Huntington disease is a progressive degenerative disease that results from an autosomal dominant mutation that typically becomes apparent in the fourth to sixth decade of life. Huntington is a triplet repeat disease in the Huntington gene, with CAG repeat expansion on the short arm of chromosome 4p16.3. Patients with Huntington disease exhibit involuntary movements. Symptoms start with chorea-like involuntary movements and ­progress to psychiatric symptoms, character change, and eventually dementia. The ­characteristic ­pathological change of Huntington disease is neuronal loss and gliosis in the striatum, especially in the caudate nucleus. The cerebral cortex also shows neuronal loss in the pyramidal cell layers.

Images from patients with Huntington disease show dilation of the anterior horns of the lateral ventricles due to volume loss in the caudate nucleus (Fig. 25.5). The putamen also shows atrophic changes. Significant striatal atrophy can be seen many years prior to the clinical onset of the disease (Aylward et al. 2004). Occasionally, hyperintensity is visible in the striatum on T2-weighted images. The hyperintensity is detectable because of gliosis. Low signal can also occur in the striatum due to iron deposition.

Chorea acanthocytosis is one type of neuroacanthocytosis that shows both abnormal red blood cells called acanthocytes and neuronal symptoms such as seizures and movement dysfunction. A mutation in the VPS13A gene on chromosome 9q21 is known to cause this disorder. This group of diseases consists of chorea acanthocytosis as well as McLeod syndrome and PKAN (pantothenate kinase-associated neurodegeneration). Chorea acanthocytosis is an autosomal recessive disorder, and onset is generally in the second to sixth decade of life. The clinical symptoms include chorea, behavioral changes, epilepsy, muscle degeneration, and increased serum creatine kinase levels.

The major imaging findings associated with this disorder are atrophy of the caudate nucleus with dilation of the anterior horns of the lateral ventricles, which is milder compared to that observed in cases of Huntington disease. Atrophy is also seen in the putamen. MRI also commonly shows hyperintensity in the caudate and putamen on T2-weighted images (Gradstein et al. 2005). Hippocampal sclerosis and atrophy are also apparent (Al-Asmi et al. 2005).

Gilles de la Tourette syndrome is a disorder that typically begins in childhood with multiple motor tics that are repetitive, stereotyped, involuntary movements, usually occurring with one or more vocal tics. The definitive pathophysiology is not well known; however, since antidopaminergic agents are effective for suppressing the symptoms, hyperactivity of the dopaminergic system is suspected to play a role.

Several reports about MRI morphologic studies have been published. Regional abnormalities in gray matter, especially in the basal ganglia region, prefrontal to the parieto-occiptal cortex, and in the cerebellum, have been reported (Peterson et al. 2003; Peterson 2001; Sowell et al. 2008; Tobe et al. 2010). High-frequency stimulation by deep electrodes in the centromedian nucleus-substantia periventricularis-nucleus ventro-oralis internus cross point is reported to reduce tic severity (Ackermans et al. 2011) (Fig. 25.6).

Fahr disease (or idiopathic calcification of the basal ganglia) is a degenerative disease in which symmetric abnormal calcium deposition occurs in the basal ganglia, dentate nucleus, and cerebral white matter (Fig. 25.7). Histologically, the calcium deposition in Fahr disease is seen in the walls of capillaries, arterioles, venules, or in perivascular spaces and may be accompanied by adjacent neural degeneration and/or gliosis. There are a wide variety of clinical symptoms, including Parkinsonism, choreoathetotic-type movement disturbances, cognitive disorders, and cerebellar ataxia. There are two patterns in the onset of Fahr disease, including early onset (around 30 years old), in which the occurrence of movement disorders is minimal, and late onset (around 50 years old), which presents with dementia and movement dysfunction (Cummings et al. 1983). Differential diagnoses of Fahr disease using imaging methods include hypoparathyroidism or pseudohypoparathyroidism. Thus, measurements of serum calcium, phosphorus, and parathyroid hormone levels are useful for diagnosis (Avrahami et al. 1994).

Non-ketotic hyperglycemic chorea-hemiballismus, diabetic hemichorea/hemiballism or hyperglycemic choreoathetosis is a rare complication of non-ketotic hyperglycemia in type 2 diabetes. Chorea and ballismus can be caused by various conditions in which the striatum, external segment of the globus pallidus, thalamus, or subthalamic nucleus is impaired, and dysfunction of inhibitory fibers to the thalamus via globus pallidus results in disinhibition of thalamic neurons. The underlying causes include neurodegenerative diseases, ­cerebrovascular disorders, infections, drugs, metabolic abnormalities, and tumors, as well as non-ketotic hyperglycemia.

MRI from patients with this disorder is characterized by hyperintensity of the striatum and/or globus pallidus on the side contralateral to the symptoms on T1-weighted images (Fig. 25.8). T2-weighted images usually do not show any signal abnormalities. Occasionally there are cases with the signal abnormality on T1-weighted images on both sides. In these cases, their symptoms are also bilateral. The signal abnormality is reversible, and T1 hyperintense lesions in the basal ganglia regress in the cases receiving follow-up MRI during the remission phase (Chang et al. 2010). There are some hypotheses for hyperintensity on T1-weighted images including reversible ischemic insult potentiated by hyperglycemia, petechial hemorrhage, myelin destruction, deposition of manganese, or microgliosis (Chang et al. 2010; Lai et al. 1996; Shan et al. 2007). However, no single definite mechanism has been proposed.

Multiple system atrophy is a sporadic, nonhereditary neurodegenerative disorder with cerebellar atrophy, autonomic disorder, and/or Parkinsonism in its course. MSA consists of olivopontocerebellar atrophy, which mainly presents cerebellar ­atrophy; striatonigral degeneration, which mainly presents Parkinsonism; and Shy-Drager syndrome, which mainly presents autonomic disorder. These three disorders are originally regarded as other entities; however, since argentaffin inclusion bodies, often called “glial cytoplasmic inclusions” in oligodendroglial cells, can be seen in these three disorders, these are regarded as a single entity. MSA predominantly presenting Parkinsonism is called MSA-P, MSA predominantly presenting cerebellar ataxia is called MSA-C, and the terminologies of olivopontocerebellar atrophy, striatonigral degeneration, and Shy-Drager syndrome are no longer used. The diagnostic criteria by the second consensus statement on MSA states that MSA is defined by neuropathologic findings of widespread and abundant central nervous system glial cytoplasmic inclusions that are positive for alpha-synuclein, in association with neurodegeneration in striatonigral or olivopontocerebellar structures (Gilman et al. 2008). Alpha-synuclein is one of the major components of intracellular fibrillary aggregates in the brains of a subset of neurodegenerative disorders, including Parkinson disease, dementia with Lewy bodies, multiple system atrophy, and Hallervorden-Spatz disease, which are referred to as alpha-synucleinopathies (Hasegawa et al. 2002). MSAs, including MSA-C and MSA-P, are categorized within a subgroup of these neurodegenerative disorders termed synucleinopathies, in which alpha-synuclein is ­polymerized into fibrils and accumulates in pathologic inclusions, such as Lewy bodies and glial cytoplasmic inclusions mentioned above. Although MSA is subdivided into two categories (MSA-P and MSA-C) according to the most prominent initial symptom, both symptoms, including Parkinsonism and cerebellar ataxia, become apparent with disease progress. Similarly, the pathological findings in the pons, which characterize MSA-C, and the findings in putamen, which characterize MSA-P, are both commonly seen in the terminal stage of disease.

Hereditary SCD includes autosomal dominant disorders such as dentatorubral-pallidoluysian atrophy (DRPLA) and spinocerebellar ataxia (SCA) and autosomal recessive disorder. Autosomal recessive disorder includes Friedreich ataxia and early-onset ataxia with ocular motor apraxia and hypoalbuminemia (EAOH). Recently, the specific gene responsible for the anomaly has been identified for a variety of disorders, and the classification of the diseases have become clearer. For example, there are 31 types of genetic disorders identified for spinocerebellar ataxia (SCA). SCA is a genetically heterogeneous group of cerebellar degenerative disorders, for which symptoms include progressive gait instability, incoordination, and dysarthria due to degeneration of the cerebellum or its connections. The characteristic clinical findings of hereditary SCD is anticipation, which is a phenomenon in which the onset age of the disease becomes earlier and the symptoms become more severe in successive generations.