The Experts below are selected from a list of 26970 Experts worldwide ranked by ideXlab platform
Elan D Louis - One of the best experts on this subject based on the ideXlab platform.
-
torpedo formation and purkinje cell loss modeling their relationship in cerebellar disease
The Cerebellum, 2014Co-Authors: Elan D Louis, Jeanpaul G Vonsattel, Phyllis L FaustAbstract:Torpedo formation and Purkinje cell (PC) loss represent standard and inter-related cerebellar responses to injury. Surprisingly, the nature of their relationship has not been carefully characterized across a range of normal and disease states. Are brains with more Torpedoes expected to have fewer PCs? We quantified Torpedoes and PCs in four groups: essential tremor (ET), spinocerebellar ataxia (SCA), multiple system atrophy-cerebellar (MSA-C), and controls. Brains from 100 individuals (58 ET, 27 controls, 7 SCA, 8 MSA-C) were available at the New York Brain Bank. After complete neuropathological assessment, a standard parasagittal neocerebellar block was harvested; a 7-μm thick section was stained with Luxol fast blue/hematoxylin and eosin; and Torpedoes and PCs were quantified. For a given PC count, SCA and MSA-C cases often had higher torpedo counts than ET cases or controls. Furthermore, the relationship between torpedo and PC counts was complex. The correlation between torpedo and PC counts was negative in ET cases (i.e., individuals with more Torpedoes had fewer PCs [i.e., more PC loss]) whereas the relationship was positive in MSA-C cases (i.e., individuals with fewer PCs [i.e., more PC loss] had fewer Torpedoes). Patients with SCA showed both patterns. When all diagnostic groups were combined, the correlation was best fit by a quadratic (i.e., parabolic) model rather than a simple linear model; this model incorporated data on the negative correlation in ET cases, the mixed results in SCA cases, and the positive correlation in MSA-C cases (r = 0.636). The relationship between torpedo and PC counts was complex and heterogeneous across a range of cerebellar disease states, and was best characterized by a quadratic rather than a simple model. With more severe cerebellar disease, Torpedoes can be quite numerous and are likely a common feature of surviving PCs, but eventually, dramatic loss of PC leads to a paradoxical reduction in observable Torpedoes.
-
purkinje cell axonal anatomy quantifying morphometric changes in essential tremor versus control brains
Brain, 2013Co-Authors: Rachel Babij, Phyllis L Faust, Jean Paul Vonsattel, Etty Cortes, Elan D LouisAbstract:Growing clinical, neuro-imaging and post-mortem data have implicated the cerebellum as playing an important role in the pathogenesis of essential tremor. Aside from a modest reduction of Purkinje cells in some post-mortem studies, Purkinje cell axonal swellings (Torpedoes) are present to a greater degree in essential tremor cases than controls. Yet a detailed study of more subtle morphometric changes in the Purkinje cell axonal compartment has not been undertaken. We performed a detailed morphological analysis of the Purkinje cell axonal compartment in 49 essential tremor and 39 control brains, using calbindin D28k immunohistochemistry on 100-µm cerebellar cortical vibratome tissue sections. Changes in axonal shape [thickened axonal profiles (P = 0.006), Torpedoes (P = 0.038)] and changes in axonal connectivity [axonal recurrent collaterals (P 40 years. In essential tremor cases, thickened axonal profiles, axonal recurrent collaterals and branched axons were 3- to 5-fold more frequently seen on the axons of Purkinje cells with Torpedoes versus Purkinje cells without Torpedoes. We document a range of changes in the Purkinje cell axonal compartment in essential tremor. Several of these are likely to be compensatory changes in response to Purkinje cell injury, thus illustrating an important feature of Purkinje cells, which is that they are relatively resistant to damage and capable of mobilizing a broad range of axonal responses to injury. The extent to which this plasticity of the Purkinje cell axon is partially neuroprotective or ultimately ineffective at slowing further cellular changes and cell death deserves further study in essential tremor.
-
Torpedoes in the cerebellar vermis in essential tremor cases vs controls
The Cerebellum, 2011Co-Authors: Elan D Louis, Jean Paul Vonsattel, Phyllis L Faust, Karen J, Etty CortesAbstract:The study of the postmortem changes in essential tremor (ET) is in its infancy, although recent evidence points to a central role of the cerebellum, where Purkinje cell axonal swellings (“Torpedoes”) are significantly more common in ET than control brains. Yet, all existing studies have been confined to the cerebellar hemispheres, and whether there is a more widely distributed cerebellar problem is presently unknown. Our aims were to address whether: (1) ET cases have greater numbers of Torpedoes in the vermis than controls, (2) there a correlation between the extent of vermal torpedo pathology and hemispheric torpedo pathology, and (3) vermal torpedo pathology is correlated with clinical features of the disease. A parasagittal neocerebellar block and a vermal block were harvested from 24 ET and 10 control brains. Paraffin sections (7 μm) were stained with Luxol fast blue/hematoxylin and eosin, and Torpedoes were quantified. All torpedo counts were corrected for Purkinje cell layer length. Vermal corrected torpedo count (VermTc) was higher in ET cases than controls (7.1 ± 6.8 [median, 4.3] vs. 2.6 ± 2.5 [median, 2]), p = 0.002). The VermTc and the hemispheric corrected torpedo count (HemTc) were correlated with one another (Spearman’s r = 0.54, p = 0.002). ET cases with neck, voice, and jaw tremors had the highest VermTc (p = 0.046). The abundance of Torpedoes in the ET brain is not confined to the ponto- or neocerebellum but is more broadly distributed, also involving the spino- or paleocerebellum. These data further confirm the central role of the cerebellum in the underlying pathophysiology of this common neurological disorder.
-
hairy baskets associated with degenerative purkinje cell changes in essential tremor
Journal of Neuropathology and Experimental Neurology, 2010Co-Authors: Cordelia Ericksondavis, Jean Paul Vonsattel, Phyllis L Faust, Lawrence S Honig, Sachin Gupta, Elan D LouisAbstract:Essential tremor (ET) is one of the most common neurologic diseases. Increased numbers of Torpedoes and Purkinje cell (PC) loss have been documented in the brains of patients with ET. We recently observed a dense and tangled appearance ("hairiness") of the basket cell axonal plexuses that surround PC soma in Bielschowsky preparations of cerebellar cortex in ET brains. Here, we assessed basket cell "hairiness" in 37 ET (32 cerebellar ET; 5 Lewy body variant ET), 21 nondisease control, and 48 disease control brains using a semiquantitative scale. In 8 cerebellar ET cases (25%), there were high basket scores (rating = 3), whereas no Lewy body variant ET, 1 nondisease control (4.8%), and 2 diseased controls (4.2%) had high basket scores (p = 0.001). The hairy basket scores correlated with numbers of Torpedoes (p < 0.001) and inversely with numbers of PCs (p = 0.06). Axonal plexus density obtained by image analysis of basket cell processes traced from digitized images was higher in ET than in nondiseased control cases (p = 0.016). Closely spaced sites of synaptic contact between basket cell processes and PCs were identified by electron microscopy in ET cases. These data indicate that structural changes are not restricted to PCs in ET, and that other neurons within their functional network may be involved in its pathogenesis.
-
Torpedoes in parkinson s disease alzheimer s disease essential tremor and control brains
Movement Disorders, 2009Co-Authors: Elan D Louis, Jean Paul Vonsattel, Phyllis L Faust, Lawrence S Honig, Alex Rajput, Ali H Rajput, Rajesh Pahwa, Kelly E Lyons, Webster G Ross, Rodger J ElbleAbstract:Background—Purkinje cell axonal swellings (“Torpedoes”), described in several cerebellar disorders as well as essential tremor (ET), have not been quantified in common neurodegenerative conditions.
Jean Paul Vonsattel - One of the best experts on this subject based on the ideXlab platform.
-
purkinje cell axonal anatomy quantifying morphometric changes in essential tremor versus control brains
Brain, 2013Co-Authors: Rachel Babij, Phyllis L Faust, Jean Paul Vonsattel, Etty Cortes, Elan D LouisAbstract:Growing clinical, neuro-imaging and post-mortem data have implicated the cerebellum as playing an important role in the pathogenesis of essential tremor. Aside from a modest reduction of Purkinje cells in some post-mortem studies, Purkinje cell axonal swellings (Torpedoes) are present to a greater degree in essential tremor cases than controls. Yet a detailed study of more subtle morphometric changes in the Purkinje cell axonal compartment has not been undertaken. We performed a detailed morphological analysis of the Purkinje cell axonal compartment in 49 essential tremor and 39 control brains, using calbindin D28k immunohistochemistry on 100-µm cerebellar cortical vibratome tissue sections. Changes in axonal shape [thickened axonal profiles (P = 0.006), Torpedoes (P = 0.038)] and changes in axonal connectivity [axonal recurrent collaterals (P 40 years. In essential tremor cases, thickened axonal profiles, axonal recurrent collaterals and branched axons were 3- to 5-fold more frequently seen on the axons of Purkinje cells with Torpedoes versus Purkinje cells without Torpedoes. We document a range of changes in the Purkinje cell axonal compartment in essential tremor. Several of these are likely to be compensatory changes in response to Purkinje cell injury, thus illustrating an important feature of Purkinje cells, which is that they are relatively resistant to damage and capable of mobilizing a broad range of axonal responses to injury. The extent to which this plasticity of the Purkinje cell axon is partially neuroprotective or ultimately ineffective at slowing further cellular changes and cell death deserves further study in essential tremor.
-
Torpedoes in the cerebellar vermis in essential tremor cases vs controls
The Cerebellum, 2011Co-Authors: Elan D Louis, Jean Paul Vonsattel, Phyllis L Faust, Karen J, Etty CortesAbstract:The study of the postmortem changes in essential tremor (ET) is in its infancy, although recent evidence points to a central role of the cerebellum, where Purkinje cell axonal swellings (“Torpedoes”) are significantly more common in ET than control brains. Yet, all existing studies have been confined to the cerebellar hemispheres, and whether there is a more widely distributed cerebellar problem is presently unknown. Our aims were to address whether: (1) ET cases have greater numbers of Torpedoes in the vermis than controls, (2) there a correlation between the extent of vermal torpedo pathology and hemispheric torpedo pathology, and (3) vermal torpedo pathology is correlated with clinical features of the disease. A parasagittal neocerebellar block and a vermal block were harvested from 24 ET and 10 control brains. Paraffin sections (7 μm) were stained with Luxol fast blue/hematoxylin and eosin, and Torpedoes were quantified. All torpedo counts were corrected for Purkinje cell layer length. Vermal corrected torpedo count (VermTc) was higher in ET cases than controls (7.1 ± 6.8 [median, 4.3] vs. 2.6 ± 2.5 [median, 2]), p = 0.002). The VermTc and the hemispheric corrected torpedo count (HemTc) were correlated with one another (Spearman’s r = 0.54, p = 0.002). ET cases with neck, voice, and jaw tremors had the highest VermTc (p = 0.046). The abundance of Torpedoes in the ET brain is not confined to the ponto- or neocerebellum but is more broadly distributed, also involving the spino- or paleocerebellum. These data further confirm the central role of the cerebellum in the underlying pathophysiology of this common neurological disorder.
-
hairy baskets associated with degenerative purkinje cell changes in essential tremor
Journal of Neuropathology and Experimental Neurology, 2010Co-Authors: Cordelia Ericksondavis, Jean Paul Vonsattel, Phyllis L Faust, Lawrence S Honig, Sachin Gupta, Elan D LouisAbstract:Essential tremor (ET) is one of the most common neurologic diseases. Increased numbers of Torpedoes and Purkinje cell (PC) loss have been documented in the brains of patients with ET. We recently observed a dense and tangled appearance ("hairiness") of the basket cell axonal plexuses that surround PC soma in Bielschowsky preparations of cerebellar cortex in ET brains. Here, we assessed basket cell "hairiness" in 37 ET (32 cerebellar ET; 5 Lewy body variant ET), 21 nondisease control, and 48 disease control brains using a semiquantitative scale. In 8 cerebellar ET cases (25%), there were high basket scores (rating = 3), whereas no Lewy body variant ET, 1 nondisease control (4.8%), and 2 diseased controls (4.2%) had high basket scores (p = 0.001). The hairy basket scores correlated with numbers of Torpedoes (p < 0.001) and inversely with numbers of PCs (p = 0.06). Axonal plexus density obtained by image analysis of basket cell processes traced from digitized images was higher in ET than in nondiseased control cases (p = 0.016). Closely spaced sites of synaptic contact between basket cell processes and PCs were identified by electron microscopy in ET cases. These data indicate that structural changes are not restricted to PCs in ET, and that other neurons within their functional network may be involved in its pathogenesis.
-
Torpedoes in parkinson s disease alzheimer s disease essential tremor and control brains
Movement Disorders, 2009Co-Authors: Elan D Louis, Jean Paul Vonsattel, Phyllis L Faust, Lawrence S Honig, Alex Rajput, Ali H Rajput, Rajesh Pahwa, Kelly E Lyons, Webster G Ross, Rodger J ElbleAbstract:Background—Purkinje cell axonal swellings (“Torpedoes”), described in several cerebellar disorders as well as essential tremor (ET), have not been quantified in common neurodegenerative conditions.
-
purkinje cell axonal Torpedoes are unrelated to advanced aging and likely reflect cerebellar injury
Acta Neuropathologica, 2009Co-Authors: Elan D Louis, Jean Paul Vonsattel, Phyllis L Faust, Cordelia EricksondavisAbstract:Torpedoes, swellings of the proximal Purkinje cell axon, are thought to represent a cellular response to injury [3]. They may occur in a variety of cerebellar disorders [7]. Most recently, their numbers were noted to be six-times higher in essential tremor (ET) than control brains [4]. Torpedoes are also often viewed as a cumulative phenomenon associated with advanced aging [3,4], yet there are surprisingly few supporting data. We quantified Torpedoes in normal human cerebella spanning a considerable age range to assess whether Torpedoes are a cumulative phenomenon of aging. These data help place the relative abundance of Torpedoes in ET in context. Control brains at the New York Brain Bank, Columbia University Medical Center (CUMC) had been controls in the Alzheimer’s Disease Research Center or non-neurologic patients at CUMC. Each had a complete neuropathologic assessment [4] including Braak AD stage [2] and CERAD [5] for Alzheimer’s tangle and plaque pathologies. As documented [4], a standard 3 × 20 × 25 mm parasagittal tissue block was harvested from each neocerebellum (N = 48) and immersion-fixed in 10% buffered formalin. Paraffin sections (7 μm thick) were stained with Luxol Fast Blue counterstained with Hematoxylin and Eosin (LH&E) [4]. Torpedoes (Figure 1) in one entire LH&E section were counted blinded to age. Purkinje cells in five randomly-selected 100x LH&E stained fields of the standard cerebellar section were counted and the mean reported. In 32 brains, a second set of sections from the same blocks were used as replicate data. Figure 1 Control cerebellar tissue showing a torpedo (arrow). LH&E 400x magnification. Non-parametric tests (Spearman’s r, Mann Whitney test, Kruskal Wallis test) were used. Because of zero values (0 Torpedoes), in linear regression analyses, log10(Torpedoes +1) was the dependent variable and age, the independent variable. Age at death ranged from 6–93 years. Mean±SD (median, range) number of Torpedoes = 1.8±2.1 (1, 0–11)(Table). Table Clinical characteristics/postmortem features (48 controls) Number of Torpedoes was correlated with age at death (r = 0.35, p = 0.02, Table), but not when the brains in the youngest age quartile (≤36 years) were excluded (i.e., in brains with age of death ranging from 37–93 years, r = −0.03, p = 0.85). While (mean±SD, median) number of Torpedoes was low in brains in the youngest quartile (quartile 1, ≤36 years, 0.5±0.9, 0), it did not differ among brains in the remaining 3 quartiles: quartile 2 (37–63 years) 1.9±1.6, 1.5; quartile 3 (64–80 years) 2.9±3.2, 2; quartile 4 (≥81 years) 2.0±1.4, 1.5 (for comparison of quartiles 2–4, p = 0.88)(Figure 2). Figure 2 Number of Torpedoes (Y axis) by age at death quartile (X axis). In a linear regression analysis, log-transformed number of Torpedoes was associated with age (beta 0.004, p = 0.01) but not in a fully adjusted model including gender, race, postmortem interval (PMI), brain weight, number of Purkinje cells, CERAD plaque score and Braak stage(beta for age −0.003, p = 0.71). In unadjusted and adjusted models restricted to age quartiles 2–4, beta = −0.001, p = 0.70 and beta = −0.003 and p = 0.69, respectively. The results of replicate analyses on 32 brains were similar to our primary analyses. The number of Torpedoes was lowest in the youngest age quartile (0.2±0.4, 0) but was similar in the remaining three age quartiles (quartile 2: 1.8±1.9, 2; quartile 3: 3.2±2.3, 3.5; quartile 4: 2.7±2.4, 2.5)(for comparison of quartiles 2–4, p = 0.82). We examined control brains spanning a wide age range. Torpedoes were rare in the first four decades of life, but thereafter, there was no aging-associated increase. Torpedoes have been commented on as rare incidental findings in normal human control brains, although it has not been demonstrated that they are more abundant as a function of advanced age. One study [3] examined 32 axons in three normal individuals (ages 64, 70, 86). The 86 year old had two Torpedoes. In a study of two normal mouse strains (age 8 days - 32 months)[1], <0.1% of Purkinje cells had Torpedoes at 6 months; this increased linearly to 13.7% by age 32 months [1]. However, in a study of other normal mice strains, Torpedoes were absent, suggesting that Torpedoes are not a “simple aging phenomena” [6]. The lack of an association here between these lesions and advanced aging suggests that the abundance of these lesions in ET is a marker of cerebellar injury and not merely representative of accelerated aging.
Phyllis L Faust - One of the best experts on this subject based on the ideXlab platform.
-
torpedo formation and purkinje cell loss modeling their relationship in cerebellar disease
The Cerebellum, 2014Co-Authors: Elan D Louis, Jeanpaul G Vonsattel, Phyllis L FaustAbstract:Torpedo formation and Purkinje cell (PC) loss represent standard and inter-related cerebellar responses to injury. Surprisingly, the nature of their relationship has not been carefully characterized across a range of normal and disease states. Are brains with more Torpedoes expected to have fewer PCs? We quantified Torpedoes and PCs in four groups: essential tremor (ET), spinocerebellar ataxia (SCA), multiple system atrophy-cerebellar (MSA-C), and controls. Brains from 100 individuals (58 ET, 27 controls, 7 SCA, 8 MSA-C) were available at the New York Brain Bank. After complete neuropathological assessment, a standard parasagittal neocerebellar block was harvested; a 7-μm thick section was stained with Luxol fast blue/hematoxylin and eosin; and Torpedoes and PCs were quantified. For a given PC count, SCA and MSA-C cases often had higher torpedo counts than ET cases or controls. Furthermore, the relationship between torpedo and PC counts was complex. The correlation between torpedo and PC counts was negative in ET cases (i.e., individuals with more Torpedoes had fewer PCs [i.e., more PC loss]) whereas the relationship was positive in MSA-C cases (i.e., individuals with fewer PCs [i.e., more PC loss] had fewer Torpedoes). Patients with SCA showed both patterns. When all diagnostic groups were combined, the correlation was best fit by a quadratic (i.e., parabolic) model rather than a simple linear model; this model incorporated data on the negative correlation in ET cases, the mixed results in SCA cases, and the positive correlation in MSA-C cases (r = 0.636). The relationship between torpedo and PC counts was complex and heterogeneous across a range of cerebellar disease states, and was best characterized by a quadratic rather than a simple model. With more severe cerebellar disease, Torpedoes can be quite numerous and are likely a common feature of surviving PCs, but eventually, dramatic loss of PC leads to a paradoxical reduction in observable Torpedoes.
-
purkinje cell axonal anatomy quantifying morphometric changes in essential tremor versus control brains
Brain, 2013Co-Authors: Rachel Babij, Phyllis L Faust, Jean Paul Vonsattel, Etty Cortes, Elan D LouisAbstract:Growing clinical, neuro-imaging and post-mortem data have implicated the cerebellum as playing an important role in the pathogenesis of essential tremor. Aside from a modest reduction of Purkinje cells in some post-mortem studies, Purkinje cell axonal swellings (Torpedoes) are present to a greater degree in essential tremor cases than controls. Yet a detailed study of more subtle morphometric changes in the Purkinje cell axonal compartment has not been undertaken. We performed a detailed morphological analysis of the Purkinje cell axonal compartment in 49 essential tremor and 39 control brains, using calbindin D28k immunohistochemistry on 100-µm cerebellar cortical vibratome tissue sections. Changes in axonal shape [thickened axonal profiles (P = 0.006), Torpedoes (P = 0.038)] and changes in axonal connectivity [axonal recurrent collaterals (P 40 years. In essential tremor cases, thickened axonal profiles, axonal recurrent collaterals and branched axons were 3- to 5-fold more frequently seen on the axons of Purkinje cells with Torpedoes versus Purkinje cells without Torpedoes. We document a range of changes in the Purkinje cell axonal compartment in essential tremor. Several of these are likely to be compensatory changes in response to Purkinje cell injury, thus illustrating an important feature of Purkinje cells, which is that they are relatively resistant to damage and capable of mobilizing a broad range of axonal responses to injury. The extent to which this plasticity of the Purkinje cell axon is partially neuroprotective or ultimately ineffective at slowing further cellular changes and cell death deserves further study in essential tremor.
-
Torpedoes in the cerebellar vermis in essential tremor cases vs controls
The Cerebellum, 2011Co-Authors: Elan D Louis, Jean Paul Vonsattel, Phyllis L Faust, Karen J, Etty CortesAbstract:The study of the postmortem changes in essential tremor (ET) is in its infancy, although recent evidence points to a central role of the cerebellum, where Purkinje cell axonal swellings (“Torpedoes”) are significantly more common in ET than control brains. Yet, all existing studies have been confined to the cerebellar hemispheres, and whether there is a more widely distributed cerebellar problem is presently unknown. Our aims were to address whether: (1) ET cases have greater numbers of Torpedoes in the vermis than controls, (2) there a correlation between the extent of vermal torpedo pathology and hemispheric torpedo pathology, and (3) vermal torpedo pathology is correlated with clinical features of the disease. A parasagittal neocerebellar block and a vermal block were harvested from 24 ET and 10 control brains. Paraffin sections (7 μm) were stained with Luxol fast blue/hematoxylin and eosin, and Torpedoes were quantified. All torpedo counts were corrected for Purkinje cell layer length. Vermal corrected torpedo count (VermTc) was higher in ET cases than controls (7.1 ± 6.8 [median, 4.3] vs. 2.6 ± 2.5 [median, 2]), p = 0.002). The VermTc and the hemispheric corrected torpedo count (HemTc) were correlated with one another (Spearman’s r = 0.54, p = 0.002). ET cases with neck, voice, and jaw tremors had the highest VermTc (p = 0.046). The abundance of Torpedoes in the ET brain is not confined to the ponto- or neocerebellum but is more broadly distributed, also involving the spino- or paleocerebellum. These data further confirm the central role of the cerebellum in the underlying pathophysiology of this common neurological disorder.
-
hairy baskets associated with degenerative purkinje cell changes in essential tremor
Journal of Neuropathology and Experimental Neurology, 2010Co-Authors: Cordelia Ericksondavis, Jean Paul Vonsattel, Phyllis L Faust, Lawrence S Honig, Sachin Gupta, Elan D LouisAbstract:Essential tremor (ET) is one of the most common neurologic diseases. Increased numbers of Torpedoes and Purkinje cell (PC) loss have been documented in the brains of patients with ET. We recently observed a dense and tangled appearance ("hairiness") of the basket cell axonal plexuses that surround PC soma in Bielschowsky preparations of cerebellar cortex in ET brains. Here, we assessed basket cell "hairiness" in 37 ET (32 cerebellar ET; 5 Lewy body variant ET), 21 nondisease control, and 48 disease control brains using a semiquantitative scale. In 8 cerebellar ET cases (25%), there were high basket scores (rating = 3), whereas no Lewy body variant ET, 1 nondisease control (4.8%), and 2 diseased controls (4.2%) had high basket scores (p = 0.001). The hairy basket scores correlated with numbers of Torpedoes (p < 0.001) and inversely with numbers of PCs (p = 0.06). Axonal plexus density obtained by image analysis of basket cell processes traced from digitized images was higher in ET than in nondiseased control cases (p = 0.016). Closely spaced sites of synaptic contact between basket cell processes and PCs were identified by electron microscopy in ET cases. These data indicate that structural changes are not restricted to PCs in ET, and that other neurons within their functional network may be involved in its pathogenesis.
-
Torpedoes in parkinson s disease alzheimer s disease essential tremor and control brains
Movement Disorders, 2009Co-Authors: Elan D Louis, Jean Paul Vonsattel, Phyllis L Faust, Lawrence S Honig, Alex Rajput, Ali H Rajput, Rajesh Pahwa, Kelly E Lyons, Webster G Ross, Rodger J ElbleAbstract:Background—Purkinje cell axonal swellings (“Torpedoes”), described in several cerebellar disorders as well as essential tremor (ET), have not been quantified in common neurodegenerative conditions.
Cordelia Ericksondavis - One of the best experts on this subject based on the ideXlab platform.
-
hairy baskets associated with degenerative purkinje cell changes in essential tremor
Journal of Neuropathology and Experimental Neurology, 2010Co-Authors: Cordelia Ericksondavis, Jean Paul Vonsattel, Phyllis L Faust, Lawrence S Honig, Sachin Gupta, Elan D LouisAbstract:Essential tremor (ET) is one of the most common neurologic diseases. Increased numbers of Torpedoes and Purkinje cell (PC) loss have been documented in the brains of patients with ET. We recently observed a dense and tangled appearance ("hairiness") of the basket cell axonal plexuses that surround PC soma in Bielschowsky preparations of cerebellar cortex in ET brains. Here, we assessed basket cell "hairiness" in 37 ET (32 cerebellar ET; 5 Lewy body variant ET), 21 nondisease control, and 48 disease control brains using a semiquantitative scale. In 8 cerebellar ET cases (25%), there were high basket scores (rating = 3), whereas no Lewy body variant ET, 1 nondisease control (4.8%), and 2 diseased controls (4.2%) had high basket scores (p = 0.001). The hairy basket scores correlated with numbers of Torpedoes (p < 0.001) and inversely with numbers of PCs (p = 0.06). Axonal plexus density obtained by image analysis of basket cell processes traced from digitized images was higher in ET than in nondiseased control cases (p = 0.016). Closely spaced sites of synaptic contact between basket cell processes and PCs were identified by electron microscopy in ET cases. These data indicate that structural changes are not restricted to PCs in ET, and that other neurons within their functional network may be involved in its pathogenesis.
-
purkinje cell axonal Torpedoes are unrelated to advanced aging and likely reflect cerebellar injury
Acta Neuropathologica, 2009Co-Authors: Elan D Louis, Jean Paul Vonsattel, Phyllis L Faust, Cordelia EricksondavisAbstract:Torpedoes, swellings of the proximal Purkinje cell axon, are thought to represent a cellular response to injury [3]. They may occur in a variety of cerebellar disorders [7]. Most recently, their numbers were noted to be six-times higher in essential tremor (ET) than control brains [4]. Torpedoes are also often viewed as a cumulative phenomenon associated with advanced aging [3,4], yet there are surprisingly few supporting data. We quantified Torpedoes in normal human cerebella spanning a considerable age range to assess whether Torpedoes are a cumulative phenomenon of aging. These data help place the relative abundance of Torpedoes in ET in context. Control brains at the New York Brain Bank, Columbia University Medical Center (CUMC) had been controls in the Alzheimer’s Disease Research Center or non-neurologic patients at CUMC. Each had a complete neuropathologic assessment [4] including Braak AD stage [2] and CERAD [5] for Alzheimer’s tangle and plaque pathologies. As documented [4], a standard 3 × 20 × 25 mm parasagittal tissue block was harvested from each neocerebellum (N = 48) and immersion-fixed in 10% buffered formalin. Paraffin sections (7 μm thick) were stained with Luxol Fast Blue counterstained with Hematoxylin and Eosin (LH&E) [4]. Torpedoes (Figure 1) in one entire LH&E section were counted blinded to age. Purkinje cells in five randomly-selected 100x LH&E stained fields of the standard cerebellar section were counted and the mean reported. In 32 brains, a second set of sections from the same blocks were used as replicate data. Figure 1 Control cerebellar tissue showing a torpedo (arrow). LH&E 400x magnification. Non-parametric tests (Spearman’s r, Mann Whitney test, Kruskal Wallis test) were used. Because of zero values (0 Torpedoes), in linear regression analyses, log10(Torpedoes +1) was the dependent variable and age, the independent variable. Age at death ranged from 6–93 years. Mean±SD (median, range) number of Torpedoes = 1.8±2.1 (1, 0–11)(Table). Table Clinical characteristics/postmortem features (48 controls) Number of Torpedoes was correlated with age at death (r = 0.35, p = 0.02, Table), but not when the brains in the youngest age quartile (≤36 years) were excluded (i.e., in brains with age of death ranging from 37–93 years, r = −0.03, p = 0.85). While (mean±SD, median) number of Torpedoes was low in brains in the youngest quartile (quartile 1, ≤36 years, 0.5±0.9, 0), it did not differ among brains in the remaining 3 quartiles: quartile 2 (37–63 years) 1.9±1.6, 1.5; quartile 3 (64–80 years) 2.9±3.2, 2; quartile 4 (≥81 years) 2.0±1.4, 1.5 (for comparison of quartiles 2–4, p = 0.88)(Figure 2). Figure 2 Number of Torpedoes (Y axis) by age at death quartile (X axis). In a linear regression analysis, log-transformed number of Torpedoes was associated with age (beta 0.004, p = 0.01) but not in a fully adjusted model including gender, race, postmortem interval (PMI), brain weight, number of Purkinje cells, CERAD plaque score and Braak stage(beta for age −0.003, p = 0.71). In unadjusted and adjusted models restricted to age quartiles 2–4, beta = −0.001, p = 0.70 and beta = −0.003 and p = 0.69, respectively. The results of replicate analyses on 32 brains were similar to our primary analyses. The number of Torpedoes was lowest in the youngest age quartile (0.2±0.4, 0) but was similar in the remaining three age quartiles (quartile 2: 1.8±1.9, 2; quartile 3: 3.2±2.3, 3.5; quartile 4: 2.7±2.4, 2.5)(for comparison of quartiles 2–4, p = 0.82). We examined control brains spanning a wide age range. Torpedoes were rare in the first four decades of life, but thereafter, there was no aging-associated increase. Torpedoes have been commented on as rare incidental findings in normal human control brains, although it has not been demonstrated that they are more abundant as a function of advanced age. One study [3] examined 32 axons in three normal individuals (ages 64, 70, 86). The 86 year old had two Torpedoes. In a study of two normal mouse strains (age 8 days - 32 months)[1], <0.1% of Purkinje cells had Torpedoes at 6 months; this increased linearly to 13.7% by age 32 months [1]. However, in a study of other normal mice strains, Torpedoes were absent, suggesting that Torpedoes are not a “simple aging phenomena” [6]. The lack of an association here between these lesions and advanced aging suggests that the abundance of these lesions in ET is a marker of cerebellar injury and not merely representative of accelerated aging.
-
structural study of purkinje cell axonal Torpedoes in essential tremor
Neuroscience Letters, 2009Co-Authors: Elan D Louis, Hong Yi, Cordelia Ericksondavis, Jean Paul Vonsattel, Phyllis L FaustAbstract:Abstract Essential tremor (ET) is one of the most common neurological diseases. A basic understanding of its neuropathology is now emerging. Aside from Purkinje cell loss, a prominent finding is an abundance of Torpedoes (rounded swellings of Purkinje cell axons). Such swellings often result from the mis-accumulation of cell constituents. Identifying the basic nature of these accumulations is an important step in understanding the underlying disease process. Torpedoes, only recently identified in ET, have not yet been characterized ultrastructurally. Light and electron microscopy were used to characterize the structural constituents of Torpedoes in ET. Formalin-fixed cerebellar cortical tissue from four prospectively collected ET brains was sectioned and immunostained with a monoclonal phosphorylated neurofilament antibody (SMI-31, Covance, Emeryville, CA). Using additional sections from three ET brains, Torpedoes were assessed using electron microscopy. Immunoreactivity for phosphorylated neurofilament protein revealed clear labeling of Torpedoes in each case. Torpedoes were strongly immunoreactive; in many instances, two or more Torpedoes were noted in close proximity to one another. On electron microscopy, Torpedoes were packed with randomly arranged 10–12 nm neurofilaments. Mitochondria and smooth endoplasmic reticulum were abundant as well, particularly at the periphery of the torpedo. We demonstrated that the Torpedoes in ET represent the mis-accumulation of disorganized neurofilaments and other organelles. It is not known where in the pathogenic cascade these accumulations occur (i.e., whether these accumulations are the primary event or a secondary/downstream event) and this deserves further study.
Jean-yves Gaubert - One of the best experts on this subject based on the ideXlab platform.
-
Embolisation of pulmonary radio frequency pathway -a randomised trial
International Journal of Hyperthermia, 2017Co-Authors: Jean Izaaryene, Julien Mancini, Guillaume Louis, Kathia Chaumoitre, Jean-michel Bartoli, Vincent Vidal, Jean-yves GaubertAbstract:PURPOSE: Pneumothorax is the most common complication following a pulmonary percutaneous radiofrequency ablation (RFA), and thoracic drainages are the most frequent causes of an extended hospital stay. Our main objective was to show that the use of gelatin Torpedoes may significantly decrease the number of chest tube placement. MATERIALS AND METHODS: Seventy-three patients were prospectively included in this study and then randomised into two groups: 34 with embolisation and without 39 without embolisation. Each group was comparable for different pneumothorax risk factors. RESULTS: There were 16 (47%) pneumothorax in Group A ("with embolisation"), which was significantly lower (p
-
Embolisation of pulmonary radio frequency pathway – a randomised trial
2017Co-Authors: Jean Izaaryene, Julien Mancini, Guillaume Louis, Kathia Chaumoitre, Jean-michel Bartoli, Vincent Vidal, Jean-yves GaubertAbstract:Purpose: Pneumothorax is the most common complication following a pulmonary percutaneous radiofrequency ablation (RFA), and thoracic drainages are the most frequent causes of an extended hospital stay. Our main objective was to show that the use of gelatin Torpedoes may significantly decrease the number of chest tube placement. Materials and methods: Seventy-three patients were prospectively included in this study and then randomised into two groups: 34 with embolisation and without 39 without embolisation. Each group was comparable for different pneumothorax risk factors. Results: There were 16 (47%) pneumothorax in Group A (“with embolisation”), which was significantly lower (p
