Table 2.
Surveillance and Management Consensus Guidelines for Neurologic Features in Patients With PHTS (Based on the Second Stage of the Modified Delphi Process)
| Statement | Clinical recommendation | Evidence grade and agreement, (%) | Key details |
| Initial diagnosis and patient education | |||
| N1/ND1 | Educate patients/caregivers at diagnosis on potential neurodevelopmental/neuropsychiatric complications | Weak (100) | Complications to discuss: Autism, mood/behavioral issues, sleep problems, IDD, learning differences, ADHD Less common: seizures, Lhermitte-Duclos disease, vasculopathy |
| N2 | Screen for seizures by history at diagnosis and as symptoms arise | Weak (83) | Look for: focal motor/sensory, convulsions, dyscognitive, developmental/language regression |
| Routine monitoring and screening | |||
| N7 | Avoid routine screening neuroimaging of brain/neuroaxis | Expert opinion (83) | Only if neurologic symptoms/signs are present |
| N12 | Perform neurologic examination to assess for intra-axial AVMs | Weak (80) | Focus on motor/sensory findings. If suspected/identified, obtain contrast MRA/MRV, consider conventional angiography, involve multidisciplinary vascular team |
| N15 | Follow established guidelines for ocular pathologies | Weak (100) | Refer to experienced ophthalmology team |
| N16 | Diagnose headaches using ICHD-3 criteria; manage per evidence-based practices | Weak (83) | Standard of care applies. Refer to headache neurology if refractory |
| Targeted interventions and management | |||
| N3 | Refer to neurology and work-up for epilepsy if concern for seizures or developmental regression | Strong (83) | Workup: detailed history, examination, EEG. Consider additional EEG/imaging (MRI/MRA) based on results. Rule out epilepsy-associated pathologies (e.g., focal cortical dysplasia, and tumors) on imaging |
| N4 | Select antiepileptic medications based on predominant seizure type | Strong (100) | No first-line mTOR inhibitors. Obtain brain MRI to rule out structural etiologies. Consider neuropsychiatric comorbidities/side effects |
| N5 | Consider MRA/MRV with MRI for focal neurologic findings | Weak (100) | Use hemosiderin-specific sequences (e.g., GRE and SWI) for cavernous malformations |
| N6 | Do not routinely image for typical headaches | Weak (100) | Image for: worrisome focal features (positional, projectile emesis, focal neuro-findings), abnormal examination, change in pattern, ICP signs, OR new-onset headaches in child <5 y |
| N8 | IV contrast (gadolinium) may be used with clinically indicated brain MRI/MRA | Expert opinion (100) | Depends on diagnostic need; helpful for delineating tumors |
| N9 | Evaluate atypical LDD with neuro-oncology/neurology and neurosurgery for biopsy/resection consideration | Moderate (100) | Atypical: noncerebellar location, contrast enhancement, diffusion restriction, rapid growth. Typical LDD (cerebellar, T1-hypo, T2-hyper, “tigroid”): monitor with serial imaging (3–12 mo) if asymptomatic/no CSF obstruction. Surgical evaluation for impending CSF obstruction |
| N10 | Conduct serial neuroimaging and clinical examinations after LDD resection | Weak (100) | Monitor for recurrence; 6–12 mo interval. Target examinations/imaging to lesion site, use specialized MRI protocols |
| N11 | Conduct serial neuroimaging and clinical examinations for identified meningiomas | Moderate (100) | Follow NCCN guidelines (e.g., serial MRI at 3, 6, and 12 mo, then every 6–12 months for 5 y, then every 1–3 y). Involve multidisciplinary team for symptomatic/critical meningiomas |
| N13 | Follow established guidelines for other CNS tumors or ocular pathologies | Weak (100) | |
| N14 | Exercise caution with diagnostic/therapeutic radiation exposure | Weak (100) | Balance benefit vs potential secondary malignancy risk (typically 10–20 y later). MRI is not a risk factor |
Abbreviations: ADHD = attention deficit hyperactivity disorder; ASD = autism spectrum disorder; AVM = arteriovenous malformation; GRE = gradient recalled echo; ICHD-3 = International Classification of Headache Disorders Version 3; ICP = intracranial pressure; LDD = Lhermitte-Duclos disease; N = neurologic; NCCN = National Comprehensive Cancer Network; PHTS = PTEN hamartoma tumor syndrome; SWI = susceptibility weighted imaging.