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Rare homozygous disease-associated sequence variants in children with spinal muscular atrophy: a phenotypic description and review of the literature

Li L, Menezes MP, Smith M, Forbes R, Züchner S, Burgess A, et al.

Neuromuscul Disord, 2024 Apr;37:29-35.
PMID: 38520993 DOI: 10.1016/j.nmd.2024.03.005

5q-associated spinal muscular atrophy (SMA) is the most common autosomal recessive neurological disease. Depletion in functional SMN protein leads to dysfunction and irreversible degeneration of the motor neurons. Over 95 % of individuals with SMA have homozygous exon 7 deletions in the SMN1 gene. Most of the remaining 4-5 % are compound heterozygous for deletion and a disease-associated sequence variant in the non-deleted allele. Individuals with SMA due to bi-allelic SMN1 sequence variants have rarely been reported. Data regarding their clinical phenotype, disease progression, outcome and treatment response are sparse. This study describes six individuals from three families, all with homozygous sequence variants in SMN1, and four of whom received treatment with disease-modifying therapies. We also describe the challenges faced during the diagnostic process and intrafamilial phenotypic variability observed between siblings.

Matched MeSH terms: Motor Neurons
Fulltext Tocotrienol-Rich Vitamin E (Tocovid) Improved Nerve Conduction Velocity in Type 2 Diabetes Mellitus Patients in a Phase II Double-Blind, Randomized Controlled Clinical Trial

Chuar PF, Ng YT, Phang SCW, Koay YY, Ho JI, Ho LS, et al.

Nutrients, 2021 Oct 25;13(11).
PMID: 34836025 DOI: 10.3390/nu13113770

Diabetic peripheral neuropathy (DPN) is the most common microvascular complication of diabetes that affects approximately half of the diabetic population. Up to 53% of DPN patients experience neuropathic pain, which leads to a reduction in the quality of life and work productivity. Tocotrienols have been shown to possess antioxidant, anti-inflammatory, and neuroprotective properties in preclinical and clinical studies. This study aimed to investigate the effects of tocotrienol-rich vitamin E (Tocovid SuprabioTM) on nerve conduction parameters and serum biomarkers among patients with type 2 diabetes mellitus (T2DM). A total of 88 patients were randomized to receive 200 mg of Tocovid twice daily, or a matching placebo for 12 months. Fasting blood samples were collected for measurements of HbA1c, renal profile, lipid profile, and biomarkers. A nerve conduction study (NCS) was performed on all patients at baseline and subsequently at 2, 6, 12 months. Patients were reassessed after 6 months of washout. After 12 months of supplementation, patients in the Tocovid group exhibited highly significant improvements in conduction velocity (CV) of both median and sural sensory nerves as compared to those in the placebo group. The between-intervention-group differences (treatment effects) in CV were 1.60 m/s (95% CI: 0.70, 2.40) for the median nerve and 2.10 m/s (95% CI: 1.50, 2.90) for the sural nerve. A significant difference in peak velocity (PV) was also observed in the sural nerve (2.10 m/s; 95% CI: 1.00, 3.20) after 12 months. Significant improvements in CV were only observed up to 6 months in the tibial motor nerve, 1.30 m/s (95% CI: 0.60, 2.20). There were no significant changes in serum biomarkers, transforming growth factor beta-1 (TGFβ-1), or vascular endothelial growth factor A (VEGF-A). After 6 months of washout, there were no significant differences from baseline between groups in nerve conduction parameters of all three nerves. Tocovid at 400 mg/day significantly improve tibial motor nerve CV up to 6 months, but median and sural sensory nerve CV in up to 12 months of supplementation. All improvements diminished after 6 months of washout.

Matched MeSH terms: Motor Neurons/drug effects
Fulltext Drug Discovery of Spinal Muscular Atrophy (SMA) from the Computational Perspective: A Comprehensive Review

Chong LC, Gandhi G, Lee JM, Yeo WWY, Choi SB

Int J Mol Sci, 2021 Aug 20;22(16).
PMID: 34445667 DOI: 10.3390/ijms22168962

Spinal muscular atrophy (SMA), one of the leading inherited causes of child mortality, is a rare neuromuscular disease arising from loss-of-function mutations of the survival motor neuron 1 (SMN1) gene, which encodes the SMN protein. When lacking the SMN protein in neurons, patients suffer from muscle weakness and atrophy, and in the severe cases, respiratory failure and death. Several therapeutic approaches show promise with human testing and three medications have been approved by the U.S. Food and Drug Administration (FDA) to date. Despite the shown promise of these approved therapies, there are some crucial limitations, one of the most important being the cost. The FDA-approved drugs are high-priced and are shortlisted among the most expensive treatments in the world. The price is still far beyond affordable and may serve as a burden for patients. The blooming of the biomedical data and advancement of computational approaches have opened new possibilities for SMA therapeutic development. This article highlights the present status of computationally aided approaches, including in silico drug repurposing, network driven drug discovery as well as artificial intelligence (AI)-assisted drug discovery, and discusses the future prospects.

Matched MeSH terms: Motor Neurons/metabolism
The potential role of miRNA therapies in spinal muscle atrophy

Gandhi G, Abdullah S, Foead AI, Yeo WWY

J Neurol Sci, 2021 08 15;427:117485.
PMID: 34015517 DOI: 10.1016/j.jns.2021.117485

Spinal muscular atrophy (SMA) is a neurodegenerative disease caused by low levels of full-length survival motor neuron (SMN) protein due to the loss of the survival motor neuron 1 (SMN1) gene and inefficient splicing of the survival motor neuron 2 (SMN2) gene, which mostly affects alpha motor neurons of the lower spinal cord. Despite the U.S. Food and Drug Administration (FDA) approved SMN-dependent therapies including Nusinersen, Zolgensma® and Evrysdi™, SMA is still a devastating disease as these existing expensive drugs may not be sufficient and thus, remains a need for additional therapies. The involvement of microRNAs (miRNAs) in SMA is expanding because miRNAs are important mediators of gene expression as each miRNA could target a number of genes. Hence, miRNA-based therapy could be utilized in treating this genetic disorder. However, the delivery of miRNAs into the target cells remains an obstacle in SMA, as there is no effective delivery system to date. This review highlights the potential strategies for intracellular miRNA delivery into target cells and current challenges in miRNA delivery. Furthermore, we provide the future prospects of miRNA-based therapeutic strategies in SMA.

Matched MeSH terms: Motor Neurons/pathology
Basilar invagination: A mimicker of bulbar-onset amyotrophic lateral sclerosis

Tan JSH, Lee S, Hiew FL

eNeurologicalSci, 2021 Mar;22:100321.
PMID: 33553704 DOI: 10.1016/j.ensci.2021.100321

Amyotrophic lateral sclerosis (ALS) is characterized by progressive onset motor deficits with heterogenous presentations ranging from dysarthria to foot drop. Approximately 20% of the patients present with focal bulbar symptoms, in which some may remain restricted to bulbar region (isolated bulbar palsy), and the remaining eventually spreads to involve other body regions (classical ALS). Without accompanying upper and lower motor neurons signs elsewhere, differential diagnoses for isolated bulbar symptoms are extensive, include ALS variants as well as potentially treatable mimics. Therefore, it is important to take heed on every possible aetiology that may disrupt the hypoglossal nucleus, nerve, or lingual muscle itself. Herein, we illustrated a rare presentation of Group A basilar invagination, which mimicked bulbar-onset ALS.

Matched MeSH terms: Motor Neurons
Implication of HMGB1 signaling pathways in Amyotrophic lateral sclerosis (ALS): From molecular mechanisms to pre-clinical results

Paudel YN, Angelopoulou E, Piperi C, Othman I, Shaikh MF

Pharmacol Res, 2020 06;156:104792.
PMID: 32278047 DOI: 10.1016/j.phrs.2020.104792

Amyotrophic lateral sclerosis (ALS) is a devastating and rapidly progressing neurodegenerative disorder with no effective disease-modifying treatment up to date. The underlying molecular mechanisms of ALS are not yet completely understood. However, the critical role of the innate immune system and neuroinflammation in ALS pathogenesis has gained increased attention. High mobility group box 1 (HMGB1) is a typical damage-associated molecular pattern (DAMP) molecule, acting as a pro-inflammatory cytokine mainly through activation of its principal receptors, the receptor for advanced glycation end products (RAGE) and toll-like receptor 4 (TLR4) which are crucial components of the innate immune system. HMGB1 is an endogenous ligand for both RAGE and TLR4 that mediate its biological effects. Herein, on the ground of pre-clinical findings we unravel the underlying mechanisms behind the plausible contribution of HMGB1 and its receptors (RAGE and TLR4) in the ALS pathogenesis. Furthermore, we provide an account of the therapeutic outcomes associated with inhibition/blocking of HMGB1 receptor signalling in preventing motor neuron's death and delaying disease progression in ALS experimental models. There is strong evidence that HMGB1, RAGE and TLR4 signaling axes might present potential targets against ALS, opening a novel headway in ALS research that could plausibly bridge the current treatment gap.

Matched MeSH terms: Motor Neurons/immunology; Motor Neurons/metabolism*; Motor Neurons/pathology
Fulltext Effect of sonic hedgehog on motor neuron positioning in the spinal cord during chicken embryonic development

Yang C, Li S, Li X, Li H, Li Y, Zhang C, et al.

J Cell Mol Med, 2019 05;23(5):3549-3562.
PMID: 30834718 DOI: 10.1111/jcmm.14254

Sonic hedgehog (SHH) is a vertebrate homologue of the secreted Drosophila protein hedgehog and is expressed by the notochord and floor plate in the developing spinal cord. Sonic hedgehog provides signals relevant for positional information, cell proliferation and possibly cell survival, depending on the time and location of expression. Although the role of SHH in providing positional information in the neural tube has been experimentally proven, the underlying mechanism remains unclear. In this study, in ovo electroporation was employed in the chicken spinal cord during chicken embryo development. Electroporation was conducted at stage 17 (E2.5), after electroporation the embryos were continued incubating to stage 28 (E6) for sampling, tissue fixation with 4% paraformaldehyde and frozen sectioning. Sonic hedgehog and related protein expressions were detected by in situ hybridization and fluorescence immunohistochemistry and the results were analysed after microphotography. Our results indicate that the ectopic expression of SHH leads to ventralization in the spinal cord during chicken embryonic development by inducing abnormalities in the structure of the motor column and motor neuron integration. In addition, ectopic SHH expression inhibits the expression of dorsal transcription factors and commissural axon projections. The correct location of SHH expression is vital to the formation of the motor column. Ectopic expression of SHH in the spinal cord not only affects the positioning of motor neurons, but also induces abnormalities in the structure of the motor column. It leads to ventralization in the spinal cord, resulting in the formation of more ventral neurons forming during neuronal formation.

Matched MeSH terms: Motor Neurons/metabolism*
Fulltext Review on Cross Talk between Neurotransmitters and Neuroinflammation in Striatum and Cerebellum in the Mediation of Motor Behaviour

Abg Abd Wahab DY, Gau CH, Zakaria R, Muthu Karuppan MK, A-Rahbi BS, Abdullah Z, et al.

Biomed Res Int, 2019;2019:1767203.
PMID: 31815123 DOI: 10.1155/2019/1767203

Neurological diseases particularly Alzheimer's disease (AD), Parkinson's disease (PD), stroke, and epilepsy are on the rise all around the world causing morbidity and mortality globally with a common symptom of gradual loss or impairment of motor behaviour. Striatum, which is a component of the basal ganglia, is involved in facilitating voluntary movement while the cerebellum is involved in the maintenance of balance and coordination of voluntary movements. Dopamine, serotonin, gamma-aminobutyric acid (GABA), and glutamate, to name a few, interact in regulating the excitation and inhibition of motor neurons. In another hand, interestingly, the motor loss associated with neurological diseases is possibly resulted from neuroinflammation induced by the neuroimmune system. Toll-like receptors (TLRs) are present in the central nervous system (CNS), specifically and primarily expressed in microglia and are also found on neurons and astrocytes, functioning mainly in the regulation of proinflammatory cytokine production. TLRs are always found to be associated or involved in the induction of neuroinflammation in neurodegenerative diseases. Activation of toll-like receptor 4 (TLR4) through TLR4 agonist, lipopolysaccharide (LPS), stimulation initiate a signaling cascade whereby the TLR4-LPS interaction has been found to result in physiological and behavioural changes including retardation of motor activity in the mouse model. TLR4 inhibitor TAK-242 was reflected in the reduction of the spinal cord pathology along with the motor improvement in ALS mouse. There is cross talk with neuroinflammation and neurochemicals. For example, TLR4 activation by LPS is noted to release proinflammatory cytokines, IL-1β, from microglia that subsequently suppresses GABA receptor activities at the postsynaptic site and reduces GABA synthesis at the presynaptic site. Glial glutamate transporter activities are also found to be suppressed, showing the association between TLR4 activation and the related neurotransmitters and corresponding receptors and transporters in the event of neuroinflammation. This review is helpful to understand the connection between neurotransmitter and neuroinflammation in striatum- and cerebellum-mediated motor behaviour.

Matched MeSH terms: Motor Neurons/drug effects*
Localization of the motor neuron somata of geniohyoid muscle in rat: A horseradish peroxidase study

Razlan ANB, Ullah M, Kapitonova MY, Liaqat Ali Khan NB, Fuad SBSA

Anat Histol Embryol, 2018 Oct;47(5):410-416.
PMID: 29888399 DOI: 10.1111/ahe.12372

The aim of the study was to investigate the location of motor neuron somata of geniohyoid muscle in rat. Nine Sprague-Dawley rats were used in this study. Operations were performed under general anaesthesia. Nembutal sodium, 40 mg per kg intraperitoneally was used for anaesthesia. 0.02 to 0.05 ml of 30% horseradish peroxidase (Sigma Type VI) solution in normal saline was injected into the exposed right geniohyoid muscle. After 48 hr, the animals were fixed by perfusion through left ventricle of heart, first by 100 ml normal saline and then with 500 ml of 1.25% glutaraldehyde and 1% paraformaldehyde in 0.1 M phosphate buffer, pH 7.4, at room temperature, and finally with 500 ml of 10% sucrose in the same buffer at 4°C. The medulla oblongata and first cervical segment of spinal cord were removed, kept in 10% sucrose in above phosphate buffer at 4°C for 24 hr. Thereafter, their serial transverse sections were cut in a cryostat at a thickness of 60 μm. The sections were treated according to tetramethyl benzidine (TMB)-horseradish peroxidase (HRP) method. HRP-labelled neuron somata were observed at the following sites: (a) In ventral part of right main hypoglossal nucleus in upper two-thirds of the closed part of medulla oblongata. (b) In ventrolateral subnucleus of hypoglossal nucleus in lower third of closed part of medulla oblongata. (c) At spinomedullary junction, they were located in dorsomedial part of right ventral grey column; a few were also seen here scattered on right side of central canal and among corticospinal fibres.

Matched MeSH terms: Motor Neurons/physiology*
Fulltext Ischaemic haemorrhagic stroke in a child with new onset type 1 diabetes mellitus

Mohd Nor NS, Fong CY, Rahmat K, Vanessa Lee WM, Zaini AA, Jalaludin MY

Eur Endocrinol, 2018 Apr;14(1):59-61.
PMID: 29922355 DOI: 10.17925/EE.2018.14.1.59

Cerebral oedema is the most common neurological complication of diabetic ketoacidosis (DKA). However, ischaemic and haemorrhagic brain injury has been reported infrequently. A 10-year old girl who was previously well presented with severe DKA. She was tachycardic with poor peripheral perfusion but normotensive. However, two fast boluses totalling 40 ml/kg normal saline were given. She was transferred to another hospital where she was intubated due to drowsiness. Rehydration fluid (maintenance and 48-hour correction for 7.5% dehydration) was started followed by insulin infusion. She was extubated within 24 hours of admission. Her ketosis resolved soon after and subcutaneous insulin was started. However, about 48 hours after admission, her Glasgow Coma Scale score dropped to 11/15 (E4M5V2) with expressive aphasia and upper motor neuron signs. One dose of mannitol was given. Her symptoms improved gradually and at 26-month follow-up she had a near-complete recovery with only minimal left lower limb weakness. Serial magnetic resonance imaging brain scans showed vascular ischaemic injury at the frontal-parietal watershed regions with haemorrhagic transformation. This case reiterates the importance of monitoring the neurological status of patient's with DKA closely for possible neurological complications including an ischaemic and haemorrhagic stroke.

Matched MeSH terms: Motor Neurons
Fulltext The Effects of Minocycline on Spinal Root Avulsion Injury in Rat Model

Chin TY, Kiat SS, Faizul HG, Wu W, Abdullah JM

Malays J Med Sci, 2017 Mar;24(1):31-39.
PMID: 28381927 MyJurnal DOI: 10.21315/mjms2017.24.1.4

BACKGROUND: The neuroprotective role of minocycline in the treatment of brachial plexus injury is controversial.
OBJECTIVE: To study the neuroprotective effect of minocycline via different routes in adult Sprague Dawley rats with brachial plexus injury.
METHODS: The C7 nerve roots of the animals were avulsed via an anterior extravertebral approach. Traction force was used to transect the ventral motor nerve roots at the preganglionic level. Intraperitoneal and intrathecal minocycline (50 mg/kg for the first week and 25 mg/kg for the second week) were administered to promote motor healing. The spinal cord was harvested six weeks after the injury, and structural changes following the avulsion injury and pharmacological intervention were analysed.
RESULTS: Motor neuron death and microglial proliferation were observed after the administration of minocycline via two different routes (intraperitoneal and intrathecal) following traumatic avulsion injury of the ventral nerve root. The administration of intraperitoneal minocycline reduced the microglia count but increased the motor neuron count. Intrathecal minocycline also reduced the microglial count, with a greater reduction than in the intraperitoneal group, but it decreased the motor neuron count.
CONCLUSIONS: Intraperitoneal minocycline increased motor neuron survival by inhibiting microglial proliferation following traumatic avulsion injury of the nerve root. The inhibitory effect was augmented by the use of intrathecal minocycline, in which the targeted drug delivery method increased the bioavailability of the therapeutic agent. However, motor neuron survival was impaired at a higher concentration of minocycline via the intrathecal route due to the more efficient method of drug delivery. Microglial suppression via minocycline can have both beneficial and damaging effects, with a moderate dose being beneficial as regards motor neuron survival but a higher dose proving neurotoxic due to impairment of the glial response and Wallerian degeneration, which is a pre-requisite for regeneration.

Matched MeSH terms: Motor Neurons
Fulltext Facial nerve palsy in a child: Bell’s palsy? Think again!

Jo Ee Sam, Nasser Abdul Wahab, Priya Sharda

Malays Fam Physician, 2017;12(3):30-32.
MyJurnal

Introduction: Half of facial paralysis in children is idiopathic at origin. However, dismissing facial
paralysis as being idiopathic without a thorough history and meticulous examination could be
disastrous as illustrated by this case.

Case report: We report a case of sphenoid wing meningioma in a 4-year-old girl. She first
presented with only facial asymmetry that was noticed by her mother. Examination suggested a
left upper motor neuron facial nerve palsy. A sphenoid wing meningioma was found on magnetic
resonance imaging (MRI) of her brain. She underwent craniotomy and total tumour excision.
Histopathological examination of the tumour showed a grade 1 transitional type meningioma.
Meningiomas in children are rare compared to the adult population. Presentations in children
may be delayed due to their inability to recognise or communicate abnormalities. Distinguishing
between upper and lower motor neuron facial palsy is crucial in decision making for facial paralysis
in children.

Matched MeSH terms: Motor Neurons
Fulltext Facial nerve palsy in a child: Bell's palsy? Think again!

Sam JE, Priya S, Nasser AW

Malays Fam Physician, 2017;12(3):30-32.
PMID: 29527278

Introduction: Half of facial paralysis in children is idiopathic at origin. However, dismissing facial paralysis as being idiopathic without a thorough history and meticulous examination could be disastrous as illustrated by this case.

Case report: We report a case of sphenoid wing meningioma in a 4-year-old girl. She first presented with only facial asymmetry that was noticed by her mother. Examination suggested a left upper motor neuron facial nerve palsy. A sphenoid wing meningioma was found on magnetic resonance imaging (MRI) of her brain. She underwent craniotomy and total tumour excision. Histopathological examination of the tumour showed a grade 1 transitional type meningioma. Meningiomas in children are rare compared to the adult population. Presentations in children may be delayed due to their inability to recognise or communicate abnormalities. Distinguishing between upper and lower motor neuron facial palsy is crucial in decision making for facial paralysis in children.

Matched MeSH terms: Motor Neurons
Fulltext View-Invariant Visuomotor Processing in Computational Mirror Neuron System for Humanoid

Dawood F, Loo CK

PLoS One, 2016;11(3):e0152003.
PMID: 26998923 DOI: 10.1371/journal.pone.0152003

Mirror neurons are visuo-motor neurons found in primates and thought to be significant for imitation learning. The proposition that mirror neurons result from associative learning while the neonate observes his own actions has received noteworthy empirical support. Self-exploration is regarded as a procedure by which infants become perceptually observant to their own body and engage in a perceptual communication with themselves. We assume that crude sense of self is the prerequisite for social interaction. However, the contribution of mirror neurons in encoding the perspective from which the motor acts of others are seen have not been addressed in relation to humanoid robots. In this paper we present a computational model for development of mirror neuron system for humanoid based on the hypothesis that infants acquire MNS by sensorimotor associative learning through self-exploration capable of sustaining early imitation skills. The purpose of our proposed model is to take into account the view-dependency of neurons as a probable outcome of the associative connectivity between motor and visual information. In our experiment, a humanoid robot stands in front of a mirror (represented through self-image using camera) in order to obtain the associative relationship between his own motor generated actions and his own visual body-image. In the learning process the network first forms mapping from each motor representation onto visual representation from the self-exploratory perspective. Afterwards, the representation of the motor commands is learned to be associated with all possible visual perspectives. The complete architecture was evaluated by simulation experiments performed on DARwIn-OP humanoid robot.

Matched MeSH terms: Motor Neurons/physiology*
Histological analysis of motoneuron survival and microglia inhibition after nerve root avulsion treated with nerve graft implantation and minocycline: an experimental study

Wu W, Jafri M Abdullah, Faizul H Ghazali

Sains Malaysiana, 2016;45:1641-1648.

Motor vehicle accidents are the most common cause of injuries involving avulsion of the brachial plexus in humans,
resulting in debilitating motor dysfunction. Lack of an established animal model to test drug treatments hinders
the introduction of new pharmacological agents. Avulsion injury of cervical ventral roots can be replicated in rats,
resulting in a progressive loss of the motoneurons and increase in neurotoxic expression of microglia. This is a report
on the effect of prompt nerve implantation and minocycline treatment on the suppression of microglia activation and
survival of motoneurons. 20 adult female Sprague-Dawley rats were used for this study, which was approved by the
Animal Ethical Committee, USM (approval number /2011/(73)(346)). The animals underwent surgical avulsion of the
C6 nerve root, followed by reimplantation with peripheral nerve graft and treatment with intraperitoneal minocycline.
At 6 weeks postoperatively, immunohistochemistry using primary antibody Iba1 (microglia) and nicotinamide adenine
dinucleotide phosphate diaphorase (NADPh) with neutral-red staining (motoneuron) under flourescence microscopy
was performed at the C6 spinal cord segment and then quantified. This study showed significant reduction of microglia
expression in the study group; mean ranks of control and study group were 15.2 and 11.6, respectively; U=9.5, Z=3.02,
p<0.05. However, this did not translate into a significant increase of motoneuron survival in the combined group;
the mean ranks of control and study group were 40.6 and 41.6, respectively; U=44.5, Z=-.0378, p>0.05. This may
be due to the effect of the surgery; the surgery has the potential to cause additional trauma to the cord parenchyma,
leading to further motoneuron loss and an increase in scarring around the avulsed region, thus impeding regeneration
of the motoneuron.

Matched MeSH terms: Motor Neurons
Fulltext Paclitaxel Inhibits Expression of Neuronal Nitric Oxide Synthase and Prevents Mitochondrial Dysfunction in Spinal Ventral Horn in Rats After C7 Spinal Root Avulsion

Sim SK, Tan YC, Tee JH, Yusoff AA, Abdullah JM

Turk Neurosurg, 2015;25(4):617-24.
PMID: 26242340 DOI: 10.5137/1019-5149.JTN.14035-15.1

This study evaluated the neuroprotective effect of intrathecally infused paclitaxel in the prevention of motoneuron death and mitochondrial dysfunction following brachial plexus avulsion injury.

Matched MeSH terms: Motor Neurons/drug effects
Fulltext Histone deacetylase inhibitors as potential treatment for spinal muscular atrophy

Mohseni J, Zabidi-Hussin ZA, Sasongko TH

Genet Mol Biol, 2013 Sep;36(3):299-307.
PMID: 24130434 DOI: 10.1590/S1415-47572013000300001

Histone acetylation plays an important role in regulation of transcription in eukaryotic cells by promoting a more relaxed chromatin structure necessary for transcriptional activation. Histone deacetylases (HDACs) remove acetyl groups and suppress gene expression. HDAC inhibitors (HDACIs) are a group of small molecules that promote gene transcription by chromatin remodeling and have been extensively studied as potential drugs for treating of spinal muscular atrophy. Various drugs in this class have been studied with regard to their efficacy in increasing the expression of survival of motor neuron (SMN) protein. In this review, we discuss the current literature on this topic and summarize the findings of the main studies in this field.

Matched MeSH terms: Motor Neurons
Serial nerve conduction studies provide insight into the pathophysiology of Guillain-Barré and Fisher syndromes

Shahrizaila N, Goh KJ, Kokubun N, Abdullah S, Yuki N

J Neurol Sci, 2011 Oct 15;309(1-2):26-30.
PMID: 21849173 DOI: 10.1016/j.jns.2011.07.042

The electrodiagnosis of Guillain-Barré syndrome (GBS) can be broadly divided into acute inflammatory demyelinating polyneuropathy (AIDP) and acute motor axonal neuropathy (AMAN). Fisher syndrome (FS) is a variant of GBS, although the underlying neuropathy of FS has yet to be established. Serial nerve conduction studies (NCS) can provide further insight into the likely pathophysiology by further subtyping of GBS and FS. We present a patient with an initial diagnosis of AIDP in whom repeated NCS revealed the AMAN variant. This led us to investigate serial NCS in five patients with GBS, FS and FS/GBS overlap presenting over a period of a year. Three patients with AIDP showed a gradual increase in distal motor latencies during the acute phase of illness. NCS of two patients with FS and FS/GBS overlap showed no demyelinating features suggesting underlying axonal neuropathy in this group of patients. The importance of serial NCS in establishing the underlying pattern of neuropathy in GBS and FS is further emphasized in this study. Larger studies incorporating serial NCS are required to confirm the observations seen in our case series especially when pathological studies are often not justified in this group of patients.

Matched MeSH terms: Motor Neurons/pathology; Motor Neurons/physiology
Fulltext New clinical sign of cervical myelopathy: Wazir hand myelopathy sign

Wazir NN, Kareem BA

Singapore Med J, 2011 Jan;52(1):47-9.
PMID: 21298241

Cervical spondylotic myelopathy (CSM) represents a spectrum of pathologies with progressive compression of the spinal cord. The clinical signs and symptoms play a key role in diagnosis. The characteristic hand myelopathy signs are of significant clinical importance. The aim of this descriptive study was to report a relatively easy to elicit new hand myelopathy sign. The basis for this is finger and wrist flexor disinhibition, which is used for the spinal specificity of cord compression at or above the C5/6 level.

Matched MeSH terms: Motor Neurons/pathology
Fulltext Tandem Spinal Stenosis

Zulkefli, A., Ramanathan, R.

Malays Orthop J, 2010;4(1):46-49.
MyJurnal

A 42 years old gentleman presented with predominant low back pain associated with bilateral lower limb neurological deficit leading to an initial diagnosis of lumbar stenosis. Further history taking and examination revealed upper limb neurological deficit, and the lower limbs actually presented with upper motor neuron instead of lower motor neuron signs. Imaging studies confirmed the clinical findings with presence of both cervical and lumbar spinal stenosis. Twostage decompression procedures were performed at 6 monthintervals starting with cervical decompression. Postoperative improvement was noted on follow-up. This case highlights the importance of accurate diagnosis of cervical pathology for patients presenting with or referred for predominantly lumbar symptomology

Matched MeSH terms: Motor Neurons

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