Lancet neurology
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Dystonia and parkinsonism may present as part of the same genetic disorder. Identification of the genetic mutations that underlie these diseases may help to shed light on the aetiological processes involved. ⋯ We describe a mutation within the gene PRKRA that segregates with a novel, autosomal recessive, dystonia parkinsonism syndrome. These patients have progressive, generalised, early-onset dystonia with axial muscle involvement, oromandibular (sardonic smile), laryngeal dystonia and, in some cases, parkinsonian features, and do not respond to levodopa therapy.
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Genetic factors are now recognised to have an even more important role in epilepsies than previously appreciated. Rare mendelian forms of epilepsy are now well recognised, and there is evidence of complex inheritance due to multiple susceptibility genes in most idiopathic epilepsies. The complexities of epilepsy classification and the variety of clinical genetic methodologies (family aggregation, twin, and multiplex family studies) have led to an apparently confusing picture. ⋯ These challenges are even greater in complex epilepsies in which gene discovery is still in its infancy. In this Review, we synthesise clinical genetic data, discuss the strengths and weaknesses of different approaches, and integrate molecular findings about the epilepsies. This knowledge not only informs clinicians about the biology of the epilepsies but also has important consequences for clinical practice and genetic counselling.
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Epilepsy is a common neurological disorder that can be complicated by neurobehavioral comorbidities, which include cognitive impairment, psychiatric disorders, and social problems. Although such comorbidities are traditionally thought to arise predominantly from the effects of recurrent seizures, iatrogenic effects of medications, and adverse social reactions to epilepsy (eg, stigma), there is a growing body of evidence that other factors are involved. These influences include altered neurodevelopment of the brain, cognition, and behaviour; exacerbation of the comorbidities due to decades of medically intractable epilepsy; and possible acceleration of common age-associated changes, leading to uncertain and understudied outcome in old age. This Review summarises, from a lifespan perspective, the evidence for the neurodevelopmental origins of these comorbidities, how they develop over time, and their endpoints, with an emphasis on future clinical and research challenges.
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Review Guideline
Intense immunosuppression in patients with rapidly worsening multiple sclerosis: treatment guidelines for the clinician.
Several lines of evidence link immunosuppression to inflammation in patients with multiple sclerosis (MS) and provide a rationale for the increasing use of immunosuppressive drugs in the treatment of MS. Treatment-refractory, clinically active MS can quickly lead to devastating and irreversible neurological disability and treating these patients can be a formidable challenge to the clinician. ⋯ Natalizumab, a new addition to the armamentarium for treating MS, might also have a role in the treatment of this MS phenotype. This Review describes the use of intense immunosuppressant drugs and natalizumab in patients with rapidly worsening MS and provides clinicians with guidelines for the use of these drugs in this patient group.