Bilateral basal ganglia calcifications visualised on CT scan.

Thirty-eight cases of basal ganglia calcification imaged on computed axial tomography were reviewed. Most cases were felt to represent senescent calcification. The possibility of a vascular aetiology in this group is discussed. A less common group of patients was identified with calcification secondary to abnormalities in calcium metabolism or radiation therapy. Three cases of basal ganglia calcifications were detected in juvenile epileptic patients receiving chronic anticonvulsants. These cases may be related to abnormalities in calcium metabolism and alkaline phosphatase activity. Clinical evidence of basal ganglia abnormality was generally absent demonstrating the preservation of neuronal pathways in most cases.     

Calcification of the basal ganglia: computerized tomography and clinical correlation

During a 1-year period, 4219 consecutive computerized tomograms (CT) were reviewed for basal ganglia calcification; 14 patients with such calcification were identified. Calcifications on CT scan were bilateral in 12 of these cases and unilateral in 2. All bilateral calcifications were symmetric. The globus pallidus was the site of calcification in 13 of the 14 patients. Bilateral dentate nucleus calcification was seen in one patient. Skull radiograms were normal in all but one. Patients had diverse symptoms that were often explained by other findings, suggesting that calcifications may be coincidental and that basal ganglia calcification may not be a nosologic entity. Disturbances of calcium metabolism were not found in these patients, minimizing the pathophysiologic significance of altered calcium metabolism and the need for extensive endocrinologic evaluation. The finding of basal ganglia calcification alone does not justify invasive diagnostic procedures. Extrapyramidal signs may be associated with basal ganglia calcification; parkinsonism associated with basal ganglia calcification differs from idiopathic parkinsonism in being resistant to levodopa therapy.     

Spinocerebellar ataxia type 20

Spinocerebellar ataxia type 20 (SCA20) was reported in 2004 in a single Australian Anglo-Celtic pedigree. The phenotype is distinctive, with palatal tremor, and hypermetric saccades, and early dentate (but not pallidal) calcification in the absence of abnormalities of calcium metabolism. Dysarthria, rather than gait ataxia, was the initial symptom in most, and was typically conjoined with dysphonia, clinically resembling adductor spasmodic dysphonia. The onset of these speech abnormalities was abrupt in some cases. MRI scanning showed mild to moderate pancerebellar atrophy with dentate calcification, with olivary pseudohypertrophy in some cases, in the absence of other brainstem or cerebral changes. Nerve conduction studies were normal. Progression appeared to be slow. SCA20 is probably rare, as despite the distinctive phenotype, only this one pedigree has been described. The locus mapped to the pericentromeric region of chromosome 11 with a LOD score of 4.47, and its candidate region overlaps that of SCA5. It seems probable that these two SCAs may be separate genetic entities, on the basis of their divergent clinical features, but formal proof awaits discovery of one or both responsible genes.     

Pituitary adenoma calcification

Three hundred and eighteen cases of functioning and non-functioning pituitary adenoma were examined by histological, immunocytochemical and electronmicroscopic technique. Fourty-four of them (13.8%) showed evidence of calcospherites in the tumor tissues. A high incidence of calcospherite is found in functioning adenoma, but not in non-functioning adenoma. Calcification was seen most frequently in cases of prolactinoma (23), GH secreting (7), or GH + PRL tumor (2) and less in adrenocorticotropic hormone secreting adenoma (2) and follicle stimulating hormone secreting adenoma (1). Prolactin and growth hormone might be involved in the control of calcium metabolism. This is because, following adenomectomy in patients with prolactinoma or GH-secreting adenoma with hypercalcemia, there is normalization of serum PRL and GH with reduction in serum calcium. Calcospherite is produced in all of metastatic calcification, arterial calcification, dystrophic calcification and calcinosis. In cases of non-functioning adenoma however, the mechanism is believed to by dystrophic calcification.     

Basal ganglia calcification on computer tomographic scan

Computerised tomography of the brain was used to demonstrate basal ganglia calcification which may be of an insufficient degree to be seen on skull X-ray.
Cases referred for CT scan from hospitals in Singapore for various reasons over a period of 12 months were studied for basal ganglia calcification. There was a startlingly high incidence of 1.5%, as 47 cases (all except 2 were Chinese) showed such calcification. In 42 cases there was no evidence of basal ganglia calcification on skull X-ray. 16 cases showed neurological affection, fits being the commonest manifestation.
An unexpected finding was that no case had abnormality of calcium metabolism or evidence of hypoparathyroidism or pseudohypopara-thyroidism.
The CT scan is very sensitive in demonstrating minimal basal ganglia calcification and our impression is that such calcification is common.     

Parvalbumin and calbindin D-28 k immunoreactivity in dorsal root ganglia in acquired immunodeficiency syndrome

Various degrees of neuronal degeneration have been found in lumbosacral dorsal root ganglia of patients with acquired immunodeficiency syndrome (AIDS). To characterize the subpopulations of primary sensory neurons affected in AIDS. we immunostained dorsal root ganglion tissues from 11 AIDS patients and six controls using antibodies to the calcium binding proteins, parvalbumin and calbindin D-28 k. In controls, the proportion of neurons containing parvalbumin and calbindin was 18.0% and 22.4%, respectively. The majority of parvalbumin-positive neurons, which are thought to be proprioceptive neurons, were of medium to large size, while calbindin was found in both large- and small-sized neurons. The density of parvalbumin-immunoreactive neurons was reduced by 7.3% in AIDS patients, but the density of calbindin-immunoreactive neurons was preserved. Furthermore, in AIDS cases, the number of parvalbumin-positive neurons was reduced more in dorsal root ganglia in which human immunodeficiency virus (HIV) antigen was detected than in HIV-negative ganglia. These results suggest that specific subpopulations of sensory neurons positive for parvalbumin may be differentially affected over the course of AIDS, and that this could be related to peripheral neuropathy which frequently occurs in the late stages of AIDS.     

Matrix Gla-protein: the calcification inhibitor in need of vitamin K

Among the proteins involved in vascular calcium metabolism, the vitamin K-dependent matrix Gla-protein (MGP) plays a dominant role. Although on a molecular level its mechanism of action is not completely understood, it is generally accepted that MGP is a potent inhibitor of arterial calcification. Its pivotal importance for vascular health is demonstrated by the fact that there seems to be no effective alternative mechanism for calcification inhibition in the vasculature. An optimal vitamin K intake is therefore important to maintain the risk and rate of calcification as low as possible. With the aid of conformation-specific antibodies MGP species in both tissue and the circulation have been detected in the healthy population, and significant differences were found in patients with cardiovascular disease (CVD). Using ELISA-based assays, uncarboxylated MGP (ucMGP) was demonstrated to be a promising biomarker for cardiovascular calcification detection. These assays may have potential value for identifying patients as well as apparently healthy subjects at high risk for CVD and/or cardiovascular calcification and for monitoring the treatment of CVD and vascular calcification.     

Abnormal deposits of chromium in the pathological human brain.

Three patients presented with encephalopathies: an undiagnosed degenerative disease of the brain, a degenerative cerebral disease in a patient with a myeloma but without a myelomatous deposit in the CNS and a malignant astrocytoma. Perivascular pallidal deposits (vascular siderosis) containing chromium, phosphorus and calcium plus sometimes traces of other elements were present in the three cases. Such deposits were present in the pallidal parenchyma and around vessels in the cerebellum in one case. Calcium and phosphorus are always present in any CNS calcification but the presence of chromium has not been reported. Chromium and its compounds (ingested, injected or inhaled) are toxic to humans and animals in trace doses. Approximately 900 cases of chromium intoxication have been reported and usually have had dermatological or pulmonary lesions (including cancer) but there is no report of involvement of the CNS. Sublethal doses of chromium nitrate injected intraperitoneally in rats and rabbits results in the presence of chromium in the brain. A thorough investigation was made to find the source of the chromium in these patients. Chromium was found to be present in trace amounts in the radiological contrast agents administered to these patients and in the KCl replacement solution and in mylanta, an antacid, given to one case. The evidence that chromium induced pathological changes in these three brains is circumstantial but shows that chromium can penetrate the human brain. This study indicates that vascular siderosis found in the brains of the majority of middle-aged and elderly humans is not simply an anecdotal pathological curiosity, but that it can serve as a route of entry for toxic products into the brain.     

Fahr's syndrome: local inflammatory factors in the pathogenesis of calcification

Summary Three cases of Fahr's syndrome are described. All patients had disturbances of calcium metabolism and had had a meningoencephalitis in childhood. It is suggested that gliovascular changes, induced by cerebral inflammation, can later facilitate the occurrence of calcification of the striopallidodentate system when abnormality of calcium metabolism develops.     

Cerebellopontine calcification: a new entity of idiopathic intracranial calcification?

We report the autopsy case of a 40-year-old woman with severe intellectual and motor disabilities, who showed calcification in the cerebellum and pons but not in the basal ganglia on CT scan, and died of intracranial hemorrhage due to intractable hypertension. At autopsy, numerous calcium deposits were noted in the cerebellar cortex, the dentate nucleus, the cerebellar white matter and the ventral pons. These deposits were distributed both in the neuropil and the white matter, but rarely within the arterial walls or in contact with capillaries. This weak relationship between calcification and the blood vessels, in addition to the paucity of basal ganglia calcification, is in contrast to the findings with other disorders involving intracranial calcification, including Fahrs disease and calcium metabolism disorders. Immunohistochemistry revealed intense staining of calbindin-D28K and parvalbumin at sites of calcium deposits both in the present case and in a case of pseudohypoparathyroidism, whereas these proteins were not localized to calcium deposits in the cerebellum of a Fahrs disease brain. We propose that the present case may represent a distinct entity among diseases characterized by idiopathic intracranial calcification. In addition, calcium-binding proteins may be involved in the calcification process in some cases with intracranial calcification.     

Diffuse neurofibrillary tangles with calcification (a form of dementia): X-ray spectrometric evidence of lead accumulation in calcified regions

Diffuse neurofibrillary tangles with calcification (DNTC) is a form of slowly progressive dementia in which no senile plaques are observed. The calcification is one of the most characteristic features of DNTC. We examined the elemental content of certain mineral deposits (lead, magnesium, phosphorus, calcium, iron, copper and zinc) in the calcified and non-calcified regions of eight cases of DNTC, five cases of Alzheimer's disease (AD) and in eight non-demented elderly controls. The study was performed using a combination of scanning electron microscopy and X-ray spectrometry on 10% formalin-fixed brain tissue. A marked abundance of calcium and phosphorus was observed in the calcified regions of DNTC and non-DNTC brains. Although no lead was observed in the non-calcified regions of DNTC and in non-DNTC brains, traces of lead were detected exclusively in the calcified regions of DNTC brains. The implications and possible significance of the lead accumulation in DNTC brains are discussed.     

Different mechanisms may generate sustained hypertonic and rhythmic bursting muscle activity in idiopathic dystonia

Despite that deep brain stimulation (DBS) of the globus pallidus internus (GPi) is emerging as the favored intervention for patients with medically intractable dystonia, the pathophysiological mechanisms of dystonia are largely unclear. In eight patients with primary dystonia who were treated with bilateral chronic pallidal stimulation, we correlated symptom-related electromyogram (EMG) activity of the most affected muscles with the local field potentials (LFPs) recorded from the globus pallidus electrodes. In 5 dystonic patients with mobile involuntary movements, rhythmic EMG bursts in the contralateral muscles were coherent with the oscillations in the pallidal LFPs at the burst frequency. In contrast, no significant coherence was seen between EMG and LFPs either for the sustained activity separated out from the compound EMGs in those 5 cases, or in the EMGs in 3 other cases without mobile involuntary movements and rhythmic EMG bursts. In comparison with the resting condition, in both active and passive movements, significant modulation in the GPi LFPs was seen in the range of 8-16 Hz. The finding of significant coherence between GPi oscillations and rhythmic EMG bursts but not sustained tonic EMG activity suggests that the synchronized pallidal activity may be directly related to the rhythmic involuntary movements. In contrast, the sustained hypertonic muscle activity may be represented by less synchronized activity in the pallidum. Thus, the pallidum may play different roles in generating different components of the dystonic symptom complex.     

Chronic acquired hepatocerebral degeneration,pallidal T1 MRI hyperintensity and manganese in a series of cirrhotic patients

Chronic acquired hepatocerebral degeneration (CAHD) is a rare neurological disorder of cirrhotic patients, characterized by parkinsonism and cognitive impairment. A T1 hyperintensity on the globus pallidum due to an accumulation of manganese (Mn) is found in these patients. The aim of the study was to investigate CAHD, Mn and the MRI pallidal signal in a series of cirrhotic patients. The association between pallidal T1 hyperintensity, CAHD, and blood levels of Mn, the effect of orthotopic liver transplantation (OLT) on the MRI signal and neurological findings, and the role of the pallidal signal as a predictor of CAHD were evaluated. Twenty-six out of 90 patients with cirrhosis had pallidal T1 hyperintensity. Seven patients had CAHD. OLT was followed by the disappearance of CAHD and MRI signal in 2/2 patients. The MRI signal disappeared after OLT in 8/13 patients after a median follow-up time of 24 months. In the patients who did not undergo OLT, CAHD did not present after a median follow-up time of 18 months. The cause of cirrhosis, episodes of acute hepatic encephalopathy and signal intensity were not correlated with CAHD. The blood levels of Mn did not reflect either the MRI signal or CAHD. In conclusion, the pallidal T1 hyperintensity is a prerequisite for the clinical manifestations of CAHD but is not sufficient. The blood levels of Mn as routinely monitored are not a useful marker of Mn burden. The MRI pallidal signal is not a predictor of CAHD.     

Basal ganglia calcification on computed tomography: clinical characteristics in 25 patients

Twenty-five patients presenting basal ganglia calcification were assessed. This finding comprised 0.68% of all skull CT scan carried out during the period. Two patients were neurologically asymptomatic and 23 presented a variety neurological disorders--headache (7 patients), stroke (5 patients), extrapyramidal syndromes (2 patients), tumor (2 patients), epilepsy (1 patient), mental retardation (1 patient), dementia (1 patient), cranial trauma (1 patient), other neurological conditions (3 patients)--or were asymptomatic from the neurological point of view (2 patients). Findings in the CT scan other than the basal ganglia calcification were observed in 15 (60%) patients. There was a clinical-CT scan correlation in these cases but not in those in which the basal ganglia calcification was an isolated finding. This study highlights the fact that basal ganglia calcification is often a nonspecific finding on CT scan and that it may not be possible to establish a clinical-pathological correlation between them.     

Spinal cord and peripheral nerve pathology in AIDS: the roles of cytomegalovirus and human immunodeficiency virus

We examined spinal cords, nerve roots, or peripheral nerves of 27 patients who died with acquired immunodeficiency syndrome (AIDS) for the presence of cytomegalovirus (CMV) and human immunodeficiency virus (HIV) by immunoperoxidase techniques in paraffin-embedded tissue. Vacuolar myelopathy was seen in 8 of 26 spinal cords (31%) and microglial nodules were seen in 13 (50%). All of the patients with lateral column vacuolar myelopathy showed severe brain pathology. HIV antigens had been detected in the brains of 15 (55%) of the 27 patients but were detected in only 3 (11%) of 26 spinal cords and were not localized to regions of vacuolar myelopathy. This suggests that the vacuolar myelopathy may be due to a remote or indirect effect of HIV or other infectious agent. CMV antigens were detected in none of the patients who showed vacuolar myelopathy but were detected in 2 of the 13 with microglial nodules. Focal nerve root or peripheral nerve inflammation was seen in 7 patients; 4 had CMV antigens and none had HIV antigens. CMV appears to be an important cause of inflammatory peripheral neuropathy in AIDS patients.     

'Psychic akinesia' following carbon monoxide poisoning

In 3 patients, carbon monoxide poisoning was followed by a modification of habits and personality without definite mental deterioration, but with loss of initiative, which led the patients to lose all their previous interests and to spend most of their time in bed. CT scans showed bilateral calcification of globi pallidi in one patient and pallidal hypodensities in another.     

Differential vulnerability of hippocampus, basal ganglia, and prefrontal cortex to long-term NMDA excitotoxicity

In human brain, nonartherosclerotic calcification is associated with normal aging and several pathological conditions without any clear significance. In all situations, calcification appears predominantly in the basal ganglia, but is also frequent in the hippocampus and cerebral cortex. alpha-Amino-(3-hydroxi-5-methyl-4-isoxazol-4-il)-propionic acid-induced lesion of the globus pallidus is associated in rats with the formation of calcium deposits similar to those observed in the human brain. To determine whether direct neuronal activation may induce calcification, N-methyl-d-aspartate (NMDA) was microinjected in rat hippocampus, globus pallidus, and lateral prefrontal cortex. Two months later, neuronal death was associated with calcium deposits that were characterized in terms of distribution and size. A unique population of deposits was present in the hippocampus and prefrontal cortex, whereas in the globus pallidus two main groups could be differentiated. Calcification was always associated with a significant microglial reaction as shown by the peripheral benzodiazepine receptor autoradiography. Monoamine oxidase B autoradiography, reflecting the astroglial reaction, was also significantly increased. Our results provide evidence that acute NMDA neuronal activation leads with time to calcification associated with a glial reaction and indicate that nonartherosclerotic calcification in the human brain may develop from an acute NMDA receptor activation. A key role of the metabotropic mGluR1 receptor is also suggested.     

Fatigue and myalgia in AIDS patients

Fatigue and myalgia are common in patients with acquired immunodeficiency syndrome (AIDS). To determine whether altered muscle metabolism or impaired activation of muscle might account for these symptoms, we utilized three different exercise protocols to produce fatigue in nine AIDS patients who complained of both fatigue and exercise-exacerbated myalgia. Five were taking azidothymidine (AZT), which may cause a mitochondrial myopathy. Simultaneous measures of force, EMG, and muscle metabolites (phosphocreatine, inorganic phosphate, adenosine triphosphate, and intracellular pH) using phosphorus nuclear magnetic resonance spectroscopy were performed during fatigue and recovery. There were no significant differences between patients and controls in terms of fatigability, muscle metabolism, or muscle activation. These results provide no support for the hypothesis that fatigue or myalgia in AIDS patients derives from altered muscle metabolism or that AZT produces mitochondrial myopathy.     

Calcium and vitamin D metabolism in Guamanian Chamorros with amyotrophic lateral sclerosis and parkinsonism-dementia

We evaluated 16 Guamanian Chamorros with amyotrophic lateral sclerosis and 33 patients with parkinsonism-dementia for disturbances of calcium and vitamin D metabolism. The serum immunoreactive parathyroid hormone level was mildly elevated in 6 patients with amyotrophic lateral sclerosis and in 5 patients with parkinsonism-dementia. There were significant positive correlations between serum immunoreactive parathyroid levels and duration of illness in male patients with motor neuron disease, but not in female patients or in patients with parkinsonism-dementia. Intestinal absorption of calcium, as assessed by serum and urinary activity of calcium 47 following oral administration, was decreased in 2 patients with amyotrophic lateral sclerosis and in 4 patients with parkinsonism-dementia, all of whom had low levels of serum 1,25-dihydroxyvitamin D. Reductions in cortical bone mass were striking in patients with motor neuron disease. A significant negative correlation was found between the percentage of cortical area of the second metacarpal bone and muscle atrophy and weakness, and significant positive correlations were found between degree of immobility and ratio of urinary hydroxyproline to creatinine in patients with amyotrophic lateral sclerosis and parkinsonism-dementia. In general, abnormalities in calcium metabolism were subtle. Thus, if the demonstrated deposition of metals, particularly calcium and aluminum, in central nervous system tissues of Guamanians with these two conditions is a cause of the diseases and of the early appearance of neurofibrillary tangles in neurons, the accumulation has apparently occurred long before onset of symptoms, and detectable abnormalities of calcium and vitamin D metabolism may already have been corrected.