Long‐term follow‐up of two siblings with adult‐onset neuronal ceroid lipofuscinosis, Kufs type A

Abstract

Aim. Reports on the clinical presentation of adult‐onset neuronal ceroid lipofuscinoses (NCL) are scarce compared to infantile‐ and childhood‐onset forms. Here, we aimed to present detailed temporal evolution of clinical and electrophysiological features of two siblings with adult‐onset NCL and homozygous mutation in the CLN6 gene. Methods. We retrospectively analysed medical records and electrophysiological data in order to delineate evolution of clinical and electrophysiological findings. Electrophysiological studies included routine EEG and video‐EEG, as well as polymyographic analysis of myoclonus and brainstem reflex studies. Results. Both patients had seizures and cerebellar signs. Despite the slow progression of ataxia, they developed no mental deterioration, but had severe obsessive compulsive disorder and depression. EEG revealed frequent generalized spikes, polyspikes, and waves, prominent on awakening and during photic stimulation without significant change throughout the clinical course. Abnormalities concerning the blink reflex, auditory startle response, and startle response to somatosensory inputs manifested within four years. The patients underwent transient and mild improvement with valproate, whereas ataxia and seizures were dramatically ameliorated following high‐dose piracetam. Conclusions. Patients with adult‐onset NCL may present with slowly progressive ataxia, persistent photosensitivity, and seizures without dementia or extrapyramidal findings. Brainstem abnormalities become more evident with time, in line with ataxia. Piracetam is effective for both seizures and ataxia.

Clinical challenges and future therapeutic approaches for neuronal ceroid lipofuscinosis

“…30,31 Photosensitivity with lowfrequency stimulation has also been reported in patients with neuronal ceroid lipofuscinosis type 6 (CLN6) disease, and especially in those with adult CLN6 disease (type A). [32][33][34] In NCL forms that rapidly progress, such as infantile CLN1 disease, early abnor malities disappear as neurons die, leading to a char acteristic flat EEG at advanced stages of disease. 1 Because of the underlying neurometabolic disease, antiepileptic drugs will not lead to normalisation of the EEG findings, 1 presumably because cells have died or are dying, and this in itself leads to seizures.…”

Recent Insight into the Genetic Basis, Clinical Features, and Diagnostic Methods for Neuronal Ceroid Lipofuscinosis

“…Photosensitivity with low-frequency stimulation has also been described in patients with CLN6 (neuronal ceroid lipofuscinosis type 6) disease, especially in adults with CLN6 (type A) disease. [ 3 , 137 , 162 , 163 ]. In forms of NCL that progress rapidly, such as infantile CLN1 disease, early abnormalities disappear as neurons die, leading to a characteristic flat EEG in advanced disease [ 3 , 13 ].…”

Reflex epilepsy: triggers and management strategies

“… 10 Adult-onset neuronal ceroid lipofuscinoses associated with the CLN6 mutation is a rare form of PME severe photosensitivity was reported in two siblings recently. 116 The other form of PME is Lafora disease where photosensitivity was enhanced during low frequency photic stimulation. 117…”