Hereditary spastic paraplegias (HSPs) comprise a heterogeneous group of rare, neurodegenerative disorders. The most prominent HSP features: spastic paraparesis, mild somatosensory deficits and bladder dysfunction may be accompanied by additional symptoms i.e.: neuropathy, epilepsy, dementia. We aimed to determine subclinical involvement of nonmotor or sensory brain structures in hereditary spastic paraplegias type 3 A (SPG3A) and type 4 (SPG4). Visual evoked potentials (VEPs), brainstem evoked potentials (BAEPs) and electroencephalography (EEG) were performed in 28 SPG4 and 9 SPG3A patients. Disease severity was evaluated with Spastic Paraplegia Rating Scale. The EEG examination revealed abnormalities in 9 SPG4 patients (35%), while it was intact in SPG3A individuals. VEPs indicated mild abnormalities in 38% SPG3A patients: 127.3±7.8ms and 48% SPG4: 122.2±6.4ms. SPG4 patients with DNA microrearrangements in the SPAST gene had statistically significantly longer VEPs latencies (95%CI, 2.78–10.10) and lower amplitudes (95%CI, -5.65 – (-1.45)) than those with single nucleotide variants. BAEPs were distracted accidentally. It appears that visual tracts, which involve shorter axons than in motor-sensory pathways, are also involved in neurodegenerative processes in SPG3A and SPG4. Additionally, in SPG4 abnormal oscillations of neurons indicated by EEG may probably result from impaired axonal transport. The online version contains supplementary material available at 10.1186/s12883-025-04624-4. Our study shows that SPG3A and SPG4 phenotypes are often combined with subclinical nonmotor or sensory brain dysfunctions. The online version contains supplementary material available at 10.1186/s12883-025-04624-4.

Pathogenic variants of IBA57 (OMIM ID: 615330) are usually associated with multiple mitochondrial dysfunction syndrome (MMDS) and hereditary spastic paraplegia type 74 (SPG74). Here, we present a novel compound heterozygous IBA57 mutation in a boy with severe global developmental delay, optic atrophy, spastic paraplegia, and focal epileptic seizures. The clinical data of a child diagnosed with MMDS were retrospectively collected. Video electroencephalogram (VEEG), cranial magnetic resonance imaging (MRI), and family whole-exome sequencing (WES) were performed. Suspected mutation sites were further confirmed using Sanger sequencing. The activities of mitochondrial respiratory chain complexes I-IV were determined in peripheral blood mononuclear cells. The phylogenetic conservation of the affected residues was assessed by multiple sequence alignment of IBA57 gene orthologs. Furthermore, we conducted a review of the relevant literature. Whole-exome sequencing identified compound heterozygous variants in the IBA57 gene: c.395_400dup (p.V132_Q133dup) and c.832delC (p.R278Afs*23), inherited from his phenotypically normal father and mother, respectively. Biochemical assays demonstrated selective reduction of complexes I and II activities, with normal complexes III and IV, consistent with impaired 4Fe-4S cluster maturation. Phylogenetic alignment revealed strict conservation of residues V132-Q133 and R278 across vertebrates. These variants had not been previously reported in domestic or international databases. According to the American College of Medical Genetics and Genomics (ACMG) guidelines, the former was classified as a variant of uncertain significance (PM4 + PM2), while the latter was classified as likely pathogenic (PVS1 + PM2). Diseases associated with IBA57 gene variants are autosomal recessive disorders with a broad clinical phenotypic spectrum. Early genetic testing and family screening are beneficial for the diagnosis, treatment, and prognosis of the disease.

Spastic paraplegia type 79 (SPG79) is a rare form of hereditary spastic paraplegia caused by variants in ubiquitin C-terminal hydrolase L1 (UCHL1). SPG79B, an early-onset autosomal recessive subtype, frequently presents with lower motor neuron involvement, with myokymia as a characteristic feature. In contrast, SPG79A, a late-onset autosomal dominant form, rarely shows lower motor neuron signs, and myokymia has not previously been reported. We report the first documented case of myokymia in SPG79A. A 74-year-old man with an 8-year history of progressive gait disturbance underwent detailed evaluation. The patient exhibited slowly progressive spastic paraplegia and impaired proprioception in the lower extremities. Myokymia was observed in the extremities and trunk. Needle electromyography revealed spontaneous, repetitive discharges of motor unit potentials consistent with myokymia. Genetic testing identified a heterozygous nonsense variant in UCHL1 (c.532C > T: p. Arg178*), confirming a diagnosis of SPG79A. The pathogenesis of both SPG79A and SPG79B likely involves partial loss of UCHL1 function, explaining their overlapping phenotypes. Symptom variability may reflect the extent of residual UCHL1 function, with SPG79B showing broader features, including myokymia. This case suggests that myokymia, though rare in hereditary spastic paraplegias, can also occur in SPG79A and may serve as a diagnostic clue.

Hereditary spastic paraplegia (HSP) refers to a group of genetic neurodegenerative diseases marked by gradually worsening spasticity and hyperreflexia in the lower extremities. This study aimed to describe the clinical and genetic characteristics of Korean patients with spastic paraplegia. We retrospectively reviewed medical records of 69 patients with spastic paraplegia from 54 unrelated families between 2002 and 2024. Genetic, clinical, electrophysiological, and radiological features were comprehensively analyzed. Causative genes were identified in 34 (63%) of 54 unrelated families; SPAST, detected in 26 families, was the most prevalent. Seven novel pathogenic variants were identified. Clinically, the median age of symptom onset was 25 years [14.0-37.0]. Out of 69 patients with spastic paraplegia, 51 (74%) presented with the pure form of spastic paraplegia, which included all patients with SPG4. Spastic gait was a universal feature in all patients. Urinary dysfunction was present in 42 (61%) patients. Additional neurologic manifestations included peripheral neuropathy 9 (13%), cognitive impairment 5 (7%), upper limb weakness 4 (6%), dysarthria 4 (6%), dysphagia 3 (4%), ataxia 3 (4%), and scoliosis 1 (3%). Brain MRI findings demonstrated a thin corpus callosum in two patients with SPG11; all patients with SPG4 had normal findings. Spine MRI revealed spinal cord atrophy in 16 (27%) patients, including 6 (21%) patients with SPG4. The study comprehensively reviewed genetic and clinical spectra of spastic paraplegia in Korean patients, emphasizing the predominance of SPAST as the causative gene and underscoring the genetic and phenotypic heterogeneity of spastic paraplegia.

Cognitive deficits often accompany brain structural changes, but the association between spinal cord atrophy and cognitive function remains unclear. Spastic paraplegia type 5 (SPG5) is a subtype of hereditary spastic paraplegias (HSPs), caused by mutations in cholesterol metabolism genes, with radiological features of spinal cord atrophy. Our study aims to explore cognitive impairment in SPG5 and its relation to spinal cord structure. We conducted a prospective cross-sectional study with 30 HSPs patients and 47 healthy controls (HC), performing brain and spinal cord MRI and neuropsychological assessments. We investigated correlations between cognitive performance and MRI measurements. Compared to HC, SPG5 patients exhibited significant impairments in the Benton Judgment of Line Orientation Test (p = 0.033), Controlled Oral Word Association Test (p = 0.028), and Symbol Digit Modalities Test (p = 0.023). SPG5 patients also demonstrated significant reductions in spinal cord and thoracic cord cross-sectional area (CSA), anterior-posterior (AP) diameter, and right-left (RL) total (All p < 0.01). Specifically, the thoracic cord RL total was positively correlated with scores on the Brief Visuospatial Memory Test - Revisited delayed recall (BVMT-R DR) and Montreal Cognitive Assessment (MoCA). The spinal cord RL total explained 81% of the variance in BVMT-R DR (p = 0.015) and 74% of the variance in MoCA (p = 0.027). SPG5 patients demonstrate deficits in visuospatial perception, executive function, and information processing speed. Thoracic spinal cord RL total was positively associated with visual memory and global cognition.