Huntington's Disease: Pathogenesis and Neuroimaging
One of the severe diseases accompanied by involuntary movements is Huntington's disease. The diagnosis must be confirmed by molecular genetic testing.
The pathogenesis is based on the expansion of trinucleotide CAG repeats in one of the alleles of the gene encoding the huntingtin protein. In a healthy individual, the number of such repeats does not exceed 38, whereas in patients with a full-blown clinical presentation, their number is significantly increased (e.g., up to 51 repeats).
Instrumental Diagnostics (Brain MRI) reveals characteristic changes:
- Specific signs: bilateral reduction in the size of the heads of the caudate nuclei, which directly indicates neuronal atrophy in this zone. On coronal T2-weighted MRI slices, the ventricles acquire a typical "box-like" shape — a pathognomonic symptom of the disease.
- Nonspecific signs: pronounced diffuse atrophy of the brain parenchyma that does not correspond to the patient's age (enlargement of the external and internal CSF spaces).
- Changes in the basal ganglia: a decrease in the volume of the caudate nucleus, globus pallidus, and putamen is recorded.
An important differential diagnostic criterion on MRI: despite pronounced atrophy, the intensity of the MR signal from the basal ganglia remains normal. This distinguishes Huntington's disease from Wilson's disease, in which signal intensity is always altered.
Therapy and Prognosis in Huntington's Disease
The disease has an unfavorable prognosis. It is characterized by relentless progression, ultimately leading to the complete loss of the patient's self-care skills and ability to work.
Antipsychotics (neuroleptics) are used as symptomatic therapy. Their mechanism of action is based on inhibiting dopaminergic neurotransmission. This achieves only a temporary reduction in the severity of motor disorders.
Ballism
Ballism is a rare movement disorder (hyperkinesia) resulting from a lesion of the subthalamic nucleus.
Clinically, ballism manifests as wide-amplitude, large-scale, and abrupt "flinging" movements in the limbs. The pathological process predominantly involves the proximal joints.
In the vast majority of cases, hyperkinesia is unilateral — a condition referred to as hemiballism. Notably, involuntary movements occur contralaterally, i.e., on the side opposite to the brain lesion.
Dystonia: Clinical Presentation and Classification
Dystonia is a movement disorder characterized by involuntary, sustained muscle contractions. These contractions result in bizarre "twisting" movements and abnormal postures. The lesion is localized in the basal ganglia, although the precise etiologic causes of these functional disorders remain poorly understood.
Features of the course of dystonia:
- The severity of hyperkinesia increases with mental activity and emotional stress.
- Symptoms decrease or disappear completely during sleep.
- During brief periods of absent dystonia, muscle tone in the affected limbs during passive movements is markedly reduced.
Classification based on distribution:
- Focal dystonia — strictly limited to a single muscle group.
- Blepharospasm: forced involuntary eye closure due to contraction of the orbicularis oculi muscle.
- Spasmodic torticollis: dystonic cervical dystonia.
- Generalized dystonia — involves all muscle groups to varying degrees. Frequently accompanied by associated disorders: dysarthria (speech becomes slurred and slow) and dysphagia.
Briefly: answers to topical questions
What hyperkinesias must be differentiated from tics?
Differential diagnosis of tics must be carried out with chorea, generalized tics, and epileptic seizures.
- Chorea — characterized by smooth hyperkinesias, whereas tics are abrupt in nature.
- Generalized tics (Gilles de la Tourette syndrome) — require differentiation from isolated childhood tics.
- Epilepsy — minor and myoclonic seizures are often mistakenly regarded by others as tics or mischievous behavior.
What are the clinical forms of focal dystonia?
Clinical forms of focal dystonia include:
- Blepharospasm — involuntary forced eye closure due to contraction of the orbicularis oculi muscle.
- Spasmodic torticollis — dystonic torticollis; torticollis, retrocollic, laterocollis, and anterocollis are possible.
- Oromandibular dystonia — involvement of the muscles of the mouth, lower jaw, and tongue.
- Writer's cramp — hand muscle tension occurring exclusively during writing and impairing writing ability.
Class and exam questions
Where is the lesion located in hemiballism, and on which side do symptoms occur?
The lesion is localized in the subthalamic nucleus. Symptoms (flinging movements) occur contralaterally — on the side opposite to the lesion.
How do emotional state and sleep affect the severity of dystonia?
During emotional stress and mental work, dystonia worsens, whereas during sleep, involuntary muscle contractions decrease or disappear completely.
What is the mechanism of action of antipsychotics in treating hyperkinesias?
Antipsychotics provide temporary alleviation of motor disorders by inhibiting dopaminergic neurotransmission.
What else to study on this topic
- MRI Findings and Signal Alterations in Wilson's Disease
- Metabolic and Systemic Causes of Involuntary Movements
- Pathogenesis of Dysphagia and Dysarthria in Generalized Dystonia
- Mechanisms of Dopaminergic Transmission in the Basal Ganglia
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