Innocenzo RAINERO, MD PhD Innocenzo RAINERO, MD PhD

Neurology II – Department of Neurology II – Department of Neuroscience, University of TorinoNeuroscience, University of Torino

ITALYITALY

VON HIPPEL-LINDAU VON HIPPEL-LINDAU DISEASE AND THE DISEASE AND THE NERVOUS SYSTEMNERVOUS SYSTEM

Corso di aggiornamento in Endocrinologia ClinicaCorso di aggiornamento in Endocrinologia Clinica

28 settembre 201128 settembre 2011

SNC SNC haemangioblastomashaemangioblastomas

CNS haemangioblastomas are a cardinal feature of VHL disease and are the presenting feature in ~40% of cases. The average age for developing these is 33 years.

Overall CNS haemangioblastomas occur in 60–80% of VHL patients and most commonly occur in the cerebellum, spinal cord and brain stem with supratentorial lesions being rare.

Patients with cerebellar haemangioblastomas typically present with symptoms of increased intracranial pressure and limb or truncal ataxia (depending on the precise location of the tumour) and the clinical presentation of CNS haemangioblastomas reflects their mass effect.

Haemangioblastomas with an associated cyst tend to become symptomatic sooner.

Haemangioblastomas: Haemangioblastomas: symptomssymptoms

Symptoms in the cerebellum include: difficulty in walking and with muscular coordination, vertigo, headaches, vomiting

Symptoms in the spinal cord include: decreased sensations in the arms and legs, weakness, difficulty in walking, difficulty with bowel and bladder function

Symptoms in brainstem include: decreased sensation, difficulty walking, difficulties swallowing, headache and poor coordination

SNC SNC haemangioblastomashaemangioblastomas

Microscopically, haemangioblastomas consist of large polygonal stromal cells enmeshed in a capillary network, and stromal cells arise from mesoderm-derived embryologically arrested haemangioblasts.

Although CNS haemangioblastomas tend to enlarge over time, they are benign tumours and the growth rate is variable so that some tumours may be static for a number of years and hence removal of asymptomatic lesions is not usually indicated

CT scan in a 34-year old patient with a CT scan in a 34-year old patient with a family hystory of VHLfamily hystory of VHL

T1-weighted MRI of the same T1-weighted MRI of the same patientpatient

Coronal vertebral Coronal vertebral angiogram angiogram

Sagittal vertebral Sagittal vertebral angiogramangiogram

Axial volume rendering of contrast enhanced CT Axial volume rendering of contrast enhanced CT scanscan

Transaxial contrast-enhanced CT Transaxial contrast-enhanced CT scansscans

Contrast enhanced CT scanContrast enhanced CT scan

MRI of the spinal cordMRI of the spinal cord

Haemangioblastomas: Haemangioblastomas: therapytherapy

Generally the results of surgery for a single peripherally located cerebellar lesion are excellent, but surgical management of multicentric tumours and brain stem and spinal tumours can be challenging and patients can benefit from being treated in units with specialised experience and expertise in VHL disease.

Haemangioblastomas: Haemangioblastomas: therapytherapy

Preoperative embolization is not generally used but may be helpful before surgical resection of endolymphatic sac tumors and hemangioblastomas in selected cases

Stereotactic radiotherapy may be an alternative to conventional neurosurgery for non-cystic small haemangioblastomas though adverse reactions may occur.

Endolymphatic sac tumours Endolymphatic sac tumours - ELST- ELST

ELSTs can be detected by MRI imaging in up to 11% of VHL patients

Bilateral ELSts are considered patho-gnomonic for VHL disease.

Although often asymptomatic, the most frequent presentation is hearing loss but tinnitus and vertigo also occur in many cases

ELST in a 18 year womanELST in a 18 year woman

Endolymphatic sac Endolymphatic sac tumourstumours

Screen for CNS Screen for CNS haemangioblastomahaemangioblastoma

ASYMPTOMATIC VHL PATIENTS: annual neurological examination – MRI of the brain and cervical spine for every 24 months

SYMPTOMATIC VHL PATIENTS: neurological examination and MRI scan for every 6-12 months

Take home messagesTake home messages Advances in the genetic basis of VHL disease have Advances in the genetic basis of VHL disease have

facilitated diagnosis and provided insights into the facilitated diagnosis and provided insights into the biology of VHL disease. biology of VHL disease.

Surveillance of affected and asymptomatic gene carriers Surveillance of affected and asymptomatic gene carriers can reduce morbidity and mortality. can reduce morbidity and mortality.

Most common manifestations of VHL disease are retinal Most common manifestations of VHL disease are retinal and central nervous haemangioblastomas.and central nervous haemangioblastomas.

The management of central nervous system lesions is The management of central nervous system lesions is highly complex and challenging. The care of VHL highly complex and challenging. The care of VHL families should be concentrated on specialist referral families should be concentrated on specialist referral centres. centres.

In the future, targeted drugs could offer new therapeutic In the future, targeted drugs could offer new therapeutic opportunities for patients affected with VHL disease.opportunities for patients affected with VHL disease.

Thank you for your Thank you for your attentionattention