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Neuroepidemiology 2014Hereditary cerebellar ataxias (HCA) and hereditary spastic paraplegias (HSP) are two groups of neurodegenerative disorders that usually present with progressive gait... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Hereditary cerebellar ataxias (HCA) and hereditary spastic paraplegias (HSP) are two groups of neurodegenerative disorders that usually present with progressive gait impairment, often leading to permanent disability. Advances in genetic research in the last decades have improved their diagnosis and brought new possibilities for prevention and future treatments. Still, there is great uncertainty regarding their global epidemiology.
SUMMARY
Our objective was to assess the global distribution and prevalence of HCA and HSP by a systematic review and meta-analysis of prevalence studies. The MEDLINE, ISI Web of Science and Scopus databases were searched (1983-2013) for studies performed in well-defined populations and geographical regions. Two independent reviewers assessed the studies and extracted data and predefined methodological parameters. Overall, 22 studies were included, reporting on 14,539 patients from 16 countries. Multisource population-based studies yielded higher prevalence values than studies based primarily on hospitals or genetic centres. The prevalence range of dominant HCA was 0.0-5.6/10(5), with an average of 2.7/10(5) (1.5-4.0/10(5)). Spinocerebellar ataxia type 3 (SCA3)/Machado-Joseph disease was the most common dominant ataxia, followed by SCA2 and SCA6. The autosomal recessive (AR) HCA (AR-HCA) prevalence range was 0.0-7.2/10(5), the average being 3.3/10(5) (1.8-4.9/10(5)). Friedreich ataxia was the most frequent AR-HCA, followed by ataxia with oculomotor apraxia or ataxia-telangiectasia. The prevalence of autosomal dominant (AD) HSP (AD-HSP) ranged from 0.5 to 5.5/10(5) and that of AR-HSP from 0.0 to 5.3/10(5), with pooled averages of 1.8/10(5) (95% CI: 1.0-2.7/10(5)) and 1.8/10(5) (95% CI: 1.0-2.6/10(5)), respectively. The most common AD-HSP form in every population was spastic paraplegia, autosomal dominant, type 4 (SPG4), followed by SPG3A, while SPG11 was the most frequent AR-HSP, followed by SPG15. In population-based studies, the number of families without genetic diagnosis after systematic testing ranged from 33 to 92% in the AD-HCA group, and was 40-46% in the AR-HCA, 45-67% in the AD-HSP and 71-82% in the AR-HSP groups.
KEY MESSAGES
Highly variable prevalence values for HCA and HSP are reported across the world. This variation reflects the different genetic make-up of the populations, but also methodological heterogeneity. Large areas of the world remain without prevalence studies. From the available data, we estimated that around 1:10,000 people are affected by HCA or HSP. In spite of advances in genetic research, most families in population-based series remain without identified genetic mutation after extensive testing. © 2014 S. Karger AG, Basel.
Topics: Cerebellar Ataxia; Cross-Sectional Studies; Humans; Paraplegia; Prevalence; Spastic Paraplegia, Hereditary; Spinocerebellar Degenerations
PubMed: 24603320
DOI: 10.1159/000358801 -
The Journal of Clinical Investigation May 2023Spastic paraplegia 50 (SPG50) is an ultrarare childhood-onset neurological disorder caused by biallelic loss-of-function variants in the AP4M1 gene. SPG50 is...
Spastic paraplegia 50 (SPG50) is an ultrarare childhood-onset neurological disorder caused by biallelic loss-of-function variants in the AP4M1 gene. SPG50 is characterized by progressive spastic paraplegia, global developmental delay, and subsequent intellectual disability, secondary microcephaly, and epilepsy. We preformed preclinical studies evaluating an adeno-associated virus (AAV)/AP4M1 gene therapy for SPG50 and describe in vitro studies that demonstrate transduction of patient-derived fibroblasts with AAV2/AP4M1, resulting in phenotypic rescue. To evaluate efficacy in vivo, Ap4m1-KO mice were intrathecally (i.t.) injected with 5 × 1011, 2.5 × 1011, or 1.25 × 1011 vector genome (vg) doses of AAV9/AP4M1 at P7-P10 or P90. Age- and dose-dependent effects were observed, with early intervention and higher doses achieving the best therapeutic benefits. In parallel, three toxicology studies in WT mice, rats, and nonhuman primates (NHPs) demonstrated that AAV9/AP4M1 had an acceptable safety profile up to a target human dose of 1 × 1015 vg. Of note, similar degrees of minimal-to-mild dorsal root ganglia (DRG) toxicity were observed in both rats and NHPs, supporting the use of rats to monitor DRG toxicity in future i.t. AAV studies. These preclinical results identify an acceptably safe and efficacious dose of i.t.-administered AAV9/AP4M1, supporting an investigational gene transfer clinical trial to treat SPG50.
Topics: Humans; Rats; Mice; Animals; Child; Spastic Paraplegia, Hereditary; Genetic Therapy; Dependovirus; Genetic Vectors; Paraplegia
PubMed: 36951961
DOI: 10.1172/JCI164575 -
Annals of the Royal College of Surgeons... Nov 1954
Topics: Humans; Paraplegia; Spinal Cord Injuries; Spinal Injuries; Spine
PubMed: 13208104
DOI: No ID Found -
Viruses Nov 2015First described in 1962 in children hospitalized for pneumonia and bronchiolitis, the Enterovirus D68 (EV-D68) is an emergent viral pathogen. Since its discovery, during... (Review)
Review
First described in 1962 in children hospitalized for pneumonia and bronchiolitis, the Enterovirus D68 (EV-D68) is an emergent viral pathogen. Since its discovery, during the long period of surveillance up to 2005, EV-D68 was reported only as a cause of sporadic outbreaks. In recent years, many reports from different countries have described an increasing number of patients with respiratory diseases due to EV-D68 associated with relevant clinical severity. In particular, an unexpectedly high number of children have been hospitalized for severe respiratory disease due to EV-D68, requiring intensive care such as intubation and mechanical ventilation. Moreover, EV-D68 has been associated with acute flaccid paralysis and cranial nerve dysfunction in children, which has caused concerns in the community. As no specific antiviral therapy is available, treatment is mainly supportive. Moreover, because no vaccines are available, conventional infection control measures (i.e., standard, for contacts and droplets) in both community and healthcare settings are recommended. However, further studies are required to fully understand the real importance of this virus. Prompt diagnosis and continued surveillance of EV-D68 infections are essential to managing and preventing new outbreaks. Moreover, if the association between EV-D68 and severe diseases will be confirmed, the development of adequate preventive and therapeutic approaches are a priority.
Topics: Disease Outbreaks; Enterovirus D, Human; Enterovirus Infections; Humans; Infection Control; Paraplegia; Respiratory Tract Infections
PubMed: 26610548
DOI: 10.3390/v7112925 -
Journal of Neurology, Neurosurgery, and... Apr 1987Between 1944 and 1984 20 patients were admitted to a spinal injuries centre with a diagnosis of traumatic paraplegia. They subsequently walked out and the diagnosis was...
Between 1944 and 1984 20 patients were admitted to a spinal injuries centre with a diagnosis of traumatic paraplegia. They subsequently walked out and the diagnosis was revised to hysterical paraplegia. A further 23 patients with incomplete traumatic injuries, who also walked from the centre, have been compared with them as controls. The features that enabled a diagnosis of hysterical paraplegia to be arrived at were: They were predominantly paraplegic, There was a high incidence of previous psychiatric illness and employment in the Health Service or allied professions, Many were actively seeking compensation. The physical findings were a disproportionate motor paralysis, non anatomical sensory loss, the presence of downgoing plantar responses, normal tone and reflexes. They made a rapid total recovery. In contrast, the control traumatic cases showed an incomplete recovery and a persistent residual neurological deficit. Investigations apart from plain radiographs of the spinal column were not warranted, and the diagnosis should be possible on clinical grounds alone.
Topics: Female; Humans; Hysteria; Male; Medical History Taking; Paraplegia; Physical Examination; Psychophysiologic Disorders; Spinal Cord Injuries
PubMed: 3585346
DOI: 10.1136/jnnp.50.4.375 -
Turkish Neurosurgery 2019To report the four most common spinal parasites for providing insight into definitive therapy.
AIM
To report the four most common spinal parasites for providing insight into definitive therapy.
MATERIAL AND METHODS
Twelve patients with spinal parasites were diagnosed between 2009 and 2016. A definite diagnosis was established in the form of histopathology (n=9) and response to drug therapy (n=3). The minimum follow-up was 0.9 years and ranged to a maximum of 8 years, with a median of 3 years.
RESULTS
Twelve patients aged between 8 and 69 years were reviewed, including nine hydatidosis and three non-hydatid cases. Occupational exposure to the endemic area and unclean food were the main routes of infestation. Spinal parasites can present symptoms that correlated with the level of the lesion. There was complete paraplegia in four patients and paraparesis in six patients before surgery. Seven hydatid patients underwent posterior decompression and pedicle screw fixation with posterolateral fusion. Two non-hydatid patients experienced laminoplasty after posterior decompression. Six hydatid patients had reoccurrences and two patients with intramedullary hydatidosis died of severe complications one year after surgery.
CONCLUSION
Spinal hydatidosis significantly differs from the three other non-hydatid parasites in diagnosis and treatment. The final prognosis of spinal hydatidosis remains poor, especially for intramedullary hydatidosis.
Topics: Adult; Aged; Animals; Child; Decompression, Surgical; Echinococcosis; Female; Humans; Laminoplasty; Male; Middle Aged; Paraplegia; Parasites; Pedicle Screws; Spinal Fusion; Spine
PubMed: 30649820
DOI: 10.5137/1019-5149.JTN.24369-18.2 -
Current Neurology and Neuroscience... Feb 2019Hereditary spastic paraplegias are a genetically heterogeneous group of neurological disorders. Patients present lower limb weakness and spasticity, complicated in... (Review)
Review
PURPOSE OF REVIEW
Hereditary spastic paraplegias are a genetically heterogeneous group of neurological disorders. Patients present lower limb weakness and spasticity, complicated in complex forms by additional neurological signs. We review here the major steps toward understanding the molecular basis of these diseases made over the last 10 years.
RECENT FINDINGS
Our perception of the intricate connections between clinical, genetic, and molecular aspects of neurodegenerative disorders has radically changed in recent years, thanks to improvements in genetic approaches. This is particularly true for hereditary spastic paraplegias, for which > 60 genes have been identified, highlighting (i) the considerable genetic heterogeneity of this group of clinically diverse disorders, (ii) the fuzzy border between recessive and dominant inheritance for several mutations, and (iii) the overlap of these mutations with other neurological conditions in terms of their clinical effects. Several hypotheses have been put forward concerning the pathophysiological mechanisms involved, based on the genes implicated and their known function and based on studies on patient samples and animal models. These mechanisms include mainly abnormal intracellular trafficking, changes to endoplasmic reticulum shaping and defects affecting lipid metabolism, lysosome physiology, autophagy, myelination, and development. Several causative genes affect multiple of these functions, which are, most of the time, interconnected. Recent major advances in our understanding of these diseases have revealed unifying pathogenic models that could be targeted in the much-needed development of new treatments.
Topics: Animals; Genetic Heterogeneity; Humans; Mutation; Paraplegia; Spastic Paraplegia, Hereditary
PubMed: 30820684
DOI: 10.1007/s11910-019-0930-2 -
Anaesthesia Jun 2013
Topics: Anesthesia, Obstetrical; Anesthesia, Spinal; Arachnoiditis; Female; Humans; Paraplegia; Pregnancy
PubMed: 23662755
DOI: 10.1111/anae.12248 -
British Journal of Sports Medicine Oct 2000
Topics: Athletic Injuries; Exercise Therapy; Humans; Osteoarthritis; Paraplegia
PubMed: 11049134
DOI: 10.1136/bjsm.34.5.319 -
British Medical Journal Jun 1979
Topics: Emigration and Immigration; Humans; Paraplegia; Tuberculosis, Spinal; United Kingdom
PubMed: 466051
DOI: No ID Found