Large Anterior Horn Research Articles

Involvement of spinal motor neurons in parkin‐positive autosomal recessive juvenile parkinsonism

We intensively examined the spinal cord of an autosomal recessive juvenile parkinsonism (ARJP) female patient with a homozygous exon 3 deletion in the parkin gene, anticipating a possible involvement of anterior horn neurons. Although the clinical features of the patient were consistent with parkinsonism as a result of parkin mutation, her tendon reflex was abolished in the lower limbs. This feature was in contrast with hyperreflexia, usually found in previous reports of ARJP. Histologically, on the level of the cervical, thoracic, and sacral spinal cord, anterior horn neurons were well preserved and normal. However, the lumbar spinal cord exhibited many swellings of proximal axons (spheroids) and degenerative changes in the somata of the large anterior horn neurons such as central chromatolysis, cystatin C-negative small eosinophilic inclusions, and eosinophilic Lewy body-like inclusions. Ultrastructurally, accumulations of neurofilaments and abnormal structures, such as inclusion bodies similar to skein-like inclusions and disorganized rough endoplasmic reticulum, were observed in the somata and neuronal processes. Lewy body-like inclusions in this study were positively immunostained for both alpha-synuclein and ubiquitin that closely resemble Lewy bodies, but are different from Lewy body-like inclusions negatively immunostained for alpha-synuclein in amyotrophic lateral sclerosis. These findings suggest that eosinophilic inclusions that closely resemble Lewy bodies may be formed in the spinal motor neurons of ARJP patients with parkin mutations and the motor neurons of these patients may be vulnerable to neurodegeneration.

Parvalbumin and calbindin D-28k immunoreactivity in transgenic mice with a G93A mutant SOD1 gene

Immunohistochemical study was performed to examine if calcium-binding proteins are involved in the degeneration of motor neurons in the brain stems and the spinal cords of transgenic mice carrying a G93A mutant human SOD1 gene. Specimens from age-matched non-transgenic wild-type mice served as controls. In the spinal cord of the controls, the density of parvalbumin-immunoreactive neurons was highest in the large anterior horn neurons and lower in the posterior horn neurons in the spinal cord. On the other hand, calbindin D-28k immunoreactivity was much less apparent than that observed with parvalbumin antisera. Rexed's lamina II was densely immunostained for calbindin D-28k, whereas, in the anterior horn, calbindin-D-28k-positive small neurons were barely dispersed in a scattered pattern. In transgenic mice, parvalbumin-positive anterior horn neurons were severely reduced, even at the presymptomatic stage, whereas calbindin-positive neurons were largely preserved. At the symptomatic stage, both parvalbumin and calbindin D-28k immunoreactivity markedly diminished or disappeared in the anterior horn. Immunoblotting analysis revealed a significant reduction of immunoreactivity to parvalbumin antibody in transgenic mice compared with the controls. In the brain stem, parvalbumin-positive oculomotor and abducens neurons and the calbindin D-28k-positive sixth nucleus were well-preserved in transgenic mice as well as in the controls. Thus, the diffuse and severe loss of parvalbumin immunoreactivity of large motor neurons even at early stages in SOD1-transgenic mice and the absence of calbindin D-28k immunoreactivity of normal large motor neurons suggest that these calcium-binding proteins may contribute to selective vulnerability and an early loss of function of large motor neurons in this SOD1-transgenic mouse model.

Impairment of axonal transport in the axon hillock and the initial segment of anterior horn neurons in transgenic mice with a G93A mutant SOD1 gene

Impaired axonal transport of the fast or slow component has been reported in patients with sporadic amyotrophic lateral sclerosis (ALS), animal models for ALS, and familial ALS-linked mutant Cu/Zn superoxide dismutase (SOD1) transgenic mice. However, little is known about the impairment of axonal transport in mutant SOD1 transgenic mice. This is the first electron microscopic investigation of the axon hillock (AH) and the initial segment (IS) of anterior horn cells in the spinal cord of transgenic mice expressing the G93A mutant human SOD1, and it was launched with a view toward examining whether the axonal transport is impaired in this region. Six transgenic mice were killed at ages ranging from the presymptomatic to symptomatic stages. Six age-matched non-transgenic wild-type mice served as controls. In the non-transgenic mice, 91 AH and IS were observed, but those with increased neurofilaments or mitochondria were rarely found. In the transgenic mice, 95 AH and IS directly emanating from normal-looking large anterior horn cells were seen. AH and IS with increased neurofilaments or, to a lesser extent, increased mitochondria, and round-shaped mitochondria in particular, were more frequently observed, even at the early presymptomatic stage, than in the controls, and the frequency increased with time through the presymptomatic stages. On the other hand, the somata of large motor neurons directly connected with the axons did not exhibit any abnormal accumulation of neurofilaments or mitochondria. These findings suggest that both the slow axonal transport of neurofilaments and the fast axonal transport of mitochondria are impaired in AH and IS before the onset of disease in this animal model.

Klotho insufficiency causes decrease of ribosomal RNA gene transcription activity, cytoplasmic RNA and rough ER in the spinal anterior horn cells

The klotho gene was identified in 1997 as the gene whose severe insufficiency (kl/kl) causes a syndrome resembling human aging, such as osteoporosis, arteriosclerosis, gonadal atrophy, emphysema, and short life span in a mouse strain. Regarding the gait disturbance reported in kl/kl mice, the present study examined the spinal cord of kl/kl mice, and revealed decreases in the number of large anterior horn cells (AHCs), the amount of cytoplasmic RNA, the number of ribosomes and rough endoplasmic reticulum (rER), and the activity of ribosomal (r) RNA gene transcription without significant loss of the total number of neurons in the ventral gray matter. Increased immunostaining of phosphorylated neurofilament in the AHCs and of glial fibrillary acidic protein in reactive astrocytes in the anterior horn of kl/kl mice were also observed. On the other hand, the posterior horn was quite well preserved. The results suggest that the kl/kl insufficiency causes atrophy and dysfunction of the spinal AHCs through decreased activity of rRNA gene transcription, which may reduce the amount of cytoplasmic RNA and the number of ribosomes and rER. These findings resemble those found in the spinal cord of patients with classic amyotrophic lateral sclerosis (ALS). The results show that klotho gene insufficiency causes dysfunction of the protein synthesizing system in the AHCs, and might indicate the klotho gene is involved in the pathological mechanism of classic ALS. The kl/kl is a new animal model of AHC degeneration, and may provide clues to understanding the etiology of classic ALS.

Neuroprotective effect of oxidized galectin-1 in a transgenic mouse model of amyotrophic lateral sclerosis

Abnormal accumulation of neurofilaments in motor neurons is a characteristic pathological finding in amyotrophic lateral sclerosis (ALS). Recently, we revealed that galectin-1, whose oxidized form has axonal regeneration-enhancing activity, accumulates in the neurofilamentous lesions in ALS. To investigate whether oxidized galectin-1 has a beneficial effect on ALS, oxidized recombinant human galectin-1 (rhGAL-1/ox) or physiological saline was injected into the left gastrocnemius muscle of the transgenic mice over-expressing a mutant copper/zinc superoxide dismutase (SOD1) with a substitution of histidine to arginine at position 46 (H46R SOD1). The H46R SOD1 transgenic mice, which represented a new animal model of familial ALS, were subsequently assessed for their disease onset, life span, duration of illness, and motor function. Furthermore, the number of remaining large anterior horn cells of spinal cords was also compared between the two groups. The results showed that administration of rhGAL-1/ox to the mice delayed the onset of their disease and prolonged the life of the mice and the duration of their illness. Motor function, as evaluated by a Rotarod performance, was improved in rhGAL-1/ox-treated mice. Significantly more anterior horn neurons of the lumbar and cervical cords were preserved in the mice injected with rhGAL-1/ox than in those injected with physiological saline. The study suggests that rhGAL-1/ox administration could be a new therapeutic strategy for ALS.

Familial amyotrophic lateral sclerosis with His46Arg mutation in Cu/Zn superoxide dismutase presenting characteristic clinical features and Lewy body-like hyaline inclusions

We evaluated the characteristic clinical features of one family of familial amyotrophic sclerosis (FALS) with a His46Arg mutation in the enzyme Cu/Zn superoxide dismutase (SOD1). Codon 46 encodes the binding site for copper and the His46Arg mutation may result in decreased copper binding and copper toxicity. The disease duration of this family was 17.8±13.2 years (mean±S.D.) with the age at onset being 42.9±4.7 years old (mean±S.D.). The initial sign was distal weakness of the unilateral lower limb, extending to the other lower limb. An autopsy was performed on a 62-year-old female member of the family who had the mutation. Her disease duration was 23 years, and she died of tonsillar herniation caused by metastasis of colon cancer in the cerebellum. Neuropathological findings showed marked loss of large anterior horn cells and very mild degeneration of corticospinal tracts as well as posterior columns. The number of nuclei of Clark's column was reduced. Lewy body-like hyaline inclusion bodies (LBHIs) were frequently seen in the remaining anterior horn cells. Astrocytic hyaline inclusions (Ast-HIs) were also seen. This is the first autopsy report of FALS with a His46Arg mutation presenting neuronal LBHIs and Ast-HIs. The formation of LBHIs and Ast-HIs may be dependent on the phenotype of the preferential lower motor neuron involvement in FALS with a SOD mutation and long disease duration.

Erratum to: Immunohistochemical and ultrastructural study of basophilic inclusions in adult-onset motor neuron disease

We immunohistochemically and ultrastructurally studied basophilic inclusions (BI) in a patient with adult-onset sporadic motor neuron disease (MND). BI were frequently observed not only in degenerated anterior horn cells, such as central chromatolytic neurons, but also in normal-appearing large anterior horn neurons. They had various shapes, round, elliptical or irregular, and occasionally they had distinct basophilic rims. They also varied in size. There were no halos around them nor core in their centers. Immunohistochemically, some BI were immunostained for ubiquitin or SOD1, but BI were not immunoreactive with anti-phosphorylated neurofilament (SMI 31), phosphorylated tau, cystatin C or Golgi (MG-160) antibodies. Ubiquitin-positive skein-like inclusions (SI) were occasionally observed in the somata of anterior horn neurons. Ultrastructurally, BI consisted of filamentous structures associated with granules, which were attached to thick filaments. The thick filaments were straight without constriction or side arms and their diameter was twice that of the neurofilaments. BI occasionally contained tubular structures among the granule-associated filaments. The granulo-filamentous profiles varied from being compactly arranged to being more loosely packed. The structure of BI resembles that of the Lewy body-like hyaline inclusions (LBHI) observed in sporadic MND patients. Bundles of filaments resembling SI, which were composed of compactly packed filaments without fine granules running parallel to the longitudinal axis, were frequently observed inside or at the periphery of BI, and occasionally clustered in the perikarya. Each filament measured approximately 15-25 nm in diameter, and a bundle of these grouped filaments was sometimes surrounded by a unit membrane. We also occasionally observed in-between structures of BI and bundles of filaments resembling SI. These findings suggest a certain relationship between BI, SI and LBHI in the pathomechanism of BI development. Further studies are needed to elucidate whether sporadic adult-onset MND characterized by BI forms a different subtype of MND.

Neuronal nitric oxide synthase immunoreactivity in the spinal cord in amyotrophic lateral sclerosis

We investigated the spinal cords of 15 patients with sporadic amyotrophic lateral sclerosis (ALS) immunohistochemically using an anti-human neuronal nitric oxide synthase (nNOS) antibody to examine whether there is increased nNOS immunoreactivity in anterior horn neurons. Specimens from 16 patients without any neurological disease served as controls. In the controls, nNOS immunoreactivity of large anterior horn neurons was detected in 10 out of 16 cases. However, there were few nNOS-positive neurons, and most of large anterior horn neurons were spared. In the ALS patients, the mean number of nNOS-positive anterior horn neurons per transverse section of L4 and L5 was significantly larger (16.2 +/- 10.9) than that in the controls (7.0 +/- 9.2) (P < 0.0001). Moreover, 41.4% of large anterior horn neurons in ALS showed nNOS immunoreactivity in remarkable contrast to 7.6% in the controls. All ALS patients, whether showing mild, moderate or severe depletion of anterior horn neurons, displayed a higher percentage of nNOS-positive anterior horn neurons than the control patients showing nNOS immunoreactivity (P < 0.01). Most of the remaining anterior horn neurons in ALS showed more intense nNOS immunoreactivity on the surface of the neurons and their neuronal processes compared with the controls. Degenerated anterior horn neurons frequently demonstrated more intense nNOS immunoreactivity on the surface of the neurons than normal-appearing neurons. Some anterior horn cells displayed nNOS immunoreactivity in the somata. Dot-like nNOS deposits on anterior horn neurons were also positively immunoreactive with anti-synaptophysin antibody. Thus, increased nNOS expression is located mainly at the synaptic sites on the anterior horn neurons in sporadic ALS, which may be related to the degeneration of anterior horn neurons in this disease. Further studies are needed to determine whether the increased nNOS immunoreactivity plays a neuroprotective or neurotoxic role in the anterior horn neurons, and to show nitric oxide production in ALS.

Increased expression of growth-associated protein 43 on the surface of the anterior horn cells in amyotrophic lateral sclerosis.

This study examined axonal terminal alterations in the anterior horn of amyotrophic lateral sclerosis (ALS) patients. An antibody against growth-associated protein 43 (GAP43), a phosphoprotein which is expressed in elongating terminals of neurites, was employed for immunohistochemical staining. Lumbar spinal cords taken at autopsy from five ALS patients and from six control adults were examined. In control patients, there were numerous GAP43-positive granules diffusely dispersed throughout the anterior horn neuropil, and individual large anterior horn cells (AHCs) showed numerous tiny immunoreactive granules and small dots on the surface. A small number of AHCs showed dense accumulation of GAP43 immunoreactivity on the surface of the cell body and proximal processes. In all ALS patients, similar accumulation of GAP43 immunoreactivity was seen on the surface of a large number of remaining AHCs. Statistical analysis revealed a significant increase in number of AHCs with such accumulation in ALS patients. These results suggest that during the ALS disease process there may be plastic alterations or a compensatory mechanism of the axonal terminals located on the surface of some AHCs for ongoing anterior horn presynaptic terminal degeneration.

Immunoreactivity of beta-amyloid precursor protein in amyotrophic lateral sclerosis.

We investigated the localization and extent of beta-amyloid precursor protein (beta-APP695) immunoreactivity as a sensitive marker for impairment of fast axonal transport in the spinal cords of 21 patients with amyotrophic lateral sclerosis (ALS), paying special attention to anterior horn neurons. Specimens from 18 patients without neurological disease served as controls. Increased beta-APP immunoreactivity was frequently recognized in the anterior horns of the ALS patients with short clinical courses or with mild depletion of anterior horn cells, while no beta-APP immunoreactivity was demonstrated in those with severe depletion of anterior horn neurons or with long-standing clinical courses. Increased beta-APP immunoreactivity in the anterior horn neurons was mainly confined to the perikarya and no immunoreactivity was recognized in the dendrites or proximal axons directly emanating from the somata, except some spheroids (proximal axonal swellings) which showed increased immunoreactivity of beta-APP. Increased beta-APP immunoreactivity was spotted or focally aggregated in the perikarya of normal-looking large anterior horn neurons, while it was frequently diffuse in that of degenerative neurons such as central chromatolytic cells and or those with simple atrophy. On the other hand, the controls showed no immunostaining with beta-APP in the spinal cord. These findings suggest that increased immunoreactivity of beta-APP in neuronal perikarya of the anterior horn cells and in some proximal axonal swellings is an early change of ALS, and may be a response of the increased synthesis of beta-APP resulting from neuronal damage, or the impairment of fast axonal transport.

Distribution of B-50(GAP-43) mRNA and protein in the normal adult human spinal cord.

B-50(GAP-43) is a phosphoprotein mainly found in the nervous system which plays a major role in neurite growth during development and regeneration as well as in synaptic remodelling. In the mature intact central nervous system, intense B-50 immunoreactivity (B-50-IR) can still be detected in regions which maintain residual capacity for structural re-organization. B-50 expression has been studied extensively in laboratory animals; however, its distribution and regulation in the human spinal cord is largely unknown. As a first step to analyze lesion-induced structural alterations, we investigated the distribution of B-50 protein and mRNA in the normal adult human spinal cord and dorsal root ganglia. Intense B-50-IR was localized to the superficial laminae of the dorsal horn at all segmental levels, the intermediolateral nucleus at thoracic levels and Onuf's nucleus at sacral levels. Scattered neurons, particularly in the ventral horn of lumbar and sacral segmental levels (and occasionally also in Clarke's nucleus) displayed intense B-50-IR in close apposition to the perikaryal and proximal dendritic surfaces. Nonradioactive in situ hybridization indicated that B-50 mRNA could also be detected in neurons of the ventral horn and also in the intermediolateral nucleus. The distribution of B-50 mRNA and protein in the normal human spinal cord shows a marked similarity to that reported in experimental animals, including the selective labelling of Onuf's nucleus. However, the strong B-50-IR on the surface of some large anterior horn motor neurons has not been observed in other mammals. This finding might reflect a particular state of readiness for synaptic plasticity.

Neuropathology of ALS: an overview.

ALS is an age-associated neurodegenerative disease that primarily affects the motor neuron system. Despite having been studied for over 100 years, its etiology is still a mystery, and no specific diagnostic laboratory test has been developed. The diagnosis of ALS is therefore based on clinical features and/or neuropathologic findings. The neuropathologic findings on patients with classic ALS are quite distinct, with loss and degeneration of the large anterior horn cells of the spinal cord and lower cranial motor nuclei of the brainstem. The striated muscles display denervation atrophy. Upper motor neurons, such as the Betz cells in the motor cortex, are also affected. The several symposia and workshops on the cytopathology of ALS held within the past 3 years are a reflection of the many new and important developments taking place in this area. [1] Although loss of motor neurons has been known for many years, cytoplasmic alterations of the lower motor neurons have been studied in detail only in recent years by using immunohistochemical and electron microscopic techniques. An overview of some of the novel findings associated with lower motor neuron alterations is presented here. The synapse is the most important site of neuronal function and is unique to the neuron. Despite many years of extensive studies on ALS, data regarding synaptic alterations are limited to a relatively small number of ultrastructural investigations. [2] This paucity of information is due to the inherent difficulties that affect the proper evaluation of synapses in autopsy material. Synaptophysin, a 38-kDa glycoprotein, is a constituent of the membrane of synaptic vesicles in presynaptic terminals. The evaluation of synaptophysin expression in the lumbar spinal cord of ALS patients was apparently presented for the first time by Kawanami et al. [3] at the Annual Meeting of the Canadian Association of Neuropathologists in September 1992. This …

Cytopathology of amyotrophic lateral sclerosis: A personal perspective of recent developments

Amyotrophic lateral sclerosis (ALS) is an age‐associated neurodegenerative disease that primarily involves the motor neuron system. Despite this disease having been studied for over 100 years, its etiology is still unknown and no specific diagnostic laboratory test is available. The diagnosis of ALS is therefore based on clinical and/or neuropathological findings with loss and degeneration of the large anterior horn cells of the spinal cord being the principal and most salient features. Several symposia and workshops on the cytopathology of ALS were held within the last 2 year period, which reflects the many new and important developments taking place. Although loss of motor neurons has been well‐known for many years, cytoplasmic alterations of the lower motor neurons have been studied in detail only in recent years by applying immunohistochemical and electron microscopic procedures. The purpose of this review is to introduce some of the novel findings associated with lower motor neuron alterations.

Acute and late neurotoxicity in the rat spinal cord in vivo induced by glutamate receptor agonists

We investigated glutamate receptor-mediated neurotoxicity in vivo by means of infusing three specific agonists for non-NMDA receptors (acromelic acid A (ACRO), kainic acid and 1-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA)) into the adult rat spinal subarachnoid space. ACRO induced long-lasting pure motor, rigid-spastic paraparesis in a dose-dependent manner (EC 50: 220 pmol/h) that was accompanied by selective degeneration of spinal interneurons; leaving large anterior horn cells intact. Kainate and AMPA induced paraplegia but with relatively non-selective neuronal damage when given in doses more than 40-fold larger than those required for ACRO. When AMPA (> 100 nmol/h) was infused continuously using a mini-osmotic pump for more than 2 days, rats displayed progressive changes in motor behavior due to extensive damage in the caudal spinal cord where small neurons in the dorsal horns were the most vulnerable. Co-administration of 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX) specifically prevented neurotoxicity, suggesting a non-NMDA receptor-mediated mechanism. These results indicate that the non-NMDA receptor is heterogeneous, mediating neuronal damage with different selectivity. It is also suggested that chronic activation of glutamate receptors is capable of inducing slowly progressive neuronal death, which suggests relevance to the pathogenesis of ALS.

Differential localization of heme oxygenase and NADPH-diaphorase in spinal cord neurons.

Western blot analysis using several antibodies showed that rat spinal cord contained abundant immunostainable heme oxygenase-2 (HO-2) and barely detectable levels of heme oxygenase-1 (HO-1). Anti-HO-2 antibody stained large anterior horn motoneurones and numerous smaller neurons throughout spinal cord gray matter including the dorsal root entry zone. HO-2+ astrocytes were not evident in gray matter although their presence cannot be ruled out. The distribution of HO-2+ neurons was compared with the distribution of cells containing NADPH-diaphorase (NADPH-d) activity, a marker for nitric oxide synthase. NADPH-d activity was restricted to far fewer neurons, many of which were close to the central canal and dorsal root entry zone.

Neuropathology of ALS: Spheroids

I briefly review spheroids observed in the anterior horns of the spinal cord in amyotrophic lateral sclerosis (ALS). Spheroids are argentophilic bodies more than 20 μm in diameter. Recently, some connections between the proximal axonal swellings including spheroids and the perikarya have been reported in some ALS patients with a short clinical course or mild depletion of anterior horn neurons. Most of the cell bodies directly connected with the axonal swellings appear normal, and spheroids are considered to be one of the hallmarks of the early histological changes in this disorder. Spheroids are strongly positive with anti‐phosphorylated neurofilament antibody, and are also positive with calcitonin gene‐related peptide and anti‐peripherin antibody. Some spheroids are immunostained with anti‐synaptophysin antibody and anti‐ubiquitin antibody. Spheroids are not immunostained with anti‐phosphorylated tau antibody, or high molecular weight microtubule associated proteins. Electron microscopically, spheroids are usually composed of densely packed accumulation of 10 nm neurofilaments with a variety of orientations, plus vesicles, dense bodies and mitochondria. When the swellings of the initial segment is relatively pronounced, the undercoating is obscured and the neurofilaments become interwoven in some parts. In the first internode of the myelinated axons, as the swellings become larger, the neurofilaments lose their parallel orientation and become intermingled. Large accumulation of neurofilaments resembling spheroids in the perikarya of large anterior horn cells suggests that spheroids could be derived not only from the axon including the proximal portion, but also from the perikarya. Structures apparently identical to axonal spheroids are observed at the light and electron microscopic levels in the proximal portion of axons of anterior horn cells in animal models intoxicated with β, β'‐iminodipropionitrile (IDPN), or with aluminum, in hereditary canine spinal muscular atrophy (HCSMA). The pathogenetic mechanism is probably associated with an impairment in slow axonal transport which particularly affects the neurofilaments in IDPN and aluminum intoxication. Impairment of slow axonal transport of neurofilaments also plays an important role in the pathogenesis of ALS. The average diameter of even normalappearing initial segment is larger in ALS than in the controls. The perikarya connected with the swollen proximal axons and their dendrites almost always appear normal. These findings suggest that the slow axonal transport of neurofilaments is probably impaired in this portion of the axon at an early stage in ALS as well as animal models for human ALS. However, techniques to analyze slow axonal transport in humans still remain tobe developed. Recently, overexpression of neurofilament subunits in transgenic mice produces a condition resembling ALS. The transgenic model may offer an interesting perspective not only for testing therapeutic strategies but also for investigating in a systematic way the various genetic and environment factors controlling the onset and progression of the disease and might yield new insights on the etiology of ALS.

The flipped meniscus sign.

Meniscal fragments may be difficult to detect on magnetic resonance (MR) imaging and yet are clinically significant. This paper describes and illustrates the MR appearance of an easily overlooked meniscal fragment. Ten knees, each appearing to show an abnormally large anterior meniscal horn (8 mm or more in height) were prospectively identified on MR images. In each case demonstrable large tears of the ipsilateral posterior horns were present (same meniscus as had large anterior horns). The lateral meniscus was involved in nine cases and the medial in one. Two of the ten patients imaged had surgically proven bucket-handle meniscal tears as well as meniscal fragments overlying the ipsilateral anterior horn. In one case previous MR imaging at our institution had demonstrated the affected anterior horn to be of normal caliber. The striking MR appearance of an abnormally enlarged anterior meniscal horn in association with a tear of the ipsilateral posterior horn suggests the presence of a meniscal fragment or of a posteriorly detached bucket-handle tear of the posterior horn of the meniscus.

Spinal cord neurofibrillary tangles of Guamanian amyotrophic lateral sclerosis and parkinsonism‐dementia complex

We studied the topographic distribution and immunohistochemical characteristics of spinal cord neurofibrillary tangles (NFTs) in 6 patients with Guamanian amyotrophic lateral sclerosis (ALS) and 6 patients with parkinsonismdementia complex (PD) on Guam, using antibodies to tau protein and ubiquitin. The NFTs were immunoreactive with both antibodies, but staining for tau was more pronounced. As identified by this reactivity, all the Guamanian ALS and PD cases examined showed spinal cord NFTs. The posterior horn had the most and the anterior horn the least. In the posterior horn the NFTs were located mainly in the marginal areas. Large anterior horn cells showed few, if any, NFTs. In addition to perikaryal NFTs, we observed tau-reactive neurites. Our results provide evidence that spinal cord NFTs are not uncommon in Guamanian ALS and PD on Guam and that they are more numerous than previously found with conventional methods.

Degenerating compartment and functioning compartment of motor neurons in ALS: possible process of motor neuron loss.

Using a morphometric method, we studied ventral spinal roots and anterior horn neurons of the fourth lumbar segment in 17 patients with ALS. Both populations of large myelinated fibers and anterior horn cells had significantly high correlations to muscle strength in the legs and duration of symptoms. However, active axonal degeneration was consistently present in terms of either large myelinated fibers or anterior horn cells.

Two and three dimenstional ultrastructure of boutons and glial cells on the motoneuronal surface in the cat spinal cord.

AbstractA method is presented for individually mounting serial sections on one‐hole specimen holders. Also a technique for constructing stereograms based upon serial sections is described including a method for obtaining perspective foreshortening. Ultrastructural findings revealed the surface of the motoneuron to be covered with synaptic boutons which frequently pressed against each other. Surface area not contacted by boutons was covered with astroglial processes. The latter processes wedged around and sometimes between the boutons. On occasion finger‐like astrocytic processes (spines) were found to invaginate the terminal boutons. No synaptic thickenings were found between adjacent boutons (axo‐axonal contacts) on the perikaryal surface. However, in view of the enormous size of the motoneuron contrasted to the small volume of tissue thus far investigated, this observation is regarded as inconclusive. Three‐dimensional studies revealed an astrocytic process with disproportionately large amounts of surface membrane in the form of many interconnected pockets. The initial unmyelinated segment of a large anterior horn cell was encountered and found to have synaptic boutons on its proximal half. Its distal half was surrounded by an extracellular space containing electron dense material similar to that found in the goldfish by Robertson, Bodenheimer, and Stage ('63).