Approximately 15% of patients with frontotemporal dementia (FTD) have co-occurring motor neuron disease (MND). FTD-MND cases have frontotemporal lobar degeneration (FTLD)-transactive response DNA-binding protein (TDP) pathology, which is divided into four subtypes (types A, B, C, and D) based on the morphological appearance, cellular location, and distribution of the abnormal TDP inclusions and dystrophic neurites. We report a patient with FTD-MND whose pathological diagnosis was FTLD-TDP type B. This is the first documented autopsy-confirmed case of FTD-MND in Korea.
Autopsy* ; Diagnosis ; Frontotemporal Dementia* ; Frontotemporal Lobar Degeneration ; Humans ; Korea ; Motor Neuron Disease* ; Motor Neurons* ; Neurites ; Pathology

Approximately 15% of patients with frontotemporal dementia (FTD) have co-occurring motor neuron disease (MND). FTD-MND cases have frontotemporal lobar degeneration (FTLD)-transactive response DNA-binding protein (TDP) pathology, which is divided into four subtypes (types A, B, C, and D) based on the morphological appearance, cellular location, and distribution of the abnormal TDP inclusions and dystrophic neurites. We report a patient with FTD-MND whose pathological diagnosis was FTLD-TDP type B. This is the first documented autopsy-confirmed case of FTD-MND in Korea.
Autopsy* ; Diagnosis ; Frontotemporal Dementia* ; Frontotemporal Lobar Degeneration ; Humans ; Korea ; Motor Neuron Disease* ; Motor Neurons* ; Neurites ; Pathology

ALS is a fatal adult-onset motor neuron disease. Motor neurons in the cortex, brain stem and spinal cord gradually degenerate in ALS patients, and most ALS patients die within 3~5 years of disease onset due to respiratory failure. The major pathological hallmark of ALS is abnormal accumulation of protein inclusions containing TDP-43, FUS or SOD1 protein. Moreover, the focality of clinical onset and regional spreading of neurodegeneration are typical features of ALS. These clinical data indicate that neurodegeneration in ALS is an orderly propagating process, which seems to share the signature of a seeded self-propagation with pathogenic prion proteins. In vitro and cell line experimental evidence suggests that SOD1, TDP-43 and FUS form insoluble fibrillar aggregates. Notably, these protein fibrillar aggregates can act as seeds to trigger the aggregation of native counterparts. Collectively, a self-propagation mechanism similar to prion replication and spreading may underlie the pathology of ALS. In this review, we will briefly summarize recent evidence to support the prion-like properties of major ALS-associated proteins and discuss the possible therapeutic strategies for ALS based on a prion-like mechanism.
Amyotrophic Lateral Sclerosis* ; Brain Stem ; Cell Line ; Humans ; Motor Neuron Disease ; Motor Neurons ; Pathology ; Prions ; Respiratory Insufficiency ; Spinal Cord

BACKGROUND AND PURPOSE: Involvement of the corpus callosum (CC) is reported to be a consistent feature of amyotrophic lateral sclerosis (ALS). We examined the CC pathology using diffusion tensor tractography analysis to identify precisely which fiber bundles are involved in ALS. METHODS: Diffusion tensor imaging was performed in 14 sporadic ALS patients and 16 age-matched healthy controls. Whole brain tractography was performed using the multiple-region of interest (ROI) approach, and CC fiber bundles were extracted in two ways based on functional and structural relevance: (i) cortical ROI selection based on Brodmann areas (BAs), and (ii) the sulcal-gyral pattern of cortical gray matter using FreeSurfer software, respectively. RESULTS: The mean fractional anisotropy (FA) values of the CC fibers interconnecting the primary motor (BA4), supplementary motor (BA6), and dorsolateral prefrontal cortex (BA9/46) were significantly lower in ALS patients than in controls, whereas those of the primary sensory cortex (BA1, BA2, BA3), Broca's area (BA44/45), and the orbitofrontal cortex (BA11/47) did not differ significantly between the two groups. The FreeSurfer ROI approach revealed a very similar pattern of abnormalities. In addition, a significant correlation was found between the mean FA value of the CC fibers interconnecting the primary motor area and disease severity, as assessed using the revised Amyotrophic Lateral Sclerosis Functional Rating Scale, and the clinical extent of upper motor neuron signs. CONCLUSIONS: Our findings suggest that there is some degree of selectivity or a gradient in the CC pathology in ALS. The CC fibers interconnecting the primary motor and dorsolateral prefrontal cortices may be preferentially involved in ALS.
Amyotrophic Lateral Sclerosis* ; Anisotropy ; Brain ; Corpus Callosum* ; Diffusion Tensor Imaging ; Diffusion* ; Humans ; Motor Neuron Disease ; Motor Neurons ; Pathology ; Prefrontal Cortex

Amyotrophic lateral sclerosis (ALS) is a progressive motor neuron degenerative disease that clinically manifests both upper and lower motor neuron signs. However, it is unknown where and how the motor neuron degeneration begins, and conflicting hypotheses have been suggested. Recent advanced radiological techniques enable us to look into ALS neuropathology in vivo. Herein, we report a case with upper motor neuron-predominant ALS in whom the results of brain magnetic resonance imaging (MRI) and myelin water fraction MRI suggest axonal degeneration.
Amyotrophic Lateral Sclerosis* ; Axons ; Brain ; Magnetic Resonance Imaging* ; Motor Neurons ; Myelin Sheath* ; Neuropathology ; Pathology ; Water*

BACKGROUNDMotor dysfunction is common in stroke patients. Clinical electrophysiological studies suggest that transsynaptic degeneration occurred in the lower motor neurons, while pathological evidence is lacked. This study aimed to combine the electrophysiological and pathological results to prove the existence of transsynaptic degeneration in the motor system after stroke.

METHODSModified neurologic severity score, electrophysiological, and pathological assessments were evaluated in rats before middle cerebral artery occlusion (MCAO), and at 24 hours, 7 days, and 14 days after MCAO. Paired and independent-sample t-tests were applied to assess the changes of electrophysiological and pathological data.

RESULTSCompound motor action potential amplitude in the paretic side was significantly lower than the nonparetic side at both 24 hours (61.9 ± 10.4 vs. 66.6 ± 8.9, P < 0.05) and 7 days (60.9 ± 8.4 vs. 67.3 ± 9.6, P < 0.05) after MCAO. Motor unit number estimation of the paretic side was significantly less than the nonparetic side (379.0 ± 84.6 vs. 445.0 ± 89.5, P < 0.05) at 7 days after MCAO. Until 14 days after stroke, the pathological loss of motor neurons was detected. Motor neurons in 14-day MCAO group were significantly decreased, compared with control group (5.3 ± 0.7 vs. 7.3 ± 1.8, P < 0.05).

CONCLUSIONSBoth electrophysiological and pathological studies showed transsynaptic degeneration after stroke. This study identified the asynchronization in changes of electrophysiology and pathology. The abnormal physiological changes and function impairment can be detected in the early stage and recovered quickly, while the pathological loss of motor neuron can be detected only in a later stage.

Animals ; Electrophysiology ; Infarction, Middle Cerebral Artery ; pathology ; physiopathology ; Male ; Motor Neurons ; pathology ; Rats ; Rats, Sprague-Dawley ; Spinal Cord ; pathology ; physiopathology

OBJECTIVETo investigate the protection effect of nerve implantation to the neurons after sciatic nerve injury to adult rats.

METHODSThirty male Sprague-Dawley rats weighing 180 - 220 g (8 - 9 weeks of age) were randomly divided into four groups. Group A consisted of normal rats without operation. In group B, the sciatic nerve of rats was transected, with the proximal stump of the sciatic nerve ligated to inhibit nerve regeneration. In group C, a sciatic nerve crushed model was set up. In group D, a sciatic nerve implantation model was established. The rats were sacrificed on postoperative days 7, 14 and 28 respectively. The L(4)-L(6) segments of the spinal cord were harvested. TUNEL technique was used to detect apoptotic motor neurons. HE and Toluidine Blue staining was used for counting motor neurons.

RESULTSThe apoptotic neurons detected on the 28th postoperative day were significantly fewer in the implantation group than in the other groups (P < 0.05). The number of motor neurons was significantly higher in the implantation group than in other two control groups (P < 0.05).

CONCLUSIONSNerve implantation exerts protective effect on neurons after nerve injury.

Animals ; Apoptosis ; Male ; Motor Neurons ; pathology ; Nerve Transfer ; Peripheral Nerve Injuries ; Peripheral Nerves ; pathology ; Rats ; Rats, Sprague-Dawley

OBJECTIVETo investigate the effect of puerarin on the neural function and the histopathological changes after ischemic spinal cord injury in rabbits.

METHODSThirty male New Zealand white rabbits were randomly divided into three groups as follows: puerarin group (n=10) receiving intravenous infusion of 30 mg/kg puerarin for 10 minutes, control group (n=10) receiving intravenous infusion of the same volume of normal saline as puerarin for 10 minutes, and sham operation group (n=10) undergoing only the surgical exposure of the abdominal aorta. Temporary spinal cord ischemia was induced by infrarenal aortic occlusion for 20 minutes and followed by reperfusion. The neural status was scored with the Tarlov criteria at 8, 12, 24 and 48 hours after reperfusion. All the animals were killed at 48 hours after reperfusion and the spinal cords (L5) were removed immediately for histopathological study.

RESULTSThe neural function scores at 8, 12, 24 and 48 hours after reperfusion were higher in the puerarin group and sham operation group than those in the control group (P<0.05). More normal motor neurons in the anterior horn of spinal cord were present in the puerarin group and sham operation group than those in the control group (P<0.01). There was a strong correlation between the final neural function scores and the number of normal motor neurons in the anterior horn of spinal cord (r=0.839, P<0.01).

CONCLUSIONSPuerarin can significantly ameliorate the neural function and the histopathological damages after transient spinal cord ischemia in rabbits.

Animals ; Isoflavones ; pharmacology ; Male ; Motor Neurons ; pathology ; Rabbits ; Spinal Cord Ischemia ; drug therapy ; pathology ; physiopathology ; Vasodilator Agents ; pharmacology

Protective effect of interleukin-1beta (IL-1beta) on motor neurons was studied after peripheral nerve injury. Twenty Wistar rats were divided into 2 groups randomly. The right sciatic nerve of each rat was resected. After silicon tubulization of sciatic nerve in rat, 15 microl 1 ng/ml IL-1beta and PBS solution were injected into the silicon capsule respectively. Enzyme histochemistry was performed to show acetyle cholesterase (AchE) and nitric oxide staining (NOS) activity of spinal alpha motor neurons in spinal segments 2 weeks later. Neurons were counted and the diameter and cross sectional (c/s) area of neurons were analyzed by using computer image analysis system. The results showed that as compared with the normal side, both enzyme activities significantly changed in motor neurons in PBS group. The diameter and c/s area of both neurons changed significantly too (P < 0.01). These results suggest that exogenous IL-1beta protects alpha-motor neurons from degeneration and necrosis after peripheral nerve injury.
Interleukin-1/*pharmacology ; Motor Neurons/*pathology ; Neuroprotective Agents/*pharmacology ; Random Allocation ; Rats, Wistar ; Sciatic Nerve/*injuries ; Spinal Cord/pathology

Amyotrophic lateral sclerosis (ALS) is the most common motor neuron disease. At present, no definite ALS biomarkers are available. In this study, exosomes from the plasma of patients with ALS and healthy controls were extracted, and differentially expressed exosomal proteins were compared. Among them, the expression of exosomal coronin-1a (CORO1A) was 5.3-fold higher than that in the controls. CORO1A increased with disease progression at a certain proportion in the plasma of patients with ALS and in the spinal cord of ALS mice. CORO1A was also overexpressed in NSC-34 motor neuron-like cells, and apoptosis, oxidative stress, and autophagic protein expression were evaluated. CORO1A overexpression resulted in increased apoptosis and oxidative stress, overactivated autophagy, and hindered the formation of autolysosomes. Moreover, CORO1A activated Ca²⁺-dependent phosphatase calcineurin, thereby blocking the fusion of autophagosomes and lysosomes. The inhibition of calcineurin activation by cyclosporin A reversed the damaged autolysosomes. In conclusion, the role of CORO1A in ALS pathogenesis was discovered, potentially affecting the disease onset and progression by blocking autophagic flux. Therefore, CORO1A might be a potential biomarker and therapeutic target for ALS.
Mice ; Animals ; Amyotrophic Lateral Sclerosis/pathology* ; Calcineurin/metabolism* ; Motor Neurons/pathology* ; Microfilament Proteins/metabolism* ; Cytoskeletal Proteins/metabolism*