Bilateral Lower Limb Spasticity Research Articles

Genetic and clinical features of pediatric-onset hereditary spastic paraplegia: a single-center study in Japan.

Hereditary spastic paraplegias (HSPs) are a set of heterogeneous neurodegenerative disorders characterized by bilateral lower limb spasticity. They may present from infancy onwards at any time. Although next-generation sequencing has allowed the identification of many causative genes, little is known about which genes are specifically associated with pediatric-onset variants. This study retrospectively evaluated the genetic analyses, family history clinical courses, magnetic resonance imaging (MRI) findings, and electrophysiologic findings of patients diagnosed with HSP in childhood at a tertiary pediatric hospital in Japan. Genetic analyses were performed using direct sequencing, disease-associated panels, and whole-exome sequencing. Of the 37 patients included, 14 had a family history of HSP and 23 had a sporadic form of the disease. In 20 patients, HSP was the pure type, whereas the remaining 17 patients had complex types of HSP. Genetic data were available for 11 of the pure-type patients and 16 of those with complex types. Of these, genetic diagnoses were possible in 5 (45%) of the pure-type and 13 (81%) of the complex-type patients. SPAST variants were found in five children, KIF1A variants in four, ALS2 variants in three, SACS and L1CAM variants in two each, and an ATL1 variant in one. One child had a 10p15.3p13 duplication. Four patients with pure-type HSPs had SPAST variants and one had an ALT1 variant. The KIF1A, ALS2, SACS, and L1CAM variants and the 10p15.3p13 duplication were seen in children with complex-type HSPs, with just one complex-type patient having a SPAST variant. The identification of brain abnormalities on MRI was significantly more common among children with complex-type (11 [69%] of 16) than pure-type HSPs (one [5%] of 19) (p < 0.001). Scores on the modified Rankin Scale for Neurologic Disability were also significantly higher among children with complex-type compared with pure-type HSPs (3.5 ± 1.0 vs. 2.1 ± 0.9, p < 0.001). Pediatric-onset HSP was found to be sporadic and genetic in a substantial proportion of patients. The causative gene patterns differed between children with pure-type and complex-type HSPs. The causative roles of SPAST and KIF1A variants in pure-type and complex-type HSPs, respectively, should be explored further.

Bi-allelic variants in PNPLA6 possibly associated with Parkinsonian features in addition to spastic paraplegia phenotype.

Variants in the PNPLA6 gene are known to cause 4 distinct phenotypes. One known phenotype is Hereditary Spastic Paraplegia type 39 (HSP 39), a rare neurodegenerative condition characterized by variable onset of lower limb spasticity, weakness and ataxia. Little is known about complications of HSP 39 in adulthood. Here, we report a family of three siblings who presented with bilateral lower limb spasticity in childhood, consistent with HSP, with confirmed bi-allellic PNPLA6 mutations. Two siblings developed parkinsonian features in middle age, a novel finding in this sibship. The proband had a positive dopamine transporter scan, indicating degeneration in dopaminergic neurons, and dopa-responsive extrapyramidal symptoms. Testing for known genetic causes of Parkinsonism was negative. The PNPLA6 gene encodes neuropathy target esterase, an enzyme involved in lipid metabolism that is critical to the stability of cell membranes. We hypothesize that the development of Parkinsonism in these patients may be related to the PNPLA6 mutations, as lipid dysregulation has been implicated in the pathogenesis of Parkinson disease.

Sjögren–Larsson Syndrome: A Case Report of a Rare Neuro-cutaneous Disorder

Sjögren–Larsson syndrome is a rare autosomal recessive neuro-cutaneous disease. The dominant features are congenital ichthyotic hyperkeratosis, spastic diplegia and mild to moderate mental retardation. The cause of this syndrome is the deficiency of microsomal fatty aldehyde dehydrogenase. The deficiency of this enzyme results in the accumulation of fatty aldehydes and fatty alcohols in various tissues including skin. Here, we report a case presented with ichthyosis, bilateral lower limb spasticity, and mental retardation, diagnosed as Sjögren–Larsson syndrome.

A 30‐year follow‐up study after selective dorsal rhizotomy: neuromuscular and functional status of adults with cerebral palsy and bilateral lower limb spasticity

A 30‐year follow‐up study after selective dorsal rhizotomy: neuromuscular and functional status of adults with cerebral palsy and bilateral lower limb spasticity

Feasibility and toxicity of hematopoietic stem cell transplant in multiple sclerosis.

Multiple sclerosis is a debilitating disease of the central nervous system. It affects people of all ages but is more prevalent among 20-40 year olds. Patients with MS can be presented with potentially any neurological symptom depending on the location of the lesion. A quarter of patients with MS suffer from bilateral lower limb spasticity among other symptoms. These devastating effects can be detrimental to the patient’s quality of life. Hematopoietic stem cells (HSCs) have been used as a treatment for MS over the past 2 decades but their safety and efficacy has are undetermined. The objective of this study is to evaluate the feasibility and toxicity of autologous HSCs transplantation in MS. A literature search was done from 1997 to 2016 using different keywords. A total of 9 articles, which met the inclusion and exclusion criteria, were included in this review. The type of conditioning regimen and technique of stem cell mobilization are summarized and compared in this study. All studies reported high-dose immunosuppressive therapy with autologous HSCs transplantation being an effective treatment option for severe cases of multiple sclerosis. Fever, sepsis, and immunosuppression side effects were the most observed adverse effects that were reported in the selected studies. HSCs is a feasible treatment for patients with MS; nevertheless the safety is still a concern due to chemo toxicity.

HIV encephalopathy with bilateral lower limb spasticity: gross motor function and antiretroviral therapy.

To describe gross motor function in children with bilateral lower limb (BLL) spasticity due to human immunodeficiency virus encephalopathy (HIVE), and to investigate the association between age, CD4 percentage, and viral load at initiation of antiretroviral therapy (ART) and current gross motor function. Thirty ambulant children with HIVE and BLL spasticity were recruited. Clinical parameters, including ART, were obtained from medical records. Gross motor function was assessed using the 88-item Gross Motor Function Measure (GMFM-88). The participant group was comprised of 14 males and 16 females (median age 8y; interquartile range [IQR] 7-11y). ART was initiated at a median age of 7 months (IQR 5-11mo) with a median CD4 percentage of 4.7% (IQR 2.3-8.0) and viral load of log10 6.0 (IQR 5.6-6.4). The median total GMFM-88 score was 89% (IQR 78-94%), with a wide range of scores in the 'Standing' domain (26-97%) and 'Walking, Running, and Jumping' domain (8-99%). No associations were detected between age at initiation of ART, CD4 percentage, or viral load and total GMFM-88 score. Limitations in gross motor function in children with HIVE and BLL spasticity range from mild to severe. ART initiation factors were not able to predict functional status in this sample.

Gait analyses 1, 3, 10, 20 and 30 years after selective dorsal rhizotomy in children with CP and bilateral lower limb spasticity

Gait analyses 1, 3, 10, 20 and 30 years after selective dorsal rhizotomy in children with CP and bilateral lower limb spasticity

HIV encephalopathy with bilateral lower limb spasticity: upper limb motor function and level of activity and participation.

To describe upper limb motor function and level of activity and participation in children with HIV encephalopathy (HIVE) and bilateral lower limb (BLL) spasticity. Thirty ambulant children with HIVE and BLL spasticity and 20 typically developing children, between 5 years and 12 years, were recruited. Upper limb motor function was assessed using the Purdue Pegboard and level of activity and participation using the Computer-Adapted Pediatric Evaluation of Disabilities Inventory (PEDI-CAT). The HIVE group comprised 14 males and 16 females (mean age [SD] 8y 8mo [2y 2mo], Gross Motor Function Classification System (GMFCS) level I [n=10], II [n=11], and III [n=9]) and the typically developing group comprised 11 males and 9 females (mean age 8y 8mo [2y 3mo]). The HIVE group had lower scores than the typically developing group for all pegboard tasks and three of the four PEDI-CAT domains (p≤0.001). However, individual outcome scores varied substantially within each GMFCS level. Children with HIVE and BLL spasticity may have significantly poorer upper limb motor performance and lower levels of activity and participation than typically developing children. These findings suggest that an assessment of upper limb motor function should form part of optimal care for this population.

Spinal anaesthesia in a patient with hereditary spastic paraplegia: case report and literature review

We report the use of spinal anaesthesia in a patient with hereditary spastic paraplegia who presented for manual removal of placenta following a normal vaginal delivery. This 18-year-old primigravida had been diagnosed with hereditary spastic paraplegia at 8 years of age when neurological examination revealed mild bilateral lower limb spasticity. A 25-gauge Whitacre spinal anaesthetic needle was inserted at the L3-4 intervertebral space and 0.5% plain bupivacaine 2 mL plus fentanyl 25 microg administered. The procedure was uneventful. At 24 hours postoperatively, there was full neurological recovery to pre-anaesthetic levels. The hereditary spastic paraplegias are a group of neurological disorders characterised by a slowly progressing spastic paraparesis. The neurological disorder and its anaesthetic implications are reviewed.