Manifestations of Tuberous Sclerosis Complex: The Experience of a Provincial Clinic

AbstractBackground: Tuberous sclerosis complex (TSC) is a neurocutaneous disorder with a wide spectrum of manifestations. Recent consensus recommendations stress the importance of multidisciplinary management of children with TSC. The objective of this study was to examine the manifestations of TSC at a large referral centre to determine the care needs of this population. Methods: A retrospective, systematic chart review was performed of children with TSC managed at British Columbia Children’s Hospital. Patients were identified through epilepsy and clinical neurophysiology databases. Results: The study population comprised 81 patients, born between 1987 and 2014, who were a median of 10 years (range, 0.2-23.2) at most recent follow-up. Epilepsy occurred in 91% of patients, including 32% with a history of infantile spasms. Nineteen patients underwent epilepsy surgery, nine (47%) of whom were seizure-free at most recent follow-up. Overall, 61% of epilepsy patients had been seizure-free for at least 1 year at the time of last follow-up. Neuropsychiatric disorders were diagnosed in 49% of children, with autism (25%), attention deficit hyperactivity order (19%) and anxiety (16%) being the most common. Cardiac rhabdomyomata occurred in 35% of children and renal angiomyolipomas were seen in 43%. A total of 91% had skin manifestations. Conclusion: This study outlines the multisystem manifestations of TSC, observed through a large pediatric referral center. Epilepsy and neuropsychiatric disorders are the major source of morbidity in this age group and provide many challenges to the treating clinician. Because a subset of the study population is still quite young, the prevalence of neuropsychiatric disorders is likely underestimated.

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The diverse manifestations of tuberous sclerosis complex: the experience of a provincial TSC clinic

Canadian Journal of Neurological Sciences / Journal Canadien des Sciences Neurologiques ◽

10.1017/cjn.2015.87 ◽

2015 ◽

Vol 42 (S1) ◽

pp. S14-S14

Author(s):

C Wilbur ◽

C Sanguansermsri ◽

H Chable ◽

A Mihaela ◽

MB Connolly

Keyword(s):

Intellectual Disability ◽

Tuberous Sclerosis ◽

Tuberous Sclerosis Complex ◽

Chart Review ◽

Retrospective Chart Review ◽

Multidisciplinary Care ◽

Care Needs ◽

History Of ◽

Study Population

Background: Recent consensus recommendations for Tuberous Sclerosis Complex (TSC) stress the importance of multidisciplinary follow-up for these patients. The objective of our study was to review the manifestations of TSC seen in our hospital to determine the care needs of this population. Methods: This was a systematic, retrospective chart review of children with TSC treated at our institution. Patients were identified through epilepsy and clinical neurophysiology databases. Results: The study population comprised 81 patients, born between 1987-2014, who were a median 10 (Range 0.2-23.2) years of age at last follow-up. 88% of patients had epilepsy, including 30% with a history of infantile spasms. Developmental delay was reported in 65%, while 40% had intellectual disability. Psychiatric co-morbidities occurred in 49%. The most common psychiatric diagnoses were autism (25%), ADHD (19%), and anxiety (16%). Cardiac rhabdomyomas occurred in 35% of patients and renal angiomyolipomas in 42%, while only 4% had polycystic kidneys. Subependymal giant cell astrocytomas were observed in 14% of patients. 86% had skin manifestations. Conclusions: This study reaffirms the multi-system manifestations of TSC and the need to provide comprehensive, multidisciplinary care. As many children are still very young, the prevalence of autism and intellectual disability is likely underestimated.

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Wide spectrum of clinical manifestations in children with tuberous sclerosis complex – Follow-up of 20 children

Brain and Development ◽

10.1016/j.braindev.2013.05.006 ◽

2014 ◽

Vol 36 (4) ◽

pp. 306-314 ◽

Cited By ~ 11

Author(s):

Roland R. Mettin ◽

Andreas Merkenschlager ◽

Matthias K. Bernhard ◽

Heidrun Elix ◽

Wolfgang Hirsch ◽

...

Keyword(s):

Tuberous Sclerosis ◽

Tuberous Sclerosis Complex ◽

Wide Spectrum ◽

Clinical Manifestations

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Tuberous sclerosis complex: Clinical spectrum and epilepsy: A retrospective chart review study

Translational Neuroscience ◽

10.1515/tnsci-2018-0023 ◽

2018 ◽

Vol 9 (1) ◽

pp. 154-160

Author(s):

Sulaiman Almobarak ◽

Mohammad Almuhaizea ◽

Musaad Abukhaled ◽

Suad Alyamani ◽

Omar Dabbagh ◽

...

Keyword(s):

Tuberous Sclerosis ◽

Gene Mutation ◽

Tuberous Sclerosis Complex ◽

Chart Review ◽

Clinical Presentation ◽

Retrospective Chart Review ◽

Neurocutaneous Disorder ◽

Development Delay ◽

Review Study ◽

New Onset

Abstract Tuberous sclerosis complex (TSC) is an autosomal dominant genetic neurocutaneous disorder, with heterogeneous manifestations. We aimed to review the clinical presentation of TSC and its association with epilepsy among Saudi population. This was a retrospective chart review study of 88 patients diagnosed with TSC with or without epilepsy. In 38.6% of patients, symptoms began before 1 year of age. The most frequent initial manifestations of TSC were new onset of seizures (68.2%), skin manifestations (46.6%) and development delay (23.9%). During the evolution of the disease 65.9% had epilepsy, 17% facial angiofibromas, 13.6% Shagreen patch, 18.2% heart rhabdomyomas and 12.5% retinal hamartomas. The genetic study for TSC diagnosis was done for 44 patients, 42 (95,4%) of them were genetically confirmed, for whom 13 patients had TSC1 mutation (29.5%), 29 patients were carrying TSC2 gene mutation (65.9%), Genetic test for TSC 1 and TSC 2 were negative for 2 patients (4.5%) despite positive gene mutation in their relative with TSC. The most common manifestations were central nervous system (predominantly epilepsy) and dermatological manifestations. Most of the patients develop epilepsy with multiple seizure types. TSC 2 mutation is more common than TSC 1 mutation.

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Hypertension Burden and the Risk of New-Onset Atrial Fibrillation

Hypertension ◽

10.1161/hypertensionaha.120.16659 ◽

2021 ◽

Vol 77 (3) ◽

pp. 919-928

Author(s):

So-Ryoung Lee ◽

Chan Soon Park ◽

Eue-Keun Choi ◽

Hyo-Jeong Ahn ◽

Kyung-Do Han ◽

...

Keyword(s):

Atrial Fibrillation ◽

Total Study Population ◽

Increased Risk ◽

Burden Scale ◽

History Of ◽

Study Population ◽

Korean National Health Insurance ◽

Stage 1 ◽

The Relationship

The association between the cumulative hypertension burden and the development of atrial fibrillation (AF) is unclear. We aimed to investigate the relationship between hypertension burden and the development of incident AF. Using the Korean National Health Insurance Service database, we identified 3 726 172 subjects who underwent 4 consecutive annual health checkups between 2009 and 2013, with no history of AF. During the median follow-up of 5.2 years, AF was newly diagnosed in 22 012 patients (0.59% of the total study population; 1.168 per 1000 person-years). Using the blood pressure (BP) values at each health checkup, we determined the burden of hypertension (systolic BP ≥130 mm Hg or diastolic BP ≥80 mm Hg), stratified as 0 to 4 per the hypertension criteria. The subjects were grouped according to hypertension burden scale 1 to 4: 20% (n=742 806), 19% (n=704 623), 19% (n=713 258), 21% (n=766 204), and 21% (n=799 281). Compared with normal people, subjects with hypertension burdens of 1, 2, 3, and 4 were associated with an 8%, 18%, 26%, and 27% increased risk of incident AF, respectively. On semiquantitative analyses with further stratification of stage 1 (systolic BP of 130–139 mm Hg or diastolic BP of 80–89 mm Hg) and stage 2 (systolic BP ≥140 mm Hg or diastolic BP ≥90 mm Hg) hypertension, the risk of AF increased with the hypertension burden by up to 71%. In this study, both a sustained exposure and the degree of increased BP were associated with an increased risk of incident AF. Tailored BP management should be emphasized to reduce the risk of AF.

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Outcomes following feeding gastrostomy (FG) insertion in patients with learning disability: a retrospective cohort study using the health improvement network (THIN) database

BMJ Open ◽

10.1136/bmjopen-2018-026714 ◽

2019 ◽

Vol 9 (6) ◽

pp. e026714 ◽

Cited By ~ 1

Author(s):

Philip R Harvey ◽

Tom Thomas ◽

Joht Singh Chandan ◽

Neeraj Bhala ◽

Krishnarajah Nirantharakumar ◽

...

Keyword(s):

Cohort Study ◽

Learning Disability ◽

Incidence Rate ◽

Retrospective Cohort Study ◽

Retrospective Cohort ◽

Health Improvement ◽

History Of ◽

Study Population ◽

The Health Improvement Network

ObjectivesTo measure the rates of lower respiratory tract infection (LRTI) and mortality following feeding gastrostomy (FG) placement in patients with learning disability (LD). Following this to compare these rates between those having LRTI prior to FG placement and those with no recent LRTI.DesignRetrospective cohort study.Setting and participantsThe study population included patients with LD undergoing FG placement in the ‘The Health Improvement Network’ database. Patients with LRTI in the year prior (LYP) to their FG placement were compared with patients without a history of LRTI in the year prior (non-LYP) to FG placement. FG placement and LD were identified using Read codes previously developed by an expert panel.Main outcome measuresIncidence rate ratio (IRR) of developing LRTI and mortality following FG, comparing patients with LRTI in the year prior to FG placement to patients without a history of LRTI.Results214 patients with LD had a FG inserted including 743.4 person years follow-up. 53.7% were males and the median age was 27.6 (IQR 19.6 to 38.6) years. 27.1% were in the LYP patients. 18.7% had a LRTI in the year following FG, with an estimated incidence rate of 254 per 1000-person years. Over the study period the incidence rate of LRTI in LYP patients was 369 per 1000-person years, in non-LYP patients this was 91 per 1000-person years (adjusted IRR 4.21 (95% CI 2.68 to 6.63) p<0.001). 27.1% of patients died during study follow-up. Incidence rate of death was 80 and 45 per 1000-person year for LYP and non-LYP patients, respectively (adjusted IRR 1.80 (1.00 to 3.23) p=0.05).ConclusionIn LD patients, no clinically meaningful reduction in LRTI incidence was observed following FG placement. Mortality and LRTI were higher in patients with at least one LRTI in the year preceding FG placement, compared with those without a preceding LRTI.

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Tuberous Sclerosis Complex

10.1093/med/9780199937837.003.0050 ◽

2017 ◽

Author(s):

Tanjala T. Gipson ◽

Andrea Poretti ◽

Rebecca McClellan ◽

Michael V. Johnston

Keyword(s):

Tuberous Sclerosis ◽

Tuberous Sclerosis Complex ◽

Scientific Discovery ◽

Skin Lesions ◽

Benign Tumors ◽

Behavioral Difficulties ◽

Future Directions ◽

Neurocutaneous Disorder ◽

The Status ◽

The Brain

Tuberous sclerosis complex (TSC) is a disease, commonly classified as a neurocutaneous disorder, which may result in benign tumors throughout the brain and body, skin lesions, epilepsy, and cognitive/behavioral difficulties. Scientific discovery in TSC has resulted in the availability of treatments designed to target the neurobiological core of TSC in children. However, research is needed to determine if these treatments are effective for multiple aspects of the TSC phenotype in children. Current pediatric research studies have focused on the effects of early treatment of epilepsy as well as identification of potential biomarkers. This chapter reviews the aspects of TSC unique to pediatric patients, the status of current research, and future directions.

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Everolimus for treatment of tuberous sclerosis complex-associated neuropsychiatric disorders

Annals of Clinical and Translational Neurology ◽

10.1002/acn3.494 ◽

2017 ◽

Vol 4 (12) ◽

pp. 877-887 ◽

Cited By ~ 43

Author(s):

Darcy A. Krueger ◽

Anjali Sadhwani ◽

Anna W. Byars ◽

Petrus J. de Vries ◽

David N. Franz ◽

...

Keyword(s):

Tuberous Sclerosis ◽

Tuberous Sclerosis Complex ◽

Neuropsychiatric Disorders

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Long-term outcomes of resective epilepsy surgery after invasive presurgical evaluation in children with tuberous sclerosis complex and bilateral multiple lesions

Journal of Neurosurgery Pediatrics ◽

10.3171/2014.10.peds14107 ◽

2015 ◽

Vol 15 (1) ◽

pp. 26-33 ◽

Cited By ~ 32

Author(s):

Ravindra Arya ◽

Jeffrey R. Tenney ◽

Paul S. Horn ◽

Hansel M. Greiner ◽

Katherine D. Holland ◽

...

Keyword(s):

Tuberous Sclerosis ◽

Epilepsy Surgery ◽

Tuberous Sclerosis Complex ◽

Refractory Epilepsy ◽

Full Scale ◽

Secondary Outcome ◽

Resective Surgery ◽

Class 1 ◽

Medically Refractory Epilepsy

OBJECT Tuberous sclerosis complex (TSC) with medically refractory epilepsy is characterized by multifocal brain abnormalities, traditionally indicating poor surgical candidacy. This single-center, retrospective study appraised seizurerelated, neuropsychological, and other outcomes of resective surgery in TSC patients with medically refractory epilepsy, and analyzed predictors for these outcomes. METHODS Patients with multilesional TSC who underwent epilepsy surgery between 2007 and 2012 were identified from an electronic database. All patients underwent multimodality noninvasive and subsequent invasive evaluation. Seizure outcomes were classified using the International League Against Epilepsy (ILAE) scale. The primary outcome measure was complete seizure remission (ILAE Class 1). Secondary outcome measures included 50% responder rate, change in full-scale IQ, electroencephalography improvement, and reduction in antiepileptic drug (AED) burden. RESULTS A total of 37 patients with TSC underwent resective surgery during the study period. After a mean follow-up of 5.68 ± 3.67 years, 56.8% achieved complete seizure freedom (ILAE Class 1) and 86.5% had ILAE Class 4 outcomes or better. The full-scale IQ on follow-up was significantly higher in patients with ILAE Class 1 outcome (66.70 ± 12.36) compared with those with ILAE Class 2 or worse outcomes (56.00 ± 1.41, p = 0.025). In 62.5% of the patients with ILAE Class 2 or worse outcomes, the number of AEDs were found to be significantly reduced (p = 0.004). CONCLUSIONS This study substantiates the evidence for efficacy of resective epilepsy surgery in patients with bilateral multilesional TSC. More than half of the patients were completely seizure free. Additionally, a high proportion achieved clinically meaningful reduction in seizure burden and the number of AEDs.

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Epilepsy surgery in tuberous sclerosis complex: the BC Children’s Hospital experience

Canadian Journal of Neurological Sciences / Journal Canadien des Sciences Neurologiques ◽

10.1017/cjn.2015.88 ◽

2015 ◽

Vol 42 (S1) ◽

pp. S14-S14

Author(s):

C Wilbur ◽

C Sanguansermsri ◽

H Chable ◽

A Mihaela ◽

P Steinbok ◽

...

Keyword(s):

Tuberous Sclerosis ◽

Epilepsy Surgery ◽

Tuberous Sclerosis Complex ◽

Chart Review ◽

Retrospective Chart Review ◽

Seizure Outcome ◽

Corpus Callosotomy ◽

Age At Surgery ◽

Second Resection

Background: Epilepsy occurs in up to 90% of patients with Tuberous Sclerosis Complex (TSC) and is often refractory to medications. Our objective was to assess the safety and outcome of epilepsy surgery in children with TSC at our institution. Methods: We performed a systematic, retrospective chart review of children with TSC who underwent epilepsy surgery at our institution. Patients were identified through epilepsy and clinical neurophysiology databases. Results: 19 patients (out of 81 with TSC) underwent surgery between 1995-2014. Median age at surgery was 4.2 (Range 1.1-15.6) years, with patients having failed a median 4 (Range 0-10) anti-seizure medications. Surgery comprised corpus callosotomy in 2 and resection of one or more tubers in 17. 2 patients had a subsequent second resection. Minor neurologic deficits occurred after 14% of surgeries. Median follow-up was 2.4 years (Range 0.3 -13.8 years) following surgery . At last follow-up, 47% were seizure free, including 2 patients off anti-seizure medication. Conclusions: Epilepsy surgery is safe and effective in carefully selected TSC patients, with the majority having a good seizure outcome. Children with epilepsy secondary to TSC should be referred for epilepsy surgery assessment.

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