Deep Cerebral White Matter Research Articles

Effect of the Ca Antagonist Nilvadipine on Stroke Occurrence or Recurrence and Extension of Asymptomatic Cerebral Infarction in Hypertensive Patients with or without History of Stroke (PICA Study)

Background: We examined the effect of a Ca antagonist (nilvadipine) on the occurrence or recurrence of symptomatic stroke in hypertensive patients with MRI-defined asymptomatic cerebral infarction (ACI), periventricular hyperintensity (PVH), and deep and subcortical white matter hyperintensity (DSWMH), with or without a history of stroke, and evaluated the effect of long-term treatment on the lesions. Methods: Patients with hypertension and incidental ACI were divided into those with (group B, 235 patients) or without (group A, 181 patients) a history of symptomatic stroke, and were given nilvadipine 4–8 mg/day for 3 years. Primary evaluation points were occurrence of symptomatic ischemic stroke and development or extension of asymptomatic ischemic lesions. Results: Male sex, hyperuricemia, diabetes, maximum diameter of infarction and PVH severity were stronger risk factors for group B. Numbers of cerebral infarctions were 31 ± 28 (group A) and 42 ± 32 (group B) at enrollment (p < 0.001). Infarctions were larger and located more frequently on the internal capsule, putamen, thalamus and brainstem in group B. The severity of PVH and DSWMH paralleled the number of cerebral infarctions in both groups. Conclusion: The study design and status of asymptomatic ischemic brain lesions in hypertensive subjects at enrollment are presented.

Relationship between periventricular and deep white matter lesions and depressive symptoms in older people. The LADIS Study

Both types of cerebral white matter hyperintensities, periventricular (PVL) and deep white matter lesions (DWML) have been previously associated with the development of depression in older subjects. However, it remains controversial as to whether PVL, DWML, or both are most strongly associated with depression and this was the aim of the current study. In a pan-European multicentre study of 626 older subjects, we examined the relationship between PVL and DWML, depressive symptoms (GDS quintile), cognitive status (MMSE), hypertension and history of stroke. In univariate analysis we found that depressive symptoms as assessed by GDS were associated with both types of white matter lesions (Spearman rho = 0.12 p = 0.002 for DWML and rho = 0.09 p = 0.01 for PVL). Using ordinal logistic regression analysis the total DWML score (p = 0.041), rather than PVL (p = 0.9) was found to predict GDS scores. DWML, but not PVL, were most strongly associated with depressive symptoms in this sample. As DWML (unlike PVL) are associated with vascular ischaemic damage, our findings are consistent with the 'vascular depression' hypothesis. Longitudinal studies are needed to clarify the time course of these relationships, in particular, whether modifying DWML alters the natural history of depression.

Cerebroretinal microangiopathy with calcifications and cysts

Extensive cerebral calcifications and leukoencephalopathy have been reported in two rare disorders Coats plus and leukoencephalopathy with calcifications and cysts. In the latter, a progressive formation of parenchymal brain cysts is a special feature, whereas Coats plus is characterized by intrauterine growth retardation, bilateral retinal telangiectasias and exudations (Coats disease), sparse hair, and dysplastic nails without cyst formation. We identified 13 patients, including two pairs of siblings, with extensive cerebral calcifications and leukoencephalopathy. We reviewed clinical, ophthalmologic, radiologic and neuropathologic data of seven deceased patients and studied five patients prospectively. Eleven patients were small for gestational age; the other symptoms emerged from infancy to adolescence. All patients had neurologic symptoms including seizures, spasticity, dystonia, ataxia, and cognitive decline. Progressive intracerebral calcifications involved deep gray nuclei, brainstem, cerebral and cerebellar white matter, and dentate nuclei and were accompanied by diffuse white matter signal changes and, in five patients, cerebral cysts. Eleven patients had retinal telangiectasias or angiomas. Additional features were skeletal and hematologic abnormalities, intestinal bleeding, and poor growth. Neuropathologic examination showed extensive calcinosis and abnormal small vessels with thickened, hyalinized wall and reduced lumen. Our data suggest that Coats plus syndrome and leukoencephalopathy with calcifications and cysts belong to the same spectrum. The primary abnormality seems to be an obliterative cerebral angiopathy involving small vessels, leading to dystrophic calcifications via slow necrosis and finally to formation of cysts and secondary white matter abnormalities.

Vascular dementia: possible role of the ischemic lesions in mild dementia

ABSTRACTUntil the first half of the 1980s, vascular disorders were the leading cause of dementia patients living in major cities of Japan; at present, Alzheimer's disease is the most common cause. The primary reason for the increase in the relative incidence of dementia due to Alzheimer's disease is the decrease in the number of cases of vascular dementia due to primary and secondary prevention of cerebrovascular disorders. However, no drug can effectively prevent lacunar infarct and the incidence of infarcts in the deep cerebral white matter has not significantly decreased, the prevalence of elderly patients with Alzheimer's disease associated with cerebral infarct is rapidly increasing.The increased relative incidence of Alzheimer's disease in Japan is also attributable to increases in the number of elderly persons and number of patients diagnosed with mild dementia. The living environment of senior citizens in Japan has changed over the last few decades by advances in the level of technology commonly used in society and by increases in the number of nuclear families. Mildly demented patients with hippocampal atrophy and ischemic lesion were increased in number. However differentiating vascular dementia from Alzheimer's disease in elderly demented patients with hippocampal atrophy associated with ischemic lesions remains difficult, asymptomatic cerebral infarcts significantly affect frontal lobular function especially in elderly persons. Appropriate prevention and treatment of ischemia in these patients may help to reduce the number of dementia patients.

Effects of Creatine Supplementation on Cerebral White Matter in Competitive Sportsmen

To determine the neurobiochemical sequelae of oral creatine monohydrate supplementation in active athletes. Eighteen sportsmen underwent single-voxel proton magnetic resonance spectroscopy of the deep frontal cerebral white matter before and after 5 days of oral ingestion: 12 of 18 swallowed 4 x 5 g creatine monohydrate per day, and the remaining swallowed a placebo. Creatine, choline, and N-acetyl spectral resonances were evaluated at both long (135 ms) and short (20 ms) echo times. A mixed-design factorial ANOVA demonstrated no interaction over time in any of the measures (P at least 0.081). The results suggest that, for the given dosage regimen, ingested creatine augmentation does not alter the magnetic resonance visible creatine pool in the deep frontal cerebral white matter of young active sportsmen.

Inflammation in white matter: Clinical and pathophysiological aspects

While the central nervous system (CNS) is generally thought of as an immunopriviledged site, immune-mediated CNS white matter damage can occur in both the perinatal period and in adults, and can result in severe and persistent neurological deficits. Periventricular leukomalacia (PVL) is an inflammatory white matter disease of premature infants that frequently results in cerebral palsy (CP). Clinical and experimental studies show that both hypoxic/ischemic and innate immune mechanisms contribute to the destruction of immature oligodendroglia and of axons in the deep cerebral white matter in PVL. No data are yet available as to whether there is any genetic predisposition to PVL or to its neurological sequelae. Multiple sclerosis (MS) is an inflammatory white matter disease that often begins in young adulthood, causes multifocal destruction of mature oligodendroglia and of axons, and eventually leads to substantial cumulative neurological disability. Certain genetic polymorphisms contribute to susceptibility to MS, and adaptive immune responses to myelin-associated self antigens, or to exogenous antigens that mimic these self antigens, play a central role in the pathophysiology of this disease.

Periventricular Leukomalacia: Overview and Recent Findings

Periventricular leukomalacia (PVL), the main substrate for cerebral palsy, is characterized by diffuse injury of deep cerebral white matter, accompanied in its most severe form by focal necrosis. The classic neuropathology of PVL has given rise to several hypotheses about the pathogenesis, largely relating to hypoxia-ischemia and reperfusion in the sick premature infant. These include free radical injury, cytokine toxicity (especially given the epidemiologic association of PVL with maternofetal infection), and excitotoxicity. Among the recent findings directly in human postmortem tissue is that immunocytochemical markers of lipid peroxidation (hydroxy-nonenal and malondialdehyde) and protein nitration (nitrotyrosine) are significantly increased in PVL. Premyelinating oligodendrocytes, which predominate in periventricular regions during the window of vulnerability to PVL (24 to 34 postconceptional weeks), are the targets of this free radical injury, and suffer cell death. Susceptibility can be attributed, at least in part, to a relative deficiency of superoxide dismutases in the preterm white matter, including premyelinating oligodendrocytes. Several cytokines, including interferon-gamma (known to be directly toxic to immature oligodendroglia in vitro), as well as tumor necrosis factor-alpha and interleukins 2 and 6, have been demonstrated in PVL. Microglia, which express toll-like receptors to bacterial products such as lipopolysaccharide, are increased in PVL white matter and may contribute to the injury. Preliminary work suggests a role for glutamate receptors and glutamate transporters in PVL, as has been seen in experimental animals. These findings pave the way for eventual therapeutic or preventive strategies for PVL.

Neuropathologic Substrate of Cerebral Palsy

Animal models have assisted in understanding the mechanisms of brain injury underlying cerebral palsy. Nevertheless, no such models replicate every aspect of the human disease. This review summarizes the classic and more recent studies of the neuropathology of human perinatal brain injury most commonly associated with cerebral palsy, for use by researchers and clinicians alike who need to analyze published animal models with respect to their fidelity to the human disorder. The neuropathology underlying cerebral palsy includes white-matter injury, known as periventricular leukomalacia, as well as germinal matrix hemorrhage with intraventricular extension, and injury to the cortex, basal ganglia, and thalamus. Each has distinctive features while sharing some risk factors, such as prematurity and/or hypoxia-ischemia in the perinatal period. Periventricular leukomalacia consists of diffuse injury of deep cerebral white matter, with or without focal necrosis. Recent work directly in human postmortem tissue has focused on the role of free radical injury, cytokine toxicity (especially in light of the epidemiologic association of periventricular leukomalacia with maternofetal infection), and excitotoxicity in the development of periventricular leukomalacia. Premyelinating oligodendrocytes, which predominate in periventricular regions during the window of vulnerability to periventricular leukomalacia (24-34 postconceptional weeks), are the targets of free radical injury, as determined by immunocytochemical markers of lipid peroxidation and protein nitration. This maturational susceptibility can be attributed in part to a relative deficiency of superoxide dismutases in developing white matter. Microglia, which respond to cytokines and to bacterial products such as lipopolysaccharide via Toll-like receptors, are increased in periventricular leukomalacia white matter and can contribute to cellular damage. Indeed, several cytokines, including tumor necrosis factor-a and interleukins 2 and 6, as well as interferon-g, have been demonstrated in periventricular leukomalacia. Preliminary work suggests a role for glutamate receptors and glutamate transporters in periventricular leukomalacia based on expression in human developing oligodendrocytes. Germinal matrix hemorrhage, with or without intraventricular hemorrhage, occurs in premature infants and can coexist with periventricular leukomalacia. Studies in human germinal matrix tissue have focused on maturation-based vascular factors, such as morphometry and expression of molecules related to the structure of the blood-brain barrier. Gray-matter injury, seen more commonly in term infants, includes cortical infarcts and status marmoratus. Subtle cortical injury overlying periventricular leukomalacia is the subject of current interest as a possible substrate for the cognitive difficulties seen in patients with cerebral palsy. In summary, it is hoped that work in human tissue, in conjunction with experimental animal models, will lead to eventual therapeutic or preventive strategies for the perinatal brain injury underlying cerebral palsy.

Brain tumor-like lesion in Behçet disease

We report a patient with longstanding Behçet disease who presented sudden onset of headache and facial paresis. The magnetic resonance imaging (MRI) showed a mass in the right thalamus, extending to the lentiform nucleus, subthalamic area, right cerebral peduncle and deep subcortical white matter. Stereotactic brain biopsy disclosed gliosis with no signs of malignancy. The diagnosis of a pseudotumoral form of neuro-Behçet disease was done and she was treated with pulse methylpredinisolone and intravenous cyclophosphamide. After 8 weeks she had improved and a new MRI showed disappearance of the tumor-like lesion. The differential diagnosis, especially with central nervous system tumor is emphasized.

Diffusion-weighted MR Imaging in Patients with Phenylketonuria: Relationship between Serum Phenylalanine Levels and ADC Values in Cerebral White Matter

To prospectively determine the relationship between serum phenylalanine levels and apparent diffusion coefficient (ADC) values in the cerebral white matter of patients with phenylketonuria (PKU). Institutional review board approval was obtained, and participants provided informed consent. Magnetic resonance (MR) imaging, which included T1- and T2-weighted, fluid-attenuated inversion-recovery (FLAIR), and diffusion-weighted examinations, was performed in 21 patients with PKU (nine male and 12 female patients; age range, 3-44 years; mean age, 19.4 years). ADC values in deep cerebral white matter were calculated for each patient. Serum phenylalanine levels were obtained in all patients within 12 days after MR imaging. Serum phenylalanine levels were measured in 16 patients 1 year before MR imaging. ADC values in cerebral white matter and serum phenylalanine levels were compared. A total of 21 control subjects (12 male and nine female patients; age range, 3-33 years; mean age, 20.6 years) underwent MR imaging. ADC values in cerebral white matter were compared with serum phenylalanine levels by using the Pearson correlation. Abnormal high signal intensity in white matter on T2-weighted and FLAIR MR images was noted in patients with PKU who had serum phenylalanine levels of more than 8.5 mg/dL (514.2 micromol/L). Diffusion in posterior deep cerebral white matter tended to be restricted in patients when increased serum phenylalanine levels were measured after MR imaging (r = -0.62). There was a correlation between ADC values in posterior cerebral white matter and serum phenylalanine levels measured 1 year before MR imaging (r = -0.77). ADCs of control subjects were significantly higher than ADCs of patients with PKU (P < .005). Posterior deep white matter in patients with PKU and a serum phenylalanine level of more than 8.5 mg/dL showed high signal intensity in white matter on T2-weighted and FLAIR MR images and revealed decreased ADC. We suggest that to avoid brain-restricted diffusion due to hyperphenylalanemia, patients with PKU should maintain serum phenylalanine levels of less than 8.5 mg/dL (514.2 micromol/L).

Magnetic Resonance Spectroscopy of Memory and Frontal Brain Region in Early Multiple Sclerosis

In vivo proton magnetic resonance spectroscopy (1H-MRS) has been used to assess biochemical changes that occur in demyelinating lesions and in normal appearing white matter (NAWM) in multiple sclerosis (MS) patients. N-acetylaspartate (NAA) levels in MS patients may indicate neural viability. In early stages of MS, patients may suffer from slight cognitive impairment. The objective of this study was to investigate memory function in relation to biochemical properties of frontal brain areas of MS patients. Twenty-one patients with relapsing-remitting MS and 21 healthy comparison subjects were examined psychometrically using the Wechsler Memory Scale (WMS) and the Multiple Sclerosis Functional Composite (MSFC) scale, and (1H-MRS) was used to examine frontal deep white matter (left hemisphere) and the frontal cingulate gyrus (Brodmann areas 24/32, bihemispheric). A significant reduction of the NAA/Creatine (Cr) ratio in the frontal cingulate gyrus among the MS patient group was detected when compared to healthy subjects. A significant decrease in the NAA/Cr ratio was also found in volumes of cerebral deep white matter, including plaques, in the MS patients. No NAA/Cr ratio changes were found in NAWM. Differences in MSFC results did not reach statistical significance, but the WMS general memory score showed a significant statistical difference between the patient group and healthy subjects. Regression analysis showed the gray matter NAA/Cr ratio of the frontal cingulate gyrus to be significantly related to distinct memory functions. The authors conclude that (1H-MRS) of gray matter in early stages of MS may be pertinent in the detections of early metabolic disturbances, particularly in subjects with or without minor neurological impairment. Findings suggest a general relationship between the metabolic status of the frontal cortices and memory function.

Magnetic Resonance Spectroscopy of Memory and Frontal Brain Region in Early Multiple Sclerosis

In vivo proton magnetic resonance spectroscopy (1H-MRS) has been used to assess biochemical changes that occur in demyelinating lesions and in normal appearing white matter (NAWM) in multiple sclerosis (MS) patients. N-acetylaspartate (NAA) levels in MS patients may indicate neural viability. In early stages of MS, patients may suffer from slight cognitive impairment. The objective of this study was to investigate memory function in relation to biochemical properties of frontal brain areas of MS patients. Twenty-one patients with relapsing-remitting MS and 21 healthy comparison subjects were examined psychometrically using the Wechsler Memory Scale (WMS) and the Multiple Sclerosis Functional Composite (MSFC) scale, and (1H-MRS) was used to examine frontal deep white matter (left hemisphere) and the frontal cingulate gyrus (Brodmann areas 24/32, bihemispheric). A significant reduction of the NAA/Creatine (Cr) ratio in the frontal cingulate gyrus among the MS patient group was detected when compared to healthy subjects. A significant decrease in the NAA/Cr ratio was also found in volumes of cerebral deep white matter, including plaques, in the MS patients. No NAA/Cr ratio changes were found in NAWM. Differences in MSFC results did not reach statistical significance, but the WMS general memory score showed a significant statistical difference between the patient group and healthy subjects. Regression analysis showed the gray matter NAA/Cr ratio of the frontal cingulate gyrus to be significantly related to distinct memory functions. The authors conclude that (1H-MRS) of gray matter in early stages of MS may be pertinent in the detections of early metabolic disturbances, particularly in subjects with or without minor neurological impairment. Findings suggest a general relationship between the metabolic status of the frontal cortices and memory function.

Intravascular malignant lymphomatosis: diffusion‐weighted magnetic resonance imaging characteristics

Intravascular malignant lymphomatosis is an unusual condition in which malignant lymphoma cells form microscopic masses within the blood vessels of the central nervous system. Occlusion of the involved blood vessels can lead to multifocal cerebral infarcts. Diffusion-weighted magnetic resonance imaging (MRI) reveals a subacute infarction pattern (bright high signal intensity on b = 1000 s/mm2 images and intermediate apparent diffusion coefficient values) in the cerebral deep white matter. We present MRI findings of a 68-year-old woman with intravascular malignant lymphomatosis involving the cerebral white matter and the thoracic cord.

Magnetization transfer ratio in neuro-Beh�et disease

The aim of this study was to determine the contribution of magnetization transfer ratios (MTRs) in detecting disease in normal-appearing brain regions of patients with neuro-Behçet (NB) disease. Thirty-two patients with NB disease were assessed. Fifteen healthy volunteers were examined as the control group. Magnetic resonance (MR) imaging of the head was performed without and with magnetization transfer (MT) contrast. Signal intensity measurements were obtained from ten anatomical regions (centrum semiovale, corona radiata, internal capsule, forceps major, forceps minor, thalamus, substantia nigra pars compacta, substantia nigra pars grisea, inferior pons and middle cerebellar peduncle) in both groups. Also measured in the NB group were parenchymal lesions in the brain stem, basal ganglia and cerebral deep white matter. MTR was calculated for each measurement. Statistical analysis was performed with Mann-Whitney U and independent t-tests with computer-based SPSS 11.0 for Windows software. A P value below 0.05 was considered statistically significant. The mean MTR of the parenchymal lesions in the NB group was lower than the mean MTR of the normal-appearing parenchyma in both the NB patients and the normal group. For the normal-appearing parenchyma the mean MTR in the NB group was higher than that for the controls for all regions except the corona radiata; however, the difference was statistically significant only for the thalamus. The MRI-visible parenchymal involvement of Behçet's disease causes a decrease in MTR. For the normal-appearing brain, although lacking statistical significance for the most regions studied, the tendency for higher MTR in NB patients compared with controls may offer an insight into the pathophysiology of Behçet's disease.

Acute Intermittent Porphyria

Acute intermittent porphyria (AIP), due to half-normal hydroxymethylbilane synthase activity,is characterized by acute life-threatening neurologic attacks whose etiology remains unclear. To date, only 3 patients confirmed to have homozygous dominant AIP (HD-AIP) have been described (hydroxymethylbilane synthase genotypes R167Q/R167Q and R167W/R173Q). To investigate the genetic, biochemical, clinical, and neuroradiologic features of a severely affected infant with HD-AIP. Clinical, imaging, and genotype/phenotype studies were performed. The proband, homoallelic for hydroxymethylbilane synthase mutation R167W, had approximately 1% of normal hydroxymethylbilane synthase activity, elevated porphyrins and porphyrin precursors, severe psychomotor delay, and central and peripheral neurologic manifestations. When expressed in vitro, the R167W mutant enzyme had less than 2% of normal activity but was markedly unstable, consistent with the proband's severe phenotype. Mitochondrial respiratory chain enzymes were normal. Neuroradiologic studies revealed a unique pattern of deep cerebral white matter injury, with relative preservation of the corpus callosum, anterior limb of the internal capsule, cerebral gray matter, and infratentorial structures. This severely affected patient with HD-AIP expanded the phenotypic spectrum of HD-AIP. His brain magnetic resonance imaging studies suggested selective cerebral oligodendrocyte postnatal involvement in HD-AIP, whereas most structures developed prenatally were intact. These findings indicate that the neurologic manifestations result from porphyrin precursor toxicity rather than heme deficiency and suggest that porphyrin precursor toxicity is primarily responsible for the acute neurologic attacks in heterozygous AIP and other porphyrias.

Posterior Reversible Encephalopathy Syndrome: Magnetic Resonance Imaging and Diffusion-Weighted Imaging in 12 Cases

Posterior reversible encephalopathy syndrome (PRES) is a potentially devastating neurologic syndrome, but timely treatment may lead to complete reversal of the disease course. We reviewed 12 cases of PRES and describe the clinical history and imaging findings, including conventional magnetic resonance imaging (MRI), diffusion-weighted imaging (DWI), and calculated apparent diffusion coefficient (ADC) maps, used to establish the diagnosis of PRES. Three male and nine female patients aged between 11 and 70 years (mean, 37 years) with clinical and imaging findings consistent with PRES were enrolled in the study. All patients had undergone conventional MRI and 10 had undergone additional DWI studies. Ten patients had follow-up MRI studies. DWI was performed using a 1.5T system with a single-shot spin-echo echoplanar pulse sequence. Initial and follow-up neuroimaging and clinical history were reviewed. Lesions were almost always present over the posterior circulation, mainly the parieto-occipital region, affecting primarily the white matter. The anterior circulation region, brainstem, cerebellum, deep cerebral white matter, and thalamus were also involved in five cases. Conventional MRI revealed hyperintensity on T2-weighted and fluid-attenuated inversion recovery images. DWI showed isointensity and increased signal intensity on ADC values in all cases, indicating vasogenic edema. Clinical and MRI follow-up showed that the symptoms and radiologic abnormalities could be reversed after appropriate treatment of the causes of PRES in most patients (9 of 10). In one patient, the ADC value was lower on follow-up images, indicating cytotoxic edema with ischemic infarct. DWI was a useful complement to MRI in the diagnosis of PRES.

Microvasculature of the human cerebral white matter: arteries of the deep white matter.

The vascular architecture of the human cerebral deep white matter was studied using soft X-ray and diaphanized specimens, achieved by intra-arterial injection of barium and vascular stain respectively, and also by electron microscopic examination of the corrosion cast of arteries in normal adult brains. The deep white matter arteries passed through the cerebral cortex with a few branches to the cortex and ran straight through the white matter. The arteries concentrated ventriculopetally to the white matter around the lateral ventricle. Anastomoses were noted around the ventricular wall at the terminals of the deep white matter arteries. No centrifugal branches irrigating the periventricular white matter from the lenticulo-striate arteries were observed in the present study. The presence of anastomoses among the terminal branches of deep white matter arteries protects against ischemic change or infarction in this area from an occlusion of a single deep white matter artery. This may lead to development of terminal zone infarction from ischemia or vascular diseases, affecting multiple deep white matter arteries. The subcortical and deep white matter arteries had thick adventitial sheaths and large adventitial spaces in the white matter but not in the cortex. The presence or absence of the adventitial space is regarded as another characteristic difference between the arteries in the white matter and cortex. This difference may influence pathological changes in vascular lesions in these respective areas.

Calcification of the Basal Ganglia in Chronic Hypoparathyroidism

An 80-yr-old man with a more than 60-yr history of postsurgical hypoparathyroidism was evaluated for hypocalcemia detected during hospitalization after a fall. The patient had long-standing intermittent paresthesias in his distal extremities, but denied muscle cramps, tetany, or seizures. His past medical history was remarkable for an episode of nephrolithiasis in his 20s. He had been taking up to 4000 mg calcium carbonate (oral, daily) before admission. On examination, Chvostek and Trousseau signs, tremor, and rigidity were absent. Laboratory studies included: 5.9 mg/dl serum calcium (normal range, 8.4–10.5), 0.78 mmol/liter ionized calcium (normal range, 1.13–1.32), 6.7 mg/dl phosphate (normal range, 2.7–4.5), 3.2 g/dl albumin (normal range, 3.5–5.3), and 1 pg/ml intact PTH (normal range, 10–65). In Fig. 1, brain computed tomography showed diffuse, symmetric parenchymal calcifications involving the dentate nuclei (A), thalami (B, curved arrow), globus palladi (B, arrowhead), caudate heads (B, straight arrow), and deep cerebral white matter (C). The patient was treated with 0.5 g calcitriol and 1000 mg calcium carbonate (oral, daily). After 1 week, his chronic paresthesias resolved and serum calcium rose to 9.2 mg/dl. Although Virchow (1) and Bamberger (2) independently described the histology of bilateral basal ganglia calcifications in 1855, it was not until 1939 that their association with chronic hypoparathyroidism was recognized by Eaton et al. (3). Microscopic colloid deposition around cerebral blood vessels is followed by calcification most commonly in the basal ganglia, but also in the thalami, dentate nuclei, cerebral cortex, centrum semiovale, and mesencephalic gray matter (4, 5). Patients may remain asymptomatic or develop Parkinsonian features.

Yeast as a model for mitochondria-related human disorders

Leukoencephalopathy with brain stem and spinal cord involvement and lactate elevation (LBSL) is a recently identified autosomal recessive disorder with early onset of symptoms and slowly progressive pyramidal, cerebellar and dorsal column dysfunction. LBSL is characterized by distinct white matter abnormalities and selective involvement of brainstem and spinal cord tracts. The purpose of this study is to assess the imaging features of the involved white matter tracts in cases of LBSL by MRI.We retrospectively reviewed the imaging features of the selectively involved white matter tracts in sixteen genetically proven cases of leukoencephalopathy with brainstem and spinal cord involvement and elevated brain lactate (LBSL). All patients presented with slowly progressive cerebellar sensory ataxia with spasticity and dorsal column dysfunction. MRI of the brain and spine using 1.5 T machine and proton magnetic resonance spectroscopy (1H MRS) on the abnormal white matter were done to all patients. The MRI and MRS data sets were analyzed according to lesion location, extent, distribution and signal pattern as well as metabolite values and ratios in MRS. Laboratory examinations ruled out classic leukodystrophies.In all cases, MRI showed high signal intensity in T2-weighted and FLAIR images within the cerebral subcortical, periventricular and deep white matter, posterior limbs of internal capsules, centrum semiovale, medulla oblongata, intraparenchymal trajectory of trigeminal nerves and deep cerebellar white matter. In the spine, the signal intensity of the dorsal column and lateral cortico-spinal tracts were altered in all patients. The subcortical U fibers, globi pallidi, thalami, midbrain and transverse pontine fibers were spared in all cases. In 11 cases (68.8%), the signal changes were inhomogeneous and confluent whereas in 5 patients (31.2%), the signal abnormalities were spotty. MRI also showed variable signal abnormalities in the sensory and pyramidal tracts in addition to the brainstem and cerebellar connections. Proton MRS showed consistent elevation of the lactate within the abnormal white matter.Distinct MRI findings in the form of selective affection of subcortical and deep white matter tracts of the brain (involving the posterior limb of internal capsules and sparing the subcortical U fibers), dorsal column and lateral cortico-spinal tracts of the spinal cord should lead to the diagnosis of LBSL supported by the presence of lactate peak in 1H MRS. The disease can be confirmed by the analysis of the disease gene DARS2.

BIPLEDs with Complete and Rapid Recovery in a Patient with AIDS Encephalopathy

ABSTRACT.A 33-year-old male with AIDS (CD4=12), dementia, spasticity, and MRI findings of cerebral atrophy and deep white matter changes was admitted for the treatment of chronic cough and cellulitis of the legs. Two days after admission, the patient exhibited the first seizure of his life—a generalized convulsion lasting five minutes. An EEG obtained 14 hours after the convulsion revealed bilateral independent periodic lateralized epileptiform discharges (BIPLEDs) with prominent asynchrony. CT and MRI showed abnormalities similar to those present one year before. CSF studies obtained the day after the seizure were normal. The only medication started in the hospital prior to the onset of the seizure was intravenous nafcillin. Immediately after the seizure, nafcillin was discontinued and a loading dose of 1500 mg PE of fosphenytoin was given followed by oral maintenance. Another EEG, three days later, demonstrated the complete resolution of BIPLEDs. No other seizures occurred. With antibiotic therapy the cellulitis and pneumonia resolved and, within two weeks, the patient was discharged home on phenytoin. We propose that in patients with AIDS encephalopathy, the occurrence of coma, seizures, and BIPLEDs should not be assumed to be a poor prognostic sign.