Huntington Chorea (HC)

Genetically transmitted progressive neurologic disease characterized by involuntary (choreiform) movements and slowly progressive dementia, leading to death 15 to 20 years after the first clinical symptoms.

Chorea Chronica Progressiva; Chorea Chronica Progressiva Hereditaria; Chorea Hereditaria Chronica; Chorea Progressiva Hereditaria; Chronic Degenerative Chorea; Chorea Major; Erb Vitus Dance; Hereditary Chorea; Huntington Disease (HD); Lund-Huntington Chorea (or Syndrome); Microcellular Striatal Syndrome.

Neurodegenerative disorder first described in 1872 by George Huntington of Ohio, U.S. as a progressive degenerative disorder of the central nervous system (CNS) of unknown etiology with involuntary movements and dementia.

Prevalence in the general population is estimated at 4-7:100,000. No sex or racial predilection. However, localized geographic clusters of disease exist (lowest frequencies have been found in South African blacks, individuals in Japan, and North American blacks).

Autosomal dominant with complete penetrance. New mutations are rare. The HC gene is located on the tip of the long arm of chromosome 4 (locus 4p16.3) and leads to increased length of a CAG triplet repeat at the end of the mRNA. This longer repeat [46 (range 37-86) in Huntington disease v 18 (range 9-37) in normals] leads to unstable gene and gene products. Fully autosomal dominant and homozygotes are no more severely affected than heterozygotes. Juvenile rigid early-onset form is usually paternally inherited.

The disease is characterized by premature degeneration of nerve cells. The abnormal protein product (huntingtin) of the HC gene accumulates in selective brain cells in the basal ganglia, particularly the caudate nucleus and putamen, which are severely damaged. The mutant huntingtin protein causes neurodegeneration by a direct effect on mitochondria (decrease in mitochondrial membrane potential and depolarization at lower calcium loads). There is a general reduction in the neuronal population in the cerebral cortex. Neurochemical analysis reveals a decreased gamma-aminobutyric acid and acetylcholine neuronal content. Neuropathologic changes in juvenile forms are similar to the adult-onset forms. Marked deficiency of the mitochondrial respiratory chain in the caudate nucleus of patients with HC, but not in the platelets, has been found.

Usually not made until the choreic movements are recognized. Although nondiagnostic, in the late stages of the disease, CT scanning of the CNS demonstrates loss of the bulge in the wall of the lateral ventricles, which is normally caused by the head of the caudate nucleus. Mean bifrontal-to-bicaudate ratio is decreased, indicating atrophy of the caudate nucleus and putamen. An electroencephalogram (EEG) is not diagnostic. A positron-emission tomography (PET) scan shows reduced glucose uptake in the caudate nucleus preceding tissue loss and may be a valuable indication of affection in the presumed presymptomatic period. Genetic counseling is necessary.

Average age of onset is 35 to 55 years, but in 1% of cases the disease manifests during the first decade of life. Affected children develop normally until 4 to 9 years of age. Early signs include changes in behavior and personality, diminished facial expression, and slurred speech. Later presentations are progressive involuntary movements of the face, tongue, and limbs, and abnormal eye movement. Clinically, there are stiff limbs, dystonia, rigidity (more common with early onset juvenile disease), and propulsive gait with involvement of proximal muscles (patients may be mistaken for being drunk). Behavioral problems may be the first noticeable issues, with patients being argumentative, impulsive, or erratic. Later, tremor and generalized tonic-clonic seizures typically resistant to anticonvulsants may occur. Ataxia and other cerebellar signs are present in 50% of cases and oculomotor apraxia in approximately 20%. Intellectual changes range from moderate intellectual impairment to progressive dementia, and mental depression with suicidal attempts is frequent. The course of disease is more rapid in children (average of 8 years) than in adults (14-17 years). Death usually occurs from aspiration pneumonia. There is no specific treatment for Huntington disease, but drugs that relieve movement disorder are helpful. Butyrophenone and phenothiazines provide the best results in movement disorder control.

With disease progression, pharyngeal muscles are involved by the disease. Check airway patency and tonus. Rule out aspiration pneumonia before induction of major surgical procedure. Check preoperative pulse rate and earlier occurrences of bradycardia. Patients affected are susceptible to body temperature changes.

Anesthetic experience consists of small series and case reports. No specific anesthetic regimen required, usually performed under general anesthesia. However, the safe use of locoregional anesthesia has been reported. Bradycardia following small doses of opiates respond to atropine at normal doses. There is a case report of delayed awakening with thiopental and good recovery with propofol. There is also a case report of exaggerated response to scoline and the report of an increased incidence of decreased pseudocholinesterase activity. Huntington patients may be sensitive to nondepolarizing neuromuscular blockers for an unexplained reason. Therefore, monitoring of the level of neuromuscular blockade is helpful. Proper measures to prevent hypothermia must be undertaken. Intravenous fluids must be warmed to prevent shivering postoperatively. If preoperative or postoperative sedation is needed, drugs that improve movement disorders are useful (butyrophenones, phenothiazines).

No specific drug is either required or is to be avoided. Decrease doses of pentothal, benzodiazepines, and nondepolarizing neuromuscular blockers. Succinylcholine effect is prolonged.

Sydenham Chorea: Major manifestation of acute rheumatic fever; occurs most commonly between the ages of 7 and 14 years, with peak incidence at 8 years of age. Characterized by rapid, irregular, aimless, involuntary movements of the muscles of the limbs, face, and trunk. More frequent in girls than boys. Patients can be affected by severe endocarditis. The diagnosis is based on evidence of streptococcal infection leading to neuroimmune disorder.

Mount Reback Syndrome: Transmitted as an autosomal dominant trait. Characterized by repeat acute episodes of choreotathetosis and torsion without loss of consciousness. The attacks never occur during sleep, and at their height are similar to Huntington chorea. Alcoholic beverages, coffee, hunger, fatigue, tobacco, and emotional stress are precipitating factors. The presence of a Kayser-Fleischer ring (copper ocular deposition) is the principal feature.

Wilson Disease: Autosomal recessive inborn error of copper metabolism in which copper initially accumulates in the liver, then in other organs of the body (brain, eyes, and kidneys). Caused by a mutation in the ATP7B gene located at 13q14.3. Characterized by cirrhosis, central nervous finding, and the presence of a Kayser-Fleischer ring in the eyes.

Dentatorubropallidoluysian Atrophy (DRPLA): Autosomal dominant neurodegenerative disorder characterized by myoclonus, epilepsy, cerebellar ataxia, choreoathetosis, and dementia. Particularly prevalent in Japan. The age of onset varies from younger than 10 years to the seventh decade. Individuals with juvenile onset usually show rapid progression compared to late-onset cases.

Haw River Syndrome (HRS, Ataxia Chorea Seizures and Dementia): Autosomal dominant neurodegenerative disease encountered in five generations of the African American population in rural North Carolina, U.S. Resembles Huntington disease, spinocerebellar atrophy, and dentatorubropallidoluysian atrophy (DRPLA). Caused by the same expanded CTG-B37 repeat observed in the DRPLA. In comparison to DRPLA, HRS is characterized by the absence of myoclonic seizures; however, patients present with ataxia, chorea, and dementia.