Anterior Horn Cells Research Articles

Morphometric analysis of spinal motor neuron degeneration in sporadic amyotrophic lateral sclerosis

ObjectivesThis study aimed to clarify the relationship between 43-kDa TAR DNA-binding protein (TDP-43) pathology and spinal cord anterior horn motor neuron (AHMN) atrophy in sporadic amyotrophic lateral sclerosis (SALS). MethodsEight patients with SALS and 12 controls were included in this study. Formalin-fixed specimens of lumbar spinal cord samples were paraffin-embedded and sectioned at the level of the fourth lumbar spinal cord with a 4 μm thickness. Using a microscope, the long diameters of the neurons with nucleoli were measured in spinal AHMNs stained with an anti-SMI-32 antibody. AHMNs were divided into medial and lateral nuclei for statistical analysis. We also used previously reported data to measure the long diameter of AHMNs with initial TDP-43 pathology, in which TDP-43 was present both in the nucleus and cytoplasm. ResultsThe long diameter of the lumbar spinal AHMNs in patients with SALS was smaller in the medial nucleus (42.54 ± 9.33 μm, n = 24) and the lateral nucleus (49.41 ± 13.86 μm, n = 129) than in controls (medial nucleus: 55.84 ± 13.49 μm, n = 85, p < 0.001; lateral nucleus: 62.39 ± 13.29 μm, n = 756, p < 0.001, Mann–Whitney U test). All 21 motor neurons with initial TDP-43 pathology were in the lateral nucleus, and their long diameter (67.60 ± 18.3 μm, p = 0.352) was not significantly different from that of controls. ConclusionMotor neuron atrophy in SALS does not occur during the initial stages of TDP-43 pathology, and TDP-43 pathology is already advanced in the atrophied motor neurons.

The Impact of Nusinersen and Risdiplam on Motor Function for Spinal Muscular Atrophy Type 2 and 3: A Meta-Analysis.

Spinal muscular atrophy (SMA) is a prevalent paediatric neuromuscular disorder characterised by muscle weakness and atrophy resulting from degeneration of spinal cord anterior horn α motor neurons. Gene therapy formulations exhibit varying benefits and limitations, driving the need for patient-friendly treatment options tailored to specific populations. The objective of this meta-analysis was to assess the effectiveness of gene therapy for motor function in children with SMA. The analysis encompassed a total of 719 participants from six randomised controlled trials (RCTs) conducted between 2017 and 2023. Among the studies, one demonstrated a significant and large standardised effect size (Cohen's d) favouring nusinersen in terms of Hammersmith Functional Motor Scale - Expanded (HFMSE) (d = 0.97) and revised upper limb module (RULM) (d = 0.96). Additionally, another study showed a moderate standardised effect size (Cohen's d) in favour of nusinersen concerning Hammersmith Infant Neurological Examination-Section 2 (HINE-2) (d = 0.48). However, it is important to note that further research with a longer duration of observation is required to strengthen the evidence. Key Words: Spinal muscular atrophy, Nusinersen, Risdiplam, Motor function, Cohen's d.

A Five-Year Review of Newborn Screening for Spinal Muscular Atrophy in the State of Utah: Lessons Learned.

Spinal muscular atrophy (SMA) is an autosomal recessive condition characterized by alpha motor neuron degeneration in the spinal cord anterior horn. Clinical symptoms manifest in the first weeks to months of life in the most severe cases, resulting in progressive symmetrical weakness and atrophy of the proximal voluntary muscles. Approximately 95% of SMA patients present with homozygous deletion of the SMN1 gene. With multiple available therapies preventing symptom development and slowing disease progression, newborn screening for SMA is essential to identify at-risk individuals. From 2018 to 2023, a total of 239,844 infants were screened. 13 positive screens were confirmed to have SMA. An additional case was determined to be a false positive. We are not aware of any false-negative cases. All patients were seen promptly, with diagnosis confirmed within 1 week of the initial clinical visit. Patients were treated with nusinersen or onasemnogene abeparvovec. Treated patients with two copies of SMN2 are meeting important developmental milestones inconsistent with the natural history of type 1 SMA. Patients with 3-4 copies of SMN2 follow normal developmental timelines. Newborn screening is an effective tool for the early identification and treatment of patients with SMA. Presymptomatic treatment dramatically shifts the natural history of SMA, with most patients meeting appropriate developmental milestones. Patients with two copies of SMN2 identified through newborn screening constitute a neurogenetic emergency. Due to the complexities of follow-up, a multidisciplinary team, including close communication with the newborn screening program, is required to facilitate timely diagnosis and treatment.

Altered expression of human myxovirus resistance protein A in amyotrophic lateral sclerosis.

Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disorder. The etiology of sporadic ALS (sALS) has not yet been clarified. An increasing body of evidence suggests the involvement of viral infections and interferons (IFNs). Human myxovirus resistance protein A (MxA) is an IFN-induced dynamin-like GTPase that acts as a potent antiviral factor. This study examined MxA expression in ALS patient spinal cords using immunohistochemistry. Thirty-two cases of sALS (pathologically proven ALS-TDP), 10 non-ALS, other neurological disease control cases were examined. In most ALS cases, MxA cytoplasmic condensates were observed in the remaining spinal anterior horn neurons. The ALS group had a significantly higher rate of MxA-highly expressing neurons than the non-ALS group. Colocalization of MxA cytoplasmic condensate and transactive response DNA-binding protein 43 kDa (TDP-43)-positive inclusions was rarely observed. Because MxA has antiviral activity induced by IFNs, our results suggest that IFNs are involved in the pathogenesis of ALS in spinal cord anterior horn neurons. Our study also suggests that monitoring viral infections and IFN activation in patients with ALS may be critically important.

Transsynaptic degeneration of ventral horn motor neurons exists but plays a minor role in lower motor system dysfunction in acute ischemic rats.

As a leading cause of mortality and long-term disability, acute ischemic stroke can produce far-reaching pathophysiological consequences. Accumulating evidence has demonstrated abnormalities in the lower motor system following stroke, while the existence of Transsynaptic degeneration of contralateral spinal cord ventral horn (VH) neurons is still debated. Using a rat model of acute ischemic stroke, we analyzed spinal cord VH neuron counts contralaterally and ipsilaterally after stroke with immunofluorescence staining. Furthermore, we estimated the overall lower motor unit abnormalities after stroke by simultaneously measuring the modified neurological severity score (mNSS), compound muscle action potential (CMAP) amplitude, repetitive nerve stimulation (RNS), spinal cord VH neuron counts, and the corresponding muscle fiber morphology. The activation status of microglia and extracellular signal-regulated kinase 1/2 (ERK 1/2) in the spinal cord VH was also assessed. At 7 days after stroke, the contralateral CMAP amplitudes declined to a nadir indicating lower motor function damage, and significant muscle disuse atrophy was observed on the same side; meanwhile, the VH neurons remained intact. At 14 days after focal stroke, lower motor function recovered with alleviated muscle disuse atrophy, while transsynaptic degeneration occurred on the contralateral side with elevated activation of ERK 1/2, along with the occurrence of neurogenic muscle atrophy. No apparent decrement of CMAP amplitude was observed with RNS during the whole experimental process. This study offered an overview of changes in the lower motor system in experimental ischemic rats. We demonstrated that transsynaptic degeneration of contralateral VH neurons occurred when lower motor function significantly recovered, which indicated the minor role of transsynaptic degeneration in lower motor dysfunction during the acute and subacute phases of focal ischemic stroke.

Management and Therapeutic Strategies for Spinal Muscular Atrophy

Spinal muscular atrophy is an autosomal recessive neuromuscular disorder characterized by progressive muscle weakness and atrophy. It is one of the most common single-gene disorders with an incidence rate of approximately 1 in 10,000 live births. The clinical manifestations are progressive hypotonia and muscle weakness due to the degeneration of alpha neurons in the anterior horn cells of the spinal cord and motor nuclei in the lower brain stem. Depending on the severity of the symptoms, SMA has five subtypes. Supportive measures can be offered for respiratory, gastrointestinal, and musculoskeletal complications. Carrier testing for all couples is recommended and this can be done by Multiplex Ligation-dependent Probe Amplification (MLPA). Prenatal diagnosis can be offered to carrier couples. Therapies must be given within the newborn period for maximum benefit and before the loss of motor neurons. It is achieved by identifying the SMA babies through Newborn screening. Several new FDA-approved drugs can reduce the progression of symptoms in SMA. However, they cannot offer a definite cure. Clinical follow-up and Neurological assessment demonstrate that SMA children can attain developmental milestones after receiving treatment, which is never normally attained in untreated cases. In utero SMA treatment with Zolgensma would enhance the survival rate and favorable neurological outcomes in the future. Base editing and Gene editing with CRISPR-Cas technologies to target the mutations and restore functional and stable SMN protein levels are the future hopes for a permanent cure of SMA.

Changes in the excitability of anterior horn cells in a mental rotation task of body parts.

Mental rotation (MR), a tool of implicit motor imagery, is the ability to rotate mental representations of two- or three-dimensional objects. Although many reports have described changes in brain activity during MR tasks, it is not clear whether the excitability of anterior horn cells in the spinal cord can be changed. In this study, we examined whether MR tasks of hand images affect the excitability of anterior horn cells using F-wave analysis. Right-handed, healthy participants were recruited for this study. F-waves of the right abductor pollicis brevis were recorded after stimulation of the right median nerve at rest, during a non-MR task, and during an MR task. The F-wave persistence and the F/M amplitude ratio were calculated and analyzed. Twenty participants (11 men and 9 women; mean age, 29.2 ± 4.4 years) were initially recruited, and data from the 18 that met the inclusion criteria were analyzed. The F-wave persistence was significantly higher in the MR task than in the resting condition (p = .001) or the non-MR task (p = .012). The F/M amplitude ratio was significantly higher in the MR task than in the resting condition (p = .019). The MR task increases the excitability of anterior horn cells corresponding to the same body part. MR tasks may have the potential for improving motor function in patients with reduced excitability of the anterior horn cells, although this methodology must be further verified in a clinical setting.

Acute neuromuscular disorders in critically ill children

Acute neuromuscular disorders are a group of neurological emergencies characterized by rapid onset of motor weakness commonly involving the respiratory and bulbar muscles. These can be acute or an exacerbation of the chronic neuromuscular disease. An accurate and timely diagnosis allows for the timely institution of specific therapies, improving long-term functional outcomes. Landry–Guillain–Barre syndrome (LGBS), acute transverse myelitis, compressive myelopathy, traumatic spinal lesions, and anterior horn cell myelitis (due to viral infections) are some of the common causes of acute motor weakness in children. LGBS is the most common among all. The diagnosis relies on clinical presentation, signs, cerebrospinal fluid analysis, electrophysiological studies, and neuroimaging of the spine. Once compressive or traumatic spinal lesions are suspected, immediate neuroimaging of the spine is essential to plan early neurosurgical intervention. Pediatric intensive care unit (PICU) admission is often required for supportive management and immunomodulation. Supportive management typically includes endotracheal intubation to protect the airway, mechanical ventilation (MV) to support breathing, monitoring, management of autonomic dysfunction, control of pain, physiotherapy, adequate nutrition, prevention of pressure sores, bladder–bowel care, psychological support, and planning of long-term care. Autonomic dysfunction can cause hemodynamic instability, arrhythmias, sudden cardiac arrest, and death, requiring close monitoring and management in PICU. Tracheostomy is often needed in children who continue to have respiratory paralysis and are predicted to require long-term term mechanical ventilation. The outcome generally depends on the primary disease and long-term care.

Cerebellar syndrome in heat stroke (literary review)

The central nervous system is very sensitive to hyperthermia, which causes neurological complications through alteration of the cerebellum, basal ganglia, anterior horn cells, and peripheral nerves. Cerebellar damage is associated with generalized atrophy and signs of Purkinje cell involvement. Heat shock (stroke) is a critical condition caused by hyperthermia, typified by symmetrical damage to the cerebellum. The critical core temperature for the brain is 40–41 °C, but damage to the cerebellum can occur at lower temperatures. In the central nervous system, cerebellar Purkinje cells are most susceptible to hyperpyrexia-induced dysfunction. The degree of their loss correlates with the severity and duration of hyperthermia. Heat hyperpyrexia-induced cerebellar atrophy usually involves both the vermis and the cerebellar hemispheres. Heat stroke can also cause neurological dysfunction, most commonly due to cerebellar damage. During the acute stage, typical neurological disorders are cerebellar ataxia, cognitive impairment, dysphagia, and aphasia. The convalescent period is characterized by transient cerebellar dysfunction; diffuse cerebellar atrophy has been described, and cerebellar degeneration is a well-known consequence of heat stroke. In permanent cerebellar dysfunction after heat stroke, permanent neurological deficit is relatively rare, and the most common manifestation is cerebellar syndrome. The most common X-ray finding in heat stroke is diffuse cerebellar atrophy with preserved brain volume, which is caused by diffuse loss of Purkinje cells and, according to computed tomography and magnetic resonance imaging, mostly affects the vermis or the cerebellar hemispheres, with the hemispheres of the brain mostly remain intact. Cerebellar disorders caused by heat stroke is a complex neurological problem. To rule out an alternative diagnosis, a thorough special examination with neuroimaging is necessary.

Refinement of the motorised laminectomy-assisted rat spinal cord injury model by analgesic treatment.

Usage and reporting of analgesia in animal models of spinal cord injury (SCI) have been sparse and requires proper attention. The majority of experimental SCI research uses rats as an animal model. This study aimed to probe into the effects of some commonly used regimens with NSAIDs and opioids on well-being of the rats as well as on the functional outcome of the model. This eight-week study used forty-two female Wistar rats (Crl: WI), randomly and equally divided into 6 treatment groups, viz. I) tramadol (5mg/kg) and buprenorphine (0.05mg/kg); II) carprofen (5mg/kg) and buprenorphine (0.05mg/kg); III) carprofen (5mg/kg); IV) meloxicam (1mg/kg) and buprenorphine (0.05mg/kg); V) meloxicam (1mg/kg); and VI) no analgesia (0.5 ml sterile saline). Buprenorphine was administered twice daily whereas other treatments were given once daily for five days post-operatively. Injections were given subcutaneously. All animals underwent dental burr-assisted laminectomy at the T10-T11 vertebra level. A custom-built calibrated spring-loaded 200 kilodynes force deliverer was used to induce severe SCI. Weekly body weight scores, Rat Grimace Scale (RGS), and dark-phase home cage activity were used as markers for well-being. Weekly Basso Beattie and Bresnahan (BBB) scores served as markers for functionality together with Novel Object Recognition test (NOR) at week 8 and terminal histopathology using area of vacuolisation and live neuronal count from the ventral horns of spinal cord. It was concluded that the usage of analgesia improved animal wellbeing while having no effects on the functional aspects of the animal model in comparison to the animals that received no analgesics.

EphrinB2 knockdown in cervical spinal cord preserves diaphragm innervation in a mutant SOD1 mouse model of ALS

Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease characterized by motor neuron loss. Importantly, non-neuronal cell types such as astrocytes also play significant roles in disease pathogenesis. However, mechanisms of astrocyte contribution to ALS remain incompletely understood. Astrocyte involvement suggests that transcellular signaling may play a role in disease. We examined contribution of transmembrane signaling molecule ephrinB2 to ALS pathogenesis, in particular its role in driving motor neuron damage by spinal cord astrocytes. In symptomatic SOD1G93A mice (a well-established ALS model), ephrinB2 expression was dramatically increased in ventral horn astrocytes. Reducing ephrinB2 in the cervical spinal cord ventral horn via viral-mediated shRNA delivery reduced motor neuron loss and preserved respiratory function by maintaining phrenic motor neuron innervation of diaphragm. EphrinB2 expression was also elevated in human ALS spinal cord. These findings implicate ephrinB2 upregulation as both a transcellular signaling mechanism in mutant SOD1-associated ALS and a promising therapeutic target.

EphrinB2 knockdown in cervical spinal cord preserves diaphragm innervation in a mutant SOD1 mouse model of ALS.

Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease characterized by motor neuron loss. Importantly, non-neuronal cell types such as astrocytes also play significant roles in disease pathogenesis. However, mechanisms of astrocyte contribution to ALS remain incompletely understood. Astrocyte involvement suggests that transcellular signaling may play a role in disease. We examined contribution of transmembrane signaling molecule ephrinB2 to ALS pathogenesis, in particular its role in driving motor neuron damage by spinal cord astrocytes. In symptomatic SOD1G93A mice (a well-established ALS model), ephrinB2 expression was dramatically increased in ventral horn astrocytes. Reducing ephrinB2 in the cervical spinal cord ventral horn via viral-mediated shRNA delivery reduced motor neuron loss and preserved respiratory function by maintaining phrenic motor neuron innervation of diaphragm. EphrinB2 expression was also elevated in human ALS spinal cord. These findings implicate ephrinB2 upregulation as both a transcellular signaling mechanism in mutant SOD1-associated ALS and a promising therapeutic target.

Biological differences and molecular mechanism of different peripheral nerves after injury.

The aim of the study was to analyze the apoptosis of neurons and the differences in expression of Bcl-2 and Bax protein in the neurons in the corresponding spinal cord segment after the repair of the tibial nerve (TN) and common peroneal nerve (CPN) in rats. 126 healthy male Sprague-Dawley (SD) rats aged 7-8 weeks were randomly divided into group A (control group), group B (TN was cut and sutured), and group C (CPN was cut and sutured), with 42 rats in each group. The spinal cord tissues of rats in different groups were stained with hematoxylin-eosin (HE) on the 1st, 3rd, 7th, 14th, 21st, and 28th day after surgery; the number of neurons in anterior horn of spinal cord, axon density (AD), axon passage rate (APR), and recovery rate (RR) of muscle cell cross-sectional area (MCCA) were calculated; and differences in the expression of Bcl-2 and Bax proteins in the three groups of rats were analyzed by immunohistochemistry. The results showed that there was no statistically significant difference in the muscle wet weight (MWW) RR of the three groups of rats on the 14th day after the surgery (p>0.05), and the MWW RRs of rats in groups B and C were higher at the 28th day after surgery in contrast to group A (p<0.05). The number of motor neurons in the anterior horn of spinal cord in group B was higher than that in group C at the 3rd, 7th, 14th, and 21st day after surgery (p<0.05); the MWW RR, MCCA, and CSARR of rats in group B were lower than those in group C (p<0.05); the proximal AD, distal AD, and APR in group B were higher than those of group C on the 14th and 28th day after the surgery (p<0.05); and there were no positive staining results in the spinal cord tissue of rats in group A after staining. The expressions of Bcl-2 and Bax in group B were higher observably than the expressions in group C (p<0.05), which indicated that the recovery ability of TN was stronger than that of the CPN; the expression of Bcl-2 and Bax in TN was notably higher than that of the CPN. The expression of Bcl-2 and Bax was related to cell apoptosis and nerve regeneration after nerve injury. It provided a reference basis for clinical diagnosis and treatment of peripheral nerves.

Comparative study of susceptibility to methylmercury cytotoxicity in cell types composing rat peripheral nerves: a higher susceptibility of dorsal root ganglion neurons.

Methylmercury is an environmental polluting organometallic compound that exhibits neurotoxicity, as observed in Minamata disease patients. Methylmercury damages peripheral nerves in Minamata patients, causing more damage to sensory nerves than motor nerves. Peripheral nerves are composed of three cell types: dorsal root ganglion (DRG) cells, anterior horn cells (AHCs), and Schwann cells. In this study, we compared cultured these three cell types derived from the rat for susceptibility to methylmercury cytotoxicity, intracellular accumulation of mercury, expression of L-type amino acid transporter 1 (LAT1), which transports methylmercury into cells, and expression of multidrug resistance-associated protein 2 (MRP2), which transports methylmercury-glutathione conjugates into the extracellular space. Of the cells examined, we found that DRG cells were the most susceptible to methylmercury with markedly higher intracellular accumulation of mercury. The constitutive level of LAT1 was higher and that of MRP2 lower in DRG cells compared with those in AHC and Schwann cells. Additionally, decreased cell viability caused by methylmercury was significantly reduced by either the LAT1 inhibitor, JPH203, or siRNA-mediated knockdown of LAT1. On the other hand, an MRP2 inhibitor, MK571, significantly intensified the decrease in the cell viability caused by methylmercury. Our results provide a cellular basis for sensory neve predominant injury in the peripheral nerves of Minamata disease patients.

Electromyography reveals the etiology of floppy infant in developing country

Background. Floppy infants are correlated with the extensive differential diagnosis. It can make diagnostic approach become more challenging. Case report. We report a 10-months-old infant referred from Pediatrician to electromyography (EMG) laboratory presenting with floppy and developmental delays. The central and motor neuron manifestations also increased of CPK levels bring ambiguity for the diagnosis. EMG may distinguish the cause from myopathy, anterior horn cell, neuromuscular junction (NMJ) or central origin when genetic testing is not routinely done in developing country. Conclusion. EMG helps clinician to distinguish the diagnosis of floppy infant.

Ferrostatin-1 improves neurological impairment induced by ischemia/reperfusion injury in the spinal cord through ERK1/2/SP1/GPX4

Spinal cord ischemia/reperfusion injury (SCIRI) induced by artificial aortic occlusion for a while during aortic surgery is a serious complication, leading to paraplegia and even death. Ferroptosis in the nervous system has been confirmed to contribute to neuronal death induced by SCIRI. Therefore, we investigated the therapeutic benefits of ferrostatin-1 (Fer-1, a ferroptosis inhibitor) and explored the mechanism and target of Fer-1 in SCIRI. Our results demonstrate that intrathecal injection of Fer-1 had a strong anti-SCIRI effect, improved ferroptosis-related indices, increased neurological function scores and motor neuron counts, and reduced BSCB leakage and neuroinflammation levels in the anterior horn. We found that SCIRI significantly elevated the levels of several important proteins, including SP1, p-ERK1/2/ERK1/2, COX2, TFR1, SLC40A1, SLC7A11, cleaved Caspase 3, GFAP, and Iba1, while reducing FTH1 and GPX4 protein expression, with no effect on ACSL4 expression. Fer-1 effectively ameliorated the ferroptosis-related changes in these proteins induced by SCIRI. However, for p-ERK1/2 and SP1, Fer-1 not only failed to reduce their expression but also significantly enhanced it. Fer-1 was injected into sham operation rats, abnormal increases in p-ERK1/2/ERK1/2 and SP1 were observed, along with an increase in GPX4. Fluorescent double labeling revealed that SP1 and GPX4 were expressed in neurons and astrocytes. Inhibitors of the ERK pathway (SCH772984) and siRNA against SP1 (AV-sh-SP1) significantly decreased the increase in SP1 and GPX4 protein levels, fluorescent density of SP1 and GPX4 in neurons, and the number of SP1-positive and GPX4-positive neurons induced by Fer-1. SCH772984 but not AV-sh-SP1 significantly reversed the decrease in GFAP and Iba1 induced by Fer-1. In conclusion, our results indicate that Fer-1 inhibited ferroptosis in spinal cord anterior horn neurons, improving neurological impairment and BSCB damage after SCIRI through the ERK1/2/SP1/GPX4 signaling pathway in rats.

Effect of nusinersen after 3 years of treatment in 57 young children with SMA in terms of SMN2 copy number or type

BackgroundSpinal muscular atrophy (SMA) is a rare genetic neuromuscular disorder due to an autosomal recessive mutation in the survival motor neuron 1 gene (SMN1), causing degeneration of the anterior horn cells of the spinal cord and resulting in muscle atrophy. This study aimed to report on the 36-month follow-up of children with SMA treated with nusinersen before the age of 3 years. Changes in motor function, nutritional and ventilatory support, and orthopedic outcomes were evaluated at baseline and 36 months after intrathecal administration of nusinersen and correlated with SMA type and SMN2 copy number. ResultsWe found that 93% of the patients gained new motor skills during the 3 years—standing without help for 12 of 37 and walking with help for 11 of 37 patients harboring three SMN2 copies. No patients with two copies of SMN2 can stand alone or walk. Patients bearing three copies of SMN2 are more likely to be spared from respiratory, nutritional, and orthopedic complications than patients with two SMN2 copies. ConclusionChildren with SMA treated with nusinersen continue to make motor acquisitions at 3 years after initiation of treatment. Children with two SMN2 copies had worse motor, respiratory, and orthopedic outcomes after 3 years of treatment than children with three copies.

Early histopathological changes of secondary degeneration in the spinal cord after total MCA territory stroke

Previous research has not demonstrated secondary degeneration of the spinal cord (SpC) motoneurons after cerebral infarct. The aim of the present study is to investigate the involvement of the anterior horn cells (AHC) in the early post-stroke period using histomorphological and immunohistochemical methods. Post-mortem analysis of the 6th cervical segment was performed in 7 patients who had total MCA stroke within 1 month before death. Nissl-stained sections were used for morphometry, while CD68 and synaptophysin (SYP) immunohistochemistry to monitor microglial activation and synaptic changes in the anterior horn (AH), respectively. Contralateral to the cerebral lesion (contralesional side), cells were smaller after 3 days and larger after 1 week of stroke, especially regarding the large alpha motoneurons. CD68 density increased mainly on the contralesional Rexed’s IX lamina of the SpC. SYP coverage of the large motoneurons was reduced on the contralesional side. Early microglial activation in the AH and electrophysiological signs has suggested the possibility of impairment of anterior horn cells (AHC-s). Our study supported that early microglial activation in the contralesional side of the SpC may primarily affect the area corresponding to the location of large motoneurons, and is accompanied by a transient shrinkage followed by increase in size of the large AHC-s with a reduction of their synaptic coverage. After MCA stroke, early involvement of the SpC motoneurons may be suspected by their morphological and synaptic changes and by the pattern of microglial activation.

A case of sporadic spino cerebellar ataxia-43 presenting as ataxia, rigidity, anterior horn cell involvement and cognitive changes

A case of sporadic spino cerebellar ataxia-43 presenting as ataxia, rigidity, anterior horn cell involvement and cognitive changes

Correlations between clinical motor scores and CMAP in patients with type 2 spinal muscular amyotrophy treated with nusinersen

BackgroundSpinal muscular atrophy (SMA) is a neuromuscular disorder characterized by the degeneration of the anterior horn cells of the spinal cord. Nusinersen for the treatment of SMA has been covered by public healthcare in France since May 2017. ObjectiveOur aim was to investigate whether there is a correlation between clinical and compound motor action potential (CMAP) measurements in SMA patients treated with nusinersen after 3 years’ follow-up. MethodMotor skills were evaluated regularly between M0 and M36 using the Motor Function Measure (MFM) score. CMAP measurements were collected regularly between M0 and M22. ResultsData for 10 patients with SMA type 2 were collected and divided into two age groups (< 5 years and > 5 years). Motor function improved, but not significantly, regarding distal motor skills (D3) in both groups, and in axial and proximal motor function (D2) in the younger group. CMAP measurements improved in all patients. CMAP increased significantly for the median nerve, and this improvement correlated significantly with global MFM and with axial and proximal tone (D2). ConclusionOur study shows gain in distal motor function with nusinersen, especially in younger patients with SMA type 2. These results encourage the screening of SMA patients and treatment as early as possible. CMAP measurements of the median nerve show clear improvement in patients treated with nusinersen and could be performed as routine follow-up.