Lhermitte-Duclos disease

Lhermitte-Duclos disease
OMIM	158350

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1] ; Associate Editor(s)-in-Chief: Vamsikrishna Gunnam M.B.B.S [2]

Synonyms and keywords: Dysplastic cerebellar gangliocytoma

Overview

Lhermitte-Duclos disease (LDD) is also called as dysplastic gangliocytoma of the cerebellum. Lhermitte-Duclos disease (LDD) is a very rare disease. Lhermitte-Duclos disease (LDD) follows an autosomal dominant pattern of inheritance. Lhermitte-Duclos disease (LDD) is a rare entity that may occur in the association of Cowden's syndrome (CS). In The United States of America in order to categorise a condition as a rare disease it should affect fewer than 200,000 people. Rare diseases also called as orphan diseases. Orphan Drug Act was passed on 1983 by congress for the rare diseases. Today an average of 25-30 million americans have been reported with rare diseases. The number of people with individual rare disease may be less but overall the number of people with rare diseases are large in number.

Historical Perspective

• Lhermitte-Duclos disease (LDD) was first discovered by Lhermitte and Duclos as "Sur un ganglioneurome diffus du cortex du cervelet", in 1920.

Classification

• Lhermitte-Duclos disease (LDD) is one of the syndrome which belong to PTEN hamartoma tumor syndromes (PHTS). These syndrome has been due to somatic mutation in phosphatase and tensin homolog (PTEN) gene. All PTEN hamartoma tumor syndromes (PHTS) follow autosomal dominant pattern of inheritance. PTEN hamartoma tumor syndromes (PHTS) include the following:
  • Cowden syndrome
  • Bannayan-Riley-Ruvalcaba syndrome
  • Adult Lhermitte-Duclos disease
  • Proteus syndrome

Pathophysiology

• Lhermitte-Duclos disease (LDD) is transmitted in autosomal dominant pattern.
• Genes involved in the pathogenesis of Lhermitte-Duclos disease (LDD) include:
• Mutations in the PTEN gene leads to oncogenesis, and somatic mutations
• Phosphatase and tensin homolog (PTEN) gene plays an important role in the following:
  • Phosphoinositide-3-kinase (PI3K)-AKT pathway and
  • Rapamycin (mTOR) signaling pathways
• PTEN track backs to 10q23 which encodes and plays a significant role in the following:
  • Effects G1 cell cycle arrest and apoptosis
  • Cellular proliferation and
  • Migration
  • Apoptosis

Microscopic Pathology

• On microscopic histopathological analysis, dysplastic hypertrophied ganglion cells in cerebellum, expansion of the granule layer, loss of Purkinje cells, and increased myelination are characteristic findings of Lhermitte–Duclos disease.

Gross appearance of a portion of the surgical specimen showing the coarse widened folia. Case courtesy by Sydney S. Schochet Jr. MD

Causes

• The most common cause of Lhermitte–Duclos disease is mutation in PTEN gene on chromosome 10q22-23 which activates rapamycin (mTOR) which in turn effects PTEN/AKT pathway and a major regulator of cell growth.

Epidemiology and Demographics

Incidence

• The incidence of Lhermitte–Duclos disease is very extremely rare worldwide.

Age

• Lhermitte–Duclos disease most commonly affects individuals between 30-50 years.
• Lhermitte–Duclos disease might also affects infants or adults over 60 years in some rare cases.

Race

• There is no racial predilection to Lhermitte–Duclos disease.

Gender

• Lhermitte–Duclos disease affects men and women equally.

Risk Factors

• There are no established risk factors for Lhermitte–Duclos disease.

Natural History, Complications and Prognosis

Natural History

• The symptoms of Lhermitte–Duclos disease typically develop over many years which is a sign that may implicate the disease is slowly progressive in nature.

Complications

• Common complications of Lhermitte–Duclos diseaseinclude:
  • Megacephaly
  • Syringomyelia
  • Breast malignancies
  • Thyroid malignancies
  • Genitourinary malignancies
  • Gastrointestinal malignancies

Prognosis

• Prognosis is generally good to poor in patients with Lhermitte–Duclos disease.

Diagnosis

History and Symptoms

• The majority of patients with Lhermitte–Duclos disease are asymptomatic.

Common symptoms of Lhermitte–Duclos disease include:

• Ataxia
• Headache
• Cranial nerve palsy
• Paroxysm of vertigo
• Psychic deterioration

Less common symptoms of Lhermitte–Duclos disease in severe cases include:

• Hydrocephalus: Which might results in signs and symptoms of intracranial hypertension.
  • Headache, blurred vision, and vomiting(Signs of intracranial hypertension)

MRI

Head MRI may be helpful in the diagnosis of Lhermitte–Duclos disease without the need for surgery. Findings on MRI diagnostic of Lhermitte–Duclos disease include:

• Hyperintense with parallel hypointense streaks which is an indication for thickening of the following:
  • Cerebellar folia
  • Cortical gyri
• Atrophy of the cerebellar white matter
• Thinning of medullary white matter
• Loss of Purkinje cells
• Thickened granule cell layer

MRI shows Tiger-striped appearance with abnormally oriented folia in the left cerebellar hemisphere, extending to the vermis. Case courtesy by Hideo Saito Et Al

MR spectroscopy

• Increased lactate
• Decreased NAA
• 30%-80% reduction in myo-inositol
• 20%-50% reduction in choline
• Decrease in Cho/Cr ratio

FDG-PET SCAN

FDG-PET scan may be helpful in the diagnosis of Lhermitte–Duclos disease about tumour pathology:

• Hypermetabolism of the LDD is seen
• 18-FDG uptake is within the solid component of the LDD
• Increased rCBV and increased 201-TI uptake

MRI shows Coarse striations resulting from irregular, abnormally thickened cerebellar folia. Case courtesy by Sydney S. Schochet Jr. MD