Overview.
Huntington’s disease dementia was first reported by Huntington in 1872, hence the name. It is a monogenic autosomal dominant disease. It is a rare idiopathic neurodegenerative disease with a wide range of brain degeneration, especially the atrophy of the caudate nucleus. The main clinical manifestations are dementia and chorea-like movements.
The disease is rare. It is estimated to be 4/100,000 to 10/100,000 people. Young-onset patients generally have more severe symptoms, with myotonia predominating, middle-aged-onset patients have choreographic symptoms predominating, and those over 60 years of age have intentional tremor predominating. Juvenile-onset patients are rare.
Etiology
Advances in the molecular genetics of Huntington’s disease dementia are one of the striking achievements of molecular biology in neuroscience in recent years, and a milestone in the application of molecular biology to clinical medicine. Huntington’s disease dementia is a single gene autosomal dominant inheritance with complete epistasis.
The pathologic changes of the disease are symmetrical atrophy of the brain, with more pronounced atrophy of the frontal lobe and caudate nucleus. The ventricular system is markedly enlarged, and the caudate nucleus is severely atrophied, causing depressions in the curved protrusions on the surface of the lateral ventricles. Microscopic examination mostly showed extensive neuronal cell loss in the frontal cortex with neuroglial hyperplasia. The caudate nucleus, the nucleus pulposus, and the white matter also show nerve fiber loss.
In patients with Huntington’s disease dementia, GABA levels are reduced in the basal ganglia and substantia nigra, and there is also a significant reduction in glutamic acid decarboxylase (GAD), a GABA synthesizing enzyme, in the nucleus accumbens and pallidal nucleus; there is a reduction in striatal ChAT, and elevated striatal and substantia nigra levels of DA and NE. Striatal DA hyperactivity may be associated with involuntary movements, and increased DA in the midbrain limbic system may be associated with the psychiatric symptoms of Huntington’s disease dementia.
Symptoms
1. Neurological symptoms
Choreiform symptoms usually appear before intellectual disability. In the early stage, they often consist of irregular muscle twitching, including finger flexion and extension movements, head nodding, and facial muscle twitching with a strange appearance. It further develops into sudden, purposeless and strong involuntary choreographic movements of the face, neck, limbs and trunk. It is characterized by rapid, irregular, sudden and sometimes slow and rhythmic movements like those of tardive dyskinesia. Accompanied by dysarthria and gait changes, extrapyramidal symptoms can also be present, and patients often use random movements in the same direction to camouflage them. It is an extrapyramidal syndrome with reduced muscle tone and increased motor function. The increasing exacerbation of abnormal movements leads to pronounced torsion-like movements with ataxia. Intellectual disability is often exacerbated by the presence of chorea.
2. Mental symptoms
Mood disorders are prominent, especially depression. Emotional apathy, retardation, depression, often suicidal behavior or personality changes, bad temper, like to quarrel, inattention, and so on. Some patients may have paranoid schizophrenic-like clinical signs and schizophrenic-like symptoms, delusions of victimization, often with exaggerated and religious overtones and personality changes, such as irritability, impulsivity, rage, and behavioral idiosyncrasies. Huntington’s disease dementia is often characterized by depressive symptoms and marked suicidal tendencies.
Intellectual disability can sometimes be the first symptom. Early patients are quite prominent in distraction, and may show sluggishness, passivity, indifference, laziness, poor comprehension, decreased work efficiency or inability to perform their jobs. Later, dementia symptoms appear and develop slowly. Early life ability declines, some self-awareness, self-reported slow thinking, forgetfulness, memory impairment is lighter than AD, judgment is often impaired, orientation is relatively maintained. Speech difficulties, disuse, and loss of recognition are rare. Motor inability reticence and dystonia occur late and often progress slowly. Memory is less affected than other cognitive functions, and self-awareness is often intact. Patients are able to recognize changes in their intelligence for a period of time, complaining of slowness, forgetfulness, and confusion, and are considered to have “subcortical dementia”. In later stages, there may be marked motor disability mutism.
Tests
Psychological examination is an important method to diagnose the presence and severity of dementia. In recent years, China has introduced and revised a number of simple and rapid screening tools that are commonly used in the international community, with high diagnostic validity, sensitivity and specificity, which are briefly summarized as follows:
1. Simple Mental Status Examination (MMSE)
Developed by Folstein in 1975, the MMSE assesses scoring criteria such as “1” for a correct answer or operation, “5” for an error, “9” for a refusal to answer or “7” for an inability to answer. “7”. The total number of items of “1” (MMSE total score) was mainly counted, ranging from 0 to 300 international standard 24 points as the cut-off value, 18-24 as mild dementia, 16-17 as moderate dementia, and ≤15 as severe dementia. In China, it was found that the critical value was different depending on the level of education; 17 points for illiteracy, 20 points for elementary school (≤6 years of education), and 24 points for secondary school and above.
2. Hasegawa Dementia Scale (HDS)
Developed by Kazuo Hasegawa in 1974. There are 11 items, including orientation (2 items), memory (4 items), general knowledge (2 items), calculation (1 item), and remembering naming recall (2 items). The scale was positively scored out of 32.5 points. The original authors’ threshold values were set as follows: dementia ≤10.5 points, suspected dementia 10.5-21.5 points, borderline state 22.0-30.5 points, and normal ≥31.0 points, and normal values could also be divided according to the education level: illiterate ≤16 points, elementary school ＜20 points, and secondary school or above ＜24 points.
3. Ability to perform activities of daily living (ADL)
The ADL was developed by Lawton and Brody in 1969, and is mainly used to assess the subjects’ ability in daily life.ADL is divided into 14 items, and the scores are 4 levels: ① can do it completely by themselves; ② has some difficulties; ③ needs help; and ④ can’t do it at all.64 points is the full score, and the total score is ≤16 points is completely normal, and ＞16 points is with different degrees of functional decline. A single score of 1 is normal, 2 to 4 points of functional decline, there are 2 or more than 2 ≥ 3 or total score ≥ 22 for the critical value, suggesting significant functional decline. The total score of our routine is 18.5±5.5.
4. Other auxiliary examinations
Cranial CT and MRI can show caudate nucleus atrophy. Positron emission tomography (PET) scan shows obvious hypometabolism of the caudate nucleus.
Diagnosis
1. A clear genetic history or clear evidence of brain lesions.
2. Progressive dementia.
3. psychotic symptoms dominated by depression, apathy, euphoria, hallucinations and delusions.
4. Choreiform movements precede the onset of dementia.
Treatment
There are no drugs that can slow down the progression of the disease, mainly for symptomatic treatment. For the treatment of Huntington’s chorea, if the movement disorder itself is not serious, there is no need for drug treatment. Instead, dopamine depleting agents such as reserpine may be used if the movement is large enough to cause falls, but blood pressure and reserpine-induced depression should be monitored. When involuntary movements are aggravated by anxiety and stress, benzodiazepines can be used as anxiolytics, and DA agonists can be used to improve muscle strength if the patient has significant muscle strength. Haloperidol, trifluoperazine, fluphenazine, etc. are effective for chorea-like symptoms and psychosis-like symptoms, but note that the above drugs can cause depression or aggravate the original depressive symptoms.
Psychotic symptoms can be used on the extrapyramidal system side effects of antipsychotics less, the dose should be small, through the DA blocking effect on the control of chorea-like movements may be effective. For depression, new generation antidepressants such as paroxetine, sertraline, and fluoxetine are effective for both anxiety and depression, while the anticholinergic side effects of tricyclic antidepressants may exacerbate chorea. If delusional psychotic symptoms are present, antipsychotics may be used, but in small doses. Methotrexate and clozapine may be more appropriate due to mild extrapyramidal reactions.
In addition, in view of the psychiatric and somatic disturbances, it is important to counsel and explain to the patient and to care for him or her at later stages of development.
Prognosis.
The course of the disease is generally longer than that of other primary dementias, and it is slowly progressive, with survival of 13 to 16 years after onset of the disease, or up to several decades, and generally longer for those with a later age of onset of the disease. About half of the patients’ deaths are not related to the disease, and suicide accounts for a certain percentage of the patients’ deaths.
Prevention
The disease is a single gene autosomal dominant disorder. Patients and their families rarely know that their children are at risk for the same disease, so early genetic counseling services are important. Hereditary diseases are characterized by heredity and lifelong incurability, which not only bring misfortune to the family and cause lifelong pain to the patient, but also cause the disease to be passed on from generation to generation. In order to control and reduce the incidence of hereditary diseases, prevention must be the mainstay. Eugenic protection laws should be implemented, and births should be avoided in cases where there is a certain or high probability of congenital diseases occurring in the offspring.