Snapshot A 20-year-old man presents with a two-year history of motor restlessness that has progressed to uncontrollable choreiform movements. He has moderate dementia with a severe gait disturbance as well as agitation and problems with his mood. MRI scan of the brain shows atrophy of the cerebral cortex and caudate nucleus. Introduction An autosomal dominant disorder characterized by choreiform movements progressive intellectual deterioration exhibits genetic anticipation Epidemiology demographics symptoms usually begin to appear in the 3rd-5th decade of life both sexes are affected equally incidence 0.38 cases per 100,000 per year Genetic inheritance autosomal dominant mutation CAG triplet repeat expansion in huntingtin gene (chromosome 4) HUNT 4 an animal, put it in a CAGe demonstrates anticipation mutation leads to atrophy of striatum (especially caudate nucleus) with neuronal loss and gliosis decrease in the levels of GABA and ACh Pathophysiology changes in neurotransmitters with Huntington's disease ↑ dopamine (in ventral tegmentum and substantia nigra) and ↓ GABA (in nucleus accumbens) and ACh (in basal nucleus of Meynert) high dopamine can act on the nigro-striatal pathway to result in hyperkinesis high dopamine can act on the meso-limbic pathway to result in psychotic symptoms Presentation Symptoms progressive choreiform movements of all limbs ataxic gait dementia depression grimacing Evaluation MRI shows atrophy of caudate Treatment Pharmacologic no known cure medications used to treat Huntington's disease include amine-depleting agents (inhibit VMAT, involved in monoamine transport) reserpine ↓ release of amines (dopamine) tetrabenazine ↑ degradation of amines (dopamine) antipsychotics haloperidol dopamine receptor antagonist ↓ effect of excess dopamine resulting in psychotic symptoms antipsychotics muscle relaxants benzodiazepines Prognosis, Prevention, and Complications Death inevitable Suicide common cause of death
QUESTIONS 1 of 5 1 2 3 4 5 Previous Next Sorry, this question is for PEAK Premium Subscribers only Upgrade to PEAK Sorry, this question is for PEAK Premium Subscribers only Upgrade to PEAK (M1.NE.15.4671) A 32-year-old woman is brought to your office by her husband. The husband says that she had been acting strange lately. She has been forgetful, and she sometimes becomes angered for no reason, which is highly unusual for her. She has also been having random, uncontrollable movements, which are also new. On examination, she appears withdrawn and flat. On further questioning, she reveals that her father died at age 45 from a movement disorder. Which of the following is the pathological hallmark of the patient's condition? QID: 107128 FIGURES: A Type & Select Correct Answer 1 Substantia nigra pars compacta 7% (15/219) 2 Alpha-synuclein intracellular inclusions 8% (17/219) 3 Loss of neurons in the caudate nucleus and putamen 66% (144/219) 4 Lipohyalinosis 1% (2/219) 5 Beta-amyloid plaques 14% (31/219) M 2 Question Complexity E Question Importance Select Answer to see Preferred Response SUBMIT RESPONSE 3 Review Tested Concept Review Full Topic Sorry, this question is for PEAK Premium Subscribers only Upgrade to PEAK Sorry, this question is for PEAK Premium Subscribers only Upgrade to PEAK