(Stroke. 1997;28:2553-2556.)
© 1997 American Heart Association, Inc.
Articles |
Upper Motor Neuron Lesions in Stroke Patients Do Not Induce Anterograde Transneuronal Degeneration in Spinal Anterior Horn Cells
From the Division of Neurology, Fourth Department of Internal Medicine (S.T., Y.O., T.M.) and the Institute for Medical Science of Aging (S.T., Y.H.), Aichi Medical University, Aichi, and the Department of Neurology, Nagoya University School of Medicine, Nagoya (M.L., G.S.), Japan.
Correspondence to Shin-ichi Terao, MD, Division of Neurology, Fourth Department of Internal Medicine, Aichi Medical University, Nagakute, Aichi 480–11, Japan.
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Abstract |
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 Top Abstract IntroductionSubjects and MethodsResultsDiscussionReferences |
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Background and Purpose To determine whether upper motor neuron lesions in stroke can cause transneuronal degeneration of lower motor neurons, we assessed spinal anterior horn cells in patients dying with poststroke hemiplegia.
Methods Subjects were four stroke patients with severe left hemiplegia and four age-matched control subjects who died of nonneurological disease. After histological processing and staining, cytoarchitectonic assessment was made of all neurons in the ventral horns of the 4th lumbar segment of the spinal cord according to cell diameter and topography.
Results In the four stroke patients, no differences were seen in anterior horn cell populations or diameter and size distribution patterns between affected and unaffected sides or between these patients and the control subjects.
Conclusions The present quantitative analysis provides no evidence of anterograde transneuronal degeneration of lower motor neurons after upper motor neuron damage in stroke patients.
Key Words: hemiplegia • spinal anterior horn cell • transneuronal degeneration • cerebrovascular disorders • corticospinal tract
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Introduction |
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TopAbstractIntroductionSubjects and MethodsResultsDiscussionReferences |
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Hemiplegia caused by cerebrovascular disease involves the CST. Muscular atrophy of extremities sometimes observed on the affected side has raised controversy about whether this atrophy results from disuse or from denervation caused by anterograde TND in response to upper motor neuron damage.1 2 3 4 We have reported morphometric studies of AHC and lateral CST fibers of the spinal cord in a range of neurodegenerative diseases relative to control populations and clarified disease-specific patterns of neuronal and fiber loss.5 6 7 8 9 10 11 The present study was designed to elucidate whether upper motor neuron lesions in cerebrovascular diseases induce anterograde TND in lower motor neurons.
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Subjects and Methods |
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TopAbstractIntroductionSubjects and MethodsResultsDiscussionReferences |
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Two patients with cerebral hemorrhage involving the right basal ganglia and thalamus and two with infarction in the territory of the right middle cerebral artery and posterior cerebral artery were subjects. All four subjects had severe spastic left hemiplegia that included the lower and upper limbs. Ages at death ranged from 20 to 89 years, and the interval from onset of stroke to death ranged from 1 to 8 years. Four age-matched control subjects without obvious abnormalities of the central nervous system were selected. Clinical details of subjects are summarized in Table 1
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Autopsies were performed within 2 hours postmortem. The 4th lumbar and
7th thoracic segments of the spinal cord were removed, fixed in a 10%
buffered formalin solution, and processed for paraffin sections.
Cytoarchitectonic assessment of the AHC was performed as described
previously.6 7 9 11 Beginning rostrally, the 4th lumbar
segment was cut transversely into 300 to 500 serial 10-µm thick
sections; every 10th section was stained by the Klüver-Barrera
technique. The spinal ventral horn was designated as the gray matter
ventral to a line through the central canal perpendicular to the
ventral spinal sulcus. Photomicrographs (x205) were taken that
included the entire ventral horn in each of the stained sections. The
diameters of neurons with clearly visualized nucleoli were measured on
the photomicrographs with a particle-size analyzer (TGZ-3, Carl
Zeiss), and AHC were classified arbitrarily into three groups according
to diameter: large (
32.8 µm), medium-sized (24.8 µm
to <32.8 µm) and small (<24.8 µm).7 9
Patterns of possible cell loss were examined in two ways. For one
approach, a two-dimensional, size-dependent topographic distribution
and then a three-dimensional neuronal density distribution in the
horizontal plane of the spinal cord were analyzed. For the
other, a size-dependent reconstruction of cell populations in the
ventral spinal horn at the 4th lumbar level was obtained. To
investigate the two-dimensional size-dependent topographic distribution
and the three-dimensional neuronal density distribution of neurons, all
AHC with distinct nucleoli identified in photomicrographs were
classified as large, medium-size, or small neurons. Their locations
were traced and plotted on a montage of the ventral horn, and
computer-generated two-dimensional and three-dimensional
reconstructions of the cell frequencies were obtained as size-dependent
cell-density maps.
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Results |
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TopAbstractIntroductionSubjects and MethodsResultsDiscussionReferences |
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In all four stroke patients, the lateral CST in the left dorsolateral column on both the thoracic and lumbar segments of the cord demonstrated extensive loss of axons. However, central chromatolysis, atrophic neurons, and neuronophagia were observed only rarely in the ventral horn on either the affected or the unaffected side. Size-dependent topographical distribution analysis of AHC in the 4th lumbar segment demonstrated no difference between the affected and unaffected sides in any of the four stroke patients (Figs 1
and 2).
Similarly, this analysis revealed no difference between right
and left ventral horns in the control subjects (Figs 1 and 2).
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Respective count of large, medium-size, and small AHC in the 4th lumbar
segment of stroke patients ranged from 1758 to 2386 per 50 sections
(mean±SD, 2070±259), 515 to 648 (mean±SD, 594±57), and 602 to 697
(mean±SD, 645±42) on the right side and 1810 to 2490, (mean±SD,
2082±279) 569 to 627 (mean±SD, 593±21) and 596 to 681 (mean±SD,
627±34) on the left. Corresponding counts for the control group were
indistinguishable from those in stroke patients on both affected and
unaffected sides (Table 2). No significant difference
was observed by Mann-Whitney U test between stroke patients
and control subjects or between affected and unaffected sides of the
spinal ventral horn for any of the determinations above.
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Discussion |
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TopAbstractIntroductionSubjects and MethodsResultsDiscussionReferences |
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Spinal AHC include three distinct types of neurons in terms of cell body size, location, and function: large
-motoneurons,
medium-size 
-motoneurons, and small neurons that are assumed to be
interneurons.7 9 12 13 14 15 The
physiological role of - and -motoneurons is
motor control of skeletal muscles, whereas many interneurons are
thought to provide a synaptic connection between the upper motor
neurons,16 17 18 19 20 21 extrapyramidal
neurons,16 22 or sensory system23 24 and -
or -motoneurons.25 26 These AHC also are known to
synapse with many afferent systems. The human CST is composed of large
myelinated fibers originating in Betz cells and more
numerous smaller myelinated fibers of mostly unknown
origin.5 8 10 11 Some large myelinated fibers
are thought to connect with -motoneurons by monosynaptic relay,
whereas most fibers connect with them by polysynaptic relay via small
interneurons.16 17 18 19 20 21
Not uncommonly, muscular atrophy is noted in the plegic extremities of
stroke patients. Much controversy has persisted as to whether this
atrophy involves TND of lower motor neurons after upper motor neuron
lesions or represents the muscular atrophy of disuse. In
humans, TND (anterograde or retrograde) is known to occur in
lesions of visual,27 limbic,28 or
dentato-rubro-olivary pathways.29 30 However, this
phenomenon is not well known in the somatic motor system. Kanemitsu et
al31 reported a case studied many years after
hemispherectomy with complete degeneration of the CST; no
anterograde TND was evident. Because motor neurons receive
input from a wide variety of afferent systems, they therefore are
considered unlikely to undergo anterograde TND even after
complete interruption of the CST.31 32 33 However, Kondo et
al34 have reported that the degree of pyramidal
tract degeneration seemed to be paralleled by fiber loss in ventral
spinal roots. Qui et al35 also suggested that atrophy of
neurons in the cervical segment occurred on the side of lateral CST
degeneration. In electrophysiological
studies, motor units reportedly are decreased in number on the side of
the spinal cord affected by cerebral stroke, with -motoneurons being
in a functionally depressed state.36 37 Although the
left-right differences were not evident morphometrically in our study,
loss of trophic effect from upper motor neurons could alter the
functional state of AHC on the affected side without loss of AHC.
In a recently reported human case, depopulation and atrophy of contralateral small AHC, and diminution of ipsilateral AHC occurred in cervical segments after a proximal upper limb amputation, with the implication that ipsilateral and commissural interneurons may undergo retrograde TND.38 This suggests that anterograde TND might result from loss of neuronal input to AHC. However, our morphometric findings indicate that CST lesions do not result in anterograde TND of spinal AHC.
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Selected Abbreviations and Acronyms |
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Acknowledgments |
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A part of this study was supported by grants from the Ministry of Welfare and Health of Japan.
Received August 26, 1997; revision received September 23, 1997; accepted September 23, 1997.
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References |
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