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Tethered cord

MedGen UID:
36387
Concept ID:
C0080218
Disease or Syndrome
Synonyms: Occult spinal dysraphism sequence; Tethered spinal cord syndrome
SNOMED CT: Occult spinal dysraphism sequence (70534000); Tethered cord malformation sequence (70534000); Tethered cord syndrome (70534000); Congenital tethering of spinal cord (70534000)
 
HPO: HP:0002144
Monarch Initiative: MONDO:0006995

Definition

During normal embryological development, the spinal cord first occupies the entire length of the vertebral column but goes on to assume a position at the level of L1 due to differential growth of the conus medullaris and the vertebral column. The filum terminale is a slender, threadlike structure that remains after the normal regression of the distal embryonic spinal cord and attaches the spinal cord to the coccyx. A tethered cord results if there is a thickened rope-like filum terminale which anchors the cord at the level of L2 or below, potentially causing neurologic signs owing to abnormal tension on the spinal cord. [from HPO]

Conditions with this feature

Pallister-Killian syndrome
MedGen UID:
120540
Concept ID:
C0265449
Disease or Syndrome
Pallister-Killian syndrome (PKS) is a dysmorphic condition involving most organ systems, but is also characterized by a tissue-limited mosaicism; most fibroblasts have 47 chromosomes with an extra small metacentric chromosome, whereas the karyotype of lymphocytes is normal. The extra metacentric chromosome is an isochromosome for part of the short arm of chromosome 12: i(12)(p10) (Peltomaki et al., 1987; Warburton et al., 1987).
Currarino triad
MedGen UID:
323460
Concept ID:
C1531773
Disease or Syndrome
The Currarino syndrome is an autosomal dominant form of hereditary sacral dysgenesis that classically consists of the triad of sacral malformation, presacral mass, and anorectal malformations. However, other features include neonatal-onset bowel obstruction, chronic constipation, recurrent perianal sepsis, renal/urinary tract anomalies, female internal genital anomalies, tethered spinal cord, and anterior meningocele. There is marked inter- and intrafamilial variability, and up to 33% of patients are asymptomatic (summary by Wang et al., 2006).
Sacral defect with anterior meningocele
MedGen UID:
325455
Concept ID:
C1838568
Disease or Syndrome
Sacral defect with anterior meningocele (SDAM) is a form of caudal dysgenesis. It is present at birth and becomes symptomatic later in life, usually because of obstructive labor in females, chronic constipation, or meningitis. Inheritance is autosomal dominant (Chatkupt et al., 1994). Welch and Aterman (1984) gave a population frequency of 0.14%. Caudal dysgenesis syndrome and caudal regression syndrome are broad terms that refer to a heterogeneous constellation of congenital caudal anomalies affecting the caudal spine and spinal cord, the hindgut, the urogenital system, and the lower limbs. Approximately 15 to 25% of mothers of children with caudal dysgenesis have insulin-dependent diabetes mellitus (222100) (Lynch et al., 2000). See also Currarino syndrome (176450), a similar disorder caused by mutation in the HLXB9 gene (142994) on chromosome 7q36. Currarino syndrome classically comprises the triad of hemisacrum, anorectal malformation, and presacral mass. However, Currarino syndrome also shows phenotypic variability: Lynch et al. (2000) stated that there is variable expressivity of clinical features and that some patients with Currarino syndrome are asymptomatic. Kochling et al. (2001) found the complete triad of Currarino syndrome in only 8 of 23 patients with mutations in the HLXB9 gene, These reports suggest that some patients previously reported as having forms of sacral agenesis, including SDAM, may have had Currarino syndrome and vice versa. See also spina bifida (182940), which can be seen in some patients with sacral agenesis or caudal regression syndrome and may be etiologically related.
Exstrophy-epispadias complex
MedGen UID:
338020
Concept ID:
C1850321
Disease or Syndrome
Carey et al. (1978) gave the name OEIS complex to a combination of defects comprising omphalocele, exstrophy of the cloaca, imperforate anus, and spinal defects. This rare complex is thought to represent the most severe end of a spectrum of birth defects, the exstrophy-epispadias sequence, which, in order of increasing severity, includes phallic separation with epispadias, pubic diastasis, exstrophy of the bladder (600057), cloacal exstrophy, and OEIS complex. Very few instances of recurrence of anomalies in this cluster have been reported.
Lateral meningocele syndrome
MedGen UID:
342070
Concept ID:
C1851710
Disease or Syndrome
NOTCH3-related lateral meningocele syndrome (LMS) is characterized by multiple lateral spinal meningoceles (protrusions of the arachnoid and dura through spinal foramina), distinctive facial features, joint hyperextensibility, hypotonia, and skeletal, cardiac, and urogenital anomalies. Neurologic sequelæ of the meningoceles depend on size and location and can include neurogenic bladder, paresthesia, back pain, and/or paraparesis. Other neurologic findings can include Chiari I malformation, syringomyelia, and rarely, hydrocephalus. Additional findings of LMS include developmental delay, mixed or conductive hearing loss, and cleft palate. Skeletal abnormalities may include scoliosis, vertebral fusion, scalloping of vertebrae, and wormian bones. Infants may demonstrate feeding difficulties with poor weight gain.
4p partial monosomy syndrome
MedGen UID:
408255
Concept ID:
C1956097
Disease or Syndrome
Wolf-Hirschhorn syndrome is a congenital malformation syndrome characterized by pre- and postnatal growth deficiency, developmental disability of variable degree, characteristic craniofacial features ('Greek warrior helmet' appearance of the nose, high forehead, prominent glabella, hypertelorism, high-arched eyebrows, protruding eyes, epicanthal folds, short philtrum, distinct mouth with downturned corners, and micrognathia), and a seizure disorder (Battaglia et al., 2008).
CLOVES syndrome
MedGen UID:
442876
Concept ID:
C2752042
Disease or Syndrome
PIK3CA-related overgrowth spectrum (PROS) encompasses a range of clinical findings in which the core features are congenital or early-childhood onset of segmental/focal overgrowth with or without cellular dysplasia. Prior to the identification of PIK3CA as the causative gene, PROS was separated into distinct clinical syndromes based on the tissues and/or organs involved (e.g., MCAP [megalencephaly-capillary malformation] syndrome and CLOVES [congenital lipomatous asymmetric overgrowth of the trunk, lymphatic, capillary, venous, and combined-type vascular malformations, epidermal nevi, skeletal and spinal anomalies] syndrome). The predominant areas of overgrowth include the brain, limbs (including fingers and toes), trunk (including abdomen and chest), and face, all usually in an asymmetric distribution. Generalized brain overgrowth may be accompanied by secondary overgrowth of specific brain structures resulting in ventriculomegaly, a markedly thick corpus callosum, and cerebellar tonsillar ectopia with crowding of the posterior fossa. Vascular malformations may include capillary, venous, and less frequently, arterial or mixed (capillary-lymphatic-venous or arteriovenous) malformations. Lymphatic malformations may be in various locations (internal and/or external) and can cause various clinical issues, including swelling, pain, and occasionally localized bleeding secondary to trauma. Lipomatous overgrowth may occur ipsilateral or contralateral to a vascular malformation, if present. The degree of intellectual disability appears to be mostly related to the presence and severity of seizures, cortical dysplasia (e.g., polymicrogyria), and hydrocephalus. Many children have feeding difficulties that are often multifactorial in nature. Endocrine issues affect a small number of individuals and most commonly include hypoglycemia (largely hypoinsulinemic hypoketotic hypoglycemia), hypothyroidism, and growth hormone deficiency.
Palatal anomalies-widely spaced teeth-facial dysmorphism-developmental delay syndrome
MedGen UID:
895943
Concept ID:
C4225229
Disease or Syndrome
Palatal anomalies-widely spaced teeth-facial dysmorphism-developmental delay syndrome is a rare, genetic multiple congenital anomalies/dysmorphic syndrome characterized by global developmental delay, axial hypotonia, palate abnormalities (including cleft palate and/or high and narrow palate), dysmorphic facial features (including prominent forehead, hypertelorism, downslanting palpebral fissures, wide nasal bridge, thin lips and widely spaced teeth), and short stature. Additional manifestations may include digital anomalies (such as brachydactyly, clinodactyly, and hypoplastic toenails), a single palmar crease, lower limb hypertonia, joint hypermobility, as well as ocular and urogenital anomalies.
VATER association
MedGen UID:
902479
Concept ID:
C4225671
Disease or Syndrome
VATER is a mnemonically useful acronym for the nonrandom association of vertebral defects (V), anal atresia (A), tracheoesophageal fistula with esophageal atresia (TE), and radial or renal dysplasia (R). This combination of associated defects was pointed out by Quan and Smith (1972). Nearly all cases have been sporadic. VACTERL is an acronym for an expanded definition of the association that includes cardiac malformations (C) and limb anomalies (L). The VACTERL association is a spectrum of various combinations of its 6 components, which can be a manifestation of several recognized disorders rather than a distinct anatomic or etiologic entity (Khoury et al., 1983). Also see VATER/VACTERL association with hydrocephalus (VACTERL-H; 276950) and VACTERL with or without hydrocephalus (VACTERLX; 314390).
Fanconi anemia complementation group R
MedGen UID:
924579
Concept ID:
C4284093
Disease or Syndrome
Fanconi anemia (FA) is characterized by physical abnormalities, bone marrow failure, and increased risk for malignancy. Physical abnormalities, present in approximately 75% of affected individuals, include one or more of the following: short stature, abnormal skin pigmentation, skeletal malformations of the upper and/or lower limbs, microcephaly, and ophthalmic and genitourinary tract anomalies. Progressive bone marrow failure with pancytopenia typically presents in the first decade, often initially with thrombocytopenia or leukopenia. The incidence of acute myeloid leukemia is 13% by age 50 years. Solid tumors – particularly of the head and neck, skin, and genitourinary tract – are more common in individuals with FA.
Short stature-brachydactyly-obesity-global developmental delay syndrome
MedGen UID:
934656
Concept ID:
C4310689
Disease or Syndrome
A rare genetic, multiple congenital anomalies syndrome characterized by short stature, hand brachydactyly with hypoplastic distal phalanges, global development delay, intellectual disability, and more variably seizures, obesity, and craniofacial dysmorphism that includes microcephaly, high forehead, flat face, hypertelorism, deep set eyes, flat nasal bridge, averted nostrils, long philtrum, thin lip vermilion, and short neck.
Vertebral, cardiac, renal, and limb defects syndrome 1
MedGen UID:
1621146
Concept ID:
C4540004
Disease or Syndrome
Vertebral, cardiac, renal, and limb defects syndrome-1 (VCRL1) is an autosomal recessive congenital malformation syndrome characterized by vertebral segmentation abnormalities, congenital cardiac defects, renal defects, and mild distal limb defects. Additional features are variable (summary by Shi et al., 2017). Genetic Heterogeneity of Vertebral, Cardiac, Renal, and Limb Defects Syndrome See also VCRL2 (617661), caused by mutation in the KYNU gene (605197) on chromosome 2q22, and VCRL3 (618845), caused by mutation in the NADSYN1 gene (608285) on chromosome 11q13.
Townes-Brocks syndrome 1
MedGen UID:
1635275
Concept ID:
C4551481
Disease or Syndrome
Townes-Brocks syndrome (TBS) is characterized by the triad of imperforate anus (84%), dysplastic ears (87%; overfolded superior helices and preauricular tags; frequently associated with sensorineural and/or conductive hearing impairment [65%]), and thumb malformations (89%; triphalangeal thumbs, duplication of the thumb [preaxial polydactyly], and rarely hypoplasia of the thumbs). Renal impairment (42%), including end-stage renal disease (ESRD), may occur with or without structural abnormalities (mild malrotation, ectopia, horseshoe kidney, renal hypoplasia, polycystic kidneys, vesicoutereral reflux). Congenital heart disease occurs in 25%. Foot malformations (52%; flat feet, overlapping toes) and genitourinary malformations (36%) are common. Intellectual disability occurs in approximately 10% of individuals. Rare features include iris coloboma, Duane anomaly, Arnold-Chiari malformation type 1, and growth retardation.
Cardiac, facial, and digital anomalies with developmental delay
MedGen UID:
1648330
Concept ID:
C4748484
Disease or Syndrome
CAFDADD is a multisystemic developmental disorder with variable cardiac and digital anomalies and facial dysmorphism. Some patients may have seizures and ocular/aural abnormalities (Tokita et al., 2018).
Hypomyelination with brain stem and spinal cord involvement and leg spasticity
MedGen UID:
1667792
Concept ID:
C4755254
Disease or Syndrome
Hypomyelination with brainstem and spinal cord involvement and leg spasticity is an autosomal recessive leukoencephalopathy characterized by onset in the first year of life of severe spasticity, mainly affecting the lower limbs and resulting in an inability to achieve independent ambulation. Affected individuals show delayed motor development and nystagmus; some may have mild mental retardation. Brain MRI shows hypomyelination and white matter lesions in the cerebrum, brainstem, cerebellum, and spinal cord (summary by Taft et al., 2013).
Menke-Hennekam syndrome 1
MedGen UID:
1675629
Concept ID:
C5193034
Disease or Syndrome
Menke-Hennekam syndrome-1 (MKHK1) is a congenital disorder characterized by variable impairment of intellectual development and facial dysmorphisms. Feeding difficulties, autistic behavior, recurrent upper airway infections, hearing impairment, short stature, and microcephaly are also frequently seen. Although mutations in the same gene cause Rubinstein-Taybi syndrome-1 (RSTS1; 180849), patients with MKHK1 do not resemble the striking phenotype of RSTS1. Genetic Heterogeneity of Menke-Hennekam Syndrome Menke-Hennekam syndrome-2 (MKHK2; 618333) is caused by heterozygous mutation in exons 30 or 31 of the EP300 gene (602700). Mutation elsewhere in that gene results in RSTS2 (613684).
Microcephaly 25, primary, autosomal recessive
MedGen UID:
1674123
Concept ID:
C5193046
Disease or Syndrome
Khan-Khan-Katsanis syndrome
MedGen UID:
1682553
Concept ID:
C5193110
Disease or Syndrome
Khan-Khan-Katsanis syndrome (3KS) is an autosomal recessive neurodevelopmental disorder with variable involvement of the ocular, renal, skeletal, and sometimes cardiac systems. Affected individuals present at birth with multiple congenital anomalies, defects in urogenital and limb morphogenesis, poor overall growth with microcephaly, and global developmental delay (summary by Khan et al., 2019).
Neurodevelopmental disorder with dysmorphic facies and thin corpus callosum
MedGen UID:
1790413
Concept ID:
C5551361
Disease or Syndrome
Neurodevelopmental disorder with dysmorphic facies and thin corpus callosum (NEDDFAC) is characterized by global developmental delay, impaired intellectual development with poor or absent speech and language, and dysmorphic facial features. Brain imaging tends to show thin corpus callosum and decreased white matter volume. Additional features such as seizures, cardiac defects, and behavioral abnormalities may also occur. The phenotype is variable (summary by Bina et al., 2020).
Neurodevelopmental-craniofacial syndrome with variable renal and cardiac abnormalities
MedGen UID:
1794194
Concept ID:
C5561984
Disease or Syndrome
Neurodevelopmental-craniofacial syndrome with variable renal and cardiac abnormalities (NECRC) is an autosomal dominant disorder characterized by dysmorphic craniofacial features associated with mild developmental delay, mildly impaired intellectual development or learning difficulties, speech delay, and behavioral abnormalities. About half of patients have congenital anomalies of the kidney and urinary tract (CAKUT) and/or congenital cardiac defects, including septal defects (Connaughton et al., 2020).
Neurodevelopmental disorder with craniofacial dysmorphism and skeletal defects
MedGen UID:
1824008
Concept ID:
C5774235
Disease or Syndrome
Neurodevelopmental disorder with craniofacial dysmorphism and skeletal defects (NEDCDS) is characterized by global developmental delay, severely impaired intellectual development with poor or absent speech, characteristic facial features, and variable skeletal abnormalities. Additional features include feeding difficulties, inability to walk or walking with an abnormal gait, and cerebellar or other abnormalities on brain imaging (Reichert et al., 2020).
Developmental delay, language impairment, and ocular abnormalities
MedGen UID:
1824035
Concept ID:
C5774262
Disease or Syndrome
Developmental delay, language impairment, and ocular abnormalities (DEVLO) is characterized by delayed acquisition of skills particularly affecting speech and language development, although many patients show mild motor delay. Most affected individuals also have a small head circumference (down to -3 SD) and may have mild dysmorphic features. Variable ocular anomalies include strabismus, cataracts, and cortical visual impairment. Older patients require special schooling and often demonstrate behavioral abnormalities (Laboy Cintron et al., 2022).

Professional guidelines

PubMed

Saletti V, Farinotti M, Peretta P, Massimi L, Ciaramitaro P, Motta S, Solari A, Valentini LG
Neurol Sci 2021 Dec;42(12):4965-4995. Epub 2021 Sep 30 doi: 10.1007/s10072-021-05565-9. PMID: 34591209
Stein R, Bogaert G, Dogan HS, Hoen L, Kocvara R, Nijman RJM, Quadackers JSLT, Rawashdeh YF, Silay MS, Tekgul S, Radmayr C
Neurourol Urodyn 2020 Jan;39(1):45-57. Epub 2019 Nov 13 doi: 10.1002/nau.24211. PMID: 31724222
Yaltırık K, El Tecle NE, Pierson MJ, Puryear A, Atalay B, Elbabaa SK
Childs Nerv Syst 2017 Nov;33(11):1899-1903. Epub 2017 Jul 10 doi: 10.1007/s00381-017-3504-0. PMID: 28695338

Curated

UK NICE Clinical guideline (CG148), Urinary incontinence in neurological disease: assessment and management, 2023

Recent clinical studies

Etiology

Galloway G, Sala F
Handb Clin Neurol 2022;186:257-270. doi: 10.1016/B978-0-12-819826-1.00018-1. PMID: 35772890
Mancarella C, Delfini R, Landi A
Acta Neurochir Suppl 2019;125:89-95. doi: 10.1007/978-3-319-62515-7_13. PMID: 30610307
Henderson FC Sr, Austin C, Benzel E, Bolognese P, Ellenbogen R, Francomano CA, Ireton C, Klinge P, Koby M, Long D, Patel S, Singman EL, Voermans NC
Am J Med Genet C Semin Med Genet 2017 Mar;175(1):195-211. Epub 2017 Feb 21 doi: 10.1002/ajmg.c.31549. PMID: 28220607
Lew SM, Kothbauer KF
Pediatr Neurosurg 2007;43(3):236-48. doi: 10.1159/000098836. PMID: 17409793
Blount JP, Elton S
Neurosurg Focus 2001 Jan 15;10(1):e3. doi: 10.3171/foc.2001.10.1.4. PMID: 16749755

Diagnosis

Lu VM, Niazi TN
Pediatr Rev 2021 Sep;42(9):486-499. doi: 10.1542/pir.2020-000661. PMID: 34470868
Mancarella C, Delfini R, Landi A
Acta Neurochir Suppl 2019;125:89-95. doi: 10.1007/978-3-319-62515-7_13. PMID: 30610307
Henderson FC Sr, Austin C, Benzel E, Bolognese P, Ellenbogen R, Francomano CA, Ireton C, Klinge P, Koby M, Long D, Patel S, Singman EL, Voermans NC
Am J Med Genet C Semin Med Genet 2017 Mar;175(1):195-211. Epub 2017 Feb 21 doi: 10.1002/ajmg.c.31549. PMID: 28220607
Agarwalla PK, Dunn IF, Scott RM, Smith ER
Neurosurg Clin N Am 2007 Jul;18(3):531-47. doi: 10.1016/j.nec.2007.04.001. PMID: 17678753
Lew SM, Kothbauer KF
Pediatr Neurosurg 2007;43(3):236-48. doi: 10.1159/000098836. PMID: 17409793

Therapy

Pan J, Boop SH, Barber JK, Susarla SM, Durfy S, Ojemann JG, Goldstein HE, Lee A, Browd S, Ellenbogen RG, Hauptman JS
J Neurosurg Pediatr 2023 Nov 1;32(5):607-616. Epub 2023 Aug 11 doi: 10.3171/2023.6.PEDS23259. PMID: 37728397
Michael MM, Garton ALA, Kuzan-Fischer CM, Uribe-Cardenas R, Greenfield JP
Childs Nerv Syst 2021 Oct;37(10):3003-3011. Epub 2021 Jul 15 doi: 10.1007/s00381-021-05287-5. PMID: 34268593
Dewan MC, Wellons JC
J Neurosurg Pediatr 2019 Aug 1;24(2):105-114. doi: 10.3171/2019.4.PEDS18383. PMID: 31370010
Lin W, Xu H, Duan G, Xie J, Chen Y, Jiao B, Lan H
Neurol Res 2018 May;40(5):340-363. Epub 2018 Mar 12 doi: 10.1080/01616412.2018.1446268. PMID: 29528274
Caldarelli M, Boscarelli A, Massimi L
Childs Nerv Syst 2013 Sep;29(9):1601-9. Epub 2013 Sep 7 doi: 10.1007/s00381-013-2150-4. PMID: 24013330

Prognosis

Morota N, Sakamoto H
Childs Nerv Syst 2023 Oct;39(10):2847-2864. Epub 2023 Jul 8 doi: 10.1007/s00381-023-06024-w. PMID: 37421423
Lu VM, Niazi TN
Pediatr Rev 2021 Sep;42(9):486-499. doi: 10.1542/pir.2020-000661. PMID: 34470868
Kobets AJ, Oliver J, Cohen A, Jallo GI, Groves ML
Childs Nerv Syst 2021 Apr;37(4):1301-1306. Epub 2020 Nov 26 doi: 10.1007/s00381-020-04978-9. PMID: 33242106
Stein R, Bogaert G, Dogan HS, Hoen L, Kocvara R, Nijman RJM, Quadackers JSLT, Rawashdeh YF, Silay MS, Tekgul S, Radmayr C
Neurourol Urodyn 2020 Jan;39(1):45-57. Epub 2019 Nov 13 doi: 10.1002/nau.24211. PMID: 31724222
Blount JP, Elton S
Neurosurg Focus 2001 Jan 15;10(1):e3. doi: 10.3171/foc.2001.10.1.4. PMID: 16749755

Clinical prediction guides

Howells M, Hamby T, Honeycutt J, Donahue DJ
Pediatr Neurosurg 2022;57(2):85-92. Epub 2022 Jan 21 doi: 10.1159/000522135. PMID: 35066504
Apaydin M
Surg Radiol Anat 2020 Feb;42(2):111-119. Epub 2019 Sep 19 doi: 10.1007/s00276-019-02341-5. PMID: 31538247
Dewan MC, Wellons JC
J Neurosurg Pediatr 2019 Aug 1;24(2):105-114. doi: 10.3171/2019.4.PEDS18383. PMID: 31370010
Lin W, Xu H, Duan G, Xie J, Chen Y, Jiao B, Lan H
Neurol Res 2018 May;40(5):340-363. Epub 2018 Mar 12 doi: 10.1080/01616412.2018.1446268. PMID: 29528274
Yaltırık K, El Tecle NE, Pierson MJ, Puryear A, Atalay B, Elbabaa SK
Childs Nerv Syst 2017 Nov;33(11):1899-1903. Epub 2017 Jul 10 doi: 10.1007/s00381-017-3504-0. PMID: 28695338

Recent systematic reviews

Rezaee H, Keykhosravi E
Br J Neurosurg 2022 Oct;36(5):574-582. Epub 2021 Oct 28 doi: 10.1080/02688697.2021.1995589. PMID: 34709093
O'Connor KP, Smitherman AD, Milton CK, Palejwala AH, Lu VM, Johnston SE, Homburg H, Zhao D, Martin MD
World Neurosurg 2020 May;137:e221-e241. Epub 2020 Jan 28 doi: 10.1016/j.wneu.2020.01.131. PMID: 32001403
Stein R, Bogaert G, Dogan HS, Hoen L, Kocvara R, Nijman RJM, Quadackers JSLT, Rawashdeh YF, Silay MS, Tekgul S, Radmayr C
Neurourol Urodyn 2020 Jan;39(1):45-57. Epub 2019 Nov 13 doi: 10.1002/nau.24211. PMID: 31724222
Lin W, Xu H, Duan G, Xie J, Chen Y, Jiao B, Lan H
Neurol Res 2018 May;40(5):340-363. Epub 2018 Mar 12 doi: 10.1080/01616412.2018.1446268. PMID: 29528274
Yaltırık K, El Tecle NE, Pierson MJ, Puryear A, Atalay B, Elbabaa SK
Childs Nerv Syst 2017 Nov;33(11):1899-1903. Epub 2017 Jul 10 doi: 10.1007/s00381-017-3504-0. PMID: 28695338

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    Curated

    • NICE, 2023
      UK NICE Clinical guideline (CG148), Urinary incontinence in neurological disease: assessment and management, 2023

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