eMedicine Specialties > Neurology > Pediatric Neurology

Tuberous Sclerosis: Differential Diagnoses & Workup

Author: David Neal Franz, MD, Professor, Departments of Pediatrics and Neurology, University of Cincinnati College of Medicine; Director, Tuberous Sclerosis Clinic, Cincinnati Children's Hospital Medical Center
Coauthor(s): Tracy A Glauser, MD, Professor, Departments of Pediatrics and Neurology, University of Cincinnati College of Medicine, Children's Comprehensive Epilepsy Program, Children's Hospital Medical Center of Cincinnati
Contributor Information and Disclosures

Updated: Feb 14, 2007

Differential Diagnoses

Complex Partial Seizures
Hydrocephalus
Epilepsy in Adults with Mental Retardation
Identification of Potential Epilepsy Surgery Candidates
Epilepsy in Children with Mental Retardation
Infantile Spasm (West Syndrome)
Glioblastoma Multiforme
Lennox-Gastaut Syndrome

Other Problems to Be Considered

Giant cell astrocytoma
Lymphangioleiomyomatosis
Angiomyolipoma
Polycystic kidney disease
Multifocal nodular pneumocyte hyperplasia
Rhabdomyoma
Angiofibromas
Hypomelanotic macules

Workup

Laboratory Studies

  • Laboratory studies are performed as indicated clinically to identify genetic mutations associated with the disorder, monitor anticonvulsant treatment, identify idiosyncratic or dose-related adverse effects, and identify or monitor underlying renal or pulmonary disease.
  • Molecular genetic testing is now commercially available in the United States through Athena Diagnositics and at other centers. Testing through Athena was recently extended to include screening for large deletions and other types of mutations, which will improve their diagnostic yield.
    • Under optimal circumstances, genetic testing identifies mutations in up to 75-80% of affected individuals. Therefore, a negative genetic diagnostic test result does not exclude a diagnosis of tuberous sclerosis.
    • Diagnosis should be possible in most cases using established clinical criteria. Molecular genetic testing is useful in uncertain or questionable cases, for prenatal diagnosis, and for screening family members of an affected individual. The utility of molecular diagnostic testing is limited by the cost (approximately $3100 for an index case and $300 for confirmatory testing in family members), which is often not covered by private insurance carriers. Patient assistance programs may be available through various laboratories.

Imaging Studies

  • Three imaging procedures are usually undertaken: CT or MRI scans of the brain, renal ultrasounds, and echocardiograms. Some centers perform these evaluations annually, at least until adulthood. This is a topic of some controversy, as the natural history of TSC and the cost-effectiveness of these types of screening examinations are not known clearly. Some are concerned that routine screening can lull the clinician into a false sense of security, and thus into ignoring symptoms that arise between serial examinations.
  • CT or MRI scans of the brain
    • CT or MRI scans of the brain are performed to identify SEGAs before obstructive hydrocephalus occurs. They also identify the extent and number of cortical tubers present. On occasion, they may reveal vascular dysplastic lesions such as aneurysms.
    • SEGAs are often large and difficult to resect by the time they produce clinical symptoms; even then, avoiding substantial complications such as blindness, hemiparesis, and shunt dependency may be impossible. Initially their manifestations may be quite subtle, such as a change in personality or behavior. They rarely exhibit significant growth after puberty, if they have not already shown evidence of this. These factors should be considered when planning serial neuroimaging examinations.
    • The author's own practice has been to perform MRI, rather than CT, scans every 2 years in asymptomatic patients, at least until puberty. In children, sedation usually is required for CT scan, as it is for MRI. MRI is superior to CT scan for detection of tubers, migrational anomalies, and vascular lesions. MRI does not involve radiation exposure, as does CT.
    • In addition to standard brain MRI protocols, fluid-attenuated inversion recovery sequences (FLAIR) should be obtained. FLAIR is superior for identification of tubers. Contrast can be administered; however, both SEGAs and SENs typically enhance. Contrast enhancement is not in itself an indication that an SEN is going to grow, or that surgical intervention is necessary. MR angiography is useful if an aneurysm or vascular dysplastic lesion is noted.
    • Some authors have performed resections on SEGAs that exhibit an interval increase in size on serial imaging. Our own practice has been to obtain more frequent imaging studies when a lesion increases in size, provided no signs/symptoms of ventricular obstruction, new focal neurological deficit, or increased intracranial pressure are noted. Lesions may stabilize or stop growing spontaneously after increasing in size (see Image 1, Image 16).
  • Renal ultrasounds
    • Renal ultrasounds are performed to assess change in AMLs or cysts, in the hope that this will allow operative intervention prior to development of renal failure.
    • Small renal cysts and AMLs usually do not grow significantly until after puberty, and often not until the third or fourth decade of life.
    • In our practice, renal ultrasounds, after an initial study, are repeated every 5 years if no or small lesions are seen. In late adolescence through adulthood, ultrasounds are performed every 2-3 years.
  • Echocardiograms
    • Echocardiography is performed as part of the baseline evaluation in a patient with newly diagnosed or suspected TSC. Identification of cardiac rhabdomyomas can aid in diagnosis. Depending on their location and size, rhabdomyomas can result in valvular dysfunction, outflow tract obstruction, ventricular hypokinesis, or arrhythmias.
    • In our practice, echocardiography is not repeated if no lesions are seen on baseline examination. If cardiac lesions are seen, echocardiography is repeated as indicated clinically.
  • Positron emission tomography
    • No current indication exists for routine positron emission tomography (PET) scanning in patients with TSC.
    • PET scans may be useful when patients are undergoing evaluation as candidates for epilepsy surgery. PET scanning with the tracer alpha-methyltryptophan may have particular utility in identifying epileptogenic tubers as part of the evaluation for epilepsy surgery.
  • Single-photon emission computed tomography
    • No current indication exists for routine single-photon emission computed tomography (SPECT) scanning in patients with TSC.
    • SPECT scans may be useful when patients are undergoing evaluation as candidates for epilepsy surgery.

Other Tests

  • Electroencephalogram
    • EEG should be performed in patients with TSC in whom seizures are suspected. Follow-up EEGs are performed as clinically indicated.
    • Some patients with TSC have a coexisting recognizable epilepsy syndrome such as West syndrome (ie, infantile spasms) or Lennox-Gastaut syndrome. If so, prolonged video/EEG telemetry may be useful to help in the following:
      • Detecting syndrome-specific EEG findings
      • Capturing and classifying each of the patient's multiple seizure types
      • Educating parents on which of the patient's "events" are seizures and which are nonepileptic behavioral events (especially atypical absences)
  • Electrocardiogram
    • Baseline ECG is recommended for all patients newly diagnosed with TSC, since cardiac arrhythmias, although rare, may have sudden death as their presenting symptom.
    • In our practice, we perform ECGs at diagnosis and every 2-3 years thereafter until puberty.

More on Tuberous Sclerosis

Overview: Tuberous Sclerosis
Differential Diagnoses & Workup: Tuberous Sclerosis
Treatment & Medication: Tuberous Sclerosis
Follow-up: Tuberous Sclerosis
Multimedia: Tuberous Sclerosis
References
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Further Reading

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Keywords

tuberous sclerosis complex, Bourneville disease. Bourneville's disease, epiloia, Vogt triad, Vogt's triad, angiomyolipoma, lymphangiomyomatosis, polycystic kidney disease, renal cell carcinoma, intractable epilepsy, medically refractory epilepsy, mental retardation, adenoma sebaceum, hamartoma, subependymal nodule, subependymal giant cell astrocytoma, SEGA

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Contributor Information and Disclosures

Author

David Neal Franz, MD, Professor, Departments of Pediatrics and Neurology, University of Cincinnati College of Medicine; Director, Tuberous Sclerosis Clinic, Cincinnati Children's Hospital Medical Center
David Neal Franz, MD is a member of the following medical societies: American Academy of Neurology, American Academy of Pediatrics, American Medical Association, Child Neurology Society, Children's Oncology Group, and Ohio State Medical Association
Disclosure: Nothing to disclose.

Coauthor(s)

Tracy A Glauser, MD, Professor, Departments of Pediatrics and Neurology, University of Cincinnati College of Medicine, Children's Comprehensive Epilepsy Program, Children's Hospital Medical Center of Cincinnati
Tracy A Glauser, MD is a member of the following medical societies: American Academy of Neurology, American Academy of Pediatrics, American Epilepsy Society, and Child Neurology Society
Disclosure: Nothing to disclose.

Medical Editor

Robert Baumann, MD, Program Director, Professor, Departments of Neurology and Pediatrics, University of Kentucky
Robert Baumann, MD is a member of the following medical societies: American Academy of Neurology, American Academy of Pediatrics, American College of Epidemiology, American Epilepsy Society, and Child Neurology Society
Disclosure: Nothing to disclose.

Pharmacy Editor

Francisco Talavera, PharmD, PhD, Senior Pharmacy Editor, eMedicine
Disclosure: Nothing to disclose.

Managing Editor

Kenneth J Mack, MD, PhD, Senior Associate Consultant, Department of Child and Adolescent Neurology, Mayo Clinic
Kenneth J Mack, MD, PhD is a member of the following medical societies: American Academy of Neurology, Child Neurology Society, Phi Beta Kappa, and Society for Neuroscience
Disclosure: Nothing to disclose.

CME Editor

Selim R Benbadis, MD, Professor, Director of Comprehensive Epilepsy Program, Departments of Neurology and Neurosurgery, University of South Florida School of Medicine, Tampa General Hospital
Selim R Benbadis, MD is a member of the following medical societies: American Academy of Neurology, American Academy of Sleep Medicine, American Clinical Neurophysiology Society, American Epilepsy Society, and American Medical Association
Disclosure: Nothing to disclose.

Chief Editor

Nicholas Y Lorenzo, MD, Chief Editor, eMedicine Neurology; Consulting Staff, Neurology Specialists and Consultants
Nicholas Y Lorenzo, MD is a member of the following medical societies: Alpha Omega Alpha and American Academy of Neurology
Disclosure: Nothing to disclose.

 
 
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