Huntington’s disease has the three main characteristics of the subcortical dementia syndrome, together with the classic choreoathetoid movement disorder and a positive family history. Huntington’s disease usually has its onset in the third or fourth decade, although juvenile forms occasionally occur. The psychopathology, both cognitive and noncognitive, may appear before the movement abnormalities. Both cognitive difficulties and mental apathy may be subtle initially. Once they appear, they tend to steadily progress to the point of very severe cognitive loss and profound self-neglect, resembling an akinetic mute state. Several authors also have reported prominent symptoms that may be difficult to differentiate from primary affective disorder, particularly depression. However, demoralization and depressive reactions are also frequent, and the risk of suicide is increased. Suspiciousness and misinterpretations are quite common, but delusions and hallucinations with paranoid and catatonic features also have been described. Huntington’s disease also may include Schneiderian first-rank symptoms, making it difficult to differentiate from schizophrenia.
The neuropathology in Huntington’s disease includes atrophy of the caudate nucleus and loss of gamma-aminobutyric acid (GABA) interneurons. The clinical findings are considered to be caused by imbalance of subcortical cholinergic and dopaminergic systems.
A subcortical, progressive dementia syndrome may occur in approximately one-third of patients with Parkinson’s disease, but contrary to Hunting-ton’s disease, it tends to occur late in the course of the illness, after the motor symptoms have advanced significantly. The classic Parkinson’s disease neurological signs in a patient with dementia point to the diagnosis. Apathy is particularly prominent and may advance to an akinetic mute state. Individual parkinsonian patients endure a wide variety of psychopathological symptoms, including frequent emotional reactions to the disease, but a depressive disorder identical to that seen in affective illness and responsive to the usual treatments is found in approximately one-third of patients.
Nigral pathology alone is probably not sufficient for the development of dementia in Parkinson’s disease and requires the spread of pathology to other subcortical nuclei, the limbic system, and the cerebral cortex. The main degenerative pathology seems to be Lewy body type, principally made of alpha-synuclein, and some controversy exists with regard to the frequency and implications of DAT-type pathology found in cases of dementia in Parkinson’s disease. Losses of cholinergic, dopaminergic, and noradrenergic innervation have been suggested to be the underlying neurochemical deficits.
Subcortical dementia with characteristic extrapyramidal signs also may be seen in Wilson’s disease. This combination of symptoms, together with onset during adolescence or early adulthood, should suggest the diagnosis. Cognitive deficits are usually mild, and psychosis is infrequent. However, depressive syndromes, irritability, disinhibition, personality changes, and poor impulse control are common, with the severity paralleling the severity of the neurological signs. The psychopathological features result from destructive deposition of copper in the basal nuclei due to an inherited defect in the copper-carrying serum protein ceruloplasmin.
NPH can present as a very characteristic neuropsychiatric syndrome, a triad of clinical symptoms combining motoric and psychopathological features: 1) an early gait disturbance, resembling the stiff steps of spastic paraparesis; 2) subcortical dementia with particularly severe apathetic features; and 3) urinary incontinence that may not appear until late in the course. An insidious onset with cognitive difficulties is common. Outbursts of hostile behavior occur sometimes, and eventually the illness may progress to a state resembling akinetic mutism if untreated. The neuropsychiatric deficits are considered to be the result of tissue destruction by stretching as a result of the chronic hydrocephalus.
Selections from the book: “Textbook of Psychosomatic Medicine”, 2005.