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
The motoneurones with axons in the common peroneal nerve (CPN) of the rat and monkey were examined using retrograde labelling with horseradish peroxidase (HRP). In both species, the CPN motoneurone pool was localized in the dorsolateral part of the ventral horn of the spinal cord. In the rat, the labelled motoneurones were located between the L3 and L6 spinal segments whereas in the monkey, they extended from the caudal end of L4 to the L6 spinal segments. In both species the majority of the labelled neurones were located within the L5 segment. The mean number of the CPN motoneurones in the rat and monkey was 458 and 1148, respectively. A bimodal size distribution of motoneurones was found in both species.
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.
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.
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.
The spinal nucleus of the accessory nerve (SNA) comprises the group of somata (perikarya) of motor neurons that supply the sternocleidomastoid and trapezius muscles. There are many conflicting views regarding the longitudinal extent and topography of the SNA, even in the same species, and these disagreements prompted the present investigation. Thirty Sprague-Dawley rats (15 males, 15 females) were used. The SNA was localized by retrograde axonal transport of horseradish peroxidase. Longitudinally, the SNA was found to be located in the caudal part (caudal 0.9-1.2 mm) of the medulla oblongata, the whole lengths of cervical spinal cord segments C1, C2, C3, C4, C5 and rostral fourth of C6. In the caudal part of the medulla oblongata, the SNA was represented by a group of perikarya of motor neurons lying immediately ventrolateral to the pyramidal fibres that were passing dorsolaterally after their decussation. In the spinal cord, the motor neuronal somata of the SNA were located in the dorsomedial and central columns at C1, in the dorsomedial, central and ventrolateral columns at C2 and in the ventrolateral column only at C3, C4, C5 and rostral quarter of C6. The perikarya of motor neurons supplying the sternocleidomastoid were located in the caudal part (caudal 0.9-1.2 mm) of the medulla oblongata ventrolateral to the pyramidal fibres that were passing dorsolaterally after their decussation. They were also located in the dorsomedial and central columns at C1, in the dorsomedial, central and ventrolateral columns at C2 and only in the ventrolateral column at the rostral three-quarters of C3. The perikarya of motor neurons supplying the trapezius muscle were located in the ventrolateral column only in the caudal three-quarters of C2, the whole lengths of C3, C4 and C5, and in the rostral quarter of C6.
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.
This study evaluated the neuroprotective effect of intrathecally infused paclitaxel in the prevention of motoneuron death and mitochondrial dysfunction following brachial plexus avulsion injury.
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
Spinal muscular atrophy (SMA), a leading genetic cause of death in childhood, is caused by deletion of the SMN1 gene, located at chromosome 5q13. The molecular pathogenesis, which results in motor neuron degeneration within the anterior horn of spinal cord, is a focus of debate among scientists. The unique nature of the duplicative 5q chromosomal region provides considerable yet challenging opportunity for disease correction as well as complication in performing molecular diagnosis and understanding the molecular pathogenesis. This article reviewed recent findings in the molecular pathogenesis of SMA as well as the research advances in the molecular diagnosis and therapeutic approaches.
A 43-year old lady presented with progressive loss of vision in both eyes followed by rapid deterioration of consciousness within the next few days. This was preceded by a viral infection one week before her presentation. At presentation she had evidence of meningism and signs of bilateral upper motor neuron lesions and was managed initially as acute meningoencephalitis with antibiotics. The brain CT was within normal limits but subsequent MRI of the brain revealed multiple foci of hyperintense lesions on T2-weighted and FLAIR images. The cerebrospinal fluid examination revealed lymphocytosis, and normal protein and glucose levels. Cultures of the CSF were negative. She was managed as acute disseminated encephalomyelitis (ADEM) with high-dose of intravenous methlyprednisolone one gram/day for three consecutive days followed by oral prednisolone 60 mg/day. Despite the management she lapsed into coma and succumbed to her illness nine days after admission.
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.
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.
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
Bell's palsy is a benign lower motor neuron facial nerve disorder. It is almost always unilateral. We report a 20-year-old nulliparous woman with five episodes of recurrent Bell's palsy. A review of recent medical literature revealed a paucity of case reports involving an individual with five episodes of recurrent Bell's palsy, with none found in Asian neurology medical literature. Despite the multiple episodes of Bell's palsy recurrences, the patient did not suffer much neurological sequelae from the disease.
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.
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.
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.
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.