Magnetic resonance imaging (MRI) has a lower sensitivity and lower specificity than CT in diagnosing intracerebral calcifications [44–48]. In T1-weighted images, the signal contrast caused by calcifications is often inconsistent. In general, calcium deposits reduce the T1 relaxation time by a surface relaxation mechanism [49]. With an increasing amount of deposits, T1 intensity is supposed to increase initially and to then decrease subsequently [49]. In the majority of cases, the T1 signal is hyperintense, but isointense or hypointense signal behavior can also be observed within the same subject or between different subjects [45, 50, 51]. The changes in T1 signal may be related to the disease stage, differences in calcium metabolism, and the volume of deposits [52]. In contrast, T2 signal changes and calcified brain regions upon CT show a varying distribution. Confluent hyperintense T2 lesions of the white matter in the centrum semiovale are common, and they do not correspond to the localization of calcifications [23, 45, 53]. It is speculated that the T2 hyperintensities represent slowly progressive metabolic and inflammatory processes that result in and correlate with progressive neurological deficits [45].

Transcranial sonography (TCS) has become a useful diagnostic tool in the differential diagnosis of movement disorders . TCS may also be helpful in establishing an early diagnosis of Parkinson’s disease [54]. Advantages of TCS are its widespread availability, cost effectiveness, noninvasiveness, and the avoidance of exposure to x-rays. The method allows unlimited repeated measures and is even applicable in agitated patients. An experienced investigator is able to perform a TCS scan within 5–10 min.

A striking finding in Parkinson’s disease is an enlarged area of hyperechogenicity projecting to the anatomical site of the midbrain substantia nigra [55]. Abnormal hyperechogenic areas within the caudate and lenticular nucleus have been reported in atypical parkinsonian syndromes [56], Huntington’s disease [57], multiple sclerosis [58], primary dystonia [59, 60], spinocerebellar ataxia type 3 [61], and Wilson’s disease [62, 63]. Several factors have been discussed as the possible underlying pathoanatomical correlate of basal ganglia hyperechogenicity: increased local iron [58, 64] and copper concentration [62], gliosis [58], and enlarged perivascular spaces or simply artifacts (see Chap. 6 for a more in-depth discussion). Moreover, diffuse hyperechogenicity of the basal ganglia and thalami is a frequent and nonpathologic finding in premature infants that is no longer detectable 1 month after delivery [65]. The most intense and striking hyperechogenicity in adulthood seems to derive from the accumulation of calcium compounds. Thus, BSPDC provides the unique opportunity to study basal ganglia alterations with a defined histopathology. Using TCS, small intracranial calcifications may occasionally be detected even prior to CT imaging [55, 62]. So far, striking basal ganglia hyperechogenicity in BSPDC has been reported in seven patients from different sites [21, 31, 66]. The hyperechogenic areas upon TCS correspond excellently to the symmetric distribution pattern as shown with either CT [21, 31] or MRI [66] and show almost the same level of intensity as the contralateral skull bone and the frequently calcified pineal gland (Fig. 16.2). Hyperechogenicity in extended calcified lesions as in BSPDC can be distinguished from the pattern observed in the context of a mixture of gliosis and iron and/or copper accumulation, which may be less striking. Apart from the high signal-to-noise ratio of the hyperechogenic signal, the highly symmetric distribution and the large conglomerates may be specific TCS features of BSPDC.

Functional radioligand imaging techniques, including single photon emission tomography (SPECT) and positron emission tomography (PET) , complement anatomical brain imaging methods such as CT and MRI. They are useful to study local brain perfusion, brain metabolism, and the nigrostriatal function in vivo.

In symptomatic BSPDC subjects, Tc-99^m hexamethylpropylene amine oxime (HMPAO) SPECT revealed hypoperfusion in widespread subcortical and cortical regions, including the basal ganglia, thalamus, cerebellum as well as frontal, parietal, temporal, and insular cortical areas [21, 34, 51, 67, 68]. In two further case reports, hypoperfusion was restricted to the right-sided basal ganglia [69] and the thalami bilaterally [70] despite the fact that the calcifications were widely dispersed in these patients. In the latter study, Tc-99^m ethylcysteinate was used instead of HMPAO to visualize the local cerebral blood flow. Using this agent, the reduction of cerebral perfusion was not per se associated with the amount of mineral deposits [70]. The clinical phenotype corresponds well to hypoperfused brain regions in BSPDC. Ones et al. [69], for example, reported a case of unilateral striatal hypoperfusion and contralateral parkinsonism . In one clinically asymptomatic subject, the regional brain perfusion was unremarkable [34].

In conformity with hypoperfusion in calcified regions and interconnected areas, ¹⁸F-fludeoxyglucose (FDG) PET revealed reductions of glucose metabolism in similar regions, including frontotemporal and cingulate cortices as well as the basal ganglia in symptomatic BSPDC, whereas asymptomatic subjects show a normal glucose brain metabolism [34, 71–73]. The hypometabolism corresponds to the clinical deficits and may result from a deafferentiation of striatal and cortical regions due to basal ganglia pathology. The multifaceted symptomatology may thus be explained by a disruption of motor, limbic, and associative cortico-subcortical neuronal circuits.

Using FP-CIT SPECT and ¹⁸F-DOPA PET, the dopaminergic nigrostriatal neurotransmission was shown to be impaired in several BSPDC patients presenting with parkinsonism . The reduced striatal tracer uptake was either asymmetric, and thus resembling idiopathic Parkinson disease [21], or symmetric [25, 68]. One patient with generalized chorea and neuropsychiatric symptoms but without features of Parkinson’s disease had a normal FP-CIT scan [21]. Normal presynaptic ¹⁸F-DOPA uptake has been observed in one asymptomatic patient and one patient with dementia and bradykinesia [44]. In two symptomatic subjects, PET displayed reduced striatal dopamine D₁ and D₂ receptor binding [25]. Thus, postsynaptic striatal dysfunction may be postulated in some affected individuals due to an interference of calcium deposits with postsynaptic dopamine receptors.

A combination of parkinsonism , cognitive deterioration, and cerebellar signs is a typical finding in BSPDC and should prompt clinicians to perform a cerebral CT scan, which remains the most effective screening tool. MRI is useful in detecting white matter pathology in uncalcified brain areas but its effectiveness in verifying intracerebral calcifications is limited. Preliminary data suggest that intracerebral calcifications show a distinct pattern of hyperechogenic areas upon TCS. In the hand of an experienced investigator, it may be justified to use TCS as a first screening tool. To date, however, a CT scan is still needed in order to verify or exclude intracerebral calcifications. Future developments in various neuroimaging modalities will provide the ability to detect changes early while improving our understanding of symptom-related changes in brain function.