The Huntington's Disease Gene Discovery.

The gene for Huntington's disease (HD) was discovered in 1993, after an international collaborative initiative that led researchers to remote regions of South America. It was the most remarkable milestone, since George Huntington's initial description. Through the phenomenological discussions led by Jean-Martin Charcot and Willian Osler, and finally Americo Negrette's reports, which served as the inspiration for the Venezuela Project led by Nancy Wexler, the journey toward discovering the Huntington's disease (HD) gene was marked by substantial efforts. This monumental achievement involved the analysis of more than 18,000 blood samples and gathered dozens of researchers in an integrated effort, enabling the mapping of the gene on chromosome 4 in 1983 and leading, a decade later, to the precise localization and identification of the HTT gene. The discovery of the HD mutation represented a pivotal moment in the field of genetics and neurology, significantly enhancing our understanding of the disease and creating opportunities for future treatments. The progress made and the knowledge gained during this journey catalyzed the development of many innovative molecular techniques that have advanced research in other medical conditions. In this article, the authors celebrate three decades of this memorable event, revisiting the historical aspects, providing insights into the techniques developed, and delving into the paths that ultimately led to the discovery of the HD gene. © 2024 International Parkinson and Movement Disorder Society.

My first dance.

Many emotions are generated within a medical consultation. These feelings are often shared among the doctor, patient, and family. In this piece, these emotions are explored as I describe them deeply during my first encounter with a Huntington's disease patient, bringing the challenges of the situation, mistakes, and the learning that emerged. Understanding the possible sentiments and how to balance these emotions may be essential to prepare the neurologist in training for the challenges inherent in treating a patient with a rare disease.

Imbalance and gait impairment in Parkinson's disease: discussing postural instability and ataxia.

Gait and balance difficulties pose significant clinical challenges in Parkinson's disease (PD). The impairment of physiological mechanisms responsible for maintaining natural orthostatism plays a central role in the pathophysiology of postural instability observed in PD. In addition to the well-known rigidity and abnormalities in muscles and joints, various brain regions involved in the regulation of posture, balance, and gait, such as the basal ganglia, cerebellum, and brainstem regions like the pontine peduncle nucleus, are affected in individuals with PD. The recognition of the cerebellum's role in PD has been increasingly acknowledged. Cortical areas and their connections are associated with freezing of gait, a type of frontal lobe ataxia commonly observed in PD. Furthermore, impairments in the peripheral nervous system, including those caused by levodopatherapy, can contribute to gait impairment and imbalance in PD patients. Consequently, individuals with PD may exhibit frontal ataxia, sensory ataxia, and even cerebellar ataxia as underlying causes of gait disturbances and imbalance, starting from the early stages of the disease. The complex interplay between dysfunctional brain regions, impaired cortical connections, and peripheral nervous system abnormalities contributes to the multifaceted nature of gait and balance difficulties in PD. Understanding the intricate mechanisms is crucial for the development of effective therapeutic approaches targeting these specific deficits in PD.

Movement Disorders in PURA Syndrome: A Video Case Series.

Background: PURA syndrome is a rare genetic disorder characterized by neonatal hypotonia, neurodevelopmental delay, facial dysmorphism, epileptic seizures, complex movement disorders, among other features. Although many pathogenic variants have been reported, there is currently no clear genotype-phenotype association identified. Cases: Four patients diagnosed with PURA syndrome, despite carrying different pathogenic variants, presented a similar mixed hyperkinetic movement disorder. The phenomenology presented a complex set of symptoms, including chorea, interspersed with dystonic and uncoordinated movements. All patients presented also hypotonia, nystagmus, feeding difficulties, craniofacial dysmorphisms. Hypersomnolence and breathing problems were common and observed in three patients, while seizures were found in three patients. Conclusions: PURA syndrome may be considered in the differential diagnosis of infants with severe hypotonia, feeding difficulties and severe developmental delay with epileptic seizures, that start to develop a mixed hyperkinetic movement disorder. These complex movements may be an important clue for the diagnosis of this rare disorder.

I Do Care.

This essay recalls the importance of compassion in medicine.

Immune-mediated ataxias: Guide to clinicians.

Immune-mediated cerebellar ataxias were initially described as a clinical entity in the 1980s, and since then, an expanding body of evidence has contributed to our understanding of this topic. These ataxias encompass various etiologies, including postinfectious cerebellar ataxia, gluten ataxia, paraneoplastic cerebellar degeneration, opsoclonus-myoclonus-ataxia syndrome and primary autoimmune cerebellar ataxia. The increased permeability of the brain-blood barrier could potentially explain the vulnerability of the cerebellum to autoimmune processes. In this manuscript, our objective is to provide a comprehensive review of the most prevalent diseases within this group, emphasizing clinical indicators, pathogenesis, and current treatment approaches.

"On Chorea": 150 Years of the Beginning of Hope.

"On Chorea" by George Huntington was published on April 13, 1872, in The Medical and Surgical Reporter of Philadelphia. Despite being a milestone in the recognition of the disease that later would bear his name, some myths and curiosities continue to surround the history of this publication and its author. In this History, the authors pay tribute to the 150th anniversary of the publication of this iconic article. © 2022 International Parkinson and Movement Disorder Society.

Adrenocorticotropic Hormone (ACTH)-Induced Dyskinesias in Infantile Spasms: A Video Case Report.

BACKGROUND Infantile spasms is an age-specific epilepsy syndrome that occurs during infancy and is characterized by tonic and/or flexor-extensor spasms, hypsarrhythmia on electroencephalography (EEG), and neurodevelopmental regression. Adrenocorticotropic hormone (ACTH) is considered one of the main therapies for the treatment of infantile spasms, but despite its great efficacy, it is still associated with potential adverse effects. CASE REPORT Four patients previously diagnosed with infantile spasms were treated with ACTH following the usual treatment regimen. All patients developed asymmetric, involuntary movements, with phenomenology characteristic of dyskinesia. The patients did not manifest loss of consciousness, and the EEG did not show epileptic activity during those episodes. In all cases, involuntary movements disappeared after the completion of the hormonal therapy. CONCLUSIONS The adverse effect of hormonal therapy in infantile spasms is not well known in the literature and could be mistaken as seizures, leading to inappropriate management.

When My Child Has Alzheimer's Disease.

The significant increment in life expectancy, associated to the existence of high-performing older adults, and the appropriate diagnosis of early dementias, lead to an uncommon scenario, of healthy parents accompanying their children with Alzheimer's disease or another dementia to medical consultations. Here, we reported three peculiar clinical vignettes of patients diagnosed with a dementia, who were accompanied by healthy parents. This is a modern situation that tends to become more frequent, and must be properly discussed, since multidisciplinary care and specific training are necessary.