MRI in CLN2 disease patients: Subtle features that support an early diagnosis

Abstract

Neuronal ceroid lipofuscinosis type 2 (CLN2) disease is a rare, paediatric-onset, neurodegenerative disorder characterised in its early stages by language delay, seizures and loss of motor function. It is rapidly progressive and ultimately results in the premature death of patients. We aim to highlight common magnetic resonance imaging (MRI) features seen in early CLN2 disease and increase disease awareness among clinicians in order to facilitate early diagnosis and treatment of patients with disease-modifying enzyme replacement therapy. We obtained MRI scans from 12 Turkish children with CLN2 disease, at symptom onset or time of diagnosis, and at various times during disease progression. Patient details including age at onset of symptoms, age at diagnosis and clinical presentation were collected. MRIs were analysed to identify common features present in patients with CLN2 disease. The median diagnostic delay in this cohort was 2 years, highlighting the need for increased disease awareness among clinicians. Key MRI features suggestive of CLN2 disease that were identified included cerebellar atrophy in 11 patients, linear hyperintensity of central white matter in 10 patients, cerebral atrophy in 8 patients and thinning of the corpus callosum in 6 patients. Thalamic hypointensity was seen in 1 patient and may also indicate CLN2 disease. It is important to consider the presenting symptoms alongside clinical test results in order to support early diagnosis of CLN2 disease. Clinical suspicion of CLN2 disease accompanied by the detection of any of the above-mentioned features on MRI should encourage healthcare professionals to test for CLN2 disease.

Gait phenotype in Batten disease: A marker of disease progression

“…We still lack results of long-term follow-up and we do not yet know the effect when treatment is initiated early or even before symptoms have started Key MRI features of CLN2 [42][43][44][45] include progression of gray matter atrophy most prominent in vermis and the cerebellar hemispheres, which virtually is present in all patients at 3-4 years of age. At that time cerebral atrophy is seen in around 50-75% of the described cases and linear hyperintensity of the central white matter in 70-80%.…”

“…At that time cerebral atrophy is seen in around 50-75% of the described cases and linear hyperintensity of the central white matter in 70-80%. The white matter changes are noted with a gradient from more severely affected posterior structures to mild affected anterior structures [42][43][44][45]. There are very few autopsy studies of patients with CLN2 and they primarily focus on electron microscopic and/or immunohistochemistry changes [46,47].…”

A Case Report on the Challenging Diagnosis of Neuronal Ceroid Lipofuscinosis Type 2 (CLN2)

“…Cerebellar and brain cortical atrophies are not specific findings of NCLs as they are also found in other neurodegenerative diseases, such as progressive myoclonic epilepsies [20]. More evidence investigating the association of CLN2 progression and the imaging findings may contribute the elucidate the role of imaging exams in the diagnosis and follow-up in CLN2 [18,19,21]. In the patient of the present case, MRI was unaltered in the first months after the disease onset.…”

“…More specifically, thalamic hipointensity, thinning of the corpus callosum and hyperintensity in both the insular cortex and in the posterior limb of the internal capsule, in addition to the cerebellar and the brain cortical atrophy, may be verified in patients this disease. It should be mentioned however that these findings may be absent in patients in the initial stage of CLN2, as described by Aydin [19]. Cerebellar and brain cortical atrophies are not specific findings of NCLs as they are also found in other neurodegenerative diseases, such as progressive myoclonic epilepsies [20].…”

Neuronal Ceroid Lipofuscinosis Type 2: A Case Series from Argentina

“…In our cohort, a first MRI was performed at a median age of 4.8 years, probably due to atypical presentation, and ventricular system enlargement, white matter changes and cerebellar atrophy were reported in more than a half of these subjects. In a previous Italian study of 14 patients with CLN2 disease, a first brain MRI was performed earlier (median age: 3.8 years) and cerebellar atrophy was identified in 100% of cases, while periventricular white matter changes were found in 79% of patients [10][11][12]. These differences among Latin American subjects clinical and imaging phenotypes and other cohorts deserve further research.…”