Lhermitte-Duclos disease
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.
- In 1937, the first ever successful surgery was done on 34 year old Lhermitte-Duclos disease (LDD) patient who experienced symptoms for almost 6 long years.

# 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
- 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
- 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
- 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 LhermitteDuclos disease.
- The characteristic dysplastic hypertrophied ganglion cells are positive for synaptophysin.

# Causes
- The most common cause of LhermitteDuclos 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.

# Differentiating LhermitteDuclos disease from other Diseases
LhermitteDuclos disease must be differentiated from medulloblastoma, Cowden disease and cerebellitis or subacute cerebellar infarction.

# Epidemiology and Demographics

## Incidence
- The incidence of LhermitteDuclos disease is very extremely rare worldwide.
- Till now hardly 200 patient cases were diagnosed with LhermitteDuclos disease worldwide.

## Age
- LhermitteDuclos disease most commonly affects individuals between 30-50 years.
- LhermitteDuclos disease might also affects infants or adults over 60 years in some rare cases.

## Race
- There is no racial predilection to LhermitteDuclos disease.

## Gender
- LhermitteDuclos disease affects men and women equally.

# Risk Factors
- There are no established risk factors for LhermitteDuclos disease.

# Natural History, Complications and Prognosis

## Natural History
- The symptoms of LhermitteDuclos disease typically develop over many years which is a sign that may implicate the disease is slowly progressive in nature.

## Complications
- Common complications of LhermitteDuclos diseaseinclude:
Megacephaly
Syringomyelia
Breast malignancies
Thyroid malignancies
Genitourinary malignancies
Gastrointestinal malignancies
- Megacephaly
- Syringomyelia
- Breast malignancies
- Thyroid malignancies
- Genitourinary malignancies
- Gastrointestinal malignancies

## Prognosis
- Prognosis is generally good to poor in patients with LhermitteDuclos disease.

# Diagnosis

## Diagnostic Study of Choice
- The diagnostic study of choice for LhermitteDuclos disease is Magnetic resonance imaging (MRI).

## History and Symptoms
- The majority of patients with LhermitteDuclos disease are asymptomatic.
Common symptoms of LhermitteDuclos disease include:
- Ataxia
- Headache
- Cranial nerve palsy
- Paroxysm of vertigo
- Psychic deterioration
Less common symptoms of LhermitteDuclos 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)
- Headache, blurred vision, and vomiting(Signs of intracranial hypertension)

# Physical Examination

## Neuromuscular
- Patient is usually oriented to persons, place, and time
- Ataxia of gait
- Turricephaly
- Occipital headache
- Facial asymmetry
- Polydactylia
- Skull abnormalities
- Reduced-hearing

# MRI
Head MRI may be helpful in the diagnosis of LhermitteDuclos disease without the need for surgery. Findings on MRI diagnostic of LhermitteDuclos disease include:
- Characteristic tiger-striped pattern on T1W and T2W images.
- Hyperintense with parallel hypointense streaks which is an indication for thickening of the following:
Cerebellar folia
Cortical gyri
- Cerebellar folia
- Cortical gyri
- Atrophy of the cerebellar white matter
- Thinning of medullary white matter
- Loss of Purkinje cells
- Thickened granule cell layer
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 LhermitteDuclos disease about tumour pathology:
- Hypermetabolism of the LhermitteDuclos disease(LDD) is seen
- 18-FDG uptake is within the solid component of the LDD
- Increased rCBV and increased 201-TI uptake
- Increased glucose metabolism
- Striations representing the folia of the cerebellum
- Increased metabolism and intensity signal similar to that of normal grey matter.

# CT scan
Head CT scan may be helpful in the diagnosis of LhermitteDuclos disease but has limited value. Findings include
- Non-specific hypoattenuating cerebellar mass
- Calcification rarely seen

# Treatment

## Medical Therapy
- Medical therapy is not indicated in patients who are asymptomatic in LhermitteDuclos disease.

## Surgery
Surgery is the mainstay of treatment for LhermitteDuclos disease.
Debulking of the tumor
- Surgical debulking of the tumor is indicated in patients with LhermitteDuclos disease
- Using surgical microscope the precise margin of abnormal tissue of this tumor has accessed and removed during surgery.
- The presence of well demarcated mass on exploration can be accounted as a successful surgical resection.
- In older patients partial resection of the cerebral mass is recommended to avoid life threatening complications.