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.

Clinical Association of White Matter Hyperintensities Localization in a Mexican Family with Spastic Paraparesis Carrying the PSEN1 A431E Mutation.

Presenilin 1 gene (PSEN1) mutations are the most common cause of familial Alzheimer's disease (FAD). One of the most abundant FAD mutations, PSEN1 A431E, has been reported to be associated with spastic paraparesis in about half of its carriers, but the determining mechanisms of this phenotype are still unknown. In our study we characterized three A431E mutation carriers, one symptomatic and two asymptomatic, from a Mexican family with a history of spastic paraparesis in all of its affected members. At cognitive assessment and MRI, the symptomatic subject showed an atypical non-amnestic mild cognitive impairment with visuospatial deficits, olfactory dysfunction and significant parieto-occipital brain atrophy. Furthermore, we found several periventricular white matter hyperintensities whose progression pattern and localization correlated with their motor impairment, cognitive profile, and non-motor symptoms. Together, our data suggests that in this family the A431E mutation leads to a divergent neurological disorder in which cognitive deterioration was clinically exceeded by motor impairment and that it involves early glial and vascular pathological changes.

Unusual Calcification in Intramedullary Epidermoid Cyst.

BACKGROUND: Calcified intraspinal epidermoids are a rare entity. We discuss the various pathogenesis and the clinical implication of such a finding during surgery. CASE DESCRIPTION: A 32-year-old female presented with progressive spastic paraparesis with incontinence. Imaging showed an unusual intralesional calcification, which was removed. Postoperatively she had no fresh deficits. CONCLUSIONS: To our knowledge this is the first reported case of spinal intramedullary epidermoid with intralesional calcification.

Case series of autosomal recessive hereditary spastic paraparesis with novel mutation in SPG 7 gene.

Autosomal recessive hereditary spastic paraparesis is rare.We present 4 patients with slowly progressive predominantly lower limb spasticity and ataxia. Only one patient had family history of ataxia but without any underlying diagnosis. All of them proved negative for the mutation of Spinocerebelalr ataxia genes SCA 1,2,3 and 6. All had mutation in the SPG 7 gene suggestive of autosomal recessive hereditary spastic paraparesis. One of the heterozygous mutatnts showed a novel c1617delC ,p(Val540fs) frameshift mutation in exon 12 of the SPG 7 gene. SPG7 mutation accounts for 1.5-7% of all the HSP but it is the cause of undiagnosed ataxia in 18.6% in a recent case series. SPG7 mutation should be remembered as an important cause of undiagnosed ataxia especially where next generation sequencing is not widely avaialbale or affordable.

The novel PSEN1 M84V mutation associated to frontal dysexecutive syndrome, spastic paraparesis, and cerebellar atrophy in a dominant Alzheimer's disease family.

We identified the novel PSEN1 pathogenic mutation M84V in 3 patients belonging to a large kindred affected by autosomal dominant Alzheimer's disease (AD). The clinical phenotype was characterized by early onset dementia in 14 affected subjects over 3 generations. Detailed clinical, imaging and genetic assessment was performed. We highlighted the presence of unusual symptoms such as frontal executive syndrome, psychosis and spastic paraparesis in these patients. Spastic paraparesis has been reported in other PSEN1 mutations in adjacent codons, suggesting that the position of the genetic defect may affect the clinical expression, although this phenotype can occur in mutations throughout the whole PSEN1 gene. Brain magnetic resonance imaging showed diffuse cortical atrophy, but also atrophy of cerebellar lobules, mainly involving Crus I, in 2 patients without cerebellar motor deficits. These neuroimaging results were consistent with recent findings about the association between sporadic AD and distinct and circumscribed cerebellar atrophy. The present work acknowledged the novel PSEN1 pathogenic mutation M84V and might contribute to the ongoing debate about the involvement of cerebellum in AD.

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.

Longstanding spastic paraparesis in a patient infected with hepatitis C virus and seropositive for aquaporin-4 antibody - Case report and review of the literature.

Nervous system involvement in Hepatitis C virus infection (HCV) has been associated to neuro-immunological deregulation, particularly in interferon-alpha treated patients. We present a case of optic and brainstem demyelinating disorder associated with aquaporin-4 (AQP4) antibodies. A 48 year-old woman, with previous diagnosis of non-treated hepatitis C, presented with a 10-year history of long-standing gait disturbance. Neurological examination disclosed a grade 4 spastic paraparesis, lower limb hyperreflexia, right positive Hoffmann sign, bilateral Babinski sign and spastic gait only possible with bilateral support. Spinal cord magnetic resonance imaging (MRI) was normal. Brain MRI showed an asymmetric, bilateral pontine and left mesencephalic hypersignal in T2 and FLAIR, with no gadolinium enhancement. Visual evoked potential revealed bilateral pre-chiasmatic conduction delay. Blood tests showed a positive anti-HCV antibody and a positive AQP4 antibody. Cerebrospinal fluid (CSF) analysis was normal, with no oligoclonal bands. The patient started intravenous (IV) methylprednisolone followed by oral prednisolone; simultaneously, interferon-alpha and ribavirin. There was a slight clinical improvement within the first weeks. There are 7 cases describing association between HCV infection and central nervous system (CNS) demyelination with positive AQP4 antibody, 4 patients under interferon-α. AQP4 antibodies should be tested in patients infected with HCV and CNS demyelination.

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.

A novel presenilin 1 mutation (V261L) associated with presenile Alzheimer's disease and spastic paraparesis.

BACKGROUND AND PURPOSE: We report a novel mutation in exon 8 of the presenilin 1 (PSEN1) gene (V261L) associated with early-onset autosomal dominant Alzheimer's disease and spastic paraparesis. METHODS AND RESULTS: The proband was a woman who developed insidious cognitive decline with predominant memory loss and gait disorder secondary to spasticity at the age of 40. Her brother and her mother had a similar disease in the fifth decade of life. The feature of amnestic presentation with spastic paraparesis is consistent with the majority of mutations in the exon 8 of the PSEN1 1 gene. CONCLUSIONS: Screening for PSEN1 mutations is especially likely to be productive when directed toward persons with positive family history and with age at onset of under 60.

SPG11 compound mutations in spastic paraparesis with thin corpus callosum.

BACKGROUND: Autosomal recessive hereditary spastic paraparesis with thin corpus callosum (ARHSP-TCC) is being increasingly recognized as a variety of spastic paraplegia with mental retardation. SPG11 gene mutations have been reported to be associated with ARHSP-TCC. METHODS: As an independent group, we investigated SPG11 gene involvement in four individuals not previously described with either recessive or sporadic HSP-TCC presentation. RESULTS: Chromosome 15q13-15 segregating autosomal disease haplotypes were different across the kindreds and sequencing of SPG11 identified four novel frameshift/nonsense segregating mutations and the R2034X mutation, which were in heterozygous compound status. The affected examined had decreased thalamic and bilateral paracentral frontal lobe metabolism on (18)F-flurodeoxyglucose PET. CONCLUSIONS: Loss-of-function SPG11 mutations are the major cause of autosomal recessive hereditary spastic paraparesis with thin corpus callosum in Southern Europe, even in apparently sporadic cases. Decreased thalamic metabolism was consistently a phenotypical SPG11 mutation hallmark.

A role for myelography in assessing paraparesis.

Imaging of the spine is a fundamental part of assessment of paraparesis. Since the advent of MRI the indications for myelograms have diminished. However, a myelogram, although an invasive test, should still be considered a useful investigation for localising lesions in the spinal cord and for identifying rare causes of myelopathy. This case illustrates how a CT myelogram identified an arachnoid cyst, which is a potentially treatable cause of paraparesis.

Symptomatic ossification of the ligamentum flavum: a clinical series from the French Antilles.

STUDY DESIGN: A series of 14 patients from the French Antilles treated for ossification of the ligamentum flavum (OLF). OBJECTIVES: To describe the clinical and radiologic aspects, as well as disease course in a group of Caribbean patients. Also describe the use of sagittal computerized tomography (CT) reconstructions to distinguish OLF from calcification of the ligamenta flava. SUMMARY OF BACKGROUND DATA: OLF is a rare disease described almost exclusively in Japanese patients. Only rarely are patients of African descent affected. No series of OLF in African American or African Caribbean subjects has previously been published. METHODS: A retrospective study of 14 consecutive patients, including 7 men and 7 women (mean age, 66.8 years), was conducted from 1996 to 2003. Diagnosis in each case was established using CT. Magnetic resonance imaging was also performed in every case. For the 11 patients treated surgically, pathology studies were performed. RESULTS: Walking difficulties were the most common presenting complaint. A picture of spastic paraparesis associated with sphincter dysfunction was the most common finding on initial examination. In each case, CT provided sufficient information to establish a diagnosis of OLF, while magnetic resonance imaging was helpful for showing spinal cord involvement. In most of the patients, OLF was located in the lower thoracic spine. Surgical decompression through a posterior approach resulted in regression of symptoms in all 11 patients treated surgically. CONCLUSIONS: This study is the first reported series of OLF in a group of Caribbean patients. The disease appears to be underreported in the African Caribbean population. OLF can lead to debilitating thoracic myelopathy. Surgery is frequently indicated and achieves favorable results.

Novel insertional presenilin 1 mutation causing Alzheimer disease with spastic paraparesis.

A four-generation pedigree exhibiting early-onset autosomal dominant Alzheimer disease (AD) with spastic paraplegia, dystonia, and dysarthria due to a novel 6-nucleotide insertional mutation in exon 3 of the presenilin 1 gene (PS1) is described. Serial examinations, PET scans, and autopsy revealed that the mutation in this highly conserved portion of PS1 causes an aggressive dementia that maintains the usual regional hierarchy of disease pathology while extending abnormalities into more widespread brain areas than typically seen in AD.