Duclos Disease Research Articles

Acute acquired comitant esotropia associated with Lhermitte–Duclos disease: a case report

BackgroundAcute acquired comitant esotropia caused by prolonged near work, such as the use of digital devices, has been frequently reported in recent years. However, intracranial examination is necessary even for patients with nonparalytic comitant esotropia. Lhermitte–Duclos disease is a rare tumor that grows in layers in the cerebellum. Among those with this disease, cases of esotropia have been reported due to abduction limitation of the eye, but there have been no reports of comitant esotropia. Here, we report the case of a young woman with acute acquired comitant esotropia who was found to have Lhermitte–Duclos disease.Case presentationA 16-year-old Japanese female patient, whose ethnicity was Asian, was referred to our hospital for acute acquired comitant esotropia. Fundus examination revealed papilledema in both eyes, and magnetic resonance imaging of the head revealed a cerebellar tumor in the right cerebellum with obstructive hydrocephalus. She underwent partial tumor resection, and a histopathological diagnosis of Lhermitte–Duclos disease was obtained. However, comitant esotropia status remained unchanged, and she underwent strabismus surgery. Finally, diplopia disappeared completely.ConclusionNeurological and intracranial imaging examinations are essential when acute acquired comitant esotropia is observed. Acute acquired comitant esotropia by Lhermitte–Duclos disease did not improve with partial tumor resection and required strabismus surgery, but good surgical results were obtained.

Anomalies of Midbrain Hindbrain Development: Midbrain Clefts, Cerebellar Nodular Heterotopia with Overlying Dysgenesis, Cerebellar Foliation Disorder, Pontine Tegmental Cap Dysplasia; Joubert Syndrome; Lhermitte Duclos Syndrome. Diagnosis, Classification and Rehabilitation Hypothesis

AbstractMidbrain and hindbrain (MBHB) malformations are a rare group of congenital abnormalities that involve the neural structure of the posterior cranial fossa, leading to significant causes of neurodevelopmental dysfunction. Recent advancements in genetic and neuroimaging technologies have significantly enhanced our understanding of these disorders. The integration of these advances has facilitated a systematic classification of these conditions. A basic understanding of MBHB embryology is fundamental in order to understand the malformations occurring in their structures: MBHB neurons are mainly generated in the neuroepithelium, lining the walls of the fourth ventricle. Moreover, the regional specificity of the neural tube is determined by a combination of transcription factors expressed, organizing the fate of the neighboring regions as well. Clinical features of MBHB malformations are typically nonspecific; some patients may be asymptomatic or may develop neurological symptoms including hypotonia, ataxia, abnormal eye movements, decreased visual attention, cranial nerve deficits, cognitive impairment, and psychiatric symptoms. Many malformations have been described. We proposed the description of some of them, reporting their main morphologic aspects, magnetic resonance imaging (MRI) peculiar signs and their clinical presentation. Midbrain clefts, for example, are malformations characterized by median separation in the ventral midbrain which involves a communication with the cerebral aqueduct giving a “keyhole” shape. Pontine tegmental cap dysplasia, instead, is a rare hindbrain malformation responsible for a nonprogressive neurological disorder and is described with hypoplastic flat ventral pons, hypoplasia of the middle cerebellar peduncles, and hypoplasia and malformation of the worm. Joubert syndrome, cerebellar nodular heterotopia, abnormal cerebellar foliation, and Lhermitte–Duclos disease, also called dysplastic cerebellar gangliocytoma, have been described as well in order to provide a general overview on this diagnostic challenge reporting the most recent findings.

A rare case of dysplastic cerebellar gangliocytoma - Lhermitte Duclos Disease

Lhermitte–Duclos disease (LDD), also known as dysplastic cerebellar gangliocytoma, is an uncommon hamartomatous lesion found in the cerebellar cortex. First described by French physicians Lhermitte and Duclos in 1920, this condition involves enlarged cerebellar folia containing abnormal ganglion cells. Clinical manifestations typically include headaches, visual disturbances, and cerebellar dysfunction. While imaging techniques like computed tomography (CT) scans may indicate the presence of mass lesions, magnetic resonance imaging (MRI) is crucial for accurate delineation of the lesion's boundaries and characterization of tissue involvement. Surgical intervention, typically in the form of respective surgery, remains the cornerstone of treatment for LDD. Despite advancements in imaging technologies and surgical techniques, the management of LDD remains fraught with complexities. The prognosis can be variable, and in some cases, despite appropriate therapeutic interventions guided by MRI-assisted surgical planning and confirmation through CT screening, the outcome may be unfavorable, as observed in this instance with the demise of the 50-year-old male patient. Further research and a deeper understanding of the pathophysiology underlying LDD are imperative to enhance diagnostic accuracy, refine treatment modalities, and potentially improve patient outcomes. This case underscores the challenges in managing this rare neurological condition and highlights the need for continued exploration into more effective therapeutic avenues.

Lhermitte-Duclos disease: A systematic review.

Lhermitte-Duclos disease (LDD) is a rare tumor, with only about 300 reported cases. It often shows comorbidity with Cowden syndrome (CS); however, it can occur by itself. Radiologically, the "tiger-stripe" appearance is considered pathognomonic. Surgical resection remains the mainstay of treatment. This report aims to describe the clinical and radiological characteristics of LDD and its relationship with CS according to age group. PubMed electronic databases were searched in August 2022. The search terms included "Lhermitte- Duclos disease" and "dysplastic gangliocytoma," which yielded 297 and 103 research articles, respectively. The articles were collected and reviewed by three researchers. Out of 400 identified articles, we analyzed 302 reported cases. The mean age at presentation was 33.6 ± 16 years; 171 patients (56.6%) were female, and 123 (40.7%) were male. The most commonly reported symptom was headache (174 patients, 57.6%), followed by ataxia (109, 36.1%). In addition, 99 cases (32.8%) were associated with CS, and 60 (19.9%) had a confirmed phosphatase and tensin homolog (PTEN) mutation. A tiger-stripe appearance was observed in 208 cases (58.7%); surgical resection was performed in 64.2% of the cases. Mortality and recurrence rates were 4.3% and 8.6%, respectively. No statistically significant difference was found between adult- and pediatric-onset LDD for the association with CS (P = 0.128). Our findings suggest that adult and pediatric LDD have major commonalities; however, further prospective studies are warranted.

A young Female of Cowden Syndrome Presenting with Lhermitte- Duclos Disease: A Case Study

Cowden Syndrome (CS) is a rare autosomal dominant inherited genetic disorder due to germline mutations in the phosphatase and tensing homologue (PTEN) tumor suppressor gene in chromosome 10 characterized by multiple hamartomata’s lesions of ectodermal, mesodermal and endodermal origin. Lhermitte-Duclos Disease (LDD), or dysplastic gangliocytoma, which is a benign hamartomata’s condition involving the cerebellum with less than 300 cases reported in the literature. Previous studies suggest an association between CS and LDD. We present here a case of a 28-year female patient presented at the emergency department of our hospital with severe headache associated with vertigo, vomiting & cerebellar ataxia. Papilledema was noted on fundoscopy. Non-attenuating hypodense mass lesion in posterior fossa was found in CT scan. MRI scan T1WI film revealed mixed intensity posterior fossa lesion and T2WI film revealed inhomogeneous hyperintense lesion with almost preserved cerebellar cortical striations. USG revealed numerous polyps in the gallbladder with cholelithiasis. Her facial skin has extensive trichilemmoma. Her symptoms improved after excision of posterior fossa lesion through suboccipital craniectomy and histopathology revealed dysplastic cerebellar gangliocytoma i.e., Lhermitte-Duclos disease. Using the Cleveland Clinic Adult Clinical Scoring for PTEN Testing, the patient had an 82-98% chance for a PTEN gene mutation. Finally, she along with her family was adequately counseled and was advised for regular screening and monitoring. Bang. J Neurosurgery 2022; 12(1): 41-46

Diagnosis of PTEN mosaicism: the relevance of additional tumor DNA sequencing. A case report and review of the literature

BackgroundPTEN hamartoma syndrome (PHTS) is an autosomal dominant disorder characterized by pathogenic variants in the tumor suppressor gene phosphatase and tensin homolog (PTEN). It is associated with an increased risk of muco-cutaneous features, hamartomatous tumors, and cancers. Mosaicism has been found in a few cases of patients with de novo PHTS, identified from blood samples. We report a PHTS patient with no variant identified from blood sample. Constitutional PTEN mosaicism was detected through sequencing of DNA from different tumoral and non-tumoral samples.Case presentationOur patient presented clinical Cowden syndrome at 56 years of age, with three major criteria (macrocephaly, Lhermitte Duclos disease, oral papillomatosis), and two minor criteria (structural thyroid lesions, esophageal glycogenic acanthosis). Deep sequencing of PTEN of blood leukocytes did not reveal any pathogenic variants. Exploration of tumoral (colonic ganglioneuroma, esophageal papilloma, diapneusia fibroids) and non-tumoral stomach tissues found the same PTEN pathogenic variant (NM_000314.4 c.389G > A; p.(Arg130Gln)), with an allelic frequency of 12 to 59%, confirming genomic mosaicism for Cowden syndrome.ConclusionsThis case report, and review of the literature, suggests that systematic tumor analysis is essential for patients presenting PTEN hamartoma syndrome in the absence of any causal variant identified in blood leukocytes, despite deep sequencing. In 65 to 70% of cases of clinical Cowden syndrome, no pathogenic variant in the PTEN is observed in blood samples: mosaicism may explain a significant number of these patients. Tumor analysis would improve our knowledge of the frequency of de novo variations in this syndrome. Finally, patients with mosaicism for PTEN may not have a mild phenotype; medical care identical to that of heterozygous carriers should be offered.

L’hermitte–Duclos Disease In An Infant: A Case Report With Review of Literature

Jacques Jean Lhermitte a French neurologist and P. Duclos in 1920 first described a growth in the cerebellum gangliocytoma, as a rare hamartomata’s lesion due to abnormal development of the cerebellum. Since then it has been called by many names Lhermitte-Duclos disease, dysplastic gangliocytoma of the cerebellum, benign hypertrophy of the cerebellar cortex, granular cell hypertrophy and Purkinjeoma. It is a characteristic radiological feature and there has been reported in over 200 cases worldwide in adolescents [1] and old people but a handful of cases are detected and reported in infants. We report a 6 month old male child whose parents reported a history of irritability and typical lion facies with normal mile stones and radiological features of L’hermitte–Duclos disease.

Diverse imaging findings of Lhermitte–Duclos disease

To evaluate the diverse clinical and imaging features of Lhermitte-Duclos disease (LDD) and its subgroup comparison. Clinical data from 21 patients with LDD were collected, including eight patients with LDD without other tumours and 13 LDD with other tumours. Redefined diagnostic criteria are used to evaluate Cowden Syndrome. Imaging indicators were analysed retrospectively to extract typical and atypical features. Imaging findings and preoperative diagnostic accuracy were compared between the subgroups. None of these patients met the redefined diagnostic criteria. The typical "tiger stripe sign" was seen in most LDD lesions (13/29, 61.9%), with lower density (29.66±2.51 versus 37.81±2.76 HU, p<0.001) and higher apparent diffusion coefficient (ADC) value (1.04±0.05×10-3 versus 0.74±0.03×10-3 mm2/s, p<0.001) than that of the normal cerebellum. Atypically, some lesions showed abnormal vessels (8/21, 38.1%), intratumoural calcification (3/21, 14.29%), intratumoural haemorrhage (4/21, 19.05%), peritumoural oedema (6/21, 28.57%), and heterogeneous enhancement (5/21, 23.81%). The typical "tiger stripe sign" was more common in LDD with other tumours (84.62% versus 25%, p=0.018). Although LDD without other tumours was more common with abnormal vessels (75% versus 15.38%, p=0.018), intratumoural calcification (37.5% versus 0, p=0.042), intratumoural haemorrhage (50% versus 0, p=0.012), peritumoural oedema (62.5% versus 7.69%, p=0.014) and heterogeneous enhancement (50% versus 7.69%, p=0.047). Preoperative diagnostic accuracy was higher in LDD with other tumours than LDD without other tumours (76.92% versus 25%, p=0.032). The "tiger stripe sign" of LDD is characteristic, but not unique. With or without other tumours, it may be associated with the imaging diversity. Combining typical and atypical signs can improve the imaging assessment of LDD.

A Radiological Curiosity of a Rare Diagnosis: Lhermitte-Duclos Disease

Lhermitte–Duclos disease (LDD) is a rare cerebellar lesion, described in 1920 by two French physicians: Lhermitte and Duclos. The clinical presentation is usually made of neurological symptoms. This lesion is characterized by a hamartomatous lesion in the posterior fossa. Mainly diagnosed by MRI, when it comes to preoperative, the T2-weightened MRI demonstrates the classical “tiger-striped” pattern. The definitive diagnosis, nonetheless, is histopathological. The treatment for LDD consists of surgical decompression or excision. We present here a rare case of a woman who developed neurological symptoms that led to LDD diagnosis to describe protocol MRI imaging, the main findings and their pathophysiological meanings.

Paresthesias and Weakness of Lower Limbs as Symptomatic Debut of Lhermitte-Duclos Disease.

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A Great Conversation With Dr. James Corbett

A Great Conversation With Dr. James Corbett

Cowden syndrome and Lhermitte - Duclos disease: A case report and review of the literature

Cowden syndrome (CS) is a rare, autosomal dominant, multisystem disease related to the mutation of Phosphatase and tensin homolog (PTEN) tumour suppressor gene. It is characterized by the occurrence of multiple hamartomas, mucocutaneous lesions, and is associated with a high risk of malignancies. Lhermitte–Duclos Disease (LDD), or dysplastic cerebellar gangliocytoma, is a rare hamartomatous lesion of the cerebellar cortex with a unique “Tiger Stripe” appearance on Magnetic Resonance Imaging (MRI). Since 1991, LDD has been considered pathognomonic and part of CS. In addition, as almost all adult onset LDD cases were associated with PTEN gene mutations, LDD and CS are both included in PTEN Harmartoma Tumour Syndrome (PHTS). In this article, we report a 48-year-old female patient, who presented with a right cerebellar lesion resulting in hydrocephalus. The histology of the cerebellar lesion confirmed the diagnosis of LDD, and her clinical history is highly suggestive of CS. Due to the high incidence of multisystemic malignancies and other disease, it is important for clinicians to be aware of the association between LDD and CS. Affected patients should be evaluated carefully and screened for cancers accordingly, so as to allow early diagnosis and treatment.

Lhermitte–Duclos Disease: Incidental Finding in Traumatic Cerebral Hemorrhage

AbstractLhermitte–Duclos disease, also known as dysplastic cerebellar gangliocytoma, is a rare hamartomatous tumor localized in cerebellum. An association with Cowden syndrome is observed in 50% of cases who present with symptoms of increased intracranial pressure and cerebellar ataxia. These patients have specific magnetic resonance imaging and histopathological findings. Surgical resection is the treatment of choice. Here, we report a case of a young female with traumatic frontal hemorrhage associated with Lhermitte–Duclos disease.

PTEN Hamartoma Tumor Syndrome/Cowden Syndrome: Genomics, Oncogenesis, and Imaging Review for Associated Lesions and Malignancy.

Simple SummaryIn this manuscript, we present the associated imaging findings and imaging screening recommendations. Knowledge of the types of cancers commonly seen in Cowden syndrome and their imaging findings can aid in early tumor recognition during cancer screening to help ensure near-normal life spans in Cowden syndrome patients.PTEN hamartoma tumor syndrome/Cowden syndrome (CS) is a rare autosomal dominant syndrome containing a germline PTEN mutation that leads to the development of multisystem hamartomas and oncogenesis. Benign tumors such as Lhermitte–Duclos disease and malignant tumors involving the breast, thyroid, kidneys, and uterus are seen in CS. Radiologists have an integral role in the comanagement of CS patients. We present the associated imaging findings and imaging screening recommendations. Knowledge of the types of cancers commonly seen in CS and their imaging findings can aid in early tumor recognition during cancer screening to help ensure near-normal life spans in CS patients.

Lhermitte&amp;ndash;Duclos Disease: Case Report and Literature Review

Lhermitte&amp;ndash;Duclos Disease: Case Report and Literature Review

Surgical treatment of Lhermitte–Duclos disease (dysplastic gangliocytoma of the cerebellum)

The study objective is to describe a clinical case of a rare disorder of the cerebellum, Lhermitte–Duclos disease.Clinical case. The Federal Neurosurgical Center (Novosibirsk) admitted a male patient, 40 years old. Medical history showed that in 2017 he underwent ventriculoperitoneal shunt due to hypertensive hydrocephalus syndrome caused by space-occupying mass of the right hemisphere of the cerebellum. In June of 2017, the patient was consulted by a neurosurgeon. Later, an increase in the mass, partial atrophy of the optic disks were observed. Due to the patient’s complaints of headache, ataxia, vertigo, as well as insufficient effect of the shunt, microsurgical removal of the space-occupying mass in the cerebellum by right paramedian suboccipital craniotomy was performed. Gangliocytoma removal was performed under constant neurophysiological control which allowed to fully resect the gangliocytoma inside intact brain tissue. Histological and immunohistological examinations allowed to diagnose grade I dysplastic gangliocytoma of the cerebellum (Lhermitte–Duclos disease). In the postoperative period, brain symptoms regressed fully, vestibulocerebellar syndrome persisted. The patient was discharged in satisfactory condition. No negative dynamics were observed in 7 months of follow-up.Conclusion. Due to the rareness of Lhermitte–Duclos disease, currently there are no established approaches to treatment, however, in symptomatic course there are indications for surgical removal of the gangliocytoma. Radicality of resection should be correlated with the risk of neurological defects. In our case, surgical treatment allowed to improve the patient’s condition, prevent further progression of the gangliocytoma and obtain an accurate histological diagnosis.

An update on the CNS manifestations of brain tumor polyposis syndromes.

Cancer predisposition syndromes are associated with an increased risk of developing primary malignancies. Here we discuss those which are associated with an increased risk of tumors of the central nervous system (CNS) and gastrointestinal (GI) tract. These can be grouped into those in which the CNS tumors predominate versus those in which the GI cancers predominate. The former include constitutional mismatch repair deficiency (CMMRD) syndrome, Li-Fraumeni syndrome (LFS), and Cowden syndrome (CS) while the latter include familial adenomatosis polyposis 1 (FAP1), Lynch syndrome and polymerase proofreading-associated polyposis syndrome (PPAP). Tumor specificity does exist as medulloblastoma occur in FAP, LFS and CMMRD while glioma are most commonly seen in all replication repair-deficient genes and LFS. Choroid plexus carcinoma is strictly observed in LFS while Cowden syndrome patients develop Lhermitte Duclos disease or meningioma. In each syndrome, specific types of low-grade and high-grade gastrointestinal cancers can occur, but these will be discussed elsewhere. Underlying cancer predisposition syndromes are important to consider when faced with brain tumors, particularly in the pediatric and young adult age groups, as identification of an underlying germ line mutation may change the upfront management of the patient and has implications for future cancer surveillance for both the patient and potentially affected family members. Considerations of family history, presence of skin lesions and consanguinity provide valuable information in identifying patients at potential increased risk.

Rare Dysplastic Gangliocytoma of Cerebellum: A Case Report

Lhermitte and Duclos first described Dysplastic Gangliocytoma in 1920. Lhermitte Duclos Disease (LDD) is an extremely rare disorder of uncertain prognosis and pathogenesis. LDD is recognised as a part of Cowden Disease, which being an autosomal-dominant phacomatosis and cancer syndrome. Till date only about 225 cases of LDD have currently been reported in medical literature. It is most commonly seen in young adults with a peak incidence in third or fourth decade with signs and symptoms of cerebellar dysfunction or increased intracranial pressure leading to obstructive hydrocephalus. A 36-year-old female came to Neuromedicine Outpatient Department (OPD) in a Tertiary Care Superspecialty Hospital with chief complaints of headache and vomiting, difficulty in swallowing liquid food since two months with no significant family history. The patient’s general condition was not good with significant weakness on presentation. The patient was conscious, oriented with pulse rate of 78/bpm, blood pressure of 118/80 mm of Hg with bilateral clear chest with normal S1 S2 sound. The Glasgow Coma Scale (GCS) was found to be Eye response-4, Verbal response-5, Motor response-6. Magnetic Resonance Imaging (MRI) of patient showed large heterogeneous non-enhancing lesion involving left cerebellar hemisphere, vermis and cerebellar peduncle with widened cerebellar folia with a “Tigroid appearance”. A diagnosis of Cerebellar Gangliocytoma was made and was treated successfully with surgery and diagnostically proven with biopsy and immunohistochemistry. The background history of Cowden syndrome was not present in index case.

Lhermitte–Duclos disease (dysplastic cerebellar gangliocytoma)

Dear Editor, We read the article entitled “Cowden syndrome diagnosed by Lhermitte–Duclos disease” in the esteemed “Formosan Journal of Surgery” with great interest. Che Chen et al. reported a case of an adult female presenting with dizziness and headache. A brain magnetic resonance imaging (MRI) showed a cerebellar lesion, in which the histological findings were of dysplastic cerebellar gangliocytoma.[1] Lhermitte–Duclos disease (LDD), also known as dysplastic cerebellar gangliocytoma, is a rare genetic disorder, which is characterized by abnormal development of the cerebellum that can increase intracranial pressure. In this context, it could occur isolated or associated with Cowden syndrome. Moreover, this disease has some histological hallmarks such as thickening and hypermyelination of the outer molecular layer, loss of Purkinje cells and white matter, dysplastic ganglion cells with rounded nuclei, and abundant mitochondria invading the inner granular layer.[2] Here, we would like to highlight some important topics that together with the study of Che Chen et al. could lead to a better comprehension of LDD. In addition, we developed a mnemonic to remember the facts of LDD that is DUCLOS: Dysplastic cerebellar gangliocytoma; Unilateral hamartomatous mass with tigroid appearance on MRI; Cowden syndrome association; Later in life 3rd and 4th decades of life; Overpressure by the tumor leads to neurological symptoms; S uppressor gene PTEN mutation in at least 10% of the individuals.[123456] A recent genetic study about LDD was published by Colby et al. They reported a case of an adult female diagnosed with LDD and wild type for phosphatase and tensin homolog. When the exome sequencing was analyzed, it revealed an extracellular domain mutation in the epidermal growth factor receptor gene, which resulted in constitutive activation. Thus, this study was important because it supports a new hypothesis for the pathophysiology of LDD and contributes to a possible new therapy for the treatment of this disease.[4] In 2015, Bosemani et al. reported a case of pseudotumoral hemicerebellitis (PTHC) mimicking LDD in children, and they raised an important question asking about if neuroimaging can differentiate these two entities. A literature review revealed that conventional evaluation may help differ the diseases. Furthermore, they provide some features that if present are suggestive of LDD such as lesion-affecting brainstem, striated folial pattern, and thickened cerebellar folia surrounded by enlarged veins. Otherwise, if brain MRI has postgadolinium enhancement and a choline peak spectroscopy, PTHC could not be ruled out.[3] Zak et al. reported a case of LDD where surgical removal was not a possible option. Hence, a rapamycin trial based on a previous study about the pathological mechanism of LDD and the use of this medication was done. Rapamycin causes a downstream of some tissue growth factors that are associated with LDD. The infant reported in their study was diagnosed with LDD at 18 months, and rapamycin was started. On follow-up, the infant had full recovery including imaging that did not reveal the previous brainstem compression and distortion of pituitary stalk.[6] In another study, high-definition fiber tractography was done for surgical planning. Fernandes-Cabral et al. concluded that tractography is an important method that should be performed in surgical cases because it could reveal abnormalities not evident on conventional assessment. Therefore, this can allow maximal resection of the lesion, avoid damaging of unaffected tracts, and decrease tumoral recurrence.[5] Financial support and sponsorship Nil. Conflicts of interest There are no conflicts of interest.

A Case Report of Lhermitte-Duclos Disease in a 10-Month-Old Child Presenting with Hydrocephalus

Lhermitte–Duclos Disease is a rare entity characterized by diffuse or focal enlargement of cerebellar folia. Clinical manifestations are usually related to a mass effect and secondary obstructive hydrocephalus. Increased intracranial pressure symptoms and cerebellar symptoms are the most frequent patient complaints. We present a 10-month-old male child with his mother who presented to the outpatient department with complaints of enlargement of size of head since the last one week. Magnetic Resonance Imaging scan revealed the features of Lhermitte–Duclos Disease involving the right cerebellar hemisphere with marked post contrast gyral enhancement. He underwent endoscopic third ventriculostomy. Lhermitte–Duclos Disease is very rare in early childhood and should be considered in the differential diagnosis of posterior fossa lesions.