TSC: An Overview Of Treatment & Management

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Information about TSC: An Overview Of Treatment & Management

Published on February 11, 2008

Author: atss

Source: slideshare.net

Description

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.

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’s Hospital Randwick For more information: www.atss.org.au

Declaration of Interest

Treatment & Management Assess the problems Work out the best treatment for them Look out for new ones

Assess the problems

Work out the best treatment for them

Look out for new ones

The Solution Education & patient / carer advocacy Medical (Professional) advisors Specialist Clinics (Re-imbursement Issues) Clinical Guidelines Bradshaw N, et al. Eur J of H Genet 1998; 6(5):445-448 Roach E S, et al. J of Child Neurol 1999; 14(6):401-407 Concentrate on transition What is important now / in the future?

Education & patient / carer advocacy

Medical (Professional) advisors

Specialist Clinics (Re-imbursement Issues)

Clinical Guidelines

Bradshaw N, et al. Eur J of H Genet 1998; 6(5):445-448

Roach E S, et al. J of Child Neurol 1999; 14(6):401-407

Concentrate on transition

What is important now / in the future?

TSC Timeline Kidneys, Lungs 20s-30s+ SEGA, Kidneys Teens Behaviour, LD, Skin Pre-Teens Seizures, Insomnia Infancy Cardiac Pre/Neonatal

Checklist 1 Neurological Problems Epilepsy SEGAs (Subependymal giant cell astrocytomas) Neurodevelopmental manifestations Learning disabilitie s Developmental disorders (ASD) Psychopathologies Psychosocial complications

Neurological Problems

Epilepsy

SEGAs (Subependymal giant cell astrocytomas)

Neurodevelopmental manifestations

Learning disabilitie s

Developmental disorders (ASD)

Psychopathologies

Psychosocial complications

Checklist 2 Cardiac Problems Skin lesions Renal manifestations Renal AMLs, PKD & Renal cell carcinoma Pulmonary complications Dental problems Hearing Eyesight

Cardiac Problems

Skin lesions

Renal manifestations

Renal AMLs, PKD & Renal cell carcinoma

Pulmonary complications

Dental problems

Hearing

Eyesight

Checklist 3 Other organs Other Issues

Other organs

Other Issues

Neurological complications Epilepsy, & Insomnia Subependymal giant cell astrocytoma

Epilepsy, & Insomnia

Subependymal giant cell astrocytoma

Neurodevelopmental manifestations Learning disabilities Developmental disorders, & Insomnia

Learning disabilities

Developmental disorders, & Insomnia

Psychopathologies Anxiety Depression Psychoses Substance Misuse Late Adolescent Blitzkrieg

Anxiety

Depression

Psychoses

Substance Misuse

Late Adolescent Blitzkrieg

Psychosocial complications Continuing Educational Support Vocational Training Sheltered employment Integration Supported Living Respite Family Support de Vries P J, et al. European Child and Adolescent Psychiatry 2005; 14:183-190.

Continuing Educational Support

Vocational Training

Sheltered employment

Integration

Supported Living

Respite Family Support

de Vries P J, et al. European Child and Adolescent Psychiatry 2005; 14:183-190.

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 Global cognitive ability Specific cognitive skills: Receptive and expressive language Social communication skills Attentional-executive skills Visuospatial skills Motor skills Evaluation of cognitive and behavioural profile to ensure the provision of appropriate educational programmes 3y to school entry Pre-school Autism and Autism Spectrum Disorders (ASD) Severe aggressive outbursts Severe Sleep Problems Quality of eye-contact, joint attention, reciprocity Global cognitive ability and adaptive behaviours Specific skills: Gross and fine motor skills Social-communication skills 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

Global cognitive ability

Specific cognitive skills:

Receptive and expressive language

Social communication skills

Attentional-executive skills

Visuospatial skills

Motor skills

Evaluation of cognitive and behavioural profile to ensure the provision of appropriate educational programmes

3y to school entry

Pre-school

Autism and Autism Spectrum Disorders (ASD)

Severe aggressive outbursts

Severe Sleep Problems

Quality of eye-contact, joint attention, reciprocity

Global cognitive ability and adaptive behaviours

Specific skills:

Gross and fine motor skills

Social-communication skills

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 Global cognitive abilities Specific cognitive skills: Attentional-executive skills Memory Newly diagnosed adults : assessment of cognitive, behavioural and vocational profile, determining bio-psycho-social needs 18y+ Adults Depressive disorders Anxiety disorders Peer problems Poor judgement, decisionmaking Global cognitive abilities Specific cognitive skills Attentional-executive skills Vocational assessment with knowledge of cognitive strengths and weaknesses Adaptive behaviour and daily living skills Determining individual needs and the support required for transition into adult life 13y – 16y Adolescence *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

Global cognitive abilities

Specific cognitive skills:

Attentional-executive skills

Memory

Newly diagnosed adults : assessment of cognitive, behavioural and vocational profile, determining bio-psycho-social needs

18y+

Adults

Depressive disorders

Anxiety disorders

Peer problems

Poor judgement, decisionmaking

Global cognitive abilities

Specific cognitive skills

Attentional-executive skills

Vocational assessment with knowledge of cognitive strengths and weaknesses

Adaptive behaviour and daily living skills

Determining individual needs and the support required for transition into adult life

13y – 16y

Adolescence

Cardiac Problems

Skin lesions Increased importance as older Laser Therapy Pulsed dye or CO2 ? Timing mTOR Inhibitors ? Topical

Increased importance as older

Laser Therapy

Pulsed dye or CO2

? Timing

mTOR Inhibitors

? Topical

 

 

Kidney manifestations 69-80% Texas Scottish Rite Hospital – Age 5-6 yrs UK TSC Cohort Study 20% renal abnormality at mean 33.3 months Renal AMLs (80%) PKD (5%) Renal cell carcinoma (1-3%)

69-80%

Texas Scottish Rite Hospital – Age 5-6 yrs

UK TSC Cohort Study

20% renal abnormality at mean 33.3 months

Renal AMLs (80%)

PKD (5%)

Renal cell carcinoma (1-3%)

Renal AMLs Haemorrhage (11%) Pulmonary LAM (5%) Bulk causing malnutrition Pain Confusion with Malignancy ? Renal Failure ? Hamartomas

Haemorrhage (11%)

Pulmonary LAM (5%)

Bulk causing malnutrition

Pain

Confusion with Malignancy

? Renal Failure

? Hamartomas

 

 

Haemorrhage The Wessex Study 9-22% [11] O'Callaghan F J, et al. BJU Int 2004 94(6):853-857 UK Renal Registry data (Approx 25%)

The Wessex Study 9-22% [11]

O'Callaghan F J, et al. BJU Int 2004 94(6):853-857

UK Renal Registry data (Approx 25%)

 

Patients with serially measured AMLs n = 52 Growth 27 (52%) bleed 11 (21%) no bleed 16 (31%) No Growth 25 (48%) bleed 2 (4%) no bleed 23 (44%) X 2 = 7.42 p < 0.01

Growth 27 (52%)

bleed 11 (21%)

no bleed 16 (31%)

No Growth 25 (48%)

bleed 2 (4%)

no bleed 23 (44%)

X 2 = 7.42 p < 0.01

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 2 Months

PKD Pain, Hypertension, Bleeding & Renal Failure [5%] Symptomatic Rx Dialysis [0.1-1%] Transplantation Tolvapten ? Other targeted Rx

Pain, Hypertension, Bleeding & Renal Failure [5%]

Symptomatic Rx

Dialysis [0.1-1%]

Transplantation

Tolvapten

? Other targeted Rx

Renal cell carcinoma Curable Diagnostic uncertainty ? Continuing risk ? Genotype specificity Malignant AMLs Rare

Curable

Diagnostic uncertainty

? Continuing risk

? Genotype specificity

Malignant AMLs

Rare

Pulmonary complications Occurrence Common (40%) Symptoms Rare (5%) Who is at risk? When to treat? How to treat? How to monitor?

Occurrence Common (40%)

Symptoms Rare (5%)

Who is at risk?

When to treat?

How to treat?

How to monitor?

Unresolved Questions Prophylactic Intervention When Benefit > Risk Medical v Surgical Intervention?

Prophylactic Intervention

When Benefit > Risk

Medical v Surgical Intervention?

AML Summary Haemorrhage Pulmonary LAM Bulk causing malnutrition Pain Confusion with Malignancy ? Renal Failure Embolisation mTOR Inhibitors Nephron Sparing Surgery Radioablation Cryotherapy

Haemorrhage

Pulmonary LAM

Bulk causing malnutrition

Pain

Confusion with Malignancy

? Renal Failure

Embolisation

mTOR Inhibitors

Nephron Sparing Surgery

Radioablation

Cryotherapy

Dental problems Dental pits, gum fibromata, gum hypertrophy & caries Ahlsen G, et al. Arch of Neurol 1994; 51(1):76-81. Easy to treat but difficult to manage

Dental pits, gum fibromata, gum hypertrophy & caries

Ahlsen G, et al. Arch of Neurol 1994; 51(1):76-81.

Easy to treat but difficult to manage

Other Organs Liver Hamartomata (25%) Gastro-Intestinal polyps Bone problems Arterial aneurysms Chordomas Endocrine dysfunction Malignancy More Research

Liver Hamartomata (25%)

Gastro-Intestinal polyps

Bone problems

Arterial aneurysms

Chordomas

Endocrine dysfunction

Malignancy

More Research

Other Issues Eyesight Hearing

Eyesight

Hearing

Other Issues Genetic counselling Risk of inheritance Investigating family members Genetic analysis of blood Prenatal testing Family Support Mutual Support / Fighting Back

Genetic counselling

Risk of inheritance

Investigating family members

Genetic analysis of blood

Prenatal testing

Family Support

Mutual Support / Fighting Back

Recommendations Ideally all TSC patients be seen at specialist TS clinic at diagnosis & at transition If not go through checklist with family or primary physician Write a surveillance plan, an IEP & a PCP

Ideally all TSC patients be seen at specialist TS clinic at diagnosis & at transition

If not go through checklist with family or primary physician

Write a surveillance plan, an IEP & a PCP

Conclusions Constant Vigilance Lots to do / Lots to treat

Constant Vigilance

Lots to do / Lots to treat

 

 

 

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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