Mineralization of the basal ganglia: implications for neuropsychiatry, pathology and neuroimaging
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.
References (245)
- et al.
Ascending paralysis due to myelitis in a newborn with congenital toxoplasmosis
Journal of Neurological Sciences
(1996) - et al.
MRI evaluation of brain iron in young adult and older normal males
Magnetic Resonance Imaging
(1997) - et al.
MRI evaluation of brain iron in earlier and late onset Parkinson's disease and normal subjects
Magnetic Resonance Imaging
(1999) - et al.
MRI in tardive dyskinesia: shortened left caudate T2
Biological Psychiatry
(1990) - et al.
Echogenicity of substantia nigra determined by transcranial ultrasound correlates with severity of Parkinsonian symptoms induced by neuroleptic therapy
Biological Psychiatry
(2001) - et al.
Differential vulnerability of hippocampus, basal ganglia and prefontral cortex to long term NMDA excitotoxity
Experimental Neurology
(2000) - et al.
Mitochondria and ischemic reperfusion damage in the adult and in the developing brain
Biochemical and Biophysical Research Communications
(2003) - et al.
No difference in basal ganglia mineralization between schizophrenic and non-schizophrenic patients: a quantitative computerized tomographic study
Biological Psychiatry
(1990) - et al.
A postmortem quantitative study of iron in the globus pallidus of schizophrenic patients
Biological Psychiatry
(1990) - et al.
Aicardi-Goutières syndrome displays genetic heterogeneity with one locus (AGS1) on chromosome 3p21
American Journal of Human Genetics
(2000)