Causes of lower extremity weaknesses after posterior lumbar spine fusion surgery and therapeutic effects of active surgical exploration.

BACKGROUND: This study was aimed at investigating the causes of lower extremity weaknesses after posterior lumbar spine fusion surgery and looking at subsequent treatment strategies. METHODS: Patients who underwent posterior lumbar spine fusion surgery in the Peking University First Hospital between January 2009 and December 2018 were counted. Those who needed secondary surgery because of subsequent lower extremity weaknesses were selected. CT scans and MRIs were used to evaluate the reasons for weaknesses before secondary surgery. Muscle strength was evaluated after surgery. RESULTS: Thirty patients (30/4078, 0.74%) required a secondary surgery because of lower extremity weaknesses after posterior lumbar spine fusion surgery. The main causes of weakness were (1) internal fixation malposition and loosening (11 patients, 36%), (2) epidural hematomas (9 patients, 30%), (3) insufficient decompression (5 patients, 17%), and (4) nerve root edemas (5 patients, 17%). Weakness occurred on average 2.9 days after surgery (1-9 days). Twenty-seven patients (90%) got improved muscle strength after their secondary surgery. CONCLUSIONS: Iatrogenic neurologic deficits and lower extremity weaknesses were rare complications after posterior lumbar spine fusion surgeries, but important to recognize and manage. The main causes of weakness were internal fixation malposition and loosening, epidural hematomas, insufficient decompression, or root edemas. There may be positive, therapeutic effects to subsequent, active surgical exploration.

Spastic paraparesis associated with advanced liver cirrhosis: a condition obscure in terms of treatment and prognosis.

Hepatic myelopathy or spastic paraparesis of liver disease is an insidious onset condition with pure motor spastic paraparesis without sensory, bladder or bowel involvement in patients with chronic liver disease, in which the neurological dysfunction cannot be explained by other causes. It is a rare, relentlessly progressive and mostly irreversible neurological complication resulting from portosystemic shunts occurring spontaneously, created surgically or due to 'functional shunting'. In some cases, no evidence of shunting is elicitable due to difficulty in locating the hidden collaterals. We report this rare case of a 33-year-old man with chronic liver disease presenting with spastic paraparesis after 11 months of resolution of an episode of hepatic encephalopathy.

Postural stability during gait for adults with hereditary spastic paraparesis.

Individuals with hereditary spastic paraparesis (HSP) are often impaired in their ability to control posture as a result of the neurological and musculoskeletal implications of their condition. This research aimed to assess postural stability during gait in a group of adults with HSP. Ten individuals with HSP and 10 healthy controls underwent computerized gait analysis while walking barefoot along a 10-m track. Two biomechanics methods were used to assess stability: the center of pressure and center of mass separation (COP-COM) method, and the extrapolated center of mass (XCOM) method. Spatiotemporal and kinematic variables were also investigated. The XCOM method identified deficits in mediolateral stability for the HSP group at both heel strike and mid-stance. The group with HSP also had slower walking velocity, lower cadence, more time spent in double stance, larger step widths, and greater lateral trunk flexion than the control group. These results suggest that individuals with HSP adjust characteristics of their gait to minimize the instability arising from their impairments but have residual deficits in mediolateral stability. This may result in an increased risk of falls, particularly in the sideways direction.

Motor Cortex Mapping in Patients With Hepatic Myelopathy After Transjugular Intrahepatic Portosystemic Shunt.

RATIONALE AND OBJECTIVES: As a special movement disorder, hepatic myelopathy (HM) is characterized by spastic paraperesis and may be secondary to transjugular intrahepatic portosystemic shunt (TIPS). The prediction and diagnosis of HM is difficult due to largely unknown neuropathological underpinnings and a lack of specific biomarkers. We aimed to delve into the alterations in motor system of HM patients' brain and their potential clinical implication. MATERIAL AND METHODS: Twenty-three patients with HM and 23 without HM after TIPS and 24 demographically matched healthy controls were enrolled. High-spatial-resolution structural imaging and functional data at rest were acquired. Motor areas were included as seed regions for functional connectivity analysis. Then, we performed brain volume analysis. RESULTS: We found decreased right supplementary motor area (SMA)-seeded functional connectivity with bilateral insula, thalamus and midbrain, left cerebellum and middle temporal gyrus, and right middle cingulate gyrus in HM compared to non-HM patients (p < 0.001). The right insula revealed decreased volume (p < 0.001), and white matter volume reduced in the right corona radiata beneath the right SMA (p < 0.001) in HM relative to non-HM patients. Furthermore, the strength of right SMA-seeded connectivity with insula was positively correlated with folic acid level in HM patients (r = 0.60, p = 0.03), showing an accuracy of 0.87 to distinguish HM from non-HM. CONCLUSION: Our study demonstrates the HM-specific dysconnectivity with an anatomical basis, and its correlation with laboratory findings and diagnostic value. Detecting these abnormalities might help to predict and diagnose post-TIPS HM.

Genome sequencing reveals a novel genetic mechanism underlying dihydropyrimidine dehydrogenase deficiency: A novel missense variant c.1700G>A and a large intragenic inversion in DPYD spanning intron 8 to intron 12.

Dihydropyrimidine dehydrogenase (DPD) deficiency is associated with a variable clinical presentation. A family with three DPD-deficient patients presented with unusual clinical phenotypes including pregnancy-induced symptoms, transient visual impairment, severe developmental delay, cortical blindness, and delayed myelination in the brain. DPYD Sanger sequencing showed heterozygosity for the c.1905+1G>A mutation and a novel missense variant c.1700G>A (p.G567E). The recombinantly expressed p.G567E DPD variant showed increased temperature lability probably caused by structural rearrangements within the DPD protein. Genome sequencing of the affected son established compound heterozygosity for the c.1700G>A and an imperfect 115,731 bp inversion with breakpoints at chr1: 98,113,121 (intron 8) and chr1: 97,997,390 (intron 12) of the DPYD associated with a 4 bp deletion (chr1: 97,997,386_97,997,389del). Whole exome and mitochondrial DNA analyses for the mother and daughter did not reveal additional mutated genes of significance. Thus, an inversion in DPYD should be considered in patients with an inconclusive genotype or unusual clinical phenotype.

Personalized upper limb training combined with anodal-tDCS for sensorimotor recovery in spastic hemiparesis: study protocol for a randomized controlled trial.

BACKGROUND: Recovery of voluntary movement is a main rehabilitation goal. Efforts to identify effective upper limb (UL) interventions after stroke have been unsatisfactory. This study includes personalized impairment-based UL reaching training in virtual reality (VR) combined with non-invasive brain stimulation to enhance motor learning. The approach is guided by limiting reaching training to the angular zone in which active control is preserved ("active control zone") after identification of a "spasticity zone". Anodal transcranial direct current stimulation (a-tDCS) is used to facilitate activation of the affected hemisphere and enhance inter-hemispheric balance. The purpose of the study is to investigate the effectiveness of personalized reaching training, with and without a-tDCS, to increase the range of active elbow control and improve UL function. METHODS: This single-blind randomized controlled trial will take place at four academic rehabilitation centers in Canada, India and Israel. The intervention involves 10 days of personalized VR reaching training with both groups receiving the same intensity of treatment. Participants with sub-acute stroke aged 25 to 80 years with elbow spasticity will be randomized to one of three groups: personalized training (reaching within individually determined active control zones) with a-tDCS (group 1) or sham-tDCS (group 2), or non-personalized training (reaching regardless of active control zones) with a-tDCS (group 3). A baseline assessment will be performed at randomization and two follow-up assessments will occur at the end of the intervention and at 1 month post intervention. Main outcomes are elbow-flexor spatial threshold and ratio of spasticity zone to full elbow-extension range. Secondary outcomes include the Modified Ashworth Scale, Fugl-Meyer Assessment, Streamlined Wolf Motor Function Test and UL kinematics during a standardized reach-to-grasp task. DISCUSSION: This study will provide evidence on the effectiveness of personalized treatment on spasticity and UL motor ability and feasibility of using low-cost interventions in low-to-middle-income countries. TRIAL REGISTRATION: ClinicalTrials.gov, ID: NCT02725853 . Initially registered on 12 January 2016.

Effects of superficial heating and insulation on walking speed in people with hereditary and spontaneous spastic paraparesis: A randomised crossover study.

OBJECTIVES: Cooling of the lower limb in people with Hereditary and Spontaneous Spastic Paraparesis (pwHSSP) has been shown to affect walking speed and neuromuscular impairments. The investigation of practical strategies, which may help to alleviate these problems is important. The potential of superficial heat to improve walking speed has not been explored in pwHSSP. Primary objective was to explore whether the application of superficial heat (hot packs) to lower limbs in pwHSSP improves walking speed. Secondary objective was to explore whether wearing insulation after heating would prolong any benefits. METHODS: A randomised crossover study design with 21 pwHSSP. On two separate occasions two hot packs and an insulating wrap (Neo-G™) were applied for 30minutes to the lower limbs of pwHSSP. On one occasion the insulating wrap was maintained for a further 30minutes and on the other occasion it was removed. Measures of temperature (skin, room and core), walking speed (10 metre timed walk) and co-ordination (foot tap time) were taken at baseline (T1), after 30 mins (T2) and at one hour (T3). RESULTS: All 21 pwHSSP reported increased lower limb stiffness and decreased walking ability when their legs were cold. After thirty minutes of heating, improvements were seen in walking speed (12.2%, P<0.0001, effect size 0.18) and foot tap time (21.5%, P<0.0001, effect size 0.59). Continuing to wear insulation for a further 30minutes gave no additional benefit; with significant improvements in walking speed maintained at one hour (9.9%, P>0.001) in both conditions. CONCLUSIONS: Application of 30minutes superficial heating moderately improved walking speed in pwHSSP with effects maintained at 1hour. The use of hot packs applied to lower limbs should be the focus of further research for the clinical management of pwHSSP who report increased stiffness of limbs in cold weather and do not have sensory deficits.

Increased lower limb muscle coactivation reduces gait performance and increases metabolic cost in patients with hereditary spastic paraparesis.

BACKGROUND: The aim of this study was to investigate the lower limb muscle coactivation and its relationship with muscles spasticity, gait performance, and metabolic cost in patients with hereditary spastic paraparesis. METHODS: Kinematic, kinetic, electromyographic and energetic parameters of 23 patients and 23 controls were evaluated by computerized gait analysis system. We computed ankle and knee antagonist muscle coactivation indexes throughout the gait cycle and during the subphases of gait. Energy consumption and energy recovery were measured as well. In addition to the correlation analysis between coactivation indexes and clinical variables, correlations between coactivation indexes and time-distance, kinematic, kinetic, and energetic parameters were estimated. FINDINGS: Increased coactivity indexes of both knee and ankle muscles throughout the gait cycle and during the subphases of gait were observed in patients compared with controls. Energetic parameters were significantly higher in patients than in controls. Both knee and ankle muscle coactivation indexes were positively correlated with knee and ankle spasticity (Ashworth score), respectively. Knee and ankle muscle coactivation indexes were both positively correlated with energy consumption and both negatively correlated with energy recovery. INTERPRETATION: Positive correlations between the Ashworth score and lower limb muscle coactivation suggest that abnormal lower limb muscle coactivation in patients with hereditary spastic paraparesis reflects a primary deficit linked to lower limb spasticity. Furthermore, these abnormalities influence the energetic mechanisms during walking. Identifying excessive muscle coactivation may be helpful in individuating the rehabilitative treatments and designing specific orthosis to restrain spasticity.

Clinical and molecular genetic features of cerebrotendinous xanthomatosis patients in Chinese families.

Cerebrotendinous xanthomatosis (CTX) is a lipid-storage disease caused by mutations in CYP27A1. Current publications of Chinese CTX were mainly based on case reports. Here we investigated the clinical manifestations, genetic features in Chinese CTX patients. The clinical materials of 4 Chinese CTX pedigrees were collected. The genetic testing was done by polymerase chain reaction plus Sanger sequencing. The features of Chinese CTX patients reported previously were also reviewed. Three novel mutations of p.Arg513Cys, c.1477-2A > C in family 1 and p.Arg188Stop in family 4 (NM 000784.3) in CYP27A1 were found. The probands in our study manifested cerebellar ataxia, tendon xanthoma and spastic paresis in family 1 and 4, tendon xanthoma plus spastic paraparesis in family 2, asymptomatic tendon xanthoma in family 3. Three known mutations of p.Arg137Gln, p.Arg127Trp and p.Arg405Gln were found respectively in Family 2, 3 and 4. For the Chinese patients reviewed, the most common findings were xanthomatosis (100%), pyramidal signs (100%), cerebellar ataxia (66.7%), cognitive impairment (66.7%), cataracts (50.0%), and peripheral neuropathy (33.3%). Chronic diarrhea was infrequently seen (5.6%). No mutation was found associated with any given clinical features. We identified 3 novel mutations in CYP27A1. In Chinese CTX patients, xanthomatosis was the most common symptom while cataracts and chronic diarrhea were less frequent. The special features in Chinese CTX patients might caused by the lack of serum cholestanol test and should be confirmed in larger number of patients in the future.

Serial Casting as an Adjunct to Botulinum Toxin Type A Treatment in Children With Cerebral Palsy and Spastic Paraparesis With Scissoring of the Lower Extremities.

The purpose of this study was to examine whether combination therapy of serial casting and botulinum toxin type A injection can further enhance the effects of botulinum toxin type A in children with cerebral palsy with scissoring of both legs. This study was a prospective and randomized trial. The children were divided into 2 groups, one of which received serial casting after botulinum toxin type A (n = 40), and the other which only received botulinum toxin type A (n = 40). Serial casting started 3 weeks after the botulinum toxin type A. Both groups received physiotherapy. Groups were assessed at baseline then compared at 6 and 12 weeks following the intervention. Significant improvements in Gross Motor Function Measure-66 and Caregiver Health Questionnaire were recorded in both groups ( P < .001). The modified Ashworth scale improved significantly following botulinum toxin type A in the serial casting group ( P < .05), but not in botulinum toxin type A only group. These results suggest that serial casting after botulinum toxin type A can enhance the benefits of botulinum toxin type A in children with cerebral palsy.

Gait Patterns in Patients with Hereditary Spastic Paraparesis.

BACKGROUND: Spastic gait is a key feature in patients with hereditary spastic paraparesis, but the gait characterization and the relationship between the gait impairment and clinical characteristics have not been investigated. OBJECTIVES: To describe the gait patterns in hereditary spastic paraparesis and to identify subgroups of patients according to specific kinematic features of walking. METHODS: We evaluated fifty patients by computerized gait analysis and compared them to healthy participants. We computed time-distance parameters of walking and the range of angular motion at hip, knee, and ankle joints, and at the trunk and pelvis. Lower limb joint moments and muscle co-activation values were also evaluated. RESULTS: We identified three distinct subgroups of patients based on the range of motion values. Subgroup one was characterized by reduced hip, knee, and ankle joint range of motion. These patients were the most severely affected from a clinical standpoint, had the highest spasticity, and walked at the slowest speed. Subgroup three was characterized by an increased hip joint range of motion, but knee and ankle joint range of motion values close to control values. These patients were the most mildly affected and had the highest walking speed. Finally, subgroup two showed reduced knee and ankle joint range of motion, and hip range of motion values close to control values. Disease severity and gait speed in subgroup two were between those of subgroups one and three. CONCLUSIONS: We identified three distinctive gait patterns in patients with hereditary spastic paraparesis that correlated robustly with clinical data. Distinguishing specific features in the gait patterns of these patients may help tailor pharmacological and rehabilitative treatments and may help evaluate therapeutic effects over time.

Widespread white matter and conduction defects in PSEN1-related spastic paraparesis.

The mechanisms underlying presenilin 1 (PSEN1) mutation-associated spastic paraparesis (SP) are not clear. We compared diffusion and volumetric magnetic resonance measures between 3 persons with SP associated with the A431E mutation and 7 symptomatic persons with PSEN1 mutations without SP matched for symptom duration. We performed amyloid imaging and central motor and somatosensory conduction studies in 1 subject with SP. We found decreases in fractional anisotropy and increases in mean diffusivity in widespread white-matter areas including the corpus callosum, occipital, parietal, and frontal lobes in PSEN1 mutation carriers with SP. Volumetric measures were not different, and amyloid imaging showed low signal in sensorimotor cortex and other areas in a single subject with SP. Electrophysiological studies demonstrated both slowed motor and sensory conduction in the lower extremities in this same subject. Our results suggest that SP in carriers of the A431E PSEN1 mutation is a manifestation of widespread white-matter abnormalities not confined to the corticospinal tract that is at most indirectly related to the mutation's effect on amyloid precursor protein processing and amyloid deposition.

Health survey of adults with hereditary spastic paraparesis compared to population study controls.

BACKGROUND: Hereditary spastic paraparesis (HSP) is a rare neurodegenerative condition characterized by slowly progressive spastic weakness of the lower limbs and urinary sphincter dysfunction. Complex HSP involves additional neurologic symptoms and signs like ataxia, extra pyramidal signs, polyneuropathy, and cognitive decline. Little is known about the disease burden for adults with HSP beyond the described core symptoms. METHODS: A cross-sectional survey of 108 adults aged 30 years and older (Mage = 57.7 years, SD = 11.5, range 30 to 81; 54.2 % females) recruited from a national center of expertise for rare disorders and a patient advocacy organization in Norway. Self-report data from the HSP sample was compared to self-report data from a large Norwegian population study, HUNT3 (N = 46,293), covering health-related variables such as overall life satisfaction, mental wellbeing, memory function, perceived pain, and co-morbid diseases. In addition, the HSP sample reported specific items developed for this study in co-operation with the patient advocacy organization. RESULTS: The HSP sample more frequently lived alone. Overall, the HSP sample reported lower life satisfaction, lower mental wellbeing and lower social support, as well as poorer memory and sleep, compared to controls. Furthermore, the HSP sample more frequently reported musculoskeletal pain, constipation, and urinary incontinence compared to controls. There was no difference between samples in frequency of physical activity and alcohol and tobacco use. Men with HSP reported higher impact of HSP, lower life satisfaction, and less ability to perform activities of daily living compared to women with HSP. CONCLUSIONS: Adults with HSP experience disease burden on a larger number of areas than previously documented, and men with HSP may represent a particularly vulnerable group.

Superficial warming and cooling of the leg affects walking speed and neuromuscular impairments in people with spastic paraparesis.

BACKGROUND: People with hereditary and spontaneous spastic paraparesis (HSSP) report that their legs are stiffer and walking is slower when their legs are cold. OBJECTIVES: This study explored the effects of prolonged superficial cooling and warming of the lower leg on walking speed and local measures of neuromuscular impairments. METHODS: This was a randomised pre- and post-intervention study of 22 HSSP participants and 19 matched healthy controls. On 2 separate occasions, one lower leg was cooled or warmed. Measurements included walking speed and measures of lower limb impairment: ankle movement, passive muscle stiffness, spasticity (stretch reflex size), amplitude and rate of force generation in dorsi- and plantarflexors and central and peripheral nerve conduction time/velocity. RESULTS: For both participants and controls, cooling decreased walking speed, especially for HSSP participants. For both groups, cooling decreased the dorsiflexor rate and amplitude of force generation and peripheral nerve conduction velocity and increased spasticity. Warming increased dorsiflexor rate of force generation and nerve conduction velocity and decreased spasticity. CONCLUSIONS: Superficial cooling significantly reduced walking speed for people with HSSP. Temperature changes were associated with changes in neuromuscular impairments for both people with spastic paraparesis and controls. This study does not support the use of localised cooling in rehabilitation for people with spastic paraparesis as reported in other neurological conditions. Rehabilitation interventions that help prevent heat loss (insulation) or improve limb temperature via passive or active means, particularly when the legs and/or environment are cool, may benefit people with spastic paraparesis.

Tau Accumulation in Primary Motor Cortex of Variant Alzheimer's Disease with Spastic Paraparesis.

We studied topographic distribution of tau and amyloid-ß in a patient with variant Alzheimer's disease with spastic paraparesis (VarAD) by comparing AD patients. The proband developed progressive memory impairment, dysarthria, and spastic paraparesis at age 23. Heterozygous missense mutation (L166P) was found in exon 6 of presenilin-1 gene. The proband showed prominently increased amyloid binding in striatum and cerebellum and asymmetrical tau binding in the primary sensorimotor cortex contralateral to the side more affected by spasticity. We suspect that upper motor neuron dysfunctions may be attributed to excessive abnormal tau accumulation rather than amyloid-ß in the primary motor cortex.

Neuromyelitis optica and myasthenia gravis in a young Nigerian girl.

Neuromyelitis optica (NMO) and myasthenia gravis (MG) are rare autoimmune disorders. The coexistence of the two disorders, although rare, has been documented. This is a case report of a 16-year-old student who presented with recurrent episodes of transverse myelitis and optic neuritis, 8 years after diagnosis of MG. She presented with visual impairment, relapsing and remitting weakness, numbness and paraesthesia of her lower limbs, with bladder and bowel incontinence. Her examination revealed bilateral optic atrophy, spastic paraparesis of the lower limbs and patchy sensory loss up to thoracic level (T4-5). She had a positive acetylcholine receptor antibody, a positive aquaporin-4 antibody and chest CT finding of thymic enlargement. We therefore confirmed the previous diagnosis of MG and performed a recent diagnosis of background NMO. A high index of suspicion is needed to make a diagnosis of this rare coexistence of NMO and MG in resource-limited settings such as Nigeria.

Coefficients of impairment in deforming spastic paresis.

This position paper introduces an assessment method using staged calculation of coefficients of impairment in spastic paresis, with its rationale and proposed use. The syndrome of deforming spastic paresis superimposes two disorders around each joint: a neural disorder comprising stretch-sensitive paresis in agonists and antagonist muscle overactivity, and a muscle disorder ("spastic myopathy") combining shortening and loss of extensibility in antagonists. Antagonist muscle overactivity includes spastic cocontraction (misdirected descending command), spastic dystonia (tonic involuntary muscle activation, at rest) and spasticity (increased velocity-dependent reflexes to phasic stretch, at rest). This understanding of various types of antagonist resistance as the key limiting factors in paretic movements prompts a stepwise, quantified, clinical assessment of antagonist resistances, elaborating on the previously developed Tardieu Scale. Step 1 quantifies limb function (e.g. ambulation speed in lower limb, Modified Frenchay Scale in upper limb). The following four steps evaluate various angles X of antagonist resistance, in degrees all measured from 0°, position of minimal stretch of the tested antagonist. Step 2 rates the functional muscle length, termed XV1 (V1, slowest stretch velocity possible), evaluated as the angle of arrest upon slow and strong passive muscle stretch. XV1 is appreciated with respect to the expected normal passive amplitude, XN, and reflects combined muscle contracture and residual spastic dystonia. Step 3 determines the angle of catch upon fast stretch, termed XV3 (V3, fastest stretch velocity possible), reflecting spasticity. Step 4 measures the maximal active range of motion against the antagonist, termed XA, reflecting agonist capacity to overcome passive (stiffness) and active (spastic cocontraction) antagonist resistances over a single movement. Finally, Step 5 rates the residual active amplitude after 15 seconds of maximal amplitude rapid alternating movements, XA15. Amplitude decrement from XA to XA15 reflects fatigability. Coefficients of shortening (XN-XV1)/XN, spasticity (XV1-XV3)/XV1, weakness (XV1-XA)/XV1 and fatigability (XA-XA15)/XA are derived. A high (e.g., >10%) coefficient of shortening prompts aggressive treatment of the muscle disorder--e.g., by stretch programs, such as prolonged stretch postures -, while high coefficients of weakness or fatigability prompt addressing the neural motor command disorder, e.g. using training programs such as repeated alternating movements of maximal amplitude.