Prodromal spinocerebellar ataxia type 2: Prospects for early interventions and ethical challenges

Abstract

The characterization of prodromal stages in neurodegenerative disorders is becoming increasingly important because of the need for early neuroprotective therapies. Research during the past 3 decades in spinocerebellar ataxia type 2 has revealed a large body of evidence suggesting that many disease features precede the manifest cerebellar syndrome, which delineates the prodromal stage of this disorder. This stage is defined by clinical, imaging, and functional criteria, which are supported by early molecular events demonstrated in animal models. Knowledge regarding prodromal spinocerebellar ataxia type 2 provides insight into the mechanisms underlying neurodegeneration from the early stages, which enables the design of promising disease-modifying clinical trials through the identification of the optimum moment to begin the therapies, the appropriate selection of individuals, and the identification of sensitive outcome measures. The management of patients in prodromal spinocerebellar ataxia type 2 may raise ethical dilemmas related to predictive diagnosis and early interventions, which impose new challenges to clinical and therapeutic research. © 2017 International Parkinson and Movement Disorder Society.

Neurorehabilitation therapy in spinocerebellar ataxia type 2: A 24‐week, rater‐blinded, randomized, controlled trial

“…SCA2 is characterized by a progressive cerebellar syndrome accompanied by severe saccadic slowing, peripheral neuropathy, autonomic disturbances, pyramidal signs, cognitive disorders, and sleep disturbances . Similar to other SCAs caused by the polyglutamine domain, the onset of SCA2 cerebellar syndrome is significantly controlled by the mutation size and is preceded by prodromal manifestations up to more than a decade before disease onset …”

Neuroinflammation and Neuromodulation in Neurological Diseases

“…This phase is followed by the prodromal or preclinical stage, characterized by unspecific neurological features such as painful muscle cramps, sensory abnormalities, subtle cerebellar manifestation (increase of the sway during tandem gait), cognitive decline, autonomic disorders, olfactory dysfunction and hyperreflexia. Electrophysiological studies showed the reduction of the maximal saccadic velocity, REM sleep disorders, increased central motor conduction time in transcranial magnetic stimulation and peripheral sensory axonal damage according of the peripheral nerve conduction studies [3,24]. …”

“…This discipline has emerged today from the research field as a mature and fully developed innovative research area that integrates not only pure topics of neuroimmunology, but also expands on wider fields such as neuroplasticity, neuronal reserve and neuromodulation. Several diseases were revised in interesting lectures to offer a major understanding of the molecular processes underlying neuroimmune pathology in neurodegenerative, neurodevelopmental and neurovascular diseases, as well as to understand some vulnerabilities occurring in these disorders [1,2,3,4,5]. …”

“…From this point of view, several diseases were revised in interesting lectures to offer a greater understanding of the molecular processes underlying neuroimmune pathology in neurodegenerative, neurodevelopmental and neurovascular diseases, as well as, to understand some comorbidities that affect disease evolution and outcome [1,2,3,4,5]. In this context, the lecture on Spinocerebellar Ataxias type 2 presented by Professor Luis Velazquez from the Cuban Academy of Sciences, showed how molecular processes underlying neuroinflammation can also affect genetic disorders influencing onset and disease progression [1,2,3,4,5].…”

“…In this context, the lecture on Spinocerebellar Ataxias type 2 presented by Professor Luis Velazquez from the Cuban Academy of Sciences, showed how molecular processes underlying neuroinflammation can also affect genetic disorders influencing onset and disease progression [1,2,3,4,5]. …”