Ezgi Demirel Özbek1, Özay Gököz2, Neşe Dericioğlu1

1Hacettepe University Faculty of Medicine, Department of Neurology, Ankara, Türkiye
2Hacettepe University Faculty of Medicine, Department of Pathology, Ankara, Türkiye

Keywords: Lipoid proteinosis, epilepsy, drug-resistant seizures, medial temporal lobe calcification, clobazam

Dear editor,

Lipoid proteinosis (LP) is a very rare autosomal recessive disease caused by ECM1 mutations, which lead to the loss of protein– protein interaction, resulting in the deposition of hyaline material in the mucous membranes, skin, and other organs. Some of the easily recognizable mucocutaneous manifestations of the disease are hoarseness due to the infiltration of laryngeal mucosa, fragile skin with blisters, and beaded eyelid papules. Common neuropsychiatric manifestations are seizures, headache, psychosis, panic attacks, anxiety, memory impairment, and abnormal emotional responses to fear and danger (1). The prominent medial temporal lobe calcifications in neuroimaging studies are considered pathognomonic (2). Epilepsy is reported in approximately 30% of cases, with most patients experiencing temporal lobe seizure characteristics (3).

Our patient was a 26-year-old man who was admitted to our neurology clinic as a result of drug-resistant epileptic seizures. His first seizure was a generalized tonic–clonic convulsion at the age of 15. This was his only generalized seizure. Afterward, he developed focal seizures with impaired awareness. Some of his seizures were preceded by a rising epigastric sensation. His past medical history revealed a weak cry and hoarseness since infancy. He had fragile, easily damaged skin. He developed scars on his face, elbows, buttocks, and hands, which tended to increase when he was exposed to the sun (Figure 1A). He also had a thickened, firm, and enlarged tongue (Figure 1B). His neurological examination was unremarkable. He was born to first-degree consanguineous parents. Nobody in his family had similar symptoms or a diagnosis of epilepsy. An interictal electroencephalography (EEG) revealed slow background activity over the left temporal region with occasional sharp waves at the T3 electrode. Ictal EEG findings also involved the left temporal lobe. Cranial computed tomography revealed calcification of both amygdalae (Figure 2A), accompanied by millimetric calcifications in the basal ganglia. His magnetic resonance imaging showed bilateral amygdaloid hypointensities that were compatible with LP (Figure 2B). A punch biopsy taken from his lower lip demonstrated pale eosinophilic deposits of hyaline-like material in the dermis and around the capillaries on hematoxylin and eosin-stained sections. The deposits were strongly positive with periodic acid-Schiff (PAS) and PAS diastase stain (Figure 2C, D). Due to the intractable course of his seizures, the patient was prescribed vigabatrin, oxcarbazepine, lamotrigine, topiramate, and levetiracetam in various doses and combinations with minimal or no impact on seizure frequency or severity. His temporal lobe seizures continued to occur once a week. In 2017, clobazam (20 mg/day) was added to the existing anti-seizure medications (levetiracetam 3.000 and lamotrigine 400 mg/day). The patient has been seizure-free with these medications since then.

In a previous case series, 57% of patients with bilateral medial temporal involvement had seizures that were not correlated with the severity of calcifications (4). In the literature, most patients are reported to be drug resistant. Older and newer generation drugs have been tried, but none of them is superior to the others (4). Only one previous paper reported a patient who “dramatically improved” with a combination of carbamazepine (1.200 mg/d) and levetiracetam (1.000 mg/d) (5).

Peer Review

Externally and internally peer-reviewed.

Author Contributions

Concept: N.D., Design: N.D., Data Collection or Processing: Ö.G., E.D.Ö., Analysis or Interpretation: N.D., Literature Search: E.D.Ö., Writing: N.D., E.D.Ö.

Conflict of Interest

No conflict of interest was declared by the authors.

Financial Disclosure

The authors declared that this study received no financial support.


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