210 Chapter 6 1 Primary chorea: 1.1 Huntington disease ■ The most common cause of chorea in adults. ■ A trinucleotide repeat disorder (CAG) of chromosome 4 that causes the production of an abnormal protein, called huntingtin. ■ There is an inverse correlation between repeat length and age of onset. 1.2 Other causes of hereditary chorea ■ Benign hereditary chorea ■ Neuroacanthocytosis 2 Secondary chorea: 2.1 Infections 2.1.1 Sydenham chorea ■ A common cause in childhood. ■ Neurological complication of group A streptococcal infection. ■ May occur as a part of manifestations of rheumatic fever. ■ Acute onset clinical syndrome that involves chorea, dysarthria, weakness, and behavior changes. ■ Self-limited illness with a good prognosis for recovery. 2.1.2 Other infectious causes ■ Bacterial and TB meningitis ■ Encephalitis ■ HIV infection 2.2 Drug-induced chorea ■ Drugs known to cause chorea include neuroleptics, dopamine agonists, levodopa, lithium, cocaine, and anticonvulsants. ■ Chorea does not always remit with the discontinuation of the offending drug. ■ Tardive dyskinesia is a term used when the chorea occurs after use of dopamine blocking agents for more than three months. 2.3 Post-cardiac surgery (in children) ■ Up to 10–18% of children with congenital heart disease, post-bypass ■ Typically resolves in weeks/months ■ Often associated with some cognitive disturbance 2.4 Immune-mediated chorea ■ 4% of patients with systemic lupus have chorea during exacerbation. ■ Associated with antiphospholipid syndrome. 2.5 Others ■ Structural lesions of the striatum have been reported to cause chorea. ■ Toxins, such as carbon monoxide ■ Multiple sclerosis ■ Anoxic encephalopathy ■ Chorea gravidarum ■ Birth control pills Movement Disorders 211 Inherited neurological disorders with prominent chorea 1 Huntington disease (HD) ◆ An autosomal dominant neurodegenerative disorder, caused by an expansion of an unstable trinucleotide repeat near the telomere of chromosome 4. ◆ Clinical features include involuntary movements of mainly chorea, psychiatric disturbances, and cognitive decline. 2 Benign hereditary chorea ◆ A distinct disease of early onset, nonprogressive uncomplicated chorea 3 Neuroacanthocytosis ◆ A rare multisystem degenerative disorder of unknown etiology that is featured clinically by the presence of deformed erythrocytes with spicules known as acanthocytes and abnormal involuntary movements. 4 Dentatorubralpallidoluysian atrophy (DRPLA) ◆ A trinucleotide repeat polyglutamine disorder with the gene defect localized to chromosome 12. It is inherited in an autosomal dominant fashion, and clinical features include chorea, myoclonus, ataxia, epilepsy, and cognitive decline. 5 Wilson disease ◆ A systemic disorder of copper metabolism that is transmitted as an autosomal recessive trait with an abnormal gene mapped to chromosome 13q. 6 Others: very rare disorders, for example; ◆ Paroxysmal choreoathetosis ◆ Familial chorea-ataxia-myoclonus syndrome ◆ Pantothenate kinase-associated neurodegeneration (PKAN or Hallervorden- Spatz syndrome) • Orofacial dyskinesias and choreiform movements can be prominent manifestations of inherited diseases of the central nervous system. • Chorea is characterized as primary, when idiopathic or genetic in origin, or secondary, when related to infectious, immunological, or other medical causes • Most of these diseases are very rare, with the exception of Huntington chorea. • Huntington disease is a choreic prototypic disorder and is probably the most common inherited movement disorder. 212 Chapter 6 Distinguishing features between Huntington disease and benign hereditary chorea Features Huntington disease (HD) Benign hereditary chorea (BHC) 1) Age of onset Approximately 40 years Early childhood 2) Genetics Unstable CAG repeats on chromosome 4 Mutation in TITF-1 gene on chromosome 14q 3) Natural history Relentlessly progressive with mean duration of 17 years Non-progressive with normal life expectancy 4) Motor impersistence Characteristically present None 5) Neuropsychiatric features Depression with tendency to suicide, agitation, aggression, global cognitive impairment None 6) Eye movement Fixational instability, slowing of saccades, increased saccadic latency Normal 7) MRI fi ndings Caudate atrophy, generalized cerebral atrophy Normal Drug-induced chorea Neuroleptic-induced chorea Levodopa-induced chorea in PD Age of onset Elderly > young Young > elderly Sex Female > male Female = male Prevalence 10% after treatment 50% after 3–5 years of treatment Characteristics Buccolinguomasticatory movements, asymmetric in the limbs Asymmetric, worse in the more severely Parkinsonian limbs Pathophysiology Unknown, possibly related to chemical denervation of striatal neurons Unknown, possibly related to denervation hypersensitivity of dopamine receptors Treatment Discontinuation of neuroleptics, reserpine, tetrabenazine Reduction of levodopa use, amantadine • Chorea may result from exposure to a variety of drugs. • Certain drugs seem to require pre-existing basal ganglia dysfunction to induce chorea, such as contraceptive pills, levodopa, and dopamine agonists. • Some other drugs, however, appear to be capable of inducing chorea to anyone exposed, for example, dopamine antagonists. • The most prevalent types of drug-induced chorea result from treatment of elderly patients with dopamine antagonists, or of PD patients with levodopa. Movement Disorders 213 Chorea in the elderly 1 Medication-induced ◆ Dopaminergics, e.g. in Parkinson disease patients on chronic levodopa treat- ment ◆ Antidopaminergics, most commonly neuroleptics (tardive syndromes) ◆ Amphetamines ◆ Anticonvulsants 2 Vascular ◆ Infarction of subthalamic nucleus may result in acute hemichorea or hemibal- lism. 3 Senile chorea ◆ Unclear identity. Some authorities do not believe that this condition exists. ◆ It is important to rule out late-onset HD and tardive syndrome. ◆ Buccolingual chorea may be seen in the edentulous elderly. 4 Metabolic derangements ◆ Hypo or hypernatremia ◆ Hypo or hyperglycemia ◆ Hyperthyroidism ◆ Hypo or hyperparathyroidism ◆ Polycythemia vera 5 Degenerative conditions ◆ Late-onset HD ◆ Dentatorubralpallidoluysian atrophy (DRPLA) 6 Others ◆ Lupus or antiphospholipid antibody syndromes ◆ Syphilis • Although Huntington disease (HD) usually begins in early to mid- adulthood, it may also begin in childhood (Westphal variant) or after age 50 (late-onset HD). • Late-onset HD accounts for approximately 25% of all HD cases, half of which do not present until after age 60. • Late-onset HD is a potential diagnostic pitfall. The family history may be unknown, hidden, or misleading. In addition, patients usually have a slower disabling course, more subtle chorea, predominant gait disorder, dysphagia, or dysarthria. • Most cases of chorea in the elderly are medication-induced or due to structural lesions, for example, in the subthalamic nucleus. 214 Chapter 6 Dystonia 1 Primary dystonia (not associated with any laboratory abnormalities) ◆ Most childhood-onset dystonia begins with a leg or arm, and then spreads to other limbs and trunk. It is due to mutations in a gene located on chromosome 9q34 and classifi ed as DYT1 or Oppenheim dystonia. ◆ Adult-onset primary dystonia usually starts in the neck, cranial muscles, or arm and progression is limited to adjacent muscles. Generalization and leg involvement are rare. 2 Secondary dystonia 2.1 Dystonia associated with environmental-exogenous factors (80% of secondary dystonia) 2.1.1 Tardive dystonia ■ The most common cause of secondary dystonia. ■ Usually secondary to dopamine receptor blockers. 2.1.2 Perinatal cerebral anoxia (15%) ■ Onset can be delayed for years. 2.1.3 Focal lesions ■ Hemidystonia can occur secondary to structural lesions (hem- orrhage, tumor, or infarction) in the basal ganglia, usually the putamen. 2.2 Inherited secondary dystonia ■ Dopa-responsive dystonia: DYT5, GTP cyclohydrolase 1 ■ Dystonia-myoclonus syndrome ■ Ataxia telangiectasia 2.3 Dystonia as a manifestation of neurodegenerative diseases (2–3% of sec- ondary causes) ■ Idiopathic Parkinson disease ■ Parkinson-plus syndrome ■ Spinocerebellar ataxias 1–8 ■ Huntington disease 2.4 Psychogenic dystonia (< 5%) • Dystonia is defi ned as a syndrome of sustained muscle contractions, frequently causing twisting, repetitive movements or abnormal postures. • Important features of dystonia include sustained contractions, consistent directional or patterned character (predictable), and exacerbation during voluntary movements. • A characteristic and unique feature of dystonia is the presence of sensory tricks (that is, tactile stimulus to a particular body part may alleviate the dystonia). • Dystonia can be classifi ed by age of onset, body region(s) affected, and etiology. Movement Disorders 215 Dopa-responsive dystonia (DRD) and important DDx Features DRD Childhood-onset ITD Childhood-onset PD Dystonic cerebral palsy Age at onset 0–12 years Less common, <6 years < 8 years Infancy Family history Often Maybe Often No Perinatal distress No No No Yes Initial signs or symptoms Arm/leg dystonia Foot dystonia, gait disorder Bradykinesia, rigidity, resting tremor Hypotonia Later signs or symptoms Axial dystonia rare, resting tremor late Axial dystonia and resting tremor rare Axial dystonia (65%) Focal or axial dystonia, choreoathetosis Diurnal worsening Prominent Sometimes No No Hyperrefl exia Common No No Yes, especially early Levodopa responsiveness Excellent at low doses Partial response Excellent at low to moderate doses No ITD – idiopathic torsion dystonia, PD – Parkinson disease. • Diagnostic errors as well as delayed diagnosis of DRD are frequent because knowledge of the disease is still limited, and also because there are many atypical presentations. • Common misdiagnoses include spastic paraparesis, paraplegia, or diplegia due to hyperrefl exia, extensor toes, and localization of disturbances in the lower limbs. • Absence of history of perinatal distress or MRI abnormalities, or the presence of mild dystonic rigid features, full term birth, and/or diurnal worsening should suggest DRD. Dystonic cerebral palsy should be diagnosed cautiously in these settings. • A dopa test is indicated even when the diagnosis of DRD is in the slightest doubt. 216 Chapter 6 Iatrogenic movement disorders Dopamine antagonist-induced movement disorders 1 Acute onset 1.1 Acute dystonic reaction ■ Usually evident soon after the initiation of neuroleptic therapy (90% within 5 days of therapy), ranging from brief jerks to prolonged muscle spasms involving the craniocervical region. ■ This reaction is often associated with psychiatric manifestations. ■ Laryngeal muscles can be involved, resulting in respiratory diffi culties. ■ Risk factors include young male (<30 years old), high neuroleptic dos- age, potency of the drug involved and familial predisposition. ■ Treatment includes parenteral administration of anticholinergics and antihistamines. 1.2 Acute akathisia ■ Very common, very early and dose-related side-effect of neuroleptics. ■ Usually self-limited upon discontinuation of neuroleptics. 2 Subacute onset 2.1 Parkinsonism 2.2 Neuroleptic-induced malignant syndrome ■ Characterized by fever (may be low-grade or high), muscle rigidity, move- ment disorders, autonomic instability, and mental status changes. ■ Usually occurs within the fi rst two weeks of initiating dopamine recep- tor antagonists. ■ Although rare (0.2%), it has rapid onset with severe medical complica- tions (50%) and a high mortality rate (20%). 3 Chronic onset 3.1 Tardive syndromes ■ Refers to persistent, sometimes irreversible, abnormal involuntary move- ments appearing over the course of prolonged neuroleptic treatment. • The administration of drugs having antagonistic effects on striatal dopamine receptors is frequently associated with the development of different types of movement disorders. • These disorders are most often seen in psychiatric patients undergoing neuroleptic treatment. • The clinical presentation and time of onset of movement disorders resulting from the use of offending drugs are quite variable. • Tardive syndromes often run a persistent fl uctuating course despite cessation of therapy. Symptoms can become permanent and irreversible. Movement Disorders 217 ■ Tardive syndromes can reproduce almost the entire spectrum of known abnormal involuntary movements of the hyperkinetic type: tardive stereotypy, tardive dystonia, tardive tourettism, tardive tremor, tardive myoclonus, tardive akathisia. ■ Buccolinguomasticatory syndrome is the most common form of tar- dive syndrome in clinical practice, especially in elderly subjects. Tardive dyskinesia: risk factors Common risk factors for developing tardive dyskinesia include: 1 Increasing age 2 Female sex 3 Neuroleptic dose 4 Cumulative duration of neuroleptic exposure 5 Presence of dementia Tardive syndromes: phenomenology • Tardive dyskinesia is an involuntary movement disorder that occurs with long-term neuroleptic use, usually after 1 year of treatment. • Patients may have buccolinguomasticatory movements and athetoid movements of the arms, legs, and trunk. • The main treatment is the withdrawal of the offending agent. The symptoms usually remit in 40% of patients after discontinuation. • Numerous medications have been used to treat this condition; reserpine is usually considered to be the most effective. Other agents include atypical antispychotics, clonazepam, valproate, baclofen, and diltiazem. • The American Psychiatric Association Task Force requires 3 months of exposure to a dopamine receptor blocking agent (DRBA) for diagnosis of tardive syndromes, although tardive syndromes can occur in individuals 60 years of age or older after only 1 month of exposure to a DRBA. • There are several phenomenologically distinct types of tardive syndromes that are historically referred to as tardive dyskinesia (TD). However, the term TD is used to refer to a specifi c subtype, characterized by oro-buccal-lingual dyskinesias. • Among all tardive syndromes, tardive dyskinesia (TD) is the most common form. • There are other types of tardive syndromes in addition to those described in the list below, including tardive myoclonus, tardive tremor, and tardive tourettism. It remains unclear if tardive Parkinsonism truly exists. 218 Chapter 6 1 Tardive dyskinesia (TD) 1.1 Defi nition: TD that presents with rapid, repetitive, stereotypic movements involving oral, buccal, and lingual areas 1.2 Epidemiology: most common of all tardive syndromes. Annual inci- dence: 5% in the young and 12% in the elderly. In general, 20% of patients on neuroleptics are affected by TD. 1.3 Differential: ■ Spontaneous buccal-lingual dyskinesia of the elderly ■ Edentulous dyskinesia ■ Hereditary choreas (e.g. HD) ■ SLE, vasculitides ■ Wilson disease 1.4 Treatment: mild TD – reducing the neuroleptic dose, switching to atypical agent, or discontinuing antipsychotic treatment. 2 Tardive dystonia 2.1 Defi nition: tardive syndrome that presents with co-contraction of agonist and antagonist muscles, resulting in twisting, abnormal posture and turn- ing. 2.2 Epidemiology: prevalence 2–20%, more common in younger men. DRBA exposure may be shorter for tardive dystonia, compared to TD. 2.3 Differential: ■ Idiopathic torsion dystonia ■ Meige syndrome ■ Oromandibular dystonia ■ Wilson disease 2.4 Treatment: same as TD. 3 Tardive akathisia 3.1 Defi nition: tardive syndrome that is characterized by a feeling of inner restlessness/jitteriness, often objectively manifest by semipurposeful movements. 3.2 Epidemiology: usually accompanied by other tardive syndromes. Exact incidence is unclear, between 20–40% of DRBA-treated patients with schizophrenia. Mean DRBA exposure of 4.5 years with mean age of onset of 58 years. 3.3 Differential: ■ Restless leg syndrome ■ Anxiety/hyperactivity disorder ■ Stereotypy ■ Drug-induced, e.g. levodopa, dopamine agonists 3.4 Treatment: same as TD. 4 Withdrawal emergent syndrome Movement Disorders 219 4.1 Defi nition: a benign tardive syndrome occurring mainly in children who were abruptly withdrawn from their chronic neuroleptic therapy. Move- ments are choreic, random, and involve mainly the limbs, trunk, and neck. 4.2 Treatment: the movements usually last for weeks, but DRBAs can be rein- stituted for immediate suppression or withdrawn gradually. Tardive syndromes: DDx The diagnosis of a tardive syndrome can be easy in most cases and should be based on a complete neuropsychiatric history and examination. However, the diagnosis can be challenging in older patients with a history of dementia. Conditions that may mimic tardive syndromes include: 1 Benign conditions in the elderly 1.1 Spontaneous buccal-lingual dyskinesias of the elderly 1.2 Edentulous dyskinesia 2 Hereditary choreas 2.1 Huntington disease (HD) ■ TD primarily involves the tongue, lips, and jaw causing twisting, protru- sion, lip smacking, and puckering. The stereotypic pattern is in contrast to the dyskinesias seen in HD, where movements are random and un- predictable. 2.2 Benign hereditary chorea 2.3 Wilson disease 3 Medical conditions 3.1 Hyperthyroidism 3.2 Systemic lupus erythematosus or other vasculitides 3.3 Polycythemia vera 3.4 Sydenham chorea 4 Non-DRBAs that can cause dyskinesias (exact mechanism unclear) ◆ Levodopa • Tardive syndromes are a group of disorders characterized by predominantly late-onset and sometimes persistent abnormal involuntary movements (or a sensation of restlessness) caused by exposure to a dopamine receptor blocking agent (DRBA) within 6 months of the onset of symptoms and persisting for at least 1 month after stopping the offending drug. • Common DRBAs include traditional neuroleptics, drugs for nausea (metoclopramide and prochlorperazine), and depression (amoxapine). • Age has been the most consistent risk factor for TD. Higher incidence and lower remission rates are noted in older patients, especially among women. • The only way to prevent these syndromes is to avoid the etiologic agents. [...]... infections Neurological manifestations of HIV Neurocysticercosis: active vs inactive presentations Prion disease Spirochete infections Viral encephalitis 243 243 2 45 247 248 249 249 250 Meningoencephalitis Bacterial meningitis pathogens by age and host Chronic meningitis Chronic meningitis: diagnostic tests Drug-induced meningitis Eosinophilic meningitis Recurrent meningitis 252 252 252 254 255 256 257 Brain... ceruloplasmin and copper levels Some differences between young-onset PD and older-onset PD are provided in the table below Features YOPD Older-onset (typical) PD Age of onset 21–39 years After 40 years Annual incidence 0. 15/ 100,000 1 .5/ 100,000 (60–64 years) Dystonia at onset 15 50 % Very rare Disease progression Slower Faster Dyskinesia 72% 28% Dose-related fluctuations 64% 28% Less common More common Motor... Parkinsonian signs and symptoms, earlier appearance of levodopa-induced dyskinesias and levodopa-dose-related motor fluctuations and frequent presence of dystonia as an early presenting sign The most important differential diagnosis in patients presenting with Parkinsonian signs before the age of 40 is Wilson disease The absence of Kayser-Fleischer rings or of a positive family history must not deter... inheritance with the gene mapped to chromosome 13 The basic defect is of P-type ATPase involved in the cellular transport of copper ◆ Neurological manifestations usually appear after the age of 10 with the dystonic form being the most common Others include pseudo-sclerotic form, rigid-akinetic form, and choreic form About one-third of patients present for fairly long periods with mental deterioration... include: Sleep-wake transition disorder NREM sleep parasomnias ■ ■ ■ ■ ■ ■ ■ ■ ■ ■ ■ ■ ■ ■ ■ Movement Disorders 237 REM sleep parasomnias Diffuse parasomnias 2.4 Nocturnal seizures, examples include Tonic seizure Benign rolandic seizure Autosomal dominant nocturnal frontal lobe seizure 2 .5 Drug-induced nocturnal dyskinesias Levodopa-induced myoclonus Tricyclic antidepressants Lithium 2.6 Others Sleep-related... or appear to be secondary to the muscle spasms and dystonic postures Neurological Differential Diagnosis: A Prioritized Approach Roongroj Bhidayasiri, Michael F Waters, Christopher C Giza, Copyright © 20 05 Roongroj Bhidayasiri, Michael F Waters and Christopher C Giza Chapter 7 Infectious, Inflammatory, and Demyelinating Disorders Neurological infectious disorders 240 Signs and syndromes Aseptic meningitis... tremor Action tremor that increases towards the end of goal-directed movement Suggests a clinical localization to the cerebellum or its outflow tracts 2.3 Kinetic tremor A tremor that occurs during any voluntary movements Kinetic tremor can occur in non-goal-directed and goal-directed movements Example includes dystonic tremor, essential tremor 2.4 Task-specific tremor ■ ■ ■ ■ ■ ■ 230 Chapter 6 Tremor which... the diagnosis of infantile botulism ◆ The treatment is largely supportive, particularly respiratory management, as respiratory arrest occurs in 30% of patients Antitoxin has been shown to accelerate recovery and reduce hospital stay if administered promptly 2 Food-borne (classic) botulism ◆ Food-borne botulism is different from infantile botulism in that a source of toxin is present, and more than 50 %... and dystonic posture of one foot 2 Conditions with a partial response to dopaminergic medications 2.1 Parkinson-plus syndromes Multisystem atrophy (MSA): 40% have a partial response to levodopa ■ ■ ■ ■ ■ ■ ■ Movement Disorders 231 Corticobasal ganglionic degeneration (CBGD), progressive supranuclear palsy (PSP): 10–20% with minimal response 2.2 Machado-Joseph disease or spinocerebellar ataxia type 3 (SCA3)... disorders Rapid-onset dystonia Parkinsonism X-linked dystonia Parkinsonism Hydrocephalic Parkinsonism ■ ■ ■ ■ ■ ■ Involuntary forceful eye closure • • Involuntary, inappropriate, forceful eye closure is termed blepharospasm The most common presentation is essential blepharospasm, which is a form of adult-onset focal dystonia It typically affects both eyes symmetrically and begins insidiously in the 5th to . usually begins in early to mid- adulthood, it may also begin in childhood (Westphal variant) or after age 50 (late-onset HD). • Late-onset HD accounts for approximately 25% of all HD cases, half. appearance of levodopa-induced dyskinesias and levodopa-dose-related motor fl uctuations and frequent presence of dystonia as an early presenting sign. • The most important differential diagnosis in. can occur in non-goal-directed and goal-directed movements. ■ Example includes dystonic tremor, essential tremor. 2.4 Task-specifi c tremor • A rhythmic oscillation of a body part produced by