic myelopathy of uncertain etiology. Compressive causes and nutritional deficiencies are important etiologies of non-traumatic myelopathies in our population.

The spinocerebellar ataxias (SCA) are a group of neurodegenerative disorders characterized by heterogeneous clinical presentation. Spinocerebellar ataxia type 7 (SCA7) is caused by an abnormal CAG repeat expansion and includes cerebellar signs associated with visual loss and ophthalmoplegia. Marked anticipation and dynamic mutation is observed in SCA7. Moreover, phenotype variability and very early onset of symptoms may occur. In this article, a large series of Brazilian patients with different SCA subtypes was evaluated, and we compared the age of onset of SCA7 with other SCA. From the 26 patients with SCA7, 4 manifested their symptoms before 10-year-old. Also, occasionally the parents may have the onset of symptoms after their children. In conclusion, our study highlights the genetic anticipation phenomenon that occurs in SCA7 families. Patients with very early onset ataxia in the context of a remarkable family history, must be considered and tested for SCA7.

Patients with adult onset non-familial progressive ataxia are classified in sporadic ataxia group. There are several disease categories that may manifest with sporadic ataxia: toxic causes, immune-mediated ataxias, vitamin deficiency, infectious diseases, degenerative disorders and even genetic conditions. Considering heterogeneity in the clinical spectrum of sporadic ataxias, the correct diagnosis remains a clinical challenge. In this review, the different disease categories that lead to sporadic ataxia with adult onset are discussed with special emphasis on their clinical and neuroimaging features, and diagnostic criteria.

OBJECTIVES: To assess balance and ability to function in patients with spinocerebellar ataxia. METHODS: A total of 44 patients with different spinocerebellar ataxia types 1, 2, 3, and 6 were evaluated using the Tinetti balance and gait assessment and the functional independence measure. The scale for the assessment and rating of ataxia and the international cooperative ataxia rating scale were used to evaluate disease severity. RESULTS: Most patients showed significant risk of falls. The balance scores were significantly different in spinocerebellar ataxia types. A significant positive correlation between balance and disease severity was found. CONCLUSION: Patients with spinocerebellar ataxia have important balance impairment and risk of falls that influence the ability to function such as self-care, transfers, and locomotion. Furthermore, the more severe ataxia is, the more compromised are postural balance, risk of falls, and ability to function.

Autosomal recessive cerebellar ataxias are a heterogeneous group of neurological disorders. In 1981, a neurological entity comprised by early onset progressive cerebellar ataxia, dysarthria, pyramidal weakness of the limbs and retained or increased upper limb reflexes and knee jerks was described. This disorder is known as early onset cerebellar ataxia with retained tendon reflexes. In this article, we aimed to call attention for the diagnosis of early onset cerebellar ataxia with retained tendon reflexes as the second most common cause of autosomal recessive cerebellar ataxias, after Friedreich ataxia, and also to perform a clinical spectrum study of this syndrome. In this data, 12 patients from different families met all clinical features for early onset cerebellar ataxia with retained tendon reflexes. Dysarthria and cerebellar atrophy were the most common features in our sample. It is uncertain, however, whether early onset cerebellar ataxia with retained tendon reflexes is a homogeneous disease or a group of phenotypically similar syndromes represented by different genetic entities. Further molecular studies are required to provide definitive answers to the questions that remain regarding early onset cerebellar ataxia with retained tendon reflexes.As ataxias cerebelares autossômicas recessivas são um grupo heterogêneo de doenças neurológicas. Em 1981, foi descrita uma entidade neurológica incluindo ataxia cerebelar progressiva de início precoce, disartria, liberação piramidal e manutenção ou aumento dos reflexos tendíneos nos membros superiores e inferiores. Essa síndrome é conhecida como ataxia cerebelar de início precoce com reflexos mantidos. Neste artigo, o objetivo foi chamar a atenção para o diagnóstico de ataxia cerebelar de início precoce com reflexos mantidos como a segunda causa mais comum de ataxia cerebelar autossômica recessiva, após a ataxia de Friedreich, e também realizar um estudo do espectro clínico da síndrome. Doze pacientes de diferentes famílias preencheram os critérios clínicos para ataxia cerebelar de início precoce com reflexos mantidos. Disartria e atrofia cerebelar foram as características mais frequentes. No entanto, não há consenso se a ataxia cerebelar de início precoce com reflexos mantidos é uma doença homogênea ou um grupo de síndromes com fenótipos semelhantes representadas por diferentes entidades genéticas. Estudos moleculares futuros são necessários para fornecer respostas definitivas para as questões pendentes em relação à ataxia cerebelar de início precoce com reflexos mantidos.

Transcranial sonography has become a useful tool in the differentialdiagnosis of parkinsonian syndromes. This is a non-invasive, low costprocedure. The main finding on transcranial sonography in patientswith idiopathic Parkinson’s disease is an increased echogenicity ofthe mesencephalic substantia nigra region. This hyperechogenicityis present in more than 90% of cases, and reflects a dysfunction inthe dopaminergic nigrostriatal pathway. This study discussed howthe hyperechogenicity of the substantia nigra may facilitate thedifferential diagnosis of parkinsonian syndromes.

Objective: To identify the effect of levodopa in language areas inParkinson’s disease patients. Methods: We evaluated 50 patientswith mild to moderate Parkinson’s disease, age and gender pairedto 47 healthy volunteers. We selected two homogeneous groupsof 18 patients taking levodopa and 7 no levodopa patients. Thefunctional magnetic resonance imaging verbal fluency task, withlow and high cognitive demands, was performed at a 3T magneticresonance imaging equipment. Data was analyzed with XBAMsoftware for group maps and ANOVA comparison. Results: Patientswithout levodopa had more activation than the ones with levodopa inthe medial frontal and in the left frontal and parieto-occipital areas.The striatal activation in patients taking levodopa had similar resultof the activation detected in the healthy volunteer group. Parietooccipitalareas were less activated in the levodopa group than in theno levodopa one. Conclusion: Parkinson’s disease patients withoutlevodopa replacement, during a verbal fluency effort, had morediffuse and intense cerebral activation in left hemisphere, mainlyin the frontal and parieto-occipital areas. The striatal activation inverbal fluency of patients with levodopa intake was more similar tothe activation found in healthy volunteers. These initial evidencessuggested a role of levodopa inhibiting activation in parieto-occipitalcompensating areas.

Neurosarcoidosis (NS) more commonly occurs in the setting of systemic disease. The diagnosis is based on a clinical history suggestive of NS, presence of noncaseating granulomas, and supportive evidence of sarcoid pathology, laboratory, and imaging studies. NS could involve any part of the nervous system and often demands high doses of steroids for symptom control. It presents low response to isolated steroids administration and frequently requires immunosuppressive agents. In NS, lymphocytes are polarized toward an excessive Th1 response, leading to overproduction of TNF-alpha and INF-gama, as well as lL-2 and IL-15. Infliximab, a chimeric monoclonal antibody that neutralizes the biological activity of TNF-alpha, is a new option in the NS treatment. We revised pathophysiology, clinical manifestations, diagnostic work up, and treatment of NS as guidance for the general neurologist.

Progressive supranuclear palsy (PSP) is a distinctive form of neurodegenerative disease which affects the brainstem and basal ganglia. Patients present supranuclear ophthalmoplegia, postural instability and mild dementia. PSP is defined neuropathologically by the accumulation of neurofibrillary tangles in the subthalamic nucleus, pallidum, red nucleus, substantia nigra, striatum, pontine tegmentum, oculomotor nucleus, medulla and dentate nucleus. Over the last decade many lines of investigations have helped refine PSP in many aspects and it is the purpose of this review to help neurologists identify PSP, to better understand its pathophysiology and to provide a more focused, symptom-based treatment approach.