Spinal MR imaging in Vitamin B12 deficiency: Case series; differential diagnosis of symmetrical posterior spinal cord lesions

We report three cases of Vitamin B12 deficiency with symmetrical posterior spinal cord lesions and discuss the differential diagnosis, some of which are not well known. Because the degree of resolution of the clinical symptoms in subacute combined degeneration depends on early detection, MRI findings should not be missed.     

Amyotrophic lateral sclerosis with dementia showing clinical parkinsonism and severe degeneration of the substantia nigra: Report of an autopsy case

An autopsy case of amyotrophic lateral sclerosis with dementia (ALS‐D) showing clinically overt parkinsonism and severe degeneration of the substantia nigra is reported. The patient was a 78‐year‐old man who died after a 2‐year clinical course characterized by parkinsonism that was responsive to Levodopa (L‐DOPA) treatment. Motor neuron symptoms and dementia were not apparent ante‐mortem. The autopsy demonstrated the severe degeneration of the substantia nigra without α‐synucleinopathy‐related changes. Finely granular mineralization of necrotic neurons was a unique finding in the substantia nigra. The mild loss of spinal anterior horn cells, the appearance of several Bunina bodies and the degeneration of the hippocampal subiculum and temporal cortex were also noted. A small number of ubiquitinated intra‐cytoplasmic inclusions were found in neurons of the dentate fascia of the hippocampus and the temporal and frontal cortices. Although the degeneration of the substantia nigra is a common finding in ALS‐D, patients seldom develop clinically overt parkinsonism. This case indicates that patients with ALS‐D rarely present with predominantly parkinsonian clinical features and these symptoms and signs can be improved by L‐DOPA treatment.     

A case of subacute combined degeneration of the spinal cord due to folic acid and copper deficiency

Subacute combined degeneration of the spinal cord (SACD) is a rare neurologic disorder manifesting progressive symptoms of paresthesia and spastic paralysis. Herein we present an autopsy case of SACD caused by folic acid and copper deficiency. A 16-year-old male presented with gradually worsening unsteady gait, and bladder and rectal dysfunction. He had a medical history of T-cell acute lymphoblastic leukemia (T-ALL), diagnosed 1.5?years previously. The patient had undergone chemotherapy, including methotrexate, as well as allogeneic bone mallow transplantation. Laboratory tests revealed normal vitamin B₁₂ and methylmalonic acid concentration, but reduced serum copper, ceruloplasmin and folic acid concentrations. Magnetic resonance imaging revealed symmetrical T2 signal hyperintensities in the posterior and lateral spinal cord. The patient was treated with oral copper, oral folate, and intravenous vitamin B₁₂. A month after this treatment, the patient’s symptoms were unchanged, and 2?months later he died of acute adrenal insufficiency. The pathological findings of the spinal cord were compatible with SACD. Because SACD is usually reversible with early treatment, it should be suspected in high-risk patients undergoing chemotherapy or those who are malnourished with characteristic symptoms of SACD, even in young patients.     

MELAS with diffuse degeneration of the cerebral white matter: Report of an autopsy case

Up to now diffuse white matter demyelination of the cerebrum has been reported in only a few cases of mitochondrial encephalopathy with lactic acidosis and stroke‐like episodes (MELAS). Here we document an autopsy case with this rare neuropathology. Most MELAS cases are diagnosed antemortem by A3243G transition of mitochondrial DNA. While cerebral damage including necrotic foci in the cerebral cortex are common findings in MELAS, prominent white matter involvement best characterizes this MELAS case. There were numerous necrotic foci, varying in size and chronological stage, in the cerebral white matter. In the areas of the white matter without necrotic foci, there was diffuse fibrillary gliosis with the loss of axons and oligodendrocytes. The gliosis was dominant in the deep white matter, sparing the U‐fiber. The cerebral cortex showed diffuse cortical atrophy with few scattered necrotic foci. Distribution of the cerebral lesions does not coincide with the territory of blood supply. The vascular wall presented only slight to mild hyalinosis. We assumed a common pathogenesis to the cortical lesions and the white matter change. The pathogenesis of the present diffuse cerebral lesions may not be just secondary to circulatory disturbance but partly due to metabolic abnormality.     

Myelopathy mimicking subacute combined degeneration in a Down syndrome patient with methotrexate treatment for B lymphoblastic leukemia: Report of an autopsy case

We report clinicopathological features of a 23‐year‐old woman with Down syndrome (DS) presenting with subacute myelopathy treated with chemotherapy, including intravenous and intrathecal administration of methotrexate (MTX), and with allogenic bone‐marrow transplantation for B lymphoblastic leukemia. Autopsy revealed severe demyelinating vacuolar myelopathy in the posterior and lateral columns of the spinal cord, associated with macrophage infiltration, marked axonal loss and some swollen axons. Pathological changes of posterior and lateral columns were observed from the medulla oblongata to lumbar cord. Proximal anterior and posterior roots were preserved. Cerebral white matter was relatively well preserved. There were no vascular lesions or meningeal dissemination of leukemia. Longitudinal extension of cord lesions was extensive, unlike typical cases of subacute combined degeneration (SACD), but distribution of lesions and histological findings were similar to that of SACD. DS patients show heightened sensitivity to MTX because of their genetic background. Risk factors for toxic myelopathy of DS are discussed, including delayed clearance of MTX despite normal renal function, alterations in MTX polyglutamation and enhanced folic acid depletion due to gene dosage effects of chromosome 21. Alteration of folate metabolism and/or vitamin B₁₂ levels through intravenous or intrathecal administration of MTX might exist, although vitamin B₁₂ and other essential nutrients were managed using intravenous hyperalimentation. To the best of our knowledge, this is the first report of an autopsy case that shows myelopathy mimicking SACD in a DS patient accompanied by B lymphoblastic leukemia. The case suggests a pathophysiological mechanism of MTX‐related myelopathy in DS patients with B lymphoblastic leukemia mimicking SACD.     

Constant involvement of the Betz cells and pyramidal tract in multiple system atrophy: a clinicopathological study of seven autopsy cases

We investigated clinicopathologically the pyramidal signs, including spasticity, hyperreflexia, and Babinski’s sign, and the involvement of the pyramidal tract and primary motor cortex, in seven Japanese autopsy cases of multiple system atrophy (MSA). Pyramidal signs were observed in six (86%) of the seven autopsy cases. Hyperreflexia and Babinski’s sign were each evident in five patients, but spasticity was observed in only one patient. Loss of Betz cells and presence of glial cytoplasmic inclusions in the primary motor cortex were noticed in all seven cases. Astrocytosis in the fifth layer of the primary motor cortex was noticed in five cases, but its presence was not related to the duration of the disease. Involvement of the pyramidal tract in the spinal cord, particularly of the small myelinated fibers, was observed in all seven cases, but no involvement of the pyramidal tract in the midbrain was evident in any of the six cases in which this structure was examined. In MSA, pyramidal signs were shown to be present more frequently than believed before, and the clinicopathological correlation between pyramidal signs and involvement of the pyramidal tract was obvious. Constant involvement of Betz cells in MSA has not been reported. Our clinicopathological findings may also make a contribution to the understanding of the clinicopathological hallmarks of MSA. Received: 28 June 1999 / Revised: 13 September 1999 / Accepted: 30 September 1999     

The role of the posterior parietal lobe in prism adaptation: Failure to adapt to optical prisms in a patient with bilateral damage to posterior parietal cortex

We studied a patient (J.J.) with bilateral damage to those regions of the posterior parietal cortex (PPC) thought to be involved in prism adaptation. We demonstrated, for the first time in a parietal patient, that J.J. was unable to adapt to the visual perturbation induced by the optical prisms with either hand within four times the number of trials required by healthy adult subjects. We offer a novel account for the role of the PPC in prism adaptation: that the reach direction to the veridical target location specified in extrinsic limb-based coordinates must be de-coupled from the gaze direction to the perceived target location specified by intrinsic oculocentric coordinates in order to produce spatially accurate movements. This spatial discrepancy between gaze direction and reach direction may provide the necessary training signal required by the cerebellum to update the current internal model used to maintain spatial congruency between visual and proprioceptive maps of peripersonal space. The hypothesis is discussed in relation to recent disconnectionist accounts of optic ataxia.     

An autopsy case of drug‐induced diffuse cerebral axonopathic leukoencephalopathy: The pathogenesis in relation to reversible posterior leukoencephalopathy syndrome

An autopsy case of diffuse axonopathic leukoencephalopathy induced by drug treatment is reported. A 70‐year‐old woman with multiple myeloma developed encephalopathy several days after completing a course of intravenous human immunoglobulin (IVIg) and granulocyte‐colony stimulating factor (G‐CSF), and died within I month. T2‐weighted MRI demonstrated multifocal high‐signal areas in the bilateral cerebral white matter, especially in the right frontal lobe. Neuropathologically, multifocal hydropic axonal swelling with a poor glial reaction was recognized diffusely in the bilateral deep cerebral white matter, being especially marked in the frontal lobe. The cortex, subcortical U‐fibers, corpus callosum, and anterior commissure were spared. The cerebellar white matter also showed similar changes, albeit less marked, but the brainstem was spared. Microscopically, the myeloma involvement of the CNS was limited to the dura, and the cerebral arteries showed slight atherosclerosis, but neither thrombi nor angitis. This case, although ultimately fatal, neurologically and neuroradiologically resembled reversible posterior leukoencephalopathy syndrome (RPLS) induced by IVIg and/or G‐CSF, and the nature and selective distribution of the neuropathological changes suggested that the pathogenesis involved vasospasm of the bilateral internal carotid artery and the main trunks of the cerebral arteries, due to unknown cause, inducing ischemia in the deep white matter, which is supplied by long nutrient arteries.     

Sporadic amyotrophic lateral sclerosis resembling primary lateral sclerosis: Report of an autopsy case and a review of the literature

This report describes the clinicopathological findings of a case of sporadic amyotrophic lateral sclerosis (ALS) resembling primary lateral sclerosis (PLS). A Japanese man developed muscle weakness in the distal part of the right upper extremity at age 59. At age 60 he presented with bradycinesia and rigidity. A neurological examination revealed fasciculation and increased deep tendon reflexes in the extremities. He developed decubitus and vesicorectal disturbance 2 months before his death at age 61. The neuropathological examination revealed not only prom-inent degeneration of the pyramidal tracts, evident in the internal capsule, but also loss of Betz's cells in the motor cortex. There was relative preservation of the neurons in the hypoglossal nuclei and anterior horns of the cervical and lumbar cord. In the anterior horn of the first sacral cord, there were small aggregates of lipofuscin-laden macrophages in locations from which large cells had presumably been lost. Bunina bodies and ubiquitin-immunoreactive neuronal inclusions were present in the anterior horn cells of the spinal cord. On the basis of these clinicopathological findings, we concluded that this case was one of sporadic ALS with predominant involvement of the upper motor neuron system and exhibiting features of PLS.     

Anaplastic large cell ki-1 lymphoma in the central nervous system: Report of an autopsy case

Summary A 45-year old immunocompetent man presented with multiple lesions in the brain. A histological examination of the tumors showed a diffuse infiltrate of lymphoid cells with cellular polymorphism and of multinucleated giant cells. These cells were immunolabeled with antibodies against B cell lineage and with a monoclonal antibody, Ber-H2 (CD30), which showed the presence of Ki-1 antigen. Recently, among systemic non-Hodgkin's lymphomas, attention has been given to Ki-1-positive lymphomas, which have been incorporated in the up-dated Kiel classification. We report here a case of Ki-1-positive lymphoma arising in the CNS and review previously reported cases.     

Distinct patterns of neuronal inputs and outputs of the juxtaparaventricular and suprafornical regions of the lateral hypothalamic area in the male rat

We have analyzed at high resolution the neuroanatomical connections of the juxtaparaventricular region of the lateral hypothalamic area (LHAjp); as a control and in comparison to this, we also performed a preliminary analysis of a nearby LHA region that is dorsal to the fornix, namely the LHA suprafornical region (LHAs). The connections of these LHA regions were revealed with a coinjection tract-tracing technique involving a retrograde (cholera toxin B subunit) and anterograde (Phaseolus vulgaris leucoagglutinin) tracer. The LHAjp and LHAs together connect with almost every major division of the cerebrum and cerebrospinal trunk, but their connection profiles are markedly different and distinct. In simple terms, the connections of the LHAjp indicate a possible primary role in the modulation of defensive behavior; for the LHAs, a role in the modulation of ingestive behavior is suggested. However, the relation of the LHAjp and LHAs to potential modulation of these behaviors, as indicated by their neuroanatomical connections, appears to be highly integrative as it includes each of the major functional divisions of the nervous system that together determine behavior, i.e., cognitive, state, sensory, and motor. Furthermore, although a primary role is indicated for each region with respect to a particular mode of behavior, intermode modulation of behavior is also indicated. In summary, the extrinsic connections of the LHAjp and LHAs (so far as we have described them) suggest that these regions have a profoundly integrative role in which they may participate in the orchestrated modulation of elaborate behavioral repertoires.