nd CXCL10 in the serum of patients with acute SC (23), it can be concluded that Th 1 (cell- mediated) mechanisms may also be involved in the pathogen- esis of this disorder. A recent investigation confi rmed that cellular immune mechanisms might be relevant to the pathogene sis of SC because there is a monocyte dysfunction (24). Infections \227\206 AIDS related (toxoplasmosis, progressive multifocal leucoencephalopathy, HIV encephalitis) \227\206 Bacteria Diphtheria \200 Scarlet fever \200 Whooping cough \227\206 Encephalitis B19 parvovirus \200 Japanese encephalitis \200 Measles \200 Mumps \200 West Nile Ri ver encephalitis \200 Others \227\206 Parasites Neurocysticercosis \227\206 Protozoan \200 Malaria \200 Syphilis Endocrine-metabolic dysfunction \227\206 Adrenal insu \203 ciency \227\206 Hyper/hypocalcaemia \227\206 Hyper/hypoglyca emia \227\206 Hypomagnesaemia \227\206 Hypernatraemia \227\206 Liver failure Currently, the weight of evidence suggests that the patho- genesis of SC is related to circ ulating cross-reactive antibodies. Streptococcus-induced antibodies can be associated with a form of acute disseminated encephalomyelitis characterized by a high frequency of dystoni a and other movement disorders as well as basal ganglia lesions on neuroimaging (25). Antin eural and anti- nuclear antibodies have also been found in patients with Tourette \200\231s syndrome, but their relationship with prior streptococcus infection remains equivocal (26) . Vascular \227\206 Post-pump chorea (cardiac surgery) \227\206 Stroke \227\206 Subdural haematoma It remains unclear why up to 50% of patients with SC develop a persistent course of the ill ness. In this subset of individuals, the titres of antibasal ganglia antibodies are low. Ta king into account this fi nding as well as our observation that serum brain-derived neurotr ophic factor (BDNF) levels are high in this group of patients, it can be hypothesized that the acute immune process causes struc- tural brain lesions, resulting in permanent dysfunct ion of the basal ganglia (27). Miscellaneous \227\206 Anoxic encephalopathy \227\206 Cerebral palsy \227\206 Kernicterus \227\206 Mu ltiple sclerosis \227\206 Normal maturation (<12 months old) \227\206 Nutritional (e.g. B 12 de \201 ciency) \227\206 Posttraumatic (brain injury) CHAPTER 22 Non-Degenerative Choreas 233 Clinical features Th e usual age of onset of SC is 8 \200\2239 years, but there are reports of patients who developed chorea during the third decade of life. In most series, there is a female preponderance (28). Typically, patients develop this disease 4 \200\2238 weeks af t er an episode of group A beta-haemolytic streptococcal pharyngitis. It does not occur aft er streptococcal infection of the skin. Th e chorea spreads rapidly and becomes generalize d, but 20% of patients remain hemichoreic (28, 29). Patients display motor impersistence, p articularly noticeable during tongue protrusion and ocular fi xation. Th e muscle tone is u sually decreased; in severe and rare cases (8% of all patients seen at the Movement Disorde rs Clinic of the Federal University of Minas Gerais, Brazil), this is so pronounced that th e patient may become bedridden (chorea paralytica). results were generally replicated by a more recent study which found that patients with ARF without chorea had more obses- sions and compulsions than healthy controls (44). Th is stu dy also tackled the issue of hyperactivity and attention defi cit disorder in SC and found that 45% of 22 patients met criteria for this con- dition. Maia and colleagues (45) investi gated behavioral abnor- malities in 50 healthy subjects, 50 patients with rheumatic fever w ithout chorea, and 56 patients with SC (45). Th e authors found that obsessive \200\223comp ulsive behavior, obsessive \200\223compulsive dis- order, and attention defi cit and hypera ctivity disorder were more frequent in the SC group (19%, 23.2%, and 30.4%, respectively) t han in the healthy controls (11%, 4%, and 8%, respectively) and in the patients with ARF wi thout chorea (14%, 6%, and 8%, respectively). In this study, the authors demonstrated that obses- sive \200\223compulsive behavior displays little degree of interference in the perfo rmance of the activities of daily living. Another study compared the phenomenology of obses sions and compulsions of patients with SC with subjects diagnosed with tic disorders. Th e authors showed that the symptoms observed among the SC patients were diff erent from those reported by patients with tic dis- orders, but were similar to those previously noted among samples of pediatric patients with primary obsessive \200\223compulsive disor- der (46). A nother investigation comparing healthy controls with patients with rheumatic fever showed t hat obsessive \200\223compulsive behavior is more commonly seen in patients with SC with re la- tives who also have obsessions and compulsions (47). Th is study makes clear that there is interplay between genetic factors and environment in the development of behavioral prob lems in SC. We recently reported that SC may rarely induce psychosis or tri- chotillomania during the acute phase of the illness (48, 49). Patients oft en display other neurological and non-neurological symptoms and signs. Th ere are reports of common occurrence of tics in SC. However, it is virtually impossible to dist inguish simple tics from fragments of chorea. Even vocal tics, found in 70% or more of pati ents with SC in one study, are not a simple diagnosis in patients with hyperkinesias (30). In a cohort of 108 SC patients carefully followed up at our unit, we have identifi ed vocal izations in just 8% of subjects. We have avoided the term \200\230tic \200\231 because the re was no premonitory sign or complex sound and, conversely, the vocalizations were associa ted with severe cranial chorea. Taken together, these fi ndings suggest that the involuntar y sounds present in a few patients with SC result from choreic contractions of the upper re spiratory tract muscles rather than true tics (31, 32). Th ere is evidence that many patien ts with active chorea have hypometric saccades, and a few of them also show oculogyric cris is. Dysarthria is common and there is also impairment of verbal fl uency. In fact, a case \200\223control study of patients described a pattern of decreased verbal fl uency which re fl ected reduced phonetic, but not semantic, output (33). Th is result is consistent with d ysfunction of the dorsolateral prefron- tal \200\223basal ganglia circuit. In a recent stud y of adults with SC, we have extended this fi nding, showing that many functions that depen d on the prefrontal area are impaired in these patients. Th e conclusion of this study is t hat SC should be included among the causes of dysexecutive syndrome (34, 35). Prosody is al so aff ected in SC. One investigation of 20 patients with SC has shown decreased vocal tess itura and increased duration of the speech (36 \200\22338). Interestingly, these fi ndings are similar to those observed in PD (39). In a survey of 100 patients with rheu- matic feve r, half of whom had chorea, we found that migraine is more frequent in SC (21.8%) than in n ormal controls (8.1%, p = 0.02) (40). Th is is similar to what has been described in Touret te \200\231s syndrome (41). In the older literature, there are also references to papilloed ema, central retinal artery occlusion, and seizures in a few patients with SC. Th e peripheral nervous system is not targeted in SC (50). Finally, it must be kept in mind that SC is a major manifestation of rheu- matic fever. Between 60 and 80% of patients disp lay cardiac involve- ment, particularly mitral valve dysfunction, in SC, whereas the associ ation with arthritis is less common (seen in 30% of patients). However, in approximately 20 % of patients, chorea is the sole fi nd- ing (28, 51). A prospective follow-up of patients with SC with and without cardiac involvement in the fi rst episode of chorea suggests that the heart remains spared in those without lesion at the onset of rheumatic fever (52). Diagnosis Th e current diagnostic criteria for SC are a modifi cation of the Jones criteria : chorea with acute or subacute onset and lack of clin- ical and laboratory evidence of an alternative cause. Th e diagnosis is further supported by the presence of additional major or minor manifestations of rheumatic fever (33, 53, 54). Of note, according to the current criteria, the diagnosis of SC is still possible in the absence of any other feature of rheu matic fever. Th e UFMG Sydenham \200\231s Chorea Rating Scale (USCRS), the fi rst validated scale to rat e SC, provides a detailed quantitative descrip- tion of the performance of activities of da ily living, behavioral abnormalities, and motor function. It comprises 27 items; each is sc ored from 0 (no symptom or sign) to 4 (severe disability or fi nding) (55). Of note, the US CRS is not intended to be used as a diagnostic tool but rather to assess patients who alrea dy have an established diagnosis of SC. Attention has also been drawn to behavioral abnormalities. Swedo and colleagues (42) found obsessive \200\223compulsive behav- iour in fi ve of thirteen SC patients, three of whom me t the cri- teria for obsessive \200\223compulsive disorder, whereas no patient in the rheum atic fever group presented with obsessive \200\223compulsive behavior (42). In another stud y of 30 patients with SC, Asbahr and colleagues (43) demonstrated that 70% of subjects pres ented with obsessions and compulsions, whereas 16.7% met the crite- ria for obsessive \200 \223compulsive disorder. None of 20 patients with ARF without chorea had obsessions or comp ulsions (43). Th ese Several conditions may present with clinical manifestations similar to SC (1). Th e most im portant diff erential diagnosis is Oxford Textbook of Movement Disorders 234 abnormalities. Similarly, head MRI is oft en normal, although there are case reports of rev ersible hyperintensity in the basal ganglia area. In one study, Giedd and colleagues (56) s howed increased signal in just two of twenty-four patients, although morphometric technique s revealed mean values for the size of the striatum and pallidum that were larger than cont rols. Unfortunately, these fi nd- ings are of little help on an individual basis because th ere was an extensive overlap between controls and patients. PET and SPECT imaging may prove to be useful tools in the evaluation, revealing transient increases in striatal metabolism during the acute phase of the illness, a fi nding confi rmed by a recent study (57 \200 \22362). Th is contrasts with other choreic disorders (such as Huntington \200\231s dis- ea se) that are associated with hypometabolism. Of note, however, a recent investigation showe d hyperperfusion in two patients with SC whereas the remaining fi ve had hypometabolism (63 ). It is pos- sible that the inconsistencies in these studies refl ect heterogeneity of the population of patients. In our own unit, we have observed a correlation between hypermetab olism of the basal ganglia on SPECT during acute SC, whereas patients with persistent chore a oft en display hypometabolism in the basal ganglia. Increasing interest is now directed t o autoimmune markers which may even- tually be useful for diagnosis. However, the test of a ntineuronal antibodies is not commercially available, and is performed only for research pu rposes. Moreover, preliminary evidence suggests that these antibodies are not specifi c for SC. Similarly, the low sensitiv- ity and specifi city of the alloantigen D8/17 renders it unsuitable as a diagnostic test. systemic lupus erythematosus (SLE), which will be discussed later in this chapter. From a c linical point of view, a majority of sub- jects with SLE will have other non-neurological m anifestations such as arthritis, pericarditis, and other serosites as well as skin abnormal ities. Moreover, the neurological picture of SLE tends to be more complex and may include p sychosis, seizures, other movement disorders, and even mental status and consciousness leve l changes. Only in rare instances will chorea, with a tendency for spontaneous remissions a nd recurrences, be an isolated mani- festation of SLE. Th e diffi culty in distinguishing t hese two condi- tions is increased since at least 20% of patients with SC display recurrenc e of the movement disorder. Eventually, patients with SLE will develop other features, meet ing diagnostic criteria for this condition (1). Primary antiphospholipid antibody syndrome (PAPS) is diff erentiated from SC by the absence of other clinical and laboratory features of rheumatic fever as well as the usual association with repeated abortions, venous thrombo sis, and other vascular events, and the presence of typical laboratory abnormali- ties. Enc ephalitides, either as a result of direct viral invasion or by means of an immune-mediated post-infectious process, can cause chorea. However, this usually happens in younger childre n; the clinical picture is more diverse and includes seizures, pyrami- dal signs, and impai red psychomotor development. Th ere are also laboratory abnormalities suggestive of the und erlying condition. Drug-induced choreas are readily distinguished by a careful his- tory de monstrating a temporal relationship between onset of the movement disorder and exposure to the agent. Children and young adults with chorea should undergo complete neurological examination and diagnostic testing to determine the etiology of various causes of chorea. As there is no sp ecifi c bio- logical marker of SC, the aim of the diagnostic work-up in patients suspected to have rheumatic chorea is threefold: (1) to identify evidence of recent streptococcal inf ection or acute phase reac- tion, (2) to search for cardiac injury associated with RF, and (3) to rule out alternative causes. Tests of acute phase reactants such as erythrocyte sedi mentation rate, C-reactive protein, leucocytosis, other blood tests like rheumatoid factor, mucoproteins, protein electrophoresis, and supporting evidence of preceding streptococ- ca l infection (increased antistreptolysin-O, antiDNAse-B, or other antistreptococcal antibodi es; positive throat culture for group A streptococcus; recent scarlet fever) are much less helpful in diag- nosing SC than in other forms of rheumatic fever because of the usual long latency between the infection and onset of the move- ment disorder. Elevated antistreptoly sin-O titre may be found commonly in populations with a high prevalence of streptococ- cal infection. Furthermore, the antistreptolysin-O titre declines if the interval between infec tion and rheumatic fever is more than 2 months. However, anti-DNase-B titres may remain ele vated for up to a year aft er streptococcal pharyngitis. Heart evaluation (i.e. Doppler ech ocardiography) is mandatory because the associa- tion of SC with carditis is found in up to 80% of patients. Cardiac lesions are the main source of serious morbidity in SC. Serologic al studies for SLE and PAPS must be ordered to rule out these condi- tions. EEG has little importance in the evaluation of these patients, showing non-specifi c generalized slowing a cutely or aft er clinical recovery. Spinal fl uid analysis is usually normal, but it may sh ow a slightly increased lymphocyte count. In general, neuroimaging will help rule out vascu lar and other structural causes such as moyamoya disease. CT scan of the brain invariably f ails to display Management In the past, physicians emphasized the need for bed rest for the treatment of SC . Currently there is no place for this measure. Quarantine to prevent contamination of othe rs is usually unneces- sary because SC is an autoimmune condition, and does not result from direct bacterial attack against the central nervous system (CNS) (64). Th e fi rst aim of the treatment of SC is to provide control of cho- rea and behavioral pro blems oft en associated with this condition. Regardless of the choice of agent for symptoma tic control, the physician should attempt a gradual decrease of the dosage of the medicatio n (25% reduction every 2 weeks) aft er the patient has remained free from the symptoms for at least a month. Another important point is that in some patients the symptoms are so mild that they do not cause meaningful disability. In these cases, it is possible not to introd uce any pharmacological intervention, since spontaneous remission of SC is the rule (54, 65 ). Th e second aim is prophylaxis against new bouts of ARF. Although it remains unproven wh ether prophylaxis of streptococcal infection prevents recurrences of SC (66), clearly it de creases the development of new cardiac lesions which are the source of the most important d isabil- ity in rheumatic fever. Th ere are no controlled studies of symptomatic treatment of SC, and the reader must be awa re that all recommendations are off - label use of the cited drugs (64). Th e fi rst choice of the authors is valproic acid with an initial dosage of 250 mg/day that is increased dur ing a 2-week period to 250 mg three times a day. If the response is not satisfactory, dosag e can be increased gradually up to 1500 mg/day. As this drug has a rather slow onset of act ion, we usually wait for 2 weeks before concluding that the regimen is ineff ective. Th is is usually well tolerated, although some patients may develop CHAPTER 22 Non-Degenerative Choreas 235 dyspepsia and diarrhea initially. Chronic exposure may be associ- ated with action tremor o f the hands and, more rarely, liver tox- icity. An open-label study demonstrated that carba mazepine (15 mg/kg/day) is as eff ective as valproic acid (20 \200\22325 mg/kg/day) to indu ce remission of chorea (1, 67, 68). If the patient fails to respond to valproic acid or as fi rst-line treatment in patients who present with chorea paralytica, the next option is to prescribe neuroleptics. Risperidone, a relatively potent dopamine D2 receptor blocker, is usually eff ective. Th e usual initial regimen is 1 mg twice a day. If the chorea is still troublesome 2 weeks later, the dosage can be increased to 2 mg twice a day. Haloperidol and pimozide are also occasionally used in the management of chorea in SC. However, they are l ess well tolerated than risperidone. Dopamine D2 receptor blockers must be used with great caution in patients with SC. Aft er observation of the development of parkinsonism, dystoni a, or both in patients treated with neuroleptics, we performed a case \200\223control study comparing the response to these drugs in patients with SC and Tourette \200\231s syndrome. We demonstrated that 5% of 100 patients with chorea developed extrapyramidal complications , whereas these fi ndings were not seen among patients with tics matched for age and dosage of neuroleptics (67). Other potential side eff ects of these agents are sedation, depressi on, and tardive dyskinesia. additional studies to confi rm the safety and eff ectiveness of these treatments, their hig h cost, and the existence of alternative effi ca- cious therapeutic options, plasmapheresis and immunoglobulin are presently considered as investigational and do not have a place in routine medical practice. Other autoimmune choreas Other immunological causes of chorea are SLE, PAPS, vasculi- tis, and paraneoplastic syndromes. SLE and PAPS are classically described as the prototypes of a utoimmune choreas (72). However, several reports show that chorea is seen in no more than 1 \200\2232% of large series of patients with these conditions (73, 74). A PET study showed that there is hypometabolism of the basal ganglia in chorea associated with SLE (75). Rarel y, autoimmune chorea has been reported in the context of paraneoplastic syndromes associ- a ted with CV2/CRMP5 antibodies in patients with small cell lung carcinoma, malignant thymoma , and, less frequently, breast cancer (76 \200\22379). Chorea associated with SLE or PAPS h as been treated with immunosuppressive measures, especially intravenous methylpred- nisolon e following a dosage regimen as described for SC, as well as intravenous immunoglobulin (80 ). As it is accepted that neu- rological complications, including chorea, in PAPS are relat ed to ischaemic events, antiplatelet agents and even anticoagulants are oft en prescribed t o treat chorea in this condition (81). However, these recommendations are based on reports of open-label studies involving small numbers of patients as well as the clinical expe- rie nce of physicians (1). Th ere is a report of the association of generalized chorea with bil ateral basal ganglia lesions in Sj gren \200\231s syndrome (82). Th ere are no published guidelines concerning the discontinu- ation of antichoreic agents. Our policy is to attempt a gradual decrease of the dosage (25% reduction every 2 weeks) aft er the patient has been free from chorea for at least a month. Finally, the most important measure in the treatment of patients with SC is sec- ondary prophylaxis. Because of the presumably autoimmune origin of SC, there have been attempts to treat patien ts with rheumatic chorea with corti- costeroids. However, this is a controversial area. Des pite mention of eff ectiveness of prednisone in suppressing chorea, this drug is only used when there is associated severe carditis. We recently reported that methylprednisolone at a dose of 25 mg/kg/day in children and 1 g/day in adults for 5 days followed by 1 mg/kg/ day of prednisone is an eff ective and well-tolerated treatment for patients with SC refractor y to conventional treatment with anti- choreic drugs and penicillin (68). At least one othe r group has replicated our fi ndings of good response to steroids in selected patients with SC (69). In one of the few randomized controlled trials in SC, the authors compared oral p rednisone (2mg/kg/ day) with placebo in a double-blind fashion. Simultanous use of haloperi dol was allowed. Th ey concluded that steroids acceler- ate recovery but the rate of remiss ion and recurrence is similar in both groups (70). However, this study had some limitations . Haloperidol use was not controlled in the two groups, and it is uncertain whether the dev elopment of side eff ects such as weight gain and moon face in the steroid group could have potentially compromised the blinding of the study (this is of particular con- cern conside ring the high dosage of prednisone). In addition, the authors used a non-validated scale to rate the severity of chorea. Th e current recommendation is to reserve steroids for patien ts with persistent disabling chorea refractory to antichoreic agents or those who develop u nacceptable side eff ects with other agents. Finally, there is one open controlled study of a small number of patients which reports that plasma exchange or intravenous immunoglobuli n are as eff ective as oral prednisone in control- ling the severity of chorea in SC (71). Surprisingly, the authors report a lack of side eff ects in all groups. Because of the lack of Vascular choreas A study in a tertiary referral center showed that cerebrovascu- lar diseas e was the most common cause of non-genetic chorea, accounting for 21 out of 42 cases (5). C onversely, chorea is an unusual complication of acute vascular lesion, seen in less than 1% of patients with acute stroke. Etiology and pathogenesis Vascular hemichorea, or hemiballism, is usually related to ischae - mic or haemorrhagic lesion of the basal ganglia and adjacent white matter in the territor y of the middle or the posterior cerebral artery (83). In contrast with classical textbook descriptions of hemibal- lism, the majority of patients with vascular chorea have lesions o utside the subthalamus (84). An uncommon cause of chorea is moyamoya disease, an intracrani al vasculopathy which presents with ischaemic lesion or, less commonly, haemorrhagic stroke of the basal ganglia (85). Another rare form of vascular chorea is \200\230post-pump chor ea \200\231, a complication of extracorporeal circulation. Th e pathogenesis of this moveme nt disorder is believed to be related to vascular insult of the basal ganglia during the su rgical procedure. Finally, it is possible that polycythaemia vera, a rare cause of chorea, induces hyperkinesia via a vascular mechanism (86). Clinical features and diagnosis Vascular chorea usually has an abrupt onset with the majori ty of patients displaying severe choreic movements, which are labeled ballism, on one hemib ody. Careful examination oft en reveals that patients have an underlying mild hemiparesis. Typically, Oxford Textbook of Movement Disorders 236 hemiballism hemichorea aff ects elderly diabetic patients. Despite the dramatic onset, spon taneous remission is the rule. In contrast, post-pump chorea is almost exclusively a compli cation of cardiac surgery in infants who commonly develop cognitive defi cits. Th e long-te rm prognosis of post-pump chorea is rather poor. For exam- ple, in one series of eight pati ents, fi ve subjects had persistent chorea and one of them died. In another study there was a clear distinction between those eight patients with onset at earlier age (median, 4.3 mo nths), all of whom recovered fully, and eleven others with older onset (median, 16.8 months ). Four of the latter died and only one of the survivors made a complete neurological recov ery (87). Rarely, paroxysmal chorea triggered by emotional stress and hyperventila- tion ma y also be caused by moyamoya syndrome, a condition of unknown cause characterized by vascul ar malformation in the base of the brain (88, 89). other antiepileptic drugs are administered (100). Th ere are occa- sional reports of chorei c dyskinesias induced by other antiepileptic drugs, such as carbamazepine (101) and lamotri gine (102). Th ere is a recent report relating valproate use to the onset of chorea which i s surprising, considering the established antichoreic action of this agent in SC (103). Chr onic exposure to amphetamines and other stimulants may induce orofacial dyskinesias and cho reic move- ments of the trunk and extremities (105). Th ere is also a report of the onset o f chorea in association with intrathecal infusion of methotrexate (106). Clinical features and diagnosis Chorea induced by drugs does not usually have distinctive f eatures. Th e exception to this statement is chorea in tardive dyskinesia, where the majori ty of patients have a combination of chorea and other phenomena, particularly stereotypies and dystonia. Another exception is levodopa-induced dyskinesia because patients also dis- p lay parkinsonian features as well as other hyperkinesias, mainly dystonia. Obviously, the d iagnosis depends on the history of onset of the movement disorder aft er exposure to the of f ending agent. Improvement or remission with withdrawal of the drug further supports the d iagnosis. However, one should be aware that in tar- dive dyskinesia there may be initial wo rsening of the movement disorder aft er the discontinuation of the antidopaminergic agent. Th e diagnosis of vascular chorea relies on the clinical features and typical imaging fi nd ings, i.e. ischaemic or haemorrhagic lesions of the basal ganglia, particularly the subthal amic area. Of note, par- ticularly among patients of Asian background with diabetes, MRI sc ans show a bilateral hypersignal in the lentiform nucleus, pre- sumed to represent microhae morrhage. Management Despite the usual favorable long-term prognosis of vascular chorea, treatment wi th antichoreic drugs such as neuroleptics or dopamine depletors may be necessary in the acu te phase. Persistent movement disorder may remain in a few patients with vascular chorea. I n this circumstance, they can be eff ectively treated with stereotactic surgery such as tha lamotomy or posteroventral palli- dotomy (90, 91). Management Th e mainstay of the treatment of drug-induced choreas is the withdrawal of the off ending agent. Chorea in the context of tar- dive dyskinesia is usually responsive to tr eatment with tetrabena- zine, a presynaptic dopamine depletor. Th e management of levodopa- related chorea and other movement disorders is beyond the scope of the chapter. Drug-induced choreas Chorea can result from exposure to a variety of drugs, and drug-induce d chorea is probably the most commonly encountered type of chorea in neurological practice and in the community (92). Infectious choreas SC could be considered a form of infectious chorea as it is induced by g roup A beta-haemolytic streptococcus. However, in a strict sense the term is limited to ins tances where chorea results from injury to the brain directly produced by a micro-organism. Human immunodefi ciency virus (HIV) and its complications is the most frequently reported infectious cause of chorea. For example, in one series of 42 consecutive patients with non- genetic chorea, AIDS was found to be the cause in 12% of the subjects (5). In HIV-positive patients, chorea is the result of either the direct action of the virus or other mechanisms such as opportunistic infections (toxoplasmo- sis, syphilis, etc.) or drugs (107). However , with the advent of highly active antiretroviral therapy, there has been a decline in HIV- related neurological complications, including movement disorders. Other infections related to chorea are new variant Creutzfeldt \200\223Jakob disease, tuberculosis, syphilis, and he rpes simplex encephalitis (108 \200\223111). Etiology and pathogenesis A list of drugs which may cause chorea is included in Table 22.1 (1, 92). Certain drugs seem to require pre-existing basal ganglia dysfunction to induce cho rea, whereas others appear to be more universally choreogenic. Examples of the former are o ral contra- ceptives, which are particularly likely to induce chorea in patients with previ ous choreic episodes such as SC, chorea with SLE, or cho- rea gravidarum (93, 94), and levo dopa, which only induces cho- rea in patients with idiopathic PD or other parkinsonian diso rders (95). Dopamine antagonists (DA), on the other hand, are capable of inducing dyskinesi as without pre-existing basal ganglia abnormal- ity. In one study of 100 consecutive patien ts with tardive dyskinesia, we demonstrated that, in contrast with the traditional assumpti on, chorea is rarely seen in association with use of DA antagonists (96). Th e most prevale nt types of drug-induced chorea result from treatment of PD patients with levodopa. Levodop a-induced chorea develops in more than 40% of PD patients, depending on age and duration an d dose of levodopa treatment. Furthermore, a variety of other agents has been associated wi th chorea in retrospective studies or anecdotal case reports. Th ese include tricyclic anti de- pressants and the SSRIs (97 \200\22399). Phenytoin may also induce invol- untary moveme nts, including orofacial chorea, particularly when Chorea in metabolic and toxic encephalopathy Chronic acquired hepatolenticular degeneration was the fi rst well-characterized metabolic cause of chorea. Originally described in the c ontext of alcoholic encephalopathy, it can occur in any form of acquired liver disease. Th e clinical picture is heterogeneous,