Elsevier

Psychiatry Research

Volume 121, Issue 1, 1 November 2003, Pages 59-87
Psychiatry Research

Mineralization of the basal ganglia: implications for neuropsychiatry, pathology and neuroimaging

https://doi.org/10.1016/S0165-1781(03)00202-6Get rights and content

Abstract

This article examines the evidence for and against the existence of basal ganglia mineralization as a defined clinico–pathological entity. In reviewing the literature on basal ganglia mineralization, this article emphasizes evidence derived from different neuroimaging modalities, genetics, metabolic studies, postmortem series and their possible neuropsychiatric correlates. Relevant articles were collected through Medline and Index Medicus searches. Researchers have encountered multiple difficulties in accepting basal ganglia mineralization as a distinct entity. This syndrome lacks set clinical criteria or a unique etiology; not surprisingly, numerous articles have applied varied definitions. Because many of the reported cases have not been examined postmortem, both the extent and nature of their mineralization remains uncertain. Furthermore, researchers have considered small foci of basal ganglia mineralization a normal phenomenon of aging. However, when brain deposits are extensive, they are associated with a set of age-dependent, progressive clinical symptoms. They include cognitive impairment, extrapyramidal symptoms and psychosis. Most cases are related to abnormalities of calcium metabolism, but rare familial cases of idiopathic origin have been reported. Overabundant mineralization of the brain is judged pathological based on its amount, distribution and accompanying clinical symptoms. Although its relation with calcium dysregulation is well known, modern studies have emphasized abnormalities of iron and dopamine metabolism. The authors suggest that these metabolic abnormalities may link basal ganglia mineralization to psychotic symptomatology.

Introduction

For many years researchers have studied the function, anatomy and pathology of the basal ganglia (BG).1 They have linked pathology of these subcortical masses to both motor abnormalities and psychiatric symptoms. Still, the possible relevance of mineral deposits within the BG remains uncertain. Thus far, research has failed to explain the tendency for certain substances to accumulate in these specific structures or to provide definite pathophysiological mechanisms for symptom expression. Similarly, we lack studies on the cause-effect relationship between early mineral deposition and later development of symptomatology. Furthermore, one researcher has conjectured that following lesions of the BG other areas of the brain may take over some of its functions (Dean, 1989). These considerations hamper attempts at correlating basal ganglia mineralization (BGM) to any given set of clinical manifestations.

In most instances BGM is considered ‘physiological’ and therefore an incidental finding of either autopsy or clinical investigation. The introduction of neuroimaging techniques requires us to reappraise this tenet. Modern imaging modalities provide two distinct advantages capable of addressing gaps in our knowledge regarding BGM. First, they can screen very large numbers of patients in a short period of time. Second, they can examine symptoms in vivo at any stage of a particular disease process.

The present article summarizes the literature on BGM with a focus upon neuropsychiatric issues. We discuss the different methods used in studying BG deposits. We also correlate the presence of BGM with clinical and pathological results and discuss the importance of properly assessing early deposits. The conclusions from this revision of the literature could help institute palliative therapy and pinpoint a pathological commonality to a variety of psychiatric conditions.

Section snippets

History

Mineralization of the brain has been known for over a century. Delacour (1850) described ossification of vascular brain structures and referred to a previously reported case. Virchow (1855) found spines protruding from the brain sections of a young man who died of tuberculosis. Bamberger (1855) independently reported similar postmortem findings in a man with progressive mental deterioration and seizures. Soon afterwards, other researchers, including Flesching, Perusini, Greenfield and Durk,

Pathology

At the microscopic level, BG concretions are recognized as basophilic globules tracking the vessel walls of arteries, arterioles, capillaries and veins (Fig. 1). Scanning electron microscopy has shown a connection between some of these bodies and surrounding glial cells (Kobayashi et al., 1987). The intima of involved vessels is usually preserved but occasionally proliferates to narrow the lumen. In severe cases minerals encase the whole vessel wall and similar deposits are found free in the

Pathophysiology

Historically, the mechanism(s) accounting for the accumulation of minerals, iron in particular, have been contested in the literature. Klotz (cited by Hurst, 1926) believed that accumulations resulted from an interaction between fatty acids and calcium. Other investigators proposed either an affinity towards necrotic material or colloid precipitation. Scattered reports have also postulated dysoric (i.e. rupture of the blood-brain barrier), toxic, inflammatory, genetic or vasculitic origin for

Animal models of basal ganglia mineralization

Researchers have occasionally found mineralization of the BG in animals. Gavier-Wider et al. (2001) described mineralization of blood vessel walls in the internal capsule of asymptomatic 7-year-old cattle. They found inflammatory vascular infiltrates in 30% of the animals (n=506 brains) and associated vascular mineralization with aging. In a group of 20 healthy 3- to 10-year-old horses, Yanai et al. (1996) found cerebral mineralization in pallidal arteries of 12 (60%) horses. They also

Radiology

Neuroimaging studies have been useful in the antemortem diagnosis of BGM. Although the medical literature has not defined the exact incidence of BGM in skull X-rays (SXR), it has considered it minimal. Muenter and Whisnant (1968) reviewed the experience of the Mayo Clinic from 1935 to 1966 and found only 38 cases. Approximately 25% of patients with BGM in SXR manifested some type of movement disorder (Muenter and Whisnant, 1968, Lowenthal and Bruyn, 1968). Almost 70% of them had abnormalities

Functional neuroimaging

Functional methods of neuroimaging include positron emission tomography (PET), single photon emission compute tomography (SPECT), magnetic resonance spectroscopy (MRS), functional magnetic resonance imaging (fMRI) and xenon compute tomography (Xe-CT). All have a long history of use to study neural physiology and psychiatric alterations (Grady and Keightley, 2002).

Various techniques for measuring regional cerebral blood flow permit the study of many psychiatric conditions. Initially, the

Clinical syndromes

Eaton et al. (1939) first described the occurrence of BGM in idiopathic hypoparathyroidism. Several years later researchers recognized its occurrence in pseudohypoparathyroidism and Albright's disease (Alexander et al., 1949, MacGregor and Whitehead, 1954, Sprague et al., 1945). The association of vascular mineralization of widespread areas of the brain with disorders of calcium metabolism and/or a positive family history enabled clinicians to propose the following nosologic classification (

Miscellaneous conditions related to basal ganglia calcification

In a review of the literature, literally hundreds of isolated descriptions relate diverse diseases and conditions to BGC. Their methods vary from radiographic, to histopathologic, to clinical. Usually the lack of unified criteria fails to permit grouping these cases by conditions, tendencies or common origin (Table 5). We have, however, selected a group of these reports that emphasizes psychiatric alterations or describes possible physiopathological mechanisms. In these cases, it is often

Basal ganglia mineralization and neuropsychiatric disorders

Modern studies have shown that psychiatric symptoms are pervasive in patients with extensive BGM. These symptoms include mood disorders, organic hallucinatory disorders, obsessive-compulsive features, drug addiction, and personality and cognitive dysfunction (Cummings et al., 1983, Gluck-Venlaer et al., 1996). Since BG/thalamo–cortical circuits damaged in BG diseases have been related to depression and motor symptoms (Sobin and Sackeim, 1997), some of the manifestations of BGM may therefore

Acknowledgements

This article is based upon work supported by the Stanley Medical Research Foundation and NIMH grants MH61606 and MH62654.

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