Epilepsy & cognitive impairment in SPG4

Seizures successfully treated

This case study describes a 21-year-old man who developed complicated SPG4 at the age of 13 when seizures began. Several commonly used drugs were ineffective in controlling the seizures, however the combination of three other drugs proved highly effective.

This case is another example of some types of SPG4 HSP with symptoms not confined to the motor system.



Hereditary spastic paraplegias (HSPs) are rare neurological disorders caused by degeneration of the corticospinal tract. Among the 79 causative genes involved in HSPs, variants in SPAST on chromosome 2p22, which encodes the microtubule-severing protein spastin, are responsible for spastic paraplegia type 4 (SPG4), the most common form of HSPs.

SPG4 is characterized by a clinically pure phenotype that is associated with restricted involvement of the corticospinal tract; however, it is often accompanied by additional neurological symptoms such as epilepsy and cognitive impairment. There are few reports regarding the clinical course and treatment of epilepsy associated with SPG4.

We describe a 21-year-old male patient with progressive weakness and spasticity of the lower limbs since infancy, which was complicated by epilepsy and cognitive impairment. Magnetic resonance imaging of the brain showed right hippocampal atrophy before the onset of epilepsy. Genetic analysis revealed a novel missense variant (NM_014946.4:c.1330G>C, p.Asp444His) in the SPAST gene. At the age of 13, the patient developed focal epilepsy, characterized by focal onset seizures that were preceded by a sensation of chest tightness.

Carbamazepine, levetiracetam, and zonisamide were ineffective in controlling the seizures; however, the use of lacosamide in combination with lamotrigine and valproate was highly effective in improving the seizure symptoms and led to the patient being seizure free for at least 2 years.

In conclusion, the missense variant in SPAST may cause a complex SPG4 phenotype accompanied by epilepsy and cognitive impairment, suggesting that the clinical manifestations of this condition do not confine to the motor system.

SOURCE:  Case Rep Neurol. 2021 Dec 7;13(3):763-771. doi: 10.1159/000520433. eCollection Sep-Dec 2021. PMID: 35082646 Copyright © 2021 by S. Karger AG, Basel.

A Complex Phenotype of a Patient with Spastic Paraplegia Type 4 Caused by a Novel Pathogenic Variant in the SPAST Gene

Yuichi Akaba  1 Ryo Takeguchi  1 Ryosuke Tanaka  1 Satoru Takahashi  1

1. Department of Pediatrics, Asahikawa Medical University, Asahikawa, Japan.

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