TSC an Overview of Treatment & Management Dr Chris Kingswood Brighton UK
Advances in Tuberous Sclerosis: From Pathway to Therapy Medical and Family Conference 3 – 4 November 2007 Sydney Children’...
Declaration of Interest
Treatment & Management <ul><li>Assess the problems </li></ul><ul><li>Work out the best treatment for them </li></ul><ul><l...
The Solution <ul><li>Education & patient / carer advocacy </li></ul><ul><li>Medical (Professional) advisors </li></ul><ul>...
TSC Timeline Kidneys, Lungs 20s-30s+ SEGA, Kidneys Teens Behaviour, LD, Skin Pre-Teens Seizures, Insomnia Infancy Cardiac ...
Checklist 1 <ul><li>Neurological Problems </li></ul><ul><ul><li>Epilepsy </li></ul></ul><ul><ul><li>SEGAs  (Subependymal g...
Checklist 2 <ul><li>Cardiac Problems </li></ul><ul><li>Skin lesions </li></ul><ul><li>Renal manifestations  </li></ul><ul>...
Checklist 3 <ul><li>Other organs </li></ul><ul><li>Other Issues </li></ul>
Neurological complications <ul><li>Epilepsy, & Insomnia </li></ul><ul><li>Subependymal giant cell astrocytoma </li></ul>
Neurodevelopmental manifestations <ul><ul><li>Learning disabilities </li></ul></ul><ul><ul><li>Developmental disorders, & ...
Psychopathologies <ul><li>Anxiety </li></ul><ul><li>Depression </li></ul><ul><li>Psychoses </li></ul><ul><li>Substance Mis...
Psychosocial complications <ul><li>Continuing Educational Support </li></ul><ul><li>Vocational Training </li></ul><ul><li>...
Specific scholastic difficulties (reading, writing, spelling, mathematics) ADHD and related disorders Peer problems Aggres...
Abbreviations: ASD = autism spectrum disorders; ADHD = attention deficit hyperactivity disorder * Many features listed in ...
Cardiac Problems
Skin lesions <ul><li>Increased importance as older </li></ul><ul><li>Laser Therapy </li></ul><ul><ul><ul><li>Pulsed dye or...
 
 
Kidney manifestations <ul><li>69-80% </li></ul><ul><li>Texas Scottish Rite Hospital – Age 5-6 yrs </li></ul><ul><li>UK TSC...
Renal AMLs <ul><li>Haemorrhage (11%) </li></ul><ul><li>Pulmonary LAM (5%) </li></ul><ul><li>Bulk causing malnutrition </li...
 
 
Haemorrhage <ul><li>The Wessex Study 9-22% [11] </li></ul><ul><ul><li>O'Callaghan F J, et al. BJU Int 2004 94(6):853-857 <...
 
Patients with serially measured AMLs n = 52 <ul><li>Growth    27 (52%) </li></ul><ul><ul><ul><li>bleed  11 (21%) </li></ul...
Are larger AMLs more likely to bleed? X 2  = 16.1 P < 0.001
Mean Reduction  in Sum LDs of Target AMLs 9.6 11.3 9.9 S.D. 26.1 17.9 14.1 Mean Reduction in sum LD (%) 12 Months 6 Months...
PKD <ul><li>Pain, Hypertension, Bleeding & Renal Failure [5%] </li></ul><ul><li>Symptomatic Rx </li></ul><ul><li>Dialysis ...
Renal cell carcinoma <ul><li>Curable </li></ul><ul><li>Diagnostic uncertainty </li></ul><ul><li>? Continuing risk </li></u...
Pulmonary complications <ul><li>Occurrence Common (40%) </li></ul><ul><li>Symptoms Rare (5%) </li></ul><ul><li>Who is at r...
Unresolved Questions <ul><li>Prophylactic Intervention </li></ul><ul><ul><li>When Benefit > Risk </li></ul></ul><ul><li>Me...
AML Summary <ul><li>Haemorrhage </li></ul><ul><li>Pulmonary LAM </li></ul><ul><li>Bulk causing malnutrition </li></ul><ul>...
Dental problems <ul><li>Dental pits, gum fibromata, gum hypertrophy & caries </li></ul><ul><ul><li>Ahlsen G,  et al. Arch ...
Other Organs <ul><li>Liver Hamartomata (25%) </li></ul><ul><li>Gastro-Intestinal polyps </li></ul><ul><li>Bone problems </...
Other Issues <ul><ul><ul><li>Eyesight </li></ul></ul></ul><ul><ul><ul><li>Hearing </li></ul></ul></ul>
Other Issues <ul><li>Genetic counselling </li></ul><ul><ul><ul><li>Risk of inheritance </li></ul></ul></ul><ul><ul><ul><li...
Recommendations <ul><li>Ideally all TSC patients be seen at specialist TS clinic at diagnosis & at transition </li></ul><u...
Conclusions <ul><li>Constant Vigilance </li></ul><ul><li>Lots to do / Lots to treat </li></ul>
 
 
 
Advances in Tuberous Sclerosis: From Pathway to Therapy Medical and Family Conference 3 – 4 November 2007 Sydney Children’...
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TSC: An Overview Of Treatment & Management

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Dr Chris Kingswood, UK, presented at the 2007 ATSS Conference - Advances in Tuberous Sclerosis: From Pathway to Therapy.
Reviews key clinical manifestations of TSC and recommended treatment and management guidelines.
Provides detailed information and images on kidney involvement in Tuberous Sclerosis.

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Transcript of "TSC: An Overview Of Treatment & Management"

  1. 1. TSC an Overview of Treatment & Management Dr Chris Kingswood Brighton UK
  2. 2. Advances in Tuberous Sclerosis: From Pathway to Therapy Medical and Family Conference 3 – 4 November 2007 Sydney Children’s Hospital Randwick For more information: www.atss.org.au
  3. 3. Declaration of Interest
  4. 4. Treatment & Management <ul><li>Assess the problems </li></ul><ul><li>Work out the best treatment for them </li></ul><ul><li>Look out for new ones </li></ul>
  5. 5. The Solution <ul><li>Education & patient / carer advocacy </li></ul><ul><li>Medical (Professional) advisors </li></ul><ul><li>Specialist Clinics (Re-imbursement Issues) </li></ul><ul><li>Clinical Guidelines </li></ul><ul><ul><ul><li>Bradshaw N, et al. Eur J of H Genet 1998; 6(5):445-448 </li></ul></ul></ul><ul><ul><ul><li>Roach E S, et al. J of Child Neurol 1999; 14(6):401-407 </li></ul></ul></ul><ul><li>Concentrate on transition </li></ul><ul><ul><li>What is important now / in the future? </li></ul></ul>
  6. 6. TSC Timeline Kidneys, Lungs 20s-30s+ SEGA, Kidneys Teens Behaviour, LD, Skin Pre-Teens Seizures, Insomnia Infancy Cardiac Pre/Neonatal
  7. 7. Checklist 1 <ul><li>Neurological Problems </li></ul><ul><ul><li>Epilepsy </li></ul></ul><ul><ul><li>SEGAs (Subependymal giant cell astrocytomas) </li></ul></ul><ul><li>Neurodevelopmental manifestations </li></ul><ul><ul><li>Learning disabilitie s </li></ul></ul><ul><ul><li>Developmental disorders (ASD) </li></ul></ul><ul><li>Psychopathologies </li></ul><ul><li>Psychosocial complications </li></ul>
  8. 8. Checklist 2 <ul><li>Cardiac Problems </li></ul><ul><li>Skin lesions </li></ul><ul><li>Renal manifestations </li></ul><ul><ul><ul><li>Renal AMLs, PKD & Renal cell carcinoma </li></ul></ul></ul><ul><li>Pulmonary complications </li></ul><ul><li>Dental problems </li></ul><ul><li>Hearing </li></ul><ul><li>Eyesight </li></ul>
  9. 9. Checklist 3 <ul><li>Other organs </li></ul><ul><li>Other Issues </li></ul>
  10. 10. Neurological complications <ul><li>Epilepsy, & Insomnia </li></ul><ul><li>Subependymal giant cell astrocytoma </li></ul>
  11. 11. Neurodevelopmental manifestations <ul><ul><li>Learning disabilities </li></ul></ul><ul><ul><li>Developmental disorders, & Insomnia </li></ul></ul>
  12. 12. Psychopathologies <ul><li>Anxiety </li></ul><ul><li>Depression </li></ul><ul><li>Psychoses </li></ul><ul><li>Substance Misuse </li></ul><ul><li>Late Adolescent Blitzkrieg </li></ul>
  13. 13. Psychosocial complications <ul><li>Continuing Educational Support </li></ul><ul><li>Vocational Training </li></ul><ul><li>Sheltered employment </li></ul><ul><li>Integration </li></ul><ul><li>Supported Living </li></ul><ul><li>Respite Family Support </li></ul><ul><ul><ul><li>de Vries P J, et al. European Child and Adolescent Psychiatry 2005; 14:183-190. </li></ul></ul></ul>
  14. 14. Specific scholastic difficulties (reading, writing, spelling, mathematics) ADHD and related disorders Peer problems Aggressive behaviours Best time to establish baseline to assess whether specific cognitive skills and scholastic performance is discrepant from global intellectual abilities Poor expressive language and word retrieval Rote learning difficulties Selective attention, sustained attention difficulties Global cognitive abilities Specific cognitive skills: Receptive and expressive language Social communication skills Memory Attentional-executive skills Visuospatial skills Motor skills Monitoring the child’s ability to make appropriate educational progress 6y – 8y Early school years Asperger’s Syndrome Peer problems Scholastic difficulties (reading, writing, spelling, mathematics) Subtle deficits of social communications. Unusual interests. Poor short term & episodic memory. Difficulties with planning, organisation & multitasking. Global cognitive abilities Specific cognitive skills: Receptive and expressive language Social communication skills Memory Attentional-executive skills Complete review of child’s abilities, specific learning difficulties and behavioural problems in preparation for the transition to secondary education 9y – 12y Middle school years Autism and ASD ADHD and related disorders Self-injurious behaviour Uneven profile of abilities Poor expressive language Poor reciprocity, peer interaction Poor regulation of affect and impulse Poor bilateral co-ordination <ul><li>Global cognitive ability </li></ul><ul><li>Specific cognitive skills: </li></ul><ul><li>Receptive and expressive language </li></ul><ul><li>Social communication skills </li></ul><ul><li>Attentional-executive skills </li></ul><ul><li>Visuospatial skills </li></ul><ul><li>Motor skills </li></ul><ul><li>Evaluation of cognitive and behavioural profile to ensure the provision of appropriate educational programmes </li></ul><ul><li>3y to school entry </li></ul><ul><li>Pre-school </li></ul><ul><li>Autism and Autism Spectrum Disorders (ASD) </li></ul><ul><li>Severe aggressive outbursts </li></ul><ul><li>Severe Sleep Problems </li></ul><ul><li>Quality of eye-contact, joint attention, reciprocity </li></ul><ul><li>Global cognitive ability and adaptive behaviours </li></ul><ul><li>Specific skills: </li></ul><ul><li>Gross and fine motor skills </li></ul><ul><li>Social-communication skills </li></ul>To identify early developmental delay or developmental disorders 1y – 2y11m Toddler Impact of seizure onset and treatment on development Global standardised assessment of infant development To perform a baseline assessment for regular monitoring of development Birth – 12 months Infancy As listed for chronological age Initial assessment of cognitive and behavioural profile At diagnosis *Behavioural and learning problems of particular concern in TSC *Areas of particular concern in TSC: General areas to assess General purpose of assessment Age range for assessment Assessment stage
  15. 15. Abbreviations: ASD = autism spectrum disorders; ADHD = attention deficit hyperactivity disorder * Many features listed in these columns can present at any age, but are listed here at stages most commonly associated with the emergence of such difficulties in TSC Depressive disorders Anxiety disorders Epilepsy-related psychotic disorders Pay particular attention to change in cognitive abilities or behaviour Pay particular attention to change in cognitive abilities, vocational performance and behaviour Dependent adults: Annual review of social care needs and support Independent adults: Vocational advice Genetic counselling as appropriate Review if problems arise Monitoring for emergence of psychiatric problems or changes in existing cognitive and behavioural difficulties 18y+ Adults (follow-up) Depressive disorders Anxiety disorders Epilepsy-related psychotic disorders Difficulty with integrational skills Working memory, episodic memory problems <ul><li>Global cognitive abilities </li></ul><ul><li>Specific cognitive skills: </li></ul><ul><li>Attentional-executive skills </li></ul><ul><li>Memory </li></ul><ul><li>Newly diagnosed adults : assessment of cognitive, behavioural and vocational profile, determining bio-psycho-social needs </li></ul><ul><li>18y+ </li></ul><ul><li>Adults </li></ul><ul><li>Depressive disorders </li></ul><ul><li>Anxiety disorders </li></ul><ul><li>Peer problems </li></ul><ul><li>Poor judgement, decisionmaking </li></ul><ul><li>Global cognitive abilities </li></ul><ul><li>Specific cognitive skills </li></ul><ul><li>Attentional-executive skills </li></ul><ul><li>Vocational assessment with knowledge of cognitive strengths and weaknesses </li></ul><ul><li>Adaptive behaviour and daily living skills </li></ul><ul><li>Determining individual needs and the support required for transition into adult life </li></ul><ul><li>13y – 16y </li></ul><ul><li>Adolescence </li></ul>*Behavioural and learning problems of particular concern in TSC *Areas of particular concern in TSC: General areas to assess General purpose of assessment Age range for assessment Assessment stage
  16. 16. Cardiac Problems
  17. 17. Skin lesions <ul><li>Increased importance as older </li></ul><ul><li>Laser Therapy </li></ul><ul><ul><ul><li>Pulsed dye or CO2 </li></ul></ul></ul><ul><ul><ul><li>? Timing </li></ul></ul></ul><ul><li>mTOR Inhibitors </li></ul><ul><ul><ul><li>? Topical </li></ul></ul></ul>
  18. 20. Kidney manifestations <ul><li>69-80% </li></ul><ul><li>Texas Scottish Rite Hospital – Age 5-6 yrs </li></ul><ul><li>UK TSC Cohort Study </li></ul><ul><ul><li>20% renal abnormality at mean 33.3 months </li></ul></ul><ul><li>Renal AMLs (80%) </li></ul><ul><li>PKD (5%) </li></ul><ul><li>Renal cell carcinoma (1-3%) </li></ul>
  19. 21. Renal AMLs <ul><li>Haemorrhage (11%) </li></ul><ul><li>Pulmonary LAM (5%) </li></ul><ul><li>Bulk causing malnutrition </li></ul><ul><li>Pain </li></ul><ul><li>Confusion with Malignancy </li></ul><ul><li>? Renal Failure </li></ul><ul><li>? Hamartomas </li></ul>
  20. 24. Haemorrhage <ul><li>The Wessex Study 9-22% [11] </li></ul><ul><ul><li>O'Callaghan F J, et al. BJU Int 2004 94(6):853-857 </li></ul></ul><ul><li>UK Renal Registry data (Approx 25%) </li></ul>
  21. 26. Patients with serially measured AMLs n = 52 <ul><li>Growth 27 (52%) </li></ul><ul><ul><ul><li>bleed 11 (21%) </li></ul></ul></ul><ul><ul><ul><li>no bleed 16 (31%) </li></ul></ul></ul><ul><li>No Growth 25 (48%) </li></ul><ul><ul><ul><li>bleed 2 (4%) </li></ul></ul></ul><ul><ul><ul><li>no bleed 23 (44%) </li></ul></ul></ul><ul><ul><ul><li>X 2 = 7.42 p < 0.01 </li></ul></ul></ul>
  22. 27. Are larger AMLs more likely to bleed? X 2 = 16.1 P < 0.001
  23. 28. Mean Reduction in Sum LDs of Target AMLs 9.6 11.3 9.9 S.D. 26.1 17.9 14.1 Mean Reduction in sum LD (%) 12 Months 6 Months 2 Months
  24. 29. PKD <ul><li>Pain, Hypertension, Bleeding & Renal Failure [5%] </li></ul><ul><li>Symptomatic Rx </li></ul><ul><li>Dialysis [0.1-1%] </li></ul><ul><li>Transplantation </li></ul><ul><li>Tolvapten </li></ul><ul><ul><li>? Other targeted Rx </li></ul></ul>
  25. 30. Renal cell carcinoma <ul><li>Curable </li></ul><ul><li>Diagnostic uncertainty </li></ul><ul><li>? Continuing risk </li></ul><ul><li>? Genotype specificity </li></ul><ul><li>Malignant AMLs </li></ul><ul><ul><ul><li>Rare </li></ul></ul></ul>
  26. 31. Pulmonary complications <ul><li>Occurrence Common (40%) </li></ul><ul><li>Symptoms Rare (5%) </li></ul><ul><li>Who is at risk? </li></ul><ul><li>When to treat? </li></ul><ul><li>How to treat? </li></ul><ul><li>How to monitor? </li></ul>
  27. 32. Unresolved Questions <ul><li>Prophylactic Intervention </li></ul><ul><ul><li>When Benefit > Risk </li></ul></ul><ul><li>Medical v Surgical Intervention? </li></ul>
  28. 33. AML Summary <ul><li>Haemorrhage </li></ul><ul><li>Pulmonary LAM </li></ul><ul><li>Bulk causing malnutrition </li></ul><ul><li>Pain </li></ul><ul><li>Confusion with Malignancy </li></ul><ul><li>? Renal Failure </li></ul><ul><li>Embolisation </li></ul><ul><li>mTOR Inhibitors </li></ul><ul><li>Nephron Sparing Surgery </li></ul><ul><li>Radioablation </li></ul><ul><li>Cryotherapy </li></ul>
  29. 34. Dental problems <ul><li>Dental pits, gum fibromata, gum hypertrophy & caries </li></ul><ul><ul><li>Ahlsen G, et al. Arch of Neurol 1994; 51(1):76-81. </li></ul></ul><ul><li>Easy to treat but difficult to manage </li></ul>
  30. 35. Other Organs <ul><li>Liver Hamartomata (25%) </li></ul><ul><li>Gastro-Intestinal polyps </li></ul><ul><li>Bone problems </li></ul><ul><li>Arterial aneurysms </li></ul><ul><li>Chordomas </li></ul><ul><li>Endocrine dysfunction </li></ul><ul><li>Malignancy </li></ul><ul><li>More Research </li></ul>
  31. 36. Other Issues <ul><ul><ul><li>Eyesight </li></ul></ul></ul><ul><ul><ul><li>Hearing </li></ul></ul></ul>
  32. 37. Other Issues <ul><li>Genetic counselling </li></ul><ul><ul><ul><li>Risk of inheritance </li></ul></ul></ul><ul><ul><ul><li>Investigating family members </li></ul></ul></ul><ul><ul><ul><li>Genetic analysis of blood </li></ul></ul></ul><ul><ul><ul><li>Prenatal testing </li></ul></ul></ul><ul><li>Family Support </li></ul><ul><li>Mutual Support / Fighting Back </li></ul>
  33. 38. Recommendations <ul><li>Ideally all TSC patients be seen at specialist TS clinic at diagnosis & at transition </li></ul><ul><li>If not go through checklist with family or primary physician </li></ul><ul><li>Write a surveillance plan, an IEP & a PCP </li></ul>
  34. 39. Conclusions <ul><li>Constant Vigilance </li></ul><ul><li>Lots to do / Lots to treat </li></ul>
  35. 43. Advances in Tuberous Sclerosis: From Pathway to Therapy Medical and Family Conference 3 – 4 November 2007 Sydney Children’s Hospital Randwick For more information: www.atss.org.au

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