Thalamic metabolic abnormalities in patients with Huntington's disease measured by magnetic resonance spectroscopy.

Huntington's disease (HD) is a neurologic disorder that is not completely understood; its fundamental physiological mechanisms and chemical effects remain somewhat unclear. Among these uncertainties, we can highlight information about the concentrations of brain metabolites, which have been widely discussed. Concentration differences in affected, compared to healthy, individuals could lead to the development of useful tools for evaluating the progression of disease, or to the advance of investigations of different/alternative treatments. The aim of this study was to compare the thalamic concentration of metabolites in HD patients and healthy individuals using magnetic resonance spectroscopy. We used a 2.0-Tesla magnetic field, repetition time of 1500 ms, and echo time of 135 ms. Spectra from 40 adult HD patients and 26 control subjects were compared. Quantitative analysis was performed using the LCModel method. There were statistically significant differences between HD patients and controls in the concentrations of N-acetylaspartate+N-acetylaspartylglutamate (NAA+NAAG; t-test, P<0.001), and glycerophosphocholine+phosphocholine (GPC+PCh; t-test, P=0.001) relative to creatine+phosphocreatine (Cr+PCr). The NAA+NAAG/Cr+PCr ratio was decreased by 9% and GPC+PCh/Cr+PCr increased by 17% in patients compared with controls. There were no correlations between the concentration ratios and clinical features. Although these results could be caused by T1 and T2 changes, rather than variations in metabolite concentrations given the short repetition time and long echo time values used, our findings point to thalamic dysfunction, corroborating prior evidence.

Thalamic metabolic abnormalities in patients with Huntington's disease measured by magnetic resonance spectroscopy

Huntington's disease (HD) is a neurologic disorder that is not completely understood; its fundamental physiological mechanisms and chemical effects remain somewhat unclear. Among these uncertainties, we can highlight information about the concentrations of brain metabolites, which have been widely discussed. Concentration differences in affected, compared to healthy, individuals could lead to the development of useful tools for evaluating the progression of disease, or to the advance of investigations of different/alternative treatments. The aim of this study was to compare the thalamic concentration of metabolites in HD patients and healthy individuals using magnetic resonance spectroscopy. We used a 2.0-Tesla magnetic field, repetition time of 1500 ms, and echo time of 135 ms. Spectra from 40 adult HD patients and 26 control subjects were compared. Quantitative analysis was performed using the LCModel method. There were statistically significant differences between HD patients and controls in the concentrations of N-acetylaspartate+N-acetylaspartylglutamate (NAA+NAAG; t-test, P<0.001), and glycerophosphocholine+phosphocholine (GPC+PCh; t-test, P=0.001) relative to creatine+phosphocreatine (Cr+PCr). The NAA+NAAG/Cr+PCr ratio was decreased by 9% and GPC+PCh/Cr+PCr increased by 17% in patients compared with controls. There were no correlations between the concentration ratios and clinical features. Although these results could be caused by T1 and T2 changes, rather than variations in metabolite concentrations given the short repetition time and long echo time values used, our findings point to thalamic dysfunction, corroborating prior evidence.

Granulomatous tissue response in germinoma, a diagnostic pitfall in endoscopic biopsy.

We report a case of a 24-year-old man with a right thalamic germinoma that initially mimicked a granulomatous inflammation, compatible with neurosarcoidosis based on clinical symptoms, imaging results and histology of an endoscopically navigated biopsy. A second biopsy, prompted by clinical course, and performed openly from parieto-lateral revealed the underlying germinoma, obscured in the first biopsy by a granulomatous tissue response, particularly at the tumor edge. The present case highlights granulomatous inflammatory tissue response on the tumor edge of germinoma as a tumor-immanent diagnostic challenge. This diagnostic problem is aggravated by stereotactic and endoscopic approaches. We conclude that granulomatous inflammation in a specimen obtained by biopsy of a midline lesion should always be considered for the differential diagnosis of germinoma. Stereotactic and endoscopic surgery should sample several different target points within the lesion. Because of tumor heterogeneity of germinoma, the open biopsy approach is advantageous compared to endoscopic or stereotactic techniques for germinoma and should be considered if a germinoma is in the differential diagnosis and if allowed by the clinical situation.

Thalamic infarct presenting with thalamic astasia.

Astasia, inability to stand unsupported despite good strength, resembles the marked balance impairment of patients with vestibulocerebellar disease. We describe a patient with unilateral thalamic infarct that presented with astasia. A 76-year-old hypertensive woman was admitted to our hospital because of marked unsteadiness. On neurological examination, she could not stand unsupported and the woman's body swayed back and forth markedly. The swaying was not compensated for by her taking a step forward or backward, and she frequently collapsed when support was withdrawn. Diffusion-weighted magnetic resonance image revealed a discrete infarct within the right posterolateral thalamus. Brain single photon emission computerized tomography revealed markedly decreased regional cerebral blood flow within in the right thalamus with concomitant left superior cerebellar region. We discuss the possible pathomechanisms of thalamic astasia.

Early uncoupling of cerebral blood flow and metabolism after bilateral thalamic infarction.

Cerebral blood flow and metabolism may be uncoupled in the early phases after stroke onset. Prior reports of bilateral thalamic stroke have described subsequent coupling of blood flow and metabolism during the chronic stage. We chronicled the evolving relationship of blood flow and metabolism with concomitant single photon emission CT and positron emission tomography from the subacute to chronic phase following bilateral thalamic infarction.

Rhabdoid tumor of the thalamus.

Rhabdoid tumors of the central nervous system are uncommon tumors. About 188 cases have been reported in the literature so far. In this report, we describe a case of a rhabdoid tumor of the thalamus in a 35-year-old male patient. Light microscopic and immunohistochemical features are discussed and the relevant literature reviewed.

Unexpected accumulation of thallium-201 in bilateral thalamic venous infarction induced by arteriovenous fistula in the posterior fossa: report of a case.

We encountered unexpected accumulation of thallium-201 in a patient with thalamic dementia resulting from bithalamic venous infarction induced by arteriovenous fistula in the posterior fossa The site and degree of abnormal accumulation varied between early and delayed thallium-201 SPECT images. This unexpected and complicated accumulation of thallium-201 appeared to depend on not only breakdown of the blood-brain barrier but also on the hemodynamics of this type of venous infarction.

Release of monoamines and nitric oxide is involved in the modulation of hyperpolarization-activated inward current during acute thalamic hypoxia.

Using slices of the dorsal lateral geniculate nucleus, it has been shown that, in the presence of excitatory and inhibitory amino acid antagonists, brief periods of hypoxia (3-4 min of 95% N(2)/5% CO(2)) induce in thalamocortical neurons an increase in instantaneous input conductance (G(N)) accompanied by an inward shift in baseline holding current (I(BH)). These effects have been suggested to be mediated, at least in part, by a positive shift in the voltage-dependence of the hyperpolarization-activated, mixed Na(+)/K(+) current (I(h)) and a change in its activation kinetics which transforms it into an almost instantaneously activated current. In this study, using the whole-cell patch-clamp technique, the contribution of an increased Ca(2+)-dependent transmitter release to the hypoxic response of thalamocortical neurons was further investigated using (i) blockers of calcineurin, a Ca(2+)/calmodulin-activated phosphatase that selectively regulates Ca(2+)-dependent release, and (ii) antagonists of neurotransmitters that are known to modulate I(h). Thalamocortical neurons (n = 23) recorded with electrodes filled with calcineurin autoinhibitory fragment (30-250 microM), a membrane impermeable blocker of calcinuerin, showed no difference either in resting, or in the hypoxia-induced changes in, G(N), I(BH) and I(h), when compared to thalamocortical cells patched with electrodes that did not contain calcineurin autoinhibitory fragment. In contrast, in 18 of these neurons recorded with calcineurin autoinhibitory fragment-filled electrodes, bath application either of cyclosporin-A (20 microM) or tacrolimus (50-100 microM), two membrane permeable blockers of calcineurin, abolished the effects of hypoxia on G(N), I(BH), and I(h). Separate application of noradrenaline, serotonin, histamine and nitric oxide antagonists produced only a small depression of the hypoxic response, while concomitant bath application of these antagonists decreased the hypoxia-induced changes in G(N) and I(BH) by 55 and 42%, respectively (n = 12). Concomitant bath application of 8-bromo-adenosine-3'5'-cyclicmonophosphate and 8-bromo-guanosine-3'5'-cyclicmonophosphate (both 1mM), which are known to mediate the action of these transmitters on I(h), increased G(N) (40%), decreased I(h) time-constant of activation (30%) and significantly occluded (50%) the hypoxia-induced effect on G(N) and I(BH). Thalamocortical neurons (n = 6) patched with electrodes filled with 8-bromo-adenosine-3'5'-cyclicmonophosphate and 8-bromo-guanosine-3'5'-cyclicmonophosphate (both 1 mM) showed a larger G(N) than the one recorded with the standard internal solution, and a significant depression of the hypoxia-induced changes in G(N) and I(BH). These results indicate that during acute thalamic hypoxia an increased release of noradrenaline, serotonin, histamine and nitric oxide is responsible for transforming I(h) into an instantaneously activating current via cyclic AMP- and cyclic GMP-mediated mechanisms.

Possible common origin of alpha-fetoprotein- and human chorionic gonadotropin--secreting cells in intracranial germ cell tumor. Case report.

A primary intracranial germ cell tumor in a 16-year-old boy secreted both alpha-fetoprotein (AFP) and human chorionic gonadotropin (HCG). The tumor, located in the right thalamus, contained germinomatous, trophoblastic, and endodermal sinus components. To identify AFP- and HCG-secreting cells, germ cells from the surgical specimen were cultured in vitro. These cultured cells secreted AFP and HCG for 10 weeks, and immunohistochemical studies showed that some of the cells secreted both AFP and HCG. These findings suggest that multipotential germ cells migrate to the encephalic region and may become germ cell tumors containing various types of tissue.

A panencephalopathic type of Creutzfeldt-Jakob disease with selective lesions of the thalamic nuclei in 2 Swiss patients.

Creutzfeldt-Jakob disease (CJD), a subacute spongiform encephalopathy, is generally included among the group of human and animal diseases which is transmissible by a non-conventional agent, the prion, whose expression is conditioned by the host's genome. The process leading to neuropathological changes is still unknown. We report the neuropathological findings in 2 cases of the "panencephalopathic" variant of CJD, which is relatively common in Japan, but extremely rare in Europe and North America. When compared with the classical form this variant is characterized by a relatively long clinical course with persistent vegetative state and primary involvement of the white matter presenting in the form of demyelination and gemistocytic gliosis. The selective involvement of certain thalamic nuclei is a particular pathological feature in both our cases. There was practically complete neuronal loss with diffuse gliosis of the anteroventral (AV) and dorsomedial (DM) nuclei, while the neuronal loss in the pulvinar remained moderate: the other nuclei were apparently spared. A similar involvement of the thalamus has been reported in fatal familial insomnia, a recently described prion disease in which these lesions are predominant. A comparable distribution has also been observed in other degenerative neurological diseases such as Steele-Richardson-Olszewski disease, Alzheimer disease, and thalamic dementia (selective thalamic atrophy or with multisystemic degeneration). The AV and DM nuclei, commonly referred to as "limbic thalamus" represent phylogenetically the most recent thalamic structures and would appear to play an important role in the superior functions in man as memory, attention and awareness. In our cases thalamic lesions are selective, bilateral, and symmetric, not explained by Wallerian degeneration. These lesions may be due to the primary pathogenetic properties of the infectious agent. The rapid clinical evolution in a persistent vegetative state could be consequential to precocious and severe disfunction of the limbic thalamus.

Pathophysiology of central (thalamic) pain: combined change of sensory thalamus with cerebral cortex around central sulcus.

In 13 patients with central (thalamic) pain after stroke, CT, MRI, PET scan and intraoperative thalamic microrecordings were performed. Electrophysiological studies showed that irregular burst discharges were often encountered in the posterolateral thalamus. The more often the irregular burst discharges were encountered, the greater the decrease of sensory response in the posterolateral thalamus. Metabolic studies showed that regional cerebral glucose metabolism decreased in both the posterolateral thalamus and in the cortical postcentral area on the lesioned side in all cases. In the thalamic lesion cases in which many irregular burst discharges were found in the posterolateral thalamus, regional cerebral glucose metabolism and the relative value of glucose to oxygen metabolism increased in the cortical precentral area on the lesioned side. It was suggested that decreased activity with abnormal burst discharge in the posterolateral (sensory) thalamus associated with changes in cortical activity adjacent to the central sulcus might be related to the genesis of central (thalamic) pain. It is emphasized that cortical activity decreased in the postcentral area, but often increased in the precentral area.

Frontal lobe dysfunction following infarction of the left-sided medial thalamus.

We treated a 62-year-old woman who developed a dramatic change in personality and behavior following a discrete left-sided medial thalamic infarction involving the dorsomedial nucleus. Neuropsychological testing demonstrated severe impairment of complex executive behaviors that are usually associated with frontal lobe function. Electroencephalography and single-photon emission computed tomography strongly implicated dysfunction of the ipsilateral frontal lobe. This case further supports a functional and physiologic thalamofrontal linkage as part of a broader cerebral network modulating complex human behavior.

Widespread functional effects of discrete thalamic infarction.

In order to investigate functional effects of various thalamic structures on metabolism in remote, morphologically intact cerebral regions, we used positron emission tomography of (18F)-2-fluoro-2-deoxy-D-glucose to study regional cerebral metabolic rates of glucose (rCMRGlu) in 11 patients with chronic unilateral or bilateral infarcts strictly confined to the thalamus. Patients were grouped according to computed tomographic scans showing anterior (three), medial (four), or posterior (four) lesions. Compared with a matched group of 11 healthy subjects (hemispheric CMRGlu 35.2 +/- 3.49 mumol/100 g per minute), glucose metabolism was significantly lower in the hemisphere ipsilateral to the infarction (31.2 +/- 2.97 mumol/100 g per minute). Patients with bilateral infarcts had lower hemispheric CMRGlu (29.9 +/- 2.74 mumol/100 g per minute) than those with unilateral lesions (32.2 +/- 2.97 mumol/100 g per minute). Depending on infarct location within the thalamus, there was differential depression of rCMRGlu, with the largest effects on frontal and occipital areas in medial infarctions. Except for ipsilateral thalamic deactivation, metabolic patterns with anterior thalamic infarcts were close to normal, while posterior infarcts mostly depressed rCMRGlu in the visual and in the inferior limbic cortex. Cerebellar metabolic rates were within normal limits in most cases. These patterns of regional cerebral deactivation may be related to categories of thalamic projections--intrathalamic, to limbic system and basal ganglia, diffuse to most cortical areas, and specific to defined neocortical areas. Even small brain lesions may have widespread functional sequelae, potentially demonstrable by positron emission tomography.

Membranous lipodystrophy (Nasu-Hakola disease) with thalamic degeneration: report of an autopsied case.

An autopsied case of membranous lipodystrophy (Nasu-Hakola disease, NHD) with thalamic degeneration was reported. A 34-year-old Japanese man was diagnosed as having NHD by bone biopsy prior to the onset of clinical symptoms. His maternal grandfather and paternal grandmother are cousins, but this family history is negative for NHD. He developed frontal lobe syndrome at the age of 35 with progressive dementia, and died of acute renal failure at the age of 46. Gross inspection of the brain detected atrophy and softening of the cerebral white matter, predominantly in the frontal lobe. Microscopically, numerous spheroids, predominant fibrillary gliosis with less prominent demyelination "dissociation glio-myélinique" and scanty sudanophilic lipid droplets were observed, indicating the sclerosing type of NHD. An unusual patholgoical finding in this case was selective involvement of the thalamic nuclei with preservation of the other gray matter except for focal cortical necrosis. The topography of the affected thalamic nuclei is similar to that of systemic thalamus degeneration. An association with thalamic degeneration in NHD has not been previously reported. The present case suggests that NHD also affects the thalamus.

Effects of capsular or thalamic stroke on metabolism in the cortex and cerebellum: a positron tomography study.

We used positron emission tomography to study the cortical and cerebellar metabolic rates in 21 strictly selected patients with pure internal capsular infarct (n = 8), thalamocapsular hemorrhage (n = 6), or pure thalamic stroke (n = 7). Significant diffuse ipsilateral cortical hypometabolism relative to 62 controls free of cerebrovascular risk factors was frequently, although not consistently, found in the 13 patients with thalamocapsular or thalamic lesions and neuropsychological impairment but was absent from the eight patients with pure internal capsule infarct and free of neuropsychological deficit. These data suggest that damage to the thalamus or the thalamocortical projections is important in the development of ipsilateral cortical hypometabolism and that the latter may underlie the associated neuropsychological impairment. Significant contralateral cerebellar hypometabolism relative to 49 controls was found in three of six patients with pure internal capsule infarct, suggesting a pathogenetic role for the corticopontocerebellar system. However, the occurrence of hypometabolism in two of six patients with thalamic lesions indicates that this phenomenon may also result either from damage to the ascending cerebellothalamocortical system or indirectly from hypofunction of the cerebral cortex. No systematic association was observed between crossed cerebellar hypometabolism and ipsilateral ataxia.

Presence of Schwann cells in neurodegenerative lesions of the central nervous system.

Ultrastructural analysis of neurodegenerative CNS lesions produced by an excitotoxic substance revealed that the majority of cells ensheathing axons were not oligodendrocytes. By their morphology and the presence of both a basal lamina and collagen fibers they were identified as Schwann cells. The presence of Schwann cells, whose growth-promoting role in the peripheral nervous system has been largely documented, may account for the development of regenerating growth cones which have been observed in the excitotoxically lesioned central nervous system. Further support for this hypothesis came from the analysis of fetal neural transplants implanted into the lesioned area. Schwann cells ensheathing axons were indeed numerous in the neuron-depleted area surrounding the transplants, where neurite outgrowth of graft origin occurred.

[Cortical hypometabolism after a thalamic lesion in man: positron tomography study]. / Hypométabolisme cortical après lésion thalamique chez l'homme: étude par la tomographie a positons.

We used positron emission tomography to study the effects of unilateral vascular thalamic lesions on cortical oxygen or glucose utilisation in 10 patients. There was a significant ipsilateral cortex hypometabolism in 9 of the 10 patients, affecting diffusely the whole cortical mantle. The only patient spared was free of neuropsychological deficit at time of PET study. In 4 patients, the magnitude of ipsilateral cortical hypometabolism was significantly less at follow-up PET study, together with improved neuropsychological function. When plotted altogether, the 14 studies showed a significant tendency for the hypometabolism to improve with time elapsed since clinical onset. On the whole, these data suggest that the ipsilateral cortical hypometabolism reflects an essentially functional alteration an not only a degenerating process. This most likely indicates a cortical deafferentation due to loss of non-specific thalamo-cortical connections, i.e. a phenomenon akin to "diaschisis". However, a causal relationship between cortical hypometabolism and neuropsychological deficit cannot be firmly established from the present data.

Depressed cerebellar glucose metabolism in supratentorial tumors.

Fifty-four patients with supratentorial tumor and one with brainstem tumor were examined with positron emission tomography (PET) using [18F]fluoro-deoxyglucose (FDG). Twenty-one of these cases had satisfactory studies of the cerebellum. Of these, 12 showed significant metabolic asymmetry between the two cerebellar hemispheres, with the rate of glucose utilization in the hemisphere contralateral to the cerebral tumor being 8-34% lower than on the ipsilateral side, as compared with a right-left asymmetry of only--1.6% +/- 2.1% standard deviation for a group of 5 normal subjects. In these 12 cases the tumor involved the sensorimotor cortex and/or the thalamus with varying degrees of hemiparesis being present. For the remaining 9 patients with no significant cerebellar metabolic asymmetry, the tumor involved regions other than the sensorimotor cortex, and unilateral motor dysfunction was not a prominent clinical feature. The correlation between cerebellar metabolic suppression and unilateral motor dysfunction observed in our cases appears to be due to impairment or interruption of the cortico-thalamo-ponto-olivo-cerebellar circuitry by either the tumor itself or by edema. These results illustrate the ability of FDG-PET scans to detect metabolic changes, not apparent on CT scans, in areas of the brain remote from the primary lesion.